External validation of the SI2NCAL2C score for outcomes following cerebral venous thrombosis.

OBJECTIVES: Prognostication for cerebral venous thrombosis (CVT) remains difficult. We sought to validate the SI2NCAL2C score in an international cohort. MATERIALS AND METHODS: The SI2NCAL2C score was originally developed to predict poor outcome (modified Rankin Scale (mRS) 3-6) at 6 months, and mortality at 30 days and 1 year using data from the International CVT Consortium. The SI2NCAL2C score uses 9 variables: the absence of any female-sex-specific risk factors, intracerebral hemorrhage, central nervous system infection, focal neurological deficits, coma, age, lower level of hemoglobin, higher level of glucose, and cancer. The ACTION-CVT study was an international retrospective study that enrolled consecutive patients across 27 centers. The poor outcome score was validated using 90-day mRS due to lack of follow-up at the 6-month time-point in the ACTION-CVT cohort. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration plots. Missing data were imputed using the additive regression and predictive mean matching methods. Bootstrapping was performed with 1000 iterations. RESULTS: Mortality data were available for 950 patients and poor outcome data were available for 587 of 1,025 patients enrolled in ACTION-CVT. Compared to the International CVT Consortium, the ACTION-CVT cohort was older, less often female, and with milder clinical presentation. Mortality was 2.5% by 30 days and 6.0% by one year. At 90-days, 16.7% had a poor outcome. The SI2NCAL2C score had an AUC of 0.74 [95% CI 0.69-0.79] for 90-day poor outcome, 0.72 [0.60-0.82] for mortality by 30 days, and 0.82 [0.76-0.88] for mortality by one year. CONCLUSIONS: The SI2NCAL2C score had acceptable to good performance in an international external validation cohort. The SI2NCAL2C score warrants additional validation studies in diverse populations and clinical implementation studies.

Delayed Diagnosis in Cerebral Venous Thrombosis: Associated Factors and Clinical Outcomes.

Background Identifying factors associated with delayed diagnosis of cerebral venous thrombosis (CVT) can inform future strategies for early detection. Methods and Results We conducted a retrospective cohort study including all participants from ACTION-CVT (Anticoagulation in the Treatment of Cerebral Venous Thrombosis) study who had dates of neurologic symptom onset and CVT diagnosis available. Delayed diagnosis was defined as CVT diagnosis occurring in the fourth (final) quartile of days from symptom onset. The primary study outcome was modified Rankin Scale score of ≤1 at 90 days; secondary outcomes included partial/complete CVT recanalization on last available imaging and modified Rankin Scale score of ≤2. Logistic regression analyses were used to identify independent variables associated with delayed diagnosis and to assess the association of delayed diagnosis and outcomes. A total of 935 patients were included in our study. Median time from symptom onset to diagnosis was 4 days (interquartile range, 1-10 days). Delayed CVT diagnosis (time to diagnosis >10 days) occurred in 212 patients (23%). Isolated headache (adjusted odds ratio [aOR], 2.36 [95% CI, 1.50-3.73]; P<0.001), older age (aOR by 1 year, 1.02 [95% CI, 1.004-1.03]; P=0.01), and papilledema (aOR, 2.00 [95% CI, 1.03-3.89]; P=0.04) were associated with diagnostic delay, whereas higher National Institutes of Health Stroke Scale score was inversely associated with diagnostic delay (aOR by 1 point, 0.95 [95% CI, 0.89-1.00]; P=0.049). Delayed diagnosis was not associated with modified Rankin Scale score of ≤1 at 90 days (aOR, 1.08 [95% CI, 0.60-1.96]; P=0.79). Conclusions In a large multicenter cohort, a quarter of included patients with CVT were diagnosed >10 days after symptom onset. Delayed CVT diagnosis was associated with the symptom of isolated headache and was not associated with adverse clinical outcomes.

Timing and Predictors of Recanalization After Anticoagulation in Cerebral Venous Thrombosis.

