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PubMed2002

[Progressive course of multiple sclerosis].

The mechanisms of MS progression are now studied with great attention and the treatment strategies at this stage of MS are widely discussed. The clinical peculiarities, genetic profile, immunological and biochemical changes, data of pathomorphological and MRI studies are discussed in this review. The data of own original immunological, biochemical and MRI studies, comparing relapsing-remitting and progressive MS course are presented. The role of axonal degeneration in the disease progression and data of the last trial of beta-interferons in secondary progressive MS are also discussed.

Adjuvants, Immunologic↗
PubMedDate not supplied

Intravenous immunoglobulin and mitoxantrone stop the progression of secondary progressive multiple sclerosis in a patient with interferon intolerance.

A 36 year-old female patient with secondary progressive multiple sclerosis accompanied by neuropsychiatric depression and history of intolerance to beta-interferon was treated with mitoxantrone (MX) and intravenous immunoglobulin (IVIG) for 2 years. Both clinical response and magnetic resonance imaging were performed at the end. With a combination of MX and IVIG long-term treatment, her disabilities improved as measured by the Expanded Disability Status Scale (EDSS). The combination therapy was well-tolerated. It represents an alternative to treat patients who do not respond well to cytostatics alone, or in those in whom intolerance to interferons may also occur. Immunomodulation with intravenous immunoglobulin stopped the progression of the disease and avoided subsequent exacerbations during 24 months. The role of high doses of immunoglobulins in the treatment of patients with secondary progressive MS deserves clinical trials to evaluate the stopping of progression of the disease in comparison to remissions induced by cytostatics, interferons and steroids.

Adult↗
PubMed2003

Clinical-MRI correlations in the secondary progressive phase of MS: lessons from the treatment trials.

Conventional MRI techniques are sensitive to detect MS lesions and their change overtime. In relapsing-remitting MS correlations with clinical measures are weak suggesting a pathological heterogeneity of these lesions. There are less data available in secondary progressive phase of the disease. The best source for clinical MRI correlations analysis is the placebo arm of the published interferon beta trials. This review presents the main clinical-MRI findings from these trials then focuses on recent promising observations obtained with non conventional MRI techniques in SP MS patients.

Clinical Trials as Topic↗
PubMed2004

Clinical characteristics of progressive relapsing multiple sclerosis.

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.

Adult↗
PubMedDate not supplied

[Primary progressive multiple sclerosis].

Mainly progressive multiple sclerosis (MPMS) is an uncommon clinical form of multiple sclerosis which includes 10 20% of all patients with the disorder. MPMS shows certain clinical characteristics which differentiate it from other forms of progression of the disease. We review the immunological and radiological behaviour of this clinical form, and discuss recent classifications of the disease and new diagnostic criteria. Finally we comment on the few therapeutic options currently available for these patients and their future prospects.

Adrenal Cortex Hormones↗
PubMed1989

Cognitive disturbances in patients with relapsing remitting multiple sclerosis.

The performance of 42 patients with relapsing remitting (RR) multiple sclerosis was compared with that of 24 age-, education-, and gender-matched control subjects on a battery of neuropsychological tests known from previous studies to be sensitive to the impairments of patients with chronic progressive (CP) multiple sclerosis. Like CP patients, RR patients exhibited deficits on tests of information-processing speed, verbal fluency, and problem solving, and on recall measures of anterograde and remote memory. Although a few patients were mildly dysnomic, the RR patients were not generally impaired on visual confrontation naming and they did not exhibit perseverative responding on verbal fluency measures. The pattern of neuropsychological deficits exhibited by RR patients closely approximates the profile observed in other subcortical dementias and does not contain the features of cortical dementia evident in some CP patients. The impairment of RR patients on cognitive tests were less severe than those observed in CP patients in our previous studies. Differences in the age of patients in the CP and RR groups did not account for group differences in the severity of cognitive impairments, but differences in disease duration or severity of disability, as well as disease course, could explain why CP patients exhibit more serious cognitive disturbances than RR patients.

