By: S. F Gottlieb and R. A. Neubauer Department of Biological Sciences, University of South Alabama, Mobile, AL 36688; and the Jo Ellen Smith Memorial Baromedical Research Institute, 4400 General Meyer Avenue, New Orleans, LA 70131; and Ocean Medical Center, 4001 Ocean Drive, Lauderdale-by-the-Sea, FL 33308 Gottlieb SF, Neubauer RA
Multiple sclerosis: its etiology, pathogenesis, and therapeutics with emphasis on the controversial use of HBO.J Hyper Med 1988; 3(3):143-164-A review of the current hypotheses in the etiology and pathogenesis of multiple sclerosis (MS) is presented together with the implications for therapy.
A new hypothesis as to etiology is presented. Special emphasis is placed on the controversy surrounding the use of hyperbaric oxygen in a critical analysis of the published double-blind studies and related discussions. Emphasis placed on the predominant infective and autoimmune hypotheses cannot be supported, either from the pathology of the disease or by the response to treatment.
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It is concluded that the evidence of beneficial effects of hyperbaric oxygen therapy, despite the use of patients with advanced disease in trials, is very impressive, especially in chronic progressive disease. It is also concluded that there is need for further research and that such studies should examine the effects of hyperbaric oxygenation alone, and in combination with other therapeutic agents, in individual patients with the methods of real time investigation now available. Meanwhile, based on comparative efficacy and safety, hyperbaric oxygenation is recommended for treating early stages of MS, especially for treating cerebellar and bowel-bladder disorders. ACTH-cortisone, antiviral agents, co-polymer 1, double-blind studies, hyperbaric oxygen therapy, immunosuppressants, Kurtzke disability scores, MS etiology, MS pathophysiology MS therapy, multiple sclerosis (MS), plasmapheresis Introduction Multiple sclerosis (MS) is classified as a demyelinating disease of the central nervous system (1) and is the most common of the demyelinating diseases. Despite over a century of investigation MS remains one of the most frustrating diseases for patients and physicians because there is no agreed upon etiology and there is no cure or agreed upon therapy.
Perhaps no other disease has had so many therapies proposed and had them fail (2, 3). The purpose of this article is to review some of the evidence for the etiology and pathophysiology of MS and match the information with current therapies. Specific attention will be directed at a critique of the basis for hyperbaric oxygen (HBO) as a new therapeutic modality for MS (summarized in Table 1). We concentrate on HBO because this therapeutic modality has generated an extremely emotional, as well as an intellectual controversy, perhaps more so than any previously proposed treatment.
Conclusions Of all the current therapies presumably based on an understanding of the etiology and pathophysiology of the disease process, HBOT has the soundest foundation. It is also the safest drug available. It is not surprising, therefore, to find that there is much positive evidence concerning the beneficial effects of HBOT on cerebellar and bowel-bladder function to sanction its use for treating MS. Based on comparative efficacy and safety considerations, it is recommended that HBOT be used for treating early MS and for treating MS associated cerebellar and bowel-bladder dysfunction.
- Lumsden CE. The neuropathology of multiple sclerosis: multiple sclerosis and other demyelinating diseases. In: Vinken P. Bruyn GW, eds. Handbook of clinical neurology, vol. 9. Amsterdam: North Holland Publishing 1970: 217-309.
- Waksman BH. Rationales of current therapies for multiple sclerosis. Arch Neurol 1983; 40:671 672.
- Van den Noort S. Therapeutic fads and quack care. Arch Neurol 1983; 40:673-674. 4. Adams CWM. Pathology of multiple sclerosis: progression of the lesion. Br Med Bull 1977; 33:15-20.
- Allen IV. The pathology of multiple sclerosis—-fact, fiction and hypotheses. Neuropathol Neurobiol 1981; 7:169-182.
- Brownell B. Hughes JT. The distribution of plaques in the cerebrum in multiple sclerosis. Neurol Neurosurg Psychiatry 1962; 25:315-320.
- Dawson Jw The histology of disseminated sclerosis. Trans R Soc Edinb 1916; 1:(3)517-540.
- Pollock M, Calder C, Alpress S. Peripheral nerve abnormality in multiple sclerosis. Ann Neurol 1977; 2:41-48.
- Han M. Periphlebitis retinae in association with multiple sclerosis. Psychiatr Neurol Scand 1953; 29:175-189. 10.AitaJF, Bennett DR, Anderson RE, Ziter F. Cranial CT appearance of acute multiple sclerosis. Neurology 1978; 28:251-255.
- Swank RL. Subcutaneous hemorrhages in multiple sclerosis. Neurology 1958; 8:497-499.
