Simplifying venous outflow: Prolonged venous transit as a novel qualitative marker correlating with acute stroke outcomes.

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.

Immune-related encephalitis after immune checkpoint inhibitor therapy.

BACKGROUND: Immune checkpoint inhibitors (ICI) have revolutionized cancer treatment but can trigger immune-related encephalitis. We report one of the largest case series of patients with immune-related encephalitis and review of the literature. METHODS: Retrospective series of patients with immune-related encephalitis and literature review. RESULTS: Fourteen patients with cancer treated with ICI (50% combination therapy) developed immune-related encephalitis. Diagnostic testing revealed cerebral spinal fluid (CSF) lymphocytic pleocytosis (85%) and elevated protein (69%), abnormal brain magnetic resonance imaging(MRI) (33%) or brain FDG-PET (25%), electroencephalogram (EEG) abnormalities (30%), and autoantibodies (31%). Encephalitis treatment included: corticosteroids (86%), intravenous immunoglobulin (IVIg) (36%), plasmapheresis (7%), and rituximab (29%). There were no deaths and 12 patients had significant recovery, although long-term complications were observed. All patients discontinued ICI. Longitudinal follow-up demonstrated anti-cancer response to ICI at 3 months (85%) and 6 months post-ICI initiation (77%). A literature review identified 132 patients with immune-related encephalitis. Most were treated with PD-1 inhibitors (18% combination). Common abnormalities included elevated CSF protein (84%) or pleocytosis (77%), abnormal brain MRI (65%), or autoantibodies (47%). Nearly all were treated with corticosteroids, many required additional therapy with IVIg (26%) or rituximab (12%). Most patients had clinical improvement (81%) but a minority (10%) had a clinical relapse after completing corticosteroid taper. ICIs were resumed in 7 patients (5%), with relapse in 3. CONCLUSIONS AND RELEVANCE: Immune-related encephalitis is treatable and improves with corticosteroids in most cases but may require additional immunosuppression. Re-emergence of encephalitis is rare and does not typically result in adverse outcomes, and this should be considered in neurological immune-related adverse event management guidelines.

Prolonged venous transit on perfusion imaging is associated with higher odds of mortality in successfully reperfused patients with large vessel occlusion stroke.

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.

Pretreatment parameters associated with hemorrhagic transformation among successfully recanalized medium vessel occlusions.

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.

Redefining CT perfusion-based ischemic core estimates for the ghost core in early time window stroke.

BACKGROUND AND PURPOSE: In large vessel occlusion (LVO) stroke patients, relative cerebral blood flow (rCBF)<30% volume thresholds are commonly used in treatment decisions. In the early time window, nearly infarcted but salvageable tissue volumes may lead to pretreatment overestimates of infarct volume, and thus potentially exclude patients who may otherwise benefit from intervention. Our multisite analysis aims to explore the strength of relationships between widely used pretreatment CT parameters and clinical outcomes for early window stroke patients. METHODS: Patients from two sites in a prospective registry were analyzed. Patients with LVOs, presenting within 3 hours of last known well, and who were successfully reperfused were included. Primary short-term neurological outcome was percent National Institutes of Health Stroke Scale (NIHSS) change from admission to discharge. Secondary long-term outcome was 90-day modified Rankin score. Spearman's correlations were performed. Significance was attributed to p-value ≤.05. RESULTS: Among 73 patients, median age was 66 (interquartile range 54-76) years. Among all pretreatment imaging parameters, rCBF<30%, rCBF<34%, and rCBF<38% volumes were significantly, inversely correlated with percentage NIHSS change (p<.048). No other parameters significantly correlated with outcomes. CONCLUSIONS: Our multisite analysis shows that favorable short-term neurological recovery was significantly correlated with rCBF volumes in the early time window. However, modest strength of correlations provides supportive evidence that the applicability of general ischemic core estimate thresholds in this subpopulation is limited. Our results support future larger-scale efforts to liberalize or reevaluate current rCBF parameter thresholds guiding treatment decisions for early time window stroke patients.

Neuro-11: a new questionnaire for the assessment of somatic symptom disorder in general hospitals.

