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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.

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.

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.

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.

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.

Background There is emerging evidence implicating mitochondrial dysfunction in the pathogenesis of acquired demyelinating disorders such as multiple sclerosis. On the other hand, some of the primary mitochondrial disorders such as mitochondrial leukoencephalopathies exhibit evidence of neuroinflammation on MRI. The inter-relationship between mitochondrial disorders and episodic CNS inflammation needs exploration because of the therapeutic implications. Objective We sought to analyze the clinical course and MRI characteristics in a cohort of patients with mitochondrial leukoencephalopathy to determine features, if any, that mimic primary demyelinating disorders. Therapeutic implications of these findings are discussed. Patients and methods Detailed analysis of the clinical course, magnetic resonance imaging findings and therapeutic response was performed in 14 patients with mitochondrial leukoencephalopathy. The diagnosis was ascertained by clinical features, histopathology, respiratory chain enzyme assays and exome sequencing. Results Fourteen patients [Age at evaluation: 2–7 yrs, M: F-1:1] were included in the study. The genetic findings included variations in NDUFA1 (1); NDUFV1 (4); NDUFS2 (2); LYRM (2); MPV17 (1); BOLA3 (2); IBA57 (2). Clinical Features which mimicked acquired demyelinating disorder included acute onset focal deficits associated with encephalopathy [10/14, 71%], febrile illness preceding the onset [7/14, 50%] unequivocal partial or complete steroid responsiveness [11/11], episodic/ relapsing remitting neurological dysfunction [10/14, 71%] and a subsequent stable rather than a progressive course [12/14, 85%]. MRI characteristics included confluent white matter lesions [14/14, 100%], diffusion restriction [11/14,78.5%], contrast enhancement [13/13,100%], spinal cord involvement [8/13,61.5%], lactate peak on MRS [13/13] and white matter cysts [13/14, 92.8%]. Conclusion Clinical presentations of mitochondrial leukoencephalopathy often mimic an acquired demyelinating disorder. The therapeutic implications of these observations require further exploration.

Objectives Studies exploring the outcome of epilepsy in patients with mitochondrial disorders are limited. This study examined the outcome of epilepsy in patients with mitochondrial disorders and its relation with the clinical phenotype, genotype and magnetic resonance imaging findings. Patients and methods The cohort was derived from the database of 67 patients with definite genetic diagnosis of mitochondrial disorders evaluated over a period of 11years (2006–2016). Among this, 27 had epilepsy and were included in final analysis. Data were analyzed with special reference to clinical phenotypes, genotypes, epilepsy characteristics, EEG findings, anti epileptic drugs used, therapeutic response, and magnetic resonance imaging findings. Patients were divided into three groups according to the seizure frequency at the time of last follow up: Group I- Seizure free; Group II- Infrequent seizures; Group III- uncontrolled seizures. For each group the clinical phenotype, genotype, magnetic resonance imaging and duration of epilepsy were compared. Results The phenotypes & genotypes included Mitochondrial Encephalopathy Lactic Acidosis and Stroke like episodes (MELAS) & m.3243A>G mutation (n = 10), Myoclonic Epilepsy Ragged Red Fiber syndrome (MERRF) & m.8344A>G mutation (n = 4), Chronic Progressive External Ophthalmoplegia plus & POLG1 mutation (CPEO, n = 6), episodic neuroregression due to nuclear mutations (n = 6; NDUFV1 (n = 3), NDUFA1, NDUFS2, MPV17-1 one each), and one patient with infantile basal ganglia stroke syndrome, mineralizing angiopathy & MT-ND5 mutations. Seven patients (25.9%) were seizure free; seven had infrequent seizures (25.9%), while thirteen (48.1%) had frequent uncontrolled seizures. Majority of the subjects in seizure free group had episodic neuroregression & leukoencephalopathy due to nuclear mutations (85.7%). Patients in group II with infrequent seizures had CPEO, POLG1 mutation and a normal MRI (71%) while 62% of the subjects in group III had MELAS, m.3243A>G mutation and stroke like lesions on MRI. Conclusions A fair correlation exists between the outcome of epilepsy, clinical phenotypes, genotypes and magnetic resonance imaging findings in patients with mitochondrial disorders. The recognition of these patterns is important clinically because of the therapeutic and prognostic implications.

