Search

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.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.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).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.

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.

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, L1CAM, and calnexin. 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 = 20 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 Total concentration in sEV, where it was observed to be higher in PD with a sensitivity of 88.24%. The striatal binding ratios in 99mTc-TRODAT-SPECT represents 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.

Niemann-Pick disease type C (NPC), is a rare lysosomal storage disorder, which has a variable presentation based on the age of onset. We describe five adult/adolescent-onset NPC cases presenting with a range of movement disorders along with vertical supranuclear gaze palsy as part of the clinical presentation. A diagnostic delay of 4–17 years from the symptom onset was found in this case series. A high index of clinical suspicion in adult/adolescent patients presenting with vertical supranuclear gaze palsy along with various movement disorder phenomenology can help in the early diagnosis of NPC.

A 42-year-old businessman had a 27-year history of multiple complaints. He had been born of a non-consanguineous marriage, but his siblings had young-onset hypertension. When aged 15 years, he developed an ulcerated skin lesion on the medial right thigh with right foot drop. This was presumptively treated as tuberculosis with corticosteroids and antituberculous therapy; the skin lesion resolved in 1–2 weeks and the foot drop recovered within 6–8 weeks. He stopped antituberculous therapy after 1 month. When aged 24 years, he developed a left foot drop that improved with oral corticosteroids in 3–4 weeks. However, on corticosteroid withdrawal he developed fever, left foot ulceration and abdominal pain. Biopsy of the skin ulcer was reported as ‘systemic lupus erythematosus-like’. His symptoms resolved with tapering corticosteroids over 4–6 months. He was also diagnosed and treated for hypertension at this time. When aged 30 years, he developed similar complaints. A rheumatologist prescribed monthly cyclophosphamide for 6 months with symptom resolution. He was then lost to follow-up for 6 years. When aged 36 years he presented with fever, abdominal and testicular pain, with skin ulcerations in the lower limbs. His viral markers for HIV, hepatitis B, hepatitis C were negative and a CT aortogram was normal. His condition responded well to pulsed corticosteroids and mycophenolate mofetil. He had further recurrent relapses every 1–2 years and tried a combination of multiple immunosuppressants: mycophenolate, azathioprine and cyclophosphamide. When aged 40 years, he had another relapse (fever, abdominal pain, left foot drop and weight loss) with significant (22 kg) unintentional weight loss over 2 months. CT scan of abdomen showed a left perirenal haematoma, with splenic and bilateral renal cortical infarcts. CT aortic angiogram showed multiple aneurysms in medium-sized abdominal aortic visceral branches. Chest X-ray and two-dimensional echocardiography were unremarkable. Upper gastrointestinal endoscopy identified oesophageal candidiasis, whereas colonoscopy showed multiple …

Introduction Cognitive impairment has now been recognised to be present in patients with several of spinocerebellar ataxias (SCAs). Cognitive impairment in patients with spinocerebellar ataxia type 12 has not been evaluated. Objective To evaluate the cognitive impairment in patients diagnosed with spinocerebellar ataxia type 12 (SCA12). Methods We conducted a cross sectional study and enrolled 30 (20 male and 10 female) genetically confirmed SCA12 patients and 30 healthy, age, gender and education matched individuals as controls. Cognitive domains were tested using a battery of validated neurocognitive tests. Result Mean age of patients was 51.6 ± 8.0 years and mean disease duration was 5.3 ± 3.0 years. Mean International Cooperative Ataxia Rating Scale (ICARS) score was 29.8 ± 12.5. SCA 12 patients scored significantly lower than controls in executive function and new learning ability. Other tested cognitive domains were also affected but did not reach statistical significance. Age, age at onset, severity of ataxia, disease duration and CAG repeat length did not correlate with cognitive impairment. Conclusion Cognitive impairment is a part of the spectrum of SCA12 and is characterized by dysfunction in executive function and new learning ability even early in the course of disease.

Background: Teleneurology consultations can be highly advantageous since neurological diseases and disabilities often limit patient's access to health care, particularly in a setting where they nee...

