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A 9-month-old male child, born of second-degree consanguinity, presented with a progressively enlarging head since early infancy. The child had normal early development, but further acquisition of milestones after 6 months was delayed. He had afebrile seizures at 9 months, followed by the appearance of appendicular spasticity. First magnetic resonance imaging (MRI) showed nonenhancing, diffuse, bilaterally symmetrical T1/fluid-attenuated inversion recovery (FLAIR) hypointensity and T2 hyperintensity of the cerebral white matter and anterior temporal cysts. Subsequently, the periventricular and deep white matter developed microcystic changes with a pattern of radial stripes. Next-generation sequencing revealed homozygous autosomal recessive variations in the MLC1 gene [c.188T > G, (p.Leu63Arg)] on exon 3 and also in the EIF2B3 gene [c.674G > A, (p.Arg225Gln)] on exon 7, the parents being heterozygous carriers for both variations. This article highlights the rare occurrence of two leukodystrophies of diverse pathogenesis in a child from a nonpredisposed community.

Objective Our objective was to describe the clinicodemographic, laboratory, and outcome profiles of a rare phenotype of pediatric acute encephalitis syndrome (AES) with acute fulminant cerebral edema (AFCE) and compare them with that of AES without AFCE.Methods We retrospectively analyzed medical records of a cluster of children hospitalized with encephalitis between June 1, 2021 and December 31, 2021. Their clinical and demographic features, laboratory investigations (hematological, biochemical, serological, microbiological, radiological, and electrophysiological tests), and follow-up data up to 3 months postdischarge were recorded. Patients with AFCE and those without it were divided into groups A and B, respectively, and their characteristics were compared.Results There were 11 and 15 patients in groups A and B, respectively. There were no significant differences between the two groups in terms of sex, neurological status at admission, hematological and cerebrospinal fluid values, pediatric intensive care unit (PICU) course, and management, etiological identification, and mortality and disabilities at discharge. Patients having reversal or having white cerebellar signs did not significantly differ in their outcomes. However, the patients in group A had significantly lower age, higher incidence of abnormal findings on head computed tomography scans at admission, longer duration of hospitalization, and neurological sequelae at 3 months. The numbers of patients with identified etiologies were zero in group A but five in group B (two Japanese encephalitis, two scrub typhus, and one dengue). Patients of group A had bilateral asymmetric temporal-parieto-occipital T2 hyperintense lesions in magnetic resonance imaging, whereas patients of group B had bifrontal predominant or thalamo-mesencephalic lesions. Multifocal epileptiform discharges were seen in electroencephalogram in both groups, which reverted to normal in 9 and 46% in groups A and B at 3 months, respectively.Conclusion Younger age is a significant risk factor for the development of AFCE in pediatric AES. AFCE patients have worse outcomes at 3 months, although they do not significantly differ from their non-AFCE counterparts at discharge. When occurring in clusters, AFCE patients exhibit the same radiological and electroencephalographic features.

A 2.5-year-old girl child patient with moderate malnutrition presented with right forehead abscess followed by ipsilateral orbital cellulitis. She also developed a left hydropneumothorax within a week. Subsequently she had left focal onset seizures with secondary generalized status epilepticus followed by development of left hemiparesis. Neuroimaging showed infarcts of varying ages in the right cerebral hemisphere and basal ganglia. Angiography revealed right internal carotid artery pseudoaneurysm. Blood and pus cultures grew methicillin-resistant Staphylococcus aureus (MRSA). Investigations for immunodeficiency were negative. The patient received vancomycin intravenously for 6 weeks and intercostal tube drainage for hydropneumothorax. She was discharged with an antiepileptic drug and aspirin. There was complete resolution of the orbital cellulitis and hydropneumothorax and also the pseudoaneurysm on follow-up angiography 3 months later.

A 1.5-year-old boy presented to us with a history of normal growth and developmental parameters until 6 months of age. However, at 7 months of age, he developed multiple types of seizures consisting initially of complex febrile seizures, followed by afebrile seizures. Multifocal clonic, generalized tonic–clonic, and myoclonic (multifocal and generalized) were the evolving seizure types. He had truncal hypotonia, but his appendicular hypotonia progressed to hypertonia over the next few months and further to decorticate posturing. Brain magnetic resonance imaging (MRI) showed generalized atrophy, predominantly frontotemporal, without any focal signal abnormalities or contrast enhancement. Computed tomography (CT) showed speckled calcification in subcortical white matter. Electroencephalogram showed bilateral frontotemporal epileptiform discharges with secondary generalization. His cerebrospinal fluid had normal cytology and biochemical results but was positive for anti–gamma aminobutyric acid B antibodies. Whole exome sequencing showed likely pathogenic, novel autosomal recessive homozygous variation of NRROS gene on chromosome 3 [c.1487G > A (p.Trp496Ter)], which impairs the functioning of anti-inflammatory cytokine transforming growth factor beta, resulting in a proinflammatory state within the central nervous system and thereby promoting autoimmune encephalitis. Parental Sanger sequencing validated the variation in both his parents. He was treated with both pulse methylprednisolone (30 mg/kg/day for 5 days) and intravenous immunoglobulin (2 g/kg), followed by slowly tapering of oral prednisolone and monthly intravenous immunoglobulin infusion (1 g/kg). There was significant reduction in seizure frequency and disappearance of epileptiform discharges from the electroencephalogram. However, the motor and cognitive improvement did not occur, and he had microcephaly and growth failure at the last follow-up. This is the 11th case report of neurodegeneration associated with NRROS gene variations, but the first report of autoimmune encephalitis being triggered by the variation in a child.

