Zurab Nadareishvili

Cervical Arterial Dissection. Time for a Therapeutic Trial

Background and Purpose— Cervical arterial dissection is a major cause of stroke in young adults, yet despite standard treatment with anticoagulants or antiplatelet drugs, its management remains uncertain. The goal of this study was to assess the natural history of the disorder and to decide on the feasibility of a therapeutic trial. Methods— Collaborating members of the Canadian Stroke Consortium prospectively enrolled consecutively referred patients with angiographically proven acute vertebral or carotid arterial dissection. Data recorded included clinical and radiological details, recurrence of ischemic cerebral events, and medical or surgical treatment. Results— Of 116 patients, 67 had vertebral and 49 had carotid dissections, with no difference in age or sex. In 68 (59%), trauma occurred at the time of dissection. During the course of a 1-year follow-up, at least 17 patients (15%) had recurrent transient ischemic attacks, stroke, or death, mainly in the weeks immediately after the dissection. In 105 patients with complete follow-up, the event rate in those treated with anticoagulants was 8.3% and in those treated with aspirin was 12.4%, a nonsignificant difference of 4.1%. Using these data, we calculate that for a 2-arm trial (aspirin versus anticoagulants) with 80% power and 5% significance, 913 patients are needed in each group. Conclusions— From our data indicating an initial relatively high recurrence rate, a multicenter trial of anticoagulants versus aspirin involving a total of 2000 patients is feasible.

Elevated pro-inflammatory CD4+CD28- lymphocytes and stroke recurrence and death.

Objective: To determine if the CD4+CD28− T-cell subset is expanded in patients with recurrent stroke or death after acute ischemic stroke. This subset of the peripheral blood T-cell lymphocyte population has a strong pro-inflammatory and tissue-damaging potential. Methods: Consecutive patients within the first 48 hours of ischemic stroke were prospectively studied. Peripheral blood CD4+CD28− cells were quantified by flow cytometry. The study endpoint was recurrent stroke or death from any cause during 1 year of follow-up. Results: One hundred six patients (mean age 75.0 ± 13.5 years; 50 women) were studied. The median CD4+CD28− cell count was 4.5% (range 0.2 to 72.2%). Twenty-seven endpoints (10 recurrent strokes and 17 deaths) occurred during follow-up. Stroke recurrence/death rates were significantly associated with increasing CD4+CD28− counts, rising from 14.2% in patients with CD4+CD28− levels of <1.0 to 48.1% for those with CD4+CD28− counts of >8.0% (p = 0.003, Cochran linear test of trend). Higher CD4+CD28− counts were also present in patients with a history of prior stroke (p = 0.03). After adjustment for age, admission NIH Stroke Scale score, prior stroke, and atrial fibrillation, CD4+CD28− counts of >8.0% were associated with a cumulative hazard ratio of 5.81 (95% CI: 1.58 to 21.32) for stroke recurrence or death. Conclusions: Rising counts of circulating CD4+CD28− cells are associated with an increasing risk of stroke recurrence and death, in addition to an observed association with prior stroke. Expansion of this T-cell subset presumably represents a biomarker and possibly a contributory pathogenic mechanism of recurrent stroke and death after ischemic stroke.

Screening with MRI for Accurate and Rapid Stroke Treatment: SMART

Objective: The objective of this study was to demonstrate the feasibility of timely multimodal MRI screening before thrombolysis in acute stroke patients. Methods: Quality improvement processes were initiated in 2013 to reduce door-to-needle (DTN) time at the 2 hospitals where the NIH stroke team provides clinical care. Acute ischemic stroke (AIS) patients who received IV tissue plasminogen activator (tPA) ≤4.5 hours from last known normal were identified. Demographic and clinical characteristics and timing metrics were analyzed comparing the time periods before, during, and after the quality improvement processes. Results: There were 157 patients treated with IV tPA for AIS during 2012–2013, of whom 135 (86%) were screened with MRI. DTN time was significantly reduced by 40% during this period from a median of 93 minutes in the first half of 2012 to 55 minutes in the last half of 2013 (p < 0.0001) with a significant 4-fold increase in the proportion of treated patients with DTN time ≤60 minutes from 13.0% to 61.5%, respectively (p < 0.00001). Improvement in DTN time was associated with reduced door-to-MRI time, and there were no differences in demographic or clinical characteristics (p = 0.21–0.76). Conclusions: It is feasible and practical to consistently and rapidly deliver IV tPA to AIS patients within national benchmark times using MRI as the routine screening modality. The processes used in the SMART (Screening with MRI for Accurate and Rapid Stroke Treatment) Study to reduce DTN time have the potential to be widely applicable to other hospitals.

