Christopher Traenka

Introduction: Most patients with Cervical Artery Dissection (CeAD) experience good long-term functional outcome. Little is known about long-term psychological sequelae in these patients. Patients and methods: In CeAD-patients, we assessed long-term quality of life (QoL), frequency of increased anxiety levels, post-traumatic stress disorder (PTSD), depression and fatigue and explored if baseline characteristics can identify patients at high risk of developing the aforementioned. We performed long-term follow-up (> = 12 months after baseline) in CeAD-patients with excellent 3-month outcome and no prior psychiatric disorder. Patients were asked to answer established questionnaires. Results: Long-term follow-up was performed on 89 CeAD-patients at a median of 53 months after baseline. Sixty-five patients had carotid artery dissection and 37 patients had vertebral artery dissection (13 patients had both). At long-term follow-up the threshold for formal diagnosis of anxiety was met by 14.6, and 11.2% met the criteria for PTSD. 29.2% had a score above threshold for significant peri-traumatic dissociation. 19.1% reported depression at any point between baseline and long-term follow-up and 48.3% scored above thresholds for abnormal fatigue. Those who experienced increased levels of anxiety and those who met criteria for PTSD reported reduced QoL. Peritraumatic dissociation at the acute phase of CeAD was associated with increased anxiety levels at long-term follow-up. Occlusion of the dissected artery, tinnitus at baseline and prior smoking were associated with PTSD at long-term follow-up. Discussion: Prognostic importance of the experience of peritraumatic dissociation as well as occlusion of the dissected artery requires further research. Further prospective and interventional studies in treatment of psychological sequela in CeAD-patients are warranted. Conclusion: CeAD-patients seem to have a high long-term risk of developing anxiety, depression or PTSD, which was accompanied by decreased QoL. These findings are exploratory and should be further confirmed.

Introduction: Levodopa did not enhance early motor recovery at 3 months after stroke in the Enhancement of Stroke Rehabilitation with Levodopa (ESTREL) trial. However, whether levodopa modifies the time course of recovery, leading to a delayed benefit remains unclear. Here, we examined levodopa’s effects on the trajectories of motor recovery up to 6 months after stroke. Patients and methods: The ESTREL trial, a double-blind, randomised controlled clinical trial, compared a 39-day regimen of levodopa/carbidopa (100 mg/25 mg, 3×/day) to placebo alongside standardised task-oriented training. We longitudinally analysed Fugl-Meyer Motor Assessment (FMA) total scores (primary outcome), mRS and NIHSS (secondary outcomes) at baseline (0–7 days post stroke), 5 weeks, 3 and 6 months using linear mixed-effects models including timepoint, treatment allocation and their interaction. Results: In total, 576 of 610 (94%) participants (median age 73 years; 40% female) were analysed. FMA scores improved over time in both groups (P < .001), with no overall levodopa effect across visits (estimate 0.65 points, 95% CI, −3.3 to 4.6; P = .75). There was no indication that levodopa modified the recovery trajectory (χ2 = 0.52, df = 3, P = .91), and estimated levodopa–placebo differences in FMA changes across visit intervals were small, ranging from −0.7 to +0.8 points, with confidence intervals crossing zero. Secondary outcomes showed similar longitudinal improvement, without evidence of a treatment effect. Conclusion: In this post hoc analysis of ESTREL participants with repeated FMA assessments, motor impairment improved from the first days after stroke up to 6 months. Levodopa added to task-oriented inpatient rehabilitation did not improve motor recovery or alter its trajectory over this period. Clinical Trial Registration: NCT03735901, available at ClinicalTrials.gov: https://clinicaltrials.gov/study/NCT03735901?cond=NCT03735901&rank=1

