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Background: MOG-IgG is associated with non-MS demyelinating disease of the optic nerves, spinal cord and brain. Specificity has been issue so we validated the live and fixed MOG-IgG CBAs against the Oxford Autoimmune Neurology Diagnostic Laboratory (OANG) live CBA as a comparator with high specificity. Methods: At BC Neuroimmunology lab (BCNI), 54 MOG-IgG serum samples previously positive by live-CBA at OANG and BCNI were blindly tested by commercial fixed CBA. All 54 MOG IgG positives came from MOG-IgG positive patients. In addition, 256 samples from healthy people and other neurolgic disease were tested. Results: The live MOG-IgG CBA performed at BCNI was 100% concordant (54/54) with OANG live CBA. In contrast, only 49/54 samples were found seropositive by the commercial fixed CBA. The BCNI live-CBA identified 3/256 control samples as positive while 6/256 controls were positive on the fixed commercial CBA. On this cohort the live CBA is 100% sensitive, 98.8% specific and has PPV of 95%. The commercial fixed MOG test is 91% sensitive, 97.6% specific and has PPV of 87.5%. Conclusions: BCNI live MOG-IgG CBAs are in 100% agreement with MOG-IgG. Three positive results in non-MOGAD associated clinical phenotype require further investigation. These data confirm the superiority of the live MOG CBA.

The clinical and radiologic impact of developing neutralizing antibodies (NAbs) to interferon beta (IFNβ) while on this therapy for multiple sclerosis (MS) is assessed. On the basis of Class II and III evidence, it is concluded that treatment of patients with MS with IFNβ (Avonex, Betaseron, or Rebif) is associated with the production of NAbs (Level A). NAbs in the serum are probably associated with a reduction in the radiographic and clinical effectiveness of IFNβ treatment (Level B). In addition, the rate of NAb production is probably less with IFNβ-1a treatment than with IFNβ-1b treatment, although the magnitude and persistence of this difference is difficult to determine (Level B). Finally, it is probable that there is a difference in seroprevalence due to variability in the dose of IFNβ injected or in the frequency or route of its administration (Level B). Regardless of the explanation, it seems clear that IFNβ-1a (as it is currently formulated for IM injection) is less immunogenic than the current IFNβ preparations (either IFNβ-1a or IFNβ-1b) given multiple times per week subcutaneously (Level A). However, because NAbs disappear in some patients even with continued IFNβ treatment (especially in patients with low titers), the persistence of this difference is difficult to determine (Level B). Although the finding of sustained high-titer NAbs (>100 to 200 NU/mL) is associated with a reduction in the therapeutic effects of IFNβ on radiographic and clinical measures of MS disease activity, there is insufficient information on the utilization of NAb testing to provide specific recommendations regarding when to test, which test to use, how many tests are necessary, or which cutoff titer to apply (Level U).

Background: Few biomarkers of progressive multiple sclerosis (MS) are sensitive to change within the two-year time frame of a clinical trial. Objective: To identify biomarkers of MS disease progression with magnetic resonance spectroscopy (MRS) in secondary progressive MS (SPMS). Methods: Forty-seven SPMS subjects were scanned at baseline and annually for two years. Concentrations of N-acetylaspartate, total creatine, total choline, myo-inositol, glutamate, glutamine, and the sum glutamate+glutamine were measured in a single white matter voxel. Results: Glutamate and glutamine were the only metabolites to show an effect with time: with annual declines of (95% confidence interval): glutamate −4.2% (−6.2% to −2.2%, p < 10−4), glutamine −7.3% (−11.8% to −2.9%, p = 0.003), and glutamate+glutamine −5.2% (−7.6% to −2.8%, p < 10−4). Metabolite rates of change were more apparent than changes in clinical scores or brain atrophy measures. Conclusions: The high rates of change of both glutamate and glutamine over two years suggest they are promising new biomarkers of MS disease progression.

BACKGROUND: The role of plasma exchange is well established in the management of myasthenia gravis, an autoimmune disorder characterized by muscle weakness and caused by circulating IgG antibodies with specificity against the acetylcholine receptor. Plasma antibody removal by conventional means, however, is nonselective and uses replacement fluids (chiefly, albumin solution) derived from human plasma. STUDY DESIGN AND METHODS: The Canadian Apheresis Group undertook a study at two Canadian apheresis centers to clinically evaluate a staphylococcal protein A immunoadsorption system (EXCORIM) in myasthenia gravis patients. RESULTS: The immunoadsorption system was safe and well tolerated. Ten of 12 patients had improvement in their neurologic status, as measured by a 20-point scoring system. The mean improvement in the weakness score was significant for the group (p = 0.0013). CONCLUSION: Patients with myasthenia gravis respond to treatment with plasma immunoadsorption. Further studies are required for a cost-benefit analysis.