Introduction. Guillain Barre Syndrome (GBS) is a monophasic immune-mediated disease of the peripheral nervous system, often triggered by antecedent gastrointestinal or respiratory infection. Compelling evidence suggests inflammatory cytokines as the critical drivers of the onset and progression in GBS. Elevated levels of pro-inflammatory cytokines were reported both in the plasma and cerebrospinal fluid (CSF) of patients with GBS. However, whether there exists a correlation between the levels of proinflammatory cytokines in plasma and CSF is inadequately explored. Methods. In this study, we recruited 37 (21 male and 16 female) patients with GBS from the emergency services of the National Institute of Mental Health and Neurosciences, Bangalore, India. Mean age of the patients was 36.65 ± 12.2 years. We analysed the levels of four Th17- pathway related cytokines, IL-6, IL-17A, IL-22 and IL-23, in both the plasma and CSF of patients with GBS by Multiplex Suspension Assay. The levels of these cytokines were correlated between plasma and CSF and also with various clinical features and electrophysiological subtypes. Results. Spearman’s correlation analysis suggests that there was no correlation in the levels of the Th17-pathway related cytokines, IL-6 (p = 0.11), IL-17A (p = 0.85), IL-22 (p = 0.45) and IL-23 (p = 0.76) between plasma and CSF in patients of GBS. Conclusion. Elevated levels of Th17 pathway related cytokines were observed both in the plasma and CSF in our earlier studies. Immune molecules in the CSF play pathogenic roles in various nervous system disorders. CSF analysis also plays important role in establishing the diagnosis of GBS. Though Th17 pathway-related cytokines are upregulated in both the plasma and CSF, however, they do not show any correlation. This may suggest that immune molecules in plasma and CSF may drive pathogenetic processes in GBS independently.

Introduction. Contactin-associated protein-like 2 (CASPR2) antibody-associated neurological disease is a rare autoimmune illness with central and peripheral manifestations. The core clinical features are peripheral nerve hyperexcitability, autonomic dysfunction, insomnia, and fluctuating encephalopathy. We aim to describe the autonomic manifestations in a cohort of patients with CASPR2 antibody-associated neurological disease. Methods. This study was a retrospective chart review that included eight patients with CASPR2 antibody-associated neurological illness. Their medical records were reviewed and details regarding clinical manifestations of autonomic dysfunction and cardiac autonomic function testing (AFT) were collected. The response of autonomic manifestations to immunotherapy was also noted on follow up. Results. Clinically, autonomic manifestations were present in 7/8 patients. Most commonly, cardiovascular manifestations (palpitations, postural dizziness, tachycardia, fluctuating blood pressure, and postural hypotension) were noted in six patients while others included gastrointestinal (diarrhea or constipation), genitourinary (urinary frequency, urinary retention), and sudomotor (hyperhidrosis) manifestations in three patients each. One patient developed a hypertensive emergency with posterior reversible encephalopathy syndrome. AFT was carried out in five patients and it showed severe cardiac autonomic dysfunction in three and definite autonomic dysfunction in two patients. All patients had a reduction in total power with sympathetic dominance. On follow-up after treatment with immunotherapy (mean duration 19.71 ± 17.61 months; range, 2–52 months), all patients had improvement in autonomic symptoms and one patient had persistent tachycardia but no symptoms. Conclusion. Autonomic dysfunction is a core feature of CASPR2 antibody-associated neurological disease and is usually multi-organ in nature with varied manifestations. Cardiac AFT shows sympathetic dominance. While the clinical response to treatment is good, cardiac autonomic dysfunction in the acute period can lead to dangerous fluctuations in blood pressure and result in complications.

