Aneurysmal Subdural Hematoma: A Systematic Review.

BACKGROUND: Aneurysmal subdural hematoma (aSDH) is a rare complication of aneurysm rupture, affecting between 0.5 and 7.9% of patients with aneurysmal subarachnoid hemorrhage (aSAH). The clinical presentation, course, and outcomes of these patients are largely unknown. OBJECTIVE: This study aims to systematically review the literature to evaluate the demographics, clinical presentation, aneurysm location, treatment options, and outcomes of patients with aSDH with and without aSAH. METHODS: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, we conducted a systematic review of three databases (PubMed, EMBASE, and Google Scholar). From identified reports, we extracted data on patients' demographics, clinical presentation, imaging findings, surgical interventions, and clinical outcomes. We compared clinical outcomes, need for surgical treatment, and aneurysm location between patients with aSDH with and without concurrent aSAH using χ2 and Fisher's exact tests. We used simple and multivariable logistic regression models to further examine the association between the presence of aSAH and surgical treatment with clinical outcomes. RESULTS: We identified 112 articles with a total of 270 patients (70% women, mean age 52.8 [± 15.5] years). The most common aneurysm locations were the middle cerebral artery, followed by the posterior communicating artery, and the internal carotid artery. Patients with isolated aSDH fully recovered more frequently than those with concomitant aSAH (38% vs. 6%). The presence of aSAH increased the odds of unfavorable outcome (odds ratio [OR] 2.68, 95% confidence interval [CI] 1.34-5.37). Surgical treatment was inversely associated with unfavorable outcome in the univariable (OR 0.48, 95% CI 0.28-0.84) but not in the multivariable analysis (OR 0.76, 95% CI 0.35-1.66). CONCLUSION: aSDH occurs infrequently. Simultaneous presence of both aSDH and aSAH from an aneurysmal source is associated with poor outcomes. Surgical treatment is associated with lower rates of unfavorable outcomes including death and severe disability.

Dual antiplatelet therapy versus intravenous tissue plasminogen activator with acute minor ischemic stroke: A systematic review and meta-analysis of safety and efficacy.

OBJECTIVES: To compare the safety and efficacy of Dual Antiplatelet Therapy (DAPT) and Intravenous (IV) Tissue Plasminogen Activator (t-PA) in minor Acute Ischemic Stroke (AIS). MATERIALS AND METHODS: Following Cochrane and PRISMA guidelines, we analyzed observational studies and clinical trials comparing DAPT and IV t-PA in patients with minor AIS. Databases included PubMed, Scopus, and Web of Science. Data extraction included study characteristics, patient demographics, and analyzed outcomes. RevMan 5.3 and OpenMetaAnalyst 2021 were used to analyze the data and assess heterogeneity, respectively. The risk of bias was determined using RoB 2.0 and the Newcastle-Ottawa scale. RESULTS: This meta-analysis included five studies with 3,978 DAPT-treated patients and 2,224 IV t-PA-treated patients. We found no significant differences in achieving modified Rankin scale (mRS) scores of 0-1 (OR 1.11, 95 % CI: 0.79, 1.55, p = 0.56) and 0-2 (OR 0.90, 95 % CI: 0.61, 1.31, p = 0.57), as well as combined mRS scores (OR 1.05, 95 % CI: 0.82, 1.34, p = 0.72). Similarly, there were no significant disparities between the two treatment groups in NIHSS score change from baseline (MD 0.32, 95 % CI: -0.35, 0.98, p = 0.35) and in mortality rates (OR 0.87, 95 % CI: 0.26, 2.93, p = 0.83). Notably, in comparison to the IV t-PA group, the DAPT group exhibited a significantly lower incidence of bleeding (OR 0.31, 95 % CI: 0.14, 0.69, p = 0.004) and symptomatic intracranial hemorrhage (sICH) (OR 0.10, 95 % CI: 0.04, 0.26, p < 0.00001). CONCLUSIONS: Our meta-analysis found no significant differences in efficacy between DAPT and IV t-PA. However, DAPT demonstrated a significantly lower risk of sICH and bleeding compared with IV t-PA.

Effect of intra-arterial thrombolysis following successful endovascular thrombectomy on functional outcomes in patients with large vessel occlusion acute ischemic stroke: A post-CHOICE meta-analysis.