BACKGROUND AND PURPOSE: Vessel recanalization after cerebral venous thrombosis (CVT) is associated with favorable outcomes and lower mortality. Several studies examined the timing and predictors of recanalization after CVT with mixed results. We aimed to investigate predictors and timing of recanalization after CVT. METHODS: We used data from the multicenter, international AntiCoagulaTION in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT) study of consecutive patients with CVT from January 2015 to December 2020. Our analysis included patients that had undergone repeat venous neuroimaging more than 30 days after initiation of anticoagulation treatment. Prespecified variables were included in univariate and multivariable analyses to identify independent predictors of failure to recanalize. RESULTS: Among the 551 patients (mean age, 44.4±16.2 years, 66.2% women) that met inclusion criteria, 486 (88.2%) had complete or partial, and 65 (11.8%) had no recanalization. The median time to first follow-up imaging study was 110 days (interquartile range, 60-187). In multivariable analysis, older age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.03-1.07), male sex (OR, 0.44; 95% CI, 0.24-0.80), and lack of parenchymal changes on baseline imaging (OR, 0.53; 95% CI, 0.29-0.96) were associated with no recanalization. The majority of improvement in recanalization (71.1%) occurred before 3 months from initial diagnosis. A high percentage of complete recanalization (59.0%) took place within the first 3 months after CVT diagnosis. CONCLUSION: Older age, male sex, and lack of parenchymal changes were associated with no recanalization after CVT. The majority recanalization occurred early in the disease course suggesting limited further recanalization with anticoagulation beyond 3 months. Large prospective studies are needed to confirm our findings.

Outcome Prediction in Cerebral Venous Thrombosis: The IN-REvASC Score.

BACKGROUND: We identified risk factors, derived and validated a prognostic score for poor neurological outcome and death for use in cerebral venous thrombosis (CVT). METHODS: We performed an international multicenter retrospective study including consecutive patients with CVT from January 2015 to December 2020. Demographic, clinical, and radiographic characteristics were collected. Univariable and multivariable logistic regressions were conducted to determine risk factors for poor outcome, mRS 3-6. A prognostic score was derived and validated. RESULTS: A total of 1,025 patients were analyzed with median 375 days (interquartile range [IQR], 180 to 747) of follow-up. The median age was 44 (IQR, 32 to 58) and 62.7% were female. Multivariable analysis revealed the following factors were associated with poor outcome at 90- day follow-up: active cancer (odds ratio [OR], 11.20; 95% confidence interval [CI], 4.62 to 27.14; P<0.001), age (OR, 1.02 per year; 95% CI, 1.00 to 1.04; P=0.039), Black race (OR, 2.17; 95% CI, 1.10 to 4.27; P=0.025), encephalopathy or coma on presentation (OR, 2.71; 95% CI, 1.39 to 5.30; P=0.004), decreased hemoglobin (OR, 1.16 per g/dL; 95% CI, 1.03 to 1.31; P=0.014), higher NIHSS on presentation (OR, 1.07 per point; 95% CI, 1.02 to 1.11; P=0.002), and substance use (OR, 2.34; 95% CI, 1.16 to 4.71; P=0.017). The derived IN-REvASC score outperformed ISCVT-RS for the prediction of poor outcome at 90-day follow-up (area under the curve [AUC], 0.84 [95% CI, 0.79 to 0.87] vs. AUC, 0.71 [95% CI, 0.66 to 0.76], χ2 P<0.001) and mortality (AUC, 0.84 [95% CI, 0.78 to 0.90] vs. AUC, 0.72 [95% CI, 0.66 to 0.79], χ2 P=0.03). CONCLUSIONS: Seven factors were associated with poor neurological outcome following CVT. The INREvASC score increased prognostic accuracy compared to ISCVT-RS. Determining patients at highest risk of poor outcome in CVT could help in clinical decision making and identify patients for targeted therapy in future clinical trials.

Trends in outpatient rehabilitation use for stroke survivors.

