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Multiple Sclerosis De Novo CNS IgG Synthesis: Effect of CNS Irradiation

Multiple Sclerosis De Novo CNS IgG Synthesis: Effect of CNS Irradiation Abstract • Megavoltage CNS irradiation was given to 20 patients with clinically definite multiple sclerosis (MS) to determine if de novo CNS IgG synthesis could be eradicated. In all five patients given 1,200 rads, a transient reduction in the de novo CNS IgG synthesis rate was noted. In ten patients given 1,800 rads, the following occurred: a reduction in synthesis rate in three patients, a reduction followed by enhancement in two, only enhancement in four, and no change in one. In all five additional patients, a therapy of adrenocorticotropic hormone (ACTH) followed by prednisone in combination with 1,800 rads produced greater and more persistent decreases in CNS IgG synthesis, but did not block the enhancement effect. Only two of 19 patients who had abnormal CNS IgG synthesis rates had reductions to normal; no patients showed changes in the number or pattern CSF IgG oligoclones. Hence, no treatment eradicated de novo CNS IgG synthesis. A persistent decrease in CSF leukocytes occurred in all 20 patients due to the reduction of small lymphocytes (not dose related). The blood-brain-barrier to albumin concentration was transiently damaged in 11 of 15 patients given irradiation, but when patients were premedicated with ACTH/ prednisone therapy, no damage was found. None of the patients demonstrated neurological improvement, change in the activity of their disease, or persistent adverse effects. References 1. Lisak RP: Multiple sclerosis: Immunologic aspects . Ann Clin Lab Sci 5:324-329, 1975. 2. Tourtellotte WW: Cerebrospinal fluid in multiple sclerosis , in Vinken P, Bruyn GW (eds): Handbook of Clinical Neurology . Amsterdam, North-Holland Publishing Co, 1970, vol 9, pp 324-382. 3. Tourtellotte WW: On cerebrospinal fluid immunoglobulin-G (IgG) quotients in multiple sclerosis and other diseases: A review and a new formula to estimate the amount of IgG synthesized per day by the central nervous system . J Neurol Sci 10:279-304, 1970.Crossref 4. Tourtellotte WW: Cerebrospinal fluid immunoglobulins and the central nervous system as an immunological organ particularly in multiple sclerosis and subacute sclerosing panencephalitis , in Rowland LP (ed): ARNMD Immunological Disorders of the Nervous System . Baltimore, Williams & Wilkins Co, 1971, vol 49, pp 112-155. 5. Tourtellotte WW: Interaction of local central nervous system immunity and systemic immunity in the spread of multiple sclerosis demyelination , in Wolfgram F, Ellison GW, Stevens JG, et al (eds): Multiple Sclerosis: Immunology, Virology and Ultrastructure . New York, Academic Press Inc, 1972, chap 16, pp 285-332. 6. Tourtellotte WW: What is multiple sclerosis? Laboratory criteria for diagnosis , in Davison AN, Humphrey JH, Liversedge AL, (eds): Multiple Sclerosis Research . New York, Elsevier Scientific Publishing Co, 1975, pp 9-26. 7. Tourtellotte WW, Ma BI: Multiple sclerosis: The blood-brain-barrier and the measurement of de novo central nervous system IgG synthesis . Neurology 28:76-83, 1978.Crossref 8. Kim SU, Murray MR, Tourtellotte WW, et al: Demonstration in tissue culture of myelinotoxicity in cerebrospinal fluid and brain extracts from multiple sclerosis patients . J Neuropathol Exp Neurol 29:420-431, 1970.Crossref 9. Tabira T, Webster H., Wray SH: Multiple sclerosis cerebrospinal fluid produces myelin lesions in tadpole optic nerves . N Engl J Med 295:644-649, 1976.Crossref 10. Stendahl-Broden L, Link H, Kristensson K: Myelinotoxic activity on tadpole optic nerve of cerebropsinal fluid from patients with optic neuritis . Neurology 29:882-886, 1979.Crossref 11. Frick VE, Stickl H: Zur pathogenese der Multiplen Sklerose. Antikörperabhängige Zytotoxizität von Lymphozyten gegen basisches Protein der Markscheide bei Multipler Sklerose . Fortschr Med 95:2235-2242, 1977. 12. Panitch HS, Huffer DA, Johnson KP: Antibodies to myelin basic protein in multiple sclerosis: Clinical conditions . Neurology 28:394, 1978. 13. Anderson RE, Warner NL: Radiosensitivity of T and B lymphocytes: III. Effect of radiation on immunoglobulin production by B cells . J Immunol 115:161-169, 1975. 