Introduction. Myasthenia gravis (MG) is an autoimmune disorder of the neuromuscular junction with 10% being refractory to conventional immunosuppressants. Rituximab is a potential therapeutic option for these patients. We aim to describe the response to rituximab and safety profile in MG. Methods. Retrospective chart review of 12 patients (M:F = 5:7, mean age: 41.08 ± 10.96 years) with MG treated with rituximab and followed up in a single neurology unit at the National Institute of Mental Health and Neurosciences, Bangalore, between 2017 and 2020. Results. Mean duration of MG was 105.16 ± 71.8 months (range 6–260 months). Pre-rituximab treatment included steroids, azathioprine, methotrexate, mycophenolate, cyclophosphamide, and thymectomy. Pre-rituximab MGFA grading included: IIa (n = 1), IIb (n = 1), IIIa (n = 2), IIIb (n = 5), IVb (n = 1), and V (n = 2). Reasons for initiation of rituximab included poor response to steroids (n=10), comorbid illnesses limiting the use of other drugs (n = 4), and drug-induced side effects (n = 2). The mean duration of follow-up was 20.33 ± 13.64 months (range 3-37 months). Two patients developed myasthenic crisis after the induction phase of rituximab and one patient died. Another patient died after 25 months of rituximab therapy due to an unrelated cause. The rest improved, pyridostigmine dose was reduced in four and was stopped in six patients. Other immunosuppressants were continued in all but one patient. Complete stable remission and pharmacological remission were achieved in one and four patients respectively while five patients had minimal manifestations. No infusion-related adverse events were noted. One patient developed transient asymptomatic neutropenia three weeks after rituximab infusion. Conclusion. Rituximab appears to be a safe and effective therapeutic option for patients with refractory MG. however, a proportion does develop worsening similar to steroid-induced exacerbation. Most of the patients in our cohort had a good response with infrequent side effects.

To evaluate the role of bodyweight-supported treadmill training (BWSTT) for chronic stroke survivors.Prospective, randomized controlled study.Patients with a first episode of supratentorial arterial stroke of more than 3months' duration were randomly allocated to 3 groups: overground gait training, treadmill training without bodyweight support, and BWSTT (20 sessions, 30min/day, 5days/week for 4weeks). The primary outcome was overground walking speed and endurance and secondary outcome was improvement by the Scandinavian Stroke Scale (SSS) and locomotion by the Functional Ambulation Category (FAC). We analyzed data within groups (pre-training vs post-training and pre-training vs 3-month follow-up) and between groups (at post-training and 3-month follow-up).We included 45 patients (36 males, mean post-stroke duration 16.51±15.14months); 40 (89.9%) completed training and 34 (75.5%) were followed up at 3months. All primary and secondary outcome measures showed significant improvement (P0.05) in the 3 groups at the end of training, which was sustained at 3-month follow-up (other than walking endurance in group I). Outcomes were better with BWSTT but not significantly (P0.05).BWSTT offers improvement in gait but has no significant advantage over conventional gait-training strategies for chronic stroke survivors.

