IV Thrombolysis in Basilar Artery Occlusion: Outcomes and Comparison With Endovascular Thrombectomy.

BACKGROUND AND OBJECTIVES: Recanalization is considered a prerequisite for favorable outcome in basilar artery occlusion (BAO). Intravenous thrombolysis (IVT) has been successfully used for eligible patients with BAO well beyond the 4.5-hour time window but has been largely underrepresented in the best medical management arms in recent randomized controlled trials of recanalization therapy in BAO. We aimed to analyze the outcomes of patients with BAO treated with IVT only and to compare IVT with endovascular thrombectomy (EVT). METHODS: This observational single-center, retrospective cohort study included consecutive patients with BAO treated with IVT and/or EVT up to 48 hours of symptom onset during 1995-2022. The primary outcome was favorable functional outcome (modified Rankin Scale 0-3) at 3 months collected by a stroke physician by phone. In the first part, we described the outcomes and factors associated with functional outcome in the IVT-only cohort during 1995-2022. In the second part, we used doubly robust inverse probability-weighted regression adjustment models to compare functional outcome of patients treated with IVT vs EVT+/-IVT during 2010-2022. RESULTS: In the whole cohort of 376 patients with acute BAO treated with recanalization therapy, 245 (65.2%) received only IVT. In the IVT-only cohort, most patients had moderate-to-severe clinical presentation (median NIH Stroke Scale 18) but no extensive early ischemic changes in the posterior circulation on admission. Half of them had onset-to-treatment time over 6 hours. 46.5% of the IVT-treated patients achieved 3-month favorable functional outcome, whereas mortality was 35.9%. sICH occurred in 11.1%. In a multivariable analysis, younger age, milder symptom severity, and less baseline ischemic changes predicted favorable functional outcome. In the 2010-2022 cohort, when compared with patients treated with EVT+/-IVT (n = 121), the IVT-only cohort (n = 122) had higher odds for favorable functional outcome (IVT 58.2% vs EVT 43.0% (aOR 2.82 [95% CI 1.31-6.05]). DISCUSSION: IVT alone produced outcomes comparable with those in recent trials of endovascular BAO recanalization. Furthermore, in head-to-head comparison in our cohort, the IVT-only approach was more often associated with favorable outcome than EVT+/-IVT. Thus, it should not be overlooked as the first-line recanalization therapy in acute BAO, even in longer time windows. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that tPA is as effective as thrombectomy for basilar artery thrombosis.

Incidence and prevalence of Hemifacial Spasm in Finland's largest hospital district.

BACKGROUND: Hemifacial spasm (HFS) is a movement disorder of facial muscles innervated by the facial nerve. This condition often demands regular utilization of healthcare resources. However, knowledge of the incidence and prevalence of this condition is based on scarce studies. This research aimed to identify the incidence and prevalence of HFS in Finland's largest hospital district. METHODS: This retrospective study was conducted in the largest hospital district in Finland (Helsinki and Uusimaa). The study included consecutive HFS patients who visited the departments of Neurology and Neurosurgery in the Hospital District of Helsinki and Uusimaa between 2014 and 2019. The demographics included sex, side of the spasm, treatment allocations, duration of symptoms before diagnosis, and age at the time of diagnosis. RESULTS: 279 patients were identified from the medical records. 62% of patients were women and had left-sided spasms. The crude mean incidence among women was almost double that of men (1.86 vs. 0.94). The highest crude mean annual incidence among men was in the age group 60-79 years, while among women, it peaked in the age group 80 years and over. The mean annual age-standardized incidence of HFS was 1.53, 1.94 in women, and 1.05 in men. The mean age-standardized yearly prevalence was 10.62, 11.62 among women, and 9.31 among men. The annual age-standardized prevalence of HFS increased steadily from 2014 to 2019. CONCLUSIONS: The incidence and prevalence of women outnumbered men. HFS is typically left-sided. The HFS incidence peaked after 80 years in women and men aged 60-79 years.

Markers of early vascular aging are not associated with cryptogenic ischemic stroke in the young: A case-control study.

