Publications by authors named "Pratibha Singhi"

229 Publications

Randomized trial of high-dose pyridoxine in combination with standard hormonal therapy in West syndrome.

Seizure 2021 May 29;91:75-80. Epub 2021 May 29.

Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Objective: To determine whether high-dose, oral pyridoxine in combination with standard adrenocorticotropic hormone (ACTH) therapy has superior effectiveness than ACTH therapy alone in increasing cessation of epileptic spasms for children with West syndrome.

Methods: This study was an open-label, randomized controlled trial with masked endpoint assessments. Eligible children with West syndrome, age ranged 3-18 months, were randomized into the intervention (n = 43) and the standard arm (n = 37) of therapy. The intervention group received oral pyridoxine at 100-300 mg/kg/day in addition to standard therapy of intramuscular ACTH at 150 IU/m/day. Primary effectiveness outcome was a complete cessation of spasms at two weeks and sustained till six weeks.

Results: Comparison of effectiveness measures between intervention and standard groups were : complete cessation of epileptic spasms (48.8% vs 58.3%; group difference -9.6%; 95% confidence interval [CI] -30% to 12.3%; p = 0.4), median EEG scores (Q1-Q3) by Jeavons Score at six weeks [3 (1-5) vs 3 (1-5); p = 0.6], median motor scores (Q1-Q3) by DASII (Development Assessment Scales for Indian Infants) at 12 weeks [35 (29-49) vs 42 (34.3-63.8), p = 0.04], and median mental scores (Q1-Q3) by DASII at 12 weeks [35 (29.5-46) vs 41.5 (31.3-60), p = 0.02]. Adverse events were comparable in both arms.

Conclusions: There was no evidence to suggest the superiority of high-dose pyridoxine in combination with ACTH versus ACTH alone for the treatment of West syndrome, considering the limitations of the study design.
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http://dx.doi.org/10.1016/j.seizure.2021.05.012DOI Listing
May 2021

Add-on Home-Centred Activity-Based Therapy vs Conventional Physiotherapy in Improving Walking Ability at 6-Months in Children with Diplegic Cerebral Palsy: A Randomized Controlled Trial.

Indian Pediatr 2021 May 28. Epub 2021 May 28.

Department of Pediatrics Neurology and Neurodevelopment, Medanta, The Medicity, Gurgaon, Haryana, India. Correspondence to: Prof Pratibha Singhi, Director, Department of Pediatrics Neurology and Neurodevelopment, Medanta, The Medicity, Gurgaon, Haryana, India.

Background: Institutional physiotherapy as a standard of care for management of cerebral palsy (CP) has certain shortcomings, especially in resource-constrained settings. This is a proof-of-concept trial to evaluate the efficacy of individualized home-centered activity-based therapy in children with spastic diplegic CP.

Design: Randomized controlled trial (open-label).

Settings: Tertiary-care hospital with pediatric neurology services (July 2014 to July 2016).

Participants: Consecutive sample of 59 children (5-12yrs) with spastic diplegic CP (Gross Motor Function Classification System scores II - III) without fixed lower-limb contractures, illnesses impeding physiotherapy or history of recent botulinum toxin injection/surgery were recruited.

Procedure: Children were randomized to Intervention or Control arms. Their 6-minute-walk Test (6MWT) scoring and clinical examination were performed at baseline, 3 and 6 months. Children in Intervention Arm (n=30) were prescribed parent-supervised home-centered activity-based therapy (walking, standing, squatting, climbing up/downstairs, kicking a ball, dancing, riding a tricycle/bicycle) in addition to their institutional physiotherapy. Children in Control Arm (n=29) were prescribed ongoing institutional physiotherapy alone. Logbooks, home videos and telephonic follow-ups were used to ensure compliance.

Main Outcome Measures: Comparison of the mean change in 6MWT scores at 6 months (from baseline) between the two groups.

Results: Median (IQR) change in 6MWT scores at 6 months (from baseline) in the Intervention and Control arms were 3.5 (-5.3, 9) m and 3 (-7.8, 6.3) m.

Conclusion: Adjunct home-centered activity-based therapy was safe and feasible, but did not result in appreciable gains over 6 months.
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May 2021

Hyperbilirubinemia and Asphyxia in Children With Dyskinetic Cerebral Palsy.

Pediatr Neurol 2021 Jul 4;120:80-85. Epub 2021 Mar 4.

Professor and Head, Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. Electronic address:

Background: We aimed to study the clinical, etiologic, and radiological characteristics in children with dyskinetic cerebral palsy (DCP) and to compare the etiologic subtypes of hyperbilirubinemia and perinatal asphyxia.

Methods: This is a cross-sectional, observational study that enrolled consecutive children with DCP, aged one to 14 years.

