Benign Course Of Multiple Sclerosis Research Articles

Clinical predictors of the benign course of multiple sclerosis in a medically underserved population

Benign multiple sclerosis (MS) is characterized by little disability accumulation over the disease course. The majority of contributions to understanding the predictors of benign MS come from high-income areas; it is unknown whether the same predictors can be derived from the resource-limited populations that have limited access to proper diagnostics and management. We aimed to study clinical predictors of benign MS in individuals with relapsing-remitting (RR) course coming from underserved areas.

Prognostic significance of intrathecal oligoclonal immunoglobulin G in multiple sclerosis

Introduction/Aim: Detection of intrathecal oligoclonal bands of immunoglobulin G (OB IgG), in addition to diagnostic, has a predictive significance in multiple sclerosis (MS). The aim of the study was to determine the prognostic significance of OB IgG and to correlate the presence of OB IgG with the progression of disability in MS patients. Methods: A retrospective-prospective cohort study included 177 MS patients examined at the Centre for MS, Clinic of Neurology, University Clinical Centre of the Republic of Srpska. In all patients, demographic data, clinical parameters, Expanded Disability Status Scale (EDSS) score, isoelectric focusing (IEF) of cerebrospinal fluid (CSF), cyto-biochemical analysis of CSF, evoked potentials (EP) and magnetic resonance (MR) of the head were analysed. MS patients were divided in two groups: with and without intrathecal synthesis of oligoclonal IgG. According to the EDSS determined in both groups, the relation between the degree of functional disability and the presence of OB in the CSF and also with characteristics of the cyto-biochemical profile were analysed. Methods of descriptive and analytical statistics, analysis of variance, chi-square test, Bonferroni's post hoc test, correlation and regression analysis were used in the analysis of the results. Results: In the examined cohort of MS patients, the sensitivity of IEF was 96.6 %. There was a statistically significant association between the detectability of intrathecally synthesised IgG and EDSS score (p = 0.004) so that individuals who do not have intrathecally synthesised IgG had lower EDSS scores. MS patients with a CSF protein concentration > 0.40 g/L were 2.45 times more likely to enter secondary progression and 2.51 times more likely to achieve EDSS 4.0. Conclusion: IEF is a very sensitive diagnostic and prognostic method for MS patients, which indicates a more benign course of MS in patients without oligoclonal bands in the CSF.

Polymerase I pathway inhibitor ameliorates experimental autoimmune encephalomyelitis

Applying high throughput gene expression microarrays we identified that the suppression of polymerase 1 (POL1) pathway is associated with benign course of multiple sclerosis (MS). This finding supports the rationale for direct targeting of the POL1 transcription machinery as an innovative strategy to suppress MS. To evaluate the effects of a specific polymerase I inhibitor (POL1-I) on experimental autoimmune encephalomyelitis (EAE), we immunized female C57BL/6J mice (8weeks) with MOG35–55/CFA. A new POL1-I was administered at a daily dose of 12.5mg/kg body weight by oral gavage either from the day of immunization until disease onset (EAE score 1.0, immunization model), at disease onset (EAE score=1.0) for the following 14days (treatment model), or by alternate daily dose of 25.0mg/kg body weight, by oral gavage from the day of immunization for the following 25days (combined model). POL1-I remarkably suppressed EAE in the immunization model; while in the Vehicle group the onset of EAE occurred on day 10.0±0.4 with maximal clinical score of 3.2±0.2, in the POL1-I treated mice onset was significantly delayed and occurred on day 16.9±1.1 (p=0.001), and maximal disease score 2.0±0.1 was reduced (p=0.004). In the treatment model POL1-I treatment significantly reduced disease activity; maximal score was 2.0±0.5 while in the Vehicle group it reached a mean maximal score of 3.9±0.1, (p=0.0008). In the combined model, POL1-I treatment completely inhibited disease activity. The effect of POL1-I treatment was modulated through decreased expression of POL1 pathway key-related genes LRPPRC, pre-RNA, POLR1D and RRN3 together with activation of P53 dependent apoptosis of CD4+ splenocytes. Our findings demonstrate that POL1 pathway inhibition delayed and suppressed the development of EAE and ameliorated the disease in mice with persistent clinical signs.

Low degree of cortical pathology is associated with benign course of multiple sclerosis

Background: Although a more favorable course of multiple sclerosis is associated with a low degree of cortical pathology, only longitudinal studies could definitely confirm this association. Materials and Methods: We followed 95 early relapsing–remitting MS (RRMS; median Expanded Disability Status Scale (EDSS) = 1.5, mean disease duration = 3.1 ± 1.3 years) and 45 benign MS patients (EDSS ≤ 3.0, disease duration ≥ 15 years, normal cognition) for 6 years, with EDSS evaluations every 6 months and brain magnetic resonance imaging (MRI) at baseline and then yearly. Results: At baseline, we detected 406 cortical lesions (CLs) in 67/95 (70.5%) early RRMS and in 24/45 (53.3%) benign MS patients (p = 0.046). After 6 years, the appearance of new CLs was observed in 80/95 (84.2%; 518 CLs) of our early RRMS and in 25/45 (55.5%; 63 CLs; p < 0.001) benign MS patients. At baseline, after corrections for age and disease duration, we observed a cortical thinning of several frontal and temporal regions in our RRMS study patients, compared to the benign MS patients (p ranging between 0.001–0.05). After 6 years, the cortical thinning had increased significantly in several cortices of RRMS patients, but only in the occipital-temporal (p = 0.036) and superior parietal gyrus (p = 0.035) of those with benign MS. Stepwise regression analysis revealed the CL volume (p = 0.006) and the cortical thickness of the temporal middle (p < 0.001), insular long (p < 0.001), superior frontal (p < 0.001) and middle frontal gyri (p < 0.001) as the most sensitive independent predictors of a favorable disease course. Conclusions: Our data confirmed that a significantly milder cortical pathology characterizes the most favorable clinical course of MS. Measures of focal and diffuse grey matter should be combined to increase the accuracy in the identification of a benign MS course.

