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Zafer Keser,1 Chia-Chun Chiang,1 John C Benson,2 Alessandro Pezzini,3 Giuseppe Lanzino4 1Department of Neurology, Mayo Clinic, Rochester, MN, USA; 2Department of Radiology, Mayo Clinic, Rochester, MN, USA; 3Department of Clinical and Experimental Sciences, Neurology Clinic, University of Brescia, Brescia, Italy; 4Department of Neurosurgery, Mayo Clinic, Rochester, MN, USACorrespondence: Zafer Keser, Department of Neurology – Mayo Clinic, 200 First St SW, Rochester, MN, 55905, USA, Email keser.zafer@mayo.eduAbstract: Cervical Artery Dissection (CeAD) is a frequent stroke etiology for patients younger than 50 years old. The most common immediate complications related to CeAD are headache and neck pain (65– 95%), TIA/ischemic stroke (> 50%), and partial Horner’s syndrome (25%). The prevailing hypothesis regarding the pathogenesis of sCeAD is that the underlying constitutional vessel wall weakness of patients with sCeAD is genetically determined and that environmental factors could act as triggers. The stroke prevention treatment of CeAD remains controversial, involving anticoagulation or antiplatelet therapy and potentially emergent stenting and/or thrombectomy or angioplasty for selected cases of carotid artery dissection with occlusion. The treatment of headache associated with CeAD depends on the headache phenotype and comorbidities. Radiographically, more than 75% of CeAD cases present with occlusion or non-occlusive stenosis. Many patients demonstrate partial and complete healing, more commonly in the carotid arteries. One-fifth of the patients develop dissecting pseudoaneurysm, but this is a benign clinical entity with an extremely low rupture and stroke recurrence risk. Good recovery is achieved in many CeAD cases, and mortality remains low. Family history of CeAD, connective tissue disorders like Ehlers-Danlos syndrome type IV, and fibromuscular dysplasia are risk factors for recurrent CeAD, which can occur in 3– 9% of the cases. This review serves as a comprehensive, updated overview of CeAD, emphasizing etiopathogenesis and management.Keywords: cervical artery dissection, genetics, stroke

Background: Recent studies show cervical artery dissection (CeAD) is equally common between sexes, and that the incidence of CeAD has risen at a greater rate in females than males. In this population-based study, we identify sex differences in patients diagnosed with spontaneous and traumatic CeAD., Methods: 144 patients with spontaneous or traumatic CeAD were studied for sex differences in medical comorbidities, presenting symptoms and outcomes., Results: Females were more likely to carry a diagnosis of migraine, while males were more likely to have hyperlipidaemia. Females were more likely to present with neck pain, males with stroke. Females were significantly more likely to develop recurrent dissections in the study period., Conclusions: These findings underscore the importance of understanding CeAD through the lens of sex differences and may explain the significant rise in the diagnosis of CeAD in females. These findings support the importance of considering sex-specific risk factors and medical comorbidities with sex predilection in the diagnosis and management of CeAD. Furthermore, it emphasises the importance of female patients understanding risk factors and presenting signs that should prompt evaluation for CeAD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The management of superior cerebellar aneurysms is still controversial. Although several techniques are available, the deep localization of the lesion and the limited number of cases increase the complexity of decision-making for optimal treatment. Only a few cases of dissecting and fusiform aneurysms of the superior cerebellar artery (SCA) are described in the literature, many of which are without long follow-ups. The study aims to offer an exhaustive retrospective analysis of patients affected by SCA fusiform and dissecting aneurysms treated at our institution from 2008 to 2023, highlighting outcomes and complications. Moreover, a comprehensive narrative review was performed. A total of seven patients were treated at our institution. After a title and abstract screen, fifty-five papers met the criteria for inclusion in the review. In our case series, conservative treatment was proposed as the first therapeutic option in four cases (57.1%), while endovascular treatment (EVT) was in three cases (42.9%). A good recovery was observed in 66% of patients presenting with subarachnoid hemorrhage (SAH), while every patient without SAH achieved a good clinical outcome. A poor outcome was observed only in one patient with a dissecting aneurysm causing SAH, who also suffered a pontine infarction. In the literature review, conservative treatment was proposed as a first therapeutic option in eleven cases (16.6%), open microsurgical techniques in 19 patients (28.8%), and EVT in 31 patients (46.9%). Fatal outcome was documented in five patients (7.5%), all characterized by the rupture of the vascular lesion, while 6.1% of cases had non-fatal poor outcomes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Purpose: The value of long-term serial imaging of dissecting pseudoaneurysm (dPSA) is poorly characterized. This study investigated the long-term radiographic evolution of dPSA., Methods: We performed a query in our institutional craniocervical artery dissection registry to identify cases with spontaneous dPSA who had at least one year of follow-up with serial angiographic imaging. We performed Wilcoxon rank-sum pairwise comparison test to determine if there was a significant change in the aneurysm size over time., Results: This observational cohort study included 76 patients (46 females; 64 dPSA in the internal carotid artery [ICA] and 12 in the vertebral artery [VA]) with a median age of 49.5 years (range 24-77). The initial median dPSA size was 8 mm (interquantile range(iqr) = 5.88-11mm), and the final median dPSA size was 7 mm (iqr = 4-11 mm). Most patients had either no change or reduction in dPSA size in the serial follow-up, with no significant change over time. All the patients had favorable outcomes at the last follow-up, and most patients were symptom-free from dPSA (92 %). Two patients (2.6%) experienced recurrent ischemic strokes in the same territory as the initial ischemic stroke without any change in dPSA size., Conclusion: Further serial scans for dPSA after one year may be deferred in the absence of interim clinical symptoms as most dPSA either remains stable or decreases in size. Recurrent stroke, although a rare event, was not associated with an increase in dPSA size., Competing Interests: Declaration of competing interest The authors declare no relevant interests for this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Few investigations examined the relationship between microstructural white matter integrity and subacute post-stroke linguistic performance or the relationship between microstructural integrity and the recovery of language function. We examined two key questions: (1) How does subacute language performance, measured in single words and discourse, relate to the microstructural integrity of key white matter regions of interest in the language network? and (2) Does the integrity of these regions before treatment predict the improvement or resolution of linguistic symptoms immediately and chronically following treatment?, Methods: 58 participants within the first three months of stroke were enrolled in a randomized, single-center, double-blind, sham-controlled, study of anodal transcranial direct current stimulation combined with a computer-delivered speech and language naming therapy for subacute aphasia and were asked to complete magnetic resonance imaging at enrollment. Microstructural integrity was evaluated using diffusion tensor imaging processed with atlas-based segmentation. Regression and correlation analyses were conducted., Results: A subset of 22 participants received diffusion tensor imaging. Picture naming accuracy significantly correlated with lower mean diffusivity (higher microstructural integrity) in the left posterior inferior temporal gyrus. Recovery of naming performance was predicted by days since stroke and baseline microstructural integrity of the left posterior middle temporal gyrus, arcuate fasciculus, and superior longitudinal fasciculus. Recovery of discourse efficiency was significantly predicted by the same model., Conclusions: This study demonstrates an association between picture naming and discourse and microstructural integrity of the key regions in the language network for patients with subacute post-stroke aphasia. Baseline microstructural integrity significantly predicts language recovery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: It is uncertain whether antiplatelets or anticoagulants are more effective in preventing early recurrent stroke in patients with cervical artery dissection. Following the publication of the observational Antithrombotic for STOP-CAD (Stroke Prevention in Cervical Artery Dissection) study, which has more than doubled available data, we performed an updated systematic review and meta-analysis comparing antiplatelets versus anticoagulation in cervical artery dissection., Methods: The systematic review was registered in PROSPERO (CRD42023468063). We searched 5 databases using a combination of keywords that encompass different antiplatelets and anticoagulants, as well as cervical artery dissection. We included relevant randomized trials and included observational studies of dissection unrelated to major trauma. Where studies were sufficiently similar, we performed meta-analyses for efficacy (ischemic stroke) and safety (major hemorrhage, symptomatic intracranial hemorrhage, and death) outcomes using relative risks., Results: We identified 11 studies (2 randomized trials and 9 observational studies) that met the inclusion criteria. These included 5039 patients (30% [1512] treated with anticoagulation and 70% [3527]) treated with antiplatelets]. In meta-analysis, anticoagulation was associated with a lower ischemic stroke risk (relative risk, 0.63 [95% CI, 0.43 to 0.94]; P =0.02; I 2 =0%) but higher major bleeding risk (relative risk, 2.25 [95% CI, 1.07 to 4.72]; P =0.03, I 2 =0%). The risks of death and symptomatic intracranial hemorrhage were similar between the 2 treatments. Effect sizes were larger in randomized trials. There are insufficient data on the efficacy and safety of dual antiplatelet therapy or direct oral anticoagulants., Conclusions: In this study of patients with cervical artery dissection, anticoagulation was superior to antiplatelet therapy in reducing ischemic stroke but carried a higher major bleeding risk. This argues for an individualized therapeutic approach incorporating the net clinical benefit of ischemic stroke reduction and bleeding risks. Large randomized clinical trials are required to clarify optimal antithrombotic strategies for management of cervical artery dissection., Competing Interests: Disclosures Dr Henninger has received funding from the National Institutes of Health ([NIH]; NS131756, NR020231) during the conduct of this study, unrelated to the present work. Dr Nguyen discloses advisory board for Brainomix and Aruna and is an Associate Editor for Stroke. Dr Siegler has served as a consultant for AstraZeneca and has received funding from the NIH (R61NS135583), vizai, Philips, and Medtronic, unrelated to this work. Dr Field has received in-kind study medication from Bayer and discloses advisory board participation for Bayer, AstraZeneca, Roche, HLS Therapeutics, and Novartis, is on the board of DESTINE Health, and has served as an expert witness. Dr Mistry receives funding from the NIH/National Institute of Neurological Disorders and Stroke and Patient Centered Outcomes Research Institute. She serves as a consultant for AbbVie and RAPID AI and serves on the steering committee for SilverCreek Pharmaceuticals. She reports a nonfinancial relationship with Translational Sciences Inc. She is also an Associate Editor for Stroke and is employed by the University of Cincinnati. Dr de Havenon is a consultant for Integra, TitinKM, and Novo Nordisk, own stocks in Certus, and receives grant support from the NIH. Dr Fletcher received funds from the Library association and is an officer of the Association of College and Research Libraries and the Medical Library Association. Dr Furie is a consultant for Janssen Biotech. Dr Markus receives infrastructural support provided by the Cambridge British Heart Foundation Centre of Research Excellence (RE/18/1/34212) and by the Cambridge University Hospitals NIHR Biomedical Research Centre (NIHR203312).

