Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “SCLEROSIS”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,225 records · Page 68Linked to original sources
PubMed1999

Decreases in T-cell tumor necrosis factor alpha binding with interferon beta treatment in patients with multiple sclerosis.

OBJECTIVE: To investigate the effects of interferon beta treatment on T-cell tumor necrosis factor alpha (TNF-alpha) binding (which is a possible marker for T-cell-dependent immune function) in patients with multiple sclerosis. DESIGN: The TNF-alpha binding on T lymphocytes from patients with stable relapsing-remitting multiple sclerosis was assayed before and 3 and 6 months after the start of treatment with interferon beta. SETTING: The study was performed on ambulatory patients in a tertiary care center. PATIENTS: Eighteen patients with clinically definite stable relapsing-remitting multiple sclerosis (13 women and 5 men; mean [+/-SD] age, 32.6+/-7.1 years) were selected consecutively. Clinical status was defined according to the Expanded Disability Status Scale. All patients were treated with 8 x 10(6) U of interferon beta-1b subcutaneously every other day. Eighteen age- and sex-matched healthy subjects, with no family history of neuropsychiatric disorders, served as controls. RESULTS: T lymphocytes from untreated patients with multiple sclerosis had significantly more TNF-alpha receptors than those from controls (mean+/-SE, 837+/-33 vs 135+/-5 receptors per cell). After 3 months of treatment with interferon beta-1b, they showed a significant decrease (P<.001) in TNF-alpha binding (452+/-29 receptors per cell). After 6 months, T-cell TNF-alpha maximal receptor numbers were even lower (345+/-35 receptors per cell). CONCLUSION: Given that increased TNF-alpha binding might be linked to lymphocyte activation, our data demonstrate that a major effect of interferon beta-lb treatment is to decrease T-cell activation.

Adjuvants, Immunologic↗
PubMed1999

Development of hypointense lesions on T1-weighted spin-echo magnetic resonance images in multiple sclerosis: relation to inflammatory activity.

OBJECTIVE: To evaluate whether degree of inflammatory activity in multiple sclerosis, expressed by frequency of gadolinium enhancement, has prognostic value for development of hypointense lesions on T1-weighted spin-echo magnetic resonance images, a putative marker of tissue destruction. DESIGN: Cohort design with long-term follow-up. Thirty-eight patients with multiple sclerosis who in the past had been monitored with monthly gadolinium-enhanced magnetic resonance imaging for a median period of 10 months (range, 6-12 months) were reexamined after a median period of 40.5 months (range, 33-80 months). SETTING: Magnetic Resonance Center for Multiple Sclerosis Research, Amsterdam, the Netherlands, referral center. MAIN OUTCOME MEASURES: The new enhancing lesion rate (median number of gadolinium-enhancing lesions per monthly scan) during initial monthly follow-up; hypointense T1 and hyperintense T2 lesion load at first and last visit. RESULTS: The number of enhancing lesions on entry scan correlated with the new enhancing lesions rate (r = 0.64; P<.001, Spearman rank correlation coefficient). The new enhancing lesion rate correlated with yearly increase in T1 (r = 0.42; P<.01, Spearman rank correlation coefficient) and T2 (r = 0.47; P<.01, Spearman rank correlation coefficient) lesion load. Initial T1 lesion load correlated more strongly with yearly increase in T1 lesion load (r = 0.68; P<.01, Spearman rank correlation coefficient). CONCLUSIONS: Degree of inflammatory activity only partially predicted increase in T1 (and T2) lesion load at long-term follow-up. Initial T1 lesion load strongly contributed to subsequent increase in hypointense T1 lesion load, suggesting that there is a subpopulation of patients with multiple sclerosis who are prone to develop destructive lesions.

Adult↗
PubMed1999

Syringomyelia and complex regional pain syndrome as complications of multiple sclerosis.

