Risk Factors for Stroke in Children with Tuberculous Meningitis: A Prospective Observational Study.

OBJECTIVE: The purpose of the study is to establish the prevalence of stroke as well as the clinical and radiological correlates of stroke in children with tuberculous meningitis (TBM). METHODS AND MATERIALS: A prospective observational study was conducted at the Pediatric Department, King George's Medical University (KGMU), Lucknow, Uttar Pradesh, India. Using a computed tomography (CT) scan/brain magnetic resonance imaging (MRI), patients were divided into stroke and non-stroke groups. Demographic characteristics, clinical presentations, cerebrospinal fluid examination, basal meningeal enhancement, hydrocephalus, tuberculoma, and clinical outcome were compared between the two groups. RESULTS: Seventy-eight TBM patients, aged between 6 months and 14 years, were included. Out of 78 enrolled patients, 3 (3.8%) had definite TBM, 73 (91%) had probable TBM, and 4 (5.1%) had possible TBM (LCS). As per the Medical Research Council (MRC) staging, 13% had Stage 1 TBM, 26% had stage 2, and 61% had stage 3 TBM. Out of 78 patients with chest X-ray findings, 42 (53%) had findings suggestive of tuberculosis (TB), which included 33 (42%) with hilar lymphadenopathy and 9 (11%) with a miliary pattern. On neuroimaging, hydrocephalous was seen in 62.8% of cases, basal meningeal enhancement in 64.1%, tuberculoma in 6.4% of cases, and infarction in 53.8% of cases. There was no statistically significant association found between the staging of TBM and the presence of infarction as the majority of cases involved were in stage 3 of the disease (61.5%). TBM patients with stroke had poor clinical outcomes. CONCLUSION: Age, altered sensorium, focal neurological deficits, vomiting, and basal meningeal enhancement can predict the occurrence of stroke in young adults with TBM.

Role of neuroimaging in children with first unprovoked seizure: A prospective observational study.

OBJECTIVE: To evaluate the incidence and type of neuroimaging abnormalities in first unprovoked seizure (FUS) in children. To investigate the association of neuroimaging abnormalities with clinical variables. METHODS: A prospective observational study enrolled children aged 6 months-14 years with FUS over one year at a tertiary-care teaching hospital, Northern India and subjected them to neuroimaging. Factors associated with abnormal neuroimaging were assessed using Chi square/Fischer Exact test. RESULTS: Out of 115 cases, 40 (34.8%) had abnormal neuroimaging. Frequent findings were inflammatory granuloma (70%) including Neurocysticercosis (NCC) (40%), ill-defined granuloma, calcified nodule and tuberculoma followed by white matter signal alterations. Inflammatory granuloma was significantly associated with age >2 years and focal seizures. Calcified nodule was more common in children >10 years. Other neuro-abnormalities like cerebral atrophy, gliosis, infarcts, and white matter changes were significantly prevalent with generalized seizures, perinatal asphyxia, and developmental delay. CONCLUSION: High prevalence of abnormalities in FUS, especially focal seizures, due to NCC warrants neuroimaging in all children with FUS in India.

Neuroradiologic Features Associated With Severe Restriction of Functional Mobility in Children With Cerebral Palsy in North India.

BACKGROUND: Few studies have focused on magnetic resonance imaging (MRI) brain findings associated with functional mobility in cerebral palsy. OBJECTIVE: To determine association between MRI findings and Gross Motor Functional Classification System (GMFCS) levels in cerebral palsy. METHODS: Prospective-observational study conducted in Pediatric Neurology Clinic at a public teaching hospital, Northern India. First 3 new cases of cerebral palsy were enrolled on particular neuro-clinic day per week for 1 year. Functional mobility was classified according to GMFCS. Association between MRI findings, cerebral palsy type, and GMFCS levels were evaluated using χ2 test. RESULTS: A total of 138 cases (mean age 2.71 [SD = 1.91] years; male [64.5%]) were enrolled. Reported types of cerebral palsy were as follows: spastic quadriplegia (47.8%), spastic diplegia (28.35%), spastic hemiplegia (11.6%), extrapyramidal (6.5%), and ataxic/hypotonic (5.8%). GMFCS were classified into level 1 (13%), level 2 (7.2%), level 3 (4.3%), level 4 (10.9%), and level 5 (64.5%). Spastic quadriplegia and extrapyramidal cerebral palsy were significantly associated with higher (severe) levels (IV and V), whereas spastic diplegia and hemiplegia were significantly associated with lower (mild) levels (I-III) of GMFCS. MRI features of periventricular white matter injury, deep gray matter injury, basal ganglia and thalamic changes, and superficial gray matter injury were significantly associated with severe levels of GMFCS (V and IV). MRI was normal in 8 children (5 = mild category, 3 = severe category). CONCLUSION: Severe cerebral palsy is most often associated with spastic quadriplegia, extrapyramidal cerebral palsy, superficial gray matter lesions, deep gray matter lesions, and periventricular white matter injury. This information is useful for anticipating and addressing the needs of children with cerebral palsy and for prognostication.

