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Primary/Progressive Multiple Sclerosis

  1. Is inflammation important in early PPMS? a longitudinal MRI study
    J Neurol NeuroSurg Psychiatry 2005 Sep;76(9):1255-8

  2. A longitudinal study of Cognition in Primary/Progressive Multiple Sclerosis
    Brain 2005 Dec;128(Pt 12):2891-8

  3. The pathogenesis of Primary/Progressive Multiple Sclerosis: AntiBody-mediated attack and no repair?
    J Clin NeuroSci 2004 Sep;11(7):689-92

  4. Occult tissue damage in Primary/Progressive Multiple Sclerosis is independent of T2-visible lesion - A Diffusion Tensor MR study
    J Neurol 2003 Apr;250(4):456-60

  5. The Normal-Appearing Gray Matter in Primary/Progressive Multiple Sclerosis A Magnetization Transfer imaging study
    J Neurol 2003 Jan;250(1):67-74

  6. Increased Nitric Oxide products in CSF in Primary/Progressive MS may reflect Brain atrophy
    Neurology 2001 Sep 11;57(5):895-896

  7. Bulk Listing Primary/Progressive Multiple Sclerosis
       #2,   &  Newest

  8. Bulk Listing
    ReMyelination in Multiple Sclerosis

  9. Bulk Listing
    Primary & Transitional/Progressive Multiple Sclerosis

  10. New diagnostic criteria for Primary/Progressive Multiple Sclerosis: A position paper
    Ann Neurol 2000 Jun;47(6):831-5

  11. Spinal Cord MRI in Multiple Sclerosis: importance of determining degree of Atrophy as a marker of disease course
    Rev Neurol (Paris) 2000 May;156(5):491-6

  12. Diagnostic Brain MRI findings in Primary/Progressive Multiple Sclerosis
    Mult Scler 2000 Apr;6(2):81-85

  13. MT of Normal-Appearing White Matter in Primary/Progressive Multiple Sclerosis
    Mult Scler 1999 Oct;5(5):313-6

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

  15. Spinal Cord MR in Multiple Sclerosis: Relation to clinical subtype and disability
    AJNR Am J NeuroRadiol 1997 Jun-Jul;18(6):1041-8

  16. InfraTentorial atrophy and disability in Multiple Sclerosis
    Brain 1999 Feb;122 ( Pt 2):291-301

  17. Long and short-term outcome of Multiple Sclerosis
    Arch Neurol 1996 Apr;53(4):353-8


    The natural history of Multiple Sclerosis: A geographic study:
  1. 5. The clinical features and natural history of Primary/Progressive Multiple Sclerosis
    Brain 1999 Apr;122 (Pt 4):625-39

  2. 6. Applications to planning and interpretation of clinical therapeutic trials in Primary/Progressive Multiple Sclerosis
    Brain 1999 Apr;122 (Pt 4):641-7

  3. 7. Progressive/Relapsing and Relapsing/Progressive Multiple Sclerosis: A re-evaluation
    Brain 1999 Oct;122 ( Pt 10):1941-50

  4. Spinal Cord atrophy and disability in Multiple Sclerosis
    Neurology, 1998 Jul, 51:1, 234-8

  5. Assessing information on T2-weighted MRI scans in Secondary/Progressive Multiple Sclerosis
    Neurology 1998 Jul;51(1):228-33

  6. Brain MRI correlates of Cognitive Impairment in Primary & Secondary/Progressive Multiple Sclerosis
    J Neurol Sci 1995 Oct;132(2):222-7

  7. Non-Specific ImmunoSuppression and MS
    Rev Neurol (Paris) 1998 Sep;154(8-9):629-34

  8. Immunological Profile Of Primary/Progressive Multiple Sclerosis: Expression Of Adhesion Molecules
    Brain 1999 Dec;122 ( Pt 12):2297-307

  9. In vivo assessment of the Brain and Cervical Cord pathology in Primary/Progressive Multiple Sclerosis
    Brain 2001 Dec;124(Pt 12):2540-9

