Updated Xviii Neurology

8/8/2019 Updated Xviii Neurology

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XVIII. Neurologic disorders IOS: Done PIR: To do PREP: Done somewhere

A. Signs and symptoms of neurologic dysfunction1. Headache: Ddx: Viral Infxn, Migraine, Neoplasm

Recognize the physical characteristics of a headache due to increase intracranial pressure-2007:22

Know the elements of history that characterize a migraine 2007;28:43

Be aware of neurologic defects that can be associated with a migraine 2007:22

Know the elements of history that characterize a headache due to stress/tension/emotion- 2009:

Know that a headache can be caused by depression 2009:51

Red flags for inc ICP: worsening pain at night or immediately upon awakening, vomiting, worsening pain withcoughing or straining, Papilledema, focal neurologic findings

Migraine headaches are periodic, may have an aura, are relieved by sleep, FH often +Complicated migraines can be accompanied by focal neurologic deficits such as hemiparesis, cranial nerve palsiesand visual/oculomotor or sensory disturbances, or dysphasia.

Migraine without aura: frontal or temporal intense headache, lasts from 1-48 hr, assoc. w. nausea, vomiting,

photophobia, phonophobia; cause avoidance of routine phys activity. .60-85% all migraines are w/o aura.

Pain from stress-related or tension headache generally is diffuse and may be described as "bandlike" or throbbing.Pain usually occurs on most days, and school absence is frequent.

Family stressors and depression are causes of headache. Children who have frequent headaches have inc rx forimpairment in academic and social functioning. Nonpharmacologic therapies, such as rest, relaxation techniques, aremoval of stress from the environment, can be effective once the stress is identified.

Know the elements of history that characterize a headache due to increased intracranial pressur2006:183

Know the signs and symptoms of a headache that indicate a need for follow-up with magneticresponse imaging or CT scan- 2006:7- Recent onset of severe headache, Change in type of h/a,Neurologic dysfunction- Focal findings, Inc. ICP, Altered MSE, Coexistence of Seizures

Know the values and limitations of ancillary neurodiagnostic tests in the evaluation of a headach2006:7

Plan the abortive treatment of an acute migraine 2007;28:43 2007:38NSAIDs, Sumatriptan, Amitryptiline, Ergot. Get good sleep, hydration, Avoid triggers (caffeine, citruschocolate, cheese)Preventive Meds: Topamax, Valproate, Gabapentin, Amitryptiline, NSAID, Verapamil, Propranolol

Plan the treatment of a headache due to stress/tension/emotion 2007;28:43 2007:38

Recognize the potential complications of using narcotics, sedatives, and nonsteroidal anti-inflammatory drugs to treat a chronic or recurrent headache 2006:38

Complications: Analgesic Overuse Headache: >5times/wk use Meds. MCC ASA, Ibuprofen, Tylenol.


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2. Altered level of consciousness

Know to measure ammonia concentration andorganic acidconcentrations in neonatal coma-2007:211

Know the common causes of an altered level of consciousness 2006;27:331 2009:217

Causes of Altered MSE: AEIOU TIPSA - alcohol, anoxia E epilepsy I - insulin (diabetes), ingestions O - overdoseU - uremia, underdose T- trauma I infection P psychiatric S - stroke(cardiovascular)

Clonidine overdose- neurologic dry muc memb, pupil constrict, and respiratory depression, hypotonia,bradycardia, hypotension, and cardiac arrhythmias. Treatment is supportive- place in ICU, ECG.

A sudden onsetover minutes in a previously healthy individual suggests trauma or a cerebrovasculaaccident; effects oftoxic ingestions may present over several hours; and a more gradual onsetsuggests infection, metabolic disease, or a space-occupying lesion. Vital signs, level of consciousnes

pupil size and reaction, motor responses, and skin findings crucial in narrowing potential causes anddetermining appropriate diagnostic studies.

Plan the initial phase of evaluation for an altered level of consciousness- 2006;27:331 2009:233

Recognize that disorders of metabolism, liver, kidneys, lungs or heart can be manifested asencephalopathy2006;27:29; 331

Encephalopathy - characterized by a deterioration in mentalstatus, which can range from a subtle change inattention toan acute confusionalstate to a marked change in arousal.

MCC of acute encephalopathy in childrenis CNS infection. Also important to considerdisturbances in systemicmetabolism.The first sign of a serious compromise in perfusion or oxygenationis a change in mental status. //Ddx includes systemic causes, such as electrolyte disturbances, toxicingestion, uremia, hypertension, and hepa

failure. More subtle disorders include

indolent infxns, postinfectious processes, rheumatologic

conditions, and inboerrors of metabolism.Importance of infectious, structural, andvascular abnormalities should be appreciated.

Know which ingestions are likely to result in neurologic toxicity 2006;27:331

In a patient with an altered level of consciousness, know the items of importance in the history oingestion 2006;27:29; 331

Avner JR. Altered states of consciousness.Pediatr Rev. 2006:27:331-338.- (Read)
http://pedsinreview.aappublications.org/cgi/content/full/27/9/331


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3. Ataxia

Know the common causes of acute ataxia 2007:54 Know the common causes of vertigo 2007:70

Know how to evaluate a child with ataxia 2006:39 2010:214

Ataxia - incoordination of motor actions due to disease or disorders of the cerebellum or its connections. Progressivataxias can be categorized as acute/subacute, episodic/paroxysmal, and chronic progressive.

When assessing children who have progressive incoordination, four key steps can narrow the ddx:

1. Localization of the problem to the cerebellum alone or cerebellum with other levels of the nervous system (brainbasal ganglia, brainstem, spinal cord, and nerves). i.e. bilateral symptoms with completely normal mental status and

no somnolence described for the boy in the vignette makes a cerebral cause less likely.

2. Clarification of the time course, such as chronic over a specific time period or intermittent worsening.

3. Identification of pattern of inheritance. Absence of an autosomal dominant disease pattern reduces thelikelihood of a number of spinocerebellar ataxias.

4. Identification, if possible, of a highly characteristic phenotype. For example, are there suggestive skin or eyefindings? For poss. eventual genetic followup.

Chronic ataxias in children are rare, but the most common diagnoses are Friedreich ataxia and ataxia telangiecta

(both autosomal recessive) // and spinocerebellar ataxias 1, 2, 3, and 7 (all aut osomal dominant). Friedreichataxia, can be confirmed genetically by identifying a more than 90 GAA repeat expansion in the Frataxin gene. Arecent clinical trial showed high-dose idebenone to be a beneficial treatment.

Ataxia telangiectasia usually presents earlier than 12 years of age with chorea/athetosis or ataxia, and althoughneurologic symptoms precede dermatologic ones, by this age, the ocular telangiectasias(Item C214) should beapparent.Hydrocephalus and Dandy Walker syndrome both can cause chronic gait problems. Progressive hydrocephalus shocause headaches and distal hyperreflexia, whereas Dandy Walker syndrome should not be progressive or beassociated with distal wasting.*

Consider MRI in young children for r/o cerebellar and brainstem neoplasms such as astrocytomas, pontine gliomasprimitive neuroectodermal tumors (medulloblastomas), or ependymomas.

Know the prognosis of childhood acute cerebellar ataxia 2010:118

Cerebellar signs: nystagmus, tremor on hand activation and finger-to-nose testing, trunk bobbing, broad-based gaitSubacute onset of symptoms suggests acute cerebellar ataxia, which usually is acquired after infxn orimmunization

*For children with acute ataxia, ddx includes neuroblastoma presenting as opsoclonus myoclonus ataxia syndrome.

Ryan MM, Engle EC. Acute ataxia in childhood.J Child Neurol. 2003;18:309-316
http://www.ncbi.nlm.nih.gov/pubmed/12822814


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4. Movement disorders (involuntary, paroxysmal)

Know the effective drugs for controlling chorea 2010:134

Chorea: restless, continuous, involuntary movements that are irregular in direction and amplitude"milk-maid's grip" and "darting tongue" signs, simple motor command cannot be maintained due to choreic intrusior involuntary relaxations (Item C134).MCC chorea: poststreptococcal, immune-mediated, aka, Sydenham chorea. Dx: antistreptococcal abs:antistreptolysin O and anti-DNAse B.Ddx: chorea associated with SLE, antiphospholipid antibody syndrome, hyperthyroidism.

Haldol- dopamine blocking agent. high-potency, but high incidence of adverse effects. Sydenham chorea is self-limited and a low dose is generally helpful. Other antipsychotics (fluphenazine or risperidone) or dopamine-depletiagents (tetrabenazine) also may be used.

* Trihexyphenidyl is an anticholinergic medication that may reduce dystonia, but it tends to worsen the symptoms Sydenham chorea.

Differentiate between tic disorder and Tourette syndrome 2006:27

Know the drugs useful in the treatment of Tourette syndrome 2008:103

Know which drugs can cause movement disorders 2007:246

Know that Tourette syndrome is associated with behavioral difficulties, learning disabilities, andattention deficit disorder 2006:44


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5. Increased intracranial pressure

Know to exclude a mass lesion by brain imaging in the presence of increased intracranial pressur2007;28:e77 2007:86

Know the common causes of pseudotumor cerebri 2006:55

Recognize the need to measure the opening pressure at lumbar puncture 2006:55

Know the signs and symptoms of increased intracranial pressure in infants 2007;28:e77 2007:86

Know the signs and symptoms of increased intracranial pressure in children 2007;28:343; e772007:86

Know the contraindications of immediate examination of the cerebrospinal fluid 2008;29:4172006:64

Focal neuro signs, inc ICP signs- i.e. vitals, vomiting, if pt is unstable

Plan the medical management of a patient who has increased intracranial pressure 2008;29:417Mannitol, Hyperventilate, Hypertonic saline, Ventriculostomy, ICP monitor


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6. Weakness and hypotonia

Distinguish among acute and chronic causes of weakness 2007:102

Know the benefits and limitations of ancillary neurodiagnostic tests in the evaluation of weaknes(eg, serum creatine kinase activity, electromyography 2007:102

Distinguish between central and peripheral nervous system causes of hypotonia2008;29:243 2007:118

Know the differential diagnosis of hypotonia in infants 2008;29:243 2010:150 2007:11

Know how to evaluate hypotonia in infants 2007:118

Hypotonia, a decrease in the muscle's postural tone, can resultfrom a wide range of disorders of the brain, spinalcord (spinalmuscular atrophies, spinal cord injury), nerves (hereditarymotor-sensory neuropathies, congenitalhypomyelinating neuropathy),neuromuscular transmission (infantile botulism, myasthenia gravis),or muscles(congenital myopathies and muscular dystrophies,metabolic myopathies such as acid maltase deficiency).

