Epilepsy in children |Classification and aetiology

Michael Carter | ACF3, paediatrics, King’s College Hospital and UCL

April 2012

Classification

Manifestations • Generalised: Arising within and rapidly engaging

bilaterally distributed networks• Focal: Originating within networks limited to one

hemisphere• Unknown (e.g. infantile spasms)

Electroclinical syndromes• Syndromic epilepsy (often categorised by age of onset,

see later)• Constellations of symptoms (e.g. mesial temporal lobe

sclerosis)• Non-syndromic epilepsy (e.g. post-stroke, perinatal

insults etc.)

Aetiology• Genetic• Structural-metabolic• Unknown

Manifestations | Generalised

Manifestation Example Investigations Treatment

Tonic-clonic (or tonic or clonic alone)

Valproate Lamotrigine

Absence EthosuxamideValproate

Atonic ValproateLamotrigine

Myoclonic Valproate

Generalised epilepsies | Drugs and SEs

Drug Mechanism Side effects

Valproate Inhibitor of GABA transaminase

GI upset, low PLTs, hepatitis, hair loss, tremor, teratogenic

Lamotrigine Na+ channel blockade

Rash including SJS, aseptic meningitis, double vision, dizziness, anxiety, GI upset (CI myoclonus)

Ethosuxamide Na+ or Ca2+ channel blockade

Anxiety and psychiatric disorders, pancytopaenia, GI upset, SJS

Note: carbamazepine worsens absence seizures; lamotrigine worsens myoclonic seizures

Fetal valproate syndrome: neural tube defects, coloboma, limb defects. Also, cardiac defects, dysmorphic features and occasional global developmental delay

Manifestations | Focal

Originate within networks limited to one hemisphere• Are described with specific reference to the symptoms

involved, such as:• Subjective sensations (e.g. auras)• Motor (e.g. twitching)• Autonomic (e.g. sweating)• Dyscognitive features (e.g. impaired consciousness –

note replaces “partial”)

And may:• Evolve to a bilateral convulsive seizure (note replaces “secondarily generalised”)

Usually denote a focal lesion within the brain, e.g. mesial temporal sclerosis, stroke etc.

The most common cause of acquired epilepsy, globally is …

(Emedicine)

Manifestations | Focal

T2-weighted magnetic resonance images reveal the increased signal and volume loss of the left hippocampus: mesial temporal sclerosis (Emedicine)

First-line drugs for focal seizure SE effects

Carbamazepine (Na+ channel blockade)

Drowsiness, headaches, pancytopaenia, hypothyroidism, cerebellar syndrome (CI absences)

Lamotrigine Rash including SJS, aseptic meningitis, double vision, dizziness, anxiety, GI upset (CI myoclonus)

Alternatives: leviracetam, valproate, oxcarbazepine

Adjuncts: clobazam, gabapentin, topiramate

Alternatives: surgical intervention for a focal lesion

Manifestations | Unknown

For example, epilepsy syndromes in infancy

Infantile spasms:

Electroclinical syndromes

An electroclinical syndromes is:

“A complex of clinical features, signs, and symptoms that together define a distinctive, recognizable clinical disorder…

Identifiable on the basis of a typical age onset, specific EEG characteristics, seizure types, and often other features which, when taken together, permit a specific diagnosis.

The diagnosis in turn often has implications for treatment, management, and prognosis.”

Electroclinical syndromes | Neonatal

• Neonatal: benign neonatal seizures, others

Syndrome Symptoms Management Note

Benign neonatal seizures

Repetitive clonic seizures. Often unilateral. Ictal EEG with Rolandic spikes and waves

None Diagnosis of exclusion. By definition, excellent prognosis

Ohtahara, early myoclonic epilepsy

Continuing, tonic-clonic seizures. Hypsarrhythmia in EME

None Prognosis poor, onset to death within short months

Electroclinical syndromes | Infancy

Syndrome Symptoms Management Notes

Febrile seizures

Generalised T-C seizure with fever in children 6 months to 6 years of age

Usually none Atypical febrile seizures: Early onset, >15 mins, focal, focal deficit, repeated same day