Background: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation., Methods: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments., Results: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; P interaction =0.009)., Conclusions: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings., Competing Interests: Disclosures Disclosures provided by Dr Nguyen in compliance with American Heart Association annual Journal Editor Disclosure Questionnaire are available at https://www.ahajournals.org/editor-coi-disclosures. Dr Arnold reports compensation from Boehringer Ingelheim, AstraZeneca, Bayer, Bristol-Myers Squibb, Covidien, Daiichi Sankyo, Novartis, Sanofi, Pfizer, Medtronic, Novo Nordisk, and Amgen for consultant services. Dr Lester reports a provisional patent for Methods and compositions for disrupting tau aggregates. Dr Touze reports compensation from Elsevier for other services and employment by Caen. J.E. Kaufman reports grants from Goldschmidt Jacobson-Stiftung. Dr Traenka reports travel support from Bayer Healthcare. Dr Aguiar de Sousa reports compensation from Daiichi Sankyo, Bayer, AstraZeneca, Johnson & Johnson, and Fundação Bial for other services; compensation from the University of British Columbia for data and safety monitoring services; compensation from Organon & Co for consultant services. Dr Rosa reports grants from Merck Sharp & Dohme Corporation. Dr Field reports compensation from HLS Therapeutics, AstraZeneca Canada, and Roche for consultant services; service as a board member for Destine Health; and compensation from the Canadian Medical Protective Association for expert witness services; and grants from Bayer. Dr Leker reports compensation from Medtronic, Ischemaview, Bayer, Abbott Diabetes Care, Biogen, Janssen Biotech, and Boehringer Ingelheim for other services. Dr Nolte reports compensation from Daiichi Sankyo Europe GmbH, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, and Alexion Pharmaceuticals for consultant services; and compensation from AstraZeneca, Abbott Canada, Deutsches Zentrum für Neurodegenerative Erkrankungen, Novartis, Portola Pharmaceuticals, Deutsches Zentrum für Herz-Kreislaufforschung, and Novartis for other services. Dr Poppe reports grants from Foundation Brain Canada, Heart and Stroke Foundation of Canada, and Stryker; and compensation from Roche for other services. Dr Liebeskind reports compensation from Medtronic, Genentech, Cerenovus, Stryker, and Rapid Medical Ltd, for consultant services. B. Mac Grory reports grants from the National Institutes of Health; employment by Duke University Medical Center; compensation from Bayer for other services; grants from the American Heart Association, Duke Bass Connections, and the Duke Office of Physician Scientist Development. Dr Al Kasab reports compensation from Stryker for other services and employment by Medical University of South Carolina. Dr Kicielinski reports compensation from Stryker, Penumbra Inc, Medtronic, and MicroVention Inc, for other services; travel support from MicroVention Inc; and employment by Medical University of South Carolina and Elsevier. Dr de Havenon reports stock options in TitinKM and Certus; grants from the National Institutes of Health; and compensation from Novo Nordisk for consultant services. Dr Siegler reports grants from Philips and employment by the University of Chicago. Dr Willey reports compensation from Edwards Lifesciences Corporation and Abbott Fund for end point review committee services; compensation from Uptodate for other services; and compensation from the Abbott Laboratories for consultant services. Dr Sharma reports a provisional patent for a stroke etiology classifier algorithm and grants from the National Institutes of Health Clinical Center. Dr Martins reports compensation from Pfizer, Medtronic, Servier Affaires Medicales, Daiichi Sankyo, Bayer, Novo Nordisk, Novartis, Penumbra Inc, and Boehringer Ingelheim for other services. Dr Simpkins reports grants from the National Institutes of Health. Dr Stretz reports grants from Massachusetts General Hospital. Dr Furie reports compensation from Janssen Biotech for consultant services. The other authors report no conflicts

