Incidence of Developmental Venous Anomalies in Patients With Multiple Sclerosis: A 3 Tesla MRI Study.

Objectives: There is evidence of involvement of the venous system in multiple sclerosis (MS). If this bears also an association with the frequency and extent of developmental venous anomalies (DVA) still has to be determined. We therefore investigated this in patients with different phenotypes of MS and in comparison, to a control population. Methods: We analyzed the contrast-enhanced T1-weighted MR scans of 431 patients (clinically isolated syndrome-CIS, n = 108; MS, n = 323) and of 162 control individuals for the presence of a DVA. We also measured the size of the DVA and draining vein and compared the DVA frequency between MS phenotypes. Results: A DVA was found in 38 (8.8 %) of patients with CIS or MS and in 11 (6.8%) controls (p = 0.4). DVA frequency was highest in CIS (14.8%) and lowest in progressive MS (4.0%). The mean cranio-caudal and axial extension of the DVA was significantly lower in MS patients than controls (p < 0.05). Conclusions: The frequency of DVA in MS patients is comparable to that in controls. Whether DVA size and appearance may change over time will have to be investigated in a longitudinal manner and with larger sample size.

Risk of intracranial haemorrhage and ischaemic stroke after convexity subarachnoid haemorrhage in cerebral amyloid angiopathy: international individual patient data pooled analysis.

OBJECTIVE: To investigate the frequency, time-course and predictors of intracerebral haemorrhage (ICH), recurrent convexity subarachnoid haemorrhage (cSAH), and ischemic stroke after cSAH associated with cerebral amyloid angiopathy (CAA). METHODS: We performed a systematic review and international individual patient-data pooled analysis in patients with cSAH associated with probable or possible CAA diagnosed on baseline MRI using the modified Boston criteria. We used Cox proportional hazards models with a frailty term to account for between-cohort differences. RESULTS: We included 190 patients (mean age 74.5 years; 45.3% female) from 13 centers with 385 patient-years of follow-up (median 1.4 years). The risks of each outcome (per patient-year) were: ICH 13.2% (95% CI 9.9-17.4); recurrent cSAH 11.1% (95% CI 7.9-15.2); combined ICH, cSAH, or both 21.4% (95% CI 16.7-26.9), ischemic stroke 5.1% (95% CI 3.1-8) and death 8.3% (95% CI 5.6-11.8). In multivariable models, there is evidence that patients with probable CAA (compared to possible CAA) had a higher risk of ICH (HR 8.45, 95% CI 1.13-75.5, p = 0.02) and cSAH (HR 3.66, 95% CI 0.84-15.9, p = 0.08) but not ischemic stroke (HR 0.56, 95% CI 0.17-1.82, p = 0.33) or mortality (HR 0.54, 95% CI 0.16-1.78, p = 0.31). CONCLUSIONS: Patients with cSAH associated with probable or possible CAA have high risk of future ICH and recurrent cSAH. Convexity SAH associated with probable (vs possible) CAA is associated with increased risk of ICH, and cSAH but not ischemic stroke. Our data provide precise risk estimates for key vascular events after cSAH associated with CAA which can inform management decisions.

Predicting atrial fibrillation after cryptogenic stroke via a clinical risk score-a prospective observational study.

