Pulmonary Function Decline in Amyotrophic Lateral Sclerosis

Background: There has been no comprehensive longitudinal study of pulmonary functions (PFTS) in ALS determining which measure is most sensitive to declines in respiratory muscle strength. Objective: To determine the longitudinal decline of PFTS in ALS and which measure supports Medicare criteria for NIV initiation first. Methods: Serial PFTs (maximum voluntary ventilation (MVV), maximum inspiratory pressure measured by mouth (MIP) or nasal sniff pressure (SNIP), maximum expiratory pressure (MEP), and Forced Vital Capacity (FVC)) were performed over 12 months on 73 ALS subjects to determine which measure showed the sentinel decline in pulmonary function. The rate of decline for each measure was determined as the median slope of the decrease over time. Medicare-based NIV initiation criteria were met if %FVC was ≤ 50% predicted or MIP was ≤ 60 cMH2O. Results: 65 subjects with at least 3 visits were included for analyses. All median slopes were significantly different than zero. MEP and sitting FVC demonstrated the largest rate of decline. Seventy subjects were analyzed for NIV initiation criteria, 69 met MIP criteria first; 11 FVC and MIP criteria simultaneously and none FVC criteria first. Conclusions: MEP demonstrated a steeper decline compared to other measures suggesting expiratory muscle strength declines earliest and faster and the use of airway clearance interventions should be initiated early. When Medicare criteria for NIV initiation are considered, MIP criteria are met earliest. These results suggest that pressure-based measurements are important in assessing the timing of NIV and the use of pulmonary clearance interventions

Early Neurologic Deterioration with Symptomatic Isolated Internal Carotid Artery Occlusion: A Cohort Study, Systematic Review, and Meta‐Analysis

Background Acute endovascular revascularization for isolated internal carotid occlusion without tandem intracranial occlusion has been proposed to prevent early neurologic deterioration (END) and improve outcome, but has not been shown to be more effective than medical therapy. We aimed to evaluate prognosis with initial medical therapy alone, and also performed a systematic review to put these results in a broader context. Methods We performed a retrospective cohort study of patients admitted over a 2‐year period with acute stroke/transient ischemic attack due to isolated internal carotid artery occlusion. Subjects with tandem intracranial occlusion or Alberta Stroke Program Early CT Score (ASPECTS) ≤5 were excluded. The primary outcome was END within 48 hours (National Institute of Health Stroke Scale [NIHSS] increase ≥4 persisting for ≥24 hours). Secondary outcomes included discharge NIHSS and disposition. We also performed a systematic review and meta‐analysis of published studies along with the data from our cohort. Results Twenty‐three patients met our inclusion criteria. Median age was 69 years, initial Alberta Stroke Program Early CT Score 10, and NIHSS score 3. END attributed to recurrent ischemia occurred in 5/23 patients (22%, 95% CI: 7%–44%). At discharge, 78% had a favorable outcome with a median NIHSS of 2 (interquartile range 1–3). END appeared more frequent in those with higher baseline NIHSS. In our systematic review, 7 prior studies met our inclusion criteria. END occurred in 17% (95% CI: 12%–23%) of patients, 18% with medical therapy versus 13% with endovascular therapy, with substantial heterogeneity among studies. Conclusion In patients with acute stroke or transient ischemic attack due to isolated internal carotid occlusion, END is relatively common (occurring in about 1 out of 6 patients). Further research is needed to evaluate the roles of maximal medical management or acute endovascular thrombectomy in these patients

Pulmonary function decline in amyotrophic lateral sclerosis

Background: There has been no comprehensive longitudinal study of pulmonary functions (PFTS) in ALS determining which measure is most sensitive to declines in respiratory muscle strength. Objective: To determine the longitudinal decline of PFTS in ALS and which measure supports Medicare criteria for NIV initiation first. Methods: Serial PFTs (maximum voluntary ventilation (MVV), maximum inspiratory pressure measured by mouth (MIP) or nasal sniff pressure (SNIP), maximum expiratory pressure (MEP), and Forced Vital Capacity (FVC)) were performed over 12 months on 73 ALS subjects to determine which measure showed the sentinel decline in pulmonary function. The rate of decline for each measure was determined as the median slope of the decrease over time. Medicare-based NIV initiation criteria were met if %FVC was ≤ 50% predicted or MIP was ≤ 60 cMH 2 O. Results: 65 subjects with at least 3 visits were included for analyses. All median slopes were significantly different than zero. MEP and sitting FVC demonstrated the largest rate of decline. Seventy subjects were analyzed for NIV initiation criteria, 69 met MIP criteria first; 11 FVC and MIP criteria simultaneously and none FVC criteria first. Conclusions: MEP demonstrated a steeper decline compared to other measures suggesting expiratory muscle strength declines earliest and faster and the use of airway clearance interventions should be initiated early. When Medicare criteria for NIV initiation are considered, MIP criteria are met earliest. These results suggest that pressure-based measurements are important in assessing the timing of NIV and the use of pulmonary clearance interventions