Patients with generalized myasthenia gravis (MG) often have associated ventilatory muscle involvement. It is not known whether patients with isolated ocular muscle involvement have identifiable involvement of their ventilatory muscles. Most studies have assessed muscle involvement by measuring muscle strength; however, we hypothesized that measures of ventilatory muscle endurance may be more sensitive tests of ventilatory muscle involvement in myasthenia gravis. We studied 17 patients with myasthenia gravis (four with ocular involvement alone and 13 with varying degrees of generalized myasthenia gravis). Spirometry, ventilatory muscle strength (maximum inspiratory and expiratory pressures (MIP and MEP)) and endurance (2 min incremental threshold loading test) were measured before and 20 min after i.m. neostigmine. We compared the results with those of 10 normal controls. We found no difference between patients with isolated ocular involvement and controls. Ocular myasthenia gravis patients did not improve after neostigmine. The patients with generalized myasthenia gravis had reduced baseline ventilatory muscle strength (MIP 67 cmH2O (70% of predicted), MEP 86 cmH2O (50% of pred) and endurance (mean maximal load achieved = 246 g, mean pressure at highest load (P) = 19.4 cmH2O) compared with controls. After neostigmine, there was a significant increase in MIP in patients with generalized myasthenia gravis and a trend towards an increased MEP. As a group, the patients with generalized myasthenia gravis did not demonstrate a change in their ventilatory muscle endurance after neostigmine; however, there was considerable interpatient variability in response. We conclude that patients with isolated ocular MG have normal ventilatory muscle strength when tested conventionally.(ABSTRACT TRUNCATED AT 250 WORDS)

An increased incidence of multiple sclerosis (MS) has been reported in patients with myasthenia gravis (MG). We reviewed records of 214 patients with MG. CNS demyelinating disease (CNSDD) occurred in five patients (2.3%). CNSDD always occurred after the diagnosis of MG. Myelitis (including recurrent myelitis) was the most common CNS manifestation. All patients had antinuclear antibodies. CNSDD occurs more frequently in patients with MG and may be related to immune-modulating treatments including thymectomy.

The ability of rubella virus to infect and replicate in various lymphocyte subpopulations was examined. Purified populations of B–cells, CD4+ T–cells and CD8+ T–cells were found to support high levels of viral replication. In addition, when mixed PBMC were infected in vitro, viral antigen was shown to be expressed on the surfaces of CD4+ and CD6+ T–cells by flow cytometry indicating that RV does not have a selective tropism for a specific type of lymphoreticular cell.

Measurements of the T2 decay curve provide estimates of total water content and myelin water fraction in white matter in-vivo, which may help in understanding the pathological progression of multiple sclerosis (MS).Thirty-three MS patients (24 relapsing remitting, 8 secondary progressive, 1 primary progressive) and 18 controls underwent MR examinations. T2 relaxation data were acquired using a 32-echo measurement. All controls and 18 of the 33 MS patients were scanned in the transverse plane through the genu and splenium of the corpus callosum. Five white matter and 6 grey matter structures were outlined in each of these subjects. The remaining 15 MS patients were scanned in other transverse planes. A total of 189 lesions were outlined in the MS patients. Water content and myelin water fraction were calculated for all regions of interest and all lesions.The normal appearing white matter (NAWM) water content was, on average, 2.2% greater than that from controls, with significant differences occurring in the posterior internal capsules, genu and splenium of the corpus callosum, minor forceps and major forceps (p0.0006). On average, MS lesions had 6.3% higher water content than contralateral NAWM (p0.0001). Myelin water fraction was 16% lower in NAWM than for controls, with significant differences in the major and minor forceps, internal capsules, and splenium (p0.05). The myelin water fraction of MS lesions averaged 52 % that of NAWM.NAWM in MS has a higher water content and lower myelin water fraction than control white matter. The cause of the myelin water fraction decrease in NAWM could potentially be due to either diffuse edema, inflammation, demyelination or any combination of these features. We present a simple model which suggests that myelin loss is the dominant feature of NAWM pathology.