Background: Somatic symptom disorder (SSD) commonly presents in general hospital settings, posing challenges for healthcare professionals lacking specialised psychiatric training. The Neuro-11 Neurosis Scale (Neuro-11) offers promise in screening and evaluating psychosomatic symptoms, comprising 11 concise items across three dimensions: somatic symptoms, negative emotions and adverse events. Prior research has validated the scale's reliability, validity and theoretical framework in somatoform disorders, indicating its potential as a valuable tool for SSD screening in general hospitals. Aims: This study aimed to establish the reliability, validity and threshold of the Neuro-11 by comparing it with standard questionnaires commonly used in general hospitals for assessing SSD. Through this comparative analysis, we aimed to validate the effectiveness and precision of the Neuro-11, enhancing its utility in clinical settings. Methods: Between November 2020 and December 2021, data were collected from 731 patients receiving outpatient and inpatient care at Shenzhen People's Hospital in China for various physical discomforts. The patients completed multiple questionnaires, including the Neuro-11, Short Form 36 Health Survey, Patient Health Questionnaire 15 items, Hamilton Anxiety Scale and Hamilton Depression Scale. Psychiatry-trained clinicians conducted structured interviews and clinical examinations to establish a gold standard diagnosis of SSD. Results: The Neuro-11 demonstrated strong content reliability and structural consistency, correlating significantly with internationally recognised and widely used questionnaires. Despite its brevity, the Neuro-11 exhibited significant correlations with other questionnaires. A test-retest analysis yielded a correlation coefficient of 1.00, Spearman-Brown coefficient of 0.64 and Cronbach's α coefficient of 0.72, indicating robust content reliability and internal consistency. Confirmatory factor analysis confirmed the validity of the three-dimensional structure (p<0.001, comparative fit index=0.94, Tucker-Lewis index=0.92, root mean square error of approximation=0.06, standardised root mean square residual=0.04). The threshold of the Neuro-11 is set at 10 points based on the maximum Youden's index from the receiver operating characteristic curve analysis. In terms of diagnostic efficacy, the Neuro-11 has an area under the curve of 0.67. Conclusions: (1) The Neuro-11 demonstrates robust associations with standard questionnaires, supporting its validity. It is applicable in general hospital settings, assessing somatic symptoms, negative emotions and adverse events. (2) The Neuro-11 exhibits strong content reliability and validity, accurately capturing the intended constructs. The three-dimensional structure demonstrates robust construct validity. (3) The threshold of the Neuro-11 is set at 10 points.

Recognizing and Responding to the Needs of Future Child and Adult Neurology Care Through the Evolution of Residency Training.

Recent insights into the frequency of occurrence and the genetic and mechanistic basis of nervous system disease have demonstrated that neurologic disorders occur as a spectrum across all ages. To meet future needs of patients with neurologic disease of all ages and prepare for increasing implementaton of precision therapies, greater integration of child and adult neurology residency training is needed. ANN NEUROL 2023;94:1005-1007.

Assessing the Efficacy of Mechanical Thrombectomy in Patients with an NIHSS < 6 Presenting with Proximal Middle Cerebral Artery Vessel Occlusion as Compared to Best Medical Management.