Objective Studies looking at the effect of anti-epileptic medications on sleep microstructure of patients with epilepsy are almost non-existent. The aim of this study was to compare sleep microstructural characteristics of drug-naive juvenile myoclonic epilepsy (JME) patients with those on valproate (VPA) monotherapy. Methods Three age- ( p = 0.287) and gender- ( p = 0.766) matched groups ( N = 20 in each group): (1) drug-naive JME (mean age: 21.2 ± 4.06 years; M : F = 9:11); (2) JME on VPA (mean age: 21.85 ± 4.28 years; M : F = 11:9); (3) healthy controls (mean age: 23.2 ± 3.82 years; M : F = 9:11) underwent overnight polysomnography. Scoring and analysis of arousals American Sleep Disorders Association (ASDA, 2002), cyclic alternating pattern (CAP) (Terzano et al., 2002) parameters were performed. Comparison of arousal and CAP parameters was performed using one-way ANOVA, followed by pairwise comparisons using Fisher's LSD test ( p ≤ 0.05). Results Rapid eye movement (REM) arousal indices were higher in JME patients (Group 1 [ p = 0.002] and Group 2 [ p 0.001]), whereas the overall and NREM arousal indices were comparable between the three groups. CAP rate was higher in JME patients as compared to controls ( p 0.001). Duration of phase A and its subtypes ( p 0.001) was reduced in drug-naive patients as compared to VPA group and controls. Finally, percentage of phase A1 ( p = 0.003) was decreased and A3 ( p = 0.045) was increased in drug-naive patients as compared to VPA group and controls. Conclusions We found significant alterations in REM arousal indices and several CAP parameters in JME patients. However, many of these alterations were not seen in the valproate group. This might indicate that anti-epileptic medications such as valproate may beneficially modulate arousal instability in JME patients, and hence promote sleep quality and continuity.

Background Large studies analyzing magnetic resonance imaging correlates in different genotypes of mitochondrial disorders are far and few. This study sought to analyze the pattern of magnetic resonance imaging findings in a cohort of genetically characterized patients with mitochondrial disorders. Methods The study cohort included 33 patients (age range 18 months–50 years, M:F — 0.9:1) with definite mitochondrial disorders seen over a period of 8 yrs. (2006–2013). Their MR imaging findings were analyzed retrospectively. Results The patients were classified into three groups according to the genotype, Mitochondrial point mutations and deletions (n = 21), SURF1 mutations (n = 7) and POLG1 (n = 5). The major findings included cerebellar atrophy (51.4%), cerebral atrophy (24.2%), signal changes in basal ganglia (45.7%), brainstem (34.2%) & white matter (18.1%) and stroke like lesions (25.7%). Spinal cord imaging showed signal changes in 4/6 patients. Analysis of the special sequences revealed, basal ganglia mineralization (7/22), lactate peak on magnetic resonance spectrometry (10/15), and diffusion restriction (6/22). Follow-up images in six patients showed that the findings are dynamic. Comparison of the magnetic resonance imaging findings in the three groups showed that cerebral atrophy and cerebellar atrophy, cortical signal changes and basal ganglia mineralization were seen mostly in patients with mitochondrial mutation. Brainstem signal changes with or without striatal lesions were characteristically noted in SURF1 group. There was no consistent imaging pattern in POLG1 group. Conclusion Magnetic resonance imaging findings in mitochondrial disorders are heterogeneous. Definite differences were noted in the frequency of anatomical involvement in the three groups. Familiarity with the imaging findings in different genotypes of mitochondrial disorders along with careful analysis of the family history, clinical presentation, biochemical findings, histochemical and structural analysis will help the physician for targeted metabolic and genetic testing.

