The underlying etiology of infantile spasms (West syndrome): Information from the International Collaborative Infantile Spasms Study (<scp>ICISS</scp>)

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>To determine the underlying etiologies in a contemporary cohort of infants with infantile spasms and to examine response to treatment.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Identification of the underlying etiology and response to treatment in 377 infants enrolled in a clinical trial of the treatment of infantile spasms between 2007 and 2014 using a systematic review of history, examination, and investigations. They were classified using the pediatric adaptation of International Classification of Diseases, Tenth Revision (<jats:styled-content style="fixed-case">ICD</jats:styled-content>‐10).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total of 219 of 377 (58%) had a proven etiology, of whom 128 (58%) responded, 58 of 108 (54%) were allocated hormonal treatment, and 70 of 111 (63%) had combination therapy. Fourteen of 17 (82%, 95% <jats:styled-content style="fixed-case">confidence interval [CI]</jats:styled-content> 59% to 94%) infants with stroke and infarct responded (compared to 114 of 202 for the rest of the proven etiology group (56%, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 48% to 62%, chi‐square 4.3, <jats:italic>P</jats:italic> = .037): the better response remains when treatment allocation and lead time are taken into account (odds ratio 5.1, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 1.1 to 23.6, <jats:italic>P</jats:italic> = .037). Twenty of 37 (54%, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 38% to 70%) infants with Down syndrome had cessation of spasms compared to 108 of 182 (59%, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 52% to 66%, chi‐square 0.35, <jats:italic>P</jats:italic> = .55) for the rest of the proven etiology group. The lack of a significant difference remains after taking treatment modality and lead‐time into account (odds ratio 0.8, 95% <jats:styled-content style="fixed-case">CI</jats:styled-content> 0.4 to 1.7, <jats:italic>P</jats:italic> = .62). In Down syndrome infants, treatment modality did not appear to affect response: 11 of 20 (55%) allocated hormonal therapy responded, compared to 9 of 17 (53%) allocated combination therapy.</jats:p></jats:sec><jats:sec><jats:title>Significance</jats:title><jats:p>This classification allows easy comparison with other classifications and with our earlier reports. Stroke and infarct have a better outcome than other etiologies, whereas Down syndrome might not respond to the addition of vigabatrin to hormonal treatment.</jats:p></jats:sec>