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Background: Primary progressive aphasia (PPA) refers to a progressive and selective decline in language due to neurodegenerative disease. There are three variants of PPA, progressive nonfluent aphasia (PNFA), semantic dementia (SD), and logopaenic progressive aphasia (LPA). All variants include impaired object naming, but distinct underlying deficits might interfere with naming. Therefore, individuals with different types of PPA may respond differently to naming therapy. Aims: To identify differences in patterns of success and generalisation in response to the same treatment in patient with LPA and a patient with SD. Furthermore, we wished to identify whether the treatment effect was item specific (trained words) or generalised to untrained words in trained or untrained categories. Methods & Procedures: Participants included an individual with LPA and one with SD. An assessment of lexical processing was administered before and after a naming treatment to assess underlying deficits and generalisation effects. Therapy consisted of a cueing hierarchy treatment. Treatment items consisted of pictured objects in the categories of fruits/vegetables and clothing. Outcomes & Results: Two different patterns of performance were observed. The LPA participant improved in naming of treated items and untreated items in both treated and untreated categories. The participant with SD improved in naming treated items only, but showed less deterioration in untreated items in treated than untreated categories. Conclusions: Individuals with PPA can show improved naming (at least temporarily) with therapy, but generalisation to untrained items may depend on the underlying cause of the naming deficit, which may differ across subtypes. [ABSTRACT FROM AUTHOR]

Hillis AE: Pharmacological, surgical, and neurovascular interventions to augment acute aphasia recovery. Am J Phys Med Rehabil 2007;86:426-434.Aphasia recovery has often been attributed to a combination of 'spontaneous recovery' and rehabilitation. However, a variety of new pharmacological, surgical, and interventional neuroradiology procedures have been developed that can complement rehabilitation in the first days to weeks after stroke by restoring blood flow to dysfunctional but salvageable brain tissue. This paper will review the medical and surgical interventions to improve regional cerebral blood flow that recently have been shown to (1) augment aphasia recovery by improving tissue function, and (2) prevent expansion of the stroke that would otherwise impede recovery. Success with such treatments facilitates aphasia rehabilitation by improving the baseline language performance that must be improved further with language therapy. [ABSTRACT FROM AUTHOR]

We hypothesized that a modified version of the Frontal Behavioral Inventory (FBI-mod), along with a few cognitive tests, would be clinically useful in distinguishing between clinically defined Alzheimer's disease (AD) and subtypes of frontotemporal lobar degeneration (FTLD): frontotemporal dementia (dysexecutive type), progressive nonfluent aphasia, and semantic dementia. We studied 80 patients who were diagnosed with AD (n = 30) or FTLD (n = 50), on the basis of a comprehensive neuropsychological battery, imaging, neurological examination, and history. We found significant between-group differences on the FBI-mod, two subtests of the Rey Auditory Verbal Learning Test (verbal learning and delayed recall), and the Trail Making Test Part B (one measure of 'executive functioning'). AD was characterized by relatively severe impairment in verbal learning, delayed recall, and executive functioning, with relatively normal scores on the FBI-mod. Frontotemporal dementia was characterized by relatively severe impairment on the FBI-mod and executive functioning in the absence of severe impairment in verbal learning and recall. Progressive nonfluent aphasia was characterized by severe impairment in executive functioning with relatively normal scores on verbal learning and recall and FBI-mod. Finally, semantic dementia was characterized by relatively severe deficits in delayed recall, but relatively normal performance on new learning, executive functioning, and on FBI-mod. Discriminant function analysis confirmed that the FBI-mod, in conjunction with the Rey Auditory Verbal Learning Test, and the Trail Making Test Part B categorized the majority of patients as subtypes of FTLD or AD in the same way as a full neuropsychological battery, neurological examination, complete history, and imaging. These tests may be useful for efficient clinical diagnosis, although progressive nonfluent aphasia and semantic dementia are likely to be best distinguished by language tests not included in standard neuropsychological test batteries. Copyright (c) 2007 S. Karger AG, Basel. [ABSTRACT FROM AUTHOR]

Presents a study which identified the location of surgical lesions and characteristics of patients who show hemispatial neglect or extinction following stereotactic thalamotomy. Localization and surgery; Results of sensory and motor testing; Discussion.

OBJECTIVE: To illustrate how magnetic resonance perfusion imaging has provided insights regarding rehabilitation of different forms of hemispatial neglect. DATA SOURCES: Recent studies of different types of neglect and their neural substrates and of rehabilitation strategies that might be differentially effective for different types of neglect. STUDY SELECTION: Author selected all articles on PubMed that were identified with the key words reference frame or perfusion-weighted imaging plus neglect plus rehabilitation and other relevant articles that were cited therein. DATA EXTRACTION: An independent reviewer determined if the data presented provided evidence relevant to planning or developing rehabilitation for stroke patients with distinct forms of neglect. DATA SYNTHESIS: Results from a number of studies converge on the hypothesis that hypoperfusion and/or infarct of right angular gyrus and intraparietal sulcus can cause viewer-centered neglect, whereas hypoperfusion and/or infarct of right superior temporal gyrus can lead to left stimulus-centered neglect. Distinct forms of rehabilitation might be differentially useful for distinct types of spatial neglect, even though an individual patient may have 2 or more types of neglect. Magnetic resonance perfusion imaging has also shown that fluctuations in neglect in the acute-subacute period after stroke are often due to changes in blood flow caused by changes in blood pressure. CONCLUSIONS: Consideration of neglect type and status of cerebral blood flow can be useful in planning strategies to ameliorate each individual's deficits. Copyright © 2006 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation [ABSTRACT FROM AUTHOR]

