Who may have durable benefit from robotic gait training?: a 2-year follow-up randomized controlled trial in patients with subacute stroke.

BACKGROUND AND PURPOSE: Robotic-assisted walking training after stroke aims to enhance the odd of regaining independent gait. Recent studies have suggested that this approach is more effective than conventional therapy alone only in severely affected patients. We determined whether these results persist at long-term follow-up. METHODS: Forty-eight nonambulant participants after subacute stroke were stratified by motricity index into high (<29) and low (≥29) motor impairment groups. Each arm was randomized to a robotic or control group at a mean of 20 days after stroke. All patients underwent 2 therapy sessions per day, 5 days per week, for 3 months. Robotic group subjects underwent 20 sessions of robotic-assisted gait training in the first 4 weeks of inpatient therapy and abbreviated conventional therapy, whereas control group patients received only conventional gait training. The primary outcome was Functional Ambulation Category, and secondary measures were the Rivermead Mobility Index and Barthel Index scores. The scales were administered before and after the inpatient stay and 2 years after discharge. RESULTS: At follow-up, as at discharge, the low motricity robotic group improved more than the control group counterpart with regard to functional ambulation category (4.7±0.5 versus 3.1±1.5, P=0.002), Barthel Index (76.9±11.5 versus 64.7±14.0, P=0.024), and Rivermead Mobility Index (11.8±3.5 versus 7.0±3.6, P=0.010), whereas conventional and robotic therapies were equally effective in the high motricity groups. CONCLUSIONS: The higher efficacy of the combination of robotic therapy and conventional therapy versus conventional therapy alone that was observed at discharge only in patients with greater motor impairments was sustained after 2 years.

Response to therapy in myasthenia gravis with anti-MuSK antibodies.

Myasthenia gravis (MG) with antibodies against the muscle-specific tyrosine kinase (MuSK abs) is often a severe disease requiring aggressive treatment. Various immunosuppressive (IS) regimens have been employed; the efficacy of plasma exchange is unanimously recognized, while the indication for thymectomy is controversial. We evaluated the response to therapy in 57 MuSK-positive patients (12 M/45 F) comparing our experience with other authors' results. Disease severity and response to treatment were graded according to MG Foundation of America; follow-up ranged from 0.5-29 years. Owing to both MG severity and the unsatisfactory response to cholinesterase inhibitors, most patients (54/57) needed IS treatment, and 35 received one or more courses of plasma exchange and intravenous immunoglobulin. At the end of follow-up, the rate of complete remission was 8.8%, and IS treatment had been withdrawn in only 10/54 patients. The extent of therapeutic response varied considerably. With conventional IS therapy (prednisone alone or in combination with azathioprine or cyclosporine), most patients achieved good control of their disease, but 30% of them were left with permanent facial and bulbar weakness. In patients with refractory disease, the use of mycophenolate mofetil and rituximab proved very effective, as also reported by other authors. In our and others' experience, MuSK-positive MG markedly improves with IS therapy, although, in comparison with the AChR-positive disease, it is characterized by a lower remission rate, as a higher proportion of patients remain dependent on treatment. Thymectomy is mostly considered scarcely effective; however, at present, no firm conclusions can be drawn on its role in the treatment of this form of MG.

Thymopoiesis, regulatory T cells, and TCRVbeta expression in thymoma with and without myasthenia gravis, and modulatory effects of steroid therapy.

We analyzed thymocyte and thymic regulatory T cell (CD4SPCD25+Foxp3+cells, Treg) development in thymoma with and without myasthenia gravis (MG, MG-thymoma, non-MG-thymoma) and in MG-associated non-neoplastic thymus (MG-NNT). An increased number of immature CD4+CD8(-)CD3(-) thymocytes through the CD4+CD8+ to CD4+CD8(-) transition and an abnormal T cell receptor Vbeta (TCRVbeta) development through the CD4+CD8+ to CD4(-)CD8+ transition were seen both in MG-and non-MG-thymomas. Terminal thymopoiesis, i.e., CD45RA+ cells within the CD4+CD8(-)CD3+ and CD8+CD4(-)CD3+ subsets, was skewed towards the CD4+ compartment in MG-thymoma and CD8+ compartment in non-MG-thymoma, but thymic export was increased only in the latter in keeping with the hypothesis that CD8+ lymphocytes may play a role in the initial stages of autosensitization and in disagreement with the relevance of an increased output of CD4+ T lymphocytes in paraneoplastic MG. Treg level in normal thymus and MG-NNT and both MG- and non-MG-thymoma was similar, and TCRVbeta development in Treg cells was slightly altered in thymoma but irrespective of MG presence. Thus, the relevance of a defective Treg development in MG context remains to be established. Most alterations in thymopoiesis were corrected by therapeutic corticosteroid administration, and the effects of steroid administration may be mediated by thymic microenvironment.