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BRAT1 biallelic variants are associated with rigidity and multifocal seizure syndrome, lethal neonatal (RMFSL), and neurodevelopmental disorder associating cerebellar atrophy with or without seizures syndrome (NEDCAS). To date, forty individuals have been reported in the literature. We collected clinical and molecular data from 57 additional cases allowing us to study a large cohort of 97 individuals and draw phenotype-genotype correlations. Fifty-nine individuals presented with BRAT1-related RMFSL phenotype. Most of them had no psychomotor acquisition (100%), epilepsy (100%), microcephaly (91%), limb rigidity (93%), and died prematurely (93%). Thirty-eight individuals presented a non-lethal phenotype of BRAT1-related NEDCAS phenotype. Seventy-six percent of the patients in this group were able to walk and 68% were able to say at least a few words. Most of them had cerebellar ataxia (82%), axial hypotonia (79%) and cerebellar atrophy (100%). Genotype-phenotype correlations in our cohort revealed that biallelic nonsense, frameshift or inframe deletion/insertion variants result in the severe BRAT1-related RMFSL phenotype (46/46; 100%). In contrast, genotypes with at least one missense were more likely associated with NEDCAS (28/34; 82%). The phenotype of patients carrying splice variants was variable: 41% presented with RMFSL (7/17) and 59% with NEDCAS (10/17).

Aim: Diabetes is a chronic progressive disease. A healthy eating pattern is essential to achieve good glycemic control (HbA1c 7%) which aids in delaying and preventing diabetes-related complications. The pivotal role of diet, a modifiable risk factor for type 2 diabetes has not been understood completely especially in India where carbohydrate consumption is high. This study, therefore, aims to identify major dietary patterns associated with uncontrolled diabetes by using data reduction methods. Objective: To study and compare the association of dietary patterns with elevated HbA1c among known diabetic adults using three data reduction methods (principal component analysis (PCA), reduced rank regression (RRR), and partial least-squares (PLS) regression). Materials and Methods: The Chennai Urban Rural Epidemiological followed up study (CURES) was completed in 2410 adults. Adults with diabetes (both genders, aged >20years), 573 were selected for the present analysis. Dietary intake was assessed using food frequency questionnaire. Results: The PCA derived the non-vegetarian and vegetarian pattern. Both showed positive association with the risk of high HbA1c. The first pattern of RRR and PLS showed a positive association with many foods especially those contributing to increased intakes of total calories. Whereas the 2nd pattern of RRR and PLS scores both showed an inverse association with HbA1c especially with the reduction in rice-based recipes and total calories. Conclusions: The low intake of certain foods, especially white rice, directly decreased the total calories, total carbohydrate, glycemic load, and glycemic index which has a beneficial effect on glycemic control among those with diabetes.

Background: Asian Indians are culturally different and have diverse dietary and culinary habits. Further, there are potential biological differences in metabolism due to genetic or cultural factors. This warrants the development of a unique population-specific food-based diet score for prevention of noncommunicable disorders. Materials and Methods: Dietary intake was assessed using a validated food frequency questionnaire in 1033 adults who participated in the 10-year follow-up study of Chennai Urban Rural Epidemiological Study (CURES). The diet score was developed considering eight food groups and one major cooking oil that were either significantly associated with a higher or lower risk of incident type 2 diabetes (T2D). The foods that showed a protective effect was assigned higher scores and vice versa for foods that increased the risk of diabetes assigned the lower. We further assessed the effect of Indian Diet Quality score (IDQS) and three popular diet quality indices: the Healthy Eating Index-2015 (HEI), the Dietary Approach to Stop Hypertension (DASH), and Diabetes Diet Score (DDS) in relation to the risk of incidence of diabetes among Indian population. Results: Higher IDQS is associated with a significant lower risk of diabetes incidence; however, no such significant association was observed with diet quality indices (DASH, HEI-2015, and DDS) and diabetes incidence. This warrants the need for population-specific diet score for Indians. Conclusion: Higher IDQS was associated with a lower risk of T2D among South Indian adults. Thus, IDQS can be a suitable tool to identify the diet–disease relationship especially in a population with diverse dietary intakes.

This study aimed to investigate the trajectories over time of health status and health service use in Rett syndrome by mutation type. Data were obtained from questionnaires administered over 6 years to 256 participants from the Australian Rett Syndrome Database. Health status (episodes of illness and medication load) and health service use (general practitioner and specialist visits and hospital stays) were summarized into composite scores with principal component analysis. Linear and mixed regression models examined effects of mutation type and other variables on these scores over time. For some mutations (such as p.R255X and p.R168X) health status was poorer at a younger age and improved over time, while for p.R133C it was better at a younger age and deteriorated with time. For those with p.R133C health service use was lowest at a younger age and highest at 25 years. With other mutations, such as p.R255X, p.R270X, p.R294X, C terminal and p.R306C, health service use was higher at a younger age, but dropped off considerably by 25 years of age. Health service use generally declined in parallel with deterioration in health status, although this pattern differed by mutation type, demonstrating important variability in the course of Rett syndrome. (Contains 3 tables and 3 figures.)

