India. Issues are published quarterly in the last week of March, June, September and December. Jo... more India. Issues are published quarterly in the last week of March, June, September and December. Journal aims to publish articles in clinical neurology, related disciplines and basic neurosciences, to serve as a medium for dissemination of information and contribute to the ad-vancement of knowledge in neuroscienc-es. Journal follows the broad guidelines for good publications practice brought out by the Committee on Publication Ethics (COPE) and recommendations of World Association of Medical Editors.All the rights are reserved. Apart from any fair dealing for the purposes of research or private study, or criticism or review, no part of the publication can be reproduced, stored, or transmitted, in any form or by any means, without the prior permission of the Editor, Annals of Indian Academy of Neurology.Annals of Indian Academy of Neurology and/or its publisher cannot be held responsible for errors or for any con-sequences arising from the use of the information contained in this journal.The appearance of advertising or product information in the various sec-tions in the journal does not constitute an endorsement or approval by the journal and/or its publisher of the quality or value of the said product or of claims made for it by its manufacturer.The journal is published and distributed by Medknow Publications. Copies are sent to subscribers directly from the publisher’s address. It is illegal to acquire copies from any other source. If a copy is received for personal use as a member of the association/society, one can not resale or give-away the copy for commercial or library use.The Journal is printed on acid free paper.
Sleep and epilepsy share a complex pathophysiological association. Juvenile myoclonic epilepsy (J... more Sleep and epilepsy share a complex pathophysiological association. Juvenile myoclonic epilepsy (JME) is a common sleep-sensitive epilepsy in which the effect of seizures could have therapeutic implications in terms of sleep disturbances and seizure control. This study aimed to analyze the effect of epilepsy on sleep in patients with JME. Fifty patients on valproic acid (VPA) monotherapy, and age-and gender-matched controls were recruited into this prospective, hospital-based, case-control study after informed consent and screening for inclusion criteria. They underwent a detailed clinical assessment, electroencephalogram (EEG) and neuroimaging, and were administered validated sleep questionnaires, which included the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and NIMHANS Sleep Disorders Questionnaire. The patient and control groups had identical numbers of males and females (M: F = 22: 28), without any significant difference in the age and body mass index (BMI). The clinical profile of JME was similar to published literature while the prevalence of EEG abnormalities was less compared to similar studies. The mean ESS and PSQI scores and the number of subjects with abnormal scores on one or both questionnaires were significantly more in patients. Patients had a higher prevalence of sleep disturbances, insomnia and excessive daytime somnolence. No significant seizure-or treatment-related factors influencing sleep could be identified. This study, the first of its kind, revealed that patients with JME have significant sleep disturbances characterized by excessive daytime sleepiness and disturbed night sleep, despite adequate medications and good seizure control. The role of VPA in the genesis of these symptoms needs clarification.
Mutations in RMND1 (required for mitotic division-1) has been associated with infantile onset mit... more 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 strengthen 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 may help the physician to do targeted metabolic testing and facilitate appropriate early interventions.
Inherited peripheral neuropathies are a group of disorders that include the hereditary motor and ... more Inherited peripheral neuropathies are a group of disorders that include the hereditary motor and sensory neuropathies (HMSN), hereditary motor neuropathies (HMN), and hereditary sensory neuropathies (HSN) or hereditary sensory, and autonomic neuropathies (HSAN). The commonest entity, HMSN is also known as Charcot-Marie-Tooth disease (CMT).This entity was first described in 1886 by Jean Marie Charcot and Pierre Marie from France and Howard Henry Tooth from England. Subsequently, Hoffman described thickened nerves in a patient of ‘peroneal muscular atrophy’. The CMTs are heterogeneous in clinical, electrophysiological, genetic, and pathological features. However, the majority of these patients manifest in the first or second decade with insidious onset and slowly progressive weakness that starts in lower extremities and later involves upper extremities.
BACKGROUND IL-33/ST2 immune axis plays crucial roles in infection and immunity. A dysregulated IL... more BACKGROUND 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. METHODS Three single nucleotide polymorphisms (SNPs) of Il33 gene (rs16924159; rs7044343; rs1342336) and three SNPs of Il1rl1 gene (rs10192157, rs1041973, rs10206753), coding for 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 (n=80) and healthy controls (n=80) by ELISA. RESULTS 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 subjects. Gene-gene interaction between Il33 and Il1rl1 genes also conferred significant risk to 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. CONCLUSIONS 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.
