eric593 wrote:Even progressive forms of MS show periods of "innate improvement" and/or stability naturally, without any treatment at all. Perhaps CCSVI treatment hasn't caused some reported improvements in those with RRMS or even progressive forms of MS, it could be a natural cycle of improvement or stabilization that has occurred. Even in those originally thought to not HAVE any improvements or stabilization due to the type of MS they had, a progressive form. This just emphasizes how critical blinded trials are to be able to distinguish if CCSVI treatment really does have any impact on MS beyond natural course of the disease and/or placebo effect.
...in the last decade, substantial pathological, immunological and imaging evidence confirmed that tissue damage in the GM is a key component of the disease process in MS and that it occurs from the earliest clinical stages [2-5]. During the past few years, the number of studies investigating GM damage in MS has increased exponentially.
In the last 5 years, numerous cross-sectional and longitudinal studies established that GM damage is a better predictor of physical disability and cognitive impairment than WM damage . Most studies examining this argument used novel imaging techniques that can indirectly assess the extent of GM damage, the most important being a measurement of GM atrophy [2,5]. Therefore, monitoring the evolution of GM damage by various imaging techniques is becoming an important marker in predicting the future disease course and response to therapy in MS patients. A number of current clinical trials examine the effects of immunomodulatory treatments on slowing down GM damage over time.
This just emphasizes how critical blinded trials are to be able to distinguish if CCSVI treatment really does have any impact on MS beyond natural course of the disease and/or placebo effect.
Although EDSS has been widely used for almost 20 years, its application still depends on the interpretation of the neurologist who performs the neurological examination, and many applications of the scale performed by different neurologist on the same patient can give different results. This is a serious problem for international trials because they lack of a reliable measure of the effects of drugs
Interrater variability with the Expanded Disability Status Scale (EDSS) and Functional Systems (FS) in a multiple sclerosis clinical trial
J. H. Noseworthy, MD,
M. K. Vandervoort, MSc,
C. J. Wong, MSc and
G. C. Ebers, MD
+ Author Affiliations
Department of Clinical Neurological Sciences (Dr. Noseworthy, Ms. Vandervoort, and Dr. Ebers), University of Western Ontario, and the Roberts Research Institute (Ms. Wong), London, ON, Canada.
We describe the interrater variability in the Expanded Disability Status Scale (EDSS) and Functional Systems (FS) in a multiple sclerosis clinical trial. Two physicians blinded to their previous assessments and to each other's scores consecutively examined 168 patients (545 paired examinations). Perfect agreement on the assignment of the disability scores ranged from 48% (cerebellar functional group) to 69% (EDSS and pyramidal functional group). Only 31% to 62% of this agreement occurred independently of that expected by chance (kappa). With the exception of the cerebellar and sensory functional groups, agreement within 1 step occurred in at least 92% of cases. These findings suggest that differences of a single step on these scales may not reflect an important functional change. We recommend that at least a 2-step change (1.0 point on the EDSS and 2 points on the FS) is needed to be confident of an important change in the degree of disability or response to treatment in this disease.
Results:From 16,132 EDSS scores, 7653 yearly and 5845 biennial EDSS intervals were available for 2961 and 2382 patients respectively. Of the yearly intervals, 14.9% showed an improvement (≥0.5 points), 8.3% ≥1 point and 2.2% ≥2 point improvement, with nearly half being sustained. Corresponding worsenings were observed in 32.9%, 20.5% and 7.9% respectively, with stability in just over half (53%). Biennial findings were similar.
The natural history of MS and implications for clinical practice
Professor Helen Tremlett, University of British Columbia Hospital, Vancouver, opened the conference with an overview of long-term natural history studies of MS in British Columbia. Data from this large cohort suggested progression of MS is slower than previously thought, which has implications for designing clinical trials and determining the long-term effectiveness of disease modifying therapies (DMTs).
Data demonstrated that by measuring time to outcomes from birth rather than from onset of MS men and women have similar disease outcomes (time to reach EDSS 6); an older age at onset is favourable; relapses do not affect long-term disability outcomes and early relapses only impact progression over the short-term. Whilst young patients with MS may gain long-term benefit from treatment with DMTs, older people may find limited benefit. Interestingly, MS relapse rates naturally decrease over time and a five year relapse-free period was common (occurring in 77% of people with relapsing remitting MS) independent of drug therapy.
Something congenital there, ya think? Or maybe it's an STD...Data demonstrated that by measuring time to outcomes from birth rather than from onset of MS...
Cece wrote:'Since birth' is of greater importance in a disease when chronic longterm neurodegeneration is the key process. 'Since diagnosis' or since relapses and/or progression began would be of greater importance if the relapses themselves cause the neurodegeneration.
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