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Objectives: We have very little information about sexual activity and concerns of patients with myelopathy from India. The objectives of this study were to assess the sexual dysfunction and sexual concerns among patients with myelopathy due to spinal cord lesion (SCL). Materials and Methods: This study was a single-center, cross-sectional, and hospital-based study among male and female patients in the age-group 18–50 years, with disability due to myelopathy due to SCL. The data were collected using a self-designed, pretested, and semi-structured questionnaire by face-to-face interview. Results: Eighty participants were recruited in the study, of which 62 (77.5%) were men. The mean standard deviation (SD) age of the participants was 33.7 (8.6) years, and mean (SD) age at time of illness was 31.4 (8.6) years with median duration of 17 months. Among 62 males, psychogenic erection was impaired in 77.2%, reflex erection was impaired in 78.9%, and ejaculation was affected in 70.7%. Orgasm was absent or reduced in 66.1% males. Among 18 female participants, psychogenic genital arousal was reduced in 66.5%, reflex genital arousal was impaired in 55.5%, and orgasm was absent in 38.8% subjects. Sexual desire in these patients was unchanged in 41 (51.2%) and decreased or absent in 39 (48.8%). Sexual activity involvement was there in 46 (57.5%) and 34 (42.5%) had not involved in any kind of sexual activity after injury/illness. The main reasons of non-involvement in sexual activity were bladder and bowel accidents, spasticity, and difficulty in positioning. Conclusion: Comprehensive neurological rehabilitation should address sexual function of affected individual to allow them highest level of function and quality of life.

The IL-33/ST2 immune axis plays crucial roles in infection and immunity. A dysregulated IL-33/ST2 axis can induce autoimmune reaction and inflammatory responses. Guillain-Barré syndrome (GBS) is an acute peripheral neuropathy, mostly caused by post-infection autoimmunity. The role of IL-33/ST2 axis is not known in GBS. This study aimed to explore the role of IL-33/ST2 axis in GBS.Three single nucleotide polymorphisms (SNPs) of Il33 gene (rs16924159, rs7044343, rs1342336) and three SNPs of Il1rl1 gene (rs10192157, rs1041973, rs10206753) coding for suppressor of tumorigenicity 2 (ST2) were genotyped in 179 GBS patients and 186 healthy controls by TaqMan Allelic Discrimination Assay. Plasma levels of IL-33 and sST2 were measured in a subset of GBS patients (n = 80) and healthy controls (n = 80) by ELISA.The frequencies of CC genotype of rs10192157 (p = 0.043) and TT genotype of rs10206753 (p = 0.036) SNPs of Il1rl1 gene differed significantly between GBS patients and healthy controls. Gene-gene interaction between Il33 and Il1rl1 genes also conferred significant risk for GBS. In addition, the plasma sST2 levels were significantly elevated in GBS patients compared to healthy subjects (24,934.31 ± 1.81 pg/ml vs. 12,518.97 ± 1.51 pg/ml, p 0.001). Plasma sST2 levels showed a significant correlation with the disability scores at the peak of neurological deficit in GBS patients.The IL-33/ST2 axis is suggested to influence the immunopathogenesis of GBS. Genetic variants of Il1rl1 gene might serve as a risk determinant of GBS and plasma sST2 levels might emerge as a biomarker of severity of GBS, if replicated further by other studies.

Context: Post stroke sexual dysfunction in adult survivors frequently goes under-considered in medical practice. Sexual dysfunction following stroke is thought to result from multiple factors like organic and/or psychosocial and physical. Aim: To study the sexual functioning, sexual concerns and sexual satisfaction in males stroke survivors. Methods: It was a cross sectional questionnaire based study in the Neurological Rehabilitation department of a tertiary care Institute in 33 adult male stroke survivors in the age more than 21 years with at least 3 months of community dwelling post discharge. The sexual functions recorded were (1) libido/desire, (2) coital frequency, (3) sexual arousal (4) erectile function using IIEF score (5) ejaculation using PEDT score and (6) sexual satisfaction Results: Thirty three eligiblemale stroke survivors in the age range from 25-54 years (mean 42.5 years) with post-stroke duration of 3-45 months (mean 16.6 months) were included in the study. Of them, 14 had experienced stroke within 12 months and 19 had experienced stroke > 12 months ago. Thirteen participants were sexually inactive and reported no coitus because of a loss of erection. The sexually active stroke survivors reported a moderate recovery of libido (60%), coital frequency (60%), erectile function (63%), orgasm (32%) and sexual satisfaction (25%) while others had poor recovery. Erectile dysfunction was present in 16 cases, an-ejaculation in 18 cases and premature ejaculation in 9 cases. Hypertension and depression with a history of smoking posed a higher risk of erectile dysfunctions. Conclusion: Exploration of sexual dysfunctions and sexual counselling by clinicians should be part of the comprehensive stroke rehabilitation program in sub-acute care.