INTRODUCTION: Endovascular thrombectomy (EVT) is the standard treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO). Although > 70% of patients in the trials assessing EVT for AIS-LVO had successful recanalization, only a third ultimately achieved favorable outcomes. A "no-reflow" phenomenon due to distal microcirculation disruption might contribute to such suboptimal outcomes. Combining intra-arterial (IA) tissue plasminogen activator (tPA) and EVT to reduce the distal microthrombi burden was investigated in a few studies. We present a pooled-data meta-analysis of the existing evidence of this combinatorial treatment. METHODS: We followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) recommendations. We aimed to include all original studies investigating EVT plus IA tPA in AIS-LVO patients. Using R software, we calculated pooled odds ratios (ORs) with corresponding 95% confidence intervals (CI). A fixed-effects model was adopted to evaluate pooled data. RESULTS: Five studies satisfied the inclusion criteria. Successful recanalization was comparable between the IA tPA and control groups at 82.9% and 82.32% respectively. The 90-day functional independence was similar between both groups (OR= 1.25; 95% CI= 0.92-1.70; P= 0.154). Symptomatic intracranial hemorrhage (sICH) was also comparable between both groups (OR= 0.66; 95% CI= 0.34-1.26; P= 0.304). CONCLUSION: Our current meta-analysis does not show significant differences between EVT alone and EVT plus IA tPA in terms of functional independence or sICH. However, with the limited number of studies and included patients, more randomized controlled trials (RCTs) are needed to further investigate the benefits and safety of combined EVT and IA tPA.

Impact of pre-treatment cerebral microbleeds on the outcomes of endovascular thrombectomy: A systematic review and meta-analysis.

OBJECTIVE/AIM: To investigate the effect of cerebral microbleeds (CMBs) on the functional and safety outcomes of endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines for systematic review and meta-analysis. We included observational studies that recruited AIS-LVO patients, used susceptibility-sensitive magnetic resonance imaging (MRI) to detect CMBs, and examined the association between them and predefined outcome events. The extracted data included study and population characteristics, risk of bias domains, and outcome measures. The outcomes of interest included functional independence, revascularization success, procedural and hemorrhagic adverse events. We conducted a meta-analysis using the Mantel-Haenszel method and calculated the risk ratios. RESULTS: Four studies with a total of 1,514 patients were included. A significant reduction in the likelihood of achieving a favorable functional outcome was observed in patients with CMBs (Risk ratio (RR) 0.69, 95% confidence interval (CI): 0.52 to 0.91, P=0.01). No significant differences were observed between the CMBs and no CMBs groups in terms of successful revascularization, mortality, intracranial hemorrhage (ICH), subarachnoid hemorrhage (SAH), and parenchymal hematoma. CONCLUSIONS: The presence of CMBs significantly reduced the likelihood of achieving functional independence post-EVT in AIS-LVO patients. However, CMBs did not impact the rates of successful revascularization, mortality, or the occurrence of various hemorrhagic events. Future research should explore the mechanisms of this association and strategies to mitigate its impact.

Direct to Angiosuite Versus Conventional Imaging in Suspected Large Vessel Occlusion: A Systemic Review and Meta-Analysis.

BACKGROUND: There is growing evidence to suggest that the direct transfer to angiography suite (DTAS) approach for patients with suspected large vessel occlusion stroke potentially requiring mechanical thrombectomy shortens treatment times and improves outcomes compared with the direct transfer to conventional imaging (DTCI) model. Therefore, we conducted this meta-analysis to compare both approaches to build more concrete evidence to support this innovative treatment concept. METHODS: All potentially relevant studies published in 4 electronic databases/search engines (PubMed, Web of Science, Cochrane Library, and Scopus) from inception to November 2021 were reviewed. Eligible studies were included if they enrolled ≥10 patients in both groups, were published in English, and reported baseline and procedural characteristics and outcomes. Relevant data were then extracted and analyzed. RESULTS: Among 4514 searched studies, 7 qualified for the analysis with 1971 patients (DTAS=675, DTCI=1296). Times from door to puncture (mean difference, -30.76 minutes [95% CI, -43.70 to -17.82]; P<0.001) as well as door-to-reperfusion (mean difference=-33.24 minutes [95% CI, -51.82 to -14.66]; P<0.001) were significantly shorter and the rates of functional independence (modified Rankin Scale score, 0-2: risk ratio [RR], 1.25 [95% CI, 1.02-1.53]; P=0.03) at 90 days were higher in the DTAS versus the DTCI approach. There was no difference across the DTAS and DTCI groups in terms of the rates of successful reperfusion (modified Thrombolysis in Cerebral Infarction score 2B-3: RR, 1.03 [95% CI, 0.95-1.12]; P=0.42), near-complete/full reperfusion (modified Thrombolysis in Cerebral Infarction 2C-3: RR, 0.89 [95% CI, 0.74-1.08]; P=0.23), symptomatic intracranial hemorrhage (RR, 0.81 [95% CI, 0.56-1.17]; P=0.26), or fair outcomes (modified Rankin Scale score, 0-3: RR, 1.14 [95% CI, 0.88-1.47]; P=0.32) or mortality (RR, 0.98 [95% CI, 0.67-1.44]; P=0.93) at 90 days. Subgroup analysis showed no significant difference in 90-day functional independence across approaches in transfer patients (RR, 1.20 [95% CI, 0.96-1.51]; P=0.11). CONCLUSIONS: Our meta-analysis showed that the DTAS approach seems to be associated with improved time metrics and functional outcomes with comparable safety to the DTCI approach. Ongoing multicenter randomized clinical trials will hopefully provide more definite data about this promising approach.

