Background Pediatric tuberculous meningitis (TBM) commonly causes death or disability. . In adults, high-dose rifampicin may reduce mortality. Fluoroquinolones’ role remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods TBM-KIDS (NCT02958709) was a Phase II open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (a) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, Arm 1); (b) high-dose rifampicin and levofloxacin (R30HZL, Arm 2); or (c) standard-dose rifampicin and ethambutol (R15HZE, Arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results Of 2487 children pre-screened, 79 were screened, and 37 enrolled. Median age was 72 months. 49%, 43%, and 8% had Stage I, II, and III disease. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in Arms 1, 2, and 3, with one death (Arm 1) and six early treatment discontinuations (4 in Arm 1, 1 each in Arms 2 and 3). By Week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in Arm 1 than Arm 3 in fine motor, receptive language, and expressive language domains (p<0.01). Conclusions In a pediatric TBM trial, functional outcomes were excellent overall. The trend towards higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial.

Context: A significant subset of autistic children exhibit abnormal isolated epileptiform discharges (IEDs) in the absence of clinical epilepsy. The etiological significance of such IEDs is under much debate. Aims: The aim is to study the relationship between IEDs with risk factors, clinical severity, behavioral problems, and social-quotient and follow-up for the occurrence of new seizures. Settings and Design: This study was a prospective double-blind comparative study of autistic children with and without IEDs. Subjects and Methods: All autistic children attending Child Psychiatry Department of tertiary care postgraduate teaching hospital in April 2013 were included in the study. Electroencephalography, risk factors, and clinical severity were assessed. The same cohort of 72 children was followed for 2 years and reassessed. Statistical Analysis Used: Independent sample t -test, Chi-square test, Pearson correlation, and linear by linear association were the statistical methods used. Results: Twenty-four (42%) of the followed up sample exhibited IEDs. 10.52% had converted to clinical seizures within the follow-up period. While there was no difference between risk factors and age at diagnosis between the IED and non-IED groups, there was a significant difference between disease severity, behavioral problems and social quotient between the groups. Conclusions: IED in a subgroup of autistic children point to more severe illness, severe behavioral problems, and severe social impairment over a 2-year follow-up period. Can IED be considered a neurobehavioral endophenotype in autism?

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