There is considerable variation in the management of infantile spasms, as evidenced by the US Consensus Report and a recent survey done on the current evaluation and treatment of infantile spasms among members of the Child Neurology Society (CNS).9,10 According to these sources, most neurologists use adrenocorticotrophic hormone (ACTH) as their preferred first-line treatment for infantile spasms not caused by TS and vigabatrin (VGB) as the first-line treatment of infantile spasms caused by TS.9,10
The 2004 American Academy of Neurology (AAN) and CNS practice parameter on the medical treatment of infantile spasms concluded that ACTH is probably effective for the short-term treatment of infantile spasms and that VGB is possibly effective for the short-term treatment of infantile spasms and for treatment of children with TS.11
A 2012 AAN evidence-based guideline, which updated the 2004 parameter, reported that ACTH or VGB may be useful for short-term treatment of infantile spasms, with ACTH being more effective than VGB, excluding cases with TS.12
According to the 2012 guideline, there is insufficient evidence to determine whether other forms of corticosteroids are as effective as ACTH.12 There is also insufficient evidence to recommend other agents or combination therapy as being effective in the short-term therapy of infantile spasms.12
ACTH is given as an intramuscular injection, and different epilepsy centers show considerable variability in dosage (high vs low), formulation (natural ACTH in the United States vs synthetic ACTH in Canada, Japan, and Europe), and duration of therapy. Side effects are common and include hypertension (up to 37%), irritability (37%-100%), infection (14%), and cerebral atrophy (62%). Higher dosage and longer duration of treatment correlate with higher incidence of side effects.
Questions regarding the optimal dose, formulation, and duration of ACTH treatment remain, although the 2012 updated guideline reported that low-dose ACTH is probably as effective as high-dose ACTH for short-term treatment of infantile spasms.12
VGB has been used in Europe since the late 1980s and in Canada since 1994 and was approved by the US Food and Drug Administration (FDA) in August 2009. VGB causes retinal toxicity in about one-third of patients. The VGB-induced retinal toxicity results in visual field constriction. The risk of this complication of VGB appears to be lower with short-term use of VGB. In children with infantile spasms being treated with VGB, the risk of retinal toxicity begins to increase after 6 months of chronic administration. This has led to an FDA black box warning in the United States for potential permanent visual impairment, where VGB currently is available only through the Lundbeck, Inc. Vigabatrin Risk Evaluation and Mitigation Strategy (REMS) Program. The Vigabatrin REMS Program is a single shared REMS program for all vigabatrin products, replacing the Sabril REMs program, and is required by the FDA because of the risk of developing vision loss with the use of vigabatrin. Lundbeck’s SHAREPlus program provides reimbursement assistance for eligible patients, a Patient Assistance Program for qualified uninsured individuals, and support for vision testing.
Baseline visual field testing or, in the case of infants, electroretinography (ERG), should be done before initiation of treatment and regularly thereafter to monitor for retinal toxicity. The initial dose of VGB is 50 mg/kg which is rapidly titrated up to 150 mg/kg divided twice a day. In order to minimize the risk of retinal toxicity, VGB should be given for no longer than 6 months.
Other medical treatments that have been used in infantile spasms include zonisamide, topiramate, valproic acid, nitrazepam, levetiracetam, pyridoxine, sulthiame, ketogenic diet, intravenous immunoglobulin, and combination therapy with ACTH and magnesium sulfate. However, the 2012 updated guideline concluded that the evidence is insufficient to recommend therapies other than ACTH and VGB for the short-term treatment of infantile spasms.12