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Beta-interferon treatment reduces human herpesvirus-6 viral load in multiple sclerosis relapses but not in remission.

To determine whether the DNA prevalence of human herpesvirus-6 (HHV-6), the viral load and the prevalence of both HHV-6 variants in relapsing-remitting multiple sclerosis (RRMS) patients in exacerbation are altered by beta-interferon (IFN-beta) treatment, in comparison with RRMS patients in remission, we analyzed HHV-6 (A and B) genomes in 189 serum samples by quantitative real-time polymerase chain reaction: 105 of the RRMS patients were receiving IFN-beta treatment (48 in exacerbation) and 84 were untreated (36 in relapse). The results were as follows. (1) Prevalence decrease because of IFN-beta treatment was not significant: 25% of RRMS patients in relapse vs. 15.9% in remission (p = 0.45). (2) Viral load was twice as much in untreated patients in relapse than in treated ones. (3) We only found variant A. Since IFN-beta treatment is able to significantly reduce HHV-6 viral load in RRMS patients in relapse, but not in remission, we suggest a role for HHV-6 in the pathogenesis of multiple sclerosis exacerbations and an antiviral role for IFN-beta treatment in RRMS.

Adult↗

Use of videotape to assess mobility in a controlled randomized crossover trial of physiotherapy in chronic multiple sclerosis.

OBJECTIVES: To determine to what degree assessment of mobility based on comparison of videotape recordings before and after courses of physiotherapy in patients with chronic multiple sclerosis (MS) is reliable, correlates with 'live' assessments and indicates benefit. DESIGN: Prospective data collection within a randomized crossover controlled trial of physiotherapy at home, as an outpatient, or 'no therapy' in 40 patients. SETTING: Hospital outpatients: outpatient and home physiotherapy. OUTCOMES: Mobility change based on a comparison of short video recordings before and after each treatment period was scored independently by two physiotherapists blinded to therapy type and other measures of outcome. Scores were compared with changes in the Rivermead Mobility Index (RMI) and other indices assessed by a physiotherapist in the patient's home. RESULTS: The two video observers agreed substantially on patient outcome. Changes in walking based on video correlated with RMI for home treatment (r = 0.41, p = 0.008) but not for hospital or no treatment periods (r = 0.14 and 0.15): video changes correlated with the 'live' assessor's global change score inconsistently ('no therapy' r = 0.48, p = 0.002, hospital r = 0.30, p = 0.06 and home r = 0.17, p = 0.30 treatment periods). Based on video data alone, improved mobility was evident following home therapy for only one observer but not for the other or the averaged scores of both. CONCLUSION: There was substantial agreement between two observers deciding on change in mobility based on independent blinded evaluation of short video sequences. However the correlations of these with 'live' assessments were variable. Physiotherapy had a less clear benefit on mobility based on video analysis alone compared with 'live' assessments. The study highlights the need for more objective measures of habitual mobility over longer periods.

Adult↗

On the horizon: possible neuroprotective role for glatiramer acetate.

Inflammation and neurodegeneration characterize the pathogenesis of multiple sclerosis (MS). Slow axonal degeneration, rather than acute inflammation, is considered the cause of chronic disability in MS. The signs of acute axonal damage and loss have been shown to occur early in the lesion development of patients with chronic MS and often correlate with demyelination and inflammation. While immune activity in the central nervous system has traditionally been considered to be a detrimental event in MS, recent studies have found that autoimmune T cells may play an important role in protecting neurons from the ongoing spreading damage. Neuroprotection in MS is a new and evolving concept, and many questions remain with regard to potential targets for therapeutic intervention. Preliminary studies, both in animals and in humans, have suggested that glatiramer acetate (GA) may confer neuroprotective activity in addition to bystander suppression. Additional research is needed to determine if these promising neuroprotective effects correlated with the long-term effect of GA in MS.

Adjuvants, Immunologic↗

Prognostic factors in multidisciplinary rehabilitation treatment in multiple sclerosis: an outcome study.

