Consensus Statement of the IAP - Neurodevelopmental Chapter On Neurodevelopmental Disorders Habilitation Process: Strategic Plan for Prevention, Early Detection and Early Intervention.

JUSTIFICATION: Neurodevelopmental disorders, as per DSM-V, are described as a group of conditions with onset in the development period of childhood. There is a need to distinguish the process of habilitation and rehabilitation, especially in a developing country like India, and define the roles of all stakeholders to reduce the burden of neurodevelopmental disorders. PROCESS: Subject experts and members of Indian Academy of Pediatrics (IAP) Chapter of Neurodevelopmental Pediatrics, who reviewed the literature on the topic, developed key questions and prepared the first draft on guidelines. The guidelines were then discussed by the whole group through online meetings, and the contentious issues were discussed until a general consensus was arrived at. Following this, the final guidelines were drafted by the writing group and approved by all contributors. OBJECTIVES: These guidelines aim to provide practical clinical guidelines for pediatricians on the prevention, early diagnosis and management of neurodevelopmental disorders (NDDs) in the Indian settings. It also defines the roles of developmental pediatricians and development nurse counselor. STATEMENT: There is a need for nationwide studies with representative sampling on epidemiology of babies with early NDD in the first 1000 days in India. Specific learning disability (SLD) has been documented as the most common NDD after 6 years in India, and special efforts should be made to establish the epidemiology of infants and toddlers at risk for SLD, where ever measures are available. Preconception counseling as part of focusing on first 1000 days; Promoting efforts to organize systematic training programs in Newborn Resuscitation Program (NRP); Lactation management; Developmental follow-up and Early stimulation for SNCU/ NICU graduates; Risk stratification of NICU graduates, Newborn Screening; Counseling parents; Screening for developmental delay by trained professionals using simple validated Indian screening tools at 4, 8, 12, 18 and 24 months; Holistic assessment of 10 NDDs at child developmental clinics (CDCs) / district early intervention centre (DEICs) by multidisciplinary team members; Confirmation of diagnosis by developmental pediatrician/developmental neurologist/child psychiatrist using clinical/diagnostic tools; Providing parent guided low intensity multimodal therapies before 3 years age as a center-based or home-based or community-based rehabilitation; Developmental pediatrician to seek guidance of pediatric neurologist, geneticist, child psychiatrist, physiatrist, and other specialists, when necessary; and Need to promote ongoing academic programs in clinical child development for capacity building of community based therapies, are the chief recommendations.

Influence of Primary Auditory Cortex in the Characterization of Autism Spectrum in Young Adults using Brain Connectivity Parameters and Deep Belief Networks: An fMRI Study.

BACKGROUND: The spectrum of autism encompasses High Functioning Autism (HFA) and Low Functioning Autism (LFA). Brain mapping studies have revealed that autism individuals have overlaps in brain behavioural characteristics. Generally, high functioning individuals are known to exhibit higher intelligence and better language processing abilities. However, specific mechanisms associated with their functional capabilities are still under research. OBJECTIVE: This work addresses the overlapping phenomenon present in autism spectrum through functional connectivity patterns along with brain connectivity parameters and distinguishes the classes using deep belief networks. METHODS: The task-based functional Magnetic Resonance Images (fMRI) of both high and low functioning autistic groups were acquired from ABIDE database, for 58 low functioning against 43 high functioning individuals while they were involved in a defined language processing task. The language processing regions of the brain, along with Default Mode Network (DMN) have been considered for the analysis. The functional connectivity maps have been plotted through graph theory procedures. Brain connectivity parameters such as Granger Causality (GC) and Phase Slope Index (PSI) have been calculated for the individual groups. These parameters have been fed to Deep Belief Networks (DBN) to classify the subjects under consideration as either LFA or HFA. RESULTS: Results showed increased functional connectivity in high functioning subjects. It was found that the additional interaction of the Primary Auditory Cortex lying in the temporal lobe, with other regions of interest complimented their enhanced connectivity. Results were validated using DBN measuring the classification accuracy of 85.85% for high functioning and 81.71% for the low functioning group. CONCLUSION: Since it is known that autism involves enhanced, but imbalanced components of intelligence, the reason behind the supremacy of high functioning group in language processing and region responsible for enhanced connectivity has been recognized. Therefore, this work that suggests the effect of Primary Auditory Cortex in characterizing the dominance of language processing in high functioning young adults seems to be highly significant in discriminating different groups in autism spectrum.

