BRV in broad clinical postmarketing use is a well-tolerated anticonvulsant drug with 50% responder rates, similar to those observed in the regulatory trials, even though 90% of the patients included had previously been exposed to LEV. An immediate switch from LEV to BRV at a ratio of 10:1 to 15:1 is feasible. The only independent significant predictor of efficacy was the start of BRV in patients not currently taking LEV. The occurrence of BAE during previous LEV exposure predicted poor psychobehavioral tolerability of BRV treatment. A switch to BRV can be considered in patients with LEV-induced BAE.

Use of BRV in GGE is well tolerated, and 50% responder rates are similar to those observed in the regulatory trials for focal epilepsies. An immediate switch from levetiracetam (LEV) to BRV at a ratio of 15:1 is feasible. The occurrence of psychobehavioral adverse events seems less prominent than under LEV, and a switch to BRV can be considered in patients with LEV-induced adverse events.

Objective: To evaluate the efficacy and tolerability of brivaracetam (BRV) in a severely drug refractory cohort of patients with epileptic encephalopathies (EE).Method: A multicenter, retrospective cohort study recruiting all patients treated with EE who began treatment with BRV in an enrolling epilepsy center between 2016 and 2017.Results: Forty-four patients (27 male [61%], mean age 29 years, range 6 to 62) were treated with BRV. The retention rate was 65% at 3 months, 52% at 6 months and 41% at 12 months. A mean retention time of 5 months resulted in a cumulative exposure to BRV of 310 months. Three patients were seizure free during the baseline. At 3 months, 20 (45%, 20/44 as per intention-to-treat analysis considering all patients that started BRV including three who were seizure free during baseline) were either seizure free (n = 4; 9%, three of them already seizure-free at baseline) or reported at least 25% (n = 4; 9%) or 50% (n = 12; 27%) reduction in seizures. An increase in seizure frequency was reported in two (5%) patients, while there was no change in the seizure frequency of the other patients. A 50% long-term responder rate was apparent in 19 patients (43%), with two (5%) free from seizures for more than six months and in nine patients (20%, with one [2 %] free from seizures) for more than 12 months. Treatment-emergent adverse events were predominantly of psychobehavioural nature and were observed in 16%.Significance: In this retrospective analysis the rate of patients with a 50% seizure reduction under BRV proofed to be similar to those seen in regulatory trials for focal epilepsies. BRV appears to be safe and relatively well tolerated in EE and might be considered in patients with psychobehavioral adverse events while on levetiracetam.

Background and Purpose: Poststroke delirium (PSD) is an independent predictor of unfavorable outcome. Despite its individual and socioeconomic burden, its frequency, clinical course, and routine detection remain unresolved. This study aimed to assess psychometric properties of established delirium screening tools and investigate the natural course of PSD. Methods: This study investigated patients presenting with high-risk transient ischemic attacks or ischemic stroke within 24 hours during a 3-month period. Twice-daily screenings for PSD were done using the confusion assessment method, nursing delirium scale, and rapid delirium assessment, and evaluated for noninferiority against Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria. We investigated demographic and stroke characteristics as predictors of PSD, neurological deficits as predictors of false screening results, and conducted a simulation study to estimate the best timing to identify PSD. Results: We enrolled 141 patients (73.8±10.4 years of age, 61 female) with a mean National Institutes of Health Stroke Scale score of 6.4±6.5. Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition based PSD incidence was 39%, which manifested within 24 hours in 25% and 72 hours in almost all cases. The confusion assessment method was the only screening tool noninferior to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ratings providing a sensitivity of 82% and specificity of 80%. Age (odds ratio, 1.07 [1.02–1.13] per year, P =0.004) and National Institutes of Health Stroke Scale (odds ratio, 1.24 [1.15–1.34] per point, P <0.001) were predictors of PSD. False-positive screening results were associated with stroke-induced disorientation (odds ratio, 6.1 [3.2–11.61], P <0.001) and neglect (odds ratio, 2.17 [1.22–3.87], P =0.008). Simulations revealed that one in 4 cases is missed with less than daily screenings. Conclusions: PSD is a common complication of stroke and transient ischemic attack. Detection is challenged by confounding effects such as focal neurological deficits and the necessity for at least daily screenings. Future studies are required to investigate implementation of these findings in clinical routine. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT03930719.

ObjectivesDalfampridine exerts beneficial effects on walking ability in a subgroup of patients with multiple sclerosis (MS). These patients are termed “responders”. Here, we investigated whether the responder status with respect to mobility measures would determine whether dalfampridine treatment exerts a beneficial effect on other MS symptoms. We therefore assessed walking ability, upper limb function, cognition, fatigue, visual evoked potentials (VEPs), depression, and quality of life in patients before and after dalfampridine treatment.MethodsPatients with MS and impaired mobility were recruited. Maximal walking distance, timed 25 Foot Walk, nine hole peg test, paced auditory serial addition test (PASAT), fatigue severity scale (FSS), VEPs, Beck Depression Inventory (BDI), EuroQol five dimensional questionnaire, and quality of life visual analogue scale were determined before and after 12–14 days of dalfampridine treatment. Repeated measures analysis of variance was applied to determine the effect of dalfampridine treatment.ResultsOf the 34 patients who completed the study, 22 patients were responders and 12 patients nonresponders, according to their performance in mobility measures. Treatment effects for the entire patient cohort were observed for PASAT (p = .029) and BDI (p = .032). Belonging to the responder cohort did not predict the response to treatment in these tests. For the FSS, response to dalfampridine treatment was dependent on the responder status (p = .001) while no effects in the total patient cohort were observed (p = .680). Other neurological functions remained unaltered. For VEP latencies, no significant improvements were detected.ConclusionIn this study, we observed beneficial effects of dalfampridine on cognition, depression, and fatigue. These effects were not limited to patients who responded to dalfampridine with improved mobility measures. These findings underscore the need to assess the beneficial effects of dalfampridine on neurological deficits in MS patients in additional randomized clinical trials.