Stroke is a major health problem world-wide and its burden has been rising in last few decades. Until now tissue plasminogen activator is only approved treatment for stroke. Angiogenesis plays a ...vital role for striatal neurogenesis after stroke. Administration of various growth factors in an early post ischemic phase, stimulate both angiogenesis and neurogenesis and lead to improved functional recovery after stroke. However vascular endothelial growth factors (VEGF) is the most potent angiogenic factor for neurovascularization and neurogenesis in ischemic injury can be modulated in different ways and thus can be used as therapy in stroke. In response to the ischemic injury VEGF is released by endothelial cells through natural mechanism and leads to angiogenesis and vascularization. This release can also be up regulated by exogenous administration of Mesenchymal stem cells, by various physical therapy regimes and electroacupuncture, which further potentiate the efficacy of VEGF as therapy in post stroke recovery. Recent published literature was searched using PubMed and Google for the article reporting on methods of up regulation of VEGF and therapeutic potential of growth factors in stroke.
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
Background India is a subtropical country with clear seasonal variations in weather conditions. Seasonal and circadian variation in occurrence of subtypes of cerebrovascular disease has been of ...interest in several studies from different countries and climate zones, but discrepant results have made the conclusions unclear. The aim of the present study was to observe the seasonal and circadian variation in the occurrence of stroke and its subtypes among our population. Methods This was a cross-sectional observational study based on new cases and past cases of stroke on follow-up, conducted between January 2011 and December 2012 in the Department of Neurology, at the All India Institute of Medical Sciences, New Delhi, India. The date and time of onset of the stroke was recorded. The categorization of months into season was in accordance with the Indian Meteorological Department guidelines. The time of onset was distributed into 6 hourly intervals. Statistical calculations were performed using Stata version 12.1 and SPSS version 20. Results A total of 583 patients were included for the study. The rate of occurrence of stroke was highest in the late morning 0600-1159 hours ( P value <.001) compared with other times of the day, regardless of gender or age for both ischemic and hemorrhagic strokes. It was lowest in late evening (1800-2359 hours) quadrant compared with other quadrants. Although there was no significant difference found by dichotomizing the groups into two 6-month periods, there was an increasing trend in number of patients with stroke during the months November-February. There was no difference in stroke occurrence between the types of stroke or within each type among different seasons with different temperatures. Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification of ischemic strokes also did not show any association with season or circadian rhythm. Conclusions There is a significant increase in occurrence of strokes between 0600 and 1159 hours and lowest between 1800-2359 hours. No significant variation in stroke occurrence or subtype for any of the seasons was observed.
ABSTRACT
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.
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.
A library of non-immersive Virtual Reality (VR) tasks were developed for post-stroke rehabilitation of distal upper extremities. The objective was to evaluate the rehabilitation impact of the ...developed VR-tasks on a patient with chronic stroke. The study involved a 50-year-old male patient with chronic (13 month) stroke. Twenty VR therapy sessions of 45 min each were given. Clinical scales, cortical-excitability measures, functional MRI (fMRI), and diffusion tensor imaging (DTI) data were acquired pre-and post-therapy to evaluate the motor recovery. Increase in Fugl-Meyer Assessment (wrist/hand) by 2 units, Barthel Index by 5 units, Brunnstrom Stage by 1 unit, Addenbrooke's Cognitive Examination by 3 units, Wrist Active Range of Motion by 5° and decrease in Modified Ashworth Scale by 1 unit were observed. Ipsilesional Motor Evoked Potential (MEP) amplitude (obtained using Transcranial Magnetic Stimulation) was increased by 60.9µV with a decrease in Resting Motor Threshold (RMT) by 7%, and contralesional MEP amplitude was increased by 56.2µV with a decrease in RMT by 7%. The fMRI-derived Laterality Index of Sensorimotor Cortex increased in precentral-gyrus (from 0.28 to 0.33) and in postcentral-gyrus (from 0.07 to 0.3). The DTI-derived FA-asymmetry decreased in precentral-gyrus (from 0.029 to 0.024) and in postcentral-gyrus (from 0.027 to 0.017). Relative reduction in task-specific performance metrics, i.e., time taken to complete the task (31.6%), smoothness of trajectory (76.7%), and relative percentage error (80.7%), were observed from day 1 to day 20 of the VR therapy. VR therapy resulted in improvement in clinical outcomes in a patient with chronic stroke. The research also gives insights to further improve the overall system of rehabilitation.
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.
ABSTRACT
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.
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.
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