Multiple sclerosis. A historical review with emphasis on the last 20 years.
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History, 19th Century↗
Biomedical subjects
H Carton
Publications and source records attributed to H Carton.
Prevention of acute autoimmune encephalomyelitis and abrogation of relapses in murine models of multiple sclerosis by the protease inhibitor D-penicillamine.
The in vitro activity of gelatinase B, an enzyme whose appearance in the cerebrospinal fluid is associated with inflammatory diseases of the central nervous system, was dose-dependently inhibited by the antirheumatic D-penicillamine. Inhibition of gelatinase B in electrophoretically pure preparations and in cell culture supernatants and human body fluids was obtained at dosages reached in the circulation of patients treated with a peroral dosis of 750 mg D-penicillamine per day. In mice, developing acute demyelination, D-penicillamine significantly reduced the mortality and morbidity rates of experimental allergic encephalomyelitis (EAE). In chronic relapsing EAE in Biozzi AB/H mice, an animal model for relapses in multiple sclerosis (MS), it attenuated the exacerbations, even when the treatment was started after the primary full-blown disease had developed. We infer protease inhibition as the mechanism of action of D-penicillamine and suggest that its use may be effective as peroral treatment for MS.
Acute Disease↗
Importance of HLA-DRB1 and DQA1 genes and of the amino acid polymorphisms in the functional domain of DR beta 1 chain in multiple sclerosis.
The association of some HLA class II alleles with multiple sclerosis (MS) has been amply documented. In the present study the role of HLA class II haplotypes and genotypes and of polymorphic amino acids at the DR beta 1 locus, located in the antigen binding groove and the CD4 binding domain of the DR beta 1 chain, were studied in 78 unrelated Caucasian chronic progressive MS (CP MS) patients and 204 controls. The results confirmed the positive association of the DRB1*1501 allele and through linkage also of the DRB1*1501-DQA1*0102 haplotype with MS. In addition, the results showed that the DRB1*1501/DRB1*0400 or DR beta 1Ala71+ His13+ genotype conferred the highest relative risk for MS (RR = 9.14). Alleles encoding for DR beta 1Phe47+, DR beta 1Asp70+ and DR beta 1Thr140+, DQ alpha 1Phe25+, DQ alpha 1Leu69+ residues were protective and the highest protection (RR = 0.24) was provided by the DR beta 1(Phe47+)-DQ alpha 1Phe25+ and DR beta 1(Ser13+)-DQ alpha 1Phe25+ haplotypes. Our results suggest that both DQ and DR alpha beta heterodimers might contribute to the increased or decreased risk to develop MS by the shape of their antigen-binding groove.
Adult↗
HTLV-negative and HTLV type I-positive tropical spastic paraparesis in northeastern Brazil.
A type-specific serological survey among 1042 random nonneurological outpatients in two cities in the state of Ceara (northeastern Brazil) shows a low prevalence of HTLV-I (0.34% in Fortaleza; 0.44% in Crato) and of HTLV-II (0.34% in Fortaleza; 0% in Crato). Among 62 chronic myelopathic patients seen in Fortaleza 27 patients were found with clinical features of tropical spastic paraparesis (TSP); 10 of 27 were found HTLV-I seropositive (37%; 95% confidence limits, 19-58%). Proviral genome detection by polymerase chain reaction in 5 seropositive and 12 seronegative patients confirmed the serological findings. This excludes HTLV-I or -II infection as a cause in the seronegative TSP patients. The HTLV-positive and -negative patients did not differ clinically and by history, except that seropositives had a longer mean disease duration, a female predominance, and a higher proportion of white Caucasians. In this population with low HTLV-I and HTLV-II prevalences, HTLV-negative TSP is at least as frequent as the HTLV-I-associated TSP.
Brazil↗
HLA and T-cell receptor polymorphisms in Belgian multiple sclerosis patients: no evidence for disease association with the T-cell receptor.
There are compelling data to indicate that the susceptibility to multiple sclerosis (MS) is inherited, at least in part. Particular HLA genotypes may be associated with MS and recently also polymorphisms in the T-cell receptor (TCR) genes have been reported to correlate with the disease; however, these data have been difficult to confirm. We investigated the TCRA and TCRB chain genes of HLA-typed Belgian CP MS patients employing four DNA restriction fragment length polymorphisms (RFLPs) detected with TCR constant (TCRAC1, TCRBC2) and variable (TCRBV8, TCRBV11) gene segments. Similar frequencies in patients and controls were observed for all RFLPs studied. Although the HLA DR2 genotype was significantly associated with MS, no interactive effects were seen with MS, DR2, TCRAC1, TCRBC2 and TCRBV alleles. We conclude that, while a clear association with HLA DR2 is observed, little convincing evidence exists for an association of CP MS with RFLPs of the TCRA or TCRB chain genes.