‘Clinically definite benign multiple sclerosis’, an unwarranted conceptual hodgepodge: evidence from a 30-year observational study

Background: Benign multiple sclerosis (BMS) is a controversial concept which is still debated. However identification of this kind of patients is crucial to prevent them from unnecessary exposure to aggressive and/or long term medical treatments. Objectives: To assess two definitions of ‘clinically definite benign multiple sclerosis’ (CDBMS) using long-term follow-up data, and to look for prognostic factors of CDBMS. Methods: In 874 patients with definite relapsing–remitting MS, followed up for at least 10 years, disability was assessed using the Disability Status Scale (DSS). CDBMS was defined by either DSS score≤2 (CDBMS1 group) or DSS score≤ 3 (CDBMS2 group) at 10 years. We estimated the proportion of patients who were still benign at 20 and 30 years after clinical onset. Results: CDBMS frequency estimates were 57.7% and 73.9% when using CDBMS1 and CDBMS2 definitions, respectively. In the CDBMS1 group, only 41.7% (105/252) of cases were still benign 10 years later, and 41.1% (23/56) after an additional decade, while there were 53.8% (162/301) and 59.5% (44/74) respectively in the CDBMS2 group. Conclusions: This 30-year observational study, which is one of the largest published series, indicates that favourable 10-year disability scores of DSS 2 or 3 fail to ensure a long-term benign course of multiple sclerosis. After every decade almost half of the CDBMS were no longer benign. CDBMS, as currently defined, is an unwarranted conceptual hodgepodge. Other criteria using new biomarkers (genetic, biologic or MRI) should be found to detect benign cases of MS.

Early prediction of a benign course of multiple sclerosis on clinical grounds: a systematic review.

There is growing consensus that neurologists should consider disease-modifying therapies early in multiple sclerosis (MS). However, there is a subgroup with a natural benign course, in which treatment could be postponed. We sought to determine the frequency of benign MS and early clinical factors that may predict a benign course. We performed a systematic review of the existing literature on benign MS, which was defined as minimal or no disability equivalent to a score on the Expanded Disability Status Scale (EDSS) < or = 3.0 at least 10 years after disease onset Only a small number of studies of adequate quality was available. In total there were nine published studies representing 2,204 patients. The estimated frequency of benign MS was 26.7%. Onset with optic neuritis, onset before the age of 40 years, absence of pyramidal signs at presentation, duration of first remission more than 1 year, and only one exacerbation in the first 5 years after onset of MS, were associated with a benign course. From the existing literature a set of unrelated clinical characteristics emerged that was associated with a benign course of MS. However, there is a need for prospective studies to define more precisely clinical and paraclinical predictors of benign MS.

Early prediction of a benign course of multiple sclerosis on clinical grounds: a systematic review

Early prediction of a benign course of multiple sclerosis on clinical grounds: a systematic review

Benign multiple sclerosis? Clinical course, long term follow up, and assessment of prognostic factors

OBJECTIVETo establish the characteristics of patients following a benign course of multiple sclerosis and evaluate the importance of potential prognostic factors. Also, an assessment of the value of the Kurtzke...

A Test of the Relationship Between Health Locus of Control and the Course of Multiple Sclerosis

This study explored the relationship between health locus of control and the trajectory of multiple sclerosis. A random sample of 100 respondents with multiple sclerosis was selected from the membership list of a state multiple sclerosis support group. The subjects were interviewed in their homes and completed study instruments. Respondents with an internal health locus of control orientation had more knowledge of their disease, practiced more self-care, and had a more benign course of multiple sclerosis than those with an external locus of control. Additional findings included an overall lower divorce rate for the respondents as well as a poor employment outlook.

Heat annd Multiple Sclerosis

To the Editor.— The article entitled Factors Associated With a Malignant or Benign Course of Multiple Sclerosis (1982;248:856) was interesting, but I was disappointed by its inherent errors. First, the authors referred to eight publications in which fever therapy in multiple sclerosis (MS) was used. In fact, the quoted articles reported the effect of raising body temperature on neurophysiological studies as an adjunct to the diagnosis of MS and not as therapy, as suggested by Clark and colleagues. Second, the authors found that malignant cases of MS more frequently reported adverse responses to heat and concluded that heat exposure effected the course of the disease. This is a circuitous argument. In 1889, Uhthoff1described temperature-induced transient deterioration in the visual acuity of patients with retrobulbar neuritis. It is now widely recognized that an increase in body temperature in MS may produce short-lived deterioration in neurological symptoms and signs.2

Factors associated with a malignant or benign course of multiple sclerosis

Factors associated with a malignant or benign course of multiple sclerosis

Relation between benign course of multiple sclerosis and low-grade humoral immune response in cerebrospinal fluid.

The prognosis in multiple sclerosis (MS) is related to the presence of an abnorma humoral immune response within the central nervous system: 14/17 MS patients (82%) without oligoclonal CSF IgG displayed no or slight disability after a mean duration of MS of 17 years, while 53% of 88 patients with oligoclonal CSF IgG had a benign course after a mean duration of 13 years (p less than 0.05). A benign course also was more often accompanied by a normal CSF IgG index. MS patients without oligoclonal CSF IgG had elevated CSF/serum ratios of albumin in 6%, and of the complement factors C3 in 0% and C4 in 6%, as against 20%, 27% and 37%, respectively, in MS patients with oligoclonal CSF IgG.