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PubMed1992

Severe periphlebitis, peripheral retinal ischemia, and preretinal neovascularization in patients with multiple sclerosis.

Two patients with definite multiple sclerosis and marked retinal periphlebitis developed occlusive peripheral retinal vasculitis, which resulted in peripheral retinal ischemia and peripheral retinal neovascularization. Results of investigation for other causes of peripheral proliferative retinopathies were negative in both patients although one patient had a positive anticardiolipin antibody. Both patients have been followed up for over seven years and have maintained good visual acuity with mild regression of the preretinal neovascularization without laser intervention. An analysis of these two cases and six other reported cases indicates that severe periphlebitis can evolve into occlusive peripheral vasculitis, which results in peripheral retinal neovascularization in patients with multiple sclerosis.

Adult↗
PubMed2006

Tumor-like manifestation, uncommon form of multiple sclerosis: report of a patient.

Multiple Sclerosis (MS) is a demyelinating disease of the central nervous system, characterised by focal neurological dysfunction with relapsing and remitting course. Acute widespread or tumor-like manifestation is one of the rare clinical variants and has poor prognosis. Here, the authors report a 36-year-old man who presented with left hemifacial and left hemibody anesthesia for one month. His symptoms gradually progressed MRI brain showed multiple large hypersignal intensity lesions in both right and left frontoparietal lobes, surrounding with brain edema. Brain biopsy showed perivenous infiltration of mature lymphocyte with demyelination. He was dramatically improved with high dose steroid. However, he later developed transverse myelitis syndrome. The second MRI showed new foci in both sides of splenium of corpus callosum and T9-10 spinal cord. The findings were compatible with an unusual form of multiple sclerosis that is rarely seen.

Acute Disease↗
PubMed2001

Late-onset multiple sclerosis.

OBJECTIVE: The onset of multiple sclerosis (MS) after age 50 is infrequent and presents a diagnostic challenge. The purpose of the present study was to review the prevalence, presentation, and clinical characteristics of late-onset MS. DESIGN: A retrospective chart review. SETTING: The Multiple Sclerosis Center at Sheba Medical Center, Israel. PARTICIPANTS: 640 patients with a definite diagnosis of MS. MEASUREMENTS: Diagnosis of MS was established according to Poser criteria and confirmed by brain magnetic resonance imaging (MRI) using our unit's computerized database. Late-onset MS was defined as the first presentation of clinical symptoms after the age of 50 years. For each patient, age, gender, clinical presentation, disease course, neurological involvement, disease duration, neurological disability assessed, and Progression Index (PI) were analyzed. All patients were interviewed using the structured clinical interview for DSM-IV, SCID-lifetime Hebrew version. RESULTS: Of 640 MS patients, 30 (4.6%) were diagnosed as suffering from late-onset MS. Mean age at onset was 53.5 +/- 3.1, range 50 to 62 years. Female to male ratio was 1.73:1. Mean disease duration was 7.6 years, range 2 to 11 years. In 50% of patients the disease course was relapsing-remitting. Motor symptoms were the most common neurological presentation at onset (63.3%). Major depressive episode was diagnosed in 6 out of 30 patients (20%) in the two years prior to the diagnosis of MS. After a mean disease duration of 7.6 years there was a marked increase in sphincteric and cerebellar involvement. In addition 7 out of 30 patients had suffered a major depressive episode within 4 years of diagnosis. Mean PI was 0.81, suggesting rapid neurological deterioration. CONCLUSIONS: Late-onset MS is not rare and may present as major depression and, although neurological presentation at onset is similar to that of young adults, progression to disability is more rapid and a primary progressive course is more prevalent.

Activities of Daily Living↗
PubMed1975

The significance of perivascular infiltrations in multiple sclerosis.

143 autopsy cases of multiple sclerosis (19 acute and 124 chronic cases) were analysed histologically for the extent of active demyelination and the degree of infiltration within and outside the demyelinating lesions and in the leptomeninges. The results were compared with the duration of the illness. Infiltrations were found in 60% of all cases but more often (74%) in those with active demyelination. Inflammatory lesions outside demyelinating foci were observed in 27% of the total, and in 80% of them active demyelination was present. Inflammatory lesions in the meninges were present in 41% of the total and in 80% of these were accompanied by active demyelination. The duration of illness correlated with decreasing severity of active demyelination and of perivascular infiltration. Patients treated with cortico-steroids and/or immunosuppressive substances showed no or only moderate inflammatory lesions. The duration of illness in both these groups was significantly longer than the average of untreated patients. The significance of these pathological findings for the CSF cytology in multiple sclerosis is discussed.

