scholarly journals Pathology and Pathogenesis of Progressive Multiple Sclerosis: Concepts and Controversies

2017 ◽  
Vol 01 (03) ◽  
pp. E171-E181
Author(s):  
Adrian-Minh Schumacher ◽  
Christoph Mahler ◽  
Martin Kerschensteiner
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Deficits ◽  
Progressive Disease ◽  
Disease Duration ◽  
Disease Process ◽  
Progressive Multiple Sclerosis ◽  
Relapsing Remitting ◽  
Inflammatory Processes ◽  
The Central Nervous System

AbstractMultiple sclerosis (MS) is an inflammatory disease of the central nervous system that initially is often dominated by relapsing-remitting neurological symptoms. With increasing disease duration these relapses are more and more superimposed by a progressive disease process that leads to an irreversible accumulation of motor, sensory and cognitive deficits. This progressive phase of MS is still only incompletely understood and by and large refractory to therapy. Here we aim to use recent pathological and pathomechanistic insights to outline a unifying concept of progressive MS. Based on this view of the disease we examine current controversies surrounding progressive MS. We discuss whether neurodegenerative or inflammatory processes drive progression, question whether the classification of primary and secondary progressive MS is all that useful and deliberate, which therapeutic strategies are best suited to limit the insidious neurological decline of progressive MS patients.

Primary progressive multiple sclerosis: a distinct syndrome?

1996 ◽  
Vol 2 (3) ◽  
pp. 137-141 ◽  
Author(s):  
GV McDonnell ◽  
SA Hawkins
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Disease ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Progressive Decline ◽  
Primary Progressive ◽  
Therapeutic Trials ◽  
Relapsing Remitting ◽  
Progressive Course

Multiple sclerosis (MS) has long been recognised to have both a relapsing-remitting and progressive course. More recently patients with progressive disease have been further sub-divided into those with a progressive course from onset (primary progressive MS) and those with progressive decline following an initially relapsing-remitting period (secondary progressive MS). Diversity in MS may not however be restricted to clinical course. There is growing evidence that the subgroups of MS also differ with respect to clinical features, epidemiology, pathogenesis, genetics and neuroimaging appearances. In this review we outline the criteria variously applied in the classification of MS patients, addressing the need for a dear nomenclature. We evaluate the proposition that primary progressive MS has a prof ile distinct from other MS categories, contrasting the separate differential diagnoses and examining the implications for future therapeutic trials.

scholarly journals Disease-modifying treatments for progressive multiple sclerosis

2013 ◽  
Vol 19 (11) ◽  
pp. 1428-1436 ◽  
Author(s):  
Giancarlo Comi
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Progressive Disease ◽  
Progressive Multiple Sclerosis ◽  
Primary Progressive Multiple Sclerosis ◽  
Laboratory Science ◽  
New Concepts ◽  
Relapsing Remitting ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Major Progress

The last 20 years have seen major progress in the treatment of relapsing–remitting multiple sclerosis (RRMS) using a variety of drugs targeting immune dysfunction. In contrast, all clinical trials of such agents in primary progressive multiple sclerosis (PPMS) have failed and there is limited evidence of their efficacy in secondary progressive disease. Evolving concepts of the complex interplay between inflammatory and neurodegenerative processes across the course of multiple sclerosis (MS) may explain this discrepancy. This paper will provide an up-to-date overview of the rationale and results of the published clinical trials that have sought to alter the trajectory of both primary and secondary MS, considering studies involving drugs with a primary immune target and also those aiming for neuroprotection. Future areas of study will be discussed, building on these results combined with the experience of treating RRMS and new concepts emerging from laboratory science and animal models.

Epilepsy in multiple sclerosis

Neurology ◽  
2017 ◽  
Vol 89 (24) ◽  
pp. 2462-2468 ◽  
Author(s):  
Joachim Burman ◽  
Johan Zelano
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Features ◽  
Cumulative Incidence ◽  
Progressive Disease ◽  
Disease Duration ◽  
Population Based ◽  
Expanded Disability Status Scale ◽  
Disability Status ◽  
Relapsing Remitting ◽  
Edss Score