Fluorescence Imaging for Cancer Screening and Surveillance.

The advent of fluorescence imaging (FI) for cancer cell detection in the field of oncology is promising for both cancer screening and surgical resection. Particularly, FI in cancer screening and surveillance is actively being evaluated in many new clinical trials with over 30 listed on Clinical Trials.gov . While surgical resection forms the foundation of many oncologic treatments, early detection is the cornerstone for improving outcomes and reducing cancer-related morbidity and mortality. The applications of FI are twofold as it can be applied to high-risk patients in addition to those undergoing active surveillance. This technology has the promise of highlighting lesions not readily detected by conventional imaging or physical examination, allowing disease detection at an earlier stage of development. Additionally, there is a persistent need for innovative, cost-effective imaging modalities to ameliorate healthcare disparities and the global burden of cancer worldwide. In this review, we outline the current utility of FI for screening and detection in a range of cancer types.

Budd-Chiari Syndrome. Changing epidemiology and clinical presentation.

Budd-Chiari Syndrome (BCS) is a rare cause of portal hypertension. Geographical variations occur, particularly in the clinical presentation, where there are distinct differences between West and South Asia. Idiopathic forms are common in south Asia, while hypercoagulable disorders are common causes of BCS in the West. The site of thrombosis is also different, with patients from South Asia presenting with combined obstruction of the hepatic veins and the inferior vena cava in contrast to isolated obstruction of the hepatic veins, common in the West. Ultrasound-Doppler studies confirm the diagnosis in the majority. Early radiological interventions, including transjugular intrahepatic portosystemic shunt, can cure the majority of cases with idiopathic forms. Prothrombotic forms are treated with long-term anticoagulants. Surgery is reserved to a selected few with long segment obstruction. Liver transplantation is indicated in patients with worsening clinical functional status not responding to medical and/or interventional management.

Acute liver failure in pregnancy: an overview.

Acute liver failure (ALF) in pregnancy is a common challenging clinical problem both in terms of correct diagnosis and management. Acute viral hepatitis is the most common cause of jaundice in pregnancy. The course of acute viral hepatitis is unaffected by pregnancy, except in patients with hepatitis E (HEV), particularly from endemic countries like India, where ALF carries a high mortality. In both HEV infection and herpes simplex infections, maternal and fetal mortality rates are significantly increased. ALF specific to pregnancy including pre-eclampsia, associated with hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome, acute fatty liver of pregnancy, and hepatic infarction result in increased maternal and fetal mortality if not recognized and acted on early. Early recognition of possible causes and prompt treatment are crucial for successful outcome of ALF in pregnancy. Treatment involves prompt delivery, whereupon the liver disease quickly reverses. This review article addresses the present understanding of ALF in pregnancy reviewing the common causes of ALF and their management in pregnancy.

Pulmonary hypertension in rheumatoid arthritis--relation with the duration of the disease.

Isolated pulmonary hypertension with clinical implication is rare in rheumatoid arthritis. We sought to study the prevalence of pulmonary arterial hypertension in an unselected population of 45 patients with rheumatoid arthritis (classified according to the ARA criteria) without cardiac disease and corresponding age and sex matched controls by Doppler echocardiography. The pulmonary artery systolic pressure was higher in patients with Rheumatoid Arthritis (27.49+/-12.66 mm Hg) than in controls (20.40+/-8.88) (p=0.003). Incidence of pulmonary artery systolic pressure>30 mm Hg suggesting pulmonary hypertension was significantly higher in patients with RA (26.7% versus 4.5% in controls; p=0.03) and 20% of patients had pulmonary hypertension without lung disease or cardiac disease evident on pulmonary function testing, and echocardiogram respectively. There was also a strong correlation between the pulmonary artery pressure and the disease duration (r=0.68, p<0.0001) suggesting a subclinical involvement of the pulmonary vasculature with disease progression and may be relevant to the high incidence of cardiovascular deaths observed in patients with Rheumatoid Arthritis.

