SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM · sion or ﬁ rst epileptic seizure. Seizures of some type occur in up to 5% of children but fortunately most are single episodes

PART 17SEIZURE DISORDERS AND DISORDERS OF

THE NERVOUS SYSTEM

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17.1Seizures and epilepsiesA. S. Harvey

Few events are more alarming to parents than their child having a breath-holding attack, febrile convul-sion or fi rst epileptic seizure. Seizures of some type occur in up to 5% of children but fortunately most are single episodes of a non-serious nature.

Terminology and classifi cationAn epileptic seizure is a neurological event in which there is a sustained and abnormal, hypersynchro-nous discharge from neurons in the cerebral cortex, either localized or widespread, usually associated with electrical, metabolic and clinical alterations. Epilepsy is classically defi ned as the group of condi-tions where a person has recurrent, unprovoked epileptic seizures. This defi nition excludes single sei-zures; febrile and other provoked seizures, seizures in newborns, seizures in the context of acute neuro-logical insults, and non-epileptic attacks such as faints and breath-holding spells.

The International League Against Epilepsy clas-sifi cation of seizures, based on clinical and electro-encephalography (EEG) features (1981), recognizes two major categories: focal (partial) seizures and generalized seizures. Focal seizures originate in a localized part (hence, partial) of the cerebrum, usually on one side, whereas generalized seizures commence synchronously in both cerebral hemi-spheres. Several, pathophysiologically-distinct gen-eralized seizures types are recognized by different clinical and EEG patterns, the most common being generalized tonic–clonic, absence and myoclonic seizures (Table 17.1.1). Focal seizures have similar pathophysiological features and are distinguished by the part of the brain involved and the resultant clini-cal manifestations.

The epilepsies or epileptic syndromes, the condi-tions that predispose to epileptic seizures, are best conceptualized in terms of the underlying aetiology and their predominant seizure types (Table 17.1.2). Idiopathic (primary) epilepsies are seizure disorders with no identifi able cause other than a presumed genetic predisposition to seizures. These epilepsies usually manifest with characteristic focal or general-ized seizures, predictable age at seizure onset, stereo-

typic EEG patterns, absence of other neurological problems, good response to treatment and favour-able neurological outcome. The idiopathic general-ized epilepsies are being gradually understood as abnormalities of neuronal ion channels. The cause of idiopathic partial epilepsies is not fully understood, although delay in cerebral maturation is postulated. Symptomatic (secondary) epilepsies are seizure disorders due to known or presumed (cryptogenic) underlying cerebral abnormalities such as cortical tumours, malformations, injuries or metabolic dis-turbances. These epilepsies tend to have variable seizure and EEG manifestations depending on the nature, location, extent and timing of the underlying cerebral abnormality. Symptomatic epilepsies usually have a poor prognosis for seizure control and are often associated with other neurological problems such as learning diffi culties, intellectual disability, behavioural problems and hemiplegia, again depend-ing on the nature and extent of the underlying cere-bral abnormality.

These terminologies and classifi cations are impre-cise and sometimes confusing, especially when terms are used to describe types of seizures and syndromes, e.g. febrile seizures, infantile spasms. Furthermore, there is much overlap of categories, with some patients having epilepsies with focal and generalized seizures, idiopathic epilepsies occurring in children with pre-existing developmental disabilities, and sei-zures arising as a result of an underlying cerebral abnormality and a genetic predisposition.

Prospective studies of new-onset epileptic seizures in childhood reveal that approximately 50% of patients with a fi rst seizure have a recurrence. Epi-lepsy as classically defi ned occurs with an annual incidence of about 60–80 in 100 000 and a prevalence of about 5 in 1000 in childhood, the incidence and prevalence being highest in infancy. Studies of new-onset epilepsy in childhood indicate a greater pro-portion with focal seizures than generalized and undetermined seizures, and about equal proportions of idiopathic, symptomatic and undetermined/cryptogenic aetiologies. Prospective studies of treated and untreated new-onset epilepsy reveal that about 80% of children go into remission, some with subsequent seizure relapses, and about 20% of chil-dren have treatment-resistant epilepsy.


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17.1 SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM

Common epilepsies of infancy, childhood and adolescenceFebrile seizures

Fever and seizures may coexist with infections of the central nervous system (not epilepsy) and with non-specifi c febrile illnesses in children with epilepsy.

However, fever and seizures most often occur together as a manifestation of the syndrome of febrile seizures, a condition in which some infants and young children have a presumed genetic predisposition to fi t in the presence of fever. Although not considered part of the classical defi nition of epilepsy, the syn-drome of febrile seizures does have several features in common with the idiopathic epilepsies, including an age-limited predisposition to seizures, a family history of seizures in more than 30% of children, an evolution to idiopathic generalized or partial epi-lepsy in a minority, and mutations in neuronal ion channel genes in some rare instances. Febrile sei-zures are the focus of ongoing epilepsy genetic research and are no longer considered just a non-specifi c susceptibility to seizure with fever in infants.

Simple febrile seizures are defi ned as a brief, gen-eralized tonic and/or clonic seizures in which there is neither clinical nor laboratory evidence of central nervous system infection, the temperature is 38°C or higher and the child has no history of previous afe-brile seizures, neurological defi cits or developmental delay to suggest an underlying neurological problem. Most febrile seizures are associated with upper respi-ratory or urinary tract infections or viral exanthe-mas and occur once at the beginning of the illness. Complicated febrile seizures are those that are pro-longed, focal or multiple.

Febrile seizures occur in approximately 3% of the population, commencing between the ages of 5 months and 5 years, with most manifesting in the fi rst 2 years of life. In approximately one-third of children febrile seizures are recurrent, the risk increasing to 50% if onset is in infancy or there is a family history of febrile seizures. Only 3% of chil-dren with febrile seizures go on to have later afebrile seizures, i.e. epilepsy, the risk being increased further if there is evidence of abnormal development or neu-rological problems, if the child has a family history of epilepsy or if the seizures are complicated. When epilepsy follows febrile seizures it is invariably a later manifestation of the same underlying seizure predis-position, i.e. idiopathic epilepsy. Very rarely, later epileptic seizures may be the result of brain injury from prolonged and focal febrile seizures. Febrile seizures are not associated with any increased mor-tality or later intellectual impairment.

Treatment

The cause of the febrile illness is investigated and treated on its own merits. There is no role for EEG or brain imaging in febrile seizures. There is debate about the role of antipyretics and gentle cooling. Seizures have usually ceased before medical help is obtained; however, if a febrile seizure continues after

Table 17.1.1 Classifi cation of epileptic seizure type, based on clinical and EEG features

Focal (partial)• Simple partial – consciousness preserved• Complex partial – consciousness impaired• Partial seizures with secondary generalization

Generalized• Tonic–clonic• Absence• Myoclonic• Clonic• Tonic (epileptic spasms are series of brief tonic seizures)• Atonic

Table 17.1.2 Common types of epilepsy in childhood, grouped by age

Infancy• Benign familial/non-familial neonatal convulsions*• Febrile seizures (not classically considered epilepsy)• Infantile epileptic encephalopathy with epileptic spasms

(West syndrome)†

• Severe myoclonic epilepsy of infancy (Dravet syndrome)• Benign familial/non-familial infantile convulsions*• Symptomatic focal epilepsies of infancy – commonly

hemispheric and multilobar†

Childhood• Typical childhood absence epilepsy *• Benign focal (rolandic) epilepsy of childhood with

centrotemporal spikes*• Benign occipital epilepsy *• Primary generalized epilepsy with tonic–clonic seizures*• Childhood epileptic encephalopathy with tonic seizures

(Lennox–Gastaut syndrome)†

• Symptomatic focal epilepsies – commonly temporal lobe epilepsy and frontal lobe epilepsy†

Adolescence• Primary generalized epilepsy with tonic–clonic seizures*• Juvenile absence epilepsy*• Juvenile myoclonic epilepsy*• Symptomatic focal epilepsies – commonly temporal lobe

epilepsy and frontal lobe epilepsy†

* classical idiopathic epilepsy syndromes, † classical symptomatic epilepsy syndromes.


SEIZURES AND EPILEPSIES 17.1

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3–5 minutes, it should be terminated urgently, usually with rectal or intravenous diazepam. Meningitis or encephalitis should be considered if the child has a history of vomiting, is younger than 6 months, has repeated seizures following presentation, has been treated with antibiotics, has not recovered promptly from the seizure or seems more ill than would be expected following a simple febrile seizure.

Antiepileptic medication does not diminish the likelihood of later epilepsy. Given the benign nature of the seizures and the potential adverse effects of antiepileptic medication, treatment is rarely pre-scribed for the syndrome of febrile seizures. Parents and carers need explanation and reassurance about the likelihood of further febrile seizures, the infre-quency of later epilepsy, the rarity of neurological problems and the management of subsequent febrile illnesses and seizures. Some children with a history of recurrent or prolonged febrile seizures may be prescribed prophylactic oral diazepam or emergency rectal diazepam, respectively, although these remain controversial issues.

Infantile spasms

The syndrome of infantile spasms is the most common symptomatic generalized epilepsy syndrome in child-hood. Onset of epileptic spasms is usually between 3 and 8 months of age and males are affected twice as commonly as females. Flexor or salaam spasms are the most common and consist of sudden drawing up of the legs, hunching forward of the neck and shoul-ders and fl inging out of the arms; opisthotonic or extensor spasms are less common. Epileptic spasms

are essentially brief tonic seizures and they typically occur in series over a minute or more, usually many times a day. The EEG usually shows a diffusely dis-organized pattern with high-voltage, multifocal epi-leptic activity, called hypsarrhythmia (Fig. 17.1.1). Development may be delayed prior to the onset of spasms, or there may be loss of visual attention and arrest of developmental progress at seizure onset. The term West syndrome is often used synonymously with infantile spasms but classically refers to the triad of epileptic spasms, developmental delay and hypsarrhythmia. Differential diagnosis includes a variety of normal or benign infant behaviours, such as sleep jerks, colic, shuddering attacks, benign myoclonus of infancy and gastro-oesophageal refl ux, as well as other less sinister myoclonic epilepsies of infancy.

Infantile spasms are an age-dependent manifesta-tion of a severe, localized or diffuse, acquired or developmental, disturbance in the immature central nervous system. An underlying cause is identifi ed in about two-thirds of infants, including prenatal/perinatal stroke or infection, focal or diffuse brain malformations, tuberous sclerosis and metabolic disorders such as pyridoxine (vitamin B6) defi ciency or phenylketonuria. In these symptomatic cases, the outcome for seizures and development is usually poor. In the cryptogenic cases where no cause is apparent from history, examination, brain imaging and metabolic screening, outcome is more variable; if there is a prior history of developmental delay and spasms are not quickly controlled with treatment, outcome is again poor. Overall, 70–80% children with infantile spasms develop some degree of

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Fig. 17.1.1 The EEG pattern of hypsarrhythmia, showing diffuse, continuous, high-amplitude, irregular sharp waves, spikes and slow waves on a disorganized background, typical of that seen in infantile spasms.


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intellectual disability and 30–50% develop a chronic, focal or generalized epilepsy. In many children with a symptomatic generalized epilepsy following infan-tile spasms, the electroclinical picture is that of the Lennox–Gastaut syndrome with refractory tonic and other seizures, generalized slow spike wave and par-oxysmal fast activity on EEG, and severe intellectual disability. The neurological sequelae of infantile spasms seem to be the result of both the underlying cerebral or metabolic abnormality and the deleteri-ous effects of frequent seizures and EEG disturbance on the developing brain.

Treatment

The syndrome of infantile spasms needs urgent diag-nosis, investigation and treatment. Treatment choices include corticosteroids (e.g. intramuscular adreno-corticotrophic hormone (ACTH), oral prednisolone), vigabatrin and benzodiazepines (e.g. nitrazepam, clonazepam). Pyridoxine should always be given as a trial, prior to commencement of antiepileptic drugs or steroids, to exclude pyridoxine dependency syn-drome. In infants with unilateral strokes or malfor-mations and drug-resistant seizures, epilepsy surgery may be considered. The aims of all treatments are to stop seizures, suppress the epileptic EEG distur-bances and maximize neurological development.

Absence epilepsies

Absence epilepsies are idiopathic generalized epilep-sies that manifest in otherwise normal children with predominantly absence seizures. Absence seizures are manifest by sudden cessation of activity with staring, usually lasting only 5–15 seconds. Blinking, upward deviation of the eyes, slight mouthing move-ments and some fi dgeting hand movements (automa-tisms) may occur. The child is unresponsive, does not fall, is rarely incontinent and returns promptly to normal activity at the offset of the absence, with no memory of the seizure. The EEG shows generalized spike-wave activity during the seizure (Fig. 17.1.2). Usually, many attacks occur in a day. Absence sei-zures can generally be precipitated in the clinic room and during EEG recordings with forced hyperventi-lation. Differential diagnosis of absence seizures includes daydreaming and complex partial seizures.

Absence seizures usually commence after the age of 4 years and there are two common types described. In typical childhood absence epilepsy (so called petit mal epilepsy), absences usually begin before the age of 7 years, tonic–clonic seizures are rare, the EEG shows runs of regular 3 Hz spike-wave activity and prognosis for seizure remission is good. In juvenile absence epilepsy, onset of absences is later, some-times in the teen years, the EEG shows faster and more irregular spike-wave activity, there may be associated tonic–clonic seizures, and prognosis for seizure remission is poorer. Intellectual development is usually normal in absence epilepsies.

Treatment

EEG is needed to confi rm absence seizures and char-acterize the epilepsy syndrome; brain imaging is unnecessary. Sodium valproate, ethosuximide and lamotrigine are the medications used commonly to treat absence seizures. Treatment is usually for 2 years in typical childhood absence epilepsy, with an expectation of seizure remission, and through puberty into the teen years in juvenile absence epi-lepsy. Rare refractory cases may respond to treat-ment with a ketogenic diet.

Benign focal epilepsies of childhood

The benign or idiopathic focal (partial) epilepsies of childhood are some of the most common epileptic syndromes in children. They occur in otherwise normal preschool and primary-school-age children and typically manifest with infrequent sleep-related focal seizures and prominent focal epileptiform pat-terns on routine EEG, these remitting in the second decade. The two most common varieties are benign rolandic epilepsy (benign epilepsy with centrotemporal

Clinical example

Baby Jonathan presented at the age of 5 months with episodes of stiffening and drawing up of his legs, thought to be colic.

The attacks lasted only seconds but occurred in clusters up to 10 times each day. During the attacks, his eyes rolled up, he appeared unaware and he would cry briefl y. Jonathan’s parents were also concerned that he seemed irritable, was not fi xing on their faces and was no longer smiling. The pregnancy, birth and early developmental milestones had been unremarkable. On examination, Jonathan fi xed and followed poorly and had poor head control. Examination revealed several depigmented patches of skin on the legs and trunk. A cluster of typical bilateral infantile spasms occurred during the assessment, with head and eye deviation to the right side. An EEG that day showed a modifi ed hypsarrhythmic pattern, confi rming West syndrome with infantile spasms, and vigabatrin was started promptly. An MRI the week following showed cortical tubers and periventricular nodules, confi rming the underlying diagnosis of tuberous sclerosis. Spasms ceased after the second day of vigabatrin and there was some improvement in visual attention the week following. However, Jonathan’s motor development was slow over subsequent months and smiling was sporadic. EEG continued to show prominent multifocal epileptic activity, although reduced.



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spikes), in which the seizure and EEG focus is low in the central sulcus (rolandic) region on one or both sides, and benign occipital epilepsy, in which the seizure and EEG focus is in the occipital lobe on one or both sides. The aetiology and pathogenesis of the idiopathic focal epilepsies is unclear in that they are not due to underlying structural brain lesions and they share only limited genetic associations with the idiopathic generalized epilepsies. The EEG abnor-malities of the benign focal epilepsies can be found in children with no history of seizures, sometimes leading to diagnostic errors.

In benign rolandic epilepsy, seizure onset is usually between 5 and 10 years of age and there is a male predominance. Focal seizures may be simple partial with tingling or twitching of the mouth and pre-served consciousness, often with associated drooling of saliva, choking noises and inability to speak. Sei-zures may progress to jerking of one side of the body, with or without impairment of consciousness. Some children have secondarily generalized seizures in which the focal onset is not recalled or witnessed. Attacks are most commonly from sleep. EEG record-ings that include sleep reveal very frequent focal epi-leptiform activity over the centrotemporal regions on one or both sides (Fig. 17.1.3). In benign occipital epilepsy, the presentation is usually before the age of 6 years and there is a female predominance. Seizures are characteristically from sleep with complex partial or secondarily generalized attacks beginning with staring, vomiting, head rotation, eye deviation and hemiclonic jerking. Seizures can sometimes be pro-longed and raise concern about encephalitis. Daytime attacks may occur with episodic visual distortions or hallucinations and migraine-like headaches. Again, EEG recordings that include sleep reveal character-istic focal epileptiform activity over the occipital region. In typical cases of benign focal epilepsy, brain imaging is unnecessary.

Treatment

Seizures tend to be infrequent in the benign focal epilepsies, many children having only one or two seizures before they ultimately remit. Because of this, and the tendency for nocturnal occurrence, treatment with antiepileptic medications is not

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Fig. 17.1.2 The EEG of typical absence epilepsy during an absence seizure, showing a paroxysm of generalized 3 Hz spike-wave activity.

Clinical example

Nadine, a 6-year-old girl, was noted by her parents to frequently ‘blank out’ while sitting at the dinner table and most recently, to stop

walking and talking while shopping with her mother. These episodes were occurring several times a day and seemed to last only a few seconds. Her class teacher had not noticed any problems. Hyperventilation in the clinic room provoked a typical absence episode lasting 12 seconds, during which Nadine was seen to stop hyperventilating, be unresponsive, fi dget with her shirt and have slight bobbing of her eyes. Typical childhood absence epilepsy was confi rmed with an EEG, which showed 3 Hz generalized spike-wave activity during spontaneous and hyperventilation-induced absence seizures. Sodium valproate was introduced slowly over 3 weeks with no absences noted after the second week of treatment and none precipitated with hyperventilation when reviewed. Slight irritability and moodiness were reported by Nadine’s parents as potential side effects of treatment.


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always necessary. If warranted, treatment with sodium valproate or low dose carbamazepine for 1–2 years is usually adequate. Prognosis is excellent, with absence of cognitive and behavioural problems, and remission of seizures by the teen years, hence the term ‘benign’. In rare instances, these epilepsies may

manifest in an atypical way with more problematic seizures, continuous bilateral EEG disturbances and deleterious effects on language and motor develop-ment; this tends to occur in children with pre-existing neurological problems.

Primary generalized epilepsies with tonic–clonic seizures

The primary or idiopathic generalized epilepsies with tonic–clonic seizures are a somewhat heteroge-nous group of seizure disorders occurring in other-wise normal children and adolescents, sometimes with additional absence and myoclonic seizures. Generalized tonic–clonic seizures typically begin with loss of consciousness, stiffening (tonic), tempo-rary cessation of breathing and falling if standing, then progress to a phase with generalized, rhythmic jerking (clonic), which is initially rapid but gradually slows. Tonic–clonic seizures invariably cease spon-taneously, usually within a few minutes, and are followed by a postictal period with depressed con-sciousness and headache, during which the person usually sleeps. There are no warning symptoms (auras), no signifi cant focal features to the seizure and no memory of the actual seizure. Generalized tonic–clonic seizures often occur during intercur-rent febrile illnesses in young children and either during sleep or following periods of sleep depriva-tion or stress in older children and adolescents.

Generalized tonic–clonic seizures may begin at any age but onset around puberty is common. Some-times there is a history of prior febrile seizures or absence seizures; in these cases, the later occurrence of tonic–clonic seizures usually represents an age-

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Fig. 17.1.3 The EEG of benign focal epilepsy of childhood with centrotemporal spikes (benign rolandic epilepsy) showing focal epileptiform activity in the left central region (lower three channels).

Clinical example

Michael, a developmentally normal 8-year-old boy, presented to the emergency department of a regional hospital after being heard fi tting

in his motel bed at 5 am while holidaying with his family. The seizure was brief, seemingly generalized tonic–clonic, associated with prominent gurgling noises and followed by a 10–15-minute period during which his speech was slurred and his face drooped on one side. The parents recalled hearing similar noises from Michael’s bedroom once or twice previously and occasionally fi nding his pillow wet with saliva in the morning. Michael described waking from his sleep in this seizure, having an fuzzy feeling in his mouth and being unable to call out to his parents, who were sleeping in the same room. An EEG arranged subsequently showed very frequent left central and temporal epileptiform discharges that became almost continuous in sleep. A diagnosis of benign rolandic epilepsy was made. Computed tomography (CT) of the brain, which was performed in the regional hospital, was normal. Following much parental counselling and reassurance about the benign nature of this type of epilepsy, it was decided to not perform a magnetic resonance imaging (MRI) scan and to defer treatment with antiepileptic medication. General safety and lifestyle advice was given about seizures, although it was appreciated that seizure occurrence in the day was unlikely.



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dependent, evolving expression of the same underly-ing, genetically determined seizure tendency. As for other idiopathic epilepsies, there is no demonstrable cerebral or metabolic abnormality, usually normal intellect and sometimes a family history of seizures. The routine EEG shows characteristic generalized spike-wave and polyspike-wave discharges. Juvenile myoclonic epilepsy is a type of primary generalized epilepsy typically beginning in the teen years with generalized tonic–clonic seizures, early morning myoclonic jerks and sometimes brief absence sei-zures, seizures often being precipitated by sleep deprivation. The EEG in this syndrome shows 4–7 Hz generalized polyspike-wave activity. Photosensitive epilepsy with generalized tonic–clonic seizures is another type of idiopathic generalized epilepsy, where the seizures and EEG abnormalities are almost exclusively related to fl ashing light stimulation.

The differential diagnosis of generalized tonic–clonic seizures includes focal seizures with second-ary generalization, convulsive syncope and psychogenic seizures. A preceding aura, focal or asymmetric features to the seizure, transient postical weakness of a limb (Todd’s paresis), focal neurologi-cal defi cits on examination, or a history of a prior cerebral trauma or infection should suggest a focal basis for an apparently generalized tonic–clonic seizure. Seizures of brief duration with rapid recov-ery and seizures occurring in typical vasovagal set-tings (see below) should suggest a syncopal rather than an epileptic basis. Psychogenic seizures are highly variable in their manifestations and can occur in patients with epilepsy, making their diagnosis sometimes diffi cult.

