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December 1967, Vol 17, No. 6 >
Article | December 1967

Origin of Cerebrospinal Fluid Gamma Globulin in Subacute Sclerosing Leukoencephalitis

Robert W. P. Cutler, MD; Gordon V. Watters, MD; John P. Hammerstad, MD; Ezio Merler, PhD
[+] Author Affiliations

Submitted for publication July 6, 1967; accepted July 24.

Read before the 92nd annual meeting of the American Neurological Association, Atlantic City, NJ, June 14, 1967.

Reprint requests to Department of Neurology, Children's Hospital Medical Center, 300 Longwood Ave, Boston 02115 (Dr. Cutler).


Arch Neurol. 1967;17(6):620-628. doi:10.1001/archneur.1967.00470300062011
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References
Comments

ONE of the characteristic features of subacute sclerosing leukoencephalitis (SSLE) is a prominent elevation of cerebrospinal fluid (CSF) γ-globulin concentration.1 In this study we have attempted to define the origin of the excess γ-globulin in the CSF. The exchange of gamma G globulin (IgG) labeled with radioactive iodine (125I) between the serum and CSF has been examined in two patients with SSLE and in three control subjects with normal CSF γ lin concentrations. In addition, the rate of flux of γ-globulin into the CSF was measured during ventriculolumbar perfusion of chemotherapeutic agents. Methotrexate was administered by the intraventricular route to two patients with pontine gliomas, and 5-iododeoxyuridine (IUDR) was administered to two patients with SSLE in an attempt to modify the course of these generally fatal diseases. Results were obtained which suggest that immunoglobulin is synthesized within the nervous system in SSLE.