BACKGROUND AND PURPOSE: We aimed to assess the association between covert atherosclerosis, arterial stiffness, and early-onset cryptogenic ischemic stroke (CIS) in a prospective case-control study. METHODS: We enrolled 123 young CIS patients (median age 41 years; 42% women) and 123 age- and sex-matched controls. Carotid intima-media thickness (CIMT), Augmentation Index (AIx), central pulse wave velocity (PWV), and subendocardial viability ratio (SEVR) were compared between patients and controls. Conditional logistic regression was used adjusting for age, systolic blood pressure, diastolic blood pressure, current smoking, total cholesterol/high-density lipoprotein cholesterol (Total-C/HDL-C) ratio, and glycated albumin to assess the independent association between CIMT, arterial stiffness and CIS. RESULTS: Patients with higher CIMT and PWV were older, more often men and they had more frequently well-documented risk factors, lower HDL and higher Total-C/HDL-C ratio compared to other tertiles. In univariate comparisons, we found no differences between patients and controls regarding CIMT, AIx, or PWV. In the entire cohort, patients had a significantly lower SEVR compared to controls (146.3%, interquartile range [IQR] 125.7-170.3 vs. 158.0%, IQR 141.3-181.0, P=0.010). SEVR was lower also in women compared to their controls (132.0%, IQR 119.4-156.1 vs. 158.7%, IQR 142.0-182.8, P=0.001) but no significant difference appeared between male patients and male controls. However, after adjusting for comorbidities and laboratory values these significant differences were lost (odds ratio [OR] 1.52, 95% confidence interval [CI] 0.47-4.91) in the entire cohort and OR 3.89, 95% CI 0.30-50.80 in women). CONCLUSIONS: Higher CIMT and PWV were associated to higher age, male sex, and several well-documented cardiovascular risk factors. However, in this study we could not prove that either covert atherosclerosis or arterial stiffness contribute to pathogenesis of early-onset CIS.

Is the weekend effect true in acute stroke patients at tertiary stroke center?

BACKGROUND: There is contradicting evidence on the outcome of emergency patients treated during weekends versus weekdays. We studied if outcome of ischemic stroke patients receiving intravenous thrombolysis (IVT) differs according to the treatment time. METHODS: Our retrospective study included consecutive patients receiving IVT within 4.5 h of stroke onset between June 1995 and December 2018 at the Helsinki University Hospital. The patients were compared based on the treatment initiation either during weekdays (Monday to Friday) or weekend (Saturday and Sunday). The primary outcome was 3-month mortality and secondary outcomes comprised 3-month modified Rankin Scale (mRS) and incidence of symptomatic intracerebral hemorrhage (sICH). Additional analyses studied the effect of IVT treatment according to non-office hours, time of day, and season. RESULTS: Of the 3980 IVT-treated patients, 28.0% received treatment during weekends. Mortality was similar after weekend (10.0%) and weekday (10.6%) admissions in the multivariable regression analysis (OR 0.78; 95% CI 0.59-1.03). Neither 3-month mRS (OR 0.98; 95% CI 0.86-1.12), nor the occurrence of sICH (4.2% vs 4.6%; OR 0.87; 95% CI 0.60-1.26) differed between the groups. No outcome difference was observed between the office vs non-office hours or by the time of day. However, odds for worse outcome were higher during autumn (OR 1.19; 95% CI 1.04-1.35) and winter (OR 1.15; 95% CI 1.01-1.30). CONCLUSION: We did not discover any weekend effect for IVT-treated stroke patients. This confirms that with standardized procedures, an equal quality of care can be provided to patients requiring urgent treatment irrespective of time.

Endothelial Dysfunction is Associated With Early-Onset Cryptogenic Ischemic Stroke in Men and With Increasing Age.