Vanishing white matter disease (VWMD) due to eIF2B mutations is a common leukodystrophy characterised by childhood onset, autosomal recessive inheritance, and progressive clinical course with episodic worsening. There are no reports of genetically confirmed adult patients from India. We describe the phenotype of two adults with genetically confirmed VWMD and typical radiological findings. Both had spastic ataxia and cognitive and behavioural disturbances. Other neurological features included myoclonic jerks and parkinsonism. At the last follow-up (duration: 2–9 years), one patient was wheelchair-bound. VWMD is rare in adults but should be suspected based on radiological findings and confirmed by eIF2B mutation.

Whole exome sequencing (WES), analyzed with GENESIS and WeGET, revealed a homozygous deletion in the C1QBP gene in a patient with progressive external ophthalmoplegia (PEO) and multiple mtDNA deletions. The gene encodes the mitochondria-located complementary 1 Q subcomponent-binding protein, involved in mitochondrial homeostasis. Biallelic mutations in C1QBP cause mitochondrial cardiomyopathy and/or PEO with variable age of onset. Our patient showed only late-onset PEO-plus syndrome without overt cardiac involvement. Available data suggest that early-onset cardiomyopathy variants localize in important structural domains and PEO-plus variants in the coiled-coil region. Our patient demonstrates that C1QBP mutations should be considered in individuals with PEO with or without cardiomyopathy. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Mitochondrial disorders are often difficult to diagnose because of diverse clinical phenotypes. FGF-21 and GDF-15 are metabolic hormones and promising biomarkers for the diagnosis of these disorders. This study has systematically evaluated serum FGF-21 and GDF-15 levels by ELISA in a well-defined cohort of patients with definite mitochondrial disorders (n = 30), neuromuscular disease controls (n = 36) and healthy controls (n = 36) and aimed to ascertain their utility in the diagnosis of mitochondrial disorders. Both serum FGF-21 and GDF-15 were significantly elevated in patients with mitochondrial disorders, especially in those with muscle involvement. The levels were higher in patients with mitochondrial deletions (both single and multiple) and translation disorders compared to respiratory chain subunit or assembly factor defects.

Ethylmalonic encephalopathy (EE) is a rare autosomal recessive inborn error of metabolism. To study the molecular effects of ETHE1 p. D165H mutation, we employed mass spectrometry-based mitochondrial proteome and phosphoproteome profiling in the human skeletal muscle. Eighty-six differentially altered proteins were identified, of which thirty-seven mitochondrial proteins were differentially expressed, and most of the proteins (37%) were down-regulated in the OXPHOS complex-IV. Also, nine phosphopeptides that correspond to eight mitochondrial proteins were significantly affected in EE patient. These altered proteins recognized are involved in several pathways and molecular functions, predominantly in oxidoreductase activity. This is the first study that has integrated proteome and phosphoproteome of skeletal muscle and identified multiple proteins associated in the pathogenesis of EE.

Hereditary folate malabsorption (HFM, congenital folate malabsorption; OMIM#229050) is a rare, potentially treatable autosomal recessive disorder with multisystem involvement.1 It is caused by homozygous or compound heterozygous mutations in SLC46A1 resulting in loss of function of proton-coupled folate transporter (PCFT),2 required for intestinal absorption and transport of folate across choroid plexus.1,2 This leads to the deficiency of folate in serum and CSF, causing hematologic, immunologic, gastrointestinal, and neurologic manifestations.1 Neuroimaging shows intracranial calcification.3 Diagnosis is confirmed by impaired absorption of an oral folate load, low CSF folate concentration (even after correction of the serum folate concentration), or the identification of pathogenic variants in SLC46A1 on molecular genetic testing.1 We describe the clinical, imaging, biochemical, and genetic findings of a patient with HFM.

