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We sought to study the etiology of and risk factors for cerebral infarction in young adults in Hordaland County, Norway. All patients aged 15-49 years living in Hordaland County with a first-ever cerebral infarction during 1988-97 were included. Etiology was analyzed in subgroups defined by sex, age (40 years versus/=40 years), circulation territory (anterior versus posterior circulation) and short-term functional outcome [modified Rankin score (mRS)/= 2 versus mRS2]. A questionnaire was used to evaluate possible risk factors amongst the patients compared with an age- and sex-matched control group. The distribution of etiology was significantly different in all subgroups. Atherosclerosis was frequent amongst men (22.8% vs. 4.2%) and patients/= 40 years (20.8% vs. 2.7%). All patients with microangiopathy had favorable short-term outcome. Significant risk factors were smoking more than 15 cigarettes per day (P0.001), hypertension (P = 0.001), and myocardial infarction (P = 0.035). Modifiable risk factors were frequent.

The extent and pattern of demyelination in the cerebral cortex was determined in 78 tissue blocks from the brains of 20 multiple sclerosis (MS) patients and 28 tissue blocks from 7 patients without neurological disease. Tissue blocks from 4 predetermined areas (cingulate gyrus, frontal, parietal, and temporal lobe) were studied, irrespective of macroscopically evident MS plaques. All tissue blocks contained cerebral cortex and periventricular and/or subcortical white matter. One hundred and nine demyelinating lesions were detected in the cerebral cortex, of which 92 (84.4%) were purely intracortical and 17 (15.6%) were lesions extending through both white and gray matter areas. In 5 of the 20 MS brains, subpial demyelination was extensive in the 4 widely spaced cortical areas studied, thus considered to represent a general cortical subpial demyelination. The percentage of demyelinated area was significantly higher in the cerebral cortex (mean 26.5%, median 14.1%) than in white matter (mean 6.5%, median 0%) (p = 0.001). Both gray and white matter demyelination was more prominent in the cingulate gyrus than in the other areas examined (p < 0.05). These results indicate that the cerebral cortex is likely to be a predilection site for MS lesions and identify general cortical subpial demyelination as a distinct pattern occurring in a significant subpopulation of MS patients.

Tumor necrosis factor (TNF)-alpha and TNF-beta are proinflammatory cytokines that have been implicated in the pathogenesis of several autoimmune diseases. The aim of this investigation was to determine whether a determinant in the first intron of the TNF-beta gene (TNF-beta(+252)) and two promoter-region polymorphisms of the TNF-alpha gene (TNF-alpha(-308) and TNF-alpha(-238)) affect susceptibility to multiple sclerosis (MS). DNA samples from 133 Caucasian MS patients and 148 healthy controls from Norway were genotyped for several polymorphic determinants, using polymerase chain reaction-based restriction fragment length polymorphisms (PCR-RFLP) methods. TNF-beta(+252) genotypes were significantly associated with MS: The frequency of TNF-beta 2,2 was increased (p = 0.00009) while the frequency of TNF-beta 1,2 was decreased (p = 0.0012) in MS patients as compared to controls. TNF-alpha genotypes were not associated with MS. These results suggest that the TNF-beta gene plays a significant role in the etiopathogenesis of MS.

Sports diving is a popular recreational activity. Sports divers presenting with acute decompression sickness may exhibit residual neurologic and neuropsychological symptoms during follow-up, in spite of appropriate treatment.A retrospective review of medical records was carried out for sports divers admitted to the department of neurology at Haukeland University Hospital during 1997.11 out of 20 divers experienced residual neurological symptoms after treatment. Five responded poorly to treatment, with 50% or more residual clinical score. These patients tended to be older, had performed deeper dives, and more repetitive diving. Seven divers had increased slow wave activity in EEG on initial recording, in two the EEG changes persisted after treatment.In this small series of sports divers with decompression sickness and arterial gas embolism, most neurologic symptoms responded to hyperbaric treatment. However, more than one half of the divers had residual neurological symptoms on discharge. Sensory loss and asymmetrical reflexes were the most common residual findings.

