Clinical Profile and Short-term Outcome of Pediatric Status Epilepticus at a Tertiary-care Center in Northern India

Objective: To assess clinical profile and short term treatmentoutcomes of pediatric status epilepticus (SE) at a tertiary-carecenter in northern India.Methods: Prospective cohort study enrolled children aged 1month to 18 years presenting with SE to the emergencydepartment. Enrolled children (109) were treated as per hospitalprotocols. Clinical features during hospitalization were noted.Pediatric overall performance category (POPC) scale was usedfor classification of outcome at the time of discharge.Results: Acute symptomatic etiology was identified in 66(60.6%) cases (CNS infections were predominant). Previousdiagnosis of epilepsy was found in 32 (29.4%) children; andbenzodiazepine responsive SE were seen in 65 (59.6%)children. Predictors of unfavorable outcome were acutesymptomatic etiology (adjusted OR 4.50; 95% CI 1.49, 13.62) andno treatment administered prior to hospital (adjusted OR 3.97;95% CI 1.06, 14.81).Conclusions: Acute symptomatic etiology, mainly acute CNSinfections, is the leading cause of SE in this region. Early and pre-hospital management with benzodiazepines may improve SEoutcome.

Diagnostic Accuracy of Indian Scale for Assessment of Autism in Indian Children Aged 2-5 Years

Objective: To determine the diagnostic accuracy of Indian Scalefor Assessment of Autism (ISAA) in children aged between 2-5years.Design: Study of diagnostic accuracySetting: Tertiary level hospital, (November 2015 – November2017).Participants: A consecutive sample of 500 children withsuspected Autism (delay or regression of developmentalmilestones, delay or regression in speech, age-inappropriateunderstanding, behaviour, play and/or social interaction) wasrecruited.Procedure: Each child underwent an expert comprehensiveassessment of Autism (reference tool) that included history,observation, examination, diagnostic criteria for Autism SpectrumDisorder (ASD) of the Diagnostic and Statistical Manual of MentalDisorders’, 5th edition, Childhood Autism Rating Scale-2(CARS2), developmental status and adaptive function. This wasfollowed by the administration of ISAA (test tool) in Hindilanguage. Parameters of diagnostic accuracy and ReceiverOperating Characteristic curves were computed.Main Outcome Measures: ASD based on (i) expert assessment,(ii) CARS-2, and (iii) ISAA.Results: In children aged 2-3 years, sensitivity of ISAA was 100%(95% CI 98.2% -100%), specificity 28.9% (95% CI 17.7% to43.4%), positive likelihood ratio 1.4 and negative likelihood ratio 0.In 3-5 year olds, sensitivity was 99.6% (95% CI 97.6% to 99.6%),specificity 33.3% (95% CI 15.1% to 58.3%), positive likelihoodration 1.5 and negative likelihood ratio 0.01. The degrees ofautism based on the existing cut off values were inaccurate.Conclusions: ISAA has sub-optimal performance in diagnosingand assessing severity in 2-5 year old children.

Injuries in Children With Epilepsy: A Hospital-based Study.

Objectives: To study the magnitude and pattern of injuries in children with epilepsy. Methods: This prospective cohort study enrolled children with epilepsy (CWE) aged 2-16 years on treatment with anti-epileptics for a minimum duration of one-month and compared them with their own siblings (controls). A semi-structured questionnaire was used to enquire about epilepsy and type and frequency of injuries sustained at monthly follow-up visits. Participants were followed up for 12-months for occurrence of injuries. Results: 208 cases and 212 controls were analyzed. 21 cases (10.1%) and 10 controls (4.7%) had sustained injuries (P=0.03) (RR 2.1; 95% CI, 1.0 - 4.4). Seizure-related injuries were present in 4.3% of cases. Conclusion: Children with epilepsy are at an increased risk of injuries and hence need supervision.

