Gian Marco De Marchis

What Is a Minor Stroke

Background and Purpose— The term “minor stroke” is often used; however a consensus definition is lacking. We explored the relationship of 6 “minor stroke” definitions and outcome and tested their validity in subgroups of patients. Methods— A total of 760 consecutive patients with acute ischemic strokes were classified according to the following definitions: A, score ≤1 on every National Institutes of Health Stroke Scale (NIHSS) item and normal consciousness; B, lacunar-like syndrome; C, motor deficits with or without sensory deficits; D, NIHSS ≤9 excluding those with aphasia, neglect, or decreased consciousness; E, NIHSS ≤9; and F, NIHSS ≤3. Short-term outcome was considered favorable when patients were discharged home, and favorable medium-term outcome was defined as a modified Rankin Scale score of ≤2 at 3 months. The following subgroup analyses were performed by definition: sex, age, anterior versus posterior and right versus left hemispheric stroke, and early (0 to 6 hours) versus late admission (6 to 24 hours) to the hospital. Results— Short-term and medium-term outcomes were most favorable in patients with definition A (74% and 90%, respectively) and F (71% and 90%, respectively). Patients with definition C and anterior circulation strokes were more likely to be discharged home than patients with posterior circulation strokes (P=0.021). The medium-term outcome of older patients with definition E was less favorable compared with the outcome of younger ones (P=0.001), whereas patients with definition A, D, and F did not show different outcomes in any subgroup. Conclusions— Patients fulfilling definition A and F had best short-term and medium-term outcomes. They would be best suited to the definition of “minor stroke.”

Endovascular Therapy of 623 Patients With Anterior Circulation Stroke

Background and Purpose— Endovascular therapy of acute ischemic stroke has been shown to be beneficial for selected patients. The purpose of this study is to determine predictors of outcome in a large cohort of patients treated with intra-arterial thrombolysis, mechanical revascularization techniques, or both. Methods— We prospectively acquired data for 623 patients with acute cerebral infarcts in the carotid artery territory who received endovascular treatment at a single center. Logistic regression analysis was performed to determine predictors of outcome. Results— Median National Institutes of Health Stroke Scale (NIHSS) at admission was 15. Partial or complete recanalization was achieved in 70.3% of patients; it was independently associated with hypercholesterolemia (P=0.02), absence of coronary artery disease (P=0.023), and more proximal occlusion site (P<0.0001). After 3 months, 80.5% of patients had survived, and 48.9% of patients reached favorable outcome (modified Rankin scale score 0–2). Good collaterals (P<0.0001), recanalization (P=0.023), hypercholesterolemia (P=0.03), lower NIHSS at admission (P=0.001), and younger age (P<0.0001) were independent predictors for survival. More peripheral occlusion site (P<0.0001), recanalization (P<0.0001), hypercholesterolemia (P=0.002), good collaterals (P=0.002), lower NIHSS (P<0.0001), younger age (P<0.0001), absence of diabetes (P=0.002), and no previous antithrombotic therapy (P=0.036) predicted favorable outcome. Time to treatment was only a predictor of outcome, when collaterals were excluded from the model. Symptomatic intracerebral hemorrhage occurred in 5.5% and was independently predicted by poor collaterals (P=0.004). Conclusions— Several independent predictors for outcome and complications were identified. Unlike in intravenous thrombolysis trials, time to treatment was a predictor of outcome only when collaterals were excluded from the model, indicating the important role of collaterals for the time window.

Diagnostic Accuracy of Plasma Glial Fibrillary Acidic Protein for Differentiating Intracerebral Hemorrhage and Cerebral Ischemia in Patients with Symptoms of Acute Stroke

