Infantile spasms and developmental epileptic encephalopathy — formative SAQs

Question 1 (10 marks)

A seven-month-old boy is referred for two weeks of sudden flexor spasms occurring in clusters on waking, each lasting one to two seconds and recurring up to 40 times per cluster. His mother says he has stopped smiling responsively and no longer babbles. (a) State the diagnosis and the three features that define it. (b) Outline the immediate investigations and the time-frame in which they should occur. (c) Explain why infantile spasms are treated as a neurodevelopmental emergency. [1]

Model answer

(a) The diagnosis is West syndrome, now termed infantile epileptic spasms syndrome (IESS). The three defining features are clustered epileptic spasms, a chaotic high-voltage hypsarrhythmic EEG, and developmental arrest or regression, in the first year of life. The loss of social smiling and babbling is the developmental regression arm of the triad. [9] [1]

(b) The single most important investigation is an urgent sleep-deprived or sleep EEG requested the same day, to confirm classic or modified hypsarrhythmia and to distinguish true spasms from non-epileptic mimics. An MRI brain looks for a structural cause such as a cortical malformation, tuberous sclerosis, or a focal gliotic lesion. A skin examination under a Wood's lamp screens for the hypomelanotic macules of tuberous sclerosis, and a genetic workup (chromosomal microarray then an epilepsy gene panel) identifies a pathogenic variant. These should be initiated within days, and first-line therapy should not be delayed while every result returns. [1] [11]

(c) Infantile spasms are a developmental and epileptic encephalopathy in which the frequent epileptiform activity disrupts ongoing synaptogenesis in the immature brain, so the seizures are an active cause of developmental harm rather than merely a symptom. The lag from spasm onset to first-line therapy is a modifiable risk factor, and each week of delay measurably worsens developmental outcome, so spasms are treated within days rather than weeks even though the child is alert between clusters. [7] [11]

Question 2 (10 marks)

A six-month-old girl has new-onset clustered epileptic spasms, a hypsarrhythmic EEG, and developmental regression. Wood's lamp examination reveals four hypomelanotic macules, and her MRI shows cortical tubers and subependymal nodules. (a) What is the most likely diagnosis, and which first-line drug is indicated with its dosing? (b) A separate infant with cryptogenic spasms is to receive hormonal therapy: give the two first-line hormonal regimens with exact doses. (c) State the principal adverse effect that limits vigabatrin duration and the rationale for the ICISS combination approach. [10]

Model answer

(a) The most likely diagnosis is tuberous sclerosis complex presenting as infantile epileptic spasms syndrome. The first-line drug is vigabatrin, started at 50 mg per kg per day and titrated up by 25 to 50 mg per kg per day every three days to a target of 100 to 150 mg per kg per day. Vigabatrin is preferred first-line for TSC-associated spasms because it achieves a higher response rate in TSC than in non-TSC cases, and TSC1 and TSC2 testing should be requested to enable cascade and reproductive counselling. [6] [10]

(b) For non-TSC (cryptogenic or other) infantile spasms, first-line hormonal therapy is either high-dose ACTH at 150 IU per square metre per day by intramuscular injection, or oral prednisolone at 40 to 60 mg per day (approximately 2 mg per kg per day). A hormonal course requires blood-pressure and glucose monitoring, gastric protection, and vigilance for infection because of immunosuppression. [3] [4]

(c) Vigabatrin can cause an irreversible bilateral concentric constriction of the visual field, with an attributable risk that rises with cumulative dose and duration, so the total course is usually limited to around six months with ophthalmological surveillance. The ICISS trial showed that adding vigabatrin to hormonal therapy improved short-term spasm cessation over hormonal therapy alone, although 18-month developmental outcomes were not significantly different, which supports combination therapy in non-TSC infants while tempering the expectation of a developmental advantage. [8] [2]