Neuro News Roundup: National Stroke Awareness Month

In recent months, the NeurologyLive® team has been covering the news on the latest updates in the clinical care of individuals with neuromuscular disorders, multiple sclerosis, movement disorders, sleep disorders, and more.

For National Stroke Awareness Month — May 2023 —the team has culminated some of the biggest pieces of news to offer updates on new developments in the literature on stroke to spread awareness on the prevention and post-treatment of the condition.

Click here for more coverage of the latest stroke news from NeurologyLive®.

Latest Literature

Clinical Factors Predict Rehabilitation Dose Therapy in Patients Poststroke

Recent research published in the journal Stroke showed that rehabilitation therapy doses are low during the first year of recovery from stroke and were predicted by clinical factors. This finding highlights the potential to address imbalances in allocation of rehabilitation therapy poststroke through the identification of patients with disability at risk for low doses of the treatment.¹

In 510 poststroke patients, data showed that most doses therapy were low and delivered within the first 3 months, as 35.0% of patients had no physical therapy, 48.8% received no occupational therapy, and 61.7% had no speech therapy. Notably, discharge destination was significantly related to cumulative therapy (for all therapy types at visit 2, P <.05; occupational therapy visits 3 and 4, P <.05; speech therapy visits 3 and 4, P <.01) and across the variety of sites, between 0% and 71% of patients were discharged to an inpatient rehabilitation facility.

In the prospective observational study, researchers examined rehabilitation therapy doses during the first year of stroke recovery, as well as identified the factors that predict rehabilitation therapy dose. Of the 763 adult poststroke patients enrolled, 510 patients were followed for 1 year (age ranged, 18-97 years; average age, 62.3 years; men, n = 302; women, n = 207). Patients were enrolled 2 to 10 days after stroke onset from 28 acute care hospitals around the United States.

Following the initial hospitalization assessment, the number of physical therapy, occupational therapy, and speech therapy sessions were determined at 3, 6, and 12 months visits. Clinical and demographic factors and their associations with therapy counts were assessed by a negative binomial regression while a false discovery rate was used to correct multiple comparison.

Higher Vascular Risk Indirectly Predicts Lower Plasma Aß42/40 in APOE ɛ4 Carriers

Findings from a cross-sectional analysis of 2 cohorts of nondemented older adults revealed that higher vascular risk score was indirectly associated with the level of plasma amyloid-ß (Aß)42/40 through cerebral amyloid burden only in apolipoprotein (APOE) ɛ4 carriers.²

The analysis took a multifactorial approach to examining how vascular and genetic risk work together using patients from the University of California, Davis-Alzheimer’s Disease Research Center (UCD-ADRC) study (n = 96). The group originally hypothesized that higher vascular risk indirectly predicts plasma Aß42/40 levels through cerebral amyloid burden and that this association will be stronger in APOE ɛ4 carriers. Findings were validated through the Alzheimer’s Disease Neuroimaging Initiative (n = 104) as a confirmatory study cohort (CSC).

Published in Stroke, vascular risk score was obtained as the sum of hypertension, diabetes, hyperlipidemia, coronary artery disease, and cerebrovascular disease. Confirming previous reported, findings not stratified by APOE ɛ4+ risk showed that higher cerebral amyloid burden was associated with lower plasma Aß42/40 in both UCD-ADRC (ß = –0.012 [SE, 0.006]; P = .039) and ADNI (ß = –0.015 [SE, 0.006]; P = .013) cohorts. Higher vascular risk score predicted greater amyloid burden in ADNI (ß = 0.043 [SE, 0.016]; P = .006) but not in the UCD-ADRC cohort (ß = 0.096 [SE, 0.050]; P = .053).

New Study Identifies Immune Dysregulation and Neurocirculatory Abnormalities in Long COVID

Findings from a small-scale, National Institutes of Health (NIH)-operated study assessing long-term outcomes of patients with SARS-CoV-2 infection found differences in immune cell profiles and autonomic dysfunction, including lower levels of CD4+ and CD8+ T cells.³

Although the study included 12 patients, the findings add to the growing evidence that widespread immunological and autonomic nervous system changes may contribute to long COVID. Conducted between October 2020 and April 2021, the cohort was comprised of mostly those with a history of mild infection (92%; n = 11) and females (83%). Led by Avindra Nath, MD, clinical director of the National Institute of Neurological Disorders and Stroke (NINDS), patients had a median time of evaluation of 9 months (range, 3-12) following infection.

Patients were intensely followed and underwent clinical examination, questionnaires and brain imaging, extensive analyses of blood and cerebrospinal fluid (CSF) samples, and autonomic testing. Although most presented with mild infection, the cohort included only those whose neurologic symptoms persisted. Of note, only 1 participant had already received a SARS-CoV-2 vaccine before being evaluated.

In comparison with healthy volunteers, immunophenotyping of cerebrospinal fluid (CSF) of patients with neuro-post acute sequelae (PASC) had lower frequencies of effector memory phenotype both for CD4+ T cells (P <.0001) and for CD8+ T cells (P = .002), as well as increased frequency of antibody-secreting B cells (P = .009), and increased frequency of cells expressing immune checkpoint molecules. There was also an increase in cells expressing with T cell immunoglobulin (IgG) and ITIM domains on CD8+ T cells (67.3 [±10] vs 53.7 [±12]; P = .006) and of programmed death ligand 1 on monocytes (CD3- CD14+: 35.9 [±21] vs 15.6 [±9]; P = .02).