Identification of Reversible Disruption of the Human Blood–Brain Barrier Following Acute Ischemia

Background and Purpose— Animal models of acute cerebral ischemia have demonstrated that diffuse blood–brain barrier (BBB) disruption can be reversible after early reperfusion. However, irreversible, focal BBB disruption in humans is associated with hemorrhagic transformation in patients receiving intravenous thrombolytic therapy. The goal of this study was to use a magnetic resonance imaging biomarker of BBB permeability to differentiate these 2 forms of BBB disruption. Methods— Acute stroke patients imaged with magnetic resonance imaging before, 2 hours after, and 24 hours after treatment with intravenous tissue-type plasminogen activator were included. The average BBB permeability of the acute ischemic region before and 2 hours after treatment was calculated using a T2* perfusion-weighted source images. Change in average permeability was compared with percent reperfusion using linear regression. Focal regions of maximal BBB permeability from the pretreatment magnetic resonance imaging were compared with the occurrence of parenchymal hematoma (PH) formation on the 24-hour magnetic resonance imaging scan using logistic regression. Results— Signals indicating reversible BBB permeability were detected in 18/36 patients. Change in average BBB permeability correlated inversely with percent reperfusion (P=0.006), indicating that early reperfusion is associated with decreased BBB permeability, whereas sustained ischemia is associated with increased BBB disruption. Focal regions of maximal BBB permeability were significantly associated with subsequent formation of PH (P=0.013). Conclusions— This study demonstrates that diffuse, mild BBB disruption in the acutely ischemic human brain is reversible with reperfusion. This study also confirms prior findings that focal severe BBB disruption confers an increased risk of hemorrhagic transformation in patients treated with intravenous tissue-type plasminogen activator.

Immediate Changes in Stroke Lesion Volumes Post Thrombolysis Predict Clinical Outcome

Background and Purpose— We hypothesize that reversal in diffusion-weighted imaging (DWI) volume at 24 hours predicts favorable clinical outcome only if accompanied by immediate reperfusion. Our aim was to quantify the immediate DWI and mean transit time changes at 2 and 24 hours after intravenous tissue-type plasminogen activator to evaluate the effect of reperfusion and DWI change on outcome. Methods— Patients were selected from the Lesion Evolution in Stroke and Ischemia On Neuroimaging Project if they had an acute MRI with evaluable DWI and perfusion-weighted imaging, were treated with standard intravenous tissue-type plasminogen activator, had post-thrombolysis MRI with evaluable DWI and perfusion-weighted imaging at 2 and 24 hours and had follow-up fluid attenuated inversion recovery MRI at discharge through 90 days. A reader measured the DWI, mean transit time, and fluid attenuated inversion recovery volumes using a validated technique. A vascular neurologist scored the National Institutes of Health Stroke Scale at admit, 2, and 24 hours and the modified Rankin Scale at discharge, 5, 30, and 90 days. Favorable clinical outcome was defined as modified Rankin Scale of 0 or 1. Results— Seventy-one patients met the study criteria with mean (±SD) age of 71.6 (±16.4) years, 58% women, median admit National Institutes of Health Stroke Scale 9 (interquartile range, 4–18), median onset to triage 45 minutes (30–65), and median first MRI to intravenous tissue-type plasminogen activator 47 minutes (39–59). In binary multiple logistic regression analysis, younger age (odds ratio, 1.165; P=0.014; 95% confidence interval [CI], 1.031–1.316), lower admit National Institutes of Health Stroke Scale (odds ratio, 1.221; P=0.012; 95% confidence interval, 1.045–1.427), decrease in mean transit time volume at 2 hours (odds ratio, 1.021; P=0.031; 95% confidence interval, 1.002–1.040), and decrease in DWI volume at 24 hours (odds ratio, 1.173; P=0.027; 95% confidence interval, 1.018–1.351) were significant predictors of favorable clinical outcome. Conclusions— Reversal of the DWI volume at 24 hours because of immediate reperfusion in patients post thrombolysis is predictive of favorable clinical outcome.

