Biopsy-Proven Amyloid-Beta Related Angiitis with Unusual Presentation and Long-Term Follow-Up.

Amyloid-beta related angiitis (ABRA) is a rare central nervous system inflammatory and vasculitic process. It is seen in patients with cerebral amyloid angiopathy (CAA) and thought to be mediated by an autoimmune reaction against cerebrovascular ß-amyloid. We describe the case of a patient with ABRA with clinical information and brain imaging over a 10-year period. The patient was hospitalized in 2018 for altered mental status, paranoia and hallucinations. Her symptoms started in 2009 with an episode of vertigo and loss of consciousness. From 2011-2019, she had multiple episodes of transient focal neurological deficits with overall cumulative progressive decline in cognition and functional status. Retrospective and comparative reviews of brain magnetic resonance imaging (MRI) from 2009-2019 showed waxing and waning vasogenic cerebral edema with overall progression of white matter hyperintensities and peripheral micro-hemorrhages consistent with inflammatory CAA. Re-examination of a brain biopsy from 2009 showed ABRA, and immunostaining was positive for ß-amyloid. She was treated with intravenous steroids with minimal symptomatic improvement. She was lost to our follow-up after hospital discharge. We describe the temporal progression of ABRA through serial brain imaging over a 10-year period. To our knowledge, this is the longest published follow-up duration of ABRA. The patient in our case had severe cognitive impairment and disability despite treatment with steroids.

3D Printed Hydrogels with Aligned Microchannels to Guide Neural Stem Cell Migration.

Following traumatic or ischemic brain injury, rapid cell death and extracellular matrix degradation lead to the formation of a cavity at the brain lesion site, which is responsible for prolonged neurological deficits and permanent disability. Transplantation of neural stem/progenitor cells (NSCs) represents a promising strategy for reconstructing the lesion cavity and promoting tissue regeneration. In particular, the promotion of neuronal migration, organization, and integration of transplanted NSCs is critical to the success of stem cell-based therapy. This is particularly important for the cerebral cortex, the most common area involved in brain injuries, because the highly organized structure of the cerebral cortex is essential to its function. Biomaterials-based strategies show some promise for conditioning the lesion site microenvironment to support transplanted stem cells, but the progress in demonstrating organized cell engraftment and integration into the brain is very limited. An effective approach to sufficiently address these challenges has not yet been developed. Here, we have implemented a digital light-processing-based 3D printer and printed hydrogel scaffolds with a designed shape, uniaxially aligned microchannels, and tunable mechanical properties. We demonstrated the capacity to achieve high shape precision to the lesion site with brain tissue-matching mechanical properties. We also established spatial control of bioactive molecule distribution within 3D printed hydrogel scaffolds. These printed hydrogel scaffolds have shown high neuro-compatibility with aligned neuronal outgrowth along with the microchannels. This study will provide a biomaterial-based approach that can serve as a protective and guidance vehicle for transplanted NSC organization and integration for brain tissue regeneration after injuries.

Preserving stroke care during the COVID-19 pandemic: Potential issues and solutions.

The coronavirus 2019 (COVID-19) pandemic requires drastic changes in allocation of resources, which can affect the delivery of stroke care, and many providers are seeking guidance. As caregivers, we are guided by 3 distinct principles that will occasionally conflict during the pandemic: (1) we must ensure the best care for those stricken with COVID-19, (2) we must provide excellent care and advocacy for patients with cerebrovascular disease and their families, and (3) we must advocate for the safety of health care personnel managing patients with stroke, with particular attention to those most vulnerable, including trainees. This descriptive review by a diverse group of experts in stroke care aims to provide advice by specifically addressing the potential impact of this pandemic on (1) the quality of the stroke care delivered, (2) ethical considerations in stroke care, (3) safety and logistic issues for providers of patients with stroke, and (4) stroke research. Our recommendations on these issues represent our best opinions given the available information, but are subject to revision as the situation related to the COVID-19 pandemic continues to evolve. We expect that ongoing emergent research will offer additional insights that will provide evidence that could prompt the modification or removal of some of these recommendations.

Impact of Stroke Call on the Stroke Neurology Workforce in the United States: Possible Challenges and Opportunities.

