Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

BACKGROUND AND OBJECTIVES: The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs. METHODS: We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs. RESULTS: In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs. DISCUSSION: These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.

Headache as the sole presenting symptom of cerebral venous sinuses thrombosis: Subgroup analysis of data from the VENOST study.

OBJECTIVES: Headache is the most common complaint in cerebral venous sinus thrombosis (CVST) and it may sometimes be the only symptom in these patients. This retrospective and prospective study was an investigation of any differences in terms of clinical risk factors, radiological findings, or prognosis in patients with CVST who presented with isolated headache (IH) and cases with other concomitant findings (non-isolated headache [NIH]). METHODS: A total of 1144 patients from a multicenter study of cerebral venous sinus thrombosis (VENOST study) were enrolled in this research. The demographic, biochemical, clinical, and radiological aspects of 287 IH cases and 857 NIH cases were compared. RESULTS: There were twice as many women as men in the study group. In the IH group, when gender distribution was evaluated by age group, no statistically significant difference was found. The onset of headache was frequently subacute and chronic in the IH group, but an acute onset was more common in the NIH group. Other neurological findings were observed in 29% of the IH group during follow-up. A previous history of deep, cerebral, or other venous thromboembolism was less common in the IH group than in the NIH group. Transverse sinus involvement was greater in the IH group, whereas sagittal sinus involvement was greater in the NIH group. The presence of a plasminogen activator inhibitor (PAI) mutation was significantly greater in the IH group. CONCLUSION: IH and CVST should be kept in mind if a patient has subacute or chronic headache. PAI, which has an important role in thrombolytic events, may be a risk factor in CVST. Detailed hematological investigations should be considered. Additional studies are needed.

Cerebral Venous Sinus Thrombosis in Women: Subgroup Analysis of the VENOST Study.

BACKGROUND: Early diagnosis of cerebral venous sinus thrombosis (CVST) associated with reproductive health-related risk factors (RHRF) including pregnancy, puerperium, and oral contraceptive (OC) use can prevent severe neurological sequelae; thus, the symptoms must be documented in detail for each group. METHODS: Out of 1144 patients with CVST, a total of 777 women were enrolled from a multicenter for the study of cerebral venous sinus thrombosis (VENOST). Demographic, biochemical, clinical, and radiological aspects were compared for 324 cases with RHRF and 453 cases without RHRF. RESULTS: The mean age of the RHRF (-) group (43.2 ± 13 years) was significantly higher than of the RHRF (+) group (34 ± 9 years). A previous history of deep venous thrombosis (3%), isolated cavernous sinus involvement (1%), cranial neuropathy (13%), comorbid malignancy (7%), and its disability scores after 12 months (9%) were significantly higher in the RHRF (-) group. The RHRF (+) group consisted of 44% cases of puerperium, 33% cases of OC users and 23% of pregnant women. The mean age was found to be higher in OC users (38 ± 9 years). A previous history of deep venous thrombosis was slightly higher in the pregnancy subgroup (4%). Epileptic seizures were more common in the puerperium group (44%). CONCLUSION: The results of our study indicate that the risk of CSVT increases parallel to age, OC use, and puerperium period. In addition, when considering the frequency of findings and symptoms, epileptic seizures in the puerperium subgroup of the RHRF (+) group and malignancies in the RHRF (-) group may accompany the CSVT. In daily practice, predicting these risks for the CSVT and early recognition of the symptoms will provide significant benefits to patients.

Epileptic seizures in cerebral venous sinus thrombosis: Subgroup analysis of VENOST study.