A 2.5-month-old infant with global developmental delay, initially had generalized tonic spasms followed by appearance of infantile spasms from 4.5 months of age. Thus, he had evolution from early infantile developmental and epileptic encephalopathy (EIDEE) to infantile epileptic spasm syndrome (IESS). Neuroimaging and screening of inborn errors of metabolism were normal, but sleep electroencephalogram showed suppression-burst pattern. Treatment with intramuscular injections of adrenocorticotropic hormone (ACTH) was associated with significant control of infantile spasms, but was followed by development of right hemichoreiform movements 2 days later. Upon continuing ACTH treatment, the dyskinesia generalized, prompting us to stop it and shift to vigabatrin which resulted in partial control of his spasms. Whole-exome sequencing revealed an autosomal dominant heterozygous variation of uncertain significance in the NPRL3 gene. At 6 months of age, he suffered of a probable sudden unexpected death, without any notable illness. The case is unique because both the phenomena—ACTH-induced dyskinesia and probable sudden unexpected death in infancy—are rarely described in the EIDEE-IESS continuum.

Multisystem inflammatory syndrome in children (MIS-C) is a hyperinflammatory process leading to multiorgan failure and shock, occurring during the acute or post-infectious stage of severe acute respiratory syndrome coronavirus (SARS-CoV-2), and has two subtypes: para-infectious and post-infectious varieties. The new onset of refractory status epilepticus has rarely been described as the presenting feature of MIS-C. This retrospective study, conducted at Dr. B.C. Roy Post Graduate Institute of Pediatric Sciences, included children hospitalized between August 1, 2020 and July 31, 2021, with new-onset refractory status epilepticus (NORSE) and subsequently diagnosed to have MIS-C. Their clinico-demographic variables, treatment courses during hospital stays, laboratory reports, radiological and electrophysiological findings, and outcomes at discharge and follow-up over 1 year were recorded. At their 12 month visits, their motor disabilities (primary) and continuation of anti-epileptic drugs, and persistence of magnetic resonance imaging (MRI) brain abnormalities (secondary) were the outcome measures. The characteristics of the patients in the para-infectious and post-infectious groups were compared using the Mann-Whitney U test for continuous variables and the Chi-square test for categorical variables. There were eight and 10 patients in groups A and B, respectively. Patients in group B had significantly higher age, more prolonged refractory status epilepticus (RSE), use of anesthetics and ventilation, and longer pediatric intensive care unit (PICU) stay, while other clinical and laboratory parameters and short and long-term outcomes were not significantly different between the two groups. Eight patients developed hemiparesis, while two had quadriparesis in the acute stage, but 15 (83%) patients had complete recovery from their motor deficits by 1 year. At 1-year follow-up, 33 and 39% of patients, respectively, had abnormal MRI and electroencephalogram (EEG). Acute disseminated encephalitis and acute leukoencephalopathy were the most commonly observed MRI abnormalities in the acute phase, with prolonged persistence of cerebritis in patients in the post-infectious group, warranting long-term immunomodulation. Combined immunotherapy with intravenous immunoglobulin and steroids was effective in the acute phase. However, long-term anti-epileptic therapy was needed in both groups.

A 9-year-old girl presented with asymmetric abnormal twisting movements affecting her left side more than the right side, initially action induced, but later persistent. Examination revealed generalized persistent dystonia with choreoathetosis and right partial tonic ocular tilt reaction. Brain magnetic resonance imaging showed T1 and T2 fluid-attenuated inversion recovery (FLAIR) hypointense and T2 hyperintense signal changes in bilateral globus pallidi. Clinical exome sequencing revealed compound heterozygous variatnts in enoyl-CoA hydratase-1 (ECHS1) gene: a novel pathogenic variant in exon 6, chr10:g.133366045G > A (p.Gln224Ter) and a likely pathogenic variant in exon 5, chr10:g.133366990G > A (p.Ala173Val). Metabolic testing and arterial lactate levels were normal. She was treated with valine restricted diet, trihexiphenidyl, clonazepam, N-acetyl cysteine and mitochondrial cocktail, without significant improvement over the 6 months follow-up period.

