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PubMed1998

Brain and spinal cord abnormalities in multiple sclerosis. Correlation between MRI parameters, clinical subtypes and symptoms.

We investigated various magnetic resonance MRI parameters for both brain and spinal cord to see if any improved the clinicoradiological correlation in multiple sclerosis. Ninety-one multiple sclerosis patients (28 relapsing-remitting, 32 secondary progressive and 31 primary progressive) were imaged using conventional T1, proton density- and T2-weighted MRI of the brain and spinal cord. Focal brain and spinal cord lesion load was scored, as were diffuse signal abnormalities, brain ventricular volume and spinal cord cross-sectional area. Clinical measures included the expanded disability status scale (EDSS), the functional systems score and a dedicated urology complaint questionnaire. Secondary progressive patients differed from relapsing-remitting and primary progressive patients by a larger number of hypointense T1 lesions in the brain, ventricular enlargement and spinal cord atrophy. Primary progressive patients more often had diffuse abnormalities in the brain and/or spinal cord than did relapsing-remitting and secondary progressive patients. In the entire study population, EDSS correlated with both brain and spinal cord MRI parameters, which were independent. The urological complaint score correlated only with spinal cord MRI parameters. In relapsing-remitting and secondary progressive multiple sclerosis, the correlation between MRI and clinical parameters was better than in the entire population. In this subgroup EDSS variance could be explained best by T1 brain lesion load, ventricle volume and spinal cord cross-sectional area. In the primary progressive subgroup the clinicoradiological correlation was weak for brain parameters but was present between spinal cord symptoms and spinal cord MRI parameters. In conclusion, the different brain and spinal cord MRI parameters currently available revealed considerable heterogeneity between clinical subtypes of multiple sclerosis. In relapsing-remitting and secondary progressive multiple sclerosis both brain and spinal cord MRI may provide a tool for monitoring patients, while in primary progressive multiple sclerosis the clinicoradiological correlation is weak for brain imaging.

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↗

PubMed2004

Neuroradiology of multiple sclerosis in children.

Neuroimaging features of multiple sclerosis in children can differ from the usual adult pattern. Frequently, lesions can be more larger and pseudo-tumoral with a variable evolution. The most critical differential diagnosis in childhood is with acute disseminated encephalomyelitis that is a relatively frequent acquired inflammatory disease of the white matter with a polymorphous appearance. Some differences between multiple sclerosis and acute disseminated encephalomyelitis in children such as distribution of white matter lesions and frequency of gray matter involvement should be pointed out. Neveretheless only follow-up examination can make the definitive diagnosis in the majority of the cases.

Brain↗

PubMed2000

CD4(+)CD45RO(+)CD49d(high) cells are involved in the pathogenesis of relapsing-remitting multiple sclerosis.

In the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis, encephalitogenic T cells differ from the non-encephalitogenic ones in their expression of CD49d. The disease-inducing CD49d(high) and not the CD49d(low) cells enter the brain parenchyma. In this context, we characterized CD4(+)(CD45RO(+))CD49d(high) cells in relapsing-remitting multiple sclerosis (RR-MS) patients. These cells, showing characteristics of activated cells able to produce pro-inflammatory cytokines, were found to be increased in peripheral blood during relapses and present in high numbers in cerebrospinal fluid. These results suggest that the CD4(+)CD45RO(+)CD49d(high) subpopulation in RR-MS patients includes autoreactive cells and may be target for immunotherapy.

Acute Disease↗

PubMed2002

Multiple sclerosis and anesthetic implications.

PURPOSE OF REVIEW: Multiple sclerosis remains prevalent among young women in the United States of America. It is a disease of the central nervous system that possesses many anesthetic implications. Anesthesia providers need to understand this disorder and its multiple anesthetic ramifications. RECENT FINDINGS: Recent work has provided more insight into the etiology of multiple sclerosis, its pathogenesis, diagnosis and natural history. A number of new medications have also been added to the therapeutic armamentarium. Optimal anesthetic care entails a thorough preoperative evaluation, medication history and neurologic examination, intraoperative awareness of conditions that may precipitate attacks and lead to potentially life-threatening complications, as well as postoperative attention to respiratory and other risks. Recommendations for management are based on information from small retrospective studies and anecdotal reports. SUMMARY: In summary, our aim is to provide an updated view of multiple sclerosis from the perspective of perioperative care, emphasizing interactions between the disease, surgery and anesthesia.

Journal Article↗

PubMed2000

[Spectrum of neuropsychological changes in multiple sclerosis].