Adult↗
PubMed1999

Magnetisation transfer of normal appearing white matter in primary progressive multiple sclerosis.

Patients with primary progressive multiple sclerosis may develop severe disability despite a paucity of lesions on conventional magnetic resonance imaging, raising the possibility that intrinsic changes in normal appearing white matter (NAWM) contribute to disability. This study has measured magnetisation transfer ratio (MTR), an index of tissue damage, of NAWM in 52 patients with primary progressive multiple sclerosis and 26 healthy controls. Absolute values of MTR were obtained from the genu of the corpus callosum and pons, and mean values were calculated from bilateral regions in the centrum semiovale, frontal white matter, parieto-occipital white matter and posterior limb of the internal capsule. The median MTR was lower in all regions in patients compared to controls. Median values (per cent units) were significantly lower in corpus callosum (39.73 vs 40.63; P=0.01), frontal white matter (39.11 vs 39.59; P=0.01) and centrum semiovale (37.21 vs37.82; P<0.05). This study has demonstrated small but widespread decreases in MTR in NAWM in primary progressive multiple sclerosis supporting the hypothesis that there are intrinsic changes in NAWM which may contribute to disability in this patient group.

Adult↗
PubMed2003

Multislice T1 relaxation time measurements in the brain using IR-EPI: reproducibility, normal values, and histogram analysis in patients with multiple sclerosis.

PURPOSE: To perform T(1) measurements using inversion recovery (IR) echoplanar imaging (EPI) to evaluate reproducibility, normal values, and T(1) histogram analysis as a measure of disease progression in multiple sclerosis (MS) patients. MATERIALS AND METHODS: Multislice IR-EPI was performed in 10 controls and 36 MS patients. Region-of-interest (ROI) and T(1) histogram analysis were performed on T(1) maps and compared to hypointense T(1) lesions and brain atrophy in MS patients. RESULTS: Coefficient of variation (COV) varied from 1.6% to 4.9%. Callosal normal (appearing) white matter (N(A)WM) showed the lowest and cortical gray matter the highest T(1) values. T(1) histogram analysis in controls showed a sharp WM peak centered on a T(1) value of 729 msec (range = 679-765) with extension into a shoulder of higher T(1) values. In MS patients, a shift toward higher T(1) values (mean = 788 msec, range = 700-957) with a lower relative peak amplitude was present, predominantly resulting from T(1) prolongation in NAWM. T(1) histogram parameters strongly related to hypointense T(1) lesion volume and brain atrophy in MS patients. CONCLUSIONS: IR-EPI provides a reproducible method to obtain T(1) values in the brain. Regional variation in T(1) values is present in N(A)WM of volunteers and MS patients. Since T(1) histogram parameters reflect changes in NAWM and correlate with conventional measures of disease burden in MS patients, T(1) histogram analysis may provide a global measure of disease progression in MS.

Adult↗
PubMed2005

[The effect of combined mitoxantrone and methylprednisolone therapy in primary and secondary progressive multiple sclerosis. An applied study in 65 patients].

Mitoxantrone (mitox) has been shown to be effective for secondary progressive (SP) and relapsing-remitting multiple sclerosis (MS). The aim of this open trial was to evaluate the effects of combined mitox and methylprednisolone (MP) therapy on patients with primary progressive (PP)-MS or with SP-MS. We present here the results of an interim analysis done after the study had lasted 5 years. Sixty-five patients (20 with PP-MS and 45 with SP-MS) have been included so far. The treatment involved ten cycles of combined mitox and MP. The intervals between the individual cycles were systematically prolonged from 3 months initially to 12 months, so the complete treatment took a total of 57 months. Conclusion This interim analysis indicates that mitox combined with MP beneficially reduces the progression of disability in patients with PP-MS and SP-MS. Therefore, this therapy regimen can also be considered a feasible option for PP-MS.

