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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]

Purpose: The purpose of the study was to evaluate Verb Network Strengthening Treatment (VNeST) paired with the transcranial direct current stimulation (tDCS) of the left inferior frontal gyrus, which was compared to VNeST paired with a sham stimulation in primary progressive aphasia (PPA)., Method: A double-blind, within-subject, sham-controlled crossover design was used. Eight participants with PPA were enrolled. Participants were enrolled in two treatment phases, one with VNeST plus real tDCS and one with VNeST plus sham. Participants received fifteen 1-hr sessions of VNeST in each phase. Linear mixed-effects models were used to compare changes between baseline and two follow-up time points (1 week and 8 weeks posttreatment) in naming trained verbs, untrained verbs, and untrained nouns; sentence production and comprehension; and producing content units and complete utterances in discourse., Results: VNeST was effective for significantly improving naming trained verbs and producing more complete utterances in discourse at 1 week posttreatment in both tDCS and sham conditions. A significant tDCS advantage yielded generalization of treatment effects to untrained verbs (at 1 week and 8 weeks posttreatment), sentence production (at 1 week posttreatment), and sentence comprehension (at 8 weeks posttreatment). Untrained verb naming and sentence comprehension declined when VNeST was not augmented with tDCS., Conclusions: Our findings provide emerging evidence that VNeST paired with tDCS can improve word finding, and other language abilities, in people with PPA. VNeST without neuromodulation can improve trained verb naming, but untrained verbs will likely decline faster when VNeST is not augmented with tDCS. Future research is required with a larger sample size to continue investigating the potential of treating word finding with VNeST and tDCS in PPA., Supplemental Material: https://doi.org/10.23641/asha.27914325.

Background and Aim: Recent studies have shown that the CT Perfusion (CTP) parameter of rCBV < 42 % lesion volume can predict 90-day functional outcomes in stroke patients. However, its correlation with discharge outcomes, including functional dependence, has not been investigated. Our study aims to evaluate the relationship between rCBV < 42 % and poor functional outcomes at discharge, defined as a modified Rankin score (mRS) of 3 or higher., Materials and Methods: This retrospective study analyzed patients with confirmed occlusion on CT angiography, who also received CT perfusion between 9/1/2017 and 10/01/2023. Statistical tests (Student's T, Mann-Whitney U, and Chi-Square) were used to assess differences. Univariable and multivariable logistic regression analyses were performed to evaluate the associations of rCBV < 42 % with discharge mRS. A p-value ≤ 0.05 was considered significant., Results: A total of 268 patients [median age: 68 years (IQR: 59-77), 56.3 % female] met the inclusion criteria. Among them, 85 patients (31.7 %) received intravenous thrombolysis (IVT), and 221 patients (82.5 %) underwent mechanical thrombectomy (MT). After adjusting for various variables, logistic regression analysis indicated that rCBV < 42 % lesion volume was associated with poor functional outcomes at discharge (aOR = 0.97, p < 0.05). T., Conclusion: The rCBV < 42 % could be a valuable tool in prognosticating AIS-LVO patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Dhairya Lakhani, Greg Albers, Jeremy Heit, and Vivek Yedavalli are consultants for Rapid (iSchemaView, Menlo Park, CA)., (Copyright © 2024 Elsevier Ltd. 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., Competing Interests: Declarations. Ethics approval: All procedures were approved by the Johns Hopkins Medicine Institutional Review Board (IRB00089018). Consent to participate: All participants or their legally authorized representatives provided written consent. Consent to Publish: The manuscript does not contain any individual person’s data in any form (including any individual details, images or videos). Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Purpose: Despite comprehensive evidence that supports the utility of aphasia therapy in persons with chronic (≥6 months) stroke-induced aphasia, the amount of therapy provided to patients in the United States is typically far less than what is likely necessary to maximize recovery. Two potential contributors to this discrepancy are limited access to rehabilitation services due to the availability of providers and logistical difficulties with transportation. One way to increase access to aphasia therapy is to rely on telerehabilitation., Methods: The TEleRehabilitation foR Aphasia (TERRA) trial is a prospective, randomized, rater-blinded, multicenter phase II non-inferiority trial to evaluate telerehabilitation for aphasia therapy in persons with chronic post-stroke aphasia. Participants are randomized (1:1) to receive either aphasia remote therapy or in-clinic therapy for 30 total days of treatment (15 days of a semantically focused approach and 15 days of a phonologically focused approach) for 45 min per day. A total of 100 adults (ages 21-80) with a history of left hemisphere ischemic or hemorrhagic stroke incurred at least 12 months prior to study enrollment will be randomized. The trial will be conducted at the clinical research facilities at two sites: the Medical University of South Carolina and the University of South Carolina., Conclusions: This paper details the design of the TERRA trial, which aims to test whether aphasia therapy delivered by a remote speech-language pathologist through videoconferencing (i.e., via telerehabilitation) is not clinically worse than in-clinic therapy for individuals with chronic post-stroke aphasia to provide an opportunity to move to a definitive phase III trial., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background and Purpose: Mechanical thrombectomy (MT) is the treatment standard for large vessel occlusion (LVO) stroke. Under current guidelines, only patients with smaller ischemic core volumes (ICV) are eligible for MT. Thus, it is of interest to quickly estimate ICV in stroke patients. The Los Angeles Motor Scale (LAMS) is a validated tool used to assess stroke severity directly in the field. This study aims to determine whether LAMS score is also associated with ICV, as defined by the CBF <30% volume on CT perfusion imaging., Methods: We performed a retrospective, multicenter cohort study of consecutive patients presenting with LVO stroke from 9/1/2017 to 10/1/2023. The inclusion criteria were patients with (1) stroke caused by large vessel occlusion confirmed on CTA and (2) diagnostically adequate, multimodal pretreatment CT imaging. Demographic, clinical, and imaging data was collected through manual chart review. Both univariate and multivariate analyses were applied to assess associations. A p -value <.05 was considered significant., Results: A total of 283 patients (median age: 69, IQR: 61-78) were included in the study. On multivariate logistic regression analysis, we found that lower admission LAMS score (adjusted OR: 0.511, 95% CI: 0.313-0.834, p = .007) was independently associated with a CBF <30% volume of less than 50cc., Conclusions: Admission LAMS is an independent predictor of a CBF <30% volume of less than 50cc. This demonstrates that LAMS can be used to estimate ICV, which will aid in the early triaging of LVO patients to thrombectomy-capable centers., 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: The authors do not have any conflict of interest to disclose except for Dr Vivek Yedavalli, who serves as a consultant for MRIOnline (Cincinnati, OH, USA), RAPID (iSchemaView, Menlo Park, CA, USA), and editorial board of Frontiers in Radiology.