Guillain Barre Syndrome as a Complication of COVID-19: A Systematic Review.

BACKGROUND: In January 2020, the first case of Guillain Barre syndrome (GBS) due to COVID-19 was documented in China. GBS is known to be postinfectious following several types of infections. Although causality can only be proven through large epidemiological studies, we intended to study this association by a thorough review of the literature. METHODS: We searched PubMed, EMBASE, and Google scholar and included all papers with English or Spanish full text and original data of patients with GBS and recent COVID infection. Variables of interest were demographics, diagnostic investigations, and the latency between arboviral and neurological symptoms. Further variables were pooled to identify GBS clinical and electrophysiological variants, used treatments, and outcomes. The certainty of GBS diagnosis was verified using Brighton criteria. RESULTS: We identified a total of 109 GBS cases. Ninety-nine cases had confirmed COVID-19 infection with an average age of 56.07 years. The average latency period between the arboviral symptoms and neurologic manifestations for confirmed COVID-19 cases was 12.2 d. The predominant GBS clinical and electromyography variants were the classical sensorimotor GBS and acute demyelinating polyneuropathy respectively. Forty cases required intensive care, 33 cases required mechanical ventilation, and 6 cases were complicated by death. CONCLUSIONS: Studies on COVID-19-related GBS commonly reported sensorimotor demyelinating GBS with frequent facial palsy. The time between the onset of infectious and neurological symptoms suggests a postinfectious mechanism. Early diagnosis of GBS in COVID-19 patients is important as it might be associated with a severe disease course requiring intensive care and mechanical ventilation.

Intravenous thrombolysis before mechanical thrombectomy for acute ischemic stroke due to large vessel occlusion; should we cross that bridge? A systematic review and meta-analysis of 36,123 patients.

BACKGROUND: The use of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) for acute ischemic stroke due to large vessel occlusion (AIS-LVO) is a debatable subject in the field of neuro-interventional surgery. We conducted this systematic review and meta-analysis to synthesize evidence from published studies on the outcomes of IVT + MT compared with MT alone in AIS-LVO patients. METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials from inception to January 2022 for relevant clinical trials and observational studies. Eligible studies were identified, and all relevant outcomes were pooled in the meta-analysis DerSimonian-Liard random-effects model. RESULTS: Forty-nine studies, with a total of 36,123 patients, were included in this meta-analysis. IVT + MT was significantly superior to MT alone in terms of successful recanalization (RR 1.06, 95% CI 1.03 to 1.09), mortality (RR 0.75, 95% CI 0.68-0.82), favorable functional outcome (RR 1.21, 95% CI 1.13 to 1.29), and complete recanalization (RR 1.06, 95% CI 1.00 to 1.11). There were no significant differences between the two groups in terms of improvement of the National Institute of Health Stroke Scale (NIHSS) score at 24 h or at discharge (p > 0.05). Complications including symptomatic intracranial hemorrhage, symptomatic intracerebral hemorrhage (sICH), procedure-related complications, and parenchymal hematoma were comparable between the two groups (p > 0.05). CONCLUSION: For AIS-LVO, IVT + MT is associated with slightly better rates of survival, successful and complete recanalization, and favorable functional outcome as compared with MT alone. Further clinical trials are needed to corroborate such benefits of bridging IVT.

