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Objectives We analyzed changes in sleep profile and architecture of patients with drug-resistant TLE-HS using three validated sleep questionnaires- Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), NIMHANS Comprehensive Sleep Disorders, and polysomnography (PSG). We studied the effect of epilepsy surgery in a subset of patients. Methods In this prospective observational cohort study, sleep profile of 40 patients with drug-resistant TLE-HS was compared to 40 healthy matched controls. Sleep architecture of 22 patients was studied by overnight PSG and compared to 22 matched controls. Sleep profile was reassessed in 20 patients after a minimum period of three months after epilepsy surgery. Results The mean PSQI was higher among patients compared to controls(P=0.0004) while mean ESS showed no difference. NCSDQ showed fewer patients feeling refreshed after a night's sleep compared to controls (p=0.006). PSG revealed a higher time in bed (p=0.0001), longer total sleep time (p=0.006) and more time spent in NREM stage 1 (p=0.001) and stage 2 (p=0.005) while spending less time in stage 3 (p=0.039) among TLE patients. Sleep efficiency was worse in patients on ≥3 ASMs compared to those on 2 ASMs (p-0.044). There was no change in mean ESS (p=0.48) or PSQI (p=0.105) after surgery. Conclusions Patients with drug-resistant TLE-HS have an altered sleep profile and architecture. Patients on ≥3 ASMs have a lower sleep efficiency. Reassessment at short intervals after epilepsy surgery did not reveal significant changes in sleep profile.

Phaeohyphomycosis causes a wide spectrum of systemic manifestations and can affect even the immunocompetent hosts. Involvement of the central nervous system is rare. A 48-year-old farmer presented with chronic headache, fever, and impaired vision and hearing. Serial MRIs of the brain showed enhancing exudates in the basal cisterns, and lesions in the sella and perichiasmatic and cerebellopontine angle regions along with enhancement of the cranial nerves and leptomeninges. Cerebrospinal fluid (CSF) showed lymphocytic pleocytosis with elevated protein and decreased glucose on multiple occasions. Clinical, imaging, and CSF abnormalities persisted despite treatment with antitubercular drugs and steroids for 2 years. Biopsy of the dura mater at the cervicomedullary junction revealed necrotizing granulomatous lesions, neutrophilic abscesses, and giant cells containing slender, pauci-septate, pigmented fungal hyphae. Fungal culture showed growth of Fonsecaea pedrosoi, which is classically known to cause brain abscesses. Here, we report the diagnostic odyssey in a patient with chronic meningitis from a region endemic for tuberculosis and describe the challenges in establishing the accurate diagnosis. Lack of therapeutic response to an adequate trial of empirical antitubercular therapy warrants search for alternative causes, including fungal meningitis. We highlight the uncommon manifestation of F. pedrosoi with chronic meningitis as well as the protracted clinical course despite not receiving antifungal therapy.

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

Ethylmalonic encephalopathy (EE; OMIM #602473) is an autosomal recessive disorder characterized by (1) progressive neurologic impairment, including global developmental delay with periods of regression during illness, progressive pyramidal and extrapyramidal signs, and seizures; and (2) generalized microvascular damage, including petechial purpura and chronic hemorrhagic diarrhea. It leads to premature death. EE is caused by mutations in ethylmalonic encephalopathy protein 1 ( ETHE1 ), and more than 60 different mutations have been reported.1,2 ETHE1 encodes a mitochondrial sulfur dioxygenase involved in the catabolism of hydrogen sulfide (H2S).2 Impairment of sulfur dioxygenase leads to the accumulation of hydrogen sulfide and its derivatives (thiosulphate) in various body fluids and tissues. Higher concentration of H2S is toxic and induces direct damage to cell membranes. It inhibits cytochrome c oxidase (COX), increases lactic acid and short-chain acyl-COA dehydrogenase, and leads to elevation of ethyl malonate and C4/C5 acylcarnitine in muscle and brain.2 We describe the clinical phenotype and MRI, pathologic, and biochemical findings of a patient with EE from India who had a novel homozygous c.493 G>C (p.D165H) variation in ETHE1 .

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is increasingly being recognised to be associated with protean neuropsychiatric manifestations. Anti-NMDAR encephalitis is considered to be the most common amongst the autoimmune-mediated encephalitic disorders. It is caused by the autoantibodies against GluN1 subunits of N-methyl-D-aspartate (NMDA) receptor and manifests with prominent psychiatric symptoms, especially during the initial phase of illness. Literature anti-NMDAR encephalitis presenting with postpartum psychosis is scant. In this report, we present a 28-year-old lady with postpartum psychosis as presenting manifestation of anti-NMDAR encephalitis and discuss the neuropsychiatric manifestations of this emerging entity.

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.

