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Multiple sclerosis: Is it transplacentally induced?
Medical
Hypotheses
MULTIPLE SCLEROSIS C.M.Reading,
5: 1251-1255,
1979
: IS IT TRANSPLACENTALLY
INDUCED ?
10 Ian Avenue, North Curl Curl, N.S.W. 2099, Australia.
The aetiology of multiple sclerosis MS is not known. Most Abstract. research workers believe a viral aetiology. An alternate theory - namely transplacental induction of MS is outlined. Correlative evidence is drawn from epidemiological studies, models of transplacentally induced conditions, metabolic disturbances in utero that can affect myelin development or result in offspring with defective immunological competence and The relationship between B group vitamin deficiencies and surveillance. Primary, secondary and tertiary mineral deficiencies and MS is considered. prevention of MS in view of this theory is outlined. Key Words. Multiple sclerosis ; transplacental induction ; vitamin B qroup deficiencies ; copper, magnesium, zinc deficiency ; relationship to other autoimmune conditions - pernicious anaemia, thyroid disorder, diabetes. etc. Relevance to primary, secondary, tertiary prevention. Introduction. The aetiology of multiple sclerosis MS is not known. Most research workers believe a viral aetiology. An alternate theory - namely transplacental induction of MS is outlined. (1) Viral aetiology : One of the main hypotheses is that MS is connected with an infective agent, possibly a virus which remains dormant in the system for a number of years. Hence antibodies for viruses have been looked for and various antibodies against certain components of measles vi,rus have been found in MS (1,2) suggesting persistent infection by measles or a closely related virus somewhere in the body could have aetiological importance. Also electron microscopic studies have shown virus-like particles in MS patients including intracytoplasmic structures resembling viruses. However, these findings are not specific for the disease, nor have any of the findings been unequivocally identified as being viral in origin (3) and attempts to recover viruses from brains of MS patients have continuously failed to yield viruses (4). I believe the above are epiphenomena and that MS is transplacentally induced and not of viral aetiology. (2) Transplacental induction of MS. (a! Epidemiological studies suggest MS is caused by exposure to some agent, whether viral or not, under the age of 15. Patients who migrate from a high
1251
risk to a low risk country carry the original percentage risk of their native country if they migrate after the age of 15. The above supports transplacental induction - that is some metabolic disturbance in utero affecting vulnerable CNS tissue at critical periods in foetal development predisposes the offspring to MS later, and metabolic disturbances combine to act during early childhood and particularly during puberty as the CNS matures. Thus the damage is done by the age of 15 (puberty). (b) Models of transplacentally induced conditions : (i) Transplacentally induced brain tumours : It is now known that brain tumours in animals can be transplacentally induced. N ethyl N nitrosourea given to pregnant rats on the 15th day of gestation resulted in offspring that later developed brain turnours(transplacentally induced) with intracytoplasmic structures resembling viruses (5). (Compare MS.) If the true aetiology werenot known, a viral aetiology might well have been suspected (as in MS). Similarly in MS with raised IgG4 (6) (like some brain tumours)(7) and virus-like particles (but no virus) it is possible metabolic disturbances in the mother transplacentally induced changes in the foetus predisposing it to MS later in life. (ii) Transplacentally induced malignant melanoma : Raised IgG4 seen in MS and in infections is also seen in certain malignant melanoma (8) and these can be transplacentally induced and are not of viral aetiology. A woman can be born with a mole (transplacentally induced) and at puberty or pregnancy (hormonal, vitamin, mineral disturbances) a malignant change is seen. (iii) Transplacentally induced clear cell adeno-carcinoma of the vagina in teenage girls (9). The hormone stilboesterol during pregnancy induces the premalignant change and puberty - hormonal disturbances - induces the proliferation of the abnormal tissue. A similar model may exist for MS where the predisposed person (transplacentally induced) succumbs to MS following a very stressful puberty. (Some MS patients complain of being severely ill or anaemic at puberty.) (c) Metabolic changes in utero and the later development of MS : The metabolic disturbances in utero (in the person at risk for MS), in early childhood, and at puberty, affecting the normal development of the CNS and spinal