Frequency of ischaemic stroke and intracranial haemorrhage in patients with reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) - A systematic review.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) may cause ischaemic stroke and intracranial haemorrhage. The aim of our study was to assess the frequency of the afore-mentioned outcomes. METHODS: We performed a PROSPERO-registered (CRD42022355704) systematic review and meta-analysis accessing PubMed until 7 November 2022. The inclusion criteria were: (1) original publication, (2) adult patients (≥18 years), (3) enrolling patients with PRES and/or RCVS, (4) English language and (5) outcome information. Outcomes were frequency of (1) ischaemic stroke and (2) intracranial haemorrhage, divided into subarachnoid haemorrhage (SAH) and intraparenchymal haemorrhage (IPH). The Cochrane Risk of Bias tool was used. RESULTS: We identified 848 studies and included 48 relevant studies after reviewing titles, abstracts and full text. We found 11 studies on RCVS (unselected patients), reporting on 2746 patients. Among the patients analysed, 15.9% (95% CI 9.6%-23.4%) had ischaemic stroke and 22.1% (95% CI 10%-39.6%) had intracranial haemorrhage. A further 20.3% (95% CI 11.2%-31.2%) had SAH and 6.7% (95% CI 3.6%-10.7%) had IPH. Furthermore, we found 28 studies on PRES (unselected patients), reporting on 1385 patients. Among the patients analysed, 11.2% (95% CI 7.9%-15%) had ischaemic stroke and 16.1% (95% CI 12.3%-20.3%) had intracranial haemorrhage. Further, 7% (95% CI 4.7%-9.9%) had SAH and 9.7% (95% CI 5.4%-15%) had IPH. CONCLUSIONS: Intracranial haemorrhage and ischaemic stroke are common outcomes in PRES and RCVS. The frequency reported in the individual studies varied considerably.

Characteristics of acute ischemic stroke and unusual aura in patients with migraine with aura.

BACKGROUND: Sometimes migraine aura changes from attack to attack, raising the question of whether the change is heralding an ischemic stroke or an unusual aura. Differentiating unusual migraine aura from the onset of an acute ischemic stroke in patients with migraine with aura (MwA) can be challenging. OBJECTIVE: The aim of this cohort study was to assess clinical characteristics that help distinguish between MwA and minor stroke in patients with a previous history of MwA who presented with suspicion of stroke. METHODS: We interviewed patients with MwA and ischemic stroke (MwA + IS) and patients with MwA and unusual aura, but without ischemic stroke (MwA - IS) from a tertiary hospital using a structured questionnaire. We assessed how symptoms of ischemic stroke or unusual aura differed from usual, that is, the typical aura in each patient. Stroke or exclusion of stroke was verified by multimodal magnetic resonance imaging. RESULTS: Seventeen patients with MwA + IS and twelve patients with MwA - IS were included. New focal neurological symptoms (13/17 [76%] vs. 3/12 [25%]), change of the first symptom (10/17 [59%] vs. 1/12 [8%]), and absence of headache (6/15 [40%] vs. 2/10 [20%]) were more often reported during ischemic stroke. The physical examination was normal in 8/17 (47%) MwA + IS and in 6/12 (50%) MwA - IS patients. In 5/17 (29%) patients with MwA + IS, there were unequivocal physical signs suggestive of stroke such as persistent visual loss, ataxia, or paresis. CONCLUSION: There are clues from the history that might help identify stroke in patients with MwA with changed aura symptoms. These might be particularly useful in patients presenting without physical findings suggestive of stroke.

Early Versus Late Initiation of Endovascular Therapy in Patients with Severe Cerebral Venous Sinus Thrombosis.