PURPOSE: The aim of this study is to evaluate the presence and prognostic impact of early seizures in cerebral venous sinus thrombosis patients (CVST). METHOD: VENOST is a retrospective and prospective national multicenter observational study. CVST patients with or without epileptic seizures (ES) were analyzed and compared in terms of demographic and imaging data, causative factors, clinical variables, and prognosis in a total of 1126 patients. RESULTS: The mean age of the patients in the ES group was 39.73 ± 12.64 and 40.17 ± 14.02 years in the non-ES group (p > 0.05). Epileptic seizures were more common (76.6 %) in females (p < 0.001). Early ES occurred in 269 of 1126 patients (23.9 %). Epileptic seizures mainly presented in the acute phase (71.4 %) of the disease (p < 0.001). Majority of these (60.5 %) were in the first 24 h of the CVST. The most common neurological signs were focal neurologic deficits (29.9 %) and altered consciousness (31.4 %) in the ES group. Superior sagittal sinus (SSS) and cortical veins (CV) involvement were the most common sites of thrombosis and the mostly related etiology were found puerperium in seizure group (30.3 % vs 13.9 %). Patients with seizures had worse outcome in the first month of the disease (p < 0.001) but these did not have any influence thereafter. CONCLUSIONS: In this largest CVST cohort (VENOST) reported female sex, presence of focal neurological deficits and altered consciousness, thrombosis of the SSS and CVs, hemorrhagic infarction were risk factors for ES occurrence in patients with CVST.

Cerebral Venous Sinus Thrombosis as a Rare Complication of Systemic Lupus Erythematosus: Subgroup Analysis of the VENOST Study.

AIM: Systemic lupus erythematosus (SLE) is an unusual risk factor for cerebral venous sinus thrombosis (CVST). As few CVST patients with SLE have been reported, little is known regarding its frequency as an underlying etiology, clinical characteristics, or long-term outcome. We evaluated a large cohort of CVST patients with SLE in a multicenter study of cerebral venous thrombosis, the VENOST study, and their clinical characteristics. MATERIAL AND METHOD: Among the 1144 CVST patients in the VENOST cohort, patients diagnosed with SLE were studied. Their demographic and clinical characteristics, etiological risk factors, venous involvement status, and outcomes were recorded. RESULTS: In total, 15 (1.31%) of 1144 CVST patients had SLE. The mean age of these patients was 39.9 ± 12.1 years and 13 (86.7%) were female. Presenting symptoms included headache (73.3%), visual field defects (40.0%), and altered consciousness (26.7%). The main sinuses involved were the transverse (60.0%), sagittal (40.0%), and sigmoid (20.0%) sinuses. Parenchymal involvement was not seen in 73.3% of the patients. On the modified Rankin scale, 92.9% of the patients scored 0-1 at the 1-month follow-up and 90.9% scored 0-1 at the 1-year follow-up. CONCLUSIONS: SLE was found in 1.31% of the CVST patients, most frequently in young women. Headache was the most common symptom and the CVST onset was chronic in the majority of cases. The patient outcomes were favorable. CVST should be suspected in SLE patients, even in those with isolated chronic headache symptoms with or without other neurological findings.

Patient with Guillain-Barré Syndrome with Posterior Spinal Root Involvement: A Case Report.

Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculoneuropathy of the peripheral nervous system. Involvement of the dorsal root ganglia and the medulla spinalis in GBS is rare, especially in an axonal form. Herein, we report the case of a 53-year-old woman with classic GBS and involvement of the T8-L1 dorsal root segments. Dorsal root and spinal involvement should be kept in mind in all types of GBS when patients present with segmental or dermatomal sensory impairment.

Brain microbleeds, anticoagulation, and hemorrhage risk: Meta-analysis in stroke patients with AF.