Diagnostic Accuracy of Indian Scale for Assessment of Autism (ISAA) in Chidren Aged 2-9 Years.

Objective: To determine the diagnostic accuracy of Indian Scale for Assessment of Autism (ISAA) in children aged 2-9 year at high risk of autism, and to ascertain the level of agreement with Childhood Autism Rating Scale (CARS). Design: Diagnostic Accuracy study Setting: Tertiary-level hospital. Participants: Children aged between 2 and 9 year and considered to be at a high risk for autism (delayed development, and age-inappropriate cognition, speech, social interaction, behavior or play) were recruited. Those with diagnosed Hearing impairment, Cerebral palsy, Attention deficit hyperactivity disorder or Pervasive developmental disorders (PDD) were excluded. Methods: Eligible children underwent a comprehensive assessment by an expert. The study group comprising of PDD, Global developmental delay (GDD) or Intellectual disability was administered ISAA by an investigator after one week. Both evaluators were blinded. ISAA results were compared to the Expert’s diagnosis and CARS scores. Results: Out of 102 eligible children, 90 formed the study group (63 males, mean age 4.5y). ISAA had a sensitivity 93.3, specificity of 97.4, positive and negative likelihood ratios 85.7 and 98.7 and positive and negative predictive values of 35.5 and 0.08, respectively. Reliability was good and validity sub-optimal (r low, in 4/6 domains). The optimal threshold point demarcating Autism from ‘No autism’ according to Receiver Operating Characteristic curve was ISAA score of 70. Level of agreement with CARS measured by Kappa coefficient was low (0.14). Conclusions: The role of ISAA in 3-9 year old children at high risk for Autism is limited to identifying and certifying Autism at ISAA score of 70. It requires re-examination in 2-3 year olds.

Consensus Guidelines on Management of Childhood Convulsive Status Epilepticus.

Justification: Status epilepticus has a wide etiological spectrum, and significant morbidity and mortality. Management using a pre-determined uniform protocol leads to better outcomes. Multiple protocols for management of childhood status epilepticus are available, without much consensus. Process: A ‘Multi-disciplinary Consensus Development Workshop on Management of Status Epilepticus in Children in India’ was organized. The invited experts included Pediatricians, Pediatric neurologists, Neurologists, Epileptologists, and Pediatric intensive care specialists from India, with experience in the relevant field. Experts had previously been divided into focus groups and had interacted on telephone and e-mail regarding their group recommendations, and developed consensus on the topic. During the meeting, each group presented their recommendations, which were deliberated upon by the house and a consensus was reached on various issues; the document was finalized after incorporating suggestions of experts on the draft document. Objective: To provide consensus guidelines on evaluation and management of convulsive status epilepticus in children in India (excluding neonatal and super-refractory status epilepticus). Recommendations: Each institution should use a predetermined protocol for management of status epilepticus; prehospital management and early stabilization is the key to a satisfactory outcome of status epilepticus. Pharmacotherapy should not be delayed for any investigations; the initial management should consist of a parenteral benzodiazepine by any route feasible. Subsequent management has been detailed. The group also felt the need for more epidemiological research on status epilepticus from India, and identified certain research areas for the purpose.

Incorporating Developmental Screening and Surveillance of Young Children in Office Practice.

Context: Developmental concerns voiced by parents need to be responded to by structured developmental screening. Screening is the use of validated developmental screening tools to identify children with high risk of developmental delay out of an apparently normal population, while surveillance is the process of monitoring children identified as high risk by screening. Absence of routine screening can be attributed to problems at the level of parents, pediatricians or National policies. Hence vulnerable children are not detected early, and are denied benefit from appropriate developmental interventions. There are no definite guidelines for screening or for suitable tools for screening and surveillance. Objectives: To review existing developmental screening and monitoring tools for children validated in Indian under-five children, and provide a proposed practice paradigm for developmental screening in office practice. Evidence Acquisition: Scientific papers were retrieved by an electronic database search using MeSH terms ‘screening tool’, ‘developmental delay’, and filter of ‘children under 5 years’. Those relevant to office practice and validated internationally or in Indian children were reviewed. Results: Screening tools applicable to Indian office practice have been compared and certain tools have been recommended according to the level of risk of developmental delay. An algorithmic approach to screening has been given along with strategies for incorporation. Conclusions: Screening and surveillance for high risk of developmental delay are essential components of child health care. It is possible to incorporate both into routine practice.

