Comparison of Pre- and Post- Therapy Real Time Cortical Excitability in West Syndrome Using Transcranial Magnetic Stimulation: A Longitudinal Cohort Study

PATIENT ENROLLMENT AND MANAGEMENT:

• Consecutive children with West Syndrome (clinical spasm with EEG correlate) will be screened in the study centre for eligibility, and after applying inclusion and exclusion criteria they will be worked up for etiology.
• History will be taken and clinical examination will be done and if either are suggestive of any underlying etiology specific investigations will be performed as indicated (Ex. Neurocutaneous markers in tuberous sclerosis).
• If there are no other etiological pointers available from history and examination or if there is any history suggestive of adverse perinatal events, MRI brain with epilepsy protocol will be done.
• If MRI is not suggestive of structural etiology, they will be given a vitamin trial (pyridoxine 30mg/kg/day, pyridoxal phosphate- 20mg/kg/day, biotin 10mg/day and folinic acid 15mg/day) for a period of 10 days for response. Those who respond to vitamin trial will be excluded from the study.
• Written informed consent will be taken from legal guardians who are willing to participate in the study. Their anti-epileptic drugs will be optimized. Inappropriate AEDs like phenytoin, phenobarbitone and carbamazepine will be discontinued and replaced with valproate/levetiracetam and clonazepam in adequate doses and will be made in tablet form.
• DASII will be administered by child psychologist and will be repeated at 6 months of follow-up wherever feasible.

ACTH therapy

• Appropriate screening for Tuberculosis as per unit protocol (Mantoux and CXR screening) will be done if going to receive ACTH therapy.
• Children fulfilling the inclusion and exclusion criteria, will be enrolled and started on high dose regimen of 150 U/m2 or 6 U/kg of ACTH.
• This high dose will be continued for 2 weeks following which they will be slowly tapered over remaining 4 weeks, for a total treatment duration of 6 weeks.
• RBS and BP monitoring to be done twice weekly.
• EEG and TMS parameters will be done at baseline, 6 weeks and 3 months of therapy.
• First follow-up will be at 6 weeks of treatment initiation, then at 8 weeks and from then on once a month for a minimum period of 3 months (+/- 7 days) upto 6 months (+/- 7 days) wherever feasible.
• Those who have had complete electroclinical spasm cessation will be continued of oral AEDs.
• The overall spasm reduction will be calculated from the mean number of spasms from the observation period week and the mean number of spasms from the 6th week of therapy. Adverse effects will be noted down in their seizure diary.
• For sustained electroclinical cessation those who had complete electroclinical response will be rechecked at the end of 3 months (+/- 7 days) upto 6 months (+/- 7 days) wherever feasible.
• Compliance rate, adverse events, >50% spasm reduction rate, clinical spasm cessation rate, complete electroclinical spasm cessation rate will also be calculated from patient seizure log and EEG correlate.
• After 3 months, those who have >/=50% spasm reduction rate will be given trial of other oral AEDs as per protocol.
• But those who have <50% spasm reduction rate will be given an option to choose between ketogenic diet and vigabatrin.

KD therapy