Magnetic resonance imaging measures of brain and spinal cord atrophy correlate with clinical impairment in secondary progressive multiple sclerosis.

BACKGROUND: Neuroaxonal loss is a pathological substrate of disability in progressive multiple sclerosis (MS) and can be estimated in vivo by measuring tissue atrophy on magnetic resonance imaging (MRI). While there is some evidence that brain atrophy correlates better with disability than T2 lesion load in secondary progressive MS, the clinical relevance of atrophy within specific regions of the central nervous system requires further evaluation. METHODS: Clinical and MRI examinations were performed in 117 subjects with secondary progressive MS. MRI analysis included measures of normalized brain volume (NBV), normalized grey matter (NGMV) and white matter volume (NWMV), central cerebral volume (CCV), spinal cord cross-sectional area (SCCA), and brain T2 and T1 lesion volume. Clinical assessments included the expanded disability status scale (EDSS) and MS functional composite (MSFC). RESULTS: All MRI measures correlated significantly with the MSFC score, with the strongest correlation being for the NBV (r = 0.47; P < 0.001). NBV and SCCA were the only significant independent predictors of the MSFC score in a stepwise regression model containing all the MRI measures, and SCCA was the only MRI measure to show a significant association with the EDSS. While NGMV had stronger correlations with the clinical variables than NWMV, NBV was more correlated with clinical impairment than either measure. CONCLUSIONS: This data suggests that measures of atrophy, particularly of the whole brain and spinal cord, are relevant and useful disease markers in secondary progressive MS.

Cognitive impairment in relapsing-remitting multiple sclerosis can be predicted by imaging performed several years earlier.

Cognitive deficits in multiple sclerosis (MS) are common and correlate with contemporary MRI brain abnormalities, particularly atrophy, but the ability of imaging early in the disease to predict later cognitive impairment remains to be determined. Thirty relapsing-remitting MS patients recruited within three years of the onset of the disease, and in whom MRI had been performed at baseline and a year later, were assessed neuropsychologically five years later. Imaging parameters accounting for significant variance in cognitive performance were identified using multiple regressions, once confounding variables were controlled. Patients performed significantly worse than expected on tests of attention/speed of information processing and half of them had experienced some decline in IQ in relation to premorbid estimates. The rate of global brain atrophy in the first year of the study accounted for significant variance in the overall cognitive performance, and in memory and attention/speed of information processing. Poor performance on attention tests was associated with high T1-weighted lesion volume and reduced magnetization transfer ratio (MTR) in normal-appearing white matter (NAWM). These results suggest that neuroaxonal loss was identified early in the disease, and its rate of progression, predicted cognitive impairment later in the disease. Neuroaxonal loss is likely to affect commissural and association fibres that subserve the cognitive processes impaired in MS.

Neutralizing anti-interferon beta antibodies are associated with reduced side effects and delayed impact on efficacy of Interferon-beta.

UNLABELLED: Interferon-beta (IFNbeta) is a biological therapy which is immunogenic, inducing anti-IFN-beta neutralizing antibodies (Nabs) in some subjects. The frequency of Nabs varies depending on IFN-beta product and the Nab assay used. OBJECTIVE: Assess frequency of Nabs using novel Luciferase assay, evaluate association with relapses, frequency of side effects and to compare results with published data. METHODS: Serum samples at 12 and 24 months and a follow up sample were tested for binding and Nabs. Titre >20 NU was considered positive. Charts were reviewed retrospectively for clinical data. RESULTS: Out of 327 subjects included, 130 subjects (40%) were binding antibody positive, 89 (27%) were Nab +ve at anytime. Risk at 12 months for being Nab +ve: Avonex 8%, Betaferon 39%, Rebif 33%, P < 10(-5); at 24 months 8, 31 and 27% respectively, P = 0.002. Nab titres were highest in Rebif Nab +ve subjects - 50% >320 NU. Annualized relapse rate was 1.53 pre-treatment, after treatment relapse rate was higher in Nab +ve group 0.67 (95% CI 0.38-0.97) versus 0.5 (0.38-0.61) Nab -ve P = 0.04. Nab status at 12 and 24 months was significantly associated with risk of subsequent relapse, risk being greatest in those with highest titres. Side effects were also significantly associated with Nab -ve status.

The management and outcome of patients with myasthenia gravis treated acutely in a neurological intensive care unit.

The management and clinical course of patients with myasthenia gravis admitted to a neurological intensive therapy unit (ITU) over a 66 month period were reviewed. Twenty-seven patients were admitted in myasthenic crisis, eight of whom had multiple admissions. One patient had a cholinergic crisis and a further patient an acute myocardial infarction. A specific aetiological factor precipitating myasthenic crisis was identified in 19 instances: infection (8), reduction in medication (5), menstruation (4), and steroid administration (2). Thirteen patients with crisis had had a previous thymectomy, six with thymoma. Twenty-three out of 35 (66%) patients admitted in crisis required intubation; nine subsequently needed a tracheostomy. Twenty-nine patients received plasma exchange and seven intravenous immunoglobulin. Four patients in myasthenic crisis died in ITU [adult respiratory distress syndrome (1), disseminated intravascular coagulation and cytomegalovirus (CMV) pneumonitis (1), cardiac failure (1) and multiple organ failure (1)]. Appropriate management of myasthenia gravis requires the easy availability of specialised neuro-intensive care facilities. Copyright Rapid Science Ltd

Thymectomy: its role in the management of myasthenia gravis.

The management and clinical course of patients with myasthenia gravis admitted to a neurological intensive therapy unit (ITU) for thymectomy over a 66 month period were reviewed. There were 53 patients, 20 male and 33 female, mean age 35.2 years (18-74) and median ITU stay of 5 days (2-30). Indications for thymectomy were thymic enlargement on computed tomography (34%), persistence of generalized symptoms (38%), a combination of both (20%), steroid side effects or dependency (4%) and progressive bulbar symptoms (4%). Following thymectomy, thymic histology revealed thymic follicular hyperplasia (26/53; 49%), atrophy (11/53; 21%), thymoma (12/53; 23%) and normal thymus (4/53; 8%). Post-operatively 23% required prolonged intubation (> 48 hrs); two patients required a tracheostomy 10 and 13 days post-operatively. Plasma exchange was required for two patients (3.8%) due to persistent severe myasthenic weakness. Three patients (6%) developed a post-operative chest infection and one pseudomembranous colitis. There were no post-operative mortalities during the study period. After 2 years, 35% of patients were in remission and 46% had ocular or mild generalized symptoms only. Thymectomy for myasthenia gravis is followed by sustained clinical improvement in the majority of patients. The appropriate post-operative management of these patients is best undertaken in a specialized neuro-intensive care setting. Copyright Rapid Science Ltd