Cerebral Amyloid Angiopathy-Related Inflammation and Biopsy-Positive Primary Angiitis of the CNS: A Comparative Study.

BACKGROUND AND OBJECTIVES: Cerebral amyloid angiopathy-related inflammation (CAA-RI) and biopsy-positive primary angiitis of the CNS (BP-PACNS) have overlapping clinicoradiologic presentations. It is unknown whether clinical and radiologic features can differentiate CAA-RI from BP-PACNS and whether both diseases have different relapse rates. The objectives of this study were to compare clinicoradiologic presentations and relapse rates in patients with CAA-RI vs BP-PACNS. METHODS: Patients with CAA-RI and BP-PACNS were enrolled from 2 retrospective multicenter cohorts. Patients with CAA-RI were biopsy-positive or met probable clinicoradiologic criteria. Patients with BP-PACNS had histopathologic confirmation of CNS angiitis, with no secondary etiology. A neuroradiologist read brain MRIs, blinded to the diagnosis of CAA-RI or BP-PACNS. Clinicoradiologic features were compared using univariable logistic regression models. Relapse rates were compared using a univariable Fine-Gray subdistribution hazard model, with death as a competing risk. RESULTS: This study enrolled 104 patients with CAA-RI (mean age 73 years, 48% female sex) and 52 patients with BP-PACNS (mean age 45 years, 48% female sex). Patients with CAA-RI more often had white matter hyperintense lesions meeting the probable CAA-RI criteria (93% vs 51%, p < 0.001), acute subarachnoid hemorrhage (15% vs 2%, p = 0.02), cortical superficial siderosis (27% vs 4%, p < 0.001), ≥1 lobar microbleed (94% vs 26%, p < 0.001), past intracerebral hemorrhage (17% vs 4%, p = 0.04), ≥21 visible centrum semiovale perivascular spaces (34% vs 4%, p < 0.01), and leptomeningeal enhancement (70% vs 27%, p < 0.001). Patients with BP-PACNS more often had headaches (56% vs 31%, p < 0.01), motor deficits (56% vs 36%, p = 0.02), and nonischemic parenchymal gadolinium enhancement (82% vs 16%, p < 0.001). The prevalence of acute ischemic lesions was 18% in CAA-RI and 22% in BP-PACNS (p = 0.57). The features with the highest specificity for CAA-RI were acute subarachnoid hemorrhage (98%), cortical superficial siderosis (96%), past intracerebral hemorrhage (96%), and ≥21 visible centrum semiovale perivascular spaces (96%). The probable CAA-RI criteria had a 71% sensitivity (95% CI 44%-90%) and 91% specificity (95% CI 79%-98%) in differentiating biopsy-positive CAA-RI from BP-PACNS. The rate of relapse in the first 2 years after remission was lower in CAA-RI than in BP-PACNS (hazard ratio 0.46, 95% CI 0.22-0.96, p = 0.04). CONCLUSION: Clinicoradiologic features differed between patients with CAA-RI and those with BP-PACNS. Specific markers for CAA-RI were hemorrhagic signs of subarachnoid involvement, past intracerebral hemorrhage, ≥21 visible centrum semiovale perivascular spaces, and the probable CAA-RI criteria. A biopsy remains necessary for diagnosis in some cases of CAA-RI. The rate of relapse in the first 2 years after disease remission was lower in CAA-RI than in BP-PACNS.

Clinical imaging factors of excellent outcome after thrombolysis in large-vessel stroke: a THRACE subgroup analysis.