Predictors of mortality in hepatic encephalopathy in acute and chronic liver disease: a preliminary observation.

BACKGROUND: Several scoring systems are available to predict the outcome of liver cell failure. Scarce information is available on predictors in hepatic encephalopathy. OBJECTIVES: To study clinical and biochemical variables that would predict the outcome in hepatic encephalopathy. METHODS: Fifty consecutive patients with hepatic encephalopathy were included in the study. Variables included clinical and biochemical parameters, discriminant function, QTc interval and the need for ventilator support. Child-Pugh's Turcotte score and Mayo Clinic model for end-stage liver disease scores were calculated at admission. Patients were followed up until discharge or death. Logistic regression analysis was computed with the variables that predicted a favorable outcome. RESULTS: Chronic liver disease precipitated hepatic encephalopathy in 39 patients (group 1) and encephalopathy followed acute liver disease in 11 patients (group 2). In group 1, high serum bilirubin (P<0.001), prolonged QTc interval (P<0.05) and requirement for support systems (P<0.003) predicted a poor outcome. In group 2, higher grades of encephalopathy (P<0.04) and native drug therapy (P<0.007), high serum bilirubin (P<0.05), requirement for support systems (P<0.02) predicted a poor outcome. Mayo Clinic model for end-stage liver disease and discriminant function in both groups and Child-Pugh-Turcotte's score in group 1 did not predict the outcome. Logistic regression identified serum bilirubin in group 1 (OR 8.55, P=0.012) and native drug therapy in group 2 (odds ratio 3.85, P=0.05) as independent poor risk factors. CONCLUSIONS: High serum bilirubin values in chronic liver disease and native drug therapy in acute liver cell failure are simple parameters that would predict a poor outcome in patients with hepatic encephalopathy.

Diastolic function abnormalities in rheumatoid arthritis: relation with duration of disease.

INTRODUCTION: There are limited studies on the prevalence of diastolic dysfunction in rheumatoid arthritis (RA) from the Indian subcontinent. The aim of this study was to evaluate left ventricular filling abnormalities in patients with RA without clinically-evident cardiovascular manifestations, and to correlate it with disease duration. METHODS: 45 patients affected with RA according to the American Rheumatism Association criteria, were selected without evidence of cardiac disease, and compared with age- and sex-matched control subjects. All patients and the control group were submitted to M-mode, two-dimensional and Doppler echocardiography. The following diastolic parameters were evaluated: peak of early diastolic (E) and late diastolic (A) mitral flow velocity, E/A ratio, isovolumic relaxation time (IVRT), ejection fraction and fractional shortening. RESULTS: In RA patients, left ventricular filling abnormalities were found characterised by a reduced E/A ratio (mean [SD] 0.98 [0.22] versus controls 1.09 [0.11]; p-value equals 0.004), prolonged IVRT (75.77 [8.12] ms versus 70.43 [2.94] ms; p-value equals 0.001) and increased late diastole flow velocity (76.91 [11.61] cm/s versus 70.11 [5.32] cm/s; p-value equals 0.001). In the group of patients, a negative correlation was found between E/A ratio and disease duration (Pearson correlation, r equals -0.56, p-value equals 0.001), indicating diastolic dysfunction with increasing disease duration. A strong correlation was also found between IVRT and disease duration (r equals 0.66, p-value equals 0.01) and also between late diastolic flow velocity and disease duration (r equals 0.61, p-value equals 0.001). CONCLUSION: The present study confirms a high frequency of left ventricular diastolic dysfunction characterised by impaired E/A ratio, prolonged IVRT and increased late diastole flow velocity in patients with RA without evident cardiovascular disease. The correlation between transmitral flow alteration and disease duration suggests a subclinical myocardial involvement with disease progression. This may be relevant to the high incidence of cardiovascular deaths observed in patients with RA.