BACKGROUND AND PURPOSE: Atrial fibrillation (AF) often remains undiagnosed in cryptogenic stroke (CS), mostly because of limited availability of cardiac long-term rhythm monitoring. There is an unmet need for a pre-selection of CS patients benefitting from such work-up. A clinical risk score was therefore developed for the prediction of AF after CS and its performance was evaluated over 1 year of follow-up. METHODS: Our proposed risk score ranges from 0 to 16 points and comprises variables known to be associated with occult AF in CS patients including age, N-terminal pro-brain natriuretic peptide, electrocardiographic and echocardiographic features (supraventricular premature beats, atrial runs, atrial enlargement, left ventricular ejection fraction) and brain imaging markers (multi-territory/prior cortical infarction). All CS patients admitted to our Stroke Unit between March 2018 and August 2019 were prospectively followed for AF detection over 1 year after discharge. RESULTS: During the 1-year follow-up, 24 (16%) out of 150 CS patients with AF (detected via electrocardiogram controls, n = 18; loop recorder monitoring, n = 6) were diagnosed. Our predefined AF Risk Score (cutoff ≥4 points; highest Youden's index) had a sensitivity of 92% and a specificity of 67% for 1-year prediction of AF. Notably, only two CS patients with <4 score points were diagnosed with AF later on (negative predictive value 98%). CONCLUSIONS: A clinical risk score for 1-year prediction of AF in CS with high sensitivity, reasonable specificity and excellent negative predictive value is presented. Generalizability of our score needs to be tested in external cohorts with continuous cardiac rhythm monitoring.

Global Differences in Risk Factors, Etiology, and Outcome of Ischemic Stroke in Young Adults-A Worldwide Meta-analysis: The GOAL Initiative.

BACKGROUND AND OBJECTIVES: There is a worldwide increase in the incidence of stroke in young adults, with major regional and ethnic differences. Advancing knowledge of ethnic and regional variation in causes and outcomes will be beneficial in implementation of regional health care services. We studied the global distribution of risk factors, causes, and 3-month mortality of young patients with ischemic stroke, by performing a patient data meta-analysis from different cohorts worldwide. METHODS: We performed a pooled analysis of individual patient data from cohort studies that included consecutive patients with ischemic stroke aged 18-50 years. We studied differences in prevalence of risk factors and causes of ischemic stroke between different ethnic and racial groups, geographic regions, and countries with different income levels. We investigated differences in 3-month mortality by mixed-effects multivariable logistic regression. RESULTS: We included 17,663 patients from 32 cohorts in 29 countries. Hypertension and diabetes were most prevalent in Black (hypertension, 52.1%; diabetes, 20.7%) and Asian patients (hypertension 46.1%, diabetes, 20.9%). Large vessel atherosclerosis and small vessel disease were more often the cause of stroke in high-income countries (HICs; both p < 0.001), whereas "other determined stroke" and "undetermined stroke" were higher in low and middle-income countries (LMICs; both p < 0.001). Patients in LMICs were younger, had less vascular risk factors, and despite this, more often died within 3 months than those from HICs (odds ratio 2.49; 95% confidence interval 1.42-4.36). DISCUSSION: Ethnoracial and regional differences in risk factors and causes of stroke at young age provide an understanding of ethnic and racial and regional differences in incidence of ischemic stroke. Our results also highlight the dissimilarities in outcome after stroke in young adults that exist between LMICs and HICs, which should serve as call to action to improve health care facilities in LMICs.

Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines.

Multiple sclerosis (MS) is the most common immune-mediated disease of the central nervous system (CNS) and progressively leads to physical disability and death, caused by white matter lesions in the spinal cord and cerebellum, as well as by demyelination in grey matter. Whilst conventional models of experimental allergic encephalomyelitis are suitable for the investigation of the cell-mediated inflammation in the spinal and cerebellar white matter, they fail to address grey matter pathologies. Here, we present the experimental protocol for a novel rat model of cortical demyelination allowing the investigation of the pathological and molecular mechanisms leading to cortical lesions. The demyelination is induced by an immunization with low-dose myelin oligodendrocyte glycoprotein (MOG) in an incomplete Freund's adjuvant followed by a catheter-mediated intracerebral delivery of pro-inflammatory cytokines. The catheter, moreover, enables multiple rounds of demyelination without causing injection-induced trauma, as well as the intracerebral delivery of potential therapeutic drugs undergoing a preclinical investigation. The method is also ethically favorable as animal pain and distress or disability are controlled and relatively minimal. The expected timeframe for the implementation of the entire protocol is around 8 - 10 weeks.

Clinical Characteristics of Patients with Tick-Borne Encephalitis (TBE): A European Multicentre Study from 2010 to 2017.