OBJECTIVES: To assess the association between cerebral microbleeds (CMBs) and future spontaneous intracerebral hemorrhage (ICH) risk in ischemic stroke patients with nonvalvular atrial fibrillation (AF) taking oral anticoagulants. METHODS: This was a meta-analysis of cohort studies with >50 patients with recent ischemic stroke and documented AF, brain MRI at baseline, long-term oral anticoagulation treatment, and ≥6 months of follow-up. Authors provided summary-level data on stroke outcomes stratified by CMB status. We estimated pooled annualized ICH and ischemic stroke rates from Poisson regression. We calculated odds ratios (ORs) of ICH by CMB presence/absence, ≥5 CMBs, and CMB topography (strictly lobar, mixed, and strictly deep) using random-effects models. RESULTS: We established an international collaboration and pooled data from 8 centers including 1,552 patients. The crude CMB prevalence was 30% and 7% for ≥5 CMBs. Baseline CMB presence (vs no CMB) was associated with ICH during follow-up (OR 2.68, 95% confidence interval [CI] 1.19-6.01, p = 0.017). Presence of ≥5 CMB was related to higher future ICH risk (OR 5.50, 95% CI 2.07-14.66, p = 0.001). The pooled annual ICH incidence increased from 0.30% (95% CI 0.04-0.55) among CMB-negative patients to 0.81% (95% CI 0.17-1.45) in CMB-positive patients (p = 0.01) and 2.48% (95% CI 1.2-6.2) in patients with ≥5 CMBs (p = 0.001). There was no association between CMBs and recurrent ischemic stroke. CONCLUSIONS: The presence of CMB on MRI and the dichotomized cutoff of ≥5 CMBs might identify subgroups of ischemic stroke patients with AF with high ICH risk and after further validation could help in risk stratification, in anticoagulation decisions, and in guiding randomized trials and ongoing large observational studies.

Lack of association between cerebral microbleeds and low serum cholesterol in patients with acute intracerebral hemorrhage.

BACKGROUND: The association of cerebral microbleeds (CMBs) with intracerebral hemorrhage (ICH) is well known and its relationship with low serum cholesterol in ICH patients might be of interest. METHODS: A total of 105 patients with ICH were evaluated. In all subjects cholesterol levels were measured after 12h of fasting and gradient-echo magnetic resonance imaging (GE-MRI) was performed for detecting CMBs. RESULTS: CMBs were more common among patients with hypertension and leukoaraiosis (p=0.008 and p=0.001). Patients with and without CMBs did not differ according to total cholesterol, LDL cholesterol, triglycerides and HDL cholesterol levels. CONCLUSION: In this study, 61% of Turkish ICH patients had CMBs, which was not associated with lipid profiles. Leukoaraiosis was independently associated with CMBs.

Frontal assessment battery in patients with Parkinson disease in a Turkish population.

OBJECTIVE: The aims of this study were to assess frontal dysfunction in Turkish patients with idiopathic Parkinson disease (PD) by using frontal assessment battery (FAB), and to determine the relationship among FAB scores and education, Mini-Mental State Examination (MMSE), and severity of the disease. BACKGROUND: Cognitive impairment in patients with PD mainly involves executive dysfunction. Executive dysfunction is mainly related to the frontal lobes and their connections with the thalamus and basal ganglia. FAB is an easily applicable and valid test to examine frontal functions. METHOD: Forty patients diagnosed with PD and 52 healthy controls were included in the study. Age, sex, disease duration, and Unified Parkinson's Disease Rating Scale scores were noted. FAB and MMSE were administered to all participants. Both groups were compared according to FAB scores, MMSE, age, and education. RESULTS: FAB scores were significantly lower in patients with PD (P=0.00) than in healthy controls. In patients with PD, FAB scores were solely correlated with MMSE. In the subgroup analysis, the performance of patients with PD was worse than the healthy participants on similarities and fluency tasks. CONCLUSIONS: FAB scores are lower in Turkish patients with PD than in the healthy participants, and could be used for the evaluation of subtle cognitive deficits in these patients.

Prevention of deep venous thrombosis and pulmonary embolism in patients with acute intracerebral hemorrhage.