- Dow RS, Berglund G. Vascular pattern of lesions of multiple sclerosis. Arc Neurol 1942; 47:118.
- Brooks DJ, Leenders KL, Head G. et al. Studies on regional cerebral oxygen utilization and cognitive function in multiple sclerosis. J Neurol Neurosurg Psychiatry 1984; 47:1182-1191.
- Kelly DL Jr, Lassiter KRL, Vongsvivut A, Smith JM. Effects of hyperbaric oxygenation and tissue Oxygen studies in experimental paraplegia.J Neurosurg 1972; 36:425-429.
- Weiner HL. COP I therapy for multiple sclerosis. N EngJ Med 1987; 317:442-444.
- Waksman BH, Reynolds WE. Multiple sclerosis as a disease of immune regulation. Proc Soc Exp Biol Med 1984; 175:282-294.
- Cook SD, Dowling PC. Multiple sclerosis and viruses: an overview. Neurobiology 1980; 30: 80-91.
- Poser CM. Pathogenesis of multiple sclerosis. Acta Neuropathol (Berl) 1986; 71:1-10
- Wolfgram F. What if multiple sclerosis isn’t an immunological or a viral disease? The case for a circulating toxin. Neurochem Res 1979; 4:1-4.
- Waksman B. Pathogenic mechanisms in multiple sclerosis. Ann NY Acad Sci 1984; 436:125-129.
- Arnason B. Relevance of experimental allergic encephalomyelitis to multiple sclerosis. Neurol Clin 1983; 1:765-782.
- Hickey WF Kimura H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 1988; 239:290 292.
- Spencer PS, Nunn PB, Hugon J. et al. Guam amyotrophic lateral sclerosis—parkinsonism— dementia linked to a plant excitant neurotoxin. Science 1987; 237:517-522.
- Lewin R. Environmental hypothesis for brain diseases strengthened by new data. Science 1987; 237:483-484.
- Kunzke JF. Epidemiologic contributions to multiple sclerosis: an overview. Neurology 1980; 30:61 -79.
- James PB. Evidence for subacute fat embolism as the cause of multiple sclerosis. Lancet 1982; 1:380-385.
- Stein EC, Schiffer RB,Jackson W. Young N. Multiple sclerosis and the work place: report of an industry-based cluster. Neurology 1987; 37:1672-1677.
- James PB. Oxygen for multiple sclerosis. Letter to editor. Lancer 1983; 1:1161-1162.
- Colover J. Oxygen for multiple sclerosis. Lancet ]983; 1:1383-1384.
- Oppenheimer DR. Oxygen for multiple sclerosis. Letter to editor. Lancet 1983; 11:632.
- James PB. Oxygen for multiple sclerosis. Lancer 1987;11:632
- Hassan HM. Chemistry and biochemistry of oxygen and its partially reduced derivatives. In: Gottlieb SF, Longmuir IS, Totter JR, eds Oxygen: an indepth study of its pathophysiology. Bethesda, MD: Undersea Medical Society 1983:307-338.
- McCord JM. Superoxide radical: a likely link between reperfusion injury and inflammation. Adv Free Radical Biol Med 1986; 2:325-345.
- Kontos HA. George E Brown memorial lecture: Oxygen radicals in cerebral vascular injury. Circ Res 1985; 57:508-516.
- Halliwell B. Oxidants and human disease: some new concepts. FASEB J. 1987; 1:358-364.
- Schmit PL, Gottlieb SF. Enhancement of cortical Nat, K + -ATPase by increased oxygen tensions: evidence of a new controlling mechanism. Brain Res 19#2; 242:271 278. l
- Pillunat LE, Stodtmeister R. Wilmanns 1. Pressure compliance of the optic nerve head in low tension glaucoma. BrJ Ophthalmol 1987; 71:181-187.
- Kitazawa Y. Shirato S. Yamamoto T. Optic disc hemorrhage in low tension glaucoma. Ophthalmology 1987; 93:853-857.
- McDonald Wl. Attitudes to the treatment of multiple sclerosis. Arch Neurol 1983; 40:667-670. 40. Ellison GW, Myers LW. Immunosuppressive drugs in multiple sclerosis: pro and con. Neurology 1980; 30:28-32.
- Johnson KP. Systemic interferon therapy for multiple sclerosis. Arch Neurol 1983; 40:681682. 42. Rose AS, Kuzme JW, Kurtzke JF, et al. Comparative study in the evaluation of therapy in multiple slerosis: ACTH vs placebo: final report. Neurology 1970; 20:1-59.