  10. Primary/Progressive Multiple Sclerosis: increasing clarity but many unanswered questions
    J Neurol Sci 2002 Jul 15;199(1-2):1-15

  11. DeMyelinating lesions in Cervical Spinal Cord and disability in Multiple Sclerosis
    Neurol NeuroChir Pol 2004 Jan-Feb;38(1):25-9

  12. Progressive change in Primary/Progressive Multiple Sclerosis Normal-Appearing White Matter: a serial Diffusion Magnetic Resonance Imaging study
    Mult Scler 2004 Apr;10(2):182-7




#1

Clinical Features Of
Primary/Progressive Multiple Sclerosis

5. The Natural History Of Multiple Sclerosis

Cottrell DA, Kremenchutzky M, Rice GP, Koopman WJ, Hader W, Baskerville J, Ebers GC
Brain 1999 Apr;122 (Pt 4):625-39
Univ of Western Ontario, Dept of Clinical Neurological Sciences, London, Canada
PMID# 10219776; UI# 99235182
Abstract

We report a natural history study of 216 patients with Primary/Progressive (PP)-Multiple Sclerosis defined by at least 1 year of exacerbation-free progression at onset.

This represents 19.8% of a largely population-based patient cohort having a mean longitudinal follow-up of 23 years. This subgroup of PP-Multiple Sclerosis patients had a mean age of onset of 38.5 years, with females predominating by a ratio of 1.3:1.0.

The rate of deterioration from disease onset was substantially more rapid than for Relapsing/Remitting Multiple Sclerosis, with a median time to Disability Status Scale (DSS) 6 and DSS 8 of 8 and 18 years, respectively. Forty-nine percent of patients were followed through to death.

Examination of the early disease course revealed two groups with adverse prognostic profiles.

Firstly, a shorter time to reach DSS 3, from onset of PP-Multiple Sclerosis significantly adversely influenced time to DSS 8.

Second, involvement of three or more Neurological systems at onset resulted in a median time to DSS 10 of 13.5 years in contrast to PP-Multiple Sclerosis patients with one system involved at onset where median time to death from Multiple Sclerosis was 33.2 years.

However, age, gender and type of Neurological system involved at onset appeared to have little influence on prognosis.

Life expectancy, cause of Mortality and familial history profile were similar in PP-Multiple Sclerosis and non-PP-Multiple Sclerosis (all other Multiple Sclerosis patients from the total population).

From clinical onset, rate of progression was faster in the PP-Multiple Sclerosis group than in the Secondary/Progressive (SP)-Multiple Sclerosis group.

When the rates of progression from onset of the Progressive phase to DSS 6, 8 and 10 were compared, SP-Multiple Sclerosis had a more rapid progressive phase.

A substantial minority (28%) of the PP-Multiple Sclerosis cohort had a distinct relapse even decades after onset of progressive deterioration.

These studies establish natural history outcomes for the subgroup of Multiple Sclerosis patients with Primary/Progressive disease.



#2

Planning & Interpretation Of Clinical Therapeutic Trials In Primary/Progressive Multiple Sclerosis

6. The Natural History Of Multiple Sclerosis: A Geographically Based Study

Cottrell DA, Kremenchutzky M, Rice GP, Hader W, Baskerville J, Ebers GC
Brain 1999 Apr;122 (Pt 4):641-7
Univ of Western Ontario, Dept of Clinical Neurological Sciences, London, Canada
PMID# 10219777; UI# 99235183
Abstract

The natural history of Primary/Progressive Multiple Sclerosis (PP-Multiple Sclerosis) recently has been defined in a geographically based Multiple Sclerosis population.

For a series of prognostically defined hypothetical entry criteria based upon current trends in presentation to the London Multiple Sclerosis Clinic, we determined the number of patients who would have been trial eligible.

Using 23 year mean longitudinal natural history data, we identified the observed rate of deterioration for frequently used trial endpoints.

Hypothetical entry criteria were based on the practical considerations which would attend the execution of clinical trials in Progressive Multiple Sclerosis.