Early disability of patients with multiple sclerosis at the able-bodied age is often caused by both a neurological disorder and the difficulties of their social and psychological adaptation that is aggravated significantly by higher cortical dysfunctions and by behavioral problems. The paper presents the results of the dynamic neuropsychological observation of 124 patients with multiple sclerosis and of their first degree relatives. Even at the early stage of the disease there were some cognitive disorders as worse transitent verbal, semantic, visual memory active attention and slower sensomotor reactions; difficulties in conceptual mentality. The cognitive functions, the activity of the disease, an actual psychological state, depression for example, and the expression of brain atrophy and the localization of the foci are bound by the certain way. The personality traits of patients and their close relatives testified a possible psychosomatic nature of this disease.

Adult↗

PubMedDate not supplied

The Lyapunov exponent of heart rate dynamics as a sensitive marker of central autonomic organization: an exemplary study of early multiple sclerosis.

In a study of central autonomic dynamics in early multiple sclerosis, we measured the temporal oscillations of the momentary heart rate (heart rate dynamics). 11 young patients suffering from relapsing remitting definite multiple sclerosis in relapse-free and early stages of illness and 11 healthy controls were examined under vagotonic and sympathicotonic conditions. The temporal structure of the heart rate dynamics was operationalized phase-space analytically through the estimation of the largest Lyapunov exponent. Positive Lyapunov exponents were found in all participants under all conditions indicating deterministically chaotic heart rate oscillations. The variance analysis of these exponents detected no significant effect of sympathetic or vagal activity (experimental condition) but a significant group difference (p < .02). The multiple sclerosis patients were characterized by significantly lower Lyapunov exponents than the healthy controls. This finding suggests a more stable and thus less adaptive central-autonomic organization in early multiple sclerosis.

Adolescent↗

PubMed2001

Interferon beta1a treatment modulates TH1 expression in gammadelta + T cells from relapsing-remitting multiple sclerosis patients.

A paradigm exists that multiple sclerosis is causally related to dysregulation of TH1 inflammatory cytokines and TH2 antiinflammatory cytokines. The cytokine source(s) that initiate the imbalances are unknown. In this study, gammadelta, CD4, and CD8 T cell receptor-positive (TCR+) cells were isolated from the blood of 26 definitive relapsing-remitting multiple sclerosis patients prior to interferon beta-1a (IFNbeta1a) therapy and following 8-10 weeks of this therapy. The bioactivities of interferon gamma (IFNgamma), interleukin 10 (IL10), and interleukin 12 (IL12) were determined. The concentrations of IFN-gamma, IL10, and IL12 from each cell type did not change significantly with IFNbeta1a treatment. The IL10 secreted by gammadelta TCR+ cells strongly correlated with the IL12 secreted by the same gammadelta TCR+ cells, supporting the paradigm. Furthermore, IFNbeta1a therapy decreased the gammadelta TCR+ cell secretion of TH1 cytokines after 8-10 weeks of therapy.

Adult↗

PubMed2004

MR spectroscopy of cervical spinal cord in patients with multiple sclerosis.

MR spectroscopy (MRS) of the brain in patients with multiple sclerosis has been well studied. However, in vivo MRS of the spinal cord in patients with MR spectroscopy has not been reported to our knowledge. We performed MRS of normal-appearing cervical spinal cords in multiple sclerosis patients and in healthy controls. N-acetyl aspartate was shown to be reduced within the cervical spinal cord of multiple sclerosis patients when compared with healthy controls. This finding supports axonal loss and damage within even normal-appearing spinal cords of multiple sclerosis patients.

Adult↗

PubMed1993

Multiple sclerosis and prions.

The etiology of Multiple Sclerosis (MS) is unknown. Existing epidemiologic data suggests that MS can be an infectious disease. MS used to be classified as one of the 'slow infections'--many of these are caused by prions. Prions are small, proteinaceous, infectious particles--distinguished from viruses by the absence of intrinsic nucleic acids. In a contrast to the 'classic' prional diseases (Kuru, Scrapie or Creutzfeldt-Jacob Disease) that in CNS affect primarily neurons, the 'target' cell in MS is an oligodendrocyte. This may explain differences in disease presentation. This paper presents a pathophysiological model of MS based on the assumption that MS is a prional disease. Processes leading to the demyelination in Multiple Sclerosis seem also to involve lymphocytes, astrocytes and macrophages as well as the interferon system.