OBJECTIVE: To describe a patient from Southeast Asia with the optic-spinal phenotype of multiple sclerosis who developed syringomyelia and resultant complex regional pain syndrome (formerly named reflex sympathetic dystrophy). DESIGN: Case report. SETTING: Department of neurology at a tertiary care hospital in the Republic of Singapore. PATIENT: A 53-year-old Chinese woman with a history of optic neuritis developed an episode of left hemiparesis leading to a diagnosis of multiple sclerosis. Serial neuroimaging studies revealed an active demyelinating plaque in the cervical area that later progressed into a syrinx. Over a period of 1 year she also developed signs of sympathetic dysfunction including Horner syndrome of the left eye and complex regional pain syndrome in the left hand. CONCLUSIONS: A case of the optic-spinal phenotype of multiple sclerosis that is commonly observed in Southeast Asia is described. This characteristically tissue-destructive form of multiple sclerosis resulted in syringomyelia complicated by a complex regional pain syndrome. Possible pathogenic mechanisms for these associations are discussed.

Cervical Vertebrae↗
PubMed1999

Multiple sclerosis that is progressive from the time of onset: clinical characteristics and progression of disability.

OBJECTIVE: To use the new consensus definitions of primary progressive multiple sclerosis (PPMS) and progressive relapsing multiple sclerosis (PRMS) to report the demographic, clinical, and natural history characteristics of multiple sclerosis (MS) that is progressive from the time of onset. DESIGN: Retrospective study by database/chart review and telephone interview. SETTING: Multiple sclerosis clinic at a university teaching hospital. PATIENTS: Eighty-three patients (prevalence, 6.9%) with PPMS and 12 patients (prevalence, 1.0%) with PRMS were studied. RESULTS: Fifty-nine percent of the patients with PPMS (n=49) and 67% of the patients with PRMS (n=8) were women. Mean +/- SD ages at the time of onset were 41.2 +/- 10.5 and 38.0 +/- 7.3 years, respectively; mean disease duration was 14.2 +/- 8.8 and 12.2 +/- 6.5 years, respectively. The initial symptoms involved leg weakness in 94% of the patients with PPMS (n = 78) and 100% of the patients with PRMS (n= 12). For the PPMS cohort, a syndrome consistent with isolated myelopathy was found in 36% of patients (n = 30) and arm weakness without leg weakness did not occur. Mean +/- SEM time of progression to a score of 6.0 on the Expanded Disability Status Scale was 10.2 +/- 1.0 years for patients with PPMS and 10.9 +/- 2.6 years for patients with PRMS. CONCLUSIONS: The clinical characteristics and disability progression of these MS subtypes were indistinguishable, with the exception of 1 or 2 relapses in patients with PRMS that occurred 8 months to 9 years after the onset of symptoms. We see little reason to consider PPMS and PRMS separate clinical entities; however, whether they can be better distinguished by radiological, histopathological, or immunological markers of disease activity remains unknown.

Adult↗
PubMed2001

Regional magnetic resonance imaging lesion burden and cognitive function in multiple sclerosis: a longitudinal study.

OBJECTIVE: To investigate the relationship between magnetic resonance imaging regional lesion burden and cognitive performance in multiple sclerosis (MS) over a 4-year follow-up period. DESIGN: Twenty-eight patients with MS underwent magnetic resonance imaging and took the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis at baseline, 1-year, and 4-year follow-up. An automated 3-dimensional lesion detection method was used to identify MS lesions within anatomical regions on proton density T2-weighted images. The relationship between magnetic resonance imaging regional lesion volumes and the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis results was examined using regression analyses. RESULTS: At all time points, frontal lesion volume represented the greatest proportion of total lesion volume, and the percentage of white matter classified as lesion was also highest in frontal and parietal regions. On neuropsychological testing, when compared with age- and educational level-matched control subjects, patients with MS showed significant impairment on tests of sustained attention, processing speed, and verbal memory (P<.001). Performance on these measures was negatively correlated with MS lesion volume in frontal and parietal regions at baseline, 1-year, and 4-year follow-up (R = -0.55 to -0.73, P<.001). CONCLUSIONS: Multiple sclerosis lesions show a propensity for frontal and parietal white matter. Lesion burden in these areas was strongly associated with performance on tasks requiring sustained complex attention and working verbal memory. This relationship was consistent over a 4-year period, suggesting that disruption of frontoparietal subcortical networks may underlie the pattern of neuropsychological impairment seen in many patients with MS.

