Atypical presentation of posterior reversible encephalopathy: in a child with bilateral grade IV vesicoureteric reflux.

Posterior reversible encephalopathy, better known as potential reversible encephalopathy syndrome (PRES), is a clinicoradiological entity mostly described in adult populations manifesting predominantly as bilateral symmetrical diffuse white matter vasogenic oedema in parieto-occipital regions. Rarely it may also present as patchy reversible areas of involvement in the basal ganglia, brainstem and deep white matter. It is reported scarcely in childhood populations. Frequent association with acute hypertension (67-80%) is reported in many studies. Involvement of the brainstem and cervical cord (apart from the typical parieto-occipital lesions) is an extremely rare imaging manifestation of PRES and its recognition is important to avoid misdiagnosis as myelitis or acute disseminated encephalomyelitis by proper clinical correlation. We hereby report a case of PRES in a 7-year-old child showing an uncommon pattern on imaging study involving the brain as well as the brainstem and cervical spinal cord.

Radiological Outcome of Neurocysticercosis in Children Six Months After Diagnosis - A Single Center Study.

OBJECTIVE: To assess proportion and predictors of lesion calcification in children aged 2-12 years with neurocysticercosis at six months follow up. METHODS: Children aged between 2 and 12 years with Neurocysticercosis diagnosed on MRI brain were initially included and followed up for 6 months. Repeat CECT brain at 6 months was done to find if the lesion persisted/calcified/ resolved. RESULTS: 16 out of 30 patients (53.3%) had calcification at six months follow up. Perilesional edema at the initial stage of the presentation was significantly associated with calcification at 6 months (P=0.042). CONCLUSIONS: Perilesional edema at the time of presentation was significantly associated with calcification in children with neurocysticercosis, six months after diagnosis.

Outcome of tuberculous meningitis in children aged 9 months to 12 years at the end of intensive phase of treatment.

BACKGROUND: Tuberculous meningitis (TBM) is associated with high morbidity and mortality. Most of the literature focuses on outcomes at the end of therapy when it may be too late for intervention to improve the outcomes. So, the present study addresses outcomes by the end of intensive course of therapy. METHODS: It was a prospective cohort observational study that enrolled 80 patients with TBM between 9 months and 12 years of age. Participants were classified into Definite, Probable and Possible TBM using Marais criteria. Survival/Mortality was evaluated at the end of hospital stay. Demographic, clinical, cerebrospinal fluid and radiological parameters were evaluated for predictors of morbidity and mortality. Standardized tools were used to assess possible impairments in different domains at the end of intensive phase of treatment, namely Gross Motor Functional Classification System for motor functional ability, Pediatric-Mini Mental score examination (MMSE), Blantyre Coma Scale (BCS) score and Vineland Social Maturity Scale (VSMS) for cognitive outcome, Auditory Brainstem Evoked Responses for hearing outcome and using Teller's/Snellen's visual acuity charts to assess visual impairment. RESULTS: A high Mortality rate of 42.5% was seen in the enrolled patients. Out of the total 80 patients, 20% recovered completely while 36.25% survived with disability (morbidity). Motor, Hearing, Cognitive and Vision impairment was present in 33.3%, 4%, 33.3% and 48.9% of the survivors respectively. On multivariate regression, raised intracranial tension and stage III disease were significantly associated with mortality. Morbidity was significantly associated with Stage III disease on multivariate analysis. CONCLUSIONS: Despite advances in treatment, Tuberculous meningitis is associated with high burden of deaths and devastating neurological sequelae. Timely diagnosis and intervention of neurological impairments is needed to improve the outcome of TBM in survivors.

BMP7 and SHH regulate Pax2 in mouse retinal astrocytes by relieving TLX repression.