OBJECTIVES: Although patients with intracerebral hemorrhage (ICH) are at risk for deep venous thrombosis (DVT), the data about preventive options for DVT prophylaxis in this population is insufficient. We investigated the safety of low dose low molecular weight heparin (LMWH) for DVT prophylaxis in patients with ICH and the effect of heparin on the enlargement of hemorrhage. METHODS: We prospectively randomized 75 primary ICH patients to subcutaneous LMWH (Enoxaparin sodium 40mg/d) or long compression stockings (CS) after the first 48 hours. All patients had cranial computed tomography (CT) scan at admittance, 24th and 72nd hours, seventh and 21st days, CT pulmonary angiography and bilateral lower extremity venous Doppler at 7th day. Hematoma volumes were calculated on the initial and follow-up CTs with ABC/2 method. RESULTS: Mean +/- SD age of the patients was 68.1 +/- 11.98 and 66.08 +/- 9.55 in LMWH and CS groups, respectively. Twenty-two of LMVH group and 8 of CS group were female. After randomization to LMWH or CS, we did not observe any hematoma enlargement at 72nd hours, 7 and 21st days in both groups. In addition, there was not any other systemic bleeding complication in LMWH group. We detected 4 asymptomatic DVT in our patients (3 in LMWH and 1 in CS group). Although asymptomatic DVT was more common in LMWH group, it was not statistically significant (P = 1). CONCLUSIONS: Low dose heparin treatment after 48 hours of stroke in ICH patients is not associated with an increased hematoma growth and should be used for DVT and PE prophylaxis.

Cerebral microbleeds in ischemic stroke patients on warfarin treatment.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are known to be indicative of bleeding prone microangiopathy. Little is known about its significance in anticoagulated patients. We aimed to determine the frequency of CMBs in ischemic stroke patients on warfarin treatment. METHODS: A total of 141 ischemic stroke patients on warfarin therapy were enrolled in this study. One hundred five patients with similar demographic features who do not use warfarin were chosen as controls. We compared vascular risk factors and radiological findings including CMBs and leukoaraiosis between the groups. RESULTS: CMBs on gradient-echo MRI (GE-MRI) were found in 31 patients (22%) and 17 controls (16%) and there was not a significant difference between 2 groups (P=0.25). Study patients with CMBs were older than patients without CMBs (P=0.04) and frequency of leukoaraiosis was significantly higher (P=0.008). Mean duration of warfarin treatment was not different between the patients with and without CMBs (P=0.83). CONCLUSIONS: Although patients with CMBs were older and had more leukoaraiosis the impact of warfarin treatment on CMBs is still controversial.

The relation of testosterone levels with fatigue and apathy in Parkinson's disease.

OBJECTIVE: Fatigue and apathy are frequent in patients with Parkinson's disease (PD). Testosterone deficiency in male patients may contribute in development of fatigue and apathy as well. We investigated whether a possible relation exists between serum testosterone levels, fatigue and apathy in male PD patients. MATERIALS AND METHODS: We included 29 non-demented and non-depressed PD patients and 30 age- and sex-matched healthy subjects. Fatigue Severity Scale (FSS) and Apathy Evaluation Scale (AES-C) were used for the evaluations. In PD patients and healthy subjects, a relationship between FSS, AES-C scores and plasma testosterone levels were assessed. In addition, a correlation between FSS, AES-C and Unified Parkinson's Disease Rating Scale was investigated in PD group. RESULTS: The mean scores of FSS and AES-C were significantly higher in PD patients than those of the control group. The Unified Parkinson's Disease Rating Scale (UPDRS) scores were significantly correlated with FSS and AES-C scores. Mean free testosterone level was significantly lower in PD patients than controls (p=0.008). f-Testosterone levels of PD patients were not correlated with FSS or AES-C scores. CONCLUSION: Apathy and fatigue are frequent in PD and show significant correlation with the severity of the disease. f-Testosterone levels are not related with apathy or fatigue in male PD patients and the role of testosterone in the pathophysiology of these non-motor symptoms is still controversial.

Triphasic EEG pattern in bilateral paramedian thalamic infarction.

Two cases of bilateral paramedian thalamic infarction (BPTI) showing triphasic waves (TWs) on the electroencephalogram (EEG) at acute stage are presented in this study. BPTI is a rare syndrome with decreased level of consciousness, gaze abnormalities and cognitive deterioration. TWs are nonspecific EEG findings occurring in both metabolic and nonmetabolic conditions. The TWs in BPTI might be related to level of consciousness and does not always predict a poor prognosis in BPTI.