He et al. Pharmacologic treatment for memory disorder in multiple sclerosis. Cochrane Database Syst Rev. 2011 Oct 5;10:CD008876.
Search Strategy: The investigators searched the Cochrane Multiple Sclerosis Group’s Trials Register (17 January 2011), PsycINFO (January 1980 – April Week 4 2011) and CBMdisc (January 1978 – 6 April 2011), and checked reference lists of identified articles, searched some relevant journals manually, registers of clinical trials and published abstracts of conference proceedings.
Selection criteria: All double-blind, randomised controlled parallel trials on pharmacologic treatment versus placebo treatment or no treatment or one or more pharmacologic treatments, without restrictions regarding dose, route of administration and frequency, administration duration≥12 weeks for memory disorder in adult MS’ers who display at least mild memory impairment at 0.5 standard deviations below age -and-sex-based normative data on a validated memory scale.
Data collection and analysis: Two review authors independently assessed trial quality and extracted data. Disagreements were discussed and resolved by consensus among review authors. Principal investigators of included studies were contacted for additional data or confirmation.
Main results: Four randomised controlled trials involving adult MS and at least mild memory impairment were included, evaluating donepezil, ginkgo biloba (GB), memantine and rivastigmine respectively vs placebo in treating memory disorder in MS.There were no serious adverse events in intervention groups.The quality of the included studies was overall low, some of important variables were not matched between groups at baseline, the samples of subjects were relatively small and the follow-up was short. Three RCTs which evaluate GB, memantine, rivastigmine respectively vs placebo are currently ongoing.
Author’s conclusions: Until the results of ongoing studies are available, there is no convincing evidence to support pharmacologic intervention as an effective treatment for memory disorder in MS’ers. However, donepezil, ginkgo biloba, memantine and rivastigmine resulted to be safe and well tolerated as adverse events such as nausea, diarrhea, somnolence, and constipation were not frequent, while no serious adverse effects were reported. Future high quality randomised controlled trials are needed.
Background: Memory impairment is one of the most frequent cognitive problems MS’ers complain about and has a great negative impact on their quality of life. A few pharmacologic agents appear to be effective to memory disorder in MS’ers in some existing randomised controlled trials.
Objectives: To assess the absolute and comparative effectiveness, tolerability and safety of pharmacologic treatments for memory disorder in adult MS’ers.
Search Strategy: The investigators searched the Cochrane Multiple Sclerosis Group’s Trials Register (17 January 2011), PsycINFO (January 1980 – April Week 4 2011) and CBMdisc (January 1978 – 6 April 2011), and checked reference lists of identified articles, searched some relevant journals manually, registers of clinical trials and published abstracts of conference proceedings.
Selection criteria: All double-blind, randomised controlled parallel trials on pharmacologic treatment versus placebo treatment or no treatment or one or more pharmacologic treatments, without restrictions regarding dose, route of administration and frequency, administration duration≥12 weeks for memory disorder in adult MS’ers who display at least mild memory impairment at 0.5 standard deviations below age -and-sex-based normative data on a validated memory scale.
Data collection and analysis: Two review authors independently assessed trial quality and extracted data. Disagreements were discussed and resolved by consensus among review authors. Principal investigators of included studies were contacted for additional data or confirmation.
Main results: Four randomised controlled trials involving adult MS and at least mild memory impairment were included, evaluating donepezil, ginkgo biloba (GB), memantine and rivastigmine respectively vs placebo in treating memory disorder in MS.There were no serious adverse events in intervention groups.The quality of the included studies was overall low, some of important variables were not matched between groups at baseline, the samples of subjects were relatively small and the follow-up was short. Three RCTs which evaluate GB, memantine, rivastigmine respectively vs placebo are currently ongoing.
Author’s conclusions: Until the results of ongoing studies are available, there is no convincing evidence to support pharmacologic intervention as an effective treatment for memory disorder in MS’ers. However, donepezil, ginkgo biloba, memantine and rivastigmine resulted to be safe and well tolerated as adverse events such as nausea, diarrhea, somnolence, and constipation were not frequent, while no serious adverse effects were reported. Future high quality randomised controlled trials are needed.
“Unfortunately no evidence to support a treatment of memory impairment for Ms’ers at present. However, the evidence base at present is so poor that there is room for improvement when designing new trials.”
“I have been lobbying the big pharma companies for several years to start development programmes for cognitive problems in MS. Memory impairment is hidden, but big, problem and any improvement in cognition will help make life a little easier for those living with the disease.”
Memory impairment, cog fog and fatigue often come together. Strangely, these symptoms are the first to improve after the CNS venous drainage is restored. Hence, they share a common underlying cause, namely, impaired intracranial blood flow due to extracranial venous obstructions.
Fatigue for eight years before diagnosis. It was the worst symptom for me. One hour CCSVI procedure changed my perception of my disease. Have you considered the fact that cerebral blood flow through the jugular veins has an effect on hypo perfusion in the brains of people with MS? It is well documented that PwMs have perfusion problems. Take a look at the research being done and there may be no need for another drug to experiment on PwMs.
Re: "Fatigue for eight years before diagnosis. It was the worst symptom for me. One hour CCSVI procedure changed my perception of my disease. Have you considered the fact that cerebral blood flow through the jugular veins has an effect on hypo perfusion in the brains of people with MS? …."Until we have randomised, blinded (sham) studies it makes is it difficult to assess ancedotal reports. The placebo effect is very strong. I would recommend reading "Bad Science" by Ben Goldacre to understand this issue.
Re "Until we have randomised, blinded (sham) studies it makes is it difficult to assess ancedotal reports. The placebo effect is very strong."It is obvious that you have got the phenomenology of the fatigue all wrong. You (neurologists) believe your patients when they come to you and describe their symptoms in the first place, but then you strip them off of any credibility. Someone who has experienced the interweaving mental-somatic character of the MS fatigue knows that it is impossible to get relieved by superimposing any kind of belief, thought or expectation.
Re: "It is obvious that you have got the phenomenology of the fatigue all wrong. You (neurologists) believe your patients when they come to you and describe their symptoms in the first place, but then you strip them off of any credibility. Someone who has experienced the interweaving mental-somatic character of the MS fatigue knows that it is impossible to get relieved by superimposing any kind of belief, thought or expectation."A very presumptuous and arrogant comment; how do you know whether or not I have MS?
That's how patients feel when they are told they are imagining improvements.
Re: "That's how patients feel when they are told they are imagining improvements."Who said the placebo effect was imagination. It is a real phenomenon with a wealth of science behind it. I suggest you read "Bad Science" by Ben Goldacre, he goes into the science of the placebo effect in some detail. Another starting point is wikipedia:http://en.wikipedia.org/wiki/Placebo#Placebo_effect_and_the_brainAs a neuroscientist and neurologist I find the functional MRI data on the placebo effect most compelling!
The comments were certainly 'presumptuous and arrogant'; the rest of your sentence is startling even as a theoretical point. I'd like to remind other readers of a statement from an earlier set of comments: 'Several people who work in my group have a very personal connection to MS'
Re "The comments were certainly 'presumptuous and arrogant';"I'm not commenting here for my personal pleasure. Nor are our lives a correctness contest. Ask the victims of Tysabri or the Stem Cell trasplantation processes about arrogance. Or maybe the almost zero-populated subgroup of MS patients that witnessed a reverse or even halt in their disease course under the command of the traditional neurology.