Background Mitochondrial disorders are clinically complex and have highly variable phenotypes among all inherited disorders. Mutations in mitochon drial DNA (mtDNA) and nuclear genome or both have been reported in mitochondrial diseases suggesting common pathophysiological pathways. Considering the clinical heterogeneity of mitochondrial encephalopathy, lactic acidosis and stroke-like episodes (MELAS) phenotype including focal neurological deficits, it is important to look beyond mitochondrial gene mutation. Methods The clinical, histopathological, biochemical analysis for OXPHOS enzyme activity, and electron microscopic, and neuroimaging analysis was performed to diagnose 11 patients with MELAS syndrome with a multisystem presentation. In addition, whole exome sequencing (WES) and whole mitochondrial genome sequencing were performed to identify nuclear and mitochondrial mutations. Results Analysis of whole mtDNA sequence identified classical pathogenic mutation m.3243A > G in seven out of 11 patients. Exome sequencing identified pathogenic mutation in several nuclear genes associated with mitochondrial encephalopathy, sensorineural hearing loss, diabetes, epilepsy, seizure and cardiomyopathy (POLG, DGUOK, SUCLG2, TRNT1, LOXHD1, KCNQ1, KCNQ2, NEUROD1, MYH7) that may contribute to classical mitochondrial disease phenotype alone or in combination with m.3243A > G mutation. Conclusion Individuals with MELAS exhibit clinical phenotypes with varying degree of severity affecting multiple systems including auditory, visual, cardiovascular, endocrine, and nervous system. This is the first report to show that nuclear genetic factors influence the clinical outcomes/manifestations of MELAS subjects alone or in combination with m.3243A > G mutation.

Polymerase γ catalytic subunit (POLG), a nuclear gene, encodes the enzyme responsible for mitochondrial DNA (mtDNA) replication. POLG mutations are a major cause of inherited mitochondrial diseases. They present with varied phenotypes, age of onset, and severity. Reports on POLG mutations from India are limited. Hence, this study aimed to describe the clinico-pathological and molecular observations of POLG mutations. A total of 446 patients with clinical diagnosis of mitochondrial disorders were sequenced for all exons and intron-exon boundaries of POLG. Of these, 19 (4.26%) patients (M:F: 10:9) had POLG mutations. The age of onset ranged from 5 to 55 years with an overlapping phenotypic spectrum. Ptosis, peripheral neuropathy, seizures, and ataxia were the common neurological features observed. The most common clinical phenotype was chronic progressive external ophthalmoplegia (CPEO) and CPEO plus (n = 14). Muscle biopsy showed characteristic features of mitochondrial myopathy in fourteen patients (14/19) and respiratory chain enzyme deficiency in eleven patients (11/19). Multiple mtDNA deletions were seen in 47.36% (9/19) patients. Eight pathogenic POLG variations including two novel variations (p.G132R and p.V1106A) were identified. The common pathogenic mutation identified was p.L304R, being present in eight patients (42.1%) predominantly in the younger age group followed by p.W748S in four patients (21%). To the best of our knowledge, this is the first extensive study from India, highlights the clinico-pathological and molecular spectrum of POLG mutations.

