4 Treatment Protocols

Regarding the 'Simplified Methylation Protocol', Dr. Neil Nathan said: "To my delight, 70% of my patients had improved within 3 months, and 20% reported that they were much better, occasionally to the point of feeling cured. " From: <a href="http://www.prohealth.com/library/showArticle.cfm?libid=16138">http://www.prohealth.com/library/showArticle.cfm?libid=16138</a>

From: <a href="https://www.healthrising.org/blog/2015/11/27/fatigue-multiple-sclerosis-chronic-fatigue-syndrome-and-fibromyalgia-is-it-the-same/">The Fatigue in Multiple Sclerosis, Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia - Is it the Same? - Health Rising</a>

The FDA has approved no less that thirteen drugs to treat MS, at least one of which, <a href="http://www.nationalmssociety.org/Treating-MS/Medications/Copaxone">Copaxone</a>(glatiramer acetate) appears to be able to reliably reduce fatigue. (Health Rising will cover Copaxone more in a blog about a person with ME/CFS who was diagnosed with MS and whose fatigue diminished markedly while she was on Copaxone). The monoclonal antibody Natalizumab also appears to be able to decrease fatigue in some MS patients.

Fatigue is common in rheumatic disorders such as rheumatoid arthritis, Sjogren’s Syndrome and systemic lupus. Because the medications used in these disorders often focus in altering immune functioning they present possibilities for ME/CFS/FM patients.

<div id="attachment_20159" class="wp-caption alignright">Immune altering drugs have worked better in altering pain than fatigue in other diseases. Newer drugs may work better.</div>

An overview of these immune altering drugs (methotrexate and leflunomide, biologics (infliximab, adalimumab, etanercept, golimumab and certolizumab), anti-IL-6 (tocilizumab), immunoglobulins (abatacept) and Rituximab) found that, at least in rheumatoid arthritis they may improve pain but generally have had small effects on fatigue.

The review concluded that “<a href="http://rheumatology.oxfordjournals.org/content/51/1/60.long">fatigue is a multi-factorial symptom</a> related to pain, functioning and psychological factors, but does not seem to be related exclusively to inflammation, which is reflected by joint disease activity”

Note that Rituximab – currently under investigation in ME/CFS – is in this list. If Rituximab turns out to have large effects on fatigue in ME/CFS it will change how people understand Rituximab and how it works.

Some new biologic drugs appear to be more effective in fighting fatigue. The first IL-17 antibody – Secukinumab and tofacitinib, an oral Janus kinase inhibitor both improved fatigue significantly. Secukinumab improved physical functioning in <a href="http://www.ncbi.nlm.nih.gov/pubmed/26267726">patients with psoriatic arthritis</a>. The success of Secukinumab is intriguing given the interest in IL-17 in ME/CFS.

Conclusion – in general immune targeted drugs do not appear to be particularly effective at reducing fatigue in other diseases. We know that Ampligen and Rituximab can be very effective in reducing fatigue in some ME/CFS patients. Further studies are needed to know how many and which ones.

Central nervous system problems appear to track best with fatigue production in ME/CFS, FM and MS at this point. Brainstem and the midbrain issues which interfere with activation of the cerebral cortex and other parts of the brain, in particular, appear to be present in both ME/CFS and MS. The thalamus and basal ganglia may feature prominently in fatigue production in these diseases.

People with ME/CFS or MS also appear to use more brain regions than normal to accomplish tasks – an inherently fatiguing process. Since the demyelinating lesions found in MS do not occur in ME/CFS/FM, other issues (low grade inflammation?) are probably affecting brain regions in these diseases.

Evidence that inflammation in the periphery (the body as opposed to the brain) is contributing to the fatigue in MS, RA and ME/CFS is inconsistent. HPA axis problems, on the other hand, appear to contribute to fatigue in both ME/CFS and MS (albeit in different directions.)

Inflammation reducing drugs can effectively relieve pain in rheumatological diseases but have had only small effects on fatigue. Some newer immune modulating drugs appear to be more effective. The field of immune altering drugs is growing rapidly and we should expect more drugs to enter the market as time goes on.

Both ME/CFS and MS patients experience fatigue but people with multiple sclerosis do not experience the extent of post-exertional malaise present in ME/CFS.

Finally one ME/CFS patient’s successful experience with an MS drug suggests that the treatment options known to reduce fatigue in MS might be able to reduce fatigue in ME/CFS.

5 TBI May Contribute to the Pathogenesis And/or Acceleration of Neurodegenerative Conditions And/or Diseases

From: <a id="null" class="null" href="http://jpet.aspetjournals.org/content/jpet/early/2018/08/03/jpet.118.250845.full.pdf">http://jpet.aspetjournals.org/content/jpet/early/2018/08/03/jpet.118.250845.full.pdf</a>

Overall, the ME/CFS phenotype has been associated with apparent abnormalities in the metabolic profile, possibly due to local inflammation in the hypothalamus. Compounds that could inhibit inflammation in the brain, such as tetramethoxyluteolin or the anti-inflammatory cytokine IL-37 (Dinarello, et al., 2016), (Mastrangelo, et al., 2018), may be potential treatment options.