Leprosy is the oldest disease known to mankind and has piqued humans since Before Christian Era (BCE) [1]. The causative agent, Mycobacterium leprae, was thefirst bacterium to be identified as causing disease in humans. Effective treatment, viz, Promin, was introduced only in the 1940s. Multi-drug therapy came into vogue in the 1970s [2,3] and was popularised by the World Health Organisation (WHO) in the 1980s. This resulted in a rapid decline in the new case detection rates [4]. Global efforts to eliminate leprosy have met with only partial success and the disease continues to prevail in certain endemic pockets in the developing countries [5–8]. In India the prevalence of leprosy reduced from 58 per 10,000 population in 1980 to 0.69 per 10,000 in 2010 [9]. Thus, leprosy has been ‘eliminated’ as a public health problem.However, this has not ensured complete interruption of disease transmission and new cases continue to occur, sometimes after several years because of the long incubation period. This underscores the need for active and continued efforts to identify new cases [9]. The primary targets of M. leprae are the skin and peripheral nerves [6]. The diagnosis of leprosy rests on the demonstration of one or more of the three cardinal signs namely anaesthetic/hypoesthetic skin patches, thickened peripheral nerves with impaired sensation in the areas innervated by the affected nerves and acid-fast bacilli in skin smear [4,10]. Characteristically, the superficial and cooler regions of the body are affected [11,12]. The commonly affected nerves in leprosy include ulnar, radial, median, lateral popliteal, tibial, facial and trigeminal [13]. Leprous neuropathy can occur in the absence of skin lesions [14]. Even in the presence of skin lesions, a mismatch in the severity of disease in the nerves vis-a-vis skin occurs. Thus the disease may be paucibacillary in the skin, but multibacillary in the nerves [15,16]. Untreated or delayed treatment of peripheral neuropathy is the major cause of disability, deformity, morbidity and social isolation in patients with leprosy [11]. Thus it is imperative to recognise and establish an early diagnosis and institute timely therapy. Meanwhile, each one of the cardinal signs is considered to be highly sensitive and specific for leprosy [4,10]. A considerable skill and experience is required for detecting their presence failing which the diagnosis is delayed or missed [17].

Audiological manifestations in a four-year-old child with Infantile Refsum disease are reported. He was born to non-consanguineous parents and had normal birth history and mildly delayed milestones prior to presentation. Clinical features were characterized by neuroregression, retinitis pigmentosa, hearing loss, peripheral neuropathy and white matter signal changes on magnetic resonance imaging. Biochemical evaluation showed elevated serum levels of long chain fatty acid and phytanic acid confirming the diagnosis. The audiological profile was characterized by absent auditory brainstem responses with robust otocoustic emissions, which indicated auditory neuropathy as the possible cause of hearing loss.

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: Epilepsy is an early and important feature in Menkes disease (MD), an X-linked recessive neurodegenerative disorder of childhood with defect in copper metabolism. There are only few reports on the electro-clinical and magnetic resonance imaging correlates in Menkes disease. The current study describes the electro-clinical features in MD in relation with the structural findings on MRI. Patients and Methods: Six patients from five families were evaluated between 2005 and 2011. Their diagnosis was based on the characteristic morphological features, microscopic evidence of pili torti and low copper and ceruloplasmin levels. All the patients underwent MRI and EEG as part of the evaluation. Results: All patients had classical form of MD with typical morphological features. All but one patient had refractory seizures. Seizure types included multifocal clonic seizures ( n = 3), myoclonic jerks ( n = 4) and tonic spasms ( n = 1). EEG was markedly abnormal in all except in the patient without clinical seizures. While focal epileptiform discharges predominated before six months of age modified hypsarrhythmia was characteristically noted thereafter. MR Imaging revealed abnormalities in all patients, with cerebral atrophy and delayed myelination being the most common observations. Other features noted were subdural effusion ( n = 3), leukoencephalopathy ( n = 3) and basal ganglia signal changes ( n = 1). Follow up imaging in three patients showed resolution of white matter signal intensity changes. Conclusions: Electro-clinical features in Menkes disease are age dependent and evolve sequentially. White matter changes coincided with acute exacerbation of seizures. There was fair correlation between the electro-clinical features and structural findings on MRI.

A comparison of the effectiveness of immunomodulatory therapies in patients with Guillain Barre syndrome (GBS) who require mechanical ventilation (MV) is important for patient treatment and cost. We aimed to compare the effectiveness of three modes of intervention on the outcome of patients with GBS receiving MV: intravenous immunoglobulin (IVIgG); small volume plasmapheresis (SVP) and large volume plasmapheresis (LVP). Patients with GBS satisfying National Institute of Neurological and Communicative Disorders and Stroke 1990 criteria and requiring MV between 1997 between 2007 were analyzed. The primary outcome parameters evaluated were mortality, duration of MV, hospital stay and Hughes scale at discharge from hospital. Of the 173 (Male: Female, 118:55) patients who required MV during the study, 106 patients received single modality treatment (IVIgG 31, LVP 45, SVP 30) based on availability, affordability and feasibility. Patients receiving IVIgG had a higher incidence of severe weakness and bulbar involvement. The mean duration of MV (p = 0.61), total hospital stay (p = 0.44) and Hughes scale at discharge (p = 0.31) did not differ among the three groups. Complications were similar in the three treatment groups except for hypoalbuminemia and anemia, which were more common in patients in the LVP group. In conclusion, the outcome of patients treated with these three immunomodulatory treatment modalities did not vary. The beneficial effects of SVP in our study warrant further randomized control trials especially in resource-constrained settings.

