Carotid plaque surface echogenicity predicts cerebrovascular events: An Echographic Multicentric Swiss Study.

BACKGROUND AND PURPOSE: To determine the prognostic value for ischemic stroke or transitory ischemic attack (TIA) of plaque surface echogenicity alone or combined to degree of stenosis in a Swiss multicenter cohort METHODS: Patients with ≥60% asymptomatic or ≥50% symptomatic carotid stenosis were included. Grey-scale based colour mapping was obtained of the whole plaque and of its surface defined as the regions between the lumen and respectively 0-0.5, 0-1, 0-1.5, and 0-2 mm of the outer border of the plaque. Red, yellow and green colour represented low, intermediate or high echogenicity. Proportion of red color on surface (PRCS) reflecting low echogenictiy was considered alone or combined to degree of stenosis (Risk index, RI). RESULTS: We included 205 asymptomatic and 54 symptomatic patients. During follow-up (median/mean 24/27.7 months) 27 patients experienced stroke or TIA. In the asymptomatic group, RI ≥0.25 and PRCS ≥79% predicted stroke or TIA with a hazard ratio (HR) of respectively 8.7 p = 0.0001 and 10.2 p < 0.0001. In the symptomatic group RI ≥0.25 and PRCS ≥81% predicted stroke or TIA occurrence with a HR of respectively 6.1 p = 0.006 and 8.9 p = 0.001. The best surface parameter was located at 0-0.5mm. Among variables including age, sex, degree of stenosis, stenosis progression, RI, PRCS, grey median scale values and clinical baseline status, only PRCS independently prognosticated stroke (p = 0.005). CONCLUSION: In this pilot study including patients with at least moderate degree of carotid stenosis, PRCS (0-0.5mm) alone or combined to degree of stenosis strongly predicted occurrence of subsequent cerebrovascular events.

Brain functional connectivity during the first day of coma reflects long-term outcome.

OBJECTIVE: In patients with disorders of consciousness (DOC), properties of functional brain networks at rest are informative of the degree of consciousness impairment and of long-term outcome. Here we investigate whether connectivity differences between patients with favorable and unfavorable outcome are already present within 24 h of coma onset. METHODS: We prospectively recorded 63-channel electroencephalography (EEG) at rest during the first day of coma after cardiac arrest. We analyzed 98 adults, of whom 57 survived beyond unresponsive wakefulness. Functional connectivity was estimated by computing the 'debiased weighted phase lag index' over epochs of five seconds duration. We evaluated the network's topological features, including clustering coefficient, path length, modularity and participation coefficient and computed their variance over time. Finally, we estimated the predictive value of these topological features for patients' outcomes by splitting the patient sample in training and test datasets. RESULTS: Group-level analysis revealed lower clustering coefficient, higher modularity and path length variance in patients with favorable compared to those with unfavorable outcomes (p < 0.01). Within all features, the path length variance in the network provided the best positive predictive value (PPV) for favorable outcome and specificity for unfavorable outcome in the test dataset (PPV: 0.83, p < 0.01; specificity: 0.86, p < 0.01) with above-chance negative predictive value and accuracy. Of note, the exclusion of patients with epileptiform activity (20 in total) eliminates all false positive predictions (n = 6) for path length variance. INTERPRETATION: Topological features of functional connectivity differ as a function of long-term outcome in patients on the first day of coma. These differences are not interpretable in terms of consciousness levels as all patients were in a deep unconscious state. The time variance of path length is informative of comatose patients' outcome, as patients with favorable outcome exhibit a richer repertoire of path length than those with unfavorable outcomes.

Stent Retriever Thrombectomy with Mindframe Capture LP in Isolated M2 Occlusions.

