Understanding the variability of the electrophysiologic laryngeal adductor reflex.

OBJECTIVE: The laryngeal adductor reflex (LAR) is vital for airway protection and can be electrophysiologically obtained under intravenous general anesthesia (IGA). This makes the electrophysiologic LAR (eLAR) an important tool for monitoring of the vagus nerves and relevant brainstem circuitry during high-risk surgeries. We investigated the intra-class variability of normal and expected abnormal eLAR. METHODS: Repeated measures of contralateral R1 (cR1) were performed under IGA in 58 patients. Data on presence/absence of cR2 and potential confounders were also collected. Review of neuroimaging, pathology and clinical exam, allowed classification into normal and expected abnormal eLAR groups. Using univariate and multivariate analysis we studied the variability of cR1 parameters and their differences between the two groups. RESULTS: In both groups, cR1 latencies had coefficients of variation of <2%. In the abnormal group, cR1 had longer latencies, required higher activation currents and was more frequently desynchronized and unsustained; cR2 was more frequently absent. CONCLUSIONS: cR1 latencies show high analytical precision for measurements. Delayed onset, difficult to elicit, desynchronized and unsustained cR1, and absence of cR2 signal an abnormal eLAR. SIGNIFICANCE: Understanding the variability and behavior of normal and abnormal eLAR under IGA can aid in the interpretation of its changes during monitoring.

Transcranial Doppler cerebrovascular reactivity: Thresholds for clinical significance in cerebrovascular disease.

BACKGROUND AND PURPOSE: Thresholds for abnormal transcranial Doppler cerebrovascular reactivity (CVR) studies are poorly understood, especially for patients with cerebrovascular disease. Using a real-world cohort with cerebral arterial stenosis, we sought to describe a clinically significant threshold for carbon dioxide reactivity (CO2R) and vasomotor range (VMR). METHODS: CVR studies were performed during conditions of breathing room air normally, breathing 8% carbon dioxide air mixture, and hyperventilation. The mean and standard deviation (SD) of CO2R and VMR were calculated for the unaffected side in patients with unilateral stenosis; a deviation of 2 SDs below the mean was chosen as the threshold for abnormal. Receiver operating characteristic (ROC) curves for both sides for patients with unilateral and bilateral stenosis were evaluated for sensitivity (Sn) and specificity (Sp). RESULTS: A total of 133 consecutive CVR studies were performed on 62 patients with stenosis with mean±SD age 55±16 years. Comorbidities included hypertension (60%), diabetes (15%), stroke (40%), and smoking (35%). In patients with unilateral stenosis, mean±SD CO2R for the unaffected side was 1.86±0.53%, defining abnormal CO2R as <0.80%. Mean±SD CO2R for the affected side was 1.27±0.90%. The CO2R threshold predicted abnormal acetazolamide single-photon emission computed tomography (SPECT) (Sn = .73, Sp = .79), CT/MRI perfusion abnormality (Sn = .42, Sp = .77), infarction on MRI (Sn = .45, Sp = .76), and pressure-dependent exam (Sn = .50, Sp = .76). For the unaffected side, mean±SD VMR was 39.5±15.8%, defining abnormal VMR as <7.9%. For the affected side, mean±SD VMR was 26.5±17.8%. The VMR threshold predicted abnormal acetazolamide SPECT (Sn = .46, Sp = .94), infarction on MRI (Sn = .27, Sp = .94), and pressure-dependent exam (Sn = .31, Sp = .90). CONCLUSIONS: In patients with multiple vascular risk factors, a reasonable threshold for clinically significant abnormal CO2R is <0.80% and VMR is <7.9%. Noninvasive CVR may aid in diagnosing and risk stratifying patients with stenosis.

Characterizing coma in large vessel occlusion stroke.