We then developed a series of sample size tables giving the number of patients with PP-Multiple Sclerosis and the length of observation that would be required to detect a significant result.

(P = 0.05) for a 25, 50 and 75% decrease in the median time to progression with 80 or 90% power, with treatment efficacy based upon the ability to slow progression on the Disability Status Scale.

It is expected that the considerations outlined here will prove useful for both trial design and interpretation of trials in PP-Multiple Sclerosis which will require multi-center collaborative efforts.



#3

Progressive/Relapsing And Relapsing/Progressive
Multiple Sclerosis: A Re-Evaluation

7. The Natural History Of Multiple Sclerosis: A Geographically Based Study

Kremenchutzky M, Cottrell D, Rice G, Hader W, Baskerville J, Koopman W, Ebers GC
Brain 1999 Oct;122 ( Pt 10):1941-50
Univ of Western Ontario, Dept of Clinical Neurological Sciences, London, Canada
PMID# 10506095; UI# 99435807
Abstract

Classifications of Multiple Sclerosis subtypes have been largely based on clinical phenomenology. Nevertheless, definitions of relapse, remission and progression have been imprecise.

Recently an international consensus group, as part of a reclassification of disease subtypes, recommended dropping the term 'Relapsing/Progressive' (RP) and retaining the term 'Progressive/Relapsing' (PR) Multiple Sclerosis.

The term 'RP' Multiple Sclerosis had been applied when the early course combined both relapses and progression and was believed to identify some patients with a worse than average outcome.

The PR group consisted of patients with Primary/Progressive disease who later in their course developed relapses.

Since the terminology has been largely arbitrary, we have evaluated the validity of the terms 'RP' and 'PR' Multiple Sclerosis in the context of long-term outcome within a large population-based cohort of Progressive Multiple Sclerosis patients seen at the London Multiple Sclerosis Clinic (Canada) between 1972 and 1984.

Mean follow-up of the entire cohort was 25 years. Designation of RP Multiple Sclerosis did identify a more rapidly Progressive subgroup.

To realign these natural history data with consensus recommendations, these patients were reassigned to Secondary/Progressive (SP) or to Primary/Progressive (PP) Multiple Sclerosis, with progression defined as at least 1 year of progressive deterioration.

PP Multiple Sclerosis patients with relapses after a year were designated as having PR Multiple Sclerosis.

Relapses in Primary/Progressive Multiple Sclerosis occurred in 27.8% of patients at some point even two to three decades after onset. In general these relapses were mild and Remitting, but served to blur the distinction between Progressive and Relapsing/Remitting disease.

The long-term outcomes of time to Kurtzke Disability Scores (DSS) of 3, 6, 8 and 10 were compared among the Progressive subtypes. Times to these disability end-points and to death were not different between PR and PP Multiple Sclerosis.

Survival curves for Progressive patients have been amended to incorporate the reassignment of PR Multiple Sclerosis patients into the PP group and the RP Multiple Sclerosis patients into the PP and SP subgroups.

The time to reach DDS 3, 6, 8 and 10 for a population-based cohort of Primary and Secondary/Progressive patients resulting from the elimination of the categories of RP Multiple Sclerosis and PR Multiple Sclerosis has been established.

These results provide justification for retaining only PP and SP Multiple Sclerosis as the subgroups of Progressive Disease.



#4

Spinal Cord Atrophy And Disability In MS
A longitudinal study

Stevenson VL; Leary SM; Losseff NA; Parker GJ; Barker GJ; Husmani Y; Miller DH; Thompson AJ
Neurology, 1998 Jul, 51:1, 234-8
Institute of Neurology, NMR Research Unit, Queens Square, London, UK
UI# 98337565
Abstract

Objective
To assess whether it is possible to measure changes in Cord cross-sectional area during a 1-year period in patients with MS reliably.

Background
Involvement of the Spinal Cord in MS is extremely common and an important element in the development of Disability.

Although little relation has been shown between the Cord lesion load and disability, a strong correlation between Spinal Cord Atrophy and the Expanded Disability Status Scale (EDSS) has been demonstrated in cross-sectional studies.