Adult↗
PubMed2004

Infratentorial lesions predict long-term disability in patients with initial findings suggestive of multiple sclerosis.

BACKGROUND: The number and volume of abnormalities on baseline brain magnetic resonance images in patients with initial findings suggestive of multiple sclerosis are known to predict outcome in terms of disability. However, no long-term data exist on specific locations or types of lesions. OBJECTIVE: To assess the long-term predictive value of baseline magnetic resonance imaging parameters, including location of lesions and gadolinium-enhancing and hypointense lesions in patients with initial findings suggestive of multiple sclerosis for the occurrence of clinically relevant disability as defined by an Expanded Disability Status Scale score of 3. PATIENTS: After a median follow-up period of 8.7 years, the medical records of 42 patients were reviewed and assessed for time until patients received an Expanded Disability Status Scale score of 3. Magnetic resonance imaging parameters were dichotomized according to maximum accuracy and then used to calculate hazard ratios using the Cox model for proportional hazard ratios. RESULTS: Conversion to clinically definite multiple sclerosis was observed in 26 patients (62%), of whom 14 (54%) progressed to an Expanded Disability Status Scale score of 3. Two or more infratentorial lesions best predicted long-term disability (hazard ratio, 6.3). Gadolinium-enhancing and hypointense T1-weighted lesions did not show prognostic value. CONCLUSION: Infratentorial lesions are related to long-term prognosis for patients with initial findings suggestive of multiple sclerosis and thus may help to identify patients at high risk for earlier occurrence of clinically relevant disability.

Adolescent↗
PubMed2005

Kinin B1 receptor expression on multiple sclerosis mononuclear cells: correlation with magnetic resonance imaging T2-weighted lesion volume and clinical disability.

BACKGROUND: We have previously shown that the inducible kinin B(1) receptor is expressed on T lymphocytes during relapses and progression in multiple sclerosis. OBJECTIVE: To evaluate the correlation between the expression of B1 receptor on peripheral blood mononuclear cells derived from patients who have multiple sclerosis with serial, clinical magnetic resonance imaging and immunological study-derived measures. DESIGN: Using frozen samples obtained from a high-frequency magnetic resonance imaging-immunological study, we analyzed B1 receptor messenger RNA (mRNA) expression in peripheral blood-derived mononuclear cells serially collected from 6 patients with multiple sclerosis and 8 healthy control subjects by semiquantitative radioactive duplex reverse transcriptase-polymerase chain reaction amplification. Time-course kinin B1-actin mRNA ratios were subsequently compared with corresponding clinical magnetic resonance imaging and immune parameters. RESULTS: The time-course kinin B1-actin mRNA ratio correlated positively with the Expanded Disability Status Scale index (P<.001), occurrence of clinical relapse (P = .02), volume of lesion on T2-weighted images (P<.003) and interleukin 2 receptor and major histocompatibility complex class II expression on CD4+ lymphocytes, but not with gadolinium-enhancing lesions. The time-course kinin B1-actin mRNA ratios were 5 to 25 times lower in samples derived from healthy controls. CONCLUSION: The correlation of kinin B1 receptor mRNA levels with dynamic clinical and magnetic resonance imaging measures suggests that expression of this receptor can serve as an index of disease activity in multiple sclerosis.

Adult↗
PubMed2006

High-dose cyclophosphamide for moderate to severe refractory multiple sclerosis.

