Effect of dalfampridine on information processing speed impairment in multiple sclerosis

Neurology ◽  
2019 ◽  
Vol 93 (8) ◽  
pp. e733-e746 ◽  
Author(s):  
Laura De Giglio ◽  
Francesca De Luca ◽  
Flavia Gurreri ◽  
Ilaria Ferrante ◽  
Luca Prosperini ◽  
...  

ObjectiveTo test a possible benefit of dalfampridine on information processing speed (IPS), a key function for cognitive impairment (CogIm) in multiple sclerosis (MS).MethodsIn this randomized, double-blind, placebo-controlled trial, we included patients with a score on the Symbol Digit Modalities Test (SDMT) under the 10th percentile of the reference value. Patients were randomized in a 2:1 ratio to receive dalfampridine 10 mg or placebo twice daily for 12 weeks. They underwent a comprehensive neuropsychological evaluation at screening (T0), at the end of treatment (T1), and after a 4-week follow-up (T2). The primary endpoint was improvement in SDMT.ResultsOut of 208 patients screened, 120 were randomized to receive either dalfampridine (n = 80) or placebo (n = 40). At T1, the dalfampridine group presented an increase of SDMT scores vs placebo group (mean change 9.9 [95% confidence interval (CI) 8.5–11.4] vs 5.2 [95% CI 2.8–7.6], p = 0.0018; d = 0.60 for raw score; and 0.8 [95% CI 0.6–1] vs 0.3 [95% CI 0.0–0.5], p = 0.0013; d = 0.61 for z scores; by linear mixed model with robust standard error). The improvement was not sustained at T2. A beneficial effect of dalfampridine was observed in the Paced Auditory Serial Addition Test and in cognitive fatigue.ConclusionDalfampridine could be considered as an effective treatment option for IPS impairment in MS.Trial registration2013-002558-64 EU Clinical Trials Register.Classification of evidenceThis study provides Class I evidence that for patients with MS with low scores on the SDMT, dalfampridine improves IPS.

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Susan Alderman ◽  
Terri Armstrong ◽  
Geri Wood ◽  
Sean Savitz ◽  
Joshua Breier

Background: One year after stroke 50-70% of survivors have information processing speed (IPS) impairment. IPS is a complex, elemental cognitive function with close but separate relationships with memory, attention, executive function, reading, and writing. IPS impairment can be devastating, even without physical deficits. Hypothesis: The frequency and severity of IPS impairment in patients with acute stroke is unrelated to stroke severity. Methods: In a longitudinal study, 30 adults with acute mild (NIHSS <5) versus moderate stroke (NIHSS 5-12) were assessed for IPS and memory impairments at three time points (< 72 hours, Week 3, and Week 12). The Symbol Digit Modalities Test (SDMT) was the primary IPS instrument, scores below the norm (51-62 points) indicate impairment. Results: Using linear mixed model regression, no significant difference was noted between patients with mild and moderate stroke in frequency and severity of IPS impairment (p=0.2). All patients had baseline abnormal SDMT scores, improving 21% by Week 12 (p=.005) with one patient scoring as unimpaired (51 points). Patients with mild stroke (n=18) had baseline scores on average 53% lower than SDMT norm (mean score 24 (12), [95% CI] 6 [18, 30], Standard Error (SEM) 3) and 32% lower at Week 12 (mean 34 (11), [95% CI] 5 [29, 40], SEM 3). Patients with moderate stroke (n=12) had baseline SDMT scores 60% lower than norm (mean 21 (11), [95% CI] 6 [15, 27], SEM 3) and 39% lower by Week 12 (mean 31 (12), [95% CI] 7 [25, 38], SEM 3). Memory impairment at enrollment (<72 hours post stroke) was noted in 100% of patients with moderate stroke and 78% of patients with mild stroke; at Week 12 the frequency of memory impairment was equal in both groups (67%). Conclusion: IPS were critically impaired, in both mild and moderate stroke, with minimal spontaneous recovery at Week 12. IPS impairment is clinically significant during stroke recovery. IPS impairment should be considered in the planning of healthcare of stroke victims even with mild stroke.


2021 ◽  
Vol 14 ◽  
pp. 175628642110112
Author(s):  
Carlo Pozzilli ◽  
Luca Prosperini ◽  
Silvia Tommasin ◽  
Claudio Gasperini ◽  
Elena Barbuti ◽  
...  

