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ObjectiveTo determine the association of chronic kidney disease (CKD) with the safety and efficacy of IV thrombolysis (IVT) among patients with acute ischemic stroke (AIS).MethodsA systematic review and pairwise meta-analysis of studies involving patients with CKD undergoing IVT for AIS were conducted to evaluate the following outcomes: symptomatic intracranial hemorrhage (sICH), asymptomatic and any intracranial hemorrhage (ICH), in-hospital and 3-month mortality, 3-month favorable functional outcome (FFO; modified Rankin Scale [mRS] score 0–1), and 3-month functional independence (FI, mRS score 0–2). CKD was defined with estimated glomerular filtration rate (eGFR) ranging from mild (eGFR 60–89 mL/min) to moderate (eGFR 30–59 mL/min) to severe (eGFR 15–29 mL/min).ResultsWe identified 20 studies comprising 60,486 patients with AIS treated with IVT. In unadjusted analyses, CKD was associated with sICH according to the National Institute of Neurological Disorders and Stroke (NINDS) (7 studies; odds ratio [OR] 1.41, 95% confidence interval [CI] 1.19–1.67) and European Cooperative Acute Stroke Study (ECASS) II (9 studies; OR 1.37, 95% CI 1.01–1.85) definitions, any ICH (8 studies; OR 1.42, 95% CI 1.18–1.70), 3-month mortality (9 studies; OR 2.20, 95% CI 1.72–2.81), 3-month FFO (8 studies; OR 0.58, 95% CI 0.47–0.72), and 3-month FI (8 studies; OR 0.57, 95% CI 0.46–0.71). In adjusted analyses, CKD was associated with sICH according to NINDS (4 studies; ORadj 1.34, 95% CI 1.01–1.79) and ECASS II (3 studies; ORadj 2.08, 95% CI 1.27–3.43) definitions, any ICH (6 studies; ORadj 1.41, 95% CI 1.01–1.97), in-hospital mortality (2 studies; ORadj 1.19, 95% CI 1.09–1.30), and 3-month FFO (6 studies; ORadj 0.80, 95% CI 0.70–0.92).ConclusionsAfter adjustment for confounders in this pairwise meta-analysis, moderate to severe CKD is associated with increased risks of ICH and worse functional outcomes among patients with AIS treated with IVT.

Graphical abstract, Highlights • MIRNA-21 is consistently upregulated in gliomas. • It suppresses apoptosis and promotes tumor invasion. • It is involved in resistance against chemo- and radiotherapy. • Research should focus on inhibiting MiRNA-21 in human brains., Gliomas are the most common primary brain tumors in adults. They are generally very resistant to treatment and are therefore associated with negative outcomes. MicroRNAs (miRNAs) are small, non-coding RNA molecules that affect many cellular processes by regulating gene expression and, post-transcriptionally, the translation of mRNAs. MiRNA-21 has been consistently shown to be upregulated in glioma and research has shown that it is involved in a wide variety of biological pathways, promoting tumor cell survival and invasiveness. Furthermore, it has been implicated in resistance to treatment, both against chemotherapy and radiotherapy. In this review, we gathered the existent data on miRNA-21 and gliomas, in terms of its expression levels, association with grade and prognosis, the pathways it involves and its targets in glioma, and finally how it leads to treatment resistance. Furthermore, we discuss how this knowledge could be applied in clinical practice in the years to come. To our knowledge, this is the first review to assess in extent and depth the role of miRNA-21 in gliomas.

Background and ObjectivesOur goal was to study hereditary transthyretin-related amyloidosis (hATTR) in Crete, Greece.MethodsWe aimed at ascertaining all hATTR cases in Crete, an island of 0.62 million people. For this, we evaluated patients with polyneuropathy, autonomic involvement, cardiomyopathy, and/or ophthalmopathy suggestive of hATTR, who presented to the physicians of this study or were referred to them by other physicians. Genetic analyses were performed on all patients suspected of suffering from hATTR. We included in our observational longitudinal cohort study all individuals, residents of Crete, who, during the study period (1993–2019), were found to carry a pathogenic TTR variant.ResultsOver the past 27 years, 30 individuals (15 female patients, 15 male patients), from 12 apparently unrelated families, were diagnosed with hATTR, whereas evaluation of their offspring identified 5 asymptomatic TTR pathogenic variant carriers. The most prevalent TTR variant detected was p.Val50Met, affecting 19 patients (11 female patients, 8 male patients) and causing a rather consistent phenotype characterized by predominant polyneuropathy of early adult onset (median age of symptom onset: 30 years; range: 18–37 years). Specifically, patients affected by the p.Val50Met TTR variant experienced progressive sensorimotor disturbances, involving mainly the lower extremities, associated with autonomic and/or gastrointestinal dysfunction. The second most frequent TTR variant was p.Val114Ala, found in 10 patients (4 female patients, 6 male patients) who were affected at an older age (median age of symptom onset: 70 years; range: 54–78 years). This variant caused a predominantly cardiomyopathic phenotype, manifested by congestive heart failure and associated with peripheral neuropathy, carpal tunnel syndrome, and/or autonomic involvement. In these patients, cardiac amyloid deposition was detected on 99m-technetium pyrophosphate scintigraphy and/or heart biopsy. The third TTR variant (p.Arg54Gly) was found in a 50-year-old male patient with ophthalmopathy due to vitreous opacities and positive family history for visual loss. As 22 patients were alive at the end of the study, we calculated the hATTR prevalence in Crete to be 35 cases per 1 million inhabitants.DiscussionOur study revealed that the prevalence of hATTR in Crete is one of the world's highest. Three different pathogenic TTR variants causing distinct clinical phenotypes were identified in this relatively small population pool.

Recent randomized controlled clinical trials (RCTs) have revolutionized acute ischemic stroke care by extending the use of intravenous thrombolysis and endovascular reperfusion therapies in time windows that have been originally considered futile or even unsafe. Both systemic and endovascular reperfusion therapies have been shown to improve outcome in patients with wake-up strokes or symptom onset beyond 4.5 h for intravenous thrombolysis and beyond 6 h for endovascular treatment; however, they require advanced neuroimaging to select stroke patients safely. Experts have proposed simpler imaging algorithms but high-quality data on safety and efficacy are currently missing. RCTs used diverse imaging and clinical inclusion criteria for patient selection during the dawn of this novel stroke treatment paradigm. After taking into consideration the dismal prognosis of nonrecanalized ischemic stroke patients and the substantial clinical benefit of reperfusion therapies in selected late presenters, we propose rescue reperfusion therapies for acute ischemic stroke patients not fulfilling all clinical and imaging inclusion criteria as an option in a subgroup of patients with clinical and radiological profiles suggesting low risk for complications, notably hemorrhagic transformation as well as local or remote parenchymal hemorrhage. Incorporating new data to treatment algorithms may seem perplexing to stroke physicians, since treatment and imaging capabilities of each stroke center may dictate diverse treatment pathways. This narrative review will summarize current data that will assist clinicians in the selection of those late presenters that will most likely benefit from acute reperfusion therapies. Different treatment algorithms are provided according to available neuroimaging and endovascular treatment capabilities.