BACKGROUND: Endovascular therapy (EVT) for severe cerebral venous sinus thrombosis (CVST) is controversial in terms of indication and clinical benefit. The impact of delay of EVT on functional recovery is unclear. This study aimed to investigate the effect of early versus late initiation of EVT in severe CVST. METHODS: From prospective EVT and CVST registries, patients with CVST diagnosed between January 2010 and December 2022 were retrospectively identified for this multicenter collaboration. EVT was considered in severe CVST with features prone to a poor prognosis. We compared early (< 24 h) with late (> 24 h) initiation of EVT after the presentation in the emergency department and subsequent CVST diagnosis. Outcome parameters included functional independence (modified Rankin Scale [mRS] score 0-2) at 90 days, mRS score at discharge, in-hospital mortality, and mortality at 3 months. RESULTS: Of 363 patients with CVST, 45 (12.4%; 31 [early EVT] vs. 14 [late EVT]) were included in this study. We found a higher proportion of patients with functional independence at 3 months among early versus late EVT (66.7% vs. 27.3%; odds ratio [OR] 5.3; 95% confidence interval 1.02-25; p = 0.036). In multivariate logistic regression, late EVT was inversely correlated with functional independence (OR 0.17 [0.04-0.83]; p = 0.011). The mortality rate was 16.7% versus 36.4% (mRS 6 at 3 months, OR 0.34, 95% confidence interval 0.07-1.75; p = 0.217) at 90 days for early versus late EVT. CONCLUSIONS: We observed a higher rate of functional independence in patients with early EVT. These preliminary findings must be confirmed in subsequent randomized controlled trials evaluating a "time-is-brain" paradigm for EVT in CVST.

Factors impacting D-dimer levels in patients with acute ischemic cerebrovascular events.

BACKGROUND AND OBJECTIVES: A better understanding of the factors influencing D-dimer levels in code stroke patients is needed to guide further investigations of concomitant thrombotic conditions. This study aimed to investigate the impact of time from symptom onset and other factors on D-dimer levels in patients with acute ischemic stroke (AIS) or transient ischemic attack (TIA). METHODS: Data on consecutive AIS and TIA patients treated at our tertiary-care stroke center between January 2015 and December 2020 were retrospectively assessed. Patients with available D-dimer levels were evaluated for eligibility. Multivariable non-linear regression analyses were performed. RESULTS: In total, 2467 AIS patients and 708 TIA patients were included. The median D-dimer levels differed between the AIS and TIA groups (746 µg/L [interquartile range 381-1468] versus 442 µg/L [interquartile range 244-800], p<0.001). In AIS patients, an early increase in D-dimer levels was demonstrated within the first 6 h (standardized beta coefficient [ß] 0.728; 95% confidence interval [CI] 0.324-1.121). This was followed by an immediate decrease (ß -13.022; 95% CI -20.401 to -5.643) and then by a second, late increase after 35 h (ß 11.750; 95% CI 4.71-18.791). No time-dependent fluctuation in D-dimer levels was observed in TIA patients. CONCLUSION: The time from symptom onset may affect D-dimer levels in patients with AIS but not those with TIA. Further studies confirming these findings and validating time-specific variations are needed to enable D-dimer levels to be used efficiently as an acute stroke and thrombotic risk biomarker.

Mortality in acute ischemic stroke patients with new cancer diagnosed during the index hospitalization versus after discharge.

BACKGROUND: Early diagnosis of previously unknown cancer (i.e., occult cancer) after an acute ischemic stroke (AIS) could result in faster initiation of cancer therapy and potentially improve clinical outcomes. Our study aimed to compare mortality rates between AIS patients with occult cancer diagnosed during the index stroke hospitalization versus those diagnosed after hospital discharge. METHODS: Among consecutive AIS patients treated at our stroke center from 2015 through 2020, we identified new cancer diagnoses made within the year after the AIS. We used multivariable Cox regression analyses to evaluate the association between the timing of occult cancer diagnosis (during the AIS hospitalization versus after discharge) and long-term survival. RESULTS: Of 3894 AIS patients with available long-term follow-up data, 59 (1.5 %) were diagnosed with a new cancer within one year after index stroke. Of these, 27 (46 %) were diagnosed during the index hospitalization and 32 (54 %) were diagnosed after discharge. During a median follow-up of 406 days (interquartile range, 89-1073), 70 % (n = 19) of patients whose cancer was diagnosed during hospitalization had died, compared to 63 % (n = 20) of patients whose cancer was diagnosed after discharge (p= 0.58). In our main multivariable model, there was no difference in long-term mortality between patient groups (adjusted hazard ratio, 1.16; 95 % confidence interval, 0.53-2.52; p= 0.71). CONCLUSIONS: In this analysis, timing of a new cancer diagnosis after AIS did not seem to influence patients' long-term survival. Given the fairly small number of included patients with previously occult cancer, larger multicenter studies are needed to confirm our results.