BACKGROUND AND PURPOSE: Mechanical thrombectomy is an effective recanalization technique in acute ischemic stroke patients with large vessel occlusions; however, it is unclear to what extent stent retriever thrombectomy may be applicable to occlusions of smaller peripheral cerebral vessels. The outcome of patients with isolated M2 occlusions treated with the Mindframe Capture low profile (LP) stent retriever was reviewed. MATERIAL AND METHODS: A retrospective review of prospectively collected data on all consecutive patients treated for isolated M2 occlusions between June 2013 and December 2017 using the Mindframe Capture LP was performed. Technical aspects of the recanalization procedure, recanalization rate, complication rate, and clinical outcome were analyzed. RESULTS: Mechanical thrombectomy with the Mindframe Capture LP was performed in 38 patients (median age 79 years) with an isolated M2 occlusion. The median National Institutes of Health Stroke Scale (NIHSS) score on admission was 7.5 (interquartile range, IQR 5-12) and successful reperfusion modified Thrombolysis in Cerebral Infarction (mTICI 2b or 3) was achieved in 28 patients (74%). A compensated/adjusted modified Rankin Scale (mRS) 0-2 at 3 months was observed in 65% when taking pre-stroke disability into account. Symptomatic intracranial hemorrhage (sICH) occurred in 1 patient (2.6%). Asymptomatic intracranial hemorrhage (aICH) was noted in 8 patients (21%) and a small subarachnoid hemorrhage (SAH) in the immediate vicinity of the target vessel was apparent in 8 patients (21%). CONCLUSION: The Mindframe Capture LP is a technically effective thrombectomy device for the treatment of isolated M2 occlusions. The lower profile of the device is advantageous when targeting peripheral intracranial occlusions.

Electroencephalography-based power spectra allow coma outcome prediction within 24 h of cardiac arrest.

BACKGROUND: Outcome prediction in comatose patients following cardiac arrest remains challenging. Here, we assess the predictive performance of electroencephalography-based power spectra within 24 h from coma onset. METHODS: We acquired electroencephalography (EEG) from comatose patients (n = 138) on the first day of coma in four hospital sites in Switzerland. Outcome was categorised as favourable or unfavourable based on the best state within three months. Data were split in training and test sets. We evaluated the predictive performance of EEG power spectra for long term outcome and its added value to standard clinical tests. RESULTS: Out of 138 patients, 80 had a favourable outcome. Power spectra comparison between favourable and unfavourable outcome in the training set yielded significant differences at 5.2-13.2 Hz and above 21 Hz. Outcome prediction based on power at 5.2-13.2 Hz was accurate in training and test sets. Overall, power spectra predicted patients' outcome with maximum specificity and positive predictive value: 1.00 (95% with CI: 0.94-1.00 and 0.89-1.00, respectively). The combination of power spectra and reactivity yielded better accuracy and sensitivity (0.81, 95% CI: 0.71-0.89) than prediction based on power spectra alone. CONCLUSIONS: On the first day of coma following cardiac arrest, low power spectra values around 10 Hz, typically linked to impaired cortico-thalamic structural connections, are highly specific of unfavourable outcome. Peaks in this frequency range can predict long-term outcome.

A novel biomarker-based prognostic score in acute ischemic stroke: The CoRisk score.

OBJECTIVES: To derive and externally validate a copeptin-based parsimonious score to predict unfavorable outcome 3 months after an acute ischemic stroke (AIS). METHODS: The derivation cohort consisted of patients with AIS enrolled prospectively at the University Hospital Basel, Switzerland. The validation cohort was prospectively enrolled after the derivation cohort at the University Hospital of Bern and University Hospital Basel, Switzerland, as well as Frankfurt a.M., Germany. The score components were copeptin levels, age, NIH Stroke Scale, and recanalization therapy (CoRisk score). Copeptin levels were measured in plasma drawn within 24 hours of AIS and before any recanalization therapy. The primary outcome of disability and death at 3 months was defined as modified Rankin Scale score of 3 to 6. RESULTS: Overall, 1,102 patients were included in the analysis; the derivation cohort contributed 319 patients, and the validation cohort contributed 783. An unfavorable outcome was observed among 436 patients (40%). For the 3-month prediction of disability and death, the CoRisk score was well calibrated in the validation cohort, for which the area under the receiver operating characteristic curve was 0.819 (95% confidence interval [CI] 0.787-0.849). The calibrated CoRisk score correctly classified 75% of patients (95% CI 72-78). The net reclassification index between the calibrated CoRisk scores with and without copeptin was 46% (95% CI 32-60). CONCLUSIONS: The biomarker-based CoRisk score for the prediction of disability and death was externally validated, was well calibrated, and performed better than the same score without copeptin. CLINICALTRIALSGOV IDENTIFIER: NCT00390962 (derivation cohort) and NCT00878813 (validation cohort).