14. Tourtellotte WW, Potvin AR, Fleming JO, et al: Multiple sclerosis: Measurement and validation of CNS IgG synthesis rate: Measurement and validation . Neurology 30:240-244, 1980.Crossref 15. Tourtellotte WW, Tavolato B, Parker JA, et al: Cerebrospinal fluid electroimmunodiffusion: An easy, rapid, sensitive, reliable, and valid method for the simultaneous determination of immunoglobulin-G and albumin . Arch Neurol 25:345-350, 1971.Crossref 16. Cawley LP, Minard BJ, Tourtellotte WW, et al: Immunofixation electrophoretic techniques applied to identification of proteins in serum and cerebrospinal fluid . Clin Chem 22:1262-1268, 1976. 17. Schumacher GA, Beebe G, Kibler RF, et al: Problems of experimental trials of therapy in multiple sclerosis: Report by the panel on the evaluation of experimental trials of therapy in multiple sclerosis . NY Acad Sci 122:552-568, 1965.Crossref 18. Rose AS, Ellison GW, Myers LW, et al: Criteria for the clinical diagnosis of multiple sclerosis . Neurology 26:20-22, 1976.Crossref 19. Kurtzke JF: Neurological impairment in multiple sclerosis and the disability status scale . Acta Neurol Scand 46:493-512, 1970.Crossref 20. Potvin AR, Tourtellotte WW, Syndulko K, et al: Multiple sclerosis clinical trials: A comprehensive system for the measurement and evaluation of neurological function , in Bauer H (ed): Progress in Multiple Sclerosis . Heidelberg, W Germany, 1980, pp 67-74. 21. Potvin AR, Tourtellotte WW: The neurological examination: Advancements in its quantification . Arch Phys Med Rehab 56:425-437, 1975. 22. Tourtellotte WW, Henderson WG, Tucker RP, et al: A randomized, double-blind clinical trial comparing the 22 vs 26-gauge needle in the production of the postlumbar puncture syndrome in normal individuals . Headache 12:78-78, 1972.Crossref 23. Verity GL: Tissue tolerance: Central nervous system . Radiology 91:1221-1225, 1968.Crossref 24. Duhain: Un cas de sclerosis en plaque, ameliore par la radiotherapie . C Acad Sci Ref Arch Elec Med , 1903, p 317. 25. Marburg O, Sgalitzer M: Rontgenbehandlung der Nervenkraukheiten , in Bumke O, Foerster 0 (eds): Hanbuch der Neurologie: Allgemeine Neurologie VIII. Allgemeine Therapie . Berlin, Verland von Julius Springer, 1936, pp 566-568. 26. Delherml, Modrel-Kahn, Targowla: A propos de la roentgentherapie de la sclerose en plaques . Soc Radiol Med Fran 24:63-69, 1936. 27. von Weisner W: Zur Rontegentherapie der multiplen skleroses . Strahlentherapie 65:283-303, 1939. 28. Rusken W: Die Behandlung der Nervenerkrankungen durch Rontgentiefenbestrahlung . Strahlentherapie 78:55-80, 1948. 29. Stutte H, Vogt A: Rontegentherapie Chronischer Nervenleiden . Strahlentherapie 78:161-200, 1948. 30. Bollini V, Manni U: Osservazieni sulla roentgenterapia della seringomielia a della sclerosi a placche . Rodiol Med 26:955-956, 1950. 31. Psenner L, Wachtler R: Radiotherapie der Errkrankungen des Nervensystem . Munchen-Berlin, Urban and Schwarzenbergo, 1970. 32. Sado T: Functional and ultrastructural studies of antibody-producing cells exposed to 10,000r in millipore diffusion chambers . Int J Rad Biol 15:1-22, 1969.Crossref 33. Simic MM, Petrovic MZ: Enhancement of residual antibody synthesis by irradiation of the spleen in pre-immunized rats . Nature 229:263-264, 1971.Crossref 34. Tourtellotte WW, Baumhefner RW, Potvin AR, et al: Multiple sclerosis de novo CNS IgG synthesis: Effect of ACTH and corticosteroids . Neurology , to be published. 35. Schettler L, Shealy NC: Experimental selective alteration of the blood-brain-barrier by x-irradiation . J Neurosurg 32:89-94, 1970.Crossref 36. Oldendorf WH, Cornford EM: A comparison of total body and local spinal cord irradiation in experimental allergic encephalomyelitis . J Neuropathol Exp Neurol 36:50-61, 1977.Crossref 37. David DS, Grieco MH, Cushman P Jr: Adrenal glucocorticoids after 20 years: A review of their clinically revelant consequences . J Chron Dis 22:637-711, 1970.Crossref 38. Thorn GW: The adrenal cortex: Reflections, progress and speculations . Trans Assoc Am Phys 86:65-81, 1973. 39. Cline MJ: The White Cell . Cambridge, Mass, Harvard University Press, 1975. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Multiple Sclerosis De Novo CNS IgG Synthesis: Effect of CNS Irradiation

