Background Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden. Methods and findings We assessed 3,964 children (with almost equal number of boys and girls distributed in 2–<6 and 6–9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6–9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2–<6 year olds ranged from 2.9% (95% CI 1.6–5.5) to 18.7% (95% CI 14.7–23.6), and for any of nine NDDs in the 6–9-year-old children, from 6.5% (95% CI 4.6–9.1) to 18.5% (95% CI 15.3–22.3). Two or more NDDs were present in 0.4% (95% CI 0.1–1.7) to 4.3% (95% CI 2.2–8.2) in the younger age category and 0.7% (95% CI 0.2–2.0) to 5.3% (95% CI 3.3–8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5–11.2) and 13.6% (95% CI 11.3–16.2) in children of 2–<6 and 6–9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6–9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population. Conclusions The study identifies NDDs in children aged 2–9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions.

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Neurodevelopmental disorders in children aged 2-9 years: Population-based burden estimates across five regions in India.

Autism spectrum disorder (ASD) is a term associated with a group of neurodevelopmental disorders. The etiology of ASD is not yet completely understood; however, a disorder in the gut-brain axis is emerging as a prominent factor leading to autism. To identify the taxonomic composition and markers associated with ASD, we compared the fecal microbiota of 30 ASD children diagnosed using Childhood Autism Rating Scale (CARS) score, DSM-5 approved AIIMS-modified INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD), and Indian Scale for Assessment of Autism (ISAA) tool, with family-matched 24 healthy children from Indian population using next-generation sequencing (NGS) of 16S rRNA gene amplicon. Our study showed prominent dysbiosis in the gut microbiome of ASD children, with higher relative abundances of families Lactobacillaceae, Bifidobacteraceae, and Veillonellaceae, whereas the gut microbiome of healthy children was dominated by the family Prevotellaceae. Comparative meta-analysis with a publicly available dataset from the US population consisting of 20 ASD and 20 healthy control samples from children of similar age, revealed a significantly high abundance of genus Lactobacillus in ASD children from both the populations. The results reveal the microbial dysbiosis and an association of selected Lactobacillus species with the gut microbiome of ASD children.

Gut Microbial Dysbiosis in Indian Children with Autism Spectrum Disorders.

Epilepsy is a frequent chronic neurologic disorder that affects nearly 70 million people worldwide The majority of people with epilepsy live in developing countries, where epilepsy remains a major public health problem Wide prevalence differences exist among various populations across sub-Saharan Africa, Latin America, and Asia In particular, prevalence is lower in Southeast Asia than in sub-Saharan Africa and Latin America Methodologic problems alone do not seem to explain these differences shown in recent review papers The distribution of numerous risk or etiologic factors such as infectious diseases with neurologic sequel, head injuries, or genetic factors could explain these differences Stigmatization of people with epilepsy could lead to underestimating the prevalence of epilepsy, even in well-conducted studies It is important to standardize the process of epidemiologic monitoring of epilepsy in order to improve the reliability in data comparison Understanding the reasons for these differences is a crucial issue for eventually raising new hypotheses or prevention strategies

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1167.2011.03099.x

Understanding the differences in prevalence of epilepsy in tropical regions

Metachromatic leukodystrophy (MLD) is an autosomal recessively inherited metabolic disease characterized by deficient activity of the lysosomal enzyme arylsulfatase A. Its deficiency results in accumulation of sulfatides in neural and visceral tissues, and causes demyelination of the central and peripheral nervous system. This leads to a broad range of neurological symptoms and eventually premature death. In asymptomatic patients with juvenile and adult MLD, treatment with allogeneic hematopoietic stem cell transplantation (HCT) provides a symptomatic and survival benefit. However, this treatment mainly impacts brain white matter, whereas the peripheral neuropathy shows no or only limited response. Data about the impact of peripheral neuropathy in MLD patients are currently lacking, although in our experience peripheral neuropathy causes significant morbidity due to neuropathic pain, foot deformities and neurogenic bladder disturbances. Besides, the reasons for residual and often progressive peripheral neuropathy after HCT are not fully understood. Preliminary studies suggest that peripheral neuropathy might respond better to gene therapy due to higher enzyme levels achieved than with HCT. However, histopathological and clinical findings also suggest a role of neuroinflammation in the pathology of peripheral neuropathy in MLD. In this literature review, we discuss clinical aspects, pathological findings, distribution of mutations, and treatment approaches in MLD with particular emphasis on peripheral neuropathy. We believe that future therapies need more emphasis on the management of peripheral neuropathy, and additional research is needed to optimize care strategies.