Results: Sixty-five children with DCP were evaluated. Most children were boys (77%, n = 50), and term gestation (80%, n = 52). Presenting concerns were global developmental delay (97%, n = 63) and involuntary movements (60%, n = 39). Hyperbilirubinemia (66%, n = 43) and perinatal asphyxia (29%, n = 19) were the most important causes. The majority (83%, n = 54) of children were severely disabled (level V and IV). The hyperbilirubinemia group had significant motor delay (63% vs 37%, P = 0.03) and upward gaze palsy (69.7% vs 31.5%, P = 0.005) when compared with the perinatal asphyxia group. Hyperbilirubinemia significantly involved pallidi (86% vs 10% P = 0.0001) and subthalamic nucleus (26% vs none, P = 0.01), whereas asphyxia significantly involved the putamen (58% vs none, P = 0.0001), thalamus (63% vs none, P = 0.0001), and periventricular white matter (79% vs 19%, P = 0.0001).

Conclusions: DCP is the dominant type of cerebral palsy seen in term-born babies with severe dystonia, developmental delay, and motor impairment. Hyperbilirubinemia is the major cause of DCP in the study. Hyperbilirubinemia is associated with motor delay, upward gaze palsy, prominent dystonia, and involvement of globus pallidi and subthalamic nuclei.
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http://dx.doi.org/10.1016/j.pediatrneurol.2021.02.002DOI Listing
July 2021

Long-term epilepsy control, motor function, cognition, sleep and quality of life in children with West syndrome.

Epilepsy Res 2021 Jul 2;173:106629. Epub 2021 Apr 2.

Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India. Electronic address:

Purpose: To assess epilepsy, motor function, cognitive, sleep, and quality of life outcomes and their predictors in a follow-up cohort with West syndrome (WS) at ≥5 years of age.

Methods: Cross-sectional evaluation in a follow-up cohort of WS (aged 5-14 years), between July 2018 and December 2019, was performed at a tertiary-care referral center in Northern India. 164 children were assessed in-person for epilepsy severity, functional status (gross motor and hand function), social quotient, behavioral comorbidities, sleep problems, and quality of life (QoL) using Early Childhood Epilepsy Severity Scale, Gross Motor Function Classification System, Manual Ability Classification System, Vineland Social Maturity Scale, Diagnostic and Statistical Manual of Mental disorders-5 criteria, Children's Sleep Habits Questionnaire, and PedsQL-Epilepsy module respectively. Furthermore, 238 children with the inability to visit the hospital were assessed through telephonic interview along with retrospective case record review for epilepsy control, gross and fine motor measures.

Results: 402 children with WS (75 % boys) with regular follow-up were studied and the majority (80 %) had underlying structural etiology. The median age (interquartile range) of the cohort was 92 (78-107) months. Of these, 60 % had evolved to Lennox-Gastaut syndrome (LGS). The following long-term outcomes were observed: ongoing epilepsy (261/402), unfavorable motor status (130/402), moderate to profound intellectual disability (111/164), autistic spectrum disorder (42/164), attention-deficit hyperactivity disorder (18/164), poor sleep (135/164), and impaired QoL (115/164). Non-structural etiology (odds ratio [OR] = 3.8, 95 % confidence interval [CI]: 2.1-5.5, p=<0·0001) and older age (>5 months) at the onset of epileptic spasms (OR = 2·9, 95 % CI: 1.5-5.0, p=<0·0001) were associated with enduring seizure freedom for more than two years.

Conclusion: The present study revealed a preponderance of structural etiology and a high rate of transition to LGS. Early age at onset of spasms (before five months) and structural etiology were the predictors of unfavorable long-term epilepsy outcome. QoL was impaired in more than two-thirds of patients and it correlated significantly with cognitive, sleep, motor, and behavioral outcomes. However, the results of our study should be interpreted in the context of significant attrition of the original cohort.
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http://dx.doi.org/10.1016/j.eplepsyres.2021.106629DOI Listing
July 2021

Brain MRI in Epstein-Barr Virus Meningoencephalitis in Children.

Ann Indian Acad Neurol 2020 Sep-Oct;23(5):621-624. Epub 2020 Feb 7.

Department of Pediatrics, Medanta, The Medicity, Gurugram, Haryana, India.

Background And Purpose: Epstein-Barr virus (EBV) meningoencephalitis can have variable and nonspecific brain magnetic resonance imaging (MRI) findings in children. This study was done with the purpose of describing brain MRI findings in children with EBV meningoencephalitis.

Materials And Methods: The study included 45 pediatric patients that presented with variable neurological symptoms and were found to have EBV meningoencephalitis based on positive EBV deoxyribonucleic acid (DNA) in the cerebrospinal fluid. All these patients had undergone brain MRI. Clinical and radiological features were evaluated.