Alterations of the alpha rhythm in visual snow syndrome: a case-control study.

BACKGROUND: Visual snow syndrome is a disorder characterized by the combination of typical perceptual disturbances. The clinical picture suggests an impairment of visual filtering mechanisms and might involve primary and secondary visual brain areas, as well as higher-order attentional networks. On the level of cortical oscillations, the alpha rhythm is a prominent EEG pattern that is involved in the prioritisation of visual information. It can be regarded as a correlate of inhibitory modulation within the visual network. METHODS: Twenty-one patients with visual snow syndrome were compared to 21 controls matched for age, sex, and migraine. We analysed the resting-state alpha rhythm by identifying the individual alpha peak frequency using a Fast Fourier Transform and then calculating the power spectral density around the individual alpha peak (+/- 1 Hz). We anticipated a reduced power spectral density in the alpha band over the primary visual cortex in participants with visual snow syndrome. RESULTS: There were no significant differences in the power spectral density in the alpha band over the occipital electrodes (O1 and O2), leading to the rejection of our primary hypothesis. However, the power spectral density in the alpha band was significantly reduced over temporal and parietal electrodes. There was also a trend towards increased individual alpha peak frequency in the subgroup of participants without comorbid migraine. CONCLUSIONS: Our main finding was a decreased power spectral density in the alpha band over parietal and temporal brain regions corresponding to areas of the secondary visual cortex. These findings complement previous functional and structural imaging data at a electrophysiological level. They underscore the involvement of higher-order visual brain areas, and potentially reflect a disturbance in inhibitory top-down modulation. The alpha rhythm alterations might represent a novel target for specific neuromodulation. TRIAL REGISTRATION: we preregistered the study before preprocessing and data analysis on the platform osf.org (DOI: https://doi.org/10.17605/OSF.IO/XPQHF , date of registration: November 19th 2022).

Management of Cerebral Venous Thrombosis Due to Adenoviral COVID-19 Vaccination.

OBJECTIVE: Cerebral venous thrombosis (CVT) caused by vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare adverse effect of adenovirus-based severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) vaccines. In March 2021, after autoimmune pathogenesis of VITT was discovered, treatment recommendations were developed. These comprised immunomodulation, non-heparin anticoagulants, and avoidance of platelet transfusion. The aim of this study was to evaluate adherence to these recommendations and its association with mortality. METHODS: We used data from an international prospective registry of patients with CVT after the adenovirus-based SARS-CoV-2 vaccination. We analyzed possible, probable, or definite VITT-CVT cases included until January 18, 2022. Immunomodulation entailed administration of intravenous immunoglobulins and/or plasmapheresis. RESULTS: Ninety-nine patients with VITT-CVT from 71 hospitals in 17 countries were analyzed. Five of 38 (13%), 11 of 24 (46%), and 28 of 37 (76%) of the patients diagnosed in March, April, and from May onward, respectively, were treated in-line with VITT recommendations (p < 0.001). Overall, treatment according to recommendations had no statistically significant influence on mortality (14/44 [32%] vs 29/55 [52%], adjusted odds ratio [OR] = 0.43, 95% confidence interval [CI] = 0.16-1.19). However, patients who received immunomodulation had lower mortality (19/65 [29%] vs 24/34 [70%], adjusted OR = 0.19, 95% CI = 0.06-0.58). Treatment with non-heparin anticoagulants instead of heparins was not associated with lower mortality (17/51 [33%] vs 13/35 [37%], adjusted OR = 0.70, 95% CI = 0.24-2.04). Mortality was also not significantly influenced by platelet transfusion (17/27 [63%] vs 26/72 [36%], adjusted OR = 2.19, 95% CI = 0.74-6.54). CONCLUSIONS: In patients with VITT-CVT, adherence to VITT treatment recommendations improved over time. Immunomodulation seems crucial for reducing mortality of VITT-CVT. ANN NEUROL 2022;92:562-573.

