Validation of external and internal exposome of the findings associated to cerebral small vessel disease: A Mendelian randomization study

The exposome characterizes all environmental exposures and their impact on a disease. To determine the causally-associated components of the exposome for cerebral small vessel disease (CSVD), we performed mendelian randomization analysis of 5365 exposures on six clinical and subclinical CSVD measures. We found statistically significant evidence (FDR-corrected P < 0.05) that hypertension, high cholesterol, longer television-watching time, lower educational qualifications, younger age of first sexual intercourse, smoking, reduced pulmonary function, higher subjective overall health rating, and frequent tiredness were associated with increased risk of intracerebral hemorrhage or small vessel stroke. Adiposity, diabetes, frequent alcoholic drinks, higher white blood cell count and neutrophil count were significantly associated with higher risk of non-lobar hemorrhage or small vessel stroke, but not lobar hemorrhage. Hypertension, higher arm or leg fat-free mass and higher sitting height were significantly associated with higher white matter hyperintensities. The results were robust to sensitivity analyses and showed no evidence of horizontal pleiotropy. We also identified 41 exposures suggestively associated (uncorrected P < 0.05) with multiple CSVD measures as the “the CSVD exposome”. This exposome-wide association study provides insight into CSVD development and prevention.

Efficacy of arterial spin labeling for detection of the ruptured micro-arteriovenous malformation: illustrative cases

BACKGROUND Diagnosis of a microarteriovenous malformation (micro-AVM) is difficult, especially in the acute stage of rupture because of the small size of the nidus and the existence of hematoma. We report two cases of ruptured micro-AVMs detected by arterial spin labeling (ASL). OBSERVATIONS In one case, a 45-year-old male was transported with a complaint of right hemiparesis. Computed tomography (CT) revealed a right parietal lobar hemorrhage. Standard magnetic resonance imaging (MRI) showed no abnormal findings as the cause of the hemorrhage. ASL 23 days after the onset demonstrated high signals on the medial wall of the hematoma. Digital subtraction angiography (DSA) showed a micro-AVM in accordance with the site of high signals on ASL. In another case, a 38-year-old female was transported with a complaint of left hemianopsia. CT on admission revealed a right parietal lobar hemorrhage. Standard MRI showed no abnormal findings as the cause of the hemorrhage. ASL 15 days after the onset demonstrated high signals on the internal wall of the hematoma. DSA showed micro-AVM in accordance with the site of high signaling on ASL. Both cases were successfully treated with open surgery. LESSONS ASL can manifest micro-AVMs as high signals within the hematoma. ASL is a useful less-invasive screening tool for the detection of ruptured micro-AVMs.

Prevalence of cerebral vein thrombosis among patients with spontaneous intracranial hypotension

Background and purpose Cerebral venous sinus thrombosis (CVST) is a rare condition but an important complication of spontaneous intracranial hypotension (SIH). We reviewed our experience of patients with SIH and assessed for the presence of CVST. Methods We reviewed the medical records and imaging studies from our tertiary referral institution, assessing patients with clinically suspected SIH as well as imaging findings of intracranial hypotension. All relevant brain MRIs were reviewed for the presence of brain sag, pachymeningeal enhancement, and CVST. Results Among 563 patients with a clinical diagnosis of SIH, 431 (76%) demonstrated brain sag. In the overall patient cohort, a total of 5 patients had CVST (0.9%) and all 5 of these patients demonstrated findings of brain sag. Of the patients with CVST, 3 had significant complications, including dural arteriovenous fistulas (2 patients) and lobar hemorrhage with seizure (1 patient). Conclusion SIH is a risk factor for the development of CVST. In our review of 563 patients with clinical and/or imaging findings of SIH, 0.9% of patients were diagnosed with CVST and 3 of these patients (60%) had additional severe complications.

Impact of Increased Hemoglobin on Spontaneous Intracerebral Hemorrhage

Background Studies of the impact of increased hemoglobin on spontaneous intracerebral hemorrhage (ICH) are limited. The present study aimed to explore the effect of increased hemoglobin on ICH. Methods A retrospective single-center study using medical records from a database processed by univariate and multivariate analyses was performed in the People’s Hospital of Tibet Autonomous Region in Lhasa, Tibet, China. Results The mean hemoglobin level in 211 patients with ICH was 165.03 ± 34.12 g/l, and a median hematoma volume was 18.5 ml. Eighty-eight (41.7%) patients had large hematomas (supratentorial hematoma ≥ 30 ml; infratentorial hematoma ≥ 10 ml). No differences in ICH risk factors between the groups with different hemoglobin levels were detected. Increased hemoglobin was independently associated with large hematomas [odds ratio (OR) 1.013, P = 0.023]. Increased hemoglobin was independently associated with ICH with subarachnoid hemorrhage (OR 1.014, P = 0.016), which was more pronounced in men (OR 1.027, P = 0.002). Increased hemoglobin was independently associated with basal ganglia hemorrhage and lobar hemorrhage in men (OR 0.986, P = 0.022; OR 1.013, P = 0.044, respectively) but not in women (P > 0.1). Conclusions Increased hemoglobin was independently associated with large hemorrhage volume. Increased hemoglobin was independently associated with lobar hemorrhage in men and ICH with subarachnoid hemorrhage, which was more pronounced in men. Additional studies are needed to confirm our findings and explore potential mechanisms.

