Badi, Mohammed K.

Background: Migraine is associated with neuroimaging differences in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). However, it is unknown if migraine-related disability (MRD) or if calcitonin gene-related peptide (CGRP), a vasoactive peptide important in migraine pathology, have radiographic implications. The aims of this study were to identify whether MRD or interictal serum CGRP levels impacted neuroimaging findings for those with CADASIL. Materials and Methods: A cross-sectional analysis was performed. The primary outcomes were neuroimaging differences associated with MRD among those with migraine or interictal serum CGRP levels of those with and without migraine. MRD was defined by 2 migraine disability scales (Migraine Disability Assessment, Headache Impact Test-6). Retrospective brain magnetic resonance imaging was reviewed (average 1.7 ± 2.0 y before enrollment). Rank-sum and χ2 tests were used. Results: Those with migraine (n=25, vs. n=14 without) were younger [median 49 (25 to 82) y vs. 60 (31 to 82) y, P<0.007], had fewer cerebral microbleeds (0 to 31 vs. 0 to 50, P=0.02) and less frequently had anterior temporal lobe T2 hyperintensities [68% (17/25) vs 100% (14/14), P=0.02]. MRD scale outcomes had no significant radiographic associations. Interictal serum CGRP did not differ (migraine: n=18, 27.0±9.6 pg/mL vs. no migraine: n=10, 26.8±15.7 pg/mL, P=0.965). Conclusions: Migraine may forestall microangiopathy in CADASIL, though possibly independent of severity as measured by MRD. Interictal serum CGRP did not differ in our cohort suggesting CGRP may not be vital to migraine pathophysiology in CADASIL. Larger studies are needed to account for age differences.

Introduction: Collateral circulation plays a crucial role in determining the extent of brain tissue ischemia and functional outcome in large vessel occlusive (LVO) stroke. Heart failure (HF) is known to cause cerebral hypoperfusion, yet the relationship between HF and robustness of collateral flow has not been well described. Here we hypothesized that HF is associated with poor collateral flow and functional outcome in patients presenting with LVO treated with mechanical thrombectomy (MT). Methods: A single center retrospective study of patients presenting with LVO ischemic stroke who underwent MT between 2012-2020 was done. Single-phase CTA of head prior to MT was used to assess collateral status with poor status defined as ≤ 50% filling and good status as >50% filling. Classification of HF by left ventricular ejection fraction (LVEF) on echocardiogram was used where HF with reduced ejection fraction (HFrEF) had LVEF ≤40%, HF with preserved EF (HFpEF) had LVEF ≥50% with evidence of structural heart disease, and no HF was LVEF≥50% without structural heart disease. Functional outcome was modified Rankin scale (mRS) at 90 days with scores of 0-2 representing good outcome and 3-6 representing poor outcome. Multivariable logistic regression analyses were performed to evaluate the association between HF and poor collaterals after adjusting for vascular risk factors. Results: We identified 235 patients, mean age was 69 ±15 years, median NIHSS was 18, and 45.5% had HF (HFrEF 12.8%, HFmrEF 4.7%, HFpEF 28.1%) while 54.5% had no HF. Poor collaterals were seen in 47.7%, and those with HF were likely to have poor collaterals compared to those without HF (56.1% vs 35.1%, P=.001). There was a dose-dependent relationship between severity of HF and poor collaterals: adjusted odds of poor collaterals were 1.63 and 2.45 in HFpEF and HFrEF, compared to those without HF (trend p=.018). Patients with poor collaterals were likely to have poor outcome at 3 months compared to those with good collaterals (75.0% vs 57.8%; p=.015). Conclusion: Patients with HFrEF were twice as likely to have poor collaterals. This study demonstrated a likely mechanism for poor outcomes seen in ischemic stroke with HF, future studies may explore whether optimization of HF may augment collaterals to improve outcomes.

Objective: To characterize migraine in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Background: CADASIL serves as a key model of a monoallelic stroke disease. A portion of patients have coexistent migraine with aura, yet the relationship between migraine and the pathophysiology of CADASIL is poorly understood. Design/Methods: We performed a prospective study of adults with a confirmed genetic diagnosis of CADASIL, age-matched controls with migraine with aura (MA), and headache-free controls. The Migraine Disability Assessment Questionnaire (MIDAS) and Headache Impact Test (HIT-6) were used to quantify migraine-related disability. Subjects were followed for one year after enrollment. Results: We enrolled 88 subjects, which included 33 subjects with CADASIL, 32 subjects without CADASIL but with MA, and 23 control subjects without CADASIL or MA. Mean age was 53.6 (range, 22-86), 64.8% (57/88) were females, and 83% (73/88) were white. Of the CADASIL subjects, 61% (20/33) suffered from MA (CAD/+MA). Aura semiology amongst the CAD/+MA and MA patients were as follows: visual (80% vs 81%), sensory (75% vs 81%), speech (75% vs 50%), motor (30% vs 50%), brain stem (60% vs 81%) and retinal (30% vs 25%). Mean MIDAS scores at enrollment were comparable between the CAD/+MA and MA populations (32.3 vs 33.5), as were mean HIT-6 scores (56.3 vs 56.9). Discussion: These preliminary results do not show a significant difference in migraine disability between CADASIL migraineurs and chronic migraineurs. Minor differences were observed in aura distribution between the two groups, although further investigations are needed to better understand the underlying pathology of CADASIL and migraine.

