Cerebral Microbleeds in a Stroke Prevention Clinic.

The objective of this study is to assess the effectiveness of a stroke clinic in stroke prevention and progression of cerebral microbleeds (CMB). We conducted a retrospective observational study of patients who visited a stroke clinic between January 2011 and March 2017. Susceptibility-weighted imaging (SWI) MRI studies were obtained at baseline and follow-up visits to identify new infarctions and CMB progression. Patients with CMB who also underwent brain computed tomography (CT) imaging were identified and their cerebral arterial calcification was quantified to evaluate the relationship between the extent of intracranial calcification and CMB burden. A total of 64 stroke patients (mean age 73.1 ± 11.0, 47% males) had CMB on baseline and follow-up MRI studies. During a mean follow-up period of 22.6 months, four strokes occurred (4/64, 6%; 3 ischemic, 1 hemorrhagic), producing mild neurological deficit. Progression of CMB was observed in 54% of patients with two MRIs and was significantly associated with length of follow-up. Subjects with intracranial calcification score > 300 cm3 had higher CMB count than those with scores <300 cm3 at both baseline (12.6 ± 11.7 vs. 4.9 ± 2.2, p = 0.02) and follow-up (14.1 ± 11.8 vs. 5.6 ± 2.4, p = 0.03) MRI evaluations. Patients with CMB had a relatively benign overall clinical course. The association between CMB burden and intracranial calcification warrants further study

The Effect of Vitamin D treatment on COVID 19- Patients, an Inverted Propensity Score Weighting (IPSW), and Inverted Probability of Treatment Weighting (IPTW) Analyzed Study

Background Vitamin D3 (1,25(OH)2 cholecalciferol) as a treatment for COVID 19 patients is being disputed, and a clear clinical benefit is not being confirmed. Methods A retrospective evaluation for COVID-19 patients who were treated with various cumulative doses of vitamin D. Data was extracted from the COVID-19 database, it included patients admitted to three hospitals in Amman, Jordan. Characteristics of patients were tabulated and compared for all-cohort, and propensity score index (PSI) adjustment, The comparison was based on two vitamin D strata ((≤ 149,000 i.u. and > 150,000 i.u.). Logistic regression analysis was utilized to predict recovery, the need for oxygen, and all-cause mortality for all-cohort, IPSW, and IPTW patients, based on vitamin D cumulative doses during their hospital stay. Results             1131 all-cohort and 768 PSI-adjusted patients were recruited. Except for antibiotics and antivirals, all other characteristics were balanced (P = NS). There were 1017 patients on vitamin D, 847 received cumulative ≤ 149,000 i.u., and 170 patients received cumulative dose ≥ 150,000 i.u. (Range 1000 – 385000). It was demonstrated that escalating cumulative doses of vitamin D did not contribute to the assessed outcomes; all-cohort patients (OR = 1.000, 95% C.I. 1.000 to 1.000), IPSW (OR = 1.000, 95% C.I. 1.000 to 1.000), and the IPTW (OR = 1.000, 95% C.I. 1.000 to 1.000). Conclusion             In our patients’ cohorts, we could not demonstrate a beneficial effect for vitamin D therapy in COVID-19 patients for recovery, the need for home oxygen, and all-cause mortality, by hospital discharge

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Stroke Preventability in Large Vessel Occlusion Treated With Mechanical Thrombectomy.