Pax2 is essential for development of the neural tube, urogenital system, optic vesicle, optic cup and optic tract. In the eye, Pax2 deficiency is associated with coloboma, a loss of astrocytes in the optic nerve and retina, and abnormal axonal pathfinding of the ganglion cell axons at the optic chiasm. Thus, appropriate expression of Pax2 is essential for astrocyte determination and differentiation. Although BMP7 and SHH have been shown to regulate Pax2 expression, the molecular mechanism by which this regulation occurs is not well understood. In this study, we determined that BMP7 and SHH activate Pax2 expression in mouse retinal astrocyte precursors in vitro. SHH appeared to play a dual role in Pax2 regulation; 1) SHH may regulate BMP7 expression, and 2) the SHH pathway cooperates with the BMP pathway to regulate Pax2 expression. BMP and SHH pathway members can interact separately or together with TLX, a repressor protein in the tailless transcription factor family. Here we show that the interaction of both pathways with TLX relieves the repression of Pax2 expression in mouse retinal astrocytes. Together these data reveal a new mechanism for the cooperative actions of signaling pathways in astrocyte determination and differentiation and suggest interactions of regulatory pathways that are applicable to other developmental programs.

Ectopic Pax2 expression in chick ventral optic cup phenocopies loss of Pax2 expression.

Pax2 is essential for the development of the urogenital system, neural tube, otic vesicle, optic cup and optic tract [Dressler, G.R., Deutsch, U., et al., 1990. PAX2, a new murine paired-box-containing gene and its expression in the developing excretory system. Development 109 (4), 787-795; Nornes, H.O., Dressler, G.R., et al., 1990. Spatially and temporally restricted expression of Pax2 during murine neurogenesis. Development 109 (4), 797-809; Eccles, M.R., Wallis, L.J., et al., 1992. Expression of the PAX2 gene in human fetal kidney and Wilms' tumor. Cell Growth Differ 3 (5), 279-289]. Within the visual system, a loss-of-function leads to lack of choroid fissure closure (known as a coloboma), a loss of optic nerve astrocytes, and anomalous axonal pathfinding at the optic chiasm [Favor, J., Sandulache, R., et al., 1996. The mouse Pax2(1Neu) mutation is identical to a human PAX2 mutation in a family with renal-coloboma syndrome and results in developmental defects of the brain, ear, eye, and kidney. Proc. Natl. Acad. Sci. U. S. A. 93 (24), 13870-13875; Torres, M., Gomez-Pardo, E., et al., 1996. Pax2 contributes to inner ear patterning and optic nerve trajectory. Development 122 (11), 3381-3391]. This study is directed at determining the effects of ectopic Pax2 expression in the chick ventral optic cup past the normal developmental period when Pax2 is found. In ovo electroporation of Pax2 into the chick ventral optic cup results in the formation of colobomas, a condition typically associated with a loss of Pax2 expression. While the overexpression of Pax2 appears to phenocopy a loss of Pax2, the mechanism of the failure of choroid fissure closure is associated with a cell fate switch from ventral retina and retinal pigmented epithelium (RPE) to an astrocyte fate. Further, ectopic expression of Pax2 in RPE appears to have non-cell autonomous effects on adjacent RPE, creating an ectopic neural retina in place of the RPE.

Association of Child Neurology-Indian Epilepsy Society Consensus Document on Parental Counseling of Children with Epilepsy.

When a child is diagnosed with epilepsy, counseling regarding the same is done by the treating doctor. Most parents are frightened and have poor knowledge about epilepsy. Therapeutic advice including drug dosage, administration and side effects takes up the major part of physician's time, thereby neglecting important issues like home seizure management, follow up and others. These lacunae in knowledge require systematic patient and family education. To address these issues, an expert group meeting of pediatric neurologists and epileptologists in India along with social workers/epilepsy educators, legal experts, parents, and teachers was held. The various aspects regarding parental counseling in children with epilepsy were discussed and a consensus document was formulated. Here authors present the group consensus statement on counseling parents and caregivers of children with epilepsy. This document is intended to help physicians and pediatricians counsel the families when a child is diagnosed with epilepsy.

Nodding syndrome- an Indian case.

BACKGROUND: Although nodding syndrome is a catastrophic epileptic encephalopathy, it is reported only from Africa so far. We describe the first case from the Indian sub-continent. METHODS: A ten-year-old child who had an episode of Guillain Barre syndrome with incomplete recovery developed emaciation secondary to bulbar palsy and depression. Subsequently, nine months later she developed head nodding, spastic quadriparesis, choreo-athetoid movement disorder, global aphasia and depression. She improved with sodium valproate, nutritional rehabilitation and anti-spasticity and anti-depressant medications. RESULTS: First case of nodding syndrome is described from India where possible etiology is malnutrition. She had anemia, her electroencephalography revealed parieto-occipital inter-ictal epileptiform discharges and Magnetic Resonance Imaging showed diffuse cerebral atrophy. CONCLUSION: Nodding syndrome is an epileptic encephalopathy of nutritional origin beyond geographical barriers but amenable to anti-convulsants and nutritional rehabilitation.

