A number of studies have shown that modulating cortical activity by means of transcranial direct current stimulation (tDCS) affects performances of both healthy and brain-damaged subjects. In this study, we investigated the potential of tDCS to enhance associative verbal learning in 10 healthy individuals and to improve word retrieval deficits in three patients with stroke-induced aphasia. In healthy individuals, tDCS (20 min, 1 mA) was applied over Wernicke's area (position CP5 of the International 10-20 EEG System) while they learned 20 new "words" (legal nonwords arbitrarily assigned to 20 different pictures). The healthy subjects participated in a randomized counterbalanced double-blind procedure in which they were subjected to one session of anodic tDCS over left Wernicke's area, one sham session over this location and one session of anodic tDCS stimulating the right occipito-parietal area. Each experimental session was performed during a different week (over three consecutive weeks) with 6 days of intersession interval. Over 2 weeks, three aphasic subjects participated in a randomized double-blind experiment involving intensive language training for their anomic difficulties in two tDCS conditions. Each subject participated in five consecutive daily sessions of anodic tDCS (20 min, 1 mA) and sham stimulation over Wernicke's area while they performed a picture-naming task. By the end of each week, anodic tDCS had significantly improved their accuracy on the picture-naming task. Both normal subjects and aphasic patients also had shorter naming latencies during anodic tDCS than during sham condition. At two follow-ups (1 and 3 weeks after the end of treatment), performed only in two aphasic subjects, response accuracy and reaction times were still significantly better in the anodic than in the sham condition, suggesting a long-term effect on recovery of their anomic disturbances.
Performance on tests of odour discrimination, naming, and matching was compared in patients with four distinct forms of neurodegenerative disease: Alzheimer's disease (AD), semantic dementia (SD), frontotemporal dementia (FTD), and corticobasal degeneration (CBD). The SD patients were found to have a severe impairment of identification from olfaction despite having normal discrimination, consistent with the multimodal semantic impairment characteristic of this patient group. The AD patients' poor odour discrimination suggests that a perceptual impairment is the root of their poor odour identification. Mild impairments in odour identification observed in FTD and CBD are consistent with their generalised executive dysfunction. The findings illustrate that breakdown in olfaction can occur at a perceptual or semantic level, analogous to the distinction between apperceptive and associative forms of deficit in the visual and auditory modalities. The findings add further insights into the nature of the semantic deficit in SD by exploring a hitherto neglected modality and may have relevance in explaining the altered eating habits commonly associated with SD.
ObjectiveTo retrospectively investigate safety and efficacy of nusinersen in a large cohort of adult Italian patients with spinal muscular atrophy (SMA).MethodsInclusion criteria were: (1) clinical and molecular diagnosis of SMA2 or SMA3; (2) nusinersen treatment started in adult age (>18 years); (3) clinical data available at least at baseline (T0-beginning of treatment) and 6 months (T6).ResultsWe included 116 patients (13 SMA2 and 103 SMA3) with median age at first administration of 34 years (range 18–72). The Hammersmith Functional Rating Scale Expanded (HFMSE) in patients with SMA3 increased significantly from baseline to T6 (median change +1 point, p<0.0001), T10 (+2, p<0.0001) and T14 (+3, p<0.0001). HFMSE changes were independently significant in SMA3 sitter and walker subgroups. The Revised Upper Limb Module (RULM) in SMA3 significantly improved between T0 and T14 (median +0.5, p=0.012), with most of the benefit observed in sitters (+2, p=0.018). Conversely, patients with SMA2 had no significant changes of median HFMSE and RULM between T0 and the following time points, although a trend for improvement of RULM was observed in those with some residual baseline function. The rate of patients showing clinically meaningful improvements (as defined during clinical trials) increased from 53% to 69% from T6 to T14.ConclusionsOur data provide further evidence of nusinersen safety and efficacy in adult SMA2 and SMA3, with the latter appearing to be cumulative over time. In patients with extremely advanced disease, effects on residual motor function are less clear.
One of the most effective techniques in the rehabilitation of visual field defects is based on implementation of oculomotor strategies to compensate for visual field loss. In the present study we develop a new rehabilitation approach based on the audio-visual stimulation of the visual field. Since it has been demonstrated that audio-visual interaction in multisensory neurons can improve temporally visual perception in patients with hemianopia, the aim of the present study was to verify whether a systematic audio-visual stimulation might induce a long-lasting amelioration of visual field disorders. Eight patients with chronic visual field defects were trained to detect the presence of visual targets. During the training, the visual stimulus could be presented alone, i.e. unimodal condition, or together with an acoustic stimulus, i.e. crossmodal conditions. In the crossmodal conditions, the spatial disparity between the visual and the acoustic stimuli were systematically varied (0, 16 and 32 degrees of disparity). Furthermore, the temporal interval between the acoustic stimulus and the visual target in the crossmodal conditions was gradually reduced from 500 to 0 ms. Patients underwent the treatment for 4 h daily, over a period of nearly 2 weeks. The results showed a progressive improvement of visual detections during the training and an improvement of visual oculomotor exploration that allowed patients to efficiently compensate for the loss of vision. More interesting, there was a transfer of treatment gains to functional measures assessing visual field exploration and to daily-life activities, which was found stable at the 1 month follow-up control session. These findings are very promising with respect to the possibility of taking advantage of human multisensory capabilities to recover from unimodal sensory impairments.
This interventional study provides Class I evidence that time-locked rTMS before or after physical therapy improves measures of dexterity and force in the affected limb in patients with chronic deficits more than 6 months poststroke.
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