T-cell subpopulations in the cerebrospinal fluid and peripheral blood of patients with multiple sclerosis: a follow-up study.

We analyzed the relative and absolute numbers of CD4+ cells positive and negative for CD45RA marker as well as the numbers of CD8+ cells positive and negative for CD11b in the cerebrospinal fluid (CSF) and peripheral blood (PB) of 17 patients with multiple sclerosis (MS) during and 60 days after an exacerbation. We also studied samples from 27 control patients, 17 of whom had a noninflammatory neurologic disease and 10 of whom had an inflammatory neurologic disease other than MS. The results confirmed the small number of CD45RA-positive (naive or suppressor inducer) CD4+ cells as well as CD11b-positive (suppressor) CD8+ cells in the CSF compared with the PB for all paired CSF-blood comparisons. The relative numbers of these cells did not significantly differ between samples taken during an exacerbation and those taken 2 months later. In PB, the percentage of CD8+ CD11b-positive lymphocytes was lower in patients with MS or in patients with an inflammatory neurologic disease than in patients with a noninflammatory neurologic disease. The results indicate that there are fewer cells responsible for suppression-related phenomena in CSF than in PB but that this phenomenon is not specific to MS.

Influx of nonactivated T lymphocytes into the cerebrospinal fluid during relapse of multiple sclerosis.

T lymphocytes were analyzed in the cerebrospinal fluid of 17 patients with multiple sclerosis during and 2 months after an exacerbation. The percentage of activated (HLA-DR+) T lymphocytes was decreased in the cerebrospinal fluid during the relapse but returned thereafter to the level comparable to that in patients with noninflammatory neurological diseases, whereas no fluctuation in the total number of these cells was found. This suggests an influx of nonactivated T lymphocytes into the cerebrospinal fluid at the beginning of the relapse.

Treatment of acute exacerbations in early multiple sclerosis: cyclosporin A or prednisolone?

Twenty-six acute exacerbations in 26 patients with early definite multiple sclerosis (MS) were treated with oral cyclosporin-A (CyA) or oral prednisolone in a double-blind, controlled and randomized trial. The duration of the treatment was 6 weeks. All of the patients showed improvement during the treatment. There were no differences in outcome between patients on CyA (7.5 mg/kg) or prednisolone (decreasing doses from 0.8 mg/kg) during the 6 week treatment. However, the improvement of clinical signs 3 months after the treatment was slightly greater in the prednisolone group. The drugs did not have significant side-effects. There was no fluctuation in the CD4/CD8 ratio during the follow-up. The two treatment groups did not differ from each other in respect to the number of CD3 (T3), CD4 (T4), CD8 (T8), CD14 (monocytes), CD20 (B cells) or CD25 (interleukin-2 receptor positive cells). The number of active T cells with the interleukin-2 receptor was high in the beginning of the exacerbation but it decreased during the treatment. To conclude, the effects of CyA and prednisolone were comparable in the treatment of acute MS relapses.

Otoneurological and ultra low field MRI findings in multiple sclerosis patients.

Otoneurological and ultra low field MRI findings in multiple sclerosis patients: 22 patients suffering from multiple sclerosis (MS) underwent thorough neurological and otological examination, extensive ENG testing and Magnetic Resonance Imaging (MRI) examination of the central nervous system. All patients fulfilled the Schumacher criteria for a diagnosis of definitive MS. 20 of the patients had been included in previous otoneurological studies three to five years ago. The general disability assessed according to Hyllested's scale was: Class 1-7, Class 2-4, Class 3-6, Class 4-3, Class 5-2 patients. Thus 11 patients had none or only slight disability. Nevertheless, all patients showed abnormal findings when classified according to the Kurtzke disability scale, which reflects the involvement of separate neuronal entities. The ENG examination revealed abnormal findings in all patients. The most common abnormalities found were as follows: abnormal pendular test 19, ocular fixation index 18, optokinetic nystagmus 14, saccadic eye movements 14 and spontaneous nystagmus 12. 14 patients had uni- or bilateral abnormally slow adduction movements in the saccadic test consistent with internuclear ophthalmoplegia (INO), which is caused by a lesion of the brain stem. MRI examination of the 21 patients studied revealed abnormal findings consistent with MS in sixteen cases. The lesions were unilateral in 5 and bilateral in 11 patients. The most common location for these abnormal findings consistent with MS plaques were in the white matter around the lateral ventricles. Plaques in the brain stem and/or cerebellum were found in only two cases despite numerous clinical and otoneurological findings that indicated the presence of functional lesions in these areas.

Immunological findings during an acute relapse of subacute sclerosing panencephalitis in a patient with an unusually prolonged disease course.