Heute wird allgemein die Auffassung vertreten, dass die multiple Sklerose (MS) durch eine fehlgeleitete Immunantwort gegen das zentrale Nervensystem (ZNS) verursacht wird. Das neuropathologische Substrat der aktiven MS-Lasion besteht vorwiegend aus einer Infiltration mononuklearer Zellen im Umfeld von Venolen. Dies fuhrt zu einem multifokalen Myelinverlust und zu narbigen Lasionen; dabei kommt es zu einer Astrozytenproliferation und zu einem Verlust von Oligodendrozyten. Die verschiedenen Tiermodelle der MS, insbesondere die experimentelle Autoimmunenzephalomyelitis (EAE), haben stichhaltige Argumente geliefert, die fur eine T-Lymphozyten-vermittelte Autoimmunkrankheit sprechen. Gleichwohl bleiben viele Fragen offen, was die Rolle von Umwelt-bzw. genetischen Faktoren bei der Entstehung der Erkrankung angeht. Infolge der jungsten rasanten Fortschritte der Molekularbiologie und der immunologischen Grundlagenforschung konnten die unterschiedlichen Aktivierungsmechanismen der autoreaktiven T-Lymphozyten bei verschiedenen Antigenen (Ag) des ZNS genauer erkannt werden, doch wie wir sehen werden, stost unser Verstandnis der Pathogenese der Lasionen angesichts einer Vielzahl potentieller myelinhaltiger und sogar nicht myelinhaltiger Strukturbestandteile an Grenzen. Die Entwicklung der Kernspintomographie ermoglichte, den kritischen Mechanismus der Schadigung der Blut-Hirn-Schranke (BHS) am lebenden Patienten nachzuweisen.

To assess the ability of baseline MRI characteristics to predict the early development of clinically definite MS (CDMS) and combined CDMS/MRI outcomes in 190 patients with a positive MRI at the time of their first demyelinating event.Based on individual and sets of baseline MRI characteristics, the authors evaluated the percentage of patients meeting outcomes of CDMS and various combined CDMS/MRI outcomes by 18 months. They also optimized a cutpoint for dichotomizing each baseline MRI characteristic and evaluated these variables using logistic regression to determine which MRI characteristics best predicted CDMS by 18 months.The presence of two or more gadolinium-enhancing lesions better predicted the development of CDMS and combined CDMS/MRI outcomes by 18 months than any other individual MRI characteristic or set of MRI characteristics. Among patients with two or more gadolinium-enhancing lesions, 52% developed CDMS compared with 24% of patients with fewer than two lesions. For those meeting the criteria of Barkhof et al., 32% of patients developed CDMS compared with 16% of those not meeting these criteria. Irrespective of individual or sets of criteria, however, the majority of patients developed either CDMS or demonstrated disease activity on brain MRI by 18 months.For patients with positive MRI at the time of their initial neurologic event, both gadolinium-enhancing lesions and the Barkhof criteria are predictors for development of CDMS over a short interval. However, these results, based on a combined CDMS/MRI outcome, suggest that the majority of these patients are already in the earliest stages of MS, regardless of whether any further MRI criteria are met.

Limbic encephalitis (LE) is often associated with lung, thymic, or testicular tumours and antibodies to Hu, CV2, or Ma2 (Ta) antigens. In these cases, it generally has a poor prognosis. Here we describe two patients with symptoms of LE, negative for typical paraneoplastic antibodies, in whom antibodies to voltage-gated potassium channels (VGKC) were detected retrospectively in serial serum samples. Patient 1 had a thymoma recurrence, but in patient 2 no tumour has been detected in the years following presentation. Plasma exchange was effective in reducing VGKC antibody levels, with substantial improvement in mental symptoms in patient 1. In patient 2, the VGKC antibodies fell spontaneously over two years, with almost complete recovery of mental function. Although neither patient had obvious neuromyotonia at presentation, both showed excessive secretions. We suggest that patients with limbic symptoms and excessive secretions should be tested for VGKC antibodies, and, if they are present, prompt and effective immunosuppressive treatment should be considered.