Evaluation of bone mineral density in thyrotoxicosis.

INTRODUCTION: This project aimed to study the incidence and profile of bone involvement in thyrotoxicosis patients by dual energy X-ray absorptiometry (DEXA) scan and the effect of treatment on the bone mineral density (BMD). METHODS: A total of 50 young patients with a mean age of 29.4 years, diagnosed to have thyrotoxicosis clinically and proven by thyroid function tests, were included in this prospective three-year study conducted at the Madras Medical College and Government General Hospital in Chennai, India. Patients were enrolled if they had bone pain or had elevation of serum alkaline phosphatase. All these patients had a baseline BMD measurement by DEXA scans in the region of the lumbar vertebrae before treatment and the T-score was computed. All other secondary causes of low BMD, like primary hyperparathyroidism, long-term steroid intake, vitamin D deficiency, was ruled out. After definitive management of hyperthyroidism by anti-thyroid drugs and surgery, all the patients with bone involvement had a repeat DEXA scan after one year and the T-score was computed. RESULTS: Out of 50 patients, 46 had bone involvement (92 percent). Based on the World Health Organisation classification, 16 (32 percent) had osteopenia and 30 patients (60 percent) had osteoporosis. After control of thyrotoxicosis, the mean bone mass increased from 0.729 g/sq cm to 0.773 g/sq cm, a statistically significant increase of 0.044 g/sq cm (p-value is less than 0.001) after one year, compared to age- and sex-matched controls. The mean percentage of the bone mass compared to the peak BMD increased from 70.2 percent to 74.2 percent after treatment, an increase of four percent (p-value is less than 0.001). The mean percentage of the bone mass compared to the age-matched BMD increased from 71.2 percent to 75.2 percent after treatment, an increase of four percent (p-value is less than 0.001), all of which were statistically significant. CONCLUSION: Metabolic bone disease should be looked for in all thyrotoxic patients, especially patients complaining of bone pain and those with elevated bone enzymes. DEXA scans offer a convenient, reliable and noninvasive modality for diagnosis and monitoring therapy.

Cerebrovascular manifestations in scorpion sting: a case series.

Cerebrovascular manifestations are uncommon presentations of scorpion sting in the Indian subcontinent. A prospective study was carried out on 50 patients with scorpion sting referred to the Government General Hospital during the period from April 2004 to March 2005. In all the patients, detailed history, physical examination with a specific neurological examination and routine biochemical testing and fundus examination were done. Computerized Tomography (CT) and Magnetic Resonance Imaging (MRI) were done in cases with neurological deficit. All these patients also underwent a complete hematological, rheumatologic and cardiovascular work-up for stroke. Cerebrovascular involvement was noted in four patients (8%). Hemorrhagic stroke was noted in two patients (4%) and thrombotic stroke was noted in two patients (4%). The mean time of presentation of neurological symptoms was 2 days. Stroke has been a common presentation in our series (8%). Contrary to world literature, there have been no reports of cranial nerve palsies or neuromuscular involvement in our series.

A typical presentation of acute myeloid leukemia.

A young man who presented with fever, altered sensorium and sudden onset tachypnea, is described. Arterial blood gas analysis, revealed the presence of severe high anion gap metabolic acidosis, with compensatory respiratory alkalosis and normal oxygen saturation. A detailed neurological, nephrological, biochemical and hematological evaluation, revealed the presence of Acute myeloid leukemia, with lactic acidosis and hyponatremia. There are very few reports of presentation of leukemia as lactic acidosis. This case report highlights the need for emergency room physicians, to consider the possibility of lactic acidosis, as one of the causes of high anion gap acidosis and to meticulously investigate the cause of lactic acidosis. We describe a rare clinical instance of lactic acidosis as the presenting manifestation of Acute myeloid leukemia.