Amyotrophic lateral sclerosis (ALS) is a serious neurodegenerative disease that affects motor neurons and leads to death within 2 to 3 years after the first symptoms manifest. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression in fundamental cellular processes and, post-transcriptionally, the translation levels of target mRNA transcripts. We searched PubMed for studies that examined miRNAs in ALS patients and attempted to group the results in order to find the strongest miRNA candidate for servings as an ALS biomarker. The studies on humans so far have been diverse, yielding considerably heterogeneous results, as they were performed on a wide variety of tissues and subjects. Among the miRNAs that were found consistently deregulated are miR-206, miR-133, miR-149, and miR-338-3p. Additively, the deregulation of some specific miRNAs seems to compose a miRNA expression profile that is specific for ALS. More research is required in order for the scientific community to reach a consensus.

Background and purpose: Modern stroke treatment has been revolutionized by image-guided selection of patients for endovascular thrombectomy. Current automated platforms allow for real-time identification of large vessel occlusion and salvageable brain tissue. We had previously demonstrated that a “CTA for all” policy for stroke patients immediately upon arrival assists in the earlier identification of treatment candidates. We now sought to evaluate the performance of these platforms under this policy. Methods: All patients that presented to Henry Ford Health System hospitals over a period of 6 weeks received CTA of the head and neck upon initial presentation. The images were processed with two automated software platforms. We prospectively collected processing times, large-vessel-occlusion alerts, performance warnings, and LVO density ratios. We compared these with the interpretations of board-certified radiologists, and analyzed the performance of each platform. Results: 276 patients presented with stroke symptoms and received CT angiography upon presentation. Both platforms were able to image all stroke patients within their FDA-approved indications. Both platforms were noted to have comparable sensitivity, specificity, PPV and NPV, and excellent accuracy. The overall prevalence of LVO was extremely low (8/276). As a result, for both, NPV was much better than PPV because of the percentage of false positive results. Further ROC analysis, demonstrated an area under the ROC curve of 0.982, and overall model quality of 0.97. Optimal LVO density cutoff was < 0.271, in order to maintain a sensitivity of 100% as an absolute priority (both significantly lower than the current threshold of Conclusions: Automated software platforms are an invaluable aid in the selection of patients for endovascular thrombectomy. Different LVO detection algorithmic thresholds may be necessary (and should be part of individual stroke center validation pathways) to avoid fatigue alert, and optimize test accuracy, when LVO prevalence is low. Stroke teams should be aware of the limitations of automated analysis and need for expert review.

SARS-CoV-2 infects endothelial cells, induces a hypercoagulable state, and, in extreme cases, can provoke a “cytokine storm.” These etiopathological mechanisms, in addition to the hemodynamic and respiratory compromises characterizing severe COVID-19, can culminate in the emergence of various acute stroke phenotypes, such as arterial and venous thromboses, and hemorrhages. COVID-19-associated strokes have been encountered in younger patients with no cerebrovascular risk factors but the disease is also found to target older patients with comorbidities who are more likely to contract the more severe forms of the disease. Anticoagulation, antiplatelets, statins, thrombolysis and endovascular thrombectomy remain the cornerstone therapies for patients with ischemic strokes and COVID-19. An important aspect of secondary stroke prevention is blood pressure management recommendations which are currently being revisited as renin-angiotensin-aldosterone antagonists were initially thought to be detrimental to infected patients due to the interaction of the virions with ACE2 receptors. We also focus our attention on the reshaping of all aspects of stroke care during the pandemic, from the prehospital stage to telehealth.

Introduction: We investigated the effectiveness of intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) and mild neurological deficits defined as National Institutes of Health Stroke Scale scores Methods: The primary efficacy outcome was three-month functional independence (FI; mRS-scores of 0-2) that was compared between patients with and without IVT treatment. Other efficacy outcomes of interest included three-month favorable functional outcome (FFO; mRS-scores of 0-1) and mRS-scores distribution at discharge and at 3 months. The safety outcomes comprised all-cause 3-month mortality, symptomatic intracranial hemorrhage (ICH), asymptomatic ICH and severe systemic bleeding. Results: We evaluated 336 AIS patients with mELVO (mean age: 63±15 years, 45% women). Patients treated with IVT (n=162) had higher FI (85.6% vs. 74.8%, p=0.027) with lower mRS scores at hospital discharge (p=0.034) compared to the rest. Three-month mRS-scores tended to be lower in the IVT group (p=0.069). No differences were detected in any of the safety outcomes including symptomatic ICH, asymptomatic ICH, severe systemic bleeding and 3-month mortality (p>0.1). IVT was associated with higher likelihood of 3-month FI (OR=2.19, 95%CI: 1.09-4.42), 3-month FFO (OR=1.99, 95%CI: 1.10-3.57) and functional improvement at discharge [cOR (per 1-point decrease in mRS-score)=2.94, 95%CI: 1.67-5.26] and at 3 months (cOR=1.72, 95%CI: 1.06-2.86) on multivariable logistic regression models adjusting for potential confounders including mechanical thrombectomy. Conclusion: IVT is independently associated with higher odds of improved discharge and three-month functional outcomes in AIS patients with mELVO. IVT does not increase the risk of systemic or intracranial bleeding.

Introduction: With more widespread anticoagulant use, anticoagulation-associated intracerebral hemorrhage (ICH) represents an increasing proportion of all ICH. We hypothesized that c ombining ischemic and hemorrhagic stroke risk estimation can guide treatment decisions, with more precision than ischemic risk estimation alone. Methods: We enrolled consecutive patients with anticoagulation-associated ICH in 15 centers in USA, Europe and Asia from 2015-2017. Each patient was assigned annual baseline ischemic stroke and hemorrhage risk based on their CHA 2 DS 2 -VASc and HAS-BLED scores without and with index ICH taken into account. We computed a net risk by subtracting the hemorrhagic from the ischemic risk. If the sum was positive the patient was assigned a “Favorable” indication for anticoagulation; if negative an “Unfavorable”. We compared clinical and neuroimaging characteristics between the two groups. Results: Our cohort comprised 357 patients (59% male, median age 76 [68-82] years). 69% used vitamin-K antagonists (VKA), 31 % Non vitamin K antagonist (NOAC). 191 (53.5%) of patients had a favorable indication for anticoagulation prior to their ICH event; the rest 166 (46.5%) had an unfavorable indication. Those with an unfavorable indication were younger (72[66-80] vs 78[73-84] years, p=0.001, had a lower CHA 2 DS 2 -VASc score (3[3-4] vs 5[4-6], p Conclusions: In this anticoagulation-associated ICH cohort, baseline hemorrhage risk exceeded ischemic risk in ~50% of patients. This finding highlights the need for careful consideration of risk/benefit ratio prior to anticoagulation decisions. The remaining ~ 50% suffered an ICH although their baseline risk of ischemia exceeded that of hemorrhage which stresses the need for imaging, serum or other biomarkers to allow more precise estimation of hemorrhagic complication risk.