Method
A highly reproducible semiautomated technique that measures the cross-sectional area of the Cord at the C2 level was applied to 13 healthy control subjects and 28 patients serially.

Results
This study confirms that patients have significantly smaller Cords than control subjects at baseline (control subjects: mean 80.95 mm2, patients: mean 71.25 mm2, p = 0.01) and demonstrates that patients have a significant loss in Cord Cross-Sectional Area during 12 months, which was not seen in control subjects (p < 0.001).

This reduction in Cord size was most marked in the Primary/Progressive patients who had a mean Cord cross-sectional area loss of 3.52 mm2 (5.2%) and least in the Secondary/Progressive MS (-0.26 mm2, 0.7%) and Benign patients (-0.41 mm2, 0.8%).

The baseline Cord cross-sectional area correlated strongly with the EDSS (r = -0.52, p = 0.005) and with disease duration (r = -0.75, p < 0.001); however, there was no significant difference in Cord area (p = 0.69) or change in Cord Area (p = 0.51) between those patients with a definite increase in EDSS and those without.

Conclusion
This study demonstrates, for the first time, that it is possible to measure changes in Cord cross-sectional area over time.

The serial measurement of Spinal Cord Atrophy may thus make an important contribution to the evaluation of therapeutic efficacy, especially in Primary/Progressive disease.



#5

Assessing Information In T2-weighted MRI Scans In Secondary/Progressive Multiple Sclerosis

Koziol JA, Wagner S, Adams HP
Neurology 1998 Jul;51(1):228-33
The Scripps Research Institute, Dept of Molecular and Experimental Medicine, La Jolla, CA 92037, USA
UI# 98337564
Abstract

Background
Magnetic Resonance Imaging is used routinely for diagnosing MS and for objective assessment of the extent of disease as a marker of treatment efficacy in MS clinical trials.

Nevertheless, in many clinical studies only weak correlations have been reported between MRI findings and clinical outcome measures.

Purpose
The purpose of this study is to compare clinical outcome measures (Neurologic Scales) with MRI findings (evaluation of T2-weighted MRI scans using a semiautomated quantitative technique and with an independent assessment by a Neurologist) in the context of a randomized clinical trial evaluating the efficacy of Cladribine for treatment in Secondary/Progressive MS.

Methods
Baseline, 6-month, and 12-month scans from 41 Secondary/Progressive MS patients were examined and ranked in terms of lesion burden from the quantitative assessment and independently in terms of severity by neurologic evaluation.

Comparison is made to monthly Expanded Disability Status Scale (EDSS) and Scripps Neurologic Rating Scale (SNRS) determinations in these patients with a nonparametric statistical procedure.

Results
Average rank correlations between any of the MRI assessment procedures and either clinical outcome measure were less than 0.15 in absolute magnitude. The average rank correlation between the two MRI assessment procedures was 0.10.

There is only a weak degree of association between the MRI assessment procedures and the clinical parameters, although the study has statistical power in excess of 0.90 to find even a moderate level of association between them.

Conclusions
Disease-related activity in T2-weighted scans of Secondary/Progressive MS patients is a multidimensional construct, and is not summarized adequately solely by quantification of overall lesion burden or by assessment of severity.

Neither method of summarizing information from T2-weighted scans is strongly related to measures of the clinical course of disease as assessed by the EDSS or SNRS.



#6

Brain MRI Correlates Of Cognitive Impairment
In Primary and Secondary/Progressive MS

Comi G, Filippi M, Martinelli V, Campi A, Rodegher M, Alberoni M, Sirabian G, Canal N
J Neurol Sci 1995 Oct;132(2):222-7
Univ of Milan, Scientific Institute, OspedaleDept of Neurology, San Raffaele, Italy
PMID# 8543952; UI# 96098615
Abstract

Brain Magnetic Resonance Imaging (MRI) and an extensive battery of NeuroPsychological tests exploring Frontal functions, short and long-term Memory, Visuo-Spatial skills, Attention and Language were applied to 14 patients with Primary/Progressive Multiple Sclerosis (PP/MS) and 17 patients with Secondary/Progressive MS (SP/MS).

