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PubMedDate not supplied

[Visual somatosensory and auditory evoked potentials in multiple sclerosis].

In a group of 15 patients with multiple sclerosis and in a control group of 20 healthy subjects visual evoked potentials produced with flashes or checkerboard pattern, auditory evoked potentials after stimulation with three different tones, and somatosensory evoked potentials after stimulation of the left, right or both median nerves, and reactions to stroboscopic stimulation at seven different frequencies were investigated. Recording was done with unipolar leads from frontal, central, occipital and temporal regions on the left and right side. In patients with multiple sclerosis the cortical responses to all these stimuli had lower amplitude than in healthy subjects, and the reponses to stroboscopic stimulation were also abnormal in the group of patients. Different clinical signs related to various defects of sensory functions showed a high correlation with electrophysiological anomalies. Non-linear discrimination analysis was carried out using 13 variants (the amplitudes were calculated from peak to peak and correlation coefficients were calculated between identical regions on the left and right side) comparing the group of patients with the control group. Using this method it was possible to establish the correct diagnosis in all cases of multiple sclerosis and 85% of healthy subjects could have been included into the asymptomatic group. Since the methods used in these investigations are easy and can be easily automated the authors think that they could be very useful in the clinical diagnosis of multiple sclerosis.

Acoustic Stimulation↗

PubMed1979

Pes cavus and claw toes deformity in patients with spinal cord injury and multiple sclerosis.

Patients with spinal cord injury or multiple sclerosis were surveyed for the presence of extreme foot deformities and spasticity. Pes cavus and claw toes were found in eight of 80 spastic spinal cord injury and two of 20 multiple sclerosis patients. Pes cavus and claw toes were not found in 29 flaccid spinal cord injury patients. Pes cavus and claw toes were associated with flexor reflexes which could be elicited by pin prick proximal to the knee, suggesting extreme spasticity--and by low excitatory thresholds for the anterior tibialis as indicated electromyographically. Complications of severe spasticity associated with spinal cord injury and multiple sclerosis include pes cavus and claw toes, mediated in part by spasms of the anterior tibialis.

Adult↗

PubMed2025

Entertainment activities and the risk of multiple sclerosis: A Mendelian randomization analysis.

Modifying environmental and lifestyle factors may have the potential to prevent and ameliorate multiple sclerosis. Further elucidating the etiology of multiple sclerosis and proposing actionable prevention measures are of significant importance, but establishing causality in epidemiological data can be challenging. This study employed a two-sample Mendelian randomization analysis to evaluate the causal effect of entertainment activity factors on the risk of multiple sclerosis. Publicly accessible summary statistics derived from genome-wide association studies were utilized to assess 14 modifiable forms of entertainment activities. The inverse variance weighted random effects method was used as the primary analytical approach to estimate causal effects. Additionally, MR-Egger, weighted median, and weighted mode methods were applied to assess robustness. Systematic sensitivity analyses and heterogeneity tests were conducted to verify the reliability of our findings. We found that spending time outdoors in the summer may prevent the development of multiple sclerosis (odds ratio = 0.995; 95% confidence interval 0.991-0.999; P = .010). In contrast, the other entertainment activities studied showed no significant causal relationship with multiple sclerosis. Our results suggest that spending time outdoors in the summer may protect against the development of multiple sclerosis, providing implications for preventive measures against the disease.

Humans↗

PubMed1975

Early sterile autopsy in etiological studies on multiple sclerosis.

The clinical findings and course in the first 2 cases of multiple sclerosis are described, in whom it was possible to isolate a virus from brain tissue by early sterile autopsy and fusion technique. It is noteworthy that in one of these cases multiple sclerosis probably occurred in female members of the family through three consecutive generations. A report is made on an additional case, in which no virus could be isolated, but in which electron microscopic studies showed two types of virus particles: nucleocapsid-like structures and particles identical in form and size with papova virus. Electron microscopic findings and attempts to cultivate a virus in multiple sclerosis published by other authors are discussed. It is pointed out, that the results described provide as yet no proof for the viral etiology of multiple sclerosis. They support the hypothesis, however, that a virus may play an essential role in the etiology and/or pathogenesis of this disease. Problems in relation to brain autopsy in multiple sclerosis are discussed. Early sterile autopsy is considered the most practicable possibility for obtaining tissue material for culturing and for ultrastructural studies in multiple sclerosis.

