Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies.

Congenital insensitivity to pain (CIP) and hereditary sensory and autonomic neuropathies (HSAN) are clinically and genetically heterogeneous disorders exclusively or predominantly affecting the sensory and autonomic neurons. Due to the rarity of the diseases and findings based mainly on single case reports or small case series, knowledge about these disorders is limited. Here, we describe the molecular workup of a large international cohort of CIP/HSAN patients including patients from normally under-represented countries. We identify 80 previously unreported pathogenic or likely pathogenic variants in a total of 73 families in the >20 known CIP/HSAN-associated genes. The data expand the spectrum of disease-relevant alterations in CIP/HSAN, including novel variants in previously rarely recognized entities such as ATL3-, FLVCR1- and NGF-associated neuropathies and previously under-recognized mutation types such as larger deletions. In silico predictions, heterologous expression studies, segregation analyses and metabolic tests helped to overcome limitations of current variant classification schemes that often fail to categorize a variant as disease-related or benign. The study sheds light on the genetic causes and disease-relevant changes within individual genes in CIP/HSAN. This is becoming increasingly important with emerging clinical trials investigating subtype or gene-specific treatment strategies.

Bifurcation dissecting aneurysm: tips and tricks to differentiate from saccular aneurysm.

Bifurcations are a common site for saccular aneurysms, but rarely can be a site for dissecting aneurysms. Identification of these aneurysms is extremely important because the management plan depends on it. We describe a rare case of a ruptured dissecting aneurysm at the right ICA bifurcation in a pre-teen child which posed a diagnostic dilemma but ultimately was successfully managed with flow diversion.

Deciphering the TLR transcriptome and downstream signaling pathway in cerebrospinal fluid in pediatric meningitis.

OBJECTIVE/DESIGN: Pediatric meningitis is characterized by a colossal inflammatory response to the pathogen in the central nervous system (CNS). This unabated inflammatory response persists even after the removal of the pathogen by antibiotics/steroids causing collateral damage to CNS tissue. Toll-like receptors (TLRs) are the key players in the recognition and elicitation of innate-immune response against bacterial/viral components in cerebrospinal fluid (CSF). Till date, the precise understanding of TLR-triggered inflammatory response in pediatric meningitis is lacking. The present study was designed to delineate the role of TLR transcriptome and downstream signaling pathways in CSF of pediatric meningitis. METHODS: Children in the age group of > 3 months to 12 years with pediatric meningitis were included. A total of 249 cases of pediatric meningitis (bacterial = 89, viral = 160) were included. In addition, 71 children who tested negative to the pathogen in CSF tap and did not have signs of infection clinically constituted the controls. RNA was extracted from the CSF samples of both cases and controls. The relative gene expression profile of 42 TLR signaling pathway genes was performed. For the analysis of secretory cytokines and chemokines in CSF, Luminex assay was performed. RESULTS: We report global upregulation of TLR genes in patients with acute bacterial meningitis (ABM). The downstream signaling molecules were upregulated as well. The CSF of pediatric ABM patients revealed a predominant pro-inflammatory milieu marked by increased levels of pro-inflammatory cytokines. A significant correlation between poor clinical outcomes of patients and an increased expression of TLR/pro-inflammatory cytokine genes was observed. CONCLUSION: Our findings provide support for future studies exploring TLR-based adjunct therapy to limit the neurological sequelae, owing to persistent inflammation in pediatric ABM patients.

Clinical Features Associated With Need for Mechanical Ventilation in Children With Guillain-Barré Syndrome: Retrospective Cohort From India.