Purpose: Cervical radiculopathy due to various mechanical causes is commonly seen, however, cervical vertebral artery dissection (cVAD)-related radiculopathy is very rare with poorly characterized clinical outcomes. Thus, we conducted a systematic review of published literature and reported an institutional case to provide a better illustration of this rare entity., Methods: We systematically reviewed the PubMed literature and queried the clinical database at our center for cVAD-related radiculopathy. We described the baseline characteristics of patients with cVAD-related radiculopathy, the involved segment, diagnostic approach and treatment options., Result: 14 previously published studies met the inclusion criteria and along with the case we identified in our center, our study included 17 patients total (median age: 35 years, 9 females). C5 was the most commonly affected root and ipsilateral shoulder/arm pain along with shoulder abduction weakness was most common presentation. Antiplatelet or anticoagulant therapy was the treatment of choice. Most cases managed conservatively (82%). Majority of the cases (92%) had either complete or partial resolution of their symptoms., Conclusion: Despite its limitations, this study show that cVAD related radiculopathy is a relatively benign entity with excellent clinical outcomes when managed medically.

Competing Interests: Disclosures None.

Background: Cervical artery dissection (CeAD) represents up to 15% to 25% of ischemic strokes in people under the age of 50 years. Noninvasive vessel imaging is increasingly used in clinical practice, but the impact on the frequency of detection of CeAD is unknown. In 2006, the yearly incidence rate of CeAD was estimated at 2.6 per 100 000 person-years, but the current incidence is unknown., Methods: In this population-based retrospective observational cohort study, we utilized the resources of the Rochester Epidemiology Project to ascertain all adult residents of Olmsted County, MN, diagnosed with internal carotid artery dissection and common carotid artery dissection or vertebral artery dissection from 2002 to 2020. Patients with only intracranial involvement or CeAD following major trauma were excluded. Age-adjusted sex-specific and age- and sex-adjusted incidence rates were estimated using the US White 2010 decennial census, with rates expressed per 100 000 person-years. We assessed longitudinal trends by dividing the data into 5-year time intervals, with the last being a 4-year interval., Results: We identified 123 patients with a diagnosis of CeAD. There were 63 patients with internal carotid artery dissection, 54 with vertebral artery dissection, 2 with concurrent internal carotid artery dissection and vertebral artery dissection, and 4 with common carotid artery dissection. There were 63 (51.2%) female patients and 60 (48.8%) male patients. The average age at diagnosis was 50.2 years (SD, 15.1 [95% CI, 20.1-90.5] years). The incidence rate of spontaneous CeAD encompassing all locations was 4.69 per 100 000 person-years (2.43 for internal carotid artery dissection and 2.01 for vertebral artery dissection). The incidence rate increased from 2.30 per 100 000 person-years from 2002 to 2006 to 8.93 per 100 000 person-years from 2017 to 2020 ( P <0.0001). The incidence rate for female patients rose from 0.81 per 100 000 person-years from 2002 to 2006 to 10.17 per 100 000 person-years from 2017 to 2020., Conclusions: The incidence rate of spontaneous CeAD increased nearly 4-fold over a 19-year period from 2002 to 2020. The incidence rate in women rose over 12-fold. The increase in incidence rates likely reflects the increased use of noninvasive vascular imaging., Competing Interests: Disclosures None.