Galectin-3: A Novel Marker for the Prediction of Stroke Incidence and Clinical Prognosis.

Stroke, whether ischemic or haemorrhagic, is one of the main causes of mortality and disability all over the world, which entails huge burdens in both healthcare environments as well as social and economic aspects of life. Therefore, there is a continuous search for novel reliable biomarkers that can enhance the recognition of stroke events in a timely manner and predict the clinical outcomes following a stroke event. Galectins are a group of proteins expressed by many types of cells and tissues including vasculature, certain immune cells, fibroblasts, and gastrointestinal epithelial cells. These proteins vary in their structure and configuration according to their type and have a diversity of functions according to the type of tissue they are expressed in. Among these proteins, a few studies investigated mainly the roles played by galectin-1 (Gal-1) and galectin-3 (Gal-3) in the molecular mechanisms of atherosclerosis and in brain tissue remodeling after a stroke event. In this review, we present an updated overview of the current understanding of Gal-3's functions and implications in stroke occurrence and the response of the brain tissue to stroke events, which may be a key to its utility as a predictor of stroke incidence and clinical prognosis in the future.

Impact of Obstructive Sleep Apnea on Cognitive and Motor Functions in Parkinson's Disease.

INTRODUCTION: Parkinson's disease (PD) is a chronic neurodegenerative disorder that presents with motor and non-motor manifestations. Amongst the non-motor features, various forms of sleep disturbances can occur, and obstructive sleep apnea (OSA) is considered to be a common comorbidity. We conducted this systematic review and meta-analysis to assess the impact of OSA on cognitive and motor functions in PD. METHODS: The information sources of for this systematic review and meta-analysis were PubMed, SCOPUS, Web of Science, and ScienceDirect. Studies meeting the following criteria were included: (1) studies including idiopathic PD patients, (2) studies using polysomnography to categorize PD patients into PD with OSA and PD without OSA, and (3) studies with observational designs (case-control, cohort, or cross-sectional). Data analysis was performed using RevMan. RESULTS: Our meta-analysis showed that OSA was associated with significantly lower scores of Montreal Cognitive Assessments (MoCA) (mean difference (MD) = -0.70, 95% confidence interval (CI) [-1.28, -0.13], P = 0.01) and Mini-Mental State Examination (MMSE) (MD = -0.69, 95% CI [-1.17, -0.21], P = 0.005). Moreover, the score of the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) was significantly higher in PD patients with OSA as compared with those without OSA (MD = 1.63, 95% CI [0.03, 3.23], P = 0.049). CONCLUSIONS: OSA is associated with increased severity of PD-associated cognitive dysfunction and motor symptoms. However, further studies are needed to corroborate these findings, assess the underlying mechanisms by which OSA influences the motor and cognitive functions in PD, and investigate whether OSA can accelerate the neurodegenerative process of PD. © 2020 International Parkinson and Movement Disorder Society.

Hypothyroidism in restless legs syndrome.

The diurnal nature of restless legs syndrome (RLS) and its response to dopamine hint that hormones are central in RLS pathophysiology. Hypothyroidism has been linked to RLS, but studies are limited. This study's objective is to determine whether RLS is more prevalent in persons with hypothyroidism and whether hypothyroidism is more prevalent in RLS sufferers. Persons with hypothyroidism and controls were recruited through an on-line registry of potential research participants. RLS was assessed using the Cambridge-Hopkins questionnaire. RLS persons and controls were recruited through RLS Foundation and on-line registry advertisements and assessed for hypothyroidism by self-report. The International RLS Study Group Severity Scale assessed RLS severity; 266 hypothyroid subjects and 321 controls were comparable in age (52.3 ± 13.4 versus 53.9 ± 11.7 years; p = .14) and gender (91.7% versus 91.3% women; p = .85), as were 354 RLS and 313 controls (59.1 ± 13.2 versus 58.2 ± 13.6 years; p = .41; 80.8% versus 78.3% women; p = .42). Hypothyroid participants versus controls had a significantly higher prevalence of RLS (14.3% versus 8.1%; p = .02). RLS participants versus controls had a significantly higher prevalence of hypothyroidism (22.3% versus. 13.8%; p = .005). RLS severity was similar in persons with and without hypothyroidism. Among 73 persons with RLS and hypothyroidism, 14 previously were hyperthyroid versus 0 of 37 persons with hypothyroidism alone (p = .004). RLS prevalence is increased in individuals with hypothyroidism; hypothyroidism prevalence is increased in individuals with RLS. Persons with hypothyroidism and RLS are significantly more likely than those with hypothyroidism alone to have had hyperthyroidism prior to hypothyroidism. Associations between RLS and thyroid disease may shed light on complex biological mechanisms underlying RLS.