OBJECTIVES: To analyze the clinical features associated with the need for mechanical ventilation (MV) in children with Guillain-Barré syndrome (GBS). DESIGN: Retrospective cohort study, 2010-2019. SETTING: PICU. PATIENTS: All children, 1 month to 12 years old, diagnosed with GBS in our single-center PICU. INTERVENTION: Retrospective chart and data review. MEASUREMENTS AND MAIN RESULTS: Out of 189 children identified with a diagnosis of GBS, 130 were boys (69%). The median (interquartile range [IQR]) age was 6 years (3-9 yr). At admission, the Hughes disability score was 5 (4-5), and cranial nerve palsies were present in 81 children (42%). Autonomic instability subsequently occurred in a total of 97 children (51%). In the 159 children with nerve conduction studies, the axonal variant of GBS (102/159; 64%) predominated, followed by the demyelinating variant (38/189; 24%). All children received IV immunoglobulins as first-line therapy at the time of admission. The median (IQR) length of PICU stay was 12 days (3-30.5 d). Ninety-nine children (52%) underwent invasive MV, and median duration of MV was 25 days (19-37 d). At admission, upper limb power less than or equal to 3 (p = 0.037; odds ratio (OR), 3.5 [1.1-11.5]), lower limb power less than or equal to 2 (p = 0.008; OR, 3.5 [1.4-8.9]), and cranial nerve palsy (p = 0.001; OR, 3.2 [1.6-6.1]) were associated with subsequent need for MV. Prolonged (> 21 d) MV was associated with more severe examination findings at admission: upper limb power less than or equal to 2 (p < 0.0001; OR, 4.2 [2.5-6.9]) and lower limb power less than or equal to 1 (p < 0.0001; OR, 4.5 [2.6-7.9]). CONCLUSIONS: In children with GBS, referred to our center in North India, severe neuromuscular weakness at admission was associated with the need for MV. Furthermore, greater severity of this examination was associated with need for prolonged (> 21 d) MV. Identification of these signs may help in prioritizing critical care needs and early PICU transfer.

Age at diagnosis for autism spectrum disorders: Does it differ by place of residence?

Background: Despite steady decline in the age of diagnosis (AOD) at the global level, it has not declined uniformly, and marked disparities are documented by income, education, race, and access to health care. Objectives: The objectives of the study are to examine the urban/rural disparities in the initial age of autism diagnosis and to understand the interplay of the underlying demographic and social factors. Methods: A retrospective case record review of all children who received their initial diagnosis of autism at the Pediatric Psychology Clinic (1997-2018) of a tertiary advanced pediatric center at Chandigarh was conducted. A structured abstraction data form was used to extract demographic, socioeconomic, and clinical information from the files maintained at the clinic. Results: A total of 1321 case records were examined. The mean AOD was 4.62 years (standard deviation = 2.38) and children from rural communities were diagnosed at 4.87 years, nearly 0.35 years later than urban children (t = 2.47, P = 0.013). Results indicated that 31.1% of the variance in the AOD for children from rural areas was predicted by two variables, namely the number of children in the family and total Childhood Autism Rating Scale (CARS) score (F = 13.62, P = 0.001). For the urban sample, three variables emerged as significant predictors including the number of children in the family, total CARS score, and maternal education and these together explained 20.2% of the variance in the AOD (F = 19.60, P = 0.001). Conclusion: The public health system must be sensitized to the unmet needs of the marginalized socioeconomic groups to access diagnostic and management services in a timely manner.

Intensive Care Unit-Acquired Weakness in Children: A Prospective Observational Study Using Simplified Serial Electrophysiological Testing (PEDCIMP Study).

BACKGROUND: To study the incidence and time of onset of intensive care unit-acquired weakness in a prospective cohort of children (2-12 years) by serial simplified electrophysiological assessment (Pediatric Critical Illness Myopathy Polyneuropathy study, PEDCIMP). METHODS: A single-center, prospective cohort study (Trial Registry Number: NCT02763709; PEDCIMP2016) was conducted at the pediatric intensive care unit of a tertiary care hospital in North India. A complete electrophysiological evaluation (4 motor nerves and 2 sensory nerves) was performed at baseline in children (2-12 years) admitted to the ICU with a pediatric risk of mortality (PRISM) of > 20 with more than 24-h stay. Following the entry evaluation, a minimal alternate day simplified electrophysiological testing of the unilateral common peroneal nerve and the sural nerve was assessed. A 25% reduction in compound muscle action potential (CMAP) and sensory nerve action potential from baseline was considered significant for ICUAW and was confirmed by complete electrophysiological re-evaluation. RESULTS: Of the total 481 children assessed for eligibility, 97 were enrolled. The median age of the cohort was 7 years. Sepsis (81%); need for vasoactive support (43%); multiorgan dysfunction (26%) were the common reasons for admission. Of the 433 eligible patient ICU days, 380 electrophysiological observations were done. A significant decrease of > 25% in CMAP of common peroneal nerve was not detected in any of the 380 observations. However, two children unfit for inclusion were diagnosed with ICUAW during the study period. CONCLUSIONS: Children admitted with PRISM > 20 have a very low incidence of intensive care unit-acquired weakness by serial clinical and abbreviated electrophysiological evaluation.