Highly Visible Wall‐Timer to Reduce Endovascular Treatment Time for Stroke

Background Endovascular therapy for acute ischemic stroke has revolutionized clinical care for patients with stroke and large vessel occlusion, but treatment remains time sensitive. At our stroke center, up to half of the door‐to‐groin time is accounted for after the patient arrives in the angio‐suite. Here, we apply the concept of a highly visible timer in the angio‐suite to quantify the impact on endovascular treatment time. Methods This was a single‐center prospective pseudorandomized study conducted over a 32‐week period. Pseudorandomization was achieved by turning the timer on and off in 2‐week intervals. The primary outcome was angio‐suite‐to‐groin time, and secondary outcomes were angio‐suite‐to‐intubation time, groin‐to‐recanalization time, and 90‐day modified Rankin scale. A stratified analysis was performed based on type of anesthesia (ie, endotracheal intubation versus not). Results During the 32‐week study period, 97 mechanical thrombectomies were performed. The timer was on and off for 38 and 59 cases, respectively. The timer resulted in faster angio‐suite‐to‐groin time (28 versus 33 minutes; P=0.02). The 5‐minute reduction in angio‐suite‐to‐groin was maintained after adjusting for intubation status in a multivariate regression (P=0.02). There was no difference in the 90‐day modified Rankin scale between groups. The timer impact was consistent across the 32‐week study period. Conclusions A highly visible timer in the angio‐suite achieved a meaningful, albeit modest, reduction in endovascular treatment time for patients with stroke. Given the lack of risk and low cost, it is reasonable for stroke centers to consider a highly visible timer in the angio‐suite to improve treatment times

Predictors of Recurrent Venous Thrombosis After Cerebral Venous Thrombosis: Analysis of the ACTION-CVT Study

BACKGROUND: and Purpose: Cerebral venous thrombosis (CVT) is a rare cause of stroke carrying a nearly 4% risk of recurrence after 1 year. There is limited data on predictors of recurrent venous thrombosis in patients with CVT. In this study, we aim to identify those predictors. METHODS: This is a secondary analysis of the ACTION-CVT study which is a multi-center international study of consecutive patients hospitalized with a diagnosis of CVT over a 6-year period. Patients with cancer associated CVT, CVT during pregnancy, or CVT in the setting of known antiphospholipid antibody syndrome were excluded per the ACTION-CVT protocol. The study outcome was recurrent venous thrombosis defined as recurrent venous thromboembolism (VTE) or de-novo CVT. We compared characteristics between patients with vs. without recurrent venous thrombosis during follow-up and performed adjusted Cox regression analyses to determine important predictors of recurrent venous thrombosis. RESULTS: 947 patients were included with a mean age was 45.2 years, 63.9% were women, and 83.6% had at least 3-months of follow-up. During a median follow-up of 308 (IQR 120-700) days, there were 5.05 recurrent venous thromboses (37 VTE and 24 CVT) per 100 patient-years. Predictors of recurrent venous thrombosis were Black race (adjusted HR 2.13, 95% CI 1.14-3.98, p = 0.018), prior history of VTE (aHR 3.40, 95% CI 1.80-6.42, p \u3c 0.001) and the presence of one or more positive antiphospholipid antibodies (aHR 3.85, 95% CI 1.97-7.50, p \u3c 0.001). Sensitivity analyses including events only occurring on oral anticoagulation yielded similar findings. CONCLUSION: Black race, history of VTE, and the presence of one or more antiphospholipid antibodies are associated with recurrent venous thrombosis among patients with CVT. Future studies are needed to validate our findings to better understand mechanisms and treatment strategies in patients with CVT

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study

BACKGROUND: A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. METHODS: This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. RESULTS: Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140-720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51-1.73]; =0.84), death (aHR, 0.78 [95% CI, 0.22-2.76]; =0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48-1.73]; =0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15-0.82]; =0.02). CONCLUSIONS: In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies

Predictors of Recurrent Venous Thrombosis After Cerebral Venous Thrombosis: Analysis of the ACTION-CVT Study.