Hyperventilation (HV) has traditionally been used to activate epileptiform discharges in EEG, esp... more Hyperventilation (HV) has traditionally been used to activate epileptiform discharges in EEG, especially in generalized epilepsies. A young girl, with complex partial seizures secondarily generalised had frequent spike discharges (1spike/4.2 sec.) in left anterior temporal region in the resting record. During hyperventilation the spike discharges became less frequent (1 spike/15 sec.) and later disappeared. The spike discharges reappeared gradually in post-hyperventilation period and 2 minutes after stopping hyperventilation the spike frequency increased to 1/3.2 sec. The decrease in spike discharges may be due to hyperventilation induced arousal response or decrease in spike discharges may be due to hyperventilation induced arousal response or decrease in Cerebral blood flow resulting in suppression of spike focus. It is also possible that HV induced slow waves may obscure the spike discharges. Such paradoxical reduction of spike discharge during HV warrants cautions interpretation of the results of EEG when HV is used as a routine activation procedure.
14 patients with the clinical diagnosis of early onset cerebellar ataxia with retained tendon ref... more 14 patients with the clinical diagnosis of early onset cerebellar ataxia with retained tendon reflexes (EOCA) were evaluated by multimodal evoked potential (EP) studies. The results were compared with observations made on 10 patients with Friedreich's ataxia (FA) and 16 patients with olivopontocerebellar atrophy (OPCA). Ten patients (71.4) with EOCA had abnormality of at least one of the EP parameters. Brainstem auditory evoked response (BAER) studies were abnormal in 50, followed by abnormalities in posterior tibial somatosensory evoked potential (SSEP) (46.1), visual evoked potential (VEP) and median SSEP (30.8 each). Only the abnormality of posterior tibial SSEP had a positive correlation with the duration of disease. The abnormalities in SSEP were more frequent in EOCA than in OPCA and were comparable to that of FA patients. On the contrary, abnormalities of VEP and BAER in EOCA patients were significantly less common (especially VEP) than in FA patients and were almost comparable to OPCA. Thus, on the basis of conventional evoked potential studies, EOCA patients seem to share some common features of FA and OPCA patients. There was no single EP feature to characterize EOCA as a distinct entity.
Canadian Journal of Neurological Sciences, Sep 2, 2021
ABSTRACT:Vanishing white matter disease (VWMD) due to eIF2B mutations is a common leukodystrophy ... more ABSTRACT: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.
Context: Familial amyloidotic polyneuropathy (FAP) is often misdiagnosed as other neuropathic ill... more Context: Familial amyloidotic polyneuropathy (FAP) is often misdiagnosed as other neuropathic illnesses. Aim: To highlight the diagnostic "odyssey" in three families of Indian origin with FAP. Settings and design: Cross-sectional, hospital-based study. Subjects and methods: Clinical, radiological, and histological features as well as causes for delayed diagnosis were analyzed in genetically confirmed patients with FAP. Statistical analysis: Descriptive. Results: 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. Conclusion: 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.
Loss of motor function due to damage to nervous system is an important cause of disability among ... more Loss of motor function due to damage to nervous system is an important cause of disability among neurologically ill patient. Recent work in man and experimental animals has suggested that motor control is not only a function of cerebral cortex but also depends significantly on circuits in the spinal cord. A variety of mechanisms for natural recovery from motor paralysis have been proposed. These include dendritic sprouting, synaptogenesis, restoration of axonal transport, remyelination, unmasking of alternative pathways, removal of the effect of diaschisis, alteration in neurotransmitters and bilaterality of brain function. However in many a situations these are inadequate to provide functional independence to patients. A number of rehabilitation strategies for motor retraining have therefore been used. These are traditional exercise programs, neuromuscular re-education techniques, corrective surgical interventions, EMG biofeedback and use of pharmacological agents. More recent use of treadmill training with body weight support system and functional electrical stimulation have provided promising results. The basic underlying mechanism for the use of these strategies, their efficacy and limitations require critical evaluation. Neural transplantation may open new avenues for these patients who are incapacitated due to motor dyscontrol.
Stroke is a leading cause of morbidity and mortality. A significant proportion of stroke victims ... more Stroke is a leading cause of morbidity and mortality. A significant proportion of stroke victims in India are below the age of 40 years and may have specific risk factors. 101 patients (42 less than 40 years of age) of ischaemic stroke were studiedat NIMHANS to estimate the relative risk of various contributing factors. Hypercholesterolaemia, hyperglycaemia and hypertension were more common in elderly group, while smoking, alcohol and tobacco abuse were more prevalent in younger age group (relative risk 1.2, 1.9 and 1.5 respectively). A better understanding of these risk factors may play a key role in the prevention of stroke in young.
