Publication

Abstract : The current study depicts the poor neurodevelopmental outcome in a follow-up cohort of Indian children with WS. There was substantial attrition (to the tune of 60%) in the present study, reflecting the difficulties in long-term follow-up in resource-constrained settings. Attrition, an important aspect of WS research, is not depicted well in the previous follow-up studies from India, which evaluated children in the desired age group who continued to follow up (without mentioning the numbers of those diagnosed and treated at their center) [20, 21]. Significant loss to follow-up might be responsible for the lack of mortality data in these cross-sectional studies [20, 21]. The dearth of prospective long-term follow-up and natural history studies on WS in India might also be accountable for the nonexistence of reliable mortality statistics for WS from India. The baseline characteristics of the cohort (age at onset, long LTTT, a preponderance of male gender, and structural etiology) were comparable with the previous literature from India [12]. Most of the enrolled children belonged to the 2–5 y age group. Of the children who could be contacted for study (132/309), mortality was nearly 10% (13/132). This might not be a truly representative figure (considering the sizeable attrition), but this is comparable with the Western literature (11%–13% mortality before the age of 3 y) [4]. Nearly half of the enrolled children had a complete cessation of spasms after any of the standard therapy. The response rate was higher than the response rate to hormonal treatment in South Asia [12]. This might probably be accounted for by attrition and the fact that EEG resolution of hypsarrhythmia was not a response criterion in the current study. At the age of two, one-third of the enrolled children had attained seizure freedom for at least 3 mo. This was lower than that reported in the other two Indian cohorts (61% and 47%) since these studies analyzed epilepsy outcomes at the last follow-up (instead of a fixed age of 2 y as done in the current study) [20, 21]. Similar to Western literature, structural etiology and response to standard therapy were significant predictors of epilepsy outcome [24, 25]. In the study by Sehgal et al., LTTT < 3 mo and response to first-line therapy were found to be associated with a favorable outcome [20]. However, none of these factors was found to be associated with epilepsy outcomes in the study by Gupta et al. [21]. LTTT was not a significant predictor in the present study since there were very few children in the group with acceptable LTTT (≤ 1 mo). In the current study, approximately three-fourths of enrolled children had an SQ < 55 and were not trainable. This was similar to the Finnish study [9]. The two Indian studies used a different psychometric tool (Developmental Profile 3) for assessment with unfavorable outcome (general development score < 70) seen in nearly 90% of children, which was comparable with an SQ < 70 in 86% of children in the current study [20, 21]. Like previous studies, structural etiology and response to standard therapy were significant predictors of neurodevelopmental outcome in the present study [9, 21, 24]. None of the analyzed factors were found to affect the neurodevelopmental outcomes in the study by Sehgal et al. [20]. Although LTTT has been identified as an important predictor of neurodevelopmental outcome in various studies, the association was not significant in the present study, probably due to the reasons stated previously [3, 9, 21]. Also, there was a trend towards significance for early age at onset as a neurodevelopmental outcome predictor in the present study similar to the Finnish cohort [9]. The present study gives a real-world reflection of difficulties (specifically attrition) in long-term research on WS in developing countries. Teleneurology can be a solution to some of these difficulties and might help maintain a robust follow-up. The COVID-19 pandemic should be taken as an opportunity for infrastructure building for telehealth services, which can later be used for rigorous follow-up [26, 27]. Besides, the current study performed an objective assessment of neurodevelopmental outcomes using a validated scale in a large cohort of children with WS. Although dedicated screening and diagnostic evaluation for comorbid neurobehavioral disorders such as autism spectrum disorders could have been helpful, this could not be done. The reasons for attrition were not clear since the patients were not contactable. Conclusions WS is associated with poor epilepsy and neurodevelopmental outcomes on follow-up. The underlying etiology and response to the standard therapy are significant predictors of epilepsy and neurodevelopmental outcomes. Further large and prospective cohort studies are needed to assess the long-term outcomes and mortality in Indian children with WS.