BACKGROUND and Purpose: Cerebral venous thrombosis (CVT) is a rare cause of stroke carrying a nearly 4% risk of recurrence after 1 year. There is limited data on predictors of recurrent venous thrombosis in patients with CVT. In this study, we aim to identify those predictors. METHODS This is a secondary analysis of the ACTION-CVT study which is a multi-center international study of consecutive patients hospitalized with a diagnosis of CVT over a 6-year period. Patients with cancer associated CVT, CVT during pregnancy, or CVT in the setting of known antiphospholipid antibody syndrome were excluded per the ACTION-CVT protocol. The study outcome was recurrent venous thrombosis defined as recurrent venous thromboembolism (VTE) or de-novo CVT. We compared characteristics between patients with vs. without recurrent venous thrombosis during follow-up and performed adjusted Cox regression analyses to determine important predictors of recurrent venous thrombosis. RESULTS 947 patients were included with a mean age was 45.2 years, 63.9% were women, and 83.6% had at least 3-months of follow-up. During a median follow-up of 308 (IQR 120-700) days, there were 5.05 recurrent venous thromboses (37 VTE and 24 de-novo CVT) per 100 patient-years. Predictors of recurrent venous thrombosis were Black race (adjusted HR 2.13, 95% CI 1.14-3.98, p = 0.018), prior history of VTE (aHR 3.40, 95% CI 1.80-6.42, p < 0.001) and the presence of one or more positive antiphospholipid antibodies (aHR 3.85, 95% CI 1.97-7.50, p < 0.001). Sensitivity analyses including events only occurring on oral anticoagulation yielded similar findings. CONCLUSION Black race, history of VTE, and the presence of one or more antiphospholipid antibodies are associated with recurrent venous thrombosis among patients with CVT. Future studies are needed to validate our findings to better understand mechanisms and treatment strategies in patients with CVT

Direct Oral Anticoagulants Versus Warfarin in the Treatment of Cerebral Venous Thrombosis (ACTION-CVT): A Multicenter International Study.

BACKGROUND A small randomized controlled trial suggested that dabigatran may be as effective as warfarin in the treatment of cerebral venous thrombosis (CVT). We aimed to compare direct oral anticoagulants (DOACs) to warfarin in a real-world CVT cohort. METHODS This multicenter international retrospective study (United States, Europe, New Zealand) included consecutive patients with CVT treated with oral anticoagulation from January 2015 to December 2020. We abstracted demographics and CVT risk factors, hypercoagulable labs, baseline imaging data, and clinical and radiological outcomes from medical records. We used adjusted inverse probability of treatment weighted Cox-regression models to compare recurrent cerebral or systemic venous thrombosis, death, and major hemorrhage in patients treated with warfarin versus DOACs. We performed adjusted inverse probability of treatment weighted logistic regression to compare recanalization rates on follow-up imaging across the 2 treatments groups. RESULTS Among 1025 CVT patients across 27 centers, 845 patients met our inclusion criteria. Mean age was 44.8 years, 64.7% were women; 33.0% received DOAC only, 51.8% received warfarin only, and 15.1% received both treatments at different times. During a median follow-up of 345 (interquartile range, 140-720) days, there were 5.68 recurrent venous thrombosis, 3.77 major hemorrhages, and 1.84 deaths per 100 patient-years. Among 525 patients who met recanalization analysis inclusion criteria, 36.6% had complete, 48.2% had partial, and 15.2% had no recanalization. When compared with warfarin, DOAC treatment was associated with similar risk of recurrent venous thrombosis (aHR, 0.94 [95% CI, 0.51-1.73]; P=0.84), death (aHR, 0.78 [95% CI, 0.22-2.76]; P=0.70), and rate of partial/complete recanalization (aOR, 0.92 [95% CI, 0.48-1.73]; P=0.79), but a lower risk of major hemorrhage (aHR, 0.35 [95% CI, 0.15-0.82]; P=0.02). CONCLUSIONS In patients with CVT, treatment with DOACs was associated with similar clinical and radiographic outcomes and favorable safety profile when compared with warfarin treatment. Our findings need confirmation by large prospective or randomized studies