Prediction Rule for Scrub Typhus Meningoencephalitis in Children: Emerging Disease in North India.

OBJECTIVES: To evaluate the proportion of scrub typhus meningoencephalitis among children with acute encephalitis syndrome and to outline its differentiating features. To develop a prediction rule for scrub typhus meningoencephalitis. METHODS: A prospective cohort study was conducted at a tertiary care public hospital in Northern India. Consecutive patients of acute encephalitis syndrome who met our inclusion criteria were enrolled over 2 years. Standardized workup including serum IgM against Orientia tsutsugamushi was performed. Clinical and laboratory features were compared between IgM-positive and IgM-negative patients. The area under the receiver operating characteristic curve of the score derived from "independent predictors" was measured. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were calculated at different cut-offs of the score. RESULTS: Scrub typhus IgM enzyme-linked immunosorbent assay was positive in 66/352 patients (18.8%). Longer duration of fever and prodromal stage along with eschar, hepatomegaly, lymphadenopathy, and pneumonia were significantly more prevalent in scrub typhus meningoencephalitis. However, petechiae were frequent in non-scrub typhus patients. Leucocytosis, lymphocytosis, thrombocytopenia, hypoalbuminemia, and elevated levels of serum bilirubin, serum transaminases, and cerebrospinal fluid protein were associated with scrub typhus meningoencephalitis. Logistic regression revealed fever for >8 days, pneumonia, absence of petechiae, cerebrospinal fluid protein >1000 mg/L, and serum glutamic oxaloacetic transaminase >100 IU/L as independent "predictors" of scrub typhus meningoencephalitis. The area under the receiver operating characteristic curve (95% confidence interval) of the prediction score was 0.832 (0.78-0.89). Score at cutoff ≥1 had 91% sensitivity, 96.1% negative predictive value, and at cutoff ≥4 had 99.7% specificity, 88.9% positive predictive value, 83.1% negative predictive value, 40.3 positive likelihood ratio, 0.88 negative likelihood ratio for identifying scrub typhus meningoencephalitis. CONCLUSION: Prediction score may help physicians in peripheral areas to identify and treat scrub typhus meningoencephalitis, an emerging cause of acute encephalitis syndrome in India.

Development of Dopamine Sensor Using Silver Nanoparticles and PEG-Functionalized Tapered Optical Fiber Structure.

This article presents a localized surface plasmon resonance (LSPR) phenomenon based optical fiber sensor (OFS) for the detection of dopamine (DA). DA functions as a hormone and a neurotransmitter in the human body and plays a crucial role in the peripheral system. To develop the OFS for DA detection, taper fiber probe was fabricated and immobilized with silver nanoparticles (AgNPs) and functionalized with Polyethylene glycol (PEG). The developed sensor shows the great selectivity in the presence of ascorbic acid (AA) oxidation due to PEG coating. The morphology of the AgNPs and uniformity of coating over the surface of sensing probe were confirmed with UV-visible spectrophotometer, transmission electron microscope (TEM), energy-dispersive X-ray spectroscopy (EDS), and scanning electron microscope (SEM). The calibration curve is found to be linear over the range of 10 nM-1 µM with the lowest detection limit of 0.058 µM. Also provides a wide dynamic range of detection (10 nm-100 µM). The parameters responsible for the performance of OFS, such as sensitivity, detection limit, and selectivity are greatly improved in the proposed sensor. The applicability of the proposed sensor has been validated and have the potential to use for routine diagnosis.

Role of oral Minocycline in acute encephalitis syndrome in India - a randomized controlled trial.

BACKGROUND: Acute encephalitis syndrome (AES) is a public health problem in India. Neuroinfections are believed to be the most important etiology. Minocycline is a semisythetic tetracycline having excellent penetration into cerebrospinal fluid, established neuroprotective and antiviral properties besides action on nonviral causes of AES. It has been shown to be effective in animal model of Japanese encephalitis (JE). A randomized, controlled trial of nasogastric/oral minocycline in JE and AES at a single centre in Uttar Pradesh, northern India, was therefore conducted. METHODS: Patients beyond 3 years of age - but excluding women aged 16-44 years - hospitalized with AES of < =7 days duration were enrolled and block randomized to receive nasogastric/oral minocycline or placebo suspension and followed up. Patients, study personnel and those entering data were blinded as to drug or placebo received. Primary outcome was cumulative mortality at 3 months from hospitalization. Analysis was by intention to treat. RESULTS: 281 patients were enrolled, 140 received drug and 141 placebo. While there was no overall statistically significant difference in 3 month mortality between drug and placebo groups [RR = 0 · 83 (0 · 6-1 · 1)], there were encouraging trends in patients older than 12 years [RR = 0.70 (0.41-1.18)] and in Glasgow Outcome Score (GOS) at 3 months (χ(2) = 7 · 44, p = 0 · 059). These trends were further accentuated if patients dying within one day of reaching hospital were excluded [OR for 3 month mortality =0 · 70 (0 · 46-1 · 07), p = 0.090; 3 month GOS p = 0 · 028]. CONCLUSIONS: A trend towards better outcomes was observed with minocycline, especially in those patients who survived the initial day in hospital. These findings should form the basis for planning a larger study and possibly including minocycline in the initial management of AES as seen here. TRIAL REGISTRATION: The trial was registered with Clinical Trials Registry of India (CTRI) - CTRI/2010/091/006143.

