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Background: The neuronal ceroid lipofuscinoses (NCL) constitute a group of gray matter neurodegenerative disorders characterized by the accumulation of ceroid lipopigment in lysosomes in neurons and other cell types. There are very few published studies on NCL from India, especially in children. Methods: A retrospective study of confirmed patients of NCL diagnosed over a period of 10 years from January 2019 to December 2019. Results: Fifty children had a definitive diagnosis of NCL based on enzymatic studies or genetic testing using next-generation sequencing. Around 15 children were diagnosed to have CLN-1 (ceroid lipofuscinoses, neuronal-1) based on palmitoyl protein thioesterase-1 deficiency; 24 children were diagnosed with CLN2 (ceroid lipofuscinoses, neuronal-2) based on deficient tripeptidyl-peptidase-1 activity; three patients were diagnosed as CLN6, five patients as CLN7, one case each of CLN8, CLN11, and CLN14 based on genetic testing. Clinical presentation was quite varied and included refractory seizures, developmental delay/regression, and abnormal movements. Visual failure was not common in the present case series. Neuroimaging patterns in different types of NCL were different. All children had a progressive downhill course resulting in death in many over a period of 5–10 years of disease onset. Conclusion: NCL is not uncommon and diagnosis can be suspected based on clinical investigations and neuroimaging findings. Diagnosis can be confirmed by enzymatic assays or genetic testing.

Objective: To study the clinico-radiological profile of children with acute leukoencephalopathy with restricted diffusion. Methods: A retrospective chart review of children with acute leukoencephalopathy with restricted diffusion was done from July 2015 to July 2018. The clinical details, neuroimaging findings, sequelae, and the final outcome on modified Rankin Score were analyzed. Results: Sixteen children with a mean age of 4.4 years were diagnosed with acute leukoencephalopathy with restricted diffusion. All, except one, had fever, seizure, and altered sensorium. The median duration of hospital stay was 3 weeks. Only one out of 16, had biphasic clinical picture that is characteristic of acute encephalopathy with biphasic seizures and restricted diffusion. Magnetic resonance imaging showed restriction diffusion in all. While it was symmetric in 13 children, in 3 children it was asymmetric, and in 2 children there was patchy involvement. Seven children (43.7%) had post-encephalopathic epilepsy. While complete neurological recovery was seen in 2 children, behavioral problems like hyperactivity in 10 (62.5%), speech problems in 8 (50%), and cognitive delay in 3 (18.8%) children were noted. Conclusion: Acute leukoencephalopathy with restricted diffusion is emerging as an important cause of acute encephalopathy in children with a protracted course and long-term sequelae such as cognitive impairment and refractory postencephalopathic epilepsy.

Nonketotic hyperglycinemia is a fatal disorder of glycine metabolism presenting with intractable epilepsy, hypotonia, and developmental delay in infancy. Diagnostic tests,such as cerebrospinal fluid glycine estimation and genetic diagnostic methods, are not widely available in developing countries and hence many cases are missed or wrongly diagnosed. The magnetic resonance imaging features, such as abnormal signal intensity in the dorsal pons, midbrain, central tegmental tract, cerebral peduncle, and posterior limb of the internal capsule indicate an important clue to the possibility of the disease and help in guiding the treating neonatologist.

Neuronal ceroid lipofuscinosis (NCL) is a group of progressive neurodegenerative disorders characterized by intracellular accumulation of ceroid lipopigments. Based on gene defect of NCL-associated proteins, 14 types of NCL have been described till date. NCL type 11 was first described in 2014 in two siblings as adult-onset NCL and was found to be due to a homozygous progranulin gene mutation. These siblings had progressive retinopathy, recurrent generalized seizures, moderate ataxia and subtle cognitive dysfunction. Palinopsia was present and MRI showed selective and severe cerebellar atrophy which was progressive with age. There have been no further reports of NCL 11 in literature. We here present a 14-year old girl born to second degree consanguineous couple who presented with gradually increasing frequency of seizures for the past 1 year without any signs of visual abnormalities and dementia. She had an elder sister who had progressive seizures and dementia from 8 years of age and died after few years. Her electroencephalogram showed frequent generalized epileptiform discharges and magnetic resonance imaging (MRI) showed pure cerebellar atrophy mainly affecting the vermis. MRI findings suggested a neurodegenerative disorder like NCL and prompted us to go for whole exome screen which revealed NCL type 11 due to homozygous mutation c.912G>A (p.Trp304Ter) in exon 9 of GRN gene (OMIM# 614706 ). To the best of our knowledge this is the third case of NCL 11 and the first from Asia.