Adrenal Cortex Hormones↗
PubMed2001

Interferon beta-1a in children with multiple sclerosis is well tolerated.

BACKGROUND: Multiple sclerosis is a chronic demyelinating disease rare in children. Currently marketed disease modifying therapies are limited to adults. OBJECTIVE: To determine the tolerability of interferon beta-1a (IFNB-1 a) 30 mcg injected intramuscularly once a week in children with clinically definite relapsing-remitting multiple sclerosis (RRMS). DESIGN/METHODS: A standardized questionnaire was sent to neurologists in the United States to determine the tolerability of IFNB-1 a in patients younger than 16 years. RESULTS: Tolerability data were available for 9 of 33 children who were reported to initiate IFNB-1 a. Mean age on initiating treatment was 12.7 years (range 8 - 15) and mean duration of therapy was 17 months (range 5 - 36). No patient discontinued therapy due to an adverse event. CONCLUSIONS: Preliminary data indicate that weekly intramuscular injections of IFNB-1 a are well tolerated.

Adjuvants, Immunologic↗
PubMed1988

[Prognostic significance of lacunar lesions in magnetic resonance tomography in multiple sclerosis].

175 patients with definite multiple sclerosis underwent nuclear magnetic resonance imaging. T1-weighted images showed in 59 patients (34%) periventricular lesions with a central area of decreased signal intensity. They appear as lacunar defects in the walls of the lateral ventricle system. In accordance with neuropathological findings we suggest that in these plaques a cystic degeneration has replaced gliosis. Patients with cystic defects are characterized by a high activity of the disease (e.d. increased annual production of plaques) and a poor prognosis. Lacunae are found in the early stages of the disease and provide a prognostic sign in multiple sclerosis.

Adult↗
PubMed2006

Cord atrophy separates early primary progressive and relapsing remitting multiple sclerosis.

BACKGROUND AND OBJECTIVE: The onset of multiple sclerosis is relapsing remitting or primary progressive. An improved understanding of the causes of early progressive disability in primary progressive multiple sclerosis (PPMS) could provide mechanistic targets for therapeutic intervention. METHODS: Five magnetic resonance imaging (MRI) parameters that could potentially cause progressive disability were investigated in 43 patients with early PPMS and in 37 patients with early relapsing remitting multiple sclerosis (RRMS): atrophy in brain, both grey matter and white matter; intrinsic abnormality in brain, both grey matter and white matter (measured by the magnetisation transfer ratio (MTR)); and atrophy of the upper cervical spinal cord. Both groups were also compared with controls. RESULTS: Patients with PPMS were older and more likely to be men. Both patient groups had atrophy of brain grey matter and white matter, and intrinsic abnormality in MTR of normal-appearing grey matter and white matter. Cord atrophy was present only in the PPMS (mean cord area: PPMS, 67.8 mm2; RRMS, 72.7 mm2; controls, 73.4 mm2; p = 0.007). This was confirmed by multivariate analysis of all five MRI parameters, age and sex. CONCLUSION: Grey matter and white matter of the brain are abnormal in both early RRMS and PPMS, but cord atrophy is present only in PPMS. This is concordant with myelopathy being the usual clinical presentation of PPMS. Measurement of cord atrophy seems to be clinically relevant in PPMS treatment trials.

Adult↗
PubMed1991

[Etiology of multiple sclerosis].

The risk of developing Multiple Sclerosis is under the combined influence of environmental and endogenous factors, as shown by epidemiological and genetic studies. Immunological abnormalities are a salient feature of the disease but their myelinotoxic effect is still to be demonstrated. The pathogenesis of the disease remains unknown. The auto-immune theory as well as the infectious theory are arguable but they may, also, be both valid. Multiple sclerosis could be a post-infectious auto-immune disease, "final common way" of common childhood infections. Anyway, no infectious agent is demonstrable inside the central nervous system at the overt disease stage.

Humans↗
PubMed1980

Disability and intellectual function in multiple sclerosis patients.

