The Drug/MRI Fallacy
Posted: Mon Jan 20, 2014 8:44 am
I believe we need to vastly transform current MS treatment. The Neurologist has determined one has MS. MS research has concluded one should begin DMD (Disease Modifying Drug) therapy as soon as possible. The condition of brain lesions monitored with the MRI will determine the effectiveness of drug therapy. Except the lesions aren’t related to MS disability. And the drugs won't prevent descent into Progressive MS and disability.
The first big breach in the drug fallacy came with a scientific study conducted by a University of British Columbia research team who published their paper in the JAMA (Journal of American Medical Association) in July 2012.
Their conclusion? Quoted from <http://www.nytimes.com/2012/07/18/healt ... html?_r=3&>
“ Using a well-validated scale, they found that those who took interferon beta were no less likely to suffer long-term disability than those who took none.” “But after controlling for sex, age at onset, disease duration, relapse rate and other factors, they could find no association between taking interferon beta and any reduction in progression to disability. Relapses and brain lesions do not, apparently, drive disability, Dr. Tremlett said.”(my emphasis)
Yes, the drugs did reduce relapses and MRI lesions which implies that the brain lesions are not in themselves adequate indicators of MS brain damage. If MRI’s are used to “monitor” effectiveness of MS drugs, they aren’t monitoring MS progression or effective treatment. This tends to discredit the entire treatment protocol over the past 25 years.
Then Dr. George Ebers published his study of MS drug outcomes over the past 25 years.
On Thisisms.com (Cheerleader) Joan Beal comments:
“Please notice that Ebers shows that relapses have no bearing on time to reach SPMS or the 6,8 and 10 markers on EDSS.
And they do not prevent disability....there's no science behind that marketing claim.
The real biomarker is not white matter lesions, it's gray matter atrophy--that's the one thing tied to disability and MS progression.
Keep your gray matter healthy, your mitochondria healthy, keep moving—“
Dr Michael Flanagan (upright doc) also of Thisisms.com comments:
“The presentation was fast paced but interesting and enlightening...it questions the efficacy of many drugs which do nothing to change the long-term progress or outcome of the condition. It is far better to do nothing than to make someone sick while trying to cure their condition.
As far as the definition of MS is concerned, basically it's a neurodegenerative condition associated with remissions and exacerbations and somewhat characteristic signs and symptoms. The signs and symptoms were previously attributed to demyelination but we know now that they aren't necessarily related. Neurological function degenerates regardless of the state of demyelination. This indicates that there are other degenerative processes at work as well."
centenarian100 commented (Dec 23, 2013) that the statistical analysis reveals that the drugs may delay decline from RRMS to SPMS which means some MSers can live better, longer.
My comment: Maybe we can do much better than that.
Standard MS therapy: http://www.aafp.org/afp/2004/1115/p1935.html
Peter A. Calabresi, M.D. Nov 15, 2004 writes about standard MS therapy on the site American Family Physician “Diagnosis and Management of Multiple Sclerosis”. At the time 5 DMD’s had been approved by the FDA. (Little has changed since 2004 except for the increased choice including monoclonal antibodies.) Presumably the FDA approved these treatments based on – SCIENCE - a clinically approved double blind protocol (meaning neither the Doctor nor the patient know what is prescribed.) The MRI with gadolinium contrast is used to monitor lesions (at least 9) both in diagnosing MS and monitoring disease progression (and treatment effectiveness, including drug trials.)
Dr. Calabresi writes
“Patients with MS often are tempted to try alternative thérapies...Sole reliance on alternative therapies should be discouraged because patients then may be deprived of therapies that have been shown to be effective in the treatment of MS...
Accumulating evidence indicates that the best time to initiate disease-modifying treatment is early in course of MS. Data indicate that irreversible axonal damage may occur early in relapsing-remitting MS and that drug thérapies appear to be more effective in preventing new lesion formation than in repairing old lesions...the National Multiple Sclerosis Society43 supports the initiation of immunomodulating therapy at the time of diagnosis...
The ability to diagnose and treat MS has improved considerably in the past 10 years because of the availability of MRI and partially effective immunomodulating thérapies. The limited efficacity of immunomodulating drugs in the later, noninflammatory stages of MS highlights the importance of developing remyelinating and neuroprotective strategies for the disease."
THE FALLACY:
It appears that these treatments and the drug trials that approved them are based on a FALLACY, the theory that white matter lesions (plaques) accurately define MS. What if, as Joan Beal suggest, grey matter is far more important in the disease progression. What if all this FDA approved science is founded on a chimera?