The aim of this outcome study was to evaluate the effectiveness and prognostic factors of inpatient multidisciplinary rehabilitation treatment in patients with multiple sclerosis (MS). We analysed 230 consecutive inpatients with MS admitted to an MS rehabilitation ward who followed an individualized, goal-oriented, multidisciplinary rehabilitation program. Every patient was submitted to a neurological examination and evaluated by means of Kurtzke's Expanded Disability Status Scale (EDSS), with its functional systems (FS), Barthel Index (BI) and the Rivermead Mobility Index (RMI). We observed an effectiveness (percentage of potential improvement achieved during rehabilitation) of nearly 16% on BI and 8% on RMI, corresponding to an improvement in 124 patients (54%) on BI and 113 patients (49%) on RMI. Basal EDSS (beta = -0.32, P <0.001), cognitive status (beta = -0.15, P <0.05) and disease duration (beta = -0.13, P <0.05) were negatively associated with effectiveness of treatment on BI (adjusted R2 = 0.176), whereas effectiveness on RMI was correlated only with the EDSS score (beta = -0.34, P <0.001, adjusted R2 = 0.113). In the logistic regression analysis, the absence of severe sphincteric disturbances was correlated with the probability of improvement on BI that was nearly twice as high (OR =2.25, 95% CI 1.24-4.08) as that of other patients. Moreover, patients without severe cognitive deficits showed a similar probability (OR =2.37, 95% CI 1.05-5.33) of improvement on RMI. The results of this study provide further evidence that intensive multidisciplinary rehabilitation in MS is effective in the majority of MS patients and that early treatment may favour functional recovery.

Activities of Daily Living↗

Expression of ADAMTS-1, -4, -5 and TIMP-3 in normal and multiple sclerosis CNS white matter.

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) -1, -4 and -5 proteases have been identified in the CNS at the mRNA level. These glutamyl endopeptidases, inhibited by tissue inhibitor of metalloproteinases (TIMP)-3, are key enzymes in the degradation of the aggregating chondroitin sulphate proteoglycans (CSPGs), and may therefore play a role in CNS extracellular matrix (ECM) changes in multiple sclerosis (MS). We have investigated ADAMTS and TIMP-3 expression in normal and MS CNS white matter by real-time RT-PCR, western blotting and immunohistochemistry. We report for the first time the presence of ADAMTS-1, -4 and -5 in normal and MS white matter. Levels of ADAMTS-1 and -5 mRNA were decreased in MS compared to normal tissue, with no significant change in ADAMTS-4 mRNA levels. Protein levels of ADAMTS-4 were significantly higher in MS tissue compared to normal tissue. Immunohistochemical studies demonstrated that ADAMTS-4 was associated predominantly with astrocytes with increased expression within MS lesions. TIMP-3 mRNA was significantly decreased in MS compared to controls. These studies suggest a role for ADAMTS-4 in the pathogenesis of MS. Further studies on the activity of ADAMTS-4 will enable a better understanding of its role in the turnover of the ECM of white matter in MS.

ADAM Proteins↗

[A neuropsychological and functional brain imaging study of visuo-imitative apraxia].

