Epilepsy syndromes by age — formative SAQs

SAQ 1 (10 marks)

A 7-month-old boy is brought in because for two weeks he has had clusters of brief symmetric jerks on waking, each lasting one to two seconds, sometimes twenty or thirty at a time, in which he flexes at the neck and trunk. His mother says he has stopped babbling and reaching for toys in the same period. His interictal EEG shows a chaotic, high-voltage, asynchronous background with multifocal spikes. Skin examination under Wood's lamp is normal. [2] [5]

1. Name the syndrome and state the diagnostic triad. (3) [2]
2. Outline your immediate management, including the first-choice treatment and the timing rationale. (4) [5]
3. Describe the role of aetiology in prognosis and how you would investigate the cause. (3) [2] [5]

Model answer — SAQ 1

(1) Syndrome and triad (3). This is West syndrome (infantile spasms), the archetype of a developmental and epileptic encephalopathy. The diagnostic triad is epileptic spasms occurring in clusters on waking, hypsarrhythmia on the EEG (the chaotic, high-voltage, asynchronous pattern with multifocal spikes), and psychomotor regression or developmental delay — here the loss of babbling and reaching. The peak age of onset is four to eight months. [2]

(2) Immediate management (4). I would confirm the diagnosis with video-EEG capturing a spasm cluster if possible, and then start first-line treatment promptly. First-line is vigabatrin or hormonal therapy (ACTH or high-dose oral prednisolone). Because the skin examination is normal and there is no clinical evidence of tuberous sclerosis, I would favour hormonal therapy, which the Cochrane review found more effective than vigabatrin for short-term spasm cessation in non-tuberous-sclerosis cases. The timing rationale is that time-to-treatment is a major determinant of developmental outcome: the epileptic encephalopathy itself drives the regression, so resolving the hypsarrhythmia is treatment of the developmental problem, not just the seizures. I would refer urgently to paediatric neurology. [5]

(3) Aetiology and investigation (3). Aetiology is the strongest determinant of prognosis: cryptogenic or unknown-cause cases treated early have a better cognitive outcome than those with an identified structural or genetic cause. I would investigate the cause with a skin examination for tuberous sclerosis (vigabatrin is first-line if present), an MRI brain to look for structural malformation or injury, and genetic testing — initially a gene panel or, increasingly, whole-exome sequencing — because monogenic causes (including CDKL5, STXBP1 and ARX) account for a substantial proportion. Metabolic studies would be guided by any suggestive features. [2] [5]

SAQ 2 (10 marks)

A 10-month-old girl began having prolonged seizures at 6 months of age, one lasting over twenty minutes with jerking of the right side during a febrile illness. She has since had further prolonged seizures triggered by fever and has developed myoclonic jerks and brief staring spells. Her development was initially normal but has slowed over the past two months. [2] [6]

1. What is the most likely syndrome and its genetic basis? (3) [2] [6]
2. Describe your definitive treatment plan and the medicines that must be avoided, with the mechanism. (4) [6]
3. Outline how you would manage a prolonged febrile seizure at home and in the emergency department for this child. (3) [6]

Model answer — SAQ 2

(1) Syndrome and genetic basis (3). This is Dravet syndrome, a developmental and epileptic encephalopathy characterised by prolonged febrile or afebrile hemiclonic seizures in the first year of life (often around six months), followed by the emergence of myoclonic, atypical absence and focal seizures with developmental slowing and later ataxia and intellectual disability. Around seventy percent of affected children carry a pathogenic loss-of-function variant in SCN1A, which encodes the Nav1.1 sodium channel of inhibitory interneurons. [2] [6]

(2) Treatment plan and drugs to avoid (4). The foundation of treatment is sodium valproate combined with a benzodiazepine such as clobazam, with stiripentol, fenfluramine or cannabidiol added for refractory disease; a ketogenic diet is an effective adjunct. The non-negotiable rule is to avoid sodium-channel blockers — carbamazepine, oxcarbazepine, lamotrigine and phenytoin. The mechanism is that SCN1A loss-of-function removes inhibition from the neural circuit by impairing the sodium channels of inhibitory interneurons; sodium-channel blockers further suppress those already-deficient inhibitory neurons and worsen the seizures. I would provide a MedicAlert-style alert and a written list of drugs to refuse. [6]

(3) Prolonged seizure management (3). At home the family would have a written emergency plan: a first-line benzodiazepine such as buccal midazolam at 0.15 mg per kilogram (or intranasal midazolam) if a convulsion lasts beyond five minutes, then call an ambulance. In the emergency department the standard paediatric status epilepticus ladder applies: reassess airway, breathing and circulation, give oxygen, check glucose and temperature, give a first-line benzodiazepine (lorazepam 0.1 mg per kilogram intravenously, or buccal or intranasal midazolam if no access), repeat once if still seizing, then a second-line agent such as levetiracetam or fosphenytoin, with escalation to intensive care and a continuous infusion for refractory status. I would treat the febrile trigger and, for a child with known Dravet, avoid phenytoin because it is a sodium-channel blocker that may worsen the underlying syndrome. [6]