BACKGROUND Glial fibrillary acidic protein (GFAP) is a biomarker candidate indicative of intracerebral hemorrhage (ICH) in patients with symptoms of acute stroke. GFAP is released rapidly in the presence of expanding intracerebral bleeding, whereas a more gradual release occurs in ischemic stroke. In this study the diagnostic accuracy of plasma GFAP was determined in a prospective multicenter approach. METHODS Within a 1-year recruitment period, patients suspected of having acute (symptom onset<4.5 h before admission) hemispheric stroke were prospectively included into the study in 14 stroke centers in Germany and Switzerland. A blood sample was collected at admission, and plasma GFAP was measured by use of an electrochemiluminometric immunoassay. The final diagnosis, established at hospital discharge, was classified as ICH, ischemic stroke, or stroke mimic. RESULTS The study included 205 patients (39 ICH, 163 ischemic stroke, 3 stroke mimic). GFAP concentrations were increased in patients with ICH compared with patients with ischemic stroke [median (interquartile range) 1.91 μg/L (0.41-17.66) vs 0.08 μg/L (0.02-0.14), P<0.001]. Diagnostic accuracy of GFAP for differentiating ICH from ischemic stroke and stroke mimic was high [area under the curve 0.915 (95% CI 0.847-0.982), P<0.001]. A GFAP cutoff of 0.29 μg/L provided diagnostic sensitivity of 84.2% and diagnostic specificity of 96.3% for differentiating ICH from ischemic stroke and stroke mimic. CONCLUSIONS Plasma GFAP analysis performed within 4.5 h of symptom onset can differentiate ICH and ischemic stroke. Studies are needed to evaluate a GFAP point-of-care system that may help optimize the prehospital triage and management of patients with symptoms of acute stroke.

Three-Month and Long-Term Outcomes and Their Predictors in Acute Basilar Artery Occlusion Treated With Intra-Arterial Thrombolysis

Background and Purpose— Intra-arterial thrombolysis can be used for treatment of basilar artery occlusion. Predictors of outcome before initiation of treatment are of special interest. Methods— From 1992 to 2010, we treated 106 consecutive patients with basilar artery occlusion with intra-arterial thrombolysis. Baseline characteristics, treatment, clinical course, and 3-month and long-term outcomes (≥12 months) were assessed. Outcome parameters were vessel recanalization after treatment, complications, modified Rankin scale (mRS) score, and mortality after 3 months and in the long-term. Results— At 3 months, clinical outcome was good (mRS score, 0–2) in 33.0% of the patients and moderate (mRS score, 3) in 11.3%. Mortality was 40.6%. Partial or complete recanalization was achieved in 69.8% of the patients, and symptomatic intracranial hemorrhage occurred in 1 patient (0.9%). Between 3-month and long-term follow-up, 22 survivors (40.8%) showed clinical improvement of at least 1 point on the mRS score, 29 (53.7%) were functionally unchanged, and 3 (5.7%) showed functional worsening (P<0.0001). Multivariate analysis identified diabetes as a predictor of poor vessel recanalization (P=0.028). Low baseline National Institutes of Health Stroke Scale score was identified as a predictor of good or moderate clinical outcome (P<0.0001) and survival (P=0.001) at 3 months, and younger age was identified as an additional predictor of survival (P=0.012). For prediction of long-term clinical outcome, age was also an independent predictor (P=0.018). Conclusions— In our series, intra-arterial thrombolysis as treatment of basilar artery occlusion was safe. National Institutes of Health Stroke Scale score at admission and age were identified as predictors of outcome, and these predictors should be considered for treatment allocation in future randomized trials.

Copeptin adds prognostic information after ischemic stroke Results from the CoRisk study

Objective: To evaluate and validate the incremental value of copeptin in the prediction of outcome and complications as compared with established clinical variables. Methods: In this prospective, multicenter, cohort study, we measured copeptin in the emergency room within 24 hours from symptom onset in 783 patients with acute ischemic stroke. The 2 primary end points were unfavorable functional outcome (modified Rankin Scale score 3–6) and mortality within 90 days. Secondary end points were any of 5 prespecified complications during hospitalization. Results: In multivariate analysis, higher copeptin independently predicted unfavorable outcome (adjusted odds ratio 2.17 for any 10-fold copeptin increase [95% confidence interval {CI}, 1.46–3.22], p < 0.001), mortality (adjusted hazard ratio 2.40 for any 10-fold copeptin increase [95% CI, 1.60–3.60], p < 0.001), and complications (adjusted odds ratio 1.93 for any 10-fold copeptin increase [95% CI, 1.33–2.80], p = 0.001). The discriminatory accuracy, calculated with the area under the receiver operating characteristic curve, improved significantly for all end points when adding copeptin to the NIH Stroke Scale score and the multivariate models. Moreover, the combination of copeptin with a validated score encompassing both the NIH Stroke Scale and age led to a net reclassification improvement of 11.8% for functional outcome and of 37.2% for mortality. Conclusions: In patients with ischemic stroke, copeptin is a validated blood marker that adds predictive information for functional outcome and mortality at 3 months beyond stroke severity and age. Copeptin seems to be a promising new blood marker for prediction of in-hospital complications.

