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Transitional/Progressive & Primary/Progressive Multiple Sclerosis

  1. Combination of Cyclophosphamide and Interferon-beta halts progression in rapidly Transitional Multiple Sclerosis
    J Neurol NeuroSurg Psychiatry 2001 Sep;71(3):404-7

  2. Cognitive function in Primary/Progressive and Transitional/Progressive Multiple Sclerosis
    Brain 1999 Jul;122(Pt 7):1341-1348

  3. Multiple Sclerosis that is Progressive from the time of onset: clinical characteristics and progression of disability
    Arch Neurol 1999 Sep;56(9):1138-42

  1. One year follow up study of Primary and Transitional/Progressive Multiple Sclerosis
    J Neurol NeuroSurg Psychiatry 2000 Jun;68(6):713-718

  2. Primary & Transitional/Progressive Multiple Sclerosis
    Neurology, 1999 Mar, 52:4, 839-45

  3. Transitional/Progressive MS vs other Progressive stages
    J Neurol NeuroSurg Psychiatry; Sep 1997; 63:396-8

  4. Clinical characteristics of Progressive/Relapsing Multiple Sclerosis
    Mult Scler 2004 Aug;10(4):451-4




#1

One Year Follow Up Study Of Primary And Transitional/Progressive Multiple Sclerosis

Stevenson VL, Miller DH, Leary SM, Rovaris M, Barkhof F, Brochet B, Dousset V, Filippi M, Hintzen R, Montalban X, Polman CH, Rovira A, de Sa J, Thompson AJ
J Neurol NeuroSurg Psychiatry 2000 Jun;68(6):713-718
Institute of Neurology, NMR Research Unit, Queen Square, London WC1 N3BG, UK
PMID# 10811693; UI# 20271961
Abstract

Objective
To document clinical and Magnetic Resonance Imaging (MRI) characteristics of a large cohort of Primary/Progressive and Transitional/Progressive Multiple Sclerosis (PP and TP MS) patients over one year.

Introduction
Patients with PP or TP MS have been shown to have low Brain T2 and T1 lesion loads and slow rates of new Lesion formation with minimal Gadolinium enhancement, despite their accumulating Disability.

Serial evaluation of these patients is needed to elucidate the pathological processes responsible for disease progression and to identify clinical and MRI measures which can monitor these processes in treatment trials.

Method
Patients, recruited from six European centers, underwent two assessments on the Expanded Disability Status Scale (EDSS) and MRI of the Brain and Spinal Cord, 1 year apart.

Results
Of the 167 patients studied (137 with PP MS and 30 with TP MS), 41 (25%; 35 PP and six TP) showed a one step increase in the EDSS.

The mean number of new Brain lesions seen was 0.88 in the PP group and 0.47 in the TP MS group.

Both groups demonstrated change in T2 Lesion Load over the year (p</=0.002), with median percentage changes of 7.3% in the PP group and 10.8% in the TP MS group.

The PP group also showed a significant change in T1 load (p< 0.001, median change 12.6%). The number of new Cord lesions seen was small (mean of 0.14 in the PP group and no new Cord lesions in the TP group).

Both groups demonstrated a decrease in Cord cross sectional area (p< 0.001, median changes; PP 3.8%, TP 4.9%), but only the PP group showed evidence of significant Brain Atrophy (p< 0.001, 0.95%).

Conclusion
Although the monitoring of disease progression in this patient group is difficult, this study demonstrates changes in both Lesion Load and Atrophy, which, if shown to correlate with clinical change over a longer time will facilitate therapeutic trial design.



#2

Primary & Transitional/Progressive MS


A clinical and MRI cross-sectional study

Stevenson VL; Miller DH; Rovaris M; Barkhof F; Brochet B; Dousset V; Dousset V; Filippi M; Montalban X; Polman CH; Rovira A; de Sa J; Thompson AJ
Neurology, 1999 Mar, 52:4, 839-45
Institute of Neurology, NMR Research Unit, London, UK
PMID# 10078736; UI# 99176622
Abstract

Background
Ten percent of patients with MS have a Progressive course from onset with no history of relapses or remissions.

A smaller subgroup follow a similar Progressive course but have a single relapse at some point (Transitional/Progressive [TP] MS). To date these patients have been excluded from receiving licensed treatments for MS and from most therapeutic trials.

Objective
To document the clinical and MRI characteristics of a large cohort of Progressive patients, including 158 with Primary/Progressive (PP) MS and 33 with TPMS.

Data from a small reference group of 20 patients with Secondary/Progressive (SP) MS are also presented for reference.

Methods
Patients were recruited from six European centers. All underwent a clinical assessment including scoring on the Expanded Disability Status Scale (EDSS) and MRI of the Brain and Spinal Cord.