Forty-eight multiple sclerosis patients were rated on the Kurtzke Disability Status Examination and tested on the Wechsler Adult Intelligence Scale. Their disability status scores, ranging from 1 to 9, with a mean of 3.98, correlated significantly only with duration of illness (r = .33, significant at the.05 level). Severity of disability was not significantly correlated with age of patient, age at onset of multiple sclerosis symptoms, Verbal IQ, Performance IQ, or Full Scale IQ. Wechsler Adult Intelligence Scale mean subtest scores ranged from average to bright normal. Scores on Performance subtests with a large motor component were lower than on Verbal subtests measuring verbal overlearned information, abstract reasoning, and vocabulary.

Adolescent↗
PubMed1989

Sudden sensorineural hearing loss as a presentation of multiple sclerosis.

While auditory involvement in multiple sclerosis is not infrequent, sensorineural hearing loss as the initial manifestation of this disease is rare. Auditory brain-stem evoked responses, speech audiometry, acoustic reflexes, and electronystagmography yield significant objective information concerning brain-stem involvement. Magnetic resonance imaging objectively documents white matter demyelinization. The acute onset of the retrocochlear type of auditory dysfunction without other evidence of central nervous system involvement can be an early manifestation of this disease. Two patients with multiple sclerosis had sudden sensorineural hearing loss, with one patient experiencing this as the sole initial complaint.

Acute Disease↗
PubMed2002

Brain metabolite changes in cortical grey and normal-appearing white matter in clinically early relapsing-remitting multiple sclerosis.

While much work has concentrated on focal white matter (WM) lesions in multiple sclerosis, there is growing evidence to suggest that normal-appearing WM (NAWM) and grey matter (GM) are also involved in the disease process. This study investigated multiple sclerosis disease effects on NAWM and cortical GM (CGM) metabolite concentrations, and the relationships between these metabolite concentrations and clinical impairment. Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) data acquired using point resolved spectroscopic (PRESS) localization (echo time 30 ms, repetition time 3000 ms, nominal voxel volume 2.3 ml) from 27 relapsing-remitting multiple sclerosis and 29 normal control (NC) subjects were processed using LCModel to estimate metabolite concentrations in millimoles per litre. (1)H-MRSI voxel tissue contents were estimated using SPM99 tissue and semi-automatic lesion segmentations of three-dimensional fast spoiled gradient recall scans acquired during the same scanning session. NAWM and CGM metabolite concentrations estimated were: choline-containing compounds (Cho); creatine and phosphocreatine (Cr); myo-inositol (Ins); N-acetyl-aspartate plus N-acetyl-aspartyl-glutamate (tNAA); and glutamate plus glutamine (Glx). CGM data came from 24 of the multiple sclerosis (mean age 35.2 years, mean disease duration 1.7 years) and 25 of the NC (mean age 34.9 years) subjects. NAWM data came from 25 of the multiple sclerosis (mean age 35.0 years, mean disease duration 1.7 years) and 28 of the NC (mean age 36.7 years) subjects. Metabolite concentrations were compared between multiple sclerosis and NC subjects using multiple (linear) regression models allowing for age, gender, (1)H-MRSI voxel tissue and CSF contents, and brain parenchymal volume. At a significance level of P < 0.05, CGM Cho, CGM and NAWM tNAA, and CGM Glx were all significantly reduced, and NAWM Ins was significantly elevated. Spearman correlations of multiple sclerosis functional composite scores with tissue metabolite concentrations were significant for the following: CGM Cr (r(s) = 0.524, P = 0.009), CGM Glx (r(s) = 0.580, P = 0.003) and NAWM Ins (r(s) = -0.559, P = 0.004). These results indicate that metabolite changes in NAWM and CGM can be detected early in the clinical course of multiple sclerosis, and that some of these changes relate to clinical status. The correlation of clinical impairment with CGM Cr and Glx but not tNAA suggests that it is more closely associated with neuronal metabolic dysfunction rather than loss in clinically early relapsing-remitting multiple sclerosis. The correlation of clinical impairment with a raised NAWM Ins may indicate that glial proliferation also relates to function at this stage of the disease.

Adult↗
PubMed1984

Effect of high-dose intravenous steroid administration on contrast-enhancing computed tomographic scan lesions in multiple sclerosis.

