Loss of Neurologic Reserve in Progressive Multiple Sclerosis

2021 ◽  
pp. 10.1212/CPJ.0000000000001106
Author(s):  
Joep Killestein ◽  
Maria Liguori
Keyword(s):  
Multiple Sclerosis ◽  
Phenotypic Variability ◽  
Disease Onset ◽  
Progressive Multiple Sclerosis ◽  
Clinical Progression ◽  
Primary Progressive ◽  
Inflammatory Phase ◽  
Relapsing Remitting ◽  
Neurologic Disability ◽  
Inflammatory Component

Phenotypic variability in multiple sclerosis (MS) remains poorly understood. At disease onset, the majority of MS patients exhibit a relapsing–remitting MS (RRMS) disease course, and in spite of the availability of effective anti-inflammatory disease-modifying therapies (DMTs), a substantial proportion of patients will eventually evolve into a secondary progressive MS (SPMS) phase.1 Apart from SPMS, about 15% of MS patients show clinical progression from onset without clear remissions, i.e., primary progressive MS (PPMS). The Lublin panel revising the definitions of the clinical course of MS in 2013 acknowledged that some evidence supports PPMS representing a distinct, noninflammatory or at least less inflammatory form of MS.2 The panel emphasized that a spectrum of progressive MS phenotypes exists and that any differences between a secondary and primary progressive course are relative rather than absolute.2 There are data to suggest that in MS the acute inflammatory phase is followed by a chronic state that may include a “smoldering” condition in which inflammation as well as myelin and axonal degeneration may coexist.1 The transition of RRMS into SPMS is characterized by gradual worsening of neurologic disability independently of the occurrence of superimposed relapses.1,2 Currently available therapeutic options in both SP and PPMS are only modestly effective and the approved DMT mainly target the inflammatory component of the disease.1

Prodrome in relapsing-remitting and primary progressive multiple sclerosis

2019 ◽  
Vol 26 (7) ◽  
pp. 1032-1036 ◽  
Author(s):  
J. M. A. Wijnands ◽  
F. Zhu ◽  
E. Kingwell ◽  
Y. Zhao ◽  
C. Evans ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Relapsing Remitting

scholarly journals Symptomatic Therapy and Rehabilitation in Primary Progressive Multiple Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-22 ◽  
Author(s):  
Fary Khan ◽  
Bhasker Amatya ◽  
Lynne Turner-Stokes
Keyword(s):  
Quality Of Life ◽  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Disease Onset ◽  
Functional Independence ◽  
Symptomatic Therapy ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Relapsing Remitting

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system and a major cause of chronic neurological disability in young adults. Primary progressive MS (PPMS) constitutes about 10% of cases, and is characterized by a steady decline in function with no acute attacks. The rate of deterioration from disease onset is more rapid than relapsing remitting and secondary progressive MS types. Multiple system involvement at onset and rapid early progression have a worse prognosis. PPMS can cause significant disability and impact on quality of life. Recent studies are biased in favour of relapsing remitting patients as treatment is now available for them and they are more likely to be seen at MS clinics. Since prognosis for PPMS is worse than other types of MS, the focus of rehabilitation is on managing disability and enhancing participation, and application of a “neuropalliative” approach as the disease progresses. This chapter presents the symptomatic treatment and rehabilitation for persons with MS, including PPMS. A multidisciplinary approach optimizes the intermediate and long-term medical, psychological and social outcomes in this population. Restoration and maintenance of functional independence and societal reintegration, and issues relating to quality of life are addressed in rehabilitation processes.

scholarly journals Retrospective unbiased plasma lipidomic of progressive multiple sclerosis patients-identifies lipids discriminating those with faster clinical deterioration

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mario Amatruda ◽  
Maria Petracca ◽  
Maureen Wentling ◽  
Benjamin Inbar ◽  
Kamilah Castro ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Disease Progression ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Disease Course ◽  
Primary Progressive ◽  
T2 Lesions ◽  
Relapsing Remitting ◽  
One Year ◽  
Multiple Sclerosis Patients