BACKGROUND: High-dose cyclophosphamide is active in immune-mediated illnesses. OBJECTIVE: To describe the effects of high-dose cyclophosphamide on severe refractory multiple sclerosis. DESIGN, SETTING, AND PATIENTS: Patients with multiple sclerosis with an Expanded Disability Status Scale (EDSS) score of 3.5 or higher after 2 or more Food and Drug Administration-approved disease-modifying therapy regimens were evaluated. INTERVENTIONS: Patients received 200 mg/kg of cyclophosphamide over 4 days. MAIN OUTCOME MEASURES: Patients had brain magnetic resonance imaging and neuro-ophthalmologic evaluations every 6 months and quarterly EDSS and quality-of-life evaluations for 2 years. RESULTS: Twelve patients were evaluated for clinical response (median follow-up, 15.0 months; follow-up range, 6-24 months). During follow-up, no patients increased their baseline EDSS scores by more than 1.0. Five patients decreased their EDSS scores by 1.0 or more (EDSS score decrease range, 1.0-5.0). Two of 11 patients had a single enhancing lesion at baseline; these lesions resolved after high-dose cyclophosphamide treatment. At 12 months, 1 patient showed 1 new enhancing lesion without a corresponding high-intensity T2-weighted or fluid-attenuated inversion recovery signal. Patients reported improvement in all of the quality-of-life parameters measured. Neurologic improvement involved changes in gait, bladder control, and visual function. Treatment response was seen regardless of the baseline presence or absence of contrast lesion activity. Patient quality-of-life improvement occurred independently of EDSS score changes. In this small group of patients with treatment-refractory multiple sclerosis, high-dose cyclophosphamide was associated with minimal morbidity and improved clinical outcomes. CONCLUSIONS: High-dose cyclophosphamide treatment in patients with severe refractory multiple sclerosis can result in disease stabilization, improved functionality, and improved quality of life. Further studies are necessary to determine the most appropriate patients for this treatment.

Adult↗
PubMed2006

Correlation of global N-acetyl aspartate with cognitive impairment in multiple sclerosis.

BACKGROUND: Whole-brain N-acetyl aspartate (NAA), a measure of neuronal function, can be assessed by multislice echo-planar spectroscopic imaging. OBJECTIVE: To test the hypothesis that the global brain NAA/creatine (Cr) ratio is a better predictor of cognitive dysfunction in multiple sclerosis than conventional magnetic resonance imaging measures. DESIGN: Survey. SETTING: Research-oriented hospitals. PATIENTS: Twenty patients, 16 women and 4 men (mean age, 36 years), with early relapsing-remitting multiple sclerosis (mean Expanded Disability Status Scale score, 2.5). MAIN OUTCOME MEASURES: Correlation between the global NAA/Cr ratio and a cognitive dysfunction factor comprising 16 measures from an extensive neuropsychological test battery that best distinguished patients with multiple sclerosis from healthy control subjects. RESULTS: A significant partial correlation between the global NAA/Cr ratio and the cognitive dysfunction factor was found (partial r = 0.62, P = .01), and 9 cognitively impaired patients had significantly lower global NAA/Cr ratios than 11 unimpaired patients (P = .04). No significant correlations were found between the cognitive dysfunction factor and conventional magnetic resonance imaging measures (ie, brain parenchymal fraction and lesion volume). CONCLUSIONS: Multislice echo-planar spectroscopic imaging provides global metabolic measures that distinguish between cognitively impaired and unimpaired patients with multiple sclerosis and correlate with a global cognitive measure. Standardization of the technique is needed, and larger-scale studies that include healthy controls are suggested.

Adult↗
PubMed2000

Hamartomas of the iris and ciliary epithelium in tuberous sclerosis complex.

