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Rare diseases form the bulk of the financial expenditure of any developing or developed economy. Among the various rare diseases, paediatric neuromuscular disorders form a major portion, with a worldwide survey estimating a prevalence of 1 in 3500 individuals. In a lower middle-income country (LMIC) like India, malnutrition still accounts for most of the under-5 mortality. However, the economic burden of rare paediatric neuromuscular disorders cannot be underestimated. The treating physician should have a basic understanding of how to approach a child presenting with weakness and how to utilise the available tests which are affordable in an LMIC setting. History and examination still form the core, and with new diagnostic methods like next-generation sequencing, more and more rare disorders are getting diagnosed. It is important for the treating physician to know about basic supportive care, recent advancements, and available treatment options for these conditions. With exciting new treatment options being available for these disorders, the perception of these diseases as being not treatable is gradually changing. This review aims to be of guidance to clinicians from an LMIC setting like India and to empower them to manage such rare paediatric neuromuscular disorders. [ABSTRACT FROM AUTHOR]

Objective: To socio-culturally adapt and validate a Hindi language version of Ages and Stages Qustionnaire (ASQ-3) in Indian children aged 2–24 months. Methods: This cross-sectional study was conducted at a tertiary-care center between March, 2017 and April, 2019, children "at-risk" for developmental delay of either gender aged 2–24 months. Socio-cultural adaptation was done through interaction among 37 subject experts followed by validation. [After piloting in 20 children, modified ASQ-3 was validated in 568 at-risk children (4 age-groups: 2–7, 7–13, 13–19 and 19–24 months). Validation was done against Development Assessment Scale for Indian Infants (DASII). Results: After screening 654 children, 568 were enrolled. Among these, 420 had developmental delay on DASII while 18 failed to be identified on ASQ-3 (4.3%). Overall sensitivity and specificity of Hindi language Indian-adaptation of ASQ-3 in detecting developmental delay were 95.9% (95%CI: 93.6%–97.5%) and 81.7% (95%CI: 74%–87.9%), respectively with a positive predictive value (PPV) of 94.6% (95%CI: 92%–96.5%) and negative predictive value (NPV) of 85.6% (95%CI: 78.2%–92.2%). The sensitivity and specificity for motor delay were 96.1% (93.8%–97.7%) and 92.4% (86.4%–96.3%) [PPV: 97.7% (95.8%–98.9%); NPV: 87.7% (81%–92.7%)]. Sensitivity and specificity for mental delay were 95.5% (93.1%–97.2%) and 95.3% (90.1%–98.3%) [PPV: 98.6% (97%–99.5%); NPV: 85.9% (79.1%–91.2%)]. Conclusion: The Hindi language Indian-adaptation of ASQ-3 had good psychometric properties with high sensitivity for developmental delay (95.9%), mental delay (95.5%), and motor delay (96.1%), suggesting it to be a good screening tool for neurodevelopmental delay. [ABSTRACT FROM AUTHOR]

Objective: The primary objective was to evaluate the postnatal maturation pattern on aEEG during first two weeks of life in clinically stable and neurologically normal preterm small for gestational age (PSGA) and gestation matched (1 week) preterm appropriate for gestational age (PAGA) neonates born between 300/7 and 346/7 weeks of gestation. Methods: Serial aEEG tracings were recorded on 3rd, 7th and 14th day of life. The primary outcome was total aEEG maturation score. Three blinded assessors assigned the scores. Results: We analyzed a total of 117 aEEG recordings in 40 (19 PSGA and 21 PAGA) neonates. The baseline characteristics were comparable except for birthweight [1186 (263) vs 1666 (230) g]. There was no difference in the mean (SD) total scores on day 3 (9.0 (1.8) vs. 9.5 (1.1), P=0.32) and day 14 of life, but was lower in PSGA infants on day 7 (8.6 (2.4) vs. 10.1 (1.1), P=0.02). On multivariate analysis, maturation of PSGA neonates was found to be significantly delayed at any point of life from day 3 to day 14 (mean difference, -0.8, 95 % CI: -1.6 to -0.02, P=0.04). Conclusion: Lower aEEG maturation score on day 7 possibly indicates delayed maturation in PSGA neonates in the first week of life. [ABSTRACT FROM AUTHOR]

