Objectives:
To identify clinical predictors of effectiveness of a motor rehabilitation treatment in a cohort of multiple sclerosis (MS) patients.
Materials and methods:
We analysed 212 consecutive ...patients who underwent a short-term (3–7 weeks) intensive (two hours per day, five days per week), individualised, goal-oriented inpatient rehabilitation program. Activity limitation and impairment were measured on admission and discharge of the rehabilitation trial using the motor sub-items of the Functional Independence Measure (mFIM) and the Expanded Disability Status Scale (EDSS) score. Multivariate logistic regression models have been tested to evaluate the role of clinical baseline features on rehabilitation effectiveness.
Results:
According to pre-defined outcome measures, 75.1% of MS patients improved in either activity limitation (≥5 points delta mFIM) or impairment (≥1.0 delta EDSS score if baseline EDSS was ≤5.5, or ≥0.5 if baseline EDSS was >5.5), and 35.4% of MS patients improved in both outcomes. A relapsing-remitting course of disease, a more severe baseline impairment and activity limitation level, a shorter disease duration and a less severe balance dysfunction were predictive of the effectiveness of rehabilitation.
Discussion:
These data confirm that an intensive inpatient rehabilitation program is able to produce a short-term relevant improvement on clinical and functional outcome measures and suggest some clinical features which can be considered as potential predictors of the outcome of rehabilitative intervention.
Little is known about the temporal evolution of gray matter damage occurring early in the course of multiple sclerosis (MS). The authors investigated the evolution of gray matter volume loss in 117 ...patients with relapsing-remitting MS, scanned monthly for a 9-month period. Time-trend analysis revealed a decrease of gray matter volumes over the study period (p < 0.001). This study shows that gray matter damage in relapsing-remitting MS evolves markedly over a short period of observation.
The measurement errors associated with two techniques for brain atrophy assessment in multiple sclerosis (MS) were estimated. The measurement error of a semiautomated, nonnormalized technique with ...partial brain coverage was about twofold higher than that of a fully automated, normalized technique with full brain coverage (Structural Image Evaluation of Normalized Atrophy software SIENA). As shown by the analysis of data from a clinical trial of glatiramer acetate, the use of SIENA increases the study power to detect a treatment effect on brain volume changes in MS patients.
Background. Magnetic Resonance (MR) diffusion tensor imaging (DTI) is able to quantify in vivo tissue microstructure properties and to detect disease related pathology of the central nervous system. ...Nevertheless, DTI is limited by low spatial resolution associated with its low signal-to-noise-ratio (SNR). Aim. The aim is to select a DTI sequence for brain clinical studies, optimizing SNR and resolution. Methods and Results. We applied 6 methods for SNR computation in 26 DTI sequences with different parameters using 4 healthy volunteers (HV). We choosed two DTI sequences for their high SNR, they differed by voxel size and b-value. Subsequently, the two selected sequences were acquired from 30 multiple sclerosis (MS) patients with different disability and lesion load and 18 age matched HV. We observed high concordance between mean diffusivity (MD) and fractional anysotropy (FA), nonetheless the DTI sequence with smaller voxel size displayed a better correlation with disease progression, despite a slightly lower SNR. The reliability of corpus callosum (CC) fiber tracking with the chosen DTI sequences was also tested. Conclusion. The sensitivity of DTI-derived indices to MS-related tissue abnormalities indicates that the optimized sequence may be a powerful tool in studies aimed at monitoring the disease course and severity.
Although it is debated whether chronic cerebro-spinal venous insufficiency (CCSVI) plays a role in multiple sclerosis (MS) development, many patients undergo endovascular treatment (ET) of CCSVI. A ...study is ongoing in Italy to evaluate the clinical outcome of ET. Severe adverse events (AEs) occurred in 15/462 subjects at a variable interval after ET: jugular thrombosis in seven patients, tetraventricular hydrocephalus, stroke, paroxysmal atrial fibrillation, status epilepticus, aspiration pneumonia, hypertension with tachicardia, or bleeding of bedsore in the remaining seven cases. One patient died because of myocardial infarction 10 weeks after ET. The risk of severe AEs related to ET for CCSVI must be carefully considered.
This study correlated the extent of abnormalities detected by different magnetic resonance imaging (MRI) techniques proton density (PD)-weighted, T1-weighted, and magnetization transfer imaging (MTI) ...with the overall cognitive, frontal lobe, and memory impairments in patients with MS.
There were 30 clinically definite MS patients, with different disease courses.
psychoactive/steroid treatments, mood disorders, acute relapse phase.
Neuropsychological test results. Total (TLL) and frontal (FLL) lesion loads assessed from PD-weighted, T1-weighted (22 patients), and MTI (22 patients) MRI scans. Average lesion MT ratios (MTR) and analysis of the MTR histograms from brain tissue axial slabs on MTI scans.
Patients with frontal lobe deficits (n=15) or memory impairment (n-17) had a higher TLL on PD scans (p=0.04 and p=0.01, respectively). Patients with frontal lobe deficits had higher FLL on PD scans (p=0.01) and TLL on MTI (p=0.03) scans. No significant relationships between the extent of T1-weighted lesion loads and the presence of any neuropsychological impairment. Mean MTR of both MS lesions and whole brain tissue was lower in patients with frontal lobe impairment (p=0.04). MRI lesion loads correlated significantly with some neuropsychological test scores.
Lesion loads on PD-weighted MRI and MTI-derived measures are associated with cognitive decline in MS patients. Overall macroscopic and microscopic brain damage is more important than the corresponding regional brain disease in determining deficits of selective cognitive domains.