Alzheimer’s disease (AD) is a complex genetic disorder. To date, published data have reported conflicting results on the role of CD33 rs3865444 polymorphism in AD. The present study aimed at evaluating the effect of rs3865444 on AD in a large cohort of Greek native patients with AD. We also conducted a meta-analysis by pooling information from different studies on the same topic. Patients with AD (n = 327) and healthy controls (n = 327) were analyzed and genotyped for rs3865444. Single locus analyses were run to explore possible associations between CD33 rs3865444 polymorphism and AD. Our analysis yielded no significant interaction between AD and the CD33 rs3865444 polymorphism. The lack of interaction between the two variables persisted even after a pooled meta-analysis of 8 studies (with 13 datasets), with 4015 AD cases and 7981 controls. The overall results do not support the hypothesis that CD33 rs3865444 polymorphism increases the risk of AD. The results also suggest that the identification of functional variants in CD33 that are indisputably correlated with AD may be an important factor to investigate in future genetic screening studies.

Blepharospasm (BSP) is a neurological movement disorder. Coffee consumption has been found to have a protective effect against BSP. BSP and apraxia of eyelid opening are particularly common among patients with PD. The CYP1A2 rs762551 and ADORA2A rs5760423 variants have been previously marginally associated with the risk of PD and are also implicated in caffeine metabolism pathways. The aim of the present study was to evaluate the effect of the CYP1A2 rs762551 and ADORA2A rs5760423 variants on BSP. A Southeastern European Caucasian (SEC) cohort of 206 BSP patients and 206 healthy controls was genotyped for rs762551 and rs5760423. CYP1A2 rs762551 was associated with a decreased BSP risk in the dominant (OR (95% CI) 0.62 (0.41–0.92), p = 0.017), log-additive (OR (95% CI) 0.68 (0.51–0.92), p = 0.011), and co-dominant modes (for the CC genotype OR (95% CI) 0.49 (0.25–0.93), p = 0.038). We provide preliminary evidence that CYP1A2 rs762551 is associated with BSP. Further studies and replication of our results are needed.

Glioblastoma multiforme is the most aggressive malignant tumor of the central nervous system. Due to the absence of effective pharmacological and surgical treatments, the identification of early diagnostic and prognostic biomarkers is of key importance to improve the survival rate of patients and to develop new personalized treatments. On these bases, the aim of this review article is to summarize the current knowledge regarding the application of molecular biology and proteomics techniques for the identification of novel biomarkers through the analysis of different biological samples obtained from glioblastoma patients, including DNA, microRNAs, proteins, small molecules, circulating tumor cells, extracellular vesicles, etc. Both benefits and pitfalls of molecular biology and proteomics analyses are discussed, including the different mass spectrometry-based analytical techniques, highlighting how these investigation strategies are powerful tools to study the biology of glioblastoma, as well as to develop advanced methods for the management of this pathology.

Introduction: Computed tomographic angiography (CTA) is an important initial assessment for detecting large vessel occlusion (LVO) in acute ischemic stroke (AIS) and for selecting patients for mechanical thrombectomy (MT). This study is designed to evaluate the impact of an emergency CTA protocol on outcome of AIS patients with LVO. Methods: On July 1, 2017 we implemented the policy of performing CTA at the same time as non-contrast CT (NCCT) in all AIS patients presenting within 24 hours of symptom onset regardless of baseline NIHSS. Previously emergency CTA was reserved for patients presenting within 6 hours with an NIHSS ≥6. We compared treatment processes and outcomes between AIS patients admitted 1-year before (N=396) and 1-year after (N=494) protocol implementation. Results: After protocol implementation, more patients underwent CTA (90% vs 60%, P < 0.001) and had CTA performed at the time of the initial NCCT (77% vs 34%, P Conclusion: Emergency CTA for all stroke patients presenting within 24 hours regardless of baseline NIHSS improves LVO detection, increases the MT treatment population, speeds intervention, and improves outcome after LVO. The benefit primarily affects patients who present within 6 hours of symptom onset.

Numerous types of cancer have been shown to be associated with either ischemic or hemorrhagic stroke. In this review, the epidemiology and pathophysiology of stroke in cancer patients is discussed, while providing vital information on the diagnosis and management of patients with cancer and stroke. Cancer may mediate stroke pathophysiology either directly or via coagulation disorders that establish a state of hypercoagulation, as well as via infections. Cancer treatment options, such as chemotherapy, radiotherapy and surgery have all been shown to aggravate the risk of stroke as well. The clinical manifestation varies greatly depending upon the underlying cause; however, in general, cancer‑associated strokes tend to appear as multifocal in neuroimaging. Furthermore, several serum markers have been identified, such as high D‑Dimer levels and fibrin degradation products. Managing cancer patients with stroke is a delicate matter. The cancer should not be considered a contraindication in applying thrombolysis and recombinant tissue plasminogen activator (rTPA) administration, since the risk of hemorrhage in cancer patients has not been reported to be higher than that in the general population. Anticoagulation, on the contrary, should be carefully examined. Clinicians should weigh the benefits and risks of anticoagulation treatment for each patient individually; the new oral anticoagulants appear promising; however, low‑molecular‑weight heparin remains the first choice. On the whole, stroke is a serious and not a rare complication of malignancy. Clinicians should be adequately trained to handle these patients efficiently.

Α number of genetic variants have been associated with Alzheimer’s disease (AD) susceptibility. Sec1 family domain-containing protein 1 (SCFD1) gene polymorphism rs10139154 has recently been implicated in the risk of developing amyotrophic lateral sclerosis (ALS). Similarities in the pathogenetic cascade of both diseases have also been described. The present study was designed to evaluate the possible contribution of SCFD1 rs10139154 to AD. A total of 327 patients with AD and an equal number of healthy controls were included in the study and genotyped for rs10139154. With logistic regression analyses, rs10139154 was examined for the association with the risk of developing AD. In the recessive mode, SCFD1 rs10139154 was associated with a decreased risk of developing AD (odds ratio (OR) (95% confidence interval (CI)) = 0.63 (0.40–0.97), p = 0.036). The current study provides preliminary evidence of the involvement of SCFD1 rs10139154 in the risk of developing AD.