Objective: Most cervical artery dissection (CeAD) cases are spontaneous or due to minor traumas, and preceding viral infections have been suggested to be a triggering event for CeAD in some. Herein, we analyze the prevalence of coronavirus disease 2019 (COVID-19) in hospitalized patients with CeAD using a national database., Methods: The National Inpatient Sample was queried from April 2020 to December 2020 for patients with a diagnosis of CeAD using International Classification of Diseases, 10th edition-Clinical Modification codes. Among these, patients with COVID-19 were identified. Multivariable logistic regression was conducted to assess the patient profile of those with COVID-19, in-patient mortality, and home discharge among patients with CeAD., Results: There were 360 (2.32%) hospitalizations involving COVID-19 among 15,500 with CeAD. Concomitant acute ischemic stroke constituted 43.06% of those with a COVID-19 diagnosis, whereas it was 43.73% among those without a COVID-19 diagnosis ( P = 0.902). Home discharges were less common in patients with COVID-19 and CeAD compared to CeAD alone (34.85% vs. 48.63%; P = 0.03), but this was likely due to other factors as multivariate regression analysis did not show an association between COVID-19 and home discharges (odds ratio: 0.69; 95% CI: 0.39 to 1.25; P = 0.22). COVID-19 diagnosis had similar odds of inpatient mortality (odds ratio: 1.11; 95% CI: 0.43 to 2.84; P = 0.84)., Conclusion: The prevalence of COVID-19 among hospitalized patients with CeAD is low with 2.32% of all CeAD cases. Concomitant COVID infection did not lead to an increased risk of stroke in CeAD. However, potentially worse functional outcomes (fewer home discharges) without an increase in mortality were seen in patients with COVID and CeAD., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Management of intracranial artery dissection (IAD) remains elusive in medical practice. Intracranially, vertebral artery dissection (VAD) is more commonly encountered than internal carotid artery dissection (ICAD). Deconstructive (EVT-d) and reconstructive (EVT-r) endovascular techniques have been utilized to treat VAD and ICAD. This meta-analysis investigates the safety and efficacy of EVT-r and EVT-d in the management of VAD and ICAD., Methods: The literature was searched for all studies with consecutive patient series evaluating EVT-d or EVT-r for VAD or ICAD management. Baseline characteristics and outcomes were compared between EVT-r and EVT-d groups using the random-effect model and meta-regression approaches., Results: Overall, 1095 cases pooled from 56 studies were included. There was no statistically significant difference in baseline characteristics between VAD and ICAD. EVT-r was applied in 647 cases (59.1%) and EVT-d in the rest There was no statistical difference in the rate of procedural complications between EVT-r and EVT-d. Although EVT-d was significantly associated with higher rates of complete aneurysm occlusion (86.4%), lower rates of good clinical outcomes (72.1%) and higher mortality (15.1%) were achieved compared to EVT-r (70.2%, 83.3%, and 9.5%; respectively). The mortality rate was higher, and good clinical outcomes were less common in ruptured aneurysms. Ischemic presentation was statistically associated with poor outcomes (mRS 3-5) but low mortality. ICAD often tended to grow following treatment and resulted in poor neurological outcomes., Conclusions: IAD has favorable outcomes when treated appropriately. Novel reconstructive endovascular techniques are promising and should be integrated well in endovascular practice. Further studies are warranted., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: Tenecteplase is a fibrin-specific plasminogen activator that has shown promising results in the treatment of acute ischemic stroke. Tenecteplase has been suggested to reduce door-to-needle time and to increase the rate of spontaneous recanalization. In February 2021, Mayo Clinic Health System switched to Tenecteplase as the standard thrombolytic therapy for acute ischemic stroke., Methods: In this center-based observational cohort study, we present clinical characteristics and outcomes of patients with acute ischemic stroke treated with tenecteplase between February 2021 and May 2022 compared with alteplase treatment between September 2019 and February 2021. We used descriptive and comparative statistics., Results: Baseline characteristics were comparable between the groups. The incidence of symptomatic intracerebral hemorrhage was significantly less among the tenecteplase group (0.65% vs. 5%, P =0.027). Both groups had a similar door-to-needle time [55 (IQR 30.5) vs. 57 (IQR 38) in the tissue plasminogen activator group, P =0.395]. Spontaneous partial or complete recanalization was more commonly observed in the tenecteplase group (10.4% vs. 1.4%, P =0.038). Mechanical thrombectomy for large vessel occlusion was deferred due to marked clinical improvement more commonly in tenecteplase (6.3% vs. 1.4%); however, this difference was not statistically significant. Ninety-day modified Rankin Scale did not show a significant difference between the groups., Conclusion: Tenecteplase use as the thrombolytic agent in acute ischemic stroke was associated with lower rates of symptomatic intracranial hemorrhage, higher rates of spontaneous recanalization, but similar door-to-needle time and 90-day modified Rankin Scale as compared with tissue plasminogen activator., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Fusiform aneurysms of the anterior cerebral artery (ACA) are uncommon, and the natural history of this entity is poorly characterized. Along with our center experience, we conducted a systematic literature review to help shed light on the clinical course of ACA fusiform aneurysms. We queried our institutional database to identify cases with fusiform aneurysms of ACA. In addition, following the PRISMA algorithm, we identified all reported cases published in the English literature from the inception of PubMed until December 2022. We categorized clinical presentations into three categories: (i) traumatic/iatrogenic, (ii) spontaneous symptomatic ruptured/unruptured, and (iii) spontaneous asymptomatic aneurysms. We utilized descriptive statistics. We identified seven cases from our center along with 235 patients from published literature. Blunt trauma was responsible for the development of 19 aneurysms. Sixty-three percent of these aneurysms tend to rupture within 2 weeks from the initial trauma, and despite treatment, only 74% of these patients had good clinical outcomes. Spontaneous symptomatic presentation occurred in 207 patients and was often associated with previous/concomitant ACA dissection. Subarachnoid hemorrhage from ruptured aneurysms was the most common presentation. Spontaneous symptomatic fusiform aneurysm is rapidly evolving lesions, and treatment is necessary. Three of our own cases were treated with an endovascular flow diverter (pipeline) stenting with good outcomes. Spontaneous asymptomatic aneurysms were reported in nine patients. These lesions are often associated with other vascular abnormalities. Treatment included surgical clipping with good clinical outcomes. Instead, four patients from our center database were managed conservatively with equally good outcomes. Our study demonstrates good clinical outcomes when fusiform aneurysms of ACA, especially when symptomatic, are treated promptly with either reconstructive or deconstructive therapies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose of Review: Stroke remains a leading disabling condition, and many survivors have permanent disability despite acute stroke treatment and subsequent standard-of-care rehabilitation therapies. Adjunctive neuromodulation is an emerging frontier in the field of stroke recovery. In this narrative review, we aim to highlight and summarize various neuromodulation techniques currently being investigated to enhance recovery and reduce impairment in patients with stroke., Recent Findings: For motor recovery, repetitive transcranial magnetic simulation (rTMS) and direct current stimulation (tDCS) have shown promising results in many smaller-scale trials. Still, their efficacy has yet to be proven in large-scale pivotal trials. A promising large-scale study investigating higher dose tDCS combined with constraint movement therapy to enhance motor recovery is currently underway. MRI-guided tDCS studies in subacute and chronic post-stroke aphasia showed promising benefits for picture-naming recovery. rTMS, particularly inhibitory stimulation over the contralesional homolog, could represent a pathway forward in post-stroke motor recovery in the setting of a well-designed and adequately powered clinical trial. Recently evidenced-based guideline actually supported Level A (definite efficacy) for the use of low-frequency rTMS of the primary motor cortex for hand motor recovery in the post-acute stage of stroke based on the meta-analysis result. Adjunctive vagal nerve stimulation has recently received FDA approval to enhance upper limb motor recovery in chronic ischemic stroke with moderate impairment, and progress has been made to implement it in real-world practice. Despite a few small and large-scale studies in epidural stimulation (EDS), further research on the utilization of EDS in post-stroke recovery is needed. Deep brain stimulation or stent-based neuromodulation has yet to be further tested regarding safety and efficacy. Adjunctive neuromodulation to rehabilitation therapy is a promising avenue for promoting post-stroke recovery and decreasing the overall burden of disability. The pipeline for neuromodulation technology remains strong as they span from the preclinical stage to the post-market stage. We are optimistic to see that more neuromodulation tools will be available to stroke survivors in the not-to-distant future., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Tremor affects up to 45% of patients with Multiple Sclerosis (PwMS). Current understanding is based on insights from other neurological disorders, thus, not fully addressing the distinctive aspects of MS pathology., Objective: To characterize the brain white matter (WM) correlates of MS-related tremor using diffusion tensor imaging (DTI)., Methods: In a prospective case-control study, PwMS with tremor were assessed for tremor severity and underwent MRI scans including DTI. PwMS without tremor served as matched controls. After tract selection and segmentation, the resulting diffusivity measures were used to calculate group differences and correlations with tremor severity., Results: This study included 72 PwMS. The tremor group (n = 36) exhibited significant changes in several pathways, notably in the right inferior longitudinal fasciculus (Cohen's d  = 1.53, q  < 0.001) and left corticospinal tract ( d  = 1.32, q  < 0.001), compared to controls (n = 36). Furthermore, specific tracts showed a significant correlation with tremor severity, notably in the left medial lemniscus (Spearman's coefficient [ r s p ] = -0.56, p  < 0.001), and forceps minor of corpus callosum ( r s p  = -0.45, p  < 0.01)., Conclusion: MS-related tremor is associated with widespread diffusivity changes in WM pathways and its severity correlates with commissural and sensory projection pathways, which suggests a role for proprioception or involvement of the dentato-rubro-olivary circuit., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2023.)

Stroke is one of the leading causes of disability worldwide despite recent advances in hyperacute interventions to lessen the initial impact of stroke. Stroke recovery therapies are crucial in reducing the long-term disability burden after stroke. Stroke recovery treatment options have rapidly expanded within the last decade, and we are in the dawn of an exciting era of multimodal therapeutic approaches to improve post-stroke recovery. In this narrative review, we highlighted various promising advances in treatment and technologies targeting stroke rehabilitation, including activity-based therapies, non-invasive and minimally invasive brain stimulation techniques, robotics-assisted therapies, brain-computer interfaces, pharmacological treatments, and cognitive therapies. These new therapies are targeted to enhance neural plasticity as well as provide an adequate dose of rehabilitation and improve adherence and participation. Novel activity-based therapies and telerehabilitation are promising tools to improve accessibility and provide adequate dosing. Multidisciplinary treatment models are crucial for post-stroke neurorehabilitation, and further adjuvant treatments with brain stimulation techniques and pharmacological agents should be considered to maximize the recovery. Among many challenges in the field, the heterogeneity of patients included in the study and the mixed methodologies and results across small-scale studies are the cardinal ones. Biomarker-driven individualized approaches will move the field forward, and so will large-scale clinical trials with a well-targeted patient population.