Results: Fever was a presenting feature in all cases. Signs of meningitis and raised intracranial pressure (ICP) were seen in 24 (53.3%) cases, encephalopathy in 15 (33.3%), and seizures were present in 33 (73.3%). MRI was abnormal in 29 (64.4%) patients. The cortical/subcortical pattern was diagnosed in 9 (20%) cases, white matter involvement in 7 (15.5%), basal ganglia in 5 (11.1%), thalamic involvement in 4 (8.8%), brain stem involvement in 2 (6.2%), substantia nigra involvement in 2 (4.4%), and cerebellar involvement in 2 (4.4%). Diffusion restriction was present in 11 (24.4%) cases and susceptibility changes in 7 (15.5%). Meningeal enhancement was present in 10 (22.2%) cases. In addition, brain abscess and subdural effusion/empyema were present in 1 (2.2%) case each.

Conclusion: Pediatric EBV meningoencephalitis has varied clinicoradiological spectrum and there is no specific MRI pattern to characterize the meningoencephalitis on imaging. Common MRI findings include cortical-subcortical involvement, white matter changes, basal ganglia, and thalamic involvement.
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http://dx.doi.org/10.4103/aian.AIAN_537_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887499PMC
February 2020

MRI Spectrum of Meningoencephalitis in Children.

Ann Indian Acad Neurol 2020 Sep-Oct;23(5):616-620. Epub 2019 Dec 24.

Department of Pediatrics, Medanta, The Medicity, Gurugram, NCR, Haryana, India.

Background And Purpose: type b (Hib) infection occurs mostly in children and is transmitted from person to person through the respiratory pathway. Hib strain is associated with meningitis or encephalitis. It is not an uncommon infection, particularly, in the developing world. This prospective cohort study was done with the aim of describing imaging findings in patients with Hib meningoencephalitis.

Materials And Methods: In a prospective cohort study, consecutive children admitted in the pediatric emergency unit with acute febrile encephalopathy were enrolled. The clinical details, CSF analysis, and microbiological and serological investigations were recorded on a case record proforma. Children with confirmed Hib meningoencephalitis were included in this study. Clinicoradiological features were assessed.

Results: A total of 16 patients with acute febrile encephalopathy, in whom CSF latex agglutination, CSF culture, or CSF multiplex PCR were positive for were included in this study. All these children were investigated with magnetic resonance imaging (MRI) brain. Important imaging findings were meningitis, predominantly around frontoparietal lobes (43%), cerebritis (28%), ventriculitis (14%), and subdural collections (21.5%). One patient had features consistent with acute disseminated encephalomyelitis (ADEM) while four patients had normal MRI scan.

Conclusions: is still a common cause of meningitis in infants and children in the developing world. We have tried to study the most common MRI features associated with Hib infection to help radiologists alert the treating clinicians to further investigate these patients for appropriate prognostication.
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http://dx.doi.org/10.4103/aian.AIAN_500_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887487PMC
December 2019

Psychopathology and Quality of Life in Children with Epilepsy: A Cross-Sectional Study.

Indian J Pediatr 2021 Jul 12;88(7):712-714. Epub 2021 Feb 12.

Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India.

The study examined the relationship between psychopathology, seizure-related variables, and quality of life in children with epilepsy. Seventy-nine children with active epilepsy (Mean = 10.1 y, SD = 2.68) were consecutively recruited from the outpatient services of an advanced pediatric hospital. The Quality-of-Life in Childhood Epilepsy questionnaire and the Childhood Psychopathology Measurement Schedule (CPMS) were administered to the parents. The most compromised health-related quality of life (HRQOL) domain was the general health domain (Mean = 61.70, SD = 26.81). The mean intelligence quotient (IQ) score was 81.59 (SD = 12.34) and only 20% had IQs in the normal average range. The mean CPMS score was 7.41 (SD = 5.41). The psychopathology score and the IQ explained 43% of the variance in the total HRQOL score (F = 28.67, P = 0.0001) in the regression analysis. Childhood epilepsy is a significant public health concern and a multidisciplinary approach to management would help in addressing the multiple needs of the children with epilepsy and their families.
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http://dx.doi.org/10.1007/s12098-021-03685-wDOI Listing
July 2021

An Update to Approach to the Childhood Electroclinical Syndromes.

Indian J Pediatr 2020 Dec 5;87(12):1029-1039. Epub 2020 Nov 5.

Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Childhood Electroclinical Syndrome (CES) is a term which refers to distinct epilepsies of childhood which have peculiar similarities such as the age of onset, seizure semiology, EEG and prognosis. With advancements in the diagnostics and genetics, pediatric epilepsy is entering in the age of precision medicine. The present paper provides an update of CES in light of recent advances in the terminologies and classifications by International League Against Epilepsy and genetic underpinnings of epilepsy. The core features of CES for diagnosing and managing some common CES is presented here.
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http://dx.doi.org/10.1007/s12098-020-03554-yDOI Listing
December 2020

A prospective cohort study to assess the frequency and risk factors for calcification in single lesion parenchymal neurocysticercosis.