A number of previous studies have indicated that Broca's area has an important role in understanding and producing syntactically complex sentences and other language functions. If Broca's area is critical for these functions, then either infarction of Broca's area or temporary hypoperfusion within this region should cause impairment of these functions, at least while the neural tissue is dysfunctional. The opportunity to identify the language functions that depend on Broca's area in a particular individual was provided by a patient with hyperacute stroke who showed selective hypoperfusion, with minimal infarct, in Broca's area, and acutely impaired production of grammatical sentences, comprehension of semantically reversible (but not non-reversible) sentences, spelling, and motor planning of speech articulation. When blood flow was restored to Broca's area, as demonstrated by repeat perfusion weighted imaging, he showed immediate recovery of these language functions. The identification of language functions that were impaired when Broca's area was dysfunctional (due to low blood flow) and recovered when Broca's area was functional again, provides evidence for the critical role of Broca's area in these language functions, at least in this individual. [ABSTRACT FROM AUTHOR]

Sharing neuroimaging datasets enables reproducibility, education, tool development, and new discoveries. Neuroimaging from many studies are publicly available, providing a glimpse into progressive disorders and human development. In contrast, few stroke studies are shared, and these datasets lack longitudinal sampling of functional imaging, diffusion imaging, as well as the behavioral and demographic data that encourage novel applications. This is surprising, as stroke is a leading cause of disability, and acquiring brain imaging is considered standard of care. The first release of the Aphasia Recovery Cohort includes imaging data, demographics and behavioral measures from 230 chronic stroke survivors who experienced aphasia. We also share scripts to illustrate how the imaging data can predict impairment. In conclusion, recent advances in machine learning thrive on large, diverse datasets. Clinical data sharing can contribute to improvements in automated detection of brain injury, identification of white matter hyperintensities, measures of brain health, and prognostic abilities to guide care., (© 2024. The Author(s).)

Background and Purpose: Ischemic strokes due to isolated posterior cerebral artery (PCA) occlusions represent 5% of all strokes but have significant impacts on patients' quality of life, primarily due to visual deficits and thalamic involvement. Current guidelines for acute PCA occlusion management are sparse, and the prognostic value of perfusion imaging parameters remains underexplored., Methods: We conducted a retrospective analysis of 32 patients with isolated PCA occlusions treated at Johns Hopkins Medical Institutions between January 2017 and March 2023. Patients underwent pretreatment perfusion imaging, with perfusion parameters analyzed using RAPID software. The primary outcome was short-term clinical outcome as measured by the National Institutes of Health Stroke Scale (NIHSS) at discharge., Results: The median age of the cohort was 70 years, with 34% female and 66% male. Significant correlations were found between NIHSS at discharge and various perfusion parameters, including time-to-maximum (Tmax) >6 seconds (ρ = .55, p = .004), Tmax >8 seconds (ρ = .59, p = .002), Tmax >10 seconds (ρ = .6, p = .001), mismatch volume (ρ = .51, p = .008), and cerebral blood volume (CBV) < 34% (ρ = .59, p = .002)., Conclusions: Tmax and CBV volumes significantly correlated with discharge NIHSS with marginal superiority of Tmax >10 seconds and CBV <42% volumes. These findings suggest that CT and MR perfusion imaging can play a crucial role in the acute management of PCA strokes, though larger, standardized studies are needed to validate these results and refine imaging thresholds specific to posterior circulation infarcts., (© 2024 American Society of Neuroimaging.)