Background: Data on safety of thrombolysis for acute ischemic stroke (AIS) in patients with hematologic malignancy is not well established. We report our single institution experience with thrombolysis in this patient population., Methods: We identified patients with pathology-confirmed hematologic malignancy from 2000-2022. Primary exposure was presence of AIS and receipt of intravenous (IV) thrombolysis. Primary outcome was safety of IV thrombolysis in this patient population. Safety was measured through imaging review for hemorrhagic transformation, post-stroke mortality, and modified Rankin Scale (mRS) at 90 days., Results: Among 45,894 patients with hematologic malignancy, 1,099 (2.4%) were identified as having a suspected AIS. Twenty (1.8%) received IV tissue plasminogen activator (tPA) for AIS, three underwent endovascular intervention, and 17 had AIS confirmed on MRI. Two patients with confirmed AIS experienced hemorrhagic transformation, one of which was symptomatic. Most patients (n=10, 59%) were functionally independent (mRS 0-2) at 90 days post-stroke, including all patients with active hematologic malignancy at the time of stroke (n=3). Four patients died within 90 days of AIS. None of these deaths were patients with active hematologic malignancy at the time of stroke., Conclusions: Without other contraindications, IV alteplase should be considered for management of AIS in patients with hematologic malignancy. The safety profile of tPA administration in this patient population may be similar to the general population, whether underlying hematologic malignancy is active or in remission., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This publication was supported by Grant Number UL1 TR002377 from the National Center for Advancing Translational Sciences (NCATS). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: Epidemiological data to characterize the individual risk profile of patients with spontaneous cervical artery dissection (sCeAD) are rather inconsistent., Methods and Results: In the setting of the Italian Project on Stroke in Young Adults Cervical Artery Dissection (IPSYS CeAD), we compared the characteristics of 1,468 patients with sCeAD (mean age = 47.3 ± 11.3 years, men = 56.7%) prospectively recruited at 39 Italian centers with those of 2 control groups, composed of (1) patients whose ischemic stroke was caused by mechanisms other than dissection (non-CeAD IS) selected from the prospective IPSYS registry and Brescia Stroke Registry and (2) stroke-free individuals selected from the staff members of participating hospitals, matched 1:1:1 by sex, age, and race. Compared to stroke-free subjects, patients with sCeAD were more likely to be hypertensive (odds ratio [OR] = 1.65, 95% confidence interval [CI] = 1.37-1.98), to have personal history of migraine with aura (OR = 2.45, 95% CI = 1.74-3.34), without aura (OR = 2.67, 95% CI = 2.15-3.32), and family history of vascular disease in first-degree relatives (OR = 1.69, 95% CI = 1.39-2.05), and less likely to be diabetic (OR = 0.65, 95% CI = 0.47-0.91), hypercholesterolemic (OR = 0.75, 95% CI = 0.62-0.91), and obese (OR = 0.41, 95% CI = 0.31-0.54). Migraine without aura was also associated with sCeAD (OR = 1.81, 95% CI = 1.47-2.22) in comparison with patients with non-CeAD IS. In the subgroup of patients with migraine, patients with sCeAD had higher frequency of migraine attacks and were less likely to take anti-migraine preventive medications, especially beta-blockers, compared with the other groups., Interpretation: The risk of sCeAD is influenced by migraine, especially migraine without aura, more than by other factors, increases with increasing frequency of attacks, and seems to be reduced by migraine preventive medications, namely beta-blockers. ANN NEUROL 2023;94:585-595., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Studies have shown that the integrity of white matter tracts connecting different regions in the left cerebral hemisphere is important for aphasia recovery after stroke. However, the impact of the underlying structural connection between the cortex and the cerebellum in post-stroke aphasia is poorly understood. We studied the microstructural integrity of the cerebellum and the corticocerebellar connections and their role in picture naming. Fifty-six patients with left cerebral infarcts (sparing the cerebellum) underwent diffusion tensor imaging (DTI) and Boston Naming Test. We compared the fractional anisotropy (FA) and mean diffusivity (MD) values of the right and the left cerebellum (lobular gray and white matter structures) and cerebellocortical connections. Recursive feature elimination and Spearman correlation analyses were performed to evaluate the relationship between naming performance and the corticocerebellar connections. We found that the right, relative to left, cerebellar structures and their connections with the left cerebrum showed lower FA and higher MD values, both reflecting lower microstructural integrity. This trend was not observed in the healthy controls. Higher MD values of the right major cerebellar outflow tract were associated with poorer picture naming performance. Our study provides the first DTI data demonstrating the critical importance of ascending and descending corticocerebellar connections for naming outcomes after stroke., (© 2023 Massachusetts Institute of Technology.)

Purpose of Review: There is enormous enthusiasm for the possibility of pharmacotherapies to treat language deficits that can arise after stroke. Speech language therapy remains the most frequently utilized and most strongly evidenced treatment, but the numerous barriers to patients receiving the therapy necessary to recover have motivated the creation of a relatively modest, yet highly cited, body of evidence to support the use of pharmacotherapy to treat post-stroke aphasia directly or to augment traditional post-stroke aphasia treatment. In this review, we survey the use of pharmacotherapy to preserve and support language and cognition in the context of stroke across phases of care, discuss key ongoing clinical trials, and identify targets that may become emerging interventions in the future., Recent Findings: Recent trials have shifted focus from short periods of drug therapy supporting therapy in the chronic phase to longer terms approaching pharmacological maintenance beginning more acutely. Recent innovations in hyperacute stroke care, such as tenecteplase, and acute initiation of neuroprotective agents and serotonin reuptake inhibitors are important areas of ongoing research that complement the ongoing search for effective adjuvants to later therapy. Currently there are no drugs approved in the United States for the treatment of aphasia. Nevertheless, pharmacological intervention may provide a benefit to all phases of stroke care., (© 2023. The Author(s).)

Background: Traumatic posterior cerebral artery (tPCA) dissection and dissecting aneurysms are rare and constitute a challenging clinical entity., Objective: We analyze existing literature on tPCA dissection and present our institutional experience., Methods: We retrospectively queried our database for tPCA isolated dissection or dissecting aneurysms from 2008 until now and conducted a systematic literature review of published cases. We analyzed the clinical and radiographic characteristics and treatment outcomes of tPCA dissection., Results: Including our case, a total of 11 cases with either isolated dissection ( n  = 2) or dissecting aneurysms ( n  = 9) were included. The median age was 27 years, and 45% were females. The median interval between trauma and tPCA dissection diagnosis was nine days. Mental status declined in four (36%) patients. Half of the patients demonstrated tentorial subdural hematoma on head CT. Ischemic stroke was detected in three (43%) patients. Four (36%) patients were conservatively managed, one (9.1%) patient was treated with surgical clipping of the proximal PCA, and six patients underwent endovascular treatments. The complication rate was 20%. Immediate total occlusion was demonstrated in five patients (100%), and the conservatively managed case showed immediate, spontaneous thrombosis of the aneurysm. Glasgow Coma Scale scores were 15 in eight (89%) and 14 in one (11%) patients at the last clinical follow-up with a median of six months. The mortality and retreatment rates were null., Conclusions: tPCA dissection is diagnosed late and commonly affects the young population. The clinical outcome for this condition is typically favorable. Current endovascular techniques showed considerable efficacy and safety.