Drooling is a challenging situation to manage especially in neurologically impaired pediatric population. Numerous surgical procedures have been described in literature but none of them is standardized. We evaluate the effectiveness of bilateral submandibular duct rerouting and sublingual gland excision in drooling paediatric patients. Prospective interventional study was conducted from November 2007 to September 2009 in twenty-eight pediatric patients with drooling who had failed conservative treatment modalities. Patients underwent bilateral submandibular duct transposition and sublingual gland excision. Patients were assessed pre-operatively, at 7, 30 and 90 days after surgery for drooling severity, frequency as per Thomas-Stonell and Greenberg classification and also number of bibs changed per day. Result was categorized using Wilkie and Brody criteria for assessing effectiveness of the surgery. Twenty-eight patients were successfully operated. All patients were followed-up for a duration of at least 3 months. The success rate achieved in term of control of drooling was 95.2 % at 3 months follow up. Statistically significant difference ( p < 0.001) was noted in pre-operative and postoperative mean values for severity and frequency of drooling and also bibs/day. Transient, minor complications (n = 5/28, 17.8 %) were encountered following this surgical procedure. Bilateral submandibular duct rerouting and sublingual gland excision in drooling paediatric patients is a simple and effective surgery with minor operative morbidity. Concomitant sublingual gland excision bilaterally helps in reducing the incidence of ranula formation significantly. [ABSTRACT FROM AUTHOR]

Objectives: 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

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. Conclusion. The INDT-EPI has high validity to identify children with epilepsy when used by primary care physicians. [ABSTRACT FROM AUTHOR]

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 Connor's 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, cdtedon 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. [ABSTRACT FROM AUTHOR]

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 κ=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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

ppropriate management of raised intracranial pressure begins with stabilization of the patient and simultaneous assessment of the level of sensorium and the cause of raised intracranial pressure. Stabilization is initiated with securing the airway, ventilation and circulatory function. The identification of surgically remediable conditions is a priority. Emergent use of external ventricular drain or ventriculo-peritoneal shunt may be lifesaving in selected patients. In children with severe coma, signs of herniation or acutely elevated intracranial pressure, treatment should be started prior to imaging or invasive monitoring. Emergent use of hyperventilation and mannitol are life saving in such situations. Medical management involves careful use of head elevation, osmotic agents, and avoiding hypotonic fluids. Appropriate care also includes avoidance of aggravating factors. For refractory intracranial hypertension, barbiturate coma, hypothermia, or decompressive craniectomy should be considered. [ABSTRACT FROM AUTHOR]

Objective: To identify pyridoxine responsive seizures among children with early onset intractable seizures, and to identify pyridoxine-dependency as a subset in this group. Methods: Patients with neonatal onset idiopathic, intractable seizures were identified over a 6-month period and subjected to a 'pyridoxine trial', at the Pediatric Neurology Clinic of a tertiary-care teaching hospital in New Delhi, India. This consisted of an intravenous infusion of 100 mg of pyridoxine over 10-min with a simultaneous EEG monitoring. This procedure was carried out in the EEG laboratory with all appropriate precautions (including availability of resuscitation equipment and trained personnel). Continuous EEG monitoring was done throughout the infusion and till 20 min later, to look for correction of EEG abnormalities. All patients were then prescribed oral pyridoxine, 10-15 mg/kg/day divided TDS for 6 weeks, in addition to their current anticonvulsant therapy. Patients were reviewed every 15 days regarding compliance and change in seizure frequency. A reduction in seizure frequency by 50% of the baseline was considered as 'response' (significant change), meriting further continuation of pyridoxine therapy. In patients who remained seizure free on pyridoxine therapy, previous anti-epileptics were gradually tapered one by one. Results: 621 children with active epilepsy were seen at the PNC, of which 48 had early-onset, medical intractable epilepsy, and 21 children (13 males and 8 females), aged between 11 month and 38 month were enrolled. The median age at onset of seizure was 5.1 months. The major seizure type was focal in 3 and generalized in 18 (including infantile spasm in 11). No patient had normalization of EEG during the 'trial'. Two patients (9.5%) had a response during the 2 weeks of oral treatment and oral therapy was continued. No toxicity or side-effects of pyridoxine were observed in these two patients over a follow-up of more than 18 months. Conclusions: Pyridoxine responsive seizures contribute a significant proportion to early-onset idiopathic intractable epilepsy in childhood. Routine use of pyridoxine in the management of early onset resistant seizures would go a long way in identifying these patients early. [ABSTRACT FROM AUTHOR]