Treatment

Sodium valproate is the drug of choice for general-ized tonic–clonic seizures, especially when there is documented generalized spike-wave on EEG or there is a history to suggest additional absence or myo-clonic seizures. Carbamazepine is sometimes used for generalized tonic–clonic seizures when other fea-tures of primary generalized epilepsy are lacking, there being a risk of exacerbating absence and myo-clonic seizures in predisposed patients. Lamotrigine, phenytoin, oxcarbazepine, topiramate and benzodi-azepines are also effective for generalized tonic–clonic seizures. Seizure control is usually possible with medication and lifestyle adjustments (e.g. avoid-ing sleep deprivation). Many children and adoles-cents with primary generalized epilepsy and isolated tonic–clonic seizures outgrow their need for medica-tion but adolescents with juvenile myoclonic epi-lepsy specifi cally usually require treatment into adult life.

Temporal and frontal lobe epilepsies

Temporal lobe epilepsy (TLE) and frontal lobe epi-lepsy (FLE) are focal epilepsies in which seizures arise in the temporal or frontal lobes on one or both sides. TLE and FLE are generally considered symp-tomatic focal epilepsies in which an underlying scar, tumour, cyst or malformation is either known or sus-pected to be the basis of the recurring focal seizures. Symptomatic focal epilepsies can arise in any part of the brain, and in infants and young children they can often be due to multilobar or hemispheric lesions. TLE and FLE are the most common varieties of symptomatic focal epilepsy in children and adults, presumably because they make up the largest brain surface area of the brain. Seizures may comm-ence at any age but often not until later childhood or adolescence, even when due to congenital malformations.

Focal seizures may be simple partial with pre-served consciousness, complex partial with impaired consciousness, or secondarily generalized, the exact clinical manifestations of the seizures depending on the location of seizure onset and propagation. Some patients with complex partial and secondarily

Clinical example

Stephanie, a 13-year-old girl with a history of a single febrile seizure in infancy, presented to a regional hospital emergency department

after having a generalized tonic–clonic seizure at school camp. The seizure occurred in the shower at 7 am, the morning after girls in Stephanie’s cabin had stayed awake until 4 am. Stephanie was heard to fall in the shower and was found by a friend convulsing on the shower fl oor. She sustained a forehead bruise and hot water scalding on her back. There was no history of staring episodes or isolated jerking of the limbs. Stephanie recalled that on one occasion she had had to walk away from a computer game that her brother was playing because she felt sick and her head started jerking. There was no family history of epilepsy. Subsequent EEG recording showed frequent bursts of generalized fast spike-wave activity at rest and during photic stimulation. A diagnosis of primary generalized epilepsy with tonic–clonic seizures and associated photosensitivity was made. Long discussions were held with Stephanie and her parents over the initial and subsequent consultations, highlighting safety and lifestyle factors. Sodium valproate was commenced after discussion of the high likelihood of further seizures. The potential for weight gain and mild hair loss as side effects of treatment was also discussed, these concerning Stephanie more than the risk of further seizures. The family was given a guarded prognosis for seizure remission in the later teen years and regular review was arranged.


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generalized seizures have prior warning symptoms, or auras, these being the simple partial phase of an evolving focal seizure.

Seizures in temporal lobe epilepsy are usually complex partial in type, characteristically manifest by motionless staring, fearful or bewildered facial expression, unresponsiveness, fi dgeting hand move-ments (automatisms) and postictal amnesia and con-fusion. In some patients there may be head turning or stiffening or jerking of the limbs on one side during the seizure. Autonomic disturbances such as facial fl ushing or pallor, lip smacking, salivation, chewing, swallowing and sometimes vomiting are common; apnoea may be the predominant manifestation of complex partial seizures in infancy. Warning of an impending seizure (aura) is often present but may not be described at the time or recalled in a young or developmentally delayed child; fear, unusual smells or tastes, abdominal discomfort and dizzy or dreamy states are the usual descriptions. Complex partial seizures may secondarily generalize. Complex partial seizures last longer than absence seizures, generally 30–60 seconds, and are followed by postictal confu-sion and sleepiness. They are usually infrequent and commonly occur in clusters over several days, alter-nating with seizure-free periods.

Seizures in frontal lobe epilepsy often occur from sleep are brief in duration and commonly manifest with prominent motor features such as unilateral or bilateral stiffening or jerking, asymmetric tonic posturing with head deviation to one side, loud vocalization and hyperkinetic behaviours (automa-tisms) such as tapping, cycling and running. Seizures may occur on a multiple nightly basis. Secondary generalization is common.

The routine EEG in symptomatic focal epilepsy may be normal, show non-specifi c abnormalities or show localized epileptic patterns over the affected

brain region. Video-EEG monitoring with recording of seizures is sometimes necessary to confi rm the diagnosis and localize the seizures. The differential diagnosis of TLE, with episodes of staring and confused behaviour, includes daydreaming, absence seizures, behavioural outbursts, migraine and psy-chogenic seizures. The differential diagnosis of FLE, with nocturnal convulsive or thrashing seizures, includes parasomnias and primary generalized epi-lepsy. Benign focal epilepsies can usually be distin-guished from TLE and FLE by their characteristic rolandic or occipital seizure and EEG manifesta-tions, occurring at typical ages in otherwise normal children. Brain imaging with MRI is needed to search for an underlying cerebral lesion in all patients with focal seizures not due an idiopathic epilepsy syndrome, although causative lesions are not always found.

Treatment

Carbamazepine is the drug of fi rst choice for seizures in all symptomatic focal epilepsies, including TLE and FLE. Seizures may be resistant to treatment and, over time, the patient may be tried on other medications (Table 17.1.3). Cognitive, physical and behavioural problems may be present in some chil-dren with TLE and FLE, as non-seizure manifesta-tions of the underlying temporal or frontal lobe disturbance or lesion. These comorbidities may require specifi c assessment and intervention in their own right. Spontaneous seizure remission occurs in some patients, mainly when a lesion is not identifi ed on MRI. In children with uncontrolled seizures that impact signifi cantly on the life of the child and family, or are exerting detrimental effects on neuro-logical development, resection of the responsible lesion or affected lobe(s) may be considered.

Table 17.1.3 Antiepileptic medications most effective in different seizure types

Seizure type Antiepileptic medication

Focal (simple, complex and secondarily Carbamazepine, oxcarbazepine, lamotrigine, sodium valproate, topiramate, generalized) levetiracetam, phenytoin, gabapentin, benzodiazepines

Generalized tonic–clonic (primary) Sodium valproate, lamotrigine, topiramate, carbamazepine, phenytoin, oxcarbazepine, benzodiazepines, levetiracetam

Absence Sodium valproate, ethosuximide, lamotrigine

Myoclonic, atonic, tonic Sodium valproate, lamotrigine, benzodiazepines, topiramate

Neonatal seizures Phenobarbital, phenytoin, clonazepam

Infantile spasms Vigabatrin, prednisolone/ACTH, benzodiazepines



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Breath-holding attacks

Attacks usually commence in the fi rst or second year of life and are reported in up to 4% of children. Crucial to the diagnosis is recognition that attacks are precipitated by either physical trauma, such as a knock or a fall, or emotional trauma such as fright, anger or frustration, the precipitants not always being signifi cant and noticed. Attacks usually com-mence with crying, but this may be brief or absent. Apnoea and bradycardia then occur, either suddenly or gradually, with cyanosis or pallor following. The attack may then terminate without loss of conscious-ness, or progress, with the child becoming uncon-scious, limp and sometimes briefl y stiffening or jerking in response to the cerebral ischaemia. Recov-ery is usually rapid, although some children are drowsy and lethargic after an attack with convulsive features. Attacks usually cease by the third or fourth year of life.

The pathophysiology of breath-holding attacks is not well understood but affected children probably have an age-related dysfunction in cardiorespiratory refl exes. Iron-defi ciency anaemia is an exacerbating factor in some children with frequent attacks or prominent convulsive features. Breath-holding attacks are not a cause of death, epilepsy, intellectual disability or cerebral damage and families should be reassured about their benign nature.

Syncope

Syncope, or fainting, is not uncommon in childhood. As in adults, it is the result of decreased cardiac output and cerebral perfusion leading to loss of con-sciousness and falling. Brief tonic stiffening, clonic jerking or incontinence can accompany the loss of consciousness and lead to misdiagnosis as an epilep-tic seizure. Recovery is usually prompt following syncope. Light-headedness, dizziness, visual loss and auditory or sensory changes may be recalled prior to loss of consciousness, being manifestations of focal cortical ischaemia. Sweating and tachycar-dia during recovery are common, as a result of refl ex sympathetic drive. However, a more important clue to the diagnosis than the recalled or observed clini-cal features is the situation in which the episode occurred. Syncope should be suspected as the basis of loss of consciousness or convulsing when attacks occur contemporaneously with vomiting illnesses, prolonged standing (e.g. classroom, church), hair-brushing, injury, venepuncture, other medical pro-cedures and veterinary procedures. Syncope without an obvious orthostatic or noxious precipitant, or syncope during exercise or while in water, should prompt concern about a primary cardiac cause, such as prolonged QTc syndrome or left ventricular

Clinical example

Steven, a 9-year-old boy with a history of learning problems and aggressive outbursts, was referred for management of refractory

seizures. Seizures began at age 5 years, occurred in clusters each week and were characterized by a scared feeling in the abdomen followed by cessation of activity, loss of responsiveness, stiffening of the right hand and rocking movements. Twice during illnesses, these seizures secondarily generalized. None of the three antiepileptic medications used over the years had controlled Steven’s seizures. An MRI showed a lesion of benign appearance in the uncus of the left temporal lobe, thought to be a developmental tumour. Video-EEG recording of seizures showed electrical onset in the left temporal lobe region. Cognitive testing showed normal intellect but decreased verbal abilities. Left temporal lesionectomy was performed and the histopathology revealed a ganglioglioma. After a 2-year period free of seizures, Steven was gradually weaned off his medication. Learning and behavioural diffi culties persisted but were better managed with understanding of their cause, abolition of seizures and institution of specifi c behavioural and educational strategies.

Non-epileptic episodic disorders

Not all episodes of neurological dysfunction in infancy and childhood are epileptic. Sleep disor-ders, movement disorders, circulatory disturbances, migraine and some normal behaviours may mimic epileptic seizures (Table 17.1.4). Disorders frequently misdiagnosed as seizures are breath-holding attacks in infancy and syncope in older children and adoles-cents, because of their paroxysmal nature with loss of consciousness and sometimes associated convul-sive movements. In such attacks, the neurological manifestations are secondary to transient cerebral ischaemia and not to any intrinsic cerebral dysfunction.

Table 17.1.4 Differential diagnosis of epileptic seizures

• Normal behaviours, e.g. sleep jerks, day dreaming, masturbation

• Parasomnias, e.g. night terrors, sleep walking• Breath holding spells• Syncope e.g. vasovagal, cardiac arrhythmia/outfl ow

obstruction• Migraine and migraine variants, e.g. benign paroxysmal

vertigo/torticollis• Movement disorders, e.g. tics, tremor, clonus,

shuddering attacks• Non-neurological, e.g. gastroesophageal refl ux,

hypoglycaemia• Psychiatric, e.g. rage attacks, psychogenic seizures


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outfl ow obstruction. No investigations, other than perhaps an ECG, are needed in syncope and most patients and families need only explanation and reassurance. Patients’ recognition of precipitating situations and presyncopal symptoms is helpful in taking evasive action.

Assessment of children with seizuresThree important and successive steps in the assess-ment of a child with suspected seizures are to:

• distinguish epileptic seizures from non-epileptic attacks

• determine the type(s) of seizure the child is having, most importantly whether they are generalized or focal, and determine if unrecognized minor sei-zures are occurring

• determine the type of epilepsy in the child having recurrent seizures, or at least try and determine whether the epilepsy is likely to be idiopathic or symptomatic.

The diagnosis of epileptic seizures should be made on clinical grounds with investigations used to confi rm the diagnosis, help characterize the seizure disorder and determine the underlying cause. Good detailed history from the patient and observers, sometimes combined with home video recordings of attacks are the basis of making a correct diagnosis. Children with epilepsy should be examined for dys-morphic features, neurocutaneous stigmata, focal neurological defi cits, signs of raised intracranial pressure and markers of systemic disease.

Metabolic disturbance, especially hypoglycaemia and hypocalcaemia, should always be considered, especially in infants with seizures and children with no identifi able cause for their epilepsy. Pyridoxine defi ciency, although very rare, should be considered in refractory infant-onset epilepsy.

EEG is invaluable in the characterization of seizures and epilepsies, and should generally be requested in all children with defi nite afebrile sei-zures, although this last point is somewhat controver-sial. EEG is of no value in the investigation of infants and young children with febrile seizures. In epilepsy, the EEG helps distinguishing focal from generalized seizures and aids diagnosis of specifi c epilepsy syn-dromes, especially idiopathic epilepsies. In this way, the EEG may assist in making the correct choice of antiepileptic medication and determining the need for brain imaging. It is important to note that the interictal EEG is normal in many patients with epi-lepsy, particularly symptomatic focal epilepsies. Conversely, epileptiform abnormalities, particularly

centrotemporal spikes and brief generalized spike-wave bursts in drowsiness, are seen in up to 4–5% children without seizures, more frequently in chil-dren with underlying neurological and developmen-tal problems. EEG should therefore not be done to exclude epilepsy in a child with undiagnosed attacks. In children with undiagnosed recurrent attacks, or children with epileptic seizures of uncertain type, simultaneous video-EEG monitoring may be needed.

Brain imaging, usually with MRI, is indicated when one suspects an underlying cerebral abnormal-ity, i.e. symptomatic epilepsy. Thus, imaging should be done in children with focal seizures or signifi cant focal EEG abnormalities, except when they are char-acteristic of a benign focal (rolandic or occipital) epilepsy. Imaging should also be performed in chil-dren with focal or generalized seizures who have signifi cant developmental delay, abnormal neuro-logical fi ndings on examination, a history of a prior neurological insult, or poorly controlled seizures. Brain imaging is unnecessary in typical cases of idio-pathic focal and generalized epilepsy.

Practical points

Diagnosis• A detailed description of the attacks and the situations

in which they occurred, sometimes supplemented with a home video recording, are the keys to correct diagnosis of epileptic and non-epileptic events

• The differential diagnosis of episodic staring includes daydreaming or inattention, absence seizures and complex partial seizures

• The differential diagnosis of collapse and convulsing includes syncope, generalized tonic–clonic seizures, focal seizures with secondary generalization and psychogenic attacks

• Seizures in the classroom, church, bathroom, medical surgery or veterinary surgery should be considered to be syncopal attacks until proved otherwise

• EEG is helpful in characterizing seizures and epilepsies but should not be done to clarify the nature of undiagnosed events. Further history, home video-recording or video-EEG monitoring may be needed for undiagnosed episodic phenomena

• Idiopathic focal and generalized epilepsies usually have prominent and characteristic epileptic patterns on routine EEG, such that their absence should prompt consideration of non-epileptic attacks or a symptomatic epilepsy requiring imaging

• Imaging is performed when the seizures, EEG, history or examination suggest an underlying cerebral abnormality. Imaging is not performed in idiopathic focal or generalized epilepsies

• Learning and behavioural problems in a child with epilepsy are often the result of the underlying neurological problem rather than being secondary to seizures or medications



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General principles of treatment of seizures in childrenExplanation and reassurance, provision of informa-tion about the child’s specifi c seizure disorder, fi rst aid advice about how to manage future seizures, discussion of potential seizure precipitants, consid-eration of lifestyle modifi cation and safety advice regarding bathing, swimming, heights and driving are all important aspects of seizure management. The decision to treat a child with antiepileptic medi-cation and the choice and duration of treatment depend on the type of epilepsy and several patient and family factors. Antiepileptic medications reduce the likelihood of seizures but do not alter the course of epilepsy: that is, seizures do not remit any sooner on treatment. The appropriate antiepileptic drug is usually indicated by the seizure type (Table 17.1.3), treatment being generally initiated after specialist assessment.

Seizures can usually be controlled with one medi-cation at an optimal dose, especially in idiopathic epilepsies. Children vary greatly in their dosage requirements and tolerance of antiepileptic drugs, patient age and associated disabilities being the main determinants. Except in status epilepticus and other situations with frequent or severe seizures, antiepi-leptic medications are usually commenced singly and in low dosage, and then increased gradually to a dose where seizure control is obtained, side effects appear or maximum dosage and serum levels are achieved. The duration of therapy depends on the type of epi-lepsy and its natural history, the degree of seizure control and the patient’s lifestyle. Several years of freedom from seizures are desirable before antiepi-

leptic drugs are ceased, and this is best done slowly over a period of months. Antiepileptic drug interac-tions are common, both pharmacokinetic and phar-macodynamic, some being advantageous (e.g. sodium valproate and lamotrigine) and others leading to side effects (e.g. barbiturates and benzodiazepines).

Almost all antiepileptic drugs produce side effects such as drowsiness and unsteadiness if given in excess (Table 17.1.5). These effects are common when medications are commenced and the dose is increased but they often wear off after the maintenance dose is reached. Some antiepileptic medications have side effects of an idiosyncratic type, such as rash or behaviour disturbance.

Use of serum levels for monitoring some antiepi-leptic medications is particularly useful if seizure control is inadequate, side effects attributable to tox-icity are suspected or compliance is uncertain. Blood level monitoring is of particular value in young infants, in children with intellectual disability and in patients with impaired consciousness, i.e. patients who are not able to describe side effects. Barbiturate and phenytoin levels correlate well with both seizure control and side effects, a weaker correlation being present with carbamazepine. However, there is little role for blood level monitoring with the other anti-epileptic medications, including sodium valproate and the benzodiazepines.

In addition to regular prescription of antiepileptic medication to prevent seizures, some parents and carers are instructed in the use of rectally adminis-tered diazepam or buccally administered midazolam to treat prolonged or recurring seizures, in children with a tendency to prolonged or clustering seizures.

For children with uncontrolled epilepsy, in whom seizures continue despite correct diagnosis

Table 17.1.5 Side effects of antiepileptic medications

Medication Side effects

ToxicityCommon to most antiepileptic Drowsiness, ataxia, tremor, nystagmus, dysarthria, confusion, nausea, vomiting, medications sleepiness or insomnia

IdiosyncraticCarbamazepine Rash, leukopenia, hyponatraemia, irritability, weight gainClonazepam Behaviour disturbance, increased bronchial and salivary secretionsLamotrigine Rash, severe hypersensitivity syndromeLevetiracetam Behaviour disturbanceOxcarbazepine HyponatraemiaPhenytoin Rash, serum-sickness-type illnessPhenobarbitone Rash, behaviour disturbanceSodium valproate Weight gain, alopecia, pancreatitis, hepatic failure (rare)Topiramate Kidney stones, weight loss, speech disturbanceVigabatrin Peripheral vision impairment, behaviour disturbance, weight gain


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and correct prescription of antiepileptic medica-tions, specialized treatments such as epilepsy surgery, a ketogenic diet and vagal nerve stimulation may be considered. Surgical treatment is reserved for chil-dren with well characterized and refractory focal epilepsy in whom seizures are impacting greatly on quality of life. Surgery is most effective when the seizure focus is discrete, away from critical func-tional cortex and associated with a lesion on MRI. Epilepsy surgery is only carried out after detailed evaluation in a centre with special experience in pae-diatric epileptology. A ketogenic diet, with high fat and low carbohydrate and protein intake, is some-times effective in refractory epilepsy, especially in younger children, uncontrolled absence and myo-clonic epilepsies. Vagal nerve stimulation, a form of chronic brain stimulation for the treatment of refrac-tory epilepsy, is being increasingly utilized in chil-dren with uncontrolled seizures where drugs and surgery are ineffective.

When treating epilepsy it is necessary to consider the whole child and family in their environment, and not only the seizures. Problems pertaining to educa-tion and vocation, problems related to adjustment to the diagnosis, and associated psychological and behavioural problems may be more diffi cult to manage than the actual seizures. Disentangling the effects of seizures, medications, underlying lesions, pre-existing states, family dynamics and psychoso-cial factors can often be diffi cult and require special-ist involvement.

Practical points

Treatment• Explanation, reassurance, lifestyle modifi cation and

fi rst-aid advice are important aspects of epilepsy management

• For febrile seizures, reinforce that febrile seizure recurrence is common, epilepsy development is uncommon and neurodevelopmental sequelae are rare

• In a child with epilepsy, the decision to treat, the choice of medication and the duration of therapy are determined by the type of seizure and epilepsy

• As a general rule in antiepileptic drug therapy, ‘start low and go slow’ and withdraw medications slowly

• Antiepileptic drug level monitoring is important with phenobarbital and phenytoin, often helpful with carbamazepine but of limited value with sodium valproate and other drugs

• If seizures continue despite treatment with antiepileptic medication, consider whether the diagnosis of epilepsy and the seizure/syndrome type are correct, whether the choice of medication is appropriate, and whether medication is being given and taken in appropriate doses


Cerebral palsyCerebral palsy is the term used for a persistent but not unchanging disorder of movement and posture due to a defect or lesion of the developing brain. It is generally applied to children with permanent motor impairment due to non-progressive brain dis-orders occurring before the age of 5 years. There are many different causes, a wide range of manifesta-tions of the motor disorder and various associated problems.

Cerebral palsy is not a single disorder but a group of disorders with diverse implications for children and their families.

For some young people with mild cerebral palsy, the only motor defi cit may be a minimal hemiplegia, causing clumsiness with certain movements. In other children with severe cerebral palsy, the motor defi cit may be spastic quadriplegia with little or no indepen-dent movement. Because each child with cerebral palsy is different, individual assessment and treat-ment are essential.

Prevalence

Cerebral palsy is the most common physical disability in childhood. Studies from several parts of the world, including Western Australia, Sweden and the UK, have shown that the prevalence of cerebral palsy is between 2.0 and 2.5 per 1000 live births. The overall prevalence of cerebral palsy has remained fairly stable since 1970 (Fig. 17.2.1).

Aetiology

The cause of cerebral palsy is unknown in many children. There is a signifi cant association with pre-maturity and low birth weight but it is important to remember that most low-birth-weight infants do not develop cerebral palsy.

In a signifi cant proportion of children who have cerebral palsy, there appears to have been no single event but rather a sequence of events responsible for the motor damage. This has led to the concept of

‘causal pathways’, a sequence of interdependent events that culminate in disease. It is likely that inter-dependent events are responsible for many cases of cerebral palsy.

Historical aspects

There has been a fundamental change in our under-standing of aetiological factors during the past 20 years. Before this time, most cases of cerebral palsy were thought to be caused by lack of oxygen either during labour or during the perinatal period and it was expected that improvement in obstetrics and neonatal care would result in lower rates of cerebral palsy. Subsequently, there was an increased use of interventions such as caesarean section and elec-tronic fetal monitoring but, despite a decline in still-birth and neonatal deaths, the cerebral palsy rate remained constant.