Endovascular Treatment Improves Functional Outcomes for Acute Basilar Artery Occlusion

Recent findings from the multicenter randomized controlled trial, ATTENTION (NCT04751708) published in the New England Journal of Medicine showed that approximately one-third of Chinese patients with basilar artery occlusion (BAO) who received intravenous thrombolysis (IVT) with endovascular thrombectomy (EVT) within 12 hours after stroke onset had better functional outcomes at 90 days than best medical care.⁴

At 90 days, good functional status was reported in 104 patients (46%) in the EVT group and in 26 (23%) in the control group (adjusted rate ratio, 2.06; 95% CI, 1.46-2.91, P <.001). Notably, symptomatic intracranial hemorrhage occurred in 12 patients (5%) in the EVT group and none in the control group.

The trial consisted of patients on EVT for BAO from 36 centers in China. The patients were randomly assigned in a 2:1 ratio within 12 hours after the estimated time of BOA to receive EVT or best medical care, which served as the control. The primary outcome was good functional status, which was defined as a score ranging from 0 to 3 on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]), at 90 days. The secondary outcomes included a modified Rankin scale score ranging from 0 to 2, distribution across the scale score categories, and quality of life. Additionally, safety outcomes measures assessed were symptomatic intracranial hemorrhage at 24 to 72 hours, 90-day mortality, and procedural complications.

Among the 507 patients who underwent screening, 340 were in the intention-to-treat population, with 226 assigned to the EVT group and 114 to the control group. IVT was used in 31% of the patients in the EVT group and in 34% of those in the control group. Results for the secondary clinical and imaging outcomes were generally in the same direction as those for the primary outcome. Mortality at 90 days was 37% in the EVT group and 55% in the control group (adjusted risk ratio, 0.66; 95% CI, 0.52-0.82). Procedural complications occurred in 14% of the patients in the EVT group, including one death due to arterial perforation.

Endovascular Thrombectomy Shows Better Functional Outcomes Than Medical Care for Ischemic Stroke

Recently published in The New England Journal of Medicine, new findings from the SELECT2 trial (NCT03876457), a phase 3 international, randomized, open-label clinical trial, showed that endovascular thrombectomy (EVT) resulted in better functional outcomes than medical care among patients with large ischemic strokes 24 hours after onset.⁵ These results provided evidence of the efficacy and safety of endovascular thrombectomy in patients with large ischemic strokes, which has been carried out in limited populations to date.

All told, the generalized odds ratio for the distribution of modified Rankin scale (mRS) scores shifted in favor of EVT (OR, 1.51; 95% CI, 1.20-1.89; P <.001). Notably, a total of 20% of the patients in the EVT group and 7% in the medical-care group had functional independence (RR, 2.97; 95% CI, 1.60-5.51).

Between September 2019 and September 2022, at the time the trial was stopped, 958 patients had been screened, and among those, 352 were eligible and enrolled. The trial included patients with stroke because of occlusion of the internal carotid artery or the first segment of the middle cerebral artery, and assessed EVT in the time span of 24 hours after onset. The patients enrolled had a large ischemic-core volume, defined by the Alberta Stroke Program Early Computed Tomography Score of 3 to 5 (range, 0- 10, with lower scores indicating larger infarction) or at least 50 mL of a core volume on computed tomography perfusion or diffusion-weighted MRI.

Patients were assigned on a 1:1 ratio to either the EVT plus medical care group (n = 178) or the medical care alone group (n = 174). The mRS score at 90 days (range, 0-6, with higher scores indicating greater disability) was the primary outcome, and functional independence was the secondary outcome. Among both groups, mortality was similar. Arterial access-site complications occurred in 5 patients, dissection in 10 patients, cerebral-vessel perforation in 7 patients, and transient vasospasm in 11 patients, all of whom were in the EVT group. One patient in the EVT group and 2 patients in the medical-care group experienced symptomatic intracranial hemorrhage.

REFERENCES
1. Young BM, Holman EA, Cramer SC; STRONG Study Investigators. Rehabilitation Therapy Doses Are Low After Stroke and Predicted by Clinical Factors. Stroke. 2023;54(3):831-839. doi:10.1161/STROKEAHA.122.041098
2. Sapkota S, Erickson K, Fletcher E, Farias SE, Jin LW, DeCarli C. Vascular risk predicts plasma amyloid ß42/40 through cerebral amyloid burden in Apolipoprotein Ee4 carriers. STROKEAHA. 2023;54:1227-1235. doi:10.1161/STROKEAHA.122.041854
3. Mina Y, Enose-Akahata Y, Hammoud DA, et al. Deep phenotyping of neurologic postacute sequelae of SARS-CoV-2 infection. 2023;10(4). doi:10.1212/NXI.00000000000200097
4. Tao C, Nogueira RG, Zhu Y, et al. Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion. N Engl J Med. 2022;387(15):1361-1372. doi:10.1056/NEJMoa2206317
5. Sarraj A, Hassan AE, Abraham MG, et al. Trial of Endovascular Thrombectomy for Large Ischemic Strokes. N Engl J Med. 2023;388(14):1259-1271. doi:10.1056/NEJMoa2214403