Background and Purpose — We sought to determine the incidence and short-term outcome of people aged 15 to 49 years with first-ever cerebral infarction in 1988–1997 in Hordaland County, Norway. Methods — Cases were found from computer search of hospital registries and detailed review of patient records. Stroke subtype was classified according to the major intracranial artery affected. Short-term outcome was evaluated by the modified Rankin Scale (mRS). Results — A total of 96 women and 136 men met the inclusion criteria. The average annual incidence was 11.4/100 000. Women outnumbered men among those aged P =0.059); men predominated among those aged ≥30 years ( P =0.004). A total of 148 patients had anterior circulation infarction (64%), and 84 had posterior circulation infarction (36%) ( P P =0.005). Eighty percent had favorable outcome (mRS score ≤2). The 30-day case fatality rate was 3.4%. The recurrence rate in hospital was 2.2%. Conclusions — The incidence was in the lower range compared with other reports from western Europe. Although men predominated, there was a strong trend toward more women among patients aged

Receptors for the Fc part of IgG (FcgammaR) constitute a family of cell-surface molecules expressed on almost every cell of the immune system. They are also present on non-lymphoid cells such as Schwann cells and endothelial cells. By linking humoral and cell-mediated responses, FcgammaR are key in defending against pathogens. Polymorphisms in some FcgammaR genes are associated with infectious and autoimmune diseases. It was found recently that certain FcgammaRIIA and FcgammaRIIIB allotypes are correlated with the disease course of Guillain-Barre syndrome (GBS) and multiple sclerosis (MS). This may imply that clearance of circulating autoantibodies and immune complexes is important in the pathogenesis of these diseases.

Background Multiple sclerosis (MS) patients accumulate both physical and mental health problems along with disease progression. Valid and sensitive outcome measures are important to measure disease effects and the effect of treatment. Objective The objective of this study was to test the performance of the physical and mental summary scales of SF-36, SF-12, and RAND-36. Methods The scales were evaluated by comparing the scores of a cohort of 194 MS patients with general population data and using the Expanded Disability Status Scale (EDSS) and the Incapacity Status Scale-mental as criterion variables for physical functioning and mental health. Results All 3 physical summary scales were markedly reduced and correlated highly with the EDSS. The SF-36 mental summary score was only slightly reduced among MS patients (0.2 SD) compared with the general population, despite significantly reduced scores on all 4 health scales being most related to mental health and despite a high prevalence of mental health problems. This results from the poor physical functioning (mean scale score, 2.3 SD below the general population) and the orthogonal factor rotation used to derive independent measures of physical and mental health. Similar results were found for the SF-12. The nonorthogonal RAND-36 physical and mental summary scores were both markedly reduced. This is more compatible with the disease progression in MS and the results of the other measures of physical and mental health used in the study. Conclusions The SF-36 and SF-12 mental health summary scales appear to overestimate mental health in people with MS.

Multiple sclerosis (MS) is a multifactorial disease in which genetic and environmental factors apparently have a major influence on the susceptibility and course of the disease. In the present study we have investigated the genetic basis and subclass levels of IgG in MS. Hundred and thirty-six Norwegian patients with MS and 92 controls were genotyped for IgG allotypes of the GM and KM systems. IgG and IgG subclasses were quantified in sera from 115 MS patients and 20 controls. Neither GM nor KM allo-, haplo- or genotypes were significantly correlated with susceptibility, severity or course of the disease. The G1M (3) (3), G2M (23) (23) and G3M (5) (5) allotypes were significantly correlated with high serum levels of IgG3, whereas high IgG2 levels were correlated with G1M (3) (3) and G2M (23) (23) in both patients and controls. Serum levels of IgG subclasses were not significantly correlated with course or severity of the disease. The results indicate no major role for IgG allotypes or IgG subclass levels in the pathogenesis of MS.

Peripheral blood granulocytes and sera from patients with relapsing/remittent (group I) and chronic progressive (group II) multiple sclerosis (MS) did not differ from control cells and sera with regard to 1) the proportion of cells bearing receptors for Fcy and C3b; 2) random or directed (chemotactic) motility of granulocytes; 3) activation as measured by chemiluminescence; 4) opsonic activity of sera. The results of this study suggest that granulocyte function in MS is normal.

The objective of the study was to examine whether the beneficial effect of treatment of interferon alfa-2a on multiple sclerosis seen by magnetic resonance imaging is reflected in a corresponding improvement in the quality of life (QoL) and to address the impact of adverse events related to this treatment on the QoL. The study was a randomised double-blinded placebo-controlled treatment trial including 97 relapsing-remitting multiple sclerosis patients. Thirty-two patients received 4.5 MIU recombinant interferon alfa-2a, 32 patients received 9.0 MIU recombinant interferon alfa- 2a and 33 patients received placebo treatment for 6 months. All patients were followed up 6 months after end of treatment. QoL was assessed according to the eight scales of the SF-36 Health Survey and measured at baseline, month 3, 6 and 12. The effect found on MRI was not reflected in a corresponding change in the QoL. We found a relationship between the presence of new enhancing lesions and reduced QoL among the placebo patients, whereas this was not found among the patients treated with interferon. The presence of the adverse events fatigue, myalgia, headache and weakness were significantly negatively correlated to several of the QoL dimensions. Conclusively, the treatment with interferon alfa- 2a does not seem to improve the patients' QoL after 6 months of treatment, in spite of a marked effect measured by MRI. The treatment is followed by adverse events that negatively affected the QoL.