Benign infantile epilepsy

Infancy-20 months. Focal seizures clusters for 1-3 days

Usually none Usually benign and relents. Atypical if no family history

West syndrome

Onset usually 5 months. Clusters of infantile spasms, hypsarrythmia

Vigabatrin Progressive encephalopathy

Dravet syndrome

Early febrile T-C seizures, myoclonus, atypical absences, focal (dyscognitive) seizures

ValproateTopiramate

Initially progressive encephalopathy that finally relents but with severe global delay

Electroclinical syndromes | Childhood

Syndrome Symptoms Management Notes

Childhood absence Brief impairment of consciousness

EthosuxamideValproate

Spike, slow-wave discharges 3-4 Hz

Panayiotopoulos syndrome

Prolonged autonomic seizures (vomiting). Focal

Carbamazepine Lamotrigine

Synonym: Early-onset occipital (misnomer)

Late-onset occipital (Gastaut)

Carbamazepine Lamotrigine

Benign epilepsy with centro-temporal spikes

Oro-pharngeal symptoms, facial sensorimotor. Focal

Carbamazepine Lamotrigine

Benign Rolandic epilepsy former name

Lennox-Gastaut Polymorphic intractable seizures

ValproateEarly referral to 3ary

EEG: generalised spike and wave

Electroclinical syndromes | Adolescence

These are also known as idiopathic generalised epilepsies, and categorised by their manifestations

Syndrome Symptoms Management Notes

Juvenile absences Brief impairment of consciousness

EthosuxamideValproate

Spike, slow-wave discharges 3-4 Hz

Juvenile generalised T-C

Generalised T-C. Preceding myo-clonus. No aura

Valproate Lamotrigine

Consider triggers (sleep deprivation, photic etc.)

Juvenile myoclonic epilepsy

Myoclonic jerks. May be subtle.

Valproate Consider triggers (sleep deprivation, photic etc.)

Aetiology

Genetic Structural-metabolic Unknown

Genetic defect directly contributes to the epilepsy and seizures are the main symptom of the disorder

Caused by a structural or metabolic disorder of the brain (formerly “symptomatic”)

Other epilepsy for whom genetic studies are currently negative

E.g. channelopathies E.g. tuberous sclerosis, stroke, tumours

Investigations in children

EEG• Indications: after second seizure (occasionally first

seizure)• Issues: Low sensitivity (useful to support a diagnosis

only)• Other: If normal, consider sleep EEG (with melatonin),

photic stimulation, hyperventilation or telemetry

MRI• Indications: <2 years of age, adults, focal onset,

resistance to first-line medication

Other • Routine biochemistry (including magnesium) and ECG in

all patients

Criteria for onward referral to 3ary

Epilepsy nursesTo be involved in the care of all children with epilepsy

Syndromes and manifestations• All children with infantile spasms• All children with suspected Dravet syndrome• All children with suspected Lennox-Gastaut syndrome• All children <2 years• All children with unilateral structural lesion• All children with drug-resistant epilepsy (after 2 drugs

with breakthrough)• All children with diagnostic doubt

Conclusions

Classification of epilepsies• By manifestation: generalised, focal, unknown• By electroclinical syndrome: usually also by typical age

of onset• By aetiology: genetic, structural-metabolic, unknown

Management• EEG (+/- MRI) after second seizure unless focal deficits

or unwell• Epilepsy nurses• Generally: valproate first-line for any generalised

epilepsy• Generally: carbamazepine (CI absences) or lamotrigine

(CI myoclonus) for focal epilepsy• Importance of explaining side-effects

References

NICE (2012) The epilepsies: the diagnosis and management of the epilepsies in adults and children in primary and secondary care. NICE Clinical Guideline 137

Berg et al. (2010) Revised terminology and concepts for organisation of seizures and the epilepsies: report of the ILAE commission on classification and terminology, 2005-2009. Epilepsia 51(4): 676-685

Panayiotopoulos (2005) The Epilepsies: seizures, syndromes and management. Bladon Medical, Oxford