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Background: Motor rehabilitation has the target to maintain the residual capacities of the affected individuals to the highest possible level. Consistent data on its efficacy on functional brain reorganization are lacking. Brain adaptation is demonstrated to occur following damage in patients with multiple sclerosis (PwMS), and an efficient motor rehabilitation might interfere with this process. Aims: In this work, we investigated the effects of upper limb motor improvements due to a rehabilitative treatment on possible changes in brain activity patterns in PwMS. Methods: Thirty PwMS were included in this study and received an active (AMT group, 15 patients) or passive motor rehabilitation treatment (PMT group, 15 patients). AMT and PMT groups underwent 20 one-hour treatment sessions, three times a week. The AMT group underwent a rehabilitative treatment based on voluntary task-oriented exercises with the overall goal to improve activities of daily living. Conversely, the PMT group was treated with passive mobilization of the shoulder, elbow, wrist and hand of both limbs. Before and after the treatment, each patient was evaluated by standard evaluation protocols for upper limb motor performance and a sensor-engineered glove to quantify finger motor performance accuracy. In the same sessions, brain activity was investigated by functional magnetic resonance imaging (fMRI) during sequences of finger opposition movements with the right hand following a metronome tone set at 2 Hz; concomitant motor performance was recorded by an MR-compatible engineered glove. Results: Unimanual finger motor performance significantly improved in both groups as an effect of motor rehabilitation. At baseline, during right hand movements both groups activated the left sensorimotor areas, cerebellum bilaterally, and right frontal and parietal areas. After the treatment, fMRI showed a reduction of activation in the left sensorimotor areas and right supplementary motor area (areas not activated in healthy subjects for the same task and thought to be ‘compensatory’) in the AMT but not in the PMT group. In particular, the AMT group showed activations only in the left hemisphere (BA 3, 4, 6, 40), while in the PMT group activations in the right BA 6 and left cerebellum were also found. Conclusions: We can conclude that a greater benefit seems to be induced by the active motor treatment, which was found to reduce brain resource demand, normally altered by the disease course.

Background: Over recent years numerous patients with severe forms of multiple sclerosis (MS) refractory to conventional therapies have been treated with intense immunosuppression followed by autologous haematopoietic stem cell transplantation (AHSCT). The clinical outcome and the toxicity of AHSCT can be diverse, depending on the various types of conditioning protocols and on the disease phase. Objectives: To report the Italian experience on all the consecutive patients with MS treated with AHSCT with an intermediate intensity conditioning regimen, named BEAM/ATG, in the period from 1996 to 2008. Methods: Clinical and magnetic resonance imaging outcomes of 74 patients were collected after a median follow-up period of 48.3 (range = 0.8–126) months. Results: Two patients (2.7%) died from transplant-related causes. After 5 years, 66% of patients remained stable or improved. Among patients with a follow-up longer than 1 year, eight out of 25 subjects with a relapsing–remitting course (31%) had a 6–12 months confirmed Expanded Disability Status Scale improvement > 1 point after AHSCT as compared with one out of 36 (3%) patients with a secondary progressive disease course ( p = 0.009). Among the 18 cases with a follow-up longer than 7 years, eight (44%) remained stable or had a sustained improvement while 10 (56%), after an initial period of stabilization or improvement with median duration of 3.5 years, showed a slow disability progression. Conclusions: This study shows that AHSCT with a BEAM/ATG conditioning regimen has a sustained effect in suppressing disease progression in aggressive MS cases unresponsive to conventional therapies. It can also cause a sustained clinical improvement, especially if treated subjects are still in the relapsing–remitting phase of the disease.

Poster Abstract

RATIONALE AND OBJECTIVES: There have been a large number of case-control studies using diffusion tensor imaging (DTI) in amyotrophic lateral sclerosis (ALS). The objective of this study was to perform an individual patient data (IPD) meta-analysis for the estimation of the diagnostic accuracy measures of DTI in the diagnosis of ALS using corticospinal tract data. MATERIALS AND METHODS: MEDLINE, EMBASE, CINAHL, and Cochrane databases (1966-April 2011) were searched. Studies were included if they used DTI region of interest or tractography techniques to compare mean cerebral corticospinal tract fractional anisotropy values between ALS subjects and healthy controls. Corresponding authors from the identified articles were contacted to collect individual patient data. IPD meta-analysis and meta-regression were performed using Stata. Meta-regression covariate analysis included age, gender, disease duration, and Revised Amyotrophic Lateral Sclerosis Functional Rating Scale scores. RESULTS: Of 30 identified studies, 11 corresponding authors provided IPD and 221 ALS patients and 187 healthy control subjects were available for study. Pooled area under the receiver operating characteristic curve (AUC) was 0.75 (95% CI: 0.66-0.83), pooled sensitivity was 0.68 (95% CI: 0.62-0.75), and pooled specificity was 0.73 (95% CI: 0.66-0.80). Meta-regression showed no significant differences in pooled AUC for each of the covariates. There was moderate to high heterogeneity of pooled AUC estimates. Study quality was generally high. Data from 19 of the 30 eligible studies were not ascertained, raising possibility of selection bias. CONCLUSION: Using corticospinal tract individual patient data, the diagnostic accuracy of DTI appears to lack sufficient discrimination in isolation. Additional research efforts and a multimodal approach that also includes ALS mimics will be required to make neuroimaging a critical component in the workup of ALS.

Relapsing Devic's neuromyelitis optica (DNO) may be clinically undistinguishable from multiple sclerosis (MS), thus the differential diagnosis relies mainly on neuroimaging and cerebrospinal fluid (CSF) findings. We studied CSF samples from 44 patients with DNO submitted to at least one lumbar puncture. Pleocytosis, IgG synthesis and blood brain barrier damage were the most frequent abnormalities, pleocytosis being very suggestive of DNO in patients fulfilling clinical and MRI diagnostic criteria. Pleocytosis > or =50 cells/mm3 is more frequent in the active phases of the disease. Oligoclonal bands (OBs) should be re-considered within the diagnostic criteria of DNO for possible variations in time: at variance with MS they may also disappear. Thus, more than one CSF examination should be done in the presence of suspected DNO, preferably in different disease phases. Although uncommon, OBs do not exclude DNO if optic nerve and spinal cord are the only sites of white matter damage, provided that cerebral MRI is normal at onset and during follow up.