Abstract The disease course of patients with a confirmed diagnosis of primary progressive multiple sclerosis (PPMS) is uncertain. In an attempt to identify potential signaling pathways involved in the evolution of the disease, we conducted an exploratory unbiased lipidomic analysis of plasma from non-diseased controls (n = 8) and patients with primary progressive MS (PPMS, n = 19) and either a rapid (PPMS-P, n = 9) or slow (PPMS-NP, n = 10) disease course based on worsening disability and/or MRI-visible appearance of new T2 lesions over a one-year-assessment. Partial least squares-discriminant analysis of the MS/MSALL lipidomic dataset, identified lipids driving the clustering of the groups. Among these lipids, sphingomyelin-d18:1/14:0 and mono-hexosylceramide-d18:1/20:0 were differentially abundant in the plasma of PPMS patients compared to controls and their levels correlated with MRI signs of disease progression. Lyso-phosphatidic acid-18:2 (LPA-18:2) was the only lipid with significantly lower abundance in PPMS patients with a rapidly deteriorating disease course, and its levels inversely correlated with the severity of the neurological deficit. Decreased levels of LPA-18:2 were detected in patients with more rapid disease progression, regardless of therapy and these findings were validated in an independent cohort of secondary progressive (SPMS) patients, but not in a third cohorts of relapsing–remitting (RRMS) patients. Collectively, our analysis suggests that sphingomyelin-d18:1/14:0, mono-hexosylceramide-d18:1/20:0, and LPA-18:2 may represent important targets for future studies aimed at understanding disease progression in MS.

scholarly journals Different cognitive profiles of Brazilian patients with relapsing-remitting and primary progressive multiple sclerosis

2011 ◽  
Vol 69 (4) ◽  
pp. 590-595 ◽  
Author(s):  
Dóra-Neide Rodrigues ◽  
Renata Alves Paes ◽  
Claudia Cristina Ferreira Vasconcelos ◽  
Jesus Landeira-Fernandez ◽  
Maria Papais Alvarenga
Keyword(s):  
Multiple Sclerosis ◽  
Neuropsychological Tests ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Cognitive Profiles ◽  
Primary Progressive ◽  
Immediate Recall ◽  
Relapsing Remitting ◽  
Healthy Control ◽  
Visual Organization

Cognitive impairment is a symptom of multiple sclerosis (MS). Different clinical forms of multiple sclerosis have different cognitive profiles, according to findings of previous studies which used extensive batteries of neuropsychological tests. OBJECTIVE: To investigate cognitive profiles of Brazilian patients with relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS) by using a brief battery of neuropsychological tests. METHOD: Sixty-six patients, within 18-65 of age and 3-18 years of education, were paired with healthy control subjects, regarding gender, age, and education level. RESULTS: On Symbol Digit Modalities Test and Hooper Visual Organization Test, cognition was affected in 50% in RRMS and 69% in PPMS. Fluency of "F" was impaired in 24% of RRMS and 81% of PPMS. Immediate recall was affected in 32% of RRMS and in 63% of PPMS; whereas late recall, in 46% of relapsing-remitting and in 69% of primary progressive. CONCLUSION: Cognitive profiles of relapsing-remitting and primary progressive patients are different

scholarly journals Multi-Platform Characterization of Cerebrospinal Fluid and Serum Metabolome of Patients Affected by Relapsing–Remitting and Primary Progressive Multiple Sclerosis

2020 ◽  
Vol 9 (3) ◽  
pp. 863 ◽  
Author(s):  
Federica Murgia ◽  
Lorena Lorefice ◽  
Simone Poddighe ◽  
Giuseppe Fenu ◽  
Maria Antonietta Secci ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Analytical Techniques ◽  
Roc Curves ◽  
Progressive Multiple Sclerosis ◽  
Glutathione Metabolism ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Relapsing Remitting ◽  
Pathways Analysis