Prognostic Utility of Clinical Epilepsy Severity Score Versus Pretreatment Hypsarrhythmia Scoring in Children With West Syndrome.

This cross-sectional study assessed the impact of clinical epilepsy severity and pretreatment hypsarrhythmia severity on epilepsy and cognitive outcomes in treated children with West syndrome. Thirty-three children, aged 1 to 5 years, with infantile spasms were enrolled if pretreatment EEG records were available, after completion of ≥1 year of onset of spasms. Neurodevelopment was assessed by Development Profile 3 and Gross Motor Function Classification System. Epilepsy severity in the past 1 year was determined by the Early Childhood Epilepsy Severity Score (E-Chess). Kramer Global Score of hypsarrhythmia severity was computed. Kramer Global Score (≤8) and E-Chess (≤9) in the past 1 year were associated with favorable epilepsy outcome but not neurodevelopmental or motor outcome.

Bone morphogenetic protein 7 increases chick photoreceptor outer segment initiation.

PURPOSE: The purpose of this study was to investigate the regulation of photoreceptor differentiation and outer segment elongation by the growth factor BMP7. METHODS: Dissociated low-density embryonic day 6 (E6) chick retinal cultures were grown for 6 days in the presence of BMP7, other members of the TGF-beta family of growth factors, or control vehicle. Cultured cells were characterized using microscopy, immunocytochemistry, and RT-PCR. Antibodies against visinin and GABA were used to distinguish photoreceptors from nonphotoreceptor cells, and monoclonal antibodies rhodopsin (rho) 4D2, OS-2, and COS-1 were used to distinguish subpopulations of cones and rods. RT-PCR was used to investigate mRNAs encoding visual pigments. RESULTS: Photoreceptors treated with BMP7 initiated outer segment elongation more frequently than photoreceptors in control cultures. The effect on outer segment initiation was confined to rods and to green opsin-expressing cones and appeared not to involve an increase in outer segment length. BMP7 did not appear to affect the survival, proliferation, or differentiation of progenitors or the fate of photoreceptors or amacrine cells in vitro. BMP5 and GDF5 showed weaker stimulatory effects than BMP7 on outer segment formation, whereas activin, BMP2, and BMP4 inhibited visual pigment expression and outer segment formation, and BMP6 had no detectable effects. CONCLUSIONS: BMP7 must be added to the list of candidate molecules capable of stimulating outer segment formation.

VEB-1 extended-spectrum ß-lactamase-producing multidrug-resistant Proteus mirabilis sepsis outbreak in a neonatal intensive care unit in India: clinical and diagnostic implications.

INTRODUCTION: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae, multidrug-resistant (MDR) pathogens, are increasingly implicated in nosocomial outbreaksworldwide, particularly in neonatal intensive care units (NICUs). Proteus mirabilis is an uncommon nosocomial pathogen causing sepsis in neonates. CASE PRESENTATION: We report an outbreak of ESBL-positive MDR P. mirabilis sepsis involving five babies within 10 days in a NICU, which was promptly detected and managed. The aim of this study was to characterize the molecular mechanism of resistance to third-generation cephalosporins (3GCs) in the bacteria. Surveillance cultures were collected from health-care personnel (hand swabs, urine) and the surrounding patient-care environment. Ribotyping was performed to determine the clonality of the strain. Thirteen P. mirabilis were recovered from the blood cultures of the five babies and surveillance cultures. Twelve isolates were positive for the VEB-1 ESBL type, and were susceptible only to ciprofloxacin and carbapenems. There was an unusual phenotypic synergy observed between the 3GCs and imipenem/cefoxitin. The source of infection was traced to a contaminated multidose vial. The outbreak was associated with a high mortality (80 %). A change of empirical antibiotic policy to ciprofloxacin, with strict infection control measures, brought the outbreak to an abrupt end. CONCLUSION: This is believed to be the first report of a nosocomial outbreak of VEB-1 ESBL-producing P. mirabilis sepsis in neonates from India. The present report of infection due to VEB-1-producing P. mirabilis, an uncommon pathogen for an epidemic in a neonatal unit, highlights the growing significance of such Gram-negative bacteria as a cause of infections in newborns. Epidemic spread in a neonatal unit of an ESBL-producing Proteus species, which also had an intrinsically reduced susceptibility to imipenem, and resistance to colistin and tigecycline, can be a threatening situation and can result in high neonatal mortality unless recognized and controlled in a timely manner.

