Beyond the Eyes: Clinico-Radiological Correlation of Bilateral Complete Horizontal Gaze Palsy in Moebius Syndrome.

Moebius syndrome is a rare disease characterized by unilateral or bilateral facial nerve palsies with/without other cranial nerve palsy. It manifests clinically with facial muscle weakness and/or ophthalmoplegia and can be associated with other physical anomalies such as various limb deformities and orofacial malformation. Herein, we have described the clinical and radiological features of Moebius syndrome in a 9-year-old female child who presented with left-side facial palsy and bilateral complete horizontal gaze palsy.

Correlation Between Optical Coherence Tomography Angiography Findings at 3 to 6 Weeks and Functional Outcome at 3 Months Following Acute Ischaemic Stroke Due to Extracranial Carotid Artery Atherosclerotic Disease.

We wanted to evaluate if optical coherence tomography angiography OCTA findings could predict the functional outcome in extracranial carotid artery atherosclerotic disease (ECAD) associated stroke. This exploratory study was performed on adults with acute ischaemic stroke due to ECAD at 3-6 weeks following stroke onset with risk factor matched controls without carotid artery stenosis. Twenty-three stroke patients (cases) and 23 controls were enrolled. There was significant difference between cases and controls in deep vessel density at the macula (p = .0007) and in radial peripapillary capillary perfusion density (RPCPD) at the optic nerve head (ONH) (p = .0007). Statistically significant difference was noted in the total superficial vessel density (SVD) at the macula (SVD within 1 standard deviation [SD] versus SVD beyond 1 SD of control data) in the ipsilateral eye and functional outcome at 3 months (poor versus very good outcome, modified Rankin scale [mRS] 0-1 versus mRS 2-6, respectively; p = .0361). There was statistically insignificant correlation between the RPCPD at the ONH and the National Institutes of Health Stroke Scale score at admission, mRS at discharge, and mRS at 3 months following stroke onset (r = .33, r = .35, r = .39; p = .11, p = .09, p = .06, respectively). The findings of this exploratory study suggested that OCTA findings may predict 3 month outcomes in cases of ECAD-related stroke and could be useful in decision making in future intervention studies as to whether intervene or not in patients having critical or non-critical ECAD for preventing stroke.

Effectiveness of Yoga in Modulating Markers of Immunity and Inflammation: A Systematic Review and Meta-Analysis.

Chronic inflammation is central to the pathogenesis of many chronic inflammatory conditions. This review aims to analyze whether the practice of yoga, or yogic meditation and breathing, has any effect on the levels of inflammatory cytokines and other inflammatory markers in patients with various chronic inflammatory diseases such as rheumatoid arthritis, neoplastic disorders, and asthma, as well as in healthy subjects, compared to usual care or sham interventions. A comprehensive search of databases (PubMed, CENTRAL, Embase, and CINAHL) was performed. Randomized controlled trials (RCTs) that evaluated the effects of yoga as an intervention on inflammatory markers were analyzed. A total of 26 studies were included. Only two studies had a low risk of bias (RoB); 24 other studies had a high RoB. Most studies (n=24) reported a favorable outcome with yoga, irrespective of the type of yoga used, the condition studied, and the duration of the intervention. The commonly reported inflammatory markers included IL-6 (n=17), tumor necrosis factor-alpha (TNF-a) (n=13), and C-reactive protein (CRP) (n=10). Most studies showed a significant reduction in inflammatory markers in the yoga group (YG) compared to the control group (CG). Few studies also showed significant improvement in markers of cellular immunity (interferon gamma (IFN-g), IL-10, and transforming growth factor-beta (TGF-b); n=2 each) and improved mucosal defense (IgA, IL-6, and IL-2; n=2 each). A meta-analysis of IL-6, TNF-a, and CRP showed yoga had a favorable effect on the levels of these markers, but it was not statistically significant. Current evidence suggests that yoga can be a complementary intervention for various chronic inflammatory conditions. However, the quality of the evidence is poor, along with considerable heterogeneity. In the future, investigators should describe the intervention better, with a uniform assortment of outcome measures and treatment conditions, to generate high-quality evidence.

