Klaas, James P.

Introduction: Small case series have suggested that cerebral amyloid angiopathy (CAA) and reversible cerebral vasoconstriction syndrome (RCVS) are the most common causes of non-traumatic convexal SAH (cSAH). Our objective was to describe the spectrum of clinical and imaging features in a large series of non-traumatic cSAH patients. Methods: A retrospective observational study of consecutive patients with non-traumatic cSAH was performed. The Mayo Clinic Medical Records Linkage system was used to identify all patients evaluated at Mayo Clinic in Rochester with potential non-traumatic cSAH between January 1, 1996 and October 1, 2014. Clinical and radiologic data were abstracted from the comprehensive medical record. Results: We identified 88 patients [median age, 64 years (range: 25-85)] with non-traumatic cSAH. The most common causes were reversible cerebral vasoconstriction syndrome (26, 29.5%), cerebral amyloid angiopathy (23, 26.1%), indeterminate (14, 15.9%), and endocarditis (9, 10.2%). Other causes include posterior reversible encephalopathy syndrome, cerebral vein thrombosis, vasculitis, carotid occlusive disease, thrombosed developmental venous anomaly, and hyperperfusion syndrome after carotid revascularization. CAA patients commonly presented at an older age than RCVS patients (75 years vs 51 years, p<0.0001). The most common clinical presentation for CAA was sensorimotor dysfunction while thunderclap headache was the most common presentation of RCVS. Thirteen patients (14.7%) had recurrent cSAH and twelve patients (13.6%) had a subsequent intracerebral hemorrhage over a median follow up of 16 months. The risk was high among CAA patients, with subsequent lobar ICH occurring in 43.5% of cases, superficial siderosis in 95%, and recurrent cSAH in 39.1%, compared to 3.8%, 28.5% and 7.7% respectively in RCVS. Conclusions: Our study demonstrates the clinical diversity of cSAH. Older age, sensorimotor dysfunctions suggest CAA as the underlying cause. Younger age and thunderclap headache predict RCVS. Various other causes also need to be considered in the differential diagnosis. CAA patients have high rates of subsequent lobar ICH, development of superficial siderosis, and recurrent cSAH.

Background & Purpose: Seizures are a recognized complication of stroke. However, available data are conflicting in terms of incidence, risk factors for occurrence, and impact on functional outcome and mortality. The aim of this study was to assess the incidence and characteristics of seizures following ischemic stroke in a well-defined population, and their effect on long-term patient outcome. Methodology: Utilizing the Rochester Epidemiology Project medical record linkage system, we identified all incident cases of ischemic stroke (IS) that occurred between January 1, 1990, and December 31, 1994. We identified all patients who developed seizures following first IS. Detailed data regarding stroke (including TOAST subtype, anatomic location, functional outcome), seizures (date, type, functional outcome, recurrence, presence of status epilepticus, complications, treatment, EEG findings), and patient status at the last follow-up were recorded and analyzed. Results: We identified 490 patients with first IS. Mean follow-up was 6.5 years (range 0.0 - 23.8). Of these, 35 (7.1%) developed seizures. Early seizures (occurring within 14 days of stroke) were present in 13 (37.1%), of which 9 (69.2%) had their seizure within the first 24 hours. Partial seizures were the most common type (23 patients, 65.7%). Status epilepticus occurred in two cases (5.7%). Tongue biting was the most common complication of poststroke seizures (4 patients, 11.4%). Treatment with antiepileptic drugs (AEDs) was initiated in 32 cases (91.4%). Only one drug was necessary for seizure control in all treated patients. The mean modified Rankin Scale score was 2.9 (SD 1.48) after the first IS, and worsened to 3.3 (SD 1.43) after the first seizure. Mortality at the last follow-up was higher in the seizure group compared to the non-seizure group, even after adjusting for TOAST subtype (HR 1.52; 95% CI 1.07 - 2.16; P = 0.02). Conclusion: Seizures are mostly a late complication of IS. They do not bear a high risk of life-threatening complications and are readily controllable by a single AED. However, patients who developed poststroke seizures tended to have a worse functional outcome and an increased mortality.