Background SLC30A10 mutations cause an autosomal recessive disorder, characterized by hypermanganesaemia, polycythemia, early-onset dystonia, paraparesis, or late-onset parkinsonism, and chronic liver disease. This is the first identified inborn error of Mn metabolism in humans, reported in 10 families thus far. Methods Methods for this study consisted of clinical examination, neuroimaging studies (MRI), serum dosages, and SLC30A10 genetic analysis. Results We describe early disease manifestations (including videos) in 5 previously unreported Indian children, carrying novel homozygous SLC30A10 mutations. Gait and speech disturbances, falls, dystonias, and central hypotonia were the presenting neurological features, starting within the first 5 years of life. All children also had severe hypermanganesemia, polycythemia, variable degree of liver disease, and marked brain MRI T1 hyperintensities. Conclusions Our findings expand the mutational and clinical spectra of this recently recognized disorder. An early diagnosis is warranted, because treatment with manganese-chelating agents, iron supplementation, or their combination might improve symptoms and prevent progression of this otherwise potentially fatal disease. © 2015 International Parkinson and Movement Disorder Society

Palmitoyl protein thioesterase-1 (PPT1)-related neuronal ceroid lipofuscinosis is a type of neuronal ceroid lipofuscinosis caused by a deficiency of the enzyme palmitoyl protein thioesterase-1. Cranial magnetic resonance imaging reveals more severe atrophy in the cerebral hemispheres than in the cerebellum. The basal ganglia and particularly the thalamus demonstrate low signal intensity on T 2 -weighted images from an early age. We present three patients with PPT1-related neuronal ceroid lipofuscinosis who exhibited isolated, symmetric signal changes in the bilateral dentate nucleus as sole early neuroimaging abnormality. Neither cerebral or cerebellar atrophy nor signal changes in the thalamus/basal ganglia were evident. This neuroimaging finding in PPT1-related neuronal ceroid lipofuscinosis was not previously reported.

Background and Objectives: Glutaric aciduria Type-I (GA-I) has characteristic clinical and neuroimaging features, which clinches the diagnosis in a majority of patients. However, there have been few case reports on GA-I from India. This study was undertaken to study the clinical presentations, metabolic profile, neuroimaging findings and outcome of patients with GA-I. Study Design: The present study was a retrospective study. Materials and Methods: Retrospective review of charts of patients with a diagnosis of GA-I was carried out from March 2008 to April 2010. The clinical, laboratory and neuroimaging findings were extracted in a predesigned proforma and the data was analyzed. Results: Eleven cases were found to have GA-1. Clinical presentation was quite varied. Follow-up of patients revealed that one patient with macrocephaly as the only clinical finding was developmentally normal. One patient with encephalitis-like illness steadily improved and started walking at 2 years. Two patients were bed ridden and had severe dystonia. One patient died during follow-up. The remaining six patients had dystonia and other abnormal movements, but had attained sitting without support and were not ambulatory. Conclusion: GA-I is not an uncommon disorder and diagnosis can be made easily based on clinical, laboratory investigations and neuroimaging findings. It is one of the treatable metabolic disorders and, if managed appropriately, favorable prognosis can be given.

Background and Objectives: Childhood Central Nervous System (CNS) inflammatory demyelinating disorders (CIDD) are being diagnosed more commonly now. There is ambiguity in the use of different terms in relation to CIDD. Recently, consensus definitions have been proposed so that there is uniformity in studies across the world. The prevalence of these disorders and the spectrum varies from place to place. This study was undertaken to study the clinico-radiological profile and outcome of children with CIDD using the recent consensus definition. Study design: Prospective descriptive study. Materials and Methods: All patients admitted in pediatric ward and pediatric intensive care with neurological symptoms and signs suggestive of CNS inflammatory demyelinating disorders from July 2007−August 2008 were enrolled. The details of clinical presentation, neuroimaging findings, laboratory results, treatment, and outcome were noted and analyzed. Results: Fifteen patients (11 with acute disseminated encephalomyelitis and 4 with clinically isolated syndrome) were diagnosed with CIDD. Clinical presentation was quite varied. Eight patients recovered completely; 4 cases were left with sequelae and 3 patients expired. There were no cases of multiple sclerosis or neuromyelitis optica. Conclusions: CNS inflammatory demyelinating disorders are common illnesses in developing countries because of recurrent infections. Even the spectrum of CIDD is different. Neuroimaging in the form of magnetic resonance imaging is essential for diagnosis.