Background Literature shows that home confinement during coronavirus disease 2019 (COVID-19) pandemic has significantly affected sleep. However, such information regarding subjects having Parkinson’s disease (PD) is unavailable. Methods This cross-sectional study was conducted using a questionnaire, developed and validated by experts. PD subjects from nine centers across India were included. Questionnaire assessed presence as well as change in sleep-related parameters and PD symptoms during home confinement. Restless legs syndrome (RLS) and REM sleep behavior disorder (REMBD) was diagnosed using validated questionnaire. Additionally, changes in physical activity, adoption of new hobbies during home confinement and perceived quality of life were assessed. Results Of 832 subjects, 35.4% reported sleep disturbances. New-onset/worsening of sleep disturbances (NOWS) was reported by 23.9% subjects. Among those with sleep disturbances (n=295), insomnia symptoms worsened in half (51.5%) and nearly one-fourth reported worsening of RLS (24.7%) and REMBD (22.7%) each. NOWS was common in subjects lacking adequate family support during home confinement (P=0.03); home confinement > 60 days (P=0.05) and duration of PD > 7 years (P=0.008). Contrarily, physical activity > 1 hour/day and engagement in new hobbies during home confinement were associated with better sleep. NOWS was associated with worsening of motor as well as non-motor symptoms of PD (P 1 hour/day and adoption of new hobbies during home confinement were associated with better sleep., Highlights • New onset/worsening of sleep (NOWS) was reported by one-fourth subjects with Parkinson’s disease (PD) during home confinement. • While insomnia symptoms worsened in half, RLS and REMBD worsened in one-fourth of those with sleep disturbances. • Duration of PD >7 years, home confinement >60 days and absence of emotional support contributed to NOWS. • Adequate physical activity and adoption of hobbies during home confinement were protective factors.

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.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.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%).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.

Parkinson’s disease is generally asymptomatic at earlier stages. The pressing need is for the 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 exosomes in progression of neurodegenerative diseases is already reported and its cargo could be potent in playing a revolutionary role in biomarker discovery. In our study, the salivary exosomes were efficiently isolated by chemical precipitation from subjects (PD = 70, healthy controls = 26 and probable PD = 08) followed by antibody-based validation through CD63, CD9, GAPDH, flotillin 1, L1CAM, and calnexin. Morphological characterization of the isolated exosomes through transmission elcetrom microscopy (TEM). The exosome quantification via fluorescence and antibody-based nanoparticle tracking analysis (NTA). The total alpha-synuclein (α-syntotal) in salivary exosomal cargo was quantified by ELISA. The disease severity staging confirmation was done by 99mTc-TRODAT-SPECT. We observed a significant increase in total exosome concentration in PD patients than the healthy control (HC) where fluorescence-tagged exosomes were observed to be higher in PD (p total concentration in exosomes where it was observed to be higher in PD with a sensitivity of 88.24%. The striatal binding ratios in 99mTc-TRODAT-SPECT shown positive correlation with fluorescent exosomes concentration r = 0.3000, α-syntotal concentration r = 0.8000. In this study for the first time we have found that the fluorescence tagged exosomes has potential to screen the progression of disease with clinically acceptable sensitivity and can be a potent early detection method for PD.

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.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.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.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.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.

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

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.

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

Human genetics research lacks diversity; over 80% of genome-wide association studies (GWAS) 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. This systematic review provides an overview of research involving Parkinson’s disease (PD) genetics in under-represented populations (URP), and sets a baseline to measure the future impact of current efforts in those populations.We searched PubMed and EMBASE until October 2021 using search strings for “PD”, “genetics”, the main “URP”, and “lower-to-upper-middle-income countries”. Inclusion criteria were original studies, written in English, reporting genetic results on PD patients from non-European populations. Two levels of independent reviewers identified and extracted relevant information.We observed considerable imbalances in PD genetic studies among URP. Asian participants from China were described in the majority of the articles published (61%), 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 seven studies using a genome-wide approach published up to 2021 including URP.This review provides insight into the significant lack of population diversity in PD research highlighting the urgent need for better representation. The Global Parkinson’s Genetics Program (GP2) and similar initiatives aim to impact research in URP, and the early metrics presented here can be used to measure progress in the field of PD genetics in the future.

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.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.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.

The objective of this paper was to report on a case of steroid-responsive chorea in a patient with κ light-chain monoclonal gammopathy. In addition to subacute-onset generalized chorea, evidence of peripheral neuropathy in this elderly gentleman led us to investigate for paraproteinemia. We treated the patient with intravenous steroids in view of elevated κ light-chain assay and bone marrow biopsy, suggestive of monoclonal gammopathy of undetermined significance. There was a remarkable improvement of paresthesias and chorea at 6 months follow-up with no evidence of evolution to malignancy at 1 year. Autoimmune chorea is a treatable condition if identified and treated timely.