In studies of patients in Norway with multiple sclerosis (MS), we have found cross reactive autoantibodies related to the Epstein Barr virus nuclear antigen-1 (EBNA-1). The MS patients had elevated IgG antibody to EBNA-1, as measured by reactivity with a synthetic glycine/alanine peptide, P62, which represents the glycine/alanine repeat in EBNA-1. The mean titer of anti-P62 in patients with acute relapse at the time of assay was significantly higher than in the remaining patients. Patients with remitting/relapsing MS also had elevated autoantibody to a lymphocyte protein, p542, cross reactive with EBNA-1 through a glycine/serine epitope. High titered anti-EBNA-1 antibodies from some MS, as well as from some SLE sera, were shown to cross react with 80-82 kDa and 60 kDa proteins in neuroglial cells.

We conducted a cross-sectional, geographically based study of functional status in an incident cohort of 124 multiple sclerosis (MS) patients with onset of disease from 1 January 1976 to 31 December 1986 in Møre and Romsdal County, Norway. The cohort comprised 58 men (46.8%) and 66 women (53.2%). One hundred and thirteen patients (91.1%) had a primary remitting course of disease and 11 (8.9%) had primary progressive MS. The mean age of onset was 33.3 years (range 14-64), and the mean duration of disease 7.8 years (range 1-23). The Minimal Record of Disability (MRD) of multiple sclerosis was applied to measure the degree of impairment, disability and handicap. The mean Kurtzke Expanded Disability Status Scale (EDSS) score was 3.76 (0-10), and the frequency distribution of the EDSS scores in the cohort was bimodal. Twenty-eight (22.6%) patients in the cohort had marked paraparesis, paraplegia of quadriplegia. Nineteen patients (15.3%) had frequent urinary incontinence, need for almost constant catheterization, or need for constant use of measures to evacuate stools. Five patients (4%) had a severe decrease in mentation or dementia. Forty-eight patients (38.7%) reported frequent problems with fatigue or fatigability preventing sustained physical function. Less than half of the cohort (42.7%) was working full-time, and 49.2% of the patients reported that they received external support to maintain their usual financial standard. Lack of ability to work full-time and accordingly the dependence upon external financial support were significantly associated with the primary progressive course of disease. Fatigue was statistically significantly related to lack of working ability. The estimated cost of MS in the county in 1991 was 48.2 million NOK (approximately 7.531.250 US $) based on the cost-of-illness methodology.

To study Guillain-Barre syndrome (GBS), the clinical files of GBS patients, 59 in northern Tanzania (1984-1992) and 56 in western Norway (1980-1992), were retrospectively reviewed and compared. The average annual incidence rate for GBS in the Kilimanjaro region was 0.83/100,000 population as compared to 1.2/100,000 reported in western Norway (25). GBS patients in the Tanzanian series were younger, had less antecedent infection and were a longer time interval from onset to admission and in hospital. On examination arm and sensory involvement were less common and urinary sphincteric involvement more common in the Tanzanian series. The overall mortality rate was higher in the Tanzanian series, 15.3% (9/59) versus 1.8% (1/56). HIV infection was found in 30.5% (11/36) of GBS patients in the Tanzanian series as compared to 3.4% (161/4687) in corresponding blood donors. There was no evidence of HIV infection in the Norwegian series. The HIV-seropositive GBS patients in comparison with HIV seronegatives had a shorter duration of onset, greater neurological involvement and a higher mortality rate, 45.5% (5/11) versus 16% (4/21). This study shows that apart from minor clinical differences and an increased mortality rate in the Tanzanian series GBS was similar in both series. GBS in the Tanzanian series was strongly associated with HIV infection, and seropositives by comparison with seronegatives appeared to have more severe disease.