A 171/2-year-old male subacute sclerosing panencephalitis patient underwent a disease relapse after an 8 year remission. A total of 14 paired peripheral blood/cerebrospinal fluid specimens were obtained during this relapse. These specimens were tested for 13 parameters of non-specific or measles virus-specific cell-mediated and humoral immunity. There was a rapid and significant fluctuation in all of these tests. Total loss of measles-specific T cells response was found during the relapse. The response re-appeared and measles-specific antibodies increased significantly later on. The results suggest that measles virus infection was reactivated in this patient and that the observed immunological changes could at least partially be explained by this.

Vibratory perception threshold in patients with mild multiple sclerosis.

The vibratory perception threshold (VPT) was measured bilaterally on both the upper and lower extremity in 69 patients with mild multiple sclerosis. In the case of the lower extremities the VPT measurements were closely correlated with qualitative vibratory perception measurements performed with a tuning fork; in the upper extremities the association was weak. The VPT was abnormal at least in one extremity in 38% of the patients. Quantitative VPT measurement seem to be a suitable technique for the detection of sensory symptoms of central origin.

Thymoma with immunodeficiency (Good's syndrome) associated with myasthenia gravis and benign IgG gammopathy.

We treated a case of thymoma with immunodeficiency (Good's syndrome) associated with a rare combination of other parathymic syndromes including myasthenia gravis, benign IgG lambda M component, pernicious anemia, and diabetes. The characterization of the patient's immunologic capacity disclosed practically normal T-cell number and mitogenic responses but impaired lymphokine production as well as B-cell function.

Stapedius reflex and brainstem auditory evoked responses in multiple sclerosis patients.

The stapedius reflex (SR), its adaptation and the brainstem auditory evoked potential (ABR) were recorded in a group of 53 multiple sclerosis patients. All cases were classified as definite according to Schumacher's criteria, and their grade of disability in Hyllested's system was 1-4: no cases of the gravest (grades 5 and 6) disability were included in the series. The peripheral hearing (pure-tone audiogram and speech threshold) was normal in 44 and slightly impaired in 8 cases. SR was abnormal in 6 (11%) and borderline in 11 (21%), whereas the ABR was considered abnormal in 21 (40%) patients. Deviant SR and ABR findings had only slight or no correlation to clinical data. Intercorrelation between SR and ABR abnormality was better but not implicit and a few cases with deviant ABR showed normal SR: The frequency of abnormal and borderline SR findings was clearly higher in bilateral than in unilateral ABR abnormality. Subclassification of ABR into an upper and a lower type of pathology did not correlate with SR abnormality.

Intrathecal antibody synthesis to virus antigens in multiple sclerosis.

Intrathecal antibody synthesis against 17 common viruses and Mycoplasma pneumoniae lipid antigen was measured in 30 multiple sclerosis patients and 30 patients with other neurological diseases. Antibody synthesis was found against all of the antigens in at least a few of the MS patients. The highest number of patients had intrathecal synthesis of antibodies to measles, rubella and paramyxo type viruses and the lowest frequency was against M. pneumoniae, herpes simplex virus, adenovirus and cytomegalovirus antigens. Simultaneous antibody synthesis occurred against 1-11 different antigens in these patients. When the summation of different antibody specificities synthesized intrathecally was compared to the CSF-IgG Index, which measures the intrathecal immunoglobulin G synthesis, a fairly close correlation was found. The control patients had occasional antibody synthesis but generally only against one single virus antigen. The intrathecal antibody synthesis against viruses did not correlate to the disability of the MS patients. The intrathecal antibody synthesis was not different in younger and older patients or patients with shorter or longer disease duration, suggesting that events leading to intrathecal antibody synthesis may occur relatively early in life in these patients. When presence of Dw2 antigen was compared to different specificities of intrathecally synthesized immunoglobulins, only measles virus antibody synthesis showed correlation.

Involvement of the central nervous system in acute, uncomplicated measles virus infection.

A prospective study on acute, uncomplicated measles infection was carried out in 59 patients hospitalized for an ordinary measles infection. A clinical and serological diagnosis of an acute measles infection was made in all cases. Serial serum and cerebrospinal fluid (CSF) specimens were taken two to five times from each patient and tested for pleocytosis, albumin, and measles-specific antibodies. Pleocytosis was found in 18 patients (30%), usually shortly after the onset of rash. Nine patients had antibodies against measles virus in their CSF. Six of them seemed to have damage to the blood-brain barrier, but in two cases there was a very high serum antibody titer with a normal serum/CSF ratio. One patient had a local antibody production against measles virus in the central nervous system. Conventional electroencephalography (EEG) was recorded on 22 children, and a separate, quantitative EEG study with two to six consecutive recordings was also performed on a group of nine patients. Moderate or strong slowing of background EEG activity was found in 50% of the patients. In the consecutive recordings, the changes culminated a few days after the onset of rash. No correlation seemed to exist between the changes in the CSF and the age of the patient, on the one hand, and slowing of the EEG, on the other.