Neuromyelitis optica (Devic's syndrome): not always multiple sclerosis

A patient is presented with clinical signs and symptoms of neuromyelitis optica (Devic's syndrome). The clinical findings, the cerebrospinal fluid findings and the Magnetic Resonance Imaging findings in our patient demonstrate that neuromyelitis optica is not always a form of Multiple Sclerosis. It can also be a manifestation of other demyelinating diseases, for example Disseminated Encephalomyelitis.     

Context-dependency of cue-elicited urge to smoke

AIMS: Earlier studies have suggested that the cue-induced urge to smoke depends on the expectation of the availability of smoking. The present study investigated whether a 'room context' change could undo the learned discrimination between two stimuli, respectively, predicting smoking availability or smoking unavailability. DESIGN: A 2 (smoking cue) x 2 (availability context cue) x 6 (trial) x 2 (room context change) within-subjects design was used. Participants were repeatedly presented with a context cue predicting smoking availability (blue serving tray) and a context cue predicting unavailability (yellow serving tray) in one room and tested for an effect of context change in a different room. SETTING: Two distinct rooms located in different department buildings of Maastricht University. PARTICIPANTS: Seventeen daily smokers who had smoked at least five cigarettes a day for at least 2 years. MEASUREMENTS: Self-reported urge to smoke using a visual analogue scale (VAS). FINDINGS AND CONCLUSIONS: Results replicated the finding that a context cue that predicted smoking elicited greater urges to smoke than a context cue that predicted no smoking, irrespective of the presence of smoking cues. In addition, this study showed that this differential effect on the urge to smoke was generalized to a context other than the context in which learning took place. These findings are discussed in relation to the significance of a context change regarding the predictive value of smoking availability.     

Sex differences in proinflammatory cytokine profiles of progressive patients in multiple sclerosis

The objective of this article is to evaluate the presence of sex differences in expression of cytokines in both CD4+ and CD8+ T cells derived from peripheral blood of untreated multiple sclerosis (MS) patients. The predominance of females in MS and other autoimmune diseases may be related to their differential responses in many immunological settings. Recent data show beneficial effect of sex hormones on proinflammatory cytokine levels and on magnetic resonance imaging in MS. Better understanding of gender differences is warranted. In this study 124 MS subjects (M:F; 56:68) and 34 healthy controls (M:F; 12:22) were included. Stimulated peripheral blood-derived CD4+ and CD8+ T cells were analysed for interferon-gamma, interleukin (IL)-2, tumour necrosis factor alpha, IL-4, IL- 10 and IL- 13 production. There were no significant differences for these cytokines between male and female MS subjects in the whole group. Compared to males, female patients had higher proinflammatory cytokine levels in the progressive phase of the disease. In conclusion, the data presented indicate that cytokine production and sex differences in cytokine production might differ between disease phases, probably related to underlying disease mechanisms.     

Expression of adhesion molecules on peripheral lymphocytes predicts future lesion development in MS

The expression of adhesion molecules (alpha4beta1-integrin, LFA-1, ICAM-1) on T cells, measured by flow cytometry, was compared in different subtypes of multiple sclerosis (MS) and related to future lesion development as seen as delta T1 and T2 lesion load per year on magnetic resonance imaging (MRI). LFA-1 and alpha4beta1-integrin showed higher expression on CD4 and CD8 T lymphocytes in the secondary progressive compared to the relapsing-remitting (CD4: p<0.01, p=ns, p<0.05; CD8: p<0.001, p<0.001, p<0.001, respectively) and primary progressive MS phase (CD4: p<0.001, p<0.01, p<0.05; CD8: p<0.01, p<0.01, p<0.001, respectively). The adhesion molecule expression of alpha4- (r=0.31; p<0.05) and beta1-integrin (r=0.38; p<0.01) on CD4+ cells and of LFA-1beta on both CD4+ and CD8+ (r=0.28, p<0.05) and r=0.29; p<0.05, respectively) cells was significantly related to increase in T2 lesion load. Our study provides further evidence for the involvement of integrins in lesion development, shown as T2 lesions on MRI in MS.     

Overdiagnosis of multiple sclerosis and magnetic resonance imaging criteria

Retrospectively, we assessed the specificity of two proposed magnetic resonance imaging (MRI) criteria for multiple sclerosis (MS) in patients suspected to have MS but who ultimately receive another diagnosis. Brain MRIs of 28 patients mixed with 28 MRIs of MS patients from the same cohort of 377 consecutively referred patients were scored by a neuroradiologist masked to the final diagnosis. The criteria for dissemination in space incorporated in the McDonald International Panel showed good specificity (89%). However, the more sensitive criteria proposed by a Subcommittee of the American Academy of Neurology resulted in a lower specificity (29%), indicating an increased risk of a false-positive diagnosis.     

