Clinical Profile and Treatment Outcomes of Hypermanganesemia with Dystonia 1 and 2 among 27 Indian Children.

Background: Hypermanganesemia with dystonia 1 and 2 (HMNDYT1 and 2) are rare, inherited disorders of manganese transport. Objectives: We aimed to describe clinical, laboratory features, and outcomes among children with HMNDYT. Methods: We conducted a retrospective multicenter study involving tertiary centers across India. We enrolled children between 1 month to 18 years of age with genetically confirmed/clinically probable HMNDYT. Clinical, laboratory profile, genetic testing, treatment details, and outcomes scored by treating physicians on a Likert scale were recorded. Results: We enrolled 27 children (19 girls). Fourteen harbored SLC30A10 mutations; nine had SLC39A14 mutations. The SLC39A14 cohort had lower median age at onset (1.3 [interquartile range (IQR), 0.7-5.5] years) versus SLC30A10 cohort (2.0 [IQR, 1.5-5.1] years). The most frequent neurological features were dystonia (100%; n = 27), gait abnormality (77.7%; n = 21), falls (66.7%; n = 18), and parkinsonism (59.3%; n = 16). Median serum manganese (Mn) levels among SLC39A14 (44.9 [IQR, 27.3-147.7] mcg/L) cohort were higher than SLC30A10 (29.4 [17.1-42.0] mcg/L); median hemoglobin was higher in SLC30A10 (16.3 [IQR, 15.2-17.5] g/dL) versus SLC39A14 cohort (12.5 [8.8-13.2] g/dL). Hepatic involvement and polycythaemia were observed exclusively in SLC30A10 variants. A total of 26/27 children underwent chelation with disodium calcium edetate. Nine demonstrated some improvement, three stabilized, two had marked improvement, and one had normalization. Children with SLC39A14 mutations had poorer response. Two children died and nine were lost to follow-up. Conclusions: We found female predominance. Children with SLC39A14 mutations presented at younger age and responded less favorably to chelation compared to SLC30A10 mutations. There is emerging need to better define management strategies, especially in low resource settings.

Measles-rubella vaccine-associated MOG-antibody positive acute demyelinating encephalomyelitis with optic neuritis in a child.

Measles-rubella (MR) vaccine-associated encephalopathy is rare and coexistence with optic neuritis (ON) has never been reported. Only two patients (one child and one adult) had 'MR Vaccine-associated myelin-oligodendrocyte-glycoprotein antibody (MOGAb) positive encephalopathy'. Myelin oligodendrocyte glycoprotein (MOG), a surface myelin protein, is the target of the immune system in this disease. We describe a critical unique case of 'post-MR Vaccine, MOG-antibody positive Acute Disseminated Encephalo-Myelitis (ADEM) with optic neuritis', who recovered with immunotherapy.

Unusual Involvement of Basal Ganglia and Dentate Nucleus in Children with Acute Encephalopathy with COVID-19.

Children account for 1% to 5% of diagnosed COVID-19 infection with relatively mild presentation compared to adults. The frequency of neurological involvement in acute COVID-19 infection in children is unclear. COVID-19 is also considered to be a neurotropic virus, but so far, in the pediatric age group, very few cases with involvement of basal ganglia and no case of dentate nucleus involvement have been reported in the literature. The present paper reports two cases of acute encephalopathy with COVID-19, the first case with basal ganglia involvement and the second with dentate nucleus involvement. Both cases required aggressive management and had complete neurological recovery on follow-up. Hence, these cases are reported to make everyone aware of the neurological presentation with atypical neuroimaging finding of acute COVID-19 infection in the pediatric age group; timely management improves the outcome.

Identification of an individual with a SYGNAP1 pathogenic mutation in India.

Exome sequencing is a prominent tool to identify novel and deleterious mutations which could be non-sense, frameshift, and canonical splice-site mutations in a specific gene. De novo mutations in SYNGAP1, which codes for synaptic RAS-GTPase activating the protein, causes Intellectual disability (ID) and Autism Spectrum Disorder (ASD). SYNGAP1 related ASD/ID is one of the rare diseases that are detrimental to the healthy neuronal developmental and disrupts the global development of a child. We report the first SYNGAP1 heterozygous patient from Indian cohort. We report a case of a child of 2-year old with global developmental delay, microcephaly subtle dysmorphism, absence seizures, disrupted sleep, delay in learning a language, and eating problems. Upon further validation, the child has a few traits of ASD. Here, based on focused exome sequencing, we report a de novo heterozygous mutation in SYNGAP1 exon 11 with c. 1861 C > T (p.arg621ter). Currently, the child is on Atorvastatin, a RAS inhibitor, already available in the market for the treatment of hypercholesterolemia and has shown considerable improvement in global behaviour and cognitive development. The long-term follow up of the child's development would contribute to the already existing knowledge of the developmental trajectory in individuals with SYNGAP1 heterozygous mutation. In this report, we discuss the finding of a novel mutation in one of the genes, SYNGAP1, implicated in ASD/ID. Besides, we discuss the current treatment prescribed to the patient and the progress of global developmental of the child.

Emergency Surgery for Refractory Status Epilepticus.

BACKGROUND: Management of refractory status epilepticus in children is extremely challenging. CASE CHARACTERISTICS: Two children with medically refractory status epilepticus, both of whom had lesional pathology on MRI and concordant data on EEG and PET scan. INTERVENTION: Emergency hemispherotomy performed in both patients. A complete, sustained seizure freedom obtained postoperatively. MESSAGE: Emergency surgery is a treatment option in selected cases of drug refractory status epilepticus with lesional pathology and concordant data.

Partial Manifestation of Anti-NMDA-R Encephalitis with Predominant Movement Disorder.

Childhood anti-N-methyl-d-aspartate receptor (NMDA-R) antibody encephalitis is a well-recognized autoimmune encephalitis presenting typically with a combination of varied movement disorders, seizures, mutism, behavioral and sleep disturbances, and autonomic changes. Monosymptomatic or incomplete forms of the disorder are rare, but have recently been reported. Here, we describe 2 children with nonparaneoplastic anti-NMDA-R encephalitis with partial presentation in the form of movement disorder and minor behavioral changes.