BACKGROUND: The Stroke & Vascular Neurology Section of the American Academy of Neurology was charged to identify challenges to the recruitment and retention of stroke neurologists and to make recommendations to address any identified problems. The Section initiated this effort by determining the impact of stroke on-call requirements as a barrier to the recruitment and retention of vascular neurologists. METHODS: This is a cross-sectional survey of a sample of US Neurologists providing acute stroke care. RESULTS: Of the 900 neurologists who were sent surveys, 313 (35%) responded. Of respondents from institutions providing stroke coverage, 71% indicated that general neurologists and 45% indicated that vascular neurologists provided that service. Of those taking stroke call, 36% agreed with the statement, "I spent too much time on stroke call," a perception that was less common among those who took less than 12-hour shifts (P < .0001); 21% who participated in stroke call were dissatisfied with their current job. Forty-six percent indicated that their stroke call duties contributed to their personal feeling of "burnout." CONCLUSIONS: Although the reasons are likely multifactorial, our survey of neurologists providing stroke care suggests that over-burdensome on-call responsibilities may be contributing to the vascular neurology workforce burnout and could be affecting recruitment and retention of vascular neurologists. Strategies to reduce the lifestyle impact of stroke call may help address this problem.

Targeting Pioglitazone Hydrochloride Therapy After Stroke or Transient Ischemic Attack According to Pretreatment Risk for Stroke or Myocardial Infarction.

Importance: There is growing recognition that patients may respond differently to therapy and that the average treatment effect from a clinical trial may not apply equally to all candidates for a therapy. Objective: To determine whether, among patients with an ischemic stroke or transient ischemic attack and insulin resistance, those at higher risk for future stroke or myocardial infarction (MI) derive more benefit from the insulin-sensitizing drug pioglitazone hydrochloride compared with patients at lower risk. Design, Setting, and Participants: A secondary analysis was conducted of the Insulin Resistance Intervention After Stroke trial, a double-blind, placebo-controlled trial of pioglitazone for secondary prevention. Patients were enrolled from 179 research sites in 7 countries from February 7, 2005, to January 15, 2013, and were followed up for a mean of 4.1 years through the study's end on July 28, 2015. Eligible participants had a qualifying ischemic stroke or transient ischemic attack within 180 days of entry and insulin resistance without type 1 or type 2 diabetes. Interventions: Pioglitazone or matching placebo. Main Outcomes and Measures: A Cox proportional hazards regression model was created using baseline features to stratify patients above or below the median risk for stroke or MI within 5 years. Within each stratum, the efficacy of pioglitazone for preventing stroke or MI was calculated. Safety outcomes were death, heart failure, weight gain, and bone fracture. Results: Among 3876 participants (1338 women and 2538 men; mean [SD] age, 63 [11] years), the 5-year risk for stroke or MI was 6.0% in the pioglitazone group among patients at lower baseline risk compared with 7.9% in the placebo group (absolute risk difference, -1.9% [95% CI, -4.4% to 0.6%]). Among patients at higher risk, the risk was 14.7% in the pioglitazone group vs 19.6% for placebo (absolute risk difference, -4.9% [95% CI, -8.6% to 1.2%]). Hazard ratios were similar for patients below or above the median risk (0.77 vs 0.75; P = .92). Pioglitazone increased weight less among patients at higher risk but increased the risk for fracture more. Conclusions and Relevance: After an ischemic stroke or transient ischemic attack, patients at higher risk for stroke or MI derive a greater absolute benefit from pioglitazone compared with patients at lower risk. However, the risk for fracture is also higher. Trial Registration: clinicaltrials.gov Identifier: NCT00091949.

Central Nervous System Complications and Outcomes After Allogeneic Hematopoietic Stem Cell Transplantation.

BACKGROUND: Central nervous system complications (CNSC) can be the cause of morbidity and mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). We aimed to determine the incidence of CNSC and its impact on survival. PATIENTS AND METHODS: This retrospective cohort study included patients with hematologic disorders who received allo-HSCT between 2002 and 2011 at the University of Nebraska Medical Center. RESULTS: Of the 351 patients identified, 45 developed CNSC (12.8%). The 100-day cumulative incidence of CNSC was 8% (95% confidence interval, 8-15). The most common CNSC included posterior reversible encephalopathy syndrome (40%), stroke or transient ischemic attack (24%), seizures (20%), and infection (9%). The 5-year overall survival was significantly lower among patients with versus without CNSC (14% vs. 44%, P = .0004). In multivariate analysis, the risk of mortality for patients with versus without CNSC was significantly higher (hazard ratio, 1.56; 95% confidence interval, 1.03-2.36; P = .04). CONCLUSION: The occurrence of CNSC after allo-HSCT was associated with reduced survival. Identifying patients at risk, monitoring, early detection, and management of CNSC after allo-HSCT are needed to improve outcomes.

Cervical arterial dissections and association with cervical manipulative therapy: a statement for healthcare professionals from the american heart association/american stroke association.