Recent literature from different countries has revealed variable results of interferon treatment ... more Recent literature from different countries has revealed variable results of interferon treatment in subacute sclerosing panencephalitis (SSPE). Twelve patients with SSPE were treated at NIMHANS by concurrent use of intravenous and intrathecal interferon ALFA-2a, manufactured by recombinant DNA technology. The diagnosis of SSPE was based on clinical profile, EEG, CT and presence of antibody radio-immunoassay measles IgG antibodies in CSF. The total dose of interferon by intrathecal as well as intravenous route varied from 15 million to 60 million units. Clinical improvement as demonstrated by a decrease in scores on Neurological disability index occurred in three. Two of them relapsed five months after stopping the therapy but one patient maintained improvement two years after stopping treatment. There was no significant change in six patients. There were 3 deaths. One of them was autopsied. A decrease in titres of antimeasles antibody in CSF was noted in two patients who showed clinical improvement but in others there was no consistent correlation. No significant changes occurred in EEG during the treatment period. No serious side effect of interferon were encountered. Two patients had iatrogenic meningitis which could be treated successfully. Use of intravenous combined with intrathecal interferon is not promising in SSPE.
Computed tomographic (CT) studies in olivopontocerebellar atrophies (OPCA) and 'early onset cereb... more Computed tomographic (CT) studies in olivopontocerebellar atrophies (OPCA) and 'early onset cerebellar ataxia with retained tendon reflexes (EOCA)' are few and vary widely in methodology and criteria for cerebellar and brainstem atrophy. In this prospective study, CT scan observations on 26 patients (EOCA-11, OPCA-15) were compared with 31 controls using qualitative and quantitative assessment of cisterns, ventricles and atrophy of brain. Vermian and/or cerebellar hemispheric (predominantly anterior) atrophy was present in 80.8% and both were equally common. Cerebral cortical atrophy (26.9%) and leukoariosis (15.4%) were less frequently seen. Statistically significant atrophy of pons, brachium pontis, cerebellum and midbrain was noted in patient group. No significant differences were observed between EOCA and OPCA groups. Evidence of atrophy did not correlate with either the duration of illness or the severity of cerebellar ataxia in both the groups. The severity of brainstem atrophy in 14 patients with and 12 patients without abnormal brainstem auditory evoked response did not differ significantly. This study highlights the methodology of CT evaluation for brainstem and cerebellar atrophy, draws attention to cerebral atrophy and emphasizes the lack of significant differences in CT morphology between OPCA and EOCA patients.
A young lady with residual polio, using axillary crutch since early childhood, presented with tin... more A young lady with residual polio, using axillary crutch since early childhood, presented with tingling, numbness and weakness in ulnar nerve distribution of five months duration. Ulnar motor conduction study revealed proximal conduction block near the axilla, at the point of pressure by the crutch while walking. Distal ulnar sensory conduction studies were normal but proximal ulnar sensory conduction studies showed absence of Erb's point potential. These findings suggested the presence of conduction block in sensory fibers as well. Proper use and change of axillary crutch resulted in clinical recovery and resolution of motor and sensory conduction block.
The objective of this study was to observe neurological and functional recovery in patients with ... more The objective of this study was to observe neurological and functional recovery in patients with acute transverse myelitis (ATM) with inpatient rehabilitation and correlate with magnetic resonance imaging (MRI) changes. Patients and methods: The study was conducted with 43 ATM patients (19 males) admitted in the tertiary university research hospital from July 2012 to June 2014. Detailed MRI findings were noted. Neurological status was assessed using the ASIA impairment scale (AIS) and functional recovery was assessed using the Barthel Index score (BI) and Spinal Cord Independence Measure (SCIM). Results: Patients showed significant neurological and functional recovery with inpatient rehabilitation using AIS, BI and SCIM scales when admission and discharge scores were compared (Po0.001). Thirty-one patients (72.1%) had rostral level in the cervical region according to MR imaging, but clinically, 17 patients had tetraplegia, whereas 26 patients had lower-limb weakness only. No definitive pattern or correlation was found between level (MRI or clinical) and neurological status (AIS). Conclusion: The neurological outcome in patients with ATM cannot be predicted on the basis of imaging findings. There is a great variation in the imaging level and clinical presentation. Patients show significant improvement with inpatient rehabilitation even with poor functional ability in acute and sub-acute phase of illness.