Background The aim of this study was to assess the association between endothelial function and early-onset cryptogenic ischemic stroke (CIS), with subgroup analyses stratified by sex and age groups. Methods and Results We prospectively enrolled 136 consecutive patients aged 18 to 49 years (median age, 41 years; 44% women) with a recent CIS and 136 age- and sex-matched (±5 years) stroke-free controls. Endothelial function was measured with an EndoPAT 2000 device and analyzed as tertiles of natural logarithm of reactive hyperemia index with lower values reflecting dysfunction. We used conditional logistic regression adjusting for age, education, hypertension, diabetes mellitus, dyslipidemia, current smoking, heavy drinking, obesity, and diet score to assess the independent association between endothelial function and CIS. Patients in the lowest tertile of natural logarithm of reactive hyperemia index were more often men and they more frequently had a history of dyslipidemia; they were also more often obese, had a lower diet score, and lower high-density lipoprotein cholesterol. In the entire cohort, we found no association in patients with endothelial function and CIS compared with stroke-free controls. In sex- and age-specific analyses, endothelial dysfunction was associated with CIS in men (adjusted odds ratio [OR], 3.50 for lowest versus highest natural logarithm of reactive hyperemia index tertile; 95% CI, 1.22-10.07) and in patients ≥41 years (OR, 5.78; 95% CI, 1.52-21.95). These associations remained significant when dyslipidemia was replaced with the ratio of total to high-density lipoprotein cholesterol. Conclusions Endothelial dysfunction appears to be an independent player in early-onset CIS in men and patients approaching middle age.

Comatose With Basilar Artery Occlusion: Still Odds of Favorable Outcome With Recanalization Therapy.

Background: Around 30-60% of patients with basilar artery occlusion (BAO) present with coma, which is often considered as a hallmark of poor prognosis. Aim: To examine factors that will help predict outcomes in patients with BAO comatose on admission. Methods: A total of 312 patients with angiography-proven BAO were analyzed. Comas were assessed as Glasgow Coma Scale (GCS) of ≤8 or impaired level of consciousness ascertained in the medical records. Outcomes were evaluated with the modified Rankin Scale (mRS) over a phone call at 3 months. In our study, 53 patients were excluded due to inadequate data on the level of consciousness. Results: In total, 103/259 (39.8%) of BAO patients were comatose on admission. Factors associated with acute coma were higher age, coronary artery disease, convulsions, extent of early ischemia by posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) < 8, absence of patent posterior collateral vasculature, and occlusion over multiple segments of BA. A total of 21/103 (20.4%) of comatose patients had a favorable outcome (mRS 0-3), and 12/103 (11.7%) had a good outcome (mRS 0-2). Factors associated with a favorable outcome in comatose BAO patients were younger age (p = 0.010), less extensive baseline ischemia (p = 0.027), recanalization (p = 0.013), and avoiding symptomatic intracranial hemorrhage (sICH) (p = 0.038). Factors associated with the poorest outcome or death (mRS 5-6) were older age (p = 0.001), diabetes (p = 0.022), atrial fibrillation (p = 0.016), lower median GCS [4 (IQR 3.6) vs. 6 (5-8); p = 0.006], pc-ASPECTS < 8 (p = 0.003), unsuccessful recanalization (p = 0.006), and sICH (p = 0.010). Futile recanalization (mRS 4-6) was significantly more common in comatose patients (49.4 vs. 18.5%, p < 0.001). Conclusions: One in five BAO patients with acute coma had a favorable outcome. Older patients with cardiovascular comorbidities and already existing ischemic lesions before reperfusion therapies tended to have a poor prognosis, especially if no recanalization is achieved and sICH occurred.

Outcomes and long-term mortality after basilar artery occlusion-A cohort with up to 20 years' follow-up.

BACKGROUND: The data on long-term outcome after basilar artery occlusion (BAO) are scarce. Little is known about BAO survivors´ outcome over decades. AIM: We set out to investigate long-term survival and causes of death in BAO patients with up to two decades of follow-up. We also evaluated differences in outcome trends. METHODS: Two hundred and seven BAO patients treated with intravenous thrombolysis (IVT) at the Department of Neurology, Helsinki University Hospital, between 1995 and 2016, were analyzed. Short-term outcome was assessed by modified Rankin Scale (mRS) at 3 months. Long-term cumulative survival rate was analyzed using Kaplan-Meier analysis. Factors associated with mortality were analyzed with Cox regression. RESULTS: Moderate outcome (mRS 0-3) was achieved in 41.1% and good outcome (mRS 0-2) in 30.4% of patients at 3 months. Three-month mortality was 39.6%, of which 89% died within the first month. The median follow-up time in 3-month survivors was 8.9 years (maximum 21.8 years). Total mortality during follow-up was 52.2%. Cumulative mortality rate was 25.7%. Older age, coronary artery disease and more extensive ischemic changes on admission brain imaging were independently associated with long-term mortality. After the acute phase, the rate of other vascular causes of death increased in relation to stroke. CONCLUSIONS: The described evolution of a large, single-center BAO cohort shows a trend towards a higher rate of good and/or moderate outcome during later years in IVT-treated patients. Survivors showed relative longevity, and the rate of cardiac and other vascular causes of death increased in relation to stroke sequelae over the long term.