Introduction: Acute stroke pre-arrival notification by emergency medical services (EMS) allows hospital personnel to mobilize resources in advance, thereby improving treatment times and outcomes. However, criteria for pre-arrival notification vary by institution. In developing our own pre-arrival notification system, we aimed to determine whether objective measures, EMS clinical impression, or a combination of both best predicted accurate stroke team activation. Methods: Retrospective review of consecutive patients presenting to our institution via EMS with suspicion of acute stroke from 2014-2015. Data recorded included age, gender, time of symptom onset, glucose, Cincinnati Prehospital Stroke Scale (CPSS), Glasgow Coma Scale (GCS), and EMS impression. Univariate logistic regression was performed with acute stroke team activation in the emergency department (ED) as the endpoint. Results: 130 patients met inclusion criteria. Of these, 88 prompted the ED provider to activate the acute stroke team. Of variables analyzed, CPSS was clinically and statistically significant (OR. 1.7, 95% CI 1.2-2.5, p=0.0035) on univariate analysis, with arm weakness being the most predictive component (OR 2.9, 95% CI 1.04-8.1, p=0.04). EMS impression was not statistically significant (p>0.05). We then performed sensitivity and specificity analyses of CPSS, EMS impression, and CPSS combined with EMS impression (Table). A CPSS score of 3 had the highest specificity, and CPSS score of 1 combined with EMS impression the highest sensitivity. Conclusion: CPSS was the key significant predictor of ED acute stroke team activation, and more specific than EMS clinical impression. By combining CPSS and EMS impression, sensitivity improved, but at the expense of specificity. This suggests that reproducible measurements and scores, such as CPSS, should be the main driver for stroke pre-notification systems and should be integrated systematically into EMS education programs.

Introduction There is increased interest in the use of artificial intelligence-based (AI) software packages in the evaluation of neuroimaging studies for acute ischemic stroke. We studied whether, compared to standard image interpretation without AI, Brainomix e-ASPECTS software improved interobserver agreement and accuracy in detecting ASPECTS regions affected in anterior circulation LVO. Methods We included 60 consecutive patients with anterior circulation LVO who had TICI 3 revascularization within 60 minutes of their baseline CT. A total of 16 readers, including senior neuroradiologists, junior neuroradiologists and vascular neurologists participated. Readers interpreted CT scans on independent workstations and assessed final ASPECTS and evaluated whether each individual ASPECTS region was affected. Two months later, readers again evaluated the CT scans, but with assistance of e-ASPECTS software. We assessed interclass correlation coefficient for total ASPECTS and interobserver agreement with Fleiss’ Kappa for each ASPECTS region with and without assistance of the e-ASPECTS. We also assessed accuracy for the readers with and without e-ASPECTS assistance. In our assessment of accuracy, ground truth was the 24 hour CT in this cohort of patients who had prompt and complete revascularization. Results Interclass correlation coefficient for total ASPECTS without e-ASPECTS assistance was 0.395, indicating fair agreement compared, to 0.574 with e-ASPECTS assistance, indicating good agreement (P < 0.01). There was significant improvement in inter-rater agreement with e-ASPECTS assistance for each individual region with the exception of M6 and caudate. The e-ASPECTS software had higher accuracy than the overall cohort of readers (with and without e-ASPECTS assistance) for every region except the caudate. Conclusions Use of Brainomix e-ASPECTS software resulted in significant improvements in inter-rater agreement and accuracy of ASPECTS score evaluation in a large group of neuroradiologists and neurologists. e-ASPECTS software was more predictive of final infarct/ASPECTS than the overall group interpreting the CT scans with and without e-ASPECTS assistance.

Background Diffuse intracranial susceptibility abnormalities have recently been described among patients with coronavirus disease 2019 (COVID-19), although prior studies have consisted of case reports and/or series. This brief literature review seeks to compile and catalogue the available data to elucidate characteristic features of such findings. Materials and methods Scientific articles and studies on intracranial microhemorrhages in the setting of COVID-19 were searched on PubMed, Google Scholar, and the Cochrane Library. Included studies described intracranial microbleed(s) on magnetic resonance imaging in patients with COVID-19. If multiple patients were described, only patients with intracranial microhemorrhage on magnetic resonance imaging were included for analysis. Patient demographics, severity of illness (e.g. intensive care unit admission and/or intubation), time from diagnosis of COVID-19 to magnetic resonance imaging, and location(s) of any observed microhemorrhages were noted. Results A total of 39 patients with suspected intracranial microhemorrhages have been described in prior studies. The average age of patients was 64.7 years; 21.9% were women. The average time between COVID-19 diagnosis and magnetic resonance imaging was 31.7 days. All patients in the cohort were admitted to critical care and were either intubated or treated with extracorporeal membrane oxygenation during their clinical course. Microhemorrhages were most commonly located in the subcortical/juxtacortical white matter and corpus callosum. Conclusions Intracranial microbleeds are a well-documented finding in patients with severe COVID-19, and are most commonly callosal and subcortical/juxtacortical in location.