Table. Selected Neurologic Causes of Hypotonia

Central NervousSystem

BrainInjury: Hypotonic cerebral palsyChromosomal:Angelman syndrome, Prader-Willi syndrome, Rett syndrome, trisomy21Metabolic: Leukodystrophies (eg, metachromatic leukodystrophy*),peroxisomal disorders (eg, neonataladrenoleukodystrophy*),GM1 and GM2 gangliosidoses (eg, Tay-Sachs disease), organicacidemiasOther: Cerebral malformations, benign centralhypotonia, autism

Spinal cordInjury: Hypoxic-ischemicmyelopathy, traumaAnterior horn cell: Spinal muscularatrophies

Peripheral Nervous System (Motor Unit)

Nerves:Hereditary motor-sensory neuropathies, acute inflammatory demyelinatingneuropathy (Guillain-Barsyndrome), congenital hypomyelinatingneuropathies

Neuromuscular Transmission: Infantile botulism,myasthenic syndromes (eg, familial infantile myasthenia) Muscle:Muscular dystrophies (eg, Duchenne muscular dystrophy, Fukuyamacongenital muscular dystrophy

congenital myopathies (eg,central core disease), metabolic myopathies (eg, acid maltasedeficiency)* May have features of both central and peripheralnervous system involvement.

CNS causes of hypotonia and developmental delay include cerebralmalformations; acquired cerebral injury that ma

occur with

hypoxia, ischemia, or infection; genetic disorders such as Prader-Willi

syndrome; and several metabolicdisorders, including disordersof the peroxisomes, lysosomes, and mitochondria.


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B. Infection1. Meningitis

Know the common acute complications of meningitis 2008;29:417 2007:76

Know the etiologies of neonatal meningitis 2008;29:417 2009:242

Neonatal meningitis risk factors prenatally (maternal fever, chorioamnionitis, prolonged rupture ofmembranes) or postnatally (bacteremia, urinary tract infection, or respiratory distress); attendant signs ofapnea, lethargy, / acidosis, and hypoglycemia.

PE: bulging or tense anterior fontanelle, irritability, fever, emesis,/ coma, and seizures; change in neuromotor toneCSF values in bacterial meningitis- elevated protein > 100; WBC > 100; Gluc < 50% of serum

Neonatal enteroviral infection may follow maternal infection, - spring and summer. have sepsis syndrome,coagulopathy, and meningitis. Hepatopathy and respiratory sx

The mortality rate of neonatal bacterial meningitis is 10%, but both mortality and late morbidity vary with the causof meningitis. MCC group B Streptococcus, Escherichia coli, other gram-negative rods, and Listeria. Althoughneonatal GBS is common, it is associated with later onset (after 7 days), and a shocklike state.[Herpes simplex viral meningoencephalitis is associated with a hemorrhagic pleocytosis, apnea,seizures, coagulopathy, and hepatic transaminase values generally greater than 1,000 U/L.]

Know the etiologies of meningitis in children 2008;29:417 2007;28:e77

Know the causes of meningitis when no bacteria are isolated (eg, partially treated, parameningefocus, Borrelia, spirochete, M. tuberculosis) 2008;29:417

Distinguish among cerebrospinal fluid findings in bacterial, fungal, and viral meningit2008;29:417

Glucose (mg/dL)(mmol/L)

Protein(g/dL)(g/L)

White Blood Cell(x103/mcL) (x109/L) DifferentialCount Gram sta

Healthy newborn 30 to 120 30 to 150 90%

Enteroviralmeningitis

>1/2 serum 40 to 60 0.05 to 0.5 >50% PMNs early (1/2 serum 0.05to 0.5 Predominance of lymphocytes andmonocytes

Negative

Tuberculousmeningitis


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6 weeks of age, acyclovir (60 mg/kg per day divided every 8 hours) should be added if HSV infection is a conceIn the young infant, if the Gram stain suggests pneumococcus, vancomycin (60 mg/kg per day given every 6hours) should be added.

For children older than 2 months, vancomycin (60 mg/kg per day divided every 6 hours) plusceftriaxone (100 mg/kg per day given in one dose or divided into two doses) or cefotaxim(200 to 300 mg/kg per day divided every 6 hours) should be used for empiric coverage. / Analternative therapy for children who have had anaphylacticreactions to penicillin or cephalosporins a carbapenem ora quinolone in addition to vancomycin

Appropriate parenteral antibiotics should be continued

for 7 days for meningococcalmeningitisand 14 days for Listeria,GBS, and pneumococcal meningitis. Lyme meningitis typicallyistreated with IV ceftriaxone (50 to 75 mg/kg per day givenonce daily) for 14 to 28 days.Meningitis caused by gram-negativeenteric bacilli requires a longer duration of therapy,generallya minimum of 21 days.Neonatal HSV CNS infection typically is treated w IV acyclovir(60 mg/kg per day divided every hours) for 21 days

2. Encephalitis

Know the common causes of encephalitis 2005;26:347 2006:231

Recognize the signs and symptoms of herpes encephalitis 2005;26:347 2006:199

Recognize the cerebrospinal fluid findings in herpes encephalitis 2005;26:347

Know the clinical symptoms of encephalitis 2005;26:347 Know the role of neurodiagnostic testing in the evaluation of a child with encephalitis 2005;26:34

2008:119

Know the appropriate microbiologic, serologic, and molecular diagnostic tests in a child withencephalitis 2005;26:347

Know how to manage encephalitis 2005;26:347

Know the common sequelae of encephalitis 2005;26:347

Encephalitis commonly due to an arbovirus or herpes simplex infection. Arbovirus more likely to occur in summbecause arbovirus is transmitted to humans by mosquitoes. On MRI may see subtle thickening. HSV results innecrotizing focal encephalitis in the temporal lobes. In both, focal infection and inflammation in the brain's cortex c

lead to seizures. In the case of herpes, outside the neonatal period, the temporal lobe infection occurs because ofreactivation of the HSV in the trigeminal nerve and spread directly into adjacent brain tissue.

Virus also can enter the brain via the blood, in which case generalized encephalitis is more likely. Examples includHSV in the neonatal period. Other viruses prone to cause encephalitis include measles, HIV, rabies and CMV.

Ingestion of the eggs ofTaenia solium (pork tapeworm) can lead to neurocysticercosis. This can present with focalonset seizures, but affected patients usually do not appear ill, and CT/MRI reveal cysts (Item C166B).Borrelia burgdorferi is transmitted by ticks, and early infection presents with the characteristic rash (erythemamigrans). Late-stage disease presents with facial nerve palsies.Listeria monocytogenes often presents with brainstem encephalitis.

American Board of Pediatrics Content Specification:Know the etiologic and therapeutic implications of focal versus generalized clinical manifestations oencephalitis

3. Abscess

Know the clinical manifestations of brain abscess 2009:6 -

Facial pain or relatively nonspecific pain, emotional problems, Confusion , psychomotor retardation - frontal lobesymptoms, inc ICP- headache on awakening , vomiting. Brain abscesses often present only with nonspecific pain anot with fever.

References:


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Goodkin HP, Harper MB, Pomeroy SL. Intracerebral abscess in children: historical trends at Children'sHospital Boston.Pediatrics. 2004;113:1765-1770.

Haslam RHA. Brain abscess. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbooof Pediatrics. 18th ed. Philadelphia, Pa: Saunders Elsevier; 2007:2524-2525

Know that many brain abscesses contain multiple organisms, including anaerobes 2006:111

Know that neuroimaging studies should be done before examination of the cerebrospinal fluid insuspected brain abscess 2006:167

Understand the imaging techniques for diagnosing brain abscess 2007;28:305

Head CT with Contrast is recommended because of the insidious onset, which could indicateeither a neoplasm or infectious process. Intravenous contrast increases the diagnostic yield ofimaging studies where either neoplasm or infection is suspected because both typically involve somdegradation of the blood-brain barrier or hypervascularity, resulting in contrast

enhancement at the site of the lesion.

Understand the treatment of brain abscess 2008:76:

initial antimicrobial therapy should be broad, such as a combination regimen ofvancomycin +metronidazole + ceftriaxone. Vancomycin provides coverage for methicillin-susceptible and-resistant Staphylococcus aureus as well as other aerobic gram-positive organisms (eg, streptococcspecies). Metronidazole penetrates the blood-brain barrier well whether administered intravenously

orally and covers a large number of anaerobes. Ceftriaxone provides not only aerobic gram-positivecoverage (eg, streptococcal species), but also addresses gram-negative organisms (eg, Haemophiluinfluenzae). The duration of antimicrobial therapy is usually 4 to 6 weeks. Know the propensity for brain abscess to complicate cyanotic heart disease, sinusitis, and

pulmonary disease 2006:127

4. Myelitis

Plan the evaluation of a patient in whom post-infectious myelitis is suspected 2006;27:463 2006
http://pediatrics.aappublications.org/cgi/content/full/113/6/1765http://pediatrics.aappublications.org/cgi/content/full/113/6/1765


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C. Degenerative conditions1. Signs and symptoms

Recognize the historical features indicative of a degenerative CNS disorder 2005;26:218 2008:13

Neurodegenerative disorders: chronic and progressive, featuring selective and symmetricloss of neurons in sensorymotor, or cognitive areas. Can affect primarily white matter (leukoencephalopathies) orgray matter. Sx of d/d: loof speech, hearing,vision, strength, coordination, intelligence, or memory. Seizures , feeding problems. MRI -

symmetric atrophy

or demyelination of specific brain regions.

