Multiple Sclerosis
Summary of the effects of HBO2 both in acute and semi-acute and long-term neurologic conditions: HBO2 reduces any pressure within the brain caused by swelling, restoring the functions of the blood brain barrier and cell membrane; It neutralizes toxic products in the brain, and over a period of time, enhances growth of new blood vessels; It also acts as a scavenger of free radicals and promotes internal cleaning of debris; HBO2 also reduces the stickiness of blood products (white blood cells and platelets), and makes oxygen available for use without energy transfer (when the hemoglobin carries oxygen, it requires energy to deliver to the tissue spaces); With HBO2 the free oxygen is available immediately for metabolic use. Interesting fact with MRI observations: MRI of people in the age bracket 20 - 40 with no symptoms shows that in this "normal" population that is white matter abnormalities present in about 40% of the people. Given that the resolution of MRI is probably at best a cubic millimetre or so, improved technology will undoubtedly uncover lesions with an even greater frequency.
The central area of the brain is known as the reticular formation which is derived from the germinal matrix. Because the nutrition of this area of the brain is largely dependent on the venous drainage it is very vulnerable to hypoxia and damage to the blood-brain barrier. The end result of this damage is a non specific sense of fatigue. This characterises the microbubble embolism of decompressin sickness and even AIDS patients where the blood brain barrier is damaged by the virus. Blood brain barrier damage leads to edema and as the extravasation of inflammatory proteins occurs complement activation. The edema reduces oxygen transport and the inflammation increases oxygen demand - hence hypoxia and fatigue. This and many other relevant references are in my Lancet article. Evidence for subacute fat embolism as the cause of multiple sclerosis.
1982;i:380 - 386. Abbot et al, Effect of hyperoxia at 1 and 2 ATA on hypoxia and hypercapnia in human skin in experimental inflammation. J Appl Physiol 1994;77:767-773.
Philip James, MD Wolfson Hyperbaric Medicine Unit, University of Dundee.
Multiple Sclerosis
Multiple sclerosis: its etiology, pathogenesis, and therapeutics with emphasis on the controversial use of HBO2 Journal Hyperbaric Medicine 1988; 3(3):143-164 Gottlieb SF, Neubauer RA. 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. 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 system1 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 (HBO2) as a new therapeutic modality for MS (summarized in Table 1). We concentrate on HBO2 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, HBO2 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 HBO2 on cerebellar and bowel bladder function to sanction its use for treating MS.
Based on comparative efficacy and safety considerations, it is recommended that HBO2 be used for treating early MS and for treating MS associated cerebellar and bowel-bladder dysfunction. References: 1. 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. 2. Waksman BH. Rationales of current therapies for multiple sclerosis. Arch Neurol 1983; 40:671 672. 3. 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. 5. Allen IV. The pathology of multiple sclerosis-fact, fiction and hypotheses. Neuropathol Neurobiol 1981; 7:169-182. 6. Brownell B. Hughes JT. The distribution of plaques in the cerebrum in multiple sclerosis. Neurol Neurosurg Psychiatry 1962; 25:315-320. 7. Dawson Jw The histology of disseminated sclerosis. Trans R Soc Edinb 1916; 1:(3)517-540. 8. Pollock M, Calder C, Alpress S. Peripheral nerve abnormality in multiple sclerosis. Ann Neurol 1977; 2:41-48. 9. 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. 11. Swank RL. Subcutaneous hemorrhages in multiple sclerosis. Neurology 1958; 8:497-499. 12. Dow RS, Berglund G. Vascular pattern of lesions of multiple sclerosis. Arc Neurol 1942; 47:118. 13. 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. 14. 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. 15. Weiner HL. COP I therapy for multiple sclerosis. N EngJ Med 1987; 317:442-444. 16. Waksman BH, Reynolds WE. Multiple sclerosis as a disease of immune regulation. Proc Soc Exp Biol Med 1984; 175:282-294. 17. Cook SD, Dowling PC. Multiple sclerosis and viruses: an overview. Neurobiology 1980; 30: 80-91. 18. Poser CM. Pathogenesis of multiple sclerosis. Acta Neuropathol (Berl) 1986; 71:1-10. 19. Wolfgram F.
