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PubMed1998

[A case of primary Sjögren's syndrome with CNS disease mimicking chronic progressive multiple sclerosis].

We report a 40-year-old woman with primary Sjögren's syndrome (SjS) with slowly progressive CNS disease. At age 38, she noticed spasticity and very gradual onset of monoparesis in the left leg. She hardly walked by herself at age 40. On admission, neurological examination revealed mild slurred speech, vertical nystagmus, spasticity in the four extremities, spastic monoparesis of the left leg, exaggerated jaw jerk, hyperreflexia in all limbs except right biceps and brachioradialis reflex, and positive bilateral Hoffmann reflexes and Babinski signs. Laboratory examinations disclosed positive anti-nuclear antibody (speckled type) and anti-SS-A/Ro antibody (64x). CSF examination revealed cell count 8/mm3, protein 42 mg/dl, 4 bands of oligoclonal band and the elevation of IgG index. MR-imaging presented multiple plaque-like lesions in white matter of cerebrum and brainstem, which did not show gadolinium enhancement. Additionally she complained of dry eyes. Lacrimal and salivary secretion tests showed hyposecretion of tears and hyposialosis. The biopsied specimen of labial minor salivary gland revealed the destruction of the ducts and periductal lymphocytic infiltrations. The diagnosis of primary SjS was confirmed. We herein report a rare case of primary SjS with CNS disease mimicking chronic progressive multiple sclerosis (MS), and discuss a difficulty in differentiating CNS disease of SjS from MS.

Adult↗
PubMed1993

High-dose methylprednisolone infusions in relapsing and in chronic progressive multiple sclerosis patients. One year follow-up.

Sixty Multiple Sclerosis patients hospitalized either in relapse (28) or in chronic progressive (32) phase of the disease were treated with high-dose methylprednisolone infusions (1 g/daily for 6 days). Clinical examinations, scored by Kurtzke's functional systems (FSs) and expanded disability status scale (EDSS), were performed before treatment, immediately after, and thereafter at 1,3,6 and 12 month intervals. In relapsing cases, 22 patients (78.6%) improved and EDSS mean value decreased by 1.39 points after the treatment; 8 patients had a new bout within one year. In chronic progressive cases, 18 patients (56.2%) improved and EDSS mean value decreased by 0.56 points after the treatment; 13 patients showed a new worsening throughout the follow-up period. The treatment proved to be safe and effective both in relapsing and in chronic progressive patients, determining rapid clinical improvement in most of the cases, and a slowing down of progression in some chronic patients.

Adolescent↗
PubMed1984

Lymphocytapheresis in chronic progressive multiple sclerosis: immunologic and clinical effects.

We studied the effects of lymphocytapheresis in five patients with chronic progressive MS. Ten lymphocytapheresis treatments were given in 2 weeks, followed by 1 treatment every 2 weeks for 2 to 6 months. Four of five patients had a fall in the circulating lymphocyte count during the initial treatment, and in three patients a modest lymphopenia was sustained with maintenance therapy. In patients with abnormal T4:T8 ratios, no improvement in the T4:T8 ratio occurred. There was no apparent clinical effect in this pilot study.

Adult↗
PubMed1994

Reversal of visuospatial hemi-inattention in patients with chronic progressive multiple sclerosis by treatment with weak electromagnetic fields.

The occurrence of cognitive impairment including visuoperceptive and visuospatial deficits have long been recognized to occur in patients with multiple sclerosis (MS) particularly among patients with a chronic progressive course. In MS visuospatial and visuoperceptive deficits have been attributed to the presence of diffuse demyelinating plaques which "disconnect" the brainstem reticular formation and other subcortical structures involved in attention and arousal from cortical areas thus causing a state of hypoarousal. It has been reported recently that brief external applications of alternating pulsed electromagnetic fields (EMFs) in the picotesla (pT) range intensity improved visuoperceptive and visuospatial functions in MS patients. The present communication concerns three female patients with chronic progressive course of MS (mean age: 52.3 +/- 2.0 yrs; mean duration of illness: 17.6 +/- 10.2 yrs) who, on tests of free drawings, demonstrated visuospatial hemi-inattention as a feature of more global cognitive deterioration. In all patients brief applications of EMFs rapidly reversed this cognitive deficit. These findings support prior observations demonstrating that pT EMFs may bring about reversal of certain cognitive deficits in MS patients which, to my knowledge, remain unaffected by any other treatment modality.

