Volumetric White Matter Hyperintensity Ranges Correspond to Fazekas Scores on Brain MRI.

INTRODUCTION: White matter hyperintensity (WMH) is an abnormal T2 signal in the deep and subcortical white matter visualized on MRI associated with hypertension, cerebrovascular disease, and aging. The Fazekas (Fz) scoring system is a commonly used qualitative tool to assess the severity of WMH. While studies have compared Fazekas scores to other scoring methods, the comparison of Fazekas scores and volume of WMH using current semiautomated volumetric techniques has not been studied. METHODS: We reviewed MRI studies acquired at our institution between 2015 and 2017. Relative WMH was scored by one author trained in Fazekas scoring. A board certified neuroradiologist scored them independently for confirmation. Manual segmentations of WMH were completed using 3D Slicer 4.9. A 3D model was formed to quantify WMH in milliliters (mL). ANOVA tests were performed to determine the association of Fazekas scores with corresponding WMH volumes. RESULTS: Among the 198 patients in our study, WMH were visualized in 163 (Fz1: n=66; Fz2: n=49; Fz3: n=48). WMH volumes significantly differed according to Fazekas score (F = 141.1, p<0.001), with increasing WMHV associated with higher Fazekas scores: Fz1, range 0.1-8.3 mL (mean 3.7, SD 2.3); Fz2, range 6.0-17.7 mL (mean 10.8, SD 3.1); Fz3, range 14.2-77.2 mL (mean 35.2, SD 17.9); and Fz3 (excluding 11 outliers above 50 mL), 14.2-47.0 mL (mean 27.1, SD 8.9). CONCLUSION: Fazekas scores correspond with distinct ranges of WMH volume with relatively little overlap, but scores based on volumes are more efficacious. A modified Fazekas from 0-4 should be considered.

Partial Recanalization of a Large Vessel Acute Ischemic Stroke With Intravenous Tissue Plasminogen Activator, Followed by Systemic Anticoagulation, in the Setting of COVID-19-Induced Hypercoagulability: A Case Report.

We report on the use of systemic heparinization following thrombolysis with intravenous tissue plasminogen activator (t-PA) for acute ischemic large vessel stroke, in the setting of COVID-19-induced hypercoagulability, with partial recanalization of the internal carotid artery. Off-label systemic heparinization was used within 12 hours of t-PA administration, after extensive multidisciplinary collaboration and family discussion, given evidence of severe hypercoagulability. We conclude that thrombolysis should be considered for all eligible patients with suspected or confirmed COVID-19 and acute ischemic stroke, and systemic anticoagulation, although with inherent risks, may be a useful adjunct treatment modality in selected patients who have received intravenous thrombolysis.

Vascular Neurologists' Involvement in the Care of Medicare Patients With Ischemic Stroke.

BACKGROUND AND PURPOSE: We sought to determine the proportion of patients with ischemic stroke evaluated by vascular neurologists in the United States. METHODS: Using 2009 to 2015 claims from a 5% nationally representative sample of Medicare beneficiaries, we identified patients ≥65 years of age who were hospitalized for ischemic stroke. We ascertained the proportion of patients evaluated during the hospitalization or within 90 days of discharge by nonvascular and vascular neurologists. We assessed the relationship between county-level socioeconomic status and the likelihood of neurologist evaluation and between neurologist evaluation and diagnostic testing. RESULTS: Among 66 989 patients with ischemic stroke, 37 820 (56.5%) were evaluated by a nonvascular neurologist and 11 700 (17.5%) by a board-certified vascular neurologist. Across increasing quartiles of county socioeconomic advantage, the proportion of patients evaluated by a vascular neurologist was 12.2%, 16.5%, 19.8%, and 23.0%. Relative to evaluation by a nonvascular neurologist, evaluation by a vascular neurologist was associated with a higher likelihood of postdischarge heart rhythm monitoring (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.6-1.9), echocardiography (OR, 1.4; 95% CI, 1.3-1.4), cervical vessel imaging (OR, 1.3; 95% CI, 1.2-1.3), and intracranial vessel imaging (OR, 2.1; 95% CI, 2.0-2.2). CONCLUSIONS: In a nationally representative cohort of Medicare beneficiaries, we found that about three quarters of patients with ischemic stroke were evaluated by a neurologist, and about one-sixth were evaluated by a vascular neurologist. Patients who were evaluated by a vascular neurologist were significantly more likely to undergo diagnostic testing.

