Prognostic Factors in Multiple Sclerosis

doi:10.1016/S0074-7742(07)79019-0

International Review of Neurobiology

Volume 79, 2007, Pages 423-447

https://doi.org/10.1016/S0074-7742(07)79019-0 Get rights and content

Prognostic factors to determine the patient's likelihood of developing MS are important for several reasons. Prognostic factors are important to the patient who wants to be informed about his/her prospects, to the clinician who needs to individuate the patients who deserve immune treatments, and to the researcher who needs to improve the design and the analysis of the therapeutic trials. In addition, with the development of new immune therapies, whose early use is strongly encouraged, it is crucial to dispose of reliable clinical predictors to identify the patients who are candidates for early or aggressive therapies.

Several studies have indicated that a poor prognosis is related to male gender; a late age at onset; motor, cerebellar, and sphincter involvement at onset; a progressive course at onset; a short inter‐attack interval; a high number of early attacks; and a relevant early residual disability. Paraclinical support for MS prognosis is given by imaging techniques, cerebrospinal fluid analysis, and evoked potential examinations. The most sensitive paraclinical test to predict conversion from suspected demyelinating disease to definite MS is MRI.

Introduction

Prognostic factors to determine the patient's likelihood of developing MS are important for several reasons. Of course, prognostic factors are important to patients who want to be informed about their diagnosis and their prospects. The uncertainty about future disease progression is a predominant factor for all MS patients, even those with low disability (Boeije and Janssens, 2004). Prognostic factors are also important to the clinician who needs to individuate at an early stage of disease those patients who deserve early/aggressive treatments, and to the researcher who necessitates to improve the design and the analysis of clinical therapeutic trials and observational studies. In addition, the trend to start new immunomodulating therapies early in the course of MS (Comi 2001, Goodin 2002, Jacobs 2000, Johnson 1995, The IFNB MS Study Group, and the University of British Columbia, MS/MRI Analysis Group 1995) makes it crucial to dispose of reliable predictors of disease's evolution, both unfavorable and favorable. As a matter of fact, the existence of a “benign” form of MS must be taken into consideration for a single patient treatment decision; studies proved that 15–25% of MS patients show a mild or absent disability despite a long duration of the disease (Pittock 2004, Ramsaransing 2001); in addition, if an MS patient has a “benign” course after 10 years with the disease, he/she has a high probability of remaining benign after another 10 years (Pittock et al., 2004).

In the present chapter, we will assess clinical and instrumental variables collected at the onset or during the course of the disease, whose occurrence could predict the conversion from clinically isolated syndrome (CIS) to clinically definite MS (CDMS), the development of relevant disability, and the conversion from relapsing‐remitting (RR) to secondary progressive (SP) form of MS.

Section snippets

Gender

The female sex is an important issue in the pathogenesis and evolution of MS, as well as of other autoimmune diseases. The high prevalence of MS in females (2:1), with a higher susceptibility during puberty (Simone et al., 2002), suggests a possible role of the female hormones in the inflammatory/neurodegenerative/neuroreparative network that characterizes MS (Cardona‐Gomez 2002, Levic 1999). In particular, hyperestrogenism is related to improvement in the inflammatory phase (Confavreux 1998,

Time from Onset to the Second Attack

Studies found that a long inter‐attack interval from clinical onset to the second neurological episode was related to a favorable course (Amato 1999, Confavreux 2003, Phadke 1990, Thompson 1986). Consequently, a short first inter‐attack interval has an unfavorable influence on the disease's evolution (Simone 2002, Trojano 1995, Weinshenker 1991).

Even in children, occurrence of severe disability was associated with short interval between first and second attack (Ghezzi, 2005).

Number and Type of Relapses During the First Years

Studies also found

Conclusions

MS is classically labeled as an unpredictable disease. The outcome of MS patients is highly variable, since they can be quite asymptomatic or severely disabled after 10–15 years with the disease. However, the present chapter proves that we dispose of several clinical (Table I) and instrumental (Table II) factors, collected at the onset or during the course of the disease, which can be able to predict a poor MS prognosis.