Introduction: Data are scarce regarding the outcomes of acute ischemic stroke (AIS) patients treated with intravenous thrombolysis (IVT) within 60 min from symptom onset, termed the “golden hour” (GH) window. We present systematic review and meta-analysis of outcomes between AIS patients treated within (+) and outside (-) the GH. Methods: We performed a systematic review in MEDLINE and SCOPUS databases for observational studies providing unadjusted rates or adjusted odds ratios (OR) for the following outcomes: symptomatic intracranial hemorrhage (sICH), mortality and favourable functional outcome (FFO), defined as mRS-scores of 0-1. Results: We identified 3 eligible studies (range of median NIHSS-scores: 10-11 points), including a total of 72,662 IVT-treated patients (1.5% treated within the GH. GH(+) patients had higher FFO rates (42%, 95%CI:35%-48%) compared to GH(-) patients (31%, 95%CI:30%-31%). In adjusted analyses, IVT within the GH was associated with a two-fold increase in the odds of FFO (OR=2.02, 95%CI: 1.55-2.63, p2 =0, p for Cochran Q=0.93; Figure). No significant differences on the risk of both sICH (OR=0.77, 95%CI: 0.53-1.13, p=0.180; I 2 =0, p for Cochran Q=0.63) and mortality (OR=0.61, 95%CI: 0.29-1.28, p=0.190; I 2 =72, p for Cochran Q=0.03) were documented between the two groups in adjusted analyses. Conclusions: AIS treated within the GH have substantially higher odds of FFO compared to IVT administered later during conventional time window independent of potential confounders. Improvement of care systems to achieve the earliest onset to treatment times should remain the goal of the front line stroke treatment.

Introduction: The modified Rankin Score (mRS) collected at approximately 90 days after stroke onset is a reliable and reproducible measure of stroke outcome. It was utilized in the randomized controlled trials that established the safety and efficacy of endovascular stroke treatment. It has been incorporated as a core metric for measuring quality of care in comprehensive stroke centers. We aimed to evaluate the value of the 90-day mRS considering that a certain percentage of patients may fail to respond to coordinator phone calls. Methods: We retrospectively analyzed patients who received endovascular stroke treatment in a comprehensive stroke center from January 2015 to March 2017, and who were prospectively enrolled in the Get With The Guidelines-Stroke Registry. We calculated the response rates to coordinator phone calls at approximately 90 days from stroke onset. Several calls were placed according to the established institutional policy. We compared the response rates of patients who had successful or unsuccessful recanalization, as reported by the endovascular specialist at the time of the procedure. Results: We identified 79 patients who received endovascular treatment, and who were contacted by the coordinators at approximately 90 days after stroke onset. 58 patients had successful recanalization (as defined by reported TICI grades IIb and III), whereas 21 patients had unsuccessful recanalization (as defined by reported TICI grades O, I, and IIa). 44/58 patients with successful recanalization responded to coordinator calls, compared to 11/21 patients with unsuccessful recanalization. The difference in proportions was statistically significant (p=0.045). Conclusions: Patients who have unsuccessful recanalization after endovascular stroke treatment are significantly less likely to respond to coordinator calls. Therefore, their mRS cannot be estimated, and the long-term outcome of the endovascular procedure cannot be assessed. Since these patients are more likely to have died, or be in a supervised facility (and therefore not accessible at their previous phone number), the telephone assessment of the mRS is likely not an accurate measure for the long-term therapeutic effect of endovascular stroke treatment.

Introduction: In pre-clinical studies, extended-release niacin has been shown to increase neurogenesis, synaptogenesis, and angiogenesis in a rat model of experimental middle cerebral artery (MCA) occlusion. Using this animal model, extended-release niacin has been shown to improve functional outcomes in rats when compared to placebo, beginning 24 hours after experimental stroke. Methods: This was a phase IIa double-blind, randomized, placebo controlled study (Henry Ford Health System funded; clinicaltrials.gov NCT00796887). At a single site (Henry Ford Hospital, Detroit, MI), patients with ischemic stroke 3 to 7 days prior and NIHSS 4-20 were randomized to two doses of oral extended-release niacin (500 mg or 1000 mg daily) or placebo. Primary outcome measures were change in mRS or NIHSS from baseline to Week 24. Results: There were 27 patients enrolled in this study. Ten patients were randomized to extended-release niacin 500 mg, 7 to 1000mg, and 10 to placebo. No significant differences were seen in baseline characteristics of enrolled patients. Significant increases in HDL-C were seen from baseline to 24 weeks among extended-release niacin treated patients (12.5 mg/dL, p=0.035), but not in placebo-treated patients (6.2 mg/dL, p=0.157). Mean improvement in NIHSS from baseline to 24 weeks of treatment was similar for both extended-release niacin and placebo treated patients (6.5 vs. 6.1, p=0.845). No differences were seen in functional outcome (mRS) at 24 weeks between extended-release niacin and placebo treated patients (2.1 vs. 2.0, p=0.860). There were a total of 40 AEs, with 27 in the extended-release niacin group and 10 in the placebo group. For these AEs, no clear interaction with treatment group could be confirmed. Conclusions: Extended-release niacin administered for 24 weeks starting between 3 and 7 days after ischemic stroke demonstrated no improvement in functional outcome as compared to placebo. Extended-release niacin was overall well tolerated. Although this small exploratory study did not identify a signal for potential efficacy, useful sample size estimates were gleaned. Any future clinical investigations may benefit from the collection of additional clinical measures of motor or gait function to differentiate treatment effects.

Introduction: Current guidelines report no benefit for patent foramen ovale (PFO) closure compared to medical treatment in patients with cryptogenic ischemic stroke (IS) or transient ischemic attack (TIA). Two recent randomized-controlled clinical trials (RCTs) have challenged these recommendations. We performed a systematic review and network meta-analysis (NMA) of RCTs to estimate the safety and efficacy of closure compared to medical treatment, and to compare available devices. Methods: We conducted pairwise meta-analyses for closure vs medical therapy, and for each device vs medical therapy. We performed subgroup analyses for the outcome of IS recurrence according to shunt size and atrial septal aneurysm (ASA) presence. For all devices we calculated the pooled rates of effective closure and serious peri-procedural complications. We used NMA to combine direct and indirect evidence for any given pair of treatments. Results: Literature search identified 6 eligible studies. PFO occlusion was associated with reduced risk of recurrent IS (RR=0.39, 95%CI:0.18-0.88) and IS/TIA (RR=0.66, 95%CI:0.46-0.94), but with increased risk of new-onset atrial fibrillation (AF; RR=4.73, 95%CI:2.09-10.71) compared to medical treatment. We detected no differences on the risk of recurrent IS according to PFO size (p=0.83) or ASA presence (p=0.39). Amplatzer and GORE HELEX/CARDIOFORM occluders were associated with more effective IS/TIA prevention (Panels A-B) and lower AF risk compared to STARFlex Septal Occluder (Panel C). Conclusions: PFO closure is related with reduced risk of recurrent IS/TIA and with increased risk of new-onset AF. These associations are independent of PFO size and ASA presence.