BACKGROUND: Coma is an unresponsive state of disordered consciousness characterized by impaired arousal and awareness. The epidemiology and pathophysiology of coma in ischemic stroke has been underexplored. We sought to characterize the incidence and clinical features of coma as a presentation of large vessel occlusion (LVO) stroke. METHODS: Individuals who presented with LVO were retrospectively identified from July 2018 to December 2020. Coma was defined as an unresponsive state of impaired arousal and awareness, operationalized as a score of 3 on NIHSS item 1a. RESULTS: 28/637 (4.4%) patients with LVO stroke were identified as presenting with coma. The median NIHSS was 32 (IQR 29-34) for those with coma versus 11 (5-18) for those without (p < 0.0001). In coma, occlusion locations included basilar (13), vertebral (2), internal carotid (5), and middle cerebral (9) arteries. 8/28 were treated with endovascular thrombectomy (EVT), and 20/28 died during the admission. 65% of patients not treated with EVT had delayed presentations or large established infarcts. In models accounting for pre-stroke mRS, basilar occlusion location, intravenous thrombolysis, and EVT, coma independently increased the odds of transitioning to comfort care during admission (aOR 6.75; 95% CI 2.87,15.84; p < 0.001) and decreased the odds of 90-day mRS 0-2 (aOR 0.12; 95% CI 0.03,0.55; p = 0.007). CONCLUSIONS: It is not uncommon for patients with LVO to present with coma, and delayed recognition of LVO can lead to poor outcomes, emphasizing the need for maintaining a high index of suspicion. While more commonly thought to result from posterior LVO, coma in our cohort was similarly likely to result from anterior LVO. Efforts to improve early diagnosis and care of patients with LVO presenting with coma are crucial.

Relationship between prior statin therapy and radiological features and clinical outcomes of intracerebral hemorrhage.

OBJECTIVES: A post-hoc analysis of the ICH Deferoxamine (i-DEF) trial was performed to examine any associations pre-ICH statin use may have with ICH volume, PHE volume, and clinical outcomes. MATERIALS AND METHODS: Baseline characteristics were assessed. Various ICH and PHE parameters were measured via a quantitative, semi-automated method at baseline and follow-up CT scans 72-96 h later. A multivariable logistic regression model was created, adjusting for the variables that were significantly different on univariable analyses (p < 0.05), to assess any associations between pre-ICH statin use and measures of ICH and PHE, as well as good clinical outcome (mRS ≤2), at 90 and 180 days. RESULTS: 262 of 291 i-DEF participants had complete data available for analysis. 69 (26.3 %) used statins prior to ICH onset. Pre-ICH statin users had higher prevalences of hypertension, diabetes, and prior ischemic stroke; higher concomitant use of antihypertensives and antiplatelets; and higher blood glucose level at baseline. On univariable analyses, pre-ICH statin users had smaller baseline ICH volume and PHE volume on repeat scan, as well as smaller changes in relative PHE (rPHE) volume and edema extension distance (EED) between the baseline and repeat scans. In the multivariable analysis, none of the ICH and PHE measures or good clinical outcome was significantly associated with pre-ICH statin use. CONCLUSION: Pre-ICH statin use was not associated with measures of ICH or PHE, their growth, or clinical outcomes. These findings do not lend support to either overall protective or deleterious effects from statin use before or after ICH.

Neuroendovascular Surgery Applications in Craniocervical Trauma.

Cerebrovascular injuries resulting from blunt or penetrating trauma to the head and neck often lead to local hemorrhage and stroke. These injuries present with a wide range of manifestations, including carotid or vertebral artery dissection, pseudoaneurysm, occlusion, transection, arteriovenous fistula, carotid-cavernous fistula, epistaxis, venous sinus thrombosis, and subdural hematoma. A selective review of the literature from 1989 to 2023 was conducted to explore various neuroendovascular surgical techniques for craniocervical trauma. A PubMed search was performed using these terms: endovascular, trauma, dissection, blunt cerebrovascular injury, pseudoaneurysm, occlusion, transection, vasospasm, carotid-cavernous fistula, arteriovenous fistula, epistaxis, cerebral venous sinus thrombosis, subdural hematoma, and middle meningeal artery embolization. An increasing array of neuroendovascular procedures are currently available to treat these traumatic injuries. Coils, liquid embolics (onyx or n-butyl cyanoacrylate), and polyvinyl alcohol particles can be used to embolize lesions, while stents, mechanical thrombectomy employing stent-retrievers or aspiration catheters, and balloon occlusion tests and super selective angiography offer additional treatment options based on the specific case. Neuroendovascular techniques prove valuable when surgical options are limited, although comparative data with surgical techniques in trauma cases is limited. Further research is needed to assess the efficacy and outcomes associated with these interventions.

Left ventricular hypertrophy and left atrial size are associated with ischemic strokes among non-vitamin K antagonist oral anticoagulant users.