Introduction. The activating role of non–rapid eye movement (NREM) sleep on epileptic cortex and conversely, the seizure remission brought about by antiepileptic medications, has been attributed to their effects on neuronal synchrony. This study aims to understand the role of neural synchrony of NREM sleep in promoting interictal epileptiform discharges (IEDs) in patients with epilepsy (PWE) by assessing the peri-IED phase synchrony during awake and sleep states. It also studies the role played by antiepileptic drugs (AEDs) on EEG desynchronization in the above cohort. Methods. A total of 120 PWE divided into 3 groups (each n = 40; juvenile myoclonic epilepsy [JME], temporal lobe epilepsy [TLE]. and extratemporal lobe epilepsy [Ex-TLE]) were subjected to overnight polysomnography. Each patient group was subdivided into drug-naive and on treatment (Each n = 20). EEG phase synchronization analysis was performed to compare peri-IED phase synchronization indices (SI) during awake and sleep stages and between drug naïve and on treatment groups in 4 frequency bands, namely delta, theta, alpha, and beta. The mean ± SD of peri-IED SI among various subgroups was compared employing a multilevel mixed effects modeling approach. Results. Patients with JME had increased peri-IED cortical synchrony in N3 sleep stage, whereas patients with partial epilepsy had increased IED cortical synchrony in N1 sleep stage. On the other hand, peri-IED synchrony was lower during wake and REM sleep. We also found that peri-IED synchronization in patients with JME was higher in drug-naive patients compared with those on sodium valproate monotherapy in theta, alpha, and beta bands. Conclusion. The findings of this study suggest that sleep stages can alter cortical synchrony in patients with JME and focal epilepsy, with NREM IEDs being more synchronized and wake/REM IEDs being less synchronized. Furthermore, it also suggests that AEDs alleviate seizures in PWE by inhibiting cortical synchrony.

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.

This case series aimed to describe clinicoradiological, electromyographic, and etiological spectra in palatal tremor (essential=1; symptomatic=26). Patients with symptomatic palatal tremor had 2 to 10 Hz arrhythmic electromyographic bursts, a spectrum of changes in inferior olivary nucleus, with/without lesions in Guillain Mollaret triangle, and varied etiologies (genetic=9, vascular=6, trauma=3, infections=3). Exome sequencing showed variations in POLG, WDR81, NDUFS8, TENM4, and EEF2. Clinical phenotypes of patients with POLG, WDR81, and NDUFS8 variations were consistent with that described in literature. We highlight salient magnetic resonance imaging features, electrophysiological observations, and diverse etiologies in a large cohort of palatal tremor.

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.

Objectives: To evaluate the pulmonary function in Guillain�Barre syndrome (GBS) patients in subacute phase and find clinical correlates of pulmonary dysfunction. Methods: This was a single-center, prospective, cross-sectional, hospital-based study in GBS patients performed in Department of Neurological Rehabilitation at a tertiary care institute. Clinical examination for pulmonary function was done by measuring chest expansion. The pulmonary function tests were carried out by Spirometry kit Microquark Cosmed, Italy. Fatigue was assessed by Fatigue Severity Scale, disability status by Hughes Disability Scale (HDS), and muscle weakness by Medical Research Council sum scores. Statistical Analysis: Statistical analysis was performed by Stata 11. The significance of P value was adjudged against an alpha of 0.05. Results: Twenty-eight patients were included with 17 (61%) men and mean age of 31 years. Median duration of symptoms was 16.5 days. There were 10 (36%) demyelinating and 18 (64%) axonal variants. Twenty-six (93%) patients scored more than 2 on HDS. All study participants reported fatigue. Twenty-two (78.6%) patients had chest expansion of

Objectives: To study the effects of cognitive retraining and inpatient rehabilitation to study the effects of cognitive retraining and inpatient rehabilitation in patients with acquired brain injury (ABI). Design and Setting: This was a prospective follow-up study in a neurological rehabilitation department of quaternary research hospital. Patients and Methods: Thirty patients with ABI, mean age 36.43 years (standard deviation [SD] 12.6, range 18–60), mean duration of illness 77.87 days (SD 91.78, range 21–300 days) with cognitive, physical, and motor-sensory deficits underwent inpatient rehabilitation for minimum of 14 sessions over a period of 3 weeks. Nineteen patients (63%) reported in the follow-up of minimum 3 months after discharge. Type of ABI, cognitive status (using Montreal Cognitive assessment scale [MoCA] and cognitive Functional Independence Measure [Cog FIM]®), and functional status (motor FIM®) were noted at admission, discharge, and follow-up and scores were compared. Results: Patients received inpatient rehabilitation addressing cognitive and functional impairments. Baseline MoCA, motor FIM, and Cog FIM scores were 15.27 (SD = 7.2, range 3–30), 31.57 (SD = 15.6, range 12–63), and 23.47 (SD = 9.7, range 5–35), respectively. All the parameters improved significantly at the time of discharge (MoCA = 19.6 ± 7.4 range 3–30, motor FIM® = 61.33 ± 18.7 range 12–89, Cog FIM® =27.23 – 8.10 range 9–35). Patients were discharged with home-based programs. Nineteen patients reported in follow-up and observed to have maintained cognition on MoCA (18.8 ± 6.8 range 6–27), significantly improved (P < 0.01) on Cog FIM® (28.0 ± 7.7 range 14–35) and motor FIM® =72.89 ± 16.2 range 40–96) as compare to discharge scores. Conclusions: Cognitive and functional outcomes improve significantly with dedicated and specialized inpatient rehabilitation in ABI patients, which is sustainable over a period.