The Clinical Characteristics and Treatment Response in Children with West Syndrome in a Developing Country: A Retrospective Case Record Analysis.

This study describes the clinical characteristics, treatment, and outcome of children with West syndrome in a tertiary care hospital in north India. Overall, 310 case records diagnosed from January 2009 to June 2012 were reviewed. The median age of onset of spasms was 5 months (interquartile range = 2.5-7 months). The predominant underlying etiology was perinatal cerebral ischemia (55%). Adrenocorticotropic hormone or oral steroids were received by 92% children, of whom 43% became seizure free. Median lag time for appropriate treatment initiation was significantly less in patients who became seizure free as compared to those with persisting seizures (11 vs 15 months, P = .001) soon after receiving treatment of choice. Later age at onset of spasms was associated with a favorable seizure outcome (P = .03). In a resource-limited setting, unawareness along with treatment costs and repeated visits to the hospital are significant obstacles to optimum management.

Mortality in newborns referred to tertiary hospital: An introspection.

BACKGROUND: India is one of the largest contributors in the pool of neonatal death in the world. However, there are inadequate data on newborns referred to tertiary care centers. The present study aimed to find out predictors of mortality among newborns delivered elsewhere and admitted in a tertiary hospital in New Delhi between February and September 2014. MATERIALS AND METHODS: Hospital data for were retrieved and analyzed for determining predictors for mortality of the newborns. Time of admission, referral and presenting clinical features were considered. RESULTS: Out of 1496 newborns included in the study, there were 300 deaths. About 43% deaths took place in first 24 hours of life. Asphyxia and low birth weight were the main causes of death in early neonatal period, whereas sepsis had maximum contribution in deaths during late neonatal period. Severe hypothermia, severe respiratory distress, admission within first 24 hours of life, absence of health personnel during transport and referral from any hospital had significant correlation with mortality. CONCLUSIONS: There is need for ensure thermoregulation, respiratory sufficiency and presence of health personnel during transport.

Giant cerebral cysticercosis in an infant confused with a thalamic glioma.

Neurocysticercosis is a common parasitic infection of the central nervous system. Intraparenchymal giant cysticercosis has been described in literature, but this is a rare report of a thalamic giant cysticercosis in a young child where the diagnosis could be made on follow-up. A 1½-year-old male child presented with seizures, hemiparesis, and features of raised intracranial pressure. Initial neuroimaging findings of thalamic swelling with minimal edema and contrast enhancement with choline peak on magnetic resonance spectroscopy were attributed to thalamic glioma. Subsequent imaging revealed a ring enhancing lesion with an eccentric nodule suggestive of neurocysticercosis. It later resolved with residual gliosis. The presence of a pathognomic scolex and the resolution of size and symptoms without definitive treatment helped in making the diagnosis. This report reinforces the importance of considering cysticercosis in diagnosis of acute presentations of large cerebral masses in infants, particularly in prevalent regions, and emphasizes the follow-up of these patients.

Neurodevelopmental and epilepsy outcome in children aged one to five years with infantile spasms--a North Indian cohort.

