1. Epilepsy in children | Classification and aetiology Michael Carter | ACF3, paediatrics, King’s College Hospital and UCL
April 2012

2. 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

4. Manifestations | Generalised
Example
Investigations
Treatment
Tonic-clonic
(or tonic or clonic alone)
Valproate
Lamotrigine
Absence
Ethosuxamide
Atonic
Myoclonic

5. Generalised epilepsies | Drugs and SEs
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

6. 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)

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

8. Manifestations | Unknown
For example, epilepsy syndromes in infancy
Infantile spasms:

9. 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.”

11. 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
Prognosis poor, onset to death within short months

12. Electroclinical syndromes | Infancy
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 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
Valproate
Topiramate
Initially progressive encephalopathy that finally relents but with severe global delay

13. Electroclinical syndromes | Childhood
Symptoms
Management
Notes
Childhood absence
Brief impairment of consciousness
Ethosuxamide
Valproate
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
Benign Rolandic epilepsy former name
Lennox-Gastaut
Polymorphic intractable seizures
Early referral to 3ary
EEG: generalised spike and wave

14. 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
Ethosuxamide
Valproate
Spike, slow-wave discharges 3-4 Hz
Juvenile generalised T-C
Generalised T-C. Preceding myo-clonus. No aura
Lamotrigine
Consider triggers (sleep deprivation, photic etc.)
Juvenile myoclonic epilepsy
Myoclonic jerks. May be subtle.

15. 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

16. 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

17. Criteria for onward referral to 3ary
Epilepsy nurses
To 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

18. 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

19. 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, Epilepsia 51(4):
Panayiotopoulos (2005) The Epilepsies: seizures, syndromes and management. Bladon Medical, Oxford