BACKGROUND AND PURPOSE: Minor acute ischemic stroke (AIS) patients-defined by an NIHSS score < 6-presenting with proximal middle cerebral artery large vessel occlusions (MCA-LVO) is a subgroup for which treatment is still debated. Although these patients present with minor symptoms initially, studies have shown that several patients afflicted with MCA-LVO in this subgroup experience cognitive and functional decline. Although mechanical thrombectomy (MT) is the standard of care for patients with an NIHSS score of 6 or higher, treatment in the minor stroke subgroup is still being explored. The purpose of this preliminary study is to report our center's experience in evaluating the potential benefit of mechanical thrombectomy (MT) in minor stroke patients when compared to medical management (MM). METHODS: We performed a retrospective study with two comprehensive stroke centers within our hospital enterprise of consecutive patients presenting with minor AIS secondary to MCA-LVO (defined as M1 or proximal M2 segments of MCA). We subsequently evaluated patients who received MT versus those who received MM. RESULTS: Between January 2017 and July 2021, we identified 46 AIS patients (11 treated with MT and 35 treated with MM) who presented with an NIHSS score < 6 secondary to MCA-LVO (47.8% 22/46 female, mean age 62.3 years, range 49-75 years). MT was associated with a significantly lower mRS at 90 days (median: 1.0 [IQR 0.0-2.0] versus 3.0 [IQR 1.0-4.0], p = <0.001), a favorable NIHSS shift (-4.0 [IQR -10.0--2.0] versus 0.0 [IQR -2.0-1.0], p = 0.002), favorable NIHSS shift dichotomization (5/11, 45.5% versus 3/35, 8.6%, p = 0.003) and favorable mRS dichotomization (7/11, 63.6% versus 14/35, 40.0%, p = 0.024). CONCLUSIONS: In our center's preliminary experience, for AIS patients presenting with an NIHSS score < 6 secondary to MCA-LVO, MT may be associated with improved clinical outcomes when compared to MM only.

Excellent Recanalization and Small Core Volumes Are Associated With Favorable AM-PAC Score in Patients With Acute Ischemic Stroke Secondary to Large Vessel Occlusion.

Objective: To assess pretreatment and interventional parameters as predictors of favorable Activity Measure for Post-Acute Care (AM-PAC) scores for optimal discharge planning. Design: In this prospectively collected, retrospectively reviewed multicenter study from 9/1/2017 to 9/22/2022, patients were dichotomized into favorable and unfavorable AM-PAC. Multivariate logistic regression and receiver operator characteristics analyses were performed for the identified significant variables. A P value of ≤.05 was significant. Setting: Hospitalized care. Participants: In total, 229 patients (mean ±SD 70.65 ±15.2 [55.9% women]) met our inclusion criteria. Inclusion criteria were (a) computed tomography (CT) angiography confirmed LVO from 9/1/2017 to 9/22/2022; (b) diagnostic CT perfusion; and (c) available AM-PAC scores. Interventions: None. Main Outcome Measures: Favorable AM-PAC, defined as a daily activity score ≥19 and basic mobility score of ≥17. Results: Patients with favorable AM-PAC were younger (61.3 vs 70.7, P<.001), had lower admission glucose (mean, 124 vs 136, P=.042), lower blood urea nitrogen (mean, 15.59 vs 19.11, P<.001), and lower admission National Institutes of Health Stroke Scale (NIHSS) (mean, 10.58 vs 16.15, P<.001). No differences in sex were noted. Multivariate regression analyses revealed age, admission NIHSS, relative cerebral blood flow (rCBF) <30% volume, and modified thrombolysis in cerebral infarction (mTICI) score to be independent predictors of favorable AM-PAC (P<.047 for all predictors). The combined model revealed an area under the curve (AUC) of 0.83 (IQR 0.75-0.86). Conclusion: Excellent recanalization, smaller core volumes, younger age, and lower stroke severity independently predict favorable outcomes as measured by AM-PAC.

The telemedicine experience: using principles of clinical excellence to identify disparities and optimize care.

ABSTRACT: The use of telemedicine has increased significantly during the Corona virus disease 2019 pandemic. This manuscript serves to identify the underlying principles of clinical excellence in telemedicine and to determine whether effective care practices can be generalized as a one-size-fits-all model or must instead be tailored to individual patient populations.A survey assessing care quality and patient satisfaction for patients using telemedicine was created and administered via email to 2 urban cohorts of varying demographics and socioeconomic backgrounds: a population of patients with prior stroke and cerebrovascular disease, and a cohort of patients followed for interstitial lung disease. Results were compared across groups to determine the generalizability of effective practices across populations.Individuals taking part in telemedicine were more likely to be White, more affluent, and woman, regardless of clinical diagnosis compared with a similar cohort of patients seen in-person the year prior. A lower-than-expected number of patients who were Black and of lower socioeconomic status followed up virtually, indicating potential barriers to access. Overall, patients who participated in televisits were satisfied with the experience and felt that the care met their medical needs; however, those who were older were more likely to experience technical difficulties and prefer in-person visits, while those with less education were less likely to feel that their questions were addressed in an understandable way.When thoughtfully designed, telemedicine practices can be an effective model for patient care, though implementation must consider population characteristics including age, education, and socioeconomic status, and strategies such as ease of access versus optimization of communication strategies should be tailored to meet individual patient needs.