PURPOSE: The present study was planned as there is paucity of outcome data of children with infantile spasms, from India where profile of patients is different from the western world. Moreover, most previous studies have either not used strict inclusion criteria or standardized psychometric tests for developmental outcome. METHODS: Ninety-five children, aged one-to-five years under follow up for more than six months in Pediatric Neurology Clinic of a tertiary care hospital with the diagnosis of infantile spasm were enrolled in this cross-sectional study if they had completed one or more years after the onset of spasms. The study period was January-December 2011. Neurodevelopment of each child was assessed using Development Profile 3 and Gross Motor Function Classification System. History regarding epilepsy frequency and control in the last one year was taken. RESULTS: Perinatal asphyxia was the commonest etiology in 43/95 children (45.2%). Favorable neurodevelopmental outcome was observed in 8/95 patients. Favorable epilepsy outcome in 58/95 (61.1%) patients was associated with treatment lag≤3 months between apparent onset of spasms and institution of therapy {OR 2 (1.1-3.8)} and response to first line antiepileptic drug {5 (2.6-10)}. CONCLUSIONS: The commonest etiology was potentially preventable perinatal cause. Early appropriate treatment may have a favorable epilepsy outcome.

Macrocephaly with diffuse white matter changes simulating a leukodystrophy in Menkes disease.

Menkes disease is a rare inherited disorder of copper metabolism caused by mutations in the ATP7A gene. Its clinical course is characterized by early neurological regression, seizures, hypotonia and kinky friable hair. Neuroimaging typically reveals severe brain atrophy with subdural fluid collections and excessive tortuosity of cerebral arteries. The authors describe a case of Menkes disease with unusual imaging findings. The patient had macrocephaly and symmetrical bilateral confluent white matter changes with temporal cystic areas, reminiscent of megalencephalic leukodystrophy.

Neonatal sepsis due to Salmonella Typhi and Paratyphi A.

Sepsis due to Salmonella enterica serovar Typhi and Paratyphi A is rare in neonates. Though described as a mild and unrecognized illness in infants, life-threatening complications and even deaths have been reported. We present five cases of neonatal septicaemia due to S. Typhi and S. Paratyphi A. The cases were presented because of their interesting clinical presentations and possible modes of transmission. Salmonella infections should be considered in the differential diagnosis of sepsis neonatorum, especially in endemic areas.

Urodynamic evaluation in primary enuresis: an investigative and treatment outcome correlation.

A prospective study was done in pediatric out-patient department of a tertiary care hospital to evaluate the role of urodynamics in the management of primary enuresis in the 5-14-year-old children and to compare the effectiveness of multidimensional behavioral therapy with pharmacological therapy. Hundred and nineteen children between 5-14 years with primary enuresis were evaluated clinically and investigated. Three patients with obvious organic causes were then excluded. The remaining patients were given either behavioral or pharmacological treatment on the basis of urodynamic assessment. Urodynamic abnormalities were seen in 80/116 (68.9%) patients namely uninhibited bladder contraction 50/116 (43.1%), small bladder capacity 20/116 (17.2%), large bladder capacity 4/116 (3.4%), decreased bladder compliance 3/116 (2.5%) and detrusor sphincter dyssenergia 3/116 (2.5%). Combination of abnormal micturition history stating daytime urgency or frequency or dysfunctional voiding symptoms like squatting and/or abnormal voiding charts could predict abnormal results of urodynamics correctly with sensitivity of 81% and specificity of 86.2%. Ultrasound identified only 38/80 enuretics with urodynamic abnormalities although it was 100% specific. Additionally one patient who was identified as having a small bladder capacity on voiding chart was seen to have mild pelvicalyceal dilatation on ultrasound and subsequently on urodynamic assessment was found to have Detrusor sphincter dyssenergia (DSD). Behavioral therapy as compared to drug therapy produced more complete remission (17/18 vs. 14/18) and lesser relapse rate (2/17 vs. 5/14) in monosymptomatic enuretics with normal urodynamics. In patients with urodynamic abnormality, response rates with behavioral therapy, imipramine, oxybutynin and flavoxate were 73.9% (CI 56-91.8%), 89.4% (CI 75.7-100%), 94.2% (CI 84.7-100%) and 89.4% (CI 75.7-100%), respectively. Specific drug therapy as per the urodynamic abnormality was significantly more effective 49/57 [86% (CI 77-95%)] vs 17/23 [73.9% (CI 56.1-91.9%)] at P < 0.05 than behavioral therapy in patients with underlying abnormal urodynamics. Micturition history and voiding chart can be used as screening tool for enuretics. Behavioral therapy should be the first line treatment for mono symptomatic and drug therapy for polysymptomatic enuretics. Urodynamic testing may be reserved for polysymptomatic enuretics with abnormal ultrasound or those who fail to respond to first line treatment.