In the past, cerebral palsy was attributed to minor obstetric and neonatal events, often incorrectly. Current research suggests that about 8–10% of cases are associated with perinatal asphyxia, the pre-ferred term to describe a situation in which there have been perinatal events likely to reduce oxygen supply, evidenced by signifi cant acidosis, followed by a failure of function in at least two organs (usually the brain and kidney). It is important to remember that perinatal asphyxia may not necessarily be the primary cause of the cerebral palsy and is generally not preventable. Because it is often impossible to ascribe clinical signs and symptoms to an event during birth, the term ‘birth asphyxia’ should be avoided.

Current knowledge about aetiology

It is helpful to consider the timing of the brain insult:

• prenatal events are thought to be responsible for approximately 75% of all cases of cerebral palsy

• perinatal events contribute 10–15%• postnatal causes account for about 10% of all

cases.593

17.2Cerebral palsy and neurodegenerative

disordersD. Reddihough, K. Collins


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A prenatal cause is assumed in the absence of clear evidence for a perinatal or postnatal cause.

Prenatal causesMalformations. Disturbances of brain develop-

ment result in a variety of abnormalities, including malformations of cortical development. These typi-cally arise at about 12–20 weeks gestation and may be identifi ed by brain imaging, particularly magnetic resonance imaging (MRI). While genetic causes are being increasingly recognized, the basis for these malformations often remains unexplained.

Vascular. Brain imaging provides evidence of pre-vious vascular events such as middle cerebral artery occlusion (Fig. 17.2.2).

Infective. Maternal infections during the fi rst and second trimesters of pregnancy, including the TORCH group of organisms (toxoplasmosis, rubella, cytomegalovirus and herpes simplex virus), may cause cerebral palsy. It has also been suggested that maternal infections in the perinatal period may form part of the causal pathway to cerebral palsy in some children.

Genetic. There are some uncommon genetic syn-dromes associated with cerebral palsy.

Metabolic. Iodine defi ciency in early pregnancy is an important cause of cerebral palsy in many parts of the world. Maternal thyroid disease has also been implicated.

Toxic. There have been reported cases associated with lead and methylmercury ingestion.

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Fig. 17.2.1 Cerebral palsy, stillbirth and neonatal death rates per 1000 births in Victoria using published and unpublished data from the Victorian Cerebral Palsy Register and the Victorian Perinatal Data Collection Unit. Reid S, Lanigan A, Reddihough DS. Report of the Victorian Cerebral Palsy Register, 2005.

Fig. 17.2.2 MRI brain scan of a 2-year-old boy with left spastic hemiparesis, showing loss of brain tissue in right frontal and parietal lobes, consistent with an old (prenatal) right middle cerebral artery territory infarct.



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Perinatal causesProblems during labour and delivery. Obstetric

emergencies such as obstructed labour, antepartum haemorrhage or cord prolapse may compromise the fetus.

Neonatal problems. Conditions such as severe hypoglycaemia or untreated jaundice may be responsible.

Premature and low-birth-weight infants. Premature and low-birth-weight infants differ from those born at term in their higher risk of cerebral palsy. The rate of cerebral palsy in children born before 33 weeks is up to 30 times higher than in those born at term. Some premature infants develop brain damage from complications of their immaturity, such as intraven-tricular haemorrhage, while others are damaged earlier in pregnancy. Intrauterine growth retardation is associated with cerebral palsy in both term and preterm infants. Periventricular leukomalacia is a common radiological fi nding in premature children with cerebral palsy. It is caused by an ischaemic process, usually occurring between 28 and 34 weeks of gestation, in the watershed zone that exists in the periventricular white matter of the immature brain. Periventricular leukomalacia may also be found in infants born at term, suggesting that the insult occurred early in the third trimester even though the pregnancy progressed to term.

Multiple pregnancy. Multiple births are associated with preterm delivery, poor intrauterine growth, birth defects and intrapartum complications and with an increased risk of both mortality and cerebral palsy. The increased risk to twins of cerebral palsy is not entirely explained by their increased risk of prematurity and low birth weight. Intrauterine death of a co-twin is a factor unique to multiple pregnan-cies and is associated with a sixfold increase in the rate of cerebral palsy per twin confi nement, or an 11-fold increase in rate per child.

Postnatal cerebral palsyInfection and injuries are responsible for most cases of postnatal cerebral palsy in developed countries:

• the introduction of vaccines against Haemophilus infl uenzae type b, meningococcus and pneumococ-cus should have a signifi cant effect on the occur-rence of bacterial meningitis in young children but other organisms remain

• injuries are an important group as there are clear prospects for prevention. Injuries may be accidental (e.g. motor vehicle accidents and near-drowning episodes) or due to physical abuse. Important preventive measures include improved road safety and mandatory fencing around home swimming pools.

Other causes of postnatal cerebral palsy include apparent life-threatening events and cerebrovascular accidents. Meningitis, septicaemia and infections such as malaria are important causes of cerebral palsy in developing countries.

Practical points

• Cerebral palsy is a diverse disorder with multiple risk factors and aetiologies

• Perinatal asphyxia is responsible for only a small proportion of cases (approximately 8–10%)

• It is important to establish the cause of cerebral palsy if at all possible. It is helpful for families and essential for genetic counselling

• When determining aetiology, distinguish risk factors from causes

• Many cases of cerebral palsy relate to events long before birth

• Take a careful history and examination to determine possible factors

• Brain imaging should be undertaken to establish timing and possible cause

Clinical example

Caitlin’s mother went into labour at 33 weeks’ gestation after an uneventful pregnancy. The delivery was rapid and Caitlin’s Apgar scores

were 6 at 1 minute and 8 at 5 minutes. Her parents remembered some panic in the labour ward and felt that more could have been done to slow the labour. Caitlin developed hyaline membrane disease and mild jaundice. In the early neonatal period she had diffi culty sucking, which was attributed to her prematurity. She was slow in her motor development and did not sit until the age of 15 months. A diagnosis of cerebral palsy was made at that time.

When Caitlin was 2 years old, her parents requested an opinion as to whether subsequent children were likely to have cerebral palsy, believing that her prematurity and problems at birth were responsible for her condition. MRI of the brain demonstrated a brain malformation with bilateral clefts in the cerebral cortex, dating the problems to early pregnancy rather than the perinatal period.

Classifi cation

There are three major ways in which cerebral palsy is classifi ed – by type, by topographical distribution and by the severity of the motor disorder.

Type of motor disorder

Cerebral palsy is a disorder of movement (diffi cul-ties with voluntary movement and/or abnormal

CEREBRAL PALSY AND NEURODEGENERATIVE DISORDERS 17.2


596

movements), posture and muscle tone. Children with cerebral palsy may present with various types of movement disorder.

Spastic cerebral palsy (70%)This is the most common type. Spasticity involves increased muscle tone with characteristic clasp knife quality. Children with spasticity often have underly-ing weakness. In spastic cerebral palsy, there is damage to the motor cortex or corticospinal tracts, in contrast to dyskinetic and ataxic cerebral palsy, which are associated with abnormalities of the basal ganglia and cerebellum, respectively.

Dyskinetic cerebral palsy (10–15%)This refers to a group of cerebral palsies with invol-untary movements and is characterized by abnor-malities of tone involving the whole body. Several terms are used within this group:

• Dystonia is a syndrome of sustained muscle contractions, frequently causing twisting and repetitive movements or abnormal postures

• Athetosis refers to slow writhing movements involving the distal parts of the limbs

• Chorea is the term for rapid jerky movements.

Ataxic cerebral palsy (less than 5%)Children have a fi ne tremor, more noticeable when movements are initiated, as well as poor balance and hypotonia. Ataxia is associated with other neuro-logical conditions that must be excluded before this diagnosis is made. Some children have a mixed motor disorder.

The topographical distribution

The terms diplegia, hemiplegia and quadriplegia are used and generally apply to children with spastic cerebral palsy as the other types usually involve four limbs:

• the term diplegia is used where the predominant problem is in the lower limbs. There is usually some upper limb involvement, which may be subtle. The majority of these children have normal intel-ligence. Spastic diplegia is the pattern most com-monly seen in premature infants who have the radiological fi nding of periventricular leukomalacia

• children with spastic hemiplegia usually have normal intelligence, frequently have epilepsy (50–70%), may have sensory impairments in the upper limb and may have visual defi cits (homonymous hemianopsia)

• children with spastic quadriplegia frequently have problems such as intellectual disability, epilepsy and visual diffi culties. There is often poor trunk control and oromotor diffi culties in addition to four limb involvement.

Severity of the motor disorder

The gross motor function classifi cation system (GMFCS), provides information about the move-ment problems of children with cerebral palsy based on their motor abilities and their need for walking frames, wheelchairs and other mobility devices. There are fi ve levels: children in levels I and II walk independently, children in level III generally need walking frames or elbow crutches and children in levels IV and V use wheelchairs. This classifi cation system does not consider cognitive and other defi cits, which may have a profound effect on the eventual outcome.

Using the GMFCS, growth motor development curves have been constructed that provide some guide to prognosis for motor development.

Practical points

• Cerebral palsy can be classifi ed according to motor type, distribution and severity (the latter using the GMFCS)

• New methods of classifying severity provide information about motor prognosis

• Co-morbidities such as epilepsy are more common in certain types of cerebral palsy

Presentation

The diagnosis of cerebral palsy is not always easy, particularly in children born prematurely. Signs may evolve during the fi rst year of life. For example, spas-ticity is not usually present in the early weeks of life, involuntary movements are generally not seen in the fi rst year of life and, conversely, abnormal neurologi-cal signs may disappear. Cerebral palsy may present as:

• follow-up of ‘at risk’ infants, such as those born prematurely or those with a history of neonatal encephalopathy

• delayed motor milestones, particularly delay in learning to sit, stand and walk

• development of asymmetric movement patterns, e.g. strong preference for one hand in the early months of life

• abnormalities of muscle tone, particularly spastic-ity or hypotonia. the latter in isolation should always be treated with caution as it may be an early sign of global developmental delay rather than cerebral palsy

• management problems, e.g. severe feeding di ffi -culties or abnormalities of behaviour such as unexplained irritability. These problems should be



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interpreted carefully, as many other conditions can present with these features.

Examination involves a search for abnormalities in muscle tone, posture and deep tendon refl exes, along with persistence of primitive refl exes. It is important to exclude other conditions that may present with motor delay, including neuromuscular, neurodegen-erative and metabolic disorders. It is generally rec-ommended that MRI be part of the investigation of the child with cerebral palsy, particularly where the cause or causes are uncertain or unknown.

Management of the associated disabilities, health problems and consequences of the motor disorder

Associated disabilities• All children require a hearing and visual

assessment• Assessment and advice about epilepsy and

prescription of anticonvulsants when appropriate• Children may benefi t from formal cognitive

assessment and may need help with their educational programme. Assessment of cognitive abilities can be diffi cult when children have severe physical disabilities

Health problems• Growth should be monitored and dietary advice sought to ensure that nutrient and calorie intake is adequate. Failure to thrive and undernutrition are frequent problems, caused by eating diffi culties due to oromotor dysfunction. Nasogastric or gastros-tomy feeds should be considered if there is diffi culty in achieving satisfactory weight gains or if the length of time taken to feed the child interferes with other activities. Conversely, obesity is a signifi cant problem and may interfere with progress in motor skills• Investigation and management of gastro-oesophageal refl ux, which occurs commonly in cere-bral palsy. It can result in oesophagitis or gastritis, causing pain and poor appetite, and, if severe, aspi-ration can result• Dietary and laxative advice regarding the frequent problem of constipation. Immobility, low-fi bre diet and poor fl uid intake are contributory factors• Lung disease. Some children with severe cerebral palsy develop chronic lung disease due to aspiration from oromotor dysfunction or severe gastro-oesoph-ageal refl ux occurring over a period of time. The presence of coughing or choking during meal times, or wheeze during or after meals, may signal the pos-sibility of aspiration but it may also occur without clinical symptoms or signs. There is no ‘gold stan-dard’ test for aspiration but barium videofl uoros-copy may be helpful. Alternative feeding regimens, such as the use of a gastrostomy, should be consid-ered if aspiration is present• Many children with cerebral palsy, particularly those born prematurely, have hydrocephalus requir-ing ventriculoperitoneal shunts• Dental health. Children are at risk of dental prob-lems and should be regularly monitored• Osteoporosis. Pathological fractures may occur in children with severe cerebral palsy• Most importantly, emotional problems can be overlooked and may be responsible for suboptimal performance, either with academic tasks or in the self-care area

Practical points

• Observation of the child often provides more information than ‘hands on’ examination. It will provide information about the presence or absence of age appropriate motor skills and their quality

Associated disorders

• Visual problems occur in about 40% of children with cerebral palsy and include strabismus, refrac-tive errors, visual fi eld defects and cortical visual impairment• Hearing defi cits occur in 3–10% of children with cerebral palsy. High-frequency hearing loss may be found in children with congenital rubella or other viral syndromes• Speech and language problems: receptive and expressive language delays and articulation prob-lems occur• Epilepsy occurs in up to 50% of children with cere-bral palsy, most commonly in those with severe motor problems• Cognitive impairments: while intellectual disabili-ties and learning problems are common, there is a wide range of intellectual ability in children with cerebral palsy and children with severe physical dis-abilities may have normal intelligence. Perceptual diffi culties are also frequent.

Some children with cerebral palsy have only a motor disorder.

Management

A team approach is essential, involving a range of health professionals and teachers, with input from the family of paramount importance. Management of the child with cerebral palsy involves:

• management of the associated disabilities, health problems and consequences of the motor disorder

• assessment of the child’s capabilities and referral to appropriate services for the child and family.



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Consequences of the motor disorder• Management of drooling (poor saliva control). Speech pathologists can assist with behavioural approaches and methods to improve oromotor control. Medication (anticholinergics) and surgery are helpful in some children• Incontinence. Children may be late in achieving bowel and bladder control due to cognitive defi cits or lack of opportunity to access toileting facilities because of physical disability and/or inability to communicate. Sometimes children have detrusor overactivity causing urgency, frequency and incontinence• The testes may be in the normal position at birth but may ascend with time (secondary to chronic spasm of the cremaster muscle), requiring the same treatment as in other boys with this problem (usually scrotal orchidopexy)• Orthopaedic problems. Children may develop con-tractures that require orthopaedic intervention. Surgery is mainly undertaken on the lower limb but is occasionally helpful in the upper limb. Physio-therapists are essential in the postoperative rehabili-tation phase • The hip. Non-walkers and those partially ambu-

lant (GMFCS levels III–V) are at risk of hip sub-luxation and dislocation. Early detection is vital and hip X-rays should be performed at yearly intervals. If there is evidence of subluxation or dislocation, children should be referred for an orthopaedic opinion. Dislocation causes pain and diffi culty with perineal hygiene. Ambulant chil-dren rarely develop hip problems

• The knee. Flexion contractures at the knee may require hamstring surgery

• The ankle. Equinus deformity at the ankle is the commonest orthopaedic problem in children with cerebral palsy. Toe-walking is treated conserva-tively in young children with orthoses, inhibitory casts and botulinum toxin A therapy. Older chil-dren benefi t from surgery for a defi nitive correc-tion of the deformity

• Multilevel surgery. Sometimes children require surgery at several different levels (e.g. hip, knee and ankle). This involves a single hospitalization and is called ‘single event multilevel surgery’. It is of most benefi t to children who walk indepen-dently or with the assistance of crutches. The usual age is between 8 and 12 years. The aims of surgery are to correct deformities and to improve both the appearance and effi ciency of walking. An accurate assessment of the walking problems is undertaken in a gait laboratory. A carefully planned intensive rehabilitation physiotherapy programme lasting up to 1 year is required to maximize the benefi ts

• The upper limb. Procedures can be offered fol-lowing careful assessment

• Scoliosis. Correction is sometimes necessary• Spasticity management is aimed at improving func-tion, comfort and care and requires a team approach. Options include: • Oral medications, e.g. diazepam, dantrolene

sodium and baclofen. These medications may not be effective or may cause unwanted effects

• Inhibitory casts aim to increase joint range and facilitate improved quality of movement. The main application is below-knee casts for equinus but occasionally casts are used in the upper limb

• Botulinum toxin A is injected into muscles and reduces localized spasticity

• Intrathecal baclofen is administered by a pump implanted under the skin. This treatment is suit-able for a small number of children with severe generalized spasticity and may enhance quality of life

• Selective dorsal rhizotomy is a neurosurgical pro-cedure whereby specifi c posterior spinal roots are sectioned to reduce spasticity. It is used mostly in young children aged 3–7 years with spastic diple-gia. Randomized trials have provided evidence of some benefi ts in carefully selected cases. An inten-sive rehabilitation period is required.

Clinical example

Tom was born at 26 weeks’ gestation. He had many neonatal problems, including a grade IV intraventricular haemorrhage. The parents

were informed that some degree of cerebral palsy was likely. At 4 months corrected age, Tom’s mother noted that his right hand was fi sted. The diagnosis of cerebral palsy was confi rmed and a physiotherapy programme was commenced.

When he began to walk independently at 24 months corrected age, Tom’s gait was noted to be asymmetrical, with a tendency to walk on his toes on the right side. This problem was more apparent by 30 months and he fell more than would be expected for his age. Inhibitory casts were applied for 4 weeks and he was fi tted with an ankle–foot orthosis (AFO). His walking pattern was much improved after this treatment but after a further 10 months the problem had recurred. This time Tom appeared not only to walk in equinus but was also fl exed at the knee. Hamstrings as well as calf muscles were tight. Botulinum toxin A injections were given to both muscle groups with an excellent result. A new AFO was made as Tom had grown considerably over this time. When Tom was 5 years old, he required further botulinum toxin A injections. At 6 years of age, surgery was undertaken by the same orthopaedic surgeon who had been monitoring him since the age of 24 months. Now he is 10 years old and no treatment is currently planned, although the family has been advised that further surgery may be required following his adolescent growth spurt.



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Assessment of the child’s capabilities and referral to appropriate services for the child and family

The role of the teamCareful assessment in conjunction with a multidisci-plinary team is essential to enable children to achieve their optimal physical potential and independence:

• Physiotherapists give practical advice to parents on positioning, handling and play to minimize the effects of abnormal muscle tone and encourage the development of movement skills. They also give advice regarding the use of orthoses, special seating, wheelchairs and other mobility aids

• Occupational therapists help parents to develop their child’s upper limb and self-care skills, and also recommend suitable toys, equipment and home adaptations

• Speech pathologists assist in the development of communication skills, including advising about augmentative communication systems for children with limited verbal skills. They provide guidance about feeding diffi culties and saliva control problems

• Orthotists, medical social workers, psychologists, special education teachers and nurses are helpful.

Therapy approachesTherapy to address movement problems and to opti-mize children’s progress in all areas of develop-ment is incorporated into early intervention and school programmes. The two most commonly used approaches by therapists in Australia are:

• Neurodevelopmental Therapy (NDT). This is a therapeutic approach to the assessment and man-agement of movement problems with the goal of maximizing the child’s functional ability. This therapy was developed by Dr and Mrs Bobath and hence is sometimes known as ‘Bobath therapy’. Family members receive education in NDT prin-ciples so that they can im plement the programme at home, preschool and school

• programmes based on the principles of Conductive Education. Conductive education is a Hungarian system for educating children and adults with movement disorders. It provides an integrated group programme where children and parents learn to develop skills in all areas of life, e.g. daily living, physical, social, emotional, cognitive and communication skills.

Assistive technologyAppropriate equipment tailored for the individual child can enhance communication, mobility, learn-ing and socialization. Examples include powered wheelchairs, electronic communication devices and computers for educational and recreational purposes.

Trends in service provisionServices are best provided within local communities. Therapists and special education teachers work with children at home and later in child-care centres, kindergartens and schools. Most children attend mainstream preschools and schools but others benefi t from attendance at centre-based early inter-vention programmes and special schools. It is essen-tial that parents are made aware of all available options.

Alternative therapiesThere are many non-mainstream (or ‘alternative’) treatments available. Sometimes great claims, usually not justifi ed, are made for alternative approaches. Families can be reassured that any new treatment that is of value will be assessed and incorporated into mainstream practice. There is no evidence to suggest that alternative methods are superior to con-ventional treatments and some may do harm. It is important that professionals are aware of alternative approaches and are prepared to critically examine their claims.

Working with familiesCare of the child with cerebral palsy involves devel-oping a trusting and cooperative relationship with the parents. The child is part of a family unit and concerns in parents or siblings must be addressed. As with all children, a supportive home environment builds self-esteem and confi dence. Parents may need practical support, such as provision of respite care, and may be helped by meeting other families in similar circumstances or by attending parent support groups. Provision of information about fi nancial allowances is an important aspect of care.

Life expectancy

Children with mild and moderate cerebral palsy have a normal life span. Those with severe motor impairment, particularly those who are wheelchair dependent and require tube feeding, have a reduced life expectancy. Chronic lung disease is the most common cause of morbidity and mortality in this group.

Practical points

• In the child with cerebral palsy, the associated disorders and health problems may require more attention than the motor disorder itself

• Optimal management of the child with cerebral palsy involves the collaborative efforts of a team



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Neurodegenerative disordersThis section addresses the problem of the child who presents because of concern about regression in development that has been normal previously, or with apparent worsening of a pre-existing neurologi-cal disorder. In infants and young children, concern may arise because of loss of gross and fi ne motor, personal social and language skills. Declining school performance may lead to referral of the older child.

An approach to this problem will be outlined, with examples of the many disorders that may present in this way. Some of these disorders are mentioned in Chapter 10.5. The suggested Further reading associ-ate with this chapter provide a more detailed account of the wide range of neurodegenerative conditions. The diagnostic process is presented here as a series of questions.

Is there evidence of regression or lack of progress in any area of development?

This is sought in a sequential history of progress in each area of development, supplemented by ques-tions such as ‘How is your child’s speech now, com-

pared with this time last year? Is there any area where your child has gone backward or shown no progress at all?’

A clear ongoing loss of former skills, as shown in the latter part of curve C in Figure 17.2.3, raises obvious concern about a progressive disorder, but this may be less certain during the earlier ‘plateau’ phase before actual regression appears.

This is to be distinguished from the pattern of abnormally slow, but consistent, progress shown in curve A. This is often found in children with an intel-lectual disability or cerebral palsy, who may be seen to fall behind other children in abilities while in fact continuing to acquire new skills, but at a slower pace because of a static brain disorder arising in the pre-natal or perinatal period.

A variation on this pattern, seen in curve B, occurs in the child whose initially normal progress is inter-rupted by an acute injury or illness (e.g. meningitis or encephalitis) causing brain damage with later slower development.

Could the apparently progressive symptoms be due to a static disorder complicated by other factors?