Home to a culturally heterogeneous population, India is also a melting pot of genetic diversity. The population architecture characterized by multiple endogamous groups with specific marriage patterns, including the widely prevalent practice of consanguinity, not only makes the Indian population distinct from rest of the world but also provides a unique advantage and niche to understand genetic diseases. Centuries of genetic isolation of population groups have amplified the founder effects, contributing to high prevalence of recessive alleles, which translates into genetic diseases, including rare genetic diseases in India.Rare genetic diseases are becoming a public health concern in India because a large population size of close to a billion people would essentially translate to a huge disease burden for even the rarest of the rare diseases. Genomics-based approaches have been demonstrated to accelerate the diagnosis of rare genetic diseases and reduce the socio-economic burden. The Genomics for Understanding Rare Diseases: India Alliance Network (GUaRDIAN) stands for providing genomic solutions for rare diseases in India. The consortium aims to establish a unique collaborative framework in health care planning, implementation, and delivery in the specific area of rare genetic diseases. It is a nation-wide collaborative research initiative catering to rare diseases across multiple cohorts, with over 240 clinician/scientist collaborators across 70 major medical/research centers. Within the GUaRDIAN framework, clinicians refer rare disease patients, generate whole genome or exome datasets followed by computational analysis of the data for identifying the causal pathogenic variations. The outcomes of GUaRDIAN are being translated as community services through a suitable platform providing low-cost diagnostic assays in India. In addition to GUaRDIAN, several genomic investigations for diseased and healthy population are being undertaken in the country to solve the rare disease dilemma.In summary, rare diseases contribute to a significant disease burden in India. Genomics-based solutions can enable accelerated diagnosis and management of rare diseases. We discuss how a collaborative research initiative such as GUaRDIAN can provide a nation-wide framework to cater to the rare disease community of India.

Objective There is limited literature on cognitive, behaviour and sleep-related adverse effects of levetiracetam and oxcarbazepine among adult epilepsy patients, except for what is available from the initial efficacy trials. This study was initiated with the aim to evaluate the incidence and prevalence of various cognitive, behaviour and sleep-related adverse effects of levetiracetam versus oxcarbazepine among people with epilepsy. Methods The study was conducted in two parts: part A was a cross-sectional study, and part B was a longitudinal study. Trail making test A & B, digit symbol substitution test, Stroop colour and word test, controlled oral word association test and PGI memory scale, Neuropsychiatric Inventory, sleep log and ESS-I were used for assessment of cognitive, behaviour and sleep-related adverse effects. Results In the cross-sectional as well as prospective study, no significant difference was observed in the cognitive performance of patients in levetiracetam and oxcarbazepine group in any of the cognitive assessment. Among 120 patients enrolled in the cross-sectional study, significantly higher number of patients in the levetiracetam group compared to the oxcarbazepine group,had agitation/aggression (20% vs10%, p = 0.047) and irritability (26.7% vs 3.3%, p = 0.007).Among 132 patients enrolled in the prospective study, significantly higher increase in the domain score of agitation/aggression (14.5% vs 1.6%, p = 0.028) and irritability (17.7% vs 1.6%, p = 0.018) was observed in the levetiracetam group compared to oxcarbazepine group. A significantly higher proportion of patients in the oxcarbazepine group had hypersomnolence (11.3% vs 1.6%, p = 0.026), as compared to the levetiracetam group. Significance On cross-sectional as well as on longitudinal assessment, nearly one-fifth of patients on levetiracetam have behaviour related adverse effects, with dose modification required for half among these. Nearly 11% of patients on oxcarbazepine reported sleep-related adverse effects (higher total sleep duration per 24 h).

AIM: The aim of this study was to detect the diagnostic accuracy of a novel app (Neurology Dx) vis-a-vis neurology residents. METHODS: A multicenter cross-sectional study involving seven leading teaching neurology institutes in India was conducted by recruiting 100 neurology residents. Primary outcome was proportion of correctly identified high likely gold standard differential diagnoses. Secondary outcomes were proportions of correctly identified first high likely, first three high likely, first five high likely, and combined moderate plus high likely gold standard differentials. RESULTS: Four sets comprising 15 movement disorder vignettes each (total 60) were tested on 100 neurology residents (one set for each resident) and also on the app (60 vignettes). Residents correctly identified the gold standard “high likely” differentials with a frequency of 13.6% as against 41.5% by the app (95% confidence interval [CI]: 21.9–34.1). On combining “high” and “moderate likely” differentials, residents could accurately identify gold standard differentials with a frequency of 10.8% as against 37.9% by the app (95% CI: 22.6–31.9). The residents correctly identified first five high likely gold standard differentials with a frequency of 13.5% versus 23.7% by the app (95% CI: 5.3–15.9). The residents correctly identified first three high likely gold standard differentials with a frequency of 13.0% versus 15.8% by the app (95% CI: -1.2–7.9). Residents correctly identified the first “high likely” gold standard differential in 32.3% as against 35% by the app (95% CI: -8.4–15.6). CONCLUSIONS AND RELEVANCE: This study suggests that an app (Neurology Dx) is capable of generating differential diagnoses to complement clinical reasoning of neurology residents (CTRI/2017/06/008838).

