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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. [ABSTRACT FROM AUTHOR]

Background: Neuropathic Tremor (NT) is a postural/kinetic tremor of the upper extremity, often encountered in patients with chronic neuropathies such as paraprotein‐associated and hereditary neuropathies. Objectives: To describe the clinical and electrophysiological features of NT in a previously underrecognized setting‐ during recovery from Guillain‐Barré Syndrome (GBS). Methods: Patients with a documented diagnosis of GBS in the past, presenting with tremor were identified from review of clinical records. Participants underwent structured, videotaped neurological examination, and electrophysiological analysis using tri‐axial accelerometry‐surface electromyography. Tremor severity was assessed using the Fahn‐Tolosa‐Marin Tremor Rating Scale. Results: We describe the clinical and electrophysiological features of 5 patients with GBS associated NT. Our cohort had a fine, fast, and slightly jerky postural tremor of frequency ranging from 8 to 10 Hz. Dystonic posturing and overflow movements were noted in 4/5 patients. Tremor appeared 3 months–5 years after the onset of GBS, when patients had regained near normal muscle strength and deep tendon jerks were well elicitable. Electrophysiological analysis of tremor strongly suggested the presence of a central oscillator in all patients. Conclusion: NT is not limited to chronic inflammatory or hereditary neuropathies and may occur in the recovery phase of GBS. The tremor is characterized by a high frequency, jerky postural tremor with dystonic posturing. Electrophysiological evaluation suggests the presence of a central oscillator, hypothetically the cerebellum driven by impaired sensorimotor feedback. [ABSTRACT FROM AUTHOR]

Background: Device‐assisted and neuromodulatory therapies are the standard of care for Parkinson's disease (PD) with disabling motor complications. We aimed to compare and rank the currently available advanced therapies for PD on patient relevant outcomes. Methods: We searched various databases for randomized controlled trials that studied subthalamic nucleus deep brain stimulation (STN‐DBS), globus pallidus interna (GPi) DBS, pallidotomy, subthalamotomy, continuous subcutaneous apomorphine infusion (CSAI), or intrajejunal levodopa infusion (IJLI), in patients with PD and motor complications. Primary outcome was the quality of life (QOL) at 6 months. Secondary outcomes included Unified Parkinson's Disease Rating Scale III and II, ON time, OFF time, levodopa equivalent daily doses, and adverse events (AE). Data were pooled using a Bayesian network meta‐analysis, summarized as mean difference (MD) with 95% credibility intervals (CrI) and visualized in forest plots/league tables. Surface under the cumulative ranking curve plots determined the ranking probability. Results: We identified 6745 citations and included 26 trials. STN‐DBS (MD, −8.0; 95% CrI, −11, −5.8), GPi‐DBS (MD, −7.1; 95% CrI, −11, −2.9), and IJLI (MD, −7.0; 95% CrI, −12, −1.8) led to better QOL than medical therapy alone, without significant differences among them. STN‐DBS had the highest probability of being ranked the best treatment for QOL (79.6%), followed by IJLI (63.5%) and GPi‐DBS (62.8%). Conclusions: In advanced PD, STN‐DBS alleviates more patient and clinician relevant outcomes, followed by GPi‐DBS and IJLI. In resource limited settings, unilateral pallidotomy may improve motor symptoms and activities of daily living, although overall QOL may not be improved. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

This article is a reply to a previous article on neuropathic tremor in Guillain Barré Syndrome. The authors thank the previous authors for their interest and highlight an important treatment option for neuropathic tremor following Guillain Barré Syndrome. They discuss the similarities between their series of patients and the patient reported by the previous authors, as well as the different treatment responses observed. The authors also provide a pathophysiological explanation for the potential effectiveness of pregabalin in treating neuropathic tremor. They conclude by suggesting that propranolol, pregabalin, and gabapentin may be initial medications to be tried for neuropathic tremors, but further studies are needed to understand the natural history and therapeutic response of this disorder. [Extracted from the article]

Background: Early evidence suggests good response to pallidal deep brain stimulation (DBS) in DYT‐KMT2B. Objectives: We aimed to conduct a systematic review and meta‐analysis to assess outcomes and identify predictors of good outcome following GPi‐DBS in DYT‐KMT2B. Methods: We searched MEDLINE, Cochrane and MDS‐abstracts databases using the MeSH terms "KMT2B and DYT28". We included studies that reported objective outcomes following GPi‐DBS in DYT‐KMT2B. The BFMDRS‐M (Burke‐Fahn‐Marsden Dystonia Rating Scale‐ Movement) total scores pre‐ and post‐surgery were used to quantify outcomes. We calculated pooled effects using a random effects meta‐analysis and used meta‐regression to identify potential effect modifiers. Multiple linear regression using individual patient data was used to identify predictors of good outcome (>50% improvement from baseline on BFMDRS‐M). Results: Initial searches screened 132 abstracts of which 34 full‐text articles were identified to be of potential interest. Ten studies reporting 42 individual patients, met the inclusion/exclusion criteria and were included in the final review. The mean age at onset was 6.4 ± 5.7 years and 40% were male. The median follow‐up was 12 months (range: 1–264 months). GPi‐DBS resulted in median BFMDRS‐M improvement of 42.7% (range: −103.5% to 95.9%) postoperatively. Pooled proportion of patients experiencing clinical improvement >50% on BFMDRS‐M was 41% (95% CI: 27%–57%). Male gender [β: 22.6, 95% CI: 8.0–37.3, P = 0.004), and higher pre‐operative BFMDRS‐M score [β: 0.62, 95% CI: 0.36–0.87, P < 0.001) were independently associated with better outcome. Conclusion: KMT2B‐associated dystonia responds effectively to pallidal stimulation. The outcome is better in males and those with more severe dystonia at baseline. [ABSTRACT FROM AUTHOR]