PURPOSE: Cervical artery dissections (CDs) are among the most common causes of stroke in young and middle-aged adults. The aim of this scientific statement is to review the current state of evidence on the diagnosis and management of CDs and their statistical association with cervical manipulative therapy (CMT). In some forms of CMT, a high or low amplitude thrust is applied to the cervical spine by a healthcare professional. METHODS: Members of the writing group were appointed by the American Heart Association Stroke Council's Scientific Statements Oversight Committee and the American Heart Association's Manuscript Oversight Committee. Members were assigned topics relevant to their areas of expertise and reviewed appropriate literature, references to published clinical and epidemiology studies, morbidity and mortality reports, clinical and public health guidelines, authoritative statements, personal files, and expert opinion to summarize existing evidence and to indicate gaps in current knowledge. RESULTS: Patients with CD may present with unilateral headaches, posterior cervical pain, or cerebral or retinal ischemia (transient ischemic or strokes) attributable mainly to artery-artery embolism, CD cranial nerve palsies, oculosympathetic palsy, or pulsatile tinnitus. Diagnosis of CD depends on a thorough history, physical examination, and targeted ancillary investigations. Although the role of trivial trauma is debatable, mechanical forces can lead to intimal injuries of the vertebral arteries and internal carotid arteries and result in CD. Disability levels vary among CD patients with many having good outcomes, but serious neurological sequelae can occur. No evidence-based guidelines are currently available to endorse best management strategies for CDs. Antiplatelet and anticoagulant treatments are both used for prevention of local thrombus and secondary embolism. Case-control and other articles have suggested an epidemiologic association between CD, particularly vertebral artery dissection, and CMT. It is unclear whether this is due to lack of recognition of preexisting CD in these patients or due to trauma caused by CMT. Ultrasonography, computed tomographic angiography, and magnetic resonance imaging with magnetic resonance angiography are useful in the diagnosis of CD. Follow-up neuroimaging is preferentially done with noninvasive modalities, but we suggest that no single test should be seen as the gold standard. CONCLUSIONS: CD is an important cause of ischemic stroke in young and middle-aged patients. CD is most prevalent in the upper cervical spine and can involve the internal carotid artery or vertebral artery. Although current biomechanical evidence is insufficient to establish the claim that CMT causes CD, clinical reports suggest that mechanical forces play a role in a considerable number of CDs and most population controlled studies have found an association between CMT and VAD stroke in young patients. Although the incidence of CMT-associated CD in patients who have previously received CMT is not well established, and probably low, practitioners should strongly consider the possibility of CD as a presenting symptom, and patients should be informed of the statistical association between CD and CMT prior to undergoing manipulation of the cervical spine.

Stroke survivors control the temporal structure of variability during reaching in dynamic environments.

Learning to control forces is known to reduce the amount of movement variability (e.g., standard deviation; SD) while also altering the temporal structure of movement variability (e.g., approximate entropy; ApEn). Such variability control has not been explored in stroke survivors during reaching movements in dynamic environments. Whether augmented feedback affects such variability control, is also unknown. Chronic stroke survivors, assigned randomly to a control/experimental group, learned reaching movements in a dynamically changing environment while receiving either true feedback of their movement (control) or augmented visual feedback (experimental). Hand movement variability was analyzed using SD and ApEn. A significant change in variability was determined for both SD and ApEn. Post hoc tests revealed that the significant decrease in SD was not retained after a week. However, the significant increase in ApEn, determined on both days of training, showed significant retention effects. In dynamically changing environments, chronic stroke survivors reduced the amount of movement variability and made their movement patterns less repeatable and possibly more flexible. These changes were not affected by augmented visual feedback. Moreover, the learning patterns characteristically involved the control of the nonlinear dynamics rather than the amount of hand movement variability. The absence of transfer effects demonstrated that variability control of hand movement after a stroke is specific to the task and the environment.

Selective infarction of the anterior genu fornices associated with giant cell arteritis.

We report a middle-aged woman presenting with acute confusion and anterograde amnesia. Magnetic resonance imaging revealed an acute infarction of the anterior genu fornices. Evaluation of an elevated erythrocyte sedimentation rate led to the diagnosis of giant cell arteritis (GCA). Cerebral infarction is a known complication of GCA; this is the first report of such an association with selective fornix infarction.

The influence of visual perception of self-motion on locomotor adaptation to unilateral limb loading.