Seizure 2020 Dec 18;83:132-138. Epub 2020 Oct 18.

Director Pediatric Neurology and Neurodevelopment, Medanta, The Medicity, Gurgaon, Haryana, India.

Background: Calcified neurocysticercosis (NCC) predisposes patients to an enduring state of epilepsy. The predictors for calcification in parenchymal neurocysticercosis are not well defined.

Method: In this prospective cohort study, consecutive children with single-lesion parenchymal NCC were enrolled and followed up for one year. All patients were investigated with brain 3 T-MRI and electroimmunotransfer blot (EITB). Clinical follow-ups were performed every 3 months. Radiology was repeated at the 6-month and one-year follow-ups. The proportion of calcified lesions at one year and the predictors of calcification were studied.

Result: During the study period from June 2013 to December 2015, 93 children with single lesion parenchymal NCC were enrolled. At presentation, 90 % of the lesions were in the colloidal stage, and 71 % of the lesions had moderate to severe perilesional oedema. All children had 6 months of follow-up, and 86 (92.5 %) had one year of follow-up. Seizure recurrence was present in 13 (14 %) children. Follow-up radiology at one year showed lesion resolution in 51 (59 %) lesions and calcification in 28 (32.5 %) lesions. Children with calcified lesions during follow-up had a higher odds of seizure recurrences {OR, 95 % CI 3.6(2.3-5.6)}. The presence at baseline of diffusion restriction {OR, 95% CI 2.9 (1.01-8.8)}, scolex or wall calcification in the T2 Star weighted angiography MRI images {OR, 95% CI 3.7 (1.7-8.2)} and >10 mm size of the lesion {OR, 95 % CI 2.4 (1.2-5.01)} predicted lesion calcification.

Conclusion: Children with calcification of the parenchymal NCC lesions have a higher risk for seizure recurrence during follow-up. The presence of diffusion restriction, calcified nidus in the colloidal nodular stage, and >10 mm size of the lesion at baseline predicted calcification of the lesion during follow-up.
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http://dx.doi.org/10.1016/j.seizure.2020.10.012DOI Listing
December 2020

Safety, Feasibility and Effectiveness of Pulse Methylprednisolone Therapy in Comparison with Intramuscular Adrenocorticotropic Hormone in Children with West Syndrome.

Indian J Pediatr 2021 Jul 26;88(7):663-667. Epub 2020 Oct 26.

Pediatric Neurology Division, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Objective: To assess the feasibility, effectiveness, and safety of pulse methylprednisolone in comparison with intramuscular adrenocorticotropic hormone (ACTH) therapy in children with West syndrome (WS).

Methods: This open-label, pilot study with a parallel-group assignment included 44 recently diagnosed children with WS. Methylprednisolone therapy was given as intravenous infusion at a dose of 30 mg/kg/d for five days followed by oral steroids 1 mg/kg gradually tapered over 5-6 wk. The efficacy outcomes included a cessation of epileptic spasms (as per caregiver reporting) and resolution of hypsarrhythmia on electroencephalogram; safety outcome was the frequency of various adverse effects.

Results: By day 14 of therapy, 6/18 (33.3%) children in the methylprednisolone group and 10/26 (38.5%) children in the ACTH group achieved cessation of epileptic spasms [group difference - 5.2%; confidence interval (CI) -30.7 to 22.8; p = 0.73]. However, by six weeks of therapy, 4/18 (22.2%) children in the methylprednisolone group and 11/26 (42.3%) children in the ACTH group had cessation of epileptic spasms (group difference - 20.1%; CI -43.0 to 8.4; p = 0.17). Hypertension was more commonly observed in the ACTH group (10 children) than in the methylprednisolone group (2 children; p = 0.046). Pulse methylprednisolone therapy was relatively safe.

Conclusions: The study observed limited effectiveness of both ACTH and pulse methylprednisolone therapy, which may partially be due to preponderance of structural etiology and a long treatment lag. However, pulse methylprednisolone therapy appeared to be safe, tolerable, and feasible for management of WS.
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http://dx.doi.org/10.1007/s12098-020-03521-7DOI Listing
July 2021

Do Atypical Food Preferences in Children with Autism Differ by Severity?

Indian J Pediatr 2021 03 20;88(3):307. Epub 2020 Oct 20.

Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India.

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http://dx.doi.org/10.1007/s12098-020-03534-2DOI Listing
March 2021

Primary Hypokalemic Periodic Paralysis: Long-term Management and Complications in a Child.

J Pediatr Neurosci 2020 Apr-Jun;15(2):132-134. Epub 2020 Jun 27.