Introduction: As the population ages, the prevalence of cognitive impairment is expanding. Given the recent pandemic, there is a need for remote testing modalities to assess cognitive deficits in individuals with neurological disorders. Self-administered, remote, tablet-based cognitive assessments would be clinically valuable if they can detect and classify cognitive deficits as effectively as traditional in-person neuropsychological testing., Methods: We tested whether the Miro application, a tablet-based neurocognitive platform, measured the same cognitive domains as traditional pencil-and-paper neuropsychological tests. Seventy-nine patients were recruited and then randomized to either undergo pencil-and-paper or tablet testing first. Twenty-nine age-matched healthy controls completed the tablet-based assessments. We identified Pearson correlations between Miro tablet-based modules and corresponding neuropsychological tests in patients and compared scores of patients with neurological disorders with those of healthy controls using t tests., Results: Statistically significant Pearson correlations between the neuropsychological tests and their tablet equivalents were found for all domains with moderate (r > 0.3) or strong (r > 0.7) correlations in 16 of 17 tests (p < 0.05). All tablet-based subtests differentiated healthy controls from neurologically impaired patients by t tests except for the spatial span forward and finger tapping modules. Participants reported enjoyment of the tablet-based testing, denied that it provoked anxiety, and noted no preference between modalities., Conclusions: This tablet-based application was found to be widely acceptable to participants. This study supports the validity of these tablet-based assessments in the differentiation of healthy controls from patients with neurocognitive deficits in a variety of cognitive domains and across multiple neurological disease etiologies., (© 2023 S. Karger AG, Basel.)

Background and Purpose: Previous studies have proposed multiple parallel channels for waste clearance from the brain, though many gaps remain in our understanding of these systems. In this study, we examined periarterial fluid drainage around intracranial and extracranial segments of the internal carotid arteries (ICAs) from the brain into the cervical lymph nodes using a noninvasive and clinical-based method., Methods: Eighty-one subjects (45 females, aged 15-80 years old) with nonlesioned epilepsy underwent high-resolution 3-dimensional T2-weighted fluid-attenuated inversion recovery (FLAIR) MRI. We utilized a noninvasive and clinical-based method with a manual semiautomated approach to characterize the periarterial lymphatic system's maximum thickness and signal intensities along the ICAs using high-resolution 3-dimensional FLAIR imaging. We conducted group comparisons and correlation analyses to investigate sex- and age-based trends. Results were corrected with Bonferroni's test for multiple comparisons, and we performed power analysis for sample size calculations., Results: Using high-resolution FLAIR images, we show evidence that fluid drainage emerges around the ICA petrous segment and joins lymphatic flow from cranial nerves in the upper neck, with this flow ultimately draining into the cervical lymph nodes bilaterally. Lymphatic signal at the petrous segment level was significantly thinner in females compared to males bilaterally (w = 413, p = .0001 on the right, w = 356, p < .0001 on the left). Lymphatic drainage around the petrous segments of the ICAs bilaterally was thicker with age in males but not in females., Conclusions: We describe the in vivo high-resolution imaging characteristics of periarterial fluid drainage along the vessel walls of ICAs. This represents a potentially major channel for brain waste clearance. We also report interesting sex- and age-based trends in these structures within our cohort., (© 2022 American Society of Neuroimaging.)

Purpose: Cervical artery dissection (CAD) represents a unique clinical entity with a high risk of ischemic stroke. Vitamin K antagonists (VKA) showed good efficacy in CAD management but are cumbersome to use with potentially higher bleeding rates. Novel oral anticoagulants (NOAC) are easier to use and may have similar effects but lower hemorrhagic risk. In this systematic review, we compare the efficacy of NOAC to VKA as a potential alternative treatment., Methods: The literature was searched on Pubmed, PMC, and Embase via API through the Nested Knowledge AutoLit software in February 2022 for studies evaluating both NOAC and VKA. Baseline characteristics, clinical and radiographic outcomes, and hemorrhagic and ischemic complications were collected for single and double-arm studies and analyzed using random-effect subgroup meta-analysis., Findings: Overall, 11 studies were included with 699 patients treated with VKA and 53 treated with NOAC (from three studies; two were head-to-head comparative studies). There was no statistical difference in the baseline characteristics of VKA and NOAC patients. The rates of TIA/stroke in VKA and NOAC groups were 12.3% (95% CI; 0%, 28.6%) and 5.7% (95% CI; 0%, 12.2%), respectively. Major bleeding or intracranial bleeding were comparable between groups. Lesions treated with VKA showed angiographic recanalization with a rate of 51.4% (95% CI; 35.6%, 67.1%) and for those treated with NOAC was 58.4% (95% CI; 23.9%, 93.9%). The rates of good clinical outcomes were 79.9% (95% CI; 67.6%, 92.2%) in the VKA group and 91.4% (95% CI; 78.1%, 100%) in NOAC. No statistical difference was noted among any of the outcomes between the two treatment groups., Discussion and Conclusion: We highlighted comparable efficacy and safety of NOAC to VKA for stroke prevention in CAD. Further head-to-head studies are warranted to validate these results., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© European Stroke Organisation 2022.)

