Subclinical optic neuropathy in multiple sclerosis. A neuro-ophthalmological investigation by means of visually evoked response, Farnworth-Munsell 100 Hue test and Ishihara test and their diagnostic value.

Affection of the optic nerves play a central role in multiple sclerosis (MS) symptomatology. In reported autopsy series the prevalence of optic neuropathy has approached 100%. In the present study subclinical affection of the optic nerves was investigated by visual evoked response (VER), Farnworth-Munsell 100 Hue test (FM 100 Hue test) and Ishihara plates in 17 patients with normal visual acuity and without a history of acute optic neuritis. Optic neuropathy was demonstrated in 72% of the eyes. The occurrence of optic neuropathy was also investigated by the same methods in 16 patients with previous acute optic neuritis, which was bilateral in 5 patients. Affection of the optic nerves was demonstrated in 95% in this group. The affection of also the fellow eye in patients with previous monolateral optic neuritis is unexplained. It may be an analogue to the symmetry of plaques found in the brain and the spinal cord. The cause of this peculiar distribution of lesions is, like the ethiology of MS, unexplained at present. In comparing the different methods of demonstrating optic neuropathy, VER is recommended as the method of choice.

Immune complexes and the complement factors C4 and C3 in cerebrospinal fluid and serum from patients with chronic progressive multiple sclerosis.

Immune complexes (IC) have been found in both serum and cerebrospinal fluid (CSF) in multiple sclerosis (MS). The complement system is known to play a major role as a mediator of inflammation in immune complex disease. Therefore, we have investigated paired samples of serum and CSF from 32 patients with progressive MS for IC, the levels of the complement factors C4 and C3, and presence of their activation products (AP). IC was found in serum from 17 of the 32 MS patients (53%) and in CSF from 9 of 31 MS patients (29%). No correlation was found between the occurrence of IC in serum and in CSF. The levels of C3 in serum and CSF from the MS patients did not differ from the levels in a control group, whereas the levels of C4 in MS-serum were elevated and the C4 levels in MS-CSF reduced. A low level of CSF-C4 correlated significantly to the occurrence of CSF-IC. AP of C4 and C3 in serum were seen in 11 of the 32 patients (34%), appearing significantly more frequently among patients with circulating IC. No C4- or C3AP could be identified in CSF.

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.

Circulating immune complexes and complement in the course of multiple sclerosis.

To evaluate the reactions of the humoral immune response in the course of multiple sclerosis (MS), 21 patients were examined approximately 10 times at regular intervals for 1 year. The study included concomitant investigations of the total neurological deficit (TND) and laboratory analyses of the complement profile, detection of circulating immune complexes (CIC) and heterophilic antibodies (HPA). CIC were found in 58.7% of the investigations, often with simultaneous activation of C4 and C3. The mean values of the complement levels of the MS patients, however, did not differ from the values in a normal population. The consecutive investigations demonstrated a negative regression of TND on C4 from one month previously, a concomitant negative regression of TND on C3 and a positive regression of CIC from one month subsequently on TND. No significant relation between the clinical type of the disease and the occurrence of CIC was demonstrated, but the occurrence of attacks seemed to correlate with development of HPA.

HLA and heterogeneity of multiple sclerosis.

Age at onset, debut symptoms, optic nerve signs, and severity of symptoms were evaluated from the medical records of 135 patients with MS. HLA-D/DR2 was significantly more frequent in rapidly progressive MS, and D/DR2 seemed to confer both susceptibility to the disease and to more rapid progression. However, D/DR3 seemed to protect against rapid progression.

On individual reference intervals based on a longitudinal study of plasma proteins and lipids in healthy subjects, and their possible clinical application.

In a longitudinal study, we determined interindividual and intra-individual variation in 20 plasma proteins and lipids and in other blood constituents by analysis of variance. Blood from 20 healthy subjects was sampled monthly for six months, a rigorous blood-sampling technique being applied. The mean proportion of interindividual variation differed for each blood constituent, ranging from 22 to 91% of the total variation. The possible clinical application of individual reference intervals of this homeostatic model was demonstrated by the fact that they were exceeded in individual cases of upper respiratory tract infection. Concordance between individual reference intervals in healthy controls and in patients--as exemplified in two chronic diseases, multiple sclerosis and chronic inactive pyelonephritis--suggests that the use of individual intervals in (chronic) disease is valid, even when derived from healthy persons. Additionally, sex- and age-related differences were significant for some constituents.

HLA-antigens and the prognosis of multiple sclerosis.

The histocompatibility pattern of 160 patients with multiple sclerosis (MS) living in the epidemiological area of Southern Lower Saxony was determined and compared to a control population. The only significant difference was the more frequent occurrence of DW2 in the patient group (44% vs. 21%). Taking a progression index (grade of disability divided by the duration of the disease) as a measure for prognosis no difference could be found between the DW2 positive and the DW2 negative patients. The reason why we could not confirm the worse prognosis for DW2 positive patients found by Jersild et al. (1973) and Raun et al. (1980) remains to be investigated.

Hereditary neurologic disorders, characterized by ataxia. Immunological in vitro parameters and HLA.

Nineteen untreated patients with hereditary ataxia, hereditary spastic paraplegia and Charcot-Marie-Tooth's syndrome were investigated for immunological in vitro parameters (lymphocyte transformation with PHA, con A, PWM, antigens, determination of T- and B-lymphocytes and HLA-typing). When compared with normal controls, no significant deviation was found.

E rosette-forming lymphocytes in multiple sclerosis patients. Basic protein stimulation of rosette-forming cells.

"Total" and "active" T cells were enumerated using sheep red blood cell (SRBC) rosetting technique. The percentages of "total" and "active" T lymphocytes were not significantly different in multiple sclerosis patients as compared to other neurological disorders and/or healthy controls. However, the number of "avid" T cells binding more than three SRBC was significantly increased in MS patients. Active E rosette test has shown hypersensitization to myelin basic protein in 50% MS patients and 31% OND patients. All healthy controls studied, except one had negative response.

Long-term transfer-factor treatment for multiple sclerosis.

In groups of 16 patients with multiple sclerosis, 13 months' double-blind treatment with transfer factor from random normal donors differed from placebo treatment only in producing a temporary restoration of lymphocyte reactivity to measles virus antigen, and did not arrest the degeneration of nerve tissue.

Lymphocyte stimulation in multiple sclerosis patients untreated and treated with transfer factor. Long-term studies on the effect of different stimulants on myo-(2-3H)inositol incorporation into phosphatidylinositol of lymphocytes.

The lymphocytes from controls, untreated MS and MS patients treated with transfer factor were stimulated with PHA, PWM, PPD, LPS and MA and the increased incorporation of myoinositol into phosphatidylinositides was determined. As compared with controls, the untreated MS patients revealed significantly lower index of stimulation with PHA, LPS, PPD and MA. The response of lymphocytes from MS patients treated with transfer factor was intermediate. No correlation between disease progression and stimulation of inositol incorporation was observed. Analysis of variance showed that the myoinositol test is not applicable in long-term studies to distinguished single subjects, however it is useful to determine differences between MS patients and controls.

Endurance test as index of paresis in patients with multiple sclerosis.

This study has been performed to evaluate slight pareses in patients with multiple sclerosis by means of mechanical endurance experiments. The results are compared with manual grading of pareses in patients and with healthy controls. On average, concordance was found between manual and mechanical estimation but the method is not advantageous for clinical purposes.