Psychometric evaluation of the multiple sclerosis impact scale (MSIS-29) for proxy use

BACKGROUND: There may be difficulties in the use of self report measurements in patients with cognitive impairment or serious mood disturbances which interfere with reliable self assessment, as may be the case in multiple sclerosis (MS). In such cases proxies may provide valuable information. However, before using any questionnaires in a proxy sample, the questionnaire should be evaluated for proxy use. OBJECTIVE: To evaluate the psychometric properties of the 29 item Multiple Sclerosis Impact Scale (MSIS-29) when used by proxies of MS patients. METHODS: A sample of 62 partners of MS patients completed the MSIS-29. The data were evaluated for the psychometric criteria of the MSIS-29, including data quality, scaling assumptions, acceptability, reliability, validity, and responsiveness. RESULTS: Psychometric evaluation was satisfactory; data quality was high, and scaling assumptions and acceptability were good. Reliability was high (alpha>0.80). Findings were consistent with results of a psychometric evaluation in a patient sample. CONCLUSIONS: The MSIS-29 can be used reliably in proxies of patients with MS. As a next step the relation between data obtained from patients and proxies needs to be studied, focusing on factors that may affect agreement and discrepancies.     

Glutamate inhibition in MS: the neuroprotective properties of riluzole

In addition to demyelination and damage to oligodendrocytes, axonal injury and neuronal cell death are dominating histopathological characteristics of multiple sclerosis (MS). Still little is known about the cause of the damage. Extracellular accumulation of glutamate contributes to excitotoxic injury of neurons and glial cells, suggesting that the maintenance of subtoxic extracellular glutamate levels may be crucial. Riluzole is a neuroprotective agent that inhibits the release of glutamate from nerve terminals and modulates glutamate, i.e., kainate and NMDA receptors. It inhibits excitotoxic injury in several experimental models of neurodegenerative disease. We performed a small run-in versus treatment MR-monitored pilot study in 16 primary progressive MS patients. The results suggest that riluzole reduces the rate of cervical cord atrophy and the development of T1 hypointense lesions on magnetic resonance imaging in primary progressive MS. The rate of brain atrophy was only slightly decreased. The results indicate an effect on mechanisms involving lesion evolution and axonal loss, but no clear effect on new lesion formation. However, the data suffer from several limitations and must be confirmed in future trials.     

Intracortical lesions in multiple sclerosis: improved detection with 3D double inversion-recovery MR imaging

PURPOSE: To prospectively compare the depiction of intracortical lesions by using multislab three-dimensional (3D) double inversion-recovery (DIR), multislab 3D fluid-attenuated inversion-recovery (FLAIR), and T2-weighted spin-echo (SE) magnetic resonance (MR) imaging in patients with multiple sclerosis. MATERIALS AND METHODS: Local ethics review board approval and informed consent were obtained. Conventional T2-weighted SE and multislab 3D FLAIR and DIR images were acquired in 10 patients with multiple sclerosis (five women, five men) and 11 age-matched healthy control subjects (seven women, four men). Mean age was 40 years (range, 25-54 years) in patients and 34 years (range, 24-55 years) in control subjects. Lesions were classified according to seven anatomic regions: intracortical, mixed white matter-gray matter, juxtacortical, deep gray matter, periventricular white matter, deep white matter, and infratentorial lesions. The numbers of lesions per category were compared between techniques (Dunnett-corrected analysis of variance). Gain or loss (with 95% confidence intervals [CIs]) of numbers of lesions detected at 3D DIR imaging was calculated in comparison with those detected at T2-weighted SE and 3D FLAIR imaging. RESULTS: Total number of lesions did not differ between 3D DIR and 3D FLAIR sequences, but the 3D DIR sequence showed a gain of 21% (95% CI: 4%, 41%) in comparison with the T2-weighted SE sequence. Because of high gray matter-white matter contrast, DIR images depicted more intracortical lesions (80 lesions in 10 patients) than both SE (10 lesions) and FLAIR (31 lesions) images; gains with DIR were 538% (95% CI: 191%, 1297%) and 152% (95% CI: 15%, 453%) compared with SE and FLAIR, respectively. Only four intracortical lesions were detected in control subjects. Also, DIR imaging enabled a better definition of mixed white matter-gray matter lesions because of greater contrast between the lesion and its surroundings. CONCLUSION: MR imaging with 3D DIR enables increased intracortical lesion detection in the multiple sclerosis brain, as well as improved distinction between juxtacortical and white matter-gray matter lesions.