Background: Interferon-beta is used to reduce disease activity in multiple sclerosis, but its action is incompletely understood, individual treatment response varies among patients, and biological ...markers predicting clinical benefits have yet to be identified. Since it is known that multiple sclerosis patients have a deficit of the regulatory T-cell subsets, we investigated whether interferon-beta therapy induced modifications of the two main categories of regulatory T cells (Tregs), natural and IL-10-secreting inducible Tr1 subset, in patients who are biologically responsive to the therapy.
Methods: T-cell phenotype was determined by flow cytometry, while real-time PCR was used to evaluate interferon-beta bioactivity through MxA determination, and to measure the RNA for IL-10 and CD46 molecule in peripheral blood mononuclear cells stimulated with anti-CD46 and anti-CD3 monoclonal antibodies, which are known to expand a Tr1-like population.
Results: Interferon-beta induced a redistribution of natural Treg subsets with a shift of naive Tregs towards the ‘central memory-like’ Treg population that expresses the CCR7 molecule required for the in vivo suppressive activity. Furthermore, in a subgroup of treated patients, the CD46/CD3 co-stimulation, probably through the Tr1-like subset modulation, increased the production of RNA for IL-10 and CD46. The same group showed a lower median EDSS score after two years of therapy.
Conclusions: The selective increase of ‘central memory-like’ subset and the involvement of the Tr1-like population may be two of the mechanisms by which interferon-beta achieves its beneficial effects. The quantification of RNA for IL-10 and CD46 could be used to identify patients with a different response to interferon-beta therapy.
Many guidelines are available for the management of lower urinary tract symptoms (LUTSs) in multiple sclerosis (MS) patients, but no agreement exists on the best approach for subjects without LUTSs. ...The objective of this study was to evaluate whether LUTSs can be detected in MS patients asymptomatic for urinary dysfunction, comparing three different tools measure of post-void residual volume (PRV), bladder diary (BD), a focused questionnaire (IPSS), and whether disability, disease duration and signs of pyramidal involvement are linked to their subclinical presence. 178 MS patients (118 women) have been included (mean age 41.2 years, mean disease duration 11.3 years, mean EDSS 2.2), and tested with the above-mentioned tools. PRV was abnormal in 14 subjects (7.8 %), associated to abnormal findings at IPSS in 3 cases, at BD in 2 cases, at both in 1. BD was abnormal in 37 subjects (20.8 %), with concomitant abnormal PRV in 2, abnormal IPSS in 10 cases, abnormal IPSS and BD in 1. IPSS was ≥ 9 in 43 subjects (24.1 %). At least one test was abnormal in 76 patients (42.7 %): 1 in 57 patients (32.0 %), 2 in 17 (9.5 %), and 3 tests in 2 (1.1 %). Patients with at least one abnormal urinary variable, compared to patients without urinary abnormalities, had a more frequent pyramidal involvement (69.5 vs. 16.8 %,
χ
2
= 48.6,
p
< 0.00001), a more frequent occurrence of EDSS ≥2 (83.1 vs. 23.5 %,
χ
2
= 56.9,
p
< 0.00001), and a longer disease duration (15.7 ± 7.3 vs. 9.1 ± 7.1,
t
= 5.7,
p
< 0.00001). Asymptomatic LUTS were frequent but none of the tests used permitted to better identify asymptomatic patients.
Objective
To investigate the medium-term evolution of grey matter (GM) damage in patients at presentation with clinically isolated syndrome suggestive of multiple sclerosis (MS), and to assess ...whether it is associated with clinical disease activity during the initial stage of MS.
Methods
In 30 patients enrolled within three months from the onset of a clinically isolated syndrome, conventional and diffusion tensor MRI scans of the brain were acquired at baseline and after 3 years. Percentage brain volume change between baseline and follow-up scans was computed. Histograms of mean diffusivity and fractional anisotropy for the normal-appearing white matter and histograms of mean diffusivity for the GM were produced.
Results
Mean percentage brain volume change was –1.04 % (p < 0.001 vs. null change). GM mean diffusivity showed an increase at follow-up (p = 0.004), whose magnitude was greater, but not significantly, in patients who relapsed than in those who did not. There was no correlation between on-study relapse rate and GM mean diffusivity changes over time.
Conclusions
In patients with clinically isolated syndrome suggestive of MS, GM damage begins to accumulate during the initial stage of the disease, possibly as a consequence of GM lesion accumulation. The magnitude of such a damage does not seem to be associated with the concomitant clinical activity.
A series of 68 patients with neurosarcoidosis is reported, with particular emphasis on clinical aspects, diagnosis and treatment. A classification system based on clinical diagnostic probability is ...proposed, consisting of probable and definite disease, the latter being dependent on finding sarcoid granulomas on nervous system histology, which was obtained in 12 patients (18%). The role of investigations, including magnetic resonance imaging (MRI), chest radiography, Kveim skin test, Gallium 67 isotope scanning and cerebrospinal fluid (CSF) studies, is considered. Sixty-two percent of patients presented with nervous system disease, most commonly affecting the optic nerve and chiasm. Other common presentations included cranial nerve palsies, spinal cord and brainstem manifestations. Investigations yielding most diagnostic information included the Kveim test (41/48, 85% positive), raised CSF protein and/or cells (50/62, 81%) and gallium 67 scan (14/31, 45%). Eleven out of 29 patients (38%) patients showed meningeal enhancement on MRI scanning and 43% of scans demonstrated multiple white-matter lesions. Mean follow-up for the group was 4.6 years. Forty-seven patients were seen for >18 months, and over half of these patients progressed despite corticosteroid and other immunosuppressive therapies. The benefit of a large patient database prospectively studied, with extended follow-up is discussed in order to learn more about prognosis and advance therapy in neurosarcoidosis.
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