Background : Pretreatment CTA-based Cortical Vein Opacification Score (COVES) has been shown to predict good functional outcomes at 90 days in patients with acute ischemic stroke secondary to large vessel occlusion (AIS-LVO). This is thought to be related to its ability to measure collateral status (CS). However, its association with the reference standard test, the DSA-based American Society of Interventional and Therapeutic Neuroradiology (ASITN) collateral score, has yet to be established. Therefore, this study assesses the relationship between COVES and ASITN CS. Methods : In this prospectively collected, retrospectively reviewed analysis, patients with anterior circulation LVO from September 1, 2017, to October 1, 2023, were included. The COVES grading, which ranges from 0 to 6, was independently assessed by two board-certified neuroradiologists. The ASITN CS was independently assessed by a board-certified neuroradiologist and the performing neurointerventionalist. Any discrepancies were resolved through consensus review. Spearman's rank correlation, univariable logistic regression, multivariable logistic regression, and receiver operating characteristic curve analysis were performed. A p-value of ≤0.05 was considered significant. Results : In total, 311 consecutive patients (median, IQR=68 years [59-78 years]; 55.9% female) met our inclusion criteria. There was significant positive correlation between COVES and ASITN CS (ρ=0.41,p<0.001), and higher COVES was significantly and independently associated with good ASITN CS (unadjusted-OR=1.74,p<0.001) and adjusted-OR=1.73, p<0.001). ROC analysis showed AUC of 0.71, p<0.001). Conclusion : In conclusion, by demonstrating the independent association of COVES with the reference standard test for collateral status assessment, the ASITN CS, we further validate the role of COVES in estimating collateral status.ABBREVIATIONS: AIS: Acute ischemic stroke; ASITN: American Society of Interventional and Therapeutic Neuroradiology; CS: Collateral status; COVES: Cortical Vein Opacification Score; HIR: Hypoperfusion Intensity Ratio; IVT: Intravenous thrombolysis; LVO: Large vessel occlusion; mRS: modified Rankin score; MT: mechanical thrombectomy; OR: odds ratio; aOR: adjusted odds ratio; ua: unadjusted odds ratio; rCBF: relative cerebral blood flow; Tmax: Time-to-Maximum., (© 2024 by American Journal of Neuroradiology.)