Introduction: Guidelines recommend screening older people (> 60–65 years) with type 2 diabetes (T2D) for cognitive impairment, as it has implications in the management of diabetes. The Montreal Cognitive Assessment (MoCA) is a sensitive test for the detection of mild cognitive impairment (MCI) in the general population, but its validity in T2D has not been established. Methods: We administered MoCA to patients with T2D (age ≥ 60 years) and controls (no T2D), along with a culturally validated neuropsychological battery and functional activity questionnaire. MCI was defined as performance in one or more cognitive domains ≥ 1.0 SD below the control group (on two tests representing a cognitive domain), with preserved functional activities. The discriminant validity of MoCA for the diagnosis of MCI at different cut-offs was ascertained. Results: We enrolled 267 patients with T2D and 120 controls; 39% of the participants with T2D met the diagnostic criteria for MCI on detailed neuropsychological testing. At the recommended cut-off on MoCA (< 26), the sensitivity (94.2%) was high, but the specificity was quite low (29.5%). The cut-off score of < 23 showed an optimal trade-off between sensitivity (69.2%), specificity (71.8%), and diagnostic accuracy (70.8%). The cut-off of < 21 exhibited the highest diagnostic accuracy (74.9%) with an excellent specificity (91.4%), a good positive and negative predictive value (78.5% and 73.7%, respectively). Conclusions: The recommended screening cut-off point on MoCA of < 26 has a suboptimal specificity and may increase the referral burden in memory clinics. A lower cut-off of < 21 on MoCA maximizes the diagnostic accuracy. Interactive Visual Abstract available for this article. Plain Language Summary: Type 2 diabetes (T2D) is a risk factor for cognitive dysfunction which potentially impacts diabetes self-management skills. Guidelines recommend screening older adults with diabetes for early detection of cognitive impairment. For screening cognitive impairment in busy endocrine clinics, we need a test that is easy and rapid to administer, sensitive enough to pick the cognitive deficits of T2D and at the same time gives less false-positive outcomes. The Montreal Cognitive Assessment (MoCA) scale is a widely available cognitive screening tool, but there are no studies evaluating its discriminant properties in people with diabetes. We evaluated the performance metrics of MoCA in this population. We found mild cognitive impairment in four out of ten participants with T2D at or above 60 years of age. At the recommended cut-off on MoCA (< 26), the sensitivity was high, but the specificity quite low. We found better diagnostic accuracy at lower cut-offs (20/21), with high specificity but a lower sensitivity. At this cut-off, approximately one out of five people screened using MoCA would require detailed neuropsychological testing, and four out of five who undergo detailed evaluation would have true cognitive impairment. [ABSTRACT FROM AUTHOR]

Background: Freezing of gait (FOG) is a disabling and refractory symptom of advanced Parkinson's disease (PD). Interleaved stimulation (ILS) is a novel paradigm which may benefit axial symptoms of PD.Objectives: To assess the effect of ILS on FOG in patients unresponsive to conventional subthalamic nucleus (STN) stimulation.Methods: 19 PD patients receiving subthalamic stimulation and experiencing FOG at both conventional (130-150Hz) and low frequency (60Hz) stimulation were given ILS.The primary outcome measure was the UPDRS part III gait score (item 29) at 3 months after ILS. A subset of patients was tested with the stand-walk-sit (SWS) test, 30 min after ILS.Results: The mean UPDRS part III gait score (baseline: 1.8 ± 0.6) improved at 30 min (1.1 ± 0.8, P = 0.017) and remained improved at 3 months (1.2 ± 0.8, P = 0.048). FOG episodes reduced during SWS test (P = 0.041).Conclusions: ILS of STN through two adjacent contacts provided significant short-term beneficial effects on FOG. [ABSTRACT FROM AUTHOR]

Neuromodulation therapies, including deep brain stimulation (DBS) and pump therapies, are currently the standard of care for PD patients with advanced disease and motor complications that are difficult to control with medical management alone. The quest for alternate lesser invasive approaches led to the development of several novel therapies like intrajejunal levodopa infusions (IJLI), continuous subcutaneous apomorphine infusions (CSAI) and Magnetic Resonance guided Focused Ultrasound (MRgFUS) in recent years. To achieve good outcomes with any of these therapeutic modalities, careful patient selection, multidisciplinary evaluation and technical expertise are equally important. In this review, we will provide an overview of the neuromodulation strategies currently available for PD, emphasizing on patient selection and choosing among the various strategies. [ABSTRACT FROM AUTHOR]

Background: Anticholinergic drugs are associated with significant cognitive and other adverse events in older adults, including those with Parkinson's disease (PD). Anticholinergic effects are considered lesser in younger individuals and the burden and outcomes in younger patients with PD are unknown. Objectives: To determine the cumulative anticholinergic burden in a cohort of younger of patients with PD and to correlate the same with cognitive impairment and freezing of gait (FOG). Methods: We conducted a cross‐sectional study to identify the cumulative anticholinergic burden from medications prescribed to patients with PD. Two standard scales, the Anticholinergic Cognitive Burden (ACB) scale and the ACB score, were used to calculate the anticholinergic burden from prescriptions. We identified commonly prescribed drugs contributing to anticholinergic effects and correlated the cumulative ACB score with cognitive impairment (Movement Disorder Society–Unified Parkinson's Disease Rating Scale item 1.1) and FOG (Movement Disorder Society–Unified Parkinson's Disease Rating Scale items 2.13 and 3.11). Results: We recruited 287 patients with PD (68.9% male) with a mean age of 56.9 ± 11.8 years and a duration of symptoms 6.3 ± 6.9 years. Median ACB score was 4 (range 0–12). A total of 164 (58.4%) patients had total ACB score > 3. ACB score > 3 was independently associated with cognitive impairment (Odds Ratio, 2.55; 95% confidence interval, 1.43–4.53; P < 0.001) and FOG using patient‐reported measures (Odds Ratio, 3.192; 95% Confidence Interval, 1.68–6.07; P < 0.001) and objective measures (odds ratio, 2.41; 95% confidence interval, 1.27–4.6, P = 0.007). Conclusion: Patients with PD are exposed to significant anticholinergic burden from drugs prescribed for PD and non‐PD indications. Higher anticholinergic burden is associated with cognitive impairment and FOG even in younger patients with PD. [ABSTRACT FROM AUTHOR]