The main clinical factors indicative of long‐term bad prognosis are male

References (102)

M.P. Amato et al.
A prospective study on the natural history of multiple sclerosis: Clues to the conduct and interpretation of clinical trials
J. Neurol. Sci.
(1999)
P. Annunziata et al.
Absence of cerebrospinal fluid oligoclonal bands is associated with delayed disability progression in relapsing‐remitting MS patients treated with interferon‐beta
J. Neurol. Sci.
(2006)
R. Bergamaschi et al.
Predicting secondary progression in relapsing‐remitting multiple sclerosis: A Bayesian analysis
J. Neurol. Sci.
(2001)
H.R. Boeije et al.
‘It might happen or it might not’: How patients with multiple sclerosis explain their perception of prognostic risk
Soc. Sci. Med.
(2004)
G. Comi et al.
Effect of early interferon treatment on conversion to definite multiple sclerosis: A randomised study
Lancet
(2001)
A.L. Hume et al.
Evoked potentials in suspected multiple sclerosis: Diagnostic value and prediction of clinical course
J. Neurol. Sci.
(1988)
E.S. Huseby et al.
Age‐dependent T cell tolerance and autoimmunity to myelin basic protein
Immunity
(2001)
L. Kappos et al.
Predictive value of gadolinium‐enhanced magnetic resonance imaging for relapse rate and changes in disability or impairment in multiple sclerosis: A meta‐analysis. Gadolinium MRI Meta‐analysis Group
Lancet
(1999)
B. Kornek et al.
Neuropathology of multiple sclerosis‐new concepts
Brain Res. Bull.
(2003)
T. Korteweg et al.
MRI criteria for dissemination in space in patients with clinically isolated syndromes: A multicentre follow‐up study
Lancet Neurol.
(2006)

A. Martinez‐Yelamos et al.

Tau protein in cerebrospinal fluid: A possible marker of poor outcome in patients with early relapsing‐remitting multiple sclerosis

Neurosci. Lett.

(2004)

Y. Mikaeloff et al.

First episode of acute CNS inflammatory demyelination in childhood: Prognostic factors for multiple sclerosis and disability

J. Pediatr.

(2004)

M.E. Smith et al.

Age dependence of clinical and pathological manifestations of autoimmune demyelination. Implications for multiple sclerosis

Am. J. Pathol.

(1999)

B.G. Weinshenker

Bayesian analysis: What does it add to studies of the natural history of MS?

J. Neurol. Sci.

(2001)

J.R. Avasarala et al.

Oligoclonal band number as a marker for prognosis in multiple sclerosis

Arch. Neurol.

(2001)

F. Barkhof et al.

Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis

Brain

(1997)

R.W. Beck

The optic neuritis treatment trial: Three‐year follow‐up results

Arch. Ophthalmol.

(1995)

R.W. Beck et al.

High and low risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: Experience of the Optic Neuritis Treatment Trial

Arch. Ophthalmol.

(2003)

R. Bergamaschi et al.

Usefulness of Bayesian graphical models for early prediction of disease progression in multiple sclerosis

Neurol. Sci.

(2000)

R. Bergamaschi et al.

Disability and mortality in a cohort of multiple sclerosis patients: A reappraisal

Neuroepidemiology

(2005)

T. Berger et al.

Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event

N. Engl. J. Med.

(2003)

C. Berzuini et al.

A unified approach for modelling longitudinal and failure time data, with application in medical monitoring

IEEE Trans Pattern Anal. Mach. Intell.

(1996)

P.A. Brex et al.

Multisequence MRI in clinically isolated syndromes and the early development of MS

Neurology

(1999)

P.A. Brex et al.