Background: The clinical spectrum of contactin-associated protein-like 2 (CASPR2) antibody-associated disease is wide and includes Morvan syndrome. Studies describing treatment and long-term outcome are limited. Aims: We report the clinical profile and emphasize response to treatment and long-term outcome in eight patients with CASPR2-antibody-associated disease. Methods: Clinical, radiological, electrophysiological, treatment, follow-up, and outcome data were collected by retrospective chart review. Results: Clinical manifestations included Morvan syndrome (n = 7) and limbic encephalitis (n = 1). None of the patients were positive for LGI1 antibody. Associated features included myasthenia (n = 1), thymoma (n = 1), and dermatological manifestations (n = 4). Patients were treated with intravenous methylprednisolone and plasma exchange during the acute symptomatic phase followed by pulsed intravenous methyl prednisolone to maintain remission. Mean-modified Rankin score at admission (pre-treatment), discharge, and last follow-up were 3.75, 2.5, and 0.42, respectively. One patient with underlying thymoma and myasthenic crisis died. The other seven patients were followed up for a mean duration of 19.71 months. All of them improved completely. Relapse occurred in one patient after 13 months but responded favorably to steroids. Conclusion: CASPR2 antibody-associated disease has favorable response to immunotherapy with complete improvement and good outcome. Underlying malignancy may be a marker for poor prognosis.

Mutations in RMND1 (required for mitotic division-1) has been associated with infantile onset mitochondrial disease and combined oxidation phosphorylation deficiency. This report describes a girl child of Indian origin with RMND1-associated mitochondrial disease. This 13-month-old girl, born to consanguineous parents presented with gradual loss of acquired milestones and recurrent vomiting from 5 months of age. She experienced failure to thrive, profound hypotonia, areflexia, and sensorineural deafness. Evaluation showed elevated serum lactate and complete heart block. Audiological evaluation done at 6 and 13 months of age revealed bilateral A type tympanogram, bilateral absent stapedial reflexes, absent otoacoustic emissions (OAE), and absent brainstem auditory evoked responses suggestive of bilateral profound sensorineural hearing loss. Muscle biopsy revealed evidence of ragged red fibers, ragged blue fibers, and Cytochrome coxidase (COX) deficient fibers on histochemistry and multiple complex deficiency on spectrophotometry. Exome sequencing revealed homozygous stop-loss variation, c.1349G > C, in exon 12 of RMDN1 resulting in substitution of amino acid serine for stop codon at position 450 and subsequent elongation of the protein by 31 amino acids (p.Ter450SerextTer31) which was verified by Sanger's sequencing. This report further strengthens the phenotype genotype correlations in RMND1-associated mitochondrial disease, especially the occurrence of the reported variation in South Asian patients. In addition, familiarity with the phenotype might help the physician to do targeted metabolic testing and facilitate appropriate early interventions.

Data indexing the contribution of various immuno-inflammatory components in the cerebrospinal fluid (CSF) towards the pathophysiology of Guillain Barre Syndrome (GBS) are limited. Th17 pathway plays crucial role in many immune mediated disorders of the nervous system. This study was aimed at exploring the role of Th17 pathway related cytokines in the CSF of patients with GBS. Levels of multiple key cytokines of Th17 pathway in CSF of patients with GBS (N = 37) and controls (N = 37) were examined in this prospective study using Bio-plex Pro Human Th17 cytokine assays in a Multiplex Suspension Array platform. The findings were correlated with clinical features and electrophysiological subtypes. Three key cytokines of Th17 pathway (IL-6, IL-17A and IL-22) were significantly elevated in CSF of patients with GBS as compared to controls. There was a positive correlation between the levels of IL-6 and IL-17A as well as between the levels of IL-17A and IL-22 in the CSF of patients with GBS. The CSF levels of IL-6 and IL-22 were negatively correlated with the duration of symptoms of GBS. None of the studied cytokines correlated with functional disability scores at admission to hospital or with the electrophysiological subtypes. Identification of Th17 pathway signatures in CSF sheds more insights into the pathogenic role of Th17 cells in GBS. These findings complement the contemporary knowledge and tender further support towards the involvement of Th17 pathway in GBS.

The overlapping clinical and neuroimaging phenotypes of leukodystrophies pose a diagnostic challenge to both clinicians and researchers alike. Studies on the application of exome sequencing in the diagnosis of leukodystrophies are emerging. We used targeted gene panel sequencing of 6440 genes to investigate the genetic etiology in a cohort of 50 children with neuroimaging diagnosis of leukodystrophy/genetic leukoencephalopathy of unknown etiology. These 50 patients without a definite biochemical or genetic diagnosis were derived from a cohort of 88 patients seen during a 2.5-year period (2015 January-2017 June). Patients who had diagnosis by biochemical or biopsy confirmation (n = 17) and patients with incomplete data or lack of follow-up (n = 21) were excluded. Exome sequencing identified variants in 30 (60%) patients, which included pathogenic or likely pathogenic variants in 28 and variants of unknown significance in 2. Among the patients with pathogenic or likely pathogenic variants, classic leukodystrophies constituted 13 (26%) and genetic leukoencephalopathies 15 (30%). The clinical and magnetic resonance imaging (MRI) findings and genetic features of the identified disorders are discussed.

