Clinical Associations and Prognostic Value of MRI-Visible Perivascular Spaces in Patients With Ischemic Stroke or TIA: A Pooled Analysis

BACKGROUND AND OBJECTIVES: Visible perivascular spaces are an MRI marker of cerebral small vessel disease and might predict future stroke. However, results from existing studies vary. We aimed to clarify this through a large collaborative multicenter analysis. METHODS: We pooled individual patient data from a consortium of prospective cohort studies. Participants had recent ischemic stroke or transient ischemic attack (TIA), underwent baseline MRI, and were followed up for ischemic stroke and symptomatic intracranial hemorrhage (ICH). Perivascular spaces in the basal ganglia (BGPVS) and perivascular spaces in the centrum semiovale (CSOPVS) were rated locally using a validated visual scale. We investigated clinical and radiologic associations cross-sectionally using multinomial logistic regression and prospective associations with ischemic stroke and ICH using Cox regression. RESULTS: We included 7,778 participants (mean age 70.6 years; 42.7% female) from 16 studies, followed up for a median of 1.44 years. Eighty ICH and 424 ischemic strokes occurred. BGPVS were associated with increasing age, hypertension, previous ischemic stroke, previous ICH, lacunes, cerebral microbleeds, and white matter hyperintensities. CSOPVS showed consistently weaker associations. Prospectively, after adjusting for potential confounders including cerebral microbleeds, increasing BGPVS burden was independently associated with future ischemic stroke (versus 0-10 BGPVS, 11-20 BGPVS: HR 1.19, 95% CI 0.93-1.53; 21+ BGPVS: HR 1.50, 95% CI 1.10-2.06; p = 0.040). Higher BGPVS burden was associated with increased ICH risk in univariable analysis, but not in adjusted analyses. CSOPVS were not significantly associated with either outcome. DISCUSSION: In patients with ischemic stroke or TIA, increasing BGPVS burden is associated with more severe cerebral small vessel disease and higher ischemic stroke risk. Neither BGPVS nor CSOPVS were independently associated with future ICH.

Evaluation of the Design and Methodology of Applications to the Local Ethics Committee.

Objectives: Proposals for scientific studies must have an original hypothesis and the appropriate design and methodology to test the premise. Methods: This study is an evaluation of the suitability of applications submitted to a local ethics committee (EC) and the rate of publication of that research. Results: A total of 899 files submitted for EC approval were retrospectively assessed. The EC found that the description of the methods in 44% of the applications was inaccurate, and that this type of error was most often seen in submissions from the surgical branch. In all, 52% of the applications for which we were informed about their final status were not published. Conclusion: The results suggest that improved training in epidemiology is required to reduce the number of application errors and that new regulations could help to motivate healthcare personnel to conduct scientific research and publish their findings.

Assessment of Patients with Intracerebral Hemorrhage or Hemorrhagic Transformation in the VENOST Study.

INTRODUCTION: Cerebral venous and sinus thrombosis (CVST) may lead to cerebral edema and increased intracranial pressure; besides, ischemic or hemorrhagic lesions may develop. Intracerebral hemorrhages occur in approximately one-third of CVST patients. We assessed and compared the findings of the cerebral hemorrhage (CH) group and the CVST group. MATERIALS AND METHODS: In the VENOST study, medical records of 1,193 patients with CVST, aged over 18 years, were obtained from 35 national stroke centers. Demographic characteristics, clinical symptoms, signs at the admission, radiological findings, etiologic factors, acute and maintenance treatment, and outcome results were reported. The number of involved sinuses or veins, localizations of thrombus, and lesions on CT and MRI scans were recorded. RESULTS: CH was detected in the brain imaging of 241 (21.1%) patients, as hemorrhagic infarction in 198 patients and intracerebral hemorrhage in 43 patients. Gynecologic causes comprised the largest percentage (41.7%) of etiology and risk factors in the CVST group. In the CH group, headache associated with other neurological symptoms was more frequent. These neurological symptoms were epileptic seizures (46.9%), nausea and/or vomiting (36.5%), altered consciousness (36.5%), and focal neurological deficits (33.6%). mRS was ≥3 in 23.1% of the patients in the CH group. DISCUSSION AND CONCLUSION: CVST, an important cause of stroke in the young, should be monitored closely if the patients have additional symptoms of headache, multiple sinus involvement, and CH. Older age and parenchymal lesion, either hemorrhagic infarction or intracerebral hemorrhage, imply poor outcome.

A Multicenter Study of 1144 Patients with Cerebral Venous Thrombosis: The VENOST Study.

