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

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.

Brain and other nervous system disorders across the lifespan - global challenges and opportunities.

This is an exciting time for scientific discovery that aims to reduce the frequency and impact of neurological, mental health and substance-use disorders. As it became increasingly clear that low- and middle-income countries have a disproportionate share of these disorders, and that many of the problems are best addressed by indigenous researchers who can seek context-sensitive solutions, the US National Institutes of Health and other research funders began to invest more in low- and middle-income country-focused research and research capacity-building to confront this significant public health challenge. In an effort to identify existing information, knowledge gaps, and emerging research and research capacity-building opportunities that are particularly relevant to low- and middle-income countries, in February 2014 the Center for Global Health Studies at the National Institutes of Health Fogarty International Center held a workshop to explore these issues with scientific experts from low- and middle-income countries and the United States. This evolved into the preparation of the Reviews in this supplement, which is designed to highlight opportunities and challenges associated with topical areas in brain-disorders research over the coming decade. This Introduction highlights some of the over-arching and intersecting priorities for addressing causes, prevention, treatment and rehabilitation as well as best practices to promote overall nervous system health. We review some brain disorders in low- and middle-income countries, while the Reviews describe relevant issues and the epidemiology of particular conditions in greater depth.

INCLEN Diagnostic Tool for Neuromotor Impairments (INDT-NMI) for primary care physician: development and validation.

OBJECTIVE: To develop and validate a diagnostic tool for use by primary care physicians for diagnosing neuro-motor impairment among 2-9 year old children in primary care settings. STUDY DESIGN: Modified Delphi technique involving national (n=49) and international (n=6) experts was used for development of INDT-NMI. The tool was then validated through a cross sectional study. SETTING: Neurology specialty clinics of three tertiary care pediatric centers in New Delhi, India. PARTICIPANTS: 454 children aged 2-9 years [mean (SD) age: 60.4 (23.7) mo], selected through systematic random sampling, underwent assessment for identification and classification of neuromotor impairments (NMI). INTERVENTION: All study subjects were first administered INDT-NMI (candidate test) by a trained physician followed by expert assessment for NMI and other neurodevelopment disorders (NDD) by team of two pediatric neurologists (Gold standard). RESULTS: According to expert evaluation, 171 (37.8%) children had neuromotor impairments. There were four categories of subjects: NMI alone (n=66); NMI+other NDDs (n=105); Other NDDs without NMI (n=225) and 'Normal' group (n=58). Using expert evaluation as gold standard, overall sensitivity of the INDT-NMI was 75.4% and specificity was 86.8%. INDT-NMI helped graduate physicians to correctly classify 86.6% (112/129) children with NMI into different types (cerebral palsy, neuromotor diseases and other NMI). Graduate physicians assigned 40 children (8.8%) as 'indeterminate', 38 (95%) of whom had either NDD and/or NMI and thus merited referral. Misclassification of NMI occurred in those with mild changes in muscle tone, dystonia, or ataxia and associated NDDs. CONCLUSIONS: Graduate primary care physicians with a structured short training can administer the new tool and diagnose NMI in 2-9 year old children with high validity. INDT-NMI requires further evaluation in actual primary care settings.

INCLEN Diagnostic Tool for Epilepsy (INDT-EPI) for primary care physicians: development and validation.

OBJECTIVE: To evaluate the diagnostic accuracy of a new diagnostic instrument for epilepsy - INCLEN Diagnostic Tool for Epilepsy (INDT-EPI) - with evaluation by expert pediatric neurologists. STUDY DESIGN: Evaluation of diagnostic test. SETTING: Tertiary care pediatric referral centers in India. METHODS: Children aged 2-9 years, enrolled by systematic random sampling at pediatric neurology out-patient clinics of three tertiary care centers were independently evaluated in a blinded manner by primary care physicians trained to administer the test, and by teams of two pediatric neurologists. OUTCOMES: A 13-item questionnaire administered by trained primary care physicians (candidate test) and comprehensive subject evaluation by pediatric neurologists (gold standard). RESULTS: There were 240 children with epilepsy and 274 without epilepsy. The candidate test for epilepsy had sensitivity and specificity of 85.8% and 95.3%; positive and negative predictive values of 94.0% and 88.5%; and positive and negative likelihood ratios of 18.25 and 0.15, respectively. CONCLUSIONS: The INDT-EPI has high validity to identify children with epilepsy when used by primary care physicians.