BACKGROUND: For patients with stroke with large-vessel occlusion (LVO), study of factors predicting response to intravenous thrombolysis (IVT) would allow identifying subgroups with high expected gain, and those for whom it could be considered as futile, and even detrimental. From patients included in the Mechanical Thrombectomy After Intravenous Alteplase vs Alteplase Alone After Stroke trial, we investigated clinical-imaging factors associated with optimal response to IVT. METHODS: We included patients receiving IVT alone. Excellent outcome was defined by a 3-month modified Rankin Scale (mRS) score ≤1. Clinical-imaging predictors were assessed on multivariate analysis after multiple imputations. The predictive performance of the model was assessed with the C-statistic. RESULTS: Among 247 patients with LVO treated with IVT alone, 77 (31%) showed 3-month mRS ≤1. Predictors of 3-month mRS ≤1 were no medical history of hypertension (OR 2.43; 95% CI 1.74 to 3.38; p=0.007); no current smoking (OR 2.76; 95% CI 1.79 to 4.26; p=0.02); onset-to-IVT time (OR 0.47 per hour increase; 95% CI 0.23 to 0.78; p=0.003); diffusion-weighted imaging (DWI) volume (OR 0.78 per 10 mL increase; 95% CI 0.68 to 0.89; p=0.0004); presence of susceptibility vessel sign (SVS) (OR 7.89; 95% CI 1.65 to 37.78; p=0.01) and SVS length (OR 0.87 per mm increase; 95% CI 0.80 to 0.94; p=0.001). The prediction models showed a C-statistic=0.79 (95% CI 0.79 to 0.80). CONCLUSIONS: In patients with stroke with anterior-circulation LVO treated with IVT alone, predictors of excellent outcome at 3 months were no medical history of hypertension or current smoking, reduced onset-to-IVT time, small DWI volume, presence of SVS and short SVS length. These predictive factors could help practitioners in decision-making for IVT implementation in reperfusion strategies, all the more for the drip and ship paradigm. TRIAL REGISTRATION NUMBER: NCT01062698.

Outcome of patients with large vessel occlusion stroke after first admission in telestroke spoke versus comprehensive stroke center.

INTRODUCTION: While telestroke allows early intravenous thrombolysis (IVT) for ischemic strokes in spoke centers, mechanical thrombectomy (MT) for large vessel occlusion (LVO) is mainly performed at comprehensive stroke centers (CSCs). We aimed to compare 3 month outcome in patients with LVO after admission to a spoke center using telestroke compared with first CSC admission in our large regional stroke network, irrespective of final treatment decision. METHODS: All consecutive LVO patients who were admitted to one of six spoke centers or to the regional CSC within 6 hours of symptom onset were prospectively included from September 1, 2015 to August 31, 2017. All patients admitted to spoke centers were assessed on site with cerebral and vessel imaging. Primary outcome was 3 month favorable outcome (modified Rankin Scale score of 0-2). RESULTS: Distances between spoke centers and CSC ranged from 36 to 77 miles. Among 207 included patients, 132 (63.8%) were first admitted to CSCs and 75 (36.2%) to spoke centers. IVT was administered more in spoke centers (81.3% vs 53.8%, p<0.0001) while MT was performed less (26.7% vs 49.2%, p=0.001) and with a longer time from onset (303 vs 200 min, p<0.0001). No difference was found in 3 month favorable outcome between spoke centers compared with CSCs (32.0% and 35.1%, respectively; OR=0.68; 95% CI 0.42 to 1.10; p=0.12). CONCLUSIONS: Despite different distribution of reperfusion therapies for LVO patients managed by telemedicine, we could not demonstrate a difference in functional outcome according to admission location in a large area with long distances between centers.

Mothership versus drip and ship for thrombectomy in patients who had an acute stroke: a systematic review and meta-analysis.