Background: Quality of life in Parkinson's disease (PD) is affected by motor and nonmotor symptoms, necessitating an integrated care approach. Existing care models vary considerably in numerous domains. The objectives of this study were to perform a systematic review and meta-analysis of PD integrated care models and develop recommendations for a representative model.Methods: We conducted a systematic review of published integrated care models and a meta-analysis of randomized, controlled trials examining integrated care versus standard care. The primary outcome was health-related quality of life using a validated PD scale. We evaluated levels of care integration using the Rainbow Model of Integrated Care.Results: Forty-eight publications were identified, including 8 randomized, controlled trials with health-related quality of life data (n = 1,149 total PD patients). Qualitative evaluation of individual care model integration guided by the Rainbow Model of Integrated Care revealed frequent clinical and professional integration, but infrequent organizational and population-based integration elements. Meta-analysis of randomized, controlled trials revealed significant heterogeneity (I2  = 90%, P < 0.0001). Subgroup analysis including only outpatient care models (n = 5) indicated homogeneity of effects (I2  = 0%, P = 0.52) and improved health-related quality of life favoring integrated care, with a small effect size (standardized mean difference [SMD], -0.17; 95% CI, -0.31 to -0.03; P = 0.02).Conclusions: Outpatient integrated PD care models may improve patient-reported health-related quality of life compared with standard care; however, because of variable methodological approaches and a high risk of bias related to inherent difficulties in study design (eg, blinding of participants and interventionists), generalizability of these results are difficult to establish. The Rainbow Model of Integrated Care is a promising method of evaluating elements and levels of integration from individual patient care to population health in a PD context. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, LLC. on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Medical training programs are witnessing immense disruptions worldwide due to the ongoing COVID-19 pandemic. Keeping in mind the trainees' future prospects, it is important to provide continuity of teaching and timely certification assessments. Overcoming the obstacles to routine functioning presented by SARS-CoV-2 spread, we recently conducted the DM Neurology exit examination in a hybrid virtual format. We created a curated case repository with history and clinical examination findings followed by structured questions that could be built upon for case discussions. The external examiners assessed the candidates virtually through a video conferencing platform. The end results were well accepted by all key stake holders. The concerns, logistics and experience of conducting the DM Neurology exit exam in a virtual format are summarized here. [ABSTRACT FROM AUTHOR]

Keywords: frontotemporal dementia; amyotrophic lateral sclerosis; SQSTM1; Sequestosome; p62 EN frontotemporal dementia amyotrophic lateral sclerosis SQSTM1 Sequestosome p62 800 802 3 07/21/21 20210701 NES 210701 A 43-year-old Asian Indian male presented with progressive gait difficulty for 3 years. Cerebellar Ataxia in Adults with SQSTM1-Associated Frontotemporal Dementia-Amyotrophic Lateral Sclerosis Spectrum of Disorders This is classified as a pathogenic variant associated with the phenotype of frontotemporal dementia (FTD)-ALS (OMIM*616437).1 This variant was also observed in his elder brother (currently asymptomatic) and younger sister (having bilateral lower limb hyperreflexia). [Extracted from the article]

Outcomes of pallidal stimulation in KMT2B dystonia have been infrequently reported prospectively. We report the six-month outcomes of bilateral GPi DBS in an Asian Indian patient with early-onset generalized dystonia associated with a novel heterozygous variant in the KMT2B gene. [ABSTRACT FROM AUTHOR]

Background: Neurological manifestations are an important cause of morbidity in antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). It is not clear whether or not they are indicative of a severe disease course with multiple organ involvement and shortened survival.Aims and Objectives: To characterize the neurological manifestations of AAV and analyze their relationship with other organ system and cumulative survival.Methods: This was a retrospective single-center cohort study of AAV patients at a tertiary care hospital in North India. Data was collected from medical records regarding clinical history, neurological examination, Birmingham Vasculitis Activity Score (BVAS), serology, electrophysiology, imaging, and histopathological examination findings of patients.Results: Ninety-two patients of systemic vasculitis were identified, 67 with granulomatosis with polyangiitis (GPA), 14 with microscopic polyangiitis, 8 with Churg-Strauss syndrome (CSS), and 3 with undifferentiated AAV. The median BVAS at presentation was 18.0 (interquartile range (IQR): 12.0). The median duration of follow-up was 31.3 months (IQR: 40.5). A total of 45.7% patients had neurological manifestations among which 23.8% presented with neurological complaints. Peripheral neuropathy was the most common manifestation noted in 23.9% of the patients. Among patients with GPA, 40.3% had neurological involvement (seen in 33.3% patients at presentation). Patients with nervous system disease were more likely to have associated musculoskeletal manifestations (P = 0.046) and less likely to have renal involvement (P = 0.017). The estimated cumulative survival of the subgroup with neurological involvement was 95.1 months from the time of diagnosis, which was not significantly different from the cohort without neurological involvement (113.8 months, P = 0.631).Conclusion: Neurological morbidity commonly accompanies systemic vasculitis. Nervous system disease does not affect the survival significantly in these patients. [ABSTRACT FROM AUTHOR]

Abstract: Background: The functional Ser9Gly single nucleotide polymorphism (SNP) in the dopamine D3 receptor gene is associated with impulse control disorders (ICD) in Parkinson's disease (PD) in Indian patients. Whether the same SNP modulates impulsivity in PD patients without active ICD is unknown. We aimed to compare decision‐making under uncertainty in PD patients with DRD3 p.S9G (rs6280) variants CT/CC or TT. Methods: We conducted a cross‐sectional study including PD patients (n = 78) whose DRD3 p.S9G (rs6280) genotypic status was known (CC, CT, and TT). Decision‐making was assessed using the Iowa Gambling Task (IGT). Results: IGT total (p = 0.267) or block scores did not differ between the DRD3 rs6280 variant groups. Deck choice analysis revealed that the CT/CC group showed a skewed preference in deck choice (p = 0.002) due to significantly fewer draws from deck B, compared to all other decks (deck A, p < 0.001; deck C, p = 0.004; deck D, p = 0.002). Conclusions: The functional Ser9Gly DRD3 variant is associated with aberrant decision‐making under uncertainty in PD patients without active ICD. This ability to modulate impulsivity may underlie its association with clinical ICD in PD. [ABSTRACT FROM AUTHOR]

Levodopa-induced dyskinesias are motor complications following long term dopaminergic therapy in Parkinson’s disease (PD). Impaired brain plasticity resulting in the creation of aberrant motor maps intended to encode normal voluntary movement is proposed to result in the development of dyskinesias. Traditionally, the various nodes in the motor network like the striato-cortical and the cerebello-thalamic loops were thought to function independent of each other with little communication among them. Anatomical evidence from primates revealed the existence of reciprocal loops between the basal ganglia and the cerebellum providing an anatomical basis for communication between the motor network loops. Dyskinetic PD patients reveal impaired brain plasticity within the motor cortex which may be modulated by cortico-cortical, cerebello-cortical or striato-cortical connections. In this article, we review the evidence for altered plasticity in the multicomponent motor network in the context of levodopa induced dyskinesias in PD. Current evidence suggests a pivotal role for the cerebellum in the larger motor network with the ability to integrate sensorimotor information and independently influence multiple nodes in this network. Targeting the cerebellum seems to be a justified approach for future interventions aimed at attenuating levodopa-induced dyskinesias. [ABSTRACT FROM AUTHOR]