Ddx :poorly controlled seizure disorders, congenital and chronicinfection (HIV), chromosomal anomalies,hypothyroidism, structural or mass lesions of the brain, subacutesclerosing panencephalitis, and inhaled solventabuse (gluesniffing).

Incidence and Cause :The genetic neurodegenerative disorders are inherited as autosomalrecessive, X-linkerecessive, or mitochondrialdisorders. Single-genedefects cause these diseases. Those appearing primarilyin infanand childhood include the leukodystrophies (X-ALD,metachromatic leukodystrophy, Krabbe disease [globoid cellleukodystrophy],Zellweger syndrome, Canavan disease); mitochondrial disorders(Kearns-Sayre syndrome,

myoclonic epilepsy with ragged red fibers,and MELAS [syndrome of mitochondrial myopathy, encephalopathy,lac

acidosis, and strokelike episodes]); diseases of the

extrapyramidal nuclei (Leigh syndrome [infantile subacutenecrotizingencephalomyelopathy]); early-onset Alzheimer disease in patientswho have Down syndrome; multiple

sclerosis; Tay-Sachs disease;and Niemann-Pick disease.

Clinical Features: Neurodegenerative diseases may present at any stage of lifefrom the newborn period toadulthood. Their presentation ishighly variable. Symptom onset in the genetic disorders dependson the buildup oftoxic metabolites or lack of substrate. Illness,diet, and other environmental factors affect signs and symptoms,which may wax and wane. Disorders presenting in neonates usuallyare severe, persistent, and rapidly progressive.Patients havingmild neurologic or behavioral symptoms may present subtly inchildhood, adolescence, or adulthoo

The hallmark of a neurodegenerative condition is regressionor an unexplained plateau in development; this stat

may evolve

rapidly in days or weeks or more insidiously over months to

years. It is important to consider aneurodegenerative disorderin any child whose mental retardation, seizures, or motor problemsare unexplainedParental consanguinity or a family historyof early infant death should raise suspicion. Many newborn metabolicscreening tests do not test for neurodegenerative disorders;thus, normal results may not be relevant. Neonates oftenpresentwith signs similar to those of sepsis.

Management, Therapy, and Prognosis Initial care focuses on correcting metabolic derangements.Definitivecare involves restricting substrate or eliminating toxic metabolites.Enzyme replacementis available forsome disorders. The prognosisvaries, depending on the underlying disorder. Parents and familiesof affected childrerequire genetic counseling.

Recognize the signs and symptoms of degenerative CNS disorders 2005;26:218 2008:135 Know the clinical presentation and course of Rett syndrome 2008;29:243 2007:11 2006:215

The hallmark of degenerative disorders of the CNS is the progressiveloss of previously acquired abilities. In infantand youngchildren, a deceleration in the rate of developmentis oftenthe first presentation: the child fallsprogressively behindother children and only subsequently loses previously acquiredmilestones. When the declinindevelopmental quotient is notdue to an extrinsic agent or event or to secondary involvementof the CNS by ageneralized systemic disease, neurodegenerative diseasebecomes a consideration.

Most degenerative CNS disorders can be divided clinically intothree groups: gray-matter diseases, white-matterdiseases, andsystem diseases. The gray-matter diseases, which primarily involvethe neurons, occur with or withou

histologic evidence of storage of

abnormal metabolic products. They lead to neuronal death and

secondary


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degeneration of axons. // In the white-matter diseases,myelin is disrupted, either by the destruction of normal myelor by the production of biochemically abnormal myelin. The system diseasesare a heterogeneous group of conditioinvolving progressive degenerationof anatomically defined systems, such as the dorsal columns, pyramidaltracts, cerebellar nuclei. Typically, both neurons and myelinare destroyed in these disorders.

The first clinical task in evaluating a child for any neurodegenerativedisorder is to document that he or she has lostpreviously acquiredmilestones or has a decelerating developmental quotient. In eitherinstance, the most importantdiagnostic tool is repeated developmentalevaluations.

The major clinical features that differentiate gray-matter from white-matterdiseases are related directly to thefunctional roles of theneurons and myelin. Neuronal involvement in gray-matter diseaseleads to the early onset ofdementia, the progressive loss of cognitiveabilities, and seizures that frequently are myoclonic. The basal gangliaacerebellar nuclei are collections of neurons, so extrapyramidal andcerebellar signs, such as ataxia, are common.Ganglion cellsof the retina are affected in many of the gray-matter disorders,producing pigmentary degeneration othe retina. Abnormal storage oflipid in retinal ganglion cells (eg, in Tay-Sachs disease) makesthe perifoveal arealook gray and opaque. The fovea, which containsno ganglion cells, appears red by contrast, producing the clinicalldetected "cherry red spot."

The majority of degenerative diseases of white matter stem frombiochemical defects resulting in abnormal myelinthat breaksdown rapidly. These "dysmyelinating" disorders are called leukodystrophies.Clinically, the earliest sign

most white-matter degenerationsis spasticity. Dementia and seizures can occur, but usuallylater in the clinicalcourse. Involvement of cerebellar pathways can cause ataxia. Ratherthan the cherry-red spot of gray-matter diseaseoptic atrophyis the most characteristic ocular change seen in white-matter disease.Some patients even have corticablindness from demyelinationof the optic pathways in the cerebral hemispheres.

***** Rettsyndrome - stereotypic hand movements, followed by seizures and dementia. RS affects girls,exclusively. Although most casesare sporadic, the disease has long been suspected of havinga genetic basis. Genetadvances suggest that the genefor RS is located on the distal arm of the X chromosome.

Stage 1 (birth to 18 mo): Deceleration of head growth, beginning between2 and 4 months of age, results in anacquired microcephaly. / Babies show decreased interestin their environment and become markedly hypotonic.

Stage 2 ( 1 to 2 y): The loss of both expressive language andgross motor milestones, and the onset of abnormahand movements,seizures, irritability, and insomnia are typical of progressing RS.

Stage 3 (2 to 10 y): Severe mental retardation, seizures, andpersistent stereotypic hand wringing movementscharacterizethe childhood phase of RS. Most patients develop ataxic and wide-basedgaits, but many affected girlsnever walk. Tremulousness isa common finding, as are breath-holding spells.

Stage 4 (older than 10 y): As girls who have RS approach adolescence, theydevelop progressive scoliosis, musclewasting, and can become wheelchair-bound.By the early teenage years, they reach a plateau in their neurologicregression, but death usually occurs during late adolescencefrom infection or cardiac arrhythmia.

Neurodegen dis ddx: hydrocephalus, hypothyroidism,mass and structural lesions of the brain, chromosomal defectpoorly controlled seizures, environmental deprivation, subduralhematomas, and congenital and chronic infections

such as human immunodeficiencyvirus. Neurodegenerative disorders, however, arepredominantly hereditary.Although the biochemical basis ofmany neurodegenerative disorders is not fully understood, aprecise biochemicaldiagnosis always should be sought to makepossible an accurate discussion of prognosis, to provide counseling,andsometimes to administer specific treatment.

The availability of molecular genetictesting has improved the accuracy of diagnosis in symptomaticpatients,prenatally when genetic risk has been identified,and for carrier testing. Many neurodegenerative disorders canbediagnosed by biochemical testing of blood or urine without invasiveprocedures to obtain tissue for direct

examination. Even so,

a diagnosis of an altered enzyme disease should be confirmed

histologically.


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In general, treatment is available for only a few of the neurodegenerative diseases.Unfortunately, most remaininvariably fatal by late childhood.Dietary therapy, restriction of a substrate or substrate precursor,modification ofenzyme activity with cofactor vitamin therapy,and enzyme replacement all have been attempted with only limitedsuccess. Hope for more effective treatment comes from developmentsin molecular genetics that may allow the repaof specificpoint mutations in the human genome.

**

2. Diagnosis

Understand the initial evaluation of a patient with suspected CNS degenerative disease- Rptdevelopmental exams, MRI if neuro deficits or to eval gray vs white dis

D. Developmental malformation, static neurologic deficit1. Malformations

Know that a myelomeningocele is usually associated with hydrocephalus 2009;30:15 2005;26:50PIR Nov 2010

Recognize the most common orthopedic problems associated with a myelomeningocele and theirelative significance 2005;26:50

Understand the evaluation and fundamental long-term management of neurogenic bladder2005;26:50

Know the fundamental long-term management of a neurogenic bowel 2005;26:50

Know the clinical and radiographic features and prognosis of spina bifida occulta 2005;26:50

Know the differential diagnosis of acute neurologic deterioration in a child with myelomeningoce2005;26:50

Identify the clinical manifestations and plan the diagnostic evaluation of spinal dysraphism2007:134

Recognize the clinical features of hydrocephalus 2009:22

Headache, gait disturbance (toe-walking), acquired ocular misalignment (right eye cannot move to tright) raises concerns for both hydrocephalus and a brainstem lesion.

Head CT scan is adequate to rule out hydrocephalus that requires emergent neurosurgical

consultation. Unfortunately, a common cause for hydrocephalus in a child of this age is a brainstemcerebellar neoplasm such as an astrocytoma, glioma, medulloblastoma, or ependymoma. When thetumors enlarge in the posterior fossa, they can obstruct the flow of cerebrospinal fluid and causeacute hydrocephalus, which is a neurosurgical emergency.)

Recognize the signs and symptoms of shunt malfunction in hydrocephalus 2006:87Obstruction (vomiting, altered MSE), Infection (fever)

Know the differential diagnosis of microcephaly 2009:182

Dx: serial Head circumferences.. do MRI

Suboptimal head growth during the first year and microcephaly at 1 year of age are associated with subnormaldevelopmental outcomes in children who had hypoxic-ischemic injuries at term birth.

