Multiple Sclerosis Prognosis

  1. Natural history of Secondary/Progressive Multiple Sclerosis
    Mult Scler 2008 Apr;14(3):314-24

  2. Change in MS - related disability in a population-based cohort: a 10-year follow-up study
    Neurology 2004 Jan 13;62(1):51-9

  3. Impaired HypotThalamus-Pituitary-Adrenal Axis activity and more severe Multiple Sclerosis with HypoThalamic lesions
    Ann Neurol 2004 Jan;55(1):37-45

  4. Predicting Multiple Sclerosis at Optic Neuritis onset
    Mult Scler 2003 Mar;9(2):135-41

  5. Bulk List
    Manifestations of Multiple Sclerosis

  6. Predicting secondary progression in Relapsing/Remitting Multiple Sclerosis: a Bayesian analysis
    J Neurol Sci 2001 Aug 15;189(1-2):13-21

  7. Serum inflammatory markers and clinical/MRI markers of disease progression in Multiple Sclerosis
    J Neurol 2001 Jun;248(6):487-95

  8. Disability and prognosis in Multiple Sclerosis: demographic and clinical variables important for the ability to walk and awarding of disability pension
    Mult Scler 2001 Feb;7(1):59-65

  9. Short-term prognosis in early Relapsing/Remitting MS
    Neurology 2000 Sep 12;55(5):689-93

  10. MRI correlates of Cognitive dysfunction in Multiple Sclerosis
    AJNR Am J NeuroRadiol 2000 Jun-Jul;21(6):1034-8

  11. The prognostic value of Brain MRI in Clinically Isolated Syndromes of the CNS - a 10-year follow-up
    Brain 1998 Mar;121 ( Pt 3):495-503

  12. Course and prognosis of Multiple Sclerosis: assessed by data processing of 349 patients
    Brain 1980 Jun;103(2):281-300

  1. A prospective study on the natural history of Multiple Sclerosis: clues to the conduct and interpretation of clinical trials
    J Neurol Sci 1999 Oct 15;168(2):96-106

  2. Multiple Sclerosis
    Dis Mon 1996 Jan;42(1):1-55

  3. Natural history of Multiple Sclerosis
    Ann Neurol 1994;36 Suppl:S6-11

  4. The natural history of Multiple Sclerosis. A regional study with some longitudinal data
    J Neurol NeuroSurg Psychiatry 1992 May;55(5):341-6

  5. Disease steps in Multiple Sclerosis. A simple approach to evaluate disease progression
    Neurology 1995 Feb;45(2):251-5

  6. Prediction of outcome in Multiple Sclerosis
    J Neurol 1994 Oct;241(10):597-604

  7. Prognostic criteria in Multiple Sclerosis. An exploratory study of an Epidemiological group
    J Neurol 1992 Feb;239(2):93-7

  8. Prognosis in Multiple Sclerosis
    Schweiz Med Wochenschr 1997 Mar 22;127(12):500-505

  9. The significance of Brain Magnetic Resonance Imaging abnormalities at presentation with Clinically Isolated Syndromes suggestive of Multiple Sclerosis
    Brain 1993 Feb;116 ( Pt 1):135-46

  10. A prospective study on the prognosis of Multiple Sclerosis
    Neurol Sci 2000;21(4 Suppl 2):S831-8

  11. Intrathecal IgM synthesis is a prognostic factor in Multiple Sclerosis
    Ann Neurol 2003 Feb;53(2):222-6

  12. Course and prognosis in Early-Onset MS: comparison with Adult-Onset forms
    Neurology 2002 Dec 24;59(12):1922-8


A Prospective Study On The Natural History Of Multiple Sclerosis: Clues To The Conduct And Interpretation Of Clinical Trials

Amato MP, Ponziani G, Bartolozzi ML, Siracusa G
J Neurol Sci 1999 Oct 15;168(2):96-106
Univ of Florence, Dept of Neurology, Viale Morgagni, 85-50134, Florence, Italy
PMID# 10526190; UI# 99456970

To assess the predictive significance of different sets of Demographic, Clinical and ExtraClinical variables in identifying Multiple Sclerosis patients with various risk levels of worsening during the follow-up.

Two hundred and twenty-four patients at their first diagnosis of Multiple Sclerosis admitted to our Dept between 1983 and 1990.