Implications of the Gut Microbiome in Parkinson's Disease.

Parkinson's disease is a common neurodegenerative disorder that presents with nonmotor and motor symptoms. The nonmotor manifestations of Parkinson's disease often begin years before the motor symptoms. Autopsy studies, including both Parkinson's disease patients and matched controls, demonstrated that α-synuclein aggregates in Parkinson's disease patients can be found in both the substantia nigra and the enteric nervous system. Therefore, it has been hypothesized that the pathological process that leads eventually to Parkinson's disease might initially take place in the enteric nervous system years before the appearance of motor features. The gut microbiome plays essential roles in the development and maintenance of different body systems. Dysbiosis of the normal gut microbiome is thought to be associated with pathophysiologic changes not only in the gastrointestinal system itself but also in the enteric and central nervous systems. These changes are thought to ultimately cause loss of dopaminergic neurons via various mechanisms including the release of neurotoxins into the systemic circulation, decreased production of neuroprotective factors, and triggering inflammatory and autoimmune responses. In this review, we review the gut microbiome changes in Parkinson's disease and discuss the mechanisms by which gut microbiome dysbiosis may be a contributing factor to the pathophysiology of Parkinson's disease. © 2020 International Parkinson and Movement Disorder Society.

Pathophysiologic mechanisms, neuroimaging and treatment in wake-up stroke.

Wake-up stroke (WUS) or ischemic stroke occurring during sleep accounts for 14%-29.6% of all ischemic strokes. Management of WUS is complicated by its narrow therapeutic time window and attributable risk factors, which can affect the safety and efficacy of administering intravenous (IV) tissue plasminogen activator (t-PA). This manuscript will review risk factors of WUS, with a focus on obstructive sleep apnea, potential mechanisms of WUS, and evaluate studies assessing safety and efficacy of IV t-PA treatment in WUS patients guided by neuroimaging to estimate time of symptom onset. The authors used PubMed (1966 to March 2018) to search for the term "Wake-Up Stroke" cross-referenced with "pathophysiology," ''pathogenesis," "pathology," "magnetic resonance imaging," "obstructive sleep apnea," or "treatment." English language Papers were reviewed. Also reviewed were pertinent papers from the reference list of the above-matched manuscripts. Studies that focused only on acute Strokes with known-onset of symptoms were not reviewed. Literature showed several potential risk factors associated with increased risk of WUS. Although the onset of WUS is unknown, a few studies investigated the potential benefit of magnetic resonance imaging (MRI) in estimating the age of onset which encouraged conducting clinical trials assessing the efficacy of MRI-guided thrombolytic therapy in WUS.

Neuropsychological performance changes following subthalamic versus pallidal deep brain stimulation in Parkinson's disease: a systematic review and metaanalysis.

BACKGROUND: Studies comparing subthalamus (STN) and globus pallidus internus (GPi) deep brain stimulation (DBS) for the management of Parkinson's disease in terms of neuropsychological performance are scarce and heterogeneous. Therefore, we performed a systematic review and metaanalysis to compare neuropsychological outcomes following STN DBS versus GPi DBS. METHODS: A computer literature search of PubMed, the Web of Science, and Cochrane Central was conducted. Records were screened for eligible studies, and data were extracted and synthesized using Review Manager (v. 5.3 for Windows). RESULTS: Seven studies were included in the qualitative synthesis. Of them, four randomized controlled trials (n=345 patients) were pooled in the metaanalysis models. The standardized mean difference (SMD) of change in the Stroop color-naming test favored the GPi DBS group (SMD=-0.31, p=0.009). However, other neuropsychological outcomes did not favor either of the two groups (Stroop word-reading: SMD=-0.21, p=0.08; the Wechsler Adult Intelligence Scale (WAIS) digits forward: SMD=0.08, p=0.47; Trail Making Test Part A: SMD=-0.05, p=0.65; WAIS-R digit symbol: SMD=-0.16, p=0.29; Trail Making Test Part B: SMD=-0.14, p=0.23; Stroop color-word interference: SMD=-0.16, p=0.18; phonemic verbal fluency: bilateral DBS SMD=-0.04, p=0.73, and unilateral DBS SMD=-0.05, p=0.83; semantic verbal fluency: bilateral DBS SMD=-0.09, p=0.37, and unilateral DBS SMD=-0.29, p=0.22; Boston Naming Test: SMD=-0.11, p=0.33; Beck Depression Inventory: bilateral DBS SMD=0.15, p=0.31, and unilateral DBS SMD=0.36, p=0.11). CONCLUSIONS: There was no statistically significant difference in most of the neuropsychological outcomes. The present evidence does not favor any of the targets in terms of neuropsychological performance.