Trigeminal neuralgia in multiple sclerosis: Prevalence and association with demyelination.

OBJECTIVES: The association of trigeminal neuralgia (TN) with multiple sclerosis (MS) is still widely unaddressed in larger, systematical clinical series. In this study, a cohort of Finnish MS patients was assessed regarding the incidence and prevalence of TN, as well as the presence of demyelinating lesions near the trigeminal ganglion, thus searching for a causative role of MS plaques in TN onset. MATERIALS & METHODS: All consecutive patients treated and followed up for MS (ICD-code G35) in Helsinki University Hospital during 2004-2017 were identified from the Finnish MS register. A hospital administrative database search was used to identify all patients treated and followed up for TN during the same period. Among the MS patients, head MRI scans available from the diagnostic phase of TN or thereafter were analysed. RESULTS: We identified a total of 2575 patients with MS and 2008 patients with TN. Both diagnoses could be verified for 55 patients, giving a prevalence of 2.1% for TN in MS. The incidence of TN in MS patients was 149/100 000 person-years (95% CI 108-190). In the general outpatient population of our neurological department, the incidence of TN was 9.9/100 000 person-years (95% CI 9.5-10.3). A demyelinating lesion in the proximity of the trigeminal ganglia was seen for 63% of the 41 patients with relevant MRI data available. CONCLUSIONS: Incidence of TN among MS patients was 15-fold higher than in the general neurological outpatient population, thus in favour of a strong association between MS and TN.

Quality of life and depression 3 months after intracerebral hemorrhage.

OBJECTIVES: Quality of life (QoL) after intracerebral hemorrhage (ICH) is poorly known. This study investigated factors affecting QoL and depression after spontaneous ICH. MATERIALS AND METHODS: This prospective study included patients admitted to Helsinki University Hospital between May 2014 and December 2016. Health-related QoL (HRQoL) at 3 months after ICH was measured using the European Quality of Life Scale (EQ-5D-5L), and the 15D scale. Logistic regression analyses were used to test factors affecting HRQoL. EQ-5D-5L anxiety/depression dimension was used to analyze factors associated with anxiety/depression. RESULTS: Of 277 patients, 220 were alive, and sent QoL questionnaire. The questionnaire was returned by 124 patients. Nonreturners had more severe strokes with admission National Institutes of Health Stroke Scale (NIHSS) 7.8 (IQR 3.0-14.8) versus 5.0 (IQR 2.3-11.0); p = 0.018, and worse outcome assessed as modified Rankin Scale 3-5 at 3 months 59.4% versus 44.4% (p = 0.030). Predictors for lower HRQoL by both scales were higher NIHSS with OR 1.28 (95% CI 1.13-1.46) for EQ-5D-5L, and OR 1.28 (1.15-1.44) for 15D, older age (OR 1.10 [1.03-1.16], and OR 1.09 [1.03-1.15]), and chronic heart failure (OR 18.12 [1.73-189.27], and OR 12.84 [1.31-126.32]), respectively. Feeling sad/depressed for more than 2 weeks during the year prior to ICH was predictor for lower EQ-5D-5L (OR 10.64 [2.39-47.28]), and history of ICH for lower 15D utility indexes (OR 11.85 [1.01-138.90]). Prior feelings of sadness/depression were associated with depression/anxiety at 3 months after ICH with OR 3.62 (1.14-11.45). CONCLUSIONS: In this cohort of ICH patients with milder deficits, HRQoL was affected by stroke severity, comorbidities and age. Feelings of depression before ICH had stronger influence on reporting depression/anxiety after ICH than stroke severity-related and outcome parameters. Thus, simple questions on patient's premorbid feelings of sadness/depression could be used to identify patients at risk of depression after ICH for focusing follow-up and treatment.

Should we thrombolyse prior to endovascular treatment in acute stroke?

