RE-OPEN: Randomised trial of biosimilar TNK versus TPA during endovascular therapy for acute ischaemic stroke due to large vessel occlusions.

Rationale: Rapid and timely treatment with intravenous thrombolysis and endovascular treatment (EVT) in patients with acute ischaemic stroke (AIS) and large vessel occlusion (LVO) significantly improves patient outcomes. Bridging therapy is the current standard of care in these patients. However, an incompletely answered question is whether one thrombolytic agent is better than another during bridging therapy. Aim: The current study aims to understand if one thrombolytic agent is superior to the other during bridging therapy in the treatment of AIS and LVO. Sample size estimates: Using 80% power and an alpha error of 5 %, presuming a 10% drop out rate, a total of 372 patients will be recruited for the study. Methods and design: This study is a prospective, randomised, multicentre, open-label trial with blinded outcome analysis design. Study outcomes: The primary outcomes include proportion of patients who will be independent at 3 months (modified Rankin score (mRS) ≤2 as good outcome) and proportion of patients who achieve recanalisation modified thrombolysis in cerebral infarction grade 2b/3 at first angiography run at the end of EVT. Secondary outcomes include proportion of patients with early neurological improvement, rate of symptomatic intracerebral haemorrhage (ICH), rate of any ICH, rate of any systemic major or minor bleeding and duration of hospital stay. Safety outcomes include any intracranial bleeding or symptomatic ICH. Discussion: This trial is envisioned to confirm the theoretical advantages and increase the strength and quality of evidence for use of tenecteplase (TNK) in practice. Also, it will help to generate data on the efficacy and safety of biosimilar TNK. Trial registration number: CTRI/2022/01/039473.

Optical Genome Mapping for the Molecular Diagnosis of Facioscapulohumeral Muscular Dystrophy: Advancement and Challenges.

Facioscapulohumeral muscular dystrophy (FSHD) is the second most common muscular dystrophy in adults, and it is associated with local D4Z4 chromatin relaxation, mostly via the contraction of the D4Z4 macrosatellite repeat array on chromosome 4q35. In this study, we aimed to investigate the use of Optical Genome Mapping (OGM) as a diagnostic tool for testing FSHD cases from the UK and India and to compare OGM performance with that of traditional techniques such as linear gel (LGE) and Pulsed-field gel electrophoresis (PFGE) Southern blotting (SB). A total of 6 confirmed and 19 suspected FSHD samples were processed with LGE and PFGE, respectively. The same samples were run using a Saphyr Genome-Imaging Instrument (1-color), and the data were analysed using custom EnFocus FSHD analysis. OGM was able to confirm the diagnosis of FSHD1 in all FSHD1 cases positive for SB (n = 17), and D4Z4 sizing highly correlated with PFGE-SB (p < 0.001). OGM correctly identified cases with mosaicism for the repeat array contraction (n = 2) and with a duplication of the D4Z4 repeat array. OGM is a promising new technology able to unravel structural variants in the genome and seems to be a valid tool for diagnosing FSHD1.

Healthcare professionals' perspectives of the provision of, and challenges for, eating, drinking and psychological support post stroke: findings from semistructured interviews across India.

AIM: This qualitative study explores with health professionals the provision of, and challenges for, postdischarge stroke care, focussing on eating, drinking and psychological support across India. DESIGN: Qualitative semistructured interviews. SETTING: Seven geographically diverse hospitals taking part in a Global Health Research Programme on Improving Stroke Care in India. PARTICIPANTS: A purposive sample of healthcare professionals with current experience of working with patients who had a stroke. RESULTS: Interviews with 66 healthcare professionals (23 nurses (14 staff nurses; 7 senior nurse officers; 1 intensive care unit nurse; 1 palliative care nurse)); 16 doctors (10 neurologists; 6 physicians); 10 physiotherapists; 5 speech and language therapists; 4 occupational therapists; 4 dieticians; 2 psychiatrists; and 2 social workers resulted in three main themes: integrated inpatient discharge care planning processes; postdischarge patient and caregiver role and challenges; patient and caregiver engagement post discharge. CONCLUSIONS: Discharge planning was integrated and customised, although resources were limited in some sites. Task shifting compensated for a lack of specialists but was limited by staff education and training. Caregivers faced challenges in accessing and providing postdischarge care. Postdischarge care was mainly hospital based, supported by teleservices, especially for rural populations. Further research is needed to understand postdischarge care provision and the needs of stroke survivors and their caregivers.