Background: Multiple sclerosis (MS) is a chronic immunemediated disease of the central nervous system with a highly variable clinical presentation and disease progression. In this study, we investigate the metabolomics profile of patients affected by relapsing–remitting MS (RRMS)and primary progressive MS (PPMS), in order to find potential biomarkers to distinguish between the two forms. Methods: Cerebrospinal Fluid CSF and blood samples of 34 patients (RRMS n = 22, PPMS n = 12) were collected. Nuclear magnetic resonance (1H-NMR) and mass spectrometry (coupled with a gas chromatography and liquid chromatography) were used as analytical techniques. Subsequently, a multivariate statistical analysis was performed; the resulting significant variables underwent U-Mann–Whitney test and correction for multiple comparisons. Receiver Operating Characteristic ROC curves were built and the pathways analysis was conducted. Results: The analysis of the serum and the CSF of the two classes, allowed the identification of several altered metabolites (lipids, biogenic amines, and amino acids). The pathways analysis indicated the following pathways were affected: Glutathione metabolism, nitrogen metabolism, glutamine–glutamate metabolism, arginine–ornithine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis etc. Conclusion: The analysis allowed the identification of a set of metabolites able to classify RRMS and PPMS patients, each of whom express different patterns of metabolites in the two biofluids.

scholarly journals Chronic white matter lesion activity predicts clinical progression in primary progressive multiple sclerosis

Brain ◽  
2019 ◽  
Vol 142 (9) ◽  
pp. 2787-2799 ◽  
Author(s):  
Colm Elliott ◽  
Shibeshih Belachew ◽  
Jerry S Wolinsky ◽  
Stephen L Hauser ◽  
Ludwig Kappos ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
White Matter Lesion ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Axonal Loss ◽  
Clinical Progression ◽  
Primary Progressive

Chronic active and slowly expanding/evolving lesions with smouldering inflammation are neuropathological correlates of progressive multiple sclerosis. Elliott et al. report that T1-weighted measures of chronic lesion activity predict clinically progressive multiple sclerosis, may represent a longitudinal neuroimaging correlate of smouldering demyelination and axonal loss, and are reduced by ocrelizumab.

Primary progressive multiple sclerosis diagnostic criteria: a reappraisal

2009 ◽  
Vol 15 (12) ◽  
pp. 1459-1465 ◽  
Author(s):  
X. Montalban ◽  
J. Sastre-Garriga ◽  
M. Filippi ◽  
Z. Khaleeli ◽  
N. Téllez ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Diagnostic Criteria ◽  
Disease Duration ◽  
Progressive Multiple Sclerosis ◽  
Added Value ◽  
Oligoclonal Bands ◽  
Primary Progressive Multiple Sclerosis ◽  
Primary Progressive ◽  
Mcdonald Criteria ◽  
Relapsing Remitting

The diagnostic criteria used in primary progressive (PP) and relapsing—remitting (RR) multiple sclerosis (MS) show substantial differences. This introduces complexity in the diagnosis of MS which could be resolved if these criteria could be unified in terms of the requirements for dissemination in space (DIS). The aim of this study was to assess whether a single algorithm may be used to demonstrate DIS in all forms of MS. Five sets of RRMS criteria for DIS were applied to a cohort of 145 patients with established PPMS (mean disease duration: 11 years — PPMS-1): C1: Barkhof—Tintoré (as in 2005 McDonald’s criteria); C2: Swanton et al. (as in JNNP 2006); C3: presence of oligoclonal bands plus two lesions (as in McDonald’s criteria); C4 and C5: a two-step approach was also followed (patients not fulfilling C1 or C2 were then assessed for C3). Two sets of PPMS criteria for DIS were applied: C6: Thompson et al. (as in 2001 McDonald’s criteria); C7: 2005 McDonald criteria. A second sample of 55 patients with less than 5 years of disease duration (PPMS-2) was also analysed using an identical approach. For PPMS-1/PPMS-2, fulfilment was: C1:73.8%/66.7%; C2:72.1%/59.3%; C3:89%/79.2%; C4:96%/92.3%; C5:96%/85.7%; C6:85.8%/78.7%; C7:91%/80.4%. Levels of fulfilment suggest that the use of a single set of criteria for DIS in RRMS and PPMS might be feasible, and reinforce the added value of cerebrospinal fluid (CSF) findings to increase fulfilment in PPMS. Unification of the DIS criteria for both RRMS and PPMS could be considered in further revisions of the MS diagnostic criteria.

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