We conducted a comprehensive review and meta-analysis to investigate clinical, radiographic characteristics, and treatment outcomes of posterior cerebral artery aneurysms (PCAA). We systematically reviewed English-language articles investigating available treatments (parent artery occlusion (PAO), microsurgery, reconstructive endovascular (rEVT), and conservative treatments) for PCAA and analyzed the based on aneurysm morphology and rupture status. Six-hundred-eighty-five patients with 698 PCAA were identified from 59 studies. Overall, 371 (54.2%) aneurysms were ruptured, 325 (49%) were saccular, and 342 (51%) were non-saccular aneurysms. The mean age of the saccular was lower (40 years) than non-saccular aneurysm group (50 years) (P < .05). In ruptured PCAA, favorable clinical outcomes were comparable between the treatment groups except for patients treated conservatively, which had lower rates of favorable clinical outcomes (35.6%) and higher mortality (55.7%) (P < .0001). Ruptured aneurysms treated with rEVT (22.6%) had the highest recanalization rates compared to PAO (9.2%, P = 0.0001) and microsurgery (3.8%, P = 0.005). In unruptured PCAA, clinical outcomes were similar; higher complication rates were noted in microsurgery (40.4%, P = 0.026) and PAO (21.5%, P = 0.015) compared to rEVT (13.2%), which had higher recanalization rates (15.6%, P < .0001). The rates of subsequent stroke following PAO were 21.8% for unruptured and 32.3% for ruptured PCAA (P = 0.078). Ruptured PCAA portend worse prognosis and typically require an intervention to achieve better outcome whereas the benefit of an intervention in unruptured PCAA is much less clear. rEVT is promising for PCAA management with a good clinical and safety profile but more recurrence compared to PAO and microsurgery., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Approximately one-quarter to one-third of patients with ischemic stroke have an embolic stroke of undetermined source (ESUS). An estimated 5% to 10% of patients with ESUS have an active cancer diagnosis. Presence of cancer potentially increases the risk of acute ischemic stroke through various mechanisms such as cancer-related hypercoagulability, intracranial tumors leading to an arterial compression, or intracardiac tumors leading to cardioembolism. Certain cancer therapeutics can also contribute to risk of ischemic stroke. Multiple vascular lesions involving bilateral anterior and posterior circulations, high plasma D-dimer levels, and elevated inflammatory markers might suggest cancer-related ischemic stroke. Patients with ischemic stroke related to malignancy are also at higher risk of stroke recurrence, early neurologic deterioration, and mortality. Cancer screening in acute ischemic stroke patients can be considered when no other etiology for stroke can be established and clinical history such as tobacco use, unexplained constitutional symptoms such as fever or night sweats, or unexplained weight loss suggests an underlying malignancy. Selection of antithrombotics for secondary stroke prevention remains controversial as clinical trial data for use of antiplatelet therapy vs anticoagulation in ESUS and cancer patients is limited. Future clinical trials should specifically focus on patients with ischemic stroke related to malignancy are needed to guide appropriate therapeutic agent selection., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Introduction: Intracranial artery dissection (IAD) is rarer than cervical artery dissections (CeAD), and information is based on limited series with small cohorts. There are only several small-scale studies attempting to characterize the natural history of the disease. Herein, we analyze the prevalence of IADs in hospitalized patients using a national database., Methods: The National Inpatient Sample was queried from 2016-2019 for patients with a diagnosis of unruptured intracranial dissection (uIAD) using ICD-10-CM codes (I67.0). Moreover, patients with acute ischemic stroke (AIS) and CeAD were extracted to compare its prevalence among patients with concomitant AIS (+/-dissections). The Cochrane-Armitage test was conducted to assess trends in the prevalence of uIADs among those with concomitant AIS or among all craniocervical dissections., Results: There were 725 hospitalizations involving uIAD, while there were 62,220 involving CeADs. uIADs represented 5.1 per million hospitalizations across 2016-2019. The average age of presentation was 56.9 years (SE: 1.62), while it was 54.4 (SE: 0.17) for CeADs (p = 0.13). Females were represented among 44.8% (n = 325) of uIADs, a similar proportion compared to CeADs (44.3%%, n = 27,530; p = 0.89). Compared to CeADs, AIS and motor deficits were more common in uIAD (71.72% vs. 47.0%; p < 0.001). There were 18.6 uIAD with concomitant AIS per 100,000 with AIS. uIADs represented 1.75% of all dissections with concomitant AIS (n = 520/29,750). There was no trend in the average age of presentation for uIADs. Proportion of females among those with uIADs increased from 36.8% in 2016 to 59.5% in 2019 (trend: +9.46% per year; 95% CI: 3.13 to 15.8; p = 0.004). There was no trend in the proportion of races among those with uIADs., Conclusion: The prevalence of uIADs among hospitalized patients is very low, and only 1.75% of craniocervical dissection-related AIS is due to uIAD. Compared to CeADs, patients were more likely to be male, and uIAD more commonly led to acute ischemic stroke and motor deficits. The trend in age remained stable across the four years analyzed, while the proportion of females increased. There was no trend in the proportion of races among uIADs, however., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A number of pharmaceuticals have been identified as potential adjuvants to speech language therapy following stroke, but it is also important to consider which pharmaceuticals may result in a less robust recovery. Here we examine whether post-stroke language recovery was meaningfully impeded by cholinergic, GABAergic, or dopaminergic medications patients received. Eighty participants with left hemisphere stroke were examined retrospectively to see whether the use of one of these three classes of medication prior to admission for acute stroke, during their inpatient stay, or at discharge was associated with differences in recovery on three common measures of language. While prescription of any of the candidate drugs was relatively uncommon, groups were very well matched for many common factors that impact performance. When age, education, and acute lesion volume were controlled, there were no significant differences in performance among those taking cholinergic, GABAergic, or dopaminergic medications and those who were not. Those who experienced a "good recovery" of language (≥10% improvement on any one language measure over time) had similar exposure to these drugs to those with a poor recovery. This work represents a first look at these drug classes with regard to their effects on the recovery of language after stroke and should not be interpreted as resolving all potential for concern, but these results do offer modest reassurance that these common classes of pharmacotherapy, when given for short periods in this population, do not appear to have marked deleterious effects on post-stroke recovery of language., Competing Interests: The authors have declared that no competing interests exist.

Craniocervical artery dissection (CAD), although uncommon, can affect the young and lead to devastating complications, including stroke and subarachnoid hemorrhage. It starts with a tear in the intima of a vessel with subsequent formation of an intramural hematoma. Most CAD occurs spontaneously or after minor trauma. Patients with CAD may exhibit isolated symptoms of an underlying subclinical connective tissue disorder or have a clinically diagnosed connective tissue disorder. Emergent evaluation and computed tomography angiography or magnetic resonance imaging/angiography of the head and neck are required to screen for and to diagnose CAD. Carotid ultrasound is not recommended as an initial test because of limited anatomic windows; diagnostic catheter-based angiography is reserved for atypical cases or acutely if severe neurologic deficits are present. Patients with CAD can present with focal neurologic deficits due to ischemia (thromboembolism or arterial occlusion) or subarachnoid hemorrhage (pseudoaneurysm formation and rupture). Also common are local symptoms, such as head and neck pain, pulsatile tinnitus, Horner syndrome, and cranial neuropathy, or cervical radiculopathy from mass effect. Acute management of transient ischemic attack/stroke in CAD is not different from the management of ischemic stroke of other causes. Patients with CAD need long-term antithrombotic therapy for secondary stroke prevention. Anticoagulation or dual antiplatelet therapy followed by single antiplatelet therapy is recommended for extracranial CAD and antiplatelet therapy for intracranial CAD. Recurrent ischemic events and dissections are rare and typically occur early. Patients with CAD should avoid deep neck massage or chiropractic neck manipulation involving sudden excessive, forced neck movements., (Copyright © 2022 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Stroke is one of the leading causes of death and disability. Despite the high prevalence of stroke, characterizing the acute neural recovery patterns that follow stroke and predicting long-term recovery remains challenging. Objective methods to quantify and characterize neural injury are still lacking. Since neuroimaging methods have a poor temporal resolution, EEG has been used as a method for characterizing post-stroke recovery mechanisms for various deficits including motor, language, and cognition as well as predicting treatment response to experimental therapies. In addition, transcranial magnetic stimulation (TMS), a form of non-invasive brain stimulation, has been used in conjunction with EEG (TMS-EEG) to evaluate neurophysiology for a variety of indications. TMS-EEG has significant potential for exploring brain connectivity using focal TMS-evoked potentials and oscillations, which may allow for the system-specific delineation of recovery patterns after stroke. In this review, we summarize the use of EEG alone or in combination with TMS in post-stroke motor, language, cognition, and functional/global recovery. Overall, stroke leads to a reduction in higher frequency activity (≥8 Hz) and intra-hemispheric connectivity in the lesioned hemisphere, which creates an activity imbalance between non-lesioned and lesioned hemispheres. Compensatory activity in the non-lesioned hemisphere leads mostly to unfavorable outcomes and further aggravated interhemispheric imbalance. Balanced interhemispheric activity with increased intrahemispheric coherence in the lesioned networks correlates with improved post-stroke recovery. TMS-EEG studies reveal the clinical importance of cortical reactivity and functional connectivity within the sensorimotor cortex for motor recovery after stroke. Although post-stroke motor studies support the prognostic value of TMS-EEG, more studies are needed to determine its utility as a biomarker for recovery across domains including language, cognition, and hemispatial neglect. As a complement to MRI-based technologies, EEG-based technologies are accessible and valuable non-invasive clinical tools in stroke neurology., Competing Interests: BL has no personal financial interests; other conflicts include named inventor (Cadence Neuroscience Inc., waived rights), investigator (Medtronic EPAS, NeuroPace RESPONSE, Neuroelectrics tDCS for Epilepsy), and consultant (Epiminder, Medtronic, Philips Neuro). GW has licensed intellectual property to Cadence Neuroscience and NeuroOne Inc., and is an investigator on projects with Medtronic, NeuroOne Inc., Cadence Neuroscience, and UNEEG Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Keser, Buchl, Seven, Markota, Clark, Jones, Lanzino, Brown, Worrell and Lundstrom.)