Pediatric Neurology Unit, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Hypokalemic periodic paralysis (HPP) is a rare genetically determined neuromuscular disorder caused by mutation in skeletal muscles calcium and sodium channels. It presents with recurrent episodes of flaccid paralysis. A 9-year-old girl presented with recurrent episodic flaccid quadriparesis with complete recovery in-between the episodes. Investigations during the acute episode revealed marked hypokalemia with electrocardiogram changes. Next-generation sequencing showed pathogenic missense mutation in gene. She responded well to oral potassium supplementation, acetazolamide, and spironolactone therapy. Muscle weakness in HPP is reversible, and long-term management reduces frequency of paralysis and prevents permanent weakness.
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http://dx.doi.org/10.4103/jpn.JPN_101_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519733PMC
June 2020

Clinico-radiological Profile of Children with Pontocerebellar Hypoplasia.

J Pediatr Neurosci 2020 Apr-Jun;15(2):94-98. Epub 2020 Jun 27.

Department of Pediatrics, Medanta - The Medicity, Gurugram, Haryana, India.

Aims And Objectives: Pontocerebellar hypoplasia (PCH) constitutes a heterogeneous group of neurodegenerative/neurodevelopmental disorder of pons and cerebellum with onset in prenatal period. This study aimed to discuss the clinical, radiological profile, and outcome of four infants with PCH attending our center.

Materials And Methods: Data of children with psychomotor retardation seen between January 2015 and December 2015 at neurodevelopmental clinic was retrieved. PCH was defined by clinical and radiological criteria. Clinical features included were delay in attainment of milestones in more than two developmental domains accompanied by severe microcephaly. Radiological evidence of cerebellar volume loss with hypoplasia of pons was included. Patient charts were reviewed for clinical features, neuroimaging, electroencephalography, and biochemical investigations including serum and cerebrospinal lactate. Molecular genetic testing for the common p.A307S mutation in of the cases and their parents were also analyzed.

Results: During this period, 101 children with psychomotor retardation were evaluated at our center. Of the 101, four children were with clinical and radiological evidence of PCH. In addition to psychomotor retardation and severe microcephaly, spasticity, bipyramidal signs, and epileptic spasms were universal in all four children. Three of the four children had optic atrophy and two had sensorineural hearing loss. Severe cerebellar hypoplasia with attenuated pons was seen in all four children. Two children had dragonfly appearance of cerebellum on coronal section. The commonest p.A307S mutation in children and their parents was not detected.

Conclusion: A heightened index of suspicion for PCH is merited in infants with progressive psychomotor retardation and severe microcephaly. Cerebellar hypoplasia with pontine attenuation forms the mainstay of diagnosis of PCH.
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http://dx.doi.org/10.4103/jpn.JPN_6_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7519739PMC
June 2020

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

Neurocrit Care 2021 06 7;34(3):927-934. Epub 2020 Oct 7.

Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India.

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.
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http://dx.doi.org/10.1007/s12028-020-01123-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538369PMC
June 2021

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

Pediatr Crit Care Med 2020 12;21(12):1071-1080

All authors: Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

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.
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http://dx.doi.org/10.1097/PCC.0000000000002557DOI Listing
December 2020

Outcome of Conversion Symptoms in Children.

Indian J Pediatr 2021 04 31;88(4):367-369. Epub 2020 Jul 31.

Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Sector 12, Chandigarh, 160012, India.

The study evaluated the short-term outcome of children diagnosed with conversion disorder and compared their pre- and post-intervention psychological functioning. Fifty children consecutively diagnosed with conversion disorder over a period of one year were recruited from the pediatrics department of a tertiary care teaching hospital in North India. The adverse life events were assessed by the Life Events Scale for Indian Children, emotional and behavioral difficulties by the Childhood Psychopathology Measurement Schedule (CPMS), and adjustment by the Pre-Adolescent Adjustment Scale (PAAS). Majority of the children improved at follow up at 3 mo after initiation of treatment. In addition, total scores on the CPMS significantly declined (t = 5.12, P = 0.0001) and self-reported adjustment improved on the PAAS (t = 5.81, P = 0.0001) as compared to functioning before the initiation of therapy. Timely recognition and multi-disciplinary management can lead to successful outcome and improved functioning in most children diagnosed with conversion disorder.
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http://dx.doi.org/10.1007/s12098-020-03465-yDOI Listing
April 2021

Comparative evaluation of IS6110 and protein antigen b PCR in cerebrospinal fluid for rapid diagnosis of tuberculous meningitis in children.