Somatosensory and auditory deviance detection for outcome prediction during postanoxic coma.

OBJECTIVE: Prominent research in patients with disorders of consciousness investigated the electrophysiological correlates of auditory deviance detection as a marker of consciousness recovery. Here, we extend previous studies by investigating whether somatosensory deviance detection provides an added value for outcome prediction in postanoxic comatose patients. METHODS: Electroencephalography responses to frequent and rare stimuli were obtained from 66 patients on the first and second day after coma onset. RESULTS: Multivariate decoding analysis revealed an above chance-level auditory discrimination in 25 patients on the first day and in 31 patients on the second day. Tactile discrimination was significant in 16 patients on the first day and in 23 patients on the second day. Single-day sensory discrimination was unrelated to patients' outcome in both modalities. However, improvement of auditory discrimination from first to the second day was predictive of good outcome with a positive predictive power (PPV) of 0.73 (CI = 0.52-0.88). Analyses considering the improvement of tactile, auditory and tactile, or either auditory or tactile discrimination showed no significant prediction of good outcome (PPVs = 0.58-0.68). INTERPRETATION: Our results show that in the acute phase of coma deviance detection is largely preserved for both auditory and tactile modalities. However, we found no evidence for an added value of somatosensory to auditory deviance detection function for coma-outcome prediction.

Impact of smoking on stroke outcome after endovascular treatment.

BACKGROUND: Recent studies suggest a paradoxical association between smoking status and clinical outcome after intravenous thrombolysis (IVT). Little is known about relationship between smoking and stroke outcome after endovascular treatment (EVT). METHODS: We analyzed data of all stroke patients treated with EVT at the tertiary stroke centre of Berne between January 2005 and December 2015. Using uni- and multivariate modeling, we assessed whether smoking was independently associated with excellent clinical outcome (modified Rankin Scale (mRS) 0-1) and mortality at 3 months. In addition, we also measured the occurrence of symptomatic intracranial hemorrhage (sICH) and recanalization. RESULTS: Of 935 patients, 204 (21.8%) were smokers. They were younger (60.5 vs. 70.1 years of age, p<0.001), more often male (60.8% vs. 52.5%, p = 0.036), had less often from hypertension (56.4% vs. 69.6%, p<0.001) and were less often treated with antithrombotics (35.3% vs. 47.7%, p = 0.004) as compared to nonsmokers. In univariate analyses, smokers had higher rates of excellent clinical outcome (39.1% vs. 23.1%, p<0.001) and arterial recanalization (85.6% vs. 79.4%, p = 0.048), whereas mortality was lower (15.6% vs. 25%, p = 0.006) and frequency of sICH similar (4.4% vs. 4.1%, p = 0.86). After correcting for confounders, smoking still independently predicted excellent clinical outcome (OR 1.758, 95% CI 1.206-2.562; p<0.001). CONCLUSION: Smoking in stroke patients may be a predictor of excellent clinical outcome after EVT. However, these data must not be misinterpreted as beneficial effect of smoking due to the observational study design. In view of deleterious effects of cigarette smoking on cardiovascular health, cessation of smoking should still be strongly recommended for stroke prevention.

Impact of Smoking on Clinical Outcome and Recanalization After Intravenous Thrombolysis for Stroke: Multicenter Cohort Study.