BACKGROUND: Ischemic strokes (IS) occurring in patients taking non-vitamin K antagonist oral anticoagulants (NOACs) are becoming increasingly more frequent. We aimed to determine the clinical, echocardiographic, and neuroimaging markers associated with developing IS in patients taking NOACs for atrial fibrillation. METHODS: From a quaternary care center, clinical/radiologic data were collected from consecutive NOAC users with IS and age-matched controls without IS. Brain MRIs were reviewed for markers of cerebral small vessel disease. Variables with significant differences between groups were entered into a multivariable regression model to determine predictors of IS. Among IS patients, a Cox regression analysis was constructed to determine predictors of IS recurrence during follow-up. RESULTS: 112 patients with IS and 94 controls were included in the study. Variables significantly different between groups included apixaban use, dabigatran use, prior cerebrovascular events, hemoglobin A1c (HbA1c), left ventricular hypertrophy, left atrial volume index, and severe white matter hyperintensities. After multivariable adjustment, prior cerebrovascular events (aOR 23.86, 95% CI [6.02-94.48]), HbA1c levels (aOR 2.36, 95% CI [1.39-3.99]), left ventricular hypertrophy (aOR 2.73, 95% CI [1.11-6.71]) and left atrial volume index (aOR 1.05, 95% CI [1.01-1.08]) increased the risk of stroke, whereas apixaban use appeared to decrease the risk (aOR 0.38, 95% CI [0.16-0.92]). Malignancy was associated with IS recurrence (aHR 4.90, 95% CI [1.35-18.42]) after adjustment for age and chronic renal failure. CONCLUSIONS: Prior cerebrovascular events, diabetes, left ventricular hypertrophy, and increased left atrial size are risk factors for developing an IS among NOAC users.

Mechanistic Implications of Cortical Superficial Siderosis in Patients With Mixed Location Intracerebral Hemorrhage and Cerebral Microbleeds.

BACKGROUND AND OBJECTIVES: Hypertensive cerebral small vessel disease (HTN-cSVD) is the predominant microangiopathy in patients with a combination of lobar and deep cerebral microbleeds (CMBs) and intracerebral hemorrhage (mixed ICH). We tested the hypothesis that cerebral amyloid angiopathy (CAA) is also a contributing microangiopathy in patients with mixed ICH with cortical superficial siderosis (cSS), a marker strongly associated with CAA. METHODS: Brain MRIs from a prospective database of consecutive patients with nontraumatic ICH admitted to a referral center were reviewed for the presence of CMBs, cSS, and nonhemorrhagic CAA markers (lobar lacunes, centrum semiovale enlarged perivascular spaces [CSO-EPVS], and multispot white matter hyperintensity [WMH] pattern). The frequencies of CAA markers and left ventricular hypertrophy (LVH), a marker for hypertensive end-organ damage, were compared between patients with mixed ICH with cSS (mixed ICH/cSS[+]) and without cSS (mixed ICH/cSS[-]) in univariate and multivariable models. RESULTS: Of 1,791 patients with ICH, 40 had mixed ICH/cSS(+) and 256 had mixed ICH/cSS(-). LVH was less common in patients with mixed ICH/cSS(+) compared with those with mixed ICH/cSS(-) (34% vs 59%, p = 0.01). The frequencies of CAA imaging markers, namely multispot pattern (18% vs 4%, p < 0.01) and severe CSO-EPVS (33% vs 11%, p < 0.01), were higher in patients with mixed ICH/cSS(+) compared with those with mixed ICH/cSS(-). In a logistic regression model, older age (adjusted odds ratio [aOR] 1.04 per year, 95% CI 1.00-1.07, p = 0.04), lack of LVH (aOR 0.41, 95% CI 0.19-0.89, p = 0.02), multispot WMH pattern (aOR 5.25, 95% CI 1.63-16.94, p = 0.01), and severe CSO-EPVS (aOR 4.24, 95% CI 1.78-10.13, p < 0.01) were independently associated with mixed ICH/cSS(+) after further adjustment for hypertension and coronary artery disease. Among ICH survivors, the adjusted hazard ratio of ICH recurrence in patients with mixed ICH/cSS(+) was 4.65 (95% CI 1.38-11.38, p < 0.01) compared with that in patients with mixed ICH/cSS(-). DISCUSSION: The underlying microangiopathy of mixed ICH/cSS(+) likely includes both HTN-cSVD and CAA, whereas mixed ICH/cSS(-) is likely driven by HTN-cSVD. These imaging-based classifications can be important to stratify ICH risk but warrant confirmation in studies incorporating advanced imaging/pathology.