- MertinJ, Rudge P. Kremer M, et al. Double-blind controlled trial of immunosuppression in the treatment of multiple sclerosis: final report. Lancet 1982;11:351-353.
- Lhermitte F. Marteau R. Roullet E. Not so benign long-term immunosuppression in multiple sclerosis. Br MedJ 1984; 28:276-277.
- Bornstein MB,, Miller A, Slagle S. et al. A pilot trial of COP I in exacerbating-remitting multiple sclerosis. N EnglJ Med 1987; 317:408 414.
- Hauser SL, Dawson DM, LehrichJR, et al. Immunosuppression and plasmapheresis in chronic progressive multiple sclerosis. Arch Neurol 1983; 40:687-690.
- Stefoski D, Davis FA, Schauf CL. Acute improvement in exacerbating multiple sclerosis produced by intravenous administration of mannitol. Ann Neurol 1985; 18:443-4S0.
- Boschetty V, Cernoch J. Aplikace kysliku za pretlaku unekterych neurologicy ch onemocneni. Bratisl Lek Listy 1970; 53:298-302.
- Baixe JH. Bilan de onze anees d’activite en medicine hyperbare. Med Aer Spatiale Med Subaquatique Hyperbare 1978; 17:90-92.
- Neubauer RA. Treatment of multiple sclerosis with monoplace hyperbaric oxygenation. J Fla Med Assoc 1978; 65:101-104.
- Neubauer RA. Exposure of multiple sclerosis patients to hyperbaric oxygen at 1.5-2.. ATA: a preliminary report. J Fla Med Assoc 1980; 67:498-S04.
- Warren J. Sacksteder, MR, Thuning CA. Oxygen immunosuppression: modification of experimental allergic encephalomyelitis in rodents.J Immunol 1978; 121:315-320.
- Powell MR, Kizer V, Hruby S. Alvord EC Jr, Martin J. The effect of daily hyperbaric oxygen (2 ATA) on the course of chronic relapsing murine experimental allergic encephalomy elitist In: Bove AA, Bachrach AJ, Greebaum LJ Jr, eds. Underwater and hyperbaric physiology DE Proceedings of the ninth international symposium on underwater and hy perbaric physiology. Bethesda, MD: Undersea and Hyperbaric Medical Society, 1987: 847-857.
- Godovkin Dl, Zaytsev VS, Lotovin AP. Hyperbaric oxygenation as an immunity stimulus in multiple sclerosis. Sov Med 1982; 12:70-75.
- Hansborough JF, Piacentine JG, Eiseman B. Immunosuppression by hyperbaric oxygenation. Surgery 1980; 87:662-663. 56. Warren J. Sacksteder MR, Thuning CA. Modification of allergic encephalomvelitis in guinea pigs by oxygen therapy. Fed Proc 1977; 36:1298.
- James PB, Hills BA. Micro-embolism multiple sclerosis and the perivenous syndrome. Lancet 1988, in press.
- Neubauer RA. The effect of hyperbaric oxygen in prolonged coma. Possible identification of marginally functioning brain zones. Med Subacquea Iperbarica 1985; 5:7S-79.
- Myers RAM, chairman. Hyperbaric oxygen therapy: a committee report. Bethesda, MD: Undersea and Hyperbaric Medical Society, 1986.
- Frey G. Lampl L, Scherb W. HBO versus ACTH in multiple sclerosis–an alternative treatment! Federal Republic of Germany: Federal Armed Forces Hospital, 1984.
- Davis JC. Hyperbaric oxygen for patients with multiple sclerosis. Letters to the editor. Br Med J 1984; 288:1831
The paper by S. F Gottlieb and R. A. Neubauer focuses on multiple sclerosis (MS), a demyelinating disease of the central nervous system with no agreed-upon etiology or cure. The authors review various hypotheses regarding the cause and progression of MS, emphasizing the controversial use of hyperbaric oxygen therapy (HBOT) as a potential treatment. They present a new hypothesis on the disease’s origin and assess the validity of existing theories.
The authors analyze the efficacy of HBOT as a therapeutic option for MS, examining double-blind studies and discussing the treatment’s benefits and potential drawbacks. Despite the ongoing debate surrounding HBOT’s applicability, the paper concludes that HBOT shows promising results, particularly in chronic progressive MS cases. The article suggests that further research should investigate HBOT’s effects both alone and in combination with other treatments, using real-time investigation methods. In the meantime, based on its comparative safety and efficacy, HBOT is recommended for early-stage MS treatment, especially for addressing cerebellar and bowel-bladder disorders. The study positions HBOT as a promising therapeutic approach for MS, supported by its solid foundation and relative safety.