The authors report a case of a 49-year-old man with long-standing, chronic cluster headache (CH) refractory to medical therapy and occipital nerve stimulation that resolved a few weeks prior to the diagnosis of glioblastoma involving primarily the right cingulate gyrus. An attempt to explore the underlying role of the cingulate cortex in pain modulation by appraising the current literature is presented. This report suggests that the cingulate gyri could be a potential target for neuromodulation in patients with medically refractory chronic CH.

Background: Cerebral small vessel disease is related to widespread endothelial dysfunction, and suspected hypoperfusion at the level of the microcirculation. Lacunar infarcts are a major manifestation of small vessel disease, and result in significant long-term neurological morbidity and mortality. Congenital hypoplastic variants of the vessels of the Circle of Willis may result in impairment of collateral channels at the time of ischemia. Hypothesis: We hypothesized that lateralization of first-ever lacunar infarcts is related to relative hypoperfusion of the ipsilateral hemisphere due to asymmetric hypoplasia of the vessels of the Circle of Willis and inadequate side-to-side collateral circulation. Methods: We analyzed 40 consecutive patients that presented to a stroke center with a first-ever supratentorial lacunar infarct. All patients were able to undergo intracranial vascular imaging. Patients with significant large-vessel disease (even if asymptomatic) were excluded. A neuroradiologist, blinded to the laterality of the lacunar infarct, assessed for lateralized hypoplasia of the Circle of Willis (either anteriorly at the level of the A1 artery and AComA as one functional unit, or posteriorly at the level of the PCA and PComA as one functional unit). Proportions of ipsilateral and contralateral hypoplasia were compared directly, as well as with historical controls, with the chi-squared test. Results: Among analyzed patients, ipsilateral and contralateral anterior pathway hypoplastic variants were not significantly different from historical controls (p=0.145 and p=0.99 respectively). However, ipsilateral and contralateral posterior pathway hypoplastic variants were significantly different from historical controls (p Conclusion: Hypoplasia of the posterior part of the Circle of Willis is significantly more common among patients with first-ever lacunar stroke, compared to historical controls. However, the asymmetry of hypoplasia does not affect the laterality of first-ever lacunar infarct. Further studies are required to explain this phenomenon.

Background and Purpose: Collateral flow can influence the pace and extent of evolution to irreversible tissue damage and thus have a significant impact on the clinical outcome of patients with acute ischemic stroke (AIS), including those treated with endovascular treatment (ET). Using prospectively collected data of a Stroke Registry, we explored the relationship between digital subtraction angiography (DSA) collateral status and clinical outcome of AIS patients with middle cerebral artery (MCA) occlusion treated with ET. Methods: We reviewed the data of all patients with acute MCA occlusion treated with ET within the past 5 years. Baseline DSA collaterals were classified as - no (0), poor (1), intermediate (2) and good (3). Clinical outcomes were assessed using the National Institute of Health Stroke Scale (NIHSS) at 24-48 hours and at the time of discharge. Multivariable regression analysis was done to evaluate association of DSA collateral score with the outcome. The regression model was adjusted for the age, baseline NIHSS, infusion of intravenous (IV) thrombolytic (tPA) and symptom-onset to angiographic recanalization time. Results: 50 patients with the MCA occlusion were treated with ET and 25 (50%) patients received IV tPA prior to ET. Median baseline NIHSS score was 19.5. Median time from the onset to IV tPA was 122 minutes and onset to angiographic recanalization was 277 minutes, respectively. Patients with DSA collateral score of 0, 1, 2 and 3 were 7 (15%), 21 (44%), 15 (31%) and 5 (10%), respectively. Every 1-point increase in the DSA collateral score was associated with 4.5-point reduction in NIHSS at 24-48 hours and 4.9-point reduction in NIHSS at discharge (Standard Error 1.4, p Conclusions: In the patients with AIS due to MCA occlusion, better collaterals on the DSA are independently associated with improved NIHSS at 24-48 hours after ET and at the time of discharge. This concept needs to be explored further in a larger dataset that will also include additional imaging parameters.

Objective:To compare the neuroimaging profile and clinical outcomes among patients with intracerebral hemorrhage (ICH) related to use of vitamin K antagonists (VKAs) or direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF).Methods:We evaluated consecutive patients with NVAF with nontraumatic, anticoagulant-related ICH admitted at 13 tertiary stroke care centers over a 12-month period. We also performed a systematic review and meta-analysis of eligible observational studies reporting baseline characteristics and outcomes among patients with VKA- or DOAC-related ICH.Results:We prospectively evaluated 161 patients with anticoagulation-related ICH (mean age 75.6 ± 9.8 years, 57.8% men, median admission NIH Stroke Scale [NIHSSadm] score 13 points, interquartile range 6–21). DOAC-related (n = 47) and VKA-related (n = 114) ICH did not differ in demographics, vascular risk factors, HAS-BLED and CHA2DS2-VASc scores, and antiplatelet pretreatment except for a higher prevalence of chronic kidney disease in VKA-related ICH. Patients with DOAC-related ICH had lower median NIHSSadm scores (8 [3–14] vs 15 [7–25] points, p = 0.003), median baseline hematoma volume (12.8 [4–40] vs 24.3 [11–58.8] cm3, p = 0.007), and median ICH score (1 [0–2] vs 2 [1–3] points, p = 0.049). Severe ICH (>2 points) was less prevalent in DOAC-related ICH (17.0% vs 36.8%, p = 0.013). In multivariable analyses, DOAC-related ICH was independently associated with lower baseline hematoma volume (p = 0.006), lower NIHSSadm scores (p = 0.022), and lower likelihood of severe ICH (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.13–0.87, p = 0.025). In meta-analysis of eligible studies, DOAC-related ICH was associated with lower baseline hematoma volumes on admission CT (standardized mean difference = −0.57, 95% CI −1.02 to −0.12, p = 0.010) and lower in-hospital mortality rates (OR = 0.44, 95% CI 0.21–0.91, p = 0.030).Conclusions:DOAC-related ICH is associated with smaller baseline hematoma volume and lesser neurologic deficit at hospital admission compared to VKA-related ICH.