Objectives To investigate the relationship between poststroke fatigue and depression and subsequent mortality in young ischaemic stroke patients in a population-based study. Design A prospective cohort study. Setting All surviving young ischaemic stroke patients living in Hordaland County. Participants Young ischaemic stroke patients aged 15–50 years at the time of the stroke were invited to a follow-up on an average 6 years after the index stroke. Psychosocial factors and risk factors were registered. Fatigue was self-assessed by the Fatigue Severity Scale (FSS). Depression was measured by Montgomery-Asberg Depression Rating Scale (MADRS). Intervention No intervention was performed. Primary and secondary outcome measure Mortality on follow-up. Results In total, 190 patients were included. The mean age on follow-up was 48 years and subsequent follow-up period was 12 years. Cox regression analysis showed that mortality was associated with FSS score (p=0.005) after adjusting for age (p=0.06) and sex (p=0.19). Cox regression analysis showed that mortality was associated with MADRS score (p=0.006) after adjusting for age (p=0.10) and sex (p=0.11). Conclusions Both fatigue and depression are associated with long-term mortality in young adults with ischaemic stroke. Depression may be linked to higher mortality because of psychosocial factors and unhealthy lifestyles whereas the link between fatigue and mortality is broader including connection to diabetes mellitus, myocardial infarction and psychosocial factors.

A retroviral aetiology has been proposed for multiple sclerosis (MS). Although there is as yet no definitive evidence of viral involvement, there have been preliminary reports of antiretroviral antibody detection in sera from MS patients. Such sera have, for example, been found to react with HTLV-I. We here describe investigations involving various immunological techniques which attempt to confirm the virus-specific nature of these antibodies against a range of human and macaque retroviruses. Sera from 25 MS patients, 25 patients with non-associated neurological diseases and 16 patients with non-neurological conditions were tested by immunoblotting methods using lysates of HIV-1-, HIV-2-, HTLV-I- and SIV-infected cells as antigens. None of the sera reacted against any of these retroviral antigens but each serum demonstrated a distinctive and reproducible reaction pattern against cellular components of the cells in which the viruses were propagated. Further examination of the sera was carried out by ELISA using synthetic oligopeptides covering the HIV-1 Gag p24 protein as antigens. None of the sera reacted with the peptides. Our results suggest that in some MS patients the repeated seropositivity to HTLV-I may be due to the reaction with host cell proteins.

In Western Norway, long-term follow up epidemiological studies have revealed significant increases in the incidence and prevalence rates of multiple sclerosis (MS) in stable populations, indicating the impact of exogenous factors. In this study 183 MS patients and 102 controls from high prevalence areas in Western Norway were investigated for human T-lymphotropic virus type I (HTLV-1) related sequences by polymerase chain reaction. Using primers targeting the gag, pol and env genes in the HTLV-1 provirus genome, no amplification products were detected in the 183 MS patients or 102 controls. The results strongly suggest that neither HTLV-1 nor a closely related retrovirus participate in the aetiology of MS.

A case-control study of multiple sclerosis (MS) has been carried out in western Norway. The study included 93% of the patients who had clinical onset of MS in the county of Hordaland during the years 1976-86 (N = 155) and 200 controls, marginally matched for age, sex and residence. There was no statistically significant difference between MS patients and controls with regard to exposure to organic solvents, exposure to the combination organic solvents and welding or to organic solvents and other chemical compounds.

A consecutive series of 34 meningiomas were re-examined as to subtype and presence of nuclear atypia, mitotic figures, areas of high cellularity and necrosis. Meningioma cells were epithelial membrane antigen (EMA) positive in 31 out of the 34 tumours. The presence of mononuclear cells and macrophages was assessed by immunohistochemistry using the monoclonal antibodies L26 (CD20, B cell marker), DF-T1 (CD43, T cell marker), KP1 (CD68, macrophage marker) and MAC387 (monocytes). L26 positive B cells were observed infrequently. CD43 positive mononuclear cells were infiltrating the parenchyma as individual cells and as groups of cells in 29 (87% of the tumours). CD68 positive macrophages were seen in 19 (59% of the tumours), as scattered single cells or groups of cells. There was a statistically significant association between the number of CD68 positive cells (necrotic areas excluded) and microscopic features of aggressiveness, i.e. high cellularity as well as the combination of nuclear atypia and frequent mitotic figures. MAC387 stained only a few cells; the immunopositive cells were present mainly within and around vessels. Meningioma cells displayed a diffuse immunopositivity for L26 (CD20) in 29 out of 34 meningiomas, but did not stain with macrophage markers. Mast cells were found in 9 out of 32 tumours; when present they were significantly more prevalent in the syncytial subtype. Thus, mononuclear cell infiltrates in meningiomas are mainly composed of T cells and macrophages, indicating an immune system surveillance and response to the tumour cells. The functional and prognostic significance of the presence of CD68 positive cells, macrophages, deserve further study in the search for more reliable histological criteria to predict recurrence and biological aggressiveness in meningiomas.