Age influences incidence and prognosis of Guillain Barre Syndrome (GBS), common cause of ascendin... more Age influences incidence and prognosis of Guillain Barre Syndrome (GBS), common cause of ascending areflexic quadriparesis. Dedicated studies on elderly GBS are infrequent. This study aimed to describe clinical features and outcome at hospital-discharge in patients aged 60 years with GBS. Medical records of 70 elderly GBS over 15 years were analysed. Mean symptom-duration was 5.78 ± 4.5 days and onsetto-peak 5.14 ± 4.4 days. Antecedent events preceded GBS by 8.07 ± 9.9 days and included: fever (n = 19), respiratory infection (n = 6), and gastroenteritis (n = 5). Clinical features were weakness of facial (n = 34), bulbar (n = 13), extraocular (n = 4) and respiratory (n = 20) muscles and recurrence (n = 4). Nine had Hughes disability score (HDS) of three or less. Sensory symptoms and signs included paresthesias (n = 40), pain (n = 24), and impaired kinaesthetic sensation (n = 14). Laboratory abnormalities included albumino-cytological dissociation (n = 50), hyponatremia (n = 36) and elevated creatine kinase (n = 18). Electrophysiological subtypes were: primary demyelinating (n = 52), inexcitable (n = 3), equivocal (n = 2) and axonal (n = 1). Fifty-seven patients treated with plasmapheresis (n = 48) or intravenous immunoglobulin (n = 9) had mean HDS of 3.53 ± 0.7 at discharge. Twenty-one were ambulant (HDS 3), one had persisting respiratory weakness and one died. Striking differences between the 'elderly' and 100 'adults' seen over 20 months were shorter symptom-duration, higher frequency of facial palsy and hyponatremia, lower frequency of pain, lower mean MRC sum score and worse HDS at studyentry and discharge (p < 0.05). Requirement for mechanical ventilation and cardiac autonomic dysfunction was higher among elderly (p:0.02). In conclusion, in this cohort of elderly GBS, there was a higher frequency severe GBS and demyelinating electrophysiology.
ABSTRACT Background: Mutation in the SURF1 is one of the most common nuclear mutations associated... more ABSTRACT Background: Mutation in the SURF1 is one of the most common nuclear mutations associated with Leigh syndrome and cytochrome c oxidase deficiency. This study aims to describe the phenotypic and imaging features in four patients with Leigh syndrome and novel SURF1 mutation. Methods: The study included four patients with Leigh syndrome and SURF1 mutations identified from a cohort of 25 children with Leigh syndrome seen over a period of six years (2006-2012). All the patients underwent a detailed neurological assessment, muscle biopsy, and sequencing of the complete mitochondrial genome and SURF1. Results: Three patients had classical presentation of Leigh syndrome. The fourth patient had a later age of onset with ataxia as the presenting manifestation and a stable course. Hypertrichosis, facial dysmorphism and hypopigmentation were the additional phenotypic features noted. On magnetic resonance imaging all patients had brainstem and cerebellar involvement and two had basal ganglia involvement in addition. The bilateral symmetrical hypertrophic olivary degeneration in these patients was striking. The SURF1 analysis identified previously unreported mutations in all the patients. On follow-up three patients expired and one had a stable course. Conclusions: Patients with Leigh syndrome and SURF1 mutation often have skin and hair abnormalities. Bilateral symmetrical hypertrophic olivary degeneration was a consistent finding on magnetic resonance imaging in these patients.
BACKGROUND AND PURPOSE Reports of central pontine myelinolysis (CPM)-like changes in Wilson's dis... more BACKGROUND AND PURPOSE Reports of central pontine myelinolysis (CPM)-like changes in Wilson's disease (WD) and its sequential changes are exceptional. The aim was to study the MRI characteristics of CPM-like changes in WD and the serial changes. METHODS Among the 121 patients of WD, twenty (M:F:9:11, age at onset: 14.2 ± 4.6 years) had features similar to CPM. All had progressive neuropsychiatric form of WD. All except five were on de-coppering treatment. None had acute deterioration or hepatic failure. Ten patients underwent repeat studies. RESULTS Twenty patients with CPM-like changes manifested with characteristic phenotype of WD. Three distinct patterns of CPM-like changes were observed: (a) characteristic round shape-7, (b) "bisected"-9, and (c) "trisected"-4. Only one had signal changes suggesting extra-pontine myelinolysis. All patients had contiguous involvement of midbrain. Serial MRI evaluation in 10 patients, at mean interval period of 17.4 ± 13.2 months, revealed complete reversal in one, partial improvement in five, and no change in three. Clinical and MRI improvement occurred pari passu, except in one. CONCLUSIONS CPM-like changes in WD are perhaps under-recognized and are distinct from the commonly known "osmotic demyelination." It is potentially reversible similar to other MRI features of WD.