J Med Microbiol 2020 Jul;69(7):979-985

Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Childhood tuberculosis meningitis is a severe form of tuberculosis with high morbidity and mortality. The diagnosis is frequently missed and delayed due to lack of sensitive tests like acid-fast bacilli (AFB) smear and delayed results by culture. To compare the role of IS6110 and protein antigen b PCR in cerebrospinal fluid (CSF) for rapid diagnosis of tuberculous meningitis (TBM) in children. Forty-five cases of TBM and 20 controls were enrolled in this prospective study. The mean ages of cases and controls were 4.2±0.5 years and 4.5±0.7 years, respectively. In the TBM group, two-thirds of the children were <4 years of age, and 62 % were males. Sensitivities of AFB smear examination, Löwenstein-Jensen (LJ) medium and bactenecin (BACTEC) culture in cases were 4.4, 0 and 2.2%, respectively. The protein antigen b PCR was most sensitive as it was positive in 35 (77.8 %) of TBM patients; IS6110 PCR was positive in 27 (60 %) patients. Both PCR-based tests had higher positivity than conventional tests and BACTEC culture. No significant difference was seen between the PCR tests. Excellent agreement was observed between both PCR-based tests as they were concordant for 26 positive samples and 35 negative samples. Protein b PCR is a sensitive and rapid method for the diagnosis of TBM (sensitivity 77.8 %). Both PCRs were more sensitive than smear, LJ and BACTEC. The specificity of both PCR was 100 %.
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http://dx.doi.org/10.1099/jmm.0.001220DOI Listing
July 2020

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

Br J Neurosurg 2020 Jun 18;34(3):258-263. Epub 2020 Mar 18.

Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

To study the clinical profile and predictors of outcome in children undergoing decompressive craniectomy (DC) for non-traumatic intracranial hypertension (ICH). 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. Thirty children, median (IQR) age of 6.5 (2, 50) months, underwent DC; of which 26 (86.7%) were boys. Altered sensorium ( = 26, 86.7%), seizures ( = 25, 83.3%), pallor ( = 19, 63.3%) and anisocoria ( = 14, 46.7%) were common signs and symptoms. Median (IQR) Glasgow Coma Scale at admission was 9 (6,11). Commonest etiology was intracranial bleed ( = 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 ( = 28) were seizures ( = 25; 89.2%) and hemiparesis ( = 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;  = 0.019]. 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.
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http://dx.doi.org/10.1080/02688697.2020.1740648DOI Listing
June 2020

Management Strategies of Melkersson-Rosenthal Syndrome: A Review.

Int J Gen Med 2020 26;13:61-65. Epub 2020 Feb 26.

Pediatric Neurology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.

Melkerrson-Rosenthal syndrome is a rare disorder of unknown aetiology and characterized by the triad of oro-facial edema, facial nerve palsy, and furrowing of the tongue. Two or more of the above are essential for making a clinical diagnosis. The mainstay of treatment is corticosteroids. Intralesional triamcinolone acetonide may be used for the treatment of oro-facial edema. Another treatment option for oro-facial edema includes intralesional betamethasone, along with oral doxycycline. The review discusses the management strategies in Melkersson-Rosenthal syndrome.
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http://dx.doi.org/10.2147/IJGM.S186315DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049838PMC
February 2020

Cognitive, Language, and Visuomotor Abilities of Very Low Birthweight Infants at Corrected Age of Two Years.

Indian Pediatr 2020 04 5;57(4):296-300. Epub 2020 Feb 5.

Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Objective: To assess the prevalence and predictors of language and visuomotor delay in very low birthweight (≤1250 g) children at corrected age (CA) of 2 years.

Design: Prospective observational.

Setting: Neonatal follow-up clinic of a level III center.

Participants: Children with birthweight £1250 g and discharged alive (n=164) from April 2012 to April 2013 were followed up till 2 years CA (n=126).

Methods: Development, neurological status, and language/visuomotor cognitive skills were assessed by Cognitive Adaptive Test/Clinical Linguistic and Auditory Milestone Scale (CAT/CLAMS). Development Quotient (DQ) was calculated.

Main Outcome: Prevalence and predictors for the language and visuomotor delay.

Results: At 2 years (n=123 CAT, 126 CLAMS), 30 (24%) children had below average DQ (<90) and 93 (74%) average and above average DQ (≥90) in full scale CAT/CLAMS test. Small for gestation infants (n=86) have higher risk of below average DQ (P=0.036). Gestational age and socioeconomic status have a positive correlation with language development at 9 months and 2 years, respectively.

Conclusions: In VLBW (birth weight ≤1250 g) infants, the prevalence of language/visuomotor delay is high. Small for gestational age infants are at higher risk for language and visuomotor development delay at 2 years corrected age.
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April 2020

Infantile Tremor Syndrome or a Neurocutaneous Infantile B12 Deficiency (NIB) Syndrome?

Indian J Pediatr 2020 03 27;87(3):179-184. Epub 2020 Jan 27.

Pediatric Neurology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education andResearch, Chandigarh, India.

Objectives: To prospectively study the clinical and developmental profile; hematological profile and the B-12 status using multiple parameters in children with Infantile tremor syndrome (ITS).