In order to provide clues to inclusion criteria and selection of primary clinical end-points in therapeutic trials, were prospectively followed-up until the end of 1996.

We considered as end-points time to reach non-reversible Disability levels corresponding to EDSS scores of 4.0 and DSS 6 and the beginning of a Secondary/Progressive phase in the Relapsing/Remitting subgroup of patients.

For the statistical treatment of our data we used the Kaplan-Meier survival curves and the Cox regression analysis.

  • Favorable Prognosis:
    1. Sensory System involvement at Onset
    2. Longer first inter-attack interval
  • No Prognostic Value:
    1. Number of relapses in the first two years


Multiple Sclerosis

Lynch SG; Rose JW
Dis Mon 1996 Jan;42(1):1-55
Univ of Kansas Medical School, Kansas City, USA
IS# 0011-5029; UI# 96152234

Multiple Sclerosis is a chronic disease that begins in late adolescence or adulthood. It is highly variable in its expression and severity.

It is believed to be AutoImmune in nature. The cause is unknown; both Genetic and Environmental factors have been implicated in the PathoGenesis.

MS generally presents with the Acute or SubAcute Onset of Neurologic Abnormalities that may wax and wane over many years. Diagnosis is generally made by means of observation of the clinical course in conjunction with a Neurologic Examination and laboratory tests.

These tests may include Magnetic Resonance Imaging of the Head and Spine, Lumbar Puncture, and Evoked Potentials.

Treatment is based on general supportive care, the use of CorticoSteroids for relapses, and symptomatic management of ongoing problems.

The frequency of relapses can be reduced with Interferon-ß (Betaseron). Copolymer-1 and Interferon-ß 1a are being evaluated by the U.S. Food and Drug Administration for approval for use for reduction in the frequency of Relapses in Relapsing/Remitting MS.

Treatment of Chronic Progression is often attempted with ImmunoSuppressive agents such as CorticoSteroids, Azathioprine, and Cyclophosphamide. Use of other agents is being investigated.


Natural History Of Multiple Sclerosis

Weinshenker BG
Ann Neurol 1994;36 Suppl:S6-11
Mayo Clinic, Dept of Neurology, Rochester, MN 55905
IS# 0364-5134; UI# 94288575

Multiple Sclerosis (MS) is the most common idiopathic inflammatory disease of the Central Nervous System.

The distinction between MS and other Benign or Fulminant Inflammatory DeMyelinating Disorders is based on quantitative, rather than qualitative, differences in chronicity and severity.

Primary/Progressive MS may differ from Relapsing/Remitting MS in MRI lesion frequency, ImmunoGenetic profile, responsiveness to ImmunoSuppressive treatment, and Histology.

In 60% of patients, MS begins as a Relapsing/Remitting disease and evolves Secondarily into a Progressive Neurological illness.

Life expectancy is not substantially altered in patients with MS, particularly in the early years of the illness. The rate of suicide has been reported to be increased sevenfold in MS patients.

Up to 40% of patients with attacks severe enough to render them nonambulatory may not recover. At 15 years from MS Onset, 50% of patients are disabled to the point at which they at least require a cane to walk a half block.

Early age at Onset, female sex, Relapsing/Remitting course at Onset, and perhaps Optic Neuritis or Sensory symptoms at Onset and relatively few attacks in the first two years are associated with a favorable course.


The Natural History Of Multiple Sclerosis

A regional study with some longitudinal data

Miller DH; Hornabrook RW; Purdie G
J Neurol NeuroSurg Psychiatry 1992 May;55(5):341-6
Wellington Hospital, Wellington School of Medicine, Dept of Medicine, Univ of Otago, New Zealand
PMID# 1602305; UI# 92291728

A regional survey of Multiple Sclerosis (MS) patients in Wellington, New Zealand in 1983 identified 245 patients, giving a prevalence (all categories included) of 72 per 100,000.

Retrospective review of the history and medical records identified a poorer prognosis for disability where there was Progressive Onset of symptoms, Secondary/Progression after a Remitting phase, older age of Onset (40 years or more), or a Motor Syndrome involving the limbs at presentation.

In 1983 follow up data were obtained on 96 patients who were seen during a previous survey in 1968.

