Torben Fog

HISTOCOMPATIBILITY DETERMINANTS IN MULTIPLE SCLEROSIS, WITH SPECIAL REFERENCE TO CLINICAL COURSE

Abstract Twenty-eight randomly selected patients with multiple sclerosis (M.S.) were typed in the mixed-lymphocyte culture test for a specific lymphocyte determinant LD-7a by means of LD-7a homozygous stimulator cells. Nineteen (70%) of the patients were LD-7a positive, a frequency much higher than the 16% observed in healthy individuals. Thirteen of the patients carried HL-A7, and all of these were LD-7a positive, which is significantly different (p=0·004) from the frequency of about 56% of this determinant in twenty-five normal HL-A7 positive individuals. Of the remaining fifteen patients, six carried LD-7a, which is also a significantly higher frequency (p=0·009) than that observed in normal HL-A7 negatives (three in forty individuals). Family studies showed that the LD-7a character is inherited and not acquired. The progression of the disease was significantly (P

THE COURSE OF MULTIPLE SCLEROSIS

A review of 73 cases of multiple sclerosis (Table 1) followed during years by the same examiner is presented. The selection of patients is based only upon the readiness of the patient to continhe to co-operate. The duration of observation time is from 3 to 15 years, making in all 515 patient-years 7 years on an average. The patient was examined every 2. to 4. months, a complete neurological examination being performed and the patient asked for changes in the subjective state and the environment.

THE LONG‐TERM TREATMENT OF MULTIPLE SCLEROSIS WITH CORTICOIDS

The use of corticoids as a long-term treatment in multiple sclerosis (m.s) is based upon the well-known earlier studies of the positive effect of ACTH-treatment in acute phases of m.s., and Alexander et al’s (1958, 1961) studies on the effect of long-term treatment in m.s. with ACTH. Several papers on the treatment of 113.5. cases with corticoids have been published in recent years, but i t is difficult to draw convincing conclusions regarding the efficiency of this treatment.

Partial purification of MS specific brain antigens

The present study was devoted to an immunochemical elucidation of antigenic similarities and differences between cytoplasmic and microsomal fractions of six multiple sclerosis (MS) and seven non‐MS brain autopsy specimens. The antigenic composition of the samples studied was traced by crossed immunoelectrophoresis using antibodies made by immunization of rabbits with the corresponding fraction. The following data were obtained:

The clinical value of assaying proteins in the cerebrospinal fluid. A comparative study in methods.

Since Llic initial discovery by I,triiyrJ in 1912 Ilia[ the degree of coagulation of a colloidal gold solulion caused by addition of cerebrospinal fluid (CSF) could be used in the clinical diagnosis of general paresis, it ha5 bccln demonstrated by Kabat, Glusmnn & Knaub (1948) that there is an increase in gamma globulin fractions of CSF in multiple sclerosis (AIS), and thesc fraclions have sincch been found to bc factors giving rise to the coagulation in the Langc’s reaclion (Koboz et nl. 1953, Hloonifirld 196-1). In agreement with this, mcthods nerc recently devclopxl lo evaluate the pathological changes i n CSF proteins o n (wmi) quantitative basis. The gamma globulin delerniinalion is used predominantly for hlS diagnosis. The electrophoretic method was first applied to CSF by HrssrlzJik (1939) , and developed as a clinical method by Kabrrt r t nl. (1942) . Laler, Kabat devcloped tlic immunoprecipitation method in free buffer systciii ( K n b a f , Glusilian & Knarih 19-18). In electrophoretic dctcrniination there is the systematic error that the immunoglol.)ulin fractions overlap other protein fractions. IJurthcrmorc, no1 all of thc inimnnoglobnlin is localizcd in the gamma

The enhancing effect of multiple sclerosis brain homogenates on the active E-rosette forming lymphocytes in neurological disorders.

Peripheral blood lymphocytes from 23 out of 27 (85%) patients with multiple sclerosis responded to MS brain homogenates by increased formation of active E‐rosettes. Lymphocytes from only six out of 78 (8 %) patients with other neurological diseases responded to MS brain homogenates. The possible value of the test in the diagnosis of MS is discussed.

THE HEXOSAMINE CONCENTRATION IN THE SPINAL FLUID IN PATIENTS WITH DISSEMINATED SCLEROSIS

Hexosamine is an important component of the mucopolysaccharides in the connective tissue and is present also in the gangliosides of the central nervous system (cf. e.g. Dyrbye 1959 and Edgar 1957). Furthermore, certain mucopolysaccharides are chemically bound to the gangliosides. In disseminated sclerosis the primary change is destruction of the myelin sheaths in the central nervous system, and it would, therefore, seem reasonable to expect certain chemical changes in the spinal fluid and blood. Investigations on this aspect have been carried out by many authors, including C . M . Plum & Torben Fog (1959) and Clausen, Worm-Pedersen, S . E . Hansen, Plum and T . Fog (1960). Mucopolysaccharides contain hexosamine and must he presumed to be partially destroyed and released in disseminated sclerosis. The object of the present study was to investigate whether this process gives rise to alterations in the spinal fluid. In patients showing definite clinical signs of disseminated sclerosis we investigated the hexosamine content of the spinal fluid. For comparison, we also studied a number of patients suffering from other somatic or mental diseases. The total material comprises two control groups (38 patients) and 28 patients with disseminated sclerosis in various phases. The hexosamine analyses were carried.out by the Elson & Morgan (1933) method, modified by Boas (1953) and Dyrbye (1959) . Spectrophotometric determinations of absorption curves (wavelengths 400-600 mrn) were performed in order to guard against interference by other substances. The results were as follows:

Multiple sclerosis specific antigens in MS brains

Antigens in MS and non‐MS brains were investigated by means of crossed immunoelectrophoresis. Two MS specific antigens were found: a measles antigen which was present in microsomes and cytosole, and an unidentified antigen present only in cytosole.

Evaluation of disability, incapacity and environmental status scales in multiple sclerosis.

From the Danish Multiple Sclerosis (MS) population a representative sample of 249 patients with a clinically definite diagnosis of MS has been tested by use of the Functional System Scale and Disability Status Scale of Kurtzke and the Incapacity and Environmental Status Scales of the IFMSS. Validity and reliability of the items and the properties of summed scales have been estimated. A statistical evaluation showed that generally the Incapacity and the Environmental Status Scales worked well. Problems encountered with the use of the Incapacity scale are mentioned and on statistical grounds a proposal of an incapacity scale with fewer items is presented.

Oligoclonal IgG and measles antibody in CSF of multiple sclerosis patients.

Cerebrospinal fluid (CSF) was obtained from 50 neurological patients, 26 of whom suffered from multiple sclerosis (MS). Agar gel electrophoresis and determination of anti‐measles antibody titre were performed on the CSF samples. The frequency of elevated measles antibody titre was higher among the MS patients than among the patients with other neurological diseases. Furthermore, oligoclonal IgG in CSF occurred more often among the MS patients than among the other neurological patients. An association between high measles antibody titre and the presence of oligoclonal IgG was observed in CSF from both the MS patients and the patients with other neurological diseases. However, the nature of the correlation between occurrence of oligoclonal IgG and high measles antibody titre remains to be explained.