BACKGROUND: Patients with cervical artery dissection (CeAD) may experience a recurrent dissection, but its frequency, risk factors, and clinical implications are not well defined. We aimed to determine the risk, associated factors, and clinical impact of recurrent CeAD. METHODS: The STOP-CAD study (Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection) was a multicenter international retrospective observational study of patients with CeAD treated between January 2015 and June 2022. Recurrent dissection was defined as a CeAD occurring at least 7 days after the diagnosis of the index event that affects a different artery or a different segment of the same artery. Patients were followed from day 7 up to 2 years. The absolute risk of recurrent CeAD over time was calculated using Kaplan-Meier survival estimates. Multivariable logistic and Cox regression models were used to assess predictors of CeAD recurrence. RESULTS: Of the 4023 patients included in STOP-CAD, 3836 (median age 46 years, 45% women) were eligible for this analysis. During a median (interquartile range) follow-up of 295 (97–720) days, 88 (2.29%) patients had a CeAD recurrence. Median time-to-recurrent CeAD was 53 (interquartile range, 18–157) days. The estimated risk of recurrent CeAD at 2 years was 3.22% (95% CI, 2.59%–4.00%). In multivariable analyses, younger age (adjusted odds ratios, 0.98 [95% CI, 0.96–0.99]), migraine (adjusted odds ratio, 1.88 [95% CI, 1.14–3.07]), and fibromuscular dysplasia (adjusted odds ratio, 2.90 [95% CI, 1.66–5.06]) were associated with CeAD recurrence, while presenting with an ischemic stroke was associated with a lower likelihood of recurrence (adjusted odds ratio, 0.47 [95% CI, 0.29–0.75]). These associations with CeAD recurrence over time were confirmed by Cox regression analyses. Among the 88 patients with recurrent CeAD, only 5 had accompanying ischemic events (3 strokes, 2 transient ischemic attacks). CONCLUSIONS: In this retrospective study, recurrent CeAD was uncommon, approximately half of the events were diagnosed within the first 2 months of the index event, and recurrent events rarely caused new ischemic events. Younger age, migraine, absence of ischemic stroke at presentation, and signs of fibromuscular dysplasia may help identify high-risk patients.

Introduction: Post-stroke fatigue (PSF) is common and impacts stroke rehabilitation. Dopaminergic treatment may have beneficial effects on PSF. This study investigated whether levodopa, compared with placebo, was associated with a lower frequency or severity of PSF during in-hospital rehabilitation. Patients and methods: Enhancement of Stroke Rehabilitation with Levodopa (ESTREL)-Fatigue was an exploratory analysis of secondary outcome data obtained in the multicentre, randomised, placebo-controlled ESTREL trial. Participants with acute stroke received levodopa 100 mg/carbidopa 25 mg or placebo 3 times daily for 39 days to enhance motor recovery. Participants who (i) reported fatigue at 5 weeks and who (ii) took at least 80% of the study medication were included in ESTREL-Fatigue. No adjustments for confounding were made. The primary endpoint was the presence of PSF at 5 weeks, defined as a T-score of ≥ 55 on the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue-Short-form-4a. As secondary endpoints, T-score cutoffs of ≥ 60 (moderate fatigue) and ≥ 70 (severe fatigue) were used. Binary logistic regression was used to compare PSF at 5 weeks between treatment groups. Results are presented as odds ratios (ORs) with 95% CI. Results: A total of 456 of 505 (90.3%) participants were included (levodopa/placebo 235/221, median age 73 years, 41% female). Post-stroke fatigue at 5 weeks was present in 63/235 (26.8%) levodopa-treated participants and in 65/221 (29.4%) placebo-treated participants (OR: 0.88; 95% CI, 0.58–1.32; risk ratio 0.91; risk difference − 2.6%). For cutoffs of ≥ 60 and ≥ 70, ORs were 0.78 (95% CI, 0.43–1.41) and 0.8 (95% CI, 0.25–2.44), respectively. A sensitivity analysis as per intention-to-treat with all 610 randomised ESTREL participants also showed no significant difference in fatigue presence between levodopa and placebo groups (OR: 0.95; 95% CI, 0.65–1.39) and a sensitivity analysis using a mixed-effects logistic regression showed no evidence of centre-related clustering. Conclusion: In ESTREL-Fatigue, levodopa, compared to placebo, was not associated with less PSF during in-hospital rehabilitation.

Cervical artery dissection (CeAD) is a major cause for stroke in young adults. A timely association with minor-to-moderate unimposing cervical trauma, which is often sports-related, is common in CeAD. Our goal was to assess whether physical activity puts patients at risk post-CeAD. Pooled data from two prospective observational CeAD cohorts with in-person follow-up of at least 1-year post-CeAD were assessed. Changes in physical activity were recorded using patient-reported assessment of change in activity compared to pre-CeAD. Baecke score-derived sports index was applied to address the association between physical activity intensity and our outcomes. Outcomes were (1) recurrent dissection and (2) cerebral ischemia upon follow-up. A total of 648 CeAD patients were recorded. Physical activity-specific follow-up data were available in 333 (59.7%). The median follow-up duration was 6.5 (IQR 3.1, 10.9) years with 17/333 (5.1%) suffering CeAD recurrence and 22/33#3 (6.6%) experiencing cerebral ischemia. A total of 197 of 333 (59.2%) patients reported a change in physical activity post-CeAD (127 [64.5%] decrease, 70 [35.5%] increase). Neither overall change, increase, or decrease of physical activity was associated with recurrent CeAD or cerebral ischemia (p > 0.2 throughout). However, regular performance of higher-intensity sports, assessed via Baecke score-derived sports index, associated in trend to dissection recurrence (OR 3.43 [0.86, 13.64]; p = 0.080). CeAD patients should be reassured that regaining physical activity after CeAD is safe. However, moderation on exertion should be discussed on an individual patient basis.