For those with Definite or Probable MS, progression to severe disability (Kurtzke Disability Status Scale (DSS) DSS 6-9) or death (DSS 10) was seen in 26/34 with moderate disability (DSS 3-5) in 1968 and in only 5/29 with mild disability (DSS 0-2).

When the analysis is confined to those with symptoms for at least five years in 1968, severe disability or death from MS occurred in 22/30 with moderate and 4/19 with mild disability (chi 2 = 10.8, p = 0.001).

It is concluded that the patient's established Disability level after five years of illness is a useful, but not infallible, prognostic indicator.

From the follow up of the 1968 patients, the probability of MS-related Mortality for a given disease duration was calculated.

Using this survival distribution to adjust the disability ratings in the 1983 population, it was found that the proportion with mild disability decreased steadily with increasing disease duration, reaching 14% when the disease duration was more than 25 years.


Disease Steps In Multiple Sclerosis

A simple approach to evaluate disease progression

Hohol MJ; Orav EJ; Weiner HL
Neurology 1995 Feb;45(2):251-5
Harvard Medical School, Dept of Medicine, Brigham and Women's Hospital, Boston, MA
PMID# 7854521; UI# 95157741

Current clinical scales in Multiple Sclerosis (MS) are often complicated to administer, suffer from interrater variability and lack of uniform representation across grades, and are insensitive to progression at certain stages.

Furthermore, they are not easily applied by Neurologists and do not clearly differentiate among functional stages of MS. For these reasons, we developed Disease Steps to assess disability in MS.

A total of 1,323 patients were classified using both Disease Steps and the Expanded Disability Status Scale (EDSS) for a total of 2,755 assessments.

    The Disease Steps Scale consists of:
  • 0 = Normal
  • 1 = Mild disability, mild symptoms or signs
  • 2 = Moderate disability, visible abnormality of gait
  • 3 = Early cane, intermittent use of cane
  • 4 = Late cane, cane-dependent
  • 5 = Bilateral support
  • 6 = Confined to wheelchair
  • U = Unclassifiable

Results demonstrate that raters could simply and quickly categorize patients using Disease Steps. Patients were uniformly distributed with Disease Steps, whereas a bimodal distribution occurred with the EDSS.

On the EDSS, 40.3% of patients scored between 1.0 and 3.5 and 36.0% scored from 6.0 to 6.5, with only 6.9% of patients scoring between 4.0 and 5.5.

For 60 patients seen by two Neurologists, concordance between raters was excellent for Disease Steps (kappa = 0.8) but only moderate for the EDSS (kappa = 0.54).

As a simple and reproducible measure of different functional steps of MS, Disease Steps can be used as a guide in therapeutic decision-making, following response to therapy, and in assessing disease progression.


Prediction Of Outcome In Multiple Sclerosis

Based on multivariate models

Runmarker B; Andersson C; Oden A; Andersen O
J Neurol 1994 Oct;241(10):597-604
Sahlgren's Hospital, Dept of Neurology, Goteborg, Sweden
IS# 0340-5354; UI# 95138749

An incidence cohort of 308 Multiple Sclerosis patients was followed up repeatedly during at least 25 years of disease.

In the patients with acute Onset, multivariate survival analyzes were performed and predictive models created. The endpoints DSS 6 and start of Progressive Disease were used. A number of variables were tested.

The most important of these for prediction and therefore included in these models were: age at Onset, sex, degree of remission after relapse, Mono- or PolyRegional symptoms, type of affected Nerve fibers, number of affected Neurological Systems. The relapse rate did not correlate with prognosis.

In the predictive models, coefficients and risk ratios are provided that can be used for calculating the risk of progression and DSS 6 or to predict the median time for these endpoints in individual patients.

It was also found that the risk of progression is not constant, but has a maximum a certain time after disease Onset.

For a patient with early Onset, the risk is low in the beginning, but reaches a maximum level, which is several times higher, after about 15 years.

The patient with a late Onset has a much higher risk of endpoint immediately after Onset, but reaches the maximum in a few years, and after that the risk decreases.


Prognostic Criteria In Multiple Sclerosis

An exploratory study of an epidemiological group

Lauer K; Firnhaber W
J Neurol 1992 Feb;239(2):93-7
Neurologische Klinik, Darmstadt-Eberstadt, Federal Republic of Germany
IS# 0340-5354; UI# 92202963

Demographic and clinical features and data on medical history and prior environmental exposure collected during an Epidemiological long-term study of Multiple Sclerosis (MS) were tested for their possible prognostic value.