Such factors are often amenable to treatment and include:

• frequent seizures, especially subtle myoclonic and atonic episodes, which may severely impair alertness and coordination

• drug toxicity, particularly from antiepileptic drugs

• psychological or emotional factors, including depression, withdrawal and psychosis; a particular problem is the tendency for children with autism to show arrest or regression in social and language skills during the second year of life

• joint deformities due to soft tissue contractures in spastic ‘cerebral palsy’, leading to worsening of postural stability and gait.

If this is a progressive disorder, what is its distribution in terms of brain anatomy?

Important anatomical patterns to consider are as follows.

One lesion

Progressive hemiparesis, perhaps associated with focal seizures, suggests a cerebral hemisphere tumour, while spinal cord tumours may produce progressive weakness and spasticity affecting the lower limbs, either alone or with variable upper limb

Age

Dev

elo

pm

ent

A

B

C

Early onset, non-progressive

Acute onset, non-progressive

Progressive disorder

Normal development

Fig. 17.2.3 Curves demonstrating the course of development over time in a child with static (A and B) and progressive neurological disease (C) compared with expected normal development. The actual age scale will vary and a different curve may apply to each aspect of development in each child or disease process.



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involvement, thus imitating diplegic cerebral palsy. This clinical pattern, sometimes with associated ataxia, is also seen in slowly progressive hydrocepha-lus, even in the absence of a cerebral neoplasm. The triad of cranial nerve palsies, corticospinal tract signs and ataxia suggests a brain-stem glioma. Most other childhood tumours of the nervous system raise clear concern because of symptoms of raised intra-cranial pressure, but the insidious visual loss associ-ated with optic nerve glioma and craniopharyngioma is often not recognized as a progressive problem until late in its course.

One functional system or group of systems

The prototype of ‘system degenerations’ is Fried-reich ataxia. In this disorder, abnormalities of spino-cerebellar, corticospinal and sensory tracts arise in the second decade of life. In other cerebellar ataxia syndromes there is involvement not only of neural pathways but of other body organs, as with ataxia telangiectasia, in which chromosomal breaks, immu-nological defects and skin lesions occur. A system disorder involving basal ganglia or extrapyramidal motor function may be inferred from the signs of dystonia, rigidity and choreoathetosis. An important example in this category is Wilson disease, which is treatable with penicillamine. Peripheral neuromus-cular diseases, which also may be regarded as system disorders, are discussed separately in Chapter 17.3.

A multifocal process, with several discrete lesions in the brain

This is exemplifi ed by recurrent cerebral infarctions associated with cyanotic congenital heart disease. In the absence of cardiac disease, repeated cerebral vas-cular occlusions are suggestive of moya-moya disease, a well recognized but poorly understood syndrome. Angiography here shows progressive occlusion of the major cerebral arteries, with a curious network of fi ne collateral vessels in the basal ganglia.

Among a group of disorders known collectively as mitochondrial encephalomyelopathies, one form (MELAS) may present with repeated stroke-like epi-sodes and multifocal brain lesions, associated with abnormal mitochondria in muscle, increased lactate levels in blood and cerebrospinal fl uid, and deletions of the nuclear or mitochondrial DNA controlling mitochondrial enzyme activity.

Homocystinuria, an inborn error of amino acid metabolism, may present with recurrent cerebral venous or arterial thromboses. While multiple scle-rosis is a major cause of multifocal lesions in young adults, it seldom begins in childhood.

A diffuse degenerative disorder of the nervous system

Diseases causing widespread loss of neurological function are generally separated into those that begin by affecting predominantly cortical grey matter, or nerve cell bodies, and those in which white matter, or nerve sheath myelin, is primarily involved. While this distinction is of clinical value, many dis-orders are not easily classifi ed in this way.

Diffuse disorders of grey matterThese tend to cause seizures (often myoclonic) and early loss of intellectual function, with progres-sive impairment of language, comprehension and memory. In addition, involvement of nerve cells in the retina leads to a variable pattern of visual loss. This clinical syndrome is seen in several of the lipid storage disorders, of which Tay–Sachs disease is the best known. Subacute sclerosing panencephalitis is an infrequent complication of measles and evolves as a sequence of behavioural change, intellectual decline, myoclonic jerks and later rigidity.

Diffuse disorders of white matterBy involving corticospinal tracts, these tend to present with early motor impairment and spasticity, and may masquerade initially as ‘cerebral palsy’. Impaired vision, when present, refl ects optic path-ways disease. Peripheral nerve myelin also may be involved, with clinical effects, as in Krabbe disease and metachromatic leukodystrophy, both of which are lipid storage disorders.

The above three questions can generally be answered after a careful clinical history and exami-nation, but the remaining steps in diagnosis require knowledge of a growing number of recognized but rare diseases. In practice, this will involve specialist consultation.

Which disorders are known to occur in children of this age, and to produce the other clinical features present in this child?

Individual neurodegenerative diseases tend to have a characteristic age of onset. It is useful to consider broad age ranges (early infancy, late infancy and later childhood) in narrowing the diagnostic fi eld. Next, by matching possible diagnoses against associ-ated clinical fi ndings, such as enlargement of liver and spleen, ocular abnormalities or unusual facial features, the physician may further refi ne the search and select the most relevant diagnostic tests.

A diagnosis is often reached merely by answering these questions. If not, it is useful next to turn from clinical features to pathophysiology.



602

Are any other, less evident diagnoses suggested by a systematic review of known mechanisms of disease?

The previous selective clinical correlations can be investigated further by considering in turn the major categories of:

• disease process, including metabolic errors, neurocutaneous disorders, slow virus infections and chronic intoxications

• biochemical substrates, such as lipids, vitamins and minerals

• cellular organelles, including lysosomes, peroxisomes and mitochondria, with their respective disorders.

This search may yield a further short list of possible diagnoses known to the clinician but not considered, usually because of limited recent experience with them.

Are there any treatable disorders among the diagnoses being considered in this child?

This important question may alter the priority of investigation, as a potentially treatable disorder, however unlikely, must be rigorously excluded at an early stage. The major groups to recognize are:

• neoplasms and other space occupying lesions involving the brain, and especially the spinal cord or optic nerves, where they are often not suspected until late, after irreversible damage

• subacute and chronic infections of the nervous system, such as tuberculous and cryptococcal meningitis and HIV infection

• intoxications: lead poisoning, glue sniffi ng, pre-scribed medications and, occasionally, chronic drug administration by a disturbed parent

• inborn errors of metabolism. The use of a modifi ed diet in phenylketonuria is well known but may also be of value in rarer disorders. Removal of toxic agents, e.g. copper chelation in Wilson disease, may be possible. In seizures due to pyridoxine dependency and in other vitamin dependency syn-dromes, large doses of vitamins may effectively compensate for the metabolic defect

• defi ciency states, especially of vitamins required for normal growth and function of the nervous system.

Effective treatment is not yet available for most degenerative neurological disorders of childhood but accurate diagnosis remains the basis for genetic counselling and for offering a realistic prognosis. A specifi c diagnosis or ‘answer’ is of great value to parents in coping with the distress of having a dis-abled child.

Clinical example

Vincent, aged 6 years, was referred to a paediatric neurologist because the teachers at his special school were concerned about

his deterioration over several months, with loss of speech and comprehension of language, impaired coordination and increasingly hyperactive, aggressive behaviour. He had been diagnosed as having developmental delay at the age of 3 because of limited speech and overactive behaviour. On examination, in addition to the developmental and behavioural fi ndings, he had slightly coarse facial features with thickened eyebrows, a palpably enlarged liver and a mild thoracic kyphosis. These features raised the clinical suspicion that he had Sanfi lippo disease, one of a group of disorders in which a defi ciency of lysosomal enzymes leads to an accumulation of mucopolysaccharides in the tissues and excretion in the urine. The diagnosis was confi rmed on specifi c blood and urine tests. Much professional support was needed by Vincent’s parents, confronted with the prospect of their son’s progressive dementia and immobility, as well as the autosomal recessive inheritance of his condition.



Neuromuscular disease in childhood has until recently received little attention. This is not surpris-ing, given that many of the conditions were diffi cult to diagnose without sophisticated investigations and they were generally untreatable. However, this group of disorders cannot be ignored because of the signifi -cant morbidity and mortality associated with them, the genetic implications and the arrival of potential therapies. The establishment of an early diagnosis is important in the rational management of these dis-orders as it allows prognostic and genetic informa-tion to be provided. Accurate diagnosis in this wide array of disorders is dependent on a careful clinical assessment followed by confi rmatory and appro-priate investigations. While recent advances have unravelled the molecular biology of many neuromus-cular conditions, the clinical assessment of patients remains the cornerstone of diagnosis and manage-ment. If clinical assessment is found wanting, the use of even the best technology may not supply the required diagnostic information.

The management of peripheral neuromuscular disease requires recognition, diagnosis, therapy and counselling.

Recognition that a child’s presenting symptoms or signs may be due to peripheral neuromuscular disease

Please listen to the patient, he’s trying to tell you what disease he has.

Michael H. Brooke, The Clinician’s View of Neuromuscular Disease

Although the hallmark of neuromuscular disease is weakness, parents do not come into the consulting room saying ‘I’m worried because my child is weak’. The physician needs to recognize that the presenting symptoms or signs relate to the peripheral neuro-muscular system before the diagnostic process begins. The failure of recognition results in diagnos-tic delay, with frequent presentations to a doctor, be it the family doctor or other specialist. While this failure does not usually affect the ultimate progno-sis, it adds considerably to patient and parental frus-tration. The main tragedy occurs when opportunities for preventive strategies are missed and a second

affected child is born in the immediate or even extended family.

Common presenting complaints of neuromuscular disease include:

• diffi culty walking and running• poor at sports• clumsy or poorly coordinated• not able to keep up with peers• frequent falls• tires easily.

Another trap in the recognition of neuromuscular disease in childhood is that classical neurological signs, readily demonstrated at the end of a disease process in adult patients, are expected to be present in children at the beginning of the disease process. For example, in Charcot–Marie–Tooth disease, adult patients will have gross pes cavus, arefl exia and the so-called ‘inverted champagne bottle legs’. In chil-dren, the early features are commonly an abnormal walk or run, clumsiness and frequent falls, with foot deformity as a presenting symptom in a minority. In addition, although arefl exia is the rule in adult patients, about 10% of children with Charcot–Marie–Tooth disease have normal refl exes at presentation. Not understanding the age-dependent symptoms and signs of various neuromuscular disorders will lead to the failure of recognition of a neuromuscular disease in childhood.

Other modes of presentation include a family history of neuromuscular disease; weakness, hypo-tonia, respiratory or feeding diffi culty in the neona-tal period; delayed motor milestones; abnormal gait (particularly toe walking) and orthopaedic abnor-mality, such as foot deformity or scoliosis. Some patients present with non-neuromuscular problems, such as intellectual disability or delayed language development, as, for example, in Duchenne muscular dystrophy.

Diagnosis of neuromuscular disease based on anatomical, electrophysiological, biochemical, histopathological or DNA identifi cation

After recognizing that the symptoms are due to neuromuscular disease, the differential diagnosis is

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17.3Neuromuscular disordersA. J. Kornberg


604

usually based on a logical anatomical approach. Although this may appear to be simplistic, as some disorders may affect more than one anatomical area or be multisystem, this approach will provide a broad differential diagnosis that may lead to a defi nitive diagnosis.

The anatomical localization is based on the clini-cal fi ndings listed in Table 17.3.1 and includes disor-ders affecting the:

• anterior horn cell• anterior and posterior nerve roots• peripheral nerve (motor, sensory, autonomic)• neuromuscular junction• muscle.

The use of a time frame of symptoms, such as acute, subacute or chronic, may also provide an important fi lter for the differential diagnosis.

The defi nitive diagnosis rests on a combination of:

• clinical history and examination• family history• serum enzymes, particularly creatine kinase (CK)• electrophysiology (e.g. nerve conduction studies,

electromyography, repetitive nerve stimulation)• histology of muscle and/or nerve• metabolic studies (e.g. muscle glycogen, carnitine

assay, mitochondrial studies)• DNA studies.

With only a few exceptions, electrophysiological, biopsy and/or DNA studies should be undertaken, as the implications of a neuromuscular disease diag-nosis are so great for the child and immediate family, and sometimes the extended family.

Anterior horn cell disordersAcute

Poliomyelitis

This disorder is rare in developed countries. It should still be considered where there is acute onset of lower motor neurone fl accid paralysis of a single limb, or with patchy asymmetrical distribution, particularly if associated with fever, vomiting, neck or spine stiff-ness and muscle pain or spasm. Sensory abnormali-ties are absent.

Hopkins syndrome

A clinical syndrome of asthma with fl accid paralysis of a limb resembling poliomyelitis has been recog-nized (Hopkins syndrome). Anterior horn cell dys-function has been identifi ed with magnetic resonance imaging through the clinically affected segments of the spinal cord. Coxsackie virus and echovirus infec-tions have occasionally produced weakness thought to be of anterior horn cell origin.

Chronic

In childhood the chronic disorders, characterized pathologically by degeneration of anterior horn cells and associated clinically with progressive muscle weakness, are called the spinal muscular atrophies (SMAs). The important clinical syndromes and their classifi cation are listed in Table 17.3.2.

Table 17.3.1 Clinical clues helpful in establishing the site of the lesion in neuromuscular disease

Clinical feature Anterior horn cell Peripheral nerve Neuromuscular junction Muscle

Weakness Proximal Distal Cranial/proximal Proximal

Hypotonia ++ + +/− ++

Hyporefl exia +/− Early +/− Late

Fasciculations +++ + − −

Sensory abnormalities − +/− − −

Myotonia − − − +/−

Autonomic dysfunction − +/− − −

Muscle enlargement − − − +/−



605

Spinal muscular atrophy type I (Werdnig–Hoffmann disease)

This autosomal recessive disorder occurs in approxi-mately 1 in 25 000 live births, making it one of the commonest fatal autosomal recessive disorders in humans. The earliest symptom may be decreased fetal movements in late pregnancy. Presentation is invariably before 6 months of age and is either at birth, with hypotonia, weakness, joint deformity and respiratory diffi culty, or more commonly later with marked hypotonia and limb weakness, poor feeding, poor cough and cry. The onset is sometimes rela-tively rapid and when fi rst seen the child is usually severely weak (Fig. 17.3.1). Weakness, although gen-eralized, is maximal proximally in the shoulder and hip girdle muscles. Intercostal muscle weakness leads to chest deformity, a poor cough and a weak cry. The respiratory pattern becomes diaphragmatic. Deep tendon refl exes are absent. Fasciculations of the tongue are an important clinical clue, but this can be an exceedingly diffi cult sign to be certain about and one can only be confi dent if the baby is relaxed and there are no ‘voluntary’ movements of the tongue. Facial weakness is only mild and extra-ocular movements remain full, giving the baby an alert appearance. Death, usually from pneumonia and respiratory failure, occurs by 18 months of age in 95% of patients, with those with onset in the fi rst 2 months of life having the shortest survival.

The genetic abnormality has been mapped to chro-mosome 5q13.3 and involves several different genes (SMN and NAIP). Prenatal diagnosis is available.

Studies of various therapeutic strategies are being trialled. Most of the therapeutic strategies are designed to upregulate SMN via a variety of mechanisms.

Spinal muscular atrophy type II (chronic childhood spinal muscular atrophy)

Clinical onset is almost invariably before 3 years of age, with SMA type II at least as common as Werdnig–Hoffmann disease. About one half of chil-dren affected by this disorder never walk, and only 5% are still walking by 20 years of age. Survival varies from 18 months through to adult life. Prompt treatment of chest infections will prolong survival.

The clinical picture is one of severe generalized weakness and wasting, with proximal predominance. Deep tendon refl exes are decreased or absent and often there are fasciculations of the tongue. The

Table 17.3.2 Clinical classifi cation of childhood-onset proximal spinal muscle atrophy

Designation Symptom onset (months) Course Death (years)

I (severe) 0–6 Never sits without support <2

II (intermediate) <18 Never stands without aid >2

III (mild) >18 Stands alone Adult

Fig. 17.3.1 Child with SMA I, showing profound hypotonia and weakness.

Practical points

• A positive diagnosis of fasciculations of the tongue should not be made unless the tongue has no voluntary movement, i.e. is not protruded, and the child is not crying or actively moving the tongue

• The presence of deep tendon refl exes makes it extremely unlikely that the child has type I SMA and an alternative diagnosis should be considered

NEUROMUSCULAR DISORDERS 17.3


606

facial muscles may be mildly weak but eye move-ments remain normal and the patient is usually normal intellectually. Some patients have a fi ne, rapid tremor of the hands. Major management problems include the prevention of orthopaedic deformity, especially scoliosis, and the management of the respiratory complications of muscle weakness. The genetic abnormality is allelic to that for SMA type I.

Spinal muscular atrophy type III (Kugelberg–Welander syndrome)

Patients with late onset and a moderately benign clinical course are classifi ed as SMA type III (Kugel-berg–Welander syndrome). Most have onset in the fi rst two decades, with only a few in the third decade, and survival is usually for many decades. While many remain ambulant over many years, particu-larly those with later onset, some do lose the ability to walk during childhood years. The genetic abnor-mality is allelic to that for SMA types I and II.

Peripheral nerve disordersA number of peripheral neuropathies occur in child-hood, with various time courses (acute, subacute or chronic). They may be inherited or acquired; they may involve motor, sensory or autonomic fi bres, or commonly mixtures of all three. Pathologically, they may be associated with combinations of demyelin-ation and axonal degeneration. Some central ner-vous system degenerative disorders, such as Krabbe disease and metachromatic leukodystrophy, may also have a peripheral neuropathy component. The commonest disorders in childhood are Guillain–Barré syndrome and peroneal muscular atrophy or Charcot–Marie–Tooth disease. Chronic infl amma-tory demyelinating peripheral neuropathy (CIDP), while uncommon, is important because it is respon-sive to immunotherapies.

Acute neuropathies

Guillain–Barré syndrome

Guillain–Barré syndrome (GBS) is the most common acute neuropathy in clinical practice and can occur at any age, although it is rare in infancy. An infec-tion, commonly of the upper respiratory tract or gastrointestinal tract (Campylobacter jejuni), pre-cedes the neurological syndrome in at least 50% of cases. Typical GBS is a monophasic illness with sym-metrical, ascending weakness involving proximal and distal muscles. Paraesthesia and muscle pain

may be presenting complaints but sensory impair-ment is usually minimal. Severe back pain and stiff-ness may occur, especially in young children. Tendon refl exes are lost early in the course of the illness. Cranial nerve involvement, particularly the facial nerve, is relatively common. Autonomic involvement can cause wide fl uctuations of the blood pressure as well as cardiac arrhythmias and bladder dysfunc-tion. Respiratory failure occurs in about 30% of patients and in addition may be associated with pha-ryngeal dysfunction. GBS typically progresses over a period of less than 4 weeks, with most patients reaching their maximal defi cit within 2 weeks of onset. Artifi cial ventilation for periods of up to 8 weeks may occasionally be required. Recovery con-tinues over weeks to many months, with most children returning to normal function. Some more severely affected children may have residual weakness, particularly with dorsifl exion. Fatigue is common during the recovery period.

Diagnosis is based on the clinical features, with elevation of the cerebrospinal fl uid (CSF) protein with only a few, if any, cells. A nerve conduction study may be useful in diffi cult diagnostic situations. Intravenous gammaglobulin or plasmaphaeresis, if used early, may hasten recovery. Supportive therapy is very important.

Management of GBS requires special expertise in medical and nursing care and children should be referred to centres used to dealing with this condi-tion. Monitor blood pressure and cardiac rhythm, as autonomic dysfunction is one of the potentially serious complications. In severely affected individu-als who are ventilated and with little movement, it may appear that the patient is unresponsive. The patient can see, hear and think. It is important to explain what is happening at all times and reassure them that they will get better.

Chronic neuropathies

Chronic infl ammatory demyelinating peripheral neuropathy

This condition is rare but treatable and is thought to be an autoimmune disorder. It usually presents as a subacute or chronic neuropathy. The course can be monophasic but is usually relapsing and remitting over many weeks or months duration. Acute presen-tations can occur and may cause confusion with Guillain–Barré syndrome. Symptoms and signs of weakness, often most prominent proximally, bring the child to medical attention. The diagnosis is con-fi rmed by nerve conduction studies, elevated CSF protein and, if there is diagnostic doubt, pathological abnormalities in a nerve biopsy.



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Intravenous immunoglobulin, corticosteroids, other immunosuppressive agents and plasmaphaere-sis have all been used with varying degrees of success. Many children regain normal strength, although some are left with muscle weakness.

Peroneal muscular atrophy (Charcot–Marie–Tooth; hereditary motor and sensory neuropathy) syndrome

Peroneal muscular atrophy (PMA) is the commonest chronic inherited neuropathy in childhood. Various forms of it are known and are based on electrophysi-ological and DNA studies. Most families show auto-somal dominant inheritance, but autosomal recessive and X-linked forms can occur. Approximately 60% have onset of symptoms in the fi rst decade of life.

Pes cavus, loss of foot dorsifl exion and eversion, hyporefl exia and sensory loss are typical clinical fea-tures in childhood. However, relatively asymptom-atic children may present because of a family history, while others present with gait disturbance, particu-larly toe walking, frequent falling or poor coordina-tion. Weakness and wasting in the legs may progress slowly and distal weakness in the arms is sometimes seen. Thickened peripheral nerves can occasionally be palpated.

The diagnosis can be confi rmed by a nerve con-duction study but readily available DNA studies are the usual fi rst step in diagnosis. The DNA studies show a duplicated region on chromosome 17p (PMP-22 gene). Parents of children with suspected PMA should be examined.

No cure is available but ankle–foot orthoses or orthopaedic procedures to correct foot deformity are often required and helpful. Progression is only relatively slow, with patients leading a fairly full life.

Children with neuromuscular disease often do not have all the clinical features seen in adults and some-times it is the family history that gives the vital clue.

The clinical severity of PMA varies considerably and some adults can be asymptomatic. Careful clinical examination of a parent and further diagnostic studies sometimes unmask the apparent missing link. The absence of foot deformity or sensory dis-turbance in a child does not exclude PMA.

Neuromuscular junction disordersAcute

Infant botulism

Infant botulism results from the production of Clos-tridium botulinum exotoxin in the gastrointestinal tract. It differs from botulism associated with food poisoning, in which there is ingestion of preformed toxin from contaminated food. In infant botulism, botulinum spores are ingested, with honey impli-cated in some cases. The disease usually occurs in infants under 9 months of age.

