Preserved brain functional plasticity after upper limb task-oriented rehabilitation in progressive multiple sclerosis.

BACKGROUND AND PURPOSE: Limited research has been dedicated to upper limb (UL) rehabilitation in progressive multiple sclerosis (PMS). The objective in this pilot study was to investigate the effect of task-oriented UL rehabilitation in PMS and to perform explorative analyses of the magnetic resonance imaging (MRI) correlates of changes in motor performance. METHODS: Twenty-six PMS patients with mild UL impairment were prospectively enrolled and randomized into two groups: an active treatment group (ATG, n = 13) and a passive treatment group (PTG, n = 13). At baseline and after training, patients underwent MRI scans with structural and functional imaging and were evaluated with the action research arm test, the nine-hole peg test, the ABILHAND scale and the modified fatigue impact scale (MFIS). Measures of motor finger performance were obtained by engineered glove measuring. RESULTS: After rehabilitation, the ATG improved in several finger motor tasks (0.001 ≤ P ≤ 0.03, 0.72 ≤ Cohen's d ≤ 1.22) and showed reduced MFIS scores compared with the PTG (P = 0.03). The ATG showed increased functional connectivity within the cerebellar and thalamic resting state networks compared with the PTG (P < 0.05). Correlations were found between several measures of motor improvement and thalamic and sensorimotor networks (0.87 ≤ r ≤ 0.93, 0.001 ≤ P ≤ 0.03). No changes in cerebral volumes and diffusion tensor imaging derived measures were detected. CONCLUSIONS: Progressive multiple sclerosis patients with mild UL dysfunction benefit from task-oriented UL rehabilitation, which seems to be more efficient than simple passive mobilization. Despite a high burden of disability and brain damage, functional adaptive capacities seem to be preserved, thus providing a rationale for the use of rehabilitative treatments in late PMS.

Box and block test, hand grip strength and nine-hole peg test: correlations between three upper limb objective measures in multiple sclerosis.

BACKGROUND AND PURPOSE: Limited data are available in the literature for upper limb impairment in multiple sclerosis (MS). This study aimed to report the distribution of values of hand grip strength (HGS), of the box and block test (BBT) and of the nine-hole peg test (9HPT) correlated with demographic and clinical data in subjects with MS. METHODS: This study involved five Italian neurological centres. The inclusion criteria were age ≥ 18, MS diagnosis, stable disease phase, right-hand dominance. All subjects underwent HGS, BBT and 9-HPT evaluation. RESULTS: In all, 202 subjects with MS were enrolled: 137 females; mean age 48.4 years; mean Expanded Disability Status Scale (EDSS) 4.17; mean disease duration 14.12 years; disease course 129 relapsing-remitting, 21 primary progressive and 52 secondary progressive MS subjects; mean right HGS 25.3 kg, left 23.2 kg; mean right BBT 45.7 blocks, left 44.9 blocks; mean right 9-HPT 30.7 s, left 33.4 s. All results were statistically significantly different compared to healthy controls. HGS, BBT and 9-HPT were associated with age, EDSS and disease duration, whilst disease course correlated with BBT and 9-HPT. The BBT and 9-HPT scores significantly differed according to level of disability (EDSS ≤3.0, 3.5-5.5, ≥6.0). CONCLUSION: Hand grip strength and BBT value distribution in a large MS population is reported. Correlations between HGS, BBT and 9-HPT were generally low.

Subclinical motor impairment assessed with an engineered glove correlates with magnetic resonance imaging tissue damage in radiologically isolated syndrome.

BACKGROUND: An engineered glove measuring finger motor performance previously showed ability to discriminate early-stage multiple sclerosis (MS) patients from healthy controls (HCs). Radiologically isolated syndrome (RIS) classifies asymptomatic subjects with brain magnetic resonance imaging (MRI) abnormalities suggestive of multiple sclerosis. METHODS: Seventeen asymptomatic subjects with RIS and 17 HCs were assessed. They performed finger-to-thumb opposition sequences at their maximal velocity, metronome-paced bimanual movements and conventional and diffusion tensor MRI. RESULTS: Subjects with RIS showed lower (P = 0.005) maximal velocity and higher (P = 0.006) bimanual coordination impairment than HCs. In RIS, bimanual coordination correlated with T2-lesion volume, fractional anisotropy and radial diffusivity in the white matter. CONCLUSIONS: These findings point out the relevance of fine hand measures as a robust marker of subclinical disability.

Impairment in explicit visuomotor sequence learning is related to loss of microstructural integrity of the corpus callosum in multiple sclerosis patients with minimal disability.