INCLEN Diagnostic Tool for Neuromotor Impairments (INDT-NMI) for Primary Care Physician: Development and Validation.

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 INDTNMI (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 INDTNMI 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.

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. Conclusion: 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 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, 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.

Newer Anti-epileptic Drugs.

Need and Purpose of review: A number of newer anti-epileptic drugs have been developed in the last few years to improve the treatment outcomes in epilepsy. In this review, we discuss the use of newer anti-epileptic drugs in children. Methods used for locating, selecting, extracting and synthesizing data: MEDLINE search (1966-2013) was performed using terms “newer anti-epileptic drugs”, “Oxcarbazepine”, vigabatrin”, topiramate”, “zonisamide”, “levetiracetam”, “lacosamide”, “rufinamide”, “stiripentol”, “retigabine”, “eslicarbazepine”, “brivaracetam”, “ganaxolone” and “perampanel” for reports on use in children. Review articles, practice parameters, guidelines, systematic reviews, meta-analyses, randomized controlled trials, cohort studies, and case series were included. The main data extracted included indications, efficacy and adverse effects in children. Main conclusions: Oxcarbazepine is established as effective initial monotherapy for children with partial-onset seizures. Vigabatrin is the drug of choice for infantile spasms associated with tuberous sclerosis. Lamotrigine , levetiracetam and lacosamide are good add-on drugs for patients with partial seizures. Lamotrigine may be considered as monotherapy in adolescent females with idiopathic generalized epilepsy. Levetiracetam is a good option as monotherapy for females with juvenile myoclonic epilepsy. Topiramate is a good add-on drug in patients with epileptic encephalopathies such as Lennox-Gastaut syndrome and myoclonic astatic epilepsy.

Prospective multi-centre sentinel surveillance for Haemophilus influenzae type b & other bacterial meningitis in Indian children.

Background & objectives: Haemophilus influenzae type b (Hib) is one of the leading bacterial causes of invasive disease in populations without access to Hib conjugate vaccines (Hib-CV). India has recently decided to introduce Hib-CV into the routine immunization programme in selected States. Longitudinal data quantifying the burden of bacterial meningitis and the proportion of disease caused by various bacteria are needed to track the impact of Hib-CV once introduced. A hospital-based sentinel surveillance network was established at four places in the country and this study reports the results of this ongoing surveillance. Methods: Children aged 1 to 23 months with suspected bacterial meningitis were enrolled in Chennai, Lucknow, New Delhi, and Vellore between July 2008 and June 2010. All cerebrospinal fluid (CSF) samples were tested using cytological, biochemical, and culture methods. Samples with abnormal CSF (≥10 WBC per μl) were tested by latex agglutination test for common paediatric bacterial meningitis pathogens. Results: A total of 708 patients with abnormal CSF were identified, 89 of whom had a bacterial pathogen confirmed. Hib accounted for the majority of bacteriologically confirmed cases, 62 (70%), while Streptococcus pneumoniae and group B Streptococcus were identified in 12 (13%) and seven (8%) cases, respectively. The other eight cases were a mix of other bacteria. The proportion of abnormal CSF and probable bacterial meningitis that was caused by Hib was 74 and 58 per cent lower at Christian Medical College (CMC), Vellore, which had a 41 per cent coverage of Hib-CV among all suspected meningitis cases, compared to the combined average proportion at the other three centres where a coverage between 1 and 8 per cent was seen (P<0.001 and P= 0.05, respectively). Interpretation & conclusions: Hib was found to be the predominant cause of bacterial meningitis in young children in diverse geographic locations in India. Possible indications of herd immunity was seen at CMC compared to sites with low immunization coverage with Hib-CV. As Hib is the most common pathogen in bacterial meningitis, Hib-CV would have a large impact on bacterial meningitis in Indian children.