The superiority of endovascular treatment (EVT) in acute stroke due to large vessel occlusion has been proven in recent randomized trials. Yet, there are no randomized trials which have tested the additive effect of standard treatment with intravenous thrombolysis (IVT) as pretreatment to EVT over EVT treatment alone. So far, the EVT treatment groups of RCTs most often had pretreatment with IVT. The current guidelines on acute stroke treatment rely on meta-analyses and systematic analyses from RCTs and observational studies on pretreatment with IVT + EVT. Clinicians also apply their clinical experience and local "in-house" protocols. We performed literature search on randomized controlled trials, systematic and meta-analyses and observational studies on recanalization therapies including intravenous thrombolysis and endovascular treatment or thrombectomy in acute stroke. Here we present a review and an opinion on the current choice of treatment modalities.

Cerebral white matter lesions and post-thrombolytic remote parenchymal hemorrhage.

OBJECTIVE: Parenchymal hematoma (PH) following intravenous thrombolysis (IVT) in ischemic stroke can occur either within the ischemic area (iPH) or as a remote PH (rPH). The latter could be, at least partly, related to cerebral amyloid angiopathy, which belongs to the continuum of cerebral small vessel disease. We hypothesized that cerebral white matter lesions (WMLs)-an imaging surrogate of small vessel disease-are associated with a higher rate of rPH. METHODS: We analyzed 2,485 consecutive patients treated with IVT at the Helsinki University Hospital. Blennow rating scale of 5 to 6 points on baseline computed tomographic head scans was considered as severe WMLs. An rPH was defined as hemorrhage that-contrary to iPH-appears in brain regions without visible ischemic damage and is clinically not related to the symptomatic acute lesion site. The associations between severe WMLs and pure rPH versus no PH, pure iPH versus no PH, and pure rPH versus pure iPH were studied in multivariate logistic regression models. RESULTS: rPHs were mostly (74%) located in lobar regions. After adjustments, the presence of severe WMLs was associated with pure rPH (odds ratio [OR] = 6.79, 95% confidence interval [CI] = 2.57-17.94) but not with pure iPH (OR = 1.45, 95% CI = 0.83-2.53) when compared to patients with no PH. In direct comparison of pure rPH with pure iPH, severe cerebral WMLs were further associated with higher iPH rates (OR = 3.60, 95% CI = 1.06-12.19). INTERPRETATION: Severe cerebral WMLs were associated with post-thrombolytic rPH but not with iPH within the ischemic area. Ann Neurol 2016;80:593-599.

Recanalization treatments in basilar artery occlusion-Systematic analysis.

BACKGROUND AND AIMS: Basilar artery occlusion is a most devastating form of stroke, and the current practice is to reverse it with revascularization therapies. Pharmacological thrombolysis, intravenous or intraarterial, has been adjuncted or replaced with invasive, endovascular thrombectomy procedures. The preferred approach remains unknown and many recanalizations are futile with no clinical benefit. We sought to determine reasons for futility and weigh the existing reports to find whether endovascular mechanical interventions provide superior outcomes over pharmacological thrombolysis alone. METHODS: After analyzing systematically the reports of outcomes produced by variable basilar artery occlusion recanalization protocols, information was retrieved and reconciled from 15 reports published from year 2005 comprising 803 patients in 17 cohorts. In the largest single-center cohort (162, Helsinki), predictors of futile recanalization (three-month modified Rankin Scale score 4 to 6) were determined. RESULTS: Good outcome was reported by mechanical approaches either alone or on demand more frequently than by pharmacological, intravenous or intraarterial thrombolysis protocols (35.5% versus 24.4%, p < 0.001), accompanied by higher recanalization rates (84.1% versus 70.9%, p < 0.001). Along with superior recanalization rate at 91%, good outcome was reached by primary thrombectomy in 36% at the cost of substantial futile recanalization rate at 60%, which was lower when using modern stentrievers only (52.8%). In the Helsinki cohort, the single most significant predictor was extensive baseline ischemia, increasing the odds of futility 20-fold (95%CI 4.39-92.29, p < 0.001). Other attributes of futility were ventilation support and history of atrial fibrillation or previous stroke. CONCLUSIONS: Endovascular mechanical approaches have been reported to provide superior outcomes over pharmacological thrombolysis in basilar artery occlusion. Stricter patient selection, most notably to exclude victims of already extended ischemia, would assist in translating excellent recanalization rates into improved clinical outcomes and more acceptable futility rates.

