Multiple sclerosis (MS) has in recent times been referred to as "the great crippler of young adults:' It usually strikes victims in the prime of their life and is one of the most dreaded degenerative diseases of the nervous system. The symptoms of MS are quite variable, ranging from one or two attacks of weakness in a limb or blurred vision, to a relentless, progressive deterioration of speech, movement and other basic functions.
MS affects various parts of the nervous system by destroying myelin, a fatty sheath that insulates nerve fibers rather as a plastic sheath insulates electrical wire. This destruction leaves scars or plaques that short circuit the electrical signals passing through the nerve fibers. The scarring process is called sclerosis.
Figure 18 shows the degeneration of the myelin sheath.
Depending on the nerves affected, patients may suffer localized weakness or stiffness, visual difficulties, diminished bladder or bowel control and other . neurological dysfunctions. Attacks may be mild, lasting only days and followed by remission, but most sufferers relapse after months or years. A few experience rapid progression of the disease and are quickly disabled.
The causes of MS are still unclear. However, many theories have been put forward. Some point to environmental and/or genetic factors, and some researchers believe that certain viruses may be involved, or view MS as an autoimmune ailment (in which the immune system mistakenly attacks healthy tissue). Others are investigating dietary factors or exposure to toxins such as lead, mercury, pesticides and carbon monoxide. Yet another theory considers the role of allergies.
Conventional medicine treats the symptoms of MS but cannot cure it. However, some newer drugs show promise in diminishing the rate of relapse. Diets of all sorts have been widely tested without consistent results. Everything about this disease is difficult to study because symptoms vary so widely, patients often recover spontaneously and one can never be sure whether or not a treatment has been instrumental.
Multiple sclerosis is one of a group of nervous system diseases called neurodegenerative disorders that also includes Alzheimer's, Parkinson's and ALS (amyotrophic lateral sclerosis or Lou Gehrig's disease). Although their specific causes are unknown, a number of studies suggest that a large role is played by oxygen-derived free radical formation and/or inadequate antioxidant defenses.
OXIDATION AND MULTIPLE SCLEROSIS
The myelin sheaths destroyed by MS are made oflipids, fatty substances highly sensitive to damage by lipid peroxidation, a particularly agressive type of oxidation. Our key metabolic defenses are GSH and SOD (super-oxide dismutase). It has been shown that elevating these natural defense systems reduces the damage of oxidative stress.
Investigations looking specifically at the breakdown products of oxidation have revealed significantly higher levels in MS patients. Pradlip Toshniwal and Edwin Zarling from Loyola University in Chicago went one step further in their studies. They were able to show that these levels of oxidative stress corresponded to the severity of the MS attack.
Some authors including S.M. LeVine from the University of Kansas suggest that the pathological process leading to the demyelination of nerves is possible because the immune system cooperates with a free radical generating system present within the myelin sheaths. This explanation combines the two hypotheses that describe MS - that it is an autoimmune disease, and is also caused by oxidative stress. He describes how during a demyelination episode, macrophages (cells of the immune system that are supposed to act protectively) seek out myelin and release powerful chemicals (lipases, proteinases, H202 and others). These biochemicals result in tremendous levels of oxidative stress.
Such a hypothesis leads us to believe that either blunting the immune response or minimizing oxidative stress could help MS patients. Immunosuppressive drugs that blunt the immune response have had only limited success. This has driven researchers to find ways to improve antioxidant protection, glutathione modulation being one of the most promising areas.
GLUTATHIONE (GSH) AND MULTIPLE SCLEROSIS
Many studies have compared groups of MS patients to healthy individuals. Among other things, they have measured levels of reactive metabolites (break-down products of oxidation) and of protective enzymes, especially glutathione.
An Italian group headed by Vince Calabrese drew samples of cerebrospinal fluid (CSF) through spinal taps. CSF analysis is a good indicator of brain metabolism. They found that glutathione -peroxidase levels in the cerebro-spinal fluid of MS patients were consistently low. Their conclusion was that in MS, the fundamental activity of anti-oxidation is abnormal and that oxidative stress plays a causative role.
Another study looking at CSF was performed by the Swedes G. Ronquist and G. Frithz who tested spinal taps from a large number of patients including those with stroke, seizures, brain tumors and MS. The cerebrospinal fluid of MS patients was found to be almost entirely lacking in glutathione.
There is further evidence of the involvement of free radical elevation and glutathione depletion in MS. Helen Langemann in Switzerland measured glutathione levels within MS plaques themselves. Without exception, they were depleted.
Researchers led by L Singh at the University of South Carolina examined the fundamental tissue abnormality in multiple sclerosis. The actual myelin breakdown occurs to a large part because of the release of strong inflammatory chemicals called cytokines. These cytokines generate huge numbers of free radicals. Pretreating neurological tissues with NAC (x-acerylcysreine] to raise glutathione levels protected these tissues from demyelination. Conversely, when glutathione was chemically depleted, the demyelination grew worse.
Simpler studies demonstrating decreased blood levels of glutathione peroxidase in MS patients have been repeated by many Scandinavian, Italian and North American researchers. These levels as well can be inversely correlated with the degree of severity of the attack.