Constipation for days or weeks typically precedes the onset of symptoms of fl oppiness, weakness and ptosis, which occur over hours or 1–2 days at most. Feeding and swallowing diffi culty, a poor cough, weak cry, hyporefl exia and respiratory insuffi ciency are typical. Extraocular movements may be impaired and dilated; sluggishly reacting pupils are often seen and can be helpful diagnostically. Deterioration may be rapid, with many patients requiring artifi cial ven-tilation for up to 2 months while the neuromuscular junctions regrow.

Diagnosis is clinical, supported by isolation of the organism and its toxin from faeces. Treatment is sup-portive. Botulinum antitoxin has been used but has not been shown to be helpful. Human intravenous botulism immune globulin (BabyBIG) may have a place in therapy if the child is treated early. The prognosis is excellent, with full recovery unless com-plications from cerebral hypoxia intervene. Prompt recognition and transfer to a facility capable of long-term ventilatory support is essential.

Chronic

Autoimmune myasthenia gravis

Myasthenia gravis in most children has an autoim-mune basis, with antibody directed against neuro-muscular junction postsynaptic acetylcholine receptors. Onset occurs at any time from the second year of life onwards. Symptoms are present for less than 1 month in the majority of patients and many have an episode of respiratory failure if untreated. Symptoms and signs are similar to those in adults, although relatively more prepubertal patients have

Clinical example

Claudine, a 5-year-old girl, was seen by her paediatrician because of frequent falling. He found mild ataxia of gait and arefl exia but no

other abnormality. There was an extensive family history (autosomal dominant inheritance pattern) of a chronic neuropathy consistent with peroneal muscular atrophy. Claudine’s mother was asymptomatic.

Examination of Claudine’s mother revealed minor sensory loss in the feet and hyporefl exia. Both mother and child had DNA evidence of the PMP-22 gene duplication, confi rming the diagnosis of peroneal muscular atrophy.



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only ocular problems. Ptosis, eye movement disor-der, diplopia, diffi culty chewing and swallowing, and slurred speech with or without predominantly proxi-mal limb muscle weakness of recent onset should raise the suspicion of myasthenia gravis. Fatigability, the hallmark of myasthenia, is usually prominent, but this is not invariable.

Suspicion of myasthenia gravis should trigger an urgent diagnostic assessment. Diagnosis is based on clinical observation of fatigability, often best seen in the upper eyelid, response to intravenous or intramuscular anticholinesterase agents such as edr ophonium or neostigmine, repetitive nerve stimu-lation and assay of acetylcholine receptor anti -bodies. Symptomatic relief may be obtained by oral administration of an anticholinesterase, commonly pyridostigmine. Corticosteroids, thymectomy, intra-venous immunoglobulin and plasmaphaeresis have a role in selected circumstances. Although myasthenia gravis is a serious long-term and potentially fatal disorder, the disease remits in some children.

Transient neonatal myasthenia gravis

Transient neonatal myasthenia gravis occurs in about 10% of offspring of mothers with myasthenia gravis. It is due to placental transfer of antiacetyl-choline receptor antibodies from a myasthenic mother to her fetus during pregnancy. This was one of the reasons why a humoral mechanism for myas-thenia gravis was considered highly likely, prior to proof of this mechanism by passive transfer of myas-thenia from human to mouse accomplished in the mid-1970s.

Onset of symptoms is not immediately after birth but is usually in the fi rst 96 hours; feeding diffi culty, respiratory diffi culty and weakness or hypotonia are the main features. Myasthenic symptoms in the mother may be minimal. Appropriate supportive measures and anticholinesterase medication are used until the syndrome resolves over the ensuing weeks. This correlates with the expected diminution of pas-sively transferred IgG antiacetylcholine antibodies that had been transferred from mother to infant. The infant returns to normal and does not subsequently have myasthenia gravis.

Congenital myasthenic syndromes

Congenital myasthenic syndromes are not one disease but many different rare genetic–biochemical disorders of the neuromuscular junction encompass-ing both the pre- and postsynaptic regions. They are not autoimmune disorders. Detailed electrophysio-logical and morphological testing, available in only a few laboratories, is usually required to diagnose

and characterize these disorders defi nitively. Hypo-tonia, limb weakness, facial weakness, ptosis, oph-thalmoplegia and apnoeic episodes, particularly with infections, may be seen but the emphasis varies with the particular syndrome. Some show improve-ment with time despite life-threatening episodic apnoea in infancy, while others have more persistent problems. Individuals do not have acetylcho-line receptor antibodies. Some respond to anti-anticholinesterase preparations while others do not or worsen. As these are not autoimmune disorders, immunomodulatory therapies normally used in myasthenia gravis are without benefi t.

Muscle disordersAcute myopathies

Myopathic disorders with acute onset of weakness are uncommon. Snake bite or drugs may rarely trigger rhabdomyolysis or acute muscle breakdown. The dominantly inherited, sometimes fatal, syn-drome of malignant hyperthermia during anaesthe-sia causes muscle necrosis and myoglobinuria. This disorder is associated with central core disease (see below). Rhabdomyolysis with myoglobinuria appears occasionally after an upper respiratory tract infec-tion or after exercise and is probably related to an underlying metabolic disorder of muscle.

Chronic myopathies

Congenital myopathies

The congenital myopathies are a group of inherited disorders clinically relatively non-specifi c but with specifi c or distinctive fi ndings on morphological analysis of the muscle biopsy. Advances in histo-chemical and electron microscopy techniques over the last 30–40 years have enabled characterization of patients into well-defi ned myopathies, whereas pre-viously they were given non-specifi c diagnoses such as ‘fl oppy infant syndrome’. The identifi cation of these disorders allows important genetic and prog-nostic information to be given to the family.

These myopathies, usually inherited, are charac-terized by onset of weakness and hypotonia at or shortly after birth, or occasionally later in childhood or adulthood. Weakness may be mild or severe and is usually only slowly progressive. Pathologically there are structural changes in individual muscle fi bres or variations in the number or size of the muscle fi bre types.

Some of the well recognized disorders are cen-tral core myopathy (Fig. 17.3.2) and nemaline myopathy.



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Progressive muscular dystrophies

The muscular dystrophies are a group of inherited disorders of muscle characterized by weakness pre-senting from birth to late adulthood, with the common feature being the pathological appearance of dystrophic muscle (Fig. 17.3.3). These disorders primarily affect skeletal muscle but other tissues may be involved; for example, congenital muscular dys-trophy may be associated with white matter abnor-malities in the brain. The dystrophies are the commonest serious muscle diseases and as a group place a signifi cant burden on the patient, the family

and the community in medical, social and economic terms.

The various forms of muscular dystrophy share a common pathogenesis of muscle plasma membrane instability secondary to the lack of, or abnormality of, proteins and glycoproteins linking the subsarco-lemmal cytoskeleton to the extracellular matrix (Fig. 17.3.4). Not all dystrophies have had the absent or abnormal protein characterized. Absence or dysfunction of these structural proteins makes the muscle fi bre more prone to damage.

Many of the muscular dystrophies share common clinical features, although the severity varies. The age of onset, pattern of weakness, family history and relatively specifi c fi ndings on examination are impor-tant in diagnosing the type of muscular dystrophy. Some of the muscular dystrophies are named because of their pattern of weakness but these labels will probably change with the identifi cation of specifi c protein defects.

The clinical features of some muscular dystrophies are described below.

Duchenne muscular dystrophyDuchenne muscular dystrophy (DMD) is the most common muscular dystrophy, occurring in 1 in 3500 live male births. It is an X-linked disorder and occurs nearly exclusively in males. It is a disease of devastat-ing proportions as it is progressive, it has signifi cant genetic implications, there are no curative treatments available and it has serious medical complications. It causes death in the second or third decade and ranks high on the list of devastating diseases as judged by its effect on the person, the family and the require-ments for community resources.

Practical points

• In a family exhibiting autosomal dominant inheritance of a muscle disorder consistent with a congenital myopathy, central core disease should be considered a possibility and precautions taken against malignant hyperthermia if an anaesthetic is given (e.g. for a muscle biopsy)

Fig. 17.3.2 Muscle biopsy in central core disease.

Fig. 17.3.3 Dystrophic muscle biopsy.

basement membrane

sarcoglycancomplex

laminin-2

α-dystroglycan

β-dystroglycan

F-actindystrophin

25

δ β

α

γ

N syntrophins

C

Fig. 17.3.4 Subsarcolemmal cytoskeleton.



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DMD is caused by a mutation at the Xp21 chromo-some site. This causes a lack of dystrophin, a muscle protein that is thought to be important in the stabil-ity of the muscle membrane. Two-thirds of patients have a family history of muscular dystrophy or are isolated cases with an unsuspecting female carrier in the family, while one-third appear to arise as spon-taneous mutations.

Development in the fi rst year of life is usually normal. The fi rst symptoms are usually recognized from 18 months to 4 years of age, with delayed walking being the most common presenting com-plaint. Approximately 50% of children with DMD do not walk before 18 months of age. Abnormal walking or running, toe walking, diffi culty in climb-ing, diffi culty in getting up from the fl oor or chair, and frequent falls are other prominent early features. A signifi cant percentage of children will also have developmental problems other than motor delay, such as intellectual impairment or delayed language development. The intellectual impairment and lan-guage delay are non-progressive and mean IQ is approximately 85. While many are intellectually normal, some children are moderately intellectually disabled. The dual problems of motor and intellec-

tual disabilities are severely incapacitating socially and educationally.

Proximal muscle weakness accounts for the motor diffi culties. This can be demonstrated on formal testing or alternatively by functional testing, such as getting the child to rise from the fl oor. Typically, with this action the Gowers sign is exhibited (Fig. 17.3.5). A Gowers sign is not specifi c for DMD and is seen in other disorders with proximal muscle weakness. Enlargement (pseudohypertrophy) and fi rmness of the calf, quadriceps and triceps muscles is commonly seen (Fig. 17.3.6).

Some variability in course is exhibited from child to child, although the following generalizations encompass most children with DMD. Between the ages of 4 and 6 years there is an apparent improve-ment in mobility, with the children typically per-forming new motor activities. This is because normal muscle development (and regeneration) outstrips the degenerative process. After this period of improve-ment, relentless decline in function occurs, with increasing proximal and distal weakness in the limbs. Trunk muscles are also weakened. This leads to a worsening waddling gait, increasing lumbar lordo-sis and increasing equinovarus foot deformities.

Fig. 17.3.5 The Gowers sign in a patient with Duchenne muscular dystrophy, illustrating the sequence of manoeuvres required to rise from the supine position. (With permission from Williams 1982.)



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Independent mobility is lost, usually between 8 and 13 years of age, with the child becoming wheelchair-bound, after which scoliosis generally develops. During the second decade of life there is a gradual decline in pulmonary function, related to the scolio-sis and progressive muscle weakness. Death is usually due to respiratory complications, although cardiac failure secondary to a cardiomyopathy can occur. Cardiac arrhythmias may be a terminal event.

The diagnosis of DMD should be based on the family history (if any), clinical features, serum CK, DNA deletion testing and muscle biopsy. Pathologi-cal confi rmation of the diagnosis is essential except where the diagnosis has been confi rmed in another family member or by a DNA deletion. The CK is a reliable screening test and is invariably grossly ele-vated in a child with DMD, even from the neonatal period. Conversely, a normal CK test after the neonatal period excludes the later development of DMD.

Effective genetic counselling can be offered only if the fi rst case in the family is diagnosed before other affected males are born. The early diagnosis of DMD can be facilitated by using the following criteria for ordering serum creatine kinase estimations in males:

• known or suspected family history of dystrophy• male not walking before 18 months of age

without obvious cause

• unexplained gait disturbance (particularly toe walking)

• unexplained mental retardation• unexplained language delay.

Detection and counselling of female carriers is a most important aspect of family management. The male offspring of a known carrier have a 50% risk of having DMD, while 50% of female offspring will be carriers. Females may still be carriers even though there is no other family history. Only 60% of known carriers have an elevated CK level and hence a normal level does not exclude the carrier state. DNA technology can now be applied to offer antenatal diagnosis by detecting deletions from the X chromo-some or by linkage analysis.

Currently there is no cure for muscular dystrophy. Corticosteroids may provide symptomatic improve-ment in strength, with the prolongation of ambula-tion. The prolongation of ambulation decreases the complications associated with being wheelchair-bound.

Management involves a very positive approach to satisfying the emotional, social and educational needs of the child and his family, together with judi-cious use of physiotherapy, orthotic devices and surgery for orthopaedic deformity.

Fig. 17.3.6 Pseudohypertrophy of muscles.

Practical points

• The commonest reason for the late diagnosis of Duchenne muscular dystrophy is not thinking of the diagnosis in a young male with delayed motor, mental or language development

Becker muscular dystrophyBecker muscular dystrophy is a disorder allelic to DMD but much less common. It is less severe than DMD and has a variable age of presentation.

Facioscapulohumeral syndromeFacioscapulohumeral (FSH) muscular dystrophy is a relatively common autosomal dominant disorder that predominantly affects the shoulder girdle, in particular the periscapular, humeral and facial muscles. It is a relatively mild disorder with very slow progression. Onset is commonly in adolescence or early adult life, although occasionally it may be very early childhood.

In a typical case, facial muscle weakness is one of the fi rst symptoms. Patients have diffi culty closing the eyes, blowing out the cheeks, whistling or sucking through a straw. The shoulder girdle weakness usually begins at the same time as the facial weakness



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is noted and can be quite asymmetric. Symptoms include diffi culty lifting the arms above the head. There is obvious winging of the scapulae in adult patients but this may not be so obvious in children. On abduction of the shoulders, the scapulae move upwards and give the shoulders a characteristic appearance. Foot drop is not uncommon. An infan-tile form has been described that presents with more severe weakness. The infantile form of FSH dystro-phy is associated with deafness and visual loss.

The locus for autosomal dominant FSH has been mapped to the distal arm of chromosome 4.

Sensorineural hearing loss and Coats disease, a proliferative retinopathy, are associated with early-onset FSH dystrophy. Aggressive treatment of these associated disorders is important.

Myotonic disorders

These are a clinically heterogeneous group, with myotonia being the characteristic clinical feature. Myotonia is the inability of muscles to relax after voluntary contraction or stimulation. Myotonia can be detected during attempted relaxation of a volun-tary contraction, such as after shaking hands or eyelid closure, by percussion of a muscle or by elec-tromyography. Older children may describe myoto-nia as stiffness or cramping.

Many of these disorders have been shown to be due to defects of muscle ion channels. In some instances different mutations within the one gene can cause myotonia and/or periodic paralysis.

Myotonia congenita (Thomsen disease)

Autosomal dominant and autosomal recessive forms occur. Onset is in infancy or early childhood with symptoms due to myotonia, such as stiffness, diffi -culty initiating rapid movements and sometimes feeding diffi culties. Muscle hypertrophy is common. The myotonia decreases with continued activity and may be aggravated by cold. Improvement occurs with increasing age. Symptomatic relief of myotonia with quinine or mexiletine may be useful.

Myotonic dystrophy (Steinert disease)

Myotonic dystrophy is an autosomal dominant dis-order but an affected parent may be relatively asymp-tomatic and not diagnosed until detailed examination and investigation is undertaken. The disease is due to an excessive number of repeats of the sequence CTG on the long arm of chromosome 19 and this can be used for diagnostic testing in diffi cult cases and for antenatal diagnosis. The spectrum of clinical severity in myotonic dystrophy is extremely broad,

requiring genetic testing to help clarify the diagnosis in minimally affected patients.

Juvenile typeThe clinical features are similar to those seen in adults, with distal muscle weakness, wasting and myotonia, an expressionless face due to facial muscle weakness, and ptosis. Cataracts, frontal alopecia, testicular atrophy, cardiopulmonary insuffi ciency and dementia may occur in adult life.

Congenital typeA syndrome of hypotonia, weakness, arthrogry -posis, feeding diffi culty, respiratory diffi culty and marked facial weakness all present at birth, along with other dysmorphic features, has been recog-nized. Invariably, the mother has myotonic dystro-phy. Intellectual disability is common if the child survives the neonatal period.

Clinical example

Mrs McGill, aged 25 years, had myotonic dystrophy, as did her father, sister and brother. She had a son and twin daughters

who were normal at birth and who remained asymptomatic. Her next child, Tessa, was 4 weeks premature and at birth was very hypotonic, had some respiratory diffi culty and required gavage feeding. There was marked bilateral facial weakness, talipes equinovarus and mild fl exion deformity at the knees. The respiratory and feeding diffi culties gradually resolved, but the facial muscle weakness remained and Tessa later showed delay in motor and language milestones. There was no clinical myotonia when she was seen at 3 years of age.

Tessa had typical features of the congenital form of myotonic dystrophy, which typically occurs if it is the mother who is the affected parent. Some babies are stillborn, while others do not survive the neonatal period. Tessa was only moderately affected and will survive into adult life, but will almost certainly require special schooling. The dominant inheritance is clear from the family history. Mrs McGill and her husband wanted to know if the other children might develop the disease. Although they were asymptomatic at the time, there was still a chance that they had inherited the abnormal gene. DNA testing for the triplet expansion on chromosome 19 could be used to allow antenatal diagnosis.

Practical points

• Facial diplegia with respiratory diffi culty or pharyngeal incoordination in a neonate should raise the suspicion of congenital myotonic dystrophy



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Infl ammatory myopathy

Acute viral myositis

Acute viral myositis is a clinically recognizable syn-drome of acute onset of pain and tenderness of the gastrocnemius and soleus muscles several days after an upper respiratory tract infection, often with infl u-enza B virus. Recovery occurs in a few days.

Chronic infl ammatory myopathy

This may occur as ‘idiopathic’ disorders, such as dermatomyositis or polymyositis, or as part of a rec-ognized collagen vascular disease.

Metabolic myopathies

A large number of individually uncommon meta-bolic disorders may produce episodic, acute or chronic muscle weakness, hypotonia, stiffness or cramping, exercise intolerance or myoglobinuria. Symptoms are sometimes accentuated or precipi-tated by exercise, rest after exercise, fasting or exces-sive carbohydrate intake.

The underlying metabolic defects usually are in glycogen metabolism (e.g. Pompe disease), lipid metabolism (e.g. carnitine defi ciency, carnitine pal-mitoyltransferase defi ciency), potassium metabolism (e.g. the periodic paralyses associated with hyper-, hypo- or normokalaemia) or a variety of mitochon-drial functions (e.g. myopathies with cytochrome oxidase defi ciency and Kearns–Sayre syndrome of progressive external ophthalmoplegia).

Knowledge of the underlying metabolic causes of many of these disorders is increasing and the hope is that, once the underlying pathophysiological pro-cesses are elucidated, more specifi c and effective therapies will become available.

The ‘fl oppy’ infant syndromeHypotonia, or fl oppiness, is a common observation in infancy and has many different causes. Normal

muscle tone depends not only on the peripheral neuromuscular system but also on spinal cord and higher centres. Indeed, disorders affecting the cen-tral nervous system are more frequently the cause of the fl oppy infant syndrome than peripheral neuromuscular causes. Muscle tone is assessed by observation of posture, assessment of the resistance of joints to passive movements and of range of movement.

When an infant or young child is found to be signifi cantly hypotonic, an important question is whether the hypotonia is ‘central’ or ‘peripheral’ in origin. Hypotonia of peripheral neuromuscular origin usually is associated with signifi cant weakness (e.g. Werdnig–Hoffmann disease), while central hypotonia is usually not associated with signifi cant weakness (e.g. Down syndrome or Prader– Willi syn-drome). In practice, the differentiation in early child-hood can sometimes be quite diffi cult. Apart from the absence of signifi cant weakness, clues to a central cause of hypotonia may be:

• a history of adverse perinatal events• abnormal behaviour in the neonatal period• delayed mental development• seizures• abnormality of head size or shape• the presence of normal or brisk deep tendon

refl exes.

Hypotonia of peripheral neuromuscular origin is usually, but not invariably, accompanied by hy -porefl exia in an alert baby with normal mental development.

AcknowledgementsI would like to thank Dr Lloyd K. Shield, who has been my mentor and the person who kindled my interest in neuromuscular disease. Dr Shield’s previ-ous contributions to this textbook form the major part of this chapter.



Large headsA large head may be due to enlargement of the brain substance or the fl uid-fi lled spaces of the brain. The more common causes include:

• a large cerebrum• an oversized, overweight brain (as in

megalencephaly)• a dilated cerebrum (as in hydrocephalus)• a tiny cerebrum (as with large chronic subdural

hygromas)• no cerebrum (as in hydranencephaly).

The two major categories of aetiology responsible for megalencephaly are anatomical and metabolic. A large head with normal-sized ventricles and normal neurodevelopmental examination may be related to familial factors, as in benign familial anatomical megalencephaly or macrocephaly. However, the large dolichocephalic head in cerebral gigantism will have large ventricles but normal ventricular pressure and associated limited intellect, poor coordination and coarse facial features.

Head enlargement in metabolic megalencephaly is a late manifestation of many cerebral degenerative disorders such as lysosomal storage diseases. Mega-lencephaly occurs in a wide variety of clinical disor-ders and syndromes, can be unilateral or bilateral, and is associated with a wide spectrum of develop-mental symptoms and signs. An acute increase in intracranial pressure should prompt consideration of the possibility of drug intoxication (tetracycline, vitamin A, nalidixic acid), lead encephalopathy, sub-dural haematoma and Reye syndrome.

Hydranencephaly is a condition of uncertain aeti-ology. The cerebral cortex is represented by a thin membrane composed of glial cells, with islands of cerebral cortex sometimes scattered in this tissue. The third ventricle, basal ganglia, brain stem and cerebellum are present but may reveal morphological abnormalities. The head size is usually normal at birth but increases rapidly within a few weeks of life.

Neurological function initially may be normal, shortly after gross neurological abnormality is evident (rigid muscle tone, tremors, and persistent and exaggerated primitive refl exes). Optic atrophy is common and the head transilluminates readily. The child sleeps excessively, is irritable, feeds poorly and has unstable thermoregulation. Electroencephalog-raphy reveals a fl at tracing or a few low voltages over islands of cerebral cortex.

Hydrocephalus

Hydrocephalus (Greek: hydro meaning ‘water’, and cephale, ‘head’) refers to a group of conditions char-acterized by:

• an increase in cerebrospinal fl uid (CSF) volume• ventricular dilatation• elevation of intraventricular pressure.

Hydrocephalus occurs when there is an imbalance between the formation and absorption of CSF. Impaired absorption is almost always due to some degree of obstruction along the CSF pathways. If the passage of CSF is obstructed within the ventricular system, the resultant hydrocephalus is labelled non-communicating, while if obstruction exists in the surface pathways, the hydrocephalus is described as being communicating. The rate of this volume change varies from patient to patient and depends in large part on the degree of obstruction. The lesions that commonly produce hydrocephalus are listed in Table 17.4.1.