Tick-borne encephalitis (TBE) virus is a major cause of central nervous system infections in endemic countries. Here, we present clinical and laboratory characteristics of a large international cohort of patients with confirmed TBE using a uniform clinical protocol. Patients were recruited in eight centers from six European countries between 2010 and 2017. A detailed description of clinical signs and symptoms was recorded. The obtained information enabled a reliable classification in 553 of 555 patients: 207 (37.3%) had meningitis, 273 (49.2%) meningoencephalitis, 15 (2.7%) meningomyelitis, and 58 (10.5%) meningoencephalomyelitis; 41 (7.4%) patients had a peripheral paresis of extremities, 13 (2.3%) a central paresis of extremities, and 25 (4.5%) had single or multiple cranial nerve palsies. Five (0.9%) patients died during acute illness. Outcome at discharge was recorded in 298 patients. Of 176 (59.1%) patients with incomplete recovery, 80 (27%) displayed persisting symptoms or signs without recovery expectation. This study provides further evidence that TBE is a severe disease with a large proportion of patients with incomplete recovery. We suggest monitoring TBE in endemic European countries using a uniform protocol to record the full clinical spectrum of the disease.

2021 MAGNIMS-CMSC-NAIMS consensus recommendations on the use of MRI in patients with multiple sclerosis.

The 2015 Magnetic Resonance Imaging in Multiple Sclerosis and 2016 Consortium of Multiple Sclerosis Centres guidelines on the use of MRI in diagnosis and monitoring of multiple sclerosis made an important step towards appropriate use of MRI in routine clinical practice. Since their promulgation, there have been substantial relevant advances in knowledge, including the 2017 revisions of the McDonald diagnostic criteria, renewed safety concerns regarding intravenous gadolinium-based contrast agents, and the value of spinal cord MRI for diagnostic, prognostic, and monitoring purposes. These developments suggest a changing role of MRI for the management of patients with multiple sclerosis. This 2021 revision of the previous guidelines on MRI use for patients with multiple sclerosis merges recommendations from the Magnetic Resonance Imaging in Multiple Sclerosis study group, Consortium of Multiple Sclerosis Centres, and North American Imaging in Multiple Sclerosis Cooperative, and translates research findings into clinical practice to improve the use of MRI for diagnosis, prognosis, and monitoring of individuals with multiple sclerosis. We recommend changes in MRI acquisition protocols, such as emphasising the value of three dimensional-fluid-attenuated inversion recovery as the core brain pulse sequence to improve diagnostic accuracy and ability to identify new lesions to monitor treatment effectiveness, and we provide recommendations for the judicious use of gadolinium-based contrast agents for specific clinical purposes. Additionally, we extend the recommendations to the use of MRI in patients with multiple sclerosis in childhood, during pregnancy, and in the post-partum period. Finally, we discuss promising MRI approaches that might deserve introduction into clinical practice in the near future.

Factors influencing daily treatment choices in multiple sclerosis: practice guidelines, biomarkers and burden of disease.

At two meetings of a Central European board of multiple sclerosis (MS) experts in 2018 and 2019 factors influencing daily treatment choices in MS, especially practice guidelines, biomarkers and burden of disease, were discussed. The heterogeneity of MS and the complexity of the available treatment options call for informed treatment choices. However, evidence from clinical trials is generally lacking, particularly regarding sequencing, switches and escalation of drugs. Also, there is a need to identify patients who require highly efficacious treatment from the onset of their disease to prevent deterioration. The recently published European Committee for the Treatment and Research in Multiple Sclerosis/European Academy of Neurology clinical practice guidelines on pharmacological management of MS cover aspects such as treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns and are based on expert consensus statements. However, the recommendations constitute an excellent framework that should be adapted to local regulations, MS center capacities and infrastructure. Further, available and emerging biomarkers for treatment guidance were discussed. Magnetic resonance imaging parameters are deemed most reliable at present, even though complex assessment including clinical evaluation and laboratory parameters besides imaging is necessary in clinical routine. Neurofilament-light chain levels appear to represent the current most promising non-imaging biomarker. Other immunological data, including issues of immunosenescence, will play an increasingly important role for future treatment algorithms. Cognitive impairment has been recognized as a major contribution to MS disease burden. Regular evaluation of cognitive function is recommended in MS patients, although no specific disease-modifying treatment has been defined to date. Finally, systematic documentation of real-life data is recognized as a great opportunity to tackle unresolved daily routine challenges, such as use of sequential therapies, but requires joint efforts across clinics, governments and pharmaceutical companies.