Head ultrasonography: alternative to MRI No sedation. lower resolution for peripheral gray matter and deepbrainstem structures. Better choice for dx macrocephaly b/c diagnoses hydrocephalus.

High-resolution karyotyping may be reasonable. However, this evaluation can be deferreduntil after additionalinformation about brain structure has been obtained. For example, if there is evidence of a stroke, hypoxic-ischemicinjury, or a congenital infection, karyotyping may not be needed.

Three-dimensional computed tomography scan is used to diagnose craniosynostosis. Craniosynostosis usuallypresents with an unusual head shape due to closure of one or more skull sutures.


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2. Cerebral palsy

Know that birth trauma and obstetric complications are not the leading causes of cerebral palsy2006:60

Recognize the clinical features of cerebral palsy, including classifications 2006:076

Know the risk factors associated with cerebral palsy 2006:60

Know the disabilities associated with cerebral palsy: cognitive, visual, communication, auditory,motor, seizure activity, behavioral, oral function, nutrition 2006:76

Know the principles of management for children with cerebral palsy (eg, feeding, spasticity,

mobility, activities of daily living, education) 2007:27

E. Seizures

A seizure is the clinical manifestation of an abnormal, excessive electrical discharge ofnerve cells

Epilepsy: a tendency toward recurrent seizures that are not a result of systemic orneurological insults

First seizure may be: Caused by an acute illness, Metabolic derangement , Infectious disorder

ILAE Classification of SeizuresI. Partial (Focal, Local) Seizures (involves part of the brain)

A. Simple Partial (consciousness retained). No postictal change in sensoriumB. Complex Partial (consciousness impaired)C. Partial evolving to Generalized Tonic ClonicII. Generalized Seizures(involves whole brain, loss of consciousness)A. AbsenceB. MyoclonicC. ClonicD. TonicE. Generalized Tonic-ClonicF. AtonicG. Infantile spasmsIII. Unclassified Epileptic Seizures

Complex means alteration in consciousness

Involves facial movements (chewing, sucking, swallowing)

Can appear to be responding to auditory or visual hallucinations

May have automatism, movements or vocalizations such as moaning or simple talking

Patients may complain of auraChildren unaware of seizureChildren can be postictal after

Generalized Seizures -non-focal seizures(involves whole brain, loss of consciousness)

Absence: Brief episodes where child stares into space with no awareness of their environment, minomotor manifestations such as blinking and lip smacking. EEG described as a 3 per second spikeand wave.

Seizure Features Generalized Partial

Aura Not Present Present

Prodrome Occasionally Occasionally

LOC Present Present

Automatisms Not usually Present

Prolonged Postictal state Not usually Present

GTC Present Present

Focal Motor Tonic or Clonic seizures Not usually Present


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Family History Possible Not usually

History of CNS infection, significant

head trauma, febrile seizure, CNS

tumor, vascular malformation, stroke

Not usually Possible

Neuroimaging Usually normal Possibly abnormal

EEG Generalizeddischarges

Focal Discharges

Neuro Exam Usually normal Possibly abnormal

**

1. General

Recognize the metabolic causes of seizures 2007;28:363

Know which drugs may precipitate or exacerbate seizures 2007;28:363 2006;27:283 2009:198medications used in certain disciplines, most commonly oncology and psychiatry, may precipitatethem. Patients receiving cyclosporine or intrathecal methotrexate may develop diffuse orpredominantly occipital white matter changes. With cyclosporine, in addition to seizures, occipitalblindness or strokelike weakness may occur. The changes seen on magnetic resonance imaging canbe reversible. Other medications that may cause or exacerbate seizures in children include isoniazidtheophylline, cocaine, psychostimulants, bupropion, / insulin, and oral hypoglycemic agents.

Know the most common causes of acute seizures 2007;28:263 2008:151

Distinguish among epileptic seizures and paraxysmal non-epileptic events (eg, breath-holdingspells, tics, self-stimulation, syncope, gastroesophageal reflux, psychogenic seizures, sleepdisturbances) 2007;28:363 2006;27:e42

Recognize the factors associated with an increased risk of seizure disorder 2007;28:363

Know the etiologic and therapeutic implications of partial versus generalized seizures 2005;26:342009:166

Know how to manage a child following a first seizure 2007;28:363 2008:167

Know how to manage a child with recurring seizures 2007;28:363

Formulate a management plan for a patient with psychogenic seizures 2007;28:363

Know that drug selection is based on seizure type 2007;28:363

Understand the indications for discontinuing anticonvulsant therapy 2007;28:363 2006:103 Know the indications for initiating anticonvulsant therapy 2007;28:363

Know the relationship between etiology and prognosis in seizures 2007;28:363 2008:182

Know the side effects and toxicities of anticonvulsants 2007;28:363 2009:214Antiseizure medications can cause a wide variety of adverse effects, including central nervous systeeffects such as sedation, dizziness, personality changes, and occasionally, worsening of seizures.Adverse effects of antiseizure medications may occur outside the central nervous system as well.Bone marrow suppression and liver toxicityare among the more serious possible systemic effects.Rashes are common in children and can occur as an adverse effect of most antiseizure medicationsSuch drug rashes tend to occur during the first month of use, as described for the girl in the vignetteRapid assessment of the child is important because in some cases, the rash may be a harbinger of a

more global, serious allergic reaction or of Stevens-Johnson syndrome (erythema multiforme major)

Know the value, limitations, and timing of serum drug concentration determinations during themanagement of seizures 2007;28:363

Know the laboratory abnormalities caused by anticonvulsants 2007;28:363

Know the interactions of anticonvulsants with other drugs, including other anticonvulsants2007;28:363

Understand the cognitive/behavioral consequences of treatment with anticonvulsants 2007;28:3

Understand the cognitive/behavioral problems associated with seizure disorders- 2007;28:363

Provide appropriate counseling regarding activities and behavior of a child with a seizure disorde(eg, athletics, school, driving, medications)- 2007;28:363

Understand the psychosocial effects of epilepsy 2007;28:363


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Know the effects of epilepsy and anticonvulsant therapy on reproductive health (eg, contraceptioand the fetus- 2008:88

AED Efficacy Comments Side Effects

Carbamazepine(400mg /day)

Partial, General CP-450 inducer Hyponatremia

Ethosuximde(250-

500mg/day)

Absence No CP-450 inductionor inhibition

Anorexia

Gabapentin(300-900mg/day)

Partial Renal clearance Weight gain, myalgia

Lamotrigine(25-50mg/day)

Partial, General Induced by PHY,CBZ. Inhibited byVPA

Steven-Johnson, insomnia

Oxcarbamazepine(600mg/day)

Partial Prodrug ofmonohydroxy CBZ

Hyponatremia

Phenobarbitol(30-90mg/day)

Partial, General CP-450 inducer Porphyria exaserbation

Phenytoin(300mg/day)

Partial, General CP-450 inducer Osteomalacia, gingival disease

Tiagabine(4mg/day)

Partial No enzyme inductionor inhibition

Seizures

Topiramate(25-50mg/day)

Partial, General May increase PHYlevels, no AEDenzyme induction,may alter efficacy ofOCP

Renal stones, glaucoma,paraesthesias, weight loss, wordfinding problems

Valproate(500-

1000mg/day)

General CP450 inhibitor Weight gain, hair loss, liverdisease, tremor

2. NeonatalNeonatal seizures tend to be focal, rather than generalized, and may be clonic (rhythmic jerking) otonic (sustained), but usually are not tonic-clonic. Focal clonic seizures may involve more than onelimb, but if jerking movements are bilateral, they are asynchronous.

3. Febrile

Know the natural history of febrile seizures 2007;28:363

Know the risk factors associated with febrile seizures related to later epilepsy 2007;28:4052010:230 2006:166

Only a small percentage of children who have febrile seizures subsequently develop recurrent nonfebrile seizures o

epilepsy. Risk factors identified by the National Collaborative Perinatal Project include abnormal neurologicdevelopment and a first febrile seizure that is complex. A family history of epilepsy may increase the risk. A familyhistory of febrile seizures and young age of onset increase the risk for future febrile seizures, but not for epilepsy . Know the diagnostic criteria for a febrile seizure 2007:28:363; 405

Know the appropriate evaluation of a child with febrile seizures 2006:182

Know the management of febrile seizures 2007;28:363; 405

4. Infantile spasms

Recognize the characteristic clinical features of infantile spasms 2006;27:389 2009:230

Know the prognosis for children with infantile spasms 2006;27:389


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West syndrome is triad of: Infantile spasms, Hypsarrhythmia on interictal EEG {in betweeseizure episodes}, Mental retardation- Devel. Delay; poor prognosis

4-6 mo of agemyoclonic-like seizures that can be subtle, such as a head drop or more dramatic, such as a "clasp-knife" spasm of tbody with arm flexion or extension. clustering is common, particularly at times of sleep-wake transition. the ictalspasms are accompanied by changes in cognitive and motor function, manifested by reduced social interaction andactivityseverely chaotic, cortical electrical pattern identified on EEG- "hypsarrhythmia." Outcome is almost uniformly poo

for infants who have pre-existing neurologic problems and develop infantile spasms. Neurologic outcomes sometimare good for those who have previously normal neurodevelopment.tuberous sclerosis may present with infantile spasms- need good PE and neuroimagingtx = ACTH, vigabatrin in Canada. May consider steroids/focal resection depending on prognosis

5. Absence epilepsies (petit mal)

Understand the drugs used to treat absence epilepsy 2007;28:363

Recognize the characteristics of absence epilepsy 2007;28:363>5y/o, F>M, No aura or postictal,


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Benign rolandic epilepsy: Most common form of epilepsy in childhood

M>F. Onset 3-13 years (peak: 9-10 years); Recovery before 15-16 years

Seizures: brief, self-limiting seizures involving the face, Unilateral sensory involvement(involving one side of the tongue)

Inheritance is autosomal dominant. centrotemporal spikes on EEG.No treatment needed because usually nocturnal seizures, infrequent, do not cause any problems the following day.A Partial seizure- use medications such as carbamazepine, if any.