BACKGROUND: Based on a number of small observational studies, cerebral venous sinus thrombosis has diverse clinical and imaging features, risk factors, and variable outcome. In a large, multicenter cerebral venous thrombosis (VENOST) study, we sought to more precisely characterize the clinical characteristics of Caucasian patients. METHODS: All data for the VENOST study were collected between the years 2000 and 2015 from the clinical follow-up files. Clinical and radiological characteristics, risk factors, and outcomes were compared in terms of age and sex distribution. RESULTS: Among 1144 patients 68% were women, and in older age group (>50 years) male patients were more prevalent (16.6% versus 27.8%). The most frequent symptoms were headache (89.4%) and visual field defects (28.9%) in men, and headache (86.1%) and epileptic seizures (26.8%) in women. Gynecological factors comprised the largest group in women, in particular puerperium (18.3%). Prothrombotic conditions (26.4%), mainly methylenetetrahydrofolate reductase mutation (6.3%) and Factor V Leiden mutation (5.1%), were the most common etiologies in both genders. 8.1% of patients had infection-associated and 5.2% had malignancy-related etiology that was significantly higher in men and older age group. Parenchymal involvement constitutively hemorrhagic infarcts, malignancy, and older age was associated with higher Rankin score. Epileptic seizures had no effect on prognosis. CONCLUSIONS: Clinical and radiological findings were consistent with previous larger studies but predisposing factors were different with a higher incidence of puerperium. Oral contraceptive use was not a prevalent risk factor in our cohort. Malignancy, older age, and hemorrhagic infarcts had worse outcome.

Validation and Reliability Study of the Turkish Version of the Stigma Scale of Epilepsy.

INTRODUCTION: We aimed to validate the Turkish version of the Stigma Scale of Epilepsy (SSE) (from Brazil) and present the results. METHOD: The SSE was completed by 33 patients with epilepsy (PWE), 25 of the patients' family members, and 23 people from the community. Subjects were interviewed on an individual basis; a physician read the questions and the subjects wrote the answers on a sheet. The form was the same for all subjects. In addition, the Beck Depression Inventory (BDI) and the Hamilton Anxiety Inventory (HAI), Short Form-36 (SF-36) were completed by the subjects. RESULTS: We interviewed 81 subjects. The internal consistency of the SSE showed Cronbach's α coefficients of 0.785 for the PWE, 0.733 for the family members and 0.798 for the people in community. The mean scores on the SSE were 57 for patients, 66 for family members and 65 for the community where a score of 0 would suggest no stigma and 100 would indicate maximum stigma. The SSE scores of patients, family members and the community who believed that patients with epilepsy are stigmatized or rejected were higher than the SSE scores of who did not believe it. Although there were strong correlation between high SSE scores and poor functionality and BDI; there were not any correlation between with SSE and HAI, age of epilepsy onset, time of epilepsy, education, and social class. CONCLUSION: The SSE has satisfactory content validity and high internal consistency. It allows for the quantification of the real perception of the epilepsy associated stigma. Prejudice and discrimination are often worse than the seizures themselves in terms of the impact on the daily lives of people with epilepsy and their families. Understanding this aspect of epilepsy is important for reducing the burden of epilepsy, and the SSE can be used for cross cultural, media, and social campaigns aimed at minimizing the negative influences of stigma.

Clinical and radiological features in CADASIL and NOTCH3-negative patients: a multicenter study from Turkey.

BACKGROUND: The diversity of clinical presentation and neuroimaging findings of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) from different regions of the world has not yet been studied in depth. Here we investigated the variability of clinical, radiological and genetic data of 48 patients analyzed for NOTCH3 mutation in Turkey. METHODS: Clinical evaluation was made according to a preformed questionnaire. Cranial neuroimaging findings were determined on the basis of T1, T2, FLAIR and proton-density magnetic resonance scans. For genetic analysis, polymerase chain reaction was performed with primers flanking exons 2-6 and 11 of NOTCH3 gene. RESULTS: Twenty-five patients (52.1%) were diagnosed as CADASIL with NOTCH3 mutation, while 23 patients (47.9%) had no mutation (NOTCH3-negative patients). The mean age and age at stroke onset were lower in male CADASIL patients (p < 0.03). A family history of migraine (p = 0.012), stroke (p < 0.001), recurrent strokes (p = 0.020) and dementia (p = 0.012) was more common in CADASIL patients. Temporal pole involvement was more common in CADASIL patients (p = 0.004). CONCLUSION: It is of clinical importance to identify the heterogeneity of CADASIL from different countries due to a low correlation of clinical and radiological data with respect to NOTCH3 mutation.

Intrathecal methotrexate-induced acute chorea.

Intrathecal methotrexate is the mainstay of central nervous system prophylaxis in acute lymphoblastic leukemia. We describe a patient who developed acute chorea after last dose of intrathecal methotrexate therapy and recovered completely.