Sequence learning can be investigated by serial reaction-time (SRT) paradigms. Explicit learning occurs when subjects have to recognize a test sequence and has been shown to activate the frontoparietal network in both contralateral and ipsilateral hemispheres. Thus, the left and right superior longitudinal fasciculi (SLF), connecting the intra-hemispheric frontoparietal circuits, could have a role in explicit unimanual visuomotor learning. Also, as both hemispheres are involved, we could hypothesize that the corpus callosum (CC) has a role in this process. Pathological damage in both SLF and CC has been detected in patients with Multiple Sclerosis (PwMS), and microstructural alterations can be quantified by Diffusion Tensor Imaging (DTI). In light of these findings, we inquired whether PwMS with minimal disability showed impairments in explicit visuomotor sequence learning and whether this could be due to loss of white matter integrity in these intra- and inter-hemispheric white matter pathways. Thus, we combined DTI analysis with a modified version of SRT task based on finger opposition movements in a group of PwMS with minimal disability. We found that the performance in explicit sequence learning was significantly reduced in these patients with respect to healthy subjects; the amount of sequence-specific learning was found to be more strongly correlated with fractional anisotropy (FA) in the CC (r=0.93) than in the left (r=0.28) and right SLF (r=0.27) (p for interaction=0.005 and 0.04 respectively). This finding suggests that an inter-hemispheric information exchange between the homologous areas is required to successfully accomplish the task and indirectly supports the role of the right (ipsilateral) hemisphere in explicit visuomotor learning. On the other hand, we found no significant correlation of the FA in the CC and in the SLFs with nonspecific learning (assessed when stimuli are randomly presented), supporting the hypothesis that inter-hemispheric integrity is specifically relevant for explicit sequence learning.

A comparison of upper limb function in subjects with multiple sclerosis and healthy controls using an inertial measurement unit.

Upper limbs (UL) dysfunction is frequent in people with Multiple Sclerosis (PwMS). Several objective measures of UL function are proposed; however, their use is mostly confined to assess subjects with mild-to-moderate disability and requires fine motor skills, often impaired in high disability level subjects. Thus, a tool to score UL function in the advanced disease stage is lacking. The aim of the study is to analyse and compare UL unilateral and bilateral movements of healthy control (HC) and PwMS, at different disability levels, using an instrumented version (Inertial Measurement Unit, IMU) of the 15-seconds finger-to-nose test (FNT). Each movement cycle was segmented in going/adjusting/returning phases. The inter-hand interval (IHI) allowed assessing bilateral coordination (i.e. synchrony) in each phase. The larger IHI, the more severe the bilateral coordination impairment is. After stratifying PwMS for disability level (PwMSLOW, Expanded Disability Status Scale, EDSS≤5.5 and PwMSHIGH, EDSS≥6), the ANOVA on IHI showed significant differences between PwMS and HC (p<0.001) in all phases. However, only the going phase IHI showed significantly higher asynchrony in PwMSHIGH than PwMSLOW and HC (p<0.001) and no differences between PwMSLOW and HC. The going phase IHI seems to be a clinical marker specific for high disability level PwMS. These findings suggest inertial sensors during FNT could be an easy-to-use method for a more detailed quantitative characterization of UL function in PwMS also in subjects with EDSS greater than 6.

Associations between clinical characteristics and dual task performance in Multiple Sclerosis depend on the cognitive and motor dual tasks used.

BACKGROUND: In persons with Multiple Sclerosis (pwMS) performing a simultaneous cognitive task while walking often results in slower gait. Clinical characteristics associated with reduced dual task (DT) performance are not yet entirely clear. This multi-centre study aimed to determine the relationship between clinical and demographical characteristics with dual task (DT) walking performance in pwMS during multiple DT conditions. METHODS: Nine DT conditions were analysed, consisting of combinations of three types of cognitive ('digit span', 'subtraction', 'vigilance') and three types of walking ('walk', 'walk with cup', 'walk over obstacles') conditions. Primary outcomes were DT gait speed (m/s) and motor DT cost of gait speed (DTCmotor, %). Secondary outcomes were clinical tests of physical and cognitive functioning and patient-reported and demographical outcomes. Firstly, univariate analyses and, subsequently, multivariate analyses with backward modelling, were conducted for each type of walking DT condition separately. Cognitive DT conditions were included in the models as main and as interaction effect with the secondary outcomes. RESULTS: Analysis were performed in 81 pwMS (EDSS 3.3 ± 1.0). In the final models of DTCmotor, the significant main effects were in 'walk' DT-conditions the Symbol Digit Modalities Test (SDMT), in 'cup' conditions the SDMT and Dynamic Gait Index and in 'obstacles' conditions age. For DT gait speed, main effects were found for the 2-Minute Walking Test (2MWT) and the Multiple Sclerosis Walking Scale for all walking conditions. Additionally, interactions between cognitive DT-conditions and SDMT, age and 2MWT were found. CONCLUSION: Clinical characteristics related to DT walking performance differed according to cognitive-motor DT-condition used. Still, in general, pwMS with a better mobility demonstrated higher DT gait speed, while a faster information processing speed was related to a lower DTCmotor.