We describe two children from a consanguineous family who manifested mega-corpus callosum, polymicrogyria, and psychomotor retardation. These patients also exhibited the brain anomalies of pontine hypoplasia and an abnormal cerebellar vermis. Our report confirms the genetic nature of megalencephaly-polymicrogyria-mega-corpus callosum syndrome, suggests a possible autosomal-recessive inheritance, and expands the spectrum of this rare entity.

Wilson's disease (WD), a familial neurological disorder involving the brain and liver secondary to altered copper metabolism, is common in South India. In view of the paucity of studies on this condition, the pathomorphological features of eight cases of WD were studied in detail at autopsy (brain alone, 1; brain and liver biopsy, 1; brain and visceral organs, 6), and are described with a discussion of the differential features of the neurological and hepatic forms. Of the six patients presenting with neurological manifestations, five had central pontine myelinolysis, five had subcortical white matter cavitations, four had putaminal softening, and six had variable ventricular dilatation, unlike the hepatic form. The presence of Opalski cells and pontine myelinolysis appear to be specific to the neurological form of WD. Liver abnormalities were observed in all cases (cirrhosis, 6; steatosis, 4; chronic active hepatitis, 2). Contrary to the rubric 'hepatolenticular degeneration', involvement of the lenticular nucleus was not universal, and nor was the pathology restricted to these anatomical areas.

Introduction Recognition of psychiatric manifestations of Wilson's disease (WD) has diagnostic and therapeutic implications. Objective To describe the clinical features and psychopathology of patients with WD who had initial or predominant psychiatric manifestations. Patient and methods Records of 15 patients with WD (M:F: 11:4), from a large cohort of 350 patients, with predominant psychiatric manifestations at onset were reviewed. Their initial diagnosis, demographic profile, family history, pre-morbid personality, clinical manifestations, treatment and outcome were recorded. Results Their mean age at diagnosis was 19.8 ± 5.8 years. Six patients were born to consanguineous parentage and two patients each had family history of WD and past history of psychiatric illness. Diagnosis of WD was suspected by detection of KF rings (all), observing sensitivity to neuroleptics ( n = 2), history of jaundice ( n = 2) and family history suggestive of WD ( n = 9). Psychiatric manifestations could be classified as affective disorder spectrum ( n = 11) and schizophreniform-illness ( n = 3). While the psychiatric symptoms improved in five patients with de-coppering therapy, seven patients needed symptomatic treatment as well. Three of the four patients who responded to de-coppering therapy were sensitive to neuroleptics. Long-term follow up of 10 patients revealed variable recovery. Conclusions Young patient with psychiatric manifestations with clues like history of jaundice, family history of neuropsychiatric manifestations and sensitivity to neuroleptics should be evaluated for WD to avoid delay in diagnosis and associated morbidity. Significant outcomes The study reemphasizes the importance of behavioral manifestations in Wilson disease in terms of diagnosis and management difficulties. Limitations Retrospective nature of the study.