Sequential mechanical thrombectomies in acute bilateral middle cerebral artery strokes: A case report and review of literature.

Simultaneous occlusion of both middle cerebral arteries (MCAs) is very rare and usually devastating. Few case reports are available in the literature where bilateral thrombectomy was done simultaneously to remove the clot. High NIH stroke scale with a low level of consciousness can be a clue for the diagnosis. Timely intervention is necessary to decrease morbidity and mortality in these patients. We also reviewed the existing literature where mechanical thrombectomies were done for bilateral MCA stroke in PubMed, Google Scholar, Cochrane, and Embase. Herein, we report a case of 47-year-old female having rheumatic heart disease presented with simultaneous bilateral MCAs occlusion, treated with mechanical thrombectomies successfully.

Emerging insights into cephalic neural crest disorders: A single center experience.

Objectives: Neural crest cells (NCCs) are transient structures in the fetal life in vertebrates, which develop at the junctional site of the non-neural and neural ectoderm, sharing a common developmental origin for diverse diseases. After Epithelio-mesenchymal (EMT) of the NCCs within the neural tube, delamination of NCCs occurs. After delamination, the transformation of these cells into various cell lineages produces melanocytes, bones, and cartilage of the skull, cells of the enteric and peripheral nervous system. After the conversion, these cells migrate into various locations of the entire body according to the cell lineage. Abnormalities in neural crest (NC) formation and migration result in various malformations and tumors, known as neurocristopathy. Material and Methods: Herein, this case series describes a single-center experience in cephalic NC disorders over the past 3 years, including 17 cases of varying composition (i.e., vascular, dysgenetic, mixed, and neoplastic forms) involving the brain and occasionally skin, eyes, and face of the patients. Results: In our study of 17 patients with cephalic NC disease, 6 (35.3%) patients had vascular form, 5 (29.4%) had dysgenetic form, 4 (23.5%) had mixed form, and 2 (11.7%) had neoplastic form. Brain involvement in the form of vascular or parenchyma or both vascular and parenchymal was seen in all of our patients (100%), skin in 6 (35.3%) patients, eye in 2 (11.7%), and face in 1 (5.9%) patient. Treatment was planned according to the various manifestations of the disease. Conclusion: Neural crest diseases (NCDs) are a rare and under-recognized group of disorders in the literature and may have been under-reported due to a lack of awareness regarding the same. More such reporting may increase the repertoire of these rare disorders such that clinicians can have a high degree of suspicion leading to early detection and timely counseling and also improve preventive strategies and help in developing new drugs for these disorders or prevent them.

Reverse Y stenting in the management of vertebrobasilar junction fenestrated aneurysm: A novel technique.

Fenestrated aneurysm at vertebrobasilar junction (VBJ) is very rare and can occur due to non-fusion of longitudinal neural axis forming basilar artery in the early stage of embryonic life. Due to defects in tunica media and weakness in its wall, these fenestrations are more likely to develop an aneurysm. Various treatment strategies are required for the management of these types of aneurysms including simple coiling, stent-assisted coiling, balloon remodeling technique, and more recently kissing flow diverters. Herein, we report the case of ruptured fenestrated VBJ aneurysm which was managed successfully with novel reverse Y stenting with coiling.

Bridging the gap between statistical significance and clinical relevance: A systematic review of minimum clinically important difference (MCID) thresholds of scales reported in movement disorders research.