Adult↗

PubMed1978

Familial multiple sclerosis: clinical, histocompatibility, and viral serological studies.

Evaluation of presumed "multiple sclerosis families" and comparison with recently reported families has led us to the following observations: (1) Seven of our original fourteen presumptive multiple sclerosis families had to be eliminated after personal clinical evaluation of family members failed to confirm the diagnosis in a second close relative. (2) No segregation of HLA type was noted between affected and unaffected individuals in our seven bona fide multiple sclerosis families, and no consistent segregation was noted in the twenty-eight families reported elsewhere. This supports other genetic evidence that there is not a single, major gene mapping in the HLA complex which predisposes to multiple sclerosis. (3) The DW2 antigen was increased in frequency among affected members of our families, and the A3 B7 haplotype was more frequent among affected members of other families reported. But unaffected members also tended to have an increased frequency of these same antigens. (4) No relationship was noted between HLA type and antimeasles antibody titer within our families.

Antibodies, Viral↗

PubMed1979

Disproportionate elevation of the immunoglobulin G1 concentration in cerebrospinal fluids of patients with multiple sclerosis.

We determined immunoglobulin G (IgG) subclass concentrations and studied their distributions in the cerebrospinal fluids of patients suffering from multiple sclerosis, other inflammatory neurological diseases, and non-inflammatory diseases of the nervous system in comparison with a control group. In addition, the four subclass concentrations were measured in serum specimens of the multiple sclerosis and control groups. These data were correlated with the extent of local IgG synthesis in the subarachnoid spaces of the patients belonging to the different groups. We found a selective elevation of the IgG1 subclass in the cerebrospinal fluids of multiple sclerosis patients, and there was only a very small overlap of the IgG1 ranges of the multiple sclerosis and control groups. No major differences were detected between the IgG subclass distributions in different courses of multiple sclerosis nor between multiple sclerosis and control sera. The group with non-inflammatory diseases showed a uniform elevation of all four subclasses and a greater overlap with the normal range. This latter feature was combined with an elevated IgG1 concentration in the group with other inflammatory diseases. It is concluded that locally synthesized IgG in the cerebrospinal fluids of multiple sclerosis patients consists mainly of IgG1.

Humans↗

PubMed1976

Genetic association of multiple sclerosis and HL-A determinants.

Segregation of HL-A haplotypes was analyzed in 10 families in which there were at least two cases of multiple sclerosis. In nine families, multiple sclerosis was associated with only one parental HL-A haplotype. Specific HL-A determinants associated with multiple sclerosis differed among the families, suggesting that another histocompatibility-linked factor, possibly a gene determining susceptibility (or lack of resistance) played an etiologic role. Lod score analysis based on nine families suggested a close association between such a gene (labeled MSS) and the HL-A gene complex. However, when all 10 available families were analyzed, the association approached but did not reach statistical significance. Thus, the HL-A haplotype segregation did not prove that a histocompatibility-linked gene is related to the cause of multiple sclerosis, but study of additional multiplex families is certainly warranted. Other factors, possibly genetic (although not HL-A-linked), environmental, or the two together, may be required for multiple sclerosis to become clinically apparent.

Epitopes↗

PubMed1975

Cerebrospinal fluid proteins in multiple sclerosis.

Various CSF proteins were studied in 255 definite multiple sclerosis patients at various disease stages and compared with corresponding values obtained from 174 controls. The CSF changes in acute multiple sclerosis patients included a significant increase of total proteins and of gamma globulin, IgG, IgA, IgM, alpha-2 ceruloplasmin, 7S-gamma-1, and cytotoxic index for nerve cells in tissue culture, and significant decreases of pre-albumin, alpha-1, and alpha-2 and of the beta/gamma globulin ratio. The CSF levels of IgG, IgA, and IgM remained significantly higher in steroid-treated multiple sclerosis patients than in controls, but the levels often were significantly reduced while patients were on treatment or in remission. During remission or treatment with ACTH and/or steroids, the alpha-2 ceruloplasmin, 7S-gamma-1, and cytotoxic index were significantly reduced and the pre-albumin, alpha-1, and alpha-2 globulin classes and the beta/gamma ratio showed a tendency to return to normal.

Adolescent↗

PubMed1979

Dorsal spinal cord stimulation in the treatment of multiple sclerosis.

