[Show abstract][Hide abstract] ABSTRACT: In Parkinson's disease (PD), skill retention is poor, even when acquisition rate is generally preserved. Recent work in normal subjects suggests that 5 Hz-repetitive transcranial magnetic stimulation (5Hz-rTMS) may induce phenomena of long-term potentiation at the cortical level.Objective/HypothesisWe thus verified whether, in PD, 5Hz-rTMS enhances retention of a visuo-motor skill that involves the activity of the right posterior parietal cortex.MethodsA group of patients with PD was tested in two two-day sessions, separated by one week (treatment and placebo sessions). The first day of each session, they learned to adapt their movements to a step-wise 60° visual rotation. Immediately after the task, either real 5Hz-rTMS (treatment) or sham (placebo) stimulation was applied over the right posterior parietal cortex (P6). Retention of this motor skill was tested the following day.ResultsIn patients with PD, adaptation achieved at the end of training was comparable in the treatment and placebo sessions and was similar to that of a group of age-matched controls. However, retention indices tested on the following day were significantly lower in the placebo compared to the treatment session in which retention indices were restored to the level of the controls. Importantly, reaction and movement time as well as other kinematic measures were the same in the treatment and placebo sessions.Conclusion
These results suggest that rTMS applied after the acquisition of a motor skill over specific areas involved in this process might enhance skill retention in PD.
[Show abstract][Hide abstract] ABSTRACT: Radial shock wave therapy (RSWT) has been extensively used in rehabilitative medicine to treat pain, and more recently muscle hypertonia, in patients with cerebral palsy and stroke.
[Show abstract][Hide abstract] ABSTRACT: To assess in a noninterventional setting the prevalence and severity of fatigue in patients with Parkinson disease (PD).METHODS: This was a cross-sectional study conducted in Italian patients with PD. Objectives included the evaluation of the current prevalence and severity of fatigue in patients with PD measured using the 16-item Parkinson Fatigue Scale (PFS-16), distressing fatigue (defined as a PFS-16 mean score ≥3.3), and assessment of its clinical correlates.RESULTS: A total of 402 patients were enrolled and 394 patients completed the PFS-16 questionnaire with a PFS-16 mean (±SD) score of 2.87 ± 0.99. Of these, 136 patients (33.8%) reported distressing fatigue (PFS-16 mean score ≥3.3). Patients with distressing fatigue were older (p = 0.044) and had a longer duration of PD (p < 0.0001) than those without distressing fatigue. The presence of distressing fatigue was associated with higher total Unified Parkinson's Disease Rating Scale (UPDRS) scores, poorer quality of life (39-item Parkinson's Disease Questionnaire [PDQ-39]), worse social and psychological behaviors, a higher severity of depressive symptoms, and a higher prevalence of sleep disorders (all p < 0.001). Logistic regression analyses revealed that higher total UPDRS scores, female sex, depression, sleep disorders, as well as higher UPDRS activities of daily living scores and PDQ-39 mobility scores increase the likelihood of distressing fatigue in patients with PD.CONCLUSIONS: Approximately one-third of patients with PD have distressing fatigue, which is significantly associated with depression and sleep disorders. The fact that the presence of fatigue worsens patient quality of life supports the need to better diagnose and treat this debilitating symptom.
[Show abstract][Hide abstract] ABSTRACT: Mirror visual feedback (MVF) therapy has been demonstrated to be successful in neurorehabilitation, probably inducing neuroplasticity changes in the primary motor cortex (M1). However, it is not known whether MVF training influences the hemispheric balance between the M1s. This topic is of extreme relevance when MVF training is applied to stroke rehabilitation, as the competitive interaction between the two hemispheres induces abnormal interhemispheric inhibition (IHI) that weakens motor function in stroke patients. In the present study, we evaluated, in a group of healthy subjects, the effect of motor training and MVF training on the excitability of the two M1s and the IHI between M1s. The IHI from the 'active' M1 to the opposite M1 (where 'active' means the M1 contralateral to the moving hand in the motor training and the M1 of the seen hand in the MVF training) increased, after training, in both the experimental conditions. Only after motor training did we observe an increase in the excitability of the active M1. Our findings show that training based on MVF may influence the excitability of the transcallosal pathway and support its use in disorders where abnormal IHI is a potential target, such as stroke, where an imbalance between the affected and unaffected M1s has been documented.
European Journal of Neuroscience 05/2014; · 3.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
Assessing the frequency of Wearing-Off (WO) in Parkinson's disease (PD) patients, and its impact on Quality of Life (QoL).
Consecutive ambulatory patients, who were on dopaminergic treatment for ≥1 year, were included in this multicentre, observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as using the validated Italian version of a patient self-rated 19-question Wearing-Off Questionnaire (WOQ-19); WO was defined for scores ≥ 2. QoL was evaluated by the 8-item Parkinson's Disease Questionnaire (PDQ-8).
