William is a 2-month-old baby who had a febrile seizure after a chest infection. Parents took him to Accident and Emergency (“A&E”) Department and William was then admitted to the paediatric ward. All biochemical and blood tests were normal. There was no family history of epilepsy. He was delivered via normal birth with no perinatal problems. Other medical history was unremarkable and early development had been normal. William was prescribed phenobarbital 8mg B.D. and magnetic resonance imaging (“MRI”) was arranged.

a) What is the pharmacological action of phenobarbital?

4 marks

MRI brain scan and cerebrospinal fluid analysis were normal. William’s seizure settled and he was discharged after four days. Over the next nine months, William experienced two further febrile Seizures after chest infections. The last febrile seizure was at 11 months and required inoavenous lorazepam and intravenous phenytoin rescue treatments.

William had shown some developmental delay, he only started crawling at 12 months of age and was unable to produce any recognisable words. When William was 14 months old, he was presented to the A&E with his first prolonged tonic-clonic afebrile seizure. William was admitted to the paediatric ward.   MRI  brain scan was normal, and an electroencephalogram  ( ‘EEG”) showed non-specific abnormalities. The paediatric neurologist considered the possibility of Dravet syndrome and ordered a genetic test to examine the mutation of sodium voltage-gated channel alpha subunit 1 (“SCNIA ’) gene.  (4 marks)

b) More than 80% of patients with Dravet syndrome have a mutation in the SCNIA gene. Explain the role of the sodium channel in the occurrence of seizure. (3 marks)

The results of the genetic test supported the clinical diagnosis of Dravet syndrome. As phenobarbital has not been effective in controlling William‘s seizures, the paediatric neurologist replaced it with sodium valproate.

c) Sodium valproate is considered first-line treatment for Dravet syndrome. What is the mechanism of action of sodium valproate? (4 marks)

d) Name ONE rare but life-threatening serious adverse drug reaction that is associated with sodium valproate in children under three years of age and what are the risk factors for such an adverse drug reaction? (4 marks)

e) Patients with Dravet syndrome are likely to suffer frequent and multiple types of seizures. Some of the prolonged seizures will require rescue medications. Suggest ONE treatment option of rescue medications that can be used at home to stop prolonged seizures and explain the mechanism of action of your suggested option. (5 marks)