BACKGROUND Three-dimensional (3D) ultrasound imaging is a new technique that maximizes the information and image quality of traditional 2-dimensional (2D) B-mode scanning. The aim of this study was to evaluate the ability of the 3D ultrasound technique to characterize ulcerated atherosclerotic carotid plaque. METHODS Using conventional 2D ultrasound, we examined 284 carotid arteries from 142 consecutive patients (101 men and 41 women; average age, 64 years). Eighty-two carotid arteries were symptomatic with atherosclerotic plaque causing 50-99% stenosis. In 62 arteries, the atherosclerotic plaques were visualized completely and were further processed to construct 3D images. Two independent observers rated plaque morphology according to a standardized protocol. RESULTS The 3D ultrasound showed carotid plaque ulceration more frequently than the 2D method (16.1% and 14.5% of plaques, for observers 1 and 2, respectively, versus 6.5% and 9.7% of plaques, for observers 1 and 2, respectively, P= .125 and P= .063, for observers 1 and 2, respectively). The interobserver reproducibility was very good for both methods (κ= .973, SE = .027, P < .001 for 3D, and κ= .885, SE = .055, P < .001 for 2D), although the 3D method was slightly superior to 2D. CONCLUSIONS 3D ultrasound reliably characterized the surface morphology of atherosclerotic carotid plaques. A trend of superiority of 3D ultrasound over 2D was found in detecting ulcers of carotid artery plaque.

Summary Purpose: To identify and describe thalamic dysfunction in patients with temporal as well as extratemporal status epilepticus (SE) and to also analyze the specific clinical, radiological, and electroencephalography (EEG) characteristics of patients with acute thalamic involvement. Methods: We retrospectively identified patients who presented with clinical and electrographic evidence of partial SE and had thalamic abnormalities on diffusion-weighted imaging (DWI) within 5 days of documentation of lateralized epileptiform discharges (group 1). The spatial and temporal characteristics of the periodic lateralized epileptiform discharges (PLEDs) and the recorded electrographic seizures were analyzed and correlated with magnetic resonance imaging (MRI)-DWI hyperintense lesions. The findings of group 1 patients were compared with those of patients with partial SE without thalamic abnormalities on DWI (group 2). Results: The two groups were similar with regard to clinical presentation and morphology of epileptiform discharges. Group 1 patients had thalamic hyperintense lesions on DWI that appeared in the region of the pulvinar nucleus, ipsilateral to the epileptiform activity. Statistically significant relationship was noted between the presence of thalamic lesions and ipsilateral cortical laminar involvement (p = 0.039) as well as seizure origin in the posterior quadrants (p = 0.038). A trend towards PLEDs originating in the posterior quadrants was also noted (p = 0.077). Discussion: Thalamic DWI hyperintense lesions may be observed after prolonged partial SE and are likely the result of excessive activity in thalamic nuclei having reciprocal connections with the involved cortex. The thalamus likely participates in the evolution and propagation of partial seizures in SE.

Studies evaluating the association between carotid plaque composition and occurrence of ischemic cerebrovascular disease reveal inconsistent results. This study correlates the carotid echomorphology with the degree of stenosis in symptomatic and asymptomatic patients.We included consecutive patients with hemispheric stroke or asymptomatic carotid artery stenosis assessed with 2D ultrasound. The echomorphology was assessed with mean gray value (MGV) of the three-dimensional (3D) volume. We used the free-hand approach for 3D image and volume acquisition. Analyses of the stored carotid plaque volumes were carried out offline using the Virtual Organ Computer-aided Analysis (VOCAL) program.We studied 110 symptomatic and 104 asymptomatic atherosclerotic carotid plaques. MGV was lower in symptomatic carotid plaques causing70% stenosis compared to plaques causingor =70% stenosis (25.95+/-7.40 vs. 32.16+/-11.35, p=0.002). There was no difference in MGV between plaques producing60% and those withor =60% in asymptomatic patients (32.08+/-8.36 vs. 31.46+/-9.25, p=0.724). There were significant differences in MGV between symptomatic and asymptomatic plaques causing60 or70% stenosis; MGV was lower in symptomatic patients.Lower plaque echogenicity is observed in symptomatic than in asymptomatic patients with moderate degree of carotid stenosis, indicating that it is a significant factor for the production of cerebral ischemia. Our method could be useful in assessing the risk of cerebral ischemia and the response of carotid artery atherosclerosis to medical therapies.

Stroke incidence and mortality are disproportionately higher among African Americans than among whites.To describe the recurrent stroke characteristics and determine the predictability of known vascular risk factors for stroke recurrence in African Americans.The authors followed 1,809 African Americans in the African-American Antiplatelet Stroke Prevention Study with recent noncardioembolic ischemic stroke for recurrent stroke, recurrent stroke subtype, and disability.Of the subjects, 10.6% experienced a recurrent stroke during follow-up. The mean interval between eligibility and recurrent stroke was 325 days (median 287 days, SD = 224 days). Stroke recurrence resulted in an average 1.5-point increase in the National Institute of Health Stroke Scale (p0.001) and a 3.5-point decrease in modified Barthel Index (p0.001). Of previously nondisabled subjects, 48% became disabled or died after stroke recurrence (p0.0001). Longitudinal analysis resulted in a hazard for recurrent stroke for each 10-mm Hg increase in systolic blood pressure of 1.103 (95% CI: 1.031 to 1.179, p = 0.004), pulse pressure 1.123 (95% CI: 1.041 to 1.213, p = 0.003), and mean arterial pressure 1.123 (95% CI: 1.001 to 1.260, p = 0.048). Multivariate analysis revealed increases in the recurrent stroke hazard for increases in baseline Glasgow Outcome Score (1.449, 95% CI: 1.071 to 1.961, p = 0.016) and increases in longitudinal pulse pressure (1.009, 95% CI: 1.001 to 1.017, p = 0.029).Recurrent stroke leads to disability and disability predicts recurrent stroke. Hypertension is the most predictive modifiable stroke risk factor.

Headache is a frequent accompaniment of acute ischaemic stroke. The predisposing factors and underlying mechanisms are currently incompletely defined. We analysed prospectively collected data relevant to headache occurring at ischaemic stroke onset in consecutive patients included in the Henry Ford Hospital Stroke Data Bank. Patients with headache (HA+) and without headache (HA–) were compared for demographic factors, medical history, medications, examination findings, laboratory findings, and stroke localization and subtype. Group comparisons for categorical data were performed with χ2 test, and for continuous variables with two-sample t-tests. Stepwise logistic regression analysis, including all variables with P < 0.25, was used to define the independent predictors of onset headache. Three hundred and seventy-five patients had complete headache and clinical datasets and were included in the analysis (HA+, N = 118; HA–, N = 257). Multivariate analysis revealed that the independent predictors of HA+ were: infarct in the distribution of the posterior circulation [ P = 0.0076, odds ratio (OR) 2.15, 95% confidence interval (CI) 1.23, 3.77], absence of history of hypertension ( P = 0.0106, OR 0.48, 95% CI 0.27, 0.84), and treatment with warfarin at the time of the index stroke ( P = 0.0135, OR 4.89, 95% CI 1.39, 17.21). The occurrence of headache at onset of ischaemic stroke is determined by posterior circulation distribution of the ischaemic event, absence of history of hypertension and treatment with warfarin at the time of the index stroke. These results suggest that preserved elasticity and maintenance of the intracranial vasculature in a relaxed state, in combination with coagulation system derangements, and activation of dense perivascular afferent nerves, play a role in the pathogenesis of onset headache.