Use of Social Media in Stroke: A Systematic Review.

Background: Stroke is a leading cause of death and disability globally. Over the last decade, digital health and related technology has emerged as a useful adjunct in the management of persons with stroke, particularly with the development of a large number of mobile phone applications dedicated to various aspects of stroke. However, whether social media can provide similar key support in stroke is an intriguing question. In this systematic review, we aimed to the scope and limits of social media platforms in care and research pertinent to persons with stroke. Methods: PubMed database was searched using Medical Subject Headings terms and exploded keywords. The search retrieved 556 abstracts, which were screened by two reviewers. Of these, 14 studies met the review inclusion criteria. Given the small number of studies and heterogeneity of outcomes, quantitative analysis was not possible. The review was registered on PROSPERO (CRD42022324384). Results: The social media platforms employed by the included studies comprised YouTube (n = 5), Twitter (n = 5), Facebook (n = 2), both Twitter and Facebook (n = 1), and WhatsApp (n = 1). Four assessed quality and accuracy of videos on YouTube available for stoke patients and caregivers. Three used social media to research link between role of gender and stroke descriptors on social media platforms, and one studied Twitter-derived racial/ethnic perceptual construction on the occurrence of cardiovascular disease. Three studies described use of social media by stroke survivors, in post-stroke care and engagement. 11 studies were assessed to be of "fair" quality and three were assessed to be of "poor" quality. Conclusions: Limited preliminary data of low quality indicates that social media is used by persons with stroke and their caregivers, and may be harnessed as a tool of education and research. Future studies must address the current lack of high-quality evidence for the use of social media in stroke care.

Zonisamide add-on in tremor-dominant Parkinson's disease- A randomized controlled clinical trial.

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.

Machine learning based reanalysis of clinical scores for distinguishing between ischemic and hemorrhagic stroke in low resource setting.

BACKGROUND: Identifying ischemic or hemorrhagic strokes clinically may help in situations where neuroimaging is unavailable to provide primary-care prior to referring to stroke-ready facility. Stroke classification-based solely on clinical scores faces two unresolved issues. One pertains to overestimation of score performance, while other is biased performance due to class-imbalance inherent in stroke datasets. After correcting the issues using Machine Learning theory, we quantitatively compared existing scores to study the capabilities of clinical attributes for stroke classification. METHODS: We systematically searched PubMed, ERIC, ScienceDirect, and IEEE-Xplore from 2001 to 2021 for studies that validated the Siriraj, Guys Hospital/Allen, Greek, and Besson scores for stroke classification. From included studies we extracted the reported cross-tabulation to identify and correct the above listed issues for an accurate comparative analysis of the performance of clinical scores. RESULTS: A total of 21 studies were included. Comparative analysis demonstrates Siriraj Score outperforms others. For Siriraj Score the reported sensitivity range (Ischemic Stroke-diagnosis) 43-97% (Median = 78% [IQR 65-88%]) is significantly higher than our calculated range 40-90% (Median = 70% [IQR 57-73%]), also the reported sensitivity range (Hemorrhagic Stroke-diagnosis) 50-95% (Median = 71% [IQR 64-82%]) is higher than our calculated range 34-86% (Median = 59% [IQR 50-79%]) which indicates overestimation of performance by the included studies. Guys Hospital/Allen and Greek Scores show similar trends. Recommended weighted-accuracy metric provides better estimate of the performance. CONCLUSION: We demonstrate that clinical attributes have a potential for stroke classification, however the performance of all scores varies across demographics, indicating the need to fine-tune scores for different demographics. To improve this variability, we suggest creating global data pool with statistically significant attributes. Machine Learning classifiers trained over such dataset may perform better and generalise at scale.

Disseminated Cysticercosis-Should we treat?