Patients with PP/MS and SPMS did not differ in degree of physical disability, but Cognitive deficits were found in 9/17 (53%) patients with SPMS and in only 1/14 (7%) of those with PP/MS (p = 0.01).

Patients with SP/MS had higher total (p = 0.004), PeriVentricular (p = 0.008) and Non-PeriVentricular (p = 0.04) MRI lesion loads than patients with PP/MS.

In detail, patients with SPMS had greater involvement of Frontal (p = 0.05) and Occipital (p = 0.02) Horns, Trigones (p = 0.04), Third Ventricle (p = 0.03), Basal Ganglia (p = 0.02), Parietal (p = 0.02), Temporal (p = 0.004) and Occipital (p = 0.03) Lobes.

Patients with SP/MS and NeuroPsychological deficits had higher Non-PeriVentricular lesion loads than patients with SP/MS who did not have such deficits (p = 0.005).

Our results indicate that both NeuroPsychological and Brain MRI abnormalities are more extensive in patients with SP/MS. Since physical disability was similar for both groups, Disability in PPMS may be predominantly due to Spinal Cord involvement.



#7

Non-Specific ImmunoSuppression & Multiple Sclerosis

Brochet B
Rev Neurol (Paris) 1998 Sep;154(8-9):629-34
Hopital Pellegrin, Service de Neurologie, CHRU de Bordeaux
PMID# 9809379; UI# 99026907
Abstract

Several series of arguments favor at least partial efficacy of ImmunoSuppression in Multiple Sclerosis. ImmunoSuppression can often treat Experimental AutoImmune Encephalitis, an imperfect model of Multiple Sclerosis.

Certain agents have been shown to affect the PathoPhysiological processes seen indirectly on Magnetic Resonance Imaging (Mitoxantrone and Campath, for example). Therapeutic trials have their methodological weaknesses but do allow certain conclusions.

The Progressive forms of Multiple Sclerosis are the most widely studied. Massive but short-term ImmunoSuppression does not appear to affect the course of progression but prolonged ImmunoSuppression would appear to slow down the process, at least in responders.

The effect on disease progression is modest and preference should go to well-tolerated treatments. ImmunoSuppression appears to effectively decrease the number of acute episodes and reduce the number of new lesions detectable by Magnetic Resonance Imaging.

The effect of ImmunoSuppression is limited however by the fact that the clinical course of Progressive forms depends less on the development of new lesions than on an aggravation of the DeMyelination process and possible Axon Loss within constituted lesions.

This is a further argument favoring early ImmunoSuppressive treatment at a stage when it can be most effective.



#8

Immunological profile of Primary/Progressive Multiple Sclerosis: Expression of Adhesion Molecules

Duran I, Martinez-Caceres EM, Rio J, Barbera N, Marzo ME, Montalban X
Brain 1999 Dec;122 ( Pt 12):2297-307
Unitat de NeuroImmunologia Clinica, Servei de Neurologia, Hospital General Universitari Vall d'Hebron, Barcelona, Spain
PMID# 10581223; UI# 20050341
Abstract

Adhesion Molecules are important in the trafficking of peripheral Leukocytes into the Central Nervous System, a major event in the PathoGenesis of Multiple Sclerosis, which is an Inflammatory and DeMyelinating Disease.

The latest MRI evidence supports clinical divergence between forms of Multiple Sclerosis with relapses and the Primary/Progressive form without relapses, which shows fewer and smaller inflammatory lesions.

With the aim of elucidating whether different pathogenic mechanisms are involved in Primary/Progressive Multiple Sclerosis, we compared membrane expression of the Adhesion Molecules ICAM-1 (CD54), LFA-1alpha (CD11a), VLA-4 [alpha(4)/ß(1) Integrin (CD49d/CD29)], L-Selectin (CD62L) and ICAM-3 (CD50) in peripheral blood and the Serum-soluble forms ICAM-1, L-Selectin, VCAM-1 and ICAM-3.