Excessive cortical synchrony within neural ensembles has been implicated as an important mechanism driving epileptiform activity. The current study measures and compares background electroencephalographic (EEG) phase synchronization in patients having various types of epilepsies and healthy controls during awake and sleep stages.A total of 120 patients with epilepsy (PWE) subdivided into 3 groups (juvenile myoclonic epilepsy [JME], temporal lobe epilepsy [TLE], and extra-temporal lobe epilepsy [Ex-TLE]; n = 40 in each group) and 40 healthy controls were subjected to overnight polysomnography. EEG phase synchronization (SI) between the 8 EEG channels was assessed for delta, theta, alpha, sigma, and high beta frequency bands using ensemble measure on 10-second representative time windows and compared between patients and controls and also between awake and sleep stages. Mean ± SD of SI was compared using 2-way analysis of variance followed by pairwise comparison ( P ≤ .05).In both delta and theta bands, the SI was significantly higher in patients with JME, TLE, and Ex-TLE compared with controls, whereas in alpha, sigma, and high beta bands, SI was comparable between the groups. On comparison of SI between sleep stages, delta band: progressive increase in SI from wake ⇒ N1 ⇒ N2 ⇒ N3, whereas REM (rapid eye movement) was comparable to wake; theta band: decreased SI during N2 and increase during N3; alpha band: SI was highest in wake and lower in N1, N2, N3, and REM; and sigma and high beta bands: progressive increase in SI from wake ⇒ N1 ⇒ N2 ⇒ N3; however, sigma band showed lower SI during REM.This study found an increased background cortical synchronization in PWE compared with healthy controls in delta and theta bands during wake and sleep. This background hypersynchrony may be an important property of epileptogenic brain circuitry in PWE, which enables them to effortlessly generate a paroxysmal EEG depolarization shift.

Objective: The objective of this study was to observe urodynamic profile of acute transverse myelitis (ATM) patients and its correlation with neurological outcome. Patients and Methods: This prospective study was conducted in the neurorehabilitation unit of a tertiary university research hospital from July 2012 to June 2014. Forty-three patients (19 men) with ATM with bladder dysfunction, admitted in the rehabilitation unit, were included in this study. Urodynamic study (UDS) was performed in all the patients. Their neurological status was assessed using ASIA impairment scale and functional status was assessed using spinal cord independence measure. Bladder management was based on UDS findings. Results: In total, 17 patients had tetraplegia and 26 had paraplegia. Thirty-six patients (83.7%) had complaints of increased frequency and urgency of urine with 26 patients reported at least one episode of urge incontinence. Seven patients reported obstructive urinary complaints in the form of straining to void with 13 patients reported both urgency and straining to void and 3 also had stress incontinence. Thirty-seven (86.1%) patients had neurogenic overactive detrusor with or without sphincter dyssynergia and five patients had acontractile detrusor on UDS. No definitive pattern was observed between neurological status and bladder characteristics. All patients showed significant neurological and functional recovery with inpatient rehabilitation (P< 0.05 and P< 0.001, respectively). Conclusions: The problem of neurogenic bladder dysfunction is integral to ATM. Bladder management in these patients should be based on UDS findings. Bladder characteristics have no definitive pattern consistent with the neurological status.

Introduction: The spectrum of various complications in critically ill Guillain–Barre syndrome (GBS) and its effect on the prognosis is lacking in literature. This study aimed at enumerating the complications in such a cohort and their significance in the prognosis and mortality. Materials and Methods: Retrospective case record analysis of all consecutive mechanically ventilated patients of GBS in neurology Intensive Care Unit (ICU) of a tertiary care institute for 10 years was done. Demographic, laboratory, and treatment details and outcome parameters were recorded. Results: Among the 173 patients were 118 men and 55 women (2.1:1), aged 1–84 years. The average number of ICU complications per patient was 6.8 ± 1.8 (median = 7, range = 1–12). The most common complication was tracheobronchitis (128). Other pulmonary complications were found in 36 patients. The next was metabolic hyponatremia (115) hypokalemia (67), hypocalcemia (13), stress hyperglycemia (10), hyperkalemia (8), hypernatremia (9). Sepsis (40), UTI (47), dysautonomia (27), hypoalbuminemia (76), anemia (75), seizures (8), paralytic ileus (5), bleeding (4), anoxic encephalopathy (3), organ failures (12), deep vein thrombosis (7), and drug rashes (1) were also noted. The complications, considered significant in causing death, Hughes scale ≤ 3 at discharge, prolonged mechanical ventilation (>21 days) and hospitalization (>36 days) were pneumonia, hyponatremia, hypokalemia, urinary infection, tracheobronchial infections, hypoalbuminemia, sepsis, anemia dysautonomia. Conclusion: Active monitoring and appropriate and early intervention by the clinician will improve the quality of life of these patients and reduce the cost of prolonged mechanical ventilation and ICU stay.