Time window for recanalization in basilar artery occlusion: Speculative synthesis.

Basilar artery occlusion (BAO) is one of the most devastating forms of stroke and few patients have good outcomes without recanalization. Most centers apply recanalization therapies for BAO up to 12-24 hours after symptom onset, which is a substantially longer time window than the 4.5 hours used in anterior circulation stroke. In this speculative synthesis, we discuss recent advances in BAO treatment in order to understand why and under which circumstances longer symptom duration might not necrotize the brainstem and turn therapeutic attempts futile. We raise the possibility that distinct features of the posterior circulation, e.g., highly developed, persistent collateral arterial network, reverse filling of the distal basilar artery, and delicate plasma flow siding the clot, might sustain brittle patency of brainstem perforators in the face of stepwise growth of the thrombus. Meanwhile, the tissue clock characterizing the rapid necrosis of a typical anterior circulation penumbra will not start. During this perilous time period, recanalization at any point would salvage the brainstem from eventual necrosis caused by imminent reinforcement and further building up of the clot.

Higher neutrophil counts before thrombolysis for cerebral ischemia predict worse outcomes.

OBJECTIVE: To determine whether higher neutrophil counts before IV recombinant tissue plasminogen activator (rtPA) administration in ischemic stroke (IS) patients are associated with symptomatic intracerebral hemorrhages (sICH) and worse outcomes at 3 months. METHODS: Blood samples for leukocyte, neutrophil, and lymphocyte counts were drawn before IV rtPA administration in IS patients included in the cohorts of Lille and Helsinki. The primary endpoint was sICH (European Cooperative Acute Stroke-II definition). Secondary endpoints were death and excellent (modified Rankin Scale [mRS] score 0-1 or equal to prestroke mRS) and good (mRS score 0-2 or equal to prestroke mRS) outcomes at 3 months. RESULTS: We included 846 patients (median age 71 years; 50.8% men). The neutrophil count and neutrophil to lymphocyte ratio (NLR) were independently associated with the 4 endpoints: sICH (adjusted odds ratio [adjOR] for an increase of 1,000 neutrophils = 1.21 and adjOR 1.11, respectively), death (adjOR 1.16 and adjOR 1.08), and excellent (adjOR 0.87 and adjOR 0.85) and good (adjOR 0.86 and adjOR 0.91) outcomes. The total leukocyte count was not associated with any of the 4 endpoints. The best discriminating factor for sICH was NLR ≥4.80 (sensitivity 66.7%, specificity 71.3%, likelihood ratio 2.32). Patients with NLR ≥4.80 had a 3.71-fold increased risk for sICH (95% confidence interval adjOR: 1.97-6.98) compared to patients with NLR <4.80. CONCLUSIONS: Higher neutrophil counts and NLR are independently associated with sICH and worse outcome at 3 months. The identification of mediators of this effect could provide new targets for neuroprotection in patients treated by rtPA.

White Matter Lesions Double the Risk of Post-Thrombolytic Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Cerebral white matter lesions (WMLs), a surrogate for small-vessel disease, are common in patients with stroke and may be related to an increased intracranial bleeding risk after intravenous thrombolysis in acute ischemic stroke. We aimed to investigate the risk of symptomatic intracerebral hemorrhage (sICH) in the presence of WMLs in a large cohort of ischemic stroke patients treated with intravenous thrombolysis. METHODS: We included 2485 consecutive patients treated with intravenous thrombolysis at the Helsinki University Central Hospital. WMLs were scored according to 4 previously published computed tomography visual rating scales from all baseline head scans. A sICH was classified according to the European Cooperative Acute Stroke Study II criteria. The associations of sICH with nominal, ordinal, and continuous variables were analyzed in a univariate binary regression model and adjusted in multivariate binary regression models. RESULTS: In univariate and multivariate regression analyses, all 4 tested visual WML rating scales (as continuous variables or dichotomized at different cutoff points) were associated with increased risk of sICH. In binary analyses, WML doubled the bleeding risk: the odds ratios of all 4 visual rating scales ranged from 2.22 (95% confidence interval, 1.49-3.30) to 2.70 (1.87-3.90) in univariable and from 2.00 (1.26-3.16) to 2.62 (1.71-4.02) in multivariable analyses. The multivariable-adjusted odds ratio for the association of high load of WMLs with remote parenchymal hemorrhage was 4.11 (2.38-7.10). CONCLUSIONS: WMLs visible on computed tomography are associated with a more than doubled risk of sICH in patients treated with intravenous thrombolysis for acute ischemic stroke.