cord and the immunological systems (T-lymphocyte defects, proneness to viral infections, etc 1 may be due to low B group vitamins, especially such vitamins as Bl, B6, B12 and low minerals such as copper, magnesium, zinc, all of which if low have been associated with defective myelin synthesis, and play an important role in hormonal metabolism and can affect inducers and organisers for normal CNS differentiation (and myelination) as well as normal functioning of the immune system. (i) Role of low B12 in utero and later development of MS : In 4 consecutive MS patients (3 women and 1 man) the mother had a history of pernicious anaemia (personal observation). Often the sibs have pernicious anaemia and in one family a woman has MS, her brother has low copper and his two
1252
daughters have borderline low copper. One MS patient whose vitamin assay showed low B12, Bl and B6 claims her mood swings decreased and she felt physically much improved on Bl, B6 and IM B12 (personal observation). It is not surprising that some of the symptoms and signs of MS are very similar to those of pernicious anaemia, and that intramuscular B12 may be helpful in MS. (ii) Role of low B6 in utero and later in the development of MS : Tt is known B6 deficient rats have offspring with defective myelin (11) and that B6 is important in linoleate acid metabolism and linoleate levels in lymphocytes in MS are lower than in controls (12). Also B6 deficiency in pregnancy in animals can lead to offspring with defective immunological competance and in MS many specific immune deficiencies exist (10). iiii) Other factors associated with MS and also B group vitamin deficiencies include : (1) \Jejunal changes such as villous and subvillous atrophy (13). (2 )
Optic neuritis and nystagmus.
(3) Mood disturbances seen in MS (14) are also seen in B group vitamin deficient patients (15). (4) Low CSF 5-HIAA in MS (16) (also seen in patients who committed suicide) can occur with low B6 and this also can cause depression. (5) Gluten-free diet has helped some MS patients. Gluten intolerance is commonly associated with B group vitamin deficiencies. Conclusion. Thus a clear understanding of the metabolic disturbances that may transplacentally induce MS could have great relevance to its primary prevention. Similarly in the latent MS patient the condition may be postponed or may never arise later if that person does not become low in the cLuster of vitamins and minerals that allowed the vulnerable tissue to develop in the first place and whose deficiency would cause degeneration later (if low). Conversely, understanding the metabolic (internal milieu) disturbances associated with the appearance of MS, or its exacerbation, may not only shed light on how to prevent the condition arising or deteriorating but may also shed light on what caused the vulnerable tissue to develop in the first place. Where it is known a mother has pernicious anaemia (or other autoimmune disease such as diabetes, thyroid disorder, etc commonly associated with low Bl, B6 etc and often seen in MS families - personal observation) 'hen proper diet during pregnancy and while breast feeding the child, and good nutrition of that child during puberty may greatly decrease the risk of MS developing later in that person.
1253
Far more research into metabolic disturbances occurring in utero, post natally and at puberty needs to be done in MS patients. Measurement of vitamins, minerals, #globulinS(increased IgM suggestive of gluten intolerance, low IgA suggesting milk intolerance and other food allergies) should become routine in MS patients so that these defects can be corrected. Patients more at risk for MS because of their HLA makeup may statistically be more at risk for the metabolic disturbances mentioned - this also could be researched. References. 1.
Salmi AA, Norrby E and Panelius M. Identification of different measles virus specific antibodies in the serum and cerebrospinal fluid from patients with subacute sclerosing panencephalitis and multiple sclerosis. Infection and Immunity 6:248-154,1972.
2.
Salmi AA, Gollmar Y, Norrby E and Panelius M. Antibodies against three different structural components of measles virus in patients with multiple sclerosis, their siblings and matched controls. Acta Pathologica et Microbiologica Scandinavica 818:627-533,1973.
3. Multiple Sclerosis Research : Proceedings of a joint conference held by the Medical Research Council of the Multiple Sclerosis Society of Great Britain and Northern Ireland. p 168 Her Majesty's Statutary Office, London, 1975. 4.
Multiple Sclerosis Research : Proceedings of a joint conference held by the Medical Research Council of the Multiple Sclerosis Society of Great Britain and Northern Ireland. p 170 Her Majesty's Statutary Office, London, 1975.