The authors assessed the effect of IV abciximab on early neurologic improvement and ischemic lesion growth in 29 patients with supratentorial stroke and NIH stroke scale score (NIHSSS) ≥ 4 (11.1 ± 5.9), treated within 3 to 24 (13.6 ± 5.5) hours of onset. The 48 to 72-hour NIHSSS improvement was 4.4 ± 3.2 and the 24-hour lesion growth on DWI was +23% (−50%, +103%); 7/26 (27%) patients experienced lesion size decrease. Treatment of sub-24-hour stroke with abciximab improves early post-treatment neurologic status and often attenuates ischemic lesion growth.

To identify early MRI characteristics of ischemic stroke that predict final infarct size three months poststroke.Multiparametric MRI (multispin echo T2-weighted [T2W] imaging, T1-weighted [T1W] imaging, and diffusion-weighted imaging [DWI]) was performed acutely (24 hours), subacutely (three to five days), and at three months. MRI was processed using maps of apparent diffusion coefficient (ADC), T2, and a self-organizing data analysis (ISODATA) technique. Analyses began with testing for individual MRI parameter effects, followed by multivariable modeling with assessment of predictive ability (R(2)) on final infarct size.A total of 45 patients were studied, 15 of whom were treated with tissue plasminogen activator (tPA) before acute MRI. The acute DWI and DWI-ISODATA mismatch lesion size, and the interactions of ADC, T2, and T2W imaging lesion with tPA remained in the final multivariable model (R(2) = 70%). A large acute DWI lesion or DWIISODATA lesion independently predicted increase in the final infract size, with predictive ability 68%. Predictive ability increased (R(2) = 83%) when subacute MRI parameters were included along with acute DWI, DWI-ISODATA mismatch, and acute T2W image lesion size by tPA treatment interaction. Subacute DWIacute DWI lesion size predicted an increased final infarct size (P0.01).Acute-phase DWI and DWI-ISODATA mismatch strongly predict the final infarct size. An acute-to-subacute DWI lesion size change further increases the predictive ability of the model.

Background and Purpose— The purpose of this study was to show that the computer segmentation algorithm Iterative Self-Organizing Data Analysis Technique (ISODATA), which integrates multiple MRI parameters (diffusion-weighted imaging [DWI], T2-weighted imaging [T2WI], and T1-weighted imaging [T1WI]) into a single composite image, is capable of defining the ischemic lesion in a time-independent manner equally as well as the MRI techniques considered the best for each phase after stroke onset (ie, perfusion weighted imaging [PWI] and DWI for the acute phase and T2WI for the outcome phase). Methods— We measured MRI parameters of PWI, DWI, T2WI, and T1WI from patients at the acute phase ( Results— We included 11 patients; 9 (82%) were women, and 7 (64%) were black. The mean±SD age was 65.5±9.3 years (range, 45 to 82 years). The median NIHSS score was 15 (minimum, 4; maximum, 24)at the acute phase and 3 (minimum, 0; maximum, 22) at the outcome phase. The median time interval from stroke symptom onset to the acute MRI study was 10 hours (range, 6 to 29 hours), and the mean time interval to the outcome study was 93±11 days (range, 72 to 106 days). In the acute phase, the ISODATA lesion size had high correlation with the PWI lesion size ( r =0.95; 95% CI, 0.89 to 0.98; P r =0.83; 95% CI, 0.66 to 0.92; P r =0.67; 95% CI, 0.39 to 0.84; P =0.008) and moderate correlation with NIHSS score ( r =0.59; 95% CI, 0.02 to 0.88; P =0.06). In the outcome phase, the ISODATA lesion size had high correlation with the T2WI lesion size ( r =0.97; 95% CI, 0.94 to 0.99; P r =0.78; 95% CI, 0.34 to 0.94; P =0.004). Conclusions— The integrated ISODATA method can identify and characterize the ischemic lesion independently of time elapsed since stroke onset. The ISODATA lesion size highly correlates with the PWI and DWI lesion size in the acute phase and with the T2WI lesion size in the outcome phase of ischemic stroke, as well as with the clinical neurological status of the patient.

Object. Vasospasm remains a significant source of neurological morbidity and mortality following aneurysmal subarachnoid hemorrhage (SAH), despite advances in current medical, surgical, and endovascular therapies. Magnesium sulfate therapy has been demonstrated to be both safe and effective in preventing neurological complications in obstetrical patients with eclampsia. Evidence obtained using experimental models of brain injury, cerebral ischemia, and SAH indicate that Mg may also have a role as a neuroprotective agent. The authors hypothesize that MgSO4 therapy is safe, feasible, and has a beneficial effect on vasospasm and, ultimately, on neurological outcome following aneurysmal SAH. Methods. A prospective randomized single-blind clinical trial of high-dose MgSO4 therapy following aneurysmal SAH (Hunt and Hess Grades II–IV) was performed in 40 patients, who were enrolled within 72 hours following SAH and given intravenous MgSO4 or control solution for 10 days. Serum Mg++ levels were maintained in the 4 to 5.5 mg/dl range throughout the treatment period. Clinical management principles were the same between groups (including early use of surgery or endovascular treatment, followed by aggressive vasospasm prophylaxis and treatment). Daily transcranial Doppler (TCD) ultrasonographic recordings were obtained, and clinical outcomes were measured using the Glasgow Outcome Scale (GOS). The patients' GOS scores and the TCD recordings were analyzed using the independent t-test. Forty patients were enrolled in the study: 20 (15 female and five male patients) received treatment and 20 (11 female and nine male patients) comprised a control group. The mean ages of the patients in these groups were 46 and 51, respectively, and the mean clinical Hunt and Hess grades were 2.6 ± 0.68 in the MgSO4 treatment group and 2.3 ± 0.73 in the control group (mean ± standard deviation [SD], p = 0.87). Fisher grades were similar in both groups. Mean middle cerebral artery velocities were 93 ± 27 cm/second in MgSO4-treated patients and 102 ± 34 cm/second in the control group (mean ± SD, p = 0.41). Symptomatic vasospasm, confirmed by angiography, occurred in six of 20 patients receiving MgSO4 and in five of 16 patients receiving placebo. Mean GOS scores were 3.8 ± 1.6 and 3.6 ± 1.5 (mean ± SD, p = 0.74) in the treatment and control groups, respectively. Significant adverse effects from treatment with MgSO4 did not occur. Conclusions. Administration of high-dose MgSO4 following aneurysmal SAH is safe, and steady Mg++ levels in the range of 4 to 5.5 mg/dl are easily maintained. This treatment does not interfere with neurological assessment, administration of anesthesia during surgery, or other aspects of clinical care. We observed a trend in which a higher percentage of patients obtained GOS scores of 4 or 5 in the group treated with MgSO4, but the trend did not reach a statistically significant level. A larger study is needed to evaluate this trend further.