BACKGROUND: Stroke survivors with residual disabling deficits who are medically stable may be recommended for acute rehabilitation or outpatient therapy, depending partly on the severity of their deficits. Here we sought to determine if the location at which patients needing rehabilitation post-stroke has shifted from inpatient to an outpatient setting. METHODS: For analysis, we used our Institutional Review Board-approved Get With The Guidelines®-Stroke Database to study stroke survivors discharged to receive either inpatient or outpatient rehabilitation services between 2014 and 2019. Logistic regression analysis was used to identify clinical factors associated with discharge type. Cochran-Armitage trend analysis was used to assess differences in rehabilitation services used over time. RESULTS: A total of 3293 patients were included. Trend analysis demonstrated a significant increase over time in the proportion of patients needing rehabilitation being discharged home with rehabilitation services (P < 0.0001). In addition, older age was associated with discharge to inpatient rehabilitation (OR = 1.018, 95%CI, 1.011-1.026), as was a higher National Institutes of Health Stroke Scale score (OR = 1.149, 95%CI, 1.130-1.168). CONCLUSIONS: We found that home discharges increased, highlighting outpatient rehabilitation as an expanding healthcare resource for reducing stroke-associated disability in adults.

Estimating Perfusion Deficits in Acute Stroke Patients Without Perfusion Imaging.

BACKGROUND: Perfusion weighted imaging (PWI) is critical for determining whether stroke patients presenting in an extended time window are candidates for mechanical thrombectomy. However, PWI is not always available. Fluid-attenuated inversion recovery hyperintense vessels (FHVs) are seen in patients with a PWI lesion. We investigated whether a scale measuring the extent FHV could serve as a surrogate for PWI to determine eligibility for thrombectomy. METHODS: The National Institutes of Health (NIH) FHV score was developed to quantify the burden of FHV and applied to magnetic resonance imaging scans of stroke patients with fluid-attenuated inversion recovery and perfusion imaging. The NIH-FHV was combined with the diffusion weighted image volume to estimate the diffusion-perfusion mismatch ratio. Linear regression was used to compare PWI volumes and mismatch ratios with estimates from the NIH-FHV score. Receiver operating characteristic analysis was used to test the ability of the NIH-FHV score to identify a significant mismatch. RESULTS: There were 101 patients included in the analysis, of whom 78% had a perfusion deficit detected on PWI with a mean lesion volume of 47 (±59) mL. The NIH-FHV score was strongly associated with the PWI lesion volume (P<0.001; R2=0.32; ß-coefficient, 0.57). When combined with diffusion weighted image lesion volume, receiver operating characteristic analysis testing the ability to detect a mismatch ratio ≥1.8 using the NIH-FHV score resulted in an area under the curve of 0.94. CONCLUSIONS: The NIH-FHV score provides an estimate of the PWI lesion volume and, when combined with diffusion weighted imaging, may be helpful when trying to determine whether there is a clinically relevant diffusion-perfusion mismatch in situations where perfusion imaging is not available. Further studies are needed to validate this approach.

The Importance of Incorporating Stroke Survivors' Health Perceptions in Addressing Health Care Disparities.

Patient-centered research in determining health care disparities among stroke patients is limited. Several studies have examined patient perceptions in stroke survivors and have utilized the Illness Perceptions Questionnaire-Revised (IPQ-R) and Brief Illness Perceptions Questionnaire (BIPQ), which are validated measures of illness beliefs. Yet, there are several domains these surveys could assess that warrant more investigation, including: perception of medication side effects; acceptance of the stroke diagnosis; consequence and long-term impact of symptoms; the importance of medications in long-term health maintenance; and perception of ease of access to equitable health care. Though these surveys are available, representation of diverse and under-represented groups within stroke surveys utilizing them is low. Also, only a limited number of studies of stroke patients' perceptions have focused on health disparities or specifically beliefs and attitudes of under-represented stroke survivors. Due to insufficient current research, future studies should focus on using these patient perception questionnaires with underrepresented populations. Improvements in this field may allow providers to offer patient-centered care among a diverse population, bridging gaps in health care equity.