In 89 patients (39 with the Primary/Progressive form, 25 with the Secondary/Progressive form and 25 with the Relapsing/Remitting form) and 38 healthy controls.

We found a significant decrease in Leukocyte surface expression of most of the Adhesion Molecules tested and an increase in soluble ICAM-1 and L-selectin levels in Secondary/Progressive and Relapsing/Remitting Multiple Sclerosis compared with Primary/Progressive Multiple Sclerosis, which gave results similar to those in controls.

These results, which are supported by MRI evidence, show that trafficking of AutoReactive Leucocytes through the Blood-Brain Barrier is crucial to the PathoGenesis of Secondary/Progressive and Relapsing/Remitting forms of Multiple Sclerosis.

Whereas other mechanisms (Wallerian Degeneration) leading to progressive Axonal Damage would account for Primary/Progressive forms of the disease.



#9

In Vivo Assessment Of The Brain And Cervical Cord Pathology In Primary/Progressive Multiple Sclerosis

Rovaris M, Bozzali M, Santuccio G, Ghezzi A, Caputo D, Montanari E, Bertolotto A, Bergamaschi R, Capra R, Mancardi G, Martinelli V, Comi G, Filippi M
Brain 2001 Dec;124(Pt 12):2540-9
Scientific Institute and University Ospedale San Raffaele, NeuroImaging Research Unit, Department of NeuroScience, Milan, Italy
PMID# 11701606
Abstract

In patients with Primary/Progressive (PP) Multiple Sclerosis, Brain MRI lesion activity and burden are low, despite the presence of severe Neurological Impairment.

On the contrary, the degree of Cord Atrophy and diffuse tissue damage in the Brain and Cervical Cord have been found to be associated with Clinical Disability.

Against this background, this study aimed at providing an in vivo indirect assessment of Brain and Cervical Cord pathology in a large cohort of PP Multiple Sclerosis patients, using conventional MRI and Magnetization Transfer Imaging (MTI).

Ninety-one PP Multiple Sclerosis patients, 36 Secondary/Progressive (SP) Multiple Sclerosis patients and 30 healthy controls underwent Brain and Cervical Cord MRI scans, using dual echo (Brain) or fast short-Tau Inversion Recovery (Cervical Cord) MTI and T1-weighted sequences.

For the Brain, T2 HyperIntense and T1 HypoIntense lesion volumes were calculated and the volume of the whole Brain tissue measured. For the Cervical Cord, the number and burden of lesions and the Cross-Sectional Area were assessed.

MTI scans were post-processed and analyzed to obtain Magnetization Transfer Ratio (MTR) Histograms from the whole Brain and Cervical Cord tissue and from the Normal-Appearing Brain Tissue in isolation.

In PP Multiple Sclerosis patients, Brain, Normal-Appearing Brain Tissue and Cervical Cord MTR Histogram-derived metrics revealed the presence of diffuse tissue damage whose characteristics did not significantly differ from those of SP Multiple Sclerosis patients.

Even though SP Multiple Sclerosis patients had higher MRI-visible lesion burdens, none of the correlations between MRI or MTI measures obtained from the Brain and the Cord were significant.

PP Multiple Sclerosis patients' Disability was significantly, albeit weakly associated with a composite MR model including measures of loss and intrinsic damage of Cervical Cord tissue.

Our data indicate the presence of a diffuse tissue damage undetectable by conventional MRI in PP Multiple Sclerosis patients, whose extent seems to match that of SP Multiple Sclerosis patients with similar levels of disability.

They also suggest that the severity of Multiple Sclerosis pathology in the Cervical Cord is one of the factors contributing to Neurological Impairment in PP Multiple Sclerosis.