Background: Minimum clinically important difference (MCID) is the smallest change in an outcome measure that is considered clinically meaningful. Using validated MCID thresholds for outcomes powers trials adequately to detect meaningful treatment effects, aids in their interpretation and guides development of new outcome measures. Objectives: To provide a comprehensive summary of MCID thresholds of various symptom severity scales reported in movement disorder. Methods: We conducted systematic review of the literature and included studies of one or more movement disorders, and reporting MCID scales. Results: 2763 reports were screened. Final review included 32 studies. Risk of bias (RoB) assessment showed most studies were of good quality. Most commonly evaluated scale was Unified Parkinson's Disease Rating Scale (UPDRS) (11 out of 32). Four studies assessing MDS-UPDRS had assessed its different sub-parts, reporting a change of 2.64,3.05,3.25 and 0.9 points to detect clinically meaningful improvement and 2.45,2.51,4.63 and 0.8 points to detect clinically meaningful worsening, for the Part I, II, III and IV, respectively. For Parts II + III, I + II + III and I + II + III + IV, MCID thresholds reported for clinically meaningful improvement were 5.73, 4.9, 6.7 and 7.1 points respectively; while those for clinically meaningful worsening were 4.7, 4.2, 5.2 and 6.3 points, respectively. MCID thresholds reported for other scales included Abnormal Involuntary Movement Scale (AIMS), Toronto Western Spasmodic Torticollis Rating Scale (TWSRS), and Burke-Fahn-Marsden Dystonia Scale (BFMD). Conclusion: This review summarizes all the MCID thresholds currently reported in Movement disorders research and provides a comprehensive resource for future trials, highlighting the need for standardized and validated MCID scales in movement disorder research.

Minimal Clinically Important Difference of Scales Reported in Stroke Trials: A Review.

There is a growing awareness of the significance of using minimum clinically important differences (MCIDs) in stroke research. An MCID is the smallest change in an outcome measure that is considered clinically meaningful. This review is the first to provide a comprehensive summary of various scales and patient-reported outcome measures (PROMs) used in stroke research and their MCID values reported in the literature, including a concise overview of the concept of and methods for determining MCIDs in stroke research. Despite the controversies and limitations surrounding the estimation of MCIDs, their importance in modern clinical trials cannot be overstated. Anchor-based and distribution-based methods are recommended for estimating MCIDs, with patient self-evaluation being a crucial component in capturing the patient's perspective on their health. A combination of methods can provide a more comprehensive understanding of the clinical relevance of treatment effects, and incorporating the patient's perspective can enhance the care of stroke patients.

Early neurological deterioration in acute ischemic stroke.

BACKGROUND AND AIMS: Early neurological deterioration (END) in acute ischemic stroke (AIS), patients is defined as clinical worsening or recurrence during first 72 h after onset of AIS. We have conducted this study to determine the association between END and functional outcome at 3 months of onset of AIS along with associated risk factors of END in AIS cases. METHODOLOGY: This study was conducted after approval of Institute Ethics Committee. Two hundred three consecutive patients were admitted from September 2020 to January 2022 at a tertiary care hospital. One hundred ninety patients were included in the study; patients were divided into two groups: (1) early neurological deterioration (END) and (2) non-early neurological deterioration (non-END). Patients were followed-up either telephonically or in person at approximately 3 months using modified Rankin Scale 0-6. All the clinically significant prognostic markers and p < 0.10 variables were considered significant in univariate analysis; P < 0.05 were considered statistically significant for the multivariate analysis. RESULTS: Out of 190 cases included in the cohort 34/190 (17.8%) cases showed END with mean age (56.56 (± 16.6)) and males (20/34 (58.8%)). END was independently associated with high blood glucose at admission (OR = 1.015; P = 0.002; 95%CI = 1.005-1.024) and low serum albumin (OR = 0.208; P = 0.002; 95%CI = 0.077-0.562). Patients with END showed poor functional outcome (mRS > 2) at end of 3 months (32 (94.1%); P < 0.001) and death was also statistically significant (22 (64.7%); P < 0.001) as compared to AIS cases having non-END. CONCLUSION: Our study showed END may be associated with poor functional outcome in AIS patients. Higher blood glucose at admission and low serum albumin may be statistically significant causing END. Future prospective cohort with larger sample size may confirm the findings.