What if multiple sclerosis isn't an immune or a viral disease? The case for a circulating toxin. Neurochem Res 1979; 4:1-4. 20. Waksman B. Pathogenic mechanisms in multiple sclerosis. Ann NY Acad Sci 1984; 436:125-129. 21. Arnason B. Relevance of experimental allergic encephalomyelitis to multiple sclerosis. Neurol Clin 1983; 1:765-782. 22. Hickey WF Kimura H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 1988; 239:290 292. 23. 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. 24. Lewin R. Environmental hypothesis for brain diseases strengthened by new data. Science 1987; 237:483-484. 25 Kunzke JF.Epidemiologic contributions to multiple sclerosis: an overview.Neurology 1980; 30:61 -79. 26. James PB.
Evidence for subacute fat embolism as the cause of multiple sclerosis. Lancet 1982; 1:380-385. 27. 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. 28. James PB. Oxygen for multiple sclerosis. Letter to editor. Lancer 1983; 1:1161-1162. 29. Colover J. Oxygen for multiple sclerosis. Lancet ]983; 1:1383-1384. 30. Oppenheimer DR. Oxygen for multiple sclerosis. Letter to editor. Lancet 1983; 11:632. 31. James PB. Oxygen for multiple sclerosis. Lancer 1987; 11:632. 32. Hassan HM. Chemistry and biochemistry of oxygen and its partially reduced derivatives. In: Gottlieb SF, Longmuir IS, Totter JR, eds Oxygen: an in-depth study of its pathophysiology. Bethesda, MD: Undersea Medical Society 1983:307-338. 33. McCord JM. Superoxide radical: a link between reperfusion injury and inflammation. Adv Free Radical Biol Med 1986; 2:325-345. 34. Kontos HA. George E Brown memorial lecture: Oxygen radicals in cerebral vascular injury. Circ Res 1985; 57:508-516. 35 Halliwell B. Oxidants and human disease: some new concepts. FASEB J. 1987; 1:358-364. 36. 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. 37. Pillunat LE, Stodtmeister R. Wilmanns 1. Pressure compliance on optic nerve head in low tension glaucoma. BrJ Opht 1987; 71:181-7. 38. Kitazawa Y. Shirato S. Yamamoto T. Optic disc hemorrhage in low tension glaucoma. Ophthalmology 1987; 93:853-857. 39. 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. 41. 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. 43. 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. 44. Lhermitte F. Marteau R. Roullet E. Not so benign long-term immunosuppression in multiple sclerosis. Br MedJ 1984; 28:276-277. 45 Bornstein MB,, Miller A, Slagle S. et al. A pilot trial of COP I in exacerbating-remitting MS. N EnglJ Med 1987; 317:408 414. 46. Hauser SL, Dawson DM, LehrichJR, et al.
Immunosuppression and plasmapheresis in chronic progressive multiple sclerosis. Arch Neurol 1983; 40:687-690. 47. Stefoski D, Davis FA, Schauf CL. Acute improvement in exacerbating multiple sclerosis produced by intravenous administration of mannitol. Ann Neurol 1985; 18:443-4S0. 48. Boschetty V, Cernoch J. Aplikace kysliku za pretlaku u nekterych neurologicy ch onemocneni. Bratisl Lek Listy 1970; 53:298-302. 49. Baixe JH. Bilan de onze anees d'activite en medicine hyperbare. Med Aer Spatiale Med Subaquatique Hyperbare 1978; 17:90-92. 50. Neubauer RA. Treatment of multiple sclerosis with monoplace hyperbaric oxygenation. J Fla Med Assoc 1978; 65:101-104. 51. 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. 52. Warren J. Sacksteder, MR, Thuning CA. Oxygen immunosuppression: modification of experimental allergic encephalomyelitis in rodents.J Immunol 1978; 121:315-320. 53. 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 hyperbaric physiology. Bethesda, MD: Undersea and Hyperbaric Medical Society, 1987: 847-857. 54. Godovkin Dl, Zaytsev VS, Lotovin AP. Hyperbaric oxygenation as an immunity stimulus in MS. Sov Med 1982; 12:70-75. 55. 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. 57. James PB, Hills BA. Micro-embolism multiple sclerosis and the perivenous syndrome. Lancet 1988, in press. 58. Neubauer RA. The effect of hyperbaric oxygen in prolonged coma. Possible identification of marginally functioning brain zones. Med Subacquea Iperbarica 1985; 5:7S-79. 59. Myers RAM, chairman. Hyperbaric oxygen therapy: a committee report. Bethesda, MD: UHMS, 1986. 60. Frey G. Lampl L, Scherb W. HBO2 versus ACTH in multiple sclerosis--an alternative treatment! Federal Republic of Germany: Federal Armed Forces Hospital, 1984. 61. Davis JC. Hyperbaric oxygen for patients with multiple sclerosis. Letters to the editor. Br Med J 1984; 288:1831.