Consensus Guidelines on Evaluation and Management of Suspected Acute Viral Encephalitis in Children in India.

Justification: Viral encephalitis is an important cause of mortality and morbidity in children. The etiological agents are varied, and physicians treating such children often feel limited by the lack of uniform guidelines on evaluation and management of these critically ill children in resource-constrained settings. Process: An ‘Expert Group Meeting on Viral Encephalitis in Children’ was held on 19th January, 2012 in Gurgaon, Haryana (under the aegis of PEDICON 2012, the National Conference of Indian Academy of Pediatrics). The invited experts included pediatricians and microbiologists with expertise in the relevant field. Various issues related to the subject were discussed and it was decided to bring out recommendations on the topic. The final recommendations were produced after circulating the draft document, and incorporating/discussing all changes, by e-mail. Objectives: To aid the pediatrician in the evaluation and management of children with suspected viral encephalitis and to assist the public health authorities in acute encephalitis surveillance. These guidelines do not cover viral encephalitis in the neonatal period and in immunocompromised children, Rabies encephalitis, and chronic viral encephalitis such as Subacute sclerosing panencephalitis (SSPE). Recommendations: Recommendation for evaluation and management of suspected viral encephalitis in children are presented. In any acute encephalitis outbreak, pediatricians should be aware of the common viral causes of encephalitis in their area, what information and samples they should collect, and the contact details of the District Surveillance Unit. Pending specific diagnosis and therapy (which may or may not be possible), prompt empirical therapy and meticulous supportive care are important to prevent ongoing brain damage, and improve outcome.

The Renal Cysts and Diabetes (RCAD) Syndrome in a Child with Deletion of the Hepatocyte Nuclear Factor-1β Gene.

The authors describe a 14-yr-old boy who presented with non-ketotic hyperglycemia, elevated serum creatinine levels and deranged liver function. There was no microalbuminuria or proteinuria. He also had mild mental retardation with learning difficulties. Ultrasonography of the abdomen revealed multiple renal cysts of varying sizes in both the kidneys. Dosage analysis of the hepatocyte nuclear factor (HNF)-1β gene by multiplex ligation-dependent probe amplification (MLPA) detected a heterozygous whole gene deletion (p.Met1_Trp557del). This finding is consistent with the diagnosis of renal cysts and diabetes (RCAD) syndrome. This is the first case of the RCAD syndrome reported in an Indian patient. Pediatricians need to be aware of this entity whenever renal disease is seen in a diabetic child in the absence of microalbuminuria or proteinuria.

Congenital langerhans cell histiocytosis with skin and lung involvement: Spontaneous regression.

Congenital self-healing Langerhans cell histiocytosis (CSHLCH) is a rare type of Langerhans Cell Histiocytosis, presenting at birth or during the neonatal period with eruption of multiple, discrete red-brown papules or nodules that undergo spontaneous regression. Systemic signs are generally absent. We describe a 4-month-old infant presenting with reddish brown nodular cutaneous lesions since birth with a past history suggestive of pulmonary involvement. Skin biopsy showed a dermal infiltrate of pleomorphic histiocytes; which were CD1a and S-100 positive, consistent with the diagnosis of CSHLCH. Both pulmonary and cutaneous lesions showed spontaneous resolution.

Ovarian tumors with elevated ca-125 levels and severe juvenile hypothyroidism: A need for increased awareness.