INCLEN diagnostic tool for attention deficit hyperactivity disorder (INDT-ADHD): development and validation.

OBJECTIVE: To develop and validate INCLEN Diagnostic Tool for Attention Deficit Hyperactivity Disorder (INDT-ADHD). DESIGN: Diagnostic test evaluation by cross sectional design. SETTING: Tertiary care pediatric centers. PARTICIPANTS: 156 children aged 65-117 months. METHODS: After randomization, INDT-ADHD and Connors 3 Parent Rating Scale (C3PS) were administered, followed by an expert evaluation by DSM-IV-TR diagnostic criteria. MAIN OUTCOME MEASURES: Psychometric evaluation of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency. RESULTS: INDT-ADHD had 18 items that quantified symptoms and impairment. Attention deficit hyperactivity disorder was identified in 57, 87 and 116 children by expert evaluation, INDT-ADHD and C3PS, respectively. Psychometric parameters of INDT-ADHD for differentiating attention deficit hyperactivity disorder and normal children were: sensitivity 87.7%, specificity 97.2%, positive predictive value 98.0% and negative predictive value 83.3%, whereas for differentiating from other neuro-developmental disorders were 87.7%, 42.9%, 58.1% and 79.4%, respectively. Internal consistency was 0.91. INDT-ADHD has a 4-factor structure explaining 60.4% of the variance. Convergent validity with Conner's Parents Rating Scale was moderate (r =0.73, P= 0.001). CONCLUSIONS: INDT-ADHD is suitable for diagnosing attention deficit hyperactivity disorder in Indian children between the ages of 6 to 9 years.

INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD): development and validation.

OBJECTIVE: To develop and validate INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD). DESIGN: Diagnostic test evaluation by cross sectional design. SETTING: Four tertiary pediatric neurology centers in Delhi and Thiruvanthapuram, India. METHODS: Children aged 2-9 years were enrolled in the study. INDT-ASD and Childhood Autism Rating Scale (CARS) were administered in a randomly decided sequence by trained psychologist, followed by an expert evaluation by DSM-IV TR diagnostic criteria (gold standard). MAIN OUTCOME MEASURES: Psychometric parameters of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency. RESULTS: 154 children (110 boys, mean age 64.2 mo) were enrolled. The overall diagnostic accuracy (AUC=0.97, 95% CI 0.93, 0.99; P<0.001) and validity (sensitivity 98%, specificity 95%, positive predictive value 91%, negative predictive value 99%) of INDT-ASD for Autism spectrum disorder were high, taking expert diagnosis using DSM-IV-TR as gold standard. The concordance rate between the INDT-ASD and expert diagnosis for 'ASD group' was 82.52% [Cohen's k=0.89; 95% CI (0.82, 0.97); P=0.001]. The internal consistency of INDT-ASD was 0.96. The convergent validity with CARS (r = 0.73, P= 0.001) and divergent validity with Binet-Kamat Test of intelligence (r = -0.37; P=0.004) were significantly high. INDT-ASD has a 4-factor structure explaining 85.3% of the variance. CONCLUSIONS: INDT-ASD has high diagnostic accuracy, adequate content validity, good internal consistency high criterion validity and high to moderate convergent validity and 4-factor construct validity for diagnosis of Autistm spectrum disorder.

National Institutes of Health State-of-the-Science Conference statement: preventing alzheimer disease and cognitive decline.

The National Institute on Aging and the Office of Medical Applications of Research of the National Institutes of Health convened a State-of-the-Science Conference on 26-28 April 2010 to assess the available scientific evidence on prevention of cognitive decline and Alzheimer disease. This article provides the panel's assessment of the available evidence.

NIH state-of-the-science conference statement: Preventing Alzheimer's disease and cognitive decline.

OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data on prevention of Alzheimer's disease and cognitive decline. PARTICIPANTS: A non-Department of Health and Human Services, nonadvocate 15-member panel representing the fields of preventive medicine, geriatrics, internal medicine, neurology, neurological surgery, psychiatry, mental health, human nutrition, pharmacology, genetic medicine, nursing, health economics, health services research, family caregiving, and a public representative. In addition, 20 experts from pertinent fields presented data to the panel and conference audience. EVIDENCE: Presentations by experts and a systematic review of the literature prepared by the Duke University Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: Cognitive decline and Alzheimer's disease are major causes of morbidity and mortality worldwide and are substantially burdensome to the affected persons, their caregivers, and society in general. Extensive research over the past 20 years has provided important insights on the nature of Alzheimer's disease and cognitive decline and the magnitude of the problem. Nevertheless, there remain important and formidable challenges in conducting research on these diseases, particularly in the area of prevention. Currently, firm conclusions cannot be drawn about the association of any modifiable risk factor with cognitive decline or Alzheimer's disease. Highly reliable consensus-based diagnostic criteria for cognitive decline, mild cognitive impairment, and Alzheimer's disease are lacking, and available criteria have not been uniformly applied. Evidence is insufficient to support the use of pharmaceutical agents or dietary supplements to prevent cognitive decline or Alzheimer's disease. We recognize that a large amount of promising research is under way; these efforts need to be increased and added to by new understandings and innovations (as noted in our recommendations for future research). For example, ongoing studies including (but not limited to) studies on antihypertensive medications, omega-3 fatty acids, physical activity, and cognitive engagement may provide new insights into the prevention or delay of cognitive decline or Alzheimer's disease. This important research needs to be supplemented by further studies. Large-scale population-based studies and randomized controlled trials (RCTs) are critically needed to investigate strategies to maintain cognitive function in individuals at risk for decline, to identify factors that may delay the onset of Alzheimer's disease among persons at risk, and to identify factors that may slow the progression of Alzheimer's disease among persons in whom the condition is already diagnosed.

Mental and neurological health research priorities setting in developing countries.

INTRODUCTION: A multi-region consultation process designed to generate locally produced regional and global research priorities on mental and neurological health in low- and middle-income countries. METHODS: Between 2003 and 2005, priority setting exercises on MNH research, using the systematic combined approach matrix (CAM) were held in the six regions of the developing world. One regional meeting per region was convened, and a global meeting was organized before and after the regional exercises. RESULTS: During regional meetings, regional agendas were created listing both research priorities and local problems in MNH. During global meetings, a global research agenda was established and four crucial areas of research priorities were identified: awareness and advocacy, enhancement of research capacity, training for service delivery, and development of evidence based policy. CONCLUSIONS: The combined matrix approach enabled the development of regional and global MNH research agendas, derived from bottom up consultations within and between low- and middle-income countries. Collaboration between regions with similar priorities was instituted. Such research agendas are designed to assist policy-makers and donors in the allocation of scarce resources, but they require regular review to reflect changing needs.

Mental and neurological health profile of Ecuador.

We assessed the mental and neurological health (MNH) situation of Ecuador in 2006-8, using the Mental and Neurological Health Country Profile (MNHCP) (Gulbinat et al, 2004; Jenkins, 2004; Jenkins et al, 2004), an instrument which helps to develop evidence-based MNH policy and services (Townsend et al, 2004). An extensive review of the literature was undertaken and consultations and consensus meetings (Schilder et al, 2004) were conducted with key mental and neurological health stakeholders, including consumers, carers and clinicians from the government and non-government sectors.

Nervous system disorders: a global epidemic.

Major new epidemiological analyses are focusing attention on disorders of the nervous system as important causes of death and disability around the world. One in every 9 individuals dies of a disorder of the nervous system. Stroke outweighs all other neurological disorders combined as a cause of mortality. Most disorders of the nervous system occur in developing countries. Developmental disability due to malnutrition, and cognitive dysfunction associated with parasitic infections are the most common neurological disorders. As the world's population ages and the effects of infectious disease decline, the relative effects of many disorders of the nervous system, including stroke and dementia, are increasing. The disorders of the nervous system causing the highest rates of death and disability are preventable and treatable. Increased awareness of the global effects of neurological disorders should help health care planners and the neurological community set appropriate priorities in research, prevention, and management of these conditions.