BACKGROUND AND PURPOSE: The impact of smoking on prognosis after stroke is controversial. We aimed to assess the relationship between smoking status and stroke outcome after intravenous thrombolysis in a large cohort study by adjusting for potential confounders and incorporating recanalization rates. METHODS: In a prospective observational multicenter study, we analyzed baseline and outcome data of consecutive patients with acute ischemic stroke treated with intravenous thrombolysis. Using uni- and multivariable modeling, we assessed whether smoking was associated with favorable outcome (modified Rankin Scale score of 0-1) and mortality. In addition, we also measured the occurrence of symptomatic intracranial hemorrhage and recanalization of middle cerebral artery. Patients reporting active cigarette use were classified as smokers. RESULTS: Of 1865 patients, 19.8% were smokers (n=369). They were younger (mean 63.5 versus 71.3 years), less often women (56% versus 72.1%), and suffered less often from hypertension (61.3% versus 70.1%) and atrial fibrillation (22.7% versus 35.6%) when compared with nonsmokers. Favorable outcome and 3-month mortality were in favor of smokers in unadjusted analyses (45.8% versus 39.5% and 9.3% versus 15.8%, respectively), whereas symptomatic intracranial hemorrhage was comparable in both cohorts. Smoking was not associated with clinical outcome and mortality after adjusting for confounders (odds ratio, 1.20; 95% confidence interval, 0.91-1.61; P=0.197 and odds ratio, 1.08; 95% confidence interval, 0.68-1.71; P=0.755, respectively). However, smoking still independently predicted recanalization of middle cerebral artery in multivariable analyses (odds ratio, 2.68; 95% confidence interval, 1.11-6.43; P=0.028). CONCLUSIONS: Our study suggests that good outcome in smokers is mainly related to differences in baseline characteristics and not to biological effects of smoking. The higher recanalization rates in smokers, however, call for further studies.

Endovascular therapy versus intravenous thrombolysis in cervical artery dissection ischemic stroke - Results from the SWISS registry.

INTRODUCTION: In patients with stroke attributable to cervical artery dissection, we compared endovascular therapy to intravenous thrombolysis regarding three-month outcome, recanalisation and complications. MATERIALS AND METHODS: In a multicentre intravenous thrombolysis/endovascular therapy-register-based cohort study, all consecutive cervical artery dissection patients with intracranial artery occlusion treated within 6 h were eligible for analysis. Endovascular therapy patients (with or without prior intravenous thrombolysis) were compared to intravenous thrombolysis patients regarding (i) excellent three-month outcome (modified Rankin Scale score 0-1), (ii) symptomatic intracranial haemorrhage, (iii) recanalisation of the occluded intracranial artery and (iv) death. Upon a systematic literature review, we performed a meta-analysis comparing endovascular therapy to intravenous thrombolysis in cervical artery dissection patients regarding three-month outcome using a random-effects Mantel-Haenszel model. RESULTS: Among 62 cervical artery dissection patients (median age 48.8 years), 24 received intravenous thrombolysis and 38 received endovascular therapy. Excellent three-month outcome occurred in 23.7% endovascular therapy and 20.8% with intravenous thrombolysis patients. Symptomatic intracranial haemorrhage occurred solely among endovascular therapy patients (5/38 patients, 13.2%) while four (80%) of these patients had bridging therapy; 6/38 endovascular therapy and 0/24 intravenous thrombolysis patients died. Four of these 6 endovascular therapy patients had bridging therapy. Recanalisation was achieved in 84.2% endovascular therapy patients and 66.7% intravenous thrombolysis patients (odds ratio 3.2, 95% confidence interval [0.9-11.38]). Sensitivity analyses in a subgroup treated within 4.5 h revealed a higher recanalisation rate among endovascular therapy patients (odds ratio 3.87, 95% confidence interval [1.00-14.95]), but no change in the key clinical findings. In a meta-analysis across eight studies (n = 212 patients), cervical artery dissection patients (110 intravenous thrombolysis and 102 endovascular therapy) showed identical odds for favourable outcome (odds ratio 0.97, 95% confidence interval [0.38-2.44]) among endovascular therapy patients and intravenous thrombolysis patients. DISCUSSION AND CONCLUSION: In this cohort study, there was no clear signal of superiority of endovascular therapy over intravenous thrombolysis in cervical artery dissection patients, which - given the limitation of our sample size - does not prove that endovascular therapy in these patients cannot be superior in future studies. The observation that symptomatic intracranial haemorrhage and deaths in the endovascular therapy group occurred predominantly in bridging patients requires further investigation.