Six consecutive patients with multiple sclerosis and lesions contrast enhancing on computed tomographic scan were treated with high-dose intravenous infusions of methylprednisolone. Double-dose delayed computed tomographic scans were repeated at varying intervals during corticosteroid treatment. Contrast enhancement of sclerotic plaques was reduced or eliminated within as little as 8 hours after the first infusion. Rapid associated partial clinical improvement was noted in four patients with recent exacerbations of disease activity. Similar attenuation of contrast-enhancing plaques and clinical improvement were less predictable following oral corticosteroid therapy in conventional dosage. These studies suggest that the dose, route of administration, and duration of corticosteroid therapy in multiple sclerosis may partially determine the effect of treatment.

Adult↗
PubMed2003

Role of costimulatory pathways in the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis.

Multiple sclerosis is an immune-mediated disorder of the central nervous system. T lymphocytes are thought to play a central role in the initiation and potentially in the propagation of this disease. Two signals are required for T-cell activation. The first signal consists of the interaction of the T-cell receptor with antigen presented by the MHC molecule on antigen-presenting cells. The second signal requires engagement of costimulatory receptors on T cells with their ligands on antigen-presenting cells. Several costimulatory pathways have been shown to play an important role in T-lymphocyte activation. Here we will review the current literature on the contribution of the B7-1/2-CD28/CTLA-4, inducible costimulatory molecule-B7h, programmed death pathway 1-programmed death pathway ligand 1/ligand 2, CD40-CD154, OX40-OX40 ligand, and CD137-CD137 ligand pathways to the pathogenesis of multiple sclerosis and their potential roles as therapeutic targets.

Animals↗
PubMed1996

Paradoxical puborectalis contraction is a feature of constipation in patients with multiple sclerosis.

OBJECTIVE: To study the disturbed anorectal physiology associated with constipation in multiple sclerosis. METHODS: Anorectal function in 10 patients with clinically definite multiple sclerosis and constipation has been compared with 10 normal persons and 11 patients with idiopathic constipation, without multiple sclerosis. RESULTS: All 10 constipated patients with multiple sclerosis had difficulty evacuating barium paste during defaecography. In four of these there was complete failure of puborectalis relaxation when straining to defaecate, and in another four there was incomplete puborectalis relaxation. There was no evidence of lower motor neuron involvement of pelvic floor muscles in the multiple sclerosis group. CONCLUSIONS: Paradoxical puborectalis contraction is common in patients with multiple sclerosis in whom constipation is a symptom. This may be a feature of the disturbed voluntary sphincter control mechanism, analogous to detrusor sphincter dyssnergia in the bladder.

Adult↗
PubMed2005

Histo-clinical variation in multiple sclerosis: Heterogeneous proteolytic immunogenic processing.

Multiple sclerosis (MS) presents an incredible histo-clinical variation. It consists of an unpredictable series of relapses, remissions and stationary phases. The initial symptoms vary considerably. Any hypothesis of the pathology of MS must include an explanation of this oddity. Current theory suggests that MS is a collection of diseases which produce generally the same result. However, this is not a satisfactory explanation. MS appears as an enormous continuum of disease paths rather than a finite group of well-defined courses. A hypothesis is presented that histo-clinical variation in MS is due to variable proteolytic processing of several potential immunogens. MS is generally thought to be caused by an autoimmune attack on myelin components. Several myelin proteins, myelin basic protein, lipoprotein, oligodendrocyte related glycoprotein and oligodendrocyte basic protein, are encephalitogenic. Within these proteins are short sequences, which themselves are encephalitogenic. In order for potential immunogens to be "seen" by the immune system they first must be processed. This processing is performed by intracellular and extracellular proteases. A large number of different proteases are located throughout the central nervous system. Their concentrations vary with location and time. Most are under strict control. While myelin has a consistent structure, the action of proteases can present variable concentrations of immunogenic peptides. Because of the differences in location, concentration and control of the central nervous system's (CNS) proteases, the same potential immunogen could be presented to the immune system in different locations within the CNS at different times. At a given time and location, the immune system may be presented with no potential immunogens, one potential immunogen or possibly many immunogens. Therefore, because of the dynamic characteristic of presentation, one would expect to see the initial MS symptoms to be variable. This variability would be continued with subsequent symptoms. This is what is seen in multiple sclerosis. A procedure for testing this hypothesis is presented.

