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Definition, prevalence and predictive factors of benign multiple sclerosis.

ABSTRACT: Background:Multiple sclerosis (MS) is characterized by a great inter-individual variability in disease course and severity. Some patients experience a rather mild course, controversially called 'benign MS' (BMS). The usefulness of this entity in clinical practice remains unclear. Methods:We performed a literature search in PubMed, Web of Science and Cochrane Library databases from November 1980 to December 2015, using the following key words: benign multiple sclerosis, diagnosis, imaging, prognosis, predictive, natural history and predefined inclusion criteria. Results:Our search yielded 26 publications. Most definitions were based on the Expanded Disease Status Scale (EDSS), which is heavily weighted towards physical disability. Between 30 and 80% of relapsing-remitting MS patients have EDSS < 3 or 4 at 10 years after onset. Having only one relapse in the first 5 years and EDSS ? 2 at 5 years or EDSS ? 3 at 10 years appears to be predictive for a prolonged benign disease course, without protecting against disease progression at a later stage. Evidence on the predictive value of MRI parameters remains limited. Conclusions:Current BMS definitions have some predictive value for future physical disability, but do not take into account the age at EDSS and the potentially disrupting effects of non-EDSS symptoms and cognitive impairment. It appears to correspond to mild RRMS in the first decades and its prevalence varies. Since early and accurate prediction of BMS is not yet possible, the clinical relevance is limited. Research approaches are suggested.

SUBMITTER: Reynders T

PROVIDER: S-EPMC5721547 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Definition, prevalence and predictive factors of benign multiple sclerosis.

Reynders Tatjana T D'haeseleer Miguel M De Keyser Jacques J Nagels Guy G D'hooghe Marie B MB

eNeurologicalSci 20170513

<h4>Background</h4>Multiple sclerosis (MS) is characterized by a great inter-individual variability in disease course and severity. Some patients experience a rather mild course, controversially called 'benign MS' (BMS). The usefulness of this entity in clinical practice remains unclear.<h4>Methods</h4>We performed a literature search in PubMed, Web of Science and Cochrane Library databases from November 1980 to December 2015, using the following key words: <i>benign multiple sclerosis</i>, <i>d ...[more]

PMID: 29260023

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Project description:Benign multiple sclerosis (BMS) occurs in about 15% of patients with relapsing-remitting multiple sclerosis (RRMS) that over time do not develop significant neurological disability. The molecular events associated with BMS are not clearly understood. This study sought to underlie the biological mechanisms associated with BMS. Blood samples obtained from a cohort of 31 patients with BMS and 36 patients with RRMS were applied for gene expression microarray analysis using HG-U133A-2 array (Affymetrix). Data were analyzed by Partek and pathway reconstruction was performed by Ingenuity for the most informative genes (MIGs). We identified a differing gene expression signature of 406 MIGs between BMS patients, mean±SE age 44.5±1.5 years, 24 females, 7 males, EDSS 1.9±0.2, disease duration 17.0±1.3 years, and RRMS patients, age 40.3±1.8 years, 24 females, 12 males, EDSS 3.5±0.2, disease duration 10.9±1.4 years. The signature was enriched by genes related RNA polymerase I (POL-1) transcription, general inflammatory response and activation of cell death. The most significant under-expressed pathway operating in BMS was the POL-1 pathway (p = 4.0*10(-5)) known while suppressed to activate P53 dependent apoptosis and to suppress NF?B induced inflammation. In accordance, of the 30 P53 target genes presented within the BMS signature, 19 had expression direction consistent with P53 activation. The transcripts within the pathway include POL-1 transcription factor 3 (RRN3, p = 4.8*10(-5)), POL-1 polypeptide D (POLR1D, p = 2.2*10(-4)), leucine-rich PPR-motif containing protein (LRPPRC p = 2.3*10(-5)), followed by suppression of the downstream family of ribosomal genes like RPL3, 6,13,22 and RPS6. In accordance POL-1 transcript and release factor PTRF that terminates POL-1 transcription, was over-expressed (p = 4.4*10(-3)). Verification of POL-1 pathway key genes was confirmed by qRT-PCR, and RRN3 silencing resulted in significant increase in the apoptosis level of PBMC sub-populations in RRMS patients. Our findings demonstrate that suppression of POL-1 pathway induce the low disease activity of BMS.

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Definition, prevalence and predictive factors of benign multiple sclerosis.

Publications

Definition, prevalence and predictive factors of benign multiple sclerosis.

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