Although interferon (IFN) β has many adverse effects, including flulike illness, increased spasticity, and laboratory abnormalities,1 autoimmune events are usually limited to autoantibodies with the thyroid the most common target organ involved.2 Liver abnormalities during IFN β therapy are usually clinically asymptomatic and transient biochemical events.1,2⇓ We report a patient who developed acute fulminant liver failure a few weeks after the initiation of IFN β and required an emergency liver transplant. Fulminant failure as a result of IFN β is not well reported in the MS literature and this is the first patient reported who required a liver transplant as a result of MS therapy. A 59-year-old Caucasian woman was transferred to the Intensive Care Unit (ICU) in hepatic coma and hepatorenal syndrome 7 weeks after starting interferon β-1a (Rebif, Serono-Canada, Oakville, Ontario, Canada). One year previously, she developed diplopia and ataxia. An MRI scan disclosed small deep white matter …

Recently, effector T-cell subpopulations have been identified that can be distinguished by expression of members of the TNF-R family: CD4+OX-40+ cells are CD4 helper-effector cells CD8+CD45RA+CD27 cells are CD8-killer-effector cells. We investigated whether these lymphocyte subsets were increased in the active phase of multiple sclerosis (MS).Multiple colour immunofluorescence staining was performed on peripheral blood lymphocytes of 28 patients with active MS and of 29 healthy controls, followed by FACS analysis.Frequencies of CD8-killer-effector cells showed a wide interindividual range in both groups and percentages of CD4 helper-effector cells were low. No significant difference between the groups was observed for these subsets, but CD8+CD45RA-CD27 were increased in MS. In healthy individuals, CD4 helper-effector cells correlated with the total percentages of memory cells. Moreover, CD4+ and CD8 memory cells were strongly correlated.The here described recently identified effector CD4 and CD8 lymphocyte subpopulations were not increased in clinically active MS. It is however still possible that in MS, myelin-specific encephalitogenic cells reside within these subsets.

We investigated the adhesion of blood mononuclear cells (MNC) isolated from patients with HTLV-1-associated myelopathy (HAM/TSP). MNC from HAM/TSP patients were significantly more adherent to activated endothelial monolayers than MNC from non-HAM/TSP (controls and HTLV-1 carriers) subjects. Blocking studies demonstrated that the adhesion molecules VLA-4 (CD49d), ICAM-1 (CD54), and L-selectin (CD62L) all contributed to increased binding. However, anti-ICAM-1 antibody was the most efficient in inhibiting binding HAM/TSP patients MNC to activated endothelial cells. Expression on MNC of molecules involved in adhesion was also studied by flow cytometry in HAM/TSP patients, HTLV-1 carriers, and healthy control subjects after two days culture without any mitogen. In HAM/TSP patients, L-selectin expression on CD4+ and CD8+ subsets was lower than in controls; interestingly, HAM/TSP patients had lower percentage of CD4+ subset expressing L-selectin than HTLV-1 carriers. The percentage of CD4+ and CD8+ cells expressing VLA-4 was found to be similar to controls in both HAM/TSP patients and HTLV-1 carriers. Following two days in culture without mitogen, the percentage of T cells expressing ICAM-1 increased in HAM/TSP and carriers, but not in controls. This study provides information regarding trans-endothelial migration of MNC across the blood brain barrier in HAM/TSP and suggests ICAM-1 and its counterpart molecule LAF-1 are involved in massive infiltration of lymphocytes observed in the spinal cord.

Epidemiological studies of HTLV-I infection have demonstrated the presence of this virus in certain Amerindian populations in Central and South America. We have recently reported the first evidence of endemic HTLV-I infection in North American Amerindians from the coastal regions of British Columbia, Canada. While the predominant HTLV-I-associated disease observed in British Columbia Amerindians is the HTLV-I associated neurological disease (HTLV-I-associated myelopathy/tropical spastic paraparesis), we report here the first two cases of HTLV-I-associated adult T cell leukemia/lymphoma (ATL). Clinical and PCR evidence to support the diagnosis of HTLV-I-associated ATL in these two Amerindians is presented. Both cases of ATL were found in the same tribe although neither patient was directly related to each other. While reports of HTLV-I-associated ATL have been reported in Circumartic native peoples, reports of ATL in North American single ancestry Amerindians have not been previously made to our knowledge.

