Evidence-based guideline update: Medical treatment of infantile spasms [RETIRED]

Abstract

Objective:To update the 2004 American Academy of Neurology/Child Neurology Society practice parameter on treatment of infantile spasms in children.Methods: MEDLINE and EMBASE were searched from 2002 to 2011 and searches of reference lists of retrieved articles were performed. Sixty-eight articles were selected for detailed review; 26 were included in the analysis. Recommendations were based on a 4-tiered classification scheme combining pre-2002 evidence and more recent evidence. Results:There is insufficient evidence to determine whether other forms of corticosteroids are as effective as adrenocorticotropic hormone (ACTH) for short-term treatment of infantile spasms. However, low-dose ACTH is probably as effective as high-dose ACTH. ACTH is more effective than vigabatrin (VGB) for short-term treatment of children with infantile spasms (excluding those with tuberous sclerosis complex). There is insufficient evidence to show that other agents and combination therapy are effective for short-term treatment of infantile spasms. Short lag time to treatment leads to better long-term developmental outcome. Successful short-term treatment of cryptogenic infantile spasms with ACTH or prednisolone leads to better long-term developmental outcome than treatment with VGB.Recommendations: Low-dose ACTH should be considered for treatment of infantile spasms.ACTH or VGB may be useful for short-term treatment of infantile spasms, with ACTH considered preferentially over VGB. Hormonal therapy (ACTH or prednisolone) may be considered for use in preference to VGB in infants with cryptogenic infantile spasms, to possibly improve developmental outcome. A shorter lag time to treatment of infantile spasms with either hormonal therapy or VGB possibly improves long-term developmental outcomes. Neurology ® 2012;78:1974-1980 GLOSSARY AAN ϭ American Academy of Neurology; ACTH ϭ adrenocorticotropic hormone; AE ϭ adverse effect; AED ϭ antiepileptic drug; BD ϭ Breslow-Day; CI ϭ confidence interval; ERG ϭ electroretinogram; FDA ϭ Food and Drug Administration; IVIg ϭ IV immunoglobulin; LEV ϭ levetiracetam; NZP ϭ nitrazepam; OR ϭ odds ratio; RCT ϭ randomized controlled trial; TPM ϭ topiramate; TRH ϭ thyrotropin-releasing hormone; TSC ϭ tuberous sclerosis complex; UKISS ϭ United Kingdom Infantile Spasms Study; VABS ϭ Vineland Adaptive Behavioral Scale; VGB ϭ vigabatrin; VPA ϭ valproic acid; ZNS ϭ zonisamide.

Recent Advances in the Pharmacotherapy of Infantile Spasms

“…A through critical review was published in 2004 by the American Academy of Neurology Central Nervous System group to provide guidelines to clinicians in the treatment of infantile spasms [15]. In a recent paper published in Neurology, the same group provides an update to these guidelines [7]. The researchers carried out database searches of MEDLINE and EMBASE for relevant studies conducted during the period 2002-2011, and place their findings in the context of pre-2002 evidence [15].…”

“…An older, prospective, large Finnish study showed no difference in response rate (cessation of infantile spasms and resolution of hypsarrhythmia) or relapse rate comparing low-dose (20-40 IU/day) [N = 54] and high-dose (80-120 IU/day) [N = 97] regimens; however, long-term cognitive outcome was better with the low-dose regimen [29,30]. Recent evidence also suggests that low-dose ACTH is probably as effective as high-dose ACTH for short-term treatment of infantile spasms (Class I and II evidence) [7]. Therefore, the following recommendation was given in 2012: ''Low-dose ACTH should be considered as an alternative to high-dose ACTH for treatment of infantile spasms (Level B)'' [7].…”

“…Recent evidence also suggests that low-dose ACTH is probably as effective as high-dose ACTH for short-term treatment of infantile spasms (Class I and II evidence) [7]. Therefore, the following recommendation was given in 2012: ''Low-dose ACTH should be considered as an alternative to high-dose ACTH for treatment of infantile spasms (Level B)'' [7].…”

“…After careful aetiological investigations, some specific aetiological subgroups can be identified for which specific therapy is recommended. Such groups include metabolic diseases [5], cytomegalovirus infection [6], cryptogenic group of infantile spasms [7] and tuberous sclerosis (TS) [8]. The number of genes associated with infantile spasms are rapidly increasing (ARX, CDKL5, FOXG, GRIN1, GRIN 2A, MAGI, MEF2C, SLC25A22, SPTANI, STXBP1 and 15q11q13) [9], therefore genetic therapy might be possible in the future.…”

“…Large excellent reviews have been recently published [7,12]; however, many questions (such as the safety profile of approved and experimental therapies) still remain unanswered [13]. The author's own experience and search for other relevant studies from the world literature has supplemented the present review.…”