Background: Endovascular thrombectomy (EVT) has shown promise in randomized controlled trials (RCTs) for large ischemic core stroke patients, yet variability in core definition and onset-to-imaging time creates heterogeneity in outcomes. This study aims to clarify the prevalence and implications of core-perfusion mismatch (MM) versus no mismatch (No MM) in such patients, utilizing established imaging criteria., Methods: A retrospective cohort study was conducted including patients from 7/29/2019 to 1/29/2023, with data extracted from a continuously maintained database. Patients were eligible if they met criteria including multimodal CT imaging performed within 24 h from last known well (LKW), AIS-LVO diagnosis, and ischemic core size defined by specific rCBF thresholds. Mismatch was assessed based on different operational definitions from the EXTEND and DEFUSE 3 trials., Results: Fifty-two patients were included, with various time windows from LKW. Using EXTEND criteria, a significant portion of early window patients exhibited MM; however, fewer patients met MM criteria in the late window. Defining MM using DEFUSE 3 criteria yielded similar patterns, but with overall lower MM prevalence in the late window. When employing rCBF <38% as a surrogate for ischemic core, a higher percentage of patients were classified as MM across both time windows compared to rCBF <30%., Conclusion: The prevalence of MM in large ischemic core patients varies significantly depending on the imaging criteria and time from LKW. Notably, MM was more prevalent in the early time window across all criteria used. Additional RCTs are needed to determine if this definition of MM identifies patients who will benefit most from EVT., Competing Interests: Declarations. Conflict of interest: V. Yedavalli, H.A. Salim, D.A. Lakhani, J. Mei, A. Balar, B. Musmar, N. Adeeb, M. Hoseinyazdi, L. Luna, F. Deng, N.Z. Hyson, A.A. Dmytriw, A. Guenego, H. Lu, V.C. Urrutia, K. Nael, E.B. Marsh, R. Llinas, A.E. Hillis, M. Wintermark, T.D. Faizy, J.J. Heit and G.W. Albers declare that they have no competing interests. Ethical standards: This study was approved through the institutional review board (JHU-IRB00269637) and follows the STROBE checklist guidelines as an observational study., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Background and Purpose: Acute ischemic strokes caused by distal medium vessel occlusions (DMVO) represent a significant proportion of all stroke cases, yet the predictors of excellent functional outcomes in these patients remain poorly understood. This study aims to identify pretreatment computed tomography perfusion (CTP) parameters associated with excellent functional outcomes, defined as a modified Rankin Scale (mRS) score of 0-1 at 90 days, in patients with anterior circulation DMVO., Materials and Methods: We conducted a retrospective multicenter study involving patients with anterior DMVO, from three stroke centers within the Johns Hopkins Medical Enterprise. Baseline demographic, clinical, and imaging data were collected, with CTP parameters analyzed using RAPIDAI software. Univariable and multivariable logistic regression models were used to identify predictors of excellent outcomes. Receiver operating characteristic (ROC) curves were constructed to assess the predictive accuracy of CTP parameters., Results: Among the 82 patients (median age, 71 years; 57% female), occlusions were located in the M2 segment in 89%, M3 in 8.5%, and A2 in 2.4%. IVT was administered to 37% of patients, and EVT was attempted in 59%. Excellent outcomes at 90 days were achieved in 45% of patients. In univariate analysis, white race (OR, 4.14; 95% CI, 1.66-10.9; P=0.003), higher CBV index (OR per 0.1-unit change, 1.45; 95% CI, 1.08-2.05; P=0.022), and lower relative cerebral blood flow (rCBF < 20%) volumes (OR, 0.91; 95% CI, 0.81-0.98; P=0.038) were significantly associated with excellent outcomes. In multivariate analysis adjusting for age, sex, race, IVT administration, EVT attempted, dyslipidemia, and premorbid mRS, higher CBV index remained a significant independent predictor (OR per 0.1-unit change, 1.72; 95% CI, 1.14-2.81; P=0.017), and lower rCBF < 20% volume was associated with better outcomes (OR, 0.91; 95% CI, 0.80-0.98; P=0.05). The multivariate model demonstrated good predictive performance (area under the ROC curve, 80%; 95% CI, 70%-90%; P < 0.001)., Conclusions: In patients with anterior circulation DMVO, a higher CBV index on pretreatment CTP is an independent predictor of excellent functional outcomes at 90 days. These findings suggest that CTP parameters, particularly the CBV index, may be useful in prognostic assessment for this stroke population. Further studies are needed to validate these results and optimize therapeutic approaches., Abbreviations: ABC＝ definition; XYZ＝ definition., (© 2024 by American Journal of Neuroradiology.)