Seizures due to pyridoxine deficiency in Parkinson's disease.

Parkinson's disease (PD) is a complex neurodegenerative disorder characterized not only by its hallmark motor symptoms but also by a myriad of non-motor manifestations, including cognitive decline, autonomic manifestations, and gastrointestinal disturbances. Amidst these, a lesser-known but critical aspect is the increased risk of functional deficiency of pyridoxine (vitamin B6) in patients with PD, which is linked to an increased risk of seizures. This review investigates the intersection of PD, new-onset seizures, and pyridoxine deficiency, aiming to elucidate the significance of these associations and their contributions to the neurologic burden in PD. Case reports documenting the occurrence of seizures in patients with PD, particularly in the context of high-dose dopaminergic therapy and the subsequent revelation of pyridoxine deficiency were included. These cases, which often featured extensive workups revealing unremarkable findings aside from pyridoxine deficiency, underscore the multifaceted nature of PD and its treatment-related complications. The findings in these case reports suggest that dietary insufficiencies, gastrointestinal dysfunctions, and drug-nutrient interactions may eventually precipitate pyridoxine deficiency, which in turn may lead to seizures by disrupting GABAergic neurotransmission. This sheds the light on the need for increased clinical awareness and routine monitoring of pyridoxine levels in patients with PD, especially those undergoing significant therapeutic adjustments or exhibiting comorbidities that might interfere with their dietary intake such as gastrointestinal manifestations or depression. Such proactive measures could potentially mitigate the impact of this complication in patients with PD, ultimately enhancing patient care and quality of life.

Nervous System Response to Neurotrauma: A Narrative Review of Cerebrovascular and Cellular Changes After Neurotrauma.

Neurotrauma is a significant cause of morbidity and mortality worldwide. For instance, traumatic brain injury (TBI) causes more than 30% of all injury-related deaths in the USA annually. The underlying cause and clinical sequela vary among cases. Patients are liable to both acute and chronic changes in the nervous system after such a type of injury. Cerebrovascular disruption has the most common and serious effect in such cases because cerebrovascular autoregulation, which is one of the main determinants of cerebral perfusion pressure, can be effaced in brain injuries even in the absence of evident vascular injury. Disruption of the blood-brain barrier regulatory function may also ensue whether due to direct injury to its structure or metabolic changes. Furthermore, the autonomic nervous system (ANS) can be affected leading to sympathetic hyperactivity in many patients. On a cellular scale, the neuroinflammatory cascade medicated by the glial cells gets triggered in response to TBI. Nevertheless, cellular and molecular reactions involved in cerebrovascular repair are not fully understood yet. Most studies were done on animals with many drawbacks in interpreting results. Therefore, future studies including human subjects are necessarily needed. This review will be of relevance to clinicians and researchers interested in understanding the underlying mechanisms in neurotrauma cases and the development of proper therapies as well as those with a general interest in the neurotrauma field.

Endovascular thrombectomy for DAWN- and DEFUSE-3 ineligible acute ischemic stroke patients: a systematic review and meta-analysis.