India. Issues are published quarterly in the last week of March, June, September and December. Jo... more India. Issues are published quarterly in the last week of March, June, September and December. Journal aims to publish articles in clinical neurology, related disciplines and basic neurosciences, to serve as a medium for dissemination of information and contribute to the ad-vancement of knowledge in neuroscienc-es. Journal follows the broad guidelines for good publications practice brought out by the Committee on Publication Ethics (COPE) and recommendations of World Association of Medical Editors.All the rights are reserved. Apart from any fair dealing for the purposes of research or private study, or criticism or review, no part of the publication can be reproduced, stored, or transmitted, in any form or by any means, without the prior permission of the Editor, Annals of Indian Academy of Neurology.Annals of Indian Academy of Neurology and/or its publisher cannot be held responsible for errors or for any con-sequences arising from the use of the information contained in this journal.The appearance of advertising or product information in the various sec-tions in the journal does not constitute an endorsement or approval by the journal and/or its publisher of the quality or value of the said product or of claims made for it by its manufacturer.The journal is published and distributed by Medknow Publications. Copies are sent to subscribers directly from the publisher’s address. It is illegal to acquire copies from any other source. If a copy is received for personal use as a member of the association/society, one can not resale or give-away the copy for commercial or library use.The Journal is printed on acid free paper.
Sleep and epilepsy share a complex pathophysiological association. Juvenile myoclonic epilepsy (J... more Sleep and epilepsy share a complex pathophysiological association. Juvenile myoclonic epilepsy (JME) is a common sleep-sensitive epilepsy in which the effect of seizures could have therapeutic implications in terms of sleep disturbances and seizure control. This study aimed to analyze the effect of epilepsy on sleep in patients with JME. Fifty patients on valproic acid (VPA) monotherapy, and age-and gender-matched controls were recruited into this prospective, hospital-based, case-control study after informed consent and screening for inclusion criteria. They underwent a detailed clinical assessment, electroencephalogram (EEG) and neuroimaging, and were administered validated sleep questionnaires, which included the Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI) and NIMHANS Sleep Disorders Questionnaire. The patient and control groups had identical numbers of males and females (M: F = 22: 28), without any significant difference in the age and body mass index (BMI). The clinical profile of JME was similar to published literature while the prevalence of EEG abnormalities was less compared to similar studies. The mean ESS and PSQI scores and the number of subjects with abnormal scores on one or both questionnaires were significantly more in patients. Patients had a higher prevalence of sleep disturbances, insomnia and excessive daytime somnolence. No significant seizure-or treatment-related factors influencing sleep could be identified. This study, the first of its kind, revealed that patients with JME have significant sleep disturbances characterized by excessive daytime sleepiness and disturbed night sleep, despite adequate medications and good seizure control. The role of VPA in the genesis of these symptoms needs clarification.
Mutations in RMND1 (required for mitotic division-1) has been associated with infantile onset mit... more 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 &amp;gt; 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&#39;s sequencing. This report further strengthen 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 may help the physician to do targeted metabolic testing and facilitate appropriate early interventions.
Inherited peripheral neuropathies are a group of disorders that include the hereditary motor and ... more Inherited peripheral neuropathies are a group of disorders that include the hereditary motor and sensory neuropathies (HMSN), hereditary motor neuropathies (HMN), and hereditary sensory neuropathies (HSN) or hereditary sensory, and autonomic neuropathies (HSAN). The commonest entity, HMSN is also known as Charcot-Marie-Tooth disease (CMT).This entity was first described in 1886 by Jean Marie Charcot and Pierre Marie from France and Howard Henry Tooth from England. Subsequently, Hoffman described thickened nerves in a patient of ‘peroneal muscular atrophy’. The CMTs are heterogeneous in clinical, electrophysiological, genetic, and pathological features. However, the majority of these patients manifest in the first or second decade with insidious onset and slowly progressive weakness that starts in lower extremities and later involves upper extremities.
BACKGROUND IL-33/ST2 immune axis plays crucial roles in infection and immunity. A dysregulated IL... more BACKGROUND 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. METHODS Three single nucleotide polymorphisms (SNPs) of Il33 gene (rs16924159; rs7044343; rs1342336) and three SNPs of Il1rl1 gene (rs10192157, rs1041973, rs10206753), coding for 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 (n=80) and healthy controls (n=80) by ELISA. RESULTS 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 subjects. Gene-gene interaction between Il33 and Il1rl1 genes also conferred significant risk to 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. CONCLUSIONS 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.