Human T-lymphotropic virus type 1 (HTLV-1) infection has been discovered recently in people of Amerindian descent living in coastal areas of British Columbia, Canada. DNA sequencing combined with phylogenetic analysis and restriction fragment length polymorphism (RFLP) typing of HTLV-1 strains recovered from these British Columbia Indians (BCI) was conducted. Sequence-based phylogenetic trees distributed the BCI isolates among the Japanese subcluster (subcluster B) and the geographically widely distributed subcluster (subcluster A) of the large HTLV-1 cosmopolitan cluster. Long terminal repeat (LTR) RFLP typing revealed three distinct, equally frequent LTR cleavage patterns, two of which were of previously recognized Japanese and widely dispersed cosmopolitan types. A third, new cleavage pattern was detected which may have arisen by recombination between two other HTLV-1 genotypes. Our results suggest multiple origins for HTLV-1 in BCI, which are equally consistent with (i) a cluster of recent sporadic infections, (ii) ancient endemic vertical transmission through Amerindian lineages, or (iii) both.

Human T-cell lymphotropic virus type 1 (HTLV-I) is responsible for HTLV-I associated myelopathy or tropical spastic paraparesis (HAM/TSP) and for adult T-cell leukemia/lymphoma (ATLL). Both diseases have been well described in individuals living in Japan, West Indies, Seychelles Islands and Columbia where infection with HTLV-I is considered endemic and in persons whose descendants originated from these endemic areas. We report here 4 cases of HAM/TSP in 4 natives from 4 different tribal groups from British Columbia (B.C.). These are the first case reports of HTLV-I linked diseases found among North American Aboriginals. Possible routes of infection for HTLV-I infection included sexual transmission, breast feeding, blood transfusions and IV drug use. The seroprevalence of HTLV-I in North American Native population is unknown and we suggest that it is endemic in this ethnic group.

The purpose of this study was to explore further the hypothesis that changes in cognitive function may occur in the mild stages of multiple sclerosis (MS) by determining whether ventricular enlargement was related to cognitive function. Ten measures of ventricular size were made in a sample of 123 MS patients with mild disability and 60 well-matched healthy controls. In addition, sixteen tests of cognitive function and the Beck Depression Inventory were administered. For the MS group, there were significant correlations between the ventricular measures and cognitive performance but not for the normal controls. Scores on the Beck Depression Inventory were not correlated with either cognitive performance or ventricular enlargement. These findings suggest that for the MS group cognitive impairment was related to the disease process but not to the level of depression.

We propose a new approach to staging the disease based on clinical and immunological response to treatment. We oppose clinical remission to immunological remission and define total clinical remission as the goal of therapy. We describe the use, side effects and indications of established therapies. Acetylcholine esterase inhibitors are only a symptomatic treatment as is plasma exchange. Usefulness and limits of thymectomy, corticosteroids and immunosuppressants are described here. Their goal is to reduce the auto-immune process. Long-term hazards from these medications are described and methods to reduce their potential risks are suggested. We suggest the number of patients having life threatening complications while undergoing aggressive immunosuppression can be reduced by a systematic approach to follow-up. In the second part of this review article, adapting management to specific situations is emphasized in refractory disease, respiratory failure, neonatal and juvenile forms of the disease. The special situation of seronegative myasthenia is discussed.

A randomized, double-blind, placebo-controlled, noncrossover trial determined the efficacy of lymphoblastoid interferon (IFN) in chronic progressive multiple sclerosis (CP MS). Fifty patients received 5 × lo6 IUIFN subcutaneously daily for 6 months while 50 received placebo. After 2 years, there were no significant differences between the 2 groups based on clinical evaluations and quantitative MRI analysis of the brain, although a trend was observed in the IFN group. Clinically, the IFN group was worse at 1 and 3 months and improved at 6 to 18 months, when compared with the placebo group. Results of MRI evaluations of the brain at 6 months support this trend. This trend likely resulted from a subpopulation of 10 IFN-treated patients, characterized by a higher women: men ratio and a lower EDSS score at entry into the trial. We cannot recommend lymphoblastoid IFN as treatment for CP MS at this time.