Continuous conventional video-electroencephalography (cVEEG), the gold standard, is not routinely available for monitoring neonatal seizures in Australia. Therefore, seizures are monitored with clinical observation and amplitude-integrated electroencephalography (aEEG), which may result in under- or over-treatment with antiseizure medications (ASMs). We aimed to investigate ASM usage and its relation to the "cVEEG-confirmed seizures" (cVEEG seizures) in the at-risk infants admitted to a tertiary referral neonatal intensive care unit (NICU). The study was a part of a diagnostic study comparing cVEEG with aEEG for the detection of neonatal seizures. Thirty-six infants ≥35 weeks gestational age and at risk of seizures and admitted to NICU were recruited after informed parental consent. The infants were monitored and treated with ASMs based on clinical observation and aEEG findings. A simultaneous cVEEG, not available for clinical decision making, was recorded for 24-h and interpreted at a later date. Data regarding ASM usage and seizure burden on cVEEG were collected. Spearman's Rho coefficient was used to assess the correlation between the number of doses of ASMs administered and seizure burden on cVEEG. cVEEG recordings of 35 infants were available for analysis. The gestational age of the infants ranged from 36 to 42 weeks, and the most common diagnosis was hypoxic-ischemic encephalopathy. Twelve infants received ASMs during the 24-h study period, of which five (42%) did not have cVEEG seizures. Maximum cVEEG seizure burden was 8.3 h, and maximum number of ASMs used was three. The correlation between the number of doses of ASMs administered in an infant and the seizure burden on cVEEG was low (Spearman's Rho: 0.44; p =.148). Treatment of neonatal seizures based on clinical observation and aEEG, without cVEEG, results in unnecessary or inadequate exposure to ASMs for many infants. [ABSTRACT FROM AUTHOR]

This is a case series of six children with unilateral cerebral palsy and hemispheric encephaloclastic lesions who were evaluated for epilepsy surgery. Seizure onset was in the neonatal period in three children, at 17 months in two, and at 5 years in one. Their ictal and interictal electroencephalogram (EEG) abnormalities showed paradoxical lateralization to the incorrect/'normal' hemisphere or showed bilateral abnormalities. After cautious discussion regarding the discordant electroclinical profile and implications for outcome, they proceeded to a functional hemispherectomy (between ages 4–11y) with good outcomes (at 1–10y follow‐up). Their clinical details, EEG findings, electrocorticography, neuroimaging, and histology are reported. Possible surgical candidacy should be evaluated early in children with refractory epilepsy, even those with complex profiles and discordant data from the different investigations. Contralateral or bilateral EEG abnormalities should not preclude consideration of hemispherectomy in children with refractory epilepsy, hemiparesis, and uniclastic lesions. This case series is commented by Rydenhag on page 285 of this issue. [ABSTRACT FROM AUTHOR]

Aim: Diabetes is a chronic progressive disease. A healthy eating pattern is essential to achieve good glycemic control (HbA1c 7%) which aids in delaying and preventing diabetes-related complications. The pivotal role of diet, a modifiable risk factor for type 2 diabetes has not been understood completely especially in India where carbohydrate consumption is high. This study, therefore, aims to identify major dietary patterns associated with uncontrolled diabetes by using data reduction methods. Objective: To study and compare the association of dietary patterns with elevated HbA1c among known diabetic adults using three data reduction methods (principal component analysis (PCA), reduced rank regression (RRR), and partial least-squares (PLS) regression). Materials and Methods: The Chennai Urban Rural Epidemiological followed up study (CURES) was completed in 2410 adults. Adults with diabetes (both genders, aged >20years), 573 were selected for the present analysis. Dietary intake was assessed using food frequency questionnaire. Results: The PCA derived the non-vegetarian and vegetarian pattern. Both showed positive association with the risk of high HbA1c. The first pattern of RRR and PLS showed a positive association with many foods especially those contributing to increased intakes of total calories. Whereas the 2nd pattern of RRR and PLS scores both showed an inverse association with HbA1c especially with the reduction in rice-based recipes and total calories. Conclusions: The low intake of certain foods, especially white rice, directly decreased the total calories, total carbohydrate, glycemic load, and glycemic index which has a beneficial effect on glycemic control among those with diabetes. [ABSTRACT FROM AUTHOR]

Neonatal seizures are frequent but underdiagnosed manifestations of acute brain dysfunction and an important contributor to unfavorable outcomes. Etiology and severity of brain injury are the single strongest outcome determinants. The authors will discuss the prognostic role of acute symptomatic seizures versus brain injury and the main neuroprotective and neurorestorative strategies for full-term and preterm infants. Prolonged acute symptomatic seizures likely contribute to long-term outcomes by independently adding further brain injury to initial insults. Correct timing and dosing of therapeutic interventions, depending on etiology and gestational ages, need careful evaluation. Although promising strategies are under study, the only standard of care is whole-body therapeutic hypothermia in full-term newborns with hypoxic-ischemic encephalopathy. [ABSTRACT FROM AUTHOR]