Plasma and Urinary Amino Acid Profile in Children with Infantile Tremor Syndrome.

BACKGROUND: Infantile Tremor Syndrome (ITS) is a disorder of infancy, and characterized by developmental delay and/or regression, pallor, skin hyperpigmentation and hypopigmented hair. It is commonly seen in infants in whom exclusive breastfeeding is given inappropriately for longer durations than recommended. ITS is predominantly reported from the Indian subcontinent and in children from a lower socioeconomic background. It is a clinical diagnosis and vitamin B12 deficiency is the most commonly accepted etiology of this entity. OBJECTIVES: The primary objectives of study were to compare the plasma and urine amino acid levels among children with ITS spectrum with those of healthy children. The secondary objectives were to compare the plasma and urine amino acid levels among children with ITS and Pre-ITS. STUDY DESIGN: This cross-sectional, observational study was carried out at a tertiary care hospital in North India. PARTICIPANTS: A total of 50 children aged < 36 months with ITS/Pre-ITS were enrolled. Children with Pre-ITS and ITS were compared with healthy age-matched study subjects. RESULTS: Thirty-nine (78%) cases and twelve (24%) healthy children had low serum vitamin B12 levels. Folate levels were normal in all the controls, while only one case had folate deficiency. There were significant differences (p < 0.05) in the values of 32 amino acids in plasma. Among 44 urinary amino acids, levels of 30 amino acids were significantly different in the cases compared with the controls (p < 0.05). CONCLUSIONS: Several changes in amino acids in the children suffering from ITS were observed. These changes may be a reflection of the metabolic derangements in ITS.

Model-based iterative reconstruction in paediatric head computed tomography: a pilot study on dose reduction in children.

PURPOSE: To evaluate the potential of model-based iterative reconstruction (MBIR) on dose reduction and image quality in children undergoing computed tomography (CT) head examinations. MATERIAL AND METHODS: This prospective study was approved by the institutional ethics committee. A total of 88 children (age range of 5 to 16 years) with a history of seizures underwent contrast-enhanced CT scan. Forty-one children underwent CT study according to the MBIR technique, while 47 children underwent CT of the head with the non-MBIR protocol. Images were reviewed by 2 blinded paediatric radiologists in a random order. Mean dose-length product, CT dose index (CTDI) volume, and mean effective dose were recorded for both groups. Image quality, image noise, and diagnostic acceptability of 2 image sets were also recorded. RESULTS: In the MBIR group, the mean dose-length product was reduced by 79.8%; the mean CTDI volume was reduced by 88.5%, while the mean effective dose was reduced by 81% when compared to the non-MBIR group. No significant difference was seen in diagnostic acceptability, image noise, and image quality between the 2 groups. CONCLUSIONS: MBIR technique is highly effective in reducing radiation dose in paediatric head CT examinations without any significant difference in image quality, image noise, and diagnostic acceptability.

Randomized Clinical Trial of 20% Mannitol Versus 3% Hypertonic Saline in Children With Raised Intracranial Pressure Due to Acute CNS Infections.