Background: Magnetic resonance guided focused ultrasound (MRgFUS) is a relatively novel technique to treat essential tremor (ET). The objective of this review was to analyze the efficacy and the safety profile of MRgFUS for ET.Methods: A systematic literature review was done. The post procedure changes in the Clinical Rating Scale for Tremor (CRST) score, hand score, disability and quality of life scores were analyzed.Results: We found 29 studies evaluating 617 patients. DTI based targeting was utilized in six cohorts. A significant difference was observed in the pooled standard mean difference between the pre and postoperative total CRST score (p-value < 0.001 and 0.0002), hand score (p-value 0.03 and 0.02); and the disability at 12 months (p-value 0.01). Head pain and dizziness were the most in procedure complications. The immediate pooled proportion of ataxia was 50%, while it was 20% for sensory complications, which, respectively, declined to 31 and 13% on long term follow up. A significant reduction (p = 0.03) in immediate ataxia related complications was seen with DTI targeting.Conclusion: MRgFUS for ET seems to be an effective procedure for relieving unilateral tremor. Use of DTI based targeting revealed a significant reduction in post procedure ataxia related complications as compared to traditional targeting techniques. Analysis of other complications further revealed a decreasing trend on follow up.

Twitter is a free, open access social media platform that is widely used in medicine by physicians, scientists, and patients. It provides an opportunity for advocacy, education, and collaboration. However, it is likely not utilized to its full advantage by many disciplines in medicine, and pitfalls exist in its use. In particular, there has not been a review of Twitter use and its applications in the field of neurology. This review seeks to provide an understanding of the current use of Twitter in the field of neurology to assist neurologists in engaging with this potentially powerful application to support their work.

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.

Central nervous system (CNS) melioidosis is a rare neurological infectious disease which carries a high mortality. We describe a previously healthy middle-aged female, who presented to us with left-sided hemiparesis and was on antitubercular therapy from a previous presumed diagnosis of CNS tuberculoma. Non-characteristic imaging picture, multiple negative body fluid cultures, and positive Cerebrospinal fluid galactomannan led to a further delay in diagnosis. Gram stain of the tissue obtained from brain biopsy revealed Gram-negative rods in “safety pin” appearance. By picking up the colonies that appeared on blood agar and MacConkey agar, the identification of the clinical isolates was performed using VITEK® matrix (BioMérieux, Marcy-L’Etoile, France)-assisted laser desorption ionization time-of-flight mass spectrometry (VITEK MALDI TOF MS database version 3.2) which revealed Burkholderia pseudomallei. After the institution of appropriate treatment, she survived but with significant morbidity. A high index of suspicion should be kept for such previously healthy individuals belonging to non-endemic areas, where presentation is suspicious of an infective etiology, but not improving despite appropriate therapy. This may help in early recognition and institution of recommended treatment so that mortality can be avoided.

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.

Background: Deep brain stimulation (DBS) is currently the preferred surgical treatment for various movement disorders. Pallidotomy is an effective procedure for patients with dystonia and Parkinson's disease and was the surgical treatment of choice before the advent of DBS. However, it can be the preferred modality in immunocompromised patients and those patients who cannot afford DBS due to financial constraints. Hypophonia, dysarthria and dysphagia are the most significant complications of bilateral pallidotomy. Objective: The aim of this study was to present the surgical technique and nuances involved in bilateral simultaneous pallidotomy in a patient with generalized dystonia. Procedure: A 30-year male with primary generalized dystonia presented to us with preoperative Burke–Fahn–Marsden (BFM) Dystonia Rating Scale of 24. After acquiring preoperative volumetric 3T MRI and stereotactic CT, bilateral pallidotomy was done under general anesthesia. There were no procedure related complications. Results: At two months of follow-up, his BFM dystonia score improved from 24 to 4.5. Conclusion: Appropriately acquired volumetric MRI, meticulous planning and meticulously performed surgical procedure can help in achieving good outcome and minimize the complications.