Report of Cases  CASE 1.—This

REFERENCES

1 +
Demerol compound composition per milliliter; meperidine hydrochloride, 25 mg; chlorpromazine hydrochloride, 6.25 mg; and promethazine, 6.25 mg.
2 +
Bauer, H.: " Cerebrospinal Fluid Findings in Panencephalitis ," in van Bogaert, L., et al (eds.): Encephalitides , Amsterdam: Elsevier Publishing Co., 1961;, pp 675-680.
3 +
McFarlane, A.S.:  Efficient Trace: Labelling of Proteins With Iodine , Nature 182:53, 1958;.
4 +
Reif, A.E.:  A Simple Procedure for High Efficiency Radioiodination of Proteins , Fed Proc 25:726, 1966;.
5 +
Rubin, R.C., et al:  Cerebrospinal Fluid Perfusion for Central Nervous System Neoplasms , Neurology 16:680-692, 1966;.
6 +
Gornall. A.G.; Bardawill, C.J; and David, M.M.:  Determination of Serum Proteins by Means of the Biuret Reaction , J Biol Chem 177:751-766, 1949;.
7 +
Patrick, R.L., and Theirs, R.E.:  The Direct Spectrophotometric Determination of Protein in Cerebrospinal Fluid , Clin Chem 9:283-295, 1963;.
8 +
Goodman, M., and Vulpe, M.:  A Quantitative Immunochemical Method for Determining Serum and Cerebrospinal Fluid Proteins , World Neurol 2:589-598, 1961;.
9 +
Scheidegger, J.J.:  Une micro-méthode de l'immuno-électrophorése , Int Arch Allerg 7:103-110, 1955;.
10 +
Merler, E., and Rosen, F.S.:  The Gamma Globulins: I. The Structure and Synthesis of the Immunoglobulins , New Eng J Med 275:536-542, 1966;.
11 +
Cohen, S., and Bannister, R.:  Immunoglobulin Synthesis Within the Central Nervous System in Disseminated Sclerosis , Lancet 1:366-367, 1967;.
12 +
Kabat, E.A.; Moore, D.H.; and Landow, H.:  An Electrophoretic Study of the Protein Components in the Cerebrospinal Fluid and Their Relationship to the Serum Proteins , J Clin Invest 21:571-577, 1942;.
13 +
Frick, E., and Scheid-Seydel, L.:  Untersuchungen mit 131I-Markiertem γ-Globulin zur Frage der Abstammung der Liquoreiweisskörper , Klin Wschr 36:857-863, 1958;.
14 +
Zilversmit, D.B.; Enterman, C.; and Fishler, M.C.:  On the Calculations of "Turnover Time" and "Turnover Rate" From Experiments Involving the Use of Labelling Agents , J Gen Physiol 26:325-331, 1943;.
15 +
Hochwald, G.M., and Wallenstein, M.:  Exchange of Albumin Between Blood, Cerebrospinal Fluid, and Brain in the Cat , Amer J Physiol 212:1199-1204, 1967;.
16 +
Hochwald, G.M.; Wallenstein, M.; and Wortis, S.B.:  Exchange of Gamma Globulin Between Cerebrospinal Fluid, Brain and Blood , Fed Proc 26:710, 1967;.
17 +
Cutler, R.W.P.; Deuel, R.K.; and Barlow, C.F.:  Albumin Exchange Between Plasma and Cerebrospinal Fluid , Arch Neurol 17:261-270, 1967;.
18 +
Tourtellotte, W.W., and Parker, J.A.:  Multiple Sclerosis: Correlation Between Immunoglobulin-G in Cerebrospinal Fluid and Brain , Science 154:1044-1046, 1966;.
19 +
Kolář, O., et al:  Zur Bedeutung der Gamma-G-Globulinfraktion in Hirngewebe bei der subakuten sklerosierenden Leukoencephalitis , Deutsch Z Nervenheilk 188:222-223, 1966;.
20 +
Dencker, S.J., and Kolář, O.:  The Cerebrospinal Fluid γ-Globulin Profile in Subacute Sclerosing Leucoencephalitis , Acta Neurol Scand 41( (suppl 13) ):135-140, 1965;.
21 +
Kolář, O.:  Immunoelectrophoretic Findings During the Course of Subacute Sclerosing Leukoencephalitis , Z Immun Forsch 131:236-246, 1966;.
22 +
Gonatas. N.K.:  Subacute Sclerosing Leukoencephalitis: Electron Microscopic and Cytochemical Observations on a Cerebral Biopsy , J Neuropath Exp Neurol 25:177-201, 1966;
23 +
Tellez-Nagel, I., and Harter, D.H.:  Subacute Sclerosing Leukoencephalitis: I. Clinico-pathological, Electron Microscopic, and Virological Observations , J Neuropath Exp Neurol 25:560-581, 1966;.
24 +
Connolly, J.H.; et al:  Measles-Virus Antibody and Antigen in Subacute Sclerosing Panencephalitis , Lancet 1:542-544, 1967;.
25 +
Webb, H.E., and Smith, C.E.G.:  Relation of Immune Response to Development of Central Nervous System Lesions in Viral Infections in Man , Brit Med J 2:1179-1181, 1966;.