Attention↗
PubMed1995

A brain MRI study of different types of chronic-progressive multiple sclerosis.

INTRODUCTION: This study was performed to define the pattern of brain magnetic resonance imaging (MRI) abnormalities in chronic-progressive MS (MS). MATERIAL AND METHODS: Brain MRIs were obtained for 17 patients with secondary progressive MS (SPMS), 14 with primary progressive MS (PPMS) and 5 with "transitional" progressive MS (TPMS). RESULTS: Total lesion loads were different for the three groups of patients (p < 0.01). At post-hoc analysis, there was no difference between patients with TPMS and those with PPMS, while both these groups had lesion loads lower than those of patients with SPMS. Patients with PPMS with clinical signs indicating involvement of both brain and spinal cord had greater total lesion loads than those with clinical isolated spinal cord involvement (p < 0.05). CONCLUSION: These data indicate that brain MRI patterns of abnormalities are related to the clinical manifestations in patients with chronic-progressive MS.

Adult↗
PubMed1991

A placebo-controlled, double-blind, randomized, two-center, pilot trial of Cop 1 in chronic progressive multiple sclerosis.

We found Cop 1 to be effective and relatively safe in a previous (exacerbating-remitting) clinical trial. This current trial involves 106 chronic-progressive patients. The major end point, confirmed progression of 1.0 or 1.5 units (depending on baseline disability) on the Kurtzke Expanded Disability Status Scale, was observed in nine (17.6%) treated and 14 (25.5%) control patients. The differences between the overall survival curves were not significant. Progression rates at 12 and 24 months were higher for the placebo group (p = 0.088) with 2-year probabilities of progressing of 20.4% for Cop 1 and 29.5% for placebo. We found a significant difference at 24 months between placebo and Cop 1 at one but not the other center. Two-year progression rates for two secondary end points, unconfirmed progression, and progression of 0.5 EDSS units, (p = 0.03) are significant.

Chronic Disease↗
PubMed1988

Course and prognosis of chronic progressive multiple sclerosis. Results of an epidemiological study.

In studies on the natural course of multiple sclerosis (MS), several forms of the disease are distinguished. The most important are the relapsing remitting and the chronic progressive forms. The relationship between these remains unclear. In a prospective epidemiological survey we studied the course of MS using the year in which the chronic-progressive phase started as a landmark. The reliability of this "year of progression" was examined in an observer agreement study. Data were acquired from 342 patients. Progression of the handicap was most rapid in case of a secondary progressive course, female sex, high relapse rate in the preceding remitting phase and "year of progression" at a higher age. Survival after the "year of progression" was lowest in the secondary progressive group. Determining the "year of progression" seems to be significant for the prognosis.

Adolescent↗
PubMed1996

Comparative evaluations of neuroperformance and clinical outcome assessments in chronic progressive multiple sclerosis: I. Reliability, validity and sensitivity to disease progression. Multiple Sclerosis Study Group.

There remains controversy regarding the most sensitive and valid outcome assessments to use in multiple sclerosis (MS) clinical trials. A double blind, placebo controlled, parallel group multicenter clinical trial to evaluate the clinical efficacy of cyclosporine A in chronic progressive MS incorporated several major clinical and performance outcome assessment modalities and a large sample size, both of which provide a unique opportunity to explore the relationship among MS disease status and the various outcome measures over time. The measures included a structured neurological examination, the Kurtzke Functional System scales and Expanded Disability Status Score, and the Incapacity Status Scale from the MS Minimal Record of Disability, the Harvard Ambulation Index, and neuroperformance testing. A test-retest reliability index, principal component analyses and a signal-to-noise ratio metric were used to comparatively evaluate the reliability, validity and sensitivity to disease progression of the various outcome assessments. The goal was to provide a rational basis for selection of behavioral outcome assessments in future MS clinical trials by identifying the primary dimensions of MS measured by the candidate outcome assessments and providing an objective basis for selecting tests that are most sensitive to MS disease and its progression over a two year trial period. We conclude that the components of the major clinical and performance measures show excellent reliability and cross validation. Principal component analyses of all outcome assessments yielded six primary underlying factors for describing disease status in chronic progressive MS that included lower extremity/pyramidal dysfunction, cerebellar/brainstem and upper extremity dysfunction, somatosensory dysfunction, visual dysfunction, mental or intellectual dysfunction and bowel/bladder problems. Signal-to-noise ratios indicated that upper and lower extremity composites of neuroperformance test items provided the most sensitive indicators of MS disease progression in the placebo group over the 2 year trial period.

