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 Example Investigations Treatment Tonic-clonic (or tonic or clonic alone) Valproate Lamotrigine Absence Ethosuxamide Atonic Myoclonic

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

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 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)

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 Prognosis poor, onset to death within short months

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

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

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.

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 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

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