617 subjects were included, with a mean anti-Parkinson treatment duration of 6.6 ± 4.6 years, 87.2% were on levodopa treatment. Neurologists identified presence of WO in 351 subjects (56.9%), whereas 415 subjects (67.3%) were identified by the self-administered WOQ-19. In patients with a <2.5 years disease duration, WO was diagnosed in 12 subjects (21.8%) by neurologists and in 23 subjects (41.8%) by the WOQ-19. The most frequent WO symptoms, as identified by WOQ-19, were “slowness of movements” (55.8%) and “reduced dexterity” (48.8%). Younger age, female gender, Unified Parkinson's Disease Rating Scale (UPDRS) part II score and duration of anti-Parkinson treatment were found significantly associated with WO. The number of motor (p < 0.0001) and non-motor (p < 0.0001) WO symptoms correlated with PDQ-8 total score.
WO is common already at the early stages of PD and is underestimated by routine neurological clinical evaluation. The number of WO symptoms, both motor and non motor, increases along with disease duration and has a negative impact on patients QoL.
Parkinsonism & Related Disorders 02/2014; 20(2):204–211. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
To evaluate the long-term effect of Deferiprone (DFP) in reducing brain iron overload and improving neurological manifestations in patients with NBIA.
6 NBIA patients (5 with genetically confirmed PKAN), received DFP solution at 15 mg/kg po bid. They were assessed by UPDRS/III and UDRS scales and blinded video rating, performed at baseline and every six months. All patients underwent brain MRI at baseline and during follow up. Quantitative assessment of brain iron was performed with T2* relaxometry, using a gradient multi-echo T2* sequence.
After 48 months of treatment clinical rating scales and blinded video rating indicated a stabilization in motor symptoms in 5/6 pts. In the same subjects MRI evaluation showed reduced hypointensity in the globus pallidus (GP); quantitative assessment confirmed a significant increment in the T2* value, and hence reduction of the iron content of the GP.
The data from our 4-years follow-up study confirm the safety of DFP as a chelator agent for iron accumulation. The clinical stabilization observed in 5/6 of our patients suggests that DFP may be a reasonable therapeutic option for the treatment of the neurological manifestations linked with iron accumulation and neurodegeneration, especially in adult patients at early stage of the disease.
(Clinicaltrials.gov identifier: NTC00907283)
Parkinsonism & Related Disorders 01/2014; · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Since 1997, focused shock waves therapy (FSWT) has been reported to be useful in the treatment of muscle hypertonia and dystonia. More recently, also radial shock wave therapy (RSWT) has been successfully used to treat muscle hypertonia. The studies where FSWT and RSWT have been used to treat muscle hypertonia and dystonia are reviewed in this paper. The more consistent and long lasting results were obtained in the lower limb muscles of patients affected by cerebral palsy with both FSWT and RSWT and in the distal upper limb muscles of adult stroke patients using FSWT. The most probable mechanism of action is a direct effect of shock waves on muscle fibrosis and other nonreflex components of muscle hypertonia. However, we believe that up to now the biological effects of shock waves on muscle hypertonia and dystonia cannot be clearly separated from a placebo effect.
BioMed Research International 01/2014; 2014:637450. · 2.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Post-activation depression (PaD) refers to the inhibition of the H-reflex induced by a preceding conditioning stimulus able to activate the afferents mediating the H-reflex itself. PaD can be investigated assessing the frequency-related depression of the H-reflex. This parameter, which is highly correlated to the severity of spasticity, has been used in the longitudinal assessment of spastic patients, in particular to assess the effect of drugs and rehabilitation over the years. However, in such longitudinal assessment, changes observed might be age related and not only disease related. The aim of this study was to investigate the possible age effects on PaD.
The frequency-related depression of the flexor carpi radialis (FCR) H-reflex was examined in two groups of young (20 subjects; 28 ± 3 years) and aged (18 subjects; 69 ± 6 years) healthy subjects. PaD was evaluated by comparing the H-reflex amplitudes obtained with a stimulation frequency of 0.1 Hz with those obtained using higher frequencies (0.33-0.5-1-2 Hz).
The results showed that frequency-related depression of the FCR H-reflex is similar in young and elderly subjects at all frequencies, with the exception of 2 Hz.
Our study shows that ageing does not affect the frequency-related depression of the FCR H-reflex at the frequencies of 1 Hz or lower, supporting the reliability of this method to assess PaD in the clinical practice, particularly for the longitudinal assessment of spasticity. A decrease of GABA-ergic presynaptic inhibition seems to be the more likely explanation for the age-related changes that we observed at the frequency of 2 Hz.