Differences and Similarities Between Spontaneous Dissections of the Internal Carotid Artery and the Vertebral Artery

Background and Purpose— To compare potential risk factors, clinical symptoms, diagnostic delay, and 3-month outcome between spontaneous internal carotid artery dissection (sICAD) and spontaneous vertebral artery dissection (sVAD). Methods— We compared patients with sICAD (n=668) and sVAD (n=302) treated in 3 university hospitals. Results— Patients with sICAD were older (46.3±9.6 versus 42.0±10.2 years; P<0.001), more often men (62.7% versus 53.0%; P=0.004), and presented more frequently with tinnitus (10.9% versus 3.4%; P<0.001) and more severe ischemic strokes (median National Institutes of Health Stroke Scale, 10±7.1 versus 5±5.9; P<0.001). Patients with sVAD had more often bilateral dissections (15.2% versus 7.6%; P<0.001) and were more often smokers (36.0% versus 28.7%; P=0.007). Thunderclap headache (9.2% versus 3.6%; P=0.001) and neck pain were more common (65.8% versus 33.5%; P<0.001) in sVAD. Subarachnoid hemorrhage (6.0% versus 0.6%; P<0.001) and ischemic stroke (69.5% versus 52.2%; P<0.001) were more frequent in sVAD. After multivariate analysis, sex difference lost its significance (P=0.21), and all other variables remained significant. Time to diagnosis was similar in sICAD and sVAD and improved between 2001 and 2012 compared with the previous 10-year period (8.0±10.5 days versus 10.7±13.2 days; P=0.004). In sVAD, favorable outcome 3 months after ischemic stroke (modified Rankin Scale, 0–2: 88.8% versus 58.4%; P<0.001), recurrent transient ischemic attack (4.8% versus 1.1%; P=0.001), and recurrent ischemic stroke (2.8% versus 0.7%; P=0.02) within 3 months were more frequent. Conclusions— sICAD and sVAD patients differ in many aspects. Future studies should perform separate analyses of these 2 entities.

Seizure burden in subarachnoid hemorrhage associated with functional and cognitive outcome

Objective: To assess the relationship between seizure burden on continuous EEG (cEEG) and functional as well as cognitive outcome 3 months after subarachnoid hemorrhage (SAH). Methods: The study included all consecutive patients with a spontaneous SAH admitted to the Columbia University Medical Center Neurological Intensive Care Unit and monitored with cEEG between 1996 and 2013. Seizure burden was defined as the duration, in hours, of seizures on cEEG. Cognitive outcomes were measured with the Telephone Interview for Cognitive Status (TICS, ranging from 0 to 51, indicating poor to good global mental status). Results: Overall, 402 patients with SAH were included with a median age of 58 years (interquartile range [IQR] 46–68 years). The median duration of cEEG monitoring was 96 hours (IQR 48–155 hours). Seizures were recorded in 50 patients (12%), in whom the median seizure burden was 6 hours (IQR 1–13 hours). At 3 months, in multivariate analysis, seizure burden was associated with unfavorable functional and cognitive outcome. Every hour of seizure on cEEG was associated with an odds ratio of 1.10 (95% confidence interval [CI] 1.01–1.21, p = 0.04) to 3-month disability and mortality, and the TICS-score decreased, on average, by 0.16 points (adjusted coefficient −0.19, 95% CI −0.33 to −0.05, p = 0.01). Conclusion: In this study, after adjusting for established predictors, seizure burden was associated with functional outcome and cognitive impairment 3 months after SAH.