Peak width of skeletonized mean diffusivity and cognitive performance in cerebral amyloid angiopathy.

Background: Cerebral Amyloid Angiopathy (CAA) is a cerebral small vessel disease that can lead to microstructural disruption of white matter (WM), which can be measured by the Peak Width of Skeletonized Mean Diffusivity (PSMD). We hypothesized that PSMD measures would be increased in patients with CAA compared to healthy controls (HC), and increased PSMD is associated with lower cognitive scores in patients with CAA. Methods: Eighty-one probable CAA patients without cognitive impairment who were diagnosed with Boston criteria and 23 HCs were included. All subjects underwent an advanced brain MRI with high-resolution diffusion-weighted imaging (DWI). PSMD scores were quantified from a probabilistic skeleton of the WM tracts in the mean diffusivity (MD) image using a combination of fractional anisotropy (FA) and the FSL Tract-Based Spatial Statistics (TBSS) algorithm (www.psmd-marker.com). Within CAA cohort, standardized z-scores of processing speed, executive functioning and memory were obtained. Results: The mean of age and sex were similar between CAA patients (69.6 ± 7.3, 59.3% male) and HCs (70.6 ± 8.5, 56.5% male) (p = 0.581 and p = 0.814). PSMD was higher in the CAA group [(4.13 ± 0.94) × 10-4 mm2/s] compared to HCs [(3.28 ± 0.51) × 10-4 mm2/s] (p < 0.001). In a linear regression model corrected for relevant variables, diagnosis of CAA was independently associated with increased PSMD compared to HCs (ß = 0.45, 95% CI 0.13-0.76, p = 0.006). Within CAA cohort, higher PSMD was associated with lower scores in processing speed (p < 0.001), executive functioning (p = 0.004), and memory (0.047). Finally, PSMD outperformed all other MRI markers of CAA by explaining most of the variance in models predicting lower scores in each cognitive domain. Discussion: Peak Width of Skeletonized Mean Diffusivity is increased in CAA, and it is associated with worse cognitive scores supporting the view that disruption of white matter has a significant role in cognitive impairment in CAA. As a robust marker, PSMD can be used in clinical trials or practice.

Improving detection of cerebral small vessel disease aetiology in patients with isolated lobar intracerebral haemorrhage.

BACKGROUND AND PURPOSE: We evaluate whether non-haemorrhagic imaging markers (NHIM) (white matter hyperintensity patterns, lacunes and enlarged perivascular spaces (EPVS)) can discriminate cerebral amyloid angiopathy (CAA) from hypertensive cerebral small vessel disease (HTN-cSVD) among patients with isolated lobar intracerebral haemorrhage (isolated-LICH). METHODS: In patients with isolated-LICH, four cSVD aetiologic groups were created by incorporating the presence/distribution of NHIM: HTN-cSVD pattern, CAA pattern, mixed NHIM and no NHIM. CAA pattern consisted of patients with any combination of severe centrum semiovale EPVS, lobar lacunes or multiple subcortical spots pattern. HTN-cSVD pattern consisted of any HTN-cSVD markers: severe basal ganglia PVS, deep lacunes or peribasal ganglia white matter hyperintensity pattern. Mixed NHIM consisted of at least one imaging marker from either pattern. Our hypothesis was that patients with HTN-cSVD pattern/mixed NHIM would have a higher frequency of left ventricular hypertrophy (LVH), which is associated with HTN-cSVD. RESULTS: In 261 patients with isolated-LICH, CAA pattern was diagnosed in 93 patients, HTN-cSVD pattern in 53 patients, mixed NHIM in 19 patients and no NHIM in 96 patients. The frequency of LVH was similar among those with HTN-cSVD pattern and mixed NHIM (50% vs 39%, p=0.418) but was more frequent in HTN-cSVD pattern compared with CAA pattern (50% vs 20%, p<0.001). In a regression model, HTN-cSVD pattern (OR: 7.38; 95% CI 2.84 to 19.20) and mixed NHIM (OR: 4.45; 95% CI 1.25 to 15.90) were found to be independently associated with LVH. CONCLUSION: Among patients with isolated-LICH, NHIM may help differentiate HTN-cSVD from CAA, using LVH as a marker for HTN-cSVD.