Finally, it has been known since the introduction of the MRI that the images produced don’t reveal anything about the nature or degree of handicap in MS. The Neurologist uses the MRI to monitor lesions which determine treatment protocol. It is understood that the drugs work only for the RelapseRemissionMS, that is to say to control lesions and that once the patient arrives at the progressive stage, drugs are no longer effective. I repeat - "Relapses and brain lesions do not, apparently, drive disability, Dr. Tremlett said."
(A side issue. I don’t understand why MSers are so eager to undergo MRI’s. I myself need a really good reason in my own self interest (not to satisfy someone’s curiosity or diagnosis protocol or research needs) to undergo a diagnostic tool which I consider harmful. Why? Because beaming a powerful magnet at my own electromagnetic field can only disrupt it. (Chinese medical practice works on the theory that meridiens are energy flows which need to be freed to heal and prevent disease. Anything which disrupts that energy is by definition harmful.) Also, the gadolinium contrast may injure the brain. http://pubs.rsna.org/doi/abs/10.1148/radiol.13131669
In any future MRI of the brain I will insist that grey matter condition is monitored.
What can I conclude from the discussion thus far? That DMD's (MS drugs) may reduce lesion damage to white matter. However, they apparently don't stop brain degeneration in general. Thus, if one feels safer taking DMD's, one must still do everything to protect the brain in general (including grey matter) through optimal nutrition, detoxification and nutritional suppléments. I would avoid drugs I can't safely stop taking. (Tysabri comes to mind.)
And I definitely focus on enhancing blood/cerebrospinal fluid circulation in the central nervous system in order to stop the blood reflux (CCSVI). And, perhaps, doing all that one can forego the drugs altogether.
Dr. Calabresi DOES inadvertently hint at the CCSVI issue as it refers to MS. Quote:
Figure 3. “T1-weighted slices, with gadolinium contrast enhancement of one of the lesions (arrow) indicating permeability of the blood-brain barrier. Enhancing lesions correlate pathologically with perivenular inflammation and are considered a surrogate marker of disease activity.”
“perivenular” means around the vein, in the connective tissue about a vein.” Here is suggested what Dr. Charcot’s 19th century autopsies of MS patients revealed, that the “plaques” (in French MS is translated as “sclérose en plaques”) are located where the veins drain the brain. It’s taken 150 years, but we are returning to a long forgotten observation. And as Leonard points out, the Dane Torben Fog noticed in 1965 that MS lesions are tied to the small veins.
The Science is slowly (very very slowly) rejecting the DMD drug model and just as reluctantly turning towards the CCSVI theory. (One shouldn’t forget that a “scientist” shared a Nobel prize for a study favoring Lobotomy. Apparently even Science has “fashions”.)
It appears that many MSers are well ahead of the Doctors and Therapists upon whom they must rely.
MS Cure Enigmas.net
The first big breach in the drug fallacy came with a scientific study conducted by a University of British Columbia research team who published their paper in the JAMA (Journal of American Medical Association) in July 2012.
Their conclusion? Quoted from <http://www.nytimes.com/2012/07/18/healt ... html?_r=3&>
“ Using a well-validated scale, they found that those who took interferon beta were no less likely to suffer long-term disability than those who took none.” “But after controlling for sex, age at onset, disease duration, relapse rate and other factors, they could find no association between taking interferon beta and any reduction in progression to disability. Relapses and brain lesions do not, apparently, drive disability, Dr. Tremlett said.”(my emphasis)
Yes, the drugs did reduce relapses and MRI lesions which implies that the brain lesions are not in themselves adequate indicators of MS brain damage. If MRI’s are used to “monitor” effectiveness of MS drugs, they aren’t monitoring MS progression or effective treatment. This tends to discredit the entire treatment protocol over the past 25 years.
Then Dr. George Ebers published his study of MS drug outcomes over the past 25 years.
On Thisisms.com (Cheerleader) Joan Beal comments:
“Please notice that Ebers shows that relapses have no bearing on time to reach SPMS or the 6,8 and 10 markers on EDSS.
And they do not prevent disability....there's no science behind that marketing claim.
The real biomarker is not white matter lesions, it's gray matter atrophy--that's the one thing tied to disability and MS progression.
Keep your gray matter healthy, your mitochondria healthy, keep moving—“
Dr Michael Flanagan (upright doc) also of Thisisms.com comments:
“The presentation was fast paced but interesting and enlightening...it questions the efficacy of many drugs which do nothing to change the long-term progress or outcome of the condition. It is far better to do nothing than to make someone sick while trying to cure their condition.
As far as the definition of MS is concerned, basically it's a neurodegenerative condition associated with remissions and exacerbations and somewhat characteristic signs and symptoms. The signs and symptoms were previously attributed to demyelination but we know now that they aren't necessarily related. Neurological function degenerates regardless of the state of demyelination. This indicates that there are other degenerative processes at work as well."
centenarian100 commented (Dec 23, 2013) that the statistical analysis reveals that the drugs may delay decline from RRMS to SPMS which means some MSers can live better, longer.