The "index vein" as a sign for migraine aura in the emergency setting.

Background and objectives To assess the usefulness of the "index vein" for making the diagnosis of migraine aura.Methods 400 patients were included when they: i) presented with an acute neurological deficit, ii) had a brain MRI, and iii) had a discharge diagnosis of migraine aura, ischemic stroke, epileptic seizure or controls (n = 100 per group).Results Compared to stroke (2%), epileptic seizure (4%) and controls (1%), the index vein is more prevalent in migraine aura (17%, p < 0.001). The index vein is highly specific for migraine aura (specificity 97%, 95% CI 95-99). The index vein has a positive predictive value for the diagnosis of migraine aura of 70% (95%CI 48-87). The index vein-score has the ability to diagnose migraine aura with a sensitivity of 94% (95%CI 87.4-97.8) and specificity of 73.5% (95%CI 66.8-79.5) at a cut-off of 4 points.Discussion The index vein serves as a good biomarker for migraine aura in the emergency setting.

A scoring tool to predict mortality and dependency after cerebral venous thrombosis.

BACKGROUND AND PURPOSE: A prognostic score was developed to predict dependency and death after cerebral venous thrombosis (CVT) to identify patients for targeted therapy in future clinical trials. METHODS: Data from the International CVT Consortium were used. Patients with pre-existent functional dependency were excluded. Logistic regression was used to predict poor outcome (modified Rankin Scale score 3-6) at 6 months and Cox regression to predict 30-day and 1-year all-cause mortality. Potential predictors derived from previous studies were selected with backward stepwise selection. Coefficients were shrunk using ridge regression to adjust for optimism in internal validation. RESULTS: Of 1454 patients with CVT, the cumulative number of deaths was 44 (3%) and 70 (5%) for 30 days and 1 year, respectively. Of 1126 patients evaluated regarding functional outcome, 137 (12%) were dependent or dead at 6 months. From the retained predictors for both models, the SI2 NCAL2 C score was derived utilizing the following components: absence of female-sex-specific risk factor, intracerebral hemorrhage, infection of the central nervous system, neurological focal deficits, coma, age, lower level of hemoglobin (g/l), higher level of glucose (mmol/l) at admission, and cancer. C-statistics were 0.80 (95% confidence interval [CI] 0.75-0.84), 0.84 (95% CI 0.80-0.88) and 0.84 (95% CI 0.80-0.88) for the poor outcome, 30-day and 1-year mortality model, respectively. Calibration plots indicated a good model fit between predicted and observed values. The SI2 NCAL2 C score calculator is freely available at www.cerebralvenousthrombosis.com. CONCLUSIONS: The SI2 NCAL2 C score shows adequate performance for estimating individual risk of mortality and dependency after CVT but external validation of the score is warranted.

Decompressive surgery in cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia.

