Impact of white matter hyperintensities on structural connectivity and cognition in cognitively intact ADNI participants.

We used indirect brain mapping with virtual lesion tractography to test the hypothesis that the extent of white matter tract disconnection due to white matter hyperintensities (WMH) is associated with corresponding tract-specific cognitive performance decrements. To estimate tract disconnection, WMH masks were extracted from FLAIR MRI data of 481 cognitively intact participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) and used as regions of avoidance for fiber tracking in diffusion MRI data from 50 healthy young participants from the Human Connectome Project. Estimated tract disconnection in the right inferior fronto-occipital fasciculus, right frontal aslant tract, and right superior longitudinal fasciculus mediated the effects of WMH volume on executive function. Estimated tract disconnection in the left uncinate fasciculus mediated the effects of WMH volume on memory and in the right frontal aslant tract on language. In a subset of ADNI control participants with amyloid data, positive status increased the probability of periventricular WMH and moderated the relationship between WMH burden and tract disconnection in executive function performance.

Young versus older subject diffusion magnetic resonance imaging data for virtual white matter lesion tractography.

White matter hyperintensity (WMH) lesions on T2 fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) and changes in adjacent normal-appearing white matter can disrupt computerized tract reconstruction and result in inaccurate measures of structural brain connectivity. The virtual lesion approach provides an alternative strategy for estimating structural connectivity changes due to WMH. To assess the impact of using young versus older subject diffusion MRI data for virtual lesion tractography, we leveraged recently available diffusion MRI data from the Human Connectome Project (HCP) Lifespan database. Neuroimaging data from 50 healthy young (39.2 ± 1.6 years) and 46 healthy older (74.2 ± 2.5 years) subjects were obtained from the publicly available HCP-Aging database. Three WMH masks with low, moderate, and high lesion burdens were extracted from the WMH lesion frequency map of locally acquired FLAIR MRI data. Deterministic tractography was conducted to extract streamlines in 21 WM bundles with and without the WMH masks as regions of avoidance in both young and older cohorts. For intact tractography without virtual lesion masks, 7 out of 21 WM pathways showed a significantly lower number of streamlines in older subjects compared to young subjects. A decrease in streamline count with higher native lesion burden was found in corpus callosum, corticostriatal tract, and fornix pathways. Comparable percentages of affected streamlines were obtained in young and older groups with virtual lesion tractography using the three WMH lesion masks of increasing severity. We conclude that using normative diffusion MRI data from young subjects for virtual lesion tractography of WMH is, in most cases, preferable to using age-matched normative data.

Anticoagulation under-utilization in atrial fibrillation patients is responsible for a large proportion of strokes requiring endovascular therapy.

OBJECTIVES: Atrial fibrillation (AF) is responsible for 30-50% of large strokes requiring endovascular thrombectomy (EVT). Anticoagulation (AC) underutilization is a common source of AF-related stroke. We compared antithrombotic medications among stroke patients with AF that did or did not undergo EVT to determine if AC underutilization disproportionately results in strokes requiring EVT, while quantifying the proportion of likely preventable thrombectomies. METHODS: This retrospective single-center cohort included consecutive patients admitted with acute ischemic stroke between 2016 and 2021. Patients were categorized based on the presence of AF, and pre-admission antithrombotic medications were compared between those who underwent EVT and those who didn't. The reason for not being on AC was abstracted from the medical record, and patients were categorized as either AC eligible or AC contraindicated. RESULTS: Of 3092 acute ischemic stroke patients, 644 had a history of AF, 213 of whom underwent EVT. Patients who required EVT were more likely to not be taking any antithrombotics prior to admission (34% vs 24%, p=0.007) or have subtherapeutic INR on admission if taking warfarin (83% vs 63%; p = 0.046). Among the AF-EVT patients, 44% were taking AC, and only 31% were adequately anticoagulated. Only 8% of AF-EVT patients who were not on pre-admission AC had a clear contraindication, and 94% were ultimately discharged on AC. CONCLUSIONS: Lack of antithrombotic therapy in AF patients disproportionately contributes to strokes requiring EVT. A small minority of AF patients have contraindications to AC, so adequate anticoagulation can prevent a remarkable number of strokes requiring EVT.

SARS-CoV-2 infection might be a predictor of mortality in intracerebral hemorrhage.