Forty commercial saturation divers, mean age 34.9 (range 24-49) years, were examined one to seven years after their last deep dive (190-500 metres of seawater). Four had by then lost their divers' licence because of neurological problems. Twenty seven (68%) had been selected by neurological examination and electroencephalography before the deep dives. The control group consisted of 100 men, mean age 34.0 (range 22-48) years. The divers reported significantly more symptoms from the nervous system. Concentration difficulties and paraesthesia in feet and hands were common. They had more abnormal neurological findings by neurological examination compatible with dysfunction in the lumbar spinal cord or roots. They also had a larger proportion of abnormal electroencephalograms than the controls. The neurological symptoms and findings were highly significantly correlated with exposure to deep diving (depth included), but even more significantly correlated to air and saturation diving and prevalence of decompression sickness. Visual evoked potentials, brainstem auditory evoked potentials, and magnetic resonance imaging of the brain did not show more abnormal findings in the divers. Four (10%) divers had had episodes of cerebral dysfunction during or after the dives; two had had seizures, one had had transitory cerebral ischaemia and one had had transitory global amnesia. It is concluded that deep diving may have a long term effect on the nervous system of the divers.

Sera from 23 patients with acute Guillain Barre syndrome (GBS), 15 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and from 40 age-matched blood donors were analysed for antibodies to acidic glycosphingolipids from human brain and peripheral nerve. Antibodies to ganglioside LM1, the major ganglioside of peripheral nerve myelin. were found in 43% of GBS and in 67% of CIDP patients' sera, and in 20% of the blood donors. However, antisulphatide antibodies were detected in 65% and 87% of the sera from GBS and CIDP patients, respectively, but only in 15% of the control sera. Sulphatide is the major acidic glycosphingolipid in myelin and its concentration in peripheral nerve myelin is 100 times higher than that of LM1. The high frequency of LM1 and, in particular of sulphatide antibodies, might thus be relevant to the pathogenesis of the GBS and CIDP.

In the brains of 7 patients with multiple sclerosis, mast cells were observed within the demyelinated plaques, in the border zone of the plaques as well as in seemingly normal white matter. The cells were mostly located in close connection with small vessels. The routine staining with toluidine blue for the demonstration of mast cells is not adequate as compared with staining of similar sections in pinacyanol erythrosine. Mast cells may be a hitherto underestimated contributor to the demyelinating process of multiple sclerosis.

Infection with Epstein-Barr virus (EBV) is considered one of the possible key environmental factors in the aetiology of multiple sclerosis (MS). Whether EBV plays an underlying role as an activator of MS remains, however, controversial. Sixty-one patients with definite relapsing-remitting multiple sclerosis (RRMS) according to the Poser criteria were followed for 1 year. Blood samples were drawn at baseline, months 3, 6 and 12, and in case of any clinical exacerbation. Twenty-three baseline-paired exacerbation samples in the same set were quantitatively analysed to examine whether exacerbations in MS were associated with a change in anti-diffuse component of the EBV-early antigen (EA-D) IgG ratio. All the 61 patients (100%) were anti-viral capsid antigen (VCA) IgG positive, one (2%) was anti-VCA IgM positive and 60 (98%) were anti-EBV nuclear antigen IgG positive. Mean anti-EA-D IgG at baseline was 0.57 (range 0.12-2.70) and at the time of exacerbations 0.61 (range 0.11-2.70). Wilcoxon signed rank test revealed no differences between the 23 baseline and paired exacerbation samples (P = 0.58). Our findings suggest that reactivation of latent EBV infection does not play a significant role for exacerbations in RRMS.

Objective: To compare the Expanded Disability Status Scale (EDSS) and self-rated quality of life scores (SF-36 Health Survey) as measures of disease impact in a representative sample of MS patients. Background: The EDSS is the most common outcome measure of impairment/disability for MS patients but is heavily weighted toward mobility. Sensitive outcome measures are needed that also capture other aspects of the effects of MS. Methods: The authors performed a cross-sectional study of the cohort of all individuals with onset of MS between 1976 and 1986 who were diagnosed before 1995 in Hordaland County, Norway. A total of 194 patients (94%) participated. Results: The patients had lower mean scores for all eight SF-36 health dimensions compared with sex- and age-adjusted scores in a general population. EDSS scores correlated highly with physical functioning ( r = −0.86, R 2 = 0.73), and explained some of the variation in social functioning ( r = −0.48, R 2 = 0.23) and general health ( r = −0.46, R 2 = 0.21) but little for the other dimensions. Conclusions: The SF-36 captures the broad effects of MS, and the results showed that patients also are bothered frequently with health problems such as bodily pain and low vitality. These problems, which are not reflected in the Expanded Disability Status Scale, should be given more attention in the treatment of MS and when evaluating interventions.