Focal T2 and FLAIR hyperintensities within the infarcted area: A suitable marker for patient selection for treatment?

BACKGROUND AND PURPOSE: Some authors use FLAIR imaging to select patients for stroke treatment. However, the effect of hyperintensity on FLAIR images on outcome and bleeding has been addressed in only few studies with conflicting results. METHODS: 466 patients with anterior circulation strokes were included in this study. They all were examined with MRI before intravenous or endovascular treatment. Baseline data and 3 months outcome were recorded prospectively. Focal T2 and FLAIR hyperintensities within the ischemic lesion were evaluated by two raters, and the PROACT II classification was applied to assess bleeding complications on follow up imaging. Logistic regression analysis was used to determine predictors of bleeding complications and outcome and to analyze the influence of T2 or FLAIR hyperintensity on outcome. RESULTS: Focal hyperintensities were found in 142 of 307 (46.3%) patients with T2 weighted imaging and in 89 of 159 (56%) patients with FLAIR imaging. Hyperintensity in the basal ganglia, especially in the lentiform nucleus, on T2 weighted imaging was the only independent predictor of any bleeding after reperfusion treatment (33.8% in patients with vs. 18.2% in those without; p = 0.003) and there was a non-significant trend for more bleedings in patients with FLAIR hyperintensity within the basal ganglia (p = 0.069). However, there was no association of hyperintensity on T2 weighted or FLAIR images and symptomatic bleeding or worse outcome. CONCLUSION: Our results question the assumption that T2 or FLAIR hyperintensities within the ischemic lesion should be used to exclude patients from reperfusion therapy, especially not from endovascular treatment.

Auditory discrimination improvement predicts awakening of postanoxic comatose patients treated with targeted temperature management at 36°C.

BACKGROUND: Outcome prognostication in postanoxic comatose patients is more accurate in predicting poor than good recovery. Using electroencephalography recordings in patients treated with targeted temperature management at 33°C (TTM 33), we have previously shown that improvement in auditory discrimination over the first days of coma predicted awakening. Given the increased application of a 36°C temperature target (TTM 36), here we aimed at validating the predictive value of auditory discrimination in the TTM 36 setting. METHODS: In this prospective multicenter study, we analyzed the EEG responses to auditory stimuli from 60 consecutive patients from the first and second coma day. A semiautomatic decoding analysis was applied to single patient data to quantify discrimination performance between frequently repeated and deviant sounds. The decoding change from the first to second day was used for predicting patient outcome. RESULTS: We observed an increase in auditory discrimination in 25 out of 60 patients. Among them, 17 awoke from coma (68% positive predictive value; 95% confidence interval: 0.46-0.85). By excluding patients with electroencephalographic epileptiform features, 15 of 18 exhibited improvement in auditory discrimination (83% positive predictive value; 95% confidence interval: 0.59-0.96). Specificity of good outcome prediction increased after adding auditory discrimination to EEG reactivity. CONCLUSION: These results suggest that tracking of auditory discrimination over time is informative of good recovery independent of the temperature target. This quantitative test provides complementary information to existing clinical tools by identifying patients with high chances of recovery and encouraging the maintenance of life support.

EEG synchronization measures are early outcome predictors in comatose patients after cardiac arrest.