Fifty-two Benign MS patients were compared with 29 patients having a Malignant course.

A Primary or Secondary/Progressive course and Cerebellar/lower BrainStem Symptoms at Onset indicated an unfavorable course.

Whereas no predictive value of sex or of any other type of Onset symptomatology was found.

Age at Onset per se had no influence on prognosis but was associated with more rapid progression only by its relationship with a Chronic/Progressive type of course.

Prior illness, surgery, trauma and childhood exposure to defined environmental factors could not be identified as relevant for prognosis.


Prognosis In Multiple Sclerosis

Kesselring J
Schweiz Med Wochenschr 1997 Mar 22; 127(12): 500-505
Rehabilitationszentrum Valens
PMID# 9148400; UI# 97260833

Prognosis of the natural course of Multiple Sclerosis is most often measured on Kurtzke's Expanded Disability Status Scale (EDSS), a non-linear scale over 20 steps, heavily weighted on mobility.

Optic Neuritis and Sensory disturbances as initial symptoms, lower age at Onset of the disease, female sex and a longer interval between relapses are indicators of a more favorable prognosis.

As a rule, disability as measured on this scale 5 years after Onset corresponds to 3/4 of the disability status after 15 years.

The number of relapses diminishes naturally over the course of the disease. Presence and extent of lesions on the initial MRI of the Brain in Clinically Isolated Syndromes are valuable predictors of dissemination of the disease process over the following 5-10 years.

New therapies (e.g. Interferon-ß 1b and 1a, Copolymer-1) reduce relapse frequency by 1/3 and diminish the extent of pathological lesions in Brain MRI, but fail to show (as yet) significant influence on disability.


The Significance Of Brain Magnetic Resonance Imaging Abnormalities At Presentation With Clinically Isolated Syndromes Suggestive Of Multiple Sclerosis

A 5-year follow-up study
Morrissey SP, Miller DH, Kendall BE, Kingsley DP, Kelly MA, Francis DA, MacManus DG, McDonald WI
Brain 1993 Feb;116 ( Pt 1):135-46
Institute of Neurology, National Hospital for Neurology and NeuroSurgery, Univ, Dept of Clinical Neurology, London, UK
PMID# 8453454; UI# 93201222

A 5-year follow-up study was performed on 89 patients who had undergone Brain Magnetic Resonance Imaging (MRI) at presentation with an acute Clinically Isolated Syndrome of the Optic Nerves, BrainStem or Spinal Cord of a type suggestive of Multiple Sclerosis.

At presentation, MRI was abnormal, revealing one or more asymptomatic Cerebral White Matter lesions in 57 (64%), and was normal in 32 (36%).

At follow-up, progression to Clinically Definite Multiple Sclerosis had occurred in 37 out of 57 (65%) with an abnormal MRI and one out of 32 (3%) with normal MRI.

Human Leucocyte Antigen (HLA) typing was performed in 70 patients and CerebroSpinal Fluid (CSF) was examined at presentation in 36.

The presence of HLA-DR2 Antigen or CerebroSpinal Fluid OligoClonal IgG Bands were both associated with a significantly increased risk of progression to Multiple Sclerosis, but MRI was much more powerful in predicting outcome.

The presence of four or more MRI lesions at presentation was associated with:

  1. Higher rate of progression to Multiple Sclerosis
  2. More frequent development of moderate or severe disabilities
  3. Greater number of new MRI lesions at follow-up

The results indicate that Brain MRI at presentation with a Clinically Isolated Syndrome suggestive of Multiple Sclerosis is a powerful predictor of the clinical course over the next 5 years.

This observation, combined with an ability to detect other sometimes treatable disorders which can also cause such syndromes, suggests that MRI is the investigation of choice in evaluating this group of patients.


A Prospective Study On The Prognosis Of Multiple Sclerosis

Amato MP, Ponziani G
Neurol Sci 2000;21(4 Suppl 2):S831-8
University of Florence, Department of Neurology, Italy
PMID# 11205358

Two hundred and twenty-four patients at their first diagnosis of Multiple Sclerosis (MS) were prospectively followed for a mean period of 9.78 years.