Self-perception of motion through visual stimulation may be important for adapting to locomotor conditions. Unilateral limb loading is a locomotor condition that can improve stability and reduce abnormal limb movement. In the present study, the authors investigated the effect of self-perception of motion through virtual reality (VR) on adaptation to unilateral limb loading. Healthy young adults, assigned to either a VR or a non-VR group, walked on a treadmill in the following 3 locomotor task periods--no load, loaded, and load removed. Subjects in the VR group viewed a virtual corridor during treadmill walking. Exposure to VR reduced cadence and muscle activity. During the loaded period, the swing time of the unloaded limb showed a larger increase in the VR group. When the load was removed, the swing time of the previously loaded limb and the stance time of the previously unloaded limb showed larger decrease and the swing time of the previously unloaded limb showed a smaller increase in the VR group. Lack of visual cues may cause the adoption of cautious strategies (higher muscle activity, shorter and more frequent steps, changes in the swing and stance times) when faced with situations that require adaptations. VR technology, providing such perceptual cues, has an important role in enhancing locomotor adaptation.

Postendarterectomy mortality in octogenarians and nonagenarians in the USA from 1993 to 1999.

BACKGROUND: Relatively little is known about trends in the utilization or outcomes of carotid endarterectomy (CEA) in the very elderly. We determined trends in the rates of CEA and perioperative (in-hospital and 30-day) and long-term (1-, 2-, 3-, 4- and 5-year) mortality in a US national sample of patients >or=80 years of age. METHODS: All fee-for-service Medicare patients (80-89 and >or=90 years of age) who had a CEA [ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification): 38.12] from 1993 to 1999 were identified using the Centers for Medicare and Medicaid Services Inpatient Standard Analytic Files. Demographic characteristics and comorbid conditions were determined using ICD-9-CM diagnostic codes within the year prior to the index hospitalization for CEA. RESULTS: A total of 140,376 CEA were performed in patients aged 80-89 years and 6,446 in those aged >or=90 years during this 7-year period. The annual number of operations increased from 13,115 in 1993 to 21,582 in 1999 for octogenarians, and from 481 in 1993 to 1,257 in 1999 for nonagenarians. Perioperative mortality was 2.2% in octogenarians and 3.3% in nonagenarians. Long-term mortality increased by approximately 10% per year after the operation, and was 43% in octogenarians and 56% in nonagenarians at 5 years. Perioperative mortality rates remained relatively stable over the 7-year period for both age groups although comorbidities increased. CONCLUSIONS: The number of CEA performed in the very elderly in the USA increased from 1993 to 1999. Perioperative mortality rates were high compared with trial results, while long-term survivorship was comparable to that of similarly-aged peers in the USA.

Outpatient practice patterns after stroke hospitalization among neurologists.

BACKGROUND AND PURPOSE: Care after stroke hospitalization can provide several opportunities to optimize vascular risk reduction. However, not much is known about poststroke practice patterns among neurologists. Such knowledge may help direct specific efforts to improve the impact of practicing neurologists on clinical outcomes after stroke. METHODS: A survey soliciting information on processes of care in the outpatient setting after recent hospitalization for ischemic stroke or transient ischemic attack was mailed to a random sample of 833 US and Canadian neurologist-members of the American Academy of Neurology. RESULTS: A total of 475 (57%) responses were received. Practice demographics of survey responders and nonresponders were largely similar. Fourteen percent of respondents identified themselves as vascular neurologists. Overall, respondents reported frequently checking for medication adherence and counseling patients on lifestyle modification. However, neurologists reported screening more frequently for diabetes, hypertension, and dyslipidemia than actually treating these conditions (all P<0.0001) Vascular neurologists were more likely than general neurologists to screen for hypertension (97% versus 86%, P=0.016), dyslipidemia (94% versus 68%, P<0.001), diabetes (89% versus 62%, P<0.001), and sleep apnea (94% versus 79%, P=0.007) as well as to treat hypertension (71% versus 45%, P<0.001), dyslipidemia (82% versus 50%, P<0.001), diabetes (45% versus 21%, P<0.001), and current smoking (77% versus 59%, P=0.005). Neurologists with mostly government-insured and uninsured patients were significantly more likely to engage in vascular risk reduction treatment than neurologists with mostly commercially insured patients. CONCLUSIONS: Self-reported rates of screening and treatment of major vascular risk factors by most neurologists after stroke hospitalization are substantial but not universal. Bridging knowledge gaps or adopting a systematic management approach in coordination with primary care physicians could help optimize poststroke care.

Long-term results of carotid stenting versus endarterectomy in high-risk patients.