Minimal Clinically Important Difference (MCID) in Patient-Reported Outcome Measures for Neurological Conditions: Review of Concept and Methods.

The concept of the minimal clinically important difference (MCID) emerged from the recognition that statistical significance alone is not enough to determine the clinical relevance of treatment effects in clinical research. In many cases, statistically significant changes in outcomes may not be meaningful to patients or may not result in any tangible improvements in their health. This has led to a growing emphasis on the importance of measuring patient-reported outcome measures (PROMs) in clinical trials and other research studies, in order to capture the patient perspective on treatment effectiveness. MCID is defined as the smallest change in scores that is considered meaningful or important to patients. MCID is particularly important in fields such as neurology, where many of the outcomes of interest are subjective or based on patient-reported symptoms. This review discusses the challenges associated with interpreting outcomes of clinical trials based solely on statistical significance, highlighting the importance of considering clinical relevance and patient perception of change. There are two main approaches to estimating MCID: anchor-based and distribution-based. Anchor-based approaches compare change scores using an external anchor, while distribution-based approaches estimate MCID values based on statistical characteristics of scores within a sample. MCID is dynamic and context-specific, and there is no single 'gold standard' method for estimating it. A range of MCID thresholds should be defined using multiple methods for a disease under targeted intervention, rather than relying on a single absolute value. The use of MCID thresholds can be an important tool for researchers, neurophysicians and patients in evaluating the effectiveness of treatments and interventions, and in making informed decisions about care.

"Shelf Technique" in braided stent (Leo Baby) in wide-necked intracranial aneurysm.

A 42-year-old female presented with sudden onset severe headache without loss of consciousness 4 days back. Non-contrast computed tomography scan of the brain showed subarachnoid hemorrhage, and angiography showed a wide-necked aneurysm in the right middle cerebral artery (MCA) bifurcation, incorporating the superior division of right M2 MCA and another small aneurysm in the inferior division of right M2 MCA. Because of the wide-necked ruptured aneurysm and another in the inferior division of right M2 MCA, braided stent-assisted coiling (Leo baby) with shelving was done to protect both the aneurysms and to protect the superior branch of M2 MCA. The patient tolerated the procedure well and had an uneventful recovery. In this report, we have also reviewed and discussed the challenges, advantages, and disadvantages of the newly discovered shelving technique with a braided stent for wide-necked bifurcation aneurysms.

Importance of high-quality evidence regarding the use of Bacopa monnieri in dementia.

Background: Bacopa monnieri (BM), a commonly used herb, has shown neuroprotective effects in animal and in vitro studies; but human studies on patients with Alzheimer's Disease (AD) have been inconclusive. Further high-quality trials are required to conclusively state the utility of BM in AD and other neurodegenerative dementias. Methods: In the present study, we did a narrative review of the current challenges in designing clinical trials of BM in dementia and their evidence-based recommendations. Results: Many facets of the BM trials need improvement, especially effect size and sample size estimation. Current assessment and outcomes measures need a more holistic approach and newer scales for diagnosing and monitoring prodromal AD. The stringent guidelines in CONSORT and STROBE are often considered difficult to implement for clinical trials in ayurvedic medications like BM. However, adherence to these guidelines will undoubtedly improve the quality of evidence and go a long way in assessing whether BM is efficacious in treating AD/prodromal AD patients and other neurodegenerative dementias. Conclusion: Future studies on BM should implement more randomized controlled trials (RCTs) with an appropriate sample size of accurately diagnosed AD/prodromal AD patients, administering a recommended dosage of BM and for a pre-specified time calculated to achieve adequate power for the study. Researchers should also develop and validate more sensitive cognitive scales, especially for prodromal AD. BM should be evaluated in accordance with the same rigorous standards as conventional drugs to generate the best quality evidence.