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.

ObjectivesVanishing white matter (VWM), an inherited leukoencephalopathy affecting the brain and the spinal cord, is most often a childhood-onset progressive disorder, generally presenting with ataxia. The adult-onset VWM is relatively rare with slowly progressive cognitive dysfunction dominating the clinical presentation. We report a case of adult-onset VWM from the Indian subcontinent.MethodsExome sequencing.ResultsA 58-year-old woman with young-onset diabetes and hypertension presented with gradually progressive cognitive decline beginning at age 40 years. She had early and predominant executive dysfunction and emotional lability and late involvement of memory and navigation. In addition to cognitive dysfunction, the patient experienced bladder and bowel incontinence along with a spastic gait. She also had primary infertility and menopause at age 40 years. Two of the patient's sisters had primary infertility; one of them had urine and stool incontinence along with gait disturbance. An MRI examination of the brain showed diffuse, symmetrical T2/fluid-attenuated inversion recovery white matter hyperintensities. On genetic testing, the patient was found to be homozygous for c.687T>G variation in the EIF2B3 gene.DiscussionAdult-onset VWM is rare. Infertility in an adult patient with progressive cognitive decline should raise a suspicion of VWM.

Introduction. SCA12 an autosomal dominant ataxia, is characterized by tremor in hands at onset followed by gait ataxia and other cortical features during the course of illness. The aim of the study was to identify and quantify spatiotemporal parameters of gait in a group of SCA12 patients and to compare it with healthy subjects. Methods. Genetically confirmed SCA12 patients (n = 25) with mean age of 55.7 ± 10.2 years and age matched healthy individuals (n = 25) with 55.2 ± 10.1 years were studied. A walkway system (by Teckscan, USA) was used to evaluate spatiotemporal parameters of gait in both groups. All the participants were instructed to walk bare foot within comfortable normal speed on sensor plates of walkway system for 30 seconds. The two sampled t test was used with the level of significance p value Results. All spatial and temporal parameter mean values were significantly different from the control group, except for single support time and swing time. Most significant findings in spatial and temporal parameters concerned stride length (106.8 ± 7.4cm in control group vs 79.0 ± 19.4 cm in patients, p = 0.000), step width (7.8 ± 1.7 cm in control group vs 13.8 ± 2.8 cm in patients, p = 0.000), double support time (0.35 ± 0.6 sec in control group vs 0.61 ± 0.30 sec in patients, p=0.005) and gait velocity (83.5 ± 14.5 cm/sec in control group vs 48.86 ± 21.6 cm/s in patients, p = 0.000). Ten patients with normal gait had mean duration of illness 4.4 ± 1.2 year and mean CAG repeat number 55.7 ± 5.4. Mean duration of illness and mean CAG repeat number of 15 patients having abnormal gait was 6.8 ± 5.4 years and 53.8 ± 7.3. Conclusion. Gait ataxia in SCA12 patients was a late feature and developed after around 5 years of illness. Gait showed significant reduction in stride length, step length, gait velocity with mark increase in step width and double support time.

Antiparasitic treatment improves the prognosis for neurocysticercosis (NCC)-induced seizures. However, patients with high lesion loads are typically denied the possible benefit of cysticidal therapy because of fear of complications, and such patients are not represented in clinical trials involving cysticidal therapy. We provide proof of concept for combination treatment with dual antiparasitic therapy and corticosteroids in patients with diffuse lesions, including starry sky patterns, or calcific NCC. The safety and efficacy of treating patients with high lesion loads or calcific NCC should be tested in a randomized controlled trial.

Highlights • Parkinson's disease symptoms worsened during home confinement. • Difficulty in availing formal neurology consultations and/or medicines. • Quality of life in Parkinson's disease patients declined during home confinement. • Use of telemedicine may benefit patients.

UNSTRUCTURED Twitter is a free, open access social media platform that is widely used in medicine by physicians, scientists, and patients. It provides an opportunity for advocacy, education, and collaboration. However, it is likely not utilized to its full advantage by many disciplines in medicine, and pitfalls exist in its use. In particular, there has not been a review of Twitter use and its applications in the field of neurology. This review seeks to provide an understanding of the current use of Twitter in the field of neurology to assist neurologists in engaging with this potentially powerful application to support their work.