We measured the pokeweed mitogen (PWM)-induced secretion of IgG by the unfractionated mononuclear cells (MNC) of young adult donors, and correlated the results with the functional activity of cell suspensions enriched for T helper (T4+) and T suppressor/cytotoxic (T8+) cells. The distribution of IgG levels secreted by MNC differs from a Gaussian curve, implying that the group is composed of distinct heterogeneous populations. When donors were compared who were judged to be very low responders or very high responders on the basis of IgG secretion levels by MNC (less than 700 ng/ml or greater than 2500 ng/ml), no differences were found in the capacity of T4+-enriched cells to support PWM-driven IgG secretion by a common B cell pool. In contrast, the addition of 0.2 X 10(5) T8+ cells from these low responders to PWM-stimulated cultures of 0.5 X 10(5) T4+ cells plus 0.5 X 10(5) B cells resulted in significantly less IgG secretion (389 +/- 121 ng/ml) than did the addition of the same number of T8+ cells from the high responders (2241 +/- 548 ng/ml, p less than 0.01). Normalized percent suppression by T8+ cells was higher in low responders than in high responders (77.0 +/- 9.9% vs 33.0 +/- 8.5%, p less than 0.01). Both high and low responders markedly suppressed IgG secretion when 0.5 X 10(5) T8+ cells were added. No correlation was found either between proportion of T3+, T8+, T4+, or M1+ cells within the MNC population and levels of IgG secretion by MNC or between T8+ numbers and levels of suppression induced by a constant number of T8+-enriched cells. Our data indicate that differences in the functional activity of T8+ cells, rather than quantitative differences, account for the wide range of PWM-induced IgG secretion by MNC.

Summary Two patients with stage Ic of SSPE were treated with subcutaneous injections of 13 and 17 units of transfer factor for seven and eight months respectirely. Regular immunity tests, clinical examinations, and electrical recordings, showed worsening of the disease, though one patient had temporary improvement in both clinical and immunity parameters (reduction of IgG of the CSF, skin tests becoming positive). It is difficult to affirm that the transfer factor was responsible for this brief remission.

Transplanted A-10 breast adenocarcinomas grew more slowly in young-adult male A/HeJ mice from which the submandibular glands had been extirpated than in sham-operated or unoperated control mice of the same strain. The mitotic index was lower in tumors from experimental animals than in those from controls. Vascularization about the tumor margins was also less prominent. The C1300 neuroblastoma grew more slowly in sialoadenectomized mice than in controls. Modulation of tumor growth by factors of salivary gland origin may have been responsible for these effects.

In the period 1976-1978 a study of the prevalence of multiple sclerosis in Brittany was conducted using data collected from hospital neurology units, Social Security offices and institutions for chronic patients. After elimination of double entries, analysis of these data showed a prevalence of 25 for 100 000 people. This was less than expected from estimates for northern France and from the known prevalences in the southern part of the British isles. When broken down according to the patients' place of residence, the figures were found to vary from one district to another, with four main foci: two near the coast, one inland and one in the town of Fougères. Disease-free areas were present near these foci.

The non-stimulation of DNA synthesis in human lymphocytes in the one way mixed lymphocyte culture conditions allows the typing for LD determinants. The authors describe their technique together with their cryo-preservation procedure and the results obtained in 24 control population and 26 multiple sclerosis patients tested for the presence of the LD7a determinant.

The authors have examined three hundred cases of sclerosis (prospective study of an hundred patients, retrospective study of two hundred observations) in order to assess the frequency of uveitis during the disease and to make out a possible relation between the two diseases. The percentage of uveitis is small: 2% and the frequency of uveitis in multiple sclerosis appears not different of that of a normal population. In spite of the simularity of the pathogenic hypothesis, it does not look that a correlation may be made between the two diseases.

The study concerns HLA typing of 261 patients with disseminated sclerosis. All patients were grouped for loci A and B. In addition, 94 were typed in HLA DR and 132 in mixed lymphocytic culture (DW2 only). Analysis of tissue group distribution among patients compared with a control population showed not only over-representation of the B7, DW2, A3 B7 and B7 DR2 types (as previously stressed by several workers), but also of A9 and of B8 DR3 and A1 B8 DR3 associations. Moreover, it would seem that there are two distinct clinical forms of disseminated sclerosis, each form being characterized by a specific antigenic HLA association. Side by side with the conventional and most common "remittent" form, which is partly responsive to treatment, has a relatively favourable course and is frequently associated with B7 and DW2/DR2, there appears to emerge around DR3, B8 DR3 and A1 B8 DR3 a rarer, "progressive" form of rapidly increasing severity and resistant to immuno-suppressants. This, however, is a mere hypothesis which needs to be confirmed by further studies on a larger scale.