Cerebrovascular injuries in traumatic brain injury.

Traumatic brain injury is a complex and highly heterogeneous disease due to the host of concomitant injuries that may accompany the initial insult. Due to the dynamic interplay between the injuries that may arise, the management of these injuries is challenging. In a small subset of patients with traumatic brain injury, cerebral vascular injury may occur, which presents its own diagnostic and therapeutic challenges. These vascular injuries often present in a delayed fashion, thereby going unnoticed by clinicians. Early recognition and treatment of these injuries is crucial, given their high morbidity and mortality. Through a critical review of the literature, we present the spectrum of cerebrovascular injuries that may occur with traumatic brain injury and discuss classification systems that are used to stratify cerebrovascular injury. We then focus on the diagnosis of cerebral vascular injury using different neuroimaging modalities. Lastly, we explore the treatment of these injuries ranging from antiplatelet therapies to endovascular and open vascular procedures. By highlighting the pitfalls and challenges of this complex disease, we hope to provide clinicians with the framework to recognize and treat vascular injuries that are seen in patients with traumatic brain injury.

Clinical and neuroimaging risk factors associated with the development of intracerebral hemorrhage while taking direct oral anticoagulants.

BACKGROUND AND AIMS: Intracerebral hemorrhage (ICH) associated with direct oral anticoagulant (DOAC) usage confers significant mortality/disability. We aimed to understand the clinical and neuroimaging features associated with developing ICH among DOAC users. METHODS: Clinical and radiological data were collected from consecutive DOAC users with ICH (DOAC-ICH) and age-matched controls without ICH from a single referral center. The frequency/distribution of MRI markers of hemorrhage risk were assessed. Baseline demographics and neuroimaging markers were compared in univariate tests. Significant associations (p < 0.1) were entered into a multivariable regression model to determine predictors of ICH. RESULTS: 86 DOAC-ICH and 94 ICH-free patients were included. Diabetes, coronary artery disease, prior ischemic stroke, smoking history, and antiplatelet usage were more common in ICH patients than ICH-free DOAC users. In the neuroimaging analyses, severe white matter hyperintensities (WMHs), lacunes, cortical superficial siderosis (cSS), and cerebral microbleeds (CMBs) were more common in the ICH cohort than the ICH-free cohort. In the multivariable regression, diabetes [OR 3.53 95% CI (1.05-11.87)], prior ischemic stroke [OR 14.80 95% CI (3.33-65.77)], smoking history [OR 3.08 95% CI (1.05-9.01)], CMBs [OR 4.07 95% CI (1.45-11.39)], and cSS [OR 39.73 95% CI (3.43-460.24)] were independently associated with ICH. CONCLUSIONS: Risk factors including diabetes, prior stroke, and smoking history as well as MRI biomarkers including CMBs and cSS are associated with ICH in DOAC users. Although screening MRIs are not typically performed prior to initiating DOAC therapy, these data suggest that patients of high-hemorrhagic risk may be identified.

Risk factors for neurological complications in left-sided infective endocarditis.

BACKGROUND AND PURPOSE: Neurological complications following infective endocarditis (IE) directly contribute to long-term morbidity. We examined the risk factors for different neurological complications of left-sided IE. METHODS: Using a database of consecutive adults admitted to a health system with left-sided IE from 2015 to 2019, the frequency of cerebral infarcts, intraparenchymal hemorrhage, cerebral microbleeds (CMB), mycotic aneurysm, and encephalopathy was determined. Variables with significant differences comparing each neurological complication (p < 0.1) were entered into regression models along with age to determine predictors. RESULTS: 211 patients with mean age 54 (±18) years, and 69 (33%) females were included. Infarcts were found in 118 (56%) patients, intraparenchymal hemorrhage was found in 17 (8%) patients, CMB were found in 58 (27%) patients, mycotic aneurysms were found in 22 (10%) patients, and encephalopathy occurred in 16 (8%) patients. In multivariable models, vegetation size ≥15 mm was associated with a higher risk of infarcts (aOR 2.26, 95% CI (1.12-4.57)), and the presence of a mycotic aneurysm was a risk factor for intraparenchymal hemorrhage (aOR 18.79, 95% CI (3.97-88.97)). Prosthetic valves (aOR 2.89, 95% CI (1.11-7.54)) and Staphylococcus aureus infection (aOR 3.50, 95% CI (1.08-11.36)) were associated with CMB. No risk factors emerged as predictors of encephalopathy. CONCLUSIONS: Large vegetation size is associated with stroke in patients with IE. Mycotic aneurysms are found at a higher frequency in young patients and are the primary cause of intraparenchymal hemorrhage. CMB may be related to prosthetic valves and Staphylococcus aureus infection.