The burden of neurological diseases in Europe: an analysis for the Global Burden of Disease Study 2017.

BACKGROUND: Neurological disorders account for a large and increasing health burden worldwide, as shown in the Global Burden of Diseases (GBD) Study 2016. Unpacking how this burden varies regionally and nationally is important to inform public health policy and prevention strategies. The population in the EU is older than that of the WHO European region (western, central, and eastern Europe) and even older than the global population, suggesting that it might be particularly vulnerable to an increasing burden of age-related neurological disorders. We aimed to compare the burden of neurological disorders in the EU between 1990 and 2017 with those of the WHO European region and worldwide. METHODS: The burden of neurological disorders was calculated for the year 2017 as incidence, prevalence, mortality, disability-adjusted life-years (DALYs), years of life lost, and years lived with disability for the countries in the EU and the WHO European region, totally and, separately. Diseases analysed were Alzheimer's disease and other dementias, epilepsy, headache (migraine and tension-type headache), multiple sclerosis, Parkinson's disease, brain cancer, motor neuron diseases, neuroinfectious diseases, and stroke. Data are presented as totals and by sex, age, year, location and socio-demographic context, and shown as counts and rates. FINDINGS: In 2017, the total number of DALYs attributable to neurological disorders was 21·0 million (95% uncertainty interval 18·5-23·9) in the EU and 41·1 million (36·7-45·9) in the WHO European region, and the total number of deaths was 1·1 million (1·09-1·14) in the EU and 1·97 million (1·95-2·01) in the WHO European region. In the EU, neurological disorders ranked third after cardiovascular diseases and cancers representing 13·3% (10·3-17·1) of total DALYs and 19·5% (18·0-21·3) of total deaths. Stroke, dementias, and headache were the three commonest causes of DALYs in the EU. Stroke was also the leading cause of DALYs in the WHO European region. During the study period we found a substantial increase in the all-age burden of neurodegenerative diseases, despite a substantial decrease in the rates of stroke and infections. The burden of neurological disorders in Europe was higher in men than in women, peaked in individuals aged 80-84 years, and varied substantially with WHO European region and country. All-age DALYs, deaths, and prevalence of neurological disorders increased in all-age measures, but decreased when using age-standardised measures in all but three countries (Azerbaijan, Turkmenistan, and Uzbekistan). The decrease was mostly attributed to the reduction of premature mortality despite an overall increase in the number of DALYs. INTERPRETATION: Neurological disorders are the third most common cause of disability and premature death in the EU and their prevalence and burden will likely increase with the progressive ageing of the European population. Greater attention to neurological diseases must be paid by health authorities for prevention and care. The data presented here suggest different priorities for health service development and resource allocation in different countries. FUNDING: European Academy of Neurology.

Minor Structural Differences in the Cervical Spine Between Patients With Cervical Dystonia and Age-Matched Healthy Controls.