BACKGROUND AND PURPOSE: Cerebral venous sinus thrombosis due to vaccine-induced immune thrombotic thrombocytopenia (CVST-VITT) is an adverse drug reaction occurring after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. CVST-VITT patients often present with large intracerebral haemorrhages and a high proportion undergoes decompressive surgery. Clinical characteristics, therapeutic management and outcomes of CVST-VITT patients who underwent decompressive surgery are described and predictors of in-hospital mortality in these patients are explored. METHODS: Data from an ongoing international registry of patients who developed CVST within 28 days of SARS-CoV-2 vaccination, reported between 29 March 2021 and 10 May 2022, were used. Definite, probable and possible VITT cases, as defined by Pavord et al. (N Engl J Med 2021; 385: 1680-1689), were included. RESULTS: Decompressive surgery was performed in 34/128 (27%) patients with CVST-VITT. In-hospital mortality was 22/34 (65%) in the surgical and 27/94 (29%) in the non-surgical group (p < 0.001). In all surgical cases, the cause of death was brain herniation. The highest mortality rates were found amongst patients with preoperative coma (17/18, 94% vs. 4/14, 29% in the non-comatose; p < 0.001) and bilaterally absent pupillary reflexes (7/7, 100% vs. 6/9, 67% with unilaterally reactive pupil, and 4/11, 36% with bilaterally reactive pupils; p = 0.023). Postoperative imaging revealed worsening of index haemorrhagic lesion in 19 (70%) patients and new haemorrhagic lesions in 16 (59%) patients. At a median follow-up of 6 months, 8/10 of surgical CVST-VITT who survived admission were functionally independent. CONCLUSIONS: Almost two-thirds of surgical CVST-VITT patients died during hospital admission. Preoperative coma and bilateral absence of pupillary responses were associated with higher mortality rates. Survivors often achieved functional independence.

Symptomatic visual snow in acute ischemic stroke: A case series.

Visual snow is the main symptom of visual snow syndrome, a disorder of predominantly visual disturbances initially described in patients without abnormalities on ancillary investigations. We present a case series of patients with visual snow in the setting of acute ischemic stroke. The first and second patient reported previous episodic visual snow with migraine attacks. The third patient experienced visual snow for the first time during the ischemic stroke. In the first patient, the ischemic stroke affected the right and left precuneus and the right lingual gyrus. In the second patient, the ischemic stroke was located in the left lingual gyrus, parts of the left fusiform and parahippocampal gyrus, left dorso-lateral thalamus, and left cerebellar hemisphere. In the third patient, occipital pole, trunk of the corpus callosum on the right, right paramedian pons, right cerebellar hemisphere, and vermis were affected. Our case series indicates that the symptom visual snow can be caused by vascular lesions in areas of visual processing. Because patients did not meet criteria for visual snow syndrome, dysfunction in the affected areas might only explain part of the complex pathophysiology of visual snow syndrome.

Changes of migraine aura with advancing age of patients.

AIM: Given the similar presentation of migraine aura and acute ischemic stroke, advancing patient age might change the characteristics of migraine with aura (MA) and be clinically important. Clinical data, however, are limited. Experimental studies indicate a decrease in the magnitude of cortical spreading depression (CSD), the pathophysiological correlate of migraine aura, with advancing age. Our study aimed to assess the influence of age on the clinical features of MA. METHODS: Three hundred and forty-three patients were interviewed using a structured questionnaire. The questions covered the headache characteristics and symptom types including the characteristics of the C-criterion, as defined by the International Classification of Headache Disorders 3rd Edition. The association of age with MA characteristics was assessed. RESULTS: The median age was 29 (IQR 28-52) and 235 of the 343 patients were women (69%). Individual symptoms of the C-criterion such as gradual aura spreading over longer than 5 min (P < 0.001), two or more aura symptoms occurring in succession (P = 0.005), duration of at least one MA symptom for longer than 60 min (P = 0.004), and associated headache (P = 0.01) were more frequent in younger patients. The number of symptoms including the C-characteristics decreased with increasing age (P < 0.001). Patients with sensory (P < 0.001), motor (P = 0.004) and speech disturbance (P = 0.02) were younger, and older patients with headache had less photophobia (P = 0.04) and phonophobia (P = 0.03). Sensitivity analyses yielded similar results. CONCLUSION: The frequency of typical characteristics of migraine aura and migraine headache including photophobia and phonophobia decreases with advancing patient age. This might have potentially difficult implications for the diagnosis of MA in the elderly.

Outcomes of Cerebral Venous Thrombosis due to Vaccine-Induced Immune Thrombotic Thrombocytopenia After the Acute Phase.