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Publisher
American Medical Association
Copyright
Copyright © 1980 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1980.00500590044005
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Abstract

Abstract • Megavoltage CNS irradiation was given to 20 patients with clinically definite multiple sclerosis (MS) to determine if de novo CNS IgG synthesis could be eradicated. In all five patients given 1,200 rads, a transient reduction in the de novo CNS IgG synthesis rate was noted. In ten patients given 1,800 rads, the following occurred: a reduction in synthesis rate in three patients, a reduction followed by enhancement in two, only enhancement in four, and no change in one. In all five additional patients, a therapy of adrenocorticotropic hormone (ACTH) followed by prednisone in combination with 1,800 rads produced greater and more persistent decreases in CNS IgG synthesis, but did not block the enhancement effect. Only two of 19 patients who had abnormal CNS IgG synthesis rates had reductions to normal; no patients showed changes in the number or pattern CSF IgG oligoclones. Hence, no treatment eradicated de novo CNS IgG synthesis. A persistent decrease in CSF leukocytes occurred in all 20 patients due to the reduction of small lymphocytes (not dose related). The blood-brain-barrier to albumin concentration was transiently damaged in 11 of 15 patients given irradiation, but when patients were premedicated with ACTH/ prednisone therapy, no damage was found. None of the patients demonstrated neurological improvement, change in the activity of their disease, or persistent adverse effects. References 1. Lisak RP: Multiple sclerosis: Immunologic aspects . Ann Clin Lab Sci 5:324-329, 1975. 2. Tourtellotte WW: Cerebrospinal fluid in multiple sclerosis , in Vinken P, Bruyn GW (eds): Handbook of Clinical Neurology . Amsterdam, North-Holland Publishing Co, 1970, vol 9, pp 324-382. 3. Tourtellotte WW: On cerebrospinal fluid immunoglobulin-G (IgG) quotients in multiple sclerosis and other diseases: A review and a new formula to estimate the amount of IgG synthesized per day by the central nervous system . J Neurol Sci 10:279-304, 1970.Crossref 4. Tourtellotte WW: Cerebrospinal fluid immunoglobulins and the central nervous system as an immunological organ particularly in multiple sclerosis and subacute sclerosing panencephalitis , in Rowland LP (ed): ARNMD Immunological Disorders of the Nervous System . Baltimore, Williams & Wilkins Co, 1971, vol 49, pp 112-155. 5. Tourtellotte WW: Interaction of local central nervous system immunity and systemic immunity in the spread of multiple sclerosis demyelination , in Wolfgram F, Ellison GW, Stevens JG, et al (eds): Multiple Sclerosis: Immunology, Virology and Ultrastructure . New York, Academic Press Inc, 1972, chap 16, pp 285-332. 6. Tourtellotte WW: What is multiple sclerosis? Laboratory criteria for diagnosis , in Davison AN, Humphrey JH, Liversedge AL, (eds): Multiple Sclerosis Research . New York, Elsevier Scientific Publishing Co, 1975, pp 9-26. 7. Tourtellotte WW, Ma BI: Multiple sclerosis: The blood-brain-barrier and the measurement of de novo central nervous system IgG synthesis . Neurology 28:76-83, 1978.Crossref 8. Kim SU, Murray MR, Tourtellotte WW, et al: Demonstration in tissue culture of myelinotoxicity in cerebrospinal fluid and brain extracts from multiple sclerosis patients . J Neuropathol Exp Neurol 29:420-431, 1970.Crossref 9. Tabira T, Webster H., Wray SH: Multiple sclerosis cerebrospinal fluid produces myelin lesions in tadpole optic nerves . N Engl J Med 295:644-649, 1976.Crossref 10. Stendahl-Broden L, Link H, Kristensson K: Myelinotoxic activity on tadpole optic nerve of cerebropsinal fluid from patients with optic neuritis . Neurology 29:882-886, 1979.Crossref 11. Frick VE, Stickl H: Zur pathogenese der Multiplen Sklerose. Antikörperabhängige Zytotoxizität von Lymphozyten gegen basisches Protein der Markscheide bei Multipler Sklerose . Fortschr Med 95:2235-2242, 1977. 12. Panitch HS, Huffer DA, Johnson KP: Antibodies to myelin basic protein in multiple sclerosis: Clinical conditions . Neurology 28:394, 1978. 13. Anderson RE, Warner NL: Radiosensitivity of T and B lymphocytes: III. Effect of radiation on immunoglobulin production by B cells . J Immunol 115:161-169, 1975. 