Recognize the clinical manifestations of juvenile myoclonic epilepsy 2007;28:363

Juvenile myoclonic epilepsy - teenage years -1) myoclonic jerks, usually in the morning; 2) generalized tonic-cloniseizures (gen. epilepsy) and 3) absence seizures.

Age-related onset (usually 12-18)

Condition usually persists throughout life

Familial or sporadic

Seizures predominantly shortly after awakening

Seizures precipitated by sleep withdrawal, light sensitive

Seizure types: myoclonic (100%), generalized tonic-clonic (90%), absence (30%)

Jerky movements within couple of hours after awakening. Normal intelligence

No loss of consciousness

Treatment: Valproic Acid is treatment of choice

Keppra, Topamax, Lamictal all other options

Patients usually require lifelong treatment with anticonvulsants, but overall prognosis igenerally good.

9. Tuberous sclerosis

Recognize the clinical manifestations of tuberous sclerosis, and manage appropriately 2009:38

seizures, hypotonia, hypopigmented macules, and MRI findings suggestive of tuberous sclerosiscomplex (TSC) (Item C38A).

Diagnostic assessment should be directed toward confirming whether this child has TSC. In manycases, this is a clinical diagnosis based on the characteristic findings of skin examination and thecerebral complications. However, many other organs may be involved at presentation or during thechild's lifetime, including the eyes, kidneys, lungs, and heart. In the future, this child is at risk fordevelopmental learning difficulties, behavior problems that can include features of autistic spectrumdisorders, and malignancies. Given the autosomal dominantinheritance, proper management involvassessment of the parents and genetic counseling. Genetic testing may have false-negative resultsdue to mosaicism, ie, some organs may be affected due to TSC1 or TSC2 mutations that are notpresent in blood.

GTC: Avg last abt 5 min, postictal state, LOC, loss of bladder ctrl with full body tonic-clonic movemeRefer to slides 26-28 for GTC outline

Drug of choice: Valproic acid

Phenytoin and carbamazepine are other options

Lamotrigine (Lamictal): Broad-spectrum anti-epileptic

A potential side-effect is Stevens-Johnson Syndrome

Myoclonic : (myo = muscle, clonic = jerk)

Single, repetitive, involuntary contractions of an isolated group of muscles


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Key characteristic is loss of muscle tone and sudden brief shock-like muscletwitches with child falling forward.

No impairment of consciousness or memory

F. Cerebrovascular disease1. Stroke

Identify the clinical features of childhood stroke 2007;28:305 2006;27:271

Know the causes of stroke in children 2007;28:305 2006:135

The ConditionStroke has emerged as a relatively common but underrecognizedcause of neurologic disability in children. Anincidence of3 to 8 per 100,000 children per year suggests that ischemicstrokes are more common than pediatric brtumors. Most ischemicstrokes in children are arterial, but 20% occur as a resultof cerebral sinovenous thrombosis

The sudden onset of focal neurologic deficits in a child shouldbe considered to represent a stroke until proven

otherwise.Children who suffer strokes usually present with abrupt onsetofhemiparesis, but other focal deficits,including hemisensorychanges, visual loss or diplopia, loss or slurring of speech,and imbalance or incoordinationshould raise suspicion. Confoundingsigns and symptoms such as headaches, seizures, and alteredconsciousness ar

common.

Table. Differential Diagnosis of Pediatric Stroke

Meningitis, Encephalitis Demyelination Hypoglycemia Seizuresor a postictal state Inborn errors of metabolism

Migraine

A risk factor is identified in more than 70% of children afflictedwith stroke, and many harbor multiple risks. Threelarge categoriesof associations are cardiac disease, arteriopathies, and prothromboticdisorders. Complex congeniheart lesions are associated commonly,with interventional or surgical procedures also increasing therisk.Arteriopathies include arterial dissection, Moyamoya disease,and sickle cell disease as well as inflammatoryconditions relatedto infection (meningitis, varicella) or vasculitic conditions.Prothrombotic disorders include thefactor V Leiden mutation,elevated lipoprotein (a) concentrations, and deficiencies ofprotein C or S. A wide varietyof acute and chronic systemicillnesses may increase the risk of pediatric stroke.

Stroke is diagnosed by clinical and neuroimaging findings. CTcan demonstrate AIS and rule out hemorrhage, but iinsensitivein the acute phase. MRI is the investigation of choice; diffusion-weightedMRI has revolutionized the ea

diagnosis of cerebral ischemia.Angiography can be accomplished with MR or CT techniques, althoughconventionangiography may be required for diagnoses suchas dissection. Additional investigations such as echocardiographyand prothrombotic testing are used to eliminate other risk factors.

ManagementA child suspected of having had a stroke should be seen urgentlyby a pediatric neurologist. Evidence-basedmanagement is lacking,but recent consensus-based publications provide useful guidelines.The immediatethrombolytic ("clot-busting") treatments provenin adult stroke remain unproven in children, but studies areunderwAcute anticoagulation therapy with heparin or LMWHappears safe and may decrease the early progression of strokand multiple strokes observed in this patient. Published guidelinesrecommend eitherinitial aspirin (ASA) therapy oacute anticoagulationuntil investigations have delineated the cause for the stroke,followed by 3 to 6 months of


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anticoagulation for arterial dissectionor a presumed cardiac cause. Early management also should providesupportive care to minimize secondary brain injury and shouldinclude maintenance of normal blood pressure, blooglucoseconcentration, and temperature, along with aggressive treatmentof infection and immediate treatment ofseizures.

Patients whose strokes are due to other or unknown causes maybe maintained on long-term ASA (3 to 5 mg/kg perday), whichalso is recommended for patients suffering dissection or cardiogenicstroke, following 3 to 6 months ofanticoagulation. Such secondarystroke prevention is important because the risk of ongoing recurrenceof AIS,particularly in the first 6 months, is 10% to 25%. Earlyand aggressive physical, occupational, and speech therapy i

essential.

Only about 33% of children will be neurologically normalaftera stroke, and the mortality rate is 5% to 10%. Mostsurvivorslive with moderate-to-severe disability. Motor deficits aremost common, but other sequelae includelanguage disorders,cognitive and behavioral problems, movement disorders, headaches,and epilepsy. The burden oillness is exacerbated because themorbidity of stroke in a child affects the entire family andlasts a lifetime.

Lessons for the ClinicianAcute onset of a focal neurologic deficit in a child is an emergencyand should be considered a stroke until provenotherwise. Ahigh degree of clinical suspicion is required to improve recognitionof pediatric stroke and avoid delayin diagnosis. Because time-dependenttreatments now are available and evolving, the importance ofimproving

awareness and diagnostic sensitivity cannot be overemphasized

2. Vascular anomalies

Identify the clinical features of CNS arteriovenous malformations of childhood 2009:54

The most common cause of hemorrhagic stroke in children is vascular malformation, of which there are two types:arteriovenous malformations (AVMs) and cavernous malformations. These can present in childhood with hemorrhathat leads to headache and seizures.

AVM:Cavernous:

G. Spinal cord disease1. Signs and symptoms

Recognize the clinical manifestations of an acute spinal cord lesion 2006;27:463

Know the association between atlantoaxial instability in Down syndrome and potential neurologiccomplications 2008:104

Recognize the significance of bladder and bowel dysfunction in spinal cord disease2007;28:1932008:39

2. Diagnosis

Plan the initial neurodiagnostic evaluation in a patient with acute spinal cord dysfunction 2009:7

Acute spinal cord lesion: neurologic emergency. In some cases, emergency neurosurgery is needed for lesions causacute spinal cord compression, and the initial diagnostic emphasis should be directed toward identifying such lesion

Back pain, acute bilateral flaccid weakness, and sensory loss below the level of the lesion localize to the spinal corRapid onset of symptoms and the preservation of vibratory and proprioceptive sensation point to the anterior cord,bilaterally, which is consistent with an anterior spinal artery stroke. Spinal cord strokes in children are uncommon bcan occur after aortic surgery or as a consequence of thrombotic disorders, infection, inflammatory diseases, or

trauma.

MRI = test of choice. This should aid in determining the specific location of the lesion and whetheremergency neurosurgery to decompress the spinal cord is needed.


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H. Peripheral nerve and nerve roots1. Guillain-Barre syndrome

Know the presenting signs and symptoms of Guillain-Barre syndrome 2006;27:147 2008:212

Know the risk factors that are associated with Guillain-Barre syndrome (eg, recent immunizationvaricella infection) 2006;27:147

Know the differential diagnosis of Guillain-Barre syndrome 2006;27:147

Know the expected results of laboratory procedures such as examination of the cerebrospinal flunerve conduction studies, and electromyography in Guillain-Barre syndrome 2006;27:147

Know that cranial nerves may be affected in Guillain-Barre syndrome 2006;27:147

Know that autonomic dysfunction in Guillain-Barre syndrome may be prominent and dangerous2006;27:147

Understand the treatment of Guillain-Barre syndrome (eg, IVIG, plasmapheresis) 2006;27:1472010:198

Differential DiagnosisThe differential diagnosis of neuromuscular disorders includesCNS disease (meningitis, encephalopathy, neoplasmperipheralnervous system disorders (drug toxicities, GBS, tick paralysis,diphtheria), and neuromuscular

junction/muscle disorders (botulism,myasthenia gravis, spinal muscular atrophy, neuromuscular blockingagents,

acute inflammatory myopathies, metabolic myopathies).CNS disease ruled out by the lack of fever to indicate aninfection, normal CSF, and normal CT andMRI. PNS ruled out with no exposure to medications, insects, insecticid

and negative urine

toxicology.

Acute,rapidly progressive, ascending symmetric muscle weakness; lack of deeptendon reflexes; prodromal viralillness (URI, Gastroenteritis), vaccines or surgery. Immune-mediated; PNS.

Dx: clinical, CSF, EMG.