Multidomain cognitive dysfunction after minor stroke suggests generalized disruption of cognitive networks.

OBJECTIVE: Although small strokes typically result in "good" functional outcomes, significant cognitive impairment can occur. This longitudinal study examined a cohort of patients with minor stroke to determine the pattern of deficits, evolution over time, and factors associated with outcome. METHODS: Patients admitted to the hospital with their first clinical minor stroke (NIH Stroke Scale [NIHSS] ≤ 10, absence of severe hemiparesis, aphasia, or neglect) were assessed at 1 month post-infarct, and a subset were followed over time (with 6- and 12-month evaluations). Composite scores at each time point were generated for global cognition, verbal memory, spatial memory, motor speed, processing speed, and executive function. Paired t-tests evaluated change in scores over time. Regression models identified factors associated with initial performance and better recovery. RESULTS: Eighty patients were enrolled, evaluated at 1 month, and prospectively followed. The average age of the participants was 62.3 years, and mean education was 13.5 years. The average stroke volume was 6.6 cc; mean NIHSS score was 2.8. At 1 month, cognitive scores were below the normative range and > 1 standard deviation below the patient's peak ("recovery") score for every cognitive domain, strongly suggesting that they were well below patients' prestroke baselines. Forty-eight patients followed up at 6 months, and 39 at 12 months. Nearly all (98%) patients significantly improved in global cognition (averaged across domains) between 1 and 6 months. Between 6 and 12 months, recovery was variable. Higher education, occupational class, and Caucasian race were associated with higher recovery scores for most domains. CONCLUSIONS: Cognitive impairment across multiple domains is common following minor stroke regardless of infarct location, suggesting a global process such as network dysfunction that improves over 6 months. Degree of recovery can be predicted using baseline factors.

Poststroke acute dysexecutive syndrome, a disorder resulting from minor stroke due to disruption of network dynamics.

Stroke patients with small central nervous system infarcts often demonstrate an acute dysexecutive syndrome characterized by difficulty with attention, concentration, and processing speed, independent of lesion size or location. We use magnetoencephalography (MEG) to show that disruption of network dynamics may be responsible. Nine patients with recent minor strokes and eight age-similar controls underwent cognitive screening using the Montreal cognitive assessment (MoCA) and MEG to evaluate differences in cerebral activation patterns. During MEG, subjects participated in a visual picture-word matching task. Task complexity was increased as testing progressed. Cluster-based permutation tests determined differences in activation patterns within the visual cortex, fusiform gyrus, and lateral temporal lobe. At visit 1, MoCA scores were significantly lower for patients than controls (median [interquartile range] = 26.0 [4] versus 29.5 [3], P = 0.005), and patient reaction times were increased. The amplitude of activation was significantly lower after infarct and demonstrated a pattern of temporal dispersion independent of stroke location. Differences were prominent in the fusiform gyrus and lateral temporal lobe. The pattern suggests that distributed network dysfunction may be responsible. Additionally, controls were able to modulate their cerebral activity based on task difficulty. In contrast, stroke patients exhibited the same low-amplitude response to all stimuli. Group differences remained, to a lesser degree, 6 mo later; while MoCA scores and reaction times improved for patients. This study suggests that function is a globally distributed property beyond area-specific functionality and illustrates the need for longer-term follow-up studies to determine whether abnormal activation patterns ultimately resolve or another mechanism underlies continued recovery.

The Post-Pipeline Headache: New Headaches Following Flow Diversion for Intracranial Aneurysm.

