Hi Bromley, Finn and Raven—
Bromley, first let me apologize for not answering some of the questions you asked several weeks ago. I’ll start there, but not without reinforcing that Finn's got it right, the fact so little is known about MS makes it easier to form my own simplistic opinions.
My idea of neurodegeneration in MS is very simplistic. As someone who is almost a decade beyond meeting entry criteria for the “Golden Age Forum", my idea of neurodegeneration and MS is basically that a) very little is actually known about MS and b) one of the things that is known is that the majority of people with MS tend to experience increasing disability over time (i.e., as they age). That’s neurodegeneration to me, the non-scientist, in a nutshell.
Finn, I agree that the concept of neurodegeneration could help explain the clinical differences between MS-subtypes. I really don’t understand the scientific basis for different clinical MS-subtypes. I have the impression that at least some ideas suggesting MS may be more than one disease are based on Lucchinetti’s work describing the four patterns of demyelination in MS patients. That work reflects lesions at a “point in time”. In the book Multiple Sclerosis in Clinical Practice
, 2003, Miller, Lublin and Coyle, make these observations about those research findings:
Of interest, in autopsy cases there was a tendency for all acute lesions to have the same pathological pattern, i.e., intrapatient homogeneity…...The major caveat for this work is that it comes from autopsy cases, which provide only one time point for pathological assessment, and in most cases do not reflect early disease events. Biopsy cases represent, at best, very atypical presentations of MS, and thus may not represent the more usual pathological changes of the illness.
Bromley, in answer to your questions about inflammation and to expand a bit on what Finn’s already said about nerve conduction and reversible RRMS, Peterson and Trapp note in an article Neuropathobiology of MS
“…inflammation, edema, and ongoing demyelination are not expected to make significant contributions to increasing permanent neurologic disability. Chronic demyelination fails to account adequately for the progressive persistent neurologic disability experienced by patients who have SPMS.”
I think treating the inflammation, edema and ongoing demyelination (no doubt all part of the nerve conduction thing) could explain the symptom relief people obtain from anti-inflammatory treatments. In other words, it’s possible that current and in the pipeline strictly anti-inflammatory agents may well diminish the clinical symptoms of MS and some axonal loss, without significantly impacting the long-term progression and increasing disability that's evident in MS.
Bruce Trapp clearly thinks that MS is an “inflammatory demyelinating and neurodegenerative disease.”
Select quotes from an abstractAxonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease
capture some ideas of that perspective.
Axonal degeneration has been identified as the major determinant of irreversible neurological disability in patients with multiple sclerosis (MS). Axonal injury begins at disease onset and correlates with the degree of inflammation within lesions, indicating that inflammatory demyelination influences axon pathology during relapsing-remitting MS (RR-MS). This axonal loss remains clinically silent for many years, and irreversible neurological disability develops when a threshold of axonal loss is reached and compensatory CNS resources are exhausted.
I am personally of the opinion that compensatory CNS resources include the hormones estrogen and progesterone. In women, estrogen and progesterone begin to decline as early as their 30’s. It’s a slow downhill course for those hormones as we age.
Finn, I do disagree with you about the use of steroids for inflammation. It’s basically my impression that in the long term they don’t appear to impact the disease course. I have serious personal questions about the use of high doses of methylprednisolone. The abstract Methylprednisolone exacerbates axonal loss following optic nerve trauma in rats
Conclusions: We conclude that methylprednisolone exacerbates axonal loss following crush injury in the rat optic nerve. Based on the results of this study, clinical studies of traumatic optic neuropathy in the future should also examine the possibility that corticosteroid treatment may have an adverse effect on visual outcome following optic nerve trauma.
I want to note and emphasize that this study was a) in rats and b) not about ON that may be a part of MS. I arrived at this abstract while pursuing my interest in hormones. I think methylprednisolone is an artificial form of the stress hormone cortisol, which is known to be high in some people with MS and associated with disease progression. In this study the axonal loss in those rats was dose dependent.
I also have serious concerns about methylprednisolone because: Methylprednisolone Increases neuronal Apoptosis during Autoimmune CNS Inflammation by Inhibition of an Endogenous Neuroprotective Pathway
…we provide evidence for negative effects of steroid treatment on neuronal survival during chronic inflammatory autoimmune disease of the CNS, which should result in a reevaluation of the current therapy regimen.
At a minimum Bromely, to answer your question, I think that treatment with steroids should be reevaluated.
Raven, it’s nice to know you’re doing so well on Campath. I wasn’t aware of the axonal connection. I also have a unified theory (unified only around hormones
) about MS. I’ll save that for another time.
Take care everyone. We are all trying to get to the same place, namely, putting MS where it rightfully belongs, behind us instead of in front of us.