Cerebral computed tomography-graded white matter lesions are associated with worse outcome after thrombolysis in patients with stroke.

BACKGROUND AND PURPOSE: Compared with other stroke causes, small-vessel disease is associated with better 3-month outcomes in patients with acute ischemic stroke treated with intravenous thrombolysis. Another question is the impact of coexisting cerebral white matter lesions (WMLs; a surrogate marker of small-vessel disease) on outcome, which was addressed in the current study. METHODS: We analyzed 2485 consecutive intravenous thrombolysis-treated patients at the Helsinki University Central Hospital, 2001 to 2014. WMLs were scored according to 4 previously published computed tomographic visual rating scales from all baseline head scans. The inter-rater agreement was calculated. The primary outcome measure was shift analysis, and the secondary examined all possible binary cutoffs in the modified Rankin Scale at 3 months. The associations of modified Rankin Scale with nominal, ordinal, and continuous variables were analyzed in univariate and adjusted in multivariate binary and ordinal regression (shift analysis) models. RESULTS: In univariate and multivariate regression analyses, all 4 tested visual WML rating scales (as continuous variables, or dichotomized at different cutoff points) were associated with worse outcome at all binary levels and in shift analyses of the modified Rankin Scale. After adjusting for confounders, the statistically strongest association in shift analyses remained for the Blennow scale dichotomized at >3 points, reflecting at least moderate WMLs (odds ratio, 1.90; 95% confidence interval, 1.48-2.44). CONCLUSIONS: WMLs on admission computed tomographic scan are independently associated with worse outcome in intravenous thrombolysis-treated patients with stroke.

Extent of secondary intraventricular hemorrhage is an independent predictor of outcomes in intracerebral hemorrhage: data from the Helsinki ICH Study.

BACKGROUND: Intraventricular hemorrhage is a severe subtype of intracerebral hemorrhage associated with high mortality and poor outcome. AIM: We analyzed various intraventricular hemorrhage scores at baseline to find common parameters associated with increased mortality. METHODS: Consecutive intracerebral hemorrhage patients treated in Helsinki University Central Hospital during 2005-2010 were included in the Helsinki Intracerebral Hemorrhage Study registry and analyzed for three-month mortality. RESULTS: After excluding lost-to-follow-up patients, 967 intracerebral hemorrhage patients were included, out of whom 398 (41%) had intraventricular hemorrhage. Intraventricular hemorrhage patients, compared with nonintraventricular hemorrhage patients, had lower baseline Glasgow Coma Scale [median 12 (IQR 6-15) vs. 15 (13-15); P < 0.001] and higher National Institutes of Health Stroke Scale [18 (10-27) vs. 7 (3-14); P < 0.001] scores; larger intracerebral hemorrhage volumes [17 ml (7.2-42) vs. 6.8 (2.4-18); P < 0.001] and more often hydrocephalus (51% vs. 9%; P < 0.001); and higher mortality rates (54% vs. 18%; P < 0.001). In multivariable analysis, the presence of intraventricular hemorrhage was independently associated with mortality [OR 2.05 (95% CI 1.36-3.09)] when adjusted for well-known prognostic factors of intracerebral hemorrhage, i.e. age, gender, baseline National Institutes of Health Stroke Scale, intracerebral hemorrhage volume, infratentorial location, and etiology. CONCLUSIONS: The presence of intraventricular hemorrhage was independently associated with increased mortality, and all the intraventricular hemorrhage scores were strong predictors of three-month mortality.

Cerebral amyloid angiopathy related hemorrhage after stroke thrombolysis: case report and literature review.