Objective: MS is immunologically mediated in genetically susceptible individuals. Receptors for the Fc fragment of immunoglobulin G (IgG) (FcγR) link the humoral and cellular immune responses by targeting immune complexes to effector cells. Different FcγR show variability in their distribution, strength, and capacity of binding different IgG subclasses.Methods: To investigate the role of FcγR in MS, 136 MS patients and 96 matched controls were genotyped for FcγRIIA and FcγRIIIB gene polymorphisms; the results were correlated to disease susceptibility and severity measured by the Expanded Disability Status Scale (EDSS).Results: The allele frequencies of the FcγRIIA and FcγRIIIB did not differ significantly between the MS patients and the controls. Patients homozygous for the FcγRIIIB neutrophil antigen (NA) 1 allele had a significantly more benign course of MS than patients heterozygous or homozygous for the FcγRIIIB NA2 allele. Patients homozygous for the FcγRIIA histidine (H) allele also had a more benign course of MS than patients heterozygous or homozygous for the FcγRIIA arginine (R) allele.Conclusion: The results implicate FcγRIIIB and to a lesser extent FcγRIIA as disease-modifying genes in MS. FcγRIIIB NA1/NA1 and FcγRIIA H/H bind more efficient IgG1/IgG3 and IgG2 subclasses, respectively, than FcγRIIIB NA2/NA2 and FcγRIIA R/R. A more effective processing of circulating immune complexes may be one mechanism for better clinical outcome in MS.

Objective: To evaluate the efficacy and safety of interferon-α2a (IFN-α2a) in relapsing-remitting MS (RRMS). Background: Several immune-modulating therapy regimens of IFN-α have shown varying results in MS. A recent pilot study suggested benefits from IFN-α2a. Methods: Ninety-seven patients were randomized to receive subcutaneous injections of placebo (33 patients) or 4.5 million international units (mIU) (32 patients) or 9.0 mIU (32 patients) of IFN-α2a three times weekly for 6 months, with a further 6 months of follow-up. Monthly gadodiamide-enhanced MRI was the primary method of evaluating efficacy. Results: IFN-α2a treatment resulted in fewer new MRI lesions during the treatment period ( p 2.5 times higher with 9.0 mIU IFN-α2a than with placebo ( p p = 0.0004), but the difference disappeared during follow-up. The total number of lesions (mean) increased by 4.78 with placebo, 0.86 with 4.5 mIU IFN-α2a, and 0.28 with 9.0 mIU IFN-α2a during treatment ( p = 0.030). No treatment effect on exacerbation rate, progression of disability, or quality of life was detected. Nine patients discontinued treatment, five because of adverse events. Conclusions: IFN-α2a treatment significantly reduced disease activity as measured by MRI, but the efficacy disappeared within 6 months after discontinuation of treatment. A long-term study of more patients using disability as a primary outcome measure is needed to evaluate the clinical impact.

The mixed haemagglutination technique (MA) was used to demonstrate antibodies to peripheral nerve tissue (PNS) in sera from patients with acute Guillain-Barré syndrome (GBS). Within the first 2 weeks of the disease IgG antibodies were detected in sera from 15 of 42 patients (36%). Antibodies were detected in 60% of the patients with severe GBS, and in 30% of those with a mild GBS. The highest titres were found in the sera from the most severely affected patients and could be detected after 48 days of the illness in one of the sera. Sera from healthy blood donors and from patients with various other diseases did not contain antibodies to PNS. The MA technique is reproducible and is more sensitive than the indirect immunofluorescence test and the antiglobulin consumption test.

To determine if such factors as first symptom, sex, age at onset and initial clinical course have any influence on life expectancy of multiple sclerosis patients, a survival analysis from date of diagnosis for 598 MS-patients in Norway was performed. To study the effect of all the variables simultaneously we used the Cox proportional hazards regression model with incomplete data. Median survival time was 27 years after diagnosis. The variable which most strongly predicted the duration of the disease was age at onset. High age at onset and a progressive course of the disease were correlated with a more unfavourable prognosis. The onset symptom, vertigo, was also correlated with a shorter life expectancy. No significant effect of sex was found. We found in this material an indication of improved survival over the study period.