Vanishing white matter disease (VWMD) due to

Guillain-Barre syndrome (GBS) is the commonest post-infectious inflammatory peripheral neuropathy with undiscerned aetiology. The commonly reported antecedent infections implicated in India include Campylobacter jejuni, chikungunya, dengue, and Japanese encephalitis (JE). In this study from south India, we investigated the role of these four agents in triggering GBS. This case-control study was performed on 150 treatment-naive patients with GBS and 150 age and sex-matched controls from the same community. IgM immunoreactivity for C. jejuni, chikungunya, and dengue was detected by enzyme-linked immunosorbent assay (ELISA) in serum of patients with GBS and control subjects. Immunoreactivity against JE was detected in serum as well as cerebrospinal fluid (CSF) from patients (n = 150) and orthopaedic control (n = 45) subjects. The immunoreactivity against infections was compared between demyelinating and axonal subtypes of GBS. Overall, 119/150 patients with GBS had serological evidence of antecedent infection. Amongst those with evidence of antecedent infection, 24 (16%), 8 (5%), and 9 (6%) patients were exclusively immunoreactive to chikungunya, JE, and C. jejuni, respectively. In the remaining patients (78/119), immunoreactivity to multiple pathogens was noted. Immunoreactivity to C. jejuni infection was found in 32% of GBS patients compared to 2.7% controls (P

Background Antibodies against ganglioside complexes (GSCs) are associated with various clinical features and subtypes of Guillain-Barre syndrome (GBS). Methods One-hundred patients were evaluated for antibodies to GSCs formed by combination of GM1, GM2, GD1a, GD1b, GT1b, and GQ1b using manual enzyme linked immuno-sorbent assay (ELISA). Results Twenty-six patients were GSC antibody-positive, most frequent being against GM1-containing GSC (76.9%). Gender distribution, mean age, symptom-duration, antecedent events, electrophysiological subtypes, requirement for mechanical ventilation, and median duration of hospital stay were comparable between the GSC antibody-positive and negative groups. There was no association between specific GSC antibody and electrophysiological subtypes or clinical variants. After controlling for false discovery rate (FDR) using the Benjamini-Hochberg method, the number of subjects who improved in overall disability sum score, modified Erasmus GBS outcome score, and neuropathy symptom score at discharge was significantly higher in the GSC antibody-positive group. Improvements in Medical Research Council sum scores and Hughes Disability Scale during the hospital stay between the GSC antibody-positive and negative groups were not significantly different after controlling for FDR. Conclusions The GSC antibody-positive group had better outcome at hospital discharge in some of the disability scores. Pathophysiological pathways among patients without GSC antibodies may be different and this requires further evaluation.

Purpose: This randomized control study was conducted to compare the efficacy of sodium valproate (SVP) and levetiracetam (LEV) following initial intravenous lorazepam in elderly patients (age: >60years) with generalized convulsive status epilepticus (GCSE) and to identify predictors of poor seizure control. Methods: A total of 118 patients (mean age: 67.5 ± 7.5 years, M:F = 1.6:1), who had presented with GCSE were randomized into the SVP or LEV treatment arms. All patients received initial intravenous lorazepam (0.1 mg/kg) followed by one of the two antiepileptic drugs (AEDs), parenteral SVP (20–25 mg/kg) or LEV (20–25 mg/kg). Those who failed to achieve control with the initial AED, were crossed over to receive the other AED. One-hundred patients (SVP = 50; LEV = 50) completed the study. Results: SE could be controlled with lorazepam and one of the AEDs (SVP or LEV) in 71.18% (84/118). Intention-to-treat analysis showed that the two groups did not differ significantly in terms of seizure control [SVP: 41/60 (68.3%); LEV: 43/58 (74.1%), p = 0.486]. Of 100 patients who completed the study, seizure control was achieved in 38/50(76%) in the SVP and 43/50(86%) in the LEV group (p = 0.202). After crossing over to the second AED, SE could be controlled in an additional in 50% (6/12) in SVP (+LEV) group and in 14.3% (1/7) in LEV (+SVP) group. Overall, after the second AED, seizure control was achieved in 77.1% (91/118). Higher STESS was associated with poor therapeutic response (p = 0.049). Conclusions: The efficacy of SVP and LEV following initial lorazepam in controlling GCSE in elderly population was comparable, hence the choice of AED could be individualized.

