Treatment of Infantile Spasms: Results of a Population‐Based Study with Vigabatrin as the First Drug for Spasms

Abstract

Summary:Purpose: The efficacy of a protocol consisting of vigabatrin (VGB) as the first and adrenocorticotropic hormone (ACTH) or valproate (VPA) as the second drug was studied in the treatment of newly diagnosed infantile spasms (IS) during 1994 to 1997 in a population-based design.Methods: Only total disappearance of the spasms with a minimal duration of 1 month was accepted as a response. The treatment response was confirmed by video-EEG study. All infants were studied by magnetic resonance imaging (MRI) or computed tomography (CT) for etiology.Results: Altogether 42 infants, 10 with cryptogenic and 32 with symptomatic etiology, were treated. Eleven (26%) responded to VGB, five (50%) with cryptogenic, and six (19%) with symptomatic etiology; 91% of infants responded to a dose of 50-100 mgikglday, and 82% of them within 1 week. ACTH was offered in combination with VGB to 22 and VPA to four infants for whom VGB failed. Eleven responded to ACTH and one to VPA. In total, 26 (62%) infants responded to the treatment protocol; all (100%) with cryptogenic etiology and 16 (50%) with symptomatic etiology. ACTH treatment was associated with more severe side effects than VGB or VPA. Only one infant relapsed after a spasm-free period with VGB of >4 months, but none after ACTH was combined with VGB.Conclusions: We suggest VGB as a first drug to all infants with IS. After a treatment trial of 10-14 days with increasing dose from 50 to 150 mgkg, ACTH should be considered. Key Words: Infantile spasms-Epilepsy-Infants-West syndrome-Vigabatrin.Infantile spasms (IS) is an age-dependent epileptic syndrome characterized by epileptic spasms and interictal epileptiform activity that may be focal or diffuse (1). Epileptic spasms start during the first year of life, usually between 4 and 7 months. They are brief axial muscular contractions and occur most often in clusters (2,3). Interictally most infants show hypsarrhythmia or multiple independent spikes on EEG (4). If hypsarrhythmia has been recorded, the term "West syndrome" (WS) also may be used (3).According to etiology, IS are classified into two main groups: a cryptogenic group characterized by normal neurologic and cognitive development before spasm onset and by absence of an identifiable cause, and a symptomatic group associated with underlying abnormalities. An idiopathic subgroup with favorable outcome, consisting of normal psychomotor development and disappearance of epilepsy, has been suggested by some authors (3,5,6 The immediate goal of treatment is complete suppression of spasms. The ultimate goals are lasting seizure control and improved intellectual outcome. Cognitive outcome is especially poor for infants with symptomatic etiology; normal or slightly impaired intelligence has been observed in only 9-18% in contrast to 53-60% of infants with cryptogenic etiology (7-10).Results achieved with adrenocorticotropic hormone (ACTH) have offered a gold standard for the treatment results of IS for 40 years. The initial response rates to steroids or ACTH have varied between 50 ...

Recent Advances in the Pharmacotherapy of Infantile Spasms

“…The high figures in the study by Aicardi et al [47] could be explained by the lack of EEG evaluation. In the two studies where video telemetry was used [11,40], the response rates were only 16-10 %. It should be noted that vigabatrin treatment may make spasms milder.…”

“…After pooling the data of eight separate prospective and retrospective studies, vigabatrin had a good response on spasms in 44 % of 478 patients [11,22,31,39,40,[45][46][47]. In the pooled data of nine separate prospective and retrospective studies, ACTH had a good response on spasms in 59 % of 476 patients [22, 24, 26-29, 34, 48, 49].…”

“…The cryptogenic group may have a normal outcome in up to 100 % of patients if the effective treatment has been started within 1 month [10]. The symptomatic group can have a favourable outcome in approximately 20 % of patients [11].…”

Practice Parameter: Medical Treatment of Infantile Spasms

“…Fourteen studies met the inclusion criteria for analysis: one randomized placebo controlled study providing class I evidence, 31 two randomized controlled studies providing class III evidence, 19,32 six prospective uncontrolled open-label trials, [33][34][35][36][37][38] and five retrospective case series, 25,[39][40][41][42] providing class IV evidence (table 4). Age at onset ranged from 1 week to 18 months, and age at treatment ranged from 2 to 28 months.…”

Espasmos infantis: experiência em treze casos

“…Em estudo publicado em 1998, Masatoshi 8 observou baixa concentração do GABA no líquor de pacientes apresentando EI. Baseados nisto e no comprovado efeito da vigabatrina nos casos de EI secundários a esclerose tuberosa 9 em que, sem dúvida é a droga de primeira escolha, existem autores que defendem este tratamento de rotina em todos os casos 10,11 . Em nossos casos usamos apenas nas recorrências, confirmando sua eficácia, principalmente na manutenção das crises a longo prazo.…”