Taly AB, Sivaraman Nair KP, Murali T, John A. Efficacy of multiwavelength light therapy in the treatment of pressure ulcers in subjects with disorders of the spinal cord: a randomized double-blind controlled trial. Arch Phys Med Rehabil 2004;85:1657–61. Objective To study the efficacy of multiwavelength light therapy in the treatment of pressure ulcers in subjects with spinal cord disorders. Design Randomized controlled trial. Setting Neurologic rehabilitation ward of a referral center in India. Participants Thirty-five subjects with spinal cord injury, with 64 pressure ulcers (stage 2, n=55; stage 3, n=8; stage 4, n=1), were randomized into treatment and control groups. One subject refused consent. Mean duration of ulcers in the treatment group was 34.2±45.5 days and in the control group, 57.1±43.5 days. Interventions Treatment group received 14 sessions of multiwavelength light therapy, with 46 probes of different wavelengths from a gallium-aluminum-arsenide laser source, 3 times a week. Energy used was 4.5J/cm 2 . Ulcers in the control group received sham treatment. Main outcome measures Healing of the ulcer, defined as the complete closure of the wound with healthy scar tissue, time taken for the ulcer to heal, and stage of the ulcer and Pressure Sore Status Tool score 14 days after last treatment. Results There was no significant difference in healing between the treatment and control groups. Eighteen ulcers in treatment group and 14 in control group healed completely ( P =.802). Mean time taken by the ulcers to heal was 2.45±2.06 weeks in the treatment group and 1.78±2.13 weeks in the control group ( P =.330). Time taken for stage 3 and 4 ulcers to reach stage 2 was 2.25±0.5 weeks in treatment group and 4.33±1.53 weeks in control group ( P =.047). Conclusions Multiwavelength light therapy from a gallium-aluminum-arsenide laser source did not influence overall healing pressure ulcers. Limited evidence suggested that it improved healing of stage 3 and 4 pressure ulcers.

Background: There are only a few reports regarding the fertility and outcome of pregnancy in Wilson's disease (WD) and none from India. The authors in this study discuss various aspects of fertility in 16 women with WD. Methods: Retrospective analysis of data from a large cohort of WD, being followed at a tertiary care center. Results: Sixteen patients had conceived on 59 occasions with 30 successful pregnancies, 24 spontaneous abortions, 2 medical terminations of pregnancy and 3 still births. Diagnosis of WD was established after conception in 10 presymptomatic patients while six patients were already on treatment. Among these 16 patients, 9 had history of spontaneous abortions and 12 had successful pregnancies. None of the clinical features of WD changed during pregnancy, with or without treatment. All the 30 babies were full-term and delivered healthy. Conclusion: Recurrent abortions are common especially in women with untreated Wilson's disease. However, successful pregnancies and uneventful full-term delivery may occur in mothers of WD on treatment and in undiagnosed, undetected presymptomatic patients. Pregnancy does not seem to have adverse effect on the clinical course of Wilson's disease. Teratogenecity was not seen in the present series with low-dose penicillamine and zinc sulphate.

Sympathetic skin response (SSR) recording is an established test of sudomotor autonomic functions. However, knowledge of its pathways in spinal cord is putative.This study involved subjects with isolated spinal cord lesions to evaluate the afferent pathways of SSR.Clinical examination was done according to standard neurological classification of spinal cord injury. Electrophysiological evaluation included: (1) conventional nerve conduction studies to exclude peripheral nerve lesions, (2) scalp somato-sensory-evoked potentials (SEP) with posterior tibial nerve (PTN) stimulation and (3) SSR recording from palm by stimulating supra orbital nerve (SON) at forehead, and PTN at ankle. Subjects with absent SSR in palm to SON stimulation were excluded. In such patients, the afferent tracts were considered abnormal when SSR was absent in palm on stimulation of PTN.Among 37 subjects (age-28.1+/-12.8 years), the afferent tracts of SSR were affected in 13. Sparing of afferent SSR tracts correlated with preservation of bladder sensations (P0.01). There was no correlation between SSR and SEP.Spinal cord lesions frequently involve afferent tracts of SSR. Spinal afferents of SSR are closely related with tracts of bladder sensations and are different from pathways for SEP.