OBJECTIVES: Mannitol is a commonly used osmotherapy agent in raised intracranial pressure. However, the side effects of mannitol are significant. In traumatic brain injury (adult and pediatric), hypertonic saline (3%) shows varied results in comparison with 20% mannitol. We compared the effect of 3% hypertonic saline versus 20% mannitol (using common dosing strategies) on raised intracranial pressure in pediatric acute CNS infections. DESIGN: Open-label randomized controlled trial. SETTING: PICU of a quaternary care academic institute. PATIENTS: Children 1-12 years old, with raised intracranial pressure and modified-Glasgow Coma Scale scores less than or equal to 8, were enrolled. INTERVENTIONS: Patients were randomly assigned to 20%-mannitol (n = 28), 0.5 gram/kg/dose versus 3%-hypertonic saline (n = 29), 10 mL/kg loading followed by 0.5-1 mL/kg/hr infusion. An intraparenchymal catheter was used to monitor the intracranial pressure. The primary outcome was the proportion of patients achieved target average intracranial pressure less than 20 mm Hg during 72 hours. Secondary outcomes were interventions, morbidity, and mortality. MEASUREMENTS AND MAIN RESULTS: The proportion of patients with target average intracranial pressure (< 20 mm Hg) was higher in hypertonic saline-group as compared to mannitol-group (79.3% vs 53.6%; adjusted hazard ratio 2.63; 95% CI: 1.23-5.61). Mean (± SE) reduction of intracranial pressure (-14.3 ± 1.7 vs -5.4 ± 1.7 mm Hg; p ≤ 0.001) and elevation of cerebral perfusion pressure (15.4 ± 2.4 vs 6 ± 2.4 mm Hg; p = 0.007) from baseline were significant in hypertonic saline-group. Mean (± SE) intracranial pressure over 72 hours was lower (14 ± 2 vs 22 ± 2 mm Hg; p = 0.009), and cerebral perfusion pressure was higher (65 ± 2.2 vs 58 ± 2.2; p = 0.032) in hypertonic saline-group. Hypertonic saline-group had higher modified-Glasgow Coma Scale score at 72 hours (median, interquartile range 10; 7-11 vs 7; 3-9; p = 0.003), lower mortality (20.7% vs 35.7%; p = 0.21), shorter duration of mechanical ventilation (5 vs 15 d; p = 0.002), and PICU stay (11 vs 19 d; p = 0.016) and less severe neurodisability at discharge (31% vs 61%; p = 0.049). CONCLUSIONS: In pediatric acute CNS infections, 3%-hypertonic saline was associated with a greater reduction of intracranial pressure as compared to 20% mannitol.

Decompressive craniectomy in pediatric non-traumatic intracranial hypertension: a single center experience.

Purpose: To study the clinical profile and predictors of outcome in children undergoing decompressive craniectomy (DC) for non-traumatic intracranial hypertension (ICH).Materials and methods: Mixed observational study of children, aged 1 month-12 years, who underwent DC for non-traumatic ICH in a tertiary care pediatric intensive care unit from 2012 to 2017. Data on clinical profile and outcome were retrieved retrospectively and survivors were assessed prospectively. The primary outcome was neurological outcome using Glasgow Outcome Scale-Extended (GOS-E) at minimum 6 months' post-discharge. GOS-E of 1-4 were classified as a poor and 5-8 as a good outcome.Results: Thirty children, median (IQR) age of 6.5 (2, 50) months, underwent DC; of which 26 (86.7%) were boys. Altered sensorium (n = 26, 86.7%), seizures (n = 25, 83.3%), pallor (n = 19, 63.3%) and anisocoria (n = 14, 46.7%) were common signs and symptoms. Median (IQR) Glasgow Coma Scale at admission was 9 (6,11). Commonest etiology was intracranial bleed (n = 24; 80%). Median (IQR) time to DC was 24 (24,72) h. Eight (26.7%) children died; 2 during PICU stay and 6 during follow-up. Neurological sequelae at discharge (n = 28) were seizures (n = 25; 89.2%) and hemiparesis (n = 16; 57.1%). Twenty-one children were followed-up at median (IQR) duration of 12 (6,54) months. Good neurological outcome was seen in 14/29 (48.2%) and hemiparesis in 10/21 (47.6%) patients. On regression analysis, anisocoria at admission was an independent predictor of poor outcome [OR 7.33; 95%CI: 1.38-38.87; p = 0.019].Conclusions: DC is beneficial in children with non-traumatic ICH due to a focal pathology and midline shift. Evidence on indications and timing of DC in NTC is still evolving.