BACKGROUND: Cerebral venous thrombosis (CVT) due to vaccine-induced immune thrombotic thrombocytopenia (VITT) is a severe condition, with high in-hospital mortality rates. Here, we report clinical outcomes of patients with CVT-VITT after SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) vaccination who survived initial hospitalization. METHODS: We used data from an international registry of patients who developed CVT within 28 days of SARS-CoV-2 vaccination, collected until February 10, 2022. VITT diagnosis was classified based on the Pavord criteria. Outcomes were mortality, functional independence (modified Rankin Scale score 0-2), VITT relapse, new thrombosis, and bleeding events (all after discharge from initial hospitalization). RESULTS: Of 107 CVT-VITT cases, 43 (40%) died during initial hospitalization. Of the remaining 64 patients, follow-up data were available for 60 (94%) patients (37 definite VITT, 9 probable VITT, and 14 possible VITT). Median age was 40 years and 45/60 (75%) patients were women. Median follow-up time was 150 days (interquartile range, 94-194). Two patients died during follow-up (3% [95% CI, 1%-11%). Functional independence was achieved by 53/60 (88% [95% CI, 78%-94%]) patients. No new venous or arterial thrombotic events were reported. One patient developed a major bleeding during follow-up (fatal intracerebral bleed). CONCLUSIONS: In contrast to the high mortality of CVT-VITT in the acute phase, mortality among patients who survived the initial hospitalization was low, new thrombotic events did not occur, and bleeding events were rare. Approximately 9 out of 10 CVT-VITT patients who survived the acute phase were functionally independent at follow-up.

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.

Migraine and atrial fibrillation: a systematic review.

BACKGROUND AND PURPOSE: Patients with migraine are at increased risk of stroke. The aim was to systematically review the current literature on the association between migraine and atrial fibrillation, which is a relevant risk factor for stroke. METHODS: PubMed was searched for 'migraine' AND 'atrial fibrillation' and selected original investigations on the association of migraine and atrial fibrillation for our analysis. Articles without original data, such as guidelines, narrative reviews, editorials and others, were excluded. RESULTS: In all, 109 publications were found. Twenty-two were included and analysed for this review. The population-based Atherosclerosis Risk in Communities study showed a significant association of migraine with visual aura and incident atrial fibrillation (hazard ratio 1.30, 95% confidence interval 1.03-1.62, p = 0.02), but not for migraine without aura, compared to non-headache persons after multivariable adjustment for vascular risk factors. An even larger population-based study in Denmark confirmed this association (odds ratio 1.25, 95% confidence interval 1.16-1.36). Studies investigating patients with ischaemic stroke and migraine are methodologically insufficient and provide contradictory results. Ablation therapy for atrial fibrillation in patients with migraine might reduce migraine attacks, but transient post-ablation new-onset migraine-like headaches in persons without a history of migraine have also been reported. CONCLUSION: Population-based studies indicate a significant association of migraine with aura and atrial fibrillation. In practical terms, screening for atrial fibrillation in patients who have a long history of migraine might be reasonable, whereas in patients with stroke or other disorders and migraine extensive screening for atrial fibrillation should be performed as in all patients without migraine.

Development of a Score for Prediction of Occult Malignancy in Stroke Patients (Occult-5 Score).

BACKGROUND AND PURPOSE: Malignancy associated acute ischemic stroke (AIS) requires specific diagnostic work-up, treatment and prevention to improve outcome. This study aimed to develop a biomarker-based score for prediction of occult malignancy in AIS patients. METHODS: Single-center cross-sectional study including consecutive AIS patients treated between July 2017 and November 2018. Patients with active malignancy at presentation, or diagnosed within 1 year thereafter and patients free of malignancy, were included and malignancy associated biomarkers were assessed. LASSO analyses of logistic regression were performed to determine biomarkers predictive of active malignancy. Predictors were derived from a predictive model for active malignancy. A comparison between known and unknown (=occult) malignancies when the index stroke occurred was used to eliminate variables not associated with occult malignancy. A predictive score (OCCULT-5 score) for occult malignancy was developed based on the remaining variables. RESULTS: From 1001 AIS patients, 61 (6%) presented an active malignancy. Thirty-nine (64%) were known and 22 (36%) occult. Five variables were included in the final OCCULT-5 score: age ≥ 77 years, embolic stroke of undetermined source, multi-territorial infarcts, D-dimer levels ≥ 820 µ/gL, and female sex. A score of ≥ 3 predicted an underlying occult malignancy with a sensitivity of 64%, specificity of 73%, positive likelihood ratio of 2.35 and a negative likelihood ratio of 0.50. CONCLUSIONS: The OCCULT-5 score might be useful to identify patients with occult malignancy. It may thus contribute to a more effective and timely treatment and thus lead to a positive impact on overall outcome.