Background: Cervical artery dissection (CeAD) is a major cause for stroke in young adults. A timely association with minor‐to‐moderate unimposing cervical trauma, which is often sports‐related, is common in CeAD. Our goal was to assess whether physical activity puts patients at risk post‐CeAD. Methods: Pooled data from two prospective observational CeAD cohorts with in‐person follow‐up of at least 1‐year post‐CeAD were assessed. Changes in physical activity were recorded using patient‐reported assessment of change in activity compared to pre‐CeAD. Baecke score‐derived sports index was applied to address the association between physical activity intensity and our outcomes. Outcomes were (1) recurrent dissection and (2) cerebral ischemia upon follow‐up. Results: A total of 648 CeAD patients were recorded. Physical activity‐specific follow‐up data were available in 333 (59.7%). The median follow‐up duration was 6.5 (IQR 3.1, 10.9) years with 17/333 (5.1%) suffering CeAD recurrence and 22/33#3 (6.6%) experiencing cerebral ischemia. A total of 197 of 333 (59.2%) patients reported a change in physical activity post‐CeAD (127 [64.5%] decrease, 70 [35.5%] increase). Neither overall change, increase, or decrease of physical activity was associated with recurrent CeAD or cerebral ischemia ( p > 0.2 throughout). However, regular performance of higher‐intensity sports, assessed via Baecke score‐derived sports index, associated in trend to dissection recurrence (OR 3.43 [0.86, 13.64]; p = 0.080). Conclusions.: CeAD patients should be reassured that regaining physical activity after CeAD is safe. However, moderation on exertion should be discussed on an individual patient basis.

Introduction: Post-stroke depression (PSD) frequently occurs after acute stroke and negatively affects rehabilitation. Dopamine has beneficial effects on motivation and emotional stability. In stroke patients, low dopamine levels are linked to PSD. This study investigated whether levodopa treatment during in-hospital rehabilitation impacts PSD compared to placebo. Patients and methods: ESTREL-Depression was a pre-planned analysis of the multicenter, randomized, double-blind, placebo-controlled ESTREL trial. Participants with an acute ischemic or hemorrhagic stroke were randomly assigned to receive either levodopa/carbidopa (100/25 mg) or placebo three times daily for 39 days. All ESTREL participants with (1) information about the presence or absence of depression at three months and (2) who took at least 80% of the study medication were eligible for the study. Participants with a history of depression were excluded. For the primary outcome, the presence of PSD was defined as having a T-score of ≥55 in the Patient-Reported Outcomes Measurement Information System short-form depression-4a 3 months after randomization. Binary logistic regression was performed to assess the effect of levodopa on PSD. Results: The study included 407 ESTREL participants (median age 72, 60% male), 209 receiving levodopa, and 198 receiving placebo. At 3 months, the frequency and odds of PSD did not differ between the levodopa group (26%) and the placebo group (28%) (OR = 0.93, 95% CI, 0.60–1.43). Conclusion: In the ESTREL-Depression study, treatment with levodopa had no impact on the occurrence of PSD. Clinical Trial Registration: ClinicalTrials.gov: NCT03735901 (https://clinicaltrials.gov/study/NCT03735901).

The impact of trait-associated genetic variants on stroke risk is by now a well-established area of research that has continued to accelerate since the introduction of genome-wide technologies. More recently, the field has seen an increasing interest in the biology of stroke recovery. Studies designed to evaluate stroke recovery have unique needs that differ from those in studies of stroke risk and acute stroke outcomes. Here we outline the essential considerations for researchers aiming to develop or contribute to blood biomarker research on stroke recovery. Our recommendations incorporate the latest evidence and technologies that have emerged since the prior International Stroke Genetics Consortium Global Alliance recommendations were published in 2015. Nominated contributors with expertise in stroke recovery and genomics met over the course of 9 months and defined the scope of topics, discussed current practice and standards, and revised the recommendations to reflect consensus achieved through 2 rounds of anonymized surveys. Our writing group defined an updated and expanded set of recommendations applicable to a range of research priorities including (1) elucidating the biology of stroke recovery, (2) determining genetic variations associated with good versus poor stroke outcomes and recovery, (3) identifying druggable (or otherwise therapeutically actionable) gene or protein targets for enhanced recovery, and (4) identifying blood biomarkers that can predict stroke outcomes and recovery. The resulting work offers comprehensive guidance on essential preanalytical considerations for blood biomarker studies, encompassing blood collection timing, specimen processing and storage procedures, and regulatory aspects such as informed consent and data sharing. These guidelines will enable the consistent collection of human data on recovery biology at scale, providing the foundational evidence necessary to drive subsequent clinical translation.