From periphery to center, untold story of pure neuritic leprosy: an electrophysiological study.

BACKGROUND: Pure neuritic leprosy (PNL) is uncommon form of leprosy involving peripheral nerves. Some isolated case reports have shown imaging changes in the central nervous system (CNS) and also impairment in visual evoked potential (VEP), somatosensory evoked potential (SSEP) and brain stem auditory-evoked potentials (BAEPs) parameters in PNL, but there is lack of large study. This prospective observational study evaluates impairment in these central conduction studies among PNL patients. METHODS: We screened patients with leprosy presenting with features of neuropathy and/or thickened nerves. Patients with bacilli-positive nerve biopsies were included in the study and subjected to routine tests along with nerve conduction study (NCS), VEP, tibial SSEP and BAEPs. Parameters of these studies were analyzed based on data from previous studies. RESULTS: Of 76 patients screened for PNL 49 had positive findings in biopsy. Most of patients were male and mean age group was 46.35 ± 15.35 years. Mononeuritis multiplex was most common NCS pattern in 46.93% (23/49) patients. We found abnormal VEP in 13 out of 35 patients (37.14%). Similarly abnormal SSEP and BAEPs among 42.85% and 40% patients respectively. DISCUSSION: This study shows that in PNL significant number of patients have subclinical CNS involvement. Exact pathophysiology of CNS involvement is not known till now but study of VEP, SSEP and BAEPs parameter may help in early diagnosis of PNL.

IMPETUS Stroke: Assessment of hospital infrastructure and workflow for implementation of uniform stroke care pathway in India.

BACKGROUND: India accounts for 13.3% of global disability-adjusted life years (DALYs) lost due to stroke with a relatively younger age of onset compared to the Western population. In India's public healthcare system, many stroke patients seek care at tertiary-level government-funded medical colleges where an optimal level of stroke care is expected. However, there are no studies from India that have assessed the quality of stroke care, including infrastructure, imaging facilities, or the availability of stroke care units in medical colleges. AIM: This study aimed to understand the existing protocols and management of acute stroke care across 22 medical colleges in India, as part of the baseline assessment of the ongoing IMPETUS stroke study. METHODS: A semi-structured quantitative pre-tested questionnaire, developed based on review of literature and expert discussion, was mailed to 22 participating sites of the IMPETUS stroke study. The questionnaire assessed comprehensively all components of stroke care, including human resources, emergency system, in-hospital care, and secondary prevention. A descriptive analysis of their status was undertaken. RESULTS: In the emergency services, limited stroke helpline numbers, 3/22 (14%); prenotification system, 5/22 (23%); and stroke-trained physicians were available, 6/22 (27%). One-third of hospitals did not have on-call neurologists. Although non-contrast computed tomography (NCCT) was always available, 39% of hospitals were not doing computed tomography (CT) angiography and 13/22 (59%) were not doing magnetic resonance imaging (MRI) after routine working hours. Intravenous thrombolysis was being done in 20/22 (91%) hospitals, but 36% of hospitals did not provide it free of cost. Endovascular therapy was available only in 6/22 (27%) hospitals. The study highlighted the scarcity of multidisciplinary stroke teams, 8/22 (36%), and stroke units, 7/22 (32%). Lifesaving surgeries like hematoma evacuation, 11/22 (50%), and decompressive craniectomy, 9/22 (41%), were performed in limited numbers. The availability of occupational therapists, speech therapists, and cognitive rehabilitation was minimal. CONCLUSION: This study highlighted the current status of acute stroke management in publicly funded tertiary care hospitals. Lack of prenotification, limited number of stroke-trained physicians and neurosurgeons, relatively lesser provision of free thrombolytic agents, limited stroke units, and lack of rehabilitation services are areas needing urgent attention by policymakers and creation of sustainable education models for uniform stroke care by medical professionals across the country.

Equipotency of lacosamide to levetiracetam in new onset focal epilepsy: A randomized controlled trial.