Pathophysiologyit has been postulated that the patient is infectedby a pathogen that shares similar antigenic sites as the hostaxon orthe peripheral nerve myelin, resulting in an autoimmuneresponse. This reaction leads to multifocal areas ofinflammation,especially at the spinal roots and peripheral nerves, followedby demyelination from macrophages

invading the basement membranes

of the Schwann cells.

The demyelination leaves the axon exposed, resulting inelectricalnerve impulse defects and eventual conduction block and flaccidparalysis. The intense inflammation at thventral and dorsalroots leads to the breakdown of the blood-brain barrier andthe transudation of the plasma proteininto the CSF. The virusesinvolved most commonly include cytomegalovirus, Epstein-Barrvirus, other herpesviruseand human immunodeficiency virus.Bacterial agents include Campylobacter jejuni (most frequentlyinvolved),typhoid, paratyphoid, Listeria, and Mycoplasma pneumoniae.Other antecedent events are surgery and vaccines.

Clinical Featuresprogressive, ascendingweakness with symmetrically decreased DTRs.GBS occurs in all age groups, although it israre in infants,and develops over hours to weeks

flaccid weakness, ataxia, sensory

disturbance, autonomic dysfunction, Cranial nerves affected

in 33% of patients. Tseverity of weakness in GBS rangesfrom mild to total paralysis. Sensory disturbance is frequent,with some patientcomplaining of pain or paresthesias in theextremities, around the mouth, and in the back. Autonomic dysfunctionmpresent as intermittent tachycardia, bradycardia, hypertension,and orthostatic hypotension. Bladder and boweldysfunction arerare.

Miller-Fishervariant: cranial nerve involvement (ophthalmoplegia),areflexia, ataxia.

DiagnosisCSF:1 to 2 weeks into the illness, the CSF analysis revealsprotein 80 - 200 mg/dL , cell count< 10 cells/mm3, withpredominantly monocytes ("cytoalbuminemicdisassociation").


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NCS: absent or reduced F waves(seen early in the disease), low-amplitude or absent sensorynerve actipotentials, and prolonged latencies. EMG may show a pattern consistentwith acute muscle denervation

Managementsupportive care, with closemonitoring for autonomic disturbance (the most common causeof death) an

detection of respiratory failure (the second mostcommon cause of death). Patients who demonstrate rapidlyprogressiveweakness, signs of aspiration, respiratory distress, or autonomicinstability require admission to anintensive care unit. 20% require mechanical ventilation. Intensive airway care andchest physiotherapy are importanin preventing pneumonia.

IVIG and plasmapheresis shorten the duration and severityof illness. IVIG is given dailyfor 5 days. Plasmapheresigenerally is administered as fourdouble-volume plasma exchanges on alternate days and is mosteffective if givenwithin 3 weeks of the onset of symptoms.The relative safety, ease, and comfort of administration tendto make IVIGthe preferred treatment choice.Physical therapy should be a part of every affected childstreatment.

AKA AIDP (acute inflammatory demyelinating polyneuropathy) manifested by progressive flaccid paralysis. The ascending,

symmetric paralysis usually follows a nonspecific viral infection or vaccination by about 2 to 4 weeks. The weakness begins in the

ower extremities and may progressively affect the trunk, upper limbs, and bulbar muscles. GBS predominantly involves the mot

nerves and occasionally the autonomic (blood pressure and heart rate variability) and sensory nerves (paresthesias). Bulbar

nvolvement may occur in up to 50% of cases. Signs of bulbar weakness include poor mobility of the palate when saying "ah",

decreased or absent gag, slurred or nasal speech, and coughing or sputtering after swallowing. // Respiratory insufficiency may l

to the need for mechanical ventilation in 20% of affected patients. Suggested indications for elective intubation include: vitalcapacity less than 10 to 15 mL/kg, maximal inspiratory pressure less than -30 to -20 cm H2O, significant bulbar

dysfunction, or a continued rise in PaCO2(Table 1).

Table 1: Ventilatory Management for GBS

Respiratory Pathophysiology Vital Capacity (mL/kg) Ventilatory Management

None 40 to 70 Observation

Poor cough and increased secretions ~30 Chest physical therapy

Sigh mechanism depressed: atelectasis and

hypoxemia

~25 Incentive spirometry

Sigh lost: atelectasis and shunting ~15 to 20 Consider NIV/intubate electively

Hypoventilation and hypercapnia ~10 to 15 Full ventilation

The lack of palate movement when asked to say "ah" and the nasal speech are suggestive of bulbar involvement.

Mechanisms for efficacy of IVIG include inhibition of complement binding, neutralization of selected cytokines, downregulation of

antibody production, and modulation of Fc-receptor mediated phagocytosis.

American Board of Pediatrics Content Specifications:

Recognize the clinical signs of Guillain-Barr Syndrome (paresthesia in the arms and legs, proximal ascendingweakness and respiratory failure closely associated with the loss of gag reflex)

Know the criteria for elective intubation in patients with Guillain-Barr Syndrome (e.g., loss of gag reflex, declining

respiratory function, pharyngeal dysfunction)

Lumbar puncture is the appropriate test for suspected Guillain-Barr syndrome (GBS), an acute inflammatorydemyelinating polyneuropathy. Typically, affected children present with weakness beginning in the proximal legs,pain, and absent reflexes. A variant of GBS can involve predominantly the brainstem and cerebellum, but usuallyweakness is more extensive than described for this child, and the weakness is not fatigable. Further, at this early stathe characteristic cerebrospinal fluid findings in GBS, normal cells and high protein, often have not emerged.Therefore, lumbar puncture is not the preferred study in this setting. Cold caloric testing evaluates vestibular functi


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This patient has no nystagmus and does not require this uncomfortable test. Neurophysiologic testing with auditoryvisual evoked potentials is not needed when no clinical evidence suggests that these systems are affected.

The evaluation of subacute generalized weakness is a medical emergency because symptoms may progress torespiratory insufficiency or dysautonomia and death. The evaluation should be systematic, considering possiblecauses at the level of brain, brainstem, spinal cord, anterior horn cell, root, nerve, junction, and muscle. The girldescribed in the vignette has generalized weakness, with normal mentation and sparing, at present, of muscles of thface and swallowing. Therefore, the problem is less likely to involve the brain or brainstem. Similarly, the absence

sensory loss makes spinal cord involvement unlikely. The back pain and absent reflexes localize the problem to rooand nerves, and the classic cerebrospinal fluid findings (high protein concentration, normal cells) confirm thediagnosis of acute inflammatory demyelinating polyneuropathy (AIDP), also known as Guillain-Barr syndrome(GBS).

The treatment of choice for AIDP/GBS in adults and children is intravenous immune globulin, administered at 2 g/total dose. Respiratory status, with forced vital capacity or negative inspiratory force, and cardiovascular status shobe monitored in the hospital due to the risk of death. Neuropathic pain also should be treated, and both gabapentin acarbamazepine are effective.

2. Neuropathy

Recognize the clinical manifestations of childhood peripheral neuropathy 2006:151

Know the common causes of peripheral neuropathy in childhood (eg, hereditary sensory and moneuropathy) 2008:55

Recognize the signs and symptoms of and plan treatment for Bell palsy 2007;28:465 2010:22

Ddx: Acute unilateral facial weakness: acute facial nerve palsy (ie, Bell palsy), a more rostral disease process of thebrainstem or brain (cerebrum, motor cortex) such as a stroke. The key diagnostic point for facial weakness is wheththe weakness involves the entire side of the face or the face below the forehead. A 7th nerve palsy affects all theinnervated muscles, weakening the entire hemi-face from forehead to chin. A lesion above the facial nerve nucleustypically weakens the face below the forehead.When the examination localizes a problem involving facial weakness to the brain or brainstem, brain magneticresonance imaging (MRI) or, if MRI is not available quickly, noncontrast head computed tomography should beobtained, whereas no imaging is needed if below the area of the brainstem.

The AAN practice parameter states that oral steroids probably are beneficial and acyclovirpossibly is beneficial fotreatment of facial nerve palsy. Many clinicians recommend administering a short course of oral prednisone for Belpalsy.

3. Brachial plexus injuries at birth

Recognize the clinical manifestations of neonatal brachial plexus injuries 2006;27:238 2008:193

Know the management and prognosis of neonatal brachial plexus injuries 2006;27:238 2008:193


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Intrapartum trauma to the brachial plexus encompasses a spectrumof injuries involving the lower cervical and uppethoracicnerves (C5 through T1), which supply the plexus. These fivespinal nerveroots combine to form the upper(C5 through C6),middle (C7), and lower (C8 through T1) trunks of the plexus,and the peripheral nerves originatinfrom the plexus innervatethe muscle groups of the shoulder, upper arm, forearm, wrist,and hand. The phrenic nercomprised of fibers from C3 throughC5, and the sympathetic fibers of T1 are affected commonly inbrachial plexusinjuries, resulting, respectively, in ipsilateraldiaphragmatic paralysis and Horner syndrome (miosis, ptosis,anhidrosis of the affected side).

The incidence of brachial plexus injury is approximately 1 in1,000 live births. Erb palsy, injury to the C5 through

spinalnerves, accounts for approximately 90% of cases. // Klumpke palsy,injury to the lower trunk (C8 through T1is rare and accountsfor 1% of cases. Total plexus injury accounts for 10%. Bilateralinjury is found in 10% to 20% cases, occurring almost exclusivelyin the setting ofbreech presentation.

Maternal, fetal, and parturitional factors can affect an infantsrisk for brachial plexus injury. Maternal risk factorsincludeuterine abnormalities, such as fibroids or a bicornuate uterus,and maternal diabetes. Fetal factors that maypredispose aninfant to injury include macrosomia, transverse lie, poor tone,and neonatal depression. Among theparturitional factors areabnormal presentations, dysfunctional labor, and the mechanicalforces of labor. Althoughthe etiology of brachial plexus maybe multifactorial, the pathogenesis of injury is believed tobe from traction orstretch injury to the plexus. The classicexample is injury from extreme lateral flexion and tractionof the head in theattempt to deliver the shoulder during cephalicdeliveries that involve shoulder dystocia. Conversely, tractioncan b

applied to the plexus via the shoulder in the processof delivering the head during breech deliveries. Abdominal waand intrauterine forces acting on a posterior shoulder pressedagainst the sacral promontory also have been implicatin brachialplexus injuries.