5.
LantZosPL. Virus like particles in brain tumours induced by N ethyl N nitrosourea in rats. Acta Neuropath. (Berl) 29, 3:211,1974.
6.
Multiple Sclerosis Research : Proceedings of a joint conference held by the Medical Research Council of the Multiple Sclerosis Society of Great Britain and Northern Ireland. p. 10 Her Majesty's Statutary Office, London, 1975.
7. Castaigne P, Lhermitte F, &huller E, Perrin J and Delasuerie N. Etude electrophoretique sed proteins du liquide cephalo-sachidien daus 104 Cas de tumeurs du neuraxe : Revue Neurologique (Paris) 127:505-515,1972. 8.
Daveau M, et al. Ig& subclasses in malignant melanoma. Collect. Ann. Inst. Pasteur 128 C/1-2:113-116.
9.
Herbst AL, Kurman RJ, Scully RG and Poskanzer DC. Clear cell Adenocarcinoma of the Genital Tract in young females. New Eng. J. Med. 287:1259,1972.
10. Lamoureux G, et al. Immunological features in Multiple Sclerosis. Brit. Med. J. l/6003:183-186,1976.
1254
:I. Stephens MC and Dakshinamurti K. Brain Lipids in pyridoxine deficient rats. Neurobiology 5/5:262-269,1975. 12. Tsang WM, Belin J, Monro JA, Smith AD, Thompson RHS and Zilkha KT. Relationship between plasma and lymphocyte linoleate in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 39:769-771,1976. 17. Lange LS and Shiner M. Small bowel abnormalities in multiple sclerosis. Lancet 11:1319,1976. 14. Young AC, et al. Mental changes as an early feature of MS. Neurosurg. Psychiatry 39:1008-1013,1976.
J. Neurol.
15. Reading CM. Latent Pernicious Anaemia : A Preliminary Study. Med. J. Aust. 1:91,1975. 16. Davidson D, et al. Monoamine metabolites in cerebrospinal fluid in MS. J. Neurol. Neurosurg. Psychiatry 40:741-745,1977.
1255
Hypotheses
MULTIPLE SCLEROSIS C.M.Reading,
5: 1251-1255,
1979
: IS IT TRANSPLACENTALLY
INDUCED ?
10 Ian Avenue, North Curl Curl, N.S.W. 2099, Australia.
The aetiology of multiple sclerosis MS is not known. Most Abstract. research workers believe a viral aetiology. An alternate theory - namely transplacental induction of MS is outlined. Correlative evidence is drawn from epidemiological studies, models of transplacentally induced conditions, metabolic disturbances in utero that can affect myelin development or result in offspring with defective immunological competence and The relationship between B group vitamin deficiencies and surveillance. Primary, secondary and tertiary mineral deficiencies and MS is considered. prevention of MS in view of this theory is outlined. Key Words. Multiple sclerosis ; transplacental induction ; vitamin B qroup deficiencies ; copper, magnesium, zinc deficiency ; relationship to other autoimmune conditions - pernicious anaemia, thyroid disorder, diabetes. etc. Relevance to primary, secondary, tertiary prevention. Introduction. The aetiology of multiple sclerosis MS is not known. Most research workers believe a viral aetiology. An alternate theory - namely transplacental induction of MS is outlined. (1) Viral aetiology : One of the main hypotheses is that MS is connected with an infective agent, possibly a virus which remains dormant in the system for a number of years. Hence antibodies for viruses have been looked for and various antibodies against certain components of measles vi,rus have been found in MS (1,2) suggesting persistent infection by measles or a closely related virus somewhere in the body could have aetiological importance. Also electron microscopic studies have shown virus-like particles in MS patients including intracytoplasmic structures resembling viruses. However, these findings are not specific for the disease, nor have any of the findings been unequivocally identified as being viral in origin (3) and attempts to recover viruses from brains of MS patients have continuously failed to yield viruses (4). I believe the above are epiphenomena and that MS is transplacentally induced and not of viral aetiology. (2) Transplacental induction of MS. (a! Epidemiological studies suggest MS is caused by exposure to some agent, whether viral or not, under the age of 15. Patients who migrate from a high
1251