Genes, Viral↗

PubMed1987

T lymphocyte-derived demyelinating activity in multiple sclerosis patients in relapse.

Supernatants of cultured T lymphocytes of multiple sclerosis patients were tested for a demyelinating activity in rat cerebellum explant cultures. Supernatants of unstimulated T lymphocytes in seven out of 10 multiple sclerosis patients in relapse produced demyelination when checked by phase contrast microscopy. Supernatants of unstimulated T lymphocytes from healthy subjects did not produce demyelination, but when T cells were stimulated by phytohaemagglutinin (PHA), 50% of tested supernatants produced demyelination, which was, however, never as advanced as in multiple sclerosis supernatant treated cerebellum cultures. The demyelinating activity proved to be heat labile. Gel filtration study revealed two fractions of the demyelinating activity 12.5-29.0 kD and 43.0-66.0 kD. The results suggest that lymphokines can be directly involved in the pathogenesis of demyelination in multiple sclerosis.

Adult↗

PubMed2005

Subjective cognitive complaints relate to mild impairment of cognition in multiple sclerosis.

Cognitive impairment is common in multiple sclerosis (MS), but cannot be reliably predicted by physical impairment. The negative impact of cognitive impairment makes early detection important, but subjective cognitive complaints may be attributed to depression. We examined the relationship between subjectively reported and objectively measured cognitive impairment in MS, adjusting for mood. A neuropsychological battery, the Multiple Sclerosis Functional Composite (MSFC), the Mental Health Inventory (MHI), the Modified Fatigue Impact Scale (MFIS), the Perceived Deficits Questionnaire (PDQ) were administered to 136 patients. Demographically-adjusted cognitive scores were calculated. Subjective impairment was defined as PDQ score >2 standard deviations above that for healthy persons. We modeled the relationship of cognitive scores (independent variables) to being subjectively impaired (dependent variable) using logistic regression. Immediate Memory (IM) and Processing Speed Index (PSI) scores were non-linearly related to subjective impairment Patients were less likely to report subjective impairment if their PSI was normal (OR =0.11; 0.02-0.73) or markedly impaired (OR =0.17; 0.03-0.91), compared to mildly reduced PSI. In young patients decreases in IM were associated with increased subjective impairment (OR = 1.25; 1.07-1.47). Subjectively reported impairment reflects subtle declines in PSI and IM independent of mood, fatigue, and physical impairment Cognitive complaints should not be discounted due to depression.

Adult↗

PubMed1998

Clinical, neurophysiological, and magnetic resonance imaging correlations in multiple sclerosis.

Magnetic resonance imaging (MRI) has a pivotal role in diagnosis of multiple sclerosis and is being increasingly used as a paraclinical measure to assess treatment efficacy in clinical trials. However, the correlations between clinical and MRI findings in patients with multiple sclerosis are weak and, therefore, newer MR techniques are being developed to increase both MRI sensitivity for detecting disease activity and its pathological specificity for better assessing disease evolution. Evoked potentials (EPs) can be used to confirm the diagnosis of multiple sclerosis and their abnormalities are correlated with symptoms and signs referable to involvement of the corresponding nervous pathways. However, their use is limited when assessing disease progression and monitoring clinical trials in multiple sclerosis. Both magnetic resonance imaging (MRI) and evoked potentials (EPs) provide information which cannot be obtained by clinical evaluation, especially for assessing disease activity. Nevertheless, both these paraclinical techniques cannot substitute for clinical measures of disability when assessing disease progression and monitoring phase III clinical trials in multiple sclerosis.

Blood-Brain Barrier↗

PubMed1999

Concepts of viral pathogenesis of multiple sclerosis.

Viral infections have long been suspected to cause or modulate the pathogenesis of multiple sclerosis. Recently, two viruses in particular have been associated with multiple sclerosis: human herpesvirus-6 and a retrovirus termed multiple sclerosis-associated retrovirus, which is a member of the human endogenous retrovirus-9 family. Reports on the detection of human herpesvirus-6-encoded proteins in and around multiple sclerosis lesions are intriguing. Serological and polymerase chain reaction analyses looking for signs of reactivation of human herpesvirus-6 in multiple sclerosis patients are ambiguous, however. If human herpesvirus-6 does play a role as an initiator or amplifier of inflammatory lesions in some multiple sclerosis patients, these individuals might benefit from antiviral therapy.

Herpesviridae Infections↗

PubMed2000

Clinical significance of the multiple sclerosis functional composite: relationship to patient-reported quality of life.