My comment: Maybe we can do much better than that.
Standard MS therapy: http://www.aafp.org/afp/2004/1115/p1935.html
Peter A. Calabresi, M.D. Nov 15, 2004 writes about standard MS therapy on the site American Family Physician “Diagnosis and Management of Multiple Sclerosis”. At the time 5 DMD’s had been approved by the FDA. (Little has changed since 2004 except for the increased choice including monoclonal antibodies.) Presumably the FDA approved these treatments based on – SCIENCE - a clinically approved double blind protocol (meaning neither the Doctor nor the patient know what is prescribed.) The MRI with gadolinium contrast is used to monitor lesions (at least 9) both in diagnosing MS and monitoring disease progression (and treatment effectiveness, including drug trials.)
Dr. Calabresi writes
“Patients with MS often are tempted to try alternative thérapies...Sole reliance on alternative therapies should be discouraged because patients then may be deprived of therapies that have been shown to be effective in the treatment of MS...
Accumulating evidence indicates that the best time to initiate disease-modifying treatment is early in course of MS. Data indicate that irreversible axonal damage may occur early in relapsing-remitting MS and that drug thérapies appear to be more effective in preventing new lesion formation than in repairing old lesions...the National Multiple Sclerosis Society43 supports the initiation of immunomodulating therapy at the time of diagnosis...
The ability to diagnose and treat MS has improved considerably in the past 10 years because of the availability of MRI and partially effective immunomodulating thérapies. The limited efficacity of immunomodulating drugs in the later, noninflammatory stages of MS highlights the importance of developing remyelinating and neuroprotective strategies for the disease."
THE FALLACY:
It appears that these treatments and the drug trials that approved them are based on a FALLACY, the theory that white matter lesions (plaques) accurately define MS. What if, as Joan Beal suggest, grey matter is far more important in the disease progression. What if all this FDA approved science is founded on a chimera?
Finally, it has been known since the introduction of the MRI that the images produced don’t reveal anything about the nature or degree of handicap in MS. The Neurologist uses the MRI to monitor lesions which determine treatment protocol. It is understood that the drugs work only for the RelapseRemissionMS, that is to say to control lesions and that once the patient arrives at the progressive stage, drugs are no longer effective. I repeat - "Relapses and brain lesions do not, apparently, drive disability, Dr. Tremlett said."
(A side issue. I don’t understand why MSers are so eager to undergo MRI’s. I myself need a really good reason in my own self interest (not to satisfy someone’s curiosity or diagnosis protocol or research needs) to undergo a diagnostic tool which I consider harmful. Why? Because beaming a powerful magnet at my own electromagnetic field can only disrupt it. (Chinese medical practice works on the theory that meridiens are energy flows which need to be freed to heal and prevent disease. Anything which disrupts that energy is by definition harmful.) Also, the gadolinium contrast may injure the brain. http://pubs.rsna.org/doi/abs/10.1148/radiol.13131669
In any future MRI of the brain I will insist that grey matter condition is monitored.
What can I conclude from the discussion thus far? That DMD's (MS drugs) may reduce lesion damage to white matter. However, they apparently don't stop brain degeneration in general. Thus, if one feels safer taking DMD's, one must still do everything to protect the brain in general (including grey matter) through optimal nutrition, detoxification and nutritional suppléments. I would avoid drugs I can't safely stop taking. (Tysabri comes to mind.)
And I definitely focus on enhancing blood/cerebrospinal fluid circulation in the central nervous system in order to stop the blood reflux (CCSVI). And, perhaps, doing all that one can forego the drugs altogether.
Dr. Calabresi DOES inadvertently hint at the CCSVI issue as it refers to MS. Quote:
Figure 3. “T1-weighted slices, with gadolinium contrast enhancement of one of the lesions (arrow) indicating permeability of the blood-brain barrier. Enhancing lesions correlate pathologically with perivenular inflammation and are considered a surrogate marker of disease activity.”
“perivenular” means around the vein, in the connective tissue about a vein.” Here is suggested what Dr. Charcot’s 19th century autopsies of MS patients revealed, that the “plaques” (in French MS is translated as “sclérose en plaques”) are located where the veins drain the brain. It’s taken 150 years, but we are returning to a long forgotten observation. And as Leonard points out, the Dane Torben Fog noticed in 1965 that MS lesions are tied to the small veins.
The Science is slowly (very very slowly) rejecting the DMD drug model and just as reluctantly turning towards the CCSVI theory. (One shouldn’t forget that a “scientist” shared a Nobel prize for a study favoring Lobotomy. Apparently even Science has “fashions”.)
It appears that many MSers are well ahead of the Doctors and Therapists upon whom they must rely.
MS Cure Enigmas.net