Methods: In this observational study (NCT02762682) (July 2015 through December 2016) children (and their mothers) with a clinical diagnosis of ITS were evaluated clinically; and development was assessed by CAPUTE scales. A complete blood count (CBC); peripheral blood smear examination; markers of vitamin B12 status (serum B12, homocysteine, folate); acylcarnitines [using Tandem mass spectrometry (TMS)] and urine methylmalonic acid (MMA) [Gas chromatography mass spectrometry (GCMS)] were estimated. A control group of children and their mothers were sampled for comparison.

Results: A total of 286 individuals were enrolled for this study. One-hundred-ten children with ITS were screened and 92 (20 with tremors; age 12.7 ± 5 mo, 61 boys) children and their mothers were enrolled. Fifty-one children and their mothers were enrolled as controls. The median clinical linguistic & auditory milestone-developmental quotient (CLAM-DQ) was 32 (IQR 20.6-45.5) and median cognitive adaptive test-developmental quotient (CAT-DQ) was 36.2 (IQR 18.7-49.0). All babies except 9 (ovo-veg) had vegetarian mothers. Head circumference below 2 SD (WHO standards) was seen in 84% and below 3 SD in 58%. The CBC findings were; Hb- 8.3 ± 1.6 g/dl, Thrombocytopenia-29 (32%), mean corpuscular volume (MCV)- 92.2 ± 13.4, MCV- more than 95 fL-38(42%), Red cell distribution width (RDW)- 21.6 ± 6.5, and macrocytes on peripheral smear in 68%. In 89 (97%) out of 92 children had laboratory features of deficient B12 status. Two-thirds of the mothers also had evidence of B12 deficiency.

Conclusions: ITS is, in all likelihood is a consequence of vitamin B12 defeciency. It has a significant impact on head growth and development of affected infants.
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http://dx.doi.org/10.1007/s12098-019-03117-wDOI Listing
March 2020

Developmental Outcomes in Children with Infantile Tremor Syndrome.

Indian J Pediatr 2020 06 24;87(6):451-453. Epub 2020 Jan 24.

Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

In this prospective, study, children with Infantile tremor syndrome (ITS) were assessed at diagnosis and at follow-up using the Developmental Assessment Scale for Indian Infants (DASII). Of the 53 children enrolled (25 children had tremor, mean age: 13.1 ± 4.9 mo), 45 (84.9%) had developmental delay and 17 (32.8%) had development regression. The mean Motor-Developmental quotient (DQ) at baseline was 39.1 ± 15.6 (no-tremors group) and 22.2 ± 12.6 (tremor group) and mean Mental-DQ at diagnosis was 29.9 ± 15.2 (no-tremors group) and 14.5 ± 10.6 (tremor group) respectively. Forty-four children were assessed at follow-up (median- 216 d). The mean Motor-DQ on follow-up was 66.2 ± 22.1 (no tremors) and 55.9 ± 15.6 (tremors); and the mean Mental-DQ was 54.3 ± 23.0 (no tremors) and 45.6 ± 11.6 (tremors) respectively. Only seven (16%) children had a follow-up mental DQ more than 70. Mental abilities are more affected than motor abilities in children with ITS and those with tremors fare poorly. Despite gains, very few children have abilities in normal range at follow-up.
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http://dx.doi.org/10.1007/s12098-020-03187-1DOI Listing
June 2020

Prevalence and Characteristics of Sensory Processing Abnormalities and its Correlation with FDG-PET Findings in Children with Autism.

Indian J Pediatr 2019 11 15;86(11):1036-1042. Epub 2019 Oct 15.

Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Objective: To study the prevalence and characteristics of Sensory processing abnormalities (SPAs) in children with autism and to study if there is any correlation between sensory processing abnormalities with FDG-PET findings in children with severe autism.

Methods: One hundred children, aged 3-12 y, diagnosed as Autistic spectrum disorder; ASD (DSM-V) and 100 age and sex matched controls were studied. SPAs were detected using Short sensory profile (SSP) questionnaire. Children with progressive neurological diseases, active epilepsy and structural brain abnormalities were excluded. On Childhood Autism rating scale, 30 children had severe and 70 had mild-moderate autism. The pattern of sensory processing abnormalities in children with severe ASD was compared with mild-moderate ASD. FDG-PET scan was done in children with severe autism and correlated with SPAs.

Results: All children with severe autism had sensory processing abnormalities as compared to only 40% children with mild-moderate autism. Underresponsiveness/seeking-sensation was affected in all children with severe ASD and 82% had movement sensitivity. In children with mild-moderate ASD, 45% had auditory filtering, 30% had movement sensitivity and 27% had underresponsiveness/seeking-sensation. FDG-PET was abnormal in 17% of children with severe autism. Diffuse cerebral/ temporal lobe hypometabolism, increased bilateral frontal lobe uptake and moderate reduction in parietal lobe (Lt > Rt) was observed.