Coma and other states of impaired consciousness represent a medical emergency. The potential causes are numerous, and the critical window for diagnosis and effective intervention is often short. The common causes of non-traumatic coma include central nervous system infections, metabolic encephalopathy (hepatic, uremic, diabetic ketoacidosis etc.), intracranial bleed, stroke and status epilepticus. The basic principles of management include 1) Rapid assessment and stabilization, 2) Focussed clinical evaluation to assess depth of coma, localization of lesion in the central nervous system and possible clues to etiology, and 3) Treatment including general and specific measures. Commonly associated problems such as raised intracranial pressure and seizures must be recognized and managed to prevent secondary neurologic injury. [ABSTRACT FROM AUTHOR]

Objective: To prospectively assess the outcome of children diagnosed with Guillain-Barré syndrome (GBS), followed up for a median duration of 25 months.Methods: Tertiary center, prospective follow up of children with GBS enrolled between, Dec 2003 to Sep 2006. Functional recovery was determined at 12 months and later using Hughes scale (0-6). Clinical, electrophysiological variables were compared between the good outcome (grade 0/1) and bad outcome groups (died or functional grade >1).Results: Among 52 children with a median age of five yr there was male preponderance (75.4%). Mortality during acute phase was 11.5% (6/52). Among the survivors long term data was obtainable in 40 of the 46 children. At one year follow up 87.5% children had fully recovered or had minimal symptoms, beyond one year this rose to 95%. Only 2 among 40 had significant symptoms at last follow up (1 grade-2 and 1 grade-3). Factors significantly associated with poor outcome were: need for artificial ventilation, inexitable nerves on nerve conduction testing and delayed independent walking.Conclusion: Children needing ventilation have the worst short-term prognosis. However, irrespective of severity during acute phase, good long-term recovery can be expected in most children. [ABSTRACT FROM AUTHOR]

People with developmental disabilities have problems with major life activities such as language, mobility, learning, self-help, and independent living. Developmental disabilities begin anytime during development upto 22 years of age and usually last throughout a person's lifetime. It reflects the person's need for a combination and sequence of special interdisciplinary or generic care, treatment or other services that are of life-long or extended duration and that are individually planned and coordinated. They currently represent a large proportion of the childhood illnesses and disorders. The causes can be environmental, genetic or multifactorial. Prevention is important to reduce the neuromorbidity in the society. Strategies for prevention are discussed which take into account the possible causal associations. [ABSTRACT FROM AUTHOR]

Unlabelled: In about 10% cases of Duchenne muscular dystrophy (DMD), death is due to cardiac dysfunction. The recognition of cardiomyopathy in DMD is thus important.Objective: To assess cardiac involvement in DMD patients by clinical, radiographic, electrocardiographic (ECG) and echocardiographic monitoring and correlate clinical parameters, CPK levels, presence of gene deletion and steroid therapy with cardiac involvement.Methods: Thirty patients beyond 6 years age, with DMD in advanced stage disease/non-ambulatory were recalled. A detailed clinical evaluation, CPK levels, gene deletion studies were carried out. Cardiac investigations included Chest X-ray, 12 lead ECG and echocardiography.Results: Nineteen patients were non-ambulatory at the time of enrollment. Symptoms or signs suggestive of cardiac dysfunction were seen in only 10%. Gene deletion was identified in 70.3%. Around one-third patients had cardiomegaly. ECG abnormalities were present in 93.3% patients and commonest abnormality was R > 4 mm in V1. Ejection fraction (EF) < 55% was observed in 64.2% and EF < 50% in 17.8%.Conclusion: Cardiomyopathy of DMD is characterized by lack of symptoms and few physical signs. Presence of subtle changes like sinus tachycardia may suggest early cardiac involvement. Thus echocardiography is required for evaluation of cardiac dysfunction. Presence of gene deletion was associated with higher CT ratio. Older children have been found to have higher heart rates. No other significant correlation with clinical parameters, CPK levels, genotype and steroid therapy was observed. Early detection possibly leads to appropriate treatment thus reducing the morbidity. [ABSTRACT FROM AUTHOR]

Objective: To study the clinical profile, immediate outcome and possible risk factors of SE in pediatric age group admitted to pediatric intensive care unit (PICU) in a tertiary care center.Methods: A retrospective study of case records of 451 neuroemergency patients admitted in PICU in a tertiary care center between January 1993 to April 2000, out of which 30 patients had status epilepticus. They were evaluated for their clinical presentation, laboratory parameters, treatment profile and immediate outcome.Results: The age group varied from 1 to 120 months with mean of 56.6+/- 46.5 months. Seventeen patients were less than 60 months. Sixteen patients (53.3%) presented with SE as first presentation without prior history of seizure activity. Nine patients died (30%) during hospital course. Seizure duration> 45 minutes (p-0.001) and presence of septic shock (p-0.001) were associated with significantly more mortality.Conclusion: There is a need to abort seizure activity at the earliest and this improves immediate outcome. [ABSTRACT FROM AUTHOR]