Serum alpha-1 antitrypsin in acute ischemic stroke: A prospective pilot study.

BACKGROUND: Alpha-1 antitrypsin (AAT) is a potent anti-protease enzyme which may play a role in arterial wall stability. A variant of its encoding gene has been recently linked to ischemic stroke due to large artery atherosclerosis (LAA). We sought to explore potential relationships between ischemic stroke mechanisms, atherosclerosis burden and serum AAT levels. METHODS: We performed a prospective observational study of consecutive patients with acute ischemic stroke who were admitted to an academic comprehensive stroke center over a three-month period. Blood samples were collected within 24 h of hospital admission, and stroke subtype classification was determined based on modified TOAST criteria. Modified Woodcock scoring system was used to quantify calcification of major cervico-cranial arteries as a surrogate for atherosclerosis burden. Linear regression analysis was used to assess the association between serum AAT levels and calcification scores, both as continuous variables. RESULTS: Among eighteen patients met our inclusion criteria and were enrolled in our study, 10 patients (56%) were men; mean age was 66 (SD 12.5); median NIH stroke scale was 4 (IQR 9.5); 8 patients (44%) had stroke due to LAA. The median serum level of AAT was 140 mg/dl (IQR 41.7) for patients with LAA-related stroke, and 148.5 mg/dl (IQR 37.7) for patients with other stroke mechanisms (p = 0.26). Higher serum AAT levels was associated with lower modified Woodcock calcification scores. (p-value = 0.038) CONCLUSIONS: Measurement of AAT levels in patients with acute stroke is feasible, and there may be associations between AAT levels and stroke mechanism that warrant further study in larger samples.

Perfusion imaging and recurrent cerebrovascular events in intracranial atherosclerotic disease or carotid occlusion.

Background Large vessel disease stroke subtype carries the highest risk of early recurrent stroke. In this study we aim to look at the association between impaired perfusion and early stroke recurrence in patients with intracranial atherosclerotic disease or total cervical carotid occlusion. Methods This is a retrospective study from a comprehensive stroke center where we included consecutive patients 18 years or older with intracranial atherosclerotic disease or total cervical carotid occlusion admitted with a diagnosis of ischemic stroke within 24 h from symptom onset with National Institute Health Stroke Scale < 15, between 1 December 2016 and 30 June 2017. Patients with (1) evidence of ≥ 50% stenosis of a large intracranial artery or total carotid artery occlusion, (2) symptoms referable to the territory of the affected artery, and (3) perfusion imaging data using the RAPID processing software were included. The primary predictor was unfavorable perfusion imaging defined as Tmax > 6 s mismatch volume (penumbra volume-infarct volume) of 15 ml or more. The outcome was recurrent cerebrovascular events at 90 days defined as worsening or new neurological symptoms in the absence of a nonvascular cause attributable to the decline, or new infarct or infarct extension in the territory of the affected artery. We used Cox proportional hazards models to determine the association between impaired perfusion and recurrent cerebrovascular events. Results Sixty-two patients met our inclusion criteria; mean age 66.4 ± 13.1 years, 64.5% male (40/62) and 50.0% (31/62) with intracranial atherosclerotic disease. When compared to patients with favorable perfusion pattern, patients with unfavorable perfusion pattern were more likely to have recurrent cerebrovascular events (55.6% (10/18) versus 9.1% (4/44), p < 0.001). This association persisted after adjusting for potential confounders (adjusted hazard ratio 10.44, 95% confidence interval 2.30-47.42, p = 0.002). Conclusion Perfusion mismatch predicts recurrent cerebrovascular events in patients with ischemic stroke due to intracranial atherosclerotic disease or total cervical carotid occlusion. Studies are needed to determine the utility of revascularization strategies in this patient population.

Insular infarction in subdural hematoma: A case series and pathophysiologic review.