Alleles↗
Pregnancy and multiple sclerosis: the influence on long term disability.
We studied 200 female patients with multiple sclerosis (MS) to investigate whether pregnancy after the onset of disease influences long term disability. As an index of progression, we used the time between disease onset and wheelchair dependence. Patients who had at least one pregnancy after onset were wheelchair dependent after 18.6 years, versus 12.5 years for the other women (P < 0.0001). This difference remains statistically significant after correction for age at onset of disease.
Activities of Daily Living↗
Familial transmission and minimal sequence variability of human T-lymphotropic virus type I (HTLV-I) in Zaire.
Our group previously reported a strong familial clustering of HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Zaire, suggesting a familial transmission of the virus together with the presence of cofactors. In the present study among 84 relatives of 16 HTLV-I-positive or HAM/TSP index cases, we found that all 15 seropositive children had a seropositive mother and that all 15 children with a seropositive father but a seronegative mother were seronegative. Lymphocytes of 17 relatives from 2 families with a familial HTLV-I-associated neuropathy were tested in 2 polymerase chain reaction (PCR) assays amplifying pol and tax/rex gene fragments. The 10 seropositive individuals were PCR positive for HTLV-I and the 7 seronegatives were negative in both PCR assays. The PCR results showed no evidence for a long lag period between infection with HTLV-I and seroconversion. The HTLV-I long terminal repeat (LTR) of these 10 individuals, related in the first to the fourth degree, was amplified and sequenced. Identical sequences were found within the families except for one woman infected with two variants, one being the familial strain and the other a mutated one with a single nucleotide substitution in the 755 sequenced nucleotides of the LTR region. The family strain and the mutant were both present in two samples taken 1 year apart. Together, the HTLV-I serology, PCR, and sequencing results point toward mother-to-child transmission as the main mode of HTLV-I infection in this population. Comparison of the LTR sequences of the two families with other HTLV-I strains from different geographical regions shows that the Zairean HTLV-I strains form a separate cluster.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Prevalence of multiple sclerosis in Flanders, Belgium.
Two hundred twenty patients fulfilling the Poser diagnostic criteria for definite and probable multiple sclerosis (MS) were ascertained in an area of Flanders (Belgium) including the city of Leuven through the general practitioners and the neurologists practicing in the area, through the medical records of the National Center for MS and through the membership list of the MS patient society. Leuven is located at a latitude of 50 degrees 53 N. A prevalence rate of 73.8 per 100,000 [95% confidence limits (95% CI) 58.7-89.0] for men and 101.3 (95% CI 80.4-114.5) for women, and of 87.9 for both sexes (95% CI 76.2-99.4) was found on October 1, 1991. This prevalence rate is not significantly different from rates recently reported for other areas in Europe at the same latitude. The female to male ratio however was only 1.41, which is significantly lower than that in neighboring regions.
Adolescent↗
[Tropical spastic paraparesis in the tropics and Brazil. A historical analysis].
The tropical spastic paraparesis (TSP) is a chronic myelopathy, predominant in the tropics, recently known to be of retroviral origin (HTLV-I). This paper aims at delineating the clinico-etiological evolution of this entity. The historical analysis of it showed that the TSP has had, along decades, many different denominations and the discovery of the retroviral origin for some of them has stimulated new paths of research and epidemiological interest in the tropics and Brazil.
Brazil↗
Brazilian studies on tropical spastic paraparesis. A meta-analysis.
Tropical spastic paraparesis (TSP) is a chronic progressive myelopathy and in most of the cases has a retroviral (HTLV-1) etiology, when it is denominated HTLV-1 associated-mielopathy (HAM/TSP). Around 433 cases of TSP have been described in Northeast and Southeast Brazil. Among these cases, 157 (36.2%) are HTLV-1 positive and 276 (63.7%) are negative. Their mean age is 43.8 years with a slight predominance of females and mulattoes, although white patients are also numerous. Clinically all patients exhibit a spastic paraparesis with variable sphincter and sensory disturbance. Pain and autonomic symptoms seem to be expressive in the HTLV-1 positive HAM/TSP Brazilian patients.
Adult↗
Carotid artery surgery in the presence of an occlusion of the contralateral carotid artery: perioperative risk analysis and follow-up.
A retrospective study of 129 carotid artery reconstructions with an occlusion of the contralateral internal carotid artery (group CO) is presented. A control group comprised 489 patients with a stenosis of < 50% at the contralateral side (group CN). Both groups had the same mean age. There were fewer women in group CO (14% versus 31%, P < 0.0001), and more patients had a history of coronary heart disease (57% versus 44%, P < 0.05). In addition more patients of group CO had suffered a stroke (36% versus 27%, P < 0.05). A temporary shunt was used selectively and more frequently in group CO (87% versus 31%, P < 0.001). Major postoperative complications occurred with equal frequency in both groups: all strokes plus non-cerebral mortality (total combined morbidity and mortality): 4.65% versus 5.5%. The late incidence of stroke was the same in both groups: 8% in CO and 7% in CN at 5 years. The authors conclude that, under the described circumstances and with the appropriate surgical technique, the presence of an occlusion of the contralateral internal carotid artery does not imply an increase in major postoperative complications nor a higher stroke rate during follow-up.