Background: Cervical dystonia is the most common form of focal dystonia. The frequency and pattern of degenerative changes of the cervical spine in patients with cervical dystonia and their relation to clinical symptoms remain unclear as no direct comparison to healthy controls has been performed yet. Here, we used magnetic resonance imaging (MRI) to investigate (1) whether structural abnormalities of the cervical spine are more common in patients with cervical dystonia compared to age-matched healthy controls, (2) if there are clinical predictors for abnormalities on MRI, and (3) to calculate the inter-rater reliability of the respective radiological scales. Methods: Twenty-five consecutive patients with cervical dystonia and 20 age-matched healthy controls were included in the study. MRI scans of the cervical spine were analyzed separately by three experienced raters blinded to clinical information, applying different MRI rating scales. Structural abnormalities were compared between groups for upper, middle, and lower cervical spine segments. The associations between scores differentiating both groups and clinical parameters were assessed in dystonia patients. Additionally, inter-rater reliability of the MRI scales was calculated. Results: Comparing structural abnormalities, we found minor differences in the middle cervical spine, indicated by a higher MRI total score in patients but no significant correlation between clinical parameters and MRI changes. Inter-rater reliability was satisfying for most of the MRI rating scales. Conclusion: Our results do not provide evidence for a role of MRI of the cervical spine in the routine work-up of patients with cervical dystonia in the absence of specific clinical signs or symptoms.

Relationship between stroke etiology and collateral status in anterior circulation large vessel occlusion.

BACKGROUND AND PURPOSE: Clinical outcome after mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke is influenced by the intracerebral collateral status. We tested the hypothesis that patients with preexisting ipsilateral extracranial carotid artery stenosis (CAS) would have a better collateral status compared to non-CAS patients. Additionally, we evaluated MT-related adverse events and outcome for both groups. METHODS: Over a 7-year period, we identified all consecutive anterior circulation MT patients (excluding extracranial carotid artery occlusion and dissection). Patients were grouped into those with CAS ≥ 50% according to the NASCET criteria and those without significant carotid stenosis (non-CAS). Collateral status was rated on pre-treatment CT- or MR-angiography according to the Tan Score. Furthermore, we assessed postinterventional infarct size, adverse events and functional outcome at 90 days. RESULTS: We studied 281 LVO stroke patients, comprising 46 (16.4%) with underlying CAS ≥ 50%. Compared to non-CAS stroke patients (n = 235), patients with CAS-related stroke more often had favorable collaterals (76.1% vs. 46.0%). Recanalization rates were comparable between both groups. LVO stroke patients with underlying CAS more frequently had adverse events after MT (19.6% vs. 6.4%). Preexisting CAS was an independent predictor for favorable collateral status in multivariable models (Odds ratio: 3.3, p = 0.002), but post-interventional infarct size and functional 90-day outcome were not different between CAS and non-CAS patients. CONCLUSIONS: Preexisting CAS ≥ 50% was associated with better collateral status in LVO stroke patients. However, functional 90-day outcome was independent from CAS, which could be related to a higher rate of adverse events.

The influence of iron oxidation state on quantitative MRI parameters in post mortem human brain.

A variety of Magnetic Resonance Imaging (MRI) techniques are known to be sensitive to brain iron content. In principle, iron sensitive MRI techniques are based on local magnetic field variations caused by iron particles in tissue. The purpose of this study was to investigate the sensitivity of MR relaxation and magnetization transfer parameters to changes in iron oxidation state compared to changes in iron concentration. Therefore, quantitative MRI parameters including R1, R2, R2∗, quantitative susceptibility maps (QSM) and magnetization transfer ratio (MTR) of post mortem human brain tissue were acquired prior and after chemical iron reduction to change the iron oxidation state and chemical iron extraction to decrease the total iron concentration. All assessed parameters were shown to be sensitive to changes in iron concentration whereas only R2, R2∗ and QSM were also sensitive to changes in iron oxidation state. Mass spectrometry confirmed that iron accumulated in the extraction solution but not in the reduction solution. R2∗ and QSM are often used as markers for iron content. Changes in these parameters do not necessarily reflect variations in iron content but may also be a result of changes in the iron's oxygenation state from ferric towards more ferrous iron or vice versa.

Serum neurofilament light levels in normal aging and their association with morphologic brain changes.