Profile and Prognosis of Spontaneous Lobar Intracerebral Hemorrhage: Comparison of 6-month Survival with STICH II and the MISTIE III Lobar Hemorrhage Subset

Background Randomized trials on spontaneous lobar intracerebral hemorrhage (ICH) provided no convincing evidence of the superiority of surgical treatment. Since recruitment in the trials was under the premise of equipoise, a selection bias toward patients who did not need surgery or were in hopeless condition must be suspected. The aim of the actual analysis was to compare outcome and patient profile of an unselected hospital series with recent randomized trials and to develop a prognostic model. Methods Of 821 patients with spontaneous ICH managed at the neurosurgical department of the University Hospital Düsseldorf between 2013 and 2018, 159 had lobar bleedings. Patient characteristics, hematoma volume, treatment modality, and 6-month survival were compared with STICH II and the subset of lobar hemorrhage in the MISTIE III trial. In addition, a prognostic model for 6-month survival in our patients was developed using a random forest classifier. Results One hundred and seven patients were managed by surgical evacuation of the hematoma and 52 without surgical evacuation. Median hemorrhage volume in our surgical cohort was 66 and 42 mL in the conservative cohort, compared with 38 and 36 mL in the STICH II trial, and 46 and 47 mL in the surgical and conservative MISTIE III lobar hemorrhage subset. Median initial Glasgow Coma Scale (GCS) score was 12 in our surgical group and 11 in the conservative group, compared with 13 in the STICH II cohorts and 12 in the MISTIE III lobar hemorrhage subset. Median age in our surgical and conservative cohorts was 73 and 74 years, respectively, compared with 65 years in both STICH II cohorts and 68 years in the MISTIE II subsets. Twenty-nine percent of our surgical cohort and 55% of our conservatively managed patients deceased within the first 6 months, compared with 18 and 24%, respectively, in STICH II and 17 and 24% in the MISTIE III subset. Our prognostic model identified large hemorrhage volumes and low admission GCS score as main unfavorable prognostic factors for 6-month survival. The random forest classifier achieved a predictive accuracy of 78% and an area under curve (AUC)- value of 88% regarding survival at 6 months, on a test set independent of the training set. Conclusions In comparison with our surgical group, the STICH II and MISTIE III cohorts, recruited under the premise of physician equipoise, underrepresented patients with large ICHs. The cohorts in the randomized trials were therefore biased toward patients with a favorable perspective under conservative management. Initial hematoma volume and admission GCS were the main prognostic factors in our patients.

The Effect of Aging and Small-Vessel Disease Burden on Hematoma Location in Patients with Acute Intracerebral Hemorrhage

<b><i>Introduction:</i></b> Intracerebral hemorrhage (ICH) is a devastating hemorrhagic event and is associated with high mortality or severe neurological sequelae. Age-associated differences in hematoma location for nonlobar ICH are not well known. The aims of the present study were to elucidate the relationship between age and hematoma location and to assess the differences in small-vessel disease (SVD) burden as a potential surrogate marker for longstanding hypertension among various hematoma locations. <b><i>Methods:</i></b> From September 2014 through July 2019, consecutive patients with acute, spontaneous ICH were retrospectively enrolled from a prospective registry. Magnetic resonance imaging was performed during admission, and the total SVD burden score (including microbleeds, lacunes, enlarged perivascular spaces, and white matter hyperintensities) was calculated. The relationships of hematoma location with aging and SVD burden were assessed by using multivariate logistic regression analyses. <b><i>Results:</i></b> A total of 444 patients (156 women [35%]; median age 69 [interquartile range 59–79] years; National Institutes of Health Stroke Scale score 9 [17][3–17]) were enrolled in the present study. Multivariate logistic regression analyses showed that advanced age was independently associated with thalamic (odds ratio [OR]: 1.48, 95% confidence interval [CI]: 1.19–1.84, <i>p</i> &#x3c; 0.001 for 10-year increment) and lobar hemorrhage (OR: 1.58, 95% CI: 1.19–2.09, <i>p</i> = 0.002) and was independently and negatively related to putaminal hemorrhage (OR: 0.55, 95% CI: 0.44–0.68, <i>p</i> &#x3c; 0.001). The total SVD burden score was independently and positively associated with thalamic hemorrhage (OR: 1.27, 95% CI: 1.01–1.59, <i>p</i> = 0.045) and negatively with lobar hemorrhage (OR: 0.74, 95% CI: 0.55–0.99, <i>p</i> = 0.042), even after adjusting by age, but not with putaminal hemorrhage (OR: 0.91, 95% CI: 0.73–1.14, <i>p</i> = 0.395). <b><i>Conclusion:</i></b> Putaminal, thalamic, and lobar hemorrhages are prone to occur in specific ages and SVD states: putaminal in young patients, thalamic in old and high SVD burden patients, and lobar hemorrhages in old and low SVD burden patients. Susceptibility to bleeding with aging or severe SVD accumulation seems to differ considerably among brain locations.