Objective:To determine the cumulative incidence of epilepsy in a population-based cohort of patients with multiple sclerosis (MS) and to investigate the association between epilepsy and clinical features of MS.Methods:All available patients in the Swedish MS register (n = 14,545) and 3 age- and sex-matched controls per patient randomly selected from the population register (n = 43,635) were included. Data on clinical features of MS were retrieved from the Swedish MS register, and data on epilepsy and death were retrieved from comprehensive patient registers.Results:The cumulative incidence of epilepsy was 3.5% (95% confidence interval [CI] 3.17–3.76) in patients with MS and 1.4% (95% CI 1.30–1.52) in controls (risk ratio 2.5, 95% CI 2.19–2.76). In a Cox proportional model, MS increased the risk of epilepsy (hazard ratio 3.2, 95% CI 2.64–3.94). Patients with relapsing-remitting MS had a cumulative incidence of epilepsy of 2.2% (95% CI 1.88–2.50), whereas patients with progressive disease had a cumulative incidence of 5.5% (95% CI 4.89–6.09). The cumulative incidence rose continuously with increasing disease duration to 5.9% (95% CI 4.90–7.20) in patients with disease duration ≥34 years. Patients with an Expanded Disability Status Scale (EDSS) score ≥7 had a cumulative incidence of epilepsy of 5.3% (95% CI 3.95–7.00). Disease duration and EDSS score were associated with epilepsy after multiple logistic regression (odds ratio [OR] 1.03, 95% CI 1.01–1.04 per year, p = 0.001; and OR 1.2, 95% CI 1.09–1.26 per EDSS step, p < 0.0001).Conclusions:Epilepsy is more common among patients with MS than in the general population, and a diagnosis of MS increases the risk of epilepsy. Our data suggest a direct link between severity of MS and epilepsy.

Cortical and meningeal pathology in progressive multiple sclerosis: a new therapeutic target?

2019 ◽  
Vol 30 (3) ◽  
pp. 221-232 ◽  
Author(s):  
Berenice Anabel Silva ◽  
Carina Cintia Ferrari
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Cortical Lesions ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Meningeal Inflammation ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Therapeutic Alternatives ◽  
Ms Pathogenesis

Abstract Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease that involves an intricate interaction between the central nervous system and the immune system. Nevertheless, its etiology is still unknown. MS exhibits different clinical courses: recurrent episodes with remission periods (‘relapsing-remitting’) that can evolve to a ‘secondary progressive’ form or persistent progression from the onset of the disease (‘primary progressive’). The discovery of an effective treatment and cure has been hampered due to the pathological and clinical heterogeneity of the disease. Historically, MS has been considered as a disease exclusively of white matter. However, patients with progressive forms of MS present with cortical lesions associated with meningeal inflammation along with physical and cognitive disabilities. The pathogenesis of the cortical lesions has not yet been fully described. Animal models that represent both the cortical and meningeal pathologies will be critical in addressing MS pathogenesis as well as the design of specific treatments. In this review, we will address the state-of-the-art diagnostic and therapeutic alternatives and the development of strategies to discover new therapeutic approaches, especially for the progressive forms.

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.

An MRI study of Chlamydia pneumoniae infection in Italian multiple sclerosis patients

2003 ◽  
Vol 9 (5) ◽  
pp. 467-471 ◽  
Author(s):  
L ME Grimaldi ◽  
A Pincherle ◽  
F Martinelli-Boneschi ◽  
M Filippi ◽  
F Patti ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Chlamydia Pneumoniae ◽  
Neurological Diseases ◽  
Disease Onset ◽  
Progressive Multiple Sclerosis ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Magnetic Resonance Imaging Mri ◽  
Multiple Sclerosis Patients ◽  
Mri Study

We amplified sequences of the Chlamydia pneumoniae (C P) major-outer membrane protein in the cerebrospinal fluid (CSF) from 23 of 107 (21.5%) relapsing-remitting or secondary progressive multiple sclerosis (MS) patients and two of 77 (2.6%) patients with other neurological diseases (OND) (P =0.00022). C P+ patients showed magnetic resonance imaging (MRI) evidence of more active disease (P =0.02) compared to CP-MS patients and tended to have an anticipation of age at disease onset (32.39-12 versus 28.59-10 years; P =ns) causing a longer disease duration (7.59-5 versus 4.49-4 years; P =0.016) at the time of clinical evaluation. These findings, although indirectly, suggest that C P infection of the central nervous system (C NS) might affect disease course in a subgroup of MS patients.