Krabbe disease has characteristic findings on brain magnetic resonance imaging (MRI) according to age of clinical onset. MRI-negative Krabbe disease has not been reported in early-onset cases. We present the serial clinical and MRI of brain findings in a case of early-onset Krabbe disease with proven enzyme deficiency. Despite clinical progression, the MRI findings of the child remained normal over a period of 15 months.

SLC30A10 mutations cause an autosomal recessive disorder, characterized by hypermanganesaemia, polycythemia, early-onset dystonia, paraparesis, or late-onset parkinsonism, and chronic liver disease. This is the first identified inborn error of Mn metabolism in humans, reported in 10 families thus far.Methods for this study consisted of clinical examination, neuroimaging studies (MRI), serum dosages, and SLC30A10 genetic analysis.We describe early disease manifestations (including videos) in 5 previously unreported Indian children, carrying novel homozygous SLC30A10 mutations. Gait and speech disturbances, falls, dystonias, and central hypotonia were the presenting neurological features, starting within the first 5 years of life. All children also had severe hypermanganesemia, polycythemia, variable degree of liver disease, and marked brain MRI T1 hyperintensities.Our findings expand the mutational and clinical spectra of this recently recognized disorder. An early diagnosis is warranted, because treatment with manganese-chelating agents, iron supplementation, or their combination might improve symptoms and prevent progression of this otherwise potentially fatal disease. © 2015 International Parkinson and Movement Disorder Society.

Acute cerebellitis constitutes a clinically isolated syndrome, and is a frequent condition in childhood, with either viral or autoimmune etiologies. The disease is reported to run a variable course, and is usually benign. Acute cerebellitis with cerebellar swelling, hydrocephalus, and brainstem compression is an exceptional but life-threatening condition. We report a 9-year-old boy in whom death resulted from acute fulminant cerebellitis because of brainstem involvement. Serial computed tomography and magnetic resonance imaging demonstrated rapid progression of the disease. The etiologies, clinical course, and therapeutic interventions regarding this potentially life-threatening condition are briefly reviewed.

Neuronal ceroid lipofuscinosis is a group of progressive neurodegenerative disorders characterized by accumulation of ceroid lipopigment in lysosomes in neurons and other cell types. This study is a retrospective review of charts of patients with a diagnosis of infantile and late-infantile neuronal ceroid lipofuscinosis seen between January 2009 and December 2011. Of the 16 patients, 5 had infantile type and 11 had late-infantile neuronal ceroid lipofuscinosis. Diagnosis was confirmed by appropriate enzyme assay. Clinical presentation was quite varied. Common presenting features included refractory seizures, developmental delay/regression, and abnormal movements. Visual failure was not common in the present case series, and novel neuroimaging finding in the form of isolated dentate nucleus hyperintensities were noted. During follow-up, all patients had a progressive downhill course and one patient died. Prenatal diagnosis could be offered to one family. This study suggests that infantile and late-infantile neuronal ceroid lipofuscinosis is not uncommon in this region of the country and the phenotype may be different.

Abnormalities of the anterior part of the temporal lobe (abnormal and swollen white matter, cysts, and focal enlargement of the anterior part of the inferior horn- either alone or more often in combination) suggest congenital cytomegalovirus (CMV) infection. This is not widely known. These can be seen in neonatal period and they continue to persist in later life.

Krabbe disease has characteristic findings on brain magnetic resonance imaging (MRI) according to age at clinical onset. Knowledge of the characteristic brain MRI findings contributes to rapid and specific diagnosis of Krabbe disease in the proper clinical setting. In the early-onset form of Krabbe disease, the leading imaging findings are signal abnormalities within cerebellar white matter, the deep gray nuclei, parieto-occipital white matter, and corpus callosum, and the pyramidal tract. In late-onset disease, MRI is characterized by signal abnormalities within the pyramidal tract, posterior corpus callosum, and parietooccipital white matter [1]. Although cases of Krabbe diseasewith selective involvement of corticospinal tract only have been reported in adults, case reports of children with predominant involvement of corticospinal tracts have been very few [1-3]. We present the case of a 2-year-old boy with late infantile onset Krabbe disease with proven enzyme deficiency and predominant involvement of corticospinal tracts on MRI as the initial feature without other characteristic features of Krabbe disease.

We describe two adolescent Indian siblings with cerebrotendinous xanthomatosis with cognitive impairment, progressive neurological deterioration, juvenile cataracts and chronic diarrhea. Both patients had bilateral Achilles tendon xanthomata. Rapid progression of disease was an unusual finding in these cases. Magnetic resonance imaging showed characteristic signal alterations in cerebellar hemispheres, brainstem and posterior cerebral white matter.