Neurological Complications and Clinical Outcomes of Infective Endocarditis.

OBJECTIVES: The aim of this study is to explore the clinical features associated with neurological complications of infective endocarditis (IE) and to assess the impact of neurological complications on clinical outcomes. MATERIALS AND METHODS: The frequency of relevant clinical features was compared in a case series of IE patients with and without neurological complications admitted to a single health care system from 2015 to 2019. Variables with significant differences (p ≤ 0.05) in baseline characteristics in univariate logistic regression models were entered into multivariable models along with age to determine associations with neurological complications, unfavorable discharge outcomes (modified Rankin score ≥ 3), and in-hospital mortality. RESULTS: 260 patients with a mean age of 51 (±18) years and 103 (40%) females were included. Neurological complications occurred in 165 (63%) patients, with the most common being septic emboli (66 patients, 25%). In the regression analyses, antiplatelet usage (aOR 1.87, 95% CI [1.05-3.32]) and mitral valve vegetations (aOR 2.66, 95% CI [1.22-5.79]) were independently associated with neurological complications. Territorial infarction (aOR 4.13, 95% CI [1.89-9.06]) and encephalopathy (aOR 3.95, 95% CI [1.19-13.05]) were associated with an increased risk of unfavorable outcome, while cardiac surgery was associated with a lower risk of both unfavorable outcome (aOR 0.40, 95% CI [0.22-0.71]) and in-hospital mortality (aOR 0.18, 95% CI [0.09-0.35]). CONCLUSIONS: Neurological complications are common in IE patients and are associated with mitral valve endocarditis and antiplatelet usage. Of the neurological complications, territorial infarcts and encephalopathy are associated with unfavorable discharge outcomes.

Screening neuroimaging in neurologically asymptomatic patients with infective endocarditis.

BACKGROUND AND PURPOSE: Neurological complications from infective endocarditis (IE) are common and often present with minimal clinical symptoms. In this study, we examine whether screening neuroimaging in asymptomatic patients results in increased detection of neurological complications and leads to improved patient outcomes. METHODS: Using a database of consecutive adults with IE admitted to a single health system from 2015 to 2019, we selected patients who presented without any neurological symptoms and determined whether these patients underwent screening neuroimaging. The presence of septic emboli, territorial infarcts, intracranial hemorrhage, and mycotic aneurysms was recorded. Variables with significant differences in univariable analyses (p < .1) between those with and without screening neuroimaging were entered into regression models with age and sex to determine predictors of neurological complications and favorable discharge outcomes (modified Rankin score ≤2). RESULTS: A total of 214 patients were included in the study, of which 154 (72%) received screening neuroimaging. Septic emboli were more common in patients who underwent screening imaging (31% vs. 15%, p = 0.02). In the first multivariate analysis, screening neuroimaging was associated with septic emboli (adjusted odds ratio [aOR] = 2.44, 95% confidence interval [CI]: [1.03-5.75], p = 0.04). In the second multivariate analysis, territorial infarcts (aOR = 0.28, 95% CI: [0.11-0.73], p = .01), but not septic emboli (aOR = 0.71, 95% CI: [0.36-1.43], p = 0.34), were associated with a favorable discharge outcome. CONCLUSIONS: Screening neuroimaging leads to the detection of more septic emboli in IE, but only territorial infarcts (in contrast to septic emboli) correlate with an unfavorable discharge outcome.

Cerebellar atrophy and its implications on gait in cerebral amyloid angiopathy.