Multiple sclerosis patients have been continuously treated by azathioprine. Only severe progressive forms were selected. The protocol of inclusion and follow-up is detailed. All cases started before 1972 have been reviewed, i.e. 102 cases. Of these 102, 35 stopped azathioprine during the first years and the reasons for this drop-out are analysed. Sixty seven treatments have been maintained for more than 5 years. An evaluation of these 67 patients through the Kurtzke scale shows that the 40 cases with a remittent progressive course have been stabilized as long as they were under treatment. Relapses were observed after discontinuing the therapy. In such cases azathioprine was restarted, leading again to stabilization. Twenty seven cases following a continuous progressive course at the time azathioprine was started showed no evidence of a benefit and kept on worsening. Complications related to treatment (as observed on 240 patients from 1967 to 1982) are detailed with special reference to infections, liver disease and malignancy. Even if the results observed on the course of severe remittent progressive forms of MS are in favor of continuous therapy by azathioprine, this should not be extended to all cases of MS at their first manifestation. It has to be limited to rapidly worsening cases, appreciated after a period of evaluation, when a threatening loss of autonomy may justify some limited risks.

A prospective study of serial magnetic resonance (MR) scans of the brain was carried out every 2 weeks for 4 to 6 months in 9 patients with mild, clinically definite, relapsing/remitting multiple sclerosis (MS). Six of the 9 patients developed a total of 12 asymptomatic new lesions in various parts of the brain. In none of the patients were the changes on MR scan accompanied by relevant new neurological symptoms or signs. New MR lesions had a characteristic temporal profile, reaching a maximum size in approximately 4 weeks before gradually shrinking, usually leaving a small residual abnormality indistinguishable from chronic MS lesions. The frequent occurrence of new asymptomatic lesions indicates that MS may be a more active process even in mildly affected asymptomatic patients than has been previously realized. The results emphasize the potential importance of using MR scanning to measure disease activity in laboratory studies of MS and in the assessment of treatment, particularly in asymptomatic patients in the early stages. We suggest that the expanding and contracting new lesions are the basic or primary lesion in MS, that the characteristic demyelinated plaque is represented by the small residual area that these lesions shrink down to, and that the typical collection of scattered white matter lesions in chronic MS may represent the accumulated residua of dozens or more of these active lesions occurring over many years.

Evidence points to the conclusion that abnormal regulation of the immune response in MS contributes to ongoing immune activity.

Antigen:antibody complexes, prepared with 125I-bovine serum albumin and guinea or rabbit antibody, were added to serum and blood cells from normal individuals and binding studied. When antigen:antibody were pre-incubated with serum in varying proportions for 30 min at 37 degrees C and then mixed with washed unseparated cells, binding increased to a maximum (70% of added complexes) and then decreased as serum to antigen:antibody proportions were increased. Separation of cells revealed that following maximal binding to unfractionated cells, complexes were predominantly associated with red blood cells (RBC), even though complexes bound less per cell to RBC than to white blood cells following addition of complexes to separated cells. Binding to RBC was reduced by zymosan treatment of serum and abolished by heat inactivation or substitution of non-primate RBC (known not to possess C3b receptors) for human RBC, indicating that binding to human RBC was via C3b receptors. When antigen:antibody were incubated at 37 degrees C directly with serum and unfractionated blood cells, maximal binding occurred after 2-4 minutes and declined thereafter. Identical kinetics were observed when purified RBC were substituted for whole blood cells. When diluted or hypocomplementemic (systemic lupus erythematosus) serum was substituted for neat serum, maximal binding was delayed and sustained. Our findings suggest that RBC in human blood can compete with other cell types for immune complexes at that stage during the sequence of reactions between complexes and complement when complexes are able to bind to C3b receptors.

The comparison of Histocompatibility Testing in 82 MS Patients and 368 controls is presented. The increase in HL-A7 and decrease in HL-A12 are confirmed. A significant increase in HL-A8 is reported. Mixed Lymphocyte Reaction confirms the LD7a increase (19 out of 24 Multiple Sclerosis patients tested); 100% of the patients bearing the HL-A7 determinant are found to be LD7a. The presence of specific Immune Response genes in Multiple Sclerosis is discussed.

The study of the genic and antigenic frequencies of the ABO and Rhesus systems amidst a population of 16559 subjects, reveals are very good correlation as regards the various autors. Considering the HLA typing of 481 subjects, one will point out the lowering of the HLA2 antigen.