A longitudinal study of abnormalities on MRI and disability from multiple sclerosis

N. Engl. J. Med.

(2002)

T. Broman et al.

Clinical studies on multiple sclerosis. I. Presentation of an incidence material from Gothenburg

Acta Neurol. Scand.

(1981)

G.P. Cardona‐Gomez et al.

Interactions of estrogens and insulin‐like growth factor‐I in the brain: Implications for neuroprotection

Brain Res. Brain Res. Rev.

(2002)

MRI predictors of early conversion to clinically definite multiple sclerosis in CHAMPS placebo group

Neurology

(2002)

A. Citterio et al.

Multiple sclerosis: Disability and mortality in a cohort of clinically diagnosed patients

Neuroepidemiology

(1989)

C. Confavreux et al.

Course and prognosis of multiple sclerosis assessed by the computerised data processing of 349 patients

Brain

(1980)

C. Confavreux et al.

Rate of pregnancy‐related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group

N. Engl. J. Med.

(1998)

C. Confavreux et al.

Relapses and progression of disability in multiple sclerosis

N. Engl. J. Med.

(2000)

C. Confavreux et al.

Early clinical predictors and progression of irreversible disability in multiple sclerosis: An amnesic process

Brain

(2003)

C.M. Dalton et al.

Progressive Ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis

J. Neurol. Neurosurg. Psychiatry

(2002)

N. De Stefano et al.

Brain damage as detected by magnetization transfer imaging is less pronounced in benign than in early relapsing multiple sclerosis

Brain

(2006)

O. Deryck et al.

Clinical characteristics and long term prognosis in early onset multiple sclerosis

J. Neurol.

(2006)

R. Detels et al.

Factors associated with a rapid course of multiple sclerosis

Arch. Neurol.

(1982)

G.C. Ebers

Prognostic factors for multiple sclerosis: The importance of natural history studies

J. Neurol.

(2005)

P. Falaschi et al.

High incidence of hyperandrogenism‐related clinical signs in patients with multiple sclerosis

Neuro. Endocrinol. Lett.

(2001)

M. Filippi et al.

Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis

Neurology

(1994)

M. Filippi et al.

Interferon beta‐1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: A randomised, double‐blind, placebo‐controlled trial

Lancet

(2004)

C. Fraser et al.

Multifocal visual evoked potential latency analysis. Predicting progression to multiple sclerosis

Arch. Neurol.

(2006)

J.L. Frederiksen

Can CSF predict the course of optic neuritis?

Mult. Scler.

(1998)

E.M. Frohman et al.

The utility of MRI in suspected MS: Report of the Therapeutic and Technology Assessment Subcommittee of the American Academy of Neurology

Neurology

(2003)

P. Fuhr et al.

Visual and motor evoked potentials in the course of multiple sclerosis

Brain

(2001)

A. Ghezzi

Childhood‐juvenile multiple sclerosis: Clinical characteristics and treatment

Expert Rev. Neurother.

(2005)

D.S. Goodin et al.

Disease modifying therapies in multiple sclerosis: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines

Neurology

(2002)

U. Held et al.

Predictors of relapse rate in MS clinical trials

Neurology

(2005)

G. Iannucci et al.

Prognostic value of MR and magnetization transfer imaging findings in patients with clinically isolated syndromes suggestive of multiple sclerosis at presentation

Am. J. Neuroradiol.

(2000)

L.D. Jacobs et al.

Intramuscular interferon beta‐1a therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS study group

N. Engl. J. Med.

(2000)

Y.P. Jin et al.

Predicting multiple sclerosis at optic neuritis onset

Mult. Scler.