The objective of this study was to determine the effectiveness and safety of mild systemic hypothermia by selective head cooling in hospital born neonates with hypoxic-ischemic encephalopathy using low-cost CoolCap. The primary outcome was to determine whether selective head cooling reduces neonatal mortality and neurodevelopmental delay (NDD) at > 30 months of age. The secondary outcome was to determine the serious adverse effects during selective head cooling such as thrombocytopenia requiring platelets transfusion, renal and hepatic dysfunction, bradycardia, hypoglycemia, and dyselectrolytemia (hyperkalemia, hyponatremia, and hypocalcemia). This is a single-center randomized control trial. The risk ratios, risk differences, and numbers needed to treat plus 95% confidence interval (CI) were measured. This study was done at the tertiary care perinatal center. Inborn neonates with ≥ 37 completed weeks of gestation with indicators of perinatal asphyxia and moderate to severe clinical encephalopathy were randomly allocated to hypothermia (n = 30) or standard care (n = 30) groups. The neonates were subjected to mild systemic hypothermia via selective head cooling using ice caps, the target rectal temperature being 34 to 35°C for 72 hours. Therapeutic hypothermia reduced the risk of death and NDD at ≥ 30 months of age: 6 of 30 infants (20%) in the hypothermia group and 18 of 30 infants (60%) in the control group died or had a NDD at ≥ 30 months (risk ratio: 0.33 [95% CI: 0.15–0.72]; p = 0 0.0015). The mortality rate decreased, and the survival rate free of any sensorineural disability increased. The benefits were statistically significant in moderately asphyxiated infants. Adverse effects of hypothermia were minimal. Selective head cooling with mild systemic hypothermia in term asphyxiated neonates is safe and inexpensive in low-resource setting. Hypothermia showed statistically significant reduction in mortality and NDD at ≥ 30 months of age when commenced within 6 hours of birth and was not associated with serious adverse effects. The Institutional Clinical Trial Registry number is CNMC/ETHI/317/P.

Case 1: An 8-year-old girl with a prodrome of fever and headache presented with generalized tonic clonic seizures. She had florid meningeal signs. Laboratory investigations revealed elevated liver enzymes. Cerebrospinal fluid had pleocytosis and elevated protein. Immunoglobulin M antibody against hepatitis A virus (HAV) was positive in serum. She recovered without sequelae. Case 2: A 10-year-old girl with HAV infection developed progressive pancytopenia, coagulopathy, and worsening liver function. She fulfilled the 2009 diagnostic criteria of hemophagocytic lymphohistiocytosis (HLH). She had spontaneous resolution of HLH without immunosuppressive therapy. Central nervous system involvements of HAV usually resolve without sequelae. HLH following hepatitis A is being increasingly reported and may resolve spontaneously.

A 4-year-old girl presented with prolonged fever for past 1 year, pallor, hepatosplenomegaly, single lytic lesion in the left frontal bone, headache, and pneumonia. Histopathology from the lytic lesion revealed chronic osteomyelitis and magnetic resonance spectroscopy showed multiple tuberculomas in the brain. She showed improvement with antitubercular drugs.

A 7-year-old male patient with a history of recurrent abdominal pain over 1 year presented with cardiac tamponade due to massive pericardial effusion, which was percutaneously drained. Contrast-enhanced computed tomography revealed a large posterior mediastinal cyst and calcified, heterogeneous pancreatic parenchyma. Elevated amylase and lipase levels of the cyst fluid confirmed the diagnosis of pancreatic pseudocyst, which was treated with an octreotide infusion and Roux-en-Y cystojejunostomy. The child was discharged on pancreatic enzyme supplement and was asymptomatic on follow-up.

We report an unusual case of a 4-year-old girl presenting with recurrent episodes of weakness with documented hypokalemia, failure to thrive, and rachitic changes. Nerve conduction study during the episode of weakness revealed reduced compound muscle action potential amplitudes and motor conduction velocity and electromyography revealed reduced interference pattern, which normalized on correction of hypokalemia and subsequent recovery of weakness. The child was diagnosed with distal renal tubular acidosis. Ultrasound revealed medullary nephrocalcinosis, which regressed on long-term treatment with alkali and potassium supplement.

Organophosphate poisoning is common in developing countries, more so in India. A 7-year-old boy with history of ingestion of unquantified amounts of malathion, presented to the pediatric emergency of Calcutta National Medical College, Kolkata in acute cholinergic crisis. He was treated with atropine and pralidoxime. The acute cholinergic crisis persisted for four days after admission, and as it subsided, the child developed respiratory distress, bulbar palsy, cyanosis, hypoxemia and hypercarbia. A diagnosis of intermediate syndrome was made and patient needed prolonged ventilation for 21 days for type II respiratory failure. Five days after discharge, the child developed distal weakness of both lower limbs, which later involved the hands. There was associated gross sensory loss. Nerve conduction velocity study and sural nerve biopsy predominantly showed evidence of sensory-motor axonopathy with associated demyelination. The child was treated with physiotherapy, but was left with disabilities like claw hand, foot drop and the inability to walk.