Previously published work indicated significant improvement in the symptoms of multiple sclerosis with dorsal spinal cord stimulation. In this study 23 patients with multiple sclerosis documented by history, examination, laboratory studies, and clinical course were treated with dorsal spinal cord stimulation and followed for 19 to 45 months (mean, 32 months). Pre- and postoperative clinical assessment was carried out using the Kurtzke Scale. Walking velocity, upper limb coordination, sphincter function, and sensory function were also evaluated quantitatively. No statistically significant objective improvement in any of these measures was demonstrated. Fifty per cent of the patients initially reported subjective symptomatic improvement, but this declined to 30% at last follow-up. Fifteen of 23 patients experienced complications related mainly to the hardware used and required a total of 21 subsequent operative procedures for correction of these complications. These results do not support the continued clinical use of dorsal spinal cord stimulation in the symptomatic treatment of multiple sclerosis.

Electric Stimulation Therapy↗

PubMed1979

[Immunoreactions of the delayed type in patients with multiple sclerosis (author's transl)].

Skin tests were performed in 34 multiple sclerosis patients. The incidence of positive reactions was reduced in these patients compared with healthy controls, with regard to different recall antigens with the exception of varidase, as well as the PHA and DNCB. No definite differences in reaction between patients who had been suffering from multiple sclerosis for a long time or for a short time, could be established. However, there was a certain dependence on the stage of the disease in so far as positive reactions were less frequent during the acute episode--more pronounced during the subsiding attack than at the onset of the episode--, than during the interval between two attacks. These results suggest that multiple sclerosis is primarily characterised by a weakness of cell-mediated immunity and that this weakness becomes more pronounced during the acute episode. The differences between the skin test reactions performed during the individual phases of the disease are too slight to assist in defining the acute episodes. It may be possible to identify changes in the reaction level via long-term studies.

Humans↗

PubMed1976

[Gustatory disturbances in multiple sclerosis].

90 patients with advanced multiple sclerosis were examined electrogustometrically and with taste solutions. In 4 cases only the bitter sensation was diminished all over the tongue. 4 other patients showed a prolonged latency. Besides a unilateral dissociated hypogenusia in 4 patients there were no further serious taste disturbances. One man showed a taste and sensory hyperpathia on one side of the body.

Adult↗

PubMedDate not supplied

[Serial studies of sterile skin exudate in patients with multiple sclerosis].

In 23 patients with multiple sclerosis (group i) and 15 other subjects (group II) cell content of sterile exudate was studied in the skin window test of Rebuck. The results were compared. Cellular reaction of the skin was greater in group I than in group II and the difference was statistically significant. The number of mononuclear cells was increased especially from 12 to 15 hours after scarification.

Adolescent↗

PubMed1976

[Methods and evaluation of visually evoked EEG potentials in cases of suspected multiple sclerosis (author's transl)].

In multiple sclerosis, average EEG potentials which are monocularly evoked by checkerboard pattern reversal frequently show increased latencies of the dominant, occipitally positive peak (more than 110 ms), and latency differences of more than 6--7 ms between responses to right and left eye stimulation. Fixation of the stimulus field at the lower border causes significantly longer latencies and smaller amplitudes than fixation at the upper border. With lower border fixation, the increase of response latency may suggest a reversal of response polarity in extreme cases. Central fixation often but not always results in responses similar to upper border fixation. In order to have minimal variability of the results, fixation of the stimulus field at the upper border is preferred over central fixation.

Electroencephalography↗

PubMed1979

Abnormal protein patterns in multiple sclerosis.

Sera from patients with multiple sclerosis (MS) and those obtained from normal subjects are indistinguishable by regular 5% or 7% polyacrylamide gel electrophoresis. However, 11 out of 15 MS sera examined by gradient polyacrylamide gel electrophoresis showed three distinct protein bands. None of the sera obtained from 10 normal subjects showed the characteristic protein patterns when they were examined by gradient gel electrophoresis. Similar results were obtained with de-albumin serum samples or with serum proteins precipitable at 50% ammonium sulfate saturation. These three proteins have now been purified to homogeneity by preparative gradient gel electrophoresis. Molecular weights of these proteins were estimated from gradient gel electrophoresis as 398,000, 363,000 and 302,000 daltons, respectively.

Blood Protein Electrophoresis↗

PubMed1978

The effect of induced hyperthermia on the blink reflex in multiple sclerosis.