Two infants with non-accidental inflicted neuro-trauma are reported. One presented with sudden onset lethargy, respiratory difficulty and unexplained seizures. There were bilateral retinal bleeds and extradural hemmorage. Other was a well thriving child who had 2 seizures and was noted to lack visual fixation. Retinal hemorrhages and chronic subdural and intraparenchymal hemorrhages were subsequently discovered. We highlight the importance of suspecting child abuse in infants with sudden unexplained unresponsiveness, seizures or respiratory difficulty and the unusual occurrence of extradual hemorrhage. [ABSTRACT FROM AUTHOR]

Lissencephaly (LIS) is a brain malformation manifested by a smooth cerebral surface, thickened cortical mantle and microscopic evidence of incomplete neuronal migration, excluding polymicrogyria and other cortical dysplasias. It is important to consider LIS in the diagnosis of developmental delay as many patients may be diagnosed as cerebral palsy. It may have familial occurrence and can occur in sibs of same family often leading to a diagnostic problem. Several lissencephaly syndromes have been described. Here a familial syndrome of lissencephaly is reported. Autosomal recessive inheritance is suggested by recurrence in sibs within the same family, but germ cell mosaicism for a dominant mutation cannot be excluded. [ABSTRACT FROM AUTHOR]

Following trauma, the commonly used radiological investigations, plain radiographs and computed tomography (CT) studies do not rule out injury to the spinal cord. This is especially true for children, as an entity known by the acronym SCIWORA (spinal cord injury without radiological abnormality) exists and the changes may be picked up only on magnetic resonance imaging (MRI). Early treatment (within 6 hours) with high dose methylprednisolone improves the outcome. Spinal trauma being common it is possible that the burden of neurological handicap following this can be reduced by increasing awareness and early treatment with steroids. In the community, pediatricians are often the first medical contact after spinal trauma and awareness of the lacune of conventional imaging techniques is important especially if clinical symptoms pertaining to the spine are present. The community pediatrician is hereby made aware of the need to investigate spinal trauma with a MRI for possible SCIWORA situation as it generates a possibility for therapeutic intervention to alter the outcome positively. [ABSTRACT FROM AUTHOR]

Familial combined hyperlipidemia is the most common genetic hyperlipidemia and is responsible for premature coronary artery disease. It is genetically heterogenous and no single diagnostic marker exists. The authors report an affected North Indian kindred spanning three successive generations with a possible autosomal dominant pattern of inheritance and all of them had combined dyslipidemia [elevated total cholesterol, predominantly the low density lipoprotein (LDL) fraction and elevated triglycerides]. The proband, a 4-month-old male baby, was incidentally discovered to have a lipaemic serum and so further evaluated. Both the index case and his maternal grandmother, a non-obese diabetic (type 2) with hypertension, had an atherogenic lipoprotein phenotype. Lipaemia retinalis was documented in this baby but xanthomas and coronary artery disease were not noted in the kindred. The present case report highlights the failure of dietary therapy in the proband and explores new options. [ABSTRACT FROM AUTHOR]

Myelofibrosis with myeloid metaplasia is defined as a myeloproliferative disorder characterized by leukoerythroblastosis, tear drop erythrocytes, extramedullary hematopoesis and varying degree of myelofibrosis. It may be idiopathic or secondary to a large number of conditions. Here is a rare case of myelofibrosis occurring in a patient with juvenile rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

A 12-yr-old boy with an atypical presentation of subacute sclerosing panencephalitis (SSPE) is described. Bilateral macular chorioretinitis preceded the neurological symptoms by 3 weeks. Both visual and neurological features had an acute onset. Clinicians need to be aware that macular chorioretinitis in a child may be the heralding feature of SSPE. [ABSTRACT FROM AUTHOR]

A one-year-boy presented with constipation, fever, failure to thrive and developmental delay from the neonatal period. Investigations revealed persistent hypernatremia and deranged renal functions. Diagnostic work-up was suggestive of nephrogenic diabetes insipidus (NDI). Computerized tomography of head revealed calcification in the frontal, thalamic and basal ganglia region. The rare association of NDI and intracranial calcification is discussed. [ABSTRACT FROM AUTHOR]

The article discusses the clinical case of a two-year-old boy who was diagnosed with linear and whorled nevoid hypermelanosis with hemiatrophy.