ObjectiveTo assess the practicality of dot-blot testing for rapid and sensitive detection of the antiacetylcholine receptor (anti-AChR) antibodies in myasthenia gravis (MG).MethodsIn this case-control study, we tested serum specimens of 85 patients with MG, 85 healthy control individuals, and 85 patients without MG who have other autoimmune and neurological illnesses. All the serum specimens were tested for anti-AChR antibodies using 3 assays: in-house enzyme-linked immunosorbent assay (ELISA), the dot-blot assay, and commercial ELISA.ResultsIn-house ELISA, commercial ELISA, and dot-blot test results were positive for anti-AChR antibodies in 65 (76.5%) patients with MG. The results of all 3 tests were negative for anti-AChR antibodies in healthy controls and patients without MG. We observed perfect concordance (K = 1, P ConclusionsThe dot-blot assay is a simple, nonradioactive immune assay for rapid detection of anti-AChR antibodies in MG.

Objective To share the experience of next-generation sequencing (NGS) in delineating molecular basis of neuro-genetic disorders in adults of Indian origin. Patients and methods Adults (aged ≥18 years) evaluated in a single neurology unit at a tertiary-care teaching hospital between August 2014 and September 2016, underwent NGS for (i) sporadic occurrence of neurological disorder where an extensive search did not reveal an acquired cause or (ii) familial or sporadic, uncommon, seemingly genetic disorder where single monogenic cause could not be ascertained based on phenotype. Presence of pathogenic/ likely-pathogenic variants, novel genetic variants, and novel phenotype associations were noted. Results Clinical phenotypes included: neuromuscular (n = 14), extrapyramidal (n = 8), ataxia (n = 7), leukoencephalopathy (n = 6), spastic paraplegia (n = 5), stroke (n = 4), progressive myoclonic epilepsy (n = 1) and epilepsy with developmental delay (n = 1). Fifty-eight variants were identified in 43 genes in 34 patients, that included 15 (25.9%) reported variants. Genetic diagnosis could be established in 14 (30.43%) subjects. Six probands (13%) harboured previously unreported variants in a clinically relevant gene. Nine probands harboured unreported variants in two or more different genes associated with the clinical phenotype. In three probands we noted novel associations between the phenotype and genetic variation. In all patients, genetic diagnosis impacted treatment and prognostication. Conclusions We present data of NGS in adults with suspected neuro-genetic disorders from India and this is the first report of its kind. It sets a platform for further basic science research to validate ‘novel’ variants and those of ‘uncertain significance’ as pathogenic or otherwise with specific reference to Indian ethnicity.