In 76 patients with multiple sclerosis, the blink reflex was elicted electrically at normal body temperature and during induced hyperthermia to observe the effect on conduction within the reflex pathway through the brainstem. Special attention was directed to 31 patients with electrophysiologic evidence of reflex slowing, presumably because of demyelination in the reflex pathway. Hyperthermia did not induce any significant changes in mean reflex latency, amplitude, or duration in either the overall group of 76 or in the 31 patients with baseline blink reflex abnormalities. While the mean reflex latency did not change, 13 (33 percent) of 39 abnormal R1 responses from the 31 patients changed by 1.5 msec or more during hyperthermia, whereas change of similar magnitude was noted in only three (3 percent) of 90 normal R1 responses.

Body Temperature↗

PubMed2026

Nimodipine in animal models of demyelination relevant to multiple sclerosis: a systematic review.

BACKGROUND: Multiple sclerosis (MS) is the most common inflammatory neurodegenerative disease in which axonal injury, neuronal death, and demyelination occur. Treatment for MS relapses remains limited, which alleviates acute loss of function but has no impact on long-term disability. This study aimed to perform a systematic review of the effects of nimodipine on experimental demyelination models, including experimental autoimmune encephalomyelitis (EAE) and Cuprizone models in rodents. METHODS: This study was conducted following the PRISMA statement. A systematic search was performed in PubMed, Scopus, the Cochrane Library, and Google Scholar. The primary outcome was EAE clinical disease severity (peak clinical score and/or cumulative disease burden). Secondary outcomes included relapse activity (when reported), histological myelin outcomes, oligodendrocyte lineage markers, neuroaxonal injury markers, and inflammatory readouts. Risk of bias was assessed using the SYRCLE tool. RESULTS: Out of 4660 results, 5 studies were included in the systematic review (four EAE studies and one cuprizone model). Nimodipine was administered using heterogeneous regimens (oral, intravenous, intraperitoneal, subcutaneous, or osmotic pump delivery; 1-30 mg/kg/day). The included studies reported the variable effects of nimodipine on relapse-related outcomes, myelination, inflammatory processes, and neuroprotection in the EAE model of MS. Across EAE studies, nimodipine generally reduced clinical disease severity or cumulative burden, although relapse-related outcomes were inconsistent. CONCLUSIONS: Preclinical evidence suggests that nimodipine may attenuate disease severity and demyelination and may promote repair-related processes in rodent models relevant to MS. However, to evaluate the clinical applicability of nimodipine in MS patients, well-powered, transparently reported preclinical replication and early-phase clinical studies are required before clinical translation.

Animals↗

PubMed1977

Myelin encephalitogenic protein fragments in cerebrospinal fluid of persons with multiple sclerosis.

With a double-antibody radioimmunoassay performed on unconcentrated cerebrospinal fluid, eight of 14 patients in an acute phase of multiple sclerosis had levels of 3.4 to 15.4 ng per milliliter of the P1 fragment (residues 43-88) of myelin encephalitogenic protein. Encephalitogenic protein-P1 was found only in the acute phase and was present in six of seven persons in the first week of an exacerbation and absent in 29 multiple sclerosis patients who were stable or had a gradually progressive course. Six of 117 controls had detectable cerebrospinal fluid encephalitogenic protein-P1. Only in two of these, one with a recent cerebral infarction and one with diabetic nephropathy who was in coma, were the levels in the range encountered in patients in the acute phase of multiple sclerosis. Although not entirely specific for multiple sclerosis, the presence of material in the cerebrospinal fluid of multiple sclerosis patients cross-reacting with encephalitogenic protein-P1 appears to be a characteristic of acute exacerbations.

Adolescent↗

PubMed1979

Idiotype anti-idiotype complexes in cerebrospinal fluids of multiple sclerosis patients.

The involvement of idiotype-anti-idiotype complexes in multiple sclerosis was approached by ultracentrifuge studies. Specimens of the immunoglobulin G fraction obtained from the cerebrospinal fluids of multiple sclerosis patients which contained distinct oligoclonal bands, were subjected to analytical ultracentrifugation. None of these samples revealed the presence of any detectable amount of oligomeric immunoglobulin G, namely dimer or trimer. By comparison with control mixtures containing known amounts of dimeric immunoglobulin, it was evaluated that the cerebrospinal fluid samples contain less than 5% dimer. These findings indicate that the spinal fluids of multiple sclerosis patients do not contain idiotype-anti-idiotype complexes to an extent that would account for the oligoclonal immunoglobulin bands as representing complementary idiotypes and anti-idiotypes.

Antibodies, Anti-Idiotypic↗