Introduction: Impulse control disorders (ICD) are reported to occur at variable frequencies in different ethnic groups. Genetic vulnerability is suspected to underlie the individual risk for ICD. We investigated whether the allelic variants of dopamine (DRD3), glutamate (GRIN2B) and serotonin (HTR2A) receptors are linked to ICD in Indian Parkinson's disease (PD) patients.Methods: We conducted a prospective, case-control study which included PD patients (70 with ICD, 100 without ICD categorized after direct psychiatric interview of patient and caregiver) and 285 healthy controls. Single nucleotide polymorphism (SNP) variants of DRD3 p.S9G (rs6280), GRIN2B c.2664C>T (rs1806201) and HTR2A c.102T>C (rs6313) were genotyped.Results: Multivariate regression analysis revealed that DRD3 p.Ser9Gly (rs6280) heterozygous variant CT (OR = 2.22, 95% CI: 1.03-4.86, p = 0.041), higher daily Levodopa equivalent doses (LED) of drugs (for 100 mg LED, OR = 1.14, 95% CI: 1.01-1.29, p = 0.041), current dopamine agonist but not Levodopa use (OR = 2.16, 95% CI: 1.03-4.55, p = 0.042) and age of onset of motor symptoms under 50 years (OR 2.09, 95% CI: 1.05-4.18, p = 0.035) were independently associated with ICD.Conclusion: DRD3 p.Ser9Gly (rs6280) CT genotype is associated with ICD in Indian PD patients and this association is novel. Enhanced D3 receptor affinity due to gain-of-function conferred by the glycine residues could impair reward-risk assessment in the mesolimbic system and contribute to development of impulsive behaviour, in carriers of this genotype. [ABSTRACT FROM AUTHOR]

This article discusses a case study of a 12-year-old boy with THAP1-associated dystonia, a condition that mimics neurodegeneration with brain iron accumulation (NBIA). The boy presented with childhood onset, generalized dystonia that progressively worsened over time. Neurological examination revealed dystonia involving various body regions, along with bradykinesia and rigidity. Magnetic resonance imaging (MRI) showed hypointensity in the bilateral globus pallidi, a finding typically associated with NBIA. However, genetic testing revealed a pathogenic mutation in the THAP1 gene, confirming the diagnosis of DYT6 dystonia. Treatment with levodopa and other medications resulted in mild improvement. This case adds to the evidence that DYT-THAP1 should be considered as a mimic of NBIA. [Extracted from the article]

Abrupt cessation of STN- DBS is an under-recognized cause of life-threatening akinetic crisis in Parkinson's disease ( PD) and can present as a movement disorder emergency. We report on 2 patients who survived severe and prolonged akinetic crisis after abrupt cessation of STN stimulation for PD (malignant STN- DBS withdrawal syndrome). We discuss the clinical similarities and possible differences in pathophysiology from the akinetic crisis in medically-treated PD. Although early implantable pulse generator ( IPG) replacement is the definitive treatment, medical and economic considerations may preclude early surgery and strategies for medical management assume importance. We reflect upon the socioeconomic concerns surrounding DBS in countries lacking health care coverage and the need for user-independent monitors and indicators of low IPG battery status. [ABSTRACT FROM AUTHOR]

Background: Although systemic endothelial function is unimpaired in migraine, it is unknown whether cerebral endothelial function impairment exists in migraineurs.Materials and Methods: We conducted a prospective study to assess endothelial function in migraineurs (n=45) and healthy volunteers (n=44). Cerebral endothelial function was assessed by Breath Holding Index (BHI) on transcranial Doppler in bilateral middle cerebral artery (MCA at 30-60 mm), posterior cerebral artery (PCA at 60-80 mm) and basilar artery (BA at 80-120 mm) using bilateral monitoring probes fixed on headband. Brachial artery flow-mediated dilation (FMD) was used as measure of systemic endothelial function.Results: There was no difference in baseline mean velocities of MCA, PCA, BA among migraineurs and controls. Mean BHI was significantly lower in PCA (p<0.001) and BA (p<0.001) in patients with migraine with no difference in MCA (p=0.909, 0.450). Cerebral endothelial dysfunction (BHI<1.15) was present in 62.2% of migraineurs in the right PCA (p<0.001), 57.8% in left PCA (p<0.001) and 77.8% in BA (BHI <0.83, p<0.001). There was no difference in BHI among migraineurs without and with aura (n=15). Cerebral and systemic endothelial function had no correlation in migraineurs. Increasing BMI was identified as a predictor of impaired BHI in the BA in migraineurs (p=0.020). Age, sex, presence of aura, lateralisation of headache, headache frequency, time to last attack and impaired FMD were not associated with impaired PCA and BA BHI in migraineurs.Conclusions: Migraineurs may have isolated cerebral endothelial dysfunction restricted to the posterior circulation in the absence of systemic endothelial dysfunction. [ABSTRACT FROM AUTHOR]

They classified the first category as "pure DIP."[[2]] There are chances of progression of the last two categories to PD and these patients may represent the preclinical stage of PD in whom the symptoms of PD are unmasked as a result of the drug-induced dopaminergic blockade.[[2]],[[10]] REFERENCES 1 Srivanitchapoom P, Pitakpatapee Y, Suengtaworn A. Parkinsonian syndromes: A review. Parkinsonism refers to a group of neurological disorders that share similar clinical symptoms. DIP is second only to PD as the cause of parkinsonism.[[7]] The drugs which cause DIP usually interfere with the postsynaptic dopamine receptors, particularly D2 receptors. [Extracted from the article]

Primary coenzyme Q10 (CoQ10) deficiency is a rare genetic disorder that affects mitochondrial respiration and can lead to various symptoms such as cerebellar ataxia, intellectual disability, seizures, and more. The most common form of this disorder is primary CoQ10 deficiency-4 (COQ10D4), which is caused by a variant in the CoQ8A gene. This article presents a case study of a young male with slowly progressive cerebellar ataxia and dystonia caused by primary CoQ10 deficiency-4. Early supplementation of CoQ10 may result in favorable outcomes, so a timely diagnosis is essential. [Extracted from the article]

The article presents the case of a 48-year-old man with rapidly progressing parkinsonism, cognitive impairment, and sleep abnormalities, resembling anti-Immunoglobulin-like cell adhesion molecule 5 (IgLON5) disease but linked to anti-amphiphysin antibodies.Topics include antibody-mediated parkinsonism, rapidly progressive parkinsonism associated with underlying malignancy, and the role of immunotherapy in treating immune-related parkinsonism.

