West Syndrome: Response to Valproate

Abstract

Management of West syndrome is unsatisfactory. In our clinic we observed that a significant proportion of patients respond to usual dose of valproate. Objective: To prospectively assess the efficacy of valproate in controlling infantile spasms in West syndrome. Methods: Consecutive patients presenting with West syndrome to the Pediatric Neurology Clinic or general outpatient department (OPD) were enrolled for study. Those who were not on any treatment were given valproate in a dose of 30 mg/kg/day while awaiting investigations. Patients were followed up every 2 weeks. Predefined criteria for definition of West syndrome and response were used. Those showing partial/poor response or relapse on valproate were given hormonal therapy. Results: One hundred children with West syndrome were enrolled. Ninety one children were started on valproate. Of these 36 (39.5%) showed a good response, but seven later relapsed while on same dose of valproate and three were lost to follow up. Later age at onset and typical hypsarrhythmia on EEG were associated with good sustained response to valproate while a history of delayed cry at birth was associated with partial or poor response. Sixty two patients who responded poorly to or relapsed on valproate were put on hormonal treatment in addition. Of these 36 (58.1%) had a good response but 11 later relapsed after stopping treatment and two were lost to follow up. Conclusion: Valproate may have a role in treatment of West syndrome in a selected group of patients.

Recent Advances in the Pharmacotherapy of Infantile Spasms

“…There are some Class IV studies of topiramate [80][81][82], valproic acid [83,84], Class I of sulthiame [85] and Class IV of zonisamide [86][87][88][89], pyridoxine [90,91], nitrazepam [92], levetiracetam [93], lamotrigine [94] and a ketogenic diet [95,96]. Topiramate is a popular second-line treatment of infantile spasms and is often used as first-line treatment, especially where there is no access to vigabatrin [74] (Class IV).…”

“…It has been used as first-line treatment (30 mg/kg/day) in 100 children with a 'complete or good' response rate on spasms of 39 % [83] (Class IV). Adverse effects include hepatotoxicity, especially in multidrug treatment when large doses have been used [84].…”

West Syndrome Treatment: New Roads for an Old Syndrome

“…Even though the study by Chandra et al (1) leaves some unsolved issues regarding the lack of demonstration of hypsarrhythmia in 70% of their cases, the long-term follow-up of cognitive profiles in the whole group, an extensive etiological work-up and the alternative use of new therapeutic drugs such as vigabatrin, it provides the scientific community with successful short-term results in 36/91 (40%) of their treated WS patients who showed “…a greater than 80% decrease in the number of spasms or complete cessation.”…”

“…The recent article by Chandra et al (1), published in Frontiers in Neurology , on the treatment of West syndrome (WS) by using valproate as monotherapy, prompted us to rethink about the past and present treatment strategies and the outcome in this severe epileptic syndrome.…”

“…For all the above reasons, the results of Chandra et al (1) highlight the multifaceted aspects of the spectrum of disorders associated to clinical spasms (i.e., good response to a classical anticonvulsant in the era of newer drugs and other-than valproate first-line treatments) and the prevalent role that etiological events could play in pre-programing the cognitive and behavioral outcomes in the setting of ISs (16). In this respect, without forgetting the current first-line treatment strategies for ISs and related phenotypes, we should also look with less strict therapeutic boundaries at patients with clinical spasms as in the near future the gold standard could be the development of new therapies (with new or old molecules) that simply target specific pathways of pathogenesis, as currently occurs in tuberous sclerosis (17, 18).…”