#ThinkCognition

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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

About the author

Prof G

Professor of Neurology, Barts & The London. MS & Preventive Neurology thinker, blogger, runner, vegetable gardener, husband, father, cook and wine & food lover.

13 comments

  • 3 questions please:
    1) Any side effects linked to long term use?
    2) does it have any “preservation value”? i.e. can it be used pre-preemptively to protect the brain?
    3) Has it been trialed as an add-on therapy to a highly effective DMT like Tysabri?

  • I’m also querying side effects and possible problems if given alongside other drugs routinely prescribed for PwMS.

    Also wondering about capacity for preservation, especially when bearing in mind that quality trials of Lipoic Acid have shown it to be effective in regards to BVL and benign in respect to side effects.

    Would I want my cognition tested without anything at all of value on offer? Not a hope-in-hells chance, unless it becomes blatantly apparent I’m becoming vulnerable to myself and for others (eg driving)

    We know that PwMS are more vulnerable to psychiatric disorders such as depression and I know I’d definitely be more vulnerable to being psychologically torn apart if my neuro routinely advised there’s evidence of cognitive impairment and then sent me on my way to simply get on and live with that!

    In the meantime therefore, I’ll stick with trying to do the best for myself, exercise, intermittent fasting etc, and with the uplifting impact of currently being able to be proactive with my fatigue and limited disability.

    Having said all this, would I want this drug available on the NHS to those experiencing severe cognitive disfunction – Yes.

  • Does Dalfampridine improve walking in a significant way?

    I remember a discussion about this drug several years ago and you raised a concern that this drug could potentially accelerate CNS loss as too much strain is placed on the surviving axons / neuros. Do you still have such a concern?

  • I get generic Dalfampridine now. It is perfectly safe. It helps a little with walking. Helps a lot with fatigue and as a result cognition.

    It is not a miracle drug. It helps. It is safe.

  • re “…It also raises the question of whether, or not, we should be doing routine cognitive testing in clinical practice? “.

    What are your thoughts on using the MSFC – MS Functional Composite in clinic, instead of the EDSS? I know it takes take time to do, (probably not enough time in clinic to do this) and a high level of training to perform. Also that is doesn’t cover all the cognitive aspects relevant to MS.

    https://www.nationalmssociety.org/For-Professionals/Researchers/Resources-for-Researchers/Clinical-Study-Measures/Multiple-Sclerosis-Functional-Composite-(MSFC)

  • Hi,
    Great blogs, succinct and spot-on.
    I have secondary progressive MS and live alone; I’m trying to keep working from home whilst staying on top of my condition but it’s hard. In early July I asked my ?????’s-based clinician if he could refer me to a centre which may accept me to try fampridine, and he agreed to see where this might be possible. Almost 3 moths on he still hasn’t done this. I really do respect clinicians are busy but my health is deteriorating pretty rapidly, and with it my independence, and also my sense of well-being and purpose.
    Does Bart’s accept patients from outside London to try fampridine assuming they are deemed suitable?

    • Unfortunately. NICE has not approved fampridine for the treatment of MS-related walking problems so it is not available under the NHS. Queen Square (National Hospital for Neurology and Neurosurgery) are able to prescribe it to a limited number of patients; the UCLH NHS Trust covers the cost of the drug and not NHS England.

      Interestingly, fampridine is now available for NHS use in both Scotland and Wales.

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