Accuracy and applicability of the revised WHO classification (2009) of dengue in children seen at a tertiary healthcare facility in northern India.

BACKGROUND: Revised case definitions of dengue into dengue with/without warning signs (DWS/D) and severe dengue (SD) was proposed by the World Health Organization (WHO)/Tropical Disease Research (TDR) in 2009. To date, there has been no Indian study that has applied this classification. AIMS AND OBJECTIVES: To assess the accuracy and applicability of the revised WHO classification (2009) of dengue in children seen at a tertiary healthcare facility in India. MATERIALS AND METHODS: Over a period of 1 year children from the pediatric ward and Out Patient Department (OPD) of the King George Medical University Hospital, Lucknow were enrolled in the study according to predefined criteria and tested for dengue. Each dengue-positive patient was classified according to both the older system [dengue fever (DF), dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS)] and the new system (D, DWS, and SD). The severity of dengue was compared to the level of treatment received. RESULTS: A total of 56 patients tested positive for dengue--51 from the pediatric ward and five from the OPD. According to the older WHO classification, 42 (75 %) patients were classified as DF and 13 (23.2 %) as DHF/DSS; one patient was unclassifiable. Five patients (8.9 %) received level 1 treatment, ten (17.8 %) received level 2 treatment, and 41 (73.2 %) received level 3 treatment. According to the new WHO/TDR classification, 46 (82.1 %) patients were classified as SD, nine (16 %) as DWS, and only one (1.7 %) as D. Many of the severe manifestations (encephalopathy, shock, mucosal bleed, platelet count <20,000, respiratory distress, liver enzymes >1,000 U/L) were seen in patients who were classified as DF according to old classification, whereas these patients were mostly classified as SD by the new classification. Sensitivity of the older and new classifications was 24.8 and 98 %, respectively. CONCLUSIONS: The revised WHO/TDR (2009) classification has very high sensitivity for identifying severe dengue and is easy to apply.

West syndrome: response to valproate.

UNLABELLED: Management of West syndrome is unsatisfactory. In our clinic we observed that a significant proportion of patients respond to usual dose of valproate. OBJECTIVE: To prospectively assess the efficacy of valproate in controlling infantile spasms in West syndrome. METHODS: Consecutive patients presenting with West syndrome to the Pediatric Neurology Clinic or general outpatient department (OPD) were enrolled for study. Those who were not on any treatment were given valproate in a dose of 30 mg/kg/day while awaiting investigations. Patients were followed up every 2 weeks. Predefined criteria for definition of West syndrome and response were used. Those showing partial/poor response or relapse on valproate were given hormonal therapy. RESULTS: One hundred children with West syndrome were enrolled. Ninety one children were started on valproate. Of these 36 (39.5%) showed a good response, but seven later relapsed while on same dose of valproate and three were lost to follow up. Later age at onset and typical hypsarrhythmia on EEG were associated with good sustained response to valproate while a history of delayed cry at birth was associated with partial or poor response. Sixty two patients who responded poorly to or relapsed on valproate were put on hormonal treatment in addition. Of these 36 (58.1%) had a good response but 11 later relapsed after stopping treatment and two were lost to follow up. CONCLUSION: Valproate may have a role in treatment of West syndrome in a selected group of patients.

Changing clinical manifestations of dengue infection in north India

Dengue infection is endemic in many parts of India, including the state of Uttar Pradesh. This study describes the changing clinical picture of dengue viral infections observed by us in children admittedto a teaching hospital in Lucknow, India.A total of 139 children with suspected dengue were admitted during this period, of which 124 couldbe tested by dengue IgM capture ELISA and 102 were positive. However, only 80 of these 102 patientscould be followed up. Average age was 5.9 (±3.1) years and 87.5% of them were from rural areas. Themale:female ratio was 1.6:1. Seizures were observed in 45% cases, altered sensorium in 53.7%, vomitingin 41.2%, haemorrhage in 38.8%, skin rash in 37.5%, abdominal pain in 25%, headache in 18.8% andjaundice in 2% cases. Gastrointestinal tract was the commonest site of bleeding. On examination,edema was present in 47.5% cases, hepatomegaly in 62.5%, splenomegaly in 60.0% and hypotensionin 10.0% cases. The investigations revealed a low platelet count of less than 100000/mm3 in 60.3%cases. Mean liver enzyme levels were mildly raised. Definitions of WHO criteria for DHF were presentin only 18 (22.5%) cases. Mean total duration of fever in survivors was 14.9±7.3 days. The overall fatality rate in hospital was 5.0%.The results indicated a significant proportion of children presented with little-described features ofencephalopathy, edema, splenomegaly and prolonged fever rather than the typical dengue presentation.These features were not noted during the past epidemics and in previous years.