Central Nervous System↗
PubMed1999

[Multiple sclerosis and pregnancy: clinical issues].

Multiple sclerosis (MS) is the most common chronic disabling neurological disease affecting young women. Paradoxically, our knowledge of the relationship between pregnancy and MS is limited. However, several conclusions emerge from the literature: 1) The rate of relapse in MS decreases during pregnancy, and it rises significantly during the first three months post partum before coming back to its level prior to pregnancy. 2) Although pregnancy and delivery cause changes of the relapse rate, they have no influence on mid and long term residual disability. 3) Breast-feeding and epidural analgesia do not seem to have any deleterious effect on the disease. 4) Lastly, MS does not seem to influence pregnancy, delivery or the child's health. The studies available to date suffer from methodological limitations. They need to be confirmed by prospective studies. This is the purpose of the study entitled "Pregnancy in multiple sclerosis, PRIMS", which has been carried out since 1992 at the European level.

Breast Feeding↗
PubMed1981

Lymphocyte blast transformation responses and viral antibodies in relation to HLA antigens in multiple sclerosis.

Fifty four clinically stable multiple sclerosis (MS) patients and 54 age- and sex-matched control subjects were HLA-typed, and their responses to herpes simplex, measles, mumps and rubella antigens were examined by the lymphocyte blast transformation test and by serum antibody titrations. Blast transformation response to purified tuberculin (PPD), mitogen phytohaemagglutinin (PHA), pokeweed mitogen (PWN) and concanavalin A (Con A) and spontaneous proliferation of lymphocytes were also studied. MS patients differed from controls by higher antibody levels to measles and rubella viruses and by lower specific blast transformation responses to rubella and measles antigens. When the relative strength of transformation responses was measured, mumps and herpes simplex responses were also lower in MS patients than in controls. In addition, spontaneous lymphocyte proliferation of MS patients in 6-day cultures was lower than that of control lymphocytes. In mitogen stimulations there were no differences between whole groups, but the oldest patients had lower responses to PHA and Con A than their matched controls. The frequency of HLA-Dw2 was 56.6% in MS patients and 32.1% in controls. The patients with and without Dw2 differed from each other only by a lower specific response to PPD in the Dw2-positive group. The immunological response of Dw2-positive controls resembled that of MS patients: low transformation response to viral antigens, low spontaneous proliferation and elevated measles antibodies. This finding supports the function of a genetically determined type of immune responsiveness with low cell-mediated immunity and high levels of certain viral antibodies as one susceptibility factor in multiple sclerosis.

Adult↗
PubMed1994

Triple-dose versus single-dose gadoteridol in multiple sclerosis patients.

Nine patients with multiple sclerosis underwent brain magnetic resonance imaging (MRI) to evaluate the contrast enhancement of individual lesions after a single dose and a triple dose of gadolinium. A single dose (0.1 mmol/kg) of gadoteridol was administered and after a delay, axial T1-weighted images were obtained. After an additional 0.2-mmol/kg dose, the same T1-weighted sequence was repeated. An unblinded reader simultaneously viewed the images from both doses, and utilizing a computer console to rule out flow artifacts, created a gold standard of "definite" enhancing lesions. Using this system, he determined that there was a total of 12 definite enhancing lesions among the patients. This reader also evaluated lesion conspicuity. The contrast-noise ratio was calculated for each lesion. A second reader, blinded to the dose used, then evaluated the number of enhancing lesions at both doses. The unblinded reader noted increased lesions at both doses. The unblinded reader noted increased lesion conspicuity after the triple dose. Contrast-noise ratios were significantly (p < 0.001) higher after the triple dose (mean, 9.19) than after the single dose (mean, 2.97). The blinded reader detected 11 of the 12 definite lesions on MRIs after the triple dose (sensitivity, 92%) but saw only 6 on MRIs after the single dose (sensitivity, 50%). The difference was significant (p < 0.001). Subjective analysis of the films revealed an increase in "ghosting artifacts" at the high dose. Administration of triple-dose gadolinium provides increased lesion conspicuity and an improved lesion detection rate when compared to single-dose gadolinium in patients with multiple sclerosis.

Brain↗