Cerebral blood flow and cognition after 3 months tadalafil treatment in small vessel disease (ETLAS-2): study protocol for a randomized controlled trial.

BACKGROUND: Targeted treatment is highly warranted for cerebral small vessel disease, a causal factor of one in four strokes and a major contributor to vascular dementia. Patients with cerebral small vessel disease have impaired cerebral blood flow and vessel reactivity. Tadalafil is a specific phosphodiesterase 5 inhibitor shown to improve vascular reactivity in the brain. METHODS: The ETLAS-2 trial is a phase 2 double-blind, randomized placebo-controlled, parallel trial with the feasibility of tadalafil as the primary outcome. The trial aims to include 100 patients with small vessel occlusion stroke or transitory ischemic attacks and signs of cerebral small vessel disease more than 6 months before administration of study medication. Patients are treated for 3 months with tadalafil 20 mg or placebo daily and undergo magnetic resonance imaging (MRI) to evaluate changes in small vessel disease according to the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE) criteria as well as cerebral blood flow, cerebrovascular reactivity, and neurovascular coupling in a functional MRI sub-study. The investigation includes comprehensive cognitive testing using paper-pencil tests and Cambridge Neuropsychological Test Automated Battery (CANTAB) tests in a cognitive sub-study. DISCUSSION: The ETLAS-2 trial tests the feasibility of long-term treatment with tadalafil and explores vascular and cognitive effects in cerebral small vessel disease in trial sub-studies. The study aims to propose a new treatment target and improve the understanding of small vessel disease. Currently, 64 patients have been included and the trial is estimated to be completed in the year 2024. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05173896. Registered on 30 December 2021.

Prognostic factors for disease activity in newly diagnosed teriflunomide-treated patients with multiple sclerosis: a nationwide Danish study.

BACKGROUND: Clinicians frequently rely on relapse counts, T2 MRI lesion load (T2L) and Expanded Disability Status Scale (EDSS) scores to guide treatment decisions for individuals diagnosed with multiple sclerosis (MS). This study evaluates how these factors, along with age and sex, influence prognosis during treatment with teriflunomide (TFL). METHODS: We conducted a nationwide cohort study using data from the Danish Multiple Sclerosis Registry.Eligible participants had relapsing-remitting MS or clinically isolated syndrome and initiated TFL as their first treatment between 2013 and 2019. The effect of age, pretreatment relapses, T2L and EDSS scores on the risk of disease activity on TFL were stratified by sex. RESULTS: In total, 784 individuals were included (57.4% females). A high number of pretreatment relapses (≥2) was associated with an increased risk of disease activity in females only (OR and (95% CI): 1.76 (1.11 to 2.81)). Age group 50+ was associated with a lower risk of disease activity in both sexes (OR females=0.28 (0.14 to 0.56); OR males=0.22 (0.09 to 0.55)), while age 35-49 showed a different impact in males and females (OR females=0.79 (0.50 to 1.23); OR males=0.42 (0.24 to 0.72)). EDSS scores and T2L did not show any consistent associations. CONCLUSION: A high number of pretreatment relapses was only associated with an increased risk of disease activity in females, while age had a differential impact on the risk of disease activity according to sex. Clinicians may consider age, sex and relapses when deciding on TFL treatment.

Blood pressure after follow-up in a stroke prevention clinic.

OBJECTIVES: In Denmark, 25% of hospital admissions with stroke are recurrent strokes. With thrombolytic treatment, more patients survive with only minor disability. This promising development should be followed up by intensive secondary prevention. Hypertension is the most important target. We aimed at testing the hypotheses that early follow-up in a preventive clinic would result in (a) a higher proportion of patients with blood pressure at target and (b) time to stroke recurrence, myocardial infarction, and death would be longer in the intervention group compared to controls. MATERIALS AND METHODS: Eligible patients admitted to the stroke unit of Herlev Hospital were randomized shortly before discharge to intervention or control group. Of 78 included participants, data from 73 were available for follow-up 9 months after inclusion. Patients in the intervention group were seen in the clinic within 1 week. In case of hypertension, treatment was initiated or supplied with a new drug. We used individual targets for blood pressure according to diagnosis of stroke and patients' comorbidity. Patients in the intervention group had a median of five visits to the preventive clinic. RESULTS: In the intervention group, blood pressure was treated to target in 25 patients (69%) versus 14 (38%) in the control group (p = .007). Median time to first event was 44 months (4-49) in the intervention group and 19 months (4-37) in controls (p = .316). CONCLUSIONS: Treatment of hypertension to individual targets after stroke is feasible. It may postpone recurrent stroke and death in stroke survivors.

How to identify fatigue in stroke patients: an investigation of the post-stroke fatigue case definition validity.