Cerebral amyloid angiopathy (CAA) predisposes to symptomatic intracerebral hemorrhage (sICH) after combined thrombolytic and anticoagulant treatment of acute myocardial infarction. However, the role of CAA in stroke thrombolysis has not been established. Here, we describe a confirmed case of CAA-related hemorrhage in a patient receiving thrombolysis for acute ischemic stroke. On autopsy, immunohistochemistry revealed amyloid-ß positive staining in thickened cortical and meningeal arteries at sites of hemorrhage. Further research is urgently needed to determine the hemorrhage risk related to CAA in stroke thrombolysis and develop better diagnostic tools to identify CAA in the emergency room.

The CAVE score for predicting late seizures after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Seizures are a common complication of intracerebral hemorrhage (ICH). We developed a novel tool to quantify this risk in individual patients. METHODS: Retrospective analysis of the observational Helsinki ICH Study (n=993; median follow-up, 2.7 years) and the Lille Prognosis of InTra-Cerebral Hemorrhage (n=325; 2.2 years) cohorts of consecutive ICH patients admitted between 2004 and 2010. Helsinki ICH Study patients' province-wide electronic records were evaluated for early seizures occurring within 7 days of ICH and among 7-day survivors (n=764) for late seizures (LSs) occurring >7 days from ICH. A Cox regression model estimating risk of LSs was used to derive a prognostic score, validated in the Prognosis of InTra-Cerebral Hemorrhage cohort. RESULTS: Of the Helsinki ICH Study patients, 109 (11.0%) had early seizures within 7 days of ICH. Among the 7-day survivors, 70 (9.2%) patients developed LSs. The cumulative risk of LSs was 7.1%, 10.0%, 10.2%, 11.0%, and 11.8% at 1 to 5 years after ICH, respectively. We created the CAVE score (0-4 points) to estimate the risk of LSs, with 1 point for each of cortical involvement, age<65 years, volume>10 mL, and early seizures within 7 days of ICH. The risk of LSs was 0.6%, 3.6%, 9.8%, 34.8%, and 46.2% for CAVE scores 0 to 4, respectively. The c-statistic was 0.81 (0.76-0.86) and 0.69 (0.59-0.78) in the validation cohort. CONCLUSIONS: One in 10 patients will develop seizures after ICH. The risk of this adverse outcome can be estimated by a simple score based on baseline variables.

Intravenous thrombolysis of basilar artery occlusion: thrombus length versus recanalization success.

BACKGROUND AND PURPOSE: In middle cerebral artery occlusion, probability of recanalization after intravenous tissue-type plasminogen activator thrombolysis (IVT) was reported to drop <1% for thrombi exceeding 8 mm. We aimed to evaluate the effect of thrombus length and location on success of recanalization after IVT in basilar artery occlusion. METHODS: We evaluated 164 consecutive patients with angiography-proven basilar artery occlusion and available thrombus length. We excluded 24 patients who underwent endovascular treatment. All included patients (n=140) received IVT. Thrombolysis in myocardial infarction 2 to 3 was considered as successful recanalization. RESULTS: Of the 140 included patients, 37 (26.4%) lacked post-treatment angiography, mostly because of early death. Of the remaining 103 patients, those with recanalization had shorter thrombi (median, 5.5 mm and mean, 9.7 mm) when compared with those with nonrecanalized (median, 15.0 mm and mean, 16.6 mm; P<0.001). Thrombi shorter than 10 mm had 70% to 80% probability of recanalization, whereas 10 to 20 mm, 20 to 30 mm, and >30 mm long thrombi had probabilities of 50% to 70%, 30% to 50%, and 20% to 30%, respectively. Patients with thrombi <10 mm (n=52) and recanalization had more frequently top-of-the basilar (92.5%) and less frequently caudal or midbasilar (7.5%) clot location (P=0.01). In multivariable analysis, thrombus length was independently associated with recanalization (P=0.001). Their relationship remained linear across all lengths. CONCLUSIONS: Although recanalization of basilar artery occlusion with IVT depends on thrombus length, its probability even in patients with thrombi >30 mm (20%-30%) was substantially higher than minimal recanalization of middle cerebral artery thrombi exceeding 8 mm. There was no threshold length, beyond which basilar artery occlusion recanalization with IVT could ad hoc be deemed hopeless.