Objective: The preventability of strokes treated by mechanical thrombectomy is unknown. The purpose of this study was to analyze stroke preventability for patients treated with mechanical thrombectomy for large vessel occlusion. Methods: We conducted retrospective analyses of 300 patients (mean ± SE age 69 ± 0.9 years, range 18-97 years; 53% male) treated with mechanical thrombectomy for large vessel occlusion from January 2008 to March 2019. We collected data including demographics, NIH Stroke Scale (NIHSS) at onset, and (beginning in 2015) classified 90-day outcome by modified Rankin Scale (mRS). Patients were evaluated using a Stroke Preventability Score (SPS, 0 to 10 points) based on how well patients had been treated given their hypertension, hyperlipidemia, atrial fibrillation, and prior stroke history. We examined the relationship of SPS with NIHSS at stroke onset and with mRS outcome at 90 days. Results: SPS was calculated for 272 of the 300 patients, with mean ± SE of 2.1 ± 0.1 (range 0-8); 89 (33%) had no preventability (score 0), 120 (44%) had low preventability (score 1-3), and 63 (23%) had high preventability (score 4 or higher). SPS was significantly correlated with age (r = 0.32, p &lt; 0.0001), while NIHSS (n = 267) was significantly higher (p = 0.03) for patients with high stroke preventability vs. low/no preventability [18.8 ± 0.92 (n = 62) vs. 16.5 ± 0.51 (n = 205)]. Among 118 patients with mRS, outcome was significantly worse (p = 0.04) in patients with high stroke preventability vs. low/no preventability [4.7 ± 0.29 (n = 28) vs. 3.8 ± 0.21 (n = 90)]. The vast majority of patients with high stroke preventability had inadequately treated atrial fibrillation (85%, 53/62). Conclusions: Nearly one quarter of stroke patients undergoing mechanical thrombectomy had highly preventable strokes. While stroke preventability showed some relationship to stroke severity at onset and outcome after treatment, preventability had the strongest association with age. These findings emphasize the need for improved stroke prevention in the elderly

Stroke Preventability in Large Vessel Occlusion Treated With Mechanical Thrombectomy.

Objective: The preventability of strokes treated by mechanical thrombectomy is unknown. The purpose of this study was to analyze stroke preventability for patients treated with mechanical thrombectomy for large vessel occlusion. Methods: We conducted retrospective analyses of 300 patients (mean ± SE age 69 ± 0.9 years, range 18-97 years; 53% male) treated with mechanical thrombectomy for large vessel occlusion from January 2008 to March 2019. We collected data including demographics, NIH Stroke Scale (NIHSS) at onset, and (beginning in 2015) classified 90-day outcome by modified Rankin Scale (mRS). Patients were evaluated using a Stroke Preventability Score (SPS, 0 to 10 points) based on how well patients had been treated given their hypertension, hyperlipidemia, atrial fibrillation, and prior stroke history. We examined the relationship of SPS with NIHSS at stroke onset and with mRS outcome at 90 days. Results: SPS was calculated for 272 of the 300 patients, with mean ± SE of 2.1 ± 0.1 (range 0-8); 89 (33%) had no preventability (score 0), 120 (44%) had low preventability (score 1-3), and 63 (23%) had high preventability (score 4 or higher). SPS was significantly correlated with age (r = 0.32, p &lt; 0.0001), while NIHSS (n = 267) was significantly higher (p = 0.03) for patients with high stroke preventability vs. low/no preventability [18.8 ± 0.92 (n = 62) vs. 16.5 ± 0.51 (n = 205)]. Among 118 patients with mRS, outcome was significantly worse (p = 0.04) in patients with high stroke preventability vs. low/no preventability [4.7 ± 0.29 (n = 28) vs. 3.8 ± 0.21 (n = 90)]. The vast majority of patients with high stroke preventability had inadequately treated atrial fibrillation (85%, 53/62). Conclusions: Nearly one quarter of stroke patients undergoing mechanical thrombectomy had highly preventable strokes. While stroke preventability showed some relationship to stroke severity at onset and outcome after treatment, preventability had the strongest association with age. These findings emphasize the need for improved stroke prevention in the elderly

The Left Atrial Septal Pouch: A New Stroke Risk Factor?