BACKGROUND: SARS-CoV-2 infection may be associated with uncommon complications such as intracerebral hemorrhage (ICH), with a high mortality rate. We compared a series of hospitalized ICH cases infected with SARS-CoV-2 with a non-SARS-CoV-2 infected control group and evaluated if the SARS-CoV-2 infection is a predictor of mortality in ICH patients. METHODS: In a multinational retrospective study, 63 cases of ICH in SARS-CoV-2 infected patients admitted to 13 tertiary centers from the beginning of the pandemic were collected. We compared the clinical and radiological characteristics and in-hospital mortality of these patients with a control group of non-SARS-CoV-2 infected ICH patients of a previous cohort from the country where the majority of cases were recruited. RESULTS: Among 63 ICH patients with SARS-CoV-2 infection, 23 (36.5%) were women. Compared to the non-SARS-CoV-2 infected control group, in SARS-CoV-2 infected patients, ICH occurred at a younger age (61.4 ± 18.1 years versus 66.8 ± 16.2 years, P = 0.044). These patients had higher median ICH scores ([3 (IQR 2-4)] versus [2 (IQR 1-3)], P = 0.025), a more frequent history of diabetes (34% versus 16%, P = 0.007), and lower platelet counts (177.8 ± 77.8 × 109/L versus 240.5 ± 79.3 × 109/L, P < 0.001). The in-hospital mortality was not significantly different between cases and controls (65% versus 62%, P = 0.658) in univariate analysis; however, SARS-CoV-2 infection was significantly associated with in-hospital mortality (aOR = 4.3, 95% CI: 1.28-14.52) in multivariable analysis adjusting for potential confounders. CONCLUSION: Infection with SARS-CoV-2 may be associated with increased odds of in-hospital mortality in ICH patients.

The Hospitalization Rate of Cerebral Venous Sinus Thrombosis before and during COVID-19 Pandemic Era: A Single-Center Retrospective Cohort Study.

OBJECTIVES: There are several reports of the association between SARS-CoV-2 infection (COVID-19) and cerebral venous sinus thrombosis (CVST). In this study, we aimed to compare the hospitalization rate of CVST before and during the COVID-19 pandemic (before vaccination program). MATERIALS AND METHODS: In this retrospective cohort study, the hospitalization rate of adult CVST patients in Namazi hospital, a tertiary referral center in the south of Iran, was compared in two periods of time. We defined March 2018 to March 2019 as the pre-COVID-19 period and March 2020 to March 2021 as the COVID-19 period. RESULTS: 50 and 77 adult CVST patients were hospitalized in the pre-COVID-19 and COVID-19 periods, respectively. The crude CVST hospitalization rate increased from 14.33 in the pre-COVID-19 period to 21.7 per million in the COVID-19 era (P = 0.021). However, after age and sex adjustment, the incremental trend in hospitalization rate was not significant (95% CrI: -2.2, 5.14). Patients > 50-year-old were more often hospitalized in the COVID-19 period (P = 0.042). SARS-CoV-2 PCR test was done in 49.3% out of all COVID-19 period patients, which were positive in 6.5%. Modified Rankin Scale (mRS) score ≥3 at three-month follow-up was associated with age (P = 0.015) and malignancy (P = 0.014) in pre-COVID period; and was associated with age (P = 0.025), altered mental status on admission time (P<0.001), malignancy (P = 0.041) and COVID-19 infection (P = 0.008) in COVID-19 period. CONCLUSION: Since there was a more dismal outcome in COVID-19 associated CVST, a high index of suspicion for CVST among COVID-19 positive is recommended.

Thrombolysis for stroke in elderly in the late window period.

OBJECTIVES: Safety of intravenous thrombolysis (IVT) within 3-4.5 hours of stroke onset in patients ≥80 years is still disputable. We evaluated the association of symptom onset-to-treatment time (SOTT) with the symptomatic intracranial hemorrhage (sICH), poor outcome, and mortality in patients≥80 years. MATERIALS AND METHODS: In a retrospective study, patients treated with IVT following stroke were registered. Outcomes were poor outcome (mRS>2), sICH/ECASS-2, and in-hospital mortality. We compared the patients≥80 years who received IVT within 3 hours with those receiving IVT within 3-4.5 hours. We further compared the patients who were <80 years with those ≥80 years and SOTT of 3-4.5 hours. RESULTS: Of 834 patients, 265 aged over 80. In those above 80 and in multivariable analysis, the associations of SOTT with poor outcome (aOR: 1.401, CI: 0.503-3.903, p=0.519), sICH (aOR=2.50, CI=0.76-8.26, p= 0.132) and mortality (aOR=1.12, CI=0.39-3.25, p= 0.833) were not significant. 106 patients received IVT within 3-4.5 hours. In multivariable analysis, the associations of age (≥80 versus <80) with poor outcome (aOR=1.87, CI=0.65-5.37, p=0.246), sICH (aOR=0.65, CI=0.14-3.11, p=0.590), and mortality (aOR=0.87, 95% CI=0.16-4.57, p=0.867) were not significant in patients with SOTT of 3-4.5 hours. CONCLUSION: IVT within 3-4.5 hours in patients ≥80 years is not associated with increased sICH, poor outcome, and mortality compared to the early time window, and also compared to the younger patients in 3-4.5 hours window period. The decision of IVT administration in this age group should not be made solely on the basis of stroke onset timing.