Objectives: Levetiracetam (LEV) is a well-established broad spectrum antiseizure medication (ASM) effective in focal, generalized, and myoclonic seizures whereas lacosamide (LCM) is a comparatively newer ASM currently approved only as an add-on agent in focal seizures. The aim of the study was to assess the efficacy and the tolerability of oral LCM as monotherapy in adult people with epilepsy (PWE) with new onset focal onset epilepsy compared with those receiving LEV. Materials and Methods: In this open-label single-center non-inferiority trial, PWE aged between 16 and 65 years suffering from new onset focal seizures, with or without secondary generalization were put on LCM monotherapy or LEV monotherapy. Data regarding demographic characteristics, seizure type and etiology, LCM and LEV daily dose, seizure frequency at baseline and at 6 months of follow-up, and seizure freedom rates were recorded. Results: Thirty-five PWE on LCM (24 males), their mean age: 38.20 ± 16.62 years and 35 PWE on LEV (25 males, mean age: 38.91 ± 17.13 years) were enrolled. The most common type of seizure observed was focal to bilateral tonic-clonic seizure >70% followed by focal impaired awareness seizure and focal awareness seizure. Structural epilepsy was found in 21 among LCM group and 22 of LEV group. In the LCM group, the seizure frequency decreased from 3.33 ± 1.88 to 0.85 ± 1.09 (P = 0.001) at 6 months and from 3.61 ± 3.12 to 0.94 ± 1.24 (P = 0.001) in LEV group, intergroup difference (P = 0.74). At 6-month follow-up period, 78.9% in LCM arm and 87.9% in the LEV arm had experienced a 50% of reduction in seizure frequency while seizure freedom was attained in 43.3% of PWE in both the arms (P = 1). The most common treatment emergent adverse effects in the LCM group were fatiguability, dyspepsia, headache, and dizziness, while in the LEV group; somnolence and behavioral abnormality. Conclusion: Treatment with LCM met the non-inferiority criteria when compared with LEV. Therefore, it might be useful as first-line monotherapy for adults with newly diagnosed focal epilepsy.

Guillain-Barre syndrome as the initial presentation of systemic lupus erythematosus: Case report with a systematic and literature review.

Systemic lupus erythematosus (SLE) can affect multiple systems in which central nervous system (CNS) involvement is common, but peripheral nervous system involvement is also increasingly being recognized. Guillian-Barre syndrome (GBS) as the first manifestation of SLE has been reported, but rare and not well understood. A 39-year female presented with GBS-like illness but on evaluation found to have features of SLE. Cerebrospinal fluid (CSF) showed characteristic albuminocytological dissociation and nerve conduction study (NCS) was suggestive of demyelinating polyradiculoneuropathy. On evaluation, she was found to have polyarthralgia, autoimmune hemolytic anemia, class I Lupus nephritis, mild splenomegaly, and pleural effusion. Serum antinuclear antibody was 4+ positive (coarse speckled) and extractable nuclear antigen profile revealed anti-dsDNA and anti-Sm antibody positivity, with low complement level. She fulfilled the diagnostic criterion of SLE and was managed with both plasmapheresis and pulse steroids followed by cyclophosphamide monthly pulse and oral hydroxychloroquine maintenance and showed significant improvement. The literature review showed only 26 cases reported till now. GBS without any obvious trigger should be extensively evaluated, as the underlying etiology will affect the treatment protocol as well as the prognosis. Our report highlights the significance of early recognition of SLE as a trigger of GBS, which changes conventional GBS treatment.

A Study of Organophosphorus Induced Delayed Myelopathy: Uncommon Sequelae of a Common Poisoning.

Introduction: Organophosphorus (OP) compounds, with their lipophilicity, are responsible for a spectrum comprising of acute cholinergic symptoms, intermediate syndrome, as well as delayed neurological sequelae in the form of OP-induced delayed neuropathy and subsequently, myeloneuropathy with predominantly thoracic cord affection, manifested on partial recovery of the neuropathy. The pathogenesis of this myeloneuropathy in humans is still not well perceived. Aim of Study: To determine the onset and course of development of delayed myeloneuropathy in patients of OP poisoning. Materials and Methods: Twelve patients of OP ingestion presenting with delayed myeloneuropathy were evaluated with prior history, examination, MR imaging, nerve conduction and electromyography studies, and various evoked potentials to elicit the pattern of disease manifestation and progression. Results: Among the included patients, a majority had consumed chlorpyrifos and permethrin composition, a majority had undergone gastric lavage. Five (41.7%) had experienced acute worsening and 8 (66.7%) patients had developed intermediate syndrome. OPIDN had appeared after a median of 4 (1-8) weeks after the poisoning. All patients had lower limb hypertonia with wasting and distal more than proximal weakness with pure motor or sensorimotor involvement. MRI showed thoracic cord atrophy in 3 (25%) patients. Motor-evoked potential with reduced amplitude was noted in lower limbs on lumbar stimulation but absent on cortical stimulation. Conclusion: Various animal models have shown similar patterns of neurotoxicity in OP poisoning with predominant thoracic cord pathology. Further research in humans may be undertaken to elicit the pathogenesis, thereby improving the treatment modality.