A 15-yr-old girl presented with bilateral gross ovarian tumors, clinical features of long-standing unrecognized hypothyroidism and markedly elevated CA-125 levels. Ovarian resection was avoided, as the presentation was consistent with the Van Wyk and Grumbach syndrome; and the patient was treated with replacement of thyroid hormone. Regression of the ovarian tumors occurred 6 months after initiation of the treatment. The authors emphasise the need for increased awareness and screening for hypothyroidism in patients with ovarian tumors, in order to prevent inadvertent operative interventions.

A study of acute febrile encephalopathy with special reference to viral etiology.

OBJECTIVE: To study the etiological profile of patients with acute febrile encephalopathy syndrome focusing chiefly on the viral etiology, and to correlate clinical and radiological features of patients with viral encephalitis. METHODS: A prospective hospital based study conducted on the consecutive patients admitted in a pediatric unit during the period of 1(st) February 2004 to 31st January 2005 based on the following inclusion criteria: (1) Age more than 1 month and less than 18 years and (2) A diagnoses of acute febrile encephalopathy, based on the following criteria: (i) fever (ii) acute depression of consciousness or mental deterioration for more than 12 hours with or without motor or sensory deficit and (iii) Total duration of illness at the time of admission 1 week or less. RESULTS: The final study group comprised of 151 patients with mean age of 3.21 +/- 2.9 (range of mth-13 years) and male: female ratio of 1.71: 1. A diagnosis other than viral encephalitis was reached in 94 patients (62.3 %). Pyogenic meningitis was the most frequent diagnosis 51(33.8 %) followed by tubercular meningitis 12 (7.9 %), and cerebral malaria 8 (5.2 %) in the patient group of non-viral causes. Fifty-seven cases (37.3%) were suspected as viral encephalitis and mean age of the cases suspected as viral encephalitis was 2.8 +/- 2.9 (Range 1 mth-10 yrs) with male: female ratio of 1.28: 1. Etiological diagnosis was reached or considered probable in 41 (72%) cases out of the suspected patients. The most common etiological agent identified was enterovirus 71 in 20 patients (35.1 %). The other viruses identified were mumps in 6 (10.5%), Japanese encephalitis in 5 (8.7%), and measles in 4 (7%) cases. MRI brain was done in 39 patients and was abnormal in 14 patients. Out of 57 cases of suspected viral encephalitis 10 patients expired within 48 hours, 2 > 48 hours and 19 atients had significant neurological sequels at discharge. CONCLUSION: The etiology of acute febrile encephalopathy varies from infectious etiologies to noninfectious metabolic disorders. There are no distinguishing clinical or radiological features to differentiate the various causes of viral encephalitis. The clinical and the radiological findings in encephalitis should be interpreted in the geographical and other epidemiological background.

Etiological profile of stroke and its relation with prothrombotic states.

OBJECTIVE: To study the etiological profile of childhood stroke and its relation with prothrombotic states. METHODS: Children with acute stroke with no evidence of CNS infection or head injury were studied. Stroke was confirmed by CT scan and further evaluated by MRI. Cardiac status was assessed with transthoracic echocardiography. Test for hypercoagulable state (antithrombin III, protein C, protein S, anticardiolipin antibody IgG and IgM and lupus anticoagulant) were done in all patients. RESULTS: A total of 66 children were enrolled--36 cases and 30 controls. Presenting symptoms were motor deficit (72%), seizure (66%), altered sensorium (36%), aphasia (27%). Causes identified were antiphospholipid antibody syndrome (25%), Moya Moya disease (16.6%), cardiac disease (11.1%), vasculitis (5.5%), ATIII deficiency (5.5%), Protein C deficiency (2.7%). Etiology remained unknown in 25% of cases with infarction. Hemorrhage was seen in 8.2% of cases and they had DIC or liver disease as the underlying cause. CONCLUSIONS: Magnetic Resonance Angiography and ELISA for antiphospholipid antibody should be done in all patients with stroke without an obvious cause.