“Spontaneous” Cervical Arterial Dissection

To the Editor: The editorial on “spontaneous” cervical arterial dissection (CAD) by Brandt and Grond-Ginsbach1 was an interesting and informed review of a subject that in the past has received inappropriately little attention, considering that CAD represents possibly the most common cause of ischemic stroke in persons below 45 years of age. However, the heavy emphasis on constitutional and genetic factors could prove misleading, and there is no conclusive evidence that such factors play a major role in CAD. The diagnosis of “spontaneous” dissection is entirely dependent on history, and retrospectively reviewing patient’s medical charts is unlikely to accurately reflect the events occurring at the time of dissection. In a current study of this topic by the Canadian Stroke Consortium, dissections were initially diagnosed as spontaneous in patients doing push-ups or lifting heavy weights and engaged …

An MRI Hyperintense Acute Reperfusion Marker Is Related to Elevated Peripheral Monocyte Count in Acute Ischemic Stroke

Blood–brain barrier (BBB) disruption detected on magnetic resonance imaging (MRI) in acute ischemic stroke as a hyperintense acute reperfusion marker (HARM) is associated with upregulation of matrix metalloproteinase‐9 (MMP‐9). Although activated leukocytes, including monocytes, are the main source of MMPs, limited data exist to support relationship between leukocyte activation and BBB disruption in patients with acute ischemic stroke. The goal of this study is to investigate the relationship between neutrophils, lymphocytes, and monocytes with BBB disruption detected as HARM (+) in patients with acute ischemic stroke.

Validity of the Georgian Montreal Cognitive Assessment for the Screening of Mild Cognitive Impairment and Dementia

Montreal Cognitive Assessment (MoCA) test has been shown to be a reliable tool to detect mild cognitive impairment (MCI), however, no Georgian language version exists. The goal of this study is to determine the validity, reliability, and accuracy of Georgian version of MoCA in the evaluation of amnestic MCI (aMCI) and Alzheimer’s disease (AD). Montreal Cognitive Assessment was translated into Georgian language and was administered to healthy participants (HP) and patients with aMCI and AD. We studied 46 HS, 20 patients with aMCI, and 20 patients with AD. There was significant difference in MoCA scores between HP, patients with aMCI, and patients with AD (P = 0.04). The area under the receiver operating characteristic curve for the aMCI and AD groups by MoCA was 0.88 and 0.95, respectively, compared to 0.43 and 0.67 by Mini-Mental State Examination (MMSE). The Georgian version of MoCA is a valid, reliable, and sensitive screening tool to detect aMCI and AD in Georgian-speaking population and is superior to MMSE.

Helistroke: neurointerventionalist helicopter transport for interventional stroke treatment: proof of concept and rationale

Background and purpose It is increasingly recognized that time is one of the key determinants in acute stroke outcome when interventional stroke therapy is applied. With increasing device efficacy and understanding of imaging triage options, reducing pre-treatment time loss may be a critical component of improving interventional stroke outcomes for the population at large. Time sensitive procedures such as organ harvest have transported physicians to the patient site to improve time to procedure. Applying this same principle to interventional stroke management may be a valid paradigm. Methods Previous logistical deliberation with hospital and Medevac companies was carried out to provide the rationale and funding for helicopter transfer of a neurointerventionalist to an in-network hospital with an on-site angiographic suite. An appropriate patient with large vessel occlusion and an NIH Stroke Scale score >8 was identified. MRI was performed, then the Medevac transport system was activated and the intervention was carried out. Times were collected during the case and assessed for time efficiency. Results The proof of concept case was identified and Medevac was consulted at 12:13 after verifying that no in-house emergencies would prevent physician departure. Weather clearance was obtained and stroke intervention confirmed as a go at 12:24. Groin puncture occurred at 13:07 and the intervention was completed at 13:41. The total time from decision-to-treat to groin puncture was 43 min and groin closure was completed at 77 min from decision-to-treat. Conclusions This proof of concept case is presented for logistical, financial and use-case analysis. As it is a first case, times can likely be improved. We assert that this model may be another option in the spoke-and-hub design of stroke systems of care.

Mild Cognitive Impairment in Republic of Georgia

Objective: The goal of this study was to estimate the prevalence of mild cognitive impairment (MCI) in Georgia. Method: A population-based study was conducted using Georgian version of the Montreal Cognitive Assessment (MoCA) and its cognitive domain index score. Results: Of the initial cohort of 1,000 subjects, 851 met inclusion criteria. The prevalence of MCI was 13.3%, and it was associated with age >65 years (odds ratio [OR] = 4.51, 95% confidence interval [CI] = [3.00, 6.75]), urban residence (OR = 0.53, 95% CI = [0.33, 0.88]), lower education (OR = 3.99, 95% CI = [2.66, 5.93]), and hypertension (OR = 2.51, 95% CI = [1.68, 3.76]), while amnestic MCI was documented in 9.3%, with higher risk in older subjects (OR = 2.69, 95% CI = [1.66, 4.20]), and diabetics (OR = 2.69, 95% CI = [1.25, 5.98]). Conclusion: In this first population-based study of MCI in Georgia, prevalence was comparable with those reported from the United States and Europe. Observed association of MCI with cardiovascular risk factors has important clinical implication for dementia prevention in Georgia.