By using enzyme-linked immunosorbent assay, Western blot and passive agglutination we have performed a pilot study involving the testing of 349 sera from the general population of 3 coastal regions in southern Norway, 230 sera from multiple sclerosis patients from western Norway, 109 age- and sex-matched controls and 34 sera from patients with other neurological diseases, for antibodies to HTLV-I. About 2% and 4% of sera from the general population had antibodies reacting with HTLV-I in ELISA and Adult T-cell Leukemia Antigen by agglutination, respectively, whereas about 8% and 5% of the multiple sclerosis sera had such antibodies. In the general population antibodies were more frequent among young individuals and there appeared to be some prevalent regional differences. Western blot confirmatory tests showed that in some instances antibodies reacted with the gag proteins, in particular p19. The results obtained in this study do not indicate an association between HTLV-I and multiple sclerosis, although at this stage we cannot rule out that another retrovirus is involved.

The mixed haemagglutination technique was used to demonstrate IgG antibodies to peripheral nerve tissue in sera from patients with the Guillain-Barré syndrome. The clinical effect and the effect on the antibodies of plasma exchange were examined in 18 patients. Neurological examination with muscle testing and neurophysiological examination of the patients were performed before and immediately after plasma exchange. Before the exchange antibodies were detected in sera from 11 of the patients. These patients showed clinical improvement during the treatment. After plasma exchange, antibodies were detected in sera from only two of the patients. The seven patients without detectable antibodies showed no clinical improvement.

A newly identified spirochete, Borrelia burgdorferi, has recently been established as the causal agent of chronic meningoradiculitis (Bannwarth's syndrome, BS). An etiological diagnosis can be obtained by specific antibody determination. To detect intrathecally produced Borrelia antibodies, we examined paired serum and CSF samples from 10 BS patients and 41 controls. CSF/serum IgG specific antibody indices were calculated by relating the CSF/serum ratio of specific antibody activity to the CSF/serum ratio of total IgG and of albumin; 8/10 BS patients compared to 4/39 controls had elevated index values. In only one of the 4 positive controls could spirochetal infection be excluded. We conclude that determination of specific antibody indices is a reliable and sensitive diagnostic test for nervous system B. burgdorferi infection.

An enzyme-linked immunosorbent assay (ELISA) was used to quantify antibodies against peripheral nerve myelin (PNM) in sera from 90 patients with Guillain-Barre syndrome (GBS) and from 70 patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Fifty-nine percent of the patients with GBS and 51% of the patients with CIDP had increased levels of anti-PNM antibodies. Antibodies were also found in 0%–14% of sera from patients with other neurological diseases and in 8% of normal blood donors. Mean levels of IgG, IgM and IgA anti-PNM antibodies were increased in sera from patients with GBS, and mean IgG and IgA anti-PNM antibody levels were increased in sera from patients with CIDP when compared with sera from normal blood donors. The mean IgG anti-PNM antibody response observed in patients with GBS or CIDP was dominated by the IgG1 and IgG3 subclasses.

Among eight sural nerve biopsies from patients with the Guillain-Barré syndrome (GBS), demyelination was observed in five and endoneural mononuclear cell infiltrates in three. Receptors for the activated third component of complement (C3b) were detected within the nerve fascicles. The receptor activity was reduced in five biopsies, and in vivo deposition of C3 within the endoneurium occurred in four. Immunoglobulins were found in four biopsies and appeared to be localized along the myelin sheaths. Both T and B lymphocytes could be detected in the mononuclear cell infiltrates, but the relative proportions of these cells could not be determined. Macrophages present in two biopsies were found to possess IgG Fc receptors. The results indicate that the complement receptors may play a role in the binding of complement-containing complexes in the nerve during the GBS disease process.

The concentrations of C3, C4, C1 inactivator, C3 proactivator and orosomucoid were determined in sera from 13 patients with Guillain-Barré syndrome. The most severely affected patients had the highest levels of C3, C4 and orosomucoid in the acute phase with a slight decline over the following 3-8 weeks. The mildly affected patients had complement concentrations in the upper normal range. In the group of patients with the highest concentrations of C3, C4 and orosomucoid, 4 out of 6 developed residual weakness, while residual weakness was only found in 1 out of 7 with normal concentrations. The measurement of C3 and C4 may, therefore, be of value in estimating the severity and prognosis in the early phase of the disease.