In supratentorial lesions, CSF obstruction is a late event, so that neurological or endocrinologi-cal abnormalities often precede symptoms of raised intracranial pressure. Less commonly, cerebral tuberculoma, torular meningitis or an aneurysm of the vein of Galen may simulate intracranial neo-plasms. The latter should be suspected if, in addition to hydrocephalus, a loud intracranial bruit, high output failure and vascular naevi are also present in the same patient.

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17.4 Large heads, hydrocephalus and neural tube defectsP. J. Flett, R. N. Russo


615

Table 17.4.1 Lesions producing hydrocephalus

Non-communicatingAqueduct stenosis or atresia• Commonest site of intraventricular obstruction in infants with congenital hydrocephalus• May occur as an isolated anomaly or be associated with myelomeningocele and the Arnold–Chiari malformation• Histologically, subependymal gliosis around the aqueduct is demonstrable• May be slowly progressive in some, not being clinically apparent for several years before obstructive symptoms appearSporadicFamilial • Inherited as a sex-linked trait; features include a short fl exed thumb, mental retardation and other cerebral abnormalities

Obstruction at the fourth ventricle• Dandy–Walker syndrome • Cystic dilatation of the fourth ventricle, with cerebellar hypoplasia; other structural brain anomalies may also occur • Associated with atresia of the exit foramina of the fourth ventricle • Hydrocephalus may be present at birth or may develop subsequently • Diagnosis is suggested in typical cases by the shape of the skull and the presence of cerebellar signs• Arachnoiditis

Obstruction due to intracranial mass lesions• Should always be considered in any child where head enlargement develops in late infancy or childhood• Neoplasm, cysts • Childhood tumours usually arise in the posterior cranial fossa and include medulloblastoma, astrocytoma and

ependymoma • Intracranial pressure develops early, because of their close proximity to the fourth ventricle • Ataxia, incoordination, nystagmus and papilloedema are suggestive of the diagnosis • Differential diagnosis includes craniopharyngioma, gliomas, pinealomas and arachnoid cysts• Haematoma• Galenic vein aneurysm

Ventricular infl ammations (rare)

CommunicatingArnold–Chiari malformationWith myelomeningocele (Type 2) (Fig 17.4.5)Without myelomeningocele (Type 1)• Consists of: • downward displacement and elongation of the hind brain • herniation of the medulla, cerebellar vermis and inferior part of the fourth ventricle into the upper cervical canal• CSF fl ow is impaired, usually within the subarachnoid space• Hydrocephalus usually develops in early infancy• Frequently associated with cranium bifi dum, myelomeningocele and hydromyelia

EncephaloceleMeningeal adhesionsPostinfl ammatoryPosthaemorrhagic• May be secondary to neonatal meningitis (post infl ammatory adhesions), or intraventricular or subarachnoid haemorrhage• Hydrocephalus is common, and is usually communicating• Neurological defi cit, developmental delay and seizures are usually the result of the infective process, but the

hydrocephalus, if not relieved, will aggravate the brain injury

Choroid plexus papilloma• A rare cause of hydrocephalus.• Hydrocephalus is produced by excessive fl uid secreted by the tumour, sometimes with obstruction to CSF fl ow• Recurrent haemorrhage from the tumour may play a role• Total excision of the tumour usually leads to a resolution of the hydrocephalic process

LARGE HEADS, HYDROCEPHALUS AND NEURAL TUBE DEFECTS 17.4


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Approach to clinical diagnosis

The clinical appraisal of the hydrocephalic child involves:

• the establishment of the diagnosis• elucidation of the aetiology• assessment of neurological and mental function• a search for other associated malformations.

It is essential to determine the age and rapidity of onset of hydrocephalus and its rate of progression. In most clinical situations, the child presents with a large head, which may already be apparent at birth or at a few months of age. Despite the obviously large head, many babies thrive and may develop normally, apart from poor head control. Other infants with hydrocephalus, however, feed poorly, are irritable, vomit excessively and fail to gain weight. In infants with congenital hydrocephalus, the birth weight, nature of delivery and neonatal course should be noted. In addition, enquiry as to whether there has been a similar illness in an older sibling or possible intrauterine infection is relevant.

Hydrocephalus that develops in an older and pre-viously normal child suggests the possibility of a posterior fossa neoplasm. Because ventricular dila-tation is generally subacute in children with cere-bellar tumours, symptoms of raised intracranial pressure are often associated with changes in behav-iour, a clumsy gait, abnormal articulation, tremors and incoordination. If elevation of ventricular pres-sure occurs abruptly, attacks of nausea, vomiting, head retraction and extensor spasms are prominent.

In very ill children, symptoms of a primary illness, such as cranial infection and haemorrhage, may obscure symptoms of intracranial hypertension. It is important in all cases to ascertain any neurological symptoms, determine the time of onset of head enlargement and assess the developmental progress of the child.

In children with myelomeningocele and shunted hydrocephalus, raised intracranial pressure is usually secondary to a blocked shunt. Children may present with features typical of a blocked shunt (irritability, headache, somnolence, vomiting, loss of conscious-ness) but may also present with atypical features such as seizures or unusual behaviours. Diagnosis requires exclusion of other underlying causes, and a high index of suspicion prompting the clinician to question shunt dysfunction.

Clinical example

Ivan, a 5-year-old boy, presented with a 2-month history of early morning headache and vomiting. This was associated with a decline

in his school performance and he was noted to be increasingly unsteady on his feet. The signifi cant fi ndings on examination included a wide-based, unsteady gait, horizontal nystagmus and severe bilateral papilloedema. A computed tomography (CT) scan revealed the presence of a large mass in the cerebellar vermis, which was distorting the fourth ventricle.

Ivan underwent a craniotomy and the tumour arising in the cerebellar vermis was excised. Following operation the symptoms of raised intracranial pressure subsided and serial CT scans showed a resolution of the dilated lateral and third ventricles.

With this patient, excision of the obstructing mass was an effective form of treatment for a signifi cant degree of non-communicating hydrocephalus. The presenting symptoms were in part due to raised intracranial pressure and in part due to interference with cerebellar function. Clinical example

William was an 11-year-old boy with spina bifi da and shunted hydrocephalus. During the course of the clinical consultation as part of

long-term follow-up of his condition, he complained that he had been experiencing some facial pain on the right side of his face for the past 3 days. He had a decreased appetite and his mother noted that he had been confused about his daily routine, which surprised her.

On examination, William had a fl accid lower limb paralysis and was wheelchair-mobile. He had mild hyperrefl exia in his upper limbs and nystagmus of gaze, both long-standing problems associated with his condition. His shunt appeared to empty, but was slow to refi ll. His fundi did not show evidence of papilloedema. There was no history of recent trauma or infection to explain his facial pain, and it was decided that he should have a CT scan to exclude hydrocephalus as a cause. This revealed enlarged ventricles and William was taken to theatre that day by the neurosurgical team to revise his shunt.

In this situation, the classical signs of raised intracranial pressure were not present and diagnosis of shunt dysfunction required a high index of suspicion. This boy might well have progressed to developing further signs later but by then the risk of an adverse outcome would probably have increased.

Physical examination

Classically, hydrocephalus is recognized by a pro-gressive increase in occipitofrontal head circumfer-ence out of proportion to other bodily dimensions. A single head circumference measurement that greatly exceeds the 97th percentile strongly suggests the existence of hydrocephalus. Where head enlarge-ment is equivocal, and neurological abnormality is



617

absent, serial head measurements will often indicate the need for further diagnostic studies. It must be emphasized that, once enlargement of the skull is clinically obvious, the ventricles are already grossly dilated and the cerebral cortex is thinned.

Clinical signs that frequently precede obvious enlargement of the head include:

• a large and bulging fontanelle• thinning of the bones of the calvarium• widening of the coronal, sagittal and lambdoidal

sutures.

With advancing hydrocephalus:

• the scalp thins and becomes shiny and pale• there is upward retraction of the eyelids• the eyes are fi xed in a downward gaze (the

‘setting sun’ sign)• hair appears sparse• superfi cial scalp veins become distended• the brow overhangs the small, triangular

face.

Despite the enormous head size, papilloedema is uncommon in congenital hydrocephalus. The shape of the skull should be noted. A large protruding occiput is typical of a Dandy–Walker cyst, while an asymmetrical head may be due to unilateral obstruc-tion at the foramen of Monro. In addition, ausculta-tion for cranial bruit should be performed over the eyeballs and over the calvarium.

Many mildly affected hydrocephalic children have remarkably normal development and minimal neu-rological defi cit. Gross abnormalities in a child with mild hydrocephalus are usually related to the underlying disorder that caused the hydrocephalus. However, prolonged stretching and compression of neural structures will lead ultimately to profound neurological injury. Where the increase in intracra-nial pressure is rapid and there has been no compen-satory increase in head size, the highly irritable child frequently gives a short, high-pitched ‘cerebral cry’. During these screaming episodes, decerebrate pos-turing may be evident. In the older child with ‘arrested’ hydrocephalus, it is important to evaluate the mental and psychological status. These chil-dren are frequently talkative, jovial and euphoric (‘cocktail party syndrome’) but their capacity for concentration, language comprehension and ab-stract thinking is often lacking. Manifestations of long-standing hydrocephalus include a variety of end ocrinological and metabolic disorders such as precocious puberty, diabetes insipidus and abnormal thermoregulation. Various anomalies, particularly neural tube defects, skeletal defects and cutane-ous naevi, are known to coexist with obstructive hydrocephalus.

Investigations

The child’s assessment, based on the history and examination, will often enable a diagnosis of hydro-cephalus to be made with some degree of certainty. However, in all cases, investigations are required to confi rm the diagnosis, determine the extent of the disorder and if possible defi ne the aetiology. Investi-gations are also of assistance in deciding the need or otherwise for active treatment and also as a means of assessing the success or otherwise of treatment. The plain skull X-ray may be a useful initial investigation.

UltrasoundThe widespread use of ultrasound scanning (Fig. 17.4.1) has in recent times greatly facilitated the assessment of infants with suspected hydrocephalus. Real-time ultrasound imaging through the open fon-tanelle provides a clear demonstration of the ventri-cles and may defi ne other structural anomalies well. This non-invasive risk-free investigation can be undertaken with little or no sedation and can be repeated as often as required. When the fontanelle closes, satisfactory imaging can no longer be obtained. Ultrasound examination during pregnancy can indicate whether the fetus has hydrocephalus.

Computed tomographyIn the older child, and occasionally in infants where more detail is required, computed tomography (CT) scanning (Fig. 17.4.2) is the investigation of choice.

Fig. 17.4.1 Frontal view of a real-time ultrasound study showing markedly dilated lateral ventricles on either side of a large posterior fossa cyst in a patient with Dandy–Walker malformation.



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This technique provides excellent detail of the intra-cranial anatomy and the images may be enhanced by the injection of contrast material. Many children can have CT scans without sedation while others will require sedation or occasionally a general anaes-thetic. The radiation involved in a single scan is of an acceptable degree but a limitation should be placed on repeated studies.

Magnetic resonance imagingMagnetic resonance imaging (MRI) (Fig. 17.4.3) is rarely undertaken as a primary investigation but may be of value in defi ning the cause of the condi-tion. Small tumours in the region of the aqueduct causing obstruction to CSF fl ow may not be visual-ized by a CT scan but are clearly defi ned by an MRI study. Special techniques can visualize CSF fl ow patterns.

Treatment

The indications for treatment are based on a clear understanding of the natural history of the disorder. Three patterns may be described:

• the process continues, followed by neurological deterioration

• the process progresses to a point, then stabilizes (‘compensated hydrocephalus’)

• the process is temporary.

In the majority of patients, the ventricles will con-tinue to enlarge and the overlying brain will become

stretched, compressed and thinned. If the process starts in infancy before the skull bones have devel-oped signifi cant attachment to each other, massive head enlargement will result and under these circum-stances signifi cant brain injury will result. This type of progression will be detected by the presence and persistence of signs of raised pressure, an excessive rate of head growth and, less commonly, by the fi nding of neurological abnormality and develop-mental delay. Serial imaging will confi rm progres-sion of ventricular dilatation. In this group treatment is essential if brain injury is to be avoided or minimized.

In a lesser number of patients limited enlargement of the ventricles will occur and then cease. The term ‘arrested hydrocephalus’ has been applied to this group. The ventricles remain somewhat larger than normal but there are no clear signs of raised intra-cranial pressure and brain function appears normal. The head may be large but the rate of growth will either be normal or only slightly excessive and serial images will show no signifi cant alternation in ven-tricle size. With this pattern, decisions regarding treatment are less well defi ned. If the degree of dila-tation is mild to moderate there is no good evidence that treatment will infl uence the outcome favourably. Under these circumstances, frequent assessment is required to ensure that stability is maintained.

With the widespread use of head imaging tech-niques, it has become apparent that hydrocephalus may be a temporary state in certain circumstances. Posthaemorrhagic hydrocephalus in the low-birth-weight infant is often of this type, as is the disorder

Fig. 17.4.2 Computed tomography scan demonstrating gross ventricular dilatation in hydrocephalus.

Fig. 17.4.3 Magnetic resonance image of a child with a spina bifi da showing the Arnold–Chiari malformation. Note the herniation of the cerebellum into the upper cervical canal.



619

complicating certain forms of meningitis. In these patients it appears likely that the CSF pathways have regained their patency. These patients are usually defi ned by repeating imaging. Such studies would show reduction in size of ventricles to normal and this satisfactory state would be associated with the disappearance of all physical signs of progressive hydrocephalus. Obviously, no long-term treatment is required in this group but intermittent removal of CSF by either a lumbar puncture or a ventricular puncture may help to resolve the process and prevent any excess ventricular dilatation during the period before effective CSF fl ow is established via normal pathways. On occasions, a reservoir may be inserted into a lateral ventricle to facilitate such intermittent removal. In addition, drugs that reduce CSF produc-tion, such as acetazolamide and isosorbide, have been used with the same intent.

Operative treatmentThe defi nitive treatment of hydrocephalus is a surgi-cal procedure. The usual method of treatment is by a shunt that diverts the CSF to some other site in the body. In some cases of non-communicating hydro-cephalus, ventriculostomy may successfully re-estab-lish normal CSF pathways.

Ventriculoperitoneal shunt. This is the operation performed most frequently in paediatric patients with hydrocephalus. A Silastic catheter is placed in a lateral ventricle through a burr hole and the other end of the tube is passed subcutaneously to the abdomen and then placed in the peritoneal cavity. A valve is interposed and an adequate length of tube is placed in the peritoneal cavity to allow for growth. The peritoneum absorbs CSF effectively.

Ventriculoatrial shunt. In this procedure the lower end of the shunt is passed via a neck vein to the right atrium. The catheter is so designed so that CSF can pass from the catheter tip but blood cannot fl ow back into the lumen. The turbulent blood fl ow in the atrium prevents thrombus formation around the catheter. This operation is not undertaken often in childhood as maintenance may involve the lengthen-ing of the atrial catheter on several occasions.

Complications of ventricular shuntsThe operation is generally well tolerated with infre-quent early diffi culties. Common complications include meningitis, ventriculitis, and shunt obstruction.

The most common presentation of a child with a blocked shunt is that of a vague illness. Irritability and vomiting are frequent and headache may be present. The symptoms are very similar to those of many childhood illnesses and diffi culties are often experienced in trying to decide whether the symp-toms are a consequence of shunt malfunction or an unrelated illness. Defi nite signs of raised intracra-

nial pressure, if present, are of great assistance but are often not ascertained readily. Palpation of the shunt mechanism may also frequently be inconclusive.

The treatment of shunt obstruction is usually a simple procedure and involves the replacement of the defective component. However, a small number of patients suffer from repeated episodes of obstruction and management can be diffi cult and may involve many variations of shunt equipment and surgical technique.

Clinical example

Sara, a 6-year-old child with a past history of having had a ventriculoperitoneal shunt inserted in infancy for congenital

hydrocephalus, presented at the outpatient clinic for review having missed a previous planned attendance. Her mother stated that Sara was generally well but was concerned by her visual function. Sara insisted on sitting immediately adjacent to the television set and had been moved to the front of her class to enable her to see the blackboard.

When examined, Sara appeared to be generally well but head measurement indicated an excessive rate of growth. Her visual acuity was markedly diminished in each eye and funduscopy revealed severe secondary optic atrophy. On palpation the shunt tubing was disconnected and an immediate CT scan showed very large ventricles. The shunt was revised immediately but unfortunately there was no improvement in Sara’s poor vision.

The shunt had obviously been malfunctioning for a prolonged period of time and had resulted in chronic raised intracranial pressure. Sara had not complained of any symptoms but the presence of intracranial pressure produced marked optic atrophy over this interval of time. If Sara had attended for the planned reviews, the abnormality might well have been recognized and corrected before visual deterioration resulted.

Neural tube defectsThe term neural tube defect (NTD) refers to a group of malformations involving the brain and/or spinal cord in association with varying degrees of absence or malformation of the overlying tissues: meninges, bone, muscle and skin. Myelomeningocele (myelo meaning ‘cord’; meninges, coverings of the spinal cord; cele, ‘sac’) involves all the tissue layers includ-ing the skin and bone and is an outpouching of the spinal cord through the posterior bony vertebral column that has failed to form. Meningocele is an outpouching of the meninges or coverings of the spinal cord only, and not the cord itself. The term spina bifi da refers to the normal bony projection over the spine being divided or ‘bifi d’. Spina bifi da occulta



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is the failure of the formation of the posterior ele-ments of the vertebrae but without any out pouching of the meninges or spinal cord. It occurs in 5–10% of the population and is most often asymptomatic. X-rays of the spine documenting the incomplete vertebral arch confi rm the diagnosis. Accompanying associated features may include dermal hyperpig-mentation, a fatty swelling, a tuft of hair or a dermal sinus on the back. Spina bifi da cystica refers to myelo-meningocele and meningocele. Myelomeningocele is the much more serious and much commoner type of spina bifi da cystica. Spinal dysraphism, which includes spina bifi da occulta, meningocele and myelomeningocele, is part of the family of neural tube defects that encompasses abnormalities of the cranium and its contents (anencephaly, encephalo-cele and cranial meningocele) as well as abnormali-ties of the spine.

Incidence

The incidence has varied in different countries, the highest rates being recorded in the past in Northern Ireland, the west of Scotland and south Wales. In South Australia, the total incidence of neural tube defects during 1966–1991 was 2.01 per 1000 births and the incidence of myelomeningocele was 0.97 per 1000 births, with no upward or downward trend. Despite the total incidence remaining stable, prena-tal diagnosis and termination of pregnancy resulted in an 84% fall in the birth prevalence of all neural tube defects during the years studied. Screening by serum alpha-fetoprotein measurements or mid tri-mester ultrasonography, or both, detected over four-fi fths of cases in 1986–1991 in South Australia.

Recurrence risks in families have been docu-mented extensively. Recurrence risk statistics suggest a polygenic or environmental aetiology. The risk of recurrence following the birth of the fi rst child with a neural tube defect is approximately 4–8%, or 1 in 25. The risk increases to at least 10% after the birth of two affected children.

Neural tube defects are found commonly in spon-taneous fi rst trimester miscarriages. Neural tube defects are more common in females and in lower socioeconomic groups and the incidence varies with different ethnic groups.

Embryology and pathogenesis

The neural tube is the embryological structure from which the brain and spinal cord develop. The human neural tube closes just before the 30th day post fer-tilization and thus any infl uence affecting the closure of the neural tube must be present before this early stage of pregnancy. The typical motor, sensory and

sphincter dysfunctions of spina bifi da and myelodys-plasia are the most evident clinical manifestations but represent only one aspect of this complex terato-logical anomaly. There is a high incidence of gross and microscopic brain-stem, cerebellar and cerebral malformations. The aetiology of neural tube defects is still debated. Polygenic inheritance and environ-mental and teratogenic factors have been implicated. It has been unequivocally demonstrated that vitamin supplementation with folic acid reduces the inci-dence of recurrence in high-risk populations. Dietary factors may therefore play a major part in low-risk populations. Many other potential aetiological causes have been examined also during the last 20 years.

Antenatal diagnosis, antenatal counselling and fetal surgery

The presence of abnormally high levels of alpha-fetoprotein in the amniotic fl uid has a high correla-tion with myelomeningocele. Alpha-fetoprotein is a component of fetal CSF and it probably leaks into the amniotic fl uid from the open neural tube defect. Closed lesions often do not cause increased alpha-fetoprotein. The false-positive rate for the determi-nation of myelomeningocele is less than 0.5% and the false-negative rate is 2%. Alpha-fetoprotein is syn-thesized by the yolk sac, hepatic cells and gastroin-testinal tract of the fetus and is normally excreted in the amniotic fl uid in fetal urine. The detection rate for open neural tube defects using maternal serum screening is approximately 80%, with a low false-positive rate. Ultrasonography can detect or confi rm the extent of the neural tube defect.

Offering counselling for the family with an ante-natal diagnosis of a neural tube defect is important, especially as the family will probably consider their options about whether to continue with the preg-nancy or elect for termination. Great care should be taken about the information conveyed. Preferably, it should be given by a specialist experienced in caring for children with a neural tube defect, in an appro-priate environment and with time available to answer the family’s questions about all the facets of raising a child with this diagnosis. The antenatal scan can offer some guidance but it must be remembered that ultrasound scan fi ndings cannot predict all aspects of functioning (physical and cognitive) accurately. In addition, families can be offered further counselling through community-based organizations (e.g. the Spina Bifi da and Hydrocephalus Association). All families should be made aware of preventative mea-sures (periconceptional folate) and offered genetic counselling if they wish to have other children in the future.



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Fetal surgery (for closure of the myelomeningocele lesion) at 20–30 weeks gestation, after which the fetus is returned to the uterus, has been developed with the hope of preventing signifi cant complications in the affected child. Early studies have demon-strated good cosmetic closure of the lesion but the complication rate (primarily due to the fetus being delivered prematurely) was found to be high. There is currently a randomized control trial being under-taken in the USA. The primary outcome is a signifi -cant reduction of the development of hydrocephalus in the treatment group. Until the results of this important trial are completed, however, this mode of treatment cannot be recommended.

Clinical features

Neural tube defects may be classifi ed as in Table 17.4.2.