Adult↗
PubMed1999

The natural history of multiple sclerosis: a geographically based study. 7. Progressive-relapsing and relapsing-progressive multiple sclerosis: a re-evaluation.

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.

Adult↗
PubMedDate not supplied

Irreversible neurological worsening following high-dose corticosteroids in advanced progressive multiple sclerosis.

BACKGROUND: A course of high-dose corticosteroids has been shown to hasten recovery from a relapse of multiple sclerosis (MS). Some patients with progressive MS ask for a course with corticosteroids outside a relapse, hoping to gain some functional improvement. OBJECTIVE: To describe 4 patients with advanced progressive MS who experienced worsening of disability after treatment with high-dose corticosteroids. RESULTS: All 4 patients had moderate to severe disability and asked for corticosteroid treatment because they were slowly progressing. None of them had a relapse. All experienced improvement by the end of the treatment course. One or 2 days after discontinuation of treatment, however, they deteriorated clinically and became more disabled than before treatment. CONCLUSION: The use of high-dose corticosteroid therapy in progressive forms of MS outside relapses can be detrimental and worsen disability.

Adrenal Cortex Hormones↗
PubMed2004

Primary progressive multiple sclerosis: clinical and paraclinical characteristics with application of the new diagnostic criteria.

The aim of our study was to analyse clinical and paraclinical characteristics of patients with multiple sclerosis (MS) with previous diagnosis of primary-progressive (PP) MS according to the Poser's criteria and further investigate if they fulfil the McDonald's diagnostic criteria for this disorder. A total of 561 MS patients were registered in the database at the Institute of Neurology, Belgrade, from 1 January 1997 to 31 December 2000 and 63 of them (11.2%) with previous diagnosis of PPMS were analysed retrospectively. Male/female ratio was 1.3:1 and mean age at onset 33.2 years. Most frequent at onset were pyramidal (in 73% of patients) and sensory symptoms (in 41% of patients); 74.6% of patients had greater than or equal to nine brain magnetic resonance imaging (MRI) lesions. Intrathecal oligoclonal immunoglobulin G (IgG) was detected in 96.7% and prolonged visual evoked potentials (VEP) P100 latency in 82.4% of patients. Of the total study group of 561 patients, 10.2% fulfilled the recently recommended McDonald's diagnostic criteria for the diagnosis of PPMS. Our findings further support the significance of the brain/spinal cord MRI, cerebrospinal fluid and VEP findings for precise diagnostic assessment in patients with suspected PP form of MS.

Adult↗
PubMed2005

The natural history of primary progressive MS in British Columbia, Canada.

BACKGROUND: Primary progressive multiple sclerosis (PPMS) has a distinct clinical phenotype and has historically been understudied with few longitudinal natural history studies spanning a reasonable time period. The authors examined patient characteristics, disease progression, and associated risk factors in the PP population of British Columbia, Canada. METHOD: The authors report on the PP population from an upcoming publication of the natural history study of definite MS in British Columbia, Canada. The main outcome was sustained progression to Expanded Disability Status Scale (EDSS) 6, secondary outcome time to EDSS 8. Risk factors for progression included sex, onset age, onset symptoms, and for time to EDSS 8, time to EDSS 6. RESULTS: Of the 2,837 patients with definite MS in the original study, 352 (12.4%) had PPMS. Mean disease duration was 17.2 years (0.3 to 49.6 years), mean onset age was 40.1 years (SD 11.5), and 53% (187) were female. One-quarter of the population had reached EDSS 6 after 7.3 years from onset, yet another 25% still did not require a cane after 25 years. Sex, onset age, and onset symptoms did not predict progression (p > 0.05). A shorter time to EDSS 6 predicted a shorter time to EDSS 8 (p < 0.0005). DISCUSSION: Progression of disability was slower than found in previous primary progressive multiple sclerosis natural history studies. However, considerable variation existed, with few predictors, other than "sooner to cane, sooner to wheelchair."

Adult↗