The patients' perspective on the perceived difficulties of dual-tasking: development and validation of the Dual-task Impact on Daily-living Activities Questionnaire (DIDA-Q).

BACKGROUND: Everyday-life activities often require performing dual tasks (DT), with consequent possible occurrence of motor-cognitive or motor-motor interference. This could reduce quality of life, in particular in people with neurological diseases. However, there is lack of validated tools to assess the patients' perspective on DT difficulties in this population. Therefore, we developed the Dual-task Impact on Daily-living Activities-Questionnaire (DIDA-Q) and tested its psychometric properties in people with multiple sclerosis (PwMS). METHODS: Items were generated based on existing scales, DT paradigms used in previous studies and the opinion of a multi-stakeholder group, including both experts and PwMS. Twenty DT constituted the preliminary version of the DIDA-Q which was administered to 230 PwMS. The psychometric properties of the scale were evaluated including internal consistency, validity and reliability. RESULTS: Nineteen items survived after exploratory factor analysis, showing a three-factor solution which identifies the components mostly contributing to DT perceived difficulty (i.e., balance and mobility, cognition and upper-limb ability). The DIDA-Q appropriately fits the graded response model, with first evaluations supporting internal consistency (Cronbach's alpha=0.95), validity (70% of the hypotheses for convergent and discriminant constructs confirmed) and reliability (intraclass correlation coefficients=0.95) of this tool. CONCLUSION: The DIDA-Q could be used in research and clinical settings to discriminate individuals with low vs. high cognitive-motor or motor-motor interference, and to develop and evaluate the efficacy of personalized DT rehabilitative treatments in PwMS.

Analysis of upper limb movement in Multiple Sclerosis subjects during common daily actions.

The goal of this study was to investigate the movement and muscle activity of the upper limb during common activities of daily life in people with Multiple Sclerosis (PwMS) with low and mild-moderate level of upper limb impairments. We found significant changes in muscles activity in PwMS compared to healthy subjects when holding and lifting objects used in everyday life. These differences were particularly remarkable in subjects with moderate level of impairment, in which the disease affected also movement smoothness. Remarkably, the smoothness of the movement during the interaction with common objects of daily activities highly correlated with the subjects' ability measured with the Abilhand scale.

Vascular rings and slings. Diagnosis and surgical treatment of 49 patients.

Forty-nine infants with symptomatic vascular rings and slings, ranging in age from 20 days to 12 months, required surgical intervention between 1973 and 1984. The following anomalies were present in our patients: double aortic arch with left descending aorta (14), double aortic arch with right descending aorta (6), anomalous innominate artery (13), right aortic arch with aberrant left subclavian artery (4), left aortic arch with aberrant right subclavian artery (10), aberrant left pulmonary artery (pulmonary sling) (2). All the babies had symptoms related to compression of the trachea and/or esophagus. Four patients required temporary tracheostomy in the early postoperative period; 1 patient, affected by a pulmonary sling, required tracheal resection and anastomosis, for severe tracheomalacia. There was one hospital death in a patient with severe tracheal compression from an anomalous innominate artery and brain damage as a result of metabolic problems. Forty-eight patients survived and follow-up ranged from 3 months to 11 years. For each type of vascular anomaly encountered, and based on personal experience, we have outlined a diagnostic scheme allowing an accurate morphological definition and a subsequent surgical procedure.

[Ototoxicity following the administration of high doses of cisplatin in children with malignant neoplasms]. / Ototossicità conseguente alla somministrazione di alte dosi di cis-platino in bambini affetti da neoplasie maligne.