Introduction: The influence of the cerebellum in poststroke aphasia recovery is poorly understood. Despite the right cerebellum being identified as a critical region involved in both language and cognitive functions, little is known about functional connections between the cerebellum and bilateral cortical hemispheres following stroke. This study investigated the relationship between chronic poststroke naming deficits and cerebello-cerebral resting-state functional connectivity (FC). Methods: Twenty-five cognitively normal participants and 42 participants with chronic poststroke aphasia underwent resting-state functional magnetic resonance imaging. Participants with aphasia also underwent language assessment. We conducted regions of interest (ROI)-to-ROI analyses to investigate the FC between the right cerebellar Crus I/II (seed ROI; Cereb1r/Cereb2r) and bilateral cortical language regions and compared these results to cognitively normal controls. Single-subject connectivity parameters were extracted and used as independent variables in a stepwise multiple linear regression model associating Boston Naming Test (BNT) score with FC measures. Results: FC analyses demonstrated correlations between the right cerebellar Crus I/II and both left and right cortical regions for both cognitively normal controls and stroke participants. Additionally, aphasia severity and lesion load had an effect on the cerebello-cerebral network connectivity in participants with aphasia. In a stepwise multiple linear regression, controlling for aphasia severity, time poststroke and lesion load, FC between the right Cereb2-left Cereb1 (standardized beta [std B]= -0.255, p < 0.004), right Cereb2-right anterior MTG (std B = 0.259, p < 0.004), and the right Cereb2-left anterior STG (std B = -0.208, p < 0.018) were significant predictors of BNT score. The overall model fit was R 2 = 0.786 ( p = 0.001). Conclusion: Functional connections between the right cerebellum and residual bilateral cerebral hemisphere regions may play a role in predicting naming ability in poststroke aphasia.

Objective: Venous outflow (VO) impairment predicts unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO). Prolonged venous transit (PVT), a visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps, has been associated with unfavorable 90-day functional outcomes despite successful reperfusion. This study investigates the association between PVT and percent change on the National Institutes of Health Stroke Scale (NIHSS) among AIS-LVO patients who have undergone successful reperfusion., Methods: We performed a retrospective analysis of prospectively collected data from consecutive adult AIS-LVO patients with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10 s in the superior sagittal sinus, torcula, or both. The primary outcome was continuous NIHSS percent change and dichotomous NIHSS percent change ≥70%. Regression analyses were performed to assess the effect of PVT on NIHSS percent change., Results: In 119 patients of median (IQR) age 71 (63-81) years, the admission and discharge NIHSS scores were significantly higher in PVT+ patients compared to PVT- patients (17 [14-23.5] vs. 13 [9.5-19], p = 0.011, and 7.5 [4-12] vs. 3 [1-7], p < 0.001, respectively). After adjusting for age, sex, hypertension, diabetes, atrial fibrillation, administration of intravenous thrombolysis (IVT), Alberta Stroke Program Early CT Scores (ASPECTS), mTICI 2c and/or 3, Tmax >6 s volume, and hemorrhagic transformation, PVT+ was significantly associated with lower NIHSS percent change (B = -0.163, 95%CI -0.326 to -0.001, p = 0.049) and was less likely to achieve higher than 70% NIHSS improvement (OR = 0.331, 95% CI 0.127-0.863, p = 0.024)., Interpretation: PVT+ was significantly associated with reduced neurological improvement despite successful reperfusion in AIS-LVO patients, highlighting the critical role of VO impairment in short-term functional outcomes. These findings further validate PVT as a valuable adjunct imaging biomarker derived from CTP for assessing VO profiles in AIS-LVO., (© 2024 The Author(s). Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

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.)

The hypoperfusion intensity ratio (HIR) is a quantitative metric used in vascular occlusion imaging to evaluate the extent of brain tissue at risk due to hypoperfusion. Defined as the ratio of tissue volume with a time-to-maximum (Tmax) of >10 seconds to that of >6 seconds, HIR assists in differentiating between the salvageable penumbra and the irreversibly injured core infarct. This review explores the role of HIR in assessing clinical outcomes and guiding treatment strategies, including mechanical thrombectomy and thrombolytic therapy, for patients with large vessel occlusions (LVOs). Evidence suggests that higher HIR values are associated with worse clinical outcomes, indicating more severe tissue damage and reduced potential for salvage through reperfusion. Additionally, HIR demonstrates predictive accuracy regarding infarct growth, collateral flow, and the risk of reperfusion hemorrhage. It has shown superiority over traditional metrics, such as core infarct volume, in predicting functional outcomes. HIR offers valuable insights for risk stratification and treatment planning in patients with LVOs and distal medium vessel occlusions (DMVOs). Incorporating HIR into clinical practice enhances patient care by improving decision-making processes, promoting timely interventions, and optimizing post-intervention management to minimize complications and improve recovery outcomes., Competing Interests: The authors declare no conflicts of interest related to the content of this article., (© 2024 by American Journal of Neuroradiology.)