Conclusions: All patients with severe autism had SPAs. However, they did not correlate with FDG-PET findings.
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http://dx.doi.org/10.1007/s12098-019-03061-9DOI Listing
November 2019

Late-Onset Citrullinemia Type I: A Radiological Mimic of Herpes Encephalitis.

J Pediatr Neurosci 2019 Jan-Mar;14(1):36-37

Department of Pediatric Neurology and Neurodevelopment, Medanta-The Medicity, Gurugram, Haryana, India.

We describe a 10 year old boy who presented with acute onset rapidly progressing encephalopathy. MRI revealed bilateral insular cortex and basifrontal involvement suggesting Herpes encephalitis.He was treated with acyclovir and his symptoms improved. Six months after the first hospitalization he reported back with two episodes of partial seizures. He was started on Valproate. A week after starting valproate he was readmitted with hyperammonemic encephalpathy, on further investigations Citrullinemia Type 1 was diagnosed. This case highlights a metabolic disorder which radiologically mimics herpes encephalitis. The management of the disorder differs remarkably from herpes encephalitis and hence its recognition and suspicion based on radiology is critical.
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http://dx.doi.org/10.4103/jpn.JPN_12_18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6601122PMC
July 2019

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

Indian J Pediatr 2019 07 8;86(7):608-616. Epub 2019 Jun 8.

Department of Pediatric Neurology, Madhukar Rainbow Children's Hospital, Malviya Nagar, Delhi, 110017, India.

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.
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http://dx.doi.org/10.1007/s12098-019-02946-zDOI Listing
July 2019

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

Childs Nerv Syst 2019 08 4;35(8):1371-1379. Epub 2019 Jun 4.

Department of Neurosurgery, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

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.
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http://dx.doi.org/10.1007/s00381-019-04209-wDOI Listing
August 2019

Progressive spastic paraparesis in a girl with short stature.

BMJ Case Rep 2019 May 31;12(5). Epub 2019 May 31.

Department of Pediatrics, Medanta, The Medicity, Gurgaon, Haryana, India.

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http://dx.doi.org/10.1136/bcr-2019-230569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557320PMC
May 2019

Thenar Hypertrophy and Electrical Myotonia in Pompe Disease.

J Clin Neuromuscul Dis 2019 03;20(3):135-137

Department of Pediatrics, Chief Pediatric Neurology and Neurodevelopment, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1097/CND.0000000000000195DOI Listing
March 2019

Hemispheric AESD: Half-Bright Tree Appearance in a Child With Hepatitis A.

Neurohospitalist 2019 Jan 24;9(1):47-48. Epub 2018 Jan 24.

Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1177/1941874417754022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327236PMC
January 2019

How Different is AMAN from AIDP in Childhood GBS? A Prospective Study from North India.

Indian J Pediatr 2019 04 12;86(4):329-334. Epub 2019 Jan 12.

Pediatric Neurology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Objectives: To compare the clinical profile and short-term outcome of children with axonal and demyelinating subtypes of childhood Guillain Barré syndrome (GBS).

Methods: This is a prospective observational study conducted in a tertiary care teaching hospital in North India. Consecutive children with Guillain Barré syndrome were recruited to compare the clinical profile and short term outcome among the subtypes.

Results: Among 9847 children admitted to the emergency, 95 had acute flaccid paralysis; 57 of whom had GBS. Electrophysiological studies were completed in 57; of whom 20 had acute inflammatory demyelinating polyneuropathy (AIDP); 19 had acute motor axonal neuropathy (AMAN); 12 had non-reactive nerves; five were unclassifiable; 1 had acute motor sensory axonal neuropathy (AMSAN). More children in AMAN group had preceding gastroenteritis (4 vs. 2), while AIDP group had upper respiratory infections (12 vs. 7). Ataxia was only seen in AIDP subtype while wrist drop, foot drop and hyperreflexia were seen only with AMAN subtype. Respiratory muscle involvement (6 vs. 3) and artificial ventilation (5 vs. 2) was more in AMAN. At discharge, children with AIDP were less likely to be non-ambulant (12 vs. 6, p = 0.036). Mean disability scores at hospital discharge (4.9 ± 1.2 vs. 4 ± 0.9, p = 0.015) and at last follow-up (0.7 ± 1.01 vs. 0.05 ± 0.2, p = 0.016) were higher in AMAN. Children with AIDP were more likely to achieve normalcy on follow-up (19 vs. 12, p = 0.023).

Conclusions: Children with AMAN appear to have a more severe clinical course; higher short-term morbidity; and slower recovery than those with AIDP.
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http://dx.doi.org/10.1007/s12098-018-2835-5DOI Listing
April 2019