CDDP is an antitumor agent which has shown effectiveness in a variety of pediatric and adult solid tumors. Main toxic effects of CDDP involve kidney, bone marrow and ear functions. Recently, CDDP has been used at "high doses" (200 mg/sq m, compared with 90-100 mg/sq m used previously) on the basis of its dose dependent antitumor activity. Ear toxicity might be higher with the "high doses" schedule, and this could be of much importance for younger patients, due the irreversibility of the lesion induced by the drug on the ear structure. In this study, the Authors have prospectively evaluated the ear function in children undergoing treatment with "high doses" CDDP and have compared it with that determined by the drug administered at "traditional" doses. Between september 1984 and march 1985, ten children aged 3-10 years, affected by tumors either resistant to first line therapy or at relapse, were treated with CDDP, 200 mg/sq m divided in five daily doses (days 2-6) (Vincristine, 2 mg/sq m and Cyclophosphamide, 600 mg/sq m, were given on day 1). Six out of ten children had been previously treated with CDDP at "traditional" doses. Acoustic function has been evaluated with tonal audiometry performed before therapy, 2 and 15 days after each cycle of therapy. A deficit was scored mild for levels between 15 and 30 dB, medium for levels between 30 and 60 dB, severe for levels greater than 60 dB. The Audiometry performed in six children who had previously been treated with CDDP at "traditional doses" demonstrated a deficit limited at 8000 Hz in five of them.(ABSTRACT TRUNCATED AT 250 WORDS)

Associative cortico-cortical plasticity may affect ipsilateral finger opposition movements.

We have recently demonstrated that cortico-cortical paired associative stimulation (cc-PAS) can modulate interhemispheric inhibition (IHI) in the human brain. Here we further explored the after effects of cc-PAS on fine hand movements. Ten healthy right-handed volunteers received 90 paired transcranial stimuli to the right and left primary motor hand area (M1(HAND)) at an interstimulus interval (ISI) of 8 ms. We studied the after effects of cc-PAS on the performance of repetitive finger opposition movements of different complexity on both hands using a sensor-engineered glove. A quantitative evaluation of the following parameters was performed: Touch Duration (TD), Inter Tapping Interval (ITI) and Number of Errors (NE). We confirmed previous data by showing that left-to-right and right-to-left cc-PAS attenuated IHI. The new finding is that both left-to-right and right-to-left cc-PAS were able to influence the performance of a simple finger opposition movement changing the duration of TD and ITI. Interestingly the effect on the two hands was opposite in direction. These results provide further insight that cc-PAS can induce associative plasticity in connections between the targeted cortical areas influencing motor hand performances. These results may be relevant for future rehabilitative applications.

Recovery of motor performance deterioration induced by a demanding finger motor task does not follow cortical excitability dynamics.

The performance of a demanding exercise can result in motor performance deterioration and depression of primary motor cortex excitability. In the present work we defined a motor task that requires measurable skilled performance to unveil motor performance changes during the execution of a demanding task and to investigate the dynamics of motor performance and cortical excitability changes in absence of overt peripheral fatigue. Twenty-one normal subjects, divided into three groups were asked to perform a sequence of finger opposition movements (SEQ) paced at 2 Hz for 5 min, quantitatively evaluated by means of a sensor-engineered glove able to perform a spatio-temporal analysis of motor performance. Maximal voluntary contraction (MVC) was evaluated before and after the motor task in group 1 while motor evoked potentials (MEP) were evaluated before and after the motor task in group 2 and 3. Group 1 and 2 performed the 5 min-SEQ while group 3 was asked to perform the 5 min-SEQ twice to assess the dynamics of motor performance and cortical excitability. As a result, we found that the execution of 5 min-SEQ induced motor performance deterioration associated with no change in MVC but a decrease in cortical excitability. We further found that the dynamics of cortical excitability and motor performance were different. In fact, a short rest period (i.e., period necessary to collect MEP) between the execution of two 5 min-SEQs was able to recover the motor performance but not the cortical excitability. Finally, no change in spinal excitability was observed. These findings suggest that although primary motor cortex seems to be mainly involved in motor performance deterioration during the execution of a demanding finger motor task, the recovery of motor performance does not follow cortical excitability dynamics.

Interaction between vision and neck proprioception in the control of stance.

Balance control depends on the interaction of multiple inputs originating from different sensory systems. Here, we investigated the effect on quiet human stance of changing the visual condition prior to a proprioceptive perturbation produced by vibration of dorsal neck muscles. In complete absence of visual references, the amplitude of the postural responses to neck vibration (forward shift of the centre of foot pressure) was the largest and became progressively larger as a function of the repetition of administered stimuli. The posture-destabilizing effect of vibration eyes-closed (EC) and the build-up effect were reduced if vibration was preceded by a period during which vision was allowed (EO). Similarly, the small destabilizing effect of vibration EO was increased if vibration was preceded by an EC period. The fore-period must last more than 3 s in order to affect the response to neck muscle vibration. The responsiveness to a proprioceptive disturbing input does not immediately change on adding or subtracting vision, but a finite time period must elapse before the postural "set" defined by vision is fully established. The findings underline the importance of time when vision is used in re-weighting the excitability of the postural control mechanisms.