(2003)

Cited by (101)

Stochastic models for the onset and disease course of multiple sclerosis
2024, Clinical Neurology and Neurosurgery
Exact causes and mechanisms regulating the onset and progression in many chronic diseases, including multiple sclerosis (MS), remain uncertain. Until now, the potential role of random process based on stochastic models in the temporal course of chronic diseases remains largely unevaluated. Therefore, the present study investigated the applicability of stochastic models for the onset and disease course of MS.
Stochastic models with random temporal process in disease activity, underlying clinical relapse and/or subclinical brain atrophy, were developed. The models incorporated parameters regarding the distribution of temporal changes in disease activity and the drift constant.
By adjusting the parameters (temporal change dispersion and drift constant) and the threshold for the onset of disease, the stochastic disease progression models could reproduce various types of subsequent disease course, such as clinically isolated syndrome (monophasic), relapsing-remitting MS, primary-progressive MS, and secondary-progressive MS. Furthermore, the disease prevalence and distribution of onset age could be also reproduced with stochastic models by adjusting the parameters. The models could further explain why approximately half of the patients with relapsing-remitting MS will eventually experience a transition to secondary-progressive MS.
Stochastic models with random temporal changes in disease activity could reproduce the characteristic onset age distribution and disease course forms in MS. Further studies by using real-world data to underscore the significance of random process in the occurrence and progression of MS are warranted.
Predictive factors and treatment challenges in malignant progression of relapsing-remitting multiple sclerosis
2024, Heliyon
Our objective was to uncover the predictive factors that can help anticipate the malignant progression of individuals with Relapsing-Remitting Multiple Sclerosis (RRMS). Additionally, we sought to analyze and compare the response to treatment between patients with benign and malignant forms of RRMS.
This cohort study included RRMS patients categorized as benign (≥10 years since disease onset, Expanded Disability Status Scale (EDSS) ≤ 1) or malignant (≤5 years since disease onset, EDSS ≥6). Patients’ data, including demographics, medical history, treatment, and MRI (Magnetic Resonance Imaging) scans, were collected and statistically analyzed.
Among the 254 patients diagnosed with RRMS, 174 were found to have benign RRMS, while the remaining 80 were diagnosed with malignant RRMS. Notably, patients with malignant RRMS exhibited a significantly higher mean age of onset (32.00 ± 7.96 vs. 25.70 ± 17.19; P < 0.001) and a greater prevalence of males (40% vs. 18.4%; P = 0.014). Additionally, within the initial five years of diagnosis, patients with malignant RRMS experienced a higher number of relapses (median: 4 vs. 2; P < 0.001) and hospitalizations (median: 2 vs. 1; P = 0.006) compared to those with benign RRMS. Clinical presentations of malignant RRMS were predominantly characterized by multifocal attacks, whereas unifocal attacks were more prevalent in patients with benign RRMS. MRI scans revealed that malignant RRMS patients displayed a higher burden of plaques in the infratentorial and cord regions, as well as a greater number of black hole lesions. Conversely, benign RRMS patients exhibited a higher number of Gadolinium-enhanced lesions. Utilizing Disease-Modifying Therapies (DMTs) with an escalating approach has shown effectiveness in managing benign RRMS. However, it has proven insufficient in addressing malignant RRMS, resulting in frequent transitions to higher-line DMTs. As a result, it places a considerable burden on patients with malignant RRMS, consuming valuable time and resources, and ultimately yielding subpar outcomes.
Our study identifies prognostic factors for malignant progression in RRMS, including older age of onset, male gender, increased relapses and hospitalizations, multifocal attacks, higher plaque load, and black hole lesions. The current escalation strategy for DMTs is insufficient for managing malignant RRMS, requiring alternative approaches for improved outcomes. In other words, MS is a spectrum rather than a single disease, and some patients progress to a malignant phenotype of MS that is not effectively treated by the current approach.
MRI features and disability in multiple sclerosis: A systematic review and meta-analysis
2024, Journal of Neuroradiology