Apparent Treatment-Resistant Hypertension Among Stroke Survivors: A Transcontinental Study Assessing Impact of Race and Geography.

BACKGROUND: Race and geographic differences in the prevalence and predictors of hypertension in stroke survivors have been reported, but apparent treatment-resistant hypertension (aTRH) among stroke survivors by race (African ancestry vs. non-Hispanic Caucasians) and by geography (continental Africa vs. the United States) are under studied. METHODS: This is a cross-sectional study using ethically approved stroke registries from the University of Florida and the Kwame Nkrumah University of Science and Technology, Kumasi, Ghana. Univariate and multivariate regression was used to evaluate for differences in prevalence of aTRH and associations with clinical covariates. RESULTS: Harmonized data were available for 3,365 stroke survivors of which 943 (28.0%) were indigenous Africans, 558 (16.6%) African Americans, and 1,864 (55.4%) non-Hispanic Caucasians with median ages (interquartile range) of 59 (49-68), 61 (55-72), and 70 (62-78) years, P < 0.0001. The overall frequency of aTRH was 18.5% (95% confidence interval [CI]: 17.2%-19.8%) with 42.7% (95% CI: 39.6%-46.0%) among indigenous Africans, 16.1% (95% CI: 13.2%-19.5%) among African Americans, and 6.9% (95% CI: 5.8%-8.2%) among non-Hispanic Caucasians, P < 0.0001. Five factors associated with aTRH: age, adjusted odds ratio (95% CI) of 0.99 (0.98-0.99), female sex 0.70 (0.56-0.87), cigarette smoking 1.98 (1.36-2.90), intracerebral hemorrhage 1.98 (1.57-2.48), and Black race namely indigenous Africans 4.42 (3.41-5.73) and African Americans 2.44 (1.81-3.29). CONCLUSIONS: Future studies are needed to investigate the contribution of socioeconomic disparities in the prevalence aTRH in those with African Ancestry to explore the long-term impact, and evaluate effective therapeutic interventions in this subpopulation.

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study.

BACKGROUND: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. METHODS: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. RESULTS: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140-720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51-1.73]; P=0.84), death (aHR, 0.78 [95% CI, 0.22-2.76]; P=0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48-1.73]; P=0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15-0.82]; P=0.02). CONCLUSIONS: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies.

Benefits of an interdisciplinary stroke clinic: addressing a gap in physical therapy at post-stroke neurology follow-up.

BACKGROUND AND PURPOSE: An interdisciplinary stroke clinic (ISC) can improve communication and identify people post-stroke who have not reached their full recovery potential. We describe the characteristics of participants who underwent physical therapy (PT) evaluation in addition to their outpatient neurology evaluation and identify the association of assessment scales that predicted referral for additional rehabilitation. METHODS: Participants' post-stroke seen in the ISC were included in the study. The PT evaluation included the Berg Balance Scale (BBS), Ten-Meter Walk Test (10MWT), Six-Minute Walk Test (6MWT), and Short Form-Stroke Impact Scale (SF-SIS). Multivariable logistic regression analysis was performed to identify factors associated with referral for additional rehabilitation. RESULTS: The study consisted of 148 participants with a mean age of 63 (SD ± 15) years; 58% were women and 76% were Whites. Additional rehabilitation was recommended for 59% of participants. In multivariate analysis, reduced speed on comfortable 10MWT (OR = 0.06; 95%CI = 0.01-0.51) and lower SF-SIS score (OR = 0.76; 95%CI = 0.66-0.87) were significantly associated with referral for additional PT or occupational therapy. CONCLUSION: A significant number of post-acute stroke survivors were found to be appropriate for additional rehabilitation when assessed clinically by a neurologic physical therapist in an ISC. The measures that most closely correlated with this in-person clinical evaluation were 10MWT and SF-SIS.IMPLICATIONS FOR REHABILITATIONAn interdisciplinary stroke clinic can improve communication and identify people post-stroke who have not reached their full recovery potential.In a pilot study, a significant number of post-acute stroke survivors were found to be appropriate for additional rehabilitation when assessed clinically by a neurologic physical therapist in an interdisciplinary stroke clinic.Reduced speed on comfortable Ten-Meter Walk Test and lower Short Form-Stroke Impact Scale scores were associated with referral for additional rehabilitation.