Hyperbaric oxygen (HBO) treatment has been reported to cause amelioration of clinical symptoms in patients with multiple sclerosis (MS). We have treated 10 MS patients with hyperbaric oxygen (100% O2 at 2 atmospheres absolute for 90 min daily for a total of 20 exposures), and performed immunological studies on peripheral blood and cerebrospinal fluid (CSF). After treatment there was a significant increase in total and helper T lymphocyte counts in peripheral blood, as well as an increase in both E, Fc gamma and C3b receptor-bearing lymphocytes. The responses to the mitogens PHA, con A and PWM were unchanged. Granulocytes showed an increased proportion of Fc gamma receptor and C3b receptor positive cells after treatment. The O2 consumption of granulocytes also increased, but phagocytosis, as measured by chemiluminescence, was unchanged. Serum IgA levels were slightly increased, while IgG and IgM concentrations remained unchanged after treatment. Cerebrospinal fluid cell counts, protein and IgG concentrations, as well as IgG indexes remained unchanged.

Median motor and sensory nerves were examined in 20 healthy subjects. Superficial stimulating and recording electrodes were used, and the nerves were examined at natural skin temperature, after cooling and after heating of the arm. The conduction velocity for the fastest and slow conducting sensory fibres (temperature range 17-37 degrees C), and for the fastest conducting motor fibres (temperature range 19-38 degrees C) increased non-linearly with increase in skin temperature. Similarly, distal motor latencies increased non-linearly with decrease in skin temperature. The effect of temperature was most pronounced in the low temperature range, and change in conduction velocity per degree centigrade was reduced toward higher skin temperature. Sensory nerve response duration increased linearly with decline in skin temperature. Sensory and motor amplitude did not show any significant relation to skin temperature.

Taurine is a sulfonic amino acid with inhibitory effects in the central nervous system. The clinical effect of taurine on dyskinesias was tested in an open trial with 14 patients. Taurine (3 g/day) was given orally in divided doses. Six patients showed an initial improvement which, however, did not persist to the end of the 6-week treatment period. No side effects were observed. It seems unlikely that taurine administration will prove effective in the symptomatic treatment of dyskinesias.

180 patients with neurological or infectious diseases and 90 normal controls were examined for blood T lymphocyte percentage by the standard method using rosette formation with untreated sheep erythrocytes (E) and a technique using 2-amino-ethyl-thio-isouronium bromide hydrobromide (AET)-treated E, with fetal calf serum (FCS) in the medium. Patients with acute meningitis had a decrease and those with infections mononucleosis had an increase in T lymphocyte percentage as measured by both assays. However, patients with active MS and with cerebral tumours had a decrease in T cell percentage by the E but not by the EAET technique. The T lymphocyte percentages of the other 4 patient groups did not differ significantly from those of the controls, regardless of the technique used. In certain diseases, the use or not of AET-treated indicator cells may thus influence the results of the rosette test.

This report describes a medulloblastoma with extracranial metastases in a 24-year-old man. Postoperatively, 60Co irradiation was given and clinical recovery was good. Cervical lymph node metastases developed 2.5 years later. The patient received cytostatic treatment and a second course of radiation therapy with 60Co and lived for 6 years after the onset of symptoms, finally dying with signs of bronchopneumonia. The possible routes of spread are discussed.

Mixed haemagglutination and complement fixation tests were used to detect serum antibodies to peripheral nerve in 36 patients with acute Guillain-Barré syndrome. Twenty patients were treated with plasma exchange, 16 served as controls. A significant antibody titre was found in 19 patients with the haemagglutination test; 30 had complement-fixing antibodies. Patients lacking complement-fixing antibodies were less disabled at entry (P less than 0.01). However, there was no correlation between the course of the disease and any of the antibodies in the two patient groups. The two tests were therefore not able to select patients for treatment by plasma exchange.

Cryostat sections of human central nervous system (CNS) tissue absorbed sheep erythrocytes (E) sensitized with rabbit IgG antibody (A). The indicator cells bound to the choroid plexus, to the leptomeninges covering the brain and spinal cord, to the arachnoid granulations and to the perivascular tissue of the neural parenchyma. Unsensitized E or E sensitized with F(ab')2 fragments of IgG were not bound. The reactions were inhibited by pooled human IgG, human IgG1 and IgG3 myeloma proteins, and Fc fragments of pooled human IgG. Whole human IgG2 myeloma protein, IgM, IgA, F(ab')2 fragments of pooled human IgG and albumin did not inhibit. Experiments with reduced and alkylated IgG, EDTA, iodoacetamide, 2-mercaptoethanol, various pHs and salt concentrations, formaldehyde, periodic acid and neuraminidase did not reveal any differences between the Fc gamma receptors in the separate anatomical areas. The Fc gamma receptors in human CNS are thus apparently very similar.