Reports of spectrum of clinical manifestations in PMP22 gene–associated neuropathies (duplication/mutations) are scarce. To identify the frequency of PMP22 gene variations and establish their genotype-phenotype correlation. Patients with suspected genetic demyelinating neuropathy (n = 128) underwent evaluation for copy number variations and point mutations in PMP22 gene by multiplex ligation-dependent probe amplification (MLPA) and direct sequencing respectively. Of these, only 27 patients (M:F:19:8) from 18 families had PMP22 gene–associated neuropathy; they were subsequently analyzed for genotype-phenotype correlation. Twenty-five patients had PMP22 duplication while two patients had PMP22 missense mutations (p.A114V and p.L80P). Age at onset of neuropathy ranged from infancy to 63 years and symptom duration ranged from 2 to 32 years. Cranial nerve dysfunction in the form of ptosis, ophthalmoplegia, bifacial weakness, and sensorineural hearing loss was observed in addition to a number of systemic features. Three patients were asymptomatic. All except one patient were ambulant. Velocity of median nerve and amplitude of evoked motor responses from common peroneal nerve were significantly reduced in male patients. There was significantly worse disability in the late-onset group as compared with the early-onset group. Otherwise, the mean age at onset, frequency of skeletal deformities, patterns of motor weakness, muscle stretch reflexes, sensory impairment, disability rating scales, and electrophysiological parameters were comparable irrespective of gender, onset age, family history and ulnar nerve conduction velocities. The relatively low frequency of PMP22 duplication in the present cohort warrants a more comprehensive search to establish the genetic etiology. Further research into the role of other genetic variants as well as modifier genes and their effect on phenotypic heterogeneity is indicated.

A 6-month-old boy born to nonconsanguineous parents presented with intractable seizures from the fourth month of age. Oligohydramnios was detected in the last trimester of pregnancy. He was born at term by normal delivery (birthweight 2.9 kg). At birth he had weak cry, microcephaly (head circumference 31 cm

Guillain Barre Syndrome (GBS) is one of the commonest acquired immune-mediated neuropathies, often preceded by infections. Although cellular immune responses are shown to substantially account for the pathophysiology of GBS, the precise mechanistic basis of risk and disease course remains enigmatic till date. Cytokines are best known for their abilities to drive cellular immunity and inflammation through their co-ordinated actions. Data obtained from clinical and animal model studies suggest important implications of some of the cytokines in the progression and recovery of GBS. However, these studies were performed on few cytokines and small set of GBS patients, thereby lacking a complete understanding of the patterns of association of cytokines representing Th1, Th2, and Th17 responses with GBS. We studied 65 well-characterized GBS patients and 73 age- and sex-matched healthy controls. A panel of 15 cytokines representing Th1, Th2 and Th17 pathways was assayed using Multiplex Suspension Array platform. Plasma levels of five cytokines were found to be altered in GBS patients compared to healthy control subjects: (i) IL-1β exhibited reduced levels, and (ii) IFN-γ, IL-4, IL-21 and IL-33 were elevated in GBS patients. The most important finding of this study was up-regulated expression of IL-21 and IL-33 in patients with GBS. Given the role of IL-33 as an alarmin, the elevated level of this cytokine provides important indication about a much broader role of cytokines in GBS. This study also provides evidence towards a multi-lineage Th cells (Th1, Th2 and Th17) associated cytokine responses in the pathophysiology of GBS.

The etiopathogenesis of Guillain Barre Syndrome (GBS) is inadequately understood. The role of immuno-inflammatory Th17 pathway was examined in GBS patients by genetic, gene expression and biochemical studies. Genotyping of G197A single nucleotide polymorphism within IL17 gene was carried out by PCR-RFLP method in 220 GBS patients. Quantification of gene expression of STAT3 and RORC and estimation of plasma level of IL-17A were carried out in a subset of patients. Significantly increased STAT3 gene expression in lymphocytes and plasma IL-17A levels were observed in GBS patients. This study adds new dimension and reinforces important implications of Th17 pathway in GBS.

Background: NMDA receptor encephalitis (NMDARE) is the most prevalent autoimmune encephalitis and it encompasses a spectrum of clinical features. It is most commonly associated with alteration in consciousness, seizures, neuro-psychiatric symptoms, and movement disorders. Electroencephalography (EEG) plays a vital role and can give clues to diagnosis in a subset of patients. Methods: We retrospectively characterized the clinical and EEG findings in our NMDARE patients (n = 48). A total of 131 EEGs were analyzed. Results: We observed that patients with seizures had a younger age of onset (p < 0.001). The most common EEG pattern that was noted was diffuse slowing (n = 20) followed by generalized rhythmic delta activity (n = 9), focal spikes and slowing (n = 8 each). Delta brush pattern was seen in only 3 EEGs. Focal ictal rhythms were seen in 3 EEGs. There was no significant difference in outcomes such as seizure recurrence, modified Rankin score (mRS) at follow up/discharge or relapse between groups of patients who had EEG abnormalities in the first EEG and with those who did not. Conclusions: NMDARE has varied EEG findings, most of them being non-specific. When combined with clinical presentation, EEG is a useful tool in the diagnosis and management of NMDARE.