We considered as endpoints the time to reach non-reversible disability levels corresponding to EDSS scores of 4.0 and 6.0, and the beginning of a Secondary/Progressive phase in the Relapsing/Remitting subgroup of patients.

An initially Progressive course and higher basal EDSS scores proved to be the best predictors of unfavorable prognosis.

A greater number of Functional Systems involved at onset as well as higher residual deficits in Pyramidal, Visual, Sphincteric and Cerebellar Systems were other factors predictive of a poor outcome, whereas Sensory System involvement turned out to be favorable.

A longer first inter-attack interval was associated with a better prognosis. However, overall number of relapses in the first two years of the disease was of no prognostic value.

The presence of OligoClonal Banding in the CerebroSpinal Fluid and a Cerebral MRI exam strongly suggestive or suggestive of MS in the early phases of the disease were associated with a higher probability of a worse outcome.


Intrathecal IgM Synthesis Is A Prognostic Factor In Multiple Sclerosis

Villar LM, Masjuan J, Gonzalez-Porque P, Plaza J, Sadaba MC, Roldan E, Bootello A, Alvarez-Cermeno JC
Ann Neurol 2003 Feb;53(2):222-6
Hospital Ramon y Cajal, Department of Immunology, Madrid, Spain
PMID# 12557289

Intrathecal IgM synthesis (ITMS) predicts a worse evolution in the first stages of Multiple Sclerosis (MS).

The aim of this study was the follow-up of a group of Relapsing/Remitting MS patients for a longer time to evaluate whether the ITMS implies a poor prognosis. OligoClonal IgM Bands were performed in 29 MS patients followed up from 5 to 16 years.

Time to conversion to Secondary/Progressive MS (SP-MS), time elapsed to reach a disability of 6 in the Expanded Disability Status Scale (EDSS), percentage of patients with a Benign MS, and changes in EDSS score were evaluated.

During the follow-up, 70.8% of patients with ITMS converted to SPMS. None of the patients without ITMS did.

At the end of the study, 63.6% of patients with ITMS had reached EDSS 6, whereas none of the patients lacking ITMS reached values above EDSS 3.

When patients with Benign MS were analyzed, 82% lacked ITMS. All patients with a NonBenign MS had ITMS.

At the end of the study, the mean EDSS score was 4.64 in patients with ITMS and 1.31 in those without. The presence of OligoClonal IgM Bands in CerebroSpinal Fluid is an unfavorable prognostic marker in MS.


Course And Prognosis In Early-Onset MS: Comparison With Adult-Onset forms

Simone IL, Carrara D, Tortorella C, Liguori M, Lepore V, Pellegrini F, Bellacosa A, Ceccarelli A, Pavone I, Livrea P
Neurology 2002 Dec 24;59(12):1922-8
University of Bari, Department of Neurological and Psychiatric Sciences, Italy
PMID# 12499484

To establish the prognostic role of clinical and demographic factors in a hospital-based cohort of MS patients categorized by age at clinical onset and clinical course.

Eighty-three patients with MS had a clinical onset of the disease in childhood (age < 16 years; Early-Onset MS [EOMS]) and 710 in adult age (between 16 and 65 years.

Adult-Onset MS [AOMS]). Patients were followed for a mean period of observation of 5 years.

Univariate and multivariate analyses of clinical and demographic predictors for rapid progression and disability were performed using a stepwise Cox regression model with time-dependent covariates.

In EOMS, the Expanded Disability Status Scale (EDSS) evaluated at last clinical examination was lower than in AOMS, despite a longer disease duration.

The probability to reach growth disability and progression was significantly lower in EOMS than in AOMS.

Median times to reach EDSS score of 4 and secondary progression were longer in EOMS than in AOMS, but the age at both endpoints was significantly lower in EOMS.

In EOMS and AOMS, an irreversible disability was related to a Secondary/Progressive course, a Sphincteric System involvement at onset, and an older age at onset (in EOMS only for the group >14 years).

In AOMS, other unfavorable factors were a Pyramidal involvement at onset and a high relapse frequency in the first 2 years.

The risk of entering secondary progression was significantly influenced by a high number of relapses in EOMS and by a higher age at onset and a short interattack interval in AOMS.

A slower rate of progression of disease characterized EOMS patients, suggesting more plasticity to recover in the developing CNS, but the early clinical manifestation cannot be considered a positive prognostic factor.

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