In this randomized, double-blind, sham-controlled trial of Cerebellar Stimulation for Aphasia Rehabilitation (CeSAR), we will determine the effectiveness of cathodal tDCS (transcranial direct current stimulation) to the right cerebellum for the treatment of chronic aphasia (>6 months post stroke). We will test the hypothesis that cerebellar tDCS in combination with an evidenced-based anomia treatment (semantic feature analysis, SFA) will be associated with greater improvement in naming untrained pictures (as measured by the change in Philadelphia Picture Naming Test), 1-week post-treatment, compared to sham plus SFA. We will also evaluate the effects of cerebellar tDCS on naming trained items as well as the effects on functional communication, content, efficiency, and word-retrieval of picture description, and quality of life. Finally, we will identify imaging and linguistic biomarkers to determine the characteristics of stroke patients that benefit from cerebellar tDCS and SFA treatment. We expect to enroll 60 participants over five years. Participants will receive 15, 25-minute sessions of cerebellar tDCS (3-5 sessions per week) or sham tDCS combined with 1 hour of SFA treatment. Participants will be evaluated prior to the start of treatment, one-week post-treatment, 1-, 3-, and 6-months post-treatment on primary and secondary outcome variables. The long-term aim of this study is to provide the basis for a Phase III randomized controlled trial of cerebellar tDCS vs sham with concurrent language therapy for treatment of chronic aphasia. Trial registration: The trial is registered with ClinicalTrials.gov NCT05093673., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lammers et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Recent large core trials have highlighted the effectiveness of mechanical thrombectomy (MT) in acute ischemic stroke with large vessel occlusion. Variable perfusion-imaging thresholds and poor Alberta Stroke Program Early Computed Tomography Score reliability underline the need for more standardized, quantitative ischemia measures for MT patient selection. We aimed to identify the computed tomography perfusion parameter most strongly associated with poor outcomes in patients with acute ischemic stroke-large vessel occlusion with significant ischemic cores., Methods: In this study from 2 comprehensive stroke centers from 2 comprehensive stroke centers within the Johns Hopkins Medical Enterprise (Johns Hopkins Hospita-East Baltimore and Bayview Medical Campus) from July 29, 2019 to January 29, 2023 in a continuously maintained database, we included patients with acute ischemic stroke-large vessel occlusion with ischemic core volumes defined as relative cerebral blood flow <30% and ≥50 mL on computed tomography perfusion or Alberta Stroke Program Early Computed Tomography Score <6. We used receiver operating characteristics to find the optimal cutoff for parameters like cerebral blood volume (CBV) <34%, 38%, 42%, and relative cerebral blood flow >20%, 30%, 34%, 38%, and time-to-maximum >4, 6, 8, and 10 seconds. The primary outcome was unfavorable outcomes (90-day modified Rankin Scale score 4-6). Multivariable models were adjusted for age, sex, diabetes, baseline National Institutes of Health Stroke Scale, intravenous thrombolysis, and MT., Results: We identified 59 patients with large ischemic cores. A receiver operating characteristic curve analysis showed that CBV<42% ≥68 mL is associated with unfavorable outcomes (90-day modified Rankin Scale score 4-6) with an area under the curve of 0.90 (95% CI, 0.82-0.99) in the total and MT-only cohorts. Dichotomizing at this CBV threshold, patients in the ≥68 mL group exhibited significantly higher relative cerebral blood flow, time-to-maximum >8 and 10 seconds volumes, higher CBV volumes, higher HIR, and lower CBV index. The multivariable model incorporating CBV<42% ≥68 mL predicted poor outcomes robustly in both cohorts (area under the curve for MT-only subgroup was 0.87 [95% CI, 0.75-1.00])., Conclusions: CBV<42% ≥68 mL most effectively forecasts poor outcomes in patients with large-core stroke, confirming its value alongside other parameters like time-to-maximum in managing acute ischemic stroke-large vessel occlusion.

Objective: Training clinician-scientists is a primary objective of many academic neurology departments, as these individuals are uniquely positioned to perform insightful clinical or laboratory-based research informed both by clinical knowledge and their own experiences caring for patients. Despite its importance, training clinician-scientists has perhaps never been so challenging. The National Institute of Neurologic Disorders and Stroke (NINDS) R25 program was designed in an attempt to support these individuals, decrease the time needed to obtain National Institutes of Health K awards, and to help educate a cohort of trainees preparing for a career in academic neurology. We endeavored to describe the structure and features of the program while examining its outcomes., Methods: R25 outcome data from 2009 to 2024 were reviewed. Statistical comparisons were made using 2-sided Mann-Whitney U testing., Results: A total of 67% of adult neurologists who received an R25 had a successful application for a National Institutes of Health K award compared with 45% of adult neurologists who had not received R25 support (p < 0.0001). Among child neurologists, 73% who applied went on to receive K funding after R25 support, compared with 45% who had not been part of the R25 program (p < 0.001). The average time between completion of residency and obtaining a K award for R25 participants was decreased by 26 months among those with an MD/PhD degree, and 32 months for those with an MD degree compared with non-R25 individuals., Interpretation: The R25 program has been successful in achieving its training goals, but stands as only one component of support for aspiring clinician-scientists. Investments and commitments made by academic neurology departments are key to supporting this success. ANN NEUROL 2024., (© 2024 American Neurological Association.)