Vogt-Koyanagi-Harada (VKH) syndrome is an immune-mediated granulomatous disease which affects melanin-rich organs like eyes, skin, nervous system, and ears. Neurological and auditory manifestations usually precede the involvement of other sites. Patients may manifest with “complete” or “incomplete” syndrome. We report two patients who presented with acute headache and impaired vision. Fundus examination revealed optic disc hyperemia and exudative retinal detachment which provided a clue for the diagnosis at the bedside. Fundus fluorescein angiogram (FFA) revealed abnormal dye leakage, whereas B scan showed choroid thickening. Cerebrospinal fluid (CSF) pleocytosis contrasted with unremarkable brain magnetic resonance imaging and lack of meningeal signs. Melanophagocytosis was evidenced by melanin-laden macrophages in CSF and skin biopsy. This finding is specific for VKH syndrome and helps to clinch the diagnosis even when the complete syndrome is not present cross-sectionally. VKH syndrome should be suspected in patients with aseptic meningitis if tests for common infectious and immune-mediated diseases are negative.

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: To describe clinical, electrophysiological, and histopathological profile of vasculitic neuropathy in elderly subjects aged 65 years or more. Design: Retrospective chart review. Setting: Departments of Neurology and Neuropathology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India. Patients and Methods: Elderly subjects, diagnosed vasculitic neuropathy by nerve biopsy over one decade, were studied. Results: The cohort consisted of 46 subjects. Symptom duration was 21.54 ± 33.53 months. Onset was chronic in majority (82.6%). Key features included paresthesias (89%), weakness (80%), sensory loss (70%), wasting (63%), and relapsing-remitting course (6.5%). Most Common clinico-electrophysiological patterns were distal symmetrical sensorimotor polyneuropathy - 19, mononeuritis multiplex - 9, and asymmetric sensorimotor neuropathy - 10. Diagnosis of vasculitis was not suspected before biopsy in 31 (67.3%). Nerve biopsy revealed definite vasculitis - 12, probable - 10, and possible - 24. Treatment included immunomodulatory agents (41), symptomatic medications only (9), and antiretroviral therapy (1). Twenty-four patients were followed up for mean period of 6.5 months. Outcome at last follow-up was improved (13), unchanged (8), and worsened (3). Conclusion: Vasculitis is an important, treatable cause of neuropathy in elderly. Nerve biopsy should be used judiciously for early diagnosis and appropriate treatment.

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.

Molybdenum cofactor deficiency (MoCD) is a rare inherited metabolic disorder characterized by neonatal onset intractable seizures, severe psychomotor retardation, dysmorphic facies, and dislocated ocular lenses.1 A characteristic biochemical profile permits early diagnosis. Although more than 100 genetically characterized patients have been reported, this number is discrepant with the actual prevalence as MoCD is often mistaken for hypoxic-ischemic encephalopathy (HIE) secondary to perinatal asphyxia. It is important to recognize MoCD to provide appropriate genetic counseling and prenatal diagnosis.2 Effective pharmacotherapies that overcome the primary biochemical defect are also in the pipeline. We present a child with biochemically and genetically confirmed MoCD and discuss the clinical, imaging, biochemical, and genetic profile of this disorder.

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].

We report three females who developed Guillain–Barre Syndrome in postpartum period (within 6 weeks of delivery) and were admitted in the Neurological Rehabilitation Department for rehabilitation after the initial diagnosis and treatment in the Department of Neurology. The first case, axonal variant (acute motor axonal neuropathy [AMAN]) had worst presentation at the time of admission, recovered well by the time of discharge. The second case, acute motor sensory axonal neuropathy variant and the third case, AMAN variant presented at the late postpartum period. Medical treatment was sought much later due to various reasons and both the patients had an incomplete recovery at discharge. Apart from their presentations, rehabilitation management is also discussed in some detail.