Transcranial Doppler and magnetic resonance angiography assessment of intracranial stenosis: An analysis of screening modalities.

BACKGROUND: Time-of-flight (TOF) magnetic resonance angiography (MRA) of the head and transcranial Doppler (TCD) are used to diagnose intracranial stenosis, an important cause of ischemic stroke. We aimed to compare TCD findings with TOF-MRA results in a population of patients with symptoms of cerebrovascular disease in whom both tests were done within a short intervening period of each other. METHODS: This is a retrospective, single-center study. Among adult patients referred for symptoms of cerebrovascular disease in both outpatient and inpatient settings, those who received a TCD with adequate insonation of all intracranial arteries and underwent MRA within 3 months intervals of TCD were included in this study. We evaluated the agreement between the results of these two modalities, and also assessed sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of TCD through receiver-operating characteristic (ROC) curve analysis, while MRA considered as a comparator. RESULTS: Among eighty included patients, 720 arteries were examined. An overall significant agreement of 96.5% was observed between TCD and MRA (Kappa = 0.377, P < 0.001). Compared to MRA, TCD had sensitivity of 42.1%, specificity of 99.6%, PPV of 72.7%, and NPV of 98.4% (ROC area: 0.708 [0.594-0.822]). TCD is specifically accurate in evaluating middle cerebral artery (MCA) (ROC area = 0.83). CONCLUSIONS: The high NPV of TCD in our study indicates the utility of TCD as a diagnostic test to exclude the presence of intracranial stenosis. This study supports TCD as a convenient, safe, and reproducible imaging modality applicable in the screening of intracranial stenosis, especially to evaluate MCA.

Cerebral venous sinus thrombosis associated with SARS-CoV-2; a multinational case series.

BACKGROUND: SARS-CoV-2 induced coagulopathy can lead to thrombotic complications such as stroke. Cerebral venous sinus thrombosis (CVST) is a less common type of stroke which might be triggered by COVID-19. We present a series of CVST cases with SARS-CoV-2 infection. METHODS: In a multinational retrospective study, we collected all cases of CVST in SARS-CoV-2 infected patients admitted to nine tertiary stroke centers from the beginning of the pandemic to June 30th, 2020. We compared the demographics, clinical and radiological characteristics, risk factors, and outcome of these patients with a control group of non-SARS-CoV-2 infected CVST patients in the same seasonal period of the years 2012-2016 from the country where the majority of cases were recruited. RESULTS: A total of 13 patients fulfilled the inclusion criteria (62% women, mean age 50.9 ± 11.2 years). Six patients were discharged with good outcomes (mRS ≤ 2) and three patients died in hospital. Compared to the control group, the SARS-CoV-2 infected patients were significantly older (50.9 versus 36.7 years, p < 0.001), had a lower rate of identified CVST risk factors (23.1% versus 84.2%, p < 0.001), had more frequent cortical vein involvement (38.5% versus 10.5%, p: 0.025), and a non-significant higher rate of in-hospital mortality (23.1% versus 5.3%, p: 0.073). CONCLUSION: CVST should be considered as potential comorbidity in SARS-CoV-2 infected patients presenting with neurological symptoms. Our data suggest that compared to non-SARS-CoV-2 infected patients, CVST occurs in older patients, with lower rates of known CVST risk factors and might lead to a poorer outcome in the SARS-CoV-2 infected group.

A history of the path towards imaging of the brain: From skull radiography through cerebral angiography.

This publication reviews the steps in the path towards obtaining a complete image of the brain. Up to the 1920s, plain X-ray films could demonstrate only calcified tumors, shifts in midline position of a calcified pineal gland due to a mass in the cranium, or foreign metallic objects within the skull. Walter Dandy reported in 1918 that he visualized cerebral ventricles by introducing air as a contrast agent through a trocar into one of the occipital lobes or the right frontal horn of the ventricular system. Dandy localized lesions that distorted or shifted the ventricles. In 1920, Dandy placed air by lumbar puncture into the spinal subarachnoid space that could visualize the brain and entire ventricles. Antonio Egas Moniz with the assistance of his neurosurgeon colleague, Almeida Lima, obtained X-ray images of cerebral arteries of dogs and decapitated human heads from corpses after injecting strontium bromide into their carotid arteries. Satisfied by these experiments, Moniz injected strontium bromide directly into carotid arteries of five patients which failed to show intracranial vessels. In the sixth patient, intracranial arteries were outlined but that patient died of cerebral thrombosis presumably due to the hyper-osmolality of that contrast agent. Finally, on June 18, 1927, Moniz injected 22% sodium iodine into a 20-year-old man and obtained clear visualization of his carotid artery and intracerebral branches after temporarily occluding the artery with a ligature. Direct percutaneous puncture of the cervical carotid artery remained the primary technique unto the 1960s to visualize intracranial blood vessels until Seldinger's technique was introduced in 1953. Computerized axial tomography (CAT) and magnetic resonance imaging (MRI) replaced cerebral arteriography for localizing tumors and epidural or subdural hemorrhage. However, angiography is used currently for embolization of aneurysms and removal of thrombi or emboli in patients with acute stroke.