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Peripheral neuropathy in metachromatic leukodystrophy: current status and future perspective

Metachromatic leukodystrophy is a lysosomal storage disease, which is characterized by damage of the myelin sheath that covers most of nerve fibers of the central and peripheral nervous systems. The disease occurs due to a deficiency of the lysosomal enzyme arylsulfatase A (ARSA) or its sphingolipid activator protein B (SapB) and it clinically manifests as progressive motor and cognitive deficiency. ARSA and SapB protein deficiency are caused by mutations in the ARSA and PSAP genes, respectively. The severity of clinical course in metachromatic leukodystrophy is determined by the residual ARSA activity, depending on the type of mutation. Currently, there is no effective treatment for this disease. Clinical cases of bone marrow or cord blood transplantation have been reported, however the therapeutic effectiveness of these methods remains insufficient to prevent aggravation of neurological disorders. Encouraging results have been obtained using gene therapy for delivering the wild-type ARSA gene using vectors based on various serotypes of adeno-associated viruses, as well as using mesenchymal stem cells and combined gene-cell therapy. This review discusses therapeutic strategies for the treatment of metachromatic leukodystrophy, as well as diagnostic methods and modeling of this pathology in animals to evaluate the effectiveness of new therapies.

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Metachromatic Leukodystrophy: Diagnosis, Modeling, and Treatment Approaches.

JUSTIFICATION
Seizures constitute the most common neurological problem in children and the majority of epilepsy has its onset in childhood. Appropriate diagnosis and management of childhood epilepsy is essential to improve quality of life in these children. Evidence-based clinical practice guidelines, modified to the Indian setting by a panel of experts, are not available.


PROCESS
The Indian Academy of Pediatrics organized a consensus meeting on the diagnosis and management of childhood epilepsy on 22-23 of July 2006 at Mumbai. An expert committee was formed consisting of pediatricians,pediatric epileptologists, pediatric and adult neurologists, electrophysiologists, neuroradiologists, neurosurgeons and intensivists. A consensus was reached during the discussion that followed presentation by each of these experts. The process of updating these recommendations and arriving at consensus continued till 2009.


OBJECTIVES
To develop practice guidelines for diagnosis and management of childhood epilepsy.


RECOMMENDATIONS
Recommendations for diagnosis and management of following childhood seizures and epilepsies are given: neonatal seizures, acute symptomatic seizures, neurocysticercosis, febrile seizures, idiopathic partial and generalized epilepsies, first unprovoked seizure, newly diagnosed epilepsy, catastrophic epilepsies of infancy, refractory epilepsies of older children and adolescents, epilepsy with cognitive deterioration and status epilepticus.

Guidelines for the Diagnosis and Management of Childhood Epilepsy

Development and validation of AIIMS modified INCLEN diagnostic instrument for epilepsy in children aged 1 month-18 years.

Leukodystrophy presenting as acute-onset polyradiculoneuropathy.

Deficiency of vitamin B12 causes megaloblastic anemia and nervous system demyelination. Structures affected in the nervous system include spinal cord, cranial and peripheral nerves, and brain white matter. A 9-year-old boy presented with knuckle hyperpigmentation and oral ulcers for 3 years, pallor and easy fatigability for 6 months, gait abnormalities for 3 months, and abnormal speech and behavioral abnormalities for 3 days. On examination, he had physical signs of megaloblastic anemia, mood swings with intermittent hallucinations, and features of cerebellar impairment. Blood investigations revealed megaloblastic anemia, and pernicious anemia was ruled out. Brain magnetic resonance imaging (MRI) revealed bilateral cerebellar signal changes. He received treatment for vitamin B12 deficiency and appropriate nutritional counseling. Three months later, he showed significant clinical and radiologic resolution. To our knowledge, isolated cerebellar involvement as the sole neurologic manifestation of vitamin B12 deficiency has not been described previously in children.

Isolated cerebellar involvement in vitamin B12 deficiency: a case report.

Autism is a neurodevelopmental disorder with an onset in early childhood. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) describes Autism spectrum disorders (ASD) as social communication impairments and restricted, repetitive patterns of behavior. Children with ASD exhibit delayed language development, difficulties in reciprocal communication and social skills, stereotypic behaviors, and sensory impairments. In March 2014, the Centers for Disease Control and Prevention (CDC) reported prevalence of ASDs as 1 in 68 children in multiple communities in the United States. This new prevalence is 30 % higher than previous estimates reported in 2012 of 1 in 88 [1]. Similar trends have been observed globally and it is not difficult to foresee that in coming decades we will have increasing number of adolescents and adults with autism. Overall long-term outcome of children with autism, when followed to adulthood remains poor and more than three fourth of them may require life long assistance in daily living. Language communication development before age of 6 years and high childhood IQ have been shown to be critical for a Bgood^ outcome [2]. It has been suggested that some children with ASD improve to such an extent that they may outgrow their diagnosis, also known as ‘optimal outcome’. It is interesting and important to know how this group is different than high functioning autism. Optimal outcome children do better on adaptive and problem behavior scores when compared to high-functioning peers with ASD. Contrary to common belief, the high functioning group may continue to show pragmatic, linguistic, social, and behavioral difficulties. The optimal outcome children are likely to be diagnosed at younger ages and more likely to receive intensive early intervention [3].

Rachana Dubey

Papers

Guidelines for the Diagnosis and Management of Childhood Epilepsy

Development and validation of AIIMS modified INCLEN diagnostic instrument for epilepsy in children aged 1 month-18 years.

Leukodystrophy presenting as acute-onset polyradiculoneuropathy.

Isolated cerebellar involvement in vitamin B12 deficiency: a case report.

Adaptive Functioning and Feeding Behavior: Key Targets in Autism Management.