Background: Opsoclonus-myoclonus-ataxia syndrome (OMAS) is a rare disorder; there is limited experience regarding its clinical course and therapeutic response. Aims and Objectives: To describe the clinical profile, investigations, and therapeutic outcome in pediatric OMAS. Patients and Methods: Fourteen children (age: 27.1 ± 7 months; male: female = 1:2.3) suffering from OMAS seen over a period of 10 years (2006–2015) were included in the study. Their clinicodemographic profile, investigations, therapeutic outcome at follow-up, and relapses were reviewed. Results: Ten children reported antecedent events (respiratory infection: 7; gastrointestinal infection: 1; vaccination: 2). The most common referral diagnosis was acute cerebellitis (n = 8). Hypotonia (n = 9), abnormal behavior (n = 10), and neuroregression (n = 6) were also the frequent manifestations. Brain magnetic resonance imaging, cerebrospinal fluid, and urinary vanillylmandelic acid were normal in all the patients. Seven patients had an underlying tumor (abdomen: 4; thorax: 2; neck: 1) detected by ultrasound (n = 2/14), computed tomography (CT) (n = 6/12), and fluorodeoxyglucose - positron emission tomography (n = 2/2). CT scan identified the tumor in 2 patients where metaiodobenzylguanidine scintigraphy was negative. All patients received steroids for 22.3 ± 20 months (3 months to 5 years). Eight required prolonged immunomodulation (>12 months). Complete remission after follow-up of 31.3 ± 19 months (7 months to 5 years) was noted in 5 patients, whereas the rest had persisting behavioral and cognitive abnormalities. Relapses were noted in 6 patients related to intercurrent infections (n = 5) and discontinuation of steroids (n = 1). The patients presented with isolated symptoms of the full-blown syndrome during their relapses. Conclusion: OMAS in children runs an indolent course requiring careful monitoring and long-term immunomodulation. An abnormal behavior is common and the outcome is variable.

Background Data on antibody profile in myasthenia gravis (MG) from India are limited. Objectives To investigate antibody profile in patients with MG and their clinical correlates. Patients and methods Patients of MG (n = 85, M:F::1.1:1, mean age: 39.29 ± 17.3 years, mean symptom duration: 72.94 ± 91.8 months) were evaluated for clinical features, MG foundation of America (MGFA) score, response to treatment, and outcome at last follow-up. Antibodies to acetylcholine receptor (AChR), muscle-specific kinase (MUSK), titin and ryanodine receptor (RYR) were analysed using ELISA. Results Based on the regional distribution of weakness, the cohort could be categorized as: generalized: 60, ocular: 16 and oculo-bulbar: 9. Sixty patients were followed up for a mean duration of 26.74 ± 13.8 months. Outcome at last follow-up was as follows: remission-22, no remission-33 and dead-5. AChR and MUSK antibodies were detected in 58 and 8 patients, respectively. Frequency of generalized MG, worse MGFA score during the disease course and thymomatous histology significantly correlated with presence of AChR-antibodies, though outcome at last follow-up was comparable between AChR-antibody positive and negative groups. Patients with MUSK antibodies had oculo-bulbar or generalized MG and frequent respiratory crisis, but majority improved or remitted with treatment. Titin antibodies were detected in 31.8% and RYR antibodies in 32.9%. Their presence did not correlate with age at onset of MG, severity or presence of thymoma. Conclusion This report highlights the spectrum of antibodies in MG in an Indian cohort. AChR-antibody positivity correlated with clinical severity. Outcome was good in majority of MUSK antibody-positive MG. The role of other antibodies, complementary vs epiphenomenon, remains open.

Objective: The objective of this study is to observe urinary symptoms in patients with Parkinson's disease (PD) and progressive supranuclear palsy (PSP) and advice bladder dysfunction management based on urodynamic study (UDS) findings. Patients and Methods: Twenty-two patients (12 males) with PD and PSP (15 and 7, respectively) with urinary symptoms were included in this study. All patients except one were on levodopa and carbidopa medication. UDS was performed, and bladder management determined. Results: Mean age was 60.4 years (range 41–73 years, standard deviation [SD] 8.4). Mean illness duration was 31.9 months (range 9–146 months, SD 31.0) and mean duration of urinary symptoms was 14.8 months (range 1–61 months, SD 15.8). Eighteen patients reported nocturia and 16 patients had urgency with or without urge incontinence. Three patients had retention and straining to void and 3 had mixed urinary complaints. Twelve out of 22 patients had absence of voluntary anal contraction on per-rectal examination. UDS was suggestive of 12 patients with neurogenic detrusor overactivity with or without sphincter dyssynergy. Six patients had normal detrusor pressure, and four patients were found to have contractile detrusor. Ten patients had significant postvoid residual. Bladder management included pharmacotherapy, supportive, and behavioral management as appropriate. Conclusions: Patients with PD/PSP are known to develop urinary symptoms during illness. Clinical complaints and UDS findings do not necessarily match. UDS is required to manage urinary symptoms. Most of the patients respond to oral antimuscarinic medications along with behavioral and supportive therapy.

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.