Super refractory status epilepticus as a possible manifestation of COVID-19 disease.

Coronavirus disease 2019 (COVID-19) is one of the worst pandemics in history, caused by severe acute respiratory syndrome coronavirus-2, a novel zoonotic coronavirus. COVID-19 disease can present from asymptomatic or mild infection to rapidly progressive, acute respiratory distress syndrome, and death. Neurological presentation is not so uncommon now. Super refractory status epilepticus (SRSE) can be a possible manifestation of COVID-19 disease. Here, we report a patient affected by COVID-19 who presented with SRSE.

Craniospinal MRI Findings in Neuromelioidosis.

Background: Melioidosis is a bacterial infection caused by Burkholderia pseudomallei that is endemic in Southeast Asia, northern Australia, and Africa. Neurological involvement is rare and reported in 3-5% of total cases. Objective: The purpose of this study was to report a series of cases of melioidosis with neurological involvement and a brief review of the literature. Materials and Methods: We collected the data from six melioidosis patients having neurological involvement. Clinical, biochemical, and imaging findings were analyzed. Result: All patients in our study were adults (age range 27 to 73 years). The presenting symptoms were fever of varying duration (range 15 days to 2 months). Altered sensorium was noted in five patients. Four cases had brain abscess, one had meningitis, and one had a spinal epidural abscess. All cases of brain abscesses were T2 hyperintense with an irregular wall showing central diffusion restriction and irregular peripheral enhancement. The trigeminal nucleus was involved in one patient, but there was no enhancement of the trigeminal nerve. Extension along the white matter tract was noted in two patients. Magnetic resonance (MR) spectroscopy done in two patients showed increased lipid/lactate and choline peak in both of them. Conclusion: Melioidosis can present as multiple micro-abscesses in the brain. Involvement of the trigeminal nucleus and extension along the corticospinal tract may raise the possibility of infection by B. pseudomallei. Meningitis and dural sinus thrombosis, although rare, can be presenting features.

Sleep quality evaluation, correlation with headache frequency, and propensity to conversion from episodic to chronic daily headache in migraine patients: A cross-sectional study.

Objective: The aim of the study was to determine the association between sleep quality with headache frequency in migraine patients and also to evaluate migraine trigger and non-headache symptoms in episodic and chronic migraine groups and evaluation of the same in poor and good sleepers (GSs) in migraine population. Materials and Methods: In a cross-sectional and observational study in a tertiary care hospital of East India between January 2018 and September 2020, migraine patients were evaluated. Migraine patients were divided into two groups: Episodic migraine (EM) and chronic migraine (CM) group according to ICHD 3 b classification and into poor sleepers (PSs, Global Pittsburgh Sleep Quality Index [PSQI] >5) and GSs (Global PSQI ≤5). Sleep was evaluated using PQSI - a self-rated questionnaire and disease pattern, associated non-headache symptoms, and triggers were evaluated in between groups. Demographic, headache character, and sleep parameters including seven "component" scores: Subjective sleep quality, sleep latency, sleeps duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction and global PQSI were compared between groups (EM and CM). Similar parameters were also compared between PSs and GSs group. Statistical analysis was performed using the χ2 test for categorical variables and the t-test and Wilcoxon rank-sum test for continuous variables. Correlation between two normally distributed numerical was tested by Pearson correlation coefficient assessment. Results: One hundred migraine patients were analyzed, among which 57 were PSs and 43 were GSs and 51 patients had EM and 49 patients had CM. Moderately significant "r" value noted in between headache frequency and global PQSI score (r = 0.45, P < 0.01). In non-headache symptoms, blurring of vision (EM 8 [16%] and CM 16 [33%] P = 0.05), nasal congestion (EM - 3 [6%] and CM - 12 [24%], P = 0.01), and cervical muscle tenderness (EM- 23 [45%] and CM - 34 [69%], P = 0.01) were more prevalent in chronic headache group along with allodynia (EM - 11 [22%] and CM - 25 [51%], P < 0.01). Conclusion: Chronic headache group had poor subjective sleep quality, increased sleep latency, decreased sleep duration, decreased sleep efficiency, and increased sleep disturbance in comparison to episodic group which has therapeutic implication. The non-headache symptoms which are more prevalent in CM patients increase the overall disability.

A Study of Diffusion Tensor Imaging in Central Post-Stroke Pain: Traveling Beyond the Pain Pathways.