Hyperventilation (HV) has traditionally been used to activate epileptiform discharges in EEG, esp... more Hyperventilation (HV) has traditionally been used to activate epileptiform discharges in EEG, especially in generalized epilepsies. A young girl, with complex partial seizures secondarily generalised had frequent spike discharges (1spike/4.2 sec.) in left anterior temporal region in the resting record. During hyperventilation the spike discharges became less frequent (1 spike/15 sec.) and later disappeared. The spike discharges reappeared gradually in post-hyperventilation period and 2 minutes after stopping hyperventilation the spike frequency increased to 1/3.2 sec. The decrease in spike discharges may be due to hyperventilation induced arousal response or decrease in spike discharges may be due to hyperventilation induced arousal response or decrease in Cerebral blood flow resulting in suppression of spike focus. It is also possible that HV induced slow waves may obscure the spike discharges. Such paradoxical reduction of spike discharge during HV warrants cautions interpretation of the results of EEG when HV is used as a routine activation procedure.
14 patients with the clinical diagnosis of early onset cerebellar ataxia with retained tendon ref... more 14 patients with the clinical diagnosis of early onset cerebellar ataxia with retained tendon reflexes (EOCA) were evaluated by multimodal evoked potential (EP) studies. The results were compared with observations made on 10 patients with Friedreich's ataxia (FA) and 16 patients with olivopontocerebellar atrophy (OPCA). Ten patients (71.4) with EOCA had abnormality of at least one of the EP parameters. Brainstem auditory evoked response (BAER) studies were abnormal in 50, followed by abnormalities in posterior tibial somatosensory evoked potential (SSEP) (46.1), visual evoked potential (VEP) and median SSEP (30.8 each). Only the abnormality of posterior tibial SSEP had a positive correlation with the duration of disease. The abnormalities in SSEP were more frequent in EOCA than in OPCA and were comparable to that of FA patients. On the contrary, abnormalities of VEP and BAER in EOCA patients were significantly less common (especially VEP) than in FA patients and were almost comparable to OPCA. Thus, on the basis of conventional evoked potential studies, EOCA patients seem to share some common features of FA and OPCA patients. There was no single EP feature to characterize EOCA as a distinct entity.
Canadian Journal of Neurological Sciences, Sep 2, 2021
ABSTRACT:Vanishing white matter disease (VWMD) due to eIF2B mutations is a common leukodystrophy ... more ABSTRACT: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.
Context: Familial amyloidotic polyneuropathy (FAP) is often misdiagnosed as other neuropathic ill... more Context: Familial amyloidotic polyneuropathy (FAP) is often misdiagnosed as other neuropathic illnesses. Aim: To highlight the diagnostic "odyssey" in three families of Indian origin with FAP. Settings and design: Cross-sectional, hospital-based study. Subjects and methods: Clinical, radiological, and histological features as well as causes for delayed diagnosis were analyzed in genetically confirmed patients with FAP. Statistical analysis: Descriptive. Results: 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. Conclusion: 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.
Loss of motor function due to damage to nervous system is an important cause of disability among ... more Loss of motor function due to damage to nervous system is an important cause of disability among neurologically ill patient. Recent work in man and experimental animals has suggested that motor control is not only a function of cerebral cortex but also depends significantly on circuits in the spinal cord. A variety of mechanisms for natural recovery from motor paralysis have been proposed. These include dendritic sprouting, synaptogenesis, restoration of axonal transport, remyelination, unmasking of alternative pathways, removal of the effect of diaschisis, alteration in neurotransmitters and bilaterality of brain function. However in many a situations these are inadequate to provide functional independence to patients. A number of rehabilitation strategies for motor retraining have therefore been used. These are traditional exercise programs, neuromuscular re-education techniques, corrective surgical interventions, EMG biofeedback and use of pharmacological agents. More recent use of treadmill training with body weight support system and functional electrical stimulation have provided promising results. The basic underlying mechanism for the use of these strategies, their efficacy and limitations require critical evaluation. Neural transplantation may open new avenues for these patients who are incapacitated due to motor dyscontrol.
Stroke is a leading cause of morbidity and mortality. A significant proportion of stroke victims ... more Stroke is a leading cause of morbidity and mortality. A significant proportion of stroke victims in India are below the age of 40 years and may have specific risk factors. 101 patients (42 less than 40 years of age) of ischaemic stroke were studiedat NIMHANS to estimate the relative risk of various contributing factors. Hypercholesterolaemia, hyperglycaemia and hypertension were more common in elderly group, while smoking, alcohol and tobacco abuse were more prevalent in younger age group (relative risk 1.2, 1.9 and 1.5 respectively). A better understanding of these risk factors may play a key role in the prevention of stroke in young.