Background: Parkinson's disease is generally asymptomatic at earlier stages. At an early stage, there is an extensive progression in the neuropathological hallmarks, although, at this stage, diagnosis is not possible with currently available diagnostic methods. Therefore, the pressing need is for susceptibility risk biomarkers that can aid in better diagnosis and therapeutics as well can objectively serve to measure the endpoint of disease progression. The role of small extracellular vesicles (sEV) in the progression of neurodegenerative diseases could be potent in playing a revolutionary role in biomarker discovery. Methods: In our study, the salivary sEV were efficiently isolated by chemical precipitation combined with ultrafiltration from subjects (PD = 70, healthy controls = 26, and prodromal PD = 08), followed by antibody-based validation with CD63, CD9, GAPDH, Flotillin-1, and L1CAM. Morphological characterization of the isolated sEV through transmission electron microscopy. The quantification of sEV was achieved by fluorescence (lipid-binding dye-labeled) nanoparticle tracking analysis and antibody-based (CD63 Alexa fluor 488 tagged sEV) nanoparticle tracking analysis. The total alpha-synuclein (α-synTotal) in salivary sEVs cargo was quantified by ELISA. The disease severity staging confirmation for n = 18 clinically diagnosed Parkinson's disease patients was done by 99mTc-TRODAT-single-photon emission computed tomography. Results: We observed a significant increase in total sEVs concentration in PD patients than in the healthy control (HC), where fluorescence lipid-binding dye-tagged sEV were observed to be higher in PD (p = 0.0001) than in the HC using NTA with a sensitivity of 94.34%. In the prodromal PD cases, the fluorescence lipid-binding dye-tagged sEV concentration was found to be higher (p = 0.008) than in HC. This result was validated through anti-CD63 tagged sEV (p = 0.0006) with similar sensitivity of 94.12%. We further validated our findings with the ELISA based on α-synTotal concentration in sEV, where it was observed to be higher in PD (p = 0.004) with a sensitivity of 88.24%. The caudate binding ratios in 99mTc-TRODAT-SPECT represent a positive correlation with sEV concentration (r = 0.8117 with p = 0.0112). Conclusions: In this study, for the first time, we have found that the fluorescence-tagged sEV has the potential to screen the progression of disease with clinically acceptable sensitivity and can be a potent early detection method for PD. [ABSTRACT FROM AUTHOR]

In patients with movement disorders, voluntary movements can sometimes be accompanied by unintentional muscle contractions in other body regions. In this review, we discuss clinical and pathophysiological aspects of several motor phenomena including mirror movements, dystonic overflow, synkinesia, entrainment and mirror dystonia, focusing on their similarities and differences. These phenomena share some common clinical and pathophysiological features, which often leads to confusion in their definition. However, they differ in several aspects, such as the body part showing the undesired movement, the type of this movement (identical or not to the intentional movement), the underlying neurological condition, and the role of primary motor areas, descending pathways and inhibitory circuits involved, suggesting that these are distinct phenomena. We summarize the main features of these fascinating clinical signs aiming to improve the clinical recognition and standardize the terminology in research studies. We also suggest that the term "mirror dystonia" may be not appropriate to describe this peculiar phenomenon which may be closer to dystonic overflow rather than to the classical mirror movements. [ABSTRACT FROM AUTHOR]

Background: Integrated care is essential for improving the management and health outcomes for people with Parkinson's disease (PD); reliable and objective measures of care integration are few. Objective: The aim of this study was to test the psychometric properties of the Rainbow Model of Integrated Care Measurement Tool (RMIC‐MT, provider version) for healthcare professionals involved in PD care. Methods: A cross‐sectional survey was administered online to an international network representing 95 neurology centers across 41 countries and 588 healthcare providers. Exploratory factor analysis with principal axis extraction method was used to assess construct validity. Confirmatory factor analysis was used to evaluate model fit of the RMIC‐MT provider version. Cronbach's alpha was used to assess the internal consistency reliability. Results: Overall, 371 care providers (62% response rate) participated in this study. No item had psychometric sensitivity problems. Nine factors (professional coordination, cultural competence, triple aims outcome, system coordination, clinical coordination, technical competence, community‐centeredness, person‐centeredness, and organizational coordination) with 42 items were determined by exploratory factor analysis. Cronbach's alpha ranged from 0.76 (clinical coordination) to 0.94 (system coordination) and showed significant correlation among all items in the scale (>0.4), indicating good internal consistency reliability. The confirmatory factor analysis model passed most goodness‐of‐fit tests, thereby confirming the factor structure of nine categories with a total of 40 items. Conclusions: The results provide evidence for the construct validity and other psychometric properties of the provider version of the RMIC‐MT to measure integrated care in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Objective: Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves motor complications and quality of life (QOL) in patients with Parkinson's disease (PD). However, it does not delay or prevent the occurrence of dementia. The deleterious effects of dementia on QOL and activities of daily living (ADL) underscore the importance of identifying predictors of dementia-free survival in PD patients considered for STN DBS.Aims and Methods: The baseline clinical and neuropsychological data and the occurrence of dementia recorded during the longitudinal follow-up of a cohort of patients with PD with at least 2 years follow-up after bilateral STN DBS, were reviewed.Results: One hundred and sixteen patients operated between 1999 to 2014 satisfied the inclusion criteria. Their mean age was 56.5 (±10) years and the mean duration of PD at surgery was 11.2 (±4.2) years. During the 542 person-years of follow-up, 30 patients developed dementia. The mean dementia-free survival after surgery was 8.7 [95% confidence interval (CI): 7.8-9.6] years. In univariate analysis, the baseline factors of older age, longer disease duration, past history of depression or psychosis, freezing of gait in OFF phase, worse ADL scores in ON phase, lower levodopa response of the Unified Parkinson's Disease Rating Scale (UPDRS) III axial sub-scores, and poor performances in the Addenbrooke's Cognitive Examination and Wisconsin Card Sorting Test (WCST) were associated with a shorter dementia-free survival. Among these, only freezing of gait and poor performance in WCST were independent predictors.Conclusion: Presence of freezing of gait in the drug OFF state and executive dysfunction predict the occurrence of earlier dementia in PD patients who otherwise qualify for bilateral STN DBS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Objective: Nearly 40–65% patients with MS develop cognitive impairment during the disease. There is no treatment clearly effective in improving the cognitive deficits. To evaluate the efficacy and safety of Rivastigmine in cognitively impaired MS patients. Materials and Methods: This was a parallel group randomized open label study with blinded end‑point assessment. The patient allocation to treatment and control arm was done by telephonic contact with an independent statistician who used a computer to generate a random sequence of allocation using permuted block randomization (varying block size of 4 and 6) in 1:1 ratio. The outcome assessor was blinded to this allocation. A total of 60 patients were in included in the study (30 in each arm). Primary outcome was improvement in memory functions (using logical memory subset of Wechsler Memory Scale III, India) assessed after 12 weeks. Secondary outcomes included fatigue, depression, and safety. Results: In modified intention to treat analysis (N = 22), treatment arm showed statistically significant improvement in memory function with mean difference of 7.56 [95% CI (0.67,14.46), p 0.032] as compared to control arm. There was no statistically significant difference in outcomes such as fatigue and depression. Vomiting was the most common side effect. No major adverse events were observed in either group. Conclusion: Rivastigmine is safe and effective in improving memory functions in cognitively impaired MS patients. However, our study has a small sample size and tested only a single domain. Larger studies with a validated single comprehensive neuropsychological test are needed. [ABSTRACT FROM AUTHOR]