Introduction: Central post-stroke pain (CPSP), seen in the aftermath of a stroke, is an underdiagnosed entity but quite a disabling complication. All the postulated theories regarding the pathogenesis of CPSP point to its origin in the central pain pathways. However, this study attempts to demonstrate the role of other contributing areas in the generation of CPSP. Materials and Methods: In this single-center tertiary care hospital-based study, 24 patients with both ischemic and hemorrhagic strokes of variable durations were recruited, and Magnetic Resonance Imaging (MRI) imaging with diffusion tensor imaging (DTI) acquisition was done. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values of the spinothalamic tract (STT), corticospinal tract (CST), superior thalamic radiation (STR), basal ganglia (BG), and primary somatosensory cortex (SSC) were compared between normal and abnormal sides and also in extrathalamic lesions separately. Results: Significant differences with lower FA were noted in STT, CST, STR, and SSC and higher ADC values in BG, STR, CST, and SSC on comparison between the normal and lesion sides. On individual sub-analysis, ischemic stroke had significant changes in the FA value of CST and the ADC value of STR and CST, while hemorrhagic stroke had significant changes in the FA and ADC values of STR and SSC, as well as the FA value of STT. In the analysis of the extrathalamic strokes, significance persisted in all the studied parameters except the BG. The CST abnormalities were evident even in patients with clinical motor improvement. On multivariate analysis, visual analogue scale score severity was correlated with thalamic lesions. Conclusion: Contrary to the belief that STT is solely responsible for CPSP, the role of CST, STR, BG, and SSC as contributing areas is evident from this study and may be more well established if studied in a larger population.

Study Protocol: IMPETUS: Implementing a Uniform Stroke Care Pathway in Medical Colleges of India: IMPETUS Stroke.

Introduction: In India, a national program for stroke (national programme for the control of cardiovascular diseases, diabetes, cancer, and stroke) and stroke management guidelines exist. Its successful implementation would need an organized system of stroke care in practice. However, many challenges exist including lack of awareness, prehospital notification systems, stroke ready hospitals, infrastructural weaknesses, and rehabilitation. We present here a protocol to investigate the feasibility and fidelity of implementing a uniform stroke care pathway in medical colleges of India. Methods and Analysis: This is a multicentric, prospective, multiphase, mixed-method, quasi-experimental implementation study intended to examine the changes in a select set of stroke care-related indicators over time within the sites exposed to the same implementation strategy. We shall conduct process evaluation of the implementation process as well as evaluate the effect of the implementation strategy using the interrupted time series design. During implementation phase, education and training about standard stroke care pathway will be provided to all stakeholders of implementing sites. Patient-level outcomes in the form of modified Rankin Scale score will be collected for all consecutive patients throughout the study. Process evaluation outcomes will be collected and reported in the form of various stroke care indicators. We will report level and trend changes in various indicators during the three study phases. Discussion: Acute stroke requires timely detection, management, and secondary prevention. Implementation of the uniform stroke care pathway is a unique opportunity to promote the requirements of homogenous stroke care in medical colleges of India.

Advances in the Understanding of Pathophysiology of TTH and its Management.

BACKGROUND: Tension-type headache (TTH) is the most common form of primary headache. OBJECTIVE: The aim of this study was to document and summarize the advances in the understanding of TTH in terms of pathogenesis and management. MATERIAL AND METHODS: We reviewed the available literature on the pathogenesis and management of TTH by searches of PubMed between 1969 and October 2020, and references from relevant articles. The search terms "tension-type headache", "episodic tension-type headache", chronic tension-type headache, "pathophysiology", and "treatment" were used. RESULTS: TTH occurs in two forms: episodic TTH (ETTH) and chronic TTH (CTTH). Unlike chronic migraine, CTTH has been less thoroughly studied and is a more difficult headache to treat. Frequent ETTH and CTTH are associated with significant disability. The pathogenesis of TTH is multifactorial and varies between the subtypes. Peripheral mechanism (myofascial nociception) and environmental factors are possibly more important in ETTH, whereas genetic and central factors (sensitization and inadequate endogenous pain control) may play a significant role in the chronic variety. The treatment of TTH consists of pharmacologic and non-pharmacologic approaches. Simple analgesics like NSAIDs are the mainstays for acute management of ETTH. CTTH requires a multimodal approach. Preventive drugs like amitriptyline or mirtazapine and non-pharmacologic measures like relaxation and stress management techniques and physical therapies are often combined. Despite these measures, the outcome remains unsatisfactory in many patients. CONCLUSION: There is clearly an urgent need to understand the pathophysiology and improve the management of TTH patients, especially the chronic form.