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1 +
Demerol compound composition per milliliter; meperidine hydrochloride, 25 mg; chlorpromazine hydrochloride, 6.25 mg; and promethazine, 6.25 mg.
2 +
Bauer, H.: " Cerebrospinal Fluid Findings in Panencephalitis ," in van Bogaert, L., et al (eds.): Encephalitides , Amsterdam: Elsevier Publishing Co., 1961;, pp 675-680.
3 +
McFarlane, A.S.:  Efficient Trace: Labelling of Proteins With Iodine , Nature 182:53, 1958;.
4 +
Reif, A.E.:  A Simple Procedure for High Efficiency Radioiodination of Proteins , Fed Proc 25:726, 1966;.
5 +
Rubin, R.C., et al:  Cerebrospinal Fluid Perfusion for Central Nervous System Neoplasms , Neurology 16:680-692, 1966;.
6 +
Gornall. A.G.; Bardawill, C.J; and David, M.M.:  Determination of Serum Proteins by Means of the Biuret Reaction , J Biol Chem 177:751-766, 1949;.
7 +
Patrick, R.L., and Theirs, R.E.:  The Direct Spectrophotometric Determination of Protein in Cerebrospinal Fluid , Clin Chem 9:283-295, 1963;.
8 +
Goodman, M., and Vulpe, M.:  A Quantitative Immunochemical Method for Determining Serum and Cerebrospinal Fluid Proteins , World Neurol 2:589-598, 1961;.
9 +
Scheidegger, J.J.:  Une micro-méthode de l'immuno-électrophorése , Int Arch Allerg 7:103-110, 1955;.
10 +
Merler, E., and Rosen, F.S.:  The Gamma Globulins: I. The Structure and Synthesis of the Immunoglobulins , New Eng J Med 275:536-542, 1966;.
11 +
Cohen, S., and Bannister, R.:  Immunoglobulin Synthesis Within the Central Nervous System in Disseminated Sclerosis , Lancet 1:366-367, 1967;.
12 +
Kabat, E.A.; Moore, D.H.; and Landow, H.:  An Electrophoretic Study of the Protein Components in the Cerebrospinal Fluid and Their Relationship to the Serum Proteins , J Clin Invest 21:571-577, 1942;.
13 +
Frick, E., and Scheid-Seydel, L.:  Untersuchungen mit 131I-Markiertem γ-Globulin zur Frage der Abstammung der Liquoreiweisskörper , Klin Wschr 36:857-863, 1958;.
14 +
Zilversmit, D.B.; Enterman, C.; and Fishler, M.C.:  On the Calculations of "Turnover Time" and "Turnover Rate" From Experiments Involving the Use of Labelling Agents , J Gen Physiol 26:325-331, 1943;.
15 +
Hochwald, G.M., and Wallenstein, M.:  Exchange of Albumin Between Blood, Cerebrospinal Fluid, and Brain in the Cat , Amer J Physiol 212:1199-1204, 1967;.
16 +
Hochwald, G.M.; Wallenstein, M.; and Wortis, S.B.:  Exchange of Gamma Globulin Between Cerebrospinal Fluid, Brain and Blood , Fed Proc 26:710, 1967;.
17 +
Cutler, R.W.P.; Deuel, R.K.; and Barlow, C.F.:  Albumin Exchange Between Plasma and Cerebrospinal Fluid , Arch Neurol 17:261-270, 1967;.
18 +
Tourtellotte, W.W., and Parker, J.A.:  Multiple Sclerosis: Correlation Between Immunoglobulin-G in Cerebrospinal Fluid and Brain , Science 154:1044-1046, 1966;.
19 +
Kolář, O., et al:  Zur Bedeutung der Gamma-G-Globulinfraktion in Hirngewebe bei der subakuten sklerosierenden Leukoencephalitis , Deutsch Z Nervenheilk 188:222-223, 1966;.
20 +
Dencker, S.J., and Kolář, O.:  The Cerebrospinal Fluid γ-Globulin Profile in Subacute Sclerosing Leucoencephalitis , Acta Neurol Scand 41( (suppl 13) ):135-140, 1965;.
21 +
Kolář, O.:  Immunoelectrophoretic Findings During the Course of Subacute Sclerosing Leukoencephalitis , Z Immun Forsch 131:236-246, 1966;.
22 +
Gonatas. N.K.:  Subacute Sclerosing Leukoencephalitis: Electron Microscopic and Cytochemical Observations on a Cerebral Biopsy , J Neuropath Exp Neurol 25:177-201, 1966;
23 +
Tellez-Nagel, I., and Harter, D.H.:  Subacute Sclerosing Leukoencephalitis: I. Clinico-pathological, Electron Microscopic, and Virological Observations , J Neuropath Exp Neurol 25:560-581, 1966;.
24 +
Connolly, J.H.; et al:  Measles-Virus Antibody and Antigen in Subacute Sclerosing Panencephalitis , Lancet 1:542-544, 1967;.
25 +
Webb, H.E., and Smith, C.E.G.:  Relation of Immune Response to Development of Central Nervous System Lesions in Viral Infections in Man , Brit Med J 2:1179-1181, 1966;.

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