Neurofilament light (NfL) protein is a marker of neuro-axonal damage and can be measured not only in cerebrospinal fluid but also in serum, which allows for repeated assessments. There is still limited knowledge regarding the association of serum NfL (sNfL) with age and subclinical morphologic brain changes and their dynamics in the normal population. We measured sNfL by a single molecule array (Simoa) assay in 335 individuals participating in a population-based cohort study and after a mean follow-up time of 5.9 years (n = 103). Detailed clinical examination, cognitive testing and 3T brain MRI were performed to assess subclinical brain damage. We show that rising and more variable sNfL in individuals >60 years indicate an acceleration of neuronal injury at higher age, which may be driven by subclinical comorbid pathologies. This is supported by a close association of sNfL with brain volume changes in a cross-sectional and especially longitudinal manner.

Single mean arterial blood pressure drops during stroke thrombectomy under general anaesthesia are associated with poor outcome.

BACKGROUND: We examined the influence of periprocedural blood pressure (BP), especially critical BP drops, on 3-month functional outcome in stroke patients undergoing mechanical thrombectomy (MT) under general anaesthesia (GA). METHODS: We screened all patients with anterior circulation large vessel occlusion receiving MT under GA at our centre from January 2011 to June 2016 and selected those who had continuous invasive periinterventional BP monitoring. Clinical and radiological data were prospectively collected as part of an ongoing cohort study, monitoring data were extracted from electronic anaesthesia records. We used uni- and multivariable regression to investigate the association of BP values with unfavourable outcome, defined as modified Rankin Scale scores 3-6 3 months post-stroke. RESULTS: 115 patients were included in this study (mean age 65.3 ± 13.0 years, 55.7% male). Periinterventional systolic, diastolic, and mean arterial BP (MAP) values averaged across MT had no effect on outcome. However, single BP drops were related to unfavourable outcome, with absolute MAP drops showing the highest association compared to both systolic and relative BP drops (with reference to pre-interventional values). The BP value with the strongest association with unfavourable outcome was identified as an MAP ever < 60 mmHg (p = 0.01) with a pronounced effect in patients with poor collaterals. An MAP < 60 mmHg remained independently associated with poor functional outcome in multivariable analysis (p < 0.01). CONCLUSIONS: For patients undergoing MT under GA, single MAP drops < 60 mmHg are independently related to unfavourable 3-month outcome. Therefore, every effort should be made to prevent periinterventional hypotensive episodes, especially below this threshold.

Postural hemodynamic parameters in older persons have a seasonal dependency : A pilot study.

AIMS: It is known that blood pressure regulation differs seasonally. It is unknown, however, how the cardiovascular system in patients with a stroke reacts to postural changes in different seasons. The aim was therefore to investigate how different temperatures in cold and warm seasons influence the reactions of haemodynamic mechanisms as well as heart rate variability during a sit-to-stand test in patients with stroke and a control group. METHODS: Hemodynamic responses were assessed in both groups during a sit-to-stand test (5 min sitting followed by 5 min standing) beat to beat within two different seasons. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), heart rate (HR), stroke index (SI), cardiac index (CI) and heart rate variability (HRV) were continuously monitored. RESULTS: During the sitting baseline period delta values of DBP (+15.1 [Standard error (SE) 3.75] mmHg, p < 0.05) and MBP (+14.35 [SE 4.18] mmHg, p < 0.05) were significantly higher in colder months compared to warmer months whereas SI (-3.86 [SE 1.43] ml/beat/m2, p < 0.05) and CI (-0.4 [SE 0.11] l/min/m2, p < 0.05) were lower in colder months compared to warmer months in non-stroke participants. In patients with stroke during sitting, baseline period delta values of DBP (+19.92 [SE 8.03] mmHg, p < 0.05) and MBP (+19.29 [SE 8.6] mmHg, p < 0.05) were significantly higher in colder months compared to warmer months but SI (-5.43 [SE 1.96] ml/beat/m2, p < 0.05) was significantly lower in colder months compared to warmer months. After standing, there was a significant decrease in SBP in warmer months (-16.84 [SE 4.38] mmHg, p < 0.05) and a decrease in DBP in warmer months (-7.8 [SE 2.3] mmHg, p < 0.05) and colder months (-6.73 [SE 1.5] mmHg, p < 0.05) in non-stroke participants and a decrease in MBP in warmer months (-12.5 [SE 2.8] mmHg, p < 0.05) and colder months (-8.93 [SE 1.8] mmHg, p < 0.05) in non-stroke participants and in warmer months (-14.54 [SE 4.1] mmHg, p < 0.05) in patients with stroke. CONCLUSION: Elderly with and without stroke respond to orthostatic stress with a greater drop in blood pressure in the warmer seasons.