Effect of add-on melatonin on seizure outcome, neuronal damage, oxidative stress, and quality of life in generalized epilepsy with generalized onset motor seizures in adults: A randomized controlled trial.

Epilepsy treatment is challenging because of multiple impediments like lack of efficacy of monotherapy, adverse drug reactions, and different comorbidities. Add-on therapy to first-line antiepileptics may be the option to overcome therapeutic hurdles. The present randomized, double-blind, add-on placebo-controlled clinical trial was conducted to evaluate the effect of add-on melatonin in the treatment of generalized epilepsy with generalized onset motor seizure in adults. The control group (n = 52) received add-on placebo, and the test group (n = 52) received add-on melatonin (3 mg/day) with valproate (20 mg/kg in two divided doses). Clinical evaluation of seizure frequency, Chalfont-National Hospital seizure severity scale (NHS3), Pittsburgh sleep quality index (PSQI), quality of life in epilepsy inventory, Epworth sleepiness scale (ESS), and biochemical estimation of serum neuron-specific enolase (NSE) and glutathione reductase were done at baseline and compared with follow-up at 8 weeks. Among 104 patients randomized [mean (SD) age of 27.6 (11.5); 84 (80.8%) male], 88 (84.6%) completed the trial. The responder rate and seizure-free rate in the test group were significantly (p = 0.006 and 0.034) higher than the control group. There was a significantly higher reduction in the frequency of seizures (p = 0.016) and NHS3 (-2.39; 95%CI: -4.56 to -0.21; p = 0.032) in the test group compared to the control group. Similarly, improvement in PSQI (-1.40; 95%CI: -2.64 to -0.15; p = 0.029) was significantly better in the test group. There was no significant difference in the change in ESS (p = 0.621) and quality of life scoring (p = 0.456) between the study groups. The decrease in serum NSE was significantly higher with the test group compared to the control group (-2.01; 95% CI: -3.74 to -0.27; p = 0.024). Add-on melatonin increased serum glutathione reductase significantly (p = 0.038), but there was no significant difference between the groups (p = 0.685). Add-on melatonin with valproate for generalized epilepsy with generalized onset motor seizures in adults can achieve a significantly better clinical outcome by reducing the seizure frequency, severity and attaining a better seizure-free rate in comparison to the control group.

Skeletal Muscle Involvement in Wilson Disease: Clinical and Magnetic Resonance Imaging (MRI) Observations in 2 Families.

OBJECTIVE: Skeletal muscle involvement in Wilson disease is rare. Calf muscle pain might be attributed as growing pain in children. We report calf muscle involvement in Wilson disease and describe the magnetic resonance imaging (MRI) findings of leg, differential diagnosis with literature review. PATIENTS AND METHODS: Our observations describe calf muscle MRI abnormality in 5 cases of Wilson disease from 2 families. The clinical presentations were neurologic in 3, hepatic in 1, and asymptomatic in 1 patient. We systematically describe the clinical characteristics and their calf muscle MRI findings. RESULTS: Three patients had bilateral calf pain and intermittent cramps. The pain was of mild to moderate intensity and managed symptomatically. Serum alkaline phosphatase, creatinine phosphokinase, and needle electromyography were normal. Turbo inversion recovery magnitude sequence MRI of calf muscle revealed hyperintensity in bilateral gastrocnemii muscles. These muscles appear hyperintense in diffusion-weighted imaging. CONCLUSION: The calf muscle involvement could be attributed to muscle edema due to copper-induced muscle toxicity mediated by inhibition of Na+/K+-ATPase on cellular membranes of fast-twitch gastrocnemii muscles which contain predominant type II myofiber. In Wilson disease patients with calf pain or cramps, muscle MRI may show nonspecific gastrocnemius hyperintensity. Further evaluation may give insight into its pathophysiology.

Skull base and calvarial tuberculosis presenting as chronic meningitis.

Calvarial tuberculosis is very rare accounting for 0.2-1.3% of skeletal tuberculosis. Diagnosis is also challenging in these areas due to insidious onset of presentation, low bacterial loads in these sites and unapproachable locations for sample collection. Rarely these patients may presents with features of meningitis when the adjacent meninges are involved. Here we describe a case where tubercular involvement of sphenoid, clivus, and frontal bone, who presented as chronic meningitis and diagnosis was made on the basis of radiological and histopathological findings. All the lesions almost resolved following antitubercular treatment at 5 months follow up. A high index of suspicion is needed for early diagnosis and management of this condition.