Management of myelomeningocele

A team approach that includes the parents is essen-tial for the proper management of myelomeningo-cele. An important factor, which compounds the disability, is that the defect is apparent at birth. Information given to the parents and the manner in which it is conveyed will infl uence their reaction at this most vulnerable time and will affect the future of the child and the family. Medical specialists in this team include the neurosurgeon, orthopaedic surgeon and urologist. The medical team leader is most appropriately a paediatrician or paediatric rehabili-tation specialist with special skills in the fi eld of child development and rehabilitation. The medical team leader will coordinate care but, importantly, will also manage and advise on the multiple problems experienced by the children and their families. These include disability issues, school integration, inter-ventions to improve functional outcome and various activities to support the parents and child through the many problems, both physical and psychological, that invariably arise. The physiotherapist, occupa-tional therapist, orthotist, psychologist and medical social worker, together with trained hospital and community-based nursing staff and teachers, are important members of this team. The team has three major goals:

• to promote good health in the short and long term

• to promote maximum function in the child so that, as nearly as possible, normal developmental sequences and timing can be followed to enable maximal independence for the child and family

• to promote good family functioning.

Table 17.4.2 Classifi cation of neural tube defects

Anencephaly• At birth, presents as an opened, malformed skull and

brain• Most babies are stillborn• No effective treatment is possible• Death usually occurs within hours or days

Cranium bifi dumCranial meningocele• The underlying brain is normal• A meningeal sac protrudes through a skull defect

Encephalocele• A midline sac protrudes that may contain brain• Hydrocephalus is common

Spina bifi da occulta• One or more vertebral arches are incomplete posteriorly

but the overlying skin is intact• Diagnosed incidentally, e.g. as the result of an X-ray of

the spinal column during other investigations• Spinal cord usually normal; however, a number of

abnormalities of the spinal cord have been described• Ectodermal abnormalities may be associated: • a dermal pit • a depression with a tuft of hair • a fatty swelling (Fig. 17.4.4)• The ectodermal component • may communicate with the dura • may pose some risk of intraspinal infection (if

associated with a dural sinus)• The fatty swelling may be a lipomeningocele• The ectodermal component, if present, warrants full

neurological examination

Spina bifi da cysticaMyelomeningocele (Figs 17.4.5, 17.4.6), in which vertebral column skin, meninges and spinal cord are involvedMeningocele (Fig. 17.4.7), where the spinal cord is not involved• Almost always obvious at birth (most frequently, a

midline sac protrudes through a spinal defect (Fig. 17.4.4))

• May occur anywhere along the length of the spinal column

• The lumbar and lumbosacral regions are the most frequent anatomical levels

• Abnormal spinal cord tissue and nerve roots may be readily apparent macroscopically

• There may be spinal abnormalities such as kyphosis at the site of the lesion

• Functional defi cits include: • paraplegia, with motor and sensory impairment • hydrocephalus • variable intellectual impairment • neuropathic sphincter dysfunction

Sacral agenesis



622

A

B

C

Dermal pit

Hairy patchon skin

Dermoid cyst

Fatty lump – skindiscolouration

Fig. 17.4.4 Schematic representation of spina bifi da occulta. A. Dermal sinus. B. Intraspinal cyst pressing on the cord. C. Lipomatous mass infi ltrating the cord elements. Fig. 17.4.5 A lumbosacral myelomeningocele.

Neural plaqueNeuralplaque

Transverse section Longitudinal section

Spinalcord

Skin

Centralcanal

Bone

Nerveroots

Fig. 17.4.6 Myelomeningocele: diagrammatic representation.

Specifi c problems in the management of the newborn with spina bifi da

It is possible to predict with considerable accuracy the potential for future impairment in a number of areas. These include ambulation and subsequent mobility, probable bowel and bladder function, and hydrocephalus, with its probable sequelae. It is much more diffi cult to predict the effects that these impair-ments will have on the lifestyle of the individual and family. Also, it is possible to recognize early those lesions that are inoperable because of massive bony deformity and extensive skin loss, which would prevent closure of the defect. The specifi c problems are as follows:

1. children with high lesions (thoracic and thoraco-lumbar), signifi cant hydrocephalus at birth, major kyphosis or other signifi cant problems (either congenital or acquired) have a signifi cantly



623

increased mortality in early life and substantial morbidity if they survive. In these circumstances, in discussion with the family, supportive care only may be recommended. If the infant survives the perinatal period, elective surgical care may be indicated. In the absence of such adverse factors, in discussion with the family, early surgical repair/removal of the lesion usually is recommended.

2. careful serial evaluation of head circumference and ventricular size by ultrasound or CT scan will indicate if hydrocephalus is developing. Once it is established that progressive hydrocephalus is present, a shunt procedure is recommended.

3. baseline orthopaedic, urology and neurosurgery assessments provide the basis for ongoing discus-sions with the family and management of the con-dition. Occasionally, active urological intervention is required for urinary retention.

4. it is critical to begin to establish an empathetic, therapeutic relationship with the parents in the newborn period that forms the foundation for ongoing support throughout childhood.

Ongoing management issues

Management of physical disability and mobility

Physiotherapists play an essential role in reducing deformities and encouraging mobility. Foot deformi-ties are common at birth as a result of unopposed muscular activity in utero. Splinting and passive stretching are the mainstays of treatment in early life. Persistent foot deformities may require correc-tive orthopaedic surgery. Surgery also may be needed for dislocated hips, particularly if the child is likely to walk. At times, three-dimensional gait analysis (3DGA) is benefi cial for surgical decision making and can assist in planning for this intervention.

The outlook for walking depends on the level of the spinal cord lesion, intelligence and motivation. Most children with a lesion at L4 or lower will walk, with or without splints and crutches. Children with higher lesions may walk with orthotics in early child-hood but most will choose wheelchair mobility by mid to late childhood.

Spinal deformities

A signifi cant percentage of children will develop sco-liosis and many of these will require spinal instru-mentation. Spinal jackets are not well tolerated and have a very limited role in the management of para-lytic scoliosis.

Neuropathic fracture

Fractures of the lower limbs, due to osteopenia, are common in children with myelomeningocele. Frac-tures may occur with minimal trauma. Encouraging children to walk, or stand in a standing frame on a regular basis may improve the mineralization of long bones and lessen the likelihood of further fractures. However, nutrition, calcium and vitamin D from sunlight may also be important factors in management.

Sensory defi cit and skin care

Pressure ulcers or burns in anaesthetic areas are common. Parents are encouraged to check anaes-thetic areas daily for the presence of pressure sores. Early recognition and treatment is essential to prevent long periods of morbidity and hospitalization.

Neuropathic bladder

Almost all children with myelomeningocele have a neuropathic bladder. Failure to empty the bladder may lead to recurrent urinary tract infections, vesi-

Cerebrospinalfluid

Nerveroot

Transverse section

Bone

Centralcanal

Longitudinal section

Spinalcord

Pia andarachnoid

Skin anddura

Fig. 17.4.7 Meningocele: diagrammatic representation.



624

coureteric refl ux, renal calculi and hydronephrosis. Hypertension and renal failure may be seen in a small number of cases. Management of the neuro-pathic bladder is by clean intermittent catheteriza-tion performed four or fi ve times daily by the parents, and later by the child. This is usually commenced at around 3–4 years of age, or earlier if repeated urinary infections occur. Prophylactic antibiotics may be required for recurrent urinary infections. Bladder augmentation and/or artifi cial sphincter operations may be indicated if the clinical situation dictates. The use of anticholinergic medications and of oxy-butynin to increase bladder capacity may be tried. Regular assessment of renal function is essential throughout the person’s life.

Neuropathic bowel

Most children have limited or absent rectal sensation and have little or no bowel control. Constipation with megacolon, faecal impaction and overfl ow incontinence is the major risk in spina bifi da. Faecal softeners may be needed in infancy. Some children can attain continence simply by regular toileting, while others may need high-fi bre diets, faecal soften-ers, suppositories or microenemas. Aperients are avoided whenever possible. Refractory cases may require regular bowel washouts.

Sexual function

Many people with spina bifi da achieve a satisfactory sexual relationship. In females, pregnancy has been achieved in many individuals and is generally a posi-tive experience. Predictably, there are a number of potential diffi culties with pregnancy and confi ne-ment. Urinary tract infections, worsening pressure sores and spinal problems are particularly common. In males, the situation is more complex. Diffi culties range from impotence to retrograde ejaculation and infertility. Sexual counselling is important in adolescence.

Tethered spinal cord

Following repair of a myelomeningocele, the lower end of the spinal cord may become tethered to the site of repair. As the child grows, this may cause progressive neurological deterioration in motor or sensory function, or in bladder control. Regular monitoring of the neurological state is essential par-ticularly during the rapidly growing phase. MRI scans are performed to demonstrate the tethering process. If the neurological deterioration is signifi -cant, consideration should be given to neurosurgical release of the tethered cord.

Arnold–Chiari malformation

This has been described earlier (Fig. 17.4.3). It is present in a signifi cant number of children with myelomeningocele and is elegantly demonstrated by MRI scan. Symptoms are variable: they may be quite minor, e.g. strabismus or mild diffi culties with chewing and swallowing, or they may be severe, with laryngeal stridor and apnoeic spells. Life-threatening episodes may necessitate neurosurgical intervention to decompress the posterior fossa.

Education

Children with myelomeningocele often have specifi c learning problems, requiring assistance at school. Overall intelligence is generally in the low average range, with a wide range of abilities. Verbal IQ is usually considerably higher than performance IQ, and many children have apparently very good expres-sive language but with a paucity of meaning and content of speech (often referred to as ‘cocktail party syndrome’). Diffi culties with mathematical concepts are very common, as are problems with abstract reasoning. Many children have a poor attention span, with distractibility. Problems with fi ne motor control and visual perceptual diffi culties are frequ-ently present. Most children with spina bifi da attend normal schools, with varying levels of assistance for physical and cognitive/learning diffi culties from support teachers. Schools may require modifi cation to provide access and suitable toilet arrangements.

Social and emotional adjustment and transition to adulthood

A child with a chronic disability places severe strains on the emotional and fi nancial resources of a family. Members of the team must be alert to signs of dis-tress and be ready to provide the necessary support. During the teenage years, the usual problems of adolescence are superimposed on the diffi culties associated with the disability, and these young people need sensitive counselling. For the families, parent groups provide valuable practical and emotional support.

There are now increasing numbers of young adults with spina bifi da. A coordinated approach to man-agement is still desirable but more diffi cult to attain, because of the wish of the young people to be inde-pendent and to break away from what they perceive as overprotection by the medical fraternity. Never-theless, problems continue to occur, particularly pressure ulcers, shunt and urinary complications. In South Australia, the Spina Bifi da and Hydrocepha-lus Association employs community nurses, who maintain close contact with all the adults with spina



625

bifi da and refer problems to appropriate agencies. This service has been invaluable in maintaining physical and emotional wellbeing and ongoing health education, and has helped to avoid hospital admis-sions among the group.

Prevention of neural tube defects

Neural tube defects (spina bifi da, anencephaly and encephalocele) result from defective closure of the neural tube in early pregnancy. The human neural tube closes just before the 30th day post-fertilization and thus any infl uence affecting the closure of the neural tube must be present before this early stage of pregnancy. Primary prevention of this group of con-ditions may now be feasible. Research has suggested a relationship between maternal diet and the birth of an affected infant. Medical evidence has confi rmed that folic acid (a water-soluble vitamin found in many fruits, leafy green vegetables, wholegrain breads, cereals and legumes) may prevent the major-ity of neural tube defects.

A randomized controlled clinical trial carried out by the Medical Research Council of the UK demon-strated a 72% reduction in risk of recurrence by peri-conceptional (i.e. before and after conception) folic acid supplementation of 4 mg daily. Other epidemio-logical research, including work done in Australia, suggests that primary occurrences of neural tube defect births may also be prevented by folic acid, either as a supplement or in the diet, and this has been confi rmed in a randomized controlled trial from Hungary, which found that a daily multivita-min supplement containing 0.8 mg folic acid was effective in reducing the occurrence of neural tube defects in fi rst births.

The National Health and Medical Research Council of Australia has recommended the following

• All women planning a pregnancy or likely to become pregnant should be offered advice about folate in the diet and encouraged to increase their dietary intake of folate-rich foods, particularly in the month before and in the fi rst 3 months of pregnancyIn addition:• Low-risk women (no family history of neural tube defects, not on anticonvulsants) should be offered periconceptional folic acid supplementation (0.5 mg daily). Generally, periconceptional supplementation with other vitamins is not necessary. When supple-ments are used, the potential risks of vitamin over-dose should be considered. In particular, large therapeutic doses of vitamin A may predispose to birth defects

• Women with a close family history of neural tube defects (e.g. they or their partner has spina bifi da, they have already had an affected child, they have a sibling or other close relative with a neural tube defect): • should be referred for genetic counselling • should be advised to take periconceptional folic

acid supplementation 5 mg daily (the 4 mg formu-lation is not available in Australia)

• should continue to be offered prenatal diagnosis with alpha-fetoprotein estimation and tertiary level ultrasound, by an operator experienced in anatomical scans, at 16–18 weeks gestation. Although the risk of recurrence is reduced signifi -cantly if folic acid supplementation is used appro-priately, there is a residual risk of about 1% in women taking supplements who have had a previ-ously affected infant

• Women on anticonvulsant drugs should take folic acid supplementation only under the supervision of and with close monitoring by their physician • because of the increased risk of neural tube

defects in the offspring of women taking some anticonvulsants (notably sodium valproate), these women also should be counselled and offered pre-natal diagnosis

Fortifi cation of staple foods with folic acid• Fortifi cation of staple foods, such as bread and cereals, with folic acid should be introduced in Aus-tralia. After mandatory wheat fl our fortifi cations in the US, there has been a 30% reduction of neural defects, with 1000 fewer cases every year. Each case of spina bifi da prevented saves an estimated US$ 500 000 in lifetime costs. In Canada and Chile substantially further reductions (50% and 70% respectively) have been proven with even higher amounts of folic acid added to fl our than in the US. More than 40 countries around the world have now made it mandatory.

Folic acid fortifi cation of fl our is cheap, less than 0.1% of the cost of fl our.

Education, research and monitoring• There should be education programmes, for health professionals and the public, on how to achieve ade-quate folate intake with diet and supplementation to prevent neural tube defects• There should be continued research into the mech-anisms of action of folic acid and the minimum dose of folic acid required for prevention• Close monitoring of both the prevalence of neural tube defects (including terminations of pregnancy) and the increase in folate intake should be under-taken to evaluate the effectiveness of any health pro-motion campaigns



626

• Further research should be monitored, and these recommendations reviewed in the light of any developments.

In Australia, health promotion campaigns have been undertaken to inform health professionals and women about folate and the prevention of neural tube defects. For example, folic acid (folate) in fruit and vegetables is easily destroyed by cooking and prolonged storage. It is wise to eat fruit and

vegetables that are fresh and either raw or lightly cooked. For good health and enough folate per day, one would need to aim for at least two servings of fruit, fi ve servings of vegetables and seven servings of bread and cereals every day. The safety of increased folate ingestion before and during early pregnancy appears to be confi rmed. Furthermore, an intake of folate from fortifi ed food is unlikely to be high enough to constitute a hazard for those people with untreated vitamin B12 defi ciency.



Headache occurs in most children at some time. In a number of these, frequent headaches are a dis-abling problem. In one study in primary schools in Australia, 23% of parents believed that their children suffered from ‘frequent headaches’.

Many processes result in headache. These will be considered in two major classes: ‘cranial’ headaches, where the cause of pain is a process directly involving the brain and associated structures, including menin-ges, cerebral blood vessels and scalp; and ‘extracra-nial’ headaches, where the primary cause is remote from the brain.

The actual mechanisms of headache are multiple but it should be recognized that the brain itself is insensitive to pain. Some neurosurgical operations for intractable epilepsy are actually performed on the brain with the patient awake.

Structures that are sensitive to pain include:

• blood vessels• meninges• cranial nerves 5, 7, 9 and 10.

Pain is also generated from integumentary struc-tures surrounding the skull, including:

• skin• muscle• periosteum• blood vessels.

This chapter will deal particularly with recurrent or chronic headaches and not with those that accom-pany acute events such as trauma, intracranial bleeds or infections of the nervous system.

Cranial causesMigraine and stress or tension types are the most common of chronic or recurrent headaches with origins in and around the brain. The migraine subset is numerically the biggest in Australian children. Stress and tension components often interact with a predisposition to migraine. Pure stress and tension headaches are less common than in adults. Often headaches in children that are classifi ed as ‘stress’ or ‘tension’ start out as migraine headaches but, as a consequence of recurrent pain, disability and fear

of the next headache, develop strong features suggesting that stress or tension is the primary cause.

Of the different headache types in children, migraine, because of its great prevalence and associ-ated morbidity, will receive most attention in this discussion.

Migraine

Epidemiological features

Migraine is:

• the commonest cause of recurrent headaches• increasing prevalence. In a 1974 Finnish study

using rigid criteria, 1.9% of children suffered from migraine headaches. In 1992 the study was repeated with the same criteria and the prevalence had increased to 5.7%. Other studies suggest up to 10% incidence

• leading cause of referrals to a child neurologist• more common in males before puberty but in

females after puberty

Clinical manifestations

Childhood migraines result from the same biological process as those in adults but clinical manifestations may be quite different. Some of these differences relate to the diffi culty a child has in describing or explaining the features; for example, young children may not be able to describe throbbing, or lateraliza-tion, or sensory associations. Nevertheless, there are some features, such as dizziness and vomiting, that are clearly more common in children.

‘Classical’ migraine (which is a relatively uncom-mon type of migraine even in adults) includes aura, or transitory neurological dysfunction, especially of the visual system, and may involve sophisticated hal-lucinations such as fortifi cation spectra, which often precede the onset of headache and then disappear as the headache commences. This classic sequence may occur in older children and adolescents but often instead there is a description of sensory hallucina-tion that occurs with, or during, the headache. This may be a visual disturbance described in unsophis-ticated terms, such as ‘fl ashing lights’, ‘seeing things double’ or ‘blurry, like looking through a curtain’, or

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17.5Children with headachesI. Wilkinson


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something more complex and bizarre-sounding and often very frightening. Such hallucinations include the appearance that objects are too big or too small, or that things moving in the environment appear to be going too fast or too slow. It is suggested that Lewis Carroll drew on personal migraine experi-ences when describing Alice’s distorted body percep-tion after she ate the magic substance.

Such hallucinations can involve the auditory process, e.g. things sounding too loud or someone speaking too fast. At times, the aura for a child defi es description but may involve a sense of unreality or depersonalization.

What can make the migraine process more diffi -cult to unravel in a child is the not uncommon situation where the actual sensory hallucination is not accompanied (during that event) by a headache. This is referred to as migraine dissociée and there is frequently more alarm and distress for a child or parent than when there is an accompanying headache.

Other variations from adult migraine involve the location of the pain. Whereas in adult migraine attacks the pain can often be lateralized (a true ‘hemi-crania’ – one origin of the word migraine), this is fre-quently not the case in young children, who will simply point to their forehead (without lateraliza-tion) as being the location. As the child grows older a description of pain that is unilateral and sometimes located in one or other temple becomes more common. The pain is more often in the frontal half of the head and pain that is only located posteriorly raises the possibility of more sinister causes of headache.

A description of the quality of the pain in migraine in children is often diffi cult for them. The pain tends to more of an aching type ‘like a tummy ache’ rather than sharp ‘like a needle’. A combination of the two may be described. Further, in adults with pure migraine attacks it is frequent for the pain to be described as throbbing, implying involvement of vas-cular structures. Children with migraine may well experience throbbing pain but may not be able to describe it as such, although, as the child becomes older, he or she may describe it as ‘beating like a drum’ or ‘like a hammer’.

Although many adults do not acknowledge head-aches as being migraine unless they are severe and resulting in cessation of usual activities, in children there can be a great range in the severity of migraine events, from the situation where the child is able to continue in school or at play, to the level where all activity must cease and the child retreats to bed in misery.

Adults with migraine attacks may not change greatly in external appearance but children are often extremely pale.

Nausea and vomiting may occur in association with adult migraine and not uncommonly continue throughout and exacerbate the headache, resulting in treatment with an antiemetic. During the attack, abdominal pain, nausea and vomiting are extremely common in children but the sequence may be that a single vomit, often followed by a sleep, seems to ter-minate the attack.

Formulating rigid diagnostic criteria for child-hood migraine has proved very controversial and strict requirements for certain features to be present in combination before a diagnosis can be made may be counterproductive in clinical practice. In prac-tice, children with headaches with some of the previ-ously mentioned features, occurring intermittently and with symptom-free periods, who are normal to neurological examination, may be considered to suffer from migraine.

The single feature that has caused most disagree-ment between those studying children with head-aches and those studying adults is a requirement for the headache to be of a certain duration. A diagnosis of migraine had originally required, by International Headache Society criteria, a duration of at least 4 hours. Eventually it was conceded that childhood migraine attacks may last as little as 1 hour.

Classic teaching about headaches due to tumours and other situations of raised intracranial pressure has been that they are present upon awakening, or actively cause the patient to waken. Although in reality this is not always the case, a contrast remains with childhood migraine, where the onset is more commonly later in the day, perhaps approaching midday or during the afternoon or evening.

Childhood migraine is a very cyclical condition. Patients may have a bout of recurrent headaches that lasts weeks or months, followed by a period of remission that may last a year or more, to be followed by another bout. Hot weather may be a factor in relapses.

Types of migraine

In the International Headache Society classifi cation (2004) there are six categories and 17 subcategories of migraine. Precise classifi cation is necessary in migraine research but is not always so important in clinical diagnosis and management, and there is often overlap between different types in children. To categorize according to the presence or absence of ‘aura’ in children can be very diffi cult. The ‘aura’, in children who can describe it, may often occur during the headache and not precede it, and frequently involves some sense of disequilibrium, perhaps true vertigo. Visual auras are often basic, such as blurring or double vision, and unsophisticated.



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There are some conditions that are considered to be part of the migraine phenomenon, although appearing to have little relationship with adult migraine types:

• in early childhood, usually before the age of 5 years, some may experience recurrent episodes with sudden onset of true vertigo. These are extremely distressing and cause the child to seek a cuddle, or lie on the ground to relieve the feeling of spinning. These events last a few minutes, sometimes hours, and may be associated with pallor, nausea and vom-iting. In some studies up to 80% of these children who are described as having benign paroxysmal vertigo subsequently develop migraine headaches

• unexplained attacks of vomiting, without associ-ated headache, may also be precursors of migraine. These attacks can be very puzzling diagnostically and often very debilitating, possibly recurring after a predictable interval and sometimes requir-ing intravenous fl uids and hospitalization. With the passage of time, headaches may become more of a feature of these attacks, which are labelled cyclical vomiting

• recurring episodes of unexplained abdominal pain defying diagnosis despite multiple investigations can also be very debilitating. There may be a family history of migraine and as time goes by the child’s abdominal pain may become associated with and eventually replaced by migraine headaches.

The most recent International Headache Society Classifi cation (2004) now includes a section ‘Child-hood periodic syndromes that are common precur-sors of migraine’, incorporating (1) cyclical vomiting, (2) abdominal migraine and (3) benign paroxysmal vertigo.