Mean Platelet Volume Does Not Predict Restenosis After Carotid Artery Stenting in Whites.

Background and Purpose- Mean platelet volume (MPV) indicates platelet activity possibly affecting patient's risk for progressive atherosclerotic disease. A recent study identified elevated MPV as a predictor of in-stent restenosis (ISR) after carotid artery stenting (CAS) in a Chinese population. However, the role of MPV on the development of ISR following CAS in whites is yet unknown. Methods- We retrospectively identified all consecutive patients who underwent CAS for atherosclerotic disease at our center from 2005 to 2017. All patients were followed clinically and by duplex sonography at 1, 3, and 6 months and annually after CAS. ISR was defined as ≥50% stenosis (NASCET [North American Symptomatic Carotid Endarterectomy Trial] criteria) in the treated vessel. MPV was assessed before CAS, at last follow-up and at the time of ISR detection. Results- Of 392 patients with CAS (mean age 68.5±9.5 years, 26.8% women, 42.3% symptomatic stenosis), 54 had ISR after a mean follow-up time of 32 months. Baseline MPV was not different in ISR compared with non-ISR patients (10.7 versus 10.6 fL, P=0.316). MPV levels did also not change from baseline to ISR detection (P=0.310) and were not associated with recurrent stroke or vascular events (P>0.5). Multivariable analysis identified active smoking as the sole risk factor for carotid ISR (odds ratio, 2.53 [95% CI, 1.21-5.29]). Conclusions- We did not identify MPV as a risk factor for ISR after CAS in whites. Smoking cessation is an important target to avoid this complication.

Predictors of Lesion Cavitation After Recent Small Subcortical Stroke.

Morphologic evolution of recent small subcortical infarcts (RSSI) ranges from lesion disappearance to lacune formation and the reasons for this variability are still poorly understood. We hypothesized that diffusion tensor imaging (DTI) and blood-brain-barrier (BBB) abnormalities early on can predict tissue damage 1 year after an RSSI. We studied prospectively recruited patients with a symptomatic MRI-defined RSSI who underwent baseline and two pre-specified MRI examinations at 1-3-month and 1-year post-stroke. We defined the extent of long-term tissue destruction, termed cavitation index, as the ratio of the 1-year T1-weighted cavity volume to the baseline RSSI volume on FLAIR. We calculated fractional anisotropy and mean diffusivity (MD) of the RSSI and normal-appearing white matter, and BBB leakage in different tissues on dynamic contrast-enhanced MRI. Amongst 60 patients, at 1-year post-stroke, 44 patients showed some degree of RSSI cavitation on FLAIR, increasing to 50 on T2- and 56 on T1-weighted high-resolution scans, with a median cavitation index of 7% (range, 1-36%). Demographic, clinical, and cerebral small vessel disease features were not associated with the cavitation index. While lower baseline MD of the RSSI (rs = - 0.371; p = 0.004) and more contrast leakage into CSF (rs = 0.347; p = 0.007) were associated with the cavitation index in univariable analysis, only BBB leakage in CSF remained independently associated with cavitation (beta = 0.315, p = 0.046). Increased BBB leakage into CSF may indicate worse endothelial dysfunction and increased risk of tissue destruction post RSSI. Although cavitation was common, it only affected a small proportion of the original RSSI.