SELENIUM AND MULTIPLE SCLEROSIS
Some research suggests that low selenium levels are connected to the development of MS. Selenium is an essential part of the glutathione peroxidase enzyme and low selenium levels certainly decrease glutathione effectiveness. A Danish team led by J. Mai supplied high-dose antioxidant supplements to MS patients made up of 6 mg selenium, 2 g vitamin C, and 480 mg of vitamin E. These patients showed few side effects and glutathione peroxidase activity increased by a factor of five within five weeks.
CONCLUSION
MS is a difficult disease to study because its spontaneous remissions and relapses make it very unpredictable. It is therefore hard to correlate any sort of intervention with changes in a patient's condition. In order to be statistically significant, prospective trials would have to include hundreds of subjects.
However, certain findings have been demonstrated consistently in multiple sclerosis patients. The breakdown products of oxidative stress are present in large numbers, and the level of free radical formation corresponds to the severity of the MS attack. Furthermore, glutathione activity is clearly impaired in this disease.
Also, individual tissues suffer less free radical damage when antioxidants and glutathione therapy are used. Although not a cure, many authors have suggested that reduced oxidative damage would help MS patients, and suggest in particular the helpful role of elevated glutathione levels.
REFERENCES
CALABRESE V, RAFFAELE R, COSENTINO E, RIZZA V. Changes in cerebrospinal fluid levels of malondialdehyde and glutathione reductase activity in multiple sclerosis. International Journal of Clinical Pharmacology Research 14( 4 ):119-123, 1994
CLAUSEN J, JENSEN GE, NIELSEN SA. Selenium in chronic neurologic diseases. Multiple sclerosis and Batten's disease. Biological Trace Element Research 15:179-203, 1988
GUY J, ELLIS EA, HOPE GM, RAO NA. Antioxidant enzymes reduce loss of blood-brain barrier integrity in experimental optic neuritis. Archives of Ophthalmology 107(9): 1359-63 1989
J ENN E R P. Oxidative damage in neurodegenerative disease. Lancet 344:796-798, 1994
JENSEN GE, CLAUSEN J. Glutathione peroxidase and reductase, glucose-6-phosphate dehydrogenase and catalase activities in multiple sclerosis.
KARG E, KLIVENYI P, NEMETH I, ET AL. Nonenzymatic antioxidants of blood in multiple sclerosis. J. Neurol. 246:533-539, 1999
KNIGHT JA. Reactive oxygen species and the neurodegenerative disorders. Annals of Clinical Laboratory Science 27(1):11-25, 1997
KORPELA H, KINNUNEN E, JUNTUNEN J, KUMULAINEN J, KOSKENVUO M. Serum selenium concentration, glutathione peroxidase activity and lipid peroxides in a co-twin control study on multiple sclerosis. Journal of the Neurological Sciences 91(1-2):79-84, 1989
LANGEMANN H, KABIERSCH A, NEWCOM BE J. Measurement of low-molecular-weight antioxidants, uric acid, tyrosine and tryptophan in plaques and white matter from patients with multiple sclerosis. European Neurology 32(5):248-252,1992
LE VINE SM. The role of reactive oxygen species in the pathogenesis of multiple sclerosis. Medical Hypothesis 39(3):271-274, 1992
MAl J, SORENSON PS, HANSEN jc, High dose antioxidant supplementation to MS patients. Effects on glutathione peroxidase, clinical safety and absorption of selenium. Biological Trace Element Research 24(2):109-117, 1990
MAZZELLA GL, SINFORIANI E, SAVOLDI F, ALLEGRINI M, LANZOLA E, SCELSI R. Blood cells glutathione peroxidase activity and selenium in multiple sclerosis. European Neurology 22(6):442-446,1983
POLIDORO G, DI ILIO C, ARDUINI A, LA ROVERE G, FEDERICI G. Superoxide dismutase, reduced glutathione and TBA-reactive products in erythrocytes of patients with multiple sclerosis. International Journal of Biochemistry 16(5):505-S09,1984
RONQUIST G, FRITHZ G. Adenylate kinase activity and glutathione concentration of cerebrospinal .fluid in different neurological disorders. European Neurology 18(2):106-110, 1979
SHUKLA VK, JENSEN GE, CLAUSEN J. Erythrocyte glutathione peroxidase deficiency in multiple sclerosis. Acta Neurology Scandinavia 56( 6):542-550, 1977
SIMONIAN NA, COYLEJT. Oxidative stress in neurodegenerative diseases. Annual Review of Pharmacology & Toxicology 36:83-106, 1996
SINGH I, PAHAN K, KHAN M, SINGH AK. Cytokine-mediated induction of ceramide production is redox-sensitive. Implications to proin.flammatory cytokine-mediated apoptosis in demyelinating diseases. J. BioI. Chern. 273:20354-20362, 1998
SZEINBERG A, GOLAN R, BEN EZZER J, SAROVA-PINHAS I, SADEH M, BRAHAM J. Decreased erythrocyte glutathione peroxidase activity in multiple sclerosis. Acta Neurology Scandinavia 60(5):265-271, 1979
TOSHNIWAL PK, ZARLING EJ. Evidence for increased lipid peroxidation in multiple sclerosis. Neurochemistry Research 17(2):205-207, 1992
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