Introduction: High-resolution vessel wall imaging (HR-VWI) of the intracranial vasculature may aid in the diagnosis and management of Moyamoya Disease (MMD). The patterns of HR-VWI findings of the cerebral vasculature of MMD patients remains uncertain, however. We sought to describe HR-VWI findings in a single-center cohort of MMD patients. Methods: Consecutive patients who were evaluated at a Midwest American medical center with a HR-VWI exam were included. Fourteen anterior circulation arterial segments in each patient were analyzed: proximal and distal supraclinoid Internal Carotid Artery, proximal M1 segment of the Middle Cerebral Artery, mid-portion of the M1, distal M1, proximal A1 segment of the Anterior Cerebral Artery and distal A1. Imaging variables that were collected from each segment included the presence of wall thickening (concentric vs eccentric), degree and pattern (concentric or eccentric) of contrast enhancement, and presence of positive or negative vessel remodeling. The total number and percentage of vessel segments demonstrating these characteristics were calculated. The number and percentage of patients with at least one segment demonstrating these characteristics were calculated. Results: Thirty-six patients (32 females, 88.9%) with a diagnosis of MMD were included. Overall, 221 of 504 segments (43.8%) demonstrated negative remodeling in 29 (75%) patients. Ninety-eight segments (19.4%) demonstrated wall enhancement (71 concentric, 27 eccentric; 22 high grade, 76 low grade) in 32 (88.9%) patients. Eighty-seven segments (17.3%) demonstrated wall thickening (52 concentric, 35 eccentric) in 32 patients (88.9%). Conclusions: Negative remodeling was the most-commonly observed vessel wall abnormality in all segments analyzed. However, a high percentage of patients had at least one segment demonstrating wall enhancement, wall thickening and negative remodeling. Continued study is necessary to further elucidate the HR-VWI patterns of the cerebral arterial system in MMD patients.

Numerous recent technological advances offer the potential to substantially enhance the MRI evaluation of moyamoya disease (MMD). These include high-resolution volumetric imaging, high-resolution vessel wall characterization, improved cerebral angiographic and perfusion techniques, high-field imaging, fast scanning methods, and artificial intelligence. This review discusses the current state-of-the-art MRI applications in these realms, emphasizing key imaging findings, clinical utility, and areas that will benefit from further investigation. Although these techniques may apply to imaging of a wide array of neurovascular or other neurological conditions, consideration of their application to MMD is useful given the comprehensive multidimensional MRI assessment used to evaluate MMD. These MRI techniques span from basic cross-sectional to advanced functional sequences, both qualitative and quantitative. The aim of this review was to provide a comprehensive summary and analysis of current key relevant literature of advanced MRI techniques for the evaluation of MMD with image-rich case examples. These imaging methods can aid clinical characterization, help direct treatment, assist in the evaluation of treatment response, and potentially improve the understanding of the pathophysiology of MMD.

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.

Mary Broadfoot Walker (1888-1974) was the first to demonstrate the ‘Mary Walker effect’ describing the weakness of other muscle groups following release of the arteriovenous occlusion of an unrelated exercising muscle group in patients with myasthenia gravis, which led to the search for a circulating causative agent for myasthenia gravis. She was the first to clearly demonstrate that strength temporarily improved in patients with myasthenia gravis with physostigmine or Prostigmin (neostigmine). This dramatic treatment response has been erroneously termed the ‘Mary Walker effect'. Further, she noted hypokalaemia during attacks of weakness in familial periodic paralysis, pioneering treatment with potassium chloride. Although Mary Walker practiced in a nonacademic setting and trained at a time when women were not allowed to train alongside men, she was the first to convincingly demonstrate three life-changing treatments in the field of neuromuscular medicine, a feat that few physicians of any era can claim.

Background: Non-traumatic convexal subarachnoid hemorrhages (cSAH) in the elderly can be a manifestation of cerebral amyloid angiopathy (CAA) and predict future intracerebral hemorrhage risk. The frequency of cSAH in the elderly population is unknown. Our objective was to determine the frequency of convexal subarachnoid hemorrhage in a population-based study among individuals who underwent amyloid PET imaging. Methods: Between 11/29/2004 and 3/11/2017 there were 1,687 participants ages 50-years and older in the population-based Mayo Clinic Study of Aging (MCSA) with Pittsburgh compound B (PiB) PET imaging. All intracerebral hemorrhages among participants were identified utilizing the Rochester Epidemiology Project’s records linkage system, and records and images were reviewed to identify those with both symptomatic and asymptomatic convexal subarachnoid hemorrhage. Neuroimaging characteristics, demographics, medications, and ApoE genotype were recorded. Results: Four (0.23%) cSAHs were identified among the individuals who underwent PiB PET imaging. Three were women and median age was 73 (range: 67-84). cSAH occurred in the following locations: right frontal (3), and right parieto-occipital (1). Two went on to develop a lobar intracerebral hemorrhage at a median of 4.75 years after cSAH. Coexisting cerebral microbleeds were identified in one case. The APOE allele combinations of the four participants were: 3/3, 3/3, 2/2, and 2/3. On PiB PET imaging, the median SUVR was 1.81 (range: 1.38-2.34). Conclusion: cSAH is a relatively rare manifestation of CAA occurring in less than 1% of the general population, but may represent a subset with a high risk of future intracerebral hemorrhage. Half of the participants with cSAH had an APOE e2 allele.