There are four types of neuronal injury, and the severity ofinjury influences the likelihood of spontaneous recoveryThemost severe form of injury, associated with poor spontaneousrecovery, involves avulsion of the nerve root fromthe spinalcord, often with injury to the cord itself. Equally poor inprognosis is neurotmesis, axonal rupture withdisruption ofthe nerve sheath. Outcome is somewhat improved with axonotmesis,which involves axonal rupture wthe nerve sheath left intact.Fortunately, the most common form of injury, neuropraxia, involvesdamage to the nervsheath alone, resulting in a temporary conductionblock. This type of injury is associated with complete spontaneourecovery.

The clinical manifestations of brachial plexus injury oftenare recognized in the labor suite. Infants who have Erbpalsyhave been described classically as having a "waiterstip" appearance. Weakness at the shoulder of abductioand externalrotation, at the elbow of flexion and supination, and at thewrist and fingers of extension results inadduction and internalrotation of the shoulder, extension of the elbow, pronationof the forearm, and flexion

the wrists and fingers. The bicepsreflex is not present, and the Moro and tonic neck reflexesare asymmetric.

Klumpkepalsy presents with weakness of the long flexors of the wristand the intrinsic muscles of the hands,resulting in an absentgrasp reflex. The biceps reflex is intact.

A flaccid arm thathas absent reflexes throughout indicates total plexus injury.An asymmetric Moro reflex

suggests a brachial plexus injury.

Management of an infant who has a brachial plexus injury requiresgentle handling of the affected limb to avoidadditional trauma.Many affected infants have a torticollis, putting them at riskof developing plagiocephaly.Radiographs of the clavicle andhumerus should be obtained to exclude bony injury. The infantshould be observedrespiratory distress (potential diaphragmaticinjury) and examined for signs of Horner syndrome. Magneticresonance imaging and electromyography have been used as adjunctiveexaminations, more in planning surgicalexploration than inroutine diagnosis and management. Prolongedimmobilization is not recommended. Generally,infants shouldbe referred to therapists for passive range of motion exercisesbeginning 7 to 10 days after birth.Therapy should include passiverange of motion of the neck and proximal arm.


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The prognosis of brachial plexus injuries depends on the severityand extent of the lesion. Upperinjuries, limited toC5 throughC6, have the best prognosis; // lower plexus and total plexus injurieshave poor prognoses. Because Erbpalsy, involving only the upperplexus, is by far the most common injury, spontaneous recoveryoccurs inapproximately 90% of cases. Onset of recovery within2 to 4 weeks is a favorable prognostic sign; flaccid paralysis

the entire limb, especially with coexisting Horner syndromeor diaphragmatic paralysis, is an adverse prognosticfactor.

Follow-up care involves serial neurologic examinations. If antigravitymovement of the affected muscle groups ispresent by the endof the third month of age, the prognosis is excellent. Satisfactory,but imperfect recovery can be

expected if perceptible contractionsare present by the end of the third month and antigravity movementis present bthe end of the fifth month. If no progress towardrecovery is made within the first 2 to 3 months after birth,referral a specialized center for evaluation is warranted.If no improvement is detected between 3 and 6 months, the likelihoof spontaneous recovery is grim, and surgical exploration maybe considered. Overall, more than90% of patients ardestinedto attain complete recovery by 4 months of age. Although recoveryof function is most rapid in the first fewpostnatal months,improvement may continue for up to 1 year of age.

I. Neuromuscular junction

Recognize that ticks may cause paralysis 2008:71

Know the signs and symptoms of myasthenia gravis 2008:242 Understand the laboratory and electrophysiologic studies to evaluate children with myasthenia

gravis 2009:102

Understand the appropriate management for a patient with myasthenia gravis 2009:102

Fatigable weakness means that after a period of sustained use, muscle strength diminishes. Such a pattern ischaracteristic of weakness due to pathology at the NMJ.

New-onset weakness mandates urgent evaluation and consideration of problems involving airway protection andrespiratory insufficiency, particularly if there is evidence of generalized weakness. If the pharyngeal muscles areaffected, speech sounds hyponasal. Negative inspiratory force or forced vitalcapacity should be documented

promptly because these findings determine whether the child should be transferred to an ICU forventilatorymonitoring and support.

Ocular fatigability suggests a neuromuscular junction problem such as myasthenia gravis.

Dx: ("Tensilon test"), acetylcholinesterase inhibitor edrophonium. Because the test can pose a risk of life-threatenbradycardia, it should be undertaken by an experienced physician with atropine at the bedside. Neurologicexamination before and after administration ideally should be documented on video (Item C102).

Treatment - immunomodulation (eg, intravenous immunoglobulin or plasmapheresis) ; acetylcholinesterase inhibitImaging to assess for the presence of a thymoma also.

American Board of Pediatrics Content Specifications:

Know the laboratory and electrophysiologic studies to evaluate children with myasthenia gravis Provide appropriate management for a patient with myasthenia gravis

J. Muscle diseases1. Signs and symptoms

Know the clinical features of dystrophinopathy (Duchenne/Becker 2006;27:83 2006:247musculardystrophy)


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Know that a Gowers sign indicates proximal muscle weakness 2006;27:83

Know the natural history and late complications of the muscular dystrophies 2006;27:83

Formulate a differential diagnosis for a patient who has weakness and an increased serum creatkinase activity 2006;27:83 2008:227

2. Pathophysiology

Know the genetics of dystrophinopathy (Duchenne/Becker muscular dystrophy) 2006;27:83

3. Diagnosis

Understand the laboratory studies available to diagnose muscle disease of childhood2006;27:83

K. Central nervous system trauma

1. Pathophysiology

Know that the outcome of a head injury is related to the duration and degree of coma 2007;28:2

Know the signs and symptoms of spinal trauma 2007:150

Recognize the clinical features of epidural hematoma 2007;28:215

Recognize the clinical features of subdural hematoma 2007;28:215

2. Management

Know the long-term neurologic and behavioral consequences of headtrauma 2007;28:215

Recognize the neuroendocrine complications of a following head injury 2007;28:215 Recognize that cerebral edema is a consequence of head trauma 2007;28:215; 305

Understand the clinical course and management of epidural hematoma 2007;28:215 2008:220:

Recognize the association of cervical cord injury with head trauma 2007;28:215

Recognize that intracranial hematomas can occur in the absence of a skull fracture 2007;28:215

Understand the clinical course and management of subdural hematoma 2007;28:215

Know the role of pharmacologic therapy in acute spinal cord or craniocerebral trauma 2007:150

L. Neurodiagnostic testing

Know the value and limitations of neurodiagnostic techniques such as magnetic resonanceimaging, computed tomography, and ultrasonography 2010:38 2010:70

MRI: gold standard imaging test for focal-onset seizuresCT:US:

Urine toxicology: first unprovoked seizure, but lack of confusion or encephalopathy with a rapid return to a normalmental status argues against a drug-induced seizure.

LP if partial seizure, fever; if confusion to evaluate for encephalitides

EEG: to look for epilepsy after two unprovoked seizures; In the setting of a single focal seizure, the initial emphasis

should be on determining whether a treatable focal lesion caused the seizure, for which EEG is unlikely to be helpfu

Understand the value and limitations of neurodiagnostic techniques such as evoked potentials,electromyography, and electroencephalography 2009:118

For a child who has a first unprovoked seizure safety concerns (no unsupervised time in bathtub or pools, wearia helmet while on a bike or scooter) and seizure first aid should be reviewed with the parents and documented in

the chart. Treatment after a single seizure in childhood is not recommended, no matter what EEG shows.


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In some cases, retrospective evaluation of children suggests that they have had subtle complex partial seizures orpreviously have been found after an unwitnessed seizure. Therefore, it is critical for the physician seeing the childafter an apparent first seizure to obtain a very careful history to be certain that the seizure is, indeed, the first.

The most important diagnostic decision after a first unprovoked seizure is whether to obtain neuroimaging to diagna focal, treatable cause for seizures. Neuroimaging should be obtained after a first unprovoked seizure when theseizure occurs in the first year after birth, is focal/asymmetric, or begins with a stare and subsequentlygeneralizes.

Obtaining an EEG is recommended by published practice guidelines. There are two primary problems to keep in mwhen deciding whether to order an EEG:

1) Inter-reader agreementin the interpretation of EEGs is low. The level of training of neurologists reading pediatrEEGs may be low in some communities, which is a particular problem for neonatal EEGs, and even experiencedEEG readers frequently differ in their visual interpretations.

2) Positive and negative predictive values are not very informative. The sensitivity of EEG varies widely, dependinon who reads it, but at best is approximately 50%; that is, about 50% of children who have epilepsy and 50% ofchildren who have a first unprovoked seizure that eventually will recur have epileptiform EEGs, but the rest have

normal EEGs. Accordingly, a normal EEG reading does not rule out recurrence or epilepsy and only means that arecurrent seizure is somewhat less likely. // The specificity after first seizure is, at best, about 70%; that is, about 30of children who do not have a seizure recurrence still have epileptiform discharges on the EEG . Thus, a positEEG also does not predict epilepsy accurately.

Repeat EEGs with sleep deprivation have been advocated by neurology practice parameters for many years in cawhere the first EEG is read as normal and sleep was not present. The best available evidence suggests, at most,modest benefit to this practice if used routinely in children. Any benefits of the higher yield should be weighedagainst the potential foradditional false-positive results, the time for the additional trip to the EEG laboratory,missed school and work, cost, and the burden of sleep deprivation .