In this systematic review and meta-analysis, we aimed to investigate the correlation between disability in patients with Multiple sclerosis (MS) measured by the Expanded Disability Status Scale (EDSS) and brain Magnetic Resonance Imaging (MRI) features to provide reliable results on which characteristics in the MRI can predict disability and prognosis of the disease.
A systematic literature search was performed using three databases including PubMed, Scopus, and Web of Science. The selected peer-reviewed studies must report a correlation between EDSS scores and MRI features. The correlation coefficients of included studies were converted to the Fisher's z scale, and the results were pooled.
Overall, 105 studies A total of 16,613 patients with MS entered our study. We found no significant correlation between total brain volume and EDSS assessment (95 % CI: -0.37 to 0.08; z-score: -0.15). We examined the potential correlation between the volume of T1 and T2 lesions and the level of disability. A positive significant correlation was found (95 % CI: 0.19 to 0.43; z-score: 0.31), (95 % CI: 0.17 to 0.33; z-score: 0.25). We observed a significant correlation between white matter volume and EDSS score in patients with MS (95 % CI: -0.37 to -0.03; z-score: -0.21). Moreover, there was a significant negative correlation between gray matter volume and disability (95 % CI: -0.025 to -0.07; z-score: -0.16).
In conclusion, this systematic review and meta-analysis revealed that disability in patients with MS is linked to extensive changes in different brain regions, encompassing gray and white matter, as well as T1 and T2 weighted MRI lesions.
Recent Advances in Diagnostic, Prognostic, and Disease-Monitoring Biomarkers in Multiple Sclerosis
2024, Neurologic Clinics
Biomarkers in multiple sclerosis
2023, Translational Neuroimmunology: Multiple Sclerosis: Volume 8
The search for biomarkers in multiple sclerosis (MS) is a wide area of interest, due to the complexity and unpredictability of the disease: from pathogenesis and disease course further down to treatment options. In the last few decades, the use of cerebrospinal fluid (CSF) biomarkers has become a staple in MS diagnosis, especially after the reintroduction of CSF study in the latest diagnostic criteria. On the other hand, evidence on serum biomarkers is rapidly growing, suggesting their potential future applications in clinical practice, as is the case with serum neurofilaments. In this chapter, we discuss the main biological markers, chosen by their utility in MS prediction, diagnosis, prognosis, disease activity, and treatment management.
Analysis of determinants of treatment change in adult paediatric-onset MS patients
2023, Multiple Sclerosis and Related Disorders
Paediatric-onset multiple sclerosis (POMS) is increasing worldwide and represents approximately 5% of all MS cases. Although this patient group has similar characteristics to the adult group, it is important for this patient group to receive effective treatment due to the early onset of cognitive involvement, higher lesion burden, and secondary progression at an earlier age than adults. In this study, we aimed to evaluate the factors that cause treatment change in POMS patients.
Adult patients with a first MS attack at age 18 years or younger who were followed up with the diagnosis of MS at the Clinical Neuroimmunology and Demyelinating Diseases outpatient clinic of Cerrahpaşa Medical School between 1987 and 2020 were included in our study. Patient files were reviewed retrospectively, and demographic and clinical characteristics, imaging, first attack characteristics, and treatment change were noted. We included 269 patients with a definite diagnosis of MS in the study, and these patients were evaluated in two groups: negative for treatment change and positive for treatment change.
Multifocal involvement was detected more frequently in the group with treatment change (p = 0,049). Cerebellar involvement as a first attack symptom was more common in male patients (p = 0,023) The age at first MS attack was found to be younger (p = 0,006), and the disease duration was longer in the positive for treatment change group (p = 0,003). Spinal cord involvement was more common in the positive for treatment change group (p = 0,016). Abnormal VEP findings were observed more frequently in the group without treatment change (p = 0.018). In multivariant analysis, spinal cord involvement, younger age at first attack, and abnormal VEP findings in the group without treatment change were found to be significant. Among the reasons for treatment change, the most common reason was radiological and clinical progression.
The higher inflammatory load in POMS patients compared with adults necessitates early initiation of treatment in this group and timely treatment change to prevent disability. Furthermore, this patient group should be followed closely and receive effective treatment.