BACKGROUND: Endovascular therapy (EVT) has been proven beneficial for treating acute ischemic strokes (AIS) with large vessel occlusion (LVO). Recent trials of DAWN and DEFUSE-3 have extended the treatment window to 6-24 h, sparking investigations into EVT outcomes for patients not eligible for DAWN/DEFUSE-3 criteria. PURPOSE: To assess the outcomes of endovascular therapy (EVT) for late-window anterior circulation large vessel occlusion (LVO) in acute ischemic stroke patients, comparing DAWN/DEFUSE-3 eligible (DD) and ineligible (NDND) groups. METHODS: This systematic review and meta-analysis examined EVT outcomes for patients with late-window anterior circulation LVO beyond 6 h. We categorized patients as DAWN/DEFUSE-3 eligible (DD) and ineligible (NDND). Our search covered PubMed, Embase, Web of Science, and Scopus. A total of 464 records were initially identified. After duplicate removal, 298 studies were screened. Nine studies were included and analyzed. Our analysis focused on study characteristics, baseline comparisons, risk of bias, and outcomes. RESULTS: Baseline characteristics showed comparable age, gender, most comorbidities, NIHSS score, and ASPECTS between DAWN/DEFUSE-3 eligible (DD) and ineligible (NDND) patients. NDND patients' history showed a higher rate of atrial fibrillation and larger infarct volumes on baseline imaging. Successful reperfusion rates (TICI 2b-3) were similar between DD and NDND with 354 out of 469 in the DD group and 364 out of 459 in the NDND group (OR = 0.86; 95% CI 0.40, 1.84; p = 0.689), though with significant heterogeneity (I2 = 73%; P = 0.002). The proportion of patients with distal occlusions was significantly higher in the NDND group as compared to the DD group (137 (39.4%) of 347 patients versus 47 (11%) of 428 patients, respectively), with significant heterogeneity across studies (I2 = 85%, p = 0.023). Functional independence at 90 days (mRS 0-2) showed no significant difference between groups with 259 out of 802 in the DD group and 197 out of 668 in the NDND group (OR = 1.12; 95% CI 0.77, 1.63; p = 0.552) but also exhibited notable heterogeneity (I2 = 46%, p = 0.063). Symptomatic intracranial hemorrhage (sICH) rates were lower in DD with 14 out of 309 in the DD group and 47 out of 400 in NDND group (OR = 0.49; 95% CI 0.25, 0.93; p = 0.029) as compared to the NDND patients, showing no heterogeneity (I2 = 0%, p = 0.552). 90-day mortality was lower in DD with 43 out of 304 in the DD group and 107 out of 399 in the NDND group (OR = 0.55; 95% CI 0.37, 0.82; p = 0.004) as compared to NDND patients, with no significant heterogeneity (I2 = 0%, p = 0.536). CONCLUSION: This meta-analysis demonstrates equivalent rates of functional independence between DD and NDND patients. However, the high proportion of distal occlusions and higher rates of sICH and mortality in NDND patients suggest caution in offering mechanical thrombectomy to DAWN/DEFUSE-3 ineligible patients. A more flexible approach to EVT eligibility criteria could benefit select patients in real-world practice. Nonetheless, further research is needed to identify which patients would benefit from expanded EVT eligibility criteria.

Impact of frailty on post-operative outcomes following subarachnoid hemorrhage: A systematic review and meta-analysis.

BACKGROUND: Subarachnoid hemorrhage (SAH) is associated with high rates of mortality and morbidity, particularly among elderly patients. The presence of frailty may impact survival rates in patients with SAH. In this study, we aim to investigate the impact of frailty on the clinical outcomes in SAH patients. METHODS: We conducted a systematic review and meta-analysis following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Relevant papers through December 2023 were retrieved from PubMed, Scopus, Web of science, and Embase. RESULTS: A total of 5 studies met inclusion/exclusion criteria with an aggregate 39,221 non-frail patients (mean age 52.4 ± 5.2 yr; 62.1 % Female), and 79,416 frail patients (mean age 61.1 ± 5.4 yr; 69.0 % Female). Frailty was significantly associated with higher mortality ratio (Odds ratio (OR)= 2.09; CI [1.04: 4.20], p= 0.04), and increased length of hospital stay (OR= 1.40; CI [1.07: 1.83], p= 0.015). Additionally, frailty was associated with higher odds of external ventricular drain insertion, the need of tracheostomy/endoscopic gastrostomy, increased risk of deep vein thrombosis, and postoperative neurological complications. CONCLUSION: Frailty is associated with worse clinical outcomes and higher mortality rates in SAH patients. Our findings highlight that frailty, when considered alongside other established prognostic factors, serves as crucial predictor for peri-operative complications and overall hospital course in SAH patients.

Endovascular Thrombectomy for Carotid Pseudo-occlusion in the Setting of Acute Ischemic Stroke: A Comparative Systematic Review and Meta-Analysis.