Background: Collateral status (CS) is an important biomarker of functional outcomes in patients with acute ischemic stroke secondary to large vessel occlusion (AIS-LVO). Pretreatment CT perfusion (CTP) parameters serve as reliable surrogates of collateral status (CS). In this study, we aim to assess the relationship between the relative cerebral blood flow less than 38% (rCBF <38%), with the reference standard American Society of Interventional and Therapeutic Neuroradiology (ASITN) collateral score (CS) on DSA., Methods: In this prospectively collected, retrospectively reviewed analysis, inclusion criteria were as follows: (a) CT angiography (CTA) confirmed anterior circulation large vessel occlusion from 9/1/2017 to 10/01/2023; (b) diagnostic CT perfusion; and (c) underwent mechanical thrombectomy with documented ASITN CS. The ratios of the CTP-derived CBF values were calculated by dividing the values of the ischemic lesion by the corresponding values of the contralateral normal region (which were defined as rCBF). Spearman's rank correlation and logistic regression analysis were performed to determine the relationship of rCBF <38% lesion volume with DSA ASITN CS. p ≤ .05 was considered significant., Results: In total, 223 patients [mean age: 67.77 ± 15.76 years, 56.1% ( n = 125) female] met our inclusion criteria. Significant negative correlation was noted between rCBF <38% volume and DSA CS (ρ = -0.37, p < .001). On multivariate logistic regression analysis, rCBF <38% volume was found to be independently associated with worse ASITN CS (unadjusted OR: 3.03, 95% CI: 1.60-5.69, p < .001, and adjusted OR: 2.73, 95% CI: 1.34-5.50, p < .01)., Conclusion: Greater volume of tissue with rCBF <38% is independently associated with better DSA CS. rCBF <38% is a useful adjunct tool in collateralization-based prognostication. Future studies are needed to expand our understanding of the role of rCBF <38% within the decision-making in patients with AIS-LVO., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: VSY, JJH, and GWA are consultants for RAPID.AI, and GWA holds RAPID.AI equity.

Background: Prolonged venous transit (PVT), defined as presence of time-to-maximum ≥ 10 s within the superior sagittal sinus (SSS) and/or torcula, is a novel, qualitatively assessed computed tomography perfusion surrogate parameter of venous outflow with potential utility in pretreatment acute ischemic stroke imaging for neuroprognostication. We aim to characterize the correlation between PVT and neurological functional outcomes in thrombectomy-treated patients., Methods: A prospectively-collected database of large vessel occlusion acute ischemic stroke patients treated with thrombectomy was retrospectively analyzed. Spearman's rank correlation coefficient and point-biserial correlations were performed between PVT status (i.e., no region, either SSS or torcula, or both), 90-day modified Rankin score (mRS), mortality (mRS 6), and poor functional outcome (mRS 4-6 vs 0-3)., Results: Of 128 patients, correlation between PVT and 90-day mRS ( ρ = 0.35, p < 0.0001), mortality (r = 0.26, p = 0.002), and poor functional outcome (r = 0.27, p = 0.002) were significant., Conclusion: There is a modest, significant correlation between PVT and severity of neurological functional outcome. Consequently, PVT is an easily-ascertained, qualitative metric that may be useful as an adjunct for anticipating a patient's clinical course. Future analyses will determine the significance of incorporating PVT in clinical decision-making., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Drs. Vivek Yedavalli, Jeremy Heit, and Gregory Albers are consultants for iSchemaView (Menlo Park, CA), not related to submitted work.

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 and Purpose: Distal medium vessel occlusions (DMVOs) are a significant contributor to acute ischemic stroke (AIS), with collateral status (CS) playing a pivotal role in modulating ischemic damage progression. We aimed to explore baseline characteristics associated with CS in AIS-DMVO., Methods: This retrospective analysis of a prospectively collected database enrolled 130 AIS-DMVO patients from two comprehensive stroke centers. Baseline characteristics, including patient demographics, admission National Institutes of Health Stroke Scale (NIHSS) score, admission Los Angeles Motor Scale (LAMS) score, and co-morbidities, including hypertension, hyperlipidemia, diabetes, coronary artery disease, atrial fibrillation, and history of transient ischemic attack or stroke, were collected. The analysis was dichotomized to good CS, reflected by hypoperfusion index ratio (HIR) <.3, versus poor CS, reflected by HIR ≥.3., Results: Good CS was observed in 34% of the patients. As to the occluded location, 43.8% occurred in proximal M2, 16.9% in mid M2, 35.4% in more distal middle cerebral artery, and 3.8% in distal anterior cerebral artery. In multivariate logistic analysis, a lower NIHSS score and a lower LAMS score were both independently associated with a good CS (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.82-0.95, p < .001 and OR: 0.77, 95% CI: 0.62-0.96, p = .018, respectively). Patients with poor CS were more likely to manifest as moderate to severe stroke (29.1% vs. 4.5%, p < .001), while patients with good CS had a significantly higher chance of having a minor stroke clinically (40.9% vs. 12.8%, p < .001)., Conclusions: CS remains an important determinant in the severity of AIS-DMVO. Collateral enhancement strategies may be a worthwhile pursuit in AIS-DMVO patients with more severe initial stroke presentation, which can be swiftly identified by the concise LAMS and serves as a proxy for underlying poor CS., (© 2024 American Society of Neuroimaging.)