Astrocytic hamartomas of the retina are the principal ocular manifestation of tuberous sclerosis complex. Iris abnormalities are rare in tuberous sclerosis complex and include focal areas of stromal depigmentation and atypical colobomata. We describe 2 patients who were found on histopathological examination to have lesions consistent with hamartomas of the iris pigment epithelium and ciliary body epithelium. Iris abnormalities, including pupillary irregularities, were noted on clinical examination prior to the development of iris neovascularization in both patients. These observations suggest that iris abnormalities, including atypical colobomas, may be caused by hamartomas of the iris pigment epithelium and ciliary epithelium in some patients with tuberous sclerosis complex. To our knowledge, hamartomas of tissues derived from the anterior part of the neuroectodermal optic cup have not been reported in cases of tuberous sclerosis complex.

Child, Preschool↗
PubMed1991

Hemifacial spasm. Occurrence in multiple sclerosis.

We present six patients with hemifacial spasm and multiple sclerosis. To our knowledge, this association has not been described previously in the North American literature. Magnetic resonance imaging was obtained in all the patients and plaques consistent with multiple sclerosis were identified. In two patients the plaques were seen in the area of the facial nucleus on the involved side. We suggest that hemifacial spasm can be a manifestation of multiple sclerosis. These cases illustrate the utility of magnetic resonance imaging in the investigation of hemifacial spasm. Our findings also support a central (nuclear) origin in multiple sclerosis associated with hemifacial spasm.

Adrenocorticotropic Hormone↗
PubMed2000

Amyotrophic lateral sclerosis: early contributions of Jean-Martin Charcot.

Amyotrophic lateral sclerosis is historically an important entity because its manifestations involve distinct signs that can be correlated with gray and white matter lesions at specific sites within the central nervous system. Working at the end of the nineteenth century, the celebrated neurologist, Jean-Martin Charcot, used this disorder as a prototypic example of the power of his research method, termed "méthode anatomoclinique." Using clinical cases and autopsy material, he showed how anatomical lesions in the nervous system could be accurately determined by the presence of carefully analyzed clinical signs. Charcot's work on amyotrophic lateral sclerosis brought together neurological entities formerly considered as disparate disorders, primary amyotrophy and primary lateral sclerosis. In addition, these studies contributed to the understanding of spinal cord and brain stem anatomy and the organization of the normal nervous system. Because of Charcot's fundamental contributions, the eponym "Charcot's disease" has been used internationally in association with amyotrophic lateral sclerosis.

Amyotrophic Lateral Sclerosis↗
PubMed1981

A goodness-of-fit test for the polygenic threshold model: application to multiple sclerosis.

Recently it has been suggested that multiple sclerosis may be a multifactorial disorder. We found in British Columbia 364 families (sibship size greater than or equal to 2) in which at least on sibling was diagnosed as having "clinically definite" multiple sclerosis. The data were tested for goodness-of-fit to the multifactorial model using an analysis that considers various parameters including ascertainment probability heritability, and sex-dependent prevalence rates. The results suggest that multiple sclerosis does not fit the multifactorial model. As an alternative genetic model we propose that a major gene could be responsible for at least a portion of the cases of multiple sclerosis.

Alleles↗
PubMed2002

Age-related disability in multiple sclerosis.

There is evidence that the clinical course of multiple sclerosis is age related. The present study evaluated the relationship between age and rate of disability progression in a large hospital-based cohort of definite cases of multiple sclerosis (n= 1,463). Patients were followed every 6 to 12 months for a total period of observation of 11,387.8 person-years. Expanded Disability Status Scale scores increased significantly with increasing current age and longer duration of disease (p=0.007). Median times to reach Expanded Disability Status Scale scores of 4.0 and 6.0, assessed using an extended Kaplan-Meier method with age as a categorical time-varying covariate, were significantly longer among patients aged 20 to 35 years compared with patients aged 36 to 50 and 51 to 65 years (p < 0.0001). Significant associations were observed between mean Expanded Disability Status Scale scores and age at disease onset, current age, and the interaction of age at disease onset and current age (p < 0.001). Current age had a greater effect (59% of variability in the model) on disease severity than did age at disease onset. Furthermore, a multiplicative effect on Expanded Disability Status Scale score was observed for age at disease onset and current age combined, indicating a faster rate of disease progression in older patients. In conclusion, the results of the current study demonstrate the impact of age on rate of disability progression in multiple sclerosis and suggest that an age-adjusted progression index may be a more relevant criterion for defining differences between multiple sclerosis groups.