Reports of magnetic resonance imaging (MRI) findings in subacute sclerosing panencephalitis (SSPE) with clinical and electroencephalography (EEG) correlation are few. To describe the MRI features of SSPE and correlate with its clinical features and EEG. Clinical, MRI and EEG data of 33 patients (male/female 19/14; age: 11.4 ± 5.3 yr) were reviewed. All patients had raised IgG anti-measles antibody (≥ 1:625) in cerebrospinal fluid. Their clinical features were myoclonus (100%), seizures (42%), visual disturbances (18%), pyramidal signs (30%), extrapyramidal symptoms (27%), and cognitive impairment (79%) and behavioral changes (21%). EEGs were universally abnormal: diffuse slowing of background activity-all; periodic complexes-27 (symmetrical): High voltage delta waves (55%) and sharp & slow wave discharges (45%). MRI findings included – normal (9%), cerebral atrophy (78%), white matter (76%) and basal ganglia (6%) changes. Restricted diffusion in periventricular/subcortical region was noted in 4/23 patients (stage 2). Magnetic resonance spectroscopy showed decreased N-acetyl aspartate peaks and elevated choline peaks in 75% and lactate peak in 25% (stage 3) of patients. Correlation of background delta activity among patients with MRI signal abnormalities and those without any signal change was noted (P=0.02). There was significant correlation between visual deficits and bilateral parieto-occipital white matter signal changes (P=0.03). There was no other EEG-MRI or clinical-MRI correlation. MRI abnormalities in SSPE are diverse and may or may not reflect underlying pathology. Visual deficits were observed in patients with parieto-occipital white matter signal change. Restricted diffusion of signal abnormalities and lactate peak in magnetic resonance spectroscopy were uncommon and it may add to better understanding.

We report the radiologic findings in two children with Griscelli syndrome who presented mainly with neurologic findings. Both children were born to consanguineous parents, had normal birth and developmental histories; both had silvery gray hair from the time of birth. The first child presented with symptoms of increased intracranial pressure and cerebellar ataxia; the second child with cerebellar ataxia alone. Microscopic examination of the hair in both the children demonstrated the characteristic melanin clumps suggestive of Griscelli syndrome. Magnetic resonance imaging of the brain in the first child demonstrated multifocal white matter hyperintensities in the cerebrum and diffuse white matter hyperintensities in the cerebellum, with intense contrast enhancement. In the second child, signal changes were confined to the cerebellum and spinal cord. The first child succumbed to rapidly progressive increased intra-cranial pressure; partial autopsy revealed necrotizing lesions involving the cerebellar hemispheres bilaterally which corresponded to the neuroimaging abnormalities. Histology revealed diffuse histiocytic infiltration of the parenchyma. Griscelli syn- drome type 2 should be a diagnostic consideration in a child with silvery hair, neurological deterioration and enhancing multifocal white matter signal intensity changes

Mutations in the mitochondrial-encoded nicotinamide adenine dinucleotide dehydrogenase 5 gene ( MT-ND5 ) has been implicated as an important genetic cause of childhood mitochondrial encephalomyopathies. This study reports the clinical and magnetic resonance imaging findings in two pediatric patients with mutations in the ND5 gene of mitochondrial DNA. The 8-month-old boy with m.13513 G > A mutation presented with infantile basal ganglia stroke syndrome secondary to mineralizing angiopathy. The 7-year-old girl with the m.13514A > G mutation had episodic regression, progressive ataxia, optic atrophy, and hyperactivity. Magnetic resonance imaging of the brain showed bilateral symmetrical signal intensity changes in the thalamus, tectal plate, and inferior olivary nucleus, which subsided on follow-up image. Both the patients had a stable course. Familiarity with the various phenotypic and magnetic resonance imaging findings and the clinical course in childhood mitochondrial encephalomyopathies may help the physician in targeted metabolic–genetic testing and prognostication.

Objectives: To observe neurogenic bladder pattern in patients with myelopathy by performing urodynamic study (UDS) and to observe whether it has any correlation with functional and neurological recovery. Patients and Methods: This prospective study was conducted with 90 patients with myelopathy, both traumatic and non-traumatic (males = 65) in a university tertiary research hospital in India between January 2011 and December 2013. Mean age was 33.5 ± 13.2 years (range 15-65 years), mean duration of injury was 82.63 ± 88.3 days (range 14-365 days) and mean length of stay (LOS) in the rehabilitation unit 42.5 ± 23.3 days (range 14-130 days). The urodynamic study was performed in all the patients to assess the neurogenic bladder pattern. Management was based on the UDS findings. Functional recovery was assessed using Barthel index (BI) scores and spinal cord independence measures (SCIM) scores. Neurological recovery was assessed using ASIA impairment scale (AIS). We tried to correlate neurogenic bladder patterns with recovery. Results: Fifty patients (55.6%) had overactive detrusor with 25 each had detrusor sphincter dyssynergia (DSD) and synergic sphincter. Thirty-eight patients had hypoactive/acontractile detrusor and two had normal studies. No significant correlation observed between neurogenic bladder pattern and change in BI scores (P = 0.696), SCIM scores (P = 0.135) or change in ASIA status (P = 0.841) in the study. Conclusions: More than half of the patients with myelopathies had overactive detrusor with or without dyssynergic sphincter according to the urodynamic study. Neurogenic bladder patterns had no significant correlation with functional and neurological recovery in these patients.