The left atrial septal pouch (LASP) occurs due to incomplete fusion of septa primum and secundum at the inter-atrial septum, creating an open flap that may serve as a thromboembolic source. Prior studies have demonstrated increased prevalence of LASP in cryptogenic strokes. The aim of the current study was to validate the above findings in a separate, larger group of stroke and non-stroke patients. We examined transesophageal echocardiograms (TEEs) performed between July 2011 and December 2018. LASP prevalence was determined in TEEs referred for ischemic stroke or transient ischemic attack ("stroke") and compared with LASP prevalence in patients undergoing TEEs for other reasons ("non-stroke"). Stroke subtyping was performed using the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. There were 306 TEEs from 144 non-stroke and 162 stroke patients. Mean age and sex distribution were 56 ± 1 (mean ± SE) and 65% male in the non-stroke group and 58 ± 1 and 54% male in the stroke group. The overall prevalence of LASP was 31%. The prevalence of LASP was 28% (41/144) in non-stroke patients, 25% (24/95) in non-cryptogenic stroke patients, and 43% (29/67) in cryptogenic stroke patients. LASP prevalence was significantly higher in the cryptogenic subgroup compared with the non-cryptogenic subgroup (p = 0.02). These findings demonstrate a significant association of LASP with risk of cryptogenic stroke, suggesting that LASP may serve as a thromboembolic nidus. Additional studies are needed to determine the generalizability of these findings, and their therapeutic implications, supporting LASP as a stroke risk factor

Enhanced setup for wired continuous long-term EEG monitoring in juvenile and adult rats: application for epilepsy and other disorders

Abstract Background The electroencephalogram (EEG) is a widely used laboratory technique in rodent models of epilepsy, traumatic brain injury (TBI), and other neurological diseases accompanied by seizures. Obtaining prolonged continuous EEG tracings over weeks to months is essential to adequately answer research questions related to the chronobiology of seizure emergence, and to the effect of potential novel treatment strategies. Current EEG recording methods include wired and the more recent but very costly wireless technologies. Wired continuous long-term EEG in rodents remains the mainstay approach but is often technically challenging due to the notorious frequent EEG cable disconnections from the rodent’s head, and to poor signal-to-noise ratio especially when simultaneously monitoring multiple animals. Premature EEG cable disconnections and cable movement-related artifacts result from the animal’s natural mobility, and subsequent tension on the EEG wires, as well as from potential vigorous and frequent seizures. These challenges are often accompanied by injuries to the scalp, and result in early terminations of costly experiments. Results Here we describe an enhanced customized swivel-balance EEG-cage system that allows tension-free rat mobility. The cage setup markedly improves the safety and longevity of current existing wired continuous long-term EEG. Prevention of EEG cable detachments is further enhanced by a special attention to surgical electrode anchoring to the skull. In addition to mechanically preventing premature disconnections, the detailed stepwise approach to the electrical shielding, wiring and grounding required for artifact-free high signal-to-noise ratio recordings is also included. The successful application of our EEG cage system in various rat models of brain insults and epilepsy is described with illustrative high quality tracings of seizures and electrographic patterns obtained during continuous and simultaneous monitoring of multiple rats early and up to 3 months post-brain insult. Conclusion Our simple-to-implement key modifications to the EEG cage setup allow the safe acquisition of substantial high quality wired EEG data without resorting to the still costly wireless technologies

Mechanisms of Cerebral Microbleeds

Cerebral microbleeds (CMB) are a common MRI finding, representing underlying cerebral microhemorrhages (CMH). The etiology of CMB and microhemorrhages is obscure. We conducted a pathological investigation of CMH, combining standard and immunohistological analyses of postmortem human brains. We analyzed 5 brain regions (middle frontal gyrus, occipital pole, rostral cingulate cortex, caudal cingulate cortex, and basal ganglia) of 76 brain bank subjects (mean age ± SE 90 ± 1.4 years). Prussian blue positivity, used as an index of CMH, was subjected to quantitative analysis for all 5 brain regions. Brains from the top and bottom quartiles (n = 19 each) were compared for quantitative immunohistological findings of smooth muscle actin, claudin-5, and fibrinogen, and for Sclerosis Index (SI) (a measure of arteriolar remodeling). Brains in the top quartile (i.e. with most extensive CMH) had significantly higher SI in the 5 brain regions combined (0.379 ± 0.007 vs 0.355 ± 0.008; p &lt; 0.05). These findings indicate significant coexistence of arteriolar remodeling with CMH. While these findings provide clues to mechanisms of microhemorrhage development, further studies of experimental neuropathology are needed to determine causal relationships