OBJECTIVE: Recent data suggest that cerebral amyloid angiopathy (CAA) causes haemorrhagic lesions in cerebellar cortex as well as subcortical cerebral atrophy. However, the potential effect of CAA on cerebellar tissue loss and its clinical implications have not been investigated. METHODS: Our study included 70 non-demented patients with probable CAA, 70 age-matched healthy controls (HCs) and 70 age-matched patients with Alzheimer's disease (AD). The cerebellum was segmented into percent of cerebellar subcortical volume (pCbll-ScV) and percent of cerebellar cortical volume (pCbll-CV) represented as percent (p) of estimated total intracranial volume. We compared pCbll-ScV and pCbll-CV between patients with CAA, HCs and those with AD. Gait velocity (metres/second) was used to investigate gait function in patients with CAA. RESULTS: Patients with CAA had significantly lower pCbll-ScV compared with both HC (1.49±0.1 vs 1.73±0.2, p<0.001) and AD (1.49±0.1 vs 1.66±0.24, p<0.001) and lower pCbll-CV compared with HCs (6.03±0.5 vs 6.23±0.6, p=0.028). Diagnosis of CAA was independently associated with lower pCbll-ScV compared with HCs (p<0.001) and patients with AD (p<0.001) in separate linear regression models adjusted for age, sex and presence of hypertension. Lower pCbll-ScV was independently associated with worse gait velocity (ß=0.736, 95% CI 0.28 to 1.19, p=0.002) in a stepwise linear regression analysis including pCbll-CV along with other relevant variables. INTERPRETATION: Patients with CAA show more subcortical cerebellar atrophy than HC or patients with AD and more cortical cerebellar atrophy than HCs. Reduced pCbll-ScV correlated with lower gait velocity in regression models including other relevant variables. Overall, this study suggests that CAA causes cerebellar injury, which might contribute to gait disturbance.

Deconstructive repair of a traumatic vertebrovertebral arteriovenous fistula via a contralateral endovascular approach.

Vertebrovertebral arteriovenous fistulas (VVAVFs) are rare entities that lack consensus guidelines for their management. Our case describes the successful treatment of a traumatic VVAVF via a contralateral deconstructive endovascular approach. A 64-year-old female presented following a traumatic fall. Computed tomography angiogram highlighted a 2 cm pseudoaneurysm of the right vertebral artery (VA) with epidural contrast enhancement and a hematoma with flow voids within the epidural space. Digital subtraction angiography showed a VVAVF at C2-3 with retrograde filling of the distal right VA. Having undergone several unsuccessful passes of the proximal dissection flap in the right VA, the patient underwent a contralateral deconstructive approach with correction of the VVAVF without complication. The remaining feeding branches had occluded after 1 week. The patient made a complete recovery without neurological sequelae at 3-month follow-up.

Understanding Delays in MRI-based Selection of Large Vessel Occlusion Stroke Patients for Endovascular Thrombectomy.

PURPOSE: Given the efficacy of endovascular thrombectomy (EVT), optimizing systems of delivery is crucial. Magnetic resonance imaging (MRI) is the gold standard for evaluating tissue viability but may require more time to obtain and interpret. We sought to identify determinants of arrival-to-puncture time for patients who underwent MRI-based EVT selection in a real-world setting. METHODS: Patients were identified from a prospectively maintained database from 2011-2019 that included demographics, presentations, treatments, and outcomes. Process times were obtained from the medical charts. MRI times were obtained from time stamps on the first sequence. Linear and logistic regressions were used to infer explanatory variables of arrival-to-puncture times and effects of arrival-to-puncture time on functional outcomes. RESULTS: In this study 192 patients (median age 70 years, 57% women, 12% non-white) underwent MRI-based EVT selection. 66% also underwent computed tomography (CT) at the hub before EVT. General anesthesia was used for 33%. Among the entire cohort, the median arrival-to-puncture was 102 min; however, among those without CT it was 77 min. Longer arrival-to-puncture times independently reduced the odds of 90-day good outcome (∆mRS ≤ 2 from pre-stroke, aOR = 0.990, 95%CI = 0.981-0.999, p = 0.040) when controlling for age, NIHSS, and good reperfusion (TICI 2b-3). Independent determinants of longer arrival-to-puncture were CT plus MRI (ß = 0.205, p = 0.003), non-white race/ethnicity (ß = 0.162, p = 0.012), coronary disease (ß = 0.205, p = 0.001), and general anesthesia (ß = 0.364, p < 0.0001). CONCLUSION: Minimizing arrival-to-puncture time is important for outcomes. Real-world challenges exist in an MRI-based EVT selection protocol; avoiding double imaging is key to saving time. Racial/ethnic disparities require further study. Understanding variables associated with delay will inform protocol changes.