BACKGROUND: The effectiveness of mechanical thrombectomy (MT) in acute ischemic stroke due to large vessel occlusion is time-dependent. While only stroke centers with endovascular capabilities perform MT, many patients who had a stroke initially present to the closest primary stroke centers capable of administering earlier intravenous thrombolysis, and then require to be transferred to a comprehensive stroke center for MT. PURPOSE: To compare the outcomes of this care pathway (drip and ship (DS)) with that whereby patients are directly transferred to a comprehensive stroke center (mothership (MS)). METHODS: We performed a systematic review and meta-analysis of published studies using several electronic databases to determine whether successful reperfusion (modified Thrombolysis In Cerebral Infarction ≥2b), functional independence at 90 days (modified Rankin Scale score ≤2), symptomatic intracranial hemorrhage, and 90-day mortality differed between those who underwent MT with the DS or the MS treatment pathway. Outcomes were meta-analyzed and the results expressed as adjusted relative risk (aRR) for the primary analysis and unadjusted relative risk (uRR) for secondary analysis. RESULTS: Eight studies including 2068 patients were selected, including one study reporting results fully adjusted for baseline characteristics. Patients undergoing MS had better functional independence than those undergoing DS (uRR=0.87, 95% CI 0.81 to 0.93; aRR=0.87, 95% CI 0.77 to 0.98). No difference was found between the treatment pathways in successful reperfusion (uRR=1.05, 95% CI 0.95 to 1.15; aRR=1.00, 95% CI 0.92 to 1.10), symptomatic intracranial hemorrhage (uRR=1.37, 95% CI 0.91 to 2.06; aRR, 1.53, 95% CI 0.79 to 2.98), and 90-day mortality (uRR=1.00, 95% CI 0.84 to 1.19; aRR=1.21, 95% CI 0.89 to 1.64). CONCLUSIONS: Patients who had an acute ischemic stroke admitted directly to a comprehensive stroke center (MS patients) with endovascular capacities may have better 90-day outcomes than those receiving DS treatment. However, major limitations of current evidence (ie, retrospective studies and selection bias) suggest a need for adequately powered studies. Multicenter randomized controlled trials are expected to answer this question.

Cerebral ischemic events in patients with pancreatic cancer: A retrospective cohort study of 17 patients and a literature review.

Stroke is a dramatic complication of pancreatic cancer with mechanisms related to oncological disease. A better description of the characteristics of cerebrovascular events would help better understand the pathogeny and protect vulnerable patients. We thus conducted a descriptive analysis of clinical, biological, and radiological features of patients from our centers and literature.We reviewed consecutive cases of patients who presented cerebrovascular events and pancreatic cancer in 4 stroke units in Lorrain (France) between January 1, 2009 and March 31, 2015, and all reported cases of literature. We identified 17 cases in our centers and 18 reported cases. Fifty-seven per cent of patients were male. Median age was 63 ±â€Š14 years and ranged from 23 to 81 years. All cerebral events were ischemic. At the onset of stroke, pancreatic cancer had already been diagnosed in 59% of the patients in our centers for a mean time of 5.4 months. Five of them (29%) were being treated with gemcitabine and 2 (12%) with folfirinox. Adenocarcinoma at metastatic stage was reported in 82% of cases overall. Brain imaging revealed disseminated infarctions in 64%. High median levels of D-dimer (7600 ±â€Š5 × 10 µg/L), C-reactive protein (63 ±â€Š43 mg/L), and elevated prothrombin time (19 ±â€Š6 seconds) were found. Thirty-six per cent of patients explored with echocardiography were diagnosed with nonbacterial thrombotic endocarditis. Ten of our patients received anticoagulant therapy as secondary stroke prevention without any documented recurrence. Nevertheless, outcome was poor with a median survival time of 28 ±â€Š14 days after stroke onset. Cerebral ischemic events occur at advanced stages of pancreatic cancer, most likely by a thromboembolic mechanism. Disseminated infarctions and high D-dimer, C-reactive protein levels, and a high prothrombin time are the most constant characteristics found in this context. All patients should be screened for nonbacterial thrombotic endocarditis as this etiology supports the use of anticoagulant therapy.

Syringomyelia Caused by Traumatic Intracranial Hypotension: Case Report and Literature Review.