scholarly journals Secondary Progressive Multiple Sclerosis: New Insights

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012323
Author(s):  
Bruce Anthony Campbell Cree ◽  
Douglas L Arnold ◽  
Jeremy Chataway ◽  
Tanuja Chitnis ◽  
Robert J. Fox ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Disease ◽  
Progressive Multiple Sclerosis ◽  
Secondary Progressive Multiple Sclerosis ◽  
Response To Treatment ◽  
Disability Progression ◽  
Long Term Outcomes ◽  
Secondary Progressive ◽  
Relapsing Remitting

In most cases, multiple sclerosis (MS) begins with a relapsing–remitting course followed by insidious disability worsening that is independent from clinically apparent relapses and is termed secondary progressive multiple sclerosis (SMPS). Major differences exist between relapsing–remitting MS (RRMS) and SPMS, especially regarding therapeutic response to treatment. This review provides an overview of the pathology, differentiation, and challenges in the diagnosis and treatment of SPMS. We emphasize the criticality of conversion from a relapsing–remitting to a secondary progressive disease course not only because such conversion is evidence of disability progression, but also because, until recently, treatments that effectively reduced disability progression in relapsing MS were not proven to be effective in SPMS. Clear clinical, imaging, immunological, or pathological criteria marking the transition from RRMS to SPMS have not yet been established. Early identification of SPMS will require tools which, together with the use of appropriate treatments, may result in better long-term outcomes for the population of patients with SPMS.

Multiple Sclerosis: A Systemic Review of Drugs and Therapeutics

2017 ◽  
Vol 1 (3) ◽  
pp. 01-03
Author(s):  
Theodore Eric
Keyword(s):  
Multiple Sclerosis ◽  
Demyelinating Disease ◽  
Disease Process ◽  
The United States ◽  
Systemic Review ◽  
Patient Response ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Individual Patient Response ◽  
Phase Ii And Iii

Multiple sclerosis (MS) is a chronic inflammatory autoimmune demyelinating disease of the central nervous system. It affects approximately 400,000 people in the United States and onset is usually during young adulthood. There are four clinical forms of MS, of which relapsing remitting type is the most common. As the etiology of MS is unknown, finding a cure will remain challenging. The main mechanism of injury appears to be inflammation and 8 agents are now FDA approved to help control MS. These agents for relapsing forms of MS target different parts of the immune system, with the end goal of decreasing and avoiding further inflammation. No agents are FDA approved for the primary progressive version of MS. FDA approved agents include four preparations of interferon β (Avonex, Rebif, Betaseron and Extavia), glatiramer acetate (Copaxone), mitoxantrone (Novantrone), natalizumab (Tysabri) and fingolimod (Gilenya). There are several drug undergoing phase II and III trials. The heterogeneity of the MS disease process, individual patient response, and medication toxicities continue to challenge the treating physician.

scholarly journals Secondary Progression is Not the Only Explanation

2014 ◽  
Vol 27 (3) ◽  
pp. 393 ◽  
Author(s):  
Filipe Palavra ◽  
Carmen Tur ◽  
Mar Tintoré ◽  
Àlex Rovira ◽  
Xavier Montalban
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Skills ◽  
Progressive Multiple Sclerosis ◽  
Clinical Expertise ◽  
Secondary Progressive ◽  
Demyelinating Disorder ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Red Flag ◽  
Progressive Course

<p>Multiple sclerosis is an inflammatory demyelinating disorder of the central nervous system. Its presentation is variable and its course and prognosis are unpredictable. Approximately 85% of individuals present a relapsing-remitting form of the disease, but some patients may evolve into a progressive course, accumulating irreversible neurological disability, defining its secondary progressive phase. Despite all the advances that had been reached in terms of diagnosis, many decisions are still taken based only on pure clinical skills. We present the case of a patient that, after being diagnosed with a clinically isolated syndrome many years ago, seemed to be entering in a secondary progressive course, developing a clinical picture dominated by a progressive gait disturbance. Nevertheless, multiple sclerosis heterogeneity asks for some clinical expertise, in order to exclude all other possible causes for patients’ complaints. Here we present an important red flag in the differential diagnosis of secondary progressive multiple sclerosis.<br /><strong>Keywords:</strong> Magnetic Resonance Imaging; Multiple Sclerosis, Chronic Progressive; Meningioma.</p>

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