Aged↗
Gelatinase B is present in the cerebrospinal fluid during experimental autoimmune encephalomyelitis and cleaves myelin basic protein.
Gelatinases in inflammatory demyelinating diseases of the central nervous system (CNS) were studied using actively induced experimental autoimmune encephalomyelitis (EAE) in mice as a model system. Clinical disease scores correlated in time and in intensity with pathology parameters such as cytosis in the cerebrospinal fluid (CSF), inflammatory infiltrates, and demyelination in the CNS. Zymographic analysis was employed to measure gelatinases A and B in the CSF from individual animals. According to their apparent molecular weight (MW), gelatinases A and B appeared with a MW of 65 and 95 kDa, respectively. The 65 kDa form was present in all samples, even in those derived from non-induced animals, whereas the 95 kDa form was present only in samples from animals developing EAE. The levels of 95 and 65 kDa gelatinase correlated with the CSF cytosis. In vitro digestion of myelin basic protein (MBP) with gelatinase B and analysis of the cleavage products by protein sequence analysis pinpointed two cleavage sites in conserved regions of MBP. Gelatinase production within the CNS may constitute an important pathogenic mechanism for both the disruption of the blood-brain barrier and the destruction of myelin, as observed in several neuroinflammatory disorders.
Amino Acid Sequence↗
Human T-cell lymphotropic virus type 1 infection and tropical spastic paraparesis in Belgian expatriates.
A case of HTLV-1 associated tropical spastic paraparesis is described in a Belgian nun who had been working as a midwife in Central Africa. Occupational exposure was the only risk factor identified. Among 2,482 Belgian expatriates in tropical countries, 92% of whom had resided in sub-Saharan Africa for an average of 15.5 years, only one Belgian-born man was found seropositive for HTLV-1. He was married to an African woman and living in Central Africa for 23 years. The risk of HTLV-1 infection is low in Belgian expatriates and on its own does not support generalised anti-HTLV screening in autochthonous Belgian blood donors.
Belgium↗
MRI of herpes simplex encephalitis.
The magnetic resonance imaging (MRI) findings in eight patients with herpes simplex meningoencephalitis were reviewed: 14 examinations were analysed. The most striking finding was high signal intensity in the temporal lobe(s) with the typical configuration known from CT. Meningeal enhancement after Gd-DTPA administration was clearly seen in four patients. Haemorrhagic changes are much better seen on MRI than on CT. When adequate motion control can be achieved, MRI becomes the examination of choice in the diagnosis and follow-up of herpes simplex encephalitis. Localized 1H MR spectroscopy also proved promising in the study of neuronal loss.
Adult↗
Gelatinase in the cerebrospinal fluid of patients with multiple sclerosis and other inflammatory neurological disorders.
A substrate conversion assay was used to detect gelatinase activity in the cerebrospinal fluid (CSF) of patients with various neurological disorders. Two main forms of gelatinase with an apparent molecular mass of 65 and 85 kDa, respectively, could be discerned. The high molecular mass gelatinase was detectable only in samples of patients with multiple sclerosis or other inflammatory neurological disorders. A statistically significant correlation was found between the level of the 85-kDa gelatinase and the CSF cytosis. This protease could play a role in the process of demyelination and breakdown of the blood-brain barrier in certain neurological disorders, such as multiple sclerosis.
Adult↗
Purulent meningitis due to aspergillosis in a patient with systemic lupus erythematosus.
We report a 39-year-old female patient with systemic lupus erythematosus under immunosuppressive therapy who developed persistent neutrophilic meningitis, for which no infectious agent could be identified. Intensifying the immunosuppressive therapy induced a short amelioration of the clinical picture. At autopsy, basal meningitis was found to be due to Aspergillus sp.
Adult↗
Magnetic resonance imaging of extrapontine lesions in central pontine myelinolysis.
A rare case of central pontine myelinolysis and associated extrapontine myelinolysis is presented. The MR findings confirmed the observations reported in recent papers.
Alcoholism↗
Apparent late-onset Cockayne syndrome and interstitial deletion of the long arm of chromosome 10 (del(10)(q11.23q21.2)).
We present the history and data on a 24-year-old man with clinical and neurological symptoms similar to the findings in patients with late-onset Cockayne syndrome. Prometaphase chromosome studies documented an interstitial 10q211 deletion in all cells. This finding may indicate that the gene for late Cockayne syndrome is at 10q211.
Adult↗