View all citing articles on Scopus

View full text

Prognostic Factors in Multiple Sclerosis

Introduction

Section snippets

Gender

Time from Onset to the Second Attack

Number and Type of Relapses During the First Years

Conclusions

J. Neurol. Sci.

J. Neurol. Sci.

J. Neurol. Sci.

Soc. Sci. Med.

Lancet

J. Neurol. Sci.

Immunity

Lancet

Brain Res. Bull.

Lancet Neurol.

Neurosci. Lett.

J. Pediatr.

Am. J. Pathol.

J. Neurol. Sci.

Oligoclonal band number as a marker for prognosis in multiple sclerosis

Arch. Neurol.

Comparison of MRI criteria at first presentation to predict conversion to clinically definite multiple sclerosis

Brain

The optic neuritis treatment trial: Three‐year follow‐up results

Arch. Ophthalmol.

High and low risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: Experience of the Optic Neuritis Treatment Trial

Arch. Ophthalmol.

Usefulness of Bayesian graphical models for early prediction of disease progression in multiple sclerosis

Neurol. Sci.

Disability and mortality in a cohort of multiple sclerosis patients: A reappraisal

Neuroepidemiology

Antimyelin antibodies as a predictor of clinically definite multiple sclerosis after a first demyelinating event

N. Engl. J. Med.

A unified approach for modelling longitudinal and failure time data, with application in medical monitoring

IEEE Trans Pattern Anal. Mach. Intell.

Multisequence MRI in clinically isolated syndromes and the early development of MS

Neurology

A longitudinal study of abnormalities on MRI and disability from multiple sclerosis

N. Engl. J. Med.

Clinical studies on multiple sclerosis. I. Presentation of an incidence material from Gothenburg

Acta Neurol. Scand.

Interactions of estrogens and insulin‐like growth factor‐I in the brain: Implications for neuroprotection

Brain Res. Brain Res. Rev.

MRI predictors of early conversion to clinically definite multiple sclerosis in CHAMPS placebo group

Neurology

Multiple sclerosis: Disability and mortality in a cohort of clinically diagnosed patients

Neuroepidemiology

Course and prognosis of multiple sclerosis assessed by the computerised data processing of 349 patients

Brain

Rate of pregnancy‐related relapse in multiple sclerosis. Pregnancy in Multiple Sclerosis Group

N. Engl. J. Med.

Relapses and progression of disability in multiple sclerosis

N. Engl. J. Med.

Early clinical predictors and progression of irreversible disability in multiple sclerosis: An amnesic process

Brain

Progressive Ventricular enlargement in patients with clinically isolated syndromes is associated with the early development of multiple sclerosis

J. Neurol. Neurosurg. Psychiatry

Brain damage as detected by magnetization transfer imaging is less pronounced in benign than in early relapsing multiple sclerosis

Brain

Clinical characteristics and long term prognosis in early onset multiple sclerosis

J. Neurol.

Factors associated with a rapid course of multiple sclerosis

Arch. Neurol.

Prognostic factors for multiple sclerosis: The importance of natural history studies

J. Neurol.

High incidence of hyperandrogenism‐related clinical signs in patients with multiple sclerosis

Neuro. Endocrinol. Lett.

Quantitative brain MRI lesion load predicts the course of clinically isolated syndromes suggestive of multiple sclerosis

Neurology

Interferon beta‐1a for brain tissue loss in patients at presentation with syndromes suggestive of multiple sclerosis: A randomised, double‐blind, placebo‐controlled trial

Lancet

Multifocal visual evoked potential latency analysis. Predicting progression to multiple sclerosis

Arch. Neurol.

Can CSF predict the course of optic neuritis?

Mult. Scler.

The utility of MRI in suspected MS: Report of the Therapeutic and Technology Assessment Subcommittee of the American Academy of Neurology

Neurology

Visual and motor evoked potentials in the course of multiple sclerosis