Adult↗
PubMed2002

Thalamic neurodegeneration in multiple sclerosis.

Multiple sclerosis is still regarded primarily as a disease of the white matter. However, recent evidence suggests that there may be significant involvement of gray matter. Here, we have used magnetic resonance imaging and magnetic resonance spectroscopy in vivo and histopathology postmortem to estimate thalamic neuronal loss in patients with multiple sclerosis. Our results show that neuronal loss in multiple sclerosis can be substantial (30-35% reduction). We conclude that a neurodegenerative pathology may make a major contribution to the genesis of symptoms in multiple sclerosis.

Adult↗
PubMed2001

Immunopathology of secondary-progressive multiple sclerosis.

Twenty-three plaques obtained at early autopsy from 2 patients with secondary-progressive multiple sclerosis were examined immunohistochemically for microglia/macrophages, and for immunoglobulins and components of activated complement. Most of the lesions examined in both cases exhibited evidence of low-grade active demyelination of an unusual type (frustrated phagocytosis) in periplaque white matter. This included linear groups of microglia engaging short segments of disrupted myelin that were associated with deposits of C3d, an opsonin formed during complement activation. Similar microglia/C3d/myelin profiles were not observed in newly forming lesions in cases of acute multiple sclerosis or other central white matter diseases. As C3d coupling is known to increase the immunogenicity of potential antigens enormously, present findings point to disrupted myelin close to plaques as a possible source of the putative multiple sclerosis antigen. Ongoing myelin destruction found in a high proportion of old, established plaques was surprising. It suggests that slowly expanding lesions (progressive plaques), in which ongoing myelin breakdown occurs in the absence of florid perivascular cell cuffing or other histological signs of acute inflammation, contribute to disease progression in cases of secondary-progressive multiple sclerosis.

Adult↗
PubMed1978

Familial multiple sclerosis: clinical, histocompatibility, and viral serological studies.

Evaluation of presumed "multiple sclerosis families" and comparison with recently reported families has led us to the following observations: (1) Seven of our original fourteen presumptive multiple sclerosis families had to be eliminated after personal clinical evaluation of family members failed to confirm the diagnosis in a second close relative. (2) No segregation of HLA type was noted between affected and unaffected individuals in our seven bona fide multiple sclerosis families, and no consistent segregation was noted in the twenty-eight families reported elsewhere. This supports other genetic evidence that there is not a single, major gene mapping in the HLA complex which predisposes to multiple sclerosis. (3) The DW2 antigen was increased in frequency among affected members of our families, and the A3 B7 haplotype was more frequent among affected members of other families reported. But unaffected members also tended to have an increased frequency of these same antigens. (4) No relationship was noted between HLA type and antimeasles antibody titer within our families.

Antibodies, Viral↗
PubMed1983

Suppressor T-lymphocytes in multiple sclerosis: analysis of patients with acute relapsing and chronic progressive disease.

T cell-specific antigens as identified by the anti-Leu 1, anti-Leu 2a, and anti-Leu 3a monoclonal antibodies were quantitated in 31 normal control subjects, 21 adults with spinal cord injury, 58 patients with stable multiple sclerosis, 31 patients with chronic progressive multiple sclerosis, and 15 patients with multiple sclerosis in acute relapse. The only significant deviations from normal values were a slightly low mean T cell (Leu 1-positive) value in patients in acute relapse and a low suppressor T cell (Leu 2a-positive) mean value in patients with chronic progressive multiple sclerosis. We were unable to confirm previous studies using the OK series of monoclonal antibodies that reported low suppressor T cell levels (OKT5 and OKT8 positive) in patients with acute relapses. We suggest that modulation (a spontaneous or induced variability in the expression) of individual cell surface antigens may explain the differences seen between our study and other reported series.

Adult↗