Recent literature from different countries has revealed variable results of interferon treatment ... more Recent literature from different countries has revealed variable results of interferon treatment in subacute sclerosing panencephalitis (SSPE). Twelve patients with SSPE were treated at NIMHANS by concurrent use of intravenous and intrathecal interferon ALFA-2a, manufactured by recombinant DNA technology. The diagnosis of SSPE was based on clinical profile, EEG, CT and presence of antibody radio-immunoassay measles IgG antibodies in CSF. The total dose of interferon by intrathecal as well as intravenous route varied from 15 million to 60 million units. Clinical improvement as demonstrated by a decrease in scores on Neurological disability index occurred in three. Two of them relapsed five months after stopping the therapy but one patient maintained improvement two years after stopping treatment. There was no significant change in six patients. There were 3 deaths. One of them was autopsied. A decrease in titres of antimeasles antibody in CSF was noted in two patients who showed clinical improvement but in others there was no consistent correlation. No significant changes occurred in EEG during the treatment period. No serious side effect of interferon were encountered. Two patients had iatrogenic meningitis which could be treated successfully. Use of intravenous combined with intrathecal interferon is not promising in SSPE.
Computed tomographic (CT) studies in olivopontocerebellar atrophies (OPCA) and 'early onset cereb... more Computed tomographic (CT) studies in olivopontocerebellar atrophies (OPCA) and 'early onset cerebellar ataxia with retained tendon reflexes (EOCA)' are few and vary widely in methodology and criteria for cerebellar and brainstem atrophy. In this prospective study, CT scan observations on 26 patients (EOCA-11, OPCA-15) were compared with 31 controls using qualitative and quantitative assessment of cisterns, ventricles and atrophy of brain. Vermian and/or cerebellar hemispheric (predominantly anterior) atrophy was present in 80.8% and both were equally common. Cerebral cortical atrophy (26.9%) and leukoariosis (15.4%) were less frequently seen. Statistically significant atrophy of pons, brachium pontis, cerebellum and midbrain was noted in patient group. No significant differences were observed between EOCA and OPCA groups. Evidence of atrophy did not correlate with either the duration of illness or the severity of cerebellar ataxia in both the groups. The severity of brainstem atrophy in 14 patients with and 12 patients without abnormal brainstem auditory evoked response did not differ significantly. This study highlights the methodology of CT evaluation for brainstem and cerebellar atrophy, draws attention to cerebral atrophy and emphasizes the lack of significant differences in CT morphology between OPCA and EOCA patients.
A young lady with residual polio, using axillary crutch since early childhood, presented with tin... more A young lady with residual polio, using axillary crutch since early childhood, presented with tingling, numbness and weakness in ulnar nerve distribution of five months duration. Ulnar motor conduction study revealed proximal conduction block near the axilla, at the point of pressure by the crutch while walking. Distal ulnar sensory conduction studies were normal but proximal ulnar sensory conduction studies showed absence of Erb's point potential. These findings suggested the presence of conduction block in sensory fibers as well. Proper use and change of axillary crutch resulted in clinical recovery and resolution of motor and sensory conduction block.
The objective of this study was to observe neurological and functional recovery in patients with ... more The objective of this study was to observe neurological and functional recovery in patients with acute transverse myelitis (ATM) with inpatient rehabilitation and correlate with magnetic resonance imaging (MRI) changes. Patients and methods: The study was conducted with 43 ATM patients (19 males) admitted in the tertiary university research hospital from July 2012 to June 2014. Detailed MRI findings were noted. Neurological status was assessed using the ASIA impairment scale (AIS) and functional recovery was assessed using the Barthel Index score (BI) and Spinal Cord Independence Measure (SCIM). Results: Patients showed significant neurological and functional recovery with inpatient rehabilitation using AIS, BI and SCIM scales when admission and discharge scores were compared (Po0.001). Thirty-one patients (72.1%) had rostral level in the cervical region according to MR imaging, but clinically, 17 patients had tetraplegia, whereas 26 patients had lower-limb weakness only. No definitive pattern or correlation was found between level (MRI or clinical) and neurological status (AIS). Conclusion: The neurological outcome in patients with ATM cannot be predicted on the basis of imaging findings. There is a great variation in the imaging level and clinical presentation. Patients show significant improvement with inpatient rehabilitation even with poor functional ability in acute and sub-acute phase of illness.