Perfusion magnetic resonance imaging in differentiation of neurocysticercosis and tuberculoma.

PURPOSE: Tuberculoma and neurocysticercosis (NCC) are two of the most common intracranial infections in developing countries and cause of seizures or focal neurological deficit. They often present on neuroimaging as ring-enhancing lesions, and in absence of typical imaging features, can cause significant diagnostic dilemma. Differentiation is extremely important to avoid empirical exposure to anti-tubercular treatment or nonspecific treatment causing disease progression. The aim our study was to evaluate the MR perfusion characteristics of brain tuberculoma and NCC and to assess the potential role of the perfusion in differentiating the two entities. METHODS: Fifty untreated patients (20 tuberculoma and 30 NCC) were prospectively evaluated by using conventional imaging and dynamic susceptibility contrast (DSC) MR perfusion. Relative cerebral blood volume (rCBV) values were calculated from the wall and core of the lesion and were compared with contralateral normal white matter. RESULTS: rCBV values from the wall of the lesion were significantly different in tuberculoma and NCC (P < 0.05). Tuberculomas showed high mean rCBV values than NCC (3.3 and 1.3 respectively). The core of these lesions showed lower rCBV values in both the lesions which were lower than normal white matter. A cutoff value of rCBV from the wall of the lesion 1.965 for tuberculoma showed 90% sensitivity and 100% specificity. CONCLUSION: Perfusion MRI in combination with conventional sequences can better characterize and differentiate similar-appearing tuberculoma and NCC and may be incorporated in routine protocol which may help in avoiding brain biopsy and empirical therapy.

Spontaneous intracranial haemorrhage in children-intensive care needs and predictors of in-hospital mortality: a 10-year single-centre experience.

PURPOSE: Spontaneous intracranial haemorrhage (SICH) in children, although uncommon, is associated with significant mortality and morbidity. Paediatric data is however limited. MATERIAL AND METHODS: Case records of 105 children with SICH, > 1 month to 12 years, admitted to a tertiary level PICU of a teaching and referral hospital between January 2009 and May 2018 were analysed retrospectively. In-hospital mortality was the primary outcome. Variables between survivors and non-survivors were compared to  determine predictors of mortality. RESULTS: The median (IQR) age of subjects was 6 (2.25, 70) months. Common clinical features were altered sensorium (n = 87, 82.9%), seizures (n = 73, 69.5%), pallor (n = 66, 62.9%) and bulging anterior fontanelle (n = 52, 49.5%). Median (IQR) Glasgow Coma Scale (GCS) at admission was 10 (6, 13) with herniation noted in 27 (25.7%) children. Vitamin K deficiency bleeding (VKDB) and arteriovenous malformation (AVM) were the most common etiology for bleeding among infants and older children respectively. The most common site of bleeding was intracerebral (n = 47, 44.8%) followed by subdural (n = 26; 24.8%). Sixteen (15.2%) children died during hospital stay. On univariate analysis, GCS < 8, Pediatric Risk of Mortality score (PRISM III) > 20, need for intubation, thiopentone coma for refractory intracranial pressure (ICP) and progression to shock and acute kidney injury (AKI) predicted mortality. Seizures were favourably associated with survival. Age, site of bleeding, etiology or type of management for raised ICP (conservative versus decompressive craniectomy) did not affect the outcome. On multivariable analysis, progression to AKI (OR 5.86; 95% CI, 1.53-22.4; p 0.01) predicted poor outcome. Seizures, however, were associated with better odds for survival (OR 0.12; 95% CI, 0.03-0.47; p 0.002). CONCLUSIONS: VKDB and AVM were the common etiologies among infants and older children respectively. Age, site, etiology of bleeding and type of management did not affect outcome. Severe decompensation at presentation, thiopentone for refractory ICP and progression to multiorgan dysfunction determined mortality.

Syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia caused by mutations in SLC30A10, a manganese transporter in man.

