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Aim: we aimed to investigate the relationship between movement disorders, changes on brain magnetic resonance imaging (MRI), and vigabatrin therapy in children with infantile spasms. Method: retrospective review and brain MRI analysis of children enrolled in the International Collaborative Infantile Spasms Study (ICISS) who developed a movement disorder on vigabatrin therapy. Comparisons were made with controls within ICISS who had no movement disorder. Results: ten of 124 infants had a movement disorder and in eight it had developed on vigabatrin therapy. Two had a movement disorder that resolved on dose-reduction of vigabatrin, one had improvement on withdrawing vigabatrin, two had resolution without any dose change, and in three it persisted despite vigabatrin withdrawal. The typical brain MRI changes associated with vigabatrin therapy were noted in two infants. Ten control infants were identified. Typical MRI changes noted with vigabatrin were noted in three controls. Interpretation: it is possible that in two out of eight cases, vigabatrin was associated with the development of a movement disorder. In six out of eight cases a causal relationship was less plausible. The majority of infants treated with vigabatrin did not develop a movement disorder. MRI changes associated with vigabatrin do not appear to be specifically related to the movement disorder

Summary Purpose: Infantile spasms is a severe infantile seizure disorder. Several factors affect developmental outcome, especially the underlying etiology of the spasms. Treatment also affects outcome. Both age at onset of spasms and lead time to treatment (the time from onset of spasms to start of treatment) may be important. We investigated these factors. Methods: Developmental assessment using Vineland Adaptive Behaviour Scales (VABS) at 4 years of age in infants enrolled in the United Kingdom Infantile Spasms Study. Date of or age at onset of spasms was obtained prospectively. Lead time to treatment was then categorized into five categories. The effects of lead time to treatment, age of onset of spasms, etiology, and treatment on developmental outcome were investigated using multiple linear regression. Key Findings: Age of onset ranged (77 infants) from 2 months in 21 and not known in 6. Each month of reduction in age at onset of spasms was associated with a 3.1 [95% confidence interval (CI) 0.64–5.5, p = 0.03] decrease, and each increase in category of lead time duration associated with a 3.9 (95% CI 7.3–0.4, p = 0.014) decrease in VABS, respectively. There was a significant interaction between treatment allocation and etiology with the benefit in VABS in those allocated steroid therapy being in children with no identified etiology (coefficient 29.9, p = 0.004). Significance: Both prompt diagnosis and prompt treatment of infantile spasms may help prevent subsequent developmental delay. Younger infants may be more at risk from the epileptic encephalopathy than older infants.

Purpose: To examine the underlying etiology of infantile spasms from the United Kingdom Infantile Spasms Study (UKISS), using the pediatric adaptation of ICD 10. Methods:?Infants were enrolled in a randomized controlled trial or a parallel epidemiologic study. Etiological information included history, examination, and investigations. The infants were classified as proven etiology, if a neurologic disease was identified; as no identified etiology, if no neurologic disease was identified; and as not fully investigated, if a major piece of information was missing. Proven etiology was subclassified using the pediatric adaptation of ICD 10. The results were then examined to identify further methods of classification. Results: Of 207 infants, 127 (61%) had proven etiology, 68 (33%) had no identified etiology, and 12 (6%) were not fully investigated. Etiologies were prenatal in 63, perinatal in 38, postnatal in 8, and 18 other. The most common etiologies were: hypoxic–ischemic encephalopathy (HIE) 21 (10%), chromosomal 16 (8%), malformations 16 (8%), stroke 16 (8%), tuberous sclerosis complex (TSC) 15 (7%), and periventricular leukomalacia or hemorrhage 11 (5%). The remaining 32 etiologies were all individually uncommon. Response to treatment is given for individual etiologies. Discussion:?Our method of classification allows the reporting of results by individual diseases, disease groups, or categories and is structured and clear. It avoids the use of poorly defined terms such as symptomatic and cryptogenic. It can adapt to new neurologic diseases, such as gene defects, and can be used for comparison of different groups of infants, thereby aiding meta-analysis.

Background Infantile spasms (West's Syndrome) is a syndrome that includes a peculiar type of epileptic seizure—the spasms—and an electroencephalographic (EEG) abnormality often called hypsarrhythmia. Psychomotor retardation is frequently found at follow-up. Approximately two-thirds of affected infants will have a detectable underlying neurological abnormality, but still little is known about the pathophysiological basis for infantile spasms, and treatment remains problematic. Objectives To compare the effects of single pharmaceutical therapies used to treat infantile spasms in terms of control of the spasms, resolution of the EEG, relapse rates, psychomotor development, subsequent epilepsy, side effects, and mortality. Search methods To identify published data, we searched the Cochrane Epilepsy Group Specialised Register (October 2012), CENTRAL (The Cochrane Library 2012, Issue 9), MEDLINE (1946 to September Week 4, 2012), EMBASE (1980 to March 2003), and the reference lists of all retrieved articles. To identify unpublished data, we searched the ISRCTN Register (www.controlled-trials.com), corresponded with colleagues and drug companies, and made requests at international conferences. Selection criteria All randomised controlled trials (RCTs) of the administration of drug therapy to patients with infantile spasms. Data collection and analysis Data collection from all relevant publications was independently undertaken by three review authors (before 2010) or by two review authors using a standard proforma. Analysis included assessment of study quality and a search for sources of heterogeneity. Main results We found 16 small RCTs (fewer than 100 patients enrolled) and 2 larger RCTs (more than 100 patients enrolled). These 18 studies looked at a total of 916 patients treated with a total of 12 different pharmaceutical agents. Overall methodology of the studies was poor, in part because of ethical dilemmas such as giving placebo injections to children. Two studies showed that placebo was not as good as active treatment in resolving the spasms. The strongest evidence suggested that hormonal treatment (prednisolone or tetracosactide depot) leads to resolution of spasms faster and in more infants than does vigabatrin. Responses without subsequent relapse may be no different. The same study suggests that hormonal treatments might improve the long-term developmental outcome compared with vigabatrin in infants not found to have an underlying cause for their infantile spasms. Authors' conclusions To date, few well-designed RCTs have considered the treatment of infantile spasms, and the numbers of patients enrolled have been small. In the majority, methodology has been poor, hence it is not clear which treatment is optimal in the treatment of this epilepsy syndrome. Hormonal treatment resolves spasms in more infants than vigabatrin, but this may or may not translate into better long-term outcomes. If prednisolone or vigabatrin is used, high dosage is recommended. Vigabatrin may be the treatment of choice in tuberous sclerosis. Resolution of the EEG features may be important, but this has not been proven. Further research using large studies with robust methodology is required.