Activities of Daily Living↗
PubMed1998

Blood levels of transforming growth factor-beta 1 (TGF-beta1) are elevated in both relapsing remitting and chronic progressive multiple sclerosis (MS) patients and are further augmented by treatment with interferon-beta 1b (IFN-beta1b).

The serum levels of TGF-beta1, measured by solid-phase ELISA, were determined to be significantly augmented in patients with both relapsing remitting (RR) and secondary chronic progressive (CP) MS compared with sex- and age-matched healthy controls. Moreover, in RR MS patients, the blood levels of the cytokine were further augmented either during relapses or, in a rapid but reversible fashion, by s.c. injection with 8 million International Units (MIU) IFN-beta1b. Because TGF-beta1 possesses multiple anti-inflammatory activities, we hypothesize that the increase in its circulating levels in RR and CP MS patients might represent an endogenous anti-inflammatory mechanism aimed at counteracting ongoing immunoinflammatory events, and that IFN-beta may further potentiate this natural defensive apparatus.

Adjuvants, Immunologic↗
PubMed1997

Antigen presentation by autoreactive proteolipid protein peptide-specific T cell clones from chronic progressive multiple sclerosis patients: roles of co-stimulatory B7 molecules and IL-12.

To assess the role of T cell antigen (Ag) presentation in multiple sclerosis (MS), proteolipid protein (PLP) peptide reactive CD4+ T cell clones (TCCs) from MS patients and normal subjects were studied. TCCs derived from chronic progressive (CP) MS patients were able to proliferate and secret cytokines in response to PLP peptide stimulation in the absence of professional antigen presenting cells (APCs), suggesting that these T cells can simultaneously present and respond to Ags. However, they did not respond to total PLP protein, suggesting that PLP-peptide TCCs were unable to process and present the whole PLP molecule. The ability of the different TCCs to act as APCs in response to Ag stimulation did not correlate with expression of HLA-class II molecules. However, the degree of expression of B7-1 and B7-2 co-stimulatory molecules showed a significant correlation with APC capacity. Furthermore, a combination of anti-B7-1 and anti-B7-2 mAbs effectively inhibited proliferative responses as well as secretion of IL-10, IFN gamma and TGF beta induced by antigen presenting T cells. By contrast, IL-4 secretion was not affected. Finally, IL-12 significantly enhanced the efficiency of T cell Ag presentation by a pathway independent of Ag processing, suggesting that IL-12 might act as an additional co-stimulatory signal for T cell activation during T-T cell interactions. Together, these observations suggest that Ag presentation by T cells might amplify and perpetuate an autoimmune response previously initiated by professional APCs. These properties may account for progression of MS into a CP phase.

Adult↗
PubMed1994

Improvement by picoTesla range magnetic fields of perceptual-motor performance and visual memory in a patient with chronic progressive multiple sclerosis.

The occurrence of cognitive deficits in multiple sclerosis (MS) has been recognized since 1877 when Charcot first observed "enfeeblement of memory." It is now recognized that visuoperceptive and visuomotor deficits commonly occur in MS patients particularly in those with a chronic progressive course of the disease. Using various drawing tests as markers of constructional performance, we reported recently that treatment with picoTesla range magnetic fields (MF) rapidly improved visuoperceptive and constructional abilities in patients with MS. We now report a 58 year old man with a 37 year history of chronic progressive MS in whom external application of MF in the picoTesla range produced rapid improvement of neurologic symptoms including walking, balance, sensory symptoms, and bladder functions. The patient's recovery was associated with a significant improvement in perceptual-motor functions as demonstrated on the Rey-Osterrieth Complex Figure and the Trail Making tests. Specifically, the patient demonstrated a 41% improvement over pretest values on copying the Complex figure and a 72% improvement in recall of the figure immediately after MF treatment. A further 4% improvement on copying the figure and a 27% improvement on recall was demonstrated 24 hours later. On the Trail Making test the patient demonstrated an overall improvement of 39% in Part A of the test and a 24% improvement in Part B of the test 24 hours after application of MF. These findings confirm the beneficial effects of picoTesla range MF in the treatment of MS and demonstrate the unique efficacy of this treatment modality in improving some of the cognitive deficits of the disease.