Perls Prussian blue stain (PPB) for hemosiderin, a marker of vascular injury is often employed as an adjunct in the diagnosis of vasculitic neuropathies. However, inflammation/vascular injury is also seen in leprosy, immune mediated, paraproteinemic, diabetic neuropathies, etc. The frequency of detection of hemosiderin in these neuropathies and its utility in diagnosis of vasculitis has not been explored.We evaluated 208 peripheral nerve biopsies for hemosiderin deposits by PPB stain in vasculitis (78) and compared with inflammatory/immune neuropathies [leprous neuritis-32, chronic inflammatory demyelinating polyneuropathy (CIDP)-15, paraproteinemic neuropathies (POEMS)-12, diabetic neuropathy-37] and nonimmune neuropathies [Charcot-Marie-Tooth (CMT) disease-15, vitamin B12 deficiency-7, and ischemic neuropathy in aged-12)].Hemosiderin deposits were most frequent in vasculitis (48.72%) [59.2% in systemic; 43.1% in nonsystemic vasculitides] and enhanced the sensitivity of diagnosis in "probable" vasculitis (34.48%) that lacked transmural inflammation. Hemosiderin was also detected in infectious/immune-mediated neuropathies (leprous neuritis-56%, POEMS-33.3%, diabetes-18.9%) but absent in CMT, B12 deficiency, and ischemic neuropathy. Hemosiderin deposits involved epineurium in vasculitis, compared to endoneurial/perineurial location in leprosy and perineurial in POEMS and diabetic neuropathy. The sensitivity of detection was high in vasculitic neuropathy (49.35%) compared to other inflammatory neuropathies (22.3%) (P0.05) with high specificity (77.69% [positive predictive value (PPV)-56.71%; negative predictive value (NPV)-71.6%]. The specificity increased to 89% if leprous neuropathy was excluded, with PPV-77.5% while NPV dropped to 68.5%.These findings suggest that PPB stain for detection of hemosiderin is a useful adjunct in diagnosis of vasculitic neuropathy with high specificity but low sensitivity.

Introduction. Myasthenia gravis (MG) is an autoimmune disease with peak incidence in fourth decade. Childhood-onset MG is uncommon. We aim to describe the clinical profile and outcome of childhood-onset MG. Methods. Retrospective chart review of 27 patients (M:F 13:14) with childhood-onset MG seen in a single neurology unit between 2000 and 2019. Diagnosis was established by decremental response in repetitive nerve stimulation, response to neostigmine, and/or antibody positivity. Congenital Myasthenic syndromes were excluded. Results. Demographic and clinical features included: mean onset-age of 12.81±4.63 years, mean symptom-duration of 23.63±36.49 months, ptosis (100%), ophthalmoplegia (63%), facial weakness (55.55%), chewing difficulty (40.74%), dysphagia (48.14%), dysarthria (14.81%), neck weakness (25.92%), shoulder-girdle weakness (44.44%), pelvic-girdle weakness (48.14%), and respiratory weakness (14.81%). Myasthenia Gravis Foundation of America (MGFA) grade at first evaluation was I (n = 11), IIa (n = 7), IIb (n = 2), IIIa (n = 4), IIIb (n = 2), and IVb (n = 1). Two patients developed myasthenic crisis during course of illness. Associated illnesses included seizure disorder (n = 2), diabetes (n = 1), hypothyroidism (n = 1), and psychiatric illnesses (n = 4). Acetylcholine receptor antibody was positive in 12 patients while MuSK was positive in one patient. Chest computed tomography (CT) showed thymic hyperplasia in 12 patients and was normal in 6 patients. Thymectomy was performed in 9 patients (hyperplasia in 7, normal histology in 2). Time from MG onset to initiation of pyridostigmine was 13.80 ± 27.83 months and mean maximum dose of pyridostigmine was 172.22 ± 127.50 mg/day. Immunosuppressants administered in 22 patients included intravenous immunoglobulin (n = 3), plasma exchange (n = 5), steroids (n = 22), azathioprine (n = 4), mycophenolate (n = 2), methotrexate (n = 3), cyclophosphamide (n = 2), and rituximab (n = 1). Of 20 patients with follow- up details, remission was achieved in 17, of which 12 could stop pyridostigmine. Conclusion. In our cohort, majority had mild-moderate MG and myasthenic crises were uncommon. Treatment response was good. Remission was achieved in majority and in many of them, pyridostigmine was discontinued.