Background: Social cognition is the study of how people make sense of themselves and others. Impairment in several domains of social cognition is increasingly being recognized in Parkinson's disease (PD). Objectives: We aimed to study multiple domains of social cognition in Indian PD patients using a culturally appropriate, validated instrument. Methods: We recruited 52 individuals with PD and 31 healthy volunteers (HV) and used the Social Cognition Rating Tools in Indian Setting (SOCRATIS) tool to assess theory of mind (ToM), attributional biases and social cue perception. Quality of life (QoL) was assessed using the PDQOL scale. Results: Baseline characteristics were comparable between PD and HV. The mean (SD) FOT index (first order ToM index) was 0.86(0.18) in PD and 0.99(0.07) in HV [P < 0.001]. The PD group showed higher Externalizing Bias [EB, 4.42(3.91)], compared to HV [1.58(3.22), P = 0.001]. The mean (SD) Faux Pas Composite Index (FPCI ALT) was 0.69(0.09) in PD and 0.78(0.13) in HV [P < 0.001]. Social cognition indices were not associated with QoL in PD. Clinical parameters—age, gender, HAM‐D, MOCA, education, levodopa equivalent daily dose of medication, number of PD drugs and trihexyphenidyl use did not predict social cognition. Conclusion: PD patients were less successful than age, gender matched controls in understanding social situations and other's thought processes and had higher tendency to attribute undesirable events to external causes. Deficits in social cognition did not impair the quality of life. [ABSTRACT FROM AUTHOR]

Introduction: and objective: Tremor is a disabling symptom of PD that usually responds poorly to available standard pharmacological agents. This study aimed to assess the effect of Zonisamide 25 mg on tremor in tremor-dominant PD patients as compared to placebo.Methods: This was a randomized, placebo-controlled, double-blind study. Parkinson's disease patients were allocated either to the intervention group (standard treatment along with Zonisamide 25 mg add-on) or the placebo group (standard treatment along with placebo). Baseline Unified Parkinson's Disease Rating Scale (UPDRS) and Tremor Research Group Essential Tremor Rating Scale (TETRAS) scores, as well as accelerometric tremor analysis were done and follow-up assessments of the same were done after 12 weeks of intervention. Percentage change from baseline in the UPDRS tremor score was the primary outcome whereas percentage change from baseline of total UPDRS score, UPDRS rigidity and bradykinesia scores, TETRAS score, and accelerometric tremor analysis values were the secondary outcomes.Results: There was no significant difference in the percentage change from baseline UPDRS tremor scores between the two groups (placebo: 8.33 [-19.89-23.86] vs drug: 26.14 [-35.58 to -16.07], p-value: 0.164, CI: 0.157-0.171). Best-case analysis for missing values showed a significant improvement in the drug group, compared to the placebo group (p-value: < 0.001, CI: <0.001 - <0.001).Conclusion: Zonisamide at a dose of 25 mg per day did not improve tremor in tremor-dominant PD patients, however, a positive trend was seen as compared to Placebo in the UPDRS tremor score. Larger studies are required to confirm this finding. [ABSTRACT FROM AUTHOR]

Background and Purpose: We aimed to explore the characteristics, clinical features, predictors of seizure, and associated clinical outcomes in patients with cerebral venous thrombosis (CVT). Methods: We enrolled patients with CVT from January 2014 to July 2020. Prospectively patients were recruited from December 2018. We analyzed predictors of seizures and associated good functional outcomes (modified Rankin Scale, mRS: 0-2) using multivariable logistic regression. Results: We enrolled 153 patients with CVT in which 77 (50%) had presented with a seizure. The median age was 31 years (IQR 16 46), and the majority were men (73.2%). Focal to bilateral tonic clonic was the most common seizure type (27%), followed by generalized seizures (22%). None of the patients had status epilepticus. Antiseizure medications (ASM) were used in 71% of patients at diagnosis, 42% having received them prophylactically. Supratentorial parenchymal involvement was seen in 72% of seizure patients compared to 38% in those without, and superior sagittal sinus was most commonly involved. Percentage of patients who achieved good clinical outcome (mRS 0 2) at 3 months did not vary significantly between both groups. The only predictor for seizures with CVT was the presence of a parenchymal lesion (OR 3.75, 95% CI 1.79 7.85), whereas seizure occurrence (OR 12.55, 95% CI 1.53 102.59) was associated with statistically significant risk for recurrent seizures, by multiple logistic regression analysis. Seizure occurrence was not associated with adverse functional outcomes. Conclusion: Seizures at presentation occurred in 50% of patients with CVT which was associated with a parenchymal lesion in the brain. There was no association between seizure at presentation and clinical outcome. [ABSTRACT FROM AUTHOR]

Anoctaminopathies are a group of autosomal recessive skeletal muscle disorders with various clinical phenotypes, caused by anoctamin 5 (ANO5) gene mutations and the abnormal expression of ANO5 protein. Patients with recessive mutations in ANO5 present with variable symptoms ranging from asymptomatic hyperCKemia and exercise-induced myalgia to proximal and/or distal muscle weakness. Here, we describe the clinical, pathological, and molecular findings of two unrelated patients with ANO5-related muscular dystrophy (MD). Ninety-six histologically identified MD cases were subjected to next-generation sequencing using a customized panel of 54 genes (IIlumina Design Studio). Two patients were diagnosed with ANO5-related MD. One patient had a pathogenic homozygous mutation of c.1406G>A in exon 14, while the other patient had a novel heterozygous mutation of c.2141C>G in exon 19 of ANO5 gene. Both showed two different phenotypes (limb girdle MD and Miyoshi myopathy) and histomorphological patterns. Muscle biopsy of one patient in addition showed amyloid deposit in the walls of interstitial blood vessels. ANO5-related MD is a heterogeneous disease with different clinical phenotypes as well as genotypes. All muscle biopsies with unclassified muscular dystrophies should be subjected to Congo red stain. The results of this study suggest that screening for ANO5 gene should represent an early step in the diagnostic work-up of the patients with undiagnosed MD and persistent asymptomatic hyperCKemia, even when muscle biopsy histomorphology is normal. [ABSTRACT FROM AUTHOR]