Quantitative Corticospinal Tract Assessment in Acute Intracerebral Hemorrhage

Intracerebral hemorrhage (ICH) prognostication during the acute phase is often subjective among physicians and often affects treatment decisions. The present study explores objective imaging parameters using quantitative corticospinal tract (CST) fiber reconstruction during the acute phase of ICH and correlates these parameters with functional outcome and patient recovery. We prospectively enrolled nonsurgical spontaneous supratentorial ICH patients and obtained an MRI scan on day 5 ± 1. Q-space diffeomorphic reconstruction was performed using DSI Studio, and quantitative anisotropy (QA) was calculated. The CST was reconstructed based on QA. The dichotomized modified Rankin Scale score on day 90 (favorable outcome = 0–2) and Barthel Index (favorable recovery = 100 on day 90 or improvement between discharge and day 90 > 60%) were assessed. Thirty-three patients, median age 72 years (interquartile range (IQR) 64–83), 21 female (64%), 21 (64%) with lobar hemorrhage, median ICH volume on admission 15.0 (IQR 7.0–27.4) mL, were included. Sixteen patients (48%) had a favorable outcome and 24 (73%) had a favorable recovery. The mean number of ipsilesional reconstructed CST fiber pathways was higher in patients with favorable outcomes (153 (standard deviation (SD) 103) vs. 60 (SD 39), p = 0.003) and predicted outcome after adjustment (Exp(B) = 1.016 (95% CI = 1.002–1.030)). QA in the ipsilesional posterior limb of the internal capsule showed a trend towards an association with favorable outcome (Exp(B) = 1.194 (95% CI = 0.991–1.439 (adjusted))). The total (ipsilesional + contralesional) number of reconstructed fiber pathways was associated with favorable recovery (Exp(B) = 1.025 (95% CI = 1.003–1.047 (adjusted))). Quantitative tractography parameters assessed in the acute phase of ICH may represent a promising predictor of long-term outcome and recovery. This might facilitate prognostic evaluation and organization of rehabilitation.

Location of Intracerebral Hemorrhage Affects Outcome After Minimally Invasive Endoscopic Hematoma Evacuation

INTRODUCTION Treatment for intracerebral hemorrhage (ICH) has been largely medical after negative findings from trials evaluating open craniotomy for hematoma evacuation. Location of hemorrhage has always been a determinant of outcome in ICH. This has ramifications for outcomes after minimally invasive (MIS) evacuation. We present analysis of ICH outcome after endoscopic evacuation stratified by hemorrhage location. METHODS Minimally invasive endoscopic ICH evacuation was performed on patients with supratentorial ICH who fit previously published clinical criteria including age = 18, National Institutes of Health Stroke Scale (NIHSS) = 6, hematoma volume = 15, and baseline modified Rankin Score (mRS) = 3 with a computed tomography angiography (CTA) negative for vascular malformation. Retrospective review was performed on patients who were treated in a single health system from December 2015 to August 2018. Hematoma location was stratified as deep or lobar. Univariate analysis and multivariate logistic regression were performed on demographic, radiographic, and clinical outcomes including the location variable with 6 mo mRS as the primary outcome measure. RESULTS Univariate analysis revealed patients with lobar hemorrhage had significantly better initial admission Glasgow Coma Scale (GCS) (11.7 vs 8.9, P < .0001) and NIHSS score (13.7 vs 19.6, P < .0001) but significantly higher preoperative volume (64.1 vs 41.4, P = .001). Those with lobar hemorrhage also had significantly lower neurosurgical and hospital length of stay (8.1 vs 12.9, P = .003 and 16.9 vs 29.0, P = .02, respectively) and higher rate of 6 mo functional independence as defined by mRS 0 to 3 (68.6% vs 31.2%, P = .001). Multivariate analysis showed lobar location was a significant predictor of functional independence at 6 mo (OR 12.8, P = .003). CONCLUSION In our experience, lobar hemorrhage is a predictor of good outcome after endoscopic ICH evacuation. Current and future trials may benefit from stricter patient selection and further studies are needed to confirm the effect of hemorrhage location on outcome.

Vascular Parkinsonism and Cognitive Impairment without Lobar Hemorrhage related to Cerebral Amyloid Angiopathy

Clinical recognition of Cerebral Amyloid Angiopathy is difficult due to clinical and imagiological heterogeneity. The Modified Boston Criteria for diagnosis of ‘probable Cerebral Amyloid Angiopathy’ pathologically validated in 2010 had an increase in sensitivity with only a modest decrease in specificity. Following case illustrates a diagnostic challenge to an elderly patient with vascular risk factors, neurodegenerative symptomatology with multiple cerebral vascular lesions (ischemic and hemorrhagic, without lobar hemorrhage). The use of a non-invasive amyloid marker would be useful in atypical clinical courses of patients with Cerebral Amyloid Angiopathy.