Age influences incidence and prognosis of Guillain Barre Syndrome (GBS), common cause of ascendin... more Age influences incidence and prognosis of Guillain Barre Syndrome (GBS), common cause of ascending areflexic quadriparesis. Dedicated studies on elderly GBS are infrequent. This study aimed to describe clinical features and outcome at hospital-discharge in patients aged 60 years with GBS. Medical records of 70 elderly GBS over 15 years were analysed. Mean symptom-duration was 5.78 ± 4.5 days and onsetto-peak 5.14 ± 4.4 days. Antecedent events preceded GBS by 8.07 ± 9.9 days and included: fever (n = 19), respiratory infection (n = 6), and gastroenteritis (n = 5). Clinical features were weakness of facial (n = 34), bulbar (n = 13), extraocular (n = 4) and respiratory (n = 20) muscles and recurrence (n = 4). Nine had Hughes disability score (HDS) of three or less. Sensory symptoms and signs included paresthesias (n = 40), pain (n = 24), and impaired kinaesthetic sensation (n = 14). Laboratory abnormalities included albumino-cytological dissociation (n = 50), hyponatremia (n = 36) and elevated creatine kinase (n = 18). Electrophysiological subtypes were: primary demyelinating (n = 52), inexcitable (n = 3), equivocal (n = 2) and axonal (n = 1). Fifty-seven patients treated with plasmapheresis (n = 48) or intravenous immunoglobulin (n = 9) had mean HDS of 3.53 ± 0.7 at discharge. Twenty-one were ambulant (HDS 3), one had persisting respiratory weakness and one died. Striking differences between the 'elderly' and 100 'adults' seen over 20 months were shorter symptom-duration, higher frequency of facial palsy and hyponatremia, lower frequency of pain, lower mean MRC sum score and worse HDS at studyentry and discharge (p < 0.05). Requirement for mechanical ventilation and cardiac autonomic dysfunction was higher among elderly (p:0.02). In conclusion, in this cohort of elderly GBS, there was a higher frequency severe GBS and demyelinating electrophysiology.
ABSTRACT Background: Mutation in the SURF1 is one of the most common nuclear mutations associated... more ABSTRACT Background: Mutation in the SURF1 is one of the most common nuclear mutations associated with Leigh syndrome and cytochrome c oxidase deficiency. This study aims to describe the phenotypic and imaging features in four patients with Leigh syndrome and novel SURF1 mutation. Methods: The study included four patients with Leigh syndrome and SURF1 mutations identified from a cohort of 25 children with Leigh syndrome seen over a period of six years (2006-2012). All the patients underwent a detailed neurological assessment, muscle biopsy, and sequencing of the complete mitochondrial genome and SURF1. Results: Three patients had classical presentation of Leigh syndrome. The fourth patient had a later age of onset with ataxia as the presenting manifestation and a stable course. Hypertrichosis, facial dysmorphism and hypopigmentation were the additional phenotypic features noted. On magnetic resonance imaging all patients had brainstem and cerebellar involvement and two had basal ganglia involvement in addition. The bilateral symmetrical hypertrophic olivary degeneration in these patients was striking. The SURF1 analysis identified previously unreported mutations in all the patients. On follow-up three patients expired and one had a stable course. Conclusions: Patients with Leigh syndrome and SURF1 mutation often have skin and hair abnormalities. Bilateral symmetrical hypertrophic olivary degeneration was a consistent finding on magnetic resonance imaging in these patients.
BACKGROUND AND PURPOSE Reports of central pontine myelinolysis (CPM)-like changes in Wilson's dis... more BACKGROUND AND PURPOSE Reports of central pontine myelinolysis (CPM)-like changes in Wilson's disease (WD) and its sequential changes are exceptional. The aim was to study the MRI characteristics of CPM-like changes in WD and the serial changes. METHODS Among the 121 patients of WD, twenty (M:F:9:11, age at onset: 14.2 ± 4.6 years) had features similar to CPM. All had progressive neuropsychiatric form of WD. All except five were on de-coppering treatment. None had acute deterioration or hepatic failure. Ten patients underwent repeat studies. RESULTS Twenty patients with CPM-like changes manifested with characteristic phenotype of WD. Three distinct patterns of CPM-like changes were observed: (a) characteristic round shape-7, (b) "bisected"-9, and (c) "trisected"-4. Only one had signal changes suggesting extra-pontine myelinolysis. All patients had contiguous involvement of midbrain. Serial MRI evaluation in 10 patients, at mean interval period of 17.4 ± 13.2 months, revealed complete reversal in one, partial improvement in five, and no change in three. Clinical and MRI improvement occurred pari passu, except in one. CONCLUSIONS CPM-like changes in WD are perhaps under-recognized and are distinct from the commonly known "osmotic demyelination." It is potentially reversible similar to other MRI features of WD.
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Papers by Arun Taly