Primary CNS Vasculitis (PCNSV) is a rare inflammatory disorder affecting the blood vessels of the central nervous system. Patients present with a combination of headaches, seizures, and focal neurological deficits. There is usually a diagnostic delay. Treatment is based on observational studies and expert opinion. Our objective was to identify clinical, laboratory, neuroimaging, pathologic or management-related associations with 2 year outcome in patients with primary CNS vasculitis. We conducted a cohort study at a single tertiary care referral centre of prospectively (2018-2019) and retrospectively (2010-2018) identified individuals with primary CNS vasculitis (diagnosis was proven by either brain biopsy or cerebral digital subtraction angiography). Clinical, imaging and histopathologic findings, treatment, and functional outcomes were recorded. Univariate and stepwise multiple logistic regression were applied. P-value<0.05 was considered statistically significant. The main outcome measures were documentation of clinical improvement or worsening (defined by mRS scores) and identification of independent predictors of good functional outcome (mRS 0-2) at 2 years. We enrolled eighty-two biopsy and/or angiographically proven PCNSV cases. The median age at presentation was 34 years with a male predilection and a median diagnostic delay of 23 months. Most patients presented with seizures (70.7%). All patients had haemorrhages on MRI. Histologically lymphocytic subtype was the commonest. Corticosteroids with cyclophosphamide was the commonest medication used. The median mRS at follow-up of 2 years was 2 (0-3), and 65.2% of patients achieved a good functional outcome. Myelitis and longer duration of illness before diagnosis were associated with poorer outcomes. The presence of hemorrhages on SWI sequence of MRI might be a sensitive imaging marker. Treatment with steroids and another immunosuppressant probably reduced relapse rates in our cohort. We have described the third largest PCNSV cohort and multi-centre randomised controlled trials are required to study the relative efficacy of various immunosuppressants. Study registration: CTRI/2018/03/012721. [ABSTRACT FROM AUTHOR]

Background: Human genetics research lacks diversity; over 80% of genome‐wide association studies have been conducted on individuals of European ancestry. In addition to limiting insights regarding disease mechanisms, disproportionate representation can create disparities preventing equitable implementation of personalized medicine. Objective: This systematic review provides an overview of research involving Parkinson's disease (PD) genetics in underrepresented populations (URP) and sets a baseline to measure the future impact of current efforts in those populations. Methods: We searched PubMed and EMBASE until October 2021 using search strings for "PD," "genetics," the main "URP," and and the countries in Latin America, Caribbean, Africa, Asia, and Oceania (excluding Australia and New Zealand). Inclusion criteria were original studies, written in English, reporting genetic results on PD from non‐European populations. Two levels of independent reviewers identified and extracted information. Results: We observed imbalances in PD genetic studies among URPs. Asian participants from Greater China were described in the majority of the articles published (57%), but other populations were less well studied; for example, Blacks were represented in just 4.0% of the publications. Also, although idiopathic PD was more studied than monogenic forms of the disease, most studies analyzed a limited number of genetic variants. We identified just nine studies using a genome‐wide approach published up to 2021, including URPs. Conclusion: This review provides insight into the significant lack of population diversity in PD research highlighting the immediate need for better representation. The Global Parkinson's Genetics Program (GP2) and similar initiatives aim to impact research in URPs, and the early metrics presented here can be used to measure progress in the field of PD genetics in the future. © 2022 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Background: Spinocerebellar ataxia is a neurodegenerative disease. Information on comparative assessment of quality of life (QoL) among SCAs, particularly SCA 12, is scarce. We aimed to compare health-related QoL in SCA 1, 2 and 12. Methods: We conducted a cross-sectional study among individuals with genetically-confirmed SCAs. Ataxia severity was assessed using Brief Ataxia Rating Scale (BARS), independence in activities of daily living (ADL) using Katz index (Katz ADL) and depression using Beck's Depression Inventory-II (BDI-II). QoL was assessed via Short Form Health Survey version 2.0 (SF-36). Results: We enrolled 89 individuals (SCA1 = 17, SCA2 = 43, SCA12 = 29; 56% males). Mean age at onset (41.0 ± 11.6 for SCA12 versus 24.9 + 7.0 for SCA1 and 28.8 ± 9.8 years for SCA2) was significantly higher among SCA12. SCA12 had lower BARS (mean score 4.1 ± 4.5 versus 10.6 ± 4.6 for SCA1 and 12.5 ± 4.5 for SCA2). SCA12 scored better on all SF-36 subdomains including Physical (PCS) and Mental Component Summary (MCS) scores. PCS score amongst SCA12 was 44.4 ± 9.0 versus 30.4 ± 9.1 for SCA1 and 33.3 ± 8.9 for SCA2. MCS score for SCA12 was 51.4 ± 11.4 versus 41.8 ± 11.5 for SCA1 and 41.8 ± 11.2 for SCA2. SCA12 had lower mean BDI scores (5.0 ± 6.0) versus SCA1 (9.5 ± 11.6) and SCA2 (10.9 ± 10.3). BARS and BDI emerged as significant predictors of most SF-36 subdomains. Conclusions: Our study suggests that despite older age and comparable disease duration, SCA12 patients experience better QoL, less severe depression and ataxia versus SCA1 and SCA2. Severity of ataxia and depression are significant predictors of QoL among the three SCA types. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