Only long-term controlled studies have shown persistent benefit of HBO for MS. A very recent publication has endorsed their findings and concludes that HBO treatment should be instigated as soon as the condition is diagnosed and before irreversible lesions have become established. -
Treatment of Multiple Sclerosis with Prolonged courses of Hyperbaric Oxygen:
A 13 year Update - Perrins D.J.D. & James P.B. In Proc. 12th International Congress on Hyperbaric Med. Sept 1996, Best Publishing
Company ISBN: 0-941332-63-2. The Permutter Hyperbaric Centre and MS Therapy. I have been involved in the controversy over the use of more oxygen for MS patients since 1981. It would be difficult to find a more convincing reason for increasing the oxygen dosage than in the disease process which underlies the formation of the scars. It begins as an acute swelling around veins in the nervous system and this process can be observed directly in many patients during acute attacks in the retina. The dispute over the etiology of the disease between the proponents of a vascular basis and the rest e.g. autoimmunity, goes back to the 1860's. (Rindfleisch and Charcot) but the evidence of blood vessel involvement is consistently ignored. Ian McDonald - who has just retired as Professor of Neurology at the National Hospital in London stated in 1986. "The occurrence of vascular lesions in an unmyelinated region (the retina) provides support for the view that the vasculas changes in multiple sclerosis are primary and not as some have suggested secondary to myelin breakdown." Optic Neuritis. eds Hess RF, Plant GT. Cambridge University Press 1986 p47. ISBN 0 521 30247 1.
Multiple and sclerosis describe the presence of scarring in the CNS - the end result of the attempts of the nervous system to heal. The trials of the use of oxygen at addtional pressure selected patients whose disease durations were typically 15 years. This is nonsense as magnetic resonance spectroscopy has demonstrated lack of oxygen in the areas affected at the onset. (Lancet 1991;337:58). However if the patient has only one area affected then they do not have MULTIPLE areas of sclerosis and must wait a minimum of a month to qualify under the "diagnostic criteria" for multiple sclerosis. The neurologists response to the evidence from the controlled studies of oxygen therapy as less than enthusiastic, despite positive findings in patients with end stage disease. It is necessary to study history to understand the powerful factors that shape medical opinion and there is no better starting point than the story of Semmelweiss and the controlled trial related to the etiology of childbed fever in Vienna.
I will be posting an article about the Fischer trial from the New England journal of Medicine on the list soon, but if you want an object lesson in medical prejudice read the isssue of the journal that carried the results - Jan 27 1983 vol 308 and the editorials. Philip James, Wolfson Hyperbaric Medicine Unit. 1. Fischer BH, Marks M, Reich T. Hyperbaric-oxygen treatment of multiple sclerosis: A randomised, placebo controlled, double-blind study. N Engl J Med 1983;308:181-6. (This is a classic). 2. Pallotta R, Longobardi G, Fabbrocini G. Experience in protracted follow-up on a group of multiple sclerosis patients periodically treated with hyperbaric oxygen therapy. In Baixe J-H, ed. Symposium sur le traitment de la sclerosse multiple par l'oxygene hyperbare. Paris, 1986; 15-19. (22 relapsing/remitting patients were followed for 8 years. The incidence of relapses fell dramatically in the 11 treated patients and increased in the 11 controls.) 3. Oriani G, Barbieri S, Pirovani C, Mariani C. Hyperbaric oxygen in chronic progressive multiple sclerosis: a placebo-controlled, double-blind, randomised study with evoked potentials evaluation. In: Oriani G, Proc. 13th annual meeting of the European Undersea Biomedical Society. Palermo:1987 196-203 (44 patients with low disability scores. 22 treated once a week for a year and compared with 22 controls when there was an appreciable difference in outcome - P < 0.01.)
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