Wednesday, November 18, 2015

Infantile spasms and topiramate

Weber A, Cole JW, Mytinger JR. Infantile Spasms Respond Poorly to Topiramate.
Pediatr Neurol. 2015 Aug;53(2):130-4.



Infantile spasms are seizures typical of an age-related epileptic encephalopathy. Although evidence supporting topiramate for infantile spasms is lacking, many clinicians use it for this indication. The aim of this study was to determine the rate of infantile spasm remission with topiramate at our institution. A low rate of infantile spasm remission was hypothesized.


This was a single-center retrospective medical record review of patients treated with topiramate for infantile spasms between January 2009 and September 2013. Records were reviewed for accuracy of diagnosis and outcome. Clinical remission of infantile spasms was defined as resolution for at least 28 days at any time during treatment with topiramate. For patients with clinical remission, posttreatment electroencephalographs were reviewed to assess for electrographic remission. To assess for confounding variables affecting remission rate, demographics and outcomes were compared with patients treated with adrenocorticotropic hormone within the same period using the same criteria for remission.


Three of 31 (9.7%) patients achieved clinical remission with topiramate, two of whom also experienced electrographic remission. The third patient had electrographic remission with previous adrenocorticotropic hormone treatment but infantile spasm remission only after receiving topiramate. All three of these patients experienced subsequent electroclinical relapse during topiramate therapy. Although there were no significant demographic differences between the topiramate and adrenocorticotropic hormone cohorts, more adrenocorticotropic hormone patients achieved clinical remission (9.7% versus 56%; P < 0.001).


Remission of infantile spasms with topiramate was uncommon and no patient experienced persistent electroclinical remission. These findings suggest that infantile spasms respond poorly to topiramate.

Courtesy of:


  1. Fallah R, Salor F, Akhavan Karbasi S, Motaghipisheh H. Randomised clinical
    efficacy trial of topiramate and nitrazepam in treatment of infantile spasms.
    Iran J Child Neurol. 2014 Winter;8(1):12-9.



    Infantile spasms (IS) are among the most catastrophic epileptic syndromes of infancy. The purpose of this study was to compare efficacy and safety of topiramate (TPM) and nitrazepam (NZP) as first-line drugs in the treatment of IS.


    In a parallel single-blinded randomized clinical trial, 50 patients with IS referred to Pediatric Neurology Clinic of Shahid Sadoughi University of Medical Sciences, Yazd, Iran, were evaluated from September 2008 to March 2010. Patients were randomly assigned to two groups to be treated with TPM or with NZP for 6 months. The primary endpoint was efficacy in cessation of all spasms or reduction of more than 50% in weekly seizure frequency, which was evaluated before and 6 months after the drug use. Secondary outcome was clinical sideeffects of the drugs.


    Twenty boys (40%) and 30 girls (60%) with the mean age of 9.4±3.8 months were evaluated. Cessation of all spasms occurred in 12 (48%) infants in TPM group and 4(16%) in NZP group. Eight (32%) children in TPM group and 7 (28%) in NZP group had more than 50% reduction in spasms frequency. So, TPM was more effective. Side effects were seen in 32% of TPM and in 36% of NZP groups.


    Topiramate is an effective and safe drug, which might be considered as the firstline drug for the treatment of ISs.

  2. Kumada T, Miyajima T, Oda N, Shimomura H, Saito K, Hiejima I, Nozaki F, Fujii
    T. [Efficacy, safety and tolerability of high-dose topiramate with rapid dose
    titration in symptomatic West syndrome]. No To Hattatsu. 2012 Nov;44(6):455-9.



    We investigated the efficacy, safety, and tolerability of high-dose topiramate with rapid dose titration in 12 children with symptomatic West syndrome who suffered from severe motor and intellectual disabilities.


    Topiramate was introduced as add-on therapy at the daily dose of 1 mg/kg/day, followed by increments of 2 mg/kg at 3- or 4-day intervals, up to a maximum of 19 or 20 mg/kg/day. The ages at the start of topiramate therapy ranged from 5 to 22 months. Prior to the topiramate therapy, the patients had received 2 to 6 antiepileptic agents with (8 patients) or without ACTH (4 patients).


    Topiramate appeared to be effective in 8 of the 12 patients (67%); four became seizure-free;three showed greater than 90% seizure reduction; one showed greater than 50% seizure reduction. The maintenance dose was 7 to 20 mg/kg/day (mean:17.9 +/- 3.9 mg/kg/day). In 4 of these 8 patients (50%), the spasms relapsed several months after complete cessation or diminution in the frequency of the spasms following treatment with topiramate. All of the 8 topiramate-responsive patients could continue the topiramate therapy throughout this study. The duration of topiramate therapy was 7 to 42 months (median: 12.5 months). There were no severe side effects that necessitated discontinuation of topiramate, including kidney stones.


    High-dose topiramate with rapid dose titration was revealed to be effective, safe, and well-tolerated in children with symptomatic West syndrome.