PSP-Like Phenotype in Genetically Confirmed SCA12 Keywords: SCA12; PSP; atypical parkinsonism; DaTSCAN EN SCA12 PSP atypical parkinsonism DaTSCAN 326 328 3 02/23/23 20230201 NES 230201 Spinocerebellar ataxia type 12 (SCA12) is an autosomal dominant cerebellar ataxia caused by CAG repeat expansions in the protein phosphatase 2 regulatory subunit B beta (PPP2R2B) gene in chromosome 5q.[1] The prevalence of SCA12 is high in Northern parts of India because of the common founder effect, and most of the affected families belong to the Agrawal community.[2] The commonest presenting symptom of SCA12 is the action tremors of upper limbs, which may precede the ataxia by many years.[[3]] Phenotypic spectrum of SCA12 also includes various non-ataxic manifestations, such as dystonia, parkinsonism, and cognitive impairment.[[1], [3]] Rarely, SCA12 can present as an "atypical atypical parkinsonism" and pose a diagnostic challenge.[5] A 61-year-old man from Punjab, India, presented with a history of progressive difficulty in walking, which worsened over the past 3 years with episodes of frequent falls. One should consider SCA12 in the differential diagnosis of atypical atypical parkinsonism with a PSP-like phenotype in a patient of ethnic origin where SCA12 is prevalent, even in the absence of family history. [Extracted from the article]

Introduction: Two pharmacological possibilities exist for an acute ischemic stroke (AIS): recanalization of the occluded artery and neuroprotection from ischaemic injury, the latter's efficacy being debatable. We sought to determine whether administration of Citicoline immediately after recanalization therapy for AIS would improve clinical and radiological outcome at three months compared to standard treatment alone. Patients and methods: CAISR was a single centre, randomized, placebo-controlled, parallel-group trial with blinded endpoint assessment. It was approved by the All India Institute of Medical Sciences Institutional ethics committee and registered at the Clinical Trial Registry of India (CTRI/2018/011900). We recruited participants with AIS undergoing recanalization therapy and randomly assigned them to receive either Citicoline or placebo in 1:1 ratio. Citicoline arm patients received Citicoline 1gm BD intravenously for three days, followed by oral citicoline 1gm BD for 39 days. Placebo arm patients received 100ml intravenous normal saline for three days, followed by multivitamin tablet BD for 39 days. All patients received standard of care. Outcome: Blinded assessors did the follow-up assessment at six weeks (MRI Brain-stroke volume) and three months (NIHSS 0–2, mRS 0–2 and Barthel index> = 95). Results: The infarct volume decreased from week 1 to week 6 by 2.6 cm3 on placebo versus 4.2 cm3 on Citicoline (p-0.483). The OR for achieving NIHSS 0–2, mRS 0–2 and Barthel index> = 95 with Citicoline was found to be 0.96(95%CI 0.39–2.40), 0.92(95%CI 0.40–2.05) and 0.87(95%CI 0.22–2.98) respectively. Conclusion: CAISR was the first to evaluate the role of Citicoline, when used immediately after recanalization therapy, when the penumbral tissue is the most susceptible either to be protected from injury or become ischemic. We did not find any significant difference between the Citicoline or placebo arms with respect to either our primary or secondary outcomes. [ABSTRACT FROM AUTHOR]

The article presents radiological observations in four patients with genetically proven mitochondrial membrane protein-associated neurodegeneration (MPAN). Topics include the characteristics of MPAN such as progressive spasticity and gait abnormalities, the prominent spasticity observed in MPAN patients, and the novel radiological indicator of MPAN.

Objective: Neurological emergencies saw a paradigm shift in approach during the coronavirus disease-2019 (COVID-19) pandemic with the challenge to manage patients with and without COVID-19. We aimed to compare the various neurological disorders and 3 months outcome in patients with and without SARS-CoV-2 infection. Methods: In an ambispective cohort study design, we enrolled patients with and without SARS CoV-2 infection coming to a medical emergency with neurological disorders between April 2020 and September 2020. Demographic, clinical, biochemical, and treatment details of these patients were collected and compared. Their outcomes, both in-hospital and at 3 months were assessed by the modified Rankin Scale (mRS). Results: Two thirty-five patients (235) were enrolled from emergency services with neurological disorders. Of them, 81 (34.5%) were COVID-19 positive. The mean (SD) age was 49.5 (17.3) years, and the majority of the patients were male (63.0%). The commonest neurological diagnosis was acute ischemic stroke (AIS) (43.0%). The in-hospital mortality was higher in the patients who were COVID-19 positive (COVID-19 positive: 29 (35.8%) versus COVID-19 negative: 12 (7.8%), P value: <0.001). The 3 months telephonic follow-up could be completed in 73.2% of the patients (142/194). Four (12.1%) deaths occurred on follow-up in the COVID-19 positive versus fifteen (13.8%) in the COVID-19 negative patients (P value: 1.00). The 3-month mRS was worse in the COVID-19 positive group (P value <0.001). However, this was driven by higher in-hospital morbidity and mortality in COVID-19 positive patients. Conclusion: Patients with neurological disorders presenting with COVID-19 infection had worse outcomes, including in-hospital and 3 months disability. [ABSTRACT FROM AUTHOR]

The article presents case studies related to Myelin Oligodendrocyte glycoprotein antibody syndrome and seizures. Topics include a 12‑year‑old girl presented with acute onset unsteadiness and imbalance while walking and diminution of vision from both eyes; and a 13‑year‑old boy presented with recurrent episodes of focal neurological deficits associated with pure motor paraparesis with stiffness of limbs, and horizontal binocular diplopia which were responsive to corticosteroids.

Background: Governments have imposed lockdowns in the wake of the COVID-19 pandemic. Hospitals have restricted outpatient clinics and elective services meant for non-COVID illnesses. This has led to patients facing unprecedented challenges and uncertainties. This study was carried out to assess patients' concerns and apprehensions about the effect of the lockdown on their treatments. Materials and Methods: An ambispective, observational cross-sectional single centre study was conducted. Patients were contacted telephonically and requested to answer a structured questionnaire. Their responses were documented and summarized as frequency and proportions. Results: A total of 727 patients were interviewed. Epilepsy (32%) was the most common neurological illness in our cohort followed by stroke (18%). About half the patients and/or their caregivers reported health-related concerns during the lockdown. The primary concern was how to connect with their treating neurologist if need arose. Forty-seven patients (6.4%) had drug default. Among patients on immunomodulatory treatments, only eight patients had drug default. High compliance rates were also observed in the stroke and epilepsy cohorts. Of the 71 patients who required emergency care during the lockdown, 24 could reach our hospital emergency. Fourteen patients either had a delay or could not seek emergency care. Two-thirds of our patients found the telemedicine experience satisfactory. Conclusion: The ongoing pandemic will continue to pose challenges to both physicians and patients. Patients in follow-up may need to be contacted regularly and counselled regarding the importance of maintaining drug compliance. Telemedicine can be used to strengthen the healthcare delivery to patients with non-COVID illnesses. [ABSTRACT FROM AUTHOR]