OBJECTIVE: Outcome prognostication in comatose patients after cardiac arrest (CA) remains a major challenge. Here we investigated the prognostic value of combinations of linear and non-linear bivariate EEG synchronization measures. METHODS: 94 comatose patients with EEG within 24h after CA were included. Clinical outcome was assessed at 3months using the Cerebral Performance Categories (CPC). EEG synchronization between the left and right parasagittal, and between the frontal and parietal brain regions was assessed with 4 different quantitative measures (delta power asymmetry, cross-correlation, mutual information, and transfer entropy). 2/3 of patients were used to assess the predictive power of all possible combinations of these eight features (4 measures×2 directions) using cross-validation. The predictive power of the best combination was tested on the remaining 1/3 of patients. RESULTS: The best combination for prognostication consisted of 4 of the 8 features, and contained linear and non-linear measures. Predictive power for poor outcome (CPC 3-5), measured with the area under the ROC curve, was 0.84 during cross-validation, and 0.81 on the test set. At specificity of 1.0 the sensitivity was 0.54, and the accuracy 0.81. CONCLUSION: Combinations of EEG synchronization measures can contribute to early prognostication after CA. In particular, combining linear and non-linear measures is important for good predictive power. SIGNIFICANCE: Quantitative methods might increase the prognostic yield of currently used multi-modal approaches.

Progressive multifocal leukoencephalopathy in common variable immunodeficiency: mitigated course under mirtazapine and mefloquine.

Demonstration of survival and outcome of progressive multifocal leukoencephalopathy (PML) in a 56-year-old patient with common variable immunodeficiency, consisting of severe hypogammaglobulinemia and CD4+ T lymphocytopenia, during continuous treatment with mirtazapine (30 mg/day) and mefloquine (250 mg/week) over 23 months. Regular clinical examinations including Rankin scale and Barthel index, nine-hole peg and box and block tests, Berg balance, 10-m walking tests, and Montreal Cognitive Assessment (MoCA) were done. Laboratory diagnostics included complete blood count and JC virus (JCV) concentration in cerebrospinal fluid (CSF). The noncoding control region (NCCR) of JCV, important for neurotropism and neurovirulence, was sequenced. Repetitive MRI investigated the course of brain lesions. JCV was detected in increasing concentrations (peak 2568 copies/ml CSF), and its NCCR was genetically rearranged. Under treatment, the rearrangement changed toward the archetype sequence, and later JCV DNA became undetectable. Total brain lesion volume decreased (8.54 to 3.97 cm(3)) and atrophy increased. Barthel (60 to 100 to 80 points) and Rankin (4 to 2 to 3) scores, gait stability, and box and block (7, 35, 25 pieces) and nine-hole peg (300, 50, 300 s) test performances first improved but subsequently worsened. Cognition and walking speed remained stable. Despite initial rapid deterioration, the patient survived under continuous treatment with mirtazapine and mefloquine even though he belongs to a PML subgroup that is usually fatal within a few months. This course was paralleled by JCV clones with presumably lower replication capability before JCV became undetectable. Neurological deficits were due to PML lesions and progressive brain atrophy.

Differences in demographic characteristics and risk factors in patients with spontaneous vertebral artery dissections with and without ischemic events.

BACKGROUND AND PURPOSE: Spontaneous vertebral artery dissection (sVADs) mainly cause cerebral ischemia, with or without associated local symptoms and signs (headache, neck pain, or cervical radiculopathy), or with local symptoms and signs only. METHODS: We compared the presenting characteristics of consecutive patients with single sVADs and ischemic events and those with local symptoms and signs only. RESULTS: Of the 186 patients with first-ever unilateral sVAD, 165 (89%) presented with cerebral ischemia, and 21 (11%) presented with local symptoms and signs only. Patients with sVAD and ischemia were more often male (63% vs 29%; P=0.002), older (mean+/-SD age, 43.6+/-9.9 vs 38.6+/-9.0 years; P=0.027), and smokers (14% vs 3%; P=0.010), but less often, they had a history of migraine without aura (17% vs 38%; P=0.025) than did patients without ischemia. The multivariate analysis confirmed independent associations between male sex (P=0.024), increasing age (0.027), and smoking (P=0.012) and sVADs causing cerebral ischemia. CONCLUSIONS: These results suggest that men, older patients, and smokers with sVADs may be at increased risk for ischemic events.