Background: When weighing potential risks versus benefits of reperfusion therapy, the functions likely to recover if blood flow can be restored should be considered. Because deep and motor areas of the brain often infarct relatively early in acute stroke, we hypothesized that reperfusion therapies are more likely to improve language function and neglect (cortical functions) more than motor function., Methods: In this retrospective review of a prospectively collected database, patients with acute stroke due to large vessel occlusion), we evaluated percent improvement (mean change in score/maximum score) for different items of the National Institutes of Health Score Scale with and without endovascular thrombectomy, and/or intravenous thrombolysis., Results: In total, 290 patients (mean age 61.8; SD 14.0; 47.9% female) met the inclusion criteria. For all outcome measures (percent change in language, total language, motor, and neglect) there were significant effects of treatment group (p<0.0001 for all), with the greatest change in the EVT +tPA group, then EVT only group, followed by tPA only, followed by no intervention. Differences between EVT + tPA and EVT only were not significant (p=.30 to 0.79 across outcomes). For patients with aphasia and/or right sided weakness before treatment, the percent change in language was significantly greater than the percent change in weakness (29.8% vs. 12.7%; t(93)=5.3;p<0.0001). Greater percent improvement in language was observed in all treatment groups (p=0.0003 to 0.03 across treatment groups)., Conclusions: In patients with acute ischemic stroke due to LVO, improvements in all neurological functions occur with tPA, and even more with EVT (with and without IV tPA). However, gains in language are even greater than gains in motor function with both interventions. Few patients had neglect before treatment, but of those who did, the majority improved, and most (92.8%) improved with EVT.

Individuals with Mild Cognitive Impairment (MCI), a transitional stage between cognitively healthy aging and dementia, are characterized by subtle neurocognitive changes. Clinically, they can be grouped into two main variants, namely patients with amnestic MCI (aMCI) and non-amnestic MCI (naMCI). The distinction of the two variants is known to be clinically significant as they exhibit different progression rates to dementia. However, it has been particularly challenging to classify the two variants robustly. Recent research indicates that linguistic changes may manifest as one of the early indicators of pathology. Therefore, we focused on MCI's discourse-level writing samples in this study. We hypothesized that a written picture description task can provide information that can be used as an ecological, cost-effective classification system between the two variants. We included one hundred sixty-nine individuals diagnosed with either aMCI or naMCI who received neurophysiological evaluations in addition to a short, written picture description task. Natural Language Processing (NLP) and a BERT pre-trained language model were utilized to analyze the writing samples. We showed that the written picture description task provided 90% overall classification accuracy for the best classification models, which performed better than cognitive measures. Written discourses analyzed by AI models can automatically assess individuals with aMCI and naMCI and facilitate diagnosis, prognosis, therapy planning, and evaluation.