Plaque Characteristics of Asymptomatic Carotid Stenosis and Risk of Stroke

Background: The optimal treatment of asymptomatic carotid stenosis (ACS) is controversial. To optimize the risk-benefit ratio of carotid artery revascularization, it is crucial to identify ACS patients who are at increased stroke risk. Recent data suggest that plaque vulnerability depends on its composition. Therefore, we assessed plaque composition in ACS to determine predictors for ipsilateral cerebrovascular events. Methods: 62 patients with 65 ACS ≥50% underwent 3-T MRI of the carotid bifurcation (TOF, special dark-blood weighted noncontrast and contrast-enhanced T1 and T2 images) and of the brain. The different plaque components (lipid core, intraplaque hemorrhage, calcification and the status of the fibrous cap) were assessed. Furthermore, the plaque volume and the volume of clinically silent cortical and subcortical infarcts in the territory of the stenosed carotid artery as seen on FLAIR images were determined by using a semi-automated software. Carotid stenosis was considered asymptomatic if there had not been any clinically apparent ischemic events in the corresponding vascular territory within the previous 6 months. During follow-up, information on the occurrence of cerebrovascular events, medical treatment and sonographic changes of the stenosis was collected. Results: At baseline, 24 ACS (37%) were classified as high grade. A lipid-rich necrotic core was the dominant plaque component in 16 ACS (25%). The plaque volume was higher in ACS with a lipid-rich necrotic core as dominant plaque component (p = 0.002) and in patients with prior stroke/TIA (p = 0.010). After a median follow-up of 18.9 months (interquartile range 3.5–30.1) there were 2 ipsilateral strokes and 3 ipsilateral TIAs. The average annual event rate was 7.7%. A lipid-rich necrotic core (HR 7.21; 95% CI 1.12–46.28; p = 0.037), sonographic progression of the stenosis (HR 7.00; 95% CI 1.13–41.34; p = 0.036), history of stroke (HR 11.03; 95% CI 1.23–99.36; p = 0.032), and the volume of clinically asymptomatic ischemic brain lesions (HR 1.14/cm3; 95% CI 1.03–1.25; p = 0.008) predicted cerebrovascular events. Patients on statin therapy at follow-up were at lower risk of events (HR 0.17; 95% CI 0.03–1.00; p = 0.05). Conclusions: In addition to medical history and sonographic findings, a lipid-rich necrotic core within the plaque turned out as a predictor of cerebrovascular events. Therefore, MR imaging of carotid plaques deserves further attention and might be helpful to improve risk stratification of asymptomatic carotid disease. The identified predictors could be combined in a risk model and tested in larger prospective studies.

Recanalization therapies in acute ischemic stroke patients: impact of prior treatment with novel oral anticoagulants on bleeding complications and outcome

Background— We explored the safety of intravenous thrombolysis (IVT) or intra-arterial treatment (IAT) in patients with ischemic stroke on non-vitamin K antagonist oral anticoagulants (NOACs, last intake <48 hours) in comparison with patients (1) taking vitamin K antagonists (VKAs) or (2) without previous anticoagulation (no-OAC). Methods and Results— This is a multicenter cohort pilot study. Primary outcome measures were (1) occurrence of intracranial hemorrhage (ICH) in 3 categories: any ICH (ICHany), symptomatic ICH according to the criteria of the European Cooperative Acute Stroke Study II (ECASS-II) (sICHECASS-II) and the National Institute of Neurological Disorders and Stroke (NINDS) thrombolysis trial (sICHNINDS); and (2) death (at 3 months). Cohorts were compared by using propensity score matching. Our NOAC cohort comprised 78 patients treated with IVT/IAT and the comparison groups of 441 VKA patients and 8938 no-OAC patients. The median time from last NOAC intake to IVT/IAT was 13 hours (interquartile range, 8–22 hours). In VKA patients, median pre-IVT/IAT international normalized ratio was 1.3 (interquartile range, 1.1–1.6). ICHany was observed in 18.4% NOAC patients versus 26.8% in VKA patients and 17.4% in no-OAC patients. sICHECASS-II and sICHNINDS occurred in 2.6%/3.9% NOAC patients, in comparison with 6.5%/9.3% of VKA patients and 5.0%/7.2% of no-OAC patients, respectively. At 3 months, 23.0% of NOAC patients in comparison with 26.9% of VKA patients and 13.9% of no-OAC patients had died. Propensity score matching revealed no statistically significant differences. Conclusions— IVT/IAT in selected patients with ischemic stroke under NOAC treatment has a safety profile similar to both IVT/IAT in patients on subtherapeutic VKA treatment or in those without previous anticoagulation. However, further prospective studies are needed, including the impact of specific coagulation tests.