Disseminated cysticercosis is defined by the presence of multiple vesicular cystic lesions in the brain with cysts demonstrable in at least two other body parts. The exact course of disseminated cysticercosis is not known and the individual cysts either become inflamed or calcify. A patient's quality of life is often poor and disseminated cysticercosis treatment is far from satisfactory. Anecdotal reports have suggested dual antiparasitic therapy to be beneficial for treating diffuse parenchymal neurocysticerci and might be worth trying in patients with massively infiltrating disseminated cysticercosis with concomitant corticosteroids.

SCA2 in the Indian population: Unified haplotype and variable phenotypic patterns in a large case series.

BACKGROUND: Spinocerebellar ataxia-2 is one of the most prevalent SCA type across the world and one of the commonest in India. We aimed to characterize SCA2 patients both clinically and genetically (ATXN2-CAG repeats and its haplotypic background). METHODS: A total of 436 SCA2 patients were recruited consecutively comprising individuals of multiple ethnicities and two large multigenerational families. A detailed clinical evaluation and genetic analysis for CAG repeat length estimation and two marker based haplotype analysis [rs695871 and rs695872 located 177 bp and 106 bp upstream of CAG sequence in Exon 1 of ATXN2] was performed. RESULTS: Generalized limb ataxia and slow saccades were prevalent features in majority of our patients, while hyporeflexia and extrapyramidal features were less commonly observed manifestations. Slow ocular saccades, upper limb ataxia and tremor showed significant associations with age of onset, CAG repeat length and disease duration. We observed a 100% association of C-C haplotype with the expanded ATXN2 repeats. CONCLUSION: This study represents the largest study of SCA2 Indian patients that highlights the clinico-genetic manifestations and haplotype analysis. A significant proportion of patients have not shown the characteristic slow saccades and hyporeflexia thus indicating the influences of other factors in modulation of the disease which warrants further investigations. The observation of CC haplotype in all our SCA2 patients indicates a common origin across all Indian sub populations and that also indicate a common global founder event in the past.

Cholesterol Embolization Syndrome After Carotid Artery Stenting Associated with Delayed Cerebral Hyperperfusion Intracerebral Hemorrhage.

BACKGROUND: The cholesterol embolization syndrome (CES) results from the distal embolization of cholesterol crystals from atheromatous plaques in large vessels such as the aorta and results in multiorgan damage. CASE DESCRIPTION: We present the case of a patient with definite CES with skin manifestations (e.g., blue toes) and renal and neurological dysfunction, including parenchymal hematoma with cytotoxic and vasogenic edema after he had undergone left carotid artery stenting for symptomatic critical left carotid artery stenosis. CONCLUSIONS: Our patient with CES had cutaneous involvement affecting the lower limbs and renal and neurological involvement. High clinical suspicion and early treatment can reduce the mortality and morbidity after endovascular procedures. The neurological symptoms had most likely resulted from delayed cerebral hyperperfusion syndrome resulting in intracerebral hemorrhage.

Acute encephalopathy followed by delayed myelopathy: A rare presentation of organophosphate poisoning.

Organophosphorus compounds (OPC) are commonly used pesticides and suicidal ingestion is a common mode of poisoning. The manifestation of OPC poisoning and its severity depend upon the type, dose and potency of the OPC consumed. Neurological presentations are well defined clinical syndromes consisting of early, intermediate and delayed manifestations (rare), categorised on the basis of time elapsed since OPC exposure. We report a rare delayed manifestation of organophosphorus poisoning in the form of pure motor spastic paraparesis due to dorsal myelopathy. A possibility of delayed manifestations of toxicity should be considered in individuals presenting with features suggestive of myelopathy and a previous history of organophosphate exposure.

Optic neuritis following anti-rabies vaccine.

Neurological complications related to anti-rabies vaccine are uncommon. The involvement of the optic nerve is extremely rare. It has been occasionally reported after Semple's vaccine administration due to the presence of highly antigenic sheep brain tissue in the vaccine. To our knowledge, this is the first case report of optic neuritis after chick embryo-derived anti-rabies vaccine.