Results
The men-to-women ratio was 81:77 (51% men) in the PP group, 14:19 (42% men) in the TP group, and 5:15 (25% men) in the SP group.

The mean age at disease onset was significantly higher in the PP group than it was in the other two groups (PP 40.2 years, TP 34.9 years, SP 28.7 years).

On MRI the PP group had lower mean Brain T2 and T1 HypoIntensity lesion loads than the SP group (T2 12.02 versus 27.74 cm3, p = 0.001; T1 4.34 versus 7.04 cm3, p = 0.015).

The SP and TP cohorts had significantly more T2-weighted lesions in the Spinal Cord than the PP patients, and the SP cohort had the greatest degree of Atrophy.

There was a correlation in the PP and TP patients between EDSS score and Brain and Spinal Cord Atrophy (r = 0.3, 0.2, p < or = 0.006) but not with Brain Lesion Load.

The PP and TP patients who presented with Spinal Cord pathology had significantly lower Brain T2 and T1 Lesion loads than those with non-Spinal Cord presentations (p = 0.002).

Conclusions
The monitoring of disease progression in PPMS is difficult, although measures of Atrophy correlate with the EDSS and appear most promising.

This study increases our understanding of this unique patient group, which will be further expanded with the acquisition of serial data.



#3

Transitional/Progressive MS vs Other Progressive Stages

A Clinical And Imaging Study

Gayou A, Brochet B, Dousset V
J Neurol NeuroSurg Psychiatry; Sep 1997; 63:396-8
Pellegrin Hospital, Dept of Neurology, and UnivVictor Segalen, Bordeaux, France
PMID# 9328264; UI# 97466924
Abstract

Objective
To study the prevalence and the natural course of Transitional/Progressive Multiple Sclerosis (TPMS). This clinical form is defined by a Progressive course beginning many years after an isolated bout.

The distinction between clinical stages of Multiple Sclerosis has gained attention with the evidence that different PathoPhysiological mechanisms are involved at different stages of the disease, and therefore that different therapeutic goals have to be achieved.

Methods
214 consecutive outpatients with Definite or Probable Multiple Sclerosis were studied. The prevalence of TPMS was established.

Patients with TPMS were compared with patients with other Progressive forms of Multiple Sclerosis according to the clinical course.

    In a population of 214 MS outpatients
  • 55 had Secondary/Progressive disease (SPMS)
  • 38 had Primary/Progressive disease (PPMS)
  • 12 were identified as having TPMS

Retrospective analysis of the clinical data of these patients shows that TPMS is very similar to SPMS at the beginning of the disease (age at onset, time before progression, clinical symptoms at onset, progression index).

In addition a cohort of patients was prospectively followed up clinically and by MRI for one year.

Conclusions
The results did not show any significant differences between the three forms during this follow up.

However, all data showed a concordant trend suggesting that at this progressive stage, TPMS is closer to PPMS in terms of progression of Disability and new MRI lesions.



#4

Clinical Characteristics Of Progressive/Relapsing Multiple Sclerosis

Tullman MJ, Oshinsky RJ, Lublin FD, Cutter GR
Mult Scler 2004 Aug;10(4):451-4
The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, Department of Neurology, The Mount Sinai Hospital, New York, NY 10029, USA
PMID# 15327045
Abstract

Objective
Patients with Progressive/Relapsing (PR) Multiple Sclerosis (MS) may accrue disability by incomplete recovery from acute exacerbations and by ongoing deterioration.

In Primary/Progressive (PP) MS, disability accumulates solely by continuous decline.

Because it is the least common form of MS, there is scant information regarding the clinical characteristics of PRMS, but relapses are reportedly uncommon.

The purpose of this study is to describe the clinical features of a cohort of patients with PRMS.

Methods
A retrospective chart review of 16 patients diagnosed with PRMS at two academic MS centres over a four-year period.

Results
Nine men and seven women had PRMS. The mean age at onset was 35.1+/-11.2 years. The most common presenting symptom was a progressive myelopathy.

The mean disease duration was 10.1+/-8.5 years and the average time to first exacerbation was 4.1+/-3.7years.

Patients had an average of 2.8+/-2.3 relapses with an annualized relapse rate of 0.6+/-0.8. Time to Expanded Disability Status Scale (EDSS) 6.0 was strongly associated with time to first exacerbation.

Although there was no correlation between the number of relapses and time to EDSS 6.0, there was a modest inverse relation between time to EDSS 6.0 and annualized relapse rate.

Conclusions
Relapses in PRMS may occur more often than previously described and disability may accumulate more rapidly in PRMS than in PPMS.

We suggest differentiating between these two forms of MS.



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