[Show abstract][Hide abstract] ABSTRACT: Cognitive impairment (CI) is a frequent feature associated with both early and advanced stages of Parkinson's disease (PD). An evaluation of cognitive functions is relevant to identify those parkinsonians at risk of developing dementia. In the present study, the Italian version of Parkinson's Disease-Cognitive Rating Scale (PD-CRS) assessing fronto-subcortical and cortical cognitive functions in PD was validated in 387 parkinsonians and was used to test the empirical validity of the item 1.1 (cognitive impairment) of the Italian version of MDS-UPDRS as screening tool for CI in PD. PD-CRS was free from floor and ceiling effect. The mean PD-CRS score was 76.1 (mean cortical score, 24.5 ± 4.6; mean subcortical score, 51.5 ± 17.5). The internal consistency was satisfactory (α = 0.89); corrected item-total correlation was 0.570 (naming) to 0.696 (working memory). The correlation between PD-CRS and part I-IV of MDS-UPDRS was weak. The low agreement between classification of PD sample into patients with mild cognitive impairment (PD-MCI), dementia (PD-D) and normal cognition (PD-NC) according to scores of item 1.1 and classification according to cutoff scores of PD-CRS for PD-MCI, PD-D and PD-NC indicated a poor empirical validity of item 1.1 of MDS-UPDRS as cognitive screening tool for CI in PD (Κ = 0.114; weighted Κ = 0.17; SE of Κ = 0.038; 95 % confidence interval from 0.040 to 0.1895). The Italian version of PD-CRS is an easy, consistent and valid tool for assessment of the cognitive cortical and subcortical impairments in PD.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE To assess the association between clinical and socio-demographic features and anti-Parkinson drug (APD) treatment modifications in patients with PD and to describe neurologist and patient opinions regarding the need for changes in APD therapy.
Subjects with PD with stable APD treatment over ≥3 months prior to baseline were enrolled and evaluated for socio-demographic data, disability, disease severity and neurologist and patient views on the need to modify APD treatment.
775 Patients were included, 51% with Hoehn and Yahr (HY) stage 1-2 (early PD) and 49% with HY stage 2.5-4 (advanced PD). Neurologists modified APD treatment in 255 patients, 97 (25%) early PD and 158 (41%; p < 0.0001) advanced PD. APD modification was strongly associated with a low educational level and UPDRS part IV score. The most common reasons behind the APD therapy changes among neurologists were presence/worsening of motor or non-motor symptoms (88% and 37% of subjects respectively). Out of 216 patients, 92% and 51% were willing to undergo APD changes to therapy because of the presence/worsening of motor or non-motor symptoms.
Neurologist decision to change APD therapy and patients reasons for dissatisfaction with it can be prevalently attributed to the presence/worsening of motor symptoms and motor fluctuations in the advanced stages. Non-motor symptoms were considered more often by patients. The patient educational level played a key role in treatment decision.
Parkinsonism & Related Disorders 08/2013; · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Parkinsonian patients can be classified in two main subgroups: tremor dominant and akinetic-rigid. The aim of this study was to evaluate whether intensive rehabilitation treatment has the same efficacy in the two subtypes.
Patients were classified according to tremor: 65 patients with absence of tremor in "on" and "off" state were assigned to Group_1 and 65 patients with tremor were assigned to Group_2. All patients underwent a 4-week intensive multidisciplinary rehabilitation treatment. The primary outcome measures were: the Unified Parkinson's Disease Rating Scale (UPDRS) II, III, UPDRS akinetic-rigid score and UPDRS tremor score. The secondary outcome measures were: the Berg Balance Scale, 6-minute walking test, self-assessment Parkinson's Disease Disability Scale, Abnormal Involuntary Movement Scale, Freezing of Gait Questionnaire.
Patients in Group_1 tended to be more affected than patients in Group_2 by dyskinesias (45% vs 29% p = 0.069) and freezing (46% vs 29%, p = 0.046). Levodopa-equivalent dosages were higher in Group_1 (802 vs 670 mg/day, p = 0.008). Considering the effect of rehabilitation, an homogeneous improvement was observed in all variables in both groups of patients (p < 0.0001).
Intensive rehabilitation treatment is effective in improving motor performance in both groups. The anatomical and biochemical differences existing between the two subgroups appear to not determine different clinical outcomes.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Pain is one of the most common and disabling "nonmotor" symptoms in patients with dystonia. No recent study evaluated the pharmacological or physical therapy approaches to specifically treat dystonic pain symptoms. OBJECTIVE: To evaluate the effectiveness of KinesioTaping in patients with cervical dystonia (CD) and focal hand dystonia (FHD) on self-reported pain (primary objective) and on sensory functions (secondary objective). METHODS: Twenty-five dystonic patients (14 with CD and 11 FHD) entered a randomized crossover pilot study. The patients were randomized to 14-day treatment with KinesioTaping or ShamTaping over neck (in CD) or forearm muscles (in FHD), and after a 30-day washout period, they received the other treatment. The MAIN OUTCOME MEASURES: were 3 visual analog scales (VASs) for usual pain, worst pain, and pain relief. Disease severity changes were evaluated by means of the Toronto Western Spasmodic Torticollis Rating Scale (CD) and the Writer's Cramp Rating Scale (FHD). Furthermore, to investigate possible KinesioTaping-induced effects on sensory functions, we evaluated the somatosensory temporal discrimination threshold. RESULTS: Treatment with KinesioTape induced a decrease in the subjective sensation of pain and a modification in the ability of sensory discrimination, whereas ShamTaping had no effect. A significant, positive correlation was found in both groups of patients between the improvement in the subjective sensation of pain and the reduction of somatosensory temporal discrimