Acute bilateral sensorineural hearing loss as presentation of leptomeningeal metastases.

We describe a rare occurrence of bilateral acute severe sensorineural hearing loss in a middle-aged man that heralded the diagnosis of metastatic gastric cancer.

Mesenchymal Stem Cell Therapy in the Treatment of Neurodegenerative Cerebellar Ataxias: a Systematic Review and Meta-analysis.

The objective of this study is to synthesise the findings of clinical studies in order to derive evidence for use of the mesenchymal stem cell (MSC) therapy in the treatment of neurodegenerative cerebellar ataxias. In order to find relevant studies for the systematic review, we searched through Medline (1985 to July 2020), PubMed and Clinical trial register. We included both single-arm and comparative studies in which MSCs were given as intervention in neurodegenerative ataxia patients at any time after the diagnosis. We used Joanna Briggs Institute (JBI) quality scale to evaluate the methodological qualities of the included studies. Our literature search obtained 81 publications. Three articles comprising a total of 47 patients were included in the meta-analysis. None of them were randomised controlled trials (RCTs). Pooled analysis noted that there was a decrease in the Berg Balance Scale (BBS)/Scale for the Assessment and Rating of Ataxia (SARA) score from pre to post assessment; however, the difference was statistically not significant (standardised mean difference (SMD) - 0.20; 95% CI - 0.78 to 0.38). No significant side effects were reported in any of the studies. We did not observe any statistically significant difference in the pooled mean difference in the International Cooperative Ataxia Rating Scale (ICARS) score between pre and post assessment in patients with ataxia after receiving the stem cells (SMD 0.36, 95% CI - 0.08 to 0.81). Our systematic review and meta-analysis concluded that MSC cell therapy appeared safe but provided insufficient evidence to support the use of MSCs to treat patients with neurodegenerative cerebellar ataxia at present. No l RCTs was available in the literature to test efficacy; therefore, well-designed RCTs are needed to ascertain the effectiveness of MSCs in patients with neurodegenerative cerebellar ataxias.

Effect of providing sudden unexpected death in epilepsy (SUDEP) information to persons with epilepsy (PWE) and their caregivers-Experience from a tertiary care hospital.

OBJECTIVE: The primary objective of present study was to observe the effect of providing SUDEP (Sudden Unexpected Death in Epilepsy) information on drug adherence in persons with epilepsy (PWE). We also looked at impact of disclosing SUDEP information on patient's quality of life and mood. MATERIAL AND METHODS: This prospective study had a pretest/post-test design. A total of 231 consecutive PWE (>15 years) were enrolled. Of these 121 PWE received information about SUDEP in addition to standard epilepsy care. One hundred and ten PWE (control group) received routine standard epilepsy care but did not receive SUDEP information. Follow up assessment was done at 6 months. The primary outcome was a change in drug adherence (measured by Modified Morisky Medication Adherence Scale, MMAS) in PWE following disclosure of SUDEP information. RESULTS: After 6 months, 116 PWE in the SUDEP information group and 106 in control group were available for follow up. A non-significant higher adherence was observed in the SUDEP information group as compared to the control group (Mean MMAS change 0.51 ± 1.66 vs 0.25 ± 1.26, P value = 0.194). No significant change was perceived in patient's anxiety and depression levels or quality of life in either group. CONCLUSION: The present study suggests that providing information on SUDEP to PWE and their caregivers may increase drug adherence without adverse effect on quality of life or mood. Well-designed studies with high methodological quality are required to determine the precise effect size associated with disclosure of SUDEP information on drug adherence in PWE.

Parkinson's disease: A review.

Parkinson's disease is a common movement disorder seen in neurological practice, but the diagnosis and management is challenging. The diagnosis is clinical and sometimes difficult, considering a large number of motor and non-motor symptoms in PD patients. The medical management of PD patients is difficult, as choices of drugs are limited and levodopa is the mainstay of treatment. However, levodopa-induced dyskinesia (LID) is commonly seen in Parkinson's disease patients treated with levodopa. This side effect is usually encountered after a long duration of treatment, but occasionally, this may be seen even after a few days or months of treatment. Different types of surgical approaches, including unilateral pallidotomy and deep brain stimulation, have given very good results in PD patients, who cannot be managed by medications alone.

Levosulpiride-Induced Dystonia: 7 Cases.

Levosulpiride is a newer prokinetic agent with increasingly extensive use in India by general physicians. Levosulpiride selectively inhibits gut and central D2 receptors and is associated with various movement disorders like- tremor, Parkinsonism, dyskinesias and rarely dystonia. We report 7 cases of levosulpirideinduced dystonia at our institute. Though all patient had at least 50% improvement after discontinuation of levosulpiride, none had complete recovery at mean follow up of 5.5 months. Through this article we want to highlight extrapyramidal side effects of levosulpiride, need of its awareness among physicians.

Decoding Autoimmune Autonomic Disorders: A Less-Recognized Overlap.

Autoimmune autonomic disorders encompass a spectrum of disorders mediated by immune responses directed against the autonomic nervous system, including the peripheral and central autonomic pathways. While centrally mediated autoimmune autonomic disorders primarily can cause autonomic hyperactivity, peripherally mediated disorders are more common and can cause either locally confined or global autonomic failure. These disorders are often underrecognized owing to vague and varied clinical signs and symptoms. The discovery of specific autoantibodies in the past decade has caused a growing recognition of autoimmune causes for these disorders. The management is also complex, as these disorders often manifest with generalized symptoms, are difficult to diagnose, invoke challenges involving robust establishment of an autoimmune syndrome, and are rare. This article presents an overview of autonomic disorders that have a suspected autoimmune etiology, as well as recent advancements in their diagnosis and management.

Loss of Ambulation Due to Calcific Myonecrosis: A Rare but Reversible Complication of Wilson's Disease.

ABSTRACT: We report two cases of established Wilson's disease (WD) presenting with calcific myonecrosis of the pelvic girdle in association with pelvic fractures. Despite initial improvement with chelation, subacute worsening of ambulation in both led to a consideration of neurologic deterioration on chelation therapy. However, evaluation revealed calcific myonecrosis of the hip joint and adjacent muscles as the cause. Both patients improved with intensive rehabilitation. A review of literature indicates that although osseomuscular complications are reported in WD, calcific myonecrosis is a hitherto unknown entity which, if recognized early, may be reversed, preventing disability and unnecessary change in chelation regimens.

Decoding Multiple Antibody Positivity: Lessons from Paraneoplastic Sensory Ataxia.

Paraneoplastic neurologic syndromes are cancer-associated, immune-mediated neurologic manifestations that may involve any part of the nervous system. They usually present with characteristic neurologic features and should be considered in high-risk phenotypes such as limbic encephalitis, encephalomyelitis, rapidly progressive cerebellar syndrome, opsoclonus-myoclonus, sensory neuronopathy, enteric neuropathy, and Lambert-Eaton myasthenic syndrome. The diagnosis is made by antibody positivity in the serum or cerebrospinal fluid, in the presence of an appropriate clinical phenotype. Findings on antibody testing by immunoblot should always be verified by immunofluorescence. We report a rare case of sensory neuronopathy with triple paraneoplastic antibody positivity (anti-Hu, anti-collapsing response-mediator protein 5, and anti-amphiphysin) on immunoblot but only anti-Hu positivity on immunofluorescence. The presence of lower facial dyskinesias should raise the possibility of an immune-mediated neurologic syndrome in the appropriate clinical context.

Essential Tremor and Essential Tremor Plus Are Essentially Similar Electrophysiologically.