Clinical and radiological characteristics and predictors of outcome of cerebral venous sinus thrombosis, a hospital-based study.

Cerebral venous sinus thrombosis is an uncommon cause of stroke, which is more prevalent in Iran and the Middle East. We aimed to assess the etiology, radiologic, and clinical manifestations of cerebral venous sinus thrombosis, specifically the predictors of patients' outcome in Namazi hospital, Shiraz, Iran. In this retrospective study, we included all adult patients with the diagnosis of cerebral venous sinus thrombosis, who were admitted in hospital, from 2012 to 2016. Demographic data, radiologic findings, clinical presentation, risk factors, treatment, and outcome according to modified Rankin Scale (mRS) on discharge were assessed and the factors associated with hospital fatality and poor outcome (mRS > 2) were investigated through univariable and multivariable analyses. Adjusted odds ratio (OR), 95% confidence interval (CI), and p values were reported. Among 174 patients, 128 (73.6%) were female. The mean age was 37.8 ± 11.2. Total of 39 patients (22.4%) had poor discharge outcome and nine patients died in hospital. Older age (OR = 1.041, CI = 1.000-1.08), decreased level of consciousness (OR = 5.46, CI = 2.17-13.72), focal neurologic deficit (OR = 5.63, CI = 2.14-14.77), and expansion of intracranial hemorrhage (ICH) (OR = 9.13, CI = 1.96-42.64) were predictors of poor outcome according to the logistic regression model. Older age (p = 0.02), focal neurologic deficit (p = 0.005), deep venous system thrombosis (p = 0.002), early intracranial hemorrhage (p = 0.049), delayed hemorrhage (p = 0.007) and hemorrhage expansion (p = 0.002), infratentorial hemorrhagic lesions (p = 0.005), and higher CRP (p = 0.011) were associated with hospital fatality. The patients with gynecologic risk factors were at lower risk of hospital death (p = 0.005). Age, decreased consciousness and focal neurological deficit on admission, and expanded intracranial hemorrhage are predictors of poor outcome. The patients who are at higher risk of unfavorable outcome should be recognized and closely monitored.

Early, delayed, and expanded intracranial hemorrhage in cerebral venous thrombosis.

OBJECTIVES: One of the most important prognostic factors of cerebral venous sinus thrombosis (CVST) is intracranial hemorrhage (ICH). We studied the risk factors, clinical, and radiologic characteristics of early, delayed, and expanded ICH in Iranian patients with CVST. MATERIALS AND METHODS: In a retrospective study, from August 2012 to September 2016, all adult patients with a confirmed diagnosis of CVST were recruited. Demographic, clinical, and radiologic characteristics of the patients were recorded. The predictors of early, delayed, and expanded ICH were assessed through logistic regression analysis. RESULTS: Among 174 eligible patients, 35.1% of the patients had early ICH. Delayed and expanded hemorrhage occurred in 5% and 7.4% of the patients, respectively. Higher age was a risk factor (odds ratio [OR] = 1.038, 95% confidence interval [CI] = 1.008-1.069), and involvement of multiple sinuses/veins was associated with lower risk of early ICH (OR = 0.432, CI = 0.226-0.827). The risk of delayed ICH was higher in the patients with early hemorrhage (OR = 4.44, CI: 0.990-19.94), men (OR = 4.18, CI: 0.919-19.05), and those with a focal neurologic deficit on admission (OR = 16.05, CI: 1.82-141.39). Acute onset was the predictor of the expansion of early ICH (OR = 8.92, CI: 1.81-43.77), whereas female gender-related conditions were associated with a lower risk of hemorrhage expansion (OR = 0.138, CI: 0.025-0.770). Administration of anticoagulants was associated with neither delayed (P value = .140) nor expanded hemorrhage (P-value = .623). CONCLUSIONS: Male gender, early hemorrhages, acute onset, and presence of focal neurologic deficit are the risk factors for delayed and/or expanded hemorrhages in the patients with CVST.