Background: Distal medium vessel occlusions (DMVOs) contribute substantially to the incidence of acute ischemic strokes (AIS) and pose distinct challenges in clinical management and prognosis. Neuroimaging techniques, such as Fluid Attenuation Inversion Recovery (FLAIR) imaging and cerebral blood volume (CBV) index derived from perfusion imaging, have significantly improved our ability to assess the impact of strokes and predict their outcomes. The primary objective of this study was to investigate relationship between follow-up infarct volume (FIV) as assessed by FLAIR imaging in patients with DMVOs., Methods: This prospectively collected, retrospective reviewed cohort study included patients from two comprehensive stroke centers within the Johns Hopkins Medical Enterprise, spanning August 2018-October 2022. The cohort consisted of adults with AIS attributable to DMVO. Detailed imaging analyses were conducted, encompassing non-contrast CT, CT angiography (CTA), CT perfusion (CTP), and FLAIR imaging. Univariable and multivariable linear regression models were employed to assess the association between different factors and FIV., Results: The study included 79 patients with DMVO stroke with a median age of 69 years (IQR, 62-77 years), and 57% (n = 45) were female. There was a negative correlation between the CBV index and FIV in a univariable linear regression analysis (Beta =  - 16; 95% CI,  - 23 to  - 8.3; p < 0.001) and a multivariable linear regression model (Beta =  - 9.1 per 0.1 change; 95% CI,  - 15 to  - 2.7; p = 0.006). Diabetes was independently associated with larger FIV (Beta = 46; 95% CI, 16 to 75; p = 0.003). Additionally, a higher baseline ASPECTS was associated with lower FIV (Beta =  - 30; 95% CI,  - 41 to  - 20; p < 0.001)., Conclusion: Our findings underscore the CBV index as an independent association with FIV in DMVOs, which highlights the critical role of collateral circulation in determining stroke outcomes in this patient population. In addition, our study confirms a negative association of ASPECTS with FLAIR FIV and identifies diabetes as independent factor associated with larger FIV. These insights pave the way for further large-scale, prospective studies to corroborate these findings, thereby refining the strategies for stroke prognostication and management., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Behavioral neurology & neuropsychiatry (BNNP) is a field that seeks to understand brain-behavior relationships, including fundamental brain organization principles and the many ways that brain structures and connectivity can be disrupted, leading to abnormalities of behavior, cognition, emotion, perception, and social cognition. In North America, BNNP has existed as an integrated subspecialty through the United Council for Neurologic Subspecialties since 2006. Nonetheless, the number of behavioral neurologists across academic medical centers and community settings is not keeping pace with increasing clinical and research demand. In this commentary, we provide a brief history of BNNP followed by an outline of the current challenges and opportunities for BNNP from the behavioral neurologist's perspective across clinical, research, and educational spheres. We provide a practical guide for promoting BNNP and addressing the shortage of behavioral neurologists to facilitate the continued growth and development of the subspecialty. We also urge a greater commitment to recruit trainees from diverse backgrounds so as to dismantle persistent obstacles that hinder inclusivity in BNNP-efforts that will further enhance the growth and impact of the subspecialty. With rapidly expanding diagnostic and therapeutic approaches across a range of conditions at the intersection of neurology and psychiatry, BNNP is well positioned to attract new trainees and expand its reach across clinical, research, and educational activities., Competing Interests: J.R.B. has received honoraria for continuing medical education (CME) lectures in behavioral neurology & neuropsychiatry (BNNP) and from Novo Nordisk. He has received funding from the National Institutes of Health (NIH), Dementia Alliance of North Carolina, and Alzheimer’s Association for work unrelated to this project. S.J.H. has received honoraria for CME lectures in BNNP. She has received funding from the Sidney R. Baer Jr. Foundation unrelated to this project. S.B. is a partner in and author for Brain Educators LLC, a neuropsychiatry education publisher. He has received honoraria for CME lectures in BNNP and receives a stipend as a psychiatry director of the American Board of Psychiatry and Neurology. B.F.B. receives author royalties from Cambridge University Press; honoraria for scientific advisory board activities for the Tau Consortium, funded by the Rainwater Charitable Foundation; and institutional research grant support from NIH and for clinical trials from Alector, Biogen, Transposon, Cognition Therapeutics, EIP Pharma, and GE Healthcare—all unrelated to this project. A.E.B. receives author royalties from Oxford University Press and Elsevier; investigator-initiated grants from the Alzheimer’s Association, VoxNeuro, and Bristol Myers Squibb; and consulting honorarium from Eli Lilly—all unrelated to this project. M.D.G. has consulted for Gerson Leherman Group and Reata Pharmaceuticals and receives research support from NIH, the National Institute of Neurological Disorders and Stroke (NINDS), and the Michael J. Homer Family Fund. A.E.H. receives honoraria from the American Heart Association as editor-in-chief of Stroke , and from Elsevier as associate editor of PracticeUpdate Neurology , unrelated to this project. S.K.H. has received honoraria for CME lectures from the American Academy of Neurology (AAN) and the Lewy Body Dementia Association. She has received research funding from NIH and the Michael J. Fox Foundation for Parkinson’s Research. I.K. receives funding from NIH and NINDS. J.D.S. is site principal investigator for Biohaven Pharmaceuticals clinical trials NCT03701399, NCT02960893, and NCT03952806; receives royalties from Oxford University Press, Elsevier, MacKeith Press, and Springer; and is the inventor of the Brief Ataxia Rating Scale, Cerebellar Cognitive Affective/Schmahmann Syndrome Scale, Patient Reported Outcome Measure of Ataxia, and Cerebellar Neuropsychiatry Rating Scale, which are licensed to the General Hospital Corporation. C.C.W. has received honoraria for creating educational content for the AAN. R.H.H. is a paid member of the board of trustees for the McKnight Brain Research Foundation and has received funding from NIH, the Department of Defense, and the Chan Zuckerberg Initiative for work unrelated to this project. D.L.P. has received honoraria for CME lectures in BNNP, royalties from Springer for a functional movement disorder textbook, and honoraria from Elsevier for a functional neurological disorder textbook, and is a paid member of the Brain and Behavior editorial board. He has received funding from NIH and the Sidney R. Baer Jr. Foundation unrelated to this project. The remaining authors declare no conflicts of interest., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Objective: To examine the relation between baseline white matter hyperintensities (WMH) and change in naming, content production, and efficiency after treatment in subacute aphasia. We hypothesized that more severe baseline WMH would result in less improvement with treatment., Design: Retrospective analysis of a cohort from a double-blind randomized controlled trial (RCT)., Setting: Outpatient clinical setting or participant home., Participants: We retrospectively reviewed imaging and behavioral data for 52 participants with subacute aphasia due to left-hemisphere ischemic stroke enrolled in the RCT. RCT inclusion criteria: English proficiency, normal/corrected-to-normal hearing/vision, and no history of neurologic conditions other than the stroke resulting aphasia. One participant with a chronic right-hemisphere lesion was retained as she presented with no residual deficits on neurologic examination. Individuals with scalp sensitivities or on medications that lower seizure threshold or any N-methyl-D-aspartate (NMDA) antagonists were excluded. Of the 52 participants, for this analysis, 2 were excluded for not having a magnetic resonance imaging, and 7 were excluded for not participating in treatment or pre/post assessment for at least 1 outcome, resulting in final sample of 43 participants (20 women sex, M [SD] age=64.4 [11.9] and M [SD] education=14.9 [3.1] years)., Interventions: Participants received 15 sessions (2-3 times/week) of computerized lexical-semantic (ie, verification) treatment with [sham/active] transcranial direct current stimulation (tDCS). Sessions were approximately 45 minutes each (tDCS for first 20 minutes)., Main Outcome Measures: Naming accuracy, content units (CUs, a measure of semantically accurate production), and efficiency (ie, syllables/CU) on a picture description task., Results: Periventricular WMH severity was independently associated with recovery in picture naming for the active tDCS group. Deep WMH severity was associated with recovery for CU production for the sham tDCS group., Conclusion: Baseline periventricular and deep WMH, among other factors, may be an important consideration for prognosis and treatment planning, especially when considered in conjunction with tDCS treatment., (Copyright © 2024. Published by Elsevier Inc.)

