If you have MS-related cognitive impairment would you want a treatment to improve your cognitive function?
The study below shows that dalfampridine, or fampridine, improves cognition in particular processing speed in MSers with cognitive impairment. Importantly the improvement on the SDMT (Symbol Digit Modalities Test) was greater than 4 points, which is considered clinically meaningful in that it is anchored to improved day-to-day functioning and quality of life.
Dalfampridine has a complex mode of action and is thought to increase the so-called safety factor of conduction and synaptic function and improves the functioning of demyelinated or thinly remyelinated axons.
Dalfampridine is currently licensed to improve walking speed in MSers. As it has not been green-lighted by NICE for use on the NHS most MSers can’t access this treatment. In London, some NHS hospitals have put in place a limited access scheme and therefore can prescribe fampridine for some of their patients. Despite this most MSers who take fampridine in the UK are having to pay for it privately, which I find totally unacceptable. Why should your ability to pay and access private healthcare dictate your access to a treatment that is being used extensively across the world?
This cognitive study below suggests that similar mechanisms underlie both motor and cognitive performance in MS. What is important about this study is that it demonstrates the principle that MS-related cognitive impairment is a potentially treatable problem. It also raises the question of whether, or not, we should be doing routine cognitive testing in clinical practice and telling our patients they have cognitive impairment and hopefully in the future being able to offer them an effective therapy to improve their cognition or processing speed.
De Giglio et al. Effect of dalfampridine on information processing speed impairment in multiple sclerosis. Neurology. 2019 Jul 22. pii: 10.1212/WNL.0000000000007970.
OBJECTIVE: To test a possible benefit of dalfampridine on information processing speed (IPS), a key function for cognitive impairment (CogIm) in multiple sclerosis (MS).
METHODS: In 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.
RESULTS: Out 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.
CONCLUSION: Dalfampridine could be considered as an effective treatment option for IPS impairment in MS.
TRIAL REGISTRATION: 2013-002558-64 EU Clinical Trials Register.
CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for patients with MS with low scores on the SDMT, dalfampridine improves IPS.
CoI: multiple