risk to a low risk country carry the original percentage risk of their native country if they migrate after the age of 15. The above supports transplacental induction - that is some metabolic disturbance in utero affecting vulnerable CNS tissue at critical periods in foetal development predisposes the offspring to MS later, and metabolic disturbances combine to act during early childhood and particularly during puberty as the CNS matures. Thus the damage is done by the age of 15 (puberty). (b) Models of transplacentally induced conditions : (i) Transplacentally induced brain tumours : It is now known that brain tumours in animals can be transplacentally induced. N ethyl N nitrosourea given to pregnant rats on the 15th day of gestation resulted in offspring that later developed brain turnours(transplacentally induced) with intracytoplasmic structures resembling viruses (5). (Compare MS.) If the true aetiology werenot known, a viral aetiology might well have been suspected (as in MS). Similarly in MS with raised IgG4 (6) (like some brain tumours)(7) and virus-like particles (but no virus) it is possible metabolic disturbances in the mother transplacentally induced changes in the foetus predisposing it to MS later in life. (ii) Transplacentally induced malignant melanoma : Raised IgG4 seen in MS and in infections is also seen in certain malignant melanoma (8) and these can be transplacentally induced and are not of viral aetiology. A woman can be born with a mole (transplacentally induced) and at puberty or pregnancy (hormonal, vitamin, mineral disturbances) a malignant change is seen. (iii) Transplacentally induced clear cell adeno-carcinoma of the vagina in teenage girls (9). The hormone stilboesterol during pregnancy induces the premalignant change and puberty - hormonal disturbances - induces the proliferation of the abnormal tissue. A similar model may exist for MS where the predisposed person (transplacentally induced) succumbs to MS following a very stressful puberty. (Some MS patients complain of being severely ill or anaemic at puberty.) (c) Metabolic changes in utero and the later development of MS : The metabolic disturbances in utero (in the person at risk for MS), in early childhood, and at puberty, affecting the normal development of the CNS and spinal cord and the immunological systems (T-lymphocyte defects, proneness to viral infections, etc 1 may be due to low B group vitamins, especially such vitamins as Bl, B6, B12 and low minerals such as copper, magnesium, zinc, all of which if low have been associated with defective myelin synthesis, and play an important role in hormonal metabolism and can affect inducers and organisers for normal CNS differentiation (and myelination) as well as normal functioning of the immune system. (i) Role of low B12 in utero and later development of MS : In 4 consecutive MS patients (3 women and 1 man) the mother had a history of pernicious anaemia (personal observation). Often the sibs have pernicious anaemia and in one family a woman has MS, her brother has low copper and his two
1252
daughters have borderline low copper. One MS patient whose vitamin assay showed low B12, Bl and B6 claims her mood swings decreased and she felt physically much improved on Bl, B6 and IM B12 (personal observation). It is not surprising that some of the symptoms and signs of MS are very similar to those of pernicious anaemia, and that intramuscular B12 may be helpful in MS. (ii) Role of low B6 in utero and later in the development of MS : Tt is known B6 deficient rats have offspring with defective myelin (11) and that B6 is important in linoleate acid metabolism and linoleate levels in lymphocytes in MS are lower than in controls (12). Also B6 deficiency in pregnancy in animals can lead to offspring with defective immunological competance and in MS many specific immune deficiencies exist (10). iiii) Other factors associated with MS and also B group vitamin deficiencies include : (1) \Jejunal changes such as villous and subvillous atrophy (13). (2 )
Optic neuritis and nystagmus.