Poststroke aphasia, which impacts expressive and receptive communication, can have detrimental effects on the psychosocial well-being and the quality of life of those affected. Aphasia recovery is multidimensional and can be influenced by several baseline, stroke-related, and treatment-related factors, including preexisting cerebrovascular conditions, stroke size and location, and amount of therapy received. Importantly, aphasia recovery can continue for many years after aphasia onset. Behavioral speech and language therapy with a speech-language pathologist is the most common form of aphasia therapy. In this review, the authors also discuss augmentative treatment methodologies, collaborative goal setting frameworks, and recommendations for future research., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Here, we review the literature on neurotypical individuals and individuals with post-stroke aphasia showing that right-hemisphere regions homologous to language network and other regions, like the right cerebellum, are activated in language tasks and support language even in healthy people. We propose that language recovery in post-stroke aphasia occurs largely by potentiating the right hemisphere network homologous to the language network and other networks that previously supported language to a lesser degree and by modulating connection strength between nodes of the right-hemisphere language network and undamaged nodes of the left-hemisphere language network. Based on this premise (supported by evidence we review), we propose that interventions should be aimed at potentiating the right-hemisphere language network through Hebbian learning or by augmenting connections between network nodes through neuroplasticity, such as non-invasive brain stimulation and perhaps modulation of neurotransmitters involved in neuroplasticity. We review aphasia treatment studies that have taken this approach. We conclude that further aphasia rehabilitation with this aim is justified., Competing Interests: Argye Hillis receives compensation from the American Heart Association as Editor-in-Chief of Stroke and from Elsevier as Associate Editor of PracticeUpdate Neurology. All authors receive salary support from NIH (NIDCD) through grants.

Pretreatment CT Perfusion (CTP) parameter rCBV < 42% lesion volume has recently been shown to predict 90-day mRS. In this study, we aim to assess the relationship between rCBV < 42% and a radiographic follow-up infarct volume delineated on FLAIR images. In this retrospective evaluation of our prospectively collected database, we included acute stroke patients triaged by multimodal CT imaging, including CT angiography and perfusion imaging, with confirmed anterior circulation large vessel occlusion between 9 January 2017 and 10 January 2023. Follow-up FLAIR imaging was used to determine the final infarct volume. Student t, Mann-Whitney-U, and Chi-Square tests were used to assess differences. Spearman's rank correlation and linear regression analysis were used to assess associations between rCBV < 42% and follow-up infarct volume on FLAIR. In total, 158 patients (median age: 68 years, 52.5% female) met our inclusion criteria. rCBV < 42% (ρ = 0.56, p < 0.001) significantly correlated with follow-up-FLAIR infarct volume. On multivariable linear regression analysis, rCBV < 42% lesion volume (beta = 0.60, p < 0.001), ASPECTS (beta = -0.214, p < 0.01), mTICI (beta = -0.277, p < 0.001), and diabetes (beta = 0.16, p < 0.05) were independently associated with follow-up infarct volume. The rCBV < 42% lesion volume is independently associated with FLAIR follow-up infarct volume.

Background: Combined quantitative susceptibility mapping and R2* relaxometry can distinguish iron and myelin components in ischemic lesions. We aimed to investigate whether longitudinal changes in magnetic susceptibility and R2* values within ischemic lesions were associated with neurological outcomes., Methods: In this single-center prospective study, we included patients, 20 to 90 years of age, who were consecutively admitted to the stroke care unit between August 2020 and March 2022 due to acute ischemic stroke. The participants underwent 2 instances of quantitative susceptibility mapping and R2* relaxometry scanning before and after stroke rehabilitation. We compared the changes in these quantitative measures across different subtypes of acute ischemic stroke. Multiple linear regression models were used to investigate the associations between the National Institutes of Health Stroke Scale scores and the mean magnetic susceptibility and R2* values in ischemic lesions., Results: Among a total of 112 patients with acute ischemic stroke, 32 participants (aged 73.3±9.4 years; 20 men and 12 women) were evaluated. The median time from stroke onset to the first imaging was 5 days and that to the second imaging was 102 days. The changes in magnetic susceptibility values of branch atheromatous disease were higher than those of cardioembolism (mean difference, 0.018 [95% CI, 0.009-0.027] ppm; P <0.001) and lacunar (mean difference, 0.013 [95% CI, 0.005-0.020] ppm; P =0.004). Across all patients, the changes in National Institutes of Health Stroke Scale scores were associated with those of magnetic susceptibility values (coefficient, 0.311 [95% CI, 0.098-0.520]; P =0.017) but not with R2* values (coefficient, 0.114 [95% CI, -0.127 to 0.345]; P =0.291)., Conclusions: The longitudinal changes in the magnetic susceptibility values within ischemic lesions were associated with neurological outcomes during the restorative stages poststroke in patients experiencing acute ischemic stroke., Registration: URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000050719., Competing Interests: Disclosures Dr Oishi is a consultant for Corporate-M and AnatomyWorks. This arrangement is being managed by Johns Hopkins University in accordance with its conflict-of-interest policies. Dr Hillis receives compensation as the editor-in-chief of Stroke and from Elsevier as an associate editor of PracticeUpdate Neurology, grant support from the National Institutes of Health, salary from the Johns Hopkins University School of Medicine, and funding from the National Institute on Deafness and Other Communication Disorders. Disclosures provided by Dr Hillis in compliance with the annual Journal Editor Disclosure Questionnaire of the American Heart Association are available at https://www.ahajournals.org/editor-coi-disclosures. The other authors report no conflicts.