BACKGROUND: Syringomyelia due to intracranial hypotension is rarely described. As a consequence, intracranial hypotension is less recognized as a potential cause of syringomyelia or mistaken with Chiari type 1 malformation. The pathogeny is poorly understood, and we lack diagnostic and therapeutic strategies for this particular setting. CASE DESCRIPTION: We describe a 45-year-old patient who developed syringomyelia after about 10 years of undiagnosed intracranial hypotension caused by traumatic C6 cerebrospinal fluid (CSF) leak. Surgical closing of the leak was required to treat intracranial hypotension after failure of conservative measures and blind epidural patches. It led to a marked improvement of cerebral and spinal signs. We discuss the pathogeny of syringomyelia caused by intracranial hypotension and highlight a mechanical theory of hyperpressure against the cervical spine due to blockage of CSF flow by descent of cerebellar tonsils at the foramen magnum level. We describe discriminating clinical and radiologic signs to differentiate intracranial hypotension from Chiari type 1 malformation and discuss mechanisms and causality relating trauma and intracranial hypotension. CONCLUSIONS: Syringomyelia can be a consequence of long-term progression of intracranial hypotension, which must be differentiated from Chiari type 1 malformation. In our case, resolution was achieved by detecting and closing the CSF leak causing the intracranial hypotension. Reports of similar cases are necessary to understand the origin of CSF leak in traumatic intracranial hypotension and assess the best therapeutic strategy.

Perioperative Bioccipital Watershed Strokes in Bilateral Fetal Posterior Cerebral Arteries During Spinal Surgery.

BACKGROUND: Vision loss due to cerebral infarction during spinal surgery is less described. Intraoperative hypotension would be a leading cause. Patients with variation of the circle of Willis could be more prone to present stroke in this context, but reports are lacking to sustain the theory. Bilateral occipital watershed ischemic strokes have never been described before. We report the case of a patient with a fetal origin of both posterior cerebral arteries (PCAs), presenting this particular anatomic stroke following lumbar laminectomy surgery for spinal stenosis during which intraoperative hypotension was observed. We discuss how this common anomaly associated with intraoperative hypotension could have promoted this serious complication. CASE DESCRIPTION: A 55-year-old man woke up with cortical blindness after he had undergone lumbar surgery during which a marked decrease in blood pressure had occurred. Magnetic resonance imaging revealed bilateral symmetric infarctions of the occipital lobes in the distal territory of both PCAs and smaller anterior watershed ischemic strokes, suggesting a hemodynamic mechanism. Extended investigations, including conventional angiography, failed to find any cause of stroke but revealed bilateral fetal PCAs supplied by internal carotid arteries only. Two years later, the patient has not recovered and remains severely visually impaired. CONCLUSIONS: The standing hypothesis would be posterior low-flow infarctions resulting from intraoperative hypotension on a variation of the circle of Willis more prone to decrease in cerebral blood flow. Moreover, this case supports the hypothesis of vascular insufficiency due to intraoperative hypotension as cause of stroke during spinal surgery.

Predictive factors of brain death in severe stroke patients identified by organ procurement and transplant coordination in Lorrain, France.

There are no established predictive factors to identify patients at the acute phase of severe stroke with a high probability of presenting brain death (BD). We retrospectively collected clinical and paraclinical data of consecutive patients at the acute phase of severe stroke with a potential progression to BD through the hospital organ procurement and transplant coordination system in five centres in Lorrain (France) between 1 January 2012 and 31 December 2013. Final endpoint was adjudicated BD. Of 400 included patients, 91 (23%) presented adjudicated BD. Initial Glasgow Coma Scale score ≤6 (P = 0.008), herniation (P = 0.009), hydrocephalus (P = 0.019), initial systolic blood pressure >150 mmHg (P = 0.002), past history of alcohol abuse (P = 0.019) and stroke volume >65 ml (P = 0.040) were significantly associated with BD progression. Two prognostic scores for stroke with unquantifiable or quantifiable volume were built according to the number of risk factors presented. Following internal validation, the respective bias-corrected predictive performance (c-index) of the two scores was 72% (95% confidence interval: 67-78%) and 77% (95% confidence interval: 72-82%). These scores could form the basis of a simple tool of six criteria to help physicians make the difficult decision of intensive care unit management to preserve organs in potential donors.