Latest Trends in Outcome Measures in Dementia and Mild Cognitive Impairment Trials.

Disease modification trials in dementia and mild cognitive impairment (MCI) have not met with success. One potential criticism of these trials is the lack of sensitive outcome measures. A large number of outcome measures have been employed in dementia and MCI trials. This review aims to describe and analyze the utility of cognitive/clinical outcome measures in Alzheimer's disease (AD) and MCI trials. Methods: A PubMed search was conducted using relevant MeSH terms and exploded keywords. The search was confined to English language publications of human studies from the last five years which describe the latest trends in the use of outcome measures. Results: Despite broad use, the outcome measures employed are heterogeneous, with little data on correlations between scales. Another problem is that most studies are over-reliant on clinician/researcher assessment and cognitive outcomes, and there is a definite lack of stakeholder input. Finetuning of the paradigm is also required for people with early-stage disease, mild to moderate disease, and advanced dementia, as the outcome measures in these subgroups have varying relevance. Disease modification/prevention is an appropriate goal in early disease, whereas palliation and freedom from discomfort are paramount in later stages. The outcome measures selected must be suitable for and sensitive to these particular care goals. Although there is a shift to enrich MCI cohorts using a biomarker-based approach, the clinical relevance of such outcome measures remains uncertain. Conclusions: Outcome measures in dementia/MCI trials remain inhomogeneous and diverse, despite extensive use. Outcome measures fall within several paradigms, including cognitive, functional, quality-of-life, biomarker-based, and patient-reported outcome measures. The success of future disease-modifying trials is reliant to a large extent on the selection of outcome measures which combine all outcomes of clinical relevance as well as clinical meaning. Outcome measures should be tied to the type and stage of dementia and to the specific interventions employed.

Moyamoya Syndrome in Schimke Immune-Osseous Dysplasia: A Rare Association.

Schimke immuno-osseous dysplasia (SIOD) is an uncommon autosomal recessive (AR) spondylo-epiphyseal dysplasia (SED) and its clinical course and phenotype are yet to be properly described. The phenotypic presentation is quite varied with involvement of the renal, skeletal, vascular, immune, and hematopoietic systems being the most common presentation. We describe a 19-year-old female who presented with adolescent-onset brain and skeletal involvement without renal manifestations. Based on imaging and clinical features, she was diagnosed with a case of SIOD. There is no definitive treatment yet for this disorder, however, clinicians should be aware of this disorder so that adequate counseling and symptomatic management, especially in controlling hypertension and dyslipidemia, can be provided to the affected patients.

Publication of neurology clinical trials registered with clinical trial registry of India: A cross-sectional study.

OBJECTIVES: Unbiased and full disclosure of trial results is vital to evidence-based medicine. Non-publication and selective publication leads to publication bias and unrealistic risk-benefit ratio. In the present study, we aim to determine the publication rate of clinical trials related to neurology registered with the Clinical Trial Registry of India (CTRI), compare the characteristics of published and unpublished trials, and evaluate the adherence of investigators to ethics-approved criteria and outcomes. MATERIALS AND METHODS: A cross-sectional search using the keyword "neurology" was carried out in CTRI registry. Two independent investigators searched Pubmed, Medline, Scopus, and Google Scholar for published manuscripts. The final literature search occurred in November 2021. RESULTS: Out of 325 trials, 102 trials were published (31.4%). Ninety-one trials were beyond 3 years of expected time of trial completion and were still unpublished. Randomized trials had a slightly higher publication rate than non-randomized ones (56% vs. 46%, p = .223); however the difference was not statistically significant. Majority of trials sponsored by pharmaceutical companies were not published, while majority of those sponsored by non-pharmaceutical institutions were published (34.5% vs. 69.3%, p < .001). Feedback to CTRI about trial status was particularly poor (31.5% - informed vs. 68.5% - not informed, p < .001). 52 (50.9%) and 65 (63.7%) of the 102 published trials had changed the registered inclusion and exclusion criteria, respectively, in the CTRI registry compared to those in the published manuscript. In 29 (28.3%) of the 102 trials, the primary outcome did not match with that registered in the CTRI and in 73 (57.8%) trials, the secondary outcomes did not match. CONCLUSION: A large proportion of neurology registered trials are still unpublished, with a majority of pharmaceutical company-sponsored trials not being published. There is scope for improving the provisions in CTRI for enlisting trial results, that may prevent publication bias and also ensure the investigators adhere to the pre-specified ethics approved trial procedures and outcomes.