process. Until recently, most patients with acute ischemic stroke were managed in the general wards, with random, nonstandardized monitoring, and similarly random treatment of complications. Admission to a critical care unit was reserved for only the small number of patients with depressed levels of consciousness who were unable to protect their airways or those with significant cardiovascular comorbidity. Nonetheless, it is clear that neurological or medical complications place the life of the acute stroke patient in danger, prolong hospitalization, and delay or prevent rehabilitation. Consequently, we are witnessing a shift toward more standardized intensive neurological monitoring and prompt intervention when neurological deterioration or systemic complications occur. The question of whether full-scale critical care management of stroke patients improves the outcome is still debatable. With today's standards, however, a significant proportion of hospitalized stroke patients, perhaps 10%, will require some form of critical care treatment for various reasons. 2 These include large cerebral hemispheric infarctions, large cerebellar infarctions, acute basilar or vertebral artery occlusions, and stroke associated with systemic complications, such as pulmonary or cardiac dysfunction. In addition, aggressive approaches to acute ischemic stroke, such as intravenous or intraarterial thrombolytic therap~ necessitate monitoring and treatment in an intensive care unit environment.

We sought to determine the rate of urine toxicology screening, differences in testing, and outcomes among patients with stroke and TIA presenting to a tertiary care emergency department.In this retrospective cohort study, patients admitted with stroke or TIA to a single tertiary care stroke center between June 2005 and January 2007 were identified through a stroke database. Factors that predicted urine toxicology screening of patients and a positive test, and discharge outcomes of patients based on toxicology result were analyzed. Stroke severity, treatment with tissue plasminogen activator, discharge status, and stroke etiology were compared between toxicology positive and negative patients.A total of 1,024 patients were identified: 704 with ischemic stroke, 133 with intracerebral hemorrhage, and 205 with TIA. Urine toxicology screening was performed in 420 patients (40%); 11% of these studies were positive for cocaine (19% younger than 50 years and 9% 50 years or older). Factors that significantly predicted the performance of a urine toxicology screen were younger age (50 years) and black race (0.001). Positive toxicology screens occurred in a broad range of patients. There were no significant differences in admission NIH Stroke Scale score, stroke etiology, and discharge status between toxicology-positive and -negative patients.In this study, patients with stroke and TIA who were young and black were more likely to have urine toxicology screening. Eleven percent of all tested patients (and 9% of patients 50 years or older) were positive for cocaine. To avoid disparities, we suggest that all stroke and TIA patients be tested.

Background: Administration of intravenous (IV) t-PA for acute ischemic stroke (AIS) improves outcomes. The most dreaded complication is intracerebral hemorrhage (ICH). Some patients have symptoms that impersonate an AIS but are later found to have an alternate diagnosis; these are termed stroke mimics (SM). SM treated with IV t-PA are exposed to hemorrhagic complications without benefit. Objectives: To describe the characteristics, safety, and outcomes of SM patients treated with t-PA under 4.5 hours. Methods: We reviewed all patients hospitalized after IV t-PA treatment at a tertiary care hospital and primary stroke center from January 2008 through December 2011. SMs were determined by review of clinical and imaging findings. SM are described and compared to t-PA treated patients with AIS for demographics, ICH, bleeding complications, and outcomes. Results: We identified 38 SM (12%) and 285 AIS (88%) t-PA treated patients. Compared to AIS, SM patients were younger (55.1 vs. 67.0 yrs, p Conclusion: SM are not uncommon. Treatment of SM with IV t-PA appears to be safe in this cohort. The most common etiologies of stroke mimics were conversion disorder, seizures, and migraine. These results are consistent with existing published data on use of IV t-PA in SMs. Until more specific diagnostics are available, suspected SM should not be a reason to withhold t-PA treatment.

Background: The 2010 American Academy of Neurology guideline for the diagnosis of acute ischemic stroke recommends MRI with diffusion weighted imaging (DWI) over noncontrast head CT. No studies have evaluated the influence of imaging choice on patient outcome. We sought to evaluate the variables that influenced one-year outcomes of stroke and TIA patients, including the type of imaging utilized. Methods: Patients were identified from a prospectively collected stroke and TIA database at a single primary stroke center during a one-year period. Data were abstracted from patient electronic medical records. The primary outcome measure was death, myocardial infarction, or recurrent stroke within the following year. Secondary outcome measures included predictors of getting an MRI study. Results: 727 consecutive patients with a discharge diagnosis of stroke or TIA were identified (616 and 111 respectively); 536 had CT and MRI, 161 had CT alone, 29 had MRI alone, and one had no neuroimaging. On multiple logistic regression analysis, there were no differences in primary or secondary outcome measures among different imaging strategies. Predictors of the primary outcome measure included age and NIHSS, while performance of a CT angiogram (CTA) predicted a decreased odds of death, stroke, or MI. The strongest predictor of having an MRI was admission to a stroke unit. Conclusions: These results suggest that long-term (one-year) patient outcomes may not be influenced by imaging strategy. Performance of a CTA was protective in this cohort. A randomized trial of different imaging modalities should be considered.

Background The emergence of prophylactic and therapeutic interventions in stroke has been accompanied by the widespread use of stroke classifications and scales that measure deficit (stroke scales) or resulting long-term handicap (handicap and disability scales). Although the accuracy of some scales and classifications has been studied, there is no updated systematic review appraising all of them. Review We reviewed the literature and selected 21 studies on classifications and scales. The International Classification of Diseases, 10th revision, achieved the highest interobserver agreement among seven stroke classifications. The National Institutes of Health Stroke Scale, the Canadian Neurological Scale, and the European Stroke Scale had the highest reliability across items among nine stroke scales. The Barthel Index was the most reliable disability scale. Conclusions The identification of the most reliable stroke classifications and scales should encourage their use in selection of homogeneous populations of patients for clinical research studies and to improve communication among scientists. Further research is needed to investigate neglected aspects of the neurological examination and the validity of stroke classifications.