#10

Primary/Progressive Multiple Sclerosis: Increasing Clarity But Many Unanswered Questions

McDonnell GV, Hawkins SA
J Neurol Sci 2002 Jul 15;199(1-2):1-15
Northern Ireland Neurology Service, Ward 21, Quin House, Royal Victoria Hospital, Northern Ireland, Belfast, Ireland
PMID# 12084436; UI# 22079896
Abstract

Heterogeneity in the clinical course of Multiple Sclerosis (MS) is well recognized and patients following a Primary/Progressive course, 10-15% of the MS population, have a distinct clinical and paraclinical phenotype.

This review examines recent advances in our understanding of this subgroup of patients and examines the new criteria to be applied in Diagnosis.

It also highlights developments in Genetic, Immunological, Magnetic Resonance and Pathological aspects of the disease, while also outlining the results of recent therapeutic trials.



#11

DeMyelinating Lesions In Cervical Spinal Cord And Disability In Multiple Sclerosis

Bonek R, Sokolska E, Kurkiewicz T, Maciejek Z
Neurol NeuroChir Pol 2004 Jan-Feb;38(1):25-9
Klinika Neurologii, 10, Wojskowy Szpital Kliniczny, ul. Powstancow Warszawy 5, 85-915 Bydgoszcz
PMID# 15049165
Abstract

Background And Purpose
In Multiple Sclerosis (MS) lesions appear both in Brain and Cervical Cord. The aim of this study was to estimate the presence of MRI changes in Cervical Cord depending on the course, duration of the disease and a disability.

Material And Methods
Clinical measures included 66 patients suffering from MS, the diagnosis was made according to McDonald's Criteria. Patients were aged from 18 to 62 (41 women and 25 men).

Results
In patients with Relapsing/Remitting form (EDSS 1-4) single lesions were seen whereas Secondary/Progressive patients (EDSS 3-7) had diffuse DeMyelinating lesions and Primary/Progressive patients (EDSS 4-8) - both kinds of changes.

It has been shown that the lesions occurred as the disease proceeds. Patients without DeMyelinating lesions in Cervical Cord had EDSS from 1 to 3 and the duration of their disease was longer than 10 years (Benign MS).

Conclusions
The duration of the disease depends on the presence and character of DeMyelinating lesions in Cervical Cord to a large extent. That dependence was not noticed in a Primary/Progressive form. In Benign MS there were no lesions in Cervical Cord.



#12

Progressive Change In Primary/Progressive Multiple Sclerosis Normal-Appearing White Matter: A Serial Diffusion Magnetic Resonance Imaging Study

Schmierer K, Altmann DR, Kassim N, Kitzler H, Kerskens CM, Doege CA, Aktas O, Lunemann JD, Miller DH, Zipp F, Villringer A
Mult Scler 2004 Apr;10(2):182-7
Humboldt-Universitat Berlin, Klinik fur Neurologie, Charite, Germany
PMID# 15124765
Abstract

In spite of marked disability, patients with Primary/Progressive Multiple Sclerosis (PPMS) display smaller lesion volumes on conventional Magnetic Resonance Imaging (MRI) compared with other forms of Multiple Sclerosis (MS).

Hence, damage to the Normal-Appearing Brain Tissue (NABT) may play an important role in explaining the pathogenesis of disability in PPMS.

Diffusion-weighted MRI (DW-MRI) probes water Diffusion in vivo that can be altered by pathologic changes. Using DW-MRI we investigated Diffusion in the NABT of 15 patients with PPMS over one year.

The average Apparent Diffusion Coefficient (ADCav) was measured in 10 regions of interest located in the Normal-Appearing Thalamus and the Normal-Appearing White Matter (NAWM). Six healthy subjects served as a reference.

In contrast to healthy subjects, patients with PPMS showed an increment within 12 months of the ADCav in NAWM which was associated with an increase of the T2- and T1-lesion volumes.

The ADCav in frontal NAWM was associated with disability as measured by the MS Functional Composite Measure. Serial DW-MRI depicts progressive changes in the NAWM of patients with PPMS.

Our preliminary findings suggest that the processes causing structural damage in NAWM and lesions in patients with PPMS are partially linked and that changes of water Diffusion in NAWM depicted by DW-MRI are clinically relevant.



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