(3) Mood disturbances seen in MS (14) are also seen in B group vitamin deficient patients (15). (4) Low CSF 5-HIAA in MS (16) (also seen in patients who committed suicide) can occur with low B6 and this also can cause depression. (5) Gluten-free diet has helped some MS patients. Gluten intolerance is commonly associated with B group vitamin deficiencies. Conclusion. Thus a clear understanding of the metabolic disturbances that may transplacentally induce MS could have great relevance to its primary prevention. Similarly in the latent MS patient the condition may be postponed or may never arise later if that person does not become low in the cLuster of vitamins and minerals that allowed the vulnerable tissue to develop in the first place and whose deficiency would cause degeneration later (if low). Conversely, understanding the metabolic (internal milieu) disturbances associated with the appearance of MS, or its exacerbation, may not only shed light on how to prevent the condition arising or deteriorating but may also shed light on what caused the vulnerable tissue to develop in the first place. Where it is known a mother has pernicious anaemia (or other autoimmune disease such as diabetes, thyroid disorder, etc commonly associated with low Bl, B6 etc and often seen in MS families - personal observation) 'hen proper diet during pregnancy and while breast feeding the child, and good nutrition of that child during puberty may greatly decrease the risk of MS developing later in that person.
1253
Far more research into metabolic disturbances occurring in utero, post natally and at puberty needs to be done in MS patients. Measurement of vitamins, minerals, #globulinS(increased IgM suggestive of gluten intolerance, low IgA suggesting milk intolerance and other food allergies) should become routine in MS patients so that these defects can be corrected. Patients more at risk for MS because of their HLA makeup may statistically be more at risk for the metabolic disturbances mentioned - this also could be researched. References. 1.
Salmi AA, Norrby E and Panelius M. Identification of different measles virus specific antibodies in the serum and cerebrospinal fluid from patients with subacute sclerosing panencephalitis and multiple sclerosis. Infection and Immunity 6:248-154,1972.
2.
Salmi AA, Gollmar Y, Norrby E and Panelius M. Antibodies against three different structural components of measles virus in patients with multiple sclerosis, their siblings and matched controls. Acta Pathologica et Microbiologica Scandinavica 818:627-533,1973.
3. Multiple Sclerosis Research : Proceedings of a joint conference held by the Medical Research Council of the Multiple Sclerosis Society of Great Britain and Northern Ireland. p 168 Her Majesty's Statutary Office, London, 1975. 4.
Multiple Sclerosis Research : Proceedings of a joint conference held by the Medical Research Council of the Multiple Sclerosis Society of Great Britain and Northern Ireland. p 170 Her Majesty's Statutary Office, London, 1975.
5.
LantZosPL. Virus like particles in brain tumours induced by N ethyl N nitrosourea in rats. Acta Neuropath. (Berl) 29, 3:211,1974.
6.
Multiple Sclerosis Research : Proceedings of a joint conference held by the Medical Research Council of the Multiple Sclerosis Society of Great Britain and Northern Ireland. p. 10 Her Majesty's Statutary Office, London, 1975.
7. Castaigne P, Lhermitte F, &huller E, Perrin J and Delasuerie N. Etude electrophoretique sed proteins du liquide cephalo-sachidien daus 104 Cas de tumeurs du neuraxe : Revue Neurologique (Paris) 127:505-515,1972. 8.
Daveau M, et al. Ig& subclasses in malignant melanoma. Collect. Ann. Inst. Pasteur 128 C/1-2:113-116.
9.
Herbst AL, Kurman RJ, Scully RG and Poskanzer DC. Clear cell Adenocarcinoma of the Genital Tract in young females. New Eng. J. Med. 287:1259,1972.
10. Lamoureux G, et al. Immunological features in Multiple Sclerosis. Brit. Med. J. l/6003:183-186,1976.
1254
:I. Stephens MC and Dakshinamurti K. Brain Lipids in pyridoxine deficient rats. Neurobiology 5/5:262-269,1975. 12. Tsang WM, Belin J, Monro JA, Smith AD, Thompson RHS and Zilkha KT. Relationship between plasma and lymphocyte linoleate in multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 39:769-771,1976. 17. Lange LS and Shiner M. Small bowel abnormalities in multiple sclerosis. Lancet 11:1319,1976. 14. Young AC, et al. Mental changes as an early feature of MS. Neurosurg. Psychiatry 39:1008-1013,1976.
J. Neurol.
15. Reading CM. Latent Pernicious Anaemia : A Preliminary Study. Med. J. Aust. 1:91,1975. 16. Davidson D, et al. Monoamine metabolites in cerebrospinal fluid in MS. J. Neurol. Neurosurg. Psychiatry 40:741-745,1977.
1255