Modified Atkins Diet Versus Topiramate In Children With Epileptic Spasms Refractory To Hormonal Treatment: A Randomized Open-Label Study

Institutional Ethics Committee approval will be taken prior to starting the study. Written informed consent will be taken from available parent. Eligible children will be randomized to either receive the modified Atkins diet or topiramate along with the on-going anti-seizure medications.

Each child will undergo detailed history and examination according to a preset performa . Spasm type, frequency, age at onset, perinatal details, family history, developmental status and treatment history will be noted.  Medications will be changed to carbohydrate free preparations, wherever available. ACTH and oral steroids will be tapered off 2 weeks before starting the diet.  A baseline video-electroencephalogram would be performed in all children at the time of enrolment for minimum of 1 hour including at least one sleep wake cycle.

The plan of the study is explained in Figure 1. Eligible children will be randomized using computer generated random number tables in two groups: the modified Atkins diet and the topiramate arm. Both groups will undergo a baseline observation period, during which parents will be trained and asked to maintain a daily seizure log ( calendar will be provided to maintain seizure log in both the groups) . Anti-seizure medications will remain unchanged in both groups during the 12 week trial period, unless medically indicated, e.g. drug toxicity, status epilepticus etc, in which case appropriate changes will be made to their medications and same will be documented. Children will be reviewed as outpatients at 2 weeks, 4 weeks, 8 weeks and 12 weeks during the trial period. A 24 hour dietary intake chart will be reviewed at each visit to compute calorie and carbohydrate intake, and to evaluate and reinforce compliance with the prescribed diet. Weight will be checked at each visit. Pill count will be performed to check the compliance with topiramate. Every third day compliance will be checked, and counseling will be reinforced telephonically in both groups.

Percentage reduction in spasm frequency as compared to the baseline will be assessed in accordance with the parental spasm records.  Spasm frequencies will be recorded daily by parents. At the end of the 12 week study period, the proportion of patients who achieve spasm freedom, and more than or equal to 50% reduction in spasms in both the groups will be noted. Parents will be asked to measure urine ketones twice weekly. A 1 hour  EEG record (video-EEG whenever possible) including at least one sleep-wake cycle will be repeated at 12 weeks. BASED scoring ( Table 4) of the EEG record will be performed at baseline and the 12 week EEG record.

The proportion of patients with  equal or more than 1 point improvement in BASED score will be noted. Tolerability and any adverse effect related to  diet and the drug will be evaluated by means of parental interview at each visit. Parents will be questioned for the following symptoms for diet - vomiting, lethargy, poor appetite, refusal to feed and constipation in particular. For topiramate ,  anorexia, lethargy and sedation will be evaluated. Any other parental concerns will also be noted.

Parents will be asked to rate the effects of the intervention on the following non-seizure domains at 12 weeks after starting the diet: alertness, activity level, speech/communication, comprehension/understanding, sleeping, motor skills, social interaction and behavior. The questions will be open ended and parents will be asked to subjectively rate the characteristics on a Likert scale ranging from much worse (1), somewhat worse (2), same (3), somewhat better (4), or much better (5).

Urinary ketones will be checked using urine dipstick at each hospital visit. Patients who have spasm freedom or more than or equal to 50% reduction in spasms at 12 weeks will be continued on the respective interventions. Patients who have less than 50% reduction in spasms will be offered the alternative intervention, but this not come under the purview of this study.