Regardless of EEG results, two or more unprovoked seizures in a child are diagnostic of epilepsy and warranttreatment and consultation with a neurologist for selection of medication. Because phenobarbital causes sedation acognitive and behavioral changes in young children, it would not be used, except in countries where resources formedical care are very limited. Phenytoin has somewhat erratic absorption and can cause gingival hyperplasia inchildren, so it is not first-line therapy for a new diagnosis of epilepsy. Carbamazepine is a good choice for a childdiagnosed with partial epilepsy, but not for generalized epilepsy. Valproic acid is a good choice for both partial angeneralized epilepsy in children older than age 2 years.

The patients clinical presentation should guide the diagnostic

evaluation. Neuroimaging is essential for any patientdemonstratingfocal neurologic findings, changes in behavior or personality,or regression in development. CT of thbrain is useful in detectingstructural abnormalities, hemorrhages, calcification, and masseffect. MRI is a bettermodality fordelineating degenerativedisease, gray-white differentiation, inflammation, and infection.

[ For patients manifesting life-threatening signs, the clinicianshould suspect a neurometabolicdisorder and obtain blood gasesand measurements of serum ammonia, lactate, pyruvate, and glucoto rule out primary metabolic acidosis, hyperammonemia, andhypoglycemia. A CBC, serum chemistpanel, thyroid panel, andliver transaminase levels are important in evaluating systemicfindings sucas growth failure or hepatomegaly. ]

Weakness and hypotonia


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Distinguish among acute and chronic causes of weakness 2007:102

Know the benefits and limitations of ancillary neurodiagnostic tests in the evaluation of weaknes(eg, serum creatine kinase activity, electromyography 2007:102

Distinguish between central and peripheral nervous system causes of hypotonia 2008;29:2432007:118

Know the differential diagnosis of hypotonia in infants 2008;29:243 2010:150 2007:118

Know how to evaluate hypotonia in infants 2007:118

Hypotonia: Resistance of muscle to stretchPhasic tone: Is a rapid contraction in response to a high-intensity stretch

POSTURAL TONE : Prolonged contraction to a low-intensity stretch

Hypotonia: Impairment of ability to sustain postural control and movement against gravity

Weakness: Reduction of maximum power that can be generated by muscle contractionHypotonia - Decreased resistance to flexion and extension of extremities

Central account for 60% to 80% of hypotonia cases

Hypoxic-Ischemic Injury Hypotonic Cerebral Palsy Intracranial Hemorrhagic Chromosomal Disorders**- Down Synd, Frag X, Prader Willi

Infants with CENTRAL hypotonia may have: Abnormal eye movements/inability to track visually; Fail to imitate facial gestures; Dysmorphic

features Fisting/Scissoring on vertical suspension; Hyperactive reflexes Early seizures, Apnea or Irregular breathing pattern

Peripheral causes account for 15% to 30%

Anterior Horn Cell Disorders Spinal Muscular Atrophy Traumatic Myelopathy Neurogenic Arthogryposis

Neuromuscular Junction Disorders Infantile Botulism; Neonatal acquired myasthenia Magnesium Toxicity; Aminoglycoside Toxicity

Congenital Myopathies Nemaline Myopathy; Myotubular Myopathy

Muscular Dystrophies Duchennes + Beckers Muscluar Dystrophy

Walker-Warburg Disease Congenital Myotonic Dystrophy Infants with PERIPHERAL Hypotonia may have:

Alertness to environment, Normal sleep-wake pattern Absent reflexes, Fasciculations of tongue, Musc atrophy

Questions to Explore: Family History (ex. Fragile X, DMD) Prenatal, Perinatal, Neonatal history

Maternal exposure to toxins Maternal infections (TORCH) Mode of Delivery: Breech delivery, Cervical Spinal injury (birth trauma)

Low APGAR Scores


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Physical Exam: Head size, shape Dysmorphic features Posture, movement Often limbs abducted and extended ? Plagiocephaly frequently present

Greek break: asymmetric distortions of one side of skull or Helmet HeadHorizontal and Vertical suspension tests, Head lag with tractionHyperlaxity of joints, exaggerated hip abduction

Older Children: Abnormal stability and movement Combat Crawl Wide-based gait Genu Recurvatum (hyperextended knee) Hyperpronation of Feet W-Sitting

Jaw laxity/lip protrusion/eyelid lag Chewing dysfunction Poor respiratory effort

Gastro-esophageal reflux DTRs :

Hyperactive (in central conditions) Normal/decreased/absent (in peripheral disorders)

Kabuki Synd, , X linked Mental Retardation

Myotonic Dystrophy

Myotonia (Slow relaxation of muscles after voluntary contraction)

Autosomal dominant inheritance

Unstable DNA-trinucleotide repeat on Chromosome 19 --> expand in successive generations

Usually begin in young adult life Weakness of face, distal limb Cataracts Frontal baldness


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Clouded lens

Congenit Myotonic Dystrophy (different)

DMD

Natural History Clinical symptoms around 3-5 years Walk late around 18 months Walk tip-toe Running, hopping, jumping awkward Trendelenberg gait (waddling gait)

Fall easilyGowers Maneuver to get up Lumbar lordosis

Late Complications Wheelchair by 8-12 years After losing ambulation, 90% develop scoliosis Join contractures Deteriorating pulmonary function EKG/ECHO changes Prognosis: Death by late-teen to mid-20s

75% respiratory, 25% left ventricular failure

SMA

Heterogeneous group of genetic disorders Intantile Form: Werdnig-Hoffman Disease

Disease Mech.: Degeneration of the anterior horn cells in the spinal cord and motor nuclei in brainstem

Gradual generalized muscle weaknessatrophy

Infantile SMA: Werdnig-Hoffman Disease 0 to 6 month old infant with progressively and rapidly expanding weakness

May have reduction in fetal movement


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Floppiness of limbs and trunk Infant in frog-leg position Affected children never sit or stand unassisted Majority will require respiratory support to survive up to age 2

Pompes Disease

Infant botulism Mech: Eating foods contaminated by exotoxin ofClostridium Botulinum --> Exotoxin blocks release of

acetylcholine at neuromuscular junction--> cholinergic blockade of skeletal muscle and autonomic nervesinnervating end organs.

Why are infants and not adults affected?- Ans: Gut pH of infants is not sufficient to kill exotoxin (add furtheexplanation with pH numbers). Only 20% of cases honey or corn syrup is identified. Affected infant is usua< 6mo.

Lives in dusty environment adjacent to construction or agricultural soil disruption

Prodrome: Constipation, lethargy, poor feeding --> 4-5 days of progressive skeletal muscle weakness--> losof DTRs

Other findings: ptosis, sluggish pupillary light reaction, poor suck, difficulty swallowing, decreased gag refl

and expressionless face

Muscle paralysis can lead to respiratory failure!! Treatment: Intravenous human botulinum immunoglobulin Mech.: Neutralizes circulating botulinum toxin Cost: Baby BIG costs $40,000!!!

Disease Course: Without treatment,usually self-limited and resolves in 2 to 6 weeks with complete recover

CBC

Rule out sepsis (pan-culture) Serum electrolytes Liver function tests Urine drug screen

Pearl: Hypotonic newborn should be considered septic until proven otherwise If hepatomegaly present

TORCH titers Urine culture for cytomegalovirus

Head ultrasound look for intracranial hemorrhage or calcifications (CMV) in neonates

If hypotonia considered central, evaluate forgenetic causes

Send karyotype (especially, if dysmorphic feat. ++) Genomic hydribization study for SMA, X-linked diseases, Duchennes Methylation study for 15q11.2 imprinting (Prader Willi/)

If complex multisystem involvmentscreen forinborn errors of metabolism Plasma amino acid/Urine org. acid (aminoacidopathy, organic acedemia) Serum lactate (carbohydrate metabolism, mitochondrial disease) Pyruvate Ammonia (Urea cycle defects) Acylcarnitine profile (Fatty acid oxidation defect)


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Pearl: Term infant born healthy, but develops floppiness over 12 to 24 hours may have inborn errorof metabolism

Further Metabolic workup:

VLCFA Peroxisomal disorders

Creatine Kinase (CK) Muscular dystrophy

Carnitine concentration Carnitine deficiency

EMG

Nerve Conduction Study Muscle Biopsy

Immunohistochemical staining Electron Microscopy

Peredo, D., Hannibal, M et. al. The Floppy Infant: Evaluation of Hypotonia. Pediatrics in Review. Vol. 30 (2066-76

Fenichel GM. Neonatal Neurology 3rd edition. Churchill Livingston Inc. 1990

Paro-Panjan D, Neubauer D. Congenital hypotonia: is there an algorithm? Journal of Child Neurology; Jun2004,

Vol.19 (6): 439-43

Prasad AN, Prasad C. The floppy infant: contribution of genetic and metabolic disorders. Brain and Development;Oct 2003, Vol.25(7): 457-76

**

Neurofibromatosis (NF) is an autosomal dominant neurocutaneous disorder of which there are at least two types.Type 1 has an incidence of approximately 1 in 3,500 people, and its characteristic features are the cutaneous caf aulait macules and benign neurofibromas (Item C181). Type 2 has an incidence of approximately 1 in 40,000, and acharacteristic feature is vestibular schwannoma. Individuals affected by NF-1 are at risk for the development of a

number of complications, including optic pathway tumors, skeletal deformations, speech impediments, and learningdisabilities. In addition, there is variable association with hypertension, short stature, constipation, and chronicheadache. Patients who have NF-2 are not at increased risk for such complications.

The child described in the vignette is at risk for the development of hypertension, particularly during ages 2 through10 years. Although most patients have idiopathic hypertension, NF-1 can be associated with renal artery stenosis anpheochromocytoma. This child's health supervision visits should include a detailed history and accurate bloodpressure measurements to ensure early identification of this complication. The child is not at an increased risk for thdevelopment of cataracts, and there is no reason to restrict him from contact sports if he has no other complicationsBecause approximately 15% of individuals who have NF-1 develop optic pathway tumors, periodic ophthalmologicevaluation is important. However, the potential high cumulative radiation dose of annual computed tomography

scanning likely outweighs the benefits; the necessity and frequency

Documents

Updated Xviii Neurology