Objective: Epalrestat, an aldose reductase inhibitor increases phosphomannomutase (PMM) enzyme activity in a PMM2-congenital disorders of glycosylation (CDG) worm model. Epalrestat also decreases sorbitol level in diabetic neuropathy. We evaluated the genetic, biochemical, and clinical characteristics, including the Nijmegen Progression CDG Rating Scale (NPCRS), urine polyol levels and fibroblast glycoproteomics in patients with PMM2-CDG. Methods: We performed PMM enzyme measurements, multiplexed proteomics, and glycoproteomics in PMM2-deficient fibroblasts before and after epalrestat treatment. Safety and efficacy of 0.8 mg/kg/day oral epalrestat were studied in a child with PMM2-CDG for 12 months. Results: PMM enzyme activity increased post-epalrestat treatment. Compared with controls, 24% of glycopeptides had reduced abundance in PMM2-deficient fibroblasts, 46% of which improved upon treatment. Total protein Nglycosylation improved upon epalrestat treatment bringing overall glycosylation toward the control fibroblasts' glycosylation profile. Sorbitol levels were increased in the urine of 74% of patients with PMM2-CDG and correlated with the presence of peripheral neuropathy, and CDG severity rating scale. In the child with PMM2-CDG on epalrestat treatment, ataxia scores improved together with significant growth improvement. Urinary sorbitol levels nearly normalized in 3 months and blood transferrin glycosylation normalized in 6 months.

Background: Opsoclonus myoclonus syndrome (OMS) is a neuroinflammatory disorder. Indian literature on its clinical profile and outcome is sparse. Objectives: The objective of this study is to describe the clinical profile and analyze outcomes and prognostic predictors in a cohort of children with OMS. Materials and Methods: This was a retrospective study of children with OMS between 2007 and 2017. Results: Twenty-two children were included in the study. The mean age at onset of symptom was 20.9 months (standard deviation [SD]: 7.5). The mean duration of delay in diagnosis was 8.4 months (SD 1.26) with acute cerebellitis being the most common misdiagnosis. Eleven children (50%) were diagnosed with tumor during evaluation and follow-up and 11 children (50%) belonged to idiopathic/postinfectious group. Magnetic resonance imaging brain was normal in all children except for one revealing cerebellar atrophy on follow-up. One child in the paraneoplastic group (neuroblastoma) had a positive PNMA2/Ta onconeural antibody. Children in the tumor group had an earlier age of onset (mean 15.5 vs. 26.3 months), shorter time to onset of opsoclonus from initial symptom (2.54 vs. 7.27 weeks), and higher severity score at presentation (13.7 vs. 11.3) compared to the nontumor group. Children in the nontumor group attained their first remission with treatment earlier (10.9 weeks, SD: 4.5) than the children with tumor (18.72 weeks, SD: 5.8). There was no significant difference in the outcome between the groups. Children with multiple relapses (>3) and late surgical intervention for tumor (>6 months after symptom onset) had a poor outcome. Discussion: A high index of suspicion coupled with early diagnosis and periodic tumor surveillance (even in the initially negative cases) along with aggressive combined multimechanistic immunotherapies is the key in improving outcomes. Conclusion: A high index of suspicion in appropriate clinical circumstances and early aggressive immunomodulation might lead to a better outcome.

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Context: Neurometabolic disorders form an important group of potentially treatable diseases. It is important to recognize the clinical phenotype and characteristic imaging patterns to make an early diagnosis and initiate appropriate treatment. L-2-hydroxy glutaric aciduria (L2HGA) is a rare organic aciduria with a consistent and highly characteristic imaging pattern, which clinches the diagnosis in most cases. Aims: The study aims to describe the clinical profile, magnetic resonance imaging (MRI) patterns, and outcome in a cohort of children with L2HGA and to assess the clinicoradiological correlation. Materials and Methods: This is a retrospective descriptive study done at the Department of Radiodiagnosis and Neurological Sciences of our institution. Clinical and radiological findings of children diagnosed with L2HGA over an 8-year period (2010–2017) were collected and analyzed. Descriptive statistical analysis of clinical and imaging data was performed. Results: There were six girls and four boys. A total of 14 MRI brain studies in 10 patients with the diagnosis were analyzed. MRI of all patients showed a similar pattern with extensive confluent subcortical white-matter signal changes with symmetrical involvement of dentate nuclei and basal ganglia. In two children who presented with acute decompensation, there was asymmetric cortical involvement and restricted diffusion, which are previously unreported. There was no significant correlation between the radiological pattern with the disease duration, clinical features, or course of the disease. Conclusion: MRI findings in L2HGA are highly consistent and diagnostic, which helps in early diagnosis, particularly in resource-constraint settings, where detailed metabolic workup is not possible. The article also describes novel clinical radiological profile of acute encephalopathic clinical presentation.

Context: Krabbe disease shows considerable heterogeneity in clinical features and disease progression. Imaging phenotypes are equally heterogeneous but show distinct age-based patterns. It is important for radiologists to be familiar with the imaging spectrum to substantially contribute toward early diagnosis, prognostication, and therapeutic decisions. Aims: The study aims to describe different magnetic resonance imaging (MRI) patterns observed in a cohort of children with Krabbe disease and to assess correlation with age-based clinical phenotypes. Materials and Methods: This is a retrospective descriptive study done at the Departments of Radiodiagnosis and Neurological Sciences of our institution, a tertiary care hospital in Southern India. Imaging features of children diagnosed with Krabbe disease over a 10-year period (2009–2018) were collected and analyzed. Results: A total of 38 MRI brain studies from 27 patients were analyzed. Four distinct MRI patterns were recognizable among the different clinical subtypes. All patients from the early and late infantile group showed deep cerebral and cerebellar white matter and dentate hilum involvement. Optic nerve thickening was, however, more common in the former group. Adult-onset subtype showed isolated involvement of corticospinal tract, posterior periventricular white matter, and callosal splenium with the absence of other supra- and infra-tentorial findings. Juvenile subgroup showed heterogeneous mixed pattern with 78% showing adult subtype pattern and 22% showing patchy involvement of deep cerebral white matter with dentate hilum signal changes. Conclusion: Krabbe disease shows distinct imaging features which correspond to different clinical age-based subtypes. This article reemphasizes these distinct imaging phenotypes, highlights a novel imaging appearance in juvenile Krabbe, and also alludes to the rare variant of saposin deficiency. Awareness of these patterns is essential in suggesting the appropriate diagnosis and guiding conclusive diagnostic workup. Large multicenter longitudinal studies are needed to further define the role of imaging in predicting the clinical course and thus to guide therapeutic options.