Comparison of Disease Profiles and Three-Month Outcomes of Patients with Neurological Disorders with and without COVID-19: An Ambispective Cohort Study.

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.

Megalencephaly-Capillary Malformation-Polymicrogyria Syndrome (MCAP): A Rare Dynamic Genetic Disorder.

Megalencephaly-capillary malformation-polymicrogyria syndrome (MCAP) is an uncommon malformation syndrome, characterized by primary megalencephaly, capillary malformations of the midline face and body, or distal limb anomalies such as syndactyly and polymicrogyria. Herein, we report a young male child, who presented with complaints of increasing head size, delay in speech, and one episode of focal seizure with distinctive morphological and neuroradiological manifestations which led to the diagnosis of MCAP. We have also reviewed recently published literature and the various diagnostic criteria proposed by authors to achieve the early clinical diagnosis of these patients in the outpatient department.

Use of Bacopa monnieri in the Treatment of Dementia Due to Alzheimer Disease: Systematic Review of Randomized Controlled Trials.

BACKGROUND: Bacopa monnieri, a herb that has been used for many centuries in India, has shown neuroprotective effects in animal and in vitro studies; human studies on patients with Alzheimer disease have been inconclusive. OBJECTIVE: The primary objective of this review was to determine the clinical efficacy and safety of B. monnieri in persons with mild, moderate, or severe dementia, or mild cognitive impairment, due to Alzheimer disease. METHODS: We searched PubMed, Embase, Cochrane Library, clinical trial registries (World Health Organization, Australia-New Zealand, United States, and South Africa), the metaRegister of Controlled Trials, and CINAHL. We intended to include all randomized and quasi-randomized controlled trials that compared B. monnieri, its extract or active ingredients (at any dosage), with a placebo or a cholinesterase inhibitor among adults with dementia due to Alzheimer disease and in those with mild cognitive impairment due to Alzheimer disease. RESULTS: Our comprehensive search yielded 5 eligible studies. A total of 3 studies used B. monnieri in combination with herbal extracts while the remaining 2 used B. monnieri extracts only. Two studies compared B. monnieri with donepezil while the others used a placebo as the control. There was considerable variation in the B. monnieri dose used (ranging between 125 mg to 500 mg twice daily) and heterogeneity in treatment duration, follow-up, and outcomes. The major outcomes were Mini-Mental State Examination scores reported in 3 trials, Cognitive subscale scores of the Alzheimer's Disease Assessment Scale in 1 study, and a battery of cognitive tests in 2 studies. Using the Cochrane risk-of-bias tool, overall, we judged all 5 studies to be at high risk of bias. While all studies reported a statistically significant difference between B. monnieri and the comparator in at least one outcome, we rated the overall quality of evidence for the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Postgraduate Institute Memory Scale, Mini-Mental State Examination, and Wechsler Memory Scale to be very low due to downgrading by 2 levels for high risk of bias and 1 more level for impreciseness due to small sample sizes and wide CIs. CONCLUSIONS: There was no difference between B. monnieri and the placebo or donepezil in the treatment of Alzheimer disease based on very low certainty evidence. No major safety issues were reported in the included trials. Future randomized controlled trials should aim to recruit more participants and report clinically meaningful outcomes. TRIAL REGISTRATION: PROSPERO CRD42020169421; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=169421.