Concussions are common among flat-track roller derby players, a unique and under-studied sport, but little has been done to assess how common they are or what players can do to manage injury risk. The purpose of this study is to provide an epidemiological investigation of concussion incidence and experience in a large international sampling of roller derby players. Six hundred sixty-five roller derby players from 25 countries responded to a comprehensive online survey about injury and sport participation. Participants also responded to a battery of psychometric assessment tools targeting risk-factors for poor injury recovery (negative bias, social support, mental toughness) and players' thoughts and feelings in response to injury. Per 1,000 athletes, 790.98 concussions were reported. Current players reported an average of 2.2 concussions, while former players reported 3.1 concussions. However, groups were matched when these figures were corrected for differences in years of play (approximately one concussion every 2 years). Other frequent injuries included fractures in extremities and upper limbs, torn knee ligaments, and sprained ankles. We found no evidence that players' position, full-contact scrimmages, or flooring impacted number of concussions. However, neurological history and uncorrected vision were more influential predictors of an individual's number of concussions during roller derby than years of participation or age, though all four contributed significantly. These findings should assist athletes in making informed decisions about participation in roller derby, though more work is needed to understand the nature of risk., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Stockbridge, Keser and Newman.)

Background and Objectives: Hemispatial neglect is a heterogeneous and complex disorder that can be classified by frame of reference for "left" vs "right," including viewer-centered neglect (VCN, affecting the contralesional side of the view), stimulus-centered neglect (SCN, affecting the contralesional side of the stimulus, irrespective of its location with respect to the viewer), or both. We investigated the effect of acute stroke lesions on the connectivity of neural networks that underlie VCN or SCN., Methods: A total of 174 patients within 48 hours of acute right hemispheric infarct underwent a detailed hemispatial neglect assessment that included oral reading, scene copy, line cancellation, gap detection, horizontal line bisection tests, and MRI. Each patient's connectivity map was generated. We performed a linear association analysis between network connectivity strength and continuous measures of neglect to identify lesion-induced disconnections associated with the presence or severity of VCN and SCN. Results were corrected for multiple comparisons., Results: About 42% of the participants with right hemisphere stroke had at least one type of neglect. The presence of any type of neglect was associated with lesions to tracts connecting the right inferior parietal cortex, orbitofrontal cortex, and right thalamus to other right-hemispheric structures. VCN only was strongly associated with tracts connecting the right putamen to other brain regions and tracts connecting right frontal regions with other brain regions. The presence of both types of neglect was most strongly associated with tracts connecting the right inferior and superior parietal cortex to other brain regions and those connecting left or right mesial temporal cortex to other brain regions., Discussion: Our study provides new evidence for the specific white matter tracts where disruption can cause hemispatial neglect in a relatively large number of participants and homogeneous time after onset. We obtained MRI and behavioral testing acutely, before the opportunity for rehabilitation or substantial recovery., Classification of Evidence: This study provides Class II evidence that damage to specific white matter tracts identified on MRI are associated with the presence of neglect following right hemispheric stroke., (© 2022 American Academy of Neurology.)

The chapter covers the clinical syndrome of a primary progressive aphasia (PPA), the demographics of this rare neurodegenerative disease, defining clinical and neuroanatomic characteristics of each PPA variant, disease progression, and behavioral features. The chapter begins with a brief introduction that includes references to seminal papers that defined this clinical syndrome and its three variants. The classic PPA subtypes discussed in the chapter are semantic variant PPA (svPPA), nonfluent/agrammatic PPA (nfaPPA), and logopenic variant PPA (lvPPA). The key language and cognitive characteristics, and language tasks that can elicit these language impairments, are detailed. Overlap in the clinical profiles of the PPA variants, which make differential diagnosis challenging, are explained. Disease progression is described, revealing that the PPA variants become more similar over time. Although PPA is language-predominant dementia, there are behavioral manifestations, particularly in svPPA. Changes in behavior in this variant are addressed as well as behavioral changes in nfaPPA and lvPPA that are less well recognized. The patterns of atrophy in the left temporal, parietal, and/or frontal cortices unique to each PPA variant are described. The underlying neuropathologies of the PPA variants are discussed, specifically tauopathies and non-tauopathies associated with svPPA and nfaPPA and Alzheimer's disease pathology in lvPPA., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Previous studies utilized lesion-centric approaches to study the role of the thalamus in language. In this study, we tested the hypotheses that non-lesioned dorsomedial and ventral anterior nuclei (DMVAC) and pulvinar lateral posterior nuclei complexes (PLC) of the thalamus and their projections to the left hemisphere show secondary effects of the strokes, and that their microstructural integrity is closely related to language-related functions. Methods: Subjects with language impairments after a left-hemispheric cortical and/or subcortical, early stroke ( n  = 31, ≤6 months) or late stroke ( n  = 30, ≥12 months) sparing thalamus underwent the Boston Naming Test (BNT) and diffusion tensor imaging (DTI). The tissue integrity of DMVAC, PLC, and their cortical projections was quantified with DTI. The right-left asymmetry profiles of these structures were evaluated in relation to the time since stroke. The association between microstructural integrity and BNT score was investigated in relation to stroke chronicity with partial correlation analyses adjusted for confounds. Results: In both early stroke and late stroke groups, left-sided tracts showed significantly higher mean diffusivities (MDs), which were likely due to Wallerian degeneration. Higher MD values of the cortical projections from the left PLC ( r = - 0.5, p  = 0.005) and DMVAC ( r = - 0.53, p  = 0.002) were correlated with lower BNT score in the late stroke but not early stroke group. Conclusion: Nonlesioned thalamic nuclei and thalamocortical pathways show rightward lateralization of the microstructural integrity after a left hemispheric stroke, and this pattern is associated with poorer naming. Impact statement To the best of our knowledge, our study is the first diffusion tensor imaging study suggesting that the thalamic nuclei and pathways of the left hemisphere spared by direct ischemic insult undergo secondary degeneration over time that is associated with poorer picture naming. Our study may pave the way for targeted interventions such as invasive or noninvasive brain stimulation techniques that engage these spared pathways to prevent secondary degeneration and lead to better outcomes in poststroke aphasia.