14. Tourtellotte WW, Potvin AR, Fleming JO, et al: Multiple sclerosis: Measurement and validation of CNS IgG synthesis rate: Measurement and validation . Neurology 30:240-244, 1980.Crossref 15. Tourtellotte WW, Tavolato B, Parker JA, et al: Cerebrospinal fluid electroimmunodiffusion: An easy, rapid, sensitive, reliable, and valid method for the simultaneous determination of immunoglobulin-G and albumin . Arch Neurol 25:345-350, 1971.Crossref 16. Cawley LP, Minard BJ, Tourtellotte WW, et al: Immunofixation electrophoretic techniques applied to identification of proteins in serum and cerebrospinal fluid . Clin Chem 22:1262-1268, 1976. 17. Schumacher GA, Beebe G, Kibler RF, et al: Problems of experimental trials of therapy in multiple sclerosis: Report by the panel on the evaluation of experimental trials of therapy in multiple sclerosis . NY Acad Sci 122:552-568, 1965.Crossref 18. Rose AS, Ellison GW, Myers LW, et al: Criteria for the clinical diagnosis of multiple sclerosis . Neurology 26:20-22, 1976.Crossref 19. Kurtzke JF: Neurological impairment in multiple sclerosis and the disability status scale . Acta Neurol Scand 46:493-512, 1970.Crossref 20. Potvin AR, Tourtellotte WW, Syndulko K, et al: Multiple sclerosis clinical trials: A comprehensive system for the measurement and evaluation of neurological function , in Bauer H (ed): Progress in Multiple Sclerosis . Heidelberg, W Germany, 1980, pp 67-74. 21. Potvin AR, Tourtellotte WW: The neurological examination: Advancements in its quantification . Arch Phys Med Rehab 56:425-437, 1975. 22. Tourtellotte WW, Henderson WG, Tucker RP, et al: A randomized, double-blind clinical trial comparing the 22 vs 26-gauge needle in the production of the postlumbar puncture syndrome in normal individuals . Headache 12:78-78, 1972.Crossref 23. Verity GL: Tissue tolerance: Central nervous system . Radiology 91:1221-1225, 1968.Crossref 24. Duhain: Un cas de sclerosis en plaque, ameliore par la radiotherapie . C Acad Sci Ref Arch Elec Med , 1903, p 317. 25. Marburg O, Sgalitzer M: Rontgenbehandlung der Nervenkraukheiten , in Bumke O, Foerster 0 (eds): Hanbuch der Neurologie: Allgemeine Neurologie VIII. Allgemeine Therapie . Berlin, Verland von Julius Springer, 1936, pp 566-568. 26. Delherml, Modrel-Kahn, Targowla: A propos de la roentgentherapie de la sclerose en plaques . Soc Radiol Med Fran 24:63-69, 1936. 27. von Weisner W: Zur Rontegentherapie der multiplen skleroses . Strahlentherapie 65:283-303, 1939. 28. Rusken W: Die Behandlung der Nervenerkrankungen durch Rontgentiefenbestrahlung . Strahlentherapie 78:55-80, 1948. 29. Stutte H, Vogt A: Rontegentherapie Chronischer Nervenleiden . Strahlentherapie 78:161-200, 1948. 30. Bollini V, Manni U: Osservazieni sulla roentgenterapia della seringomielia a della sclerosi a placche . Rodiol Med 26:955-956, 1950. 31. Psenner L, Wachtler R: Radiotherapie der Errkrankungen des Nervensystem . Munchen-Berlin, Urban and Schwarzenbergo, 1970. 32. Sado T: Functional and ultrastructural studies of antibody-producing cells exposed to 10,000r in millipore diffusion chambers . Int J Rad Biol 15:1-22, 1969.Crossref 33. Simic MM, Petrovic MZ: Enhancement of residual antibody synthesis by irradiation of the spleen in pre-immunized rats . Nature 229:263-264, 1971.Crossref 34. Tourtellotte WW, Baumhefner RW, Potvin AR, et al: Multiple sclerosis de novo CNS IgG synthesis: Effect of ACTH and corticosteroids . Neurology , to be published. 35. Schettler L, Shealy NC: Experimental selective alteration of the blood-brain-barrier by x-irradiation . J Neurosurg 32:89-94, 1970.Crossref 36. Oldendorf WH, Cornford EM: A comparison of total body and local spinal cord irradiation in experimental allergic encephalomyelitis . J Neuropathol Exp Neurol 36:50-61, 1977.Crossref 37. David DS, Grieco MH, Cushman P Jr: Adrenal glucocorticoids after 20 years: A review of their clinically revelant consequences . J Chron Dis 22:637-711, 1970.Crossref 38. Thorn GW: The adrenal cortex: Reflections, progress and speculations . Trans Assoc Am Phys 86:65-81, 1973. 39. Cline MJ: The White Cell . Cambridge, Mass, Harvard University Press, 1975.

Journal

Archives of Neurology – American Medical Association

Published: Oct 1, 1980

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