Impact of Admission Glucose and Diabetes on Recanalization and Outcome after Intra-Arterial Thrombolysis for Ischaemic Stroke

Background Stroke patients with diabetes and admission hyperglycaemia have worse outcomes than non-diabetics, with or without intravenous thrombolysis. Poor vessel recanalization was reported in diabetics treated with intravenous thrombolysis. Aims This study aimed to determine the impact of admission glucose and diabetes on recanalization and outcome after intra-arterial thrombolysis. Methods We analysed 389 patients (213 men, 176 women) treated with intra-arterial thrombolysis. The association of diabetes and admission glucose value with recanalization, outcome, mortality, and symptomatic intracranial haemorrhage was determined. Recanalization was classified according to thrombolysis in myocardial infarction grades. Outcome was measured using the modified Rankin Scale at three-months and categorized as favourable (modified Rankin Scale 0–2) or poor (modified Rankin Scale 3–6). Results The rate of partial or complete recanalization (thrombolysis in myocardial infarction 2–3) did not differ between patients with and without diabetes (67% vs. 66%; P = 1·000). Mean admission glucose values were similar in patients with poor recanalization (thrombolysis in myocardial infarction 0–1) and patients with partial or complete recanalization (thrombolysis in myocardial infarction 2–3; 7·3 vs. 7·3 mmol/l; P = 0·746). Follow-up at three-months was obtained in 388 of 389 patients. Clinical outcome was favourable (modified Rankin Scale 0–2) in 189 patients (49%) and poor (modified Rankin Scale 3–6) in 199 patients (51%). Mortality at three-months was 20%. Diabetics were more likely to have poor outcome (72% vs. 48%; P = 0·001) and to be dead (30% vs. 19%; P = 0·044) at three-months. After multivariable analysis, there remained an independent relationship between diabetes and outcome (P = 0·003; odds ratio 3·033, 95% confidence interval 1·452–6·336), but not with mortality (P = 0·310; odds ratio 1·436; 95% confidence interval 0·714–2·888). Moreover, higher age (P = 0·001; odds ratio 1·039; 95% confidence interval 1·017–1·061), higher baseline National Institutes of Health Stroke Scale score (P < 0·0001; odds ratio 1·130; 95% confidence interval 1·079–1·182), location of vessel occlusion as categorical variable (P < 0·0001), poor collaterals (P = 0·02; odds ratio 1·587; 95% confidence interval 1·076–2·341), poor vessel recanalization (P < 0·0001; odds ratio 4·713; 95% confidence interval 2·627–8·454), and higher leucocyte count (P = 0·032; odds ratio 1·094; 95% confidence interval 1·008–1·188) were independent baseline predictors of poor outcome. Higher admission glucose was associated with poor outcome (P = 0·006) and mortality (P < 0·0001). After multivariate analyses, glucose remained independently associated with poor outcome (P = 0·019; odds ratio 1·150; 95% confidence interval 1·023-1-292) and mortality (P = 0·005; odds ratio 1·183; 95% confidence interval 1052–1·331). The rate of symptomatic intracranial haemorrhage was similar in diabetics and non-diabetics (6·7% vs. 4·6%; P = 0·512). Mean admission glucose was higher in patients with symptomatic intracranial haemorrhage than without (8·58 vs. 7·26 mmol/l; P = 0·010). Multivariable analysis confirmed an independent association between admission glucose and symptomatic intracranial haemorrhage (P = 0·027; odds ratio 1·187; 95% confidence interval 1·020–1·381). Conclusions Diabetes and glucose value on admission did not influence recanalization after intra-arterial thrombolysis; nevertheless, they were independent predictors of poor outcome after intra-arterial thrombolysis and a higher admission glucose value was an independent predictor of symptomatic intracranial haemorrhage. This indicates that factors on the capillary, cellular, or metabolic level may account for the worse outcome in patients with elevated glucose value and diabetes.