BACKGROUND: The effective treatment for acute ischemic stroke (AIS) patients with cervical internal carotid pseudo-occlusion (cICA-PO) requires comprehensive research on the safety and outcomes of endovascular thrombectomy (EVT). However, there is limited data available, highlighting the need for further research to ensure better treatment strategies and improve the quality of care for these patients. PURPOSE: This study aims to assess the management and outcomes in this population group compared to patients with true carotid occlusion. DATA SOURCES: Following the PRISMA guidelines, a comprehensive systematic review was conducted using PubMed, Embase, Web of Science, and Scopus from data base inception to November 2023. STUDY SELECTION: The size of the included studies ranged from 16 patients to 146 patients. Through the 4 full-text articles, a total of 259 patients were collected. We compared outcomes between patients with cICA-PO compared to patients with true carotid occlusions undergoing EVT due to AIS. We excluded studies with patients with carotid pseudo-occlusion without stroke, review articles, duplicate studies, overlapped data that included the same patients presented in another included study, case reports, case series with fewer than 5 patients, and meeting abstracts that did not contain the outcomes of interest. We did not pose any limitations regarding sample size or patients' characteristics. DATA ANALYSIS: We utilized the R statistical software (V.4.3.1; R package meta, R Foundation for Statistical Computing, Vienna, Austria) to conduct the analysis of all the data obtained. We calculated the odds ratio (OR) for binary variables, and the corresponding 95% confidence interval (CI). To synthesize the data, random-effect models, as well as forest plots were generated to visually represent the synthesis of the data. Additionally, we assessed heterogeneity using Cochran's Q and I2 tests. A P-value less than 0.05 for the Q statistic or I2 more than 50% suggests significant heterogeneity. Based on a small number of studies (less than 10), the assessment of publication bias could not be reliably performed. DATA SYNTHESIS: This meta-analysis encompassed data from 4 studies. Patients with cICA-PO and AIS who underwent EVT (n = 135) exhibited lower rates of functional independence (OR 0.35, 95% CI 0.20-0.61, p= <0.001) compared to patients with true occlusions (n = 103), as well as successful recanalization rates (OR 0.39, 95% CI 0.20-0.74, p=0.004). In addition, the cICA-PO group experienced higher mortality and sICH compared to the group with true carotid occlusions (OR 2.62, 95% CI 0.21-7.24, and OR 2.23, 95% CI 1.00-4.95, p= 0.049, respectively). LIMITATIONS: Individual patient data was not available. Studies were a retrospective design and some of the studies had small sample sizes. The included studies in our metaanalysis did not exclude patients with tandem occlusions which might influence the results of the comparison. CONCLUSIONS: As compared to patients with true carotid occlusion, the cICA-PO group with AIS undergoing EVT presented poor outcomes with lower functional independence and successful recanalization, as well as higher sICH and mortality rates.

Endovascular thrombectomy for large ischemic strokes: An updated living systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Recent studies indicate endovascular thrombectomy (EVT) as a safe, effective treatment for acute ischemic stroke (AIS) with large ischemic regions. Our study updates an ongoing living systematic review and meta-analysis of randomized controlled trials (RCTs) comparing outcomes of EVT to medical management only. METHODS: We searched MEDLINE, EMBASE, and the Cochrane Library for RCTs comparing EVT to medical management in AIS patients with large ischemic areas. Using fixed-effect models, we conducted a meta-analysis to compare functional independence, mortality, and symptomatic intracranial hemorrhage (sICH) between EVT and standard medical management. We evaluated bias risk with the Cochrane tool and graded the certainty of evidence using the GRADE approach. RESULTS: Of 1363 new citations, we included six RCTs with a total of 1876 patients. We found low-certainty evidence of improved functional independence (risk difference [RD] 29.9%, 95% CI 17.2% to 46.9%), increase in sICH (RD 2.6%, 95% CI 0.3% to 6.4%), and a non-significant decrease in mortality (RD -1.8%, 95% CI -3.9% to 0.6%) for AIS patients with large infarcts who underwent EVT compared to medical management only. CONCLUSION: Our revised meta-analysis suggests low-certainty evidence that there is improved functional independence, a non-significant decrease in mortality, and an increase in sICH among AIS patients with large infarcts who undergo EVT compared to those receiving medical management alone. SYSTEMATIC REVIEW PROTOCOL REGISTRATION: PROSPERO (CRD42023398742).