Objective: To evaluate baseline characteristics predictive of improving information processing speed in multiple sclerosis (MS) and the relationship between cognitive and motor response to dalfampridine (DA) treatment. Methods: This is a post hoc analysis of a randomized, double-blind, placebo-controlled trial in patients with MS randomized to receive DA 10 mg or placebo twice daily for 12 consecutive weeks. Here, we include only data from 71 patients in the arm treated with DA. According to the median value of Symbol Digit Modalities Test (SDMT) response, patients were categorized as “full responders” (FR) or “partially responders” (PR). Results: There was higher possibility of being FR in the presence of a baseline lower Expanded Disability Status Scale [odds ratio (OR) 0.69; 95% confidence interval (CI) 0.5–0.97, p = 0.034], a higher Multiple Sclerosis Functional Composite value (OR 1.37; 95%CI 1.05–1.8, p = 0.022), a lower Timed 25-Foot Walk Test (OR 0.76; 95% CI 0.6–0.98, p = 0.033), and a lower 9-Hole Peg Test with dominant hand (OR 0.92; 95% CI 0.86–0.99, p = 0.029). FR group did not show any significant improvement of motor performance compared with PR group. Conclusion: The current analysis shows that in MS patients with cognitive deficit, the greatest improvement in SDMT provided by DA was observed in patients with milder motor impairment; cognitive and motor responses to treatments are not related. Trial registration: EU Clinical Trials Register; ID 2013-002558-64 ( https://www.clinicaltrialsregister.eu/ctr-search/search?query=2013-002558-64 )


2013 ◽  
Vol 19 (5) ◽  
pp. 613-620 ◽  
Author(s):  
Emily M. Owens ◽  
Douglas R. Denney ◽  
Sharon G. Lynch

AbstractPrevious studies show that MS patients take longer than healthy controls to plan their solutions to Tower of London (TOL) problems but yield conflicting results regarding the quality of their solutions. The present study evaluated performance under untimed or timed conditions to assess the possibility that differences in planning ability only occur when restrictions in solution times are imposed. MS patients (n = 39) and healthy controls (n = 43) completed a computerized version of the TOL under one of two conditions. In the untimed condition, participants were allowed as much time as needed on each problem. In the timed condition, limits were imposed on solution times and time remaining was displayed with each problem. Patients exhibited longer planning times than controls, and the disparity between groups increased with problem difficulty. Planning performance depended upon condition. In the untimed condition, patients and controls performed equally well. When solution times were restricted, however, patients solved fewer problems than controls. MS patients’ planning ability is intact when permitted sufficient time to formulate the required plan. Deficiencies in planning are only evident when time is restricted, and, therefore, are more accurately considered a relative consequence of disease-related problems in information processing speed. (JINS, 2013, 19, 1–8)


2017 ◽  
Vol 47 (15) ◽  
pp. 2708-2719 ◽  
Author(s):  
C. Hindocha ◽  
T. P. Freeman ◽  
J. X. Xia ◽  
N. D. C. Shaban ◽  
H. V. Curran

BackgroundCannabis and tobacco have contrasting cognitive effects. Smoking cannabis with tobacco is prevalent in many countries and although this may well influence cognitive and mental health outcomes, the possibility has rarely been investigated in human experimental psychopharmacological research.MethodThe individual and interactive effects of cannabis and tobacco were evaluated in 24 non-dependent cannabis and tobacco smokers in a randomized, placebo-controlled, double-blind, 2 (cannabis, placebo) × 2 (tobacco, placebo) crossover design. Verbal memory (prose recall), working memory (WM) performance including maintenance, manipulation and attention (N-back), psychotomimetic, subjective and cardiovascular measures were recorded on each of four sessions.ResultsCannabis alone impaired verbal memory. A priori contrasts indicated that tobacco offset the effects of cannabis on delayed recall. However, this was not supported by linear mixed model analysis. Cannabis load-dependently impaired WM. By contrast, tobacco improved WM across all load levels. The acute psychotomimetic effects and ratings of ‘stoned’ and ‘dizzy’ induced by cannabis were not altered by tobacco. Cannabis and tobacco had independent effects on increasing heart rate and interacting effects on increasing diastolic blood pressure.ConclusionsRelative to placebo, acute cannabis impaired verbal memory and WM. Tobacco enhanced performance on WM, independently of cannabis. Moreover, we found some preliminary evidence that tobacco may offset the effects of cannabis on delayed, but not immediate, verbal recall. In contrast, the psychotomimetic and subjective effects of cannabis were unaffected by tobacco co-administration. By reducing the cognitive impairment from cannabis, tobacco co-administration may perpetuate use despite adverse health consequences.


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