Chronic Disease↗
PubMed1994

Urinary free kappa light chain levels in chronic progressive multiple sclerosis.

Previous studies have shown elevated levels of free kappa light chains (FKLC) in the urine of patients with relapsing-remitting multiple sclerosis (MS). The levels correlated well with clinical relapses, indicating that they could serve as useful markers of disease activity. In this study, we performed monthly measurements of urinary FKLC in patients with the chronic progressive form of MS, and correlated them with clinical indicators of disease activity, as expressed by Kurtzke's expanded disability status scale (EDSS) and brain magnetic resonance imaging (MRI). We noted wide fluctuations in the FKLC levels, which correlated poorly with EDSS scores or MRI changes. Longer follow-up periods may be needed before definite conclusions can be drawn.

Adult↗
PubMed1993

Interleukin-2, soluble interleukin-2-receptor, neopterin, L-tryptophan and beta 2-microglobulin levels in CSF and serum of patients with relapsing-remitting or chronic-progressive multiple sclerosis.

Cerebrospinal fluid (CSF) and serum levels of interleukin-2 (IL-2), soluble IL-2 receptors (sIL-2R), neopterin, L-tryptophan (L-TRP) and beta 2-microglobulin (beta 2-M) were measured in 31 untreated multiple sclerosis patients in acute exacerbation and 27 normal controls. Twenty-six patients showed the relapsing-remitting type of disease (RRMS); 5 had a chronic-progressive course (CPMS). No changes in serum IL-2 and sIL-2R were found between RRMS patients and controls, whereas serum and CSF levels as well as the CSF/serum ratio of neopterin were significantly elevated in the RRMS group. IL-2 was not detectable in CSF of patients or controls and sIL-2R levels were at the level of the lower detection (LD) sensitivity of the ELISA method. Four of 23 RRMS patients versus 1 of 25 controls showed CSF sIL-2R levels above the LD sensitivity, indicating a trend towards elevation in acute relapse. No difference was found in serum and CSF L-TRP and beta 2-M of patients and controls. In CSF of RRMS patients neopterin and L-TRP correlated negatively, reflecting the interferon-gamma mediated activation of macrophages in acute relapse. A significant positive correlation (Spearman rank 0.57, P = 0.001) between serum IL-2 levels and duration of acute relapse (mean 30 days) warrants further evaluation.

Acute Disease↗
PubMed1990

Prostaglandin production in chronic progressive multiple sclerosis.

Peripheral blood monocytes have been implicated in the immune reactions that accompany demyelination in patients with multiple sclerosis (MS). We measured prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) release from peripheral monocytes exposed in vitro to complement. Our studies suggest that there is a significantly higher production of PGE2 in monocytes from patients with chronic progressive MS than in those with exacerbation or remitting MS and healthy controls. No significant differences in TxB2 release were noted between the three groups.

Chromatography, High Pressure Liquid↗
PubMed1991

Antibodies to brain tissue in sera of patients with chronic progressive multiple sclerosis.

Using a blind indirect immunofluorescence assay we examined the sera of 30 multiple sclerosis (MS) patients and 30 age- and sex-matched controls for autoantibodies to brain tissue. Binding was found in 33% of the patients' sera and in only 3% of the controls' sera. Positive and negative patients differed significantly in the course of MS, since eight of the ten positive patients showed a chronic progressive form. None of the patients with a large deficit in a chronic state showed antibodies to brain tissue, while eight of the 11 active chronic progressive cases were positive. Therefore it seems possible that these brain antibodies could be used as an activity parameter, at least for this form of the disease.

Adult↗
PubMed1987

Cyclophosphamide 'pulses' in chronic progressive multiple sclerosis. A preliminary clinical trial.

To our knowledge, this is the first clinical trial in multiple sclerosis (MS) demonstrating the feasibility of directing immunomodulating therapy by monitoring immunologic results. Cyclophosphamide was administered at monthly intervals, escalating the dose until there was a significant reduction in both the number of blood B lymphocytes and helper/inducer (CD4) T cells of 14 patients with chronic progressive MS. The frequency and severity of adverse effects led us to conclude that the regimen is too toxic for the long-term treatment of patients with MS.

Adult↗