BACKGROUND: The Multiple Sclerosis Functional Composite (MSFC) was recommended by a task force of the National Multiple Sclerosis Society as a new clinical outcome measure for clinical trials. The task force recommended that the MSFC be validated against other measures of the disease, such as patient-reported quality of life. METHODS: Three hundred patients with multiple sclerosis (MS) representing the spectrum of disease severity were included in this cross-sectional study. The MSFC and Kurtzke Expanded Disability Status Scale (EDSS) were used as measures of disease severity. Clinical relevance of the disease severity scores was analyzed using measures included in the Multiple Sclerosis Quality of Life Inventory. The MSFC and EDSS scores were correlated with self-reported employment status, the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), and the Sickness Impact Profile (SIP). RESULTS: The MSFC and EDSS scores were strongly correlated (r = -0.80, P<.001). The MSFC scores were correlated with patient-reported physical functioning (SIP Physical Summary Scale: r = -0.71, P<.001; SF-36 Physical Component Score: r = -0.41, P<.001). The MSFC scores were significantly but more weakly correlated with emotional functioning (SIP Psychosocial Summary Scale: r = -0.34, P<.001). After controlling for EDSS scores, there were significant residual correlations between the MSFC scores and measures of health-related quality of life, suggesting that the MSFC accounts for the variability in health-related quality of life measures not reflected by the EDSS. CONCLUSIONS: The observed strong correlations between MSFC scores and validated measures of self-reported quality of life indicate that the MSFC scores are clinically relevant. This study supports a recommendation by the National Multiple Sclerosis Society Task Force to use the MSFC as a clinical outcome measure.

Adult↗

PubMed1987

Radiopaque markers transit and anorectal manometry in 16 patients with multiple sclerosis and urinary bladder dysfunction.

Fecal incontinence and/or constipation are frequent complaints in multiple sclerosis associated with urinary bladder dysfunction, incontinence, and/or retention. Total and segmental colonic transit were studied by determination of radiopaque markers, and anorectal function by anorectal manometry, in 16 multiple sclerosis patients clinically defined (with urinary bladder dysfunction shown by urodynamic examination). Fifteen multiple sclerosis patients had constipation and 14 had increased colonic transit time; ten multiple sclerosis patients had fecal incontinence and five had spontaneous rectal contractions. It is suggested that increased colonic transit and anorectal dysfunction were secondary to neurologic disorders just as urinary bladder dysfunction is due to neurologic disorders in multiple sclerosis.

Adult↗

PubMedDate not supplied

Antigen-specific therapies in multiple sclerosis: going beyond proteins and peptides.

Multiple sclerosis (MS) is a complex immune-mediated disease resulting largely from an autoimmune attack against components of central nervous system myelin, including several proteins and lipids. Knowledge about the details of this anomalous immune response has come mostly from studies in the animal model experimental autoimmune encephalomyelitis (EAE). In this model, it has been possible to prevent and effectively treat established disease through several antigen-specific therapeutic strategies, which have included administration of whole myelin or myelin proteins by various routes, random copolymers consisting of the main major histocompatability complex (MHC) and T-cell receptor (TCR) contact amino acid residues, altered peptide ligands of dominant myelin epitopes in which one or more residues are selectively substituted, and lately DNA vaccination encoding self-myelin antigens. However, there have been difficulties in making successful transitions from animal models to human clinical trials, due either to lack of efficacy or unforeseen complications. Despite these problems, antigen-specific therapies have retained their attraction for clinicians and scientists alike, and hopefully the upcoming generation of agents--including altered peptide ligands and DNA vaccines--will benefit from the increasing knowledge about this disease and surmount existing difficulties to make an impact in the treatment of multiple sclerosis.

Animals↗

PubMed1993

Cognitive-linguistic assessment of individuals with multiple sclerosis.

Four individuals diagnosed as having multiple sclerosis (MS) and four matched controls were assessed with the Arizona Battery for Communication Disorders (ABCD), a standardized battery of memory and cognitive-linguistic tasks. Subjects with MS and controls performed in an equivalent or nearly equivalent fashion for nine of the ABCD subtests. For five of the subtests (Object Description, Generative Naming, Concept Definition, Generative Writing, and Picture Description), subjects with MS performed substantially lower than the control subjects. Results of this pilot study suggest that portions of the ABCD may be useful in identifying profiles of memory, and cognitive-linguistic impairment among individuals with multiple sclerosis. Further research using a larger sampling of individuals with MS is needed to more fully assess the usefulness of the ABCD with this population.

Adult↗