Objective: To study the utilityof nerve biopsy in providing diagnostic, therapeutic or prognostic information that aid in clinical management in elderly subjects with peripheral neuropathy. Methods: Clinico-pathological data of 100 elderly subjects aged 65 and above with peripheral neuropathy who underwent nerve biopsy in the last decade (2002–2011) was reviewed. Results: The study included 100 subjects (M : F 78 : 22). Mean age at biopsy and symptom duration was 69.62 ± 4.8 years and 24.17 ± 40.4 months, respectively. The most common pattern of was distal symmetric sensorimotor polyneuropathy (35%), followed by multiple mononeuropathy (29%) and asymmetric sensorimotor neuropathy (15%). The nerve biopsy was ‘diagnostic’ in 24%, (definite vasculitis in 12, leprosy in 10 and acute inflammatory demyelinating polyradiculoneuropathy in 2) and proved ‘essential’ or ‘helpful’ in therapeutic management in 81% subjects. In 60 (60%) patients, where a pre-biopsy aetiological diagnosis could be arrived at based on the available data, nerve biopsy confirmed the diagnosis in 29 of 60 (48.3%), and offered a new diagnosis in 25 (41.7%). A higher yield of biopsy was noted in subjects with asymmetric/multiple mononeuropathy compared with symmetric neuropathies (32.7% versus 17.7%). In 40 (40%) patients without a pre-biopsy aetiological diagnosis, nerve biopsy was ‘essential’ in 7 of 40 (17.5%) as it provided a definitive diagnosis (definite vasculitis: 5, leprosy: 2), and ‘helpful’ in 21 of 40 (52.5%) (ischaemic neuropathy: 10, possible vasculitis: 9, probable vasculitis: 2). Conclusion: Nerve biopsy aided in the detection of potentially treatable disorders and influenced patient management in a significant proportion of elderly subjects with peripheral neuropathy (81%), particularly in subset with undiagnosed neuropathies confirming that it’s a useful tool in diagnosis of neuropathy in the elderly. With minor differences, the aetiological profile in our biopsied neuropathic elderly subjects may reflect the findings in other similar cohorts.

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.

Tangier disease is an autosomal recessive disorder characterized by an abnormal accumulation of cholesterol esters in various organs secondary to adenotriphosphate binding cassette transporter A-1 (ABCA-1) transporter deficiency and disrupted reverse cholesterol transport. It causes neuropathy in half of the affected individuals. We present the clinical, electrophysiological, and histopathological findings in a middle aged gentleman of Tangier disease who was initially misdiagnosed leprosy and treated with antileprosy drugs. The presence of a demyelinating neuropathy on electrophysiology in a patient with predominant upper limb involvement and facial diplegia should raise the suspicion of Tangier disease. The characteristic lipid profile of Tangier disease was noted in this patient viz. extremely low high density lipoprotein (HDL), elevated triglyceride (TG), and reduced apolipoprotein A1. Estimation of serum lipids should form a part of routine evaluation in order to avoid misdiagnosis.

Objective Although psychiatric manifestations are one of the most common presentations of pediatric N-methyl-D-aspartate receptor (NMDAR) encephalitis, there is a lack of studies that characterize psychiatric aspects of this disorder. This study was designed to address this gap. Methods Initial clinical presentations including psychiatric symptoms, treatment details, and outcome with respect to psychiatric symptoms were collected from medical case records of children aged less than 18 years with seropositive NMDAR encephalitis from a single tertiary care center (May 2010-November 2016). The Brief Psychiatric Rating Scale for Children (BPRS-C) was administered at the time of presentation and at follow-up. Results Clinical records from 16 girls and 5 boys of whom 12 were prepubertal (< 12 years) and 9 were postpubertal (≥ 12 years) were analyzed. All 21 children presented with psychiatric symptoms at initial presentation. In 10 children (47.6%), psychiatric symptom was the first symptom. Major psychiatric symptoms included inappropriate crying (most common, 66.7%, n = 14), social withdrawal (57.1%, n = 12), unprovoked anger outburst (47.6%, n = 10), unprovoked screaming behavior (38.1%, n = 8), and talking to self irrelevantly (42.9%, n = 9). In addition to psychiatric symptoms, at least 1 of the following was also seen in all children: speech disturbance (85.7%, n = 18), seizure (85.7%, n = 18), or movement disorder (76.2%, n = 16). Mood symptoms (85.7%, n = 18) were the most common psychopathology. A comorbid psychiatric diagnosis (ICD-10 criteria) was made in 11 children (52.4%); the most common was organic mood disorder (n = 6). The mean BPRS-C score at presentation in prepubertal children was higher than that of postpubertal children (21 vs 17). After immune modulation, clinical improvement was noted after a mean ± SD of 7.4 ± 4.8 months in all 20 children followed up. Three of the 4 children with residual psychiatric symptoms and persistent academic difficulties were prepubertal. Conclusions Psychiatric manifestations that are usually mood related are quite common in pediatric NMDAR encephalitis. Prepubertal presentation of this disorder appears to be more severe and may lead to persistent psychiatric and cognitive symptoms.