Cerebral Microembolism in Intracerebral Hemorrhage: A Prospective Case-Control Study.

BACKGROUND: Small and remote acute ischemic lesions may occur in up to one-third of patients with spontaneous intracerebral hemorrhage (ICH). Possible mechanisms include cerebral embolism, small vessel disease, blood pressure variability and others. The embolic mechanism has not been adequately studied. Using transcranial Doppler (TCD), we assessed the incidence of spontaneous microembolic signals (MESs) in patients with acute ICH. METHODS: Twenty acute ICH patients were prospectively evaluated within 48 h of hospital admission. Clinical and imaging data were collected. Continuous TCD monitoring was performed in both middle cerebral arteries for a one-hour period on days 1, 3 and 7 of hospital admission. Monitoring was performed in the emergency room, ICU or ward, according to patient location. We compared the frequency and risk factors for MES in patients with ICH and in 20 age- and gender-matched controls without history of ischemic or hemorrhagic stroke. RESULTS: The mean age was 57.5 ± 14.1 years, and 60% were male. MESs were detected in 7 patients with ICH and in one control patient without ICH (35% vs 5%, p = 0.048). The frequency of MES on day 1 was 15% (3 of 20 patients), on day 3, 26% (5 of 19 patients) and on day 7, 37.5% (3 of 8 patients). Among patients with ICH, those with MES had a tendency to higher frequencies of dyslipidemia (83% vs 33%, p = 0.13) and lobar location of hemorrhages (71% vs 30%, p = 0.15). Two out of 6 patients with ICH who also underwent MRI had remote DWI lesions, of whom one showed MES on TCD. CONCLUSION: Micro-embolic signals occur in over one-third of patients with ICH. Further research is needed to identify the sources of cerebral microembolism and their relationship with small acute infarcts in ICH.

Reduced Ischemic Lesion Growth with Heparin in Acute Ischemic Stroke.

OBJECTIVE: The role of heparin in acute ischemic stroke is controversial. We investigated the effect of heparin on ischemic lesion growth. METHODS: Data were analyzed on nonthrombolyzed ischemic stroke patients in whom diffusion-weighted imaging (DWI)/perfusion-weighted imaging (PWI) MRI was performed less than 12 hours of last known well and showed a PWI-DWI lesion mismatch, and who underwent follow-up neuroimaging at least 4 days after admission. Lesion growth was assessed by (1) absolute lesion growth and (2) percentage mismatch lost (PML). Univariate and multivariate regression analysis, and propensity score matching, were used to determine the effects of heparin on ischemic lesion growth. RESULTS: Of the 113 patients meeting study criteria, 59 received heparin within 24 hours. Heparin use was associated with ∼5-fold reductions in PML (3.5% versus 19.2%, P = .002) and absolute lesion growth (4.7 versus 20.5 mL, P = .009). In multivariate regression models, heparin independently predicted reduced PML (P = .04) and absolute lesion growth (P = .04) in the entire cohort, and in multiple subgroups (patients with and without proximal artery occlusion; DWI volume greater than 5 mL; cardio-embolic mechanism; DEFUSE-3 target mismatch). In propensity score matching analysis where patients were matched by admission NIHSS, DWI volume and proximal artery occlusion, heparin remained an independent predictor of PML (P = .048) and tended to predict absolute lesion growth (P = .06). Heparin treatment did not predict functional outcome at discharge or 90 days. CONCLUSION: Early heparin treatment in acute ischemic stroke patients with PWI-DWI mismatch attenuates ischemic lesion growth. Clinical trials with careful patient selection are warranted to investigate the potential ischemic protective effects of heparin.

Isolated Upper Limb Weakness From Ischemic Stroke: Mechanisms and Outcome.