OBJECTIVE: Flow diversion using devices such as the "pipeline" stent is now a common treatment for unruptured intracranial aneurysms. Though much is known about the efficacy of the device, less is reported regarding potential side effects. In this study, we report the frequency and characteristics of the "post-pipeline headache." METHODS: We prospectively enrolled a cohort of 222 patients who underwent pipeline stenting for the treatment of intracranial aneurysm between 2015 and 2018. A follow-up telephone survey was conducted with a mean 21.6 months postprocedure evaluating postprocedure headaches and previous headache history. A post-pipeline headache was defined as a new headache or pain distinct from their prior headache syndrome. Information was collected regarding patient demographics, headache characteristics, headache history, and whether symptoms were ongoing. Logistic regression was used to determine factors associated with post-pipeline headache and the risk of long-term headache persistence. RESULTS: Eighty-eight individuals were reached by phone for follow-up; 48 (55%) of whom reported a new headache postprocedure. Patients experiencing post-pipeline headache were more likely to be young (OR 0.9; 95% CI: 0.85-0.94) and have a history of prior headaches (OR 2.4, 95% CI: 1.02-5.81). Associated motor (OR 6.1; 95% CI: 1.19-31.47), cognitive (OR 7.0; 95% CI: 081-60.33), visual (OR 5.4; 95% CI: 1.05-27.89), and vestibular (OR 4.8; 95% CI: 1.14-20.23) symptoms were associated with ongoing headache. CONCLUSIONS: Post-pipeline headache is common, particularly in younger individuals with prior headache history, and has distinctive features. Symptoms can remit over time; however, two-thirds experience ongoing headaches, particularly those with associated migrainous features.

Early Post-stroke Cognition: In-hospital Predictors and the Association With Functional Outcome.

Purpose: To characterize and predict early post-stroke cognitive impairment by describing cognitive changes in stroke patients 4-8 weeks post-infarct, determining the relationship between cognitive ability and functional status at this early time point, and identifying the in-hospital risk factors associated with early dysfunction. Materials and Methods: Data were collected for 214 patients with ischemic stroke and 39 non-stroke controls. Montreal Cognitive Assessment (MoCA) exams were administered at post-hospitalization clinic visits approximately 4-8 weeks after infarct. MoCA scores were compared for patients with: no stroke, minor stroke [NIH Stroke Scale (NIHSS) < 5], and major stroke. Ordinal logistic regression was performed to assess the relationship between MoCA score and functional status [modified Rankin Scale score (mRS)] at follow-up. Predictors of MoCA < 26 and < 19 (cutoffs for mild and severe cognitive impairment, respectively) at follow-up were identified by multivariable logistic regression using variables available during hospitalization. Results: Post stroke cognitive impairment was common, with 66.8% of patients scoring < 26 on the MoCA and 22.9% < 19. The average total MoCA score at follow-up was 18.7 (SD 7.0) among major strokes, 23.6 (SD 4.8) among minor strokes, and 27.2 (SD 13.0) among non-strokes (p = <0.0001). The follow-up MoCA score was associated with the follow-up mRS in adjusted analysis (OR 0.69; 95% C.I. 0.59-0.82). Among patients with no prior cognitive impairment (N = 201), a lack of pre-stroke employment, admission NIHSS > 6, and left-sided infarct predicted a follow-up MoCA < 26 (c-statistic 0.75); while admission NIHSS > 6 and infarct volume > 17 cc predicted a MoCA < 19 (c-statistic 0.75) at follow-up. Conclusion: Many patients experience early post-stroke cognitive dysfunction that significantly impacts function during a critical time period for decision-making regarding return to work and future independence. Dysfunction measured at 4-8 weeks can be predicted during the inpatient hospitalization. These high-risk individuals should be identified for targeted rehabilitation and counseling to improve longer-term post-stroke outcomes.

The role of CT perfusion in the evaluation of seizures, the post-ictal state, and status epilepticus.

Rapid identification of stroke mimics, such as seizures, is a critical part of the evaluation of patients presenting with acute focal neurological deficits. The primary role of CT perfusion is in identification of patients with acute ischemic stroke who may be candidates for reperfusion therapy, but also holds promise as a modality for identifying a seizure etiology. We review the literature on this topic and attempt to define characteristic CT perfusion findings at various points along the ictal-interictal (epileptic) continuum. We suggest an approach for using CT perfusion to differentiate stroke from seizure in patients with acute onset focal neurological deficits.