Association of Infarct Topography and Outcome After Endovascular Thrombectomy in Patients With Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: The care of patients with large vessel occlusion (LVO) stroke has been revolutionized by endovascular thrombectomy (EVT). While EVT has a large effect size, most patients treated with EVT remain disabled or die within 90 days. A better understanding of outcomes may influence EVT selection criteria, novel therapies, and prognostication. We sought to identify associations between outcomes and brain regions involved in ischemic lesions. METHODS: For this cohort study, consecutive patients with LVO who were treated with EVT and underwent post-EVT MRI were identified from a tertiary referral center (2011-2019). Acute ischemic lesions were manually segmented from diffusion-weighted imaging and spatially normalized. Individual lesions were parcellated (atlas-defined 94 cortical regions, 14 subcortical nuclei, 20 white matter tracts) and reduced to 10 essential lesion patterns with the use of unsupervised dimensionality reduction techniques. Ninety-day modified Rankin Scale (mRS) score (>2) was modeled via bayesian regression, taking the 10 lesion patterns as inputs and controlling for lesion size, age, sex, acute NIH Stroke Scale (NIHSS) score, alteplase, prior stroke, intracerebral hemorrhage, and good reperfusion (Thrombolysis in Cerebral Infarction 2b-3). In comparative analyses, 90-day mRS score was modeled considering covariates only, and compartment-wise relevances for acute stroke severity and 90-day mRS score were evaluated. RESULTS: There were 151 patients with LVO identified (age 68 ± 15 years, 52% female). The median NIHSS score was 16 (interquartile range 13-20); 56% had mRS score >2. Lesion locations predictive of 90-day mRS score involved bilateral but left hemispherically more pronounced precentral and postcentral gyri, insular and opercular cortex, and left putamen and caudate (area under the curve 0.91, highest probability density interval [HPDI] covering 90% certainty 0.90-0.92). The lesion location model outperformed the simpler model relying on covariates only (bayesian model comparison of 97% weight to the model with vs 3% weight to the model without lesion location). While lesions affecting subcortical nuclei had the highest relevance for stroke severity (posterior distribution mean 0.75, 90% HPDI 0.256-1.31), lesions affecting white matter tracts had the highest relevance for 90-day mRS score (0.656, 90% HPDI 0.0864-1.12). DISCUSSION: These data describe the significance for outcomes of specific brain regions involved in ischemic lesions on MRI after EVT. Future work in additional datasets is needed to confirm these granular findings.

Effect of vascular amyloid on white matter disease is mediated by vascular dysfunction in cerebral amyloid angiopathy.

We postulated that vascular dysfunction mediates the relationship between amyloid load and white matter hyperintensities (WMH) in cerebral amyloid angiopathy (CAA). Thirty-eight cognitively healthy patients with CAA (mean age 70 ± 7.1) were evaluated. WMH was quantified and expressed as percent of total intracranial volume (pWMH) using structural MRI. Mean global cortical Distribution Volume Ratio representing Pittsburgh Compound B (PiB) uptake (PiB-DVR) was calculated from PET scans. Time-to-peak [TTP] of blood oxygen level-dependent response to visual stimulation was used as an fMRI measure of vascular dysfunction. Higher PiB-DVR correlated with prolonged TTP (r = 0.373, p = 0.021) and higher pWMH (r = 0.337, p = 0.039). Prolonged TTP also correlated with higher pWMH (r = 0.485, p = 0.002). In a multivariate linear regression model, TTP remained independently associated with pWMH (p = 0.006) while PiB-DVR did not (p = 0.225). In a bootstrapping model, TTP had a significant indirect effect (ab = 0.97, 95% CI: 0.137-2.461), supporting that the association between PiB-DVR and pWMH is mediated by TTP response. There was no longer a direct effect independent of the hypothesized pathway. Our study suggests that the effect of vascular amyloid load on white matter disease is mediated by vascular dysfunction in CAA. Amyloid lowering strategies might prevent pathophysiological processes leading to vascular dysfunction, therefore limiting ischemic brain injury.