Frequency of Thrombocytopenia and Platelet Factor 4/Heparin Antibodies in Patients With Cerebral Venous Sinus Thrombosis Prior to the COVID-19 Pandemic.

Importance: Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism. Objective: To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4/heparin antibodies in patients diagnosed with cerebral venous sinus thrombosis prior to the COVID-19 pandemic. Design, Setting, and Participants: This was a descriptive analysis of a retrospective sample of consecutive patients diagnosed with cerebral venous sinus thrombosis between January 1987 and March 2018 from 7 hospitals participating in the International Cerebral Venous Sinus Thrombosis Consortium from Finland, the Netherlands, Switzerland, Sweden, Mexico, Iran, and Costa Rica. Of 952 patients, 865 with available baseline platelet count were included. In a subset of 93 patients, frozen plasma samples collected during a previous study between September 2009 and February 2016 were analyzed for the presence of platelet factor 4/heparin antibodies. Exposures: Diagnosis of cerebral venous sinus thrombosis. Main Outcomes and Measures: Frequencies of admission thrombocytopenia (platelet count <150 ×103/µL), heparin-induced thrombocytopenia (as diagnosed by the treating physician), and platelet factor 4/heparin IgG antibodies (optical density >0.4, in a subset of patients with previously collected plasma samples). Results: Of 865 patients (median age, 40 years [interquartile range, 29-53 years], 70% women), 73 (8.4%; 95% CI, 6.8%-10.5%) had thrombocytopenia, which was mild (100-149 ×103/µL) in 52 (6.0%), moderate (50-99 ×103/µL) in 17 (2.0%), and severe (<50 ×103/µL) in 4 (0.5%). Heparin-induced thrombocytopenia with platelet factor 4/heparin antibodies was diagnosed in a single patient (0.1%; 95% CI, <0.1%-0.7%). Of the convenience sample of 93 patients with cerebral venous sinus thrombosis included in the laboratory analysis, 8 (9%) had thrombocytopenia, and none (95% CI, 0%-4%) had platelet factor 4/heparin antibodies. Conclusions and Relevance: In patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopenia was uncommon, and heparin-induced thrombocytopenia and platelet factor 4/heparin antibodies were rare. These findings may inform investigations of the possible association between the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines and cerebral venous sinus thrombosis with thrombocytopenia.

[Primary and Secondary Stroke Prevention: Physical Activity]. / Primär- und Sekundärprävention des Hirnschlags: Körperliche Aktivität.

Primary and Secondary Stroke Prevention: Physical Activity Abstract. The evidence of positive effects of physical activity in primary and secondary stroke prevention has steadily increased in the last years. It is established that physical activity on a regular basis has a positive influence on the majority of vascular risk factors (e. g. on obesity, arterial hypertension, atrial fibrillation and so on). After a stroke, one of the main challenges is reducing the risk of a recurrent event and its possible consequences. Other important challenges are improving impaired brain functions, quality of life and independence in the activity of daily living as well as reintegration into the community [1]. Stroke-induced impairment of brain function has, besides its effects on motor, sensory, visual and speech functions, an influence on cognition and mood, which are determinants of physical activity after stroke [2]. Type, intensity and amount of physical activity have to be adjusted according to comorbidities and, if present, to residual neurologic impairments after a stroke.