OBJECTIVE: To characterize isolated upper extremity (UE) weakness from stroke. METHODS: In our Get with the Guidelines-Stroke dataset (n = 7643), 87 patients (1.14%) had isolated UE weakness and underwent thorough stroke evaluation with diffusion-weighted magnetic resonance imaging and good-quality arterial imaging. We analyzed clinical-imaging features, etiology, management, and outcome. Since isolated UE weakness is typically associated with contralateral hand-knob area infarcts, patients were classified into Group-A (motor strip infarct) or Group-B (non-motor strip infarct). RESULTS: The mean age was 68 years; 66% were male, 72% had hypertension, 22% diabetes, 53% hyperlipidemia, and 16% were smokers. In Group-A (n = 71), 18 patients had single and 53 had multiple infarcts involving the contralateral motor strip. In Group-B (n = 16), 6 patients had contralateral subcortical white matter infarcts, 9 had bihemispheric infarcts and 1 had a brainstem infarct. Compared to Group-B, patients in Group-A more often had carotid artery stenosis or irregular plaque (84.5% versus 50%, P = .006) and large-artery atherosclerosis mechanism (46% versus 19%, P = .05), and less often cardioembolic mechanism (13% versus 44%, P = .008). Among 36 patients with large-artery mechanism, 27 had less than 70% stenosis including 19 with plaque ulceration/thrombus. Recurrent strokes occurred in 10 patients (11.5%), including 5 with mild-moderate carotid stenosis and plaque ulceration/thrombosis, over 1515 days follow-up. CONCLUSION: Stroke mechanism in acute isolated UE weakness is variable. Contralateral motor-strip infarcts are associated with carotid stenosis, often with plaque ulceration ("vulnerable carotid plaque"), and infarcts in other locations with cardioembolism. Recurrent stroke risk is high especially with mild-moderate carotid artery stenosis and plaque ulceration/thrombus.

Post-stroke Recrudescence from Infection: an Immunologic Mechanism?

Post-stroke recrudescence (PSR) usually occurs in the setting of infection, hypotension, hyponatremia, insomnia or stress, and benzodiazepine use. Animal studies have suggested an infection-related immunologic mechanism for PSR. This retrospective study was designed to assess whether infection-triggered PSR is related to a prior infection during the index stroke. We identified 95 patients admitted to Massachusetts General Hospital from 2000 to 2015 with post-stroke recrudescence who had adequate medical record information concerning the index stroke. The frequency of infections, as well as other triggers such as hypotension, hyponatremia, insomnia/stress, and benzodiazepine use, was compared between the index stroke and the PSR episode. Independent predictors of infection-related PSR were identified using a logistic regression model. The mean age was 66 ± 17 years (53% female); 29 (31%) had infections during the index stroke as compared to 40 (42%) during the PSR episode. The frequency of PSR triggered by infection was higher in patients with infections during the index stroke (65% vs 32%, p = 0.003). The same relationship occurred with benzodiazepine-triggered PSR (41% vs 12%, p = 0.008). The frequencies of other triggers such as hypotension, hyponatremia and insomnia/stress were not significantly different between the index stroke and the PSR episode. In a logistic regression model, infection during the index stroke was an independent predictor of infection-triggered PSR (odds ratio 4.85, 95% C.I. 1.7, 13.7). The association between infection during index stroke and infection-triggered PSR supports the immunologic mechanism postulated in animal models.

RCVS2 score and diagnostic approach for reversible cerebral vasoconstriction syndrome.

OBJECTIVE: To develop a method to distinguish reversible cerebral vasoconstriction syndrome (RCVS) from other large/medium-vessel intracranial arteriopathies. METHODS: We identified consecutive patients from our institutional databases admitted in 2013-2017 with newly diagnosed RCVS (n = 30) or non-RCVS arteriopathy (n = 80). Admission clinical and imaging features were compared. Multivariate logistic regression modeling was used to develop a discriminatory score. Score validity was tested in a separate cohort of patients with RCVS and its closest mimic, primary angiitis of the CNS (PACNS). In addition, key variables were used to develop a bedside approach to distinguish RCVS from non-RCVS arteriopathies. RESULTS: The RCVS group had significantly more women, vasoconstrictive triggers, thunderclap headaches, normal brain imaging results, and better outcomes. Beta coefficients from the multivariate regression model yielding the best c-statistic (0.989) were used to develop the RCVS2 score (range -2 to +10; recurrent/single thunderclap headache; carotid artery involvement; vasoconstrictive trigger; sex; subarachnoid hemorrhage). Score ≥5 had 99% specificity and 90% sensitivity for diagnosing RCVS, and score ≤2 had 100% specificity and 85% sensitivity for excluding RCVS. Scores 3-4 had 86% specificity and 10% sensitivity for diagnosing RCVS. The score showed similar performance to distinguish RCVS from PACNS in the validation cohort. A clinical approach based on recurrent thunderclap headaches, trigger and normal brain scans, or convexity subarachnoid hemorrhage correctly diagnosed 25 of 37 patients with RCVS2 scores 3-4 across the derivation and validation cohorts. CONCLUSION: RCVS can be accurately distinguished from other intracranial arteriopathies upon admission, using widely available clinical and imaging features. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that the RCVS2 score accurately distinguishes patients with RCVS from those with other intracranial arteriopathies.