Adapting Clinical Practice of Thrombolysis for Acute Ischemic Stroke Beyond 4.5 Hours: A Review of the Literature.

Several clinical trials have demonstrated that advanced neuroimaging can select patients for recanalization therapy in an extended time window. The favorable functional outcomes and safety profile of these studies have led to the incorporation of neuroimaging in endovascular treatment guidelines, and most recently, also extended to decision making on thrombolysis. Two randomized clinical trials have demonstrated that patients who are not amenable to endovascular thrombectomy within 4.5 hours from symptoms discovery or beyond 4.5 hours from the last-known-well time may also be safely treated with intravenous thrombolysis and have a clinical benefit above the risk of safety concerns. With the growing aging population, increased stroke incidence in the young, and the impact of evolving medical practice, healthcare and stroke systems of care need to adapt continuously to provide evidence-based care efficiently. Therefore, understanding and incorporating appropriate screening strategies is critical for the prompt recognition of potentially eligible patients for extended-window intravenous thrombolysis. Here we review the clinical trial evidence for thrombolysis for acute ischemic stroke in the extended time window and provide a review of new enrolling clinical trials that include thrombolysis intervention beyond the 4.5 hour window.

Electric Fence Artifact on Ambulatory EEG and Review of Common EEG Electrical Artifacts.

Ambulatory electroencephalogram (AEEG) can be a cost-effective and valuable alternative to in-patient long-term EEG monitoring. A potential benefit of AEEG is that it allows monitoring in the patient's unique home environment. While this can be more affordable and convenient for the patient, it can also present unique challenges for the reviewer. Unlike long-term monitoring in an epilepsy unit, the AEEG recording occurs in a less controlled environment and most often without immediate EEG technical assistance during the recording. As a result, unique EEG artifacts can occur with AEEG. Their recognition and correct interpretation are crucial for proper EEG analysis. This report presents a case of a patient who underwent a 72-hour AEEG to evaluate symptoms initially concerning for subclinical seizures. During the AEEG recording, the patient had a tactile encounter with an electric fence. This tactile event resulted in a unique, not previously reported, pattern clouding an otherwise normal study. By conducting a brief review of the most common non-physiologic environmental artifacts encountered in modern EEG monitoring, we aim to emphasize the importance of patient education to prevent artifactual pollution. This knowledge can facilitate planning and help avoid environmental influences that may create artifacts when recording in an uncontrolled setting.

Erratum to "Impact of COVID-19 on Future Ischemic Stroke Incidence" [eNeurologicalSci, 22C (2021) 100325].

[This corrects the article DOI: 10.1016/j.ensci.2021.100325.].

Failure of Anticoagulation to Prevent Stroke in Context of Lupus-Associated Anti-Phospholipid Syndrome and Mild COVID-19.

Hypercoagulability and virally-mediated vascular inflammation have become well-recognized features of the SARS-CoV-2 virus infection, COVID-19. Of growing concern is the apparent ineffectiveness of therapeutic anticoagulation in preventing thromboembolic events among some at-risk patient subtypes with COVID-19. We present a 43-year-old female with a history of seropositive-antiphospholipid syndrome and systemic lupus erythematosus who developed an acute ischemic stroke in the setting of mild COVID-19 infection despite adherence to chronic systemic anticoagulation. The clinical significance of SARS-CoV-2-mediated endothelial cell dysfunction and its potential to cause macrovascular events in spite of full anticoagulation warrants further investigation and likely represents another disease-defining pathology of COVID-19.