Although pretreatment radiographic biomarkers are well established for hemorrhagic transformation (HT) following successful mechanical thrombectomy (MT) in large vessel occlusion (LVO) strokes, they are yet to be explored for medium vessel occlusion (MeVO) acute ischemic strokes. We aim to investigate pretreatment imaging biomarkers representative of collateral status, namely the hypoperfusion intensity ratio (HIR) and cerebral blood volume (CBV) index, and their association with HT in successfully recanalized MeVOs. A prospectively collected registry of acute ischemic stroke patients with MeVOs successfully recanalized with MT between 2019 and 2023 was retrospectively reviewed. A multivariate logistic regression for HT of any subtype was derived by combining significant univariate predictors into a forward stepwise regression with minimization of Akaike information criterion. Of 60 MeVO patients successfully recanalized with MT, HT occurred in 28.3% of patients. Independent factors for HT included: diabetes mellitus history (p = 0.0005), CBV index (p = 0.0071), and proximal versus distal occlusion location (p = 0.0062). A multivariate model with these factors had strong diagnostic performance for predicting HT (area under curve [AUC] 0.93, p < 0.001). Lower CBV indexes, distal occlusion location, and diabetes history are significantly associated with HT in MeVOs successfully recanalized with MT. Of note, HIR was not found to be significantly associated with HT., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background: Poor venous outflow (VO) profiles are associated with unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO), despite achieving successful reperfusion. The objective of this study is to assess the association between mortality and prolonged venous transit (PVT), a novel visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps., Methods: We performed a retrospective analysis of prospectively collected data from consecutive adult patients with AIS-LVO with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10 s timing on CTP Tmax maps in at least one of the following: superior sagittal sinus (proximal venous drainage) and/or torcula (deep venous drainage). PVT- was defined as lacking this in both regions. The primary outcome was mortality at 90 days. In a 1:1 propensity score-matched cohort, regressions were performed to determine the effect of PVT on 90-day mortality., Results: In 127 patients of median (IQR) age 71 (64-81) years, mortality occurred in a significantly greater proportion of PVT+ patients than PVT- patients (32.5% vs 12.6%, P=0.01). This significant difference persisted after matching (P=0.03). PVT+ was associated with a significantly increased likelihood of 90-day mortality (OR 1.22 (95% CI 1.02 to 1.46), P=0.03) in the matched cohort., Conclusions: PVT+ was significantly associated with 90-day mortality despite successful reperfusion therapy in patients with AIS-LVO. PVT is a simple VO profile marker with potential as an adjunctive metric during acute evaluation of AIS-LVO patients. Future studies will expand our understanding of using PVT in the evaluation of patients with AIS-LVO., Competing Interests: Competing interests: VSY, JJH and GWA are consultants for iSchemaView (Menlo Park, California, USA) not related to the submitted work., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The pretreatment CT perfusion (CTP) marker the relative cerebral blood volume (rCBV) < 42% lesion volume has recently been shown to predict 90-day functional outcomes; however, studies assessing correlations of the rCBV < 42% lesion volume with other outcomes remain sparse. Here, we aim to assess the relationship between the rCBV < 42% lesion volume and the reference standard digital subtraction angiography (DSA)-derived American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN) collateral score, hereby referred as the DSA CS. Methods: In this retrospective evaluation of our prospectively collected database, we included acute stroke patients triaged by multimodal CT imaging, including CT angiography and perfusion imaging, with confirmed anterior circulation large vessel occlusion between 1 September 2017 and 1 October 2023. Group differences were assessed using the Student's t test, Mann-Whitney U test and Chi-Square test. Spearman's rank correlation and logistic regression analyses were used to assess associations between rCBV < 42% and DSA CS. Results: In total, 222 patients (median age: 69 years, 56.3% female) met our inclusion criteria. In the multivariable logistic regression analysis, taking into account age, sex, race, hypertension, hyperlipidemia, diabetes, atrial fibrillation, prior stroke or transient ischemic attack, the admission National Institute of Health stroke scale, the premorbid modified Rankin score, the Alberta stroke program early CT score (ASPECTS), and segment occlusion, the rCBV < 42% lesion volume (adjusted OR: 0.98, p < 0.05) was independently associated with the DSA CS. Conclusion: The rCBV < 42% lesion volume is independently associated with the DSA CS.