Subdural hematoma (SDH) is among the most common conditions managed by neurologists and neurosurgeons. As SDH incidence rates increase, a wider spectrum of SDH related complications have become evident. We prospectively identified a series of three patients with similar patterns of ipsilateral insular diffusion weighted imaging (DWI) hyperintensity associated with subdural hematoma. Detailed chart review was performed, and cases are described in relation to anatomy and proposed pathophysiology of venous hypertension and arterial vasospasm. The DWI changes were evident in all cases where clinical deficits following SDH evacuation were out of proportion to computed tomography findings. Therefore SDH-associated insular infarction may be a marker of greater disease severity, and further study of management and outcomes is needed.

Mechanical embolectomy for acute ischemic stroke beyond six hours from symptom onset using MRI based perfusion imaging.

INTRODUCTION: There is very limited data on the use of MRI based perfusion imaging to select patients with acute ischemic stroke and large vessel occlusion (LVO) for intraarterial therapy beyond 6h from onset. Our aim is to report the outcome of patients with acute ischemic stroke and large artery occlusion who presented beyond 6h from onset, had favorable MRI imaging profile, and underwent mechanical embolectomy. METHODS: This is a single institution (Rhode Island Hospital) retrospective study between December 1st, 2015, and July 30th, 2016 that included patients with acute ischemic stroke and proximal LVO with CT ASPECTS of 6 or more and 6-24h from symptom onset who were assessed for mechanical embolectomy using MRI based perfusion imaging. Favorable imaging profile was defined based on prior studies as 1) DWI lesion volume (as defined as apparent diffusion coefficient<620×10-6mm2/s) of 70ml or less; 2) Penumbra volume (as defined by volume of tissue with Tmax>6s) of 15ml or greater; 3) A mismatch ratio of 1.8 or more; and 4) Volume of tissue with perfusion lesion with Tmax>10s is <100ml. Good outcome was defined as a 90-day mRS≤2. RESULTS: 41 patients met the inclusion criteria; 22 (53.7%) had favorable imaging profile and underwent mechanical embolectomy. The rate of good outcomes in this series was similar to that in a patient level pooled meta-analysis of the recent endovascular trials (63.6% vs. 46%, p=0.13). None of the patients in our cohort had symptomatic intracereberal hemorrhage. CONCLUSIONS: MRI perfusion based imaging may help select patients with acute ischemic stroke and proximal emergent LVO for embolectomy beyond the treatment window used in most endovascular trials. This provides compelling evidence for stroke centers to participate in ongoing trials using advanced imaging to study endovascular treatment in this patient population.

Characterizing age-related changes in remembering the past and imagining the future.

When remembering past events or imagining possible future events, older adults generate fewer episodic details than do younger adults. These results support the constructive episodic simulation hypothesis: deficits in retrieving episodic details underlie changes during memory and imagination. To examine the extent of this age-related reduction in specificity, we compared performance on memory and imagination tasks to a picture description task that does not require episodic memory. In two experiments, older adults exhibited comparable specificity reductions across all conditions. These findings emphasize the need to consider age-related changes in imagination and memory in a broader theoretical context.

Episodic simulation of future events is impaired in mild Alzheimer's disease.

Recent neuroimaging studies have demonstrated that both remembering the past and simulating the future activate a core neural network including the medial temporal lobes. Regions of this network, in particular the medial temporal lobes, are prime sites for amyloid deposition and are structurally and functionally compromised in Alzheimer's disease (AD). While we know some functions of this core network, specifically episodic autobiographical memory, are impaired in AD, no study has examined whether future episodic simulation is similarly impaired. We tested the ability of sixteen AD patients and sixteen age-matched controls to generate past and future autobiographical events using an adapted version of the Autobiographical Interview. Participants also generated five remote autobiographical memories from across the lifespan. Event transcriptions were segmented into distinct details, classified as either internal (episodic) or external (non-episodic). AD patients exhibited deficits in both remembering past events and simulating future events, generating fewer internal and external episodic details than healthy older controls. The internal and external detail scores were strongly correlated across past and future events, providing further evidence of the close linkages between the mental representations of past and future.