In infancy, paroxysmal torticollis, where the head becomes tilted strongly to one or either side for periods of hours or days, may be a precursor of migraine, although simultaneous headache may not be apparent. A similar process involving the trunk has been described. These infants have been demon-strated to be at greater risk of later developing migraine headaches.

Hemiplegic migraine may present with unilateral weakness, or unilateral sensory disturbance, and this often precedes the actual headache.

Expressive or receptive language diffi culties also may be a presenting feature of some attacks, with the headache not occurring till an hour or so later.

In acute confusional migraine the patient is quite disoriented and distressed, with short-term memory loss. This condition raises concerns about more sin-ister neurological processes, or drug intoxication, perhaps leading to invasive investigations. Again, the headache may not become apparent until later.

Aetiology

The basic mechanisms causing migraine in adults have been investigated extensively and there has been controversy, contradiction and revision of theo-ries as to causation. It is beyond the scope of this text to detail all the theories, but historically the two main schools have postulated either:

• an initial central process involving neuronal pathways or

• a peripheral process involving blood vessels.

Current thinking suggests a very complex multifac-torial mechanism, perhaps centred on the brain stem, where there is sensitization of nociceptor sites and central pain facilitation and receipt of various trigger inputs. There is also sensitivity of the cerebral cortex, leading to auras, and neurogenic infl amma-tion and dilatation of blood vessels in pain-sensitive structures.

At a chemical level both noradrenergic and sero-tonergic transmitter pathways are implicated, and this has relevance for drug therapy.

Genetic factors play a major role in childhood migraine. As many as 90% of children with migraine have a fi rst-degree relative with the condition. In some types, such as hemiplegic migraine, genetic loci have been found on particular chromosomes. In more common types of migraine it has been vari-ously proposed that inheritance may be autosomal dominant, recessive, sex-linked or polygenic.

Given that some children are at risk genetically of developing migraine, it is clear that there may be provoking factors for individual attacks. These include head injuries, not necessarily severe ones. The head injury may be the commencing point for recurrent bouts of migraine headache, and this may have legal ramifi cations. Other provoking factors are:

• intercurrent systemic infections, particularly with fever

• strenuous physical exercise• hot weather• dehydration• worry and stress, either domestic, social or

educational in origin. While these factors remain, they may greatly complicate treatment. The distinction from ‘stress’ or ‘tension’ headaches without an underlying migraine basis may be very diffi cult

• foodstuffs. This is a very controversial area, with evidence for and against. Citrus fruit, cheese, chocolate and processed meat have been implicated

• food additives, such as monosodium glutamate, sodium nitrite, benzoic acid, tartrazine.

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Treatment

Treatment can be divided into the following tiers:

• avoidance of triggers• non-specifi c analgesia for attacks• specifi c antimigraine medication for attacks• prophylactic medication• non-medication treatments.

Avoiding specifi c triggers in childhood migraine can be diffi cult. In many they do not exist. In Australia, hot weather and exercise are common precipitants that are part of a normal childhood lifestyle. Ensur-ing adequate hydration in the above situations may be helpful.

The role of restrictive diets is controversial. If it is evident that certain foodstuffs or drinks regularly provoke attacks then they should be avoided. Placing children on very limited diets is not only unpleasant and diffi cult to enforce but may even have nutritional consequences.

The use of non-specifi c analgesics in attacks is the simplest means of treatment. The most commonly used is paracetamol, best given in an initial dose of 20 mg/kg. Unfortunately, children may not seek medication, or as a result of being at school may not be able to access medication, until the attack is advanced. The paracetamol may not be effective at this time, or may be vomited. There may be a role for rectal paracetamol in this latter situation.

A recent study has indicated that ibuprofen in a dose of 10 mg/kg may be more effective then paracetamol. Other non-steroidal anti-infl ammatory drugs (NSAIDs) may be helpful.

In recent years aspirin has been avoided in child-hood because of concerns about its relationship with Reye syndrome, a rare but severe acute encephalopa-thy with potentially fatal outcome. Nevertheless, aspirin in doses of 15 mg/kg may be employed in older children with recurrent headaches.

The use of codeine and powerful narcotics in child-hood headache is not usually necessary and is poten-tially hazardous, although restricted infrequent use of combinations of paracetamol and codeine in older children may be necessary and effective.

Ergotamine has long been a useful antimigraine drug in adults, particularly at the beginning of the attack. Although some studies have shown effi cacy of oral dihydroergotamine in children, ergotamines have had limited use because children often delay seeking treatment and also because they may pro-duce side effects such as vomiting and abdominal discomfort.

Triptans are a new generation of serotonin-active drugs that abort migraine attacks. There have now been controlled trials in children supporting their use, but triptans have not yet been accepted for childhood use in some countries. Nasal sumatriptan

has been shown to be effective but administration by the oral route has not been successful. Subcutaneous sumatriptan may be effective but is unpleasant to administer. Other triptans have generally not been proved to be effective.

Prophylactic medications may be considered for frequent disabling attacks. What constitutes ‘fre-quent’ is arbitrary but more than two severe attacks per month may justify treatment. Controlled trials of prophylaxis in childhood migraine are confounded by the cyclical nature of childhood migraine and the tendency to remit spontaneously, as well as the high placebo response rate.

A 2004 Cochrane data base study confi rmed the paucity of evidence for successful treatment of child-hood migraine and concluded that only one study each for propranolol and fl unarizine was identifi ed showing effi cacy as prophylaxis for paediatric migraine. Nevertheless, the following medications are commonly used in clinical practice:

• cyproheptadine, an antihistamine with serotonin-blocking and calcium-channel-blocking properties. Side effects include drowsiness (which may be mini-mized with a single night-time dose regimen) and increased appetite. Effective doses range from 0.1–0.3 mg/kg per day, given either once or twice daily

• propranolol, a beta-adrenergic blocking drug, also blocks release of serotonin from platelets. It is con-traindicated in asthma. Doses range from 0.5–2.0 mg/kg per day in two or three equal doses. Propranolol and similar drugs have been proven in adults but trials in children have produced confl ict-ing results

• pizotifen, with antiserotonin and antihistamine properties, has side effects of increased appetite, weight gain and drowsiness. The latter may be avoided by a single night-time dose. Doses are limited by the single-size pill format (0.5 mg) but range from one to three at night

• fl unarizine, a calcium-channel blocker, has been widely used in children in Europe but has restricted availability in Australia

• clonidine, a vasoactive drug, has been trialled in a range of conditions in children but lacks good evi-dence for use in migraine and has signifi cant poten-tial side effects

• amitriptyline, originally marketed as an antide-pressant, has been used for migraine prophylaxis in children. It may be particularly useful where there are stress and depressive features, but care must be taken to avoid provoking cardiac arrhythmias.

Because of the high remission rates in children, pro-phylactic medications should not be used continu-ously for more than 6 months without attempting to wean patients from them.



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Not surprisingly, given that there has been a swing towards accepting primary brain-stem and other neu-rological mechanisms as a major mechanism in the aetiology of migraine, anticonvulsant drugs are now being employed in prophylaxis. Studies of valproate, lamotrigine topiramate, gabapentin and levetirace-tam in adults and to a limited extent in children have been promising but at this time they have not gained approval in Australia. Ribofl avine (vitamin B2) has been shown to be effective in one study in adults, and there is a trial of this under way in Australian children.

Non-medication treatments may at times be suc-cessful but again there is a paucity of controlled trials in children. Biofeedback and relaxation tech-niques have been used, particularly in Europe and North America. Acupuncture has proved to be successful in adults but is a potentially painful pro-cedure. Homeopathic formulations are enjoying increased popularity in many conditions but lack evidence in childhood migraine. Chiropractic treat-ments are controversial, lack controlled trials and may be dangerous in young children.

Although discussion in this section has focused on migraine, the non-specifi c medications and treat-ments cited may be useful in all headache types.

Prognosis

Childhood migraine is often cyclical, with bad bouts followed by prolonged remissions, sometimes fol-lowed by relapses in later childhood or adult life. Various studies have indicated an overall 30–40% 10-year remission rate. It is not uncommon when taking a family history to fi nd that parents, when pressed, remember childhood migraines long since in remission. Similarly, in apparent adult-onset migraine, a long forgotten history of severe child-hood headaches may eventually be recalled.

Other children, like adults, will have a history of infrequent migraines throughout their developing years.

Stress and tension headaches

There is a broad spectrum of headache types in some way associated with emotional factors, perhaps more frequently seen in older children and adoles-cents. At one end is a small group where the symp-toms of headaches may be used in a conscious and malingering way to avoid a situation. Examples include:

• the child who consistently develops a severe headache on a Monday morning in a setting of school diffi culties

• the child who develops a severe headache when an unwelcome visit to a disliked non-custodial parent is planned.

Further along the spectrum is the situation where the child is being exposed to a great deal of stress, often multifactorial, and this apparently constitutes the sole underlying aetiological basis for headaches. High parental expectations may be major factors here. It is a reality of modern urban life that children may be involved in a demanding combination of schooling, additional tutoring, competitive sport, training in the performing arts and so on to the point where their life allows for little relaxation or personal time.

In situations such as this, a pattern of headache may develop. The nature of this headache may differ from that of migraine. In migraine the headache does not usually occur daily, and indeed daily head-aches by many defi nitions are not migraine. In addi-tion, the quality of the headache may differ; for example, they:

• may occur at all times and throughout the day• cannot be localized or described in other than

vague terms• lack an association with pallor, nausea, vomiting,

or disturbance of vision or balance.

For the clinician it may be frustratingly diffi cult to come to grips with the nature of these headaches.

Somewhere along this spectrum is the child who has a primary psychiatric disorder and in whom the symptom of headache may be part of a conversion reaction or a major psychosis.

Perhaps the more common situation is where the child with a past history of intermittent headaches sounding just like migraine, and a family history of this, experiences a crescendo effect, in which the headaches become daily, unremitting but not always severe. Although daily headaches may be indicative of a more sinister process, such as raised intracranial pressure, this is not necessarily the case. In this group where the crescendo effect is seen, it may be that the exposure to frequent pain and the expecta-tion of further severe pain results in secondary stress

Clinical example

Jason, who was 8 years old, presented in March with headaches that had occurred about twice a week for the previous 3 months,

although he had had some following soccer last winter. They commenced after lunch at school, were frontal and throbbing, and Jason looked very pale. Paracetamol sometimes helped him but often he would vomit, go to sleep and then awake without headache and eat his evening meal.

His mother had a history of migraine. Neurological examination in Jason was normal. After daily treatment with cyproheptadine for 2 weeks his headaches ceased.

The history is consistent with childhood migraine.



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and anxiety, which in turn provokes further head-aches, becoming a vicious circle.

The sequence whereby individual stress events provoke a severe migraine attack is perhaps less fre-quently seen in children than in adults, but can still occur. Sometimes it is the ‘let down’ phenomenon following a period of stress that provokes a headache.

In childhood headaches associated with emotional aetiologies there is usually no abnormality on neu-rological examination. The facial appearance can range from complete indifference through to intense anxiety.

Radiological investigations rarely contribute in any positive sense but sometimes the performance of a normal brain scan in an extremely anxious patient may be the only way to allay anxiety and enable suc-cessful treatment. On the other hand, where there is a conversion reaction it may produce a reinforcement that there really is an organic problem.

Treatment is often diffi cult. Where there appears to be an original underlying basis of migraine, treat-ment with adequate doses of analgesia, possibly NSAIDs, may be able to break the cycle. It may be prudent to commence migraine prophylaxis as well.

Where the headache appears to be further along the spectrum towards psychiatric disorders, then consultation with a child psychiatrist is strongly advised.

As mentioned earlier, the tricyclic antidepressants may have a separate specifi c analgesic effect and can be particularly useful where an element of depression is a factor. Although monoamine oxidase inhibitors can also be useful in treating migraines in adults, the use of these in children may present dangers because of dietary interactions.

Caution must be exercised in drug treatment in this group of headaches, as it is common for such patients to fi nish up on combinations of medications in large doses and they may become dependent on these medications.

Several non-pharmacological therapies may have a role. These include:

• muscle relaxation• stress avoidance• biofeedback• hypnosis• acupuncture.

These therapies are used quite widely in Europe and North America but are often resource-intensive.

Headaches due to raised intracranial pressure

The possibility of childhood headaches being caused by raised intracranial pressure, especially due to

tumours, is often a cause for great concern in the treating physician as well as the child and family. In reality, only a very small number of childhood head-aches are due to raised pressure. Even when there is pressure, the ability of the child’s skull to expand may mitigate some of the effects.

Although headaches due to raised intracranial pressure have classically been described as worse in the morning upon awakening, or causing the patient to awaken, and associated with vomiting, this is not always the case.

Raised intracranial pressure can be a result of abnormal fl uid collections, solid masses or vascular malformations. Interference with fl uid dynamics without discrete collections can result in the condi-tion of benign intracranial hypertension.

Fluid can collect abnormally either within ventri-cles, within the substance of the brain or over the surfaces:

• build up of fl uid within the ventricles is referred to as hydrocephalus (Ch. 17.4). This often presents in infancy, and the ability of the skull to expand, coupled with the inability of the child to report the pain, may be the reason that headache is not a presenting feature. In older children, the onset of hydrocephalus is often associated with a mass lesion obstructing the intracerebral cerebrospinal fl uid pathways, and this may result in major headaches

• intracranial abscesses are uncommon in children in Western society. Children with cystic fi brosis or cyanotic heart disease are at increased risk. Abscesses can develop by spread from infections of the paranasal sinuses. Headaches resulting from abscesses are often associated with systemic mani-festations such as fever, and tend to build up in severity over days or weeks

• arachnoid cysts occur in a number of different locations, often adjacent to the surface of the brain. They result from fl uid collecting within a split arachnoid membrane and may be asymptomatic, but can produce headaches

• fl uid, including blood, can collect in the subdural or extradural spaces, often as a result of trauma. Accompanying headaches are often crescendo in frequency and severity, and may be associated with focal signs

• headaches due to tumours are most often due to mass effect, or obstruction of cerebrospinal fl uid pathways, and are less likely to be due to direct local involvement of pain-sensitive structures. Intracra-nial tumours in children are usually primary and are most frequently found in the posterior fossa, where they readily obstruct fl uid pathways. It is not uncommon that there is a substantial delay in detec-tion of the tumour in such headaches



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• aneurysms are uncommon in children but arterio-venous malformations or cavernous angiomas are found at this age. These may produce headache due to their size or obstruction of fl uid pathways.

The signs associated with raised pressure often involve the eyes.

Papilloedema may take days to develop, even in the presence of grossly elevated pressure. Abnor-malities of ocular movements, particularly failure of abduction with resultant paralytic convergent stra-bismus, or failure of upward gaze, can occur. Slug-gish pupillary light refl exes may be found. Deep tendon refl exes are often brisk. There may be neck stiffness. Bradycardia and systemic hypertension are later effects.

Treatment of such headaches usually involves sur-gical approaches, either directly to the mass or to drain fl uid from the ventricles or brain surface via a shunt. Oedema surrounding a mass may be treated with corticosteroids or osmotic diuretics, but these are temporary measures only.

Benign intracranial hypertension

This condition, also known as ‘pseudotumour cerebri’ because the clinical feature can mimic a tumour, occurs in children and adults. It results from a build-up in intracranial pressure, without a space occupying lesion, probably due to an imbalance between production and resorption of cerebrospinal fl uid. It is potentially serious as it can eventually result in visual loss. There is often an association with adolescent females, who may be overweight but otherwise apparently healthy. This may have a hor-monal basis.

Other proposed causes in individual cases include:

• recurrent middle ear infections, sometimes associated with mastoiditis, where the draining cerebral venous sinuses near the ear become obstructed

• head trauma• oral contraceptives• the use or withdrawal of corticosteroids• excessive amounts of vitamin A• tetracyclines• growth hormone treatment.

In some cases a specifi c cause is not found and the entity of ‘benign intracranial hypertension’ should probably be divided into idiopathic and symptom-atic categories.

The clinical features include:

• headache, which tends to be daily, often worse in the morning but not necessarily severe

• abnormalities of the eyes, most commonly papilloedema (which may be asymptomatic) and lateral rectus palsies due to pressure on the abducens nerves

• nausea and vomiting• raised pressure at lumbar puncture, to fi gures of

20–40 cmH2O or more• normal laboratory fi ndings in cerebrospinal fl uid.

In the presence of papilloedema or other eye signs it is prudent to perform a structural study (computed tomography (CT) or magnetic resonance imaging (MRI)) before performing the lumbar puncture. A magnetic resonance venogram may be helpful in demonstrating obstructed venous sinuses.

Cerebral images are usually otherwise quite normal, without a space-occupying lesion or dilata-tion of the ventricles. Even in the presence of a normal scan, it is reasonable to examine the cerebro-spinal fl uid for malignant cells, as in rare cases undifferentiated tumours can present with raised intracranial pressure in the presence of apparently normal scans.

Treatment is varied but includes:

• repeated lumbar punctures to remove fl uid; this is quite traumatic and not always effective

• acetazolamide, which potentially reduces production of cerebrospinal fl uid by interfering with the carbonic anhydrase enzymes, or more powerful diuretics, such as furosemide, if acetazolamide fails

• steroids• shunting procedures to remove fl uid from the

cranial cavity; these should be reserved for drug-resistant cases

Clinical example

Lisa, 14 years old, developed daily headaches. These were often present by the time she had breakfast and were distressing, but she could

get to school most days. The pain continued throughout the day and was all over her head. She had noticed some visual diffi culty. The problem started after she was placed on an oral contraceptive for dysmenorrhoea.

On examination, Lisa was obese. There was papilloedema but no other neurological abnormality. Her blood pressure was normal. Cranial tomography was normal and a lumbar puncture resulted in the fl uid pressure rising out of the top of the tube. The fl uid was normal in the laboratory.

Lisa responded to cessation of the contraceptive and treatment with 250 mg acetazolamide each morning.

The history is consistent with benign intracranial hypertension.



634

• decompression procedures on the optic nerves• anticoagulation if there are thrombosed draining

venous sinuses.

Patients must be seen by an ophthalmologist, to monitor visual function, as prolonged papilloedema can lead to optic nerve damage.

The prognosis for benign intracranial hyperten-sion is generally good. The process, particularly where no underlying cause is demonstrated, often remits spontaneously.

Seizure-related headaches

In adults, severe headaches are common following a major seizure. In young children, postictal head-aches tend to be less debilitating. Children may describe a headache during an actual epileptic event, while conscious. This is often associated with focal discharges, possibly from the temporal lobe, and may be only a brief event, not always associated with other clinical features. Electrical discharges in the occipital region may give visual hallucinations, vom-iting and headaches not always associated with motor convulsions. This condition may be familial and often diffi cult to diagnose.

Extracranial causesHeadache is a frequent associate of systemic illness, without there being a primary pathological process in the nervous system:

• the most frequent association is with systemic febrile illnesses not directly involving the nervous system

• connective tissue disease, especially ‘mixed con-nective tissue disease’, may lead to vascular-type headaches

• systemic hypertension is much less common in children, and hypertensive encephalopathy is not seen frequently. Nevertheless, in persistent severe hypertension in children a major encephalopathy may develop, with headache, seizures and altered consciousness. Acute glomerulonephritis may pre-sent in this way

• metabolic pathway disturbances such as urea cycle defects can produce headaches, especially during biochemical decompensation

• hypoglycaemia is a potent trigger for migraine but can also result in non-specifi c headaches and may be a result of poor diabetic control

• hunger without demonstrable hypoglycaemia may also provoke headaches

• although controversial, allergic disorders may be associated with migraines and other headaches

• obstructive sleep apnoea and other sleep disorders may produce a clinical picture of daytime head-aches and somnolence.

In these situations treatment of the underlying cause is preferable to symptomatic relief.

Overrated causes of childhood headachesChildren with recurrent headaches are frequently initially referred to optometrists or ophthal-mologists. The basis for these headaches is often migraine.

Glaucoma (rarely seen in children) and iritis may product aching in and around the orbit. Convergence insuffi ciency and other ocular muscle imbalances are common fi ndings in children. Headaches may be attributed to these problems but the evidence is not convincing.

Minor refractive errors detected on examination, but with doubtful clinical relevance, may be blamed incorrectly as a cause of childhood headache. Spec-tacles or ocular movement exercises may result in apparent temporary relief of the headaches, but not infrequently they return.

Acute sinusitis is a potential cause of headache in children, often associated with other features such as fever, purulent nasal or postnasal discharge, local tenderness and puffi ness around the eyes. The pain can be widespread in the skull and the location can be confusing. This is a potentially dangerous condi-tion, occasionally leading to intracranial abscesses.

More frequently seen is the situation where recur-rent frontal migraine headaches are attributed to chronic sinusitis and referral for a radiographic series is the fi rst investigation. These are frequently negative. With the increasing availability of CT and MRI performed for other reasons, it is not uncom-mon that asymptomatic fl uid collections are dete-cted in paranasal sinuses, usually with no clinical consequences.

The frontal and other sinuses are not formed in early childhood and may be not be capable of har-bouring infections until the end of the fi rst decade.

Headaches found in adults but not children• Giant cell or temporal arteritis is a potentially serious cause of headaches in the elderly and can lead to visual impairment or cerebrovascular accidents if not treated. Fortunately, it is not a condition of childhood



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• Acute angle closure glaucoma is another cause of pain in the ocular region. It is uncommon for this to occur in isolation in childhood• Cluster headaches are a condition of adult life and can result in some of the most severe headaches known. They can be very resistant to treatment. Although there are isolated reports, they are fortu-nately rarely seen in childhood• Headaches due to arthritic changes in the neck, often chronic disabling headaches, generally relate to long-standing degenerative processes and are not common in children

InvestigationsChildhood headaches are frequently overinvesti-gated. In general, blood investigations have little

yield. Plain radiographs of the skull may demon-strate signs of chronically raised pressure, or sinus-itis, but are of little use in most situations.

CT is necessary only rarely but is most useful in hydrocephalus, other fl uid collections and tumours, although it is not ideal for visualization of the middle or posterior fossae and is associated with signifi cant radiation exposure and risk of subsequent malig-nancy. MRI is more likely to detect tumours and masses, particularly in the middle and posterior fossa. Magnetic resonance arteriography or venog-raphy is quite sensitive for detecting vascular abnormalities and is relatively non-invasive. Lumbar puncture is the diagnostic test for benign intracra-nial hypertension.

Specialist consultation is frequently more rewarding and less expensive then laboratory investigation.




Documents

SEIZURE DISORDERS AND DISORDERS OF THE NERVOUS SYSTEM · sion or ﬁ rst epileptic seizure. Seizures of some type occur in up to 5% of children but fortunately most are single episodes