BACKGROUND: Fatigue is a common and often debilitating stroke sequela, and it is important to accurately define and detect post-stroke fatigue. Often questionnaires are used but a case definition has been developed and proposed as a better tool. OBJECTIVES: The aim of the study was to determine validity and inter-rater agreement of the case definition of post-stroke fatigue, and to determine optimal cutoff scores for marked fatigue on the Multidimensional Fatigue Inventory-20 and the Fatigue Severity Scale-7 questionnaires. METHODS: Stroke patients were interviewed with the structured interview schedule for the case definition and asked to complete the two questionnaires. To examine the inter-rater agreement of the case definition a second interviewer did another interview blinded to the result of the first interview. RESULTS: Seventy patients were enrolled, 44% women. The median age was 74 years (interquartile range: 67-80) and the median time from stroke to interview was 8 days. The median Fatigue Severity Scale-7 score and the median Multidimensional Fatigue Inventory-20 (General Fatigue subscale) score were higher in the case definition positive than in the negative group (p < .001). The kappa value for the inter-rater agreement was 0.63. A cutoff score of 4.9 for the Fatigue Severity Scale-7 and a cutoff score of 12 on the Multidimensional Fatigue Inventory-20 were optimal to identify marked fatigue according to the case definition. CONCLUSIONS: The case definition was valid and had a substantial inter-rater agreement. A score ≥ 5 using the Fatigue Severity Scale-7 or a score ≥ 12 using the Multidimensional Fatigue Inventory-20 (General Fatigue subscale) may be used to detect potentially debilitating post-stroke fatigue in stroke survivors.

Stroke rehabilitation at home before and after discharge reduced disability and improved quality of life: a randomised controlled trial.

OBJECTIVE: To evaluate if home-based rehabilitation of inpatients improved outcome compared to standard care. DESIGN: Interventional, randomised, safety/efficacy open-label trial. SETTING: University hospital stroke unit in collaboration with three municipalities. SUBJECTS: Seventy-one eligible stroke patients (41 women) with focal neurological deficits hospitalised in a stroke unit for more than three days and in need of rehabilitation. INTERVENTIONS: Thirty-eight patients were randomised to home-based rehabilitation during hospitalization and for up to four weeks after discharge to replace part of usual treatment and rehabilitation services. Thirty-three control patients received treatment and rehabilitation following usual guidelines for the treatment of stroke patients. MAIN MEASURES: Ninety days post-stroke the modified Rankin Scale score was the primary endpoint. Other outcome measures were the modified Barthel-100 Index, Motor Assessment Scale, CT-50 Cognitive Test, EuroQol-5D, Body Mass Index and treatment-associated economy. RESULTS: Thirty-one intervention and 30 control patients completed the study. Patients in the intervention group achieved better modified Rankin Scale score (Intervention median = 2, IQR = 2-3; Control median = 3, IQR = 2-4; P=0.04). EuroQol-5D quality of life median scores were improved in intervention patients (Intervention median = 0.77, IQR = 0.66-0.79; Control median = 0.66, IQR = 0.56 - 0.72; P=0.03). The total amount of home-based training in minutes highly correlated with mRS, Barthel, Motor Assessment Scale and EuroQol-5D™ scores (P-values ranging from P<0.00001 to P=0.01). Economical estimations of intervention costs were lower than total costs of standard treatment. CONCLUSION: Early home-based rehabilitation reduced disability and increased quality of life. Compared to standard care, home-based stroke rehabilitation was more cost-effective.

Modafinil May Alleviate Poststroke Fatigue: A Randomized, Placebo-Controlled, Double-Blinded Trial.

BACKGROUND AND PURPOSE: Poststroke fatigue is common and reduces quality of life. Current evidence for intervention is limited, and this is the first placebo-controlled trial to investigate treatment of poststroke fatigue with the wakefulness promoting drug modafinil. METHODS: The trial was randomized, double-blinded, and placebo-controlled. Patients were treated with 400-mg modafinil or placebo for 90 days. Assessments were done at inclusion, 30, 90, and 180 days. The primary end point was fatigue at 90 days measured by the Multidimensional Fatigue Inventory-20 general fatigue domain. Secondary end points included the Fatigue Severity Scale, the Montreal Cognitive Assessment, the modified Rankin Scale and the Stroke-specific quality of Life questionnaire. Adult patients with a recent stroke achieving a score of ≥12 on the Multidimensional Fatigue Inventory-20 general fatigue domain were consecutively included. Exclusion criteria were severe cognitive disabilities and contraindications for modafinil treatment. RESULTS: One thousand one hundred twenty-one patients with stroke were screened and 41 patients included, 21 received modafinil. The primary end point, the Multidimensional Fatigue Inventory-20 general fatigue score, did not differ between groups. Patients in the modafinil group obtained better scores on the Fatigue Severity Scale (P=0.02) and in some subscales of the stroke-specific quality of life questionnaire (0.001

[Inflammation as part of cerebral amyloid angiopathy disguised as a tumour].

A male with probable cerebral amyloid angiopathy (CAA)-related inflammation presented with headache and subacute hemi-paresis. After admission he developed a disturbance of consciousness and a CT brain scan showed oedema with significant midline shift. He was treated with corticosteroids with prompt clinical improvement. A MR brain scan after treatment showed confluent T2-weighted lesions, microbleeds and regression of oedema. The patient was discharged in habitual status. During withdrawal of corticosteroids he showed clinical and radiological signs of relapsing CAA-related inflammation.