BACKGROUND: The merits of classifying the heterogeneous group of essential tremors into essential tremor (ET) and essential tremor plus (ETP) are debated. OBJECTIVES: We studied the electrophysiological and spiral characteristics of tremor in ET and ETP. METHODS: We reviewed standardized videos from a tremor database and clinically classified patients into ET, ETP, or dystonic tremor (DT). The following variables were derived from combined tri-axial accelerometry-surface electromyography (EMG)-peak frequency, total power, peak power, full width half maximum, tremor stability index and EMG-coherence. We analyzed hand-drawn spirals to derive mean deviation, tremor variability, inter-, and intra-loop widths. We compared these variables among the groups. RESULTS: We recruited 72 participants (81.9% male) with mean age 47.7 ± 16.1 years and Fahn-Tolosa-Marin Tremor Rating Scale total score 31.1 ± 14.1. Patients with ET were younger (P = 0.014) and had less severe tremor (P = 0.020) compared to ETP and DT. In ETP group, 48.6% had subtle dystonia. Peak frequency was greater in ETP (7.3 ± 0.3 Hz) compared to DT (6.1 ± 0.4 Hz; P = 0.024). Peak power was greater in ETP and DT for postural tremor. Rest tremor was recordable on accelerometry in 26.7% of ET. Other variables were similar among the groups. CONCLUSION: Electrophysiological evaluation revealed postural tremor of frequency 6 to 7 Hz in ET, ETP, and DT with subtle differences more severe tremor in ETP and DT, and higher frequency in ETP compared to DT. Our findings suggest a similar tremor oscillator in these conditions, supporting the view that these entities are part of a spectrum of tremor disorders, rather than distinct etiological entities.

Phenomenological patterns and aetiological spectrum in patients visiting a tertiary care Movement disorders service in India: An observational study.

OBJECTIVE: Although previous studies have described phenomenological diagnoses, they lacked description of aetiological spectrum in patients visiting movement disorders (MD) service. Herein, we classify the MD phenomenology and describe aetiology wise distribution of each phenomenology in patients visiting a tertiary care movement disorders service. METHODS: Collected information included demographic profile (age of onset, age at presentation, gender, duration of illness before presentation), predominant MD phenomenology [such as parkinsonism, dystonia, ataxia, tremor, chorea, ballism, myoclonus, tics, stereotypy, restless legs syndrome (RLS) and others], diagnostic evaluations and detected aetiology. RESULTS: This observational study included 1140 MD patients over a span of 5 years. The median (IQR) age of onset was 49 (35-60) years and age at presentation was 54 (40-65) years, with median duration of illness being 36 (18-72) months. Nearly two-third of patients were males (M:F=731:409). Parkinsonism (n=494, 43.3 %) was the most common MD phenomenology observed, followed by dystonia (n=219, 19.2 %), ataxia (n=125, 11 %), tremor (n=118, 10.4 %), myoclonus (n=73, 6.4 %), chorea (n=40, 3.5 %), spasticity (n=22, 1.9 %), tics (n=8, 0.7 %), and RLS (n=8, 0.7 %). Thirty-three (2.9 %) patients were grouped under miscellaneous MDs. Overall, neurodegenerative disorders (57.4 %) were the most common cause of MDs. Parkinson's disease, genetic dystonia, essential tremor, genetic ataxias, hemifacial spasm, and Huntington's disease were the most common aetiologies for parkinsonism, dystonia, tremor, ataxia, myoclonus, and chorea, respectively. CONCLUSION: Parkinsonism was the most common phenomenology observed in MD patients, and was followed by dystonia, ataxia and tremor. Neurodegenerative disorders were the most common aetiology detected.

Expanding the phenotypic and genotypic spectrum of DYT-TUBB4A with seven patients from India.

BACKGROUND: Variants in the TUBB4A gene are associated with dystonia (DYT-TUBB4A), Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-ABC) and spastic paraplegia. Phenotypes intermediate to these three broad phenotypes are also observed. These are rare disorders, and data from diverse populations remains limited. We report seven Indian cases with dystonia phenotype related to TUBB4A mutation. CASES: Among these seven patients, age at onset ranged from 5 to 48 years. Five patients had cranio-cervical onset of dystonia. One patient had prominent parkinsonism with dystonia. Patients responded well to botulinum toxin injected for laryngeal, cervical and jaw dystonia. The patient with parkinsonism responded well to levodopa, albeit with development of dyskinesias. Apart from the common p.Arg2Gly variant in three patients with DYT-TUBB4A, other variants included p.Arg262Pro, p.Arg39Cys and p.Asp245Asn. CONCLUSIONS: We report the first collection of cases with TUBB4A mutation from India. We expand the phenotype to include levodopa-responsive parkinsonism. Indian patients, consistent with global literature, harbor prominent adductor dysphonia, cervical and jaw dystonia, which responds well to botulinum treatment.

Safety and Efficacy of Injection Tenecteplase in 4.5 to 24 Hours Imaging Eligible Window Patients with Acute Ischemic Stroke (EAST-AIS) - Study Protocol.

BACKGROUND AND AIMS: Tenecteplase is used as the standard of care treatment for thrombolysis in acute ischemic stroke (AIS) patients within 4.5 h of symptom onset. Documented reports were less certain to claim the benefits of it in an extended window period. EAST-AIS (CTRI/2022/03/040718) trial is designed to determine the success rate of thrombolysis in an extended window period for good clinical outcomes. STUDY DESIGN: It is a randomized, placebo-controlled trial of tenecteplase administered within 4.5-24 h of stroke onset (with or without large vessel occlusion) based on evidence of salvageable tissue through baseline computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) scan. Criteria of patient inclusion are as follows: patients of both genders (male and female), age >18 years, pre-stroke modified Ranking Scale (mRS) <2, baseline NIHSS >5, CTP showing penumbra-ischemic core ratio >1.8, absolute difference in volume >10 ml, and ischemic core volume <70 ml. The sample size for the study is 100 patients: 50 in the tenecteplase arm (0.25 mg/kg body weight; maximum- 25 mg) and 50 in the placebo arm (controls). STUDY OUTCOMES: The study's primary objective is safety endpoints along with the efficacy of tenecteplase assessed using the mRS score at 90 days of stroke onset. CONCLUSION: The result obtained from EAST-AIS will determine the safety and efficacy of tenecteplase injection administered 4.5-24 h following the symptom onset for AIS patients within the territory of Internal Carotid Artery (ICA), Middle Cerebral Artery (MCA), or Anterior Cerebral Artery (ACA) occlusion.

The role of susceptibility-weighted imaging & contrast-enhanced MRI in the diagnosis of primary CNS vasculitis: a large case series.

Primary CNS Vasculitis (PCNSV) is a rare, diverse, and polymorphic CNS blood vessel inflammatory condition. Due to its rarity, clinical variability, heterogeneous imaging results, and lack of definitive laboratory markers, PCNSV diagnosis is challenging. This retrospective cohort analysis identified patients with histological diagnosis of PCNSV. Demographic data, clinical presentation, neuroimaging studies, and histopathologic findings were recorded. We enrolled 56 patients with a positive biopsy of CNS vasculitis. Most patients had cerebral hemisphere or brainstem symptoms. Most brain MRI lesions were bilateral, diffuse discrete to confluent white matter lesions. Frontal lobe lesions predominated, followed by inferior cerebellar lesions. Susceptibility-weighted imaging (SWI) hemorrhages in 96.4% (54/56) of patients, either solitary microhemorrhages or a combination of micro and macrohemorrhages. Contrast-enhanced T1-WIs revealed parenchymal enhancement in 96.3% (52/54 patients). The most prevalent pattern of enhancement observed was dot-linear (87%), followed by nodular (61.1%), perivascular (25.9%), and patchy (16.7%). Venulitis was found in 19 of 20 individuals in cerebral DSA. Hemorrhages in SWI and dot-linear enhancement pattern should be incorporated as MINOR diagnostic criteria to diagnose PCNSV accurately within an appropriate clinical context. Microhemorrhages in SWI and venulitis in DSA, should be regarded as a potential marker for PCNSV.