We describe the case of a 58-years-old right-handed women suffering from an occipital-parietal lesion. The administration of a cognitively based assessment tool for limb praxis (Batterie d'Evaluation des Praxies, B.E.P., Peigneux and Van der Linden, 1998) demonstrated bilateral visuo-imitative apraxia. Gesture production was mainly characterised by spatial, errors, and imitation of meaningful gestures was worse than their pantomime on verbal command. Moreover, the imitation of meaningless gestures and their reproduction on a manikin were worse than imitation of their matched meaningful gestures. In a cognitive perspective, adapted from the Rothi et al. (1997) and Goldenberg (1995) contributions to our understanding of limb praxis, this configuration of performance suggests deficits occurring at multiple levels. On one hand, it suggests either access difficulties or alteration of the output praxicon, i.e., the lexicon for visuo-kinesthetic engrams of meaningful gestures. On the other hand, the simultaneous deficit for meaningless gesture reproduction on the subject's own body and on a manikin favors an alteration of the structural descriptions of the human body (i.e., human body knowledge), underlying the mental transposition processes occurring between the visual analysis of a meaningless gestural configuration and its effective reproduction on oneself or on a manikin, thus contradicting the classic view of a direct pathway linking visual analysis and motor planning in meaningless gesture imitation. Finally, due to the output praxicon deficit, imitation of meaningful gestures is partly processed in the same way as meaningless gestures (also impaired in this case), leading to an interference effect between both degraded memory-based and visually-transposed traces, which account for imitation of meaningful gestures being worse than their pantomime on verbal command. We also assess regional cerebral metabolism using positron emission tomography (PET). Comparison with 41 healthy subjects (SPM96) demonstrated a statistically significant hypometabolism in the left intraparietal sulcus and superior parietal lobule, and in the right dorsal prestriate cortex. These results, together with a review of the other studies of visuo-imitative apraxia, suggest that the left intraparietal sulcus may be associated with access or integration of information from the output praxicon. The left superior parietal and the right dorsal prestriate deficits functionally impaired a bilateral dorsal network implied in the mental transformations of the body, thus suggesting that these mental transformations are underlined by knowledge of the human body, which may subsequently explain the deficit for the reproduction of meaningless and meaningful configurations.

Aged↗

[Intravascular papillary endothelial hyperplasia: multiple lesions appearing in the course of treatment with interferon beta].

INTRODUCTION: Intravascular papillary endothelial hyperplasia is a benign and rare vascular lesion. We report a case of multiple vascular lesions of the hand following 3 months treatment with beta-interferon injections for multiple sclerosis. OBSERVATION: A 50 year-old man had multiple vascular nodules of the hands. He was treated with beta interferon injections for multiple sclerosis for 3 months. Histology showed typical changes of intravascular papillary endothelial hyperplasia: papillary endothelial proliferation in a dilated cavity associated with thrombosis. DISCUSSION: Intravascular papillary endothelial hyperplasia is a benign and rare vascular lesion usually presenting as a simple nodule. It may be painful. Diagnosis is histologic, characterized by papillary endothelial proliferation associated with a thrombus within a vessel. It may be confused with hemangiosarcoma. Treatment is surgical and recurrence after treatment is rare. Intravascular papillary endothelial hyperplasia is generally considered as an unusual form of thrombus organization. Intravascular papillary endothelial hyperplasia is divided into two groups: a pure form occurring within a dilated vessel and a mixed form appearing in benign vascular lesions. The originality of this case is the rarity and the multiplicity of the lesions. The possible pathogenesis of interferon-induced cutaneous vascular lesions is discussed.

Cell Division↗

Multiple sclerosis and Lyme borreliosis.

In a deductive approach the two disease entities of multiple sclerosis and chronic progressive neuroborreliosis are discussed. Various clinical features, seroepidemiology, neuroimaging, CSF findings, CSF serology, specific proteins within the CSF and antibodies against neuronal structures as well as the most recent findings of different dendritic cells within the CSF are discussed as a means of differentiating these two disease entities.

Antibodies, Bacterial↗

Enkephalins and immune inflammatory reactions.

Methionine-enkephalin (Met-Enk) and leucine-enkephalin (Leu-Enk) belong to family of opioid peptides. In vivo studies on immunomodulating activity of enkephalins performed in the rat revealed the following: (a) both neuropentapeptides showed a dual, dose-dependent effect, i.e., high doses suppressed while low doses potentiated immune responses; (b) Met-Enk is more potent immunomodulator than Leu-Enk; (c) high doses of Met-Enk suppressed immune inflammatory reactions, such as systemic anaphylactic shock, Arthus and delayed hypersensitivity skin reactions to protein antigen, allograft rejection, adjuvant arthritis, and experimental allergic encephalomyelitis. Met-Enk is more efficient when applied intracerebroventricularly. A preliminary clinical trial showed that intrathecally given Met-Enk exerted a beneficial effect on 13 patients with chronic severe progressive multiple sclerosis.

Anaphylaxis↗