Objectives To study the effect of monthly pulses of intravenous methylprednisolone (IVMP) on seizure and global outcomes in children with epileptic encephalopathy (EE). Methods This retrospective study was undertaken in a tertiary care epilepsy center in India. Consecutive patients with EE who had received IVMP as adjunctive therapy for a minimum of 3 months and had at least one pre-and post-steroid EEG each, were identified and a structured questionnaire was used to collect information including outcomes at 3 months post-steroid course completion and beyond, as available. Results Ninety-seven patients (M:F=71:26) fulfilling the inclusion criteria with a mean age at onset of seizures being 20.52 ± 25.69 months were included. Commonest seizure types were myoclonic (66%); Lennaux-Gastaut and West Syndromes accounted for 57 % and 24 % patients respectively. The etiology was unknown in 52 %. All children were on a combination of standard anti-seizure drugs. The duration of IVMP pulse therapy was 7.72 ± 6.25 months. One-fourth (26 %) patients experienced minor adverse events. Greater than 50 % seizure burden reduction was seen in 66 % patients at 3 months with seizure-freedom in 25 %. A total of 45 (46 %) patients became seizure-free in the cohort eventually with continuation of steroids beyond 3 months. Children with idiopathic EEs, normal neuroimaging, myoclonic jerks, and West syndrome showed the best response. The presence of burst-suppression and generalized paroxysmal fast activity (GPFA) predicted inadequate response. Conclusions Adjunct pulse doses of IVMP are safe, well-tolerated, and effective in reducing seizures and improving global outcomes in children with idiopathic EEs, West syndrome, normal neuroimaging, and myoclonic jerks. Seizure freedom might be delayed in a subset of these patients, hence duration of therapy beyond 3 months may be warranted.

Familial amyloidotic polyneuropathy (FAP) is often misdiagnosed as other neuropathic illnesses.To highlight the diagnostic "odyssey" in three families of Indian origin with FAP.Cross-sectional, hospital-based study.Clinical, radiological, and histological features as well as causes for delayed diagnosis were analyzed in genetically confirmed patients with FAP.Descriptive.Age at evaluation ranged from 24 to 42 years and symptom duration from 1 to 10 years. Referral diagnoses included: (i) in patients 1 and 2-familial dysautonomia, Shy-Drager syndrome, and spino-cerebellar ataxia with seizures, (ii) in patient 3-chronic inflammatory demyelinating polyradiculoneuropathy, and (iii) in patient 4-porphyria. In addition, patients 1 and 2 developed leptomeningeal involvement that was mistaken for tubercular meningitis. Reasons for missed diagnosis included: clinician's lack of awareness, not paying sufficient attention to family history, presence of laboratory distractors such as elevated urinary porphyrins, lack of meticulous search for amyloid in the biopsy, and not performing specific stain for amyloid viz. Congo red. Evidence of amyloid in histological studies of nerve and skin supported by genetic variations in transthyretin gene clinched the diagnosis. The variants identified in our cohort included p.Gly73Glu, p.Val71Ala, and p.Val50Met.Lack of awareness and meticulous work-up by clinicians and pathologists contributed to delayed diagnosis of FAP. It is important to establish an accurate diagnosis as these patients may be candidates for upcoming therapies.

Sensory nerve conduction parameters in Guillain Barre Syndrome (GBS) are underemphasized.To describe abnormalities on sensory conduction studies in a large cohort of prospectively evaluated patients of GBS and to correlate with clinico-electrophysiological features.Sensory conduction parameters of three nerves (median, ulnar, and sural) were analyzed using standard protocols in 238 patients (M: F 163:75, mean age: 35.76 ± 15.9 years). Electrophysiological subtyping was based on criteria of Hadden et al., and Rajabally et al.Among patients with "typical" GBS who underwent electrophysiological testing within 30 days of symptom-onset (n = 219), 183 (83.5%) had abnormal sensory potentials (one nerve = 52, two nerves = 77, all three nerves = 54). Frequency of abnormalities in sensory potentials increased with duration of illness. Commonest abnormality was reduced amplitude or in-excitable nerves. Mean amplitude and velocity of median and ulnar nerve sensory potentials were significantly lower among those with demyelinating electrophysiology (P0.05). Proportion of subjects with reduced amplitude and velocity of median and ulnar nerve sensory potentials was higher among those who required mechanical ventilation (P0.05). Frequency of "sural sparing" ranged from 10.5% to 84.5% depending on the criteria used and almost always was significantly associated with demyelinating neuropathy.This prospective study provides comprehensive data on sensory conduction parameters in GBS. Abnormalities are frequent and vary with duration of illness. While median nerve is most frequently and more severely affected, involvement of sural nerve may have prognostic value.