BACKGROUND: We previously reported that, in a randomized trial, carotid stenting with the use of an emboli-protection device is not inferior to carotid endarterectomy for the treatment of carotid artery disease at 30 days and at 1 year. We now report the 3-year results. METHODS: The trial evaluated carotid artery stenting with the use of an emboli-protection device as compared with endarterectomy in 334 patients at increased risk for complications from endarterectomy who had either a symptomatic carotid artery stenosis of at least 50% of the luminal diameter or an asymptomatic stenosis of at least 80%. The prespecified major secondary end point at 3 years was a composite of death, stroke, or myocardial infarction within 30 days after the procedure or death or ipsilateral stroke between 31 days and 1080 days (3 years). RESULTS: At 3 years, data were available for 260 patients (77.8%), including 85.6% of patients in the stenting group and 70.1% of those in the endarterectomy group. The prespecified major secondary end point occurred in 41 patients in the stenting group (cumulative incidence, 24.6%; Kaplan-Meier estimate, 26.2%) and 45 patients in the endarterectomy group (cumulative incidence, 26.9%; Kaplan-Meier estimate, 30.3%) (absolute difference in cumulative incidence for the stenting group, -2.3%; 95% confidence interval, -11.8 to 7.0). There were 15 strokes in each of the two groups, of which 11 in the stenting group and 9 in the endarterectomy group were ipsilateral. CONCLUSIONS: In our trial of patients with severe carotid artery stenosis and increased surgical risk, no significant difference could be shown in long-term outcomes between patients who underwent carotid artery stenting with an emboli-protection device and those who underwent endarterectomy. (ClinicalTrials.gov number, NCT00231270 [ClinicalTrials.gov].).

Endarterectomy and stenting for asymptomatic carotid stenosis: a race at breakneck speed.

Atherosclerotic carotid stenosis has been recognized for the past several decades as being responsible for a significant portion of ischemic stroke, particularly the major and disabling ones. This category of stroke distinguished itself as being one of the first ones to have an effective preventive treatment in carotid endarterectomy. It took over 4 decades before major randomized, controlled trials were completed in North America and Europe to provide enough definitive information about its effectiveness, risks, limitations, and categories of patients that most benefit from it. Just like any invasive surgery, endarterectomy is being challenged by minimally invasive stenting, which has already made major technologic leaps and rapid clinical inroads. Stenting has started by tackling patient populations like surgical high-risk patients who were largely avoided in the endarterectomy trials and demonstrated equivalence to it in such populations. The broader applicability of the technique, however, has not been yet adequately investigated. The results so far are greatly reassuring and encouraging to enroll patients in the ongoing randomized trials that will hopefully provide more definitive answers to this issue.

Feasibility trial of carotid stenting with and without an embolus protection device.

PURPOSE: To evaluate the feasibility of stenting and cerebral protection in patients with carotid bifurcation disease. METHODS: Carotid stenting with self-expanding nitinol stents was evaluated in 261 patients (157 men; mean age 70.9+/-9.7 years, range 41-90) treated at 33 clinical sites. Among these patients, 141 (54.3%) were symptomatic, and 71 (27.2%) had postendarterectomy restenotic lesions. An embolus protection device became available in the latter third of the study. The primary endpoint of the study was the 30-day composite occurrence of major adverse clinical events (all deaths, strokes, or myocardial infarctions [MI]). At 1 year, the endpoint included all deaths, strokes, or MIs at 30 days, plus all deaths or ipsilateral strokes between 31 days and 1 year. RESULTS: SMART stents were placed in 147 (56%) patients and Precise stents in 107 (41%); 7 (3%) patients were treated with non-study stents. Lesion success, defined as <30% postprocedural residual stenosis, was achieved in 249 (95%). An AngioGuard filter was used in 85 patients; of 90 filters employed, 78 (87%) were successfully deployed and retrieved. Visible material was noted in 42 (54%) retrieved filters. One (0.4%) stent thrombosis occurred at <30 days, and no restenotic lesions >80% were noted in up to 1 year of follow-up. At 30 days, stroke occurred in 16 (6.1%) patients, MI in 1 (0.4%), and 2 (0.8%) patients died. The 30-day rate of stroke, MI, or death was 6.9%. Major ipsilateral stroke occurred in 4 (1.5%) patients between 0 and 30 days; no new major ipsilateral strokes were noted up to 1 year. By Kaplan-Meier analysis, the 1-year risk of stroke, MI, or death was 10.9%+/-2.0%. The 1-year risk of major ipsilateral stroke was significantly lower in patients treated with embolus protection devices (0.0% versus 2.3%, p=0.05). CONCLUSIONS: The use of nitinol self-expanding stents in the carotid position appears to be a safe and efficacious alternative for the treatment of carotid bifurcation disease. The addition of embolus protection devices may diminish the risk of postprocedural major ipsilateral strokes.