Tuberculosis of the Spinal Cord.

Tuberculosis involving the spinal cord is associated with high mortality and disabling long-term sequelae. Although tuberculous radiculomyelitis is the most frequent complication, pleomorphic clinical manifestations exist. Diagnosis can be challenging among patients with isolated spinal cord tuberculosis due to diverse clinical and radiological presentations. The principles of management of tuberculosis of the spinal cord are primarily derived from, and dependent upon, trials on tuberculous meningitis (TBM). Although facilitating mycobacterial killing and controlling host inflammatory response within the nervous system remain the primary objectives, several unique features require attention. The paradoxical worsening is more frequent, often with devastating outcomes. The role of anti-inflammatory agents such as steroids in adhesive tuberculous radiculomyelitis remains unclear. Surgical interventions may benefit a small proportion of patients with spinal cord tuberculosis. Currently, the evidence base in the management of spinal cord tuberculosis is limited to uncontrolled small-scale data. Despite the gargantuan burden of tuberculosis, particularly in lower and middle-income countries, large-scale cohesive data are surprisingly sparse. In this review, we highlight the varied clinical and radiological presentations, performance of various diagnostic modalities, summarize data on the efficacy of treatment options, and propose a way forward to improve outcomes in these patients.

Sarcoidosis presenting as progressive multifocal leukoencephalopathy in an apparently immunocompetent adult.

Neurological involvement in sarcoidosis is termed as neurosarcoidosis. It usually leads to cranial neuropathies, although it can involve any part of the neuroaxis. Although sarcoidosis is a proinflammatory state, there is an associated anergic state demonstrable by a feeble tuberculin response. Lymphocytic sequestration in granulomas can be associated with peripheral CD4 lymphocytopenia (40% of patients with sarcoidosis) predisposing to opportunistic infections. Here we have described a young, otherwise immunocompetent male presenting with subacute onset right hemiparesis with motor aphasia, who was diagnosed to have progressive multifocal leukoencephalopathy (PML) secondary to pulmonary sarcoidosis. We want to emphasize that PML should be considered as a differential in all cases of secondary demyelination (even apparently immunocompetent individuals) as early diagnosis and treatment of the underlying cause is likely to yield better outcomes.

De Novo Movement Disorders Associated with COVID-19- A Systematic Review of Individual Patients.

Background: COVID-19 infection is associated with neurological manifestations, including various types of movement disorders (MD). A thorough review of individual patients with COVID-19-induced MD would help in better understanding the clinical profile and outcome of these patients and in prognostication. Objective: We conducted an individual patient-systematic review to study the clinical and imaging profile and outcomes of patients with COVID-19-associated MD. Methods: A systematic literature search of PubMed, EMBASE, and Cochrane databases was conducted by two independent reviewers. Individual patient data COVID from case reports and case series on COVID-19-associated MD, published between December 2019 and December 2022, were extracted and analyzed. Results: Data of 133 patients with COVID-19-associated MD from 82 studies were analyzed. Mean age was 55 ± 18 years and 77% were males. A mixed movement disorder was most commonly seen (41%); myoclonus-ataxia was the most frequent (44.4%). Myoclonus significantly correlated with age (odds ratio (OR) 1.02 P = 0.03, CI 1-1.04). Tremor had the longest latency to develop after SARS-CoV-2 infection [median (IQR) 21 (10-40) days, P = 0.009, CI 1.01-1.05]. At short-term follow-up, myoclonus improved (OR 14.35, P value = 0.01, CI 1.71-120.65), whereas parkinsonism (OR 0.09, P value = 0.002, CI 0.19-0.41) and tremor (OR 0.16, P value = 0.016, CI 0.04-0.71) persisted. Conclusion: Myoclonus-ataxia was the most common movement disorder after COVID-19 infection. Myoclonus was seen in older individuals and usually improved. Tremor and parkinsonism developed after a long latency and did not improve in the short-term.