Environmental manganese (Mn) toxicity causes an extrapyramidal, parkinsonian-type movement disorder with characteristic magnetic resonance images of Mn accumulation in the basal ganglia. We have recently reported a suspected autosomal recessively inherited syndrome of hepatic cirrhosis, dystonia, polycythemia, and hypermanganesemia in cases without environmental Mn exposure. Whole-genome mapping of two consanguineous families identified SLC30A10 as the affected gene in this inherited type of hypermanganesemia. This gene was subsequently sequenced in eight families, and homozygous sequence changes were identified in all affected individuals. The function of the wild-type protein and the effect of sequence changes were studied in the manganese-sensitive yeast strain Δpmr1. Expressing human wild-type SLC30A10 in the Δpmr1 yeast strain rescued growth in high Mn conditions, confirming its role in Mn transport. The presence of missense (c.266T>C [p.Leu89Pro]) and nonsense (c.585del [p.Thr196Profs(∗)17]) mutations in SLC30A10 failed to restore Mn resistance. Previously, SLC30A10 had been presumed to be a zinc transporter. However, this work has confirmed that SLC30A10 functions as a Mn transporter in humans that, when defective, causes Mn accumulation in liver and brain. This is an important step toward understanding Mn transport and its role in neurodegenerative processes.

Bedside burr hole for intracranial pressure monitoring performed by pediatric intensivists in children with CNS infections in a resource-limited setting: 10-year experience at a single center.

OBJECTIVE: Intracranial pressure monitoring can help in early identification of raised intracranial pressure and in setting more informed goals for treatment. We describe our 10-year experience of bedside burr holes performed by pediatric intensivists to establish intracranial pressure monitoring in children with CNS infections in a resource-limited setting and the technical difficulties and complications encountered. DESIGN: Descriptive study of prospectively recorded data. SETTING: PICU of a tertiary care academic institute. PATIENTS: Consecutive comatose patients with raised intracranial pressure who underwent intracranial pressure monitoring from 2004 to 2013. INTERVENTION: An intraparenchymal (1.2 mm) or an intraventricular transducer (3.4 mm) (Codman) was placed by a pediatric intensivist through a micro burr hole using a standard protocol. Technical difficulties during the procedure and complications were recorded. MEASUREMENTS AND MAIN RESULTS: Over 10 years, 265 intracranial pressure catheters were placed in 259 patients, mainly for acute CNS infections (n = 242, 93.4%). Median age of patients was 4.8 years, youngest being 6 weeks; 21 patients (8.1%) were younger than 1 year. Intraparenchymal transducer was used in 252 patients (97.3%). Median (interquartile range) duration of intracranial pressure monitoring was 96 hours (72-144 hr). Complications were seen in 3.5% of patients (n = 9/259); the incidence was 0.28 per 1,000 hours of intracranial pressure monitoring. Procedure-related ventriculitis occurred in three of seven patients (42.8%) with intraventricular catheter, in contrast to none in patients with intraparenchymal transducer. Overall mortality was 32.8% (n = 85). On Cox-regression analysis, "blood component therapy" was an independent predictor of poor outcome defined as death or severe neurodisability (adjusted hazard ratio, 1.58; 95% CI, 1.16-2.16; p = 0.004). CONCLUSIONS: In a resource-limited setting, pediatric intensivists can safely and successfully perform burr holes at bedside for establishing intraparenchymal intracranial pressure monitoring in children with acute CNS infections. However, our data do not support placement of ventriculostomy catheters by pediatric intensivists in similar settings.

Randomized controlled trial comparing cerebral perfusion pressure-targeted therapy versus intracranial pressure-targeted therapy for raised intracranial pressure due to acute CNS infections in children.