Background: Mechanical thrombectomy (MT) is the treatment standard in eligible patients with acute ischemic stroke (AIS) secondary to large vessel occlusions (LVO). Studies have shown that good collateral status is a strong predictor of MT efficacy, thus making collateral status important to quickly assess. The Los Angeles Motor Scale is a clinically validated tool for identifying LVO in the field. The aim of this study is to investigate whether admission LAMS score is also associated with the American Society of Interventional and Therapeutic Neuroradiology (ASITN) collateral score on digital subtraction angiography (DSA)., Methods: We conducted a retrospective multicenter cohort study of consecutive patients presenting with AIS caused by LVO from 9/1/2017 to 10/1/2023 with diagnostically adequate DSA imaging. Demographic, clinical, and imaging data was collected through manual chart review. Both univariate and multivariate analysis were applied to assess associations. A p -value <0.05 was considered significant., Results: A total of 308 patients (median age: 68, IQR: 57.5-77) were included in the study. On multivariate logistic regression analysis, we found that lower admission LAMS score (adjusted OR: 0.82, 95% CI: 0.68-0.98, p  < 0.05) and higher ASPECTS score (adjusted OR: 1.21, 95% CI: 1.02-1.42, p  < 0.05) were independently associated with good DSA ASITN collateral score of 3-4., Conclusions: Admission LAMS and ASPECTS score are both independently associated with DSA ASITN collateral score. This demonstrates the capability of LAMS to act as a surrogate marker of CS in the field.

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., Competing Interests: Dr Yedavalli reports compensation from IschemaView (RAPID AI) for consultant services and compensation from MRIOnline for consultant services. Dr Guenego reports compensation from Acandis for consultant services; compensation from Rapid Medical Ltd for consultant services; and compensation from phenox, Inc, for consultant services. Dr Heit reports compensation from iSchemaView for consultant services; compensation from Medtronic for consultant services; and compensation from MicroVention Inc for consultant services. Dr Albers reports compensation from iSchemaView for consultant services; compensation from Genentech for consultant services; and stock holdings in iSchemaView. Dr Urrutia reports grants from Genentech and employment by Johns Hopkins University School of Medicine. Dr Nael reports compensation from BRAINOMIX LIMITED for consultant services and compensation from Olea Medical for consultant services. Dr Hillis reports compensation from American Heart Association for other services; compensation from Elsevier Publishing for other services; employment by Johns Hopkins University School of Medicine; compensation from National Institute on Deafness and Other Communication Disorders for other services; and grants from National Institute on Deafness and Other Communication Disorders. The other authors report no conflicts.

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;96:625-632., (© 2024 American Neurological Association.)

Background and Purpose: Acute ischemic stroke due to anterior circulation large-vessel occlusion (AIS-LVO) remains a leading cause of disability despite successful reperfusion therapies. Prolonged venous transit (PVT) has emerged as a potential prognostic imaging biomarker in AIS-LVO. We aimed to investigate whether PVT is associated with a decreased likelihood of excellent functional outcome (modified Rankin Scale [mRS] score of 0-1 at 90 days) after successful reperfusion., Methods: In our prospectively collected, retrospectively reviewed database, we analyzed data from 104 patients with AIS-LVO who achieved successful reperfusion (modified Thrombolysis in Cerebral Infarction score of 2b/2c/3) between September 2017 and September 2022. PVT was defined as a time to maximum (Tmax) of ≥10 s in the superior sagittal sinus and/or torcula on computed tomography perfusion (CTP) imaging. Patients were categorized into PVT-positive (PVT+) and PVT-negative (PVT-) groups. The primary outcome was excellent functional recovery at 90 days., Results: Of the 104 patients, 30 (29%) were PVT+. Excellent functional outcome was achieved in 38 patients (37%). PVT+ patients had a significantly lower rate of excellent recovery compared to PVT- patients (11% vs. 39%; p < 0.001). After adjusting for possible confounders, PVT positivity was independently associated with lower odds of excellent recovery (adjusted odds ratio 0.11, 95% confidence interval 0.02 to 0.48; p = 0.006)., Conclusions: Among patients with AIS-LVO who achieved successful reperfusion, PVT positivity was independently associated with a decreased likelihood of excellent functional outcome at 90 days. Assessment of PVT on CTP may provide valuable prognostic information and aid in clinical decision making for patients with AIS-LVO., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

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).)

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: 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 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.