Background and Purpose: To describe the neurological and cerebrovascular findings in patients who tested positive for SARS-CoV-2 and underwent head imaging in ambulatory and inpatient settings. Methods: Consecutive patients aged ≥18 years with SARS-CoV-2 infection diagnosed or treated at Mayo Clinic sites from 3/11/2020 to 7/23/2020 with head CT or brain MRI within 30 days of SARS-CoV-2 diagnosis were included. Demographics, medical history, indication for SARS-CoV-2 testing, neurologic symptoms, indication for brain imaging, neuroimaging findings, etiology of cerebrovascular events, and hospital course were abstracted from medical records. Results: Of 8,675 patients with SARS-CoV-2, 180 (2.07%) had head imaging. Mean age of the entire cohort was 42 ± 18 years, whereas mean age of those with head imaging was 62 ± 19 years. Common indications for imaging were headache (34.4%), encephalopathy (33.4%), focal neurologic symptom (16.7%), and trauma (13.9%). While 86.1% of patients who underwent head imaging had normal exams, cerebrovascular events occurred in 18 patients (0.21% of the total cohort). Of patients with cerebrovascular events, 8 (44.5%) had acute infarct; 6 (33.3%), acute intracranial hemorrhage; 5 (2.8%), subacute infarct; and 1 (0.6%) posterior reversible encephalopathy syndrome. In the thirteen patients with ischemic stroke, 6 (46.2%) had cryptogenic stroke; 3 (23.1%), other defined causes; 2 (15.4%), small vessel stroke; 1 (7.7%), large vessel stroke; and 1 (7.7%) cardioembolic stroke. Conclusion: In ambulatory and hospitalized patients with SARS-CoV-2 infection, the rate of head imaging is low, with common indications of encephalopathy and headache. Cerebrovascular events occurred rarely, and cryptogenic stroke was the most common stroke mechanism.

Plasma neurofilament light is a reliable, uniform marker to estimate neuroaxonal injury and forecast all-cause mortality across major stroke types.

Objectives: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is inherited microangiopathy characterized by recurrent subcortical infarcts. A majority of those with CADASIL report coexistent migraine with aura. The authors aim to quantitatively describe migraine-related disability within a CADASIL cohort. Methods: A cross-sectional analysis was performed in a cohort of CADASIL. The Migraine Disability Assessment (MIDAS) quantified migraine-related disability. Further metrics obtained include first and last migraine, aura semiology, and therapeutic measures. Results: Twenty-four individuals were included [63% (15/24) female individuals; mean age, 56 y; range, 34 to 81 y]. Fifty-four percent (13/24) reported migraine, whereas 46% (11/24) reporting varying degrees of migraine-related disability. MIDAS Questionnaire scores appeared bimodal: 58% (14/24) scored 0 to 5, 7% (1/24) scored 6 to 10, 7% (1/24) scored 11 to 20 and 33% (8/24) scored over 20. Severe disability was associated with the multiplicity of aura semiologies and poor response to pharmacologic prophylaxis. Conclusions: A bimodal distribution of migraine-related disability was observed. A third of individuals had a severe disability and appeared medically refractory to medical migraine prophylactic measures. This study may serve as a reference point for future trials quantitatively gauging response of novel migraine treatment strategies within this unique population.

Introduction: White matter hyperintensities (WMH) is the most prominent neuroimaging feature of small vessel disease (SVD). SVD is thought to be a result of arteriolosclerosis, chronic hypoperfusion of white matter, selective oligodendrocyte death and degeneration of myelinated fibers. The risk of ischemic stroke is significantly increased with the presence of WMH. The presence of intracranial collaterals is a strong predictor of salvageable neurological function in acute stroke; however, the factors affecting the ability to recruit collaterals are poorly understood. We wanted to study if the presence and severity of small vessel white matter disease had an adverse effect on cerebral collateral flow in acute embolic large vessel stroke. Methods: We identified a consecutive series of adult subjects with acute embolic large vessel strokes confirmed on CT angiography (CTA) from a 10-year institutional database. Patients without a brain MRI within six months of CTA were excluded. Collateral scores of the affected hemisphere were calculated on CTA using the modified Tan scale (0-4) by two independent trained reviewers and confirmed by a neuroradiologist. The WMH was quantified using the Fazekas scale (0-3) incorporating both deep and periventricular components. Areas of restricted diffusion on brain MRI in the peri-stroke period were eliminated from the assessment of Fazekas score. Spearman’s correlation tests were performed for the association between collateral scores and WMH. Results: A total of 234 patients (mean age 70±14 years, 47% [110/234] women) satisfied the inclusion criteria. The prevalence of periventricular and deep WMH was 83% and 87% respectively. Aging had a significant impact on periventricular WMH (r=0.48, p <0.001) and deep WMH (r=0.47, p <0.001). However, collateral scores exhibited no statistically significant relationship with the presence or severity of periventricular scores (r=0.08, p=0.17) or deep WMH scores (r=0.01, p=0.77). Conclusions: Our results indicate that the presence of SVD does not affect cerebral collateral flow. The vascular niche and risk factors of SVD appear to be distinct from that of intracranial vessels responsible for collateral reperfusion of ischemic territory in acute large vessel embolic stroke.