OBJECTIVE: In children with acute CNS infection, management of raised intracranial pressure improves mortality and neuromorbidity. We compared cerebral perfusion pressure-targeted approach with the conventional intracranial pressure-targeted approach to treat raised intracranial pressure in these children. DESIGN: Prospective open-label randomized controlled trial. SETTING: PICU in a tertiary care academic institute. PATIENTS: Hundred ten children (1-12 yr) with acute CNS infections having raised intracranial pressure and a modified Glasgow Coma Scale score less than or equal to 8 were enrolled. INTERVENTIONS: Patients were randomized to receive either cerebral perfusion pressure-targeted therapy (n = 55) (maintaining cerebral perfusion pressure ≥ 60 mm Hg, using normal saline bolus and vasoactive therapy-dopamine, and if needed noradrenaline) or intracranial pressure-targeted therapy (n = 55) (maintaining intracranial pressure < 20 mm Hg using osmotherapy while ensuring normal blood pressure). The primary outcome was mortality up to 90 days after discharge from PICU. Secondary outcome was modified Glasgow Coma Scale score at 72 hours after enrollment, length of PICU stay, duration of mechanical ventilation, and hearing deficit and functional neurodisability at discharge and 90-day follow-up. MEASUREMENTS AND MAIN RESULTS: A 90-day mortality in intracranial pressure group (38.2%) was significantly higher than cerebral perfusion pressure group (18.2%; relative risk = 2.1; 95% CI, 1.09-4.04; p = 0.020). The cerebral perfusion pressure group in comparison with intracranial pressure group had significantly higher median (interquartile range) modified Glasgow Coma Scale score at 72 hours (10 [8-11] vs 7 [4-9], p < 0.001), shorter length of PICU stay (13 d [10.8-15.2 d] vs. 18 d [14.5-21.5 d], p = 0.002) and mechanical ventilation (7.5 d [5.4-9.6 d] vs. 11.5 d [9.5-13.5 d], p = 0.003), lower prevalence of hearing deficit (8.9% vs 37.1%; relative risk = 0.69; 95% CI, 0.53-0.90; p = 0.005), and neurodisability at discharge from PICU (53.3% vs. 82.9%; relative risk = 0.37; 95% CI, 0.17-0.81; p = 0.005) and 90 days after discharge (37.8% vs. 70.6%; relative risk = 0.47; 95% CI, 0.27-0.83; p = 0.004). CONCLUSION: Cerebral perfusion pressure-targeted therapy, which relied on more frequent use of vasopressors and lesser use of hyperventilation and osmotherapy, was superior to intracranial pressure-targeted therapy for management of raised intracranial pressure in children with acute CNS infection in reducing mortality and morbidity.

Analysis of 26 amino acids in human plasma by HPLC using AQC as derivatizing agent and its application in metabolic laboratory.

The present study reports the simultaneous analysis of 26 physiological amino acids in plasma along with total cysteine and homocysteine by high-performance liquid chromatography (HPLC) employing 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate (AQC) as precolumn derivatizing reagent. Separations were carried out using Lichrospher 100 RP-18e (5 µm) 250 × 4.0 mm column connected to 100 CN 4.0 × 4.0 mm guard column on a quaternary HPLC system and run time was 53 min. Linearity of the peak areas for different concentrations ranging from 2.5 to 100 pmol/µL of individual amino acids was determined. A good linearity (R (2) > 0.998) was achieved in the standard mixture for each amino acid. Recovery of amino acids incorporated at the time of derivatization ranged from 95 to 106 %. Using this method we have established the normative data of amino acids in plasma, the profile being comparable to the range reported in literature and identified cases of classical homocystinuria, cobalamin defect/deficiency, non-ketotic hyperglycinemia, hyperprolinemia, ketotic hyperglycinemia, urea cycle defect and maple syrup urine disease.

Prevalence and treatment gap in childhood epilepsy in a north Indian city: a community-based study.

BACKGROUND: Epilepsy is one of the most common neurological disorders prevalent in childhood period. There is scarcity of epidemiological data, required to plan services in resource constrained developing nations. OBJECTIVE: To study the prevalence and treatment gap in childhood epilepsy in north Indian city, in the age group of 1-18 years. METHODS: A two stage stratified cluster sampling; probability proportionate to size (PPS) was employed. A ten question screening questionnaire was employed to identify the presence of epilepsy. Definitions provided by International League against Epilepsy (ILAE) were used to classify screen positive subjects as epilepsy and to calculate the treatment gap. RESULTS: The prevalence rate for epilepsy was 6.24/1000 population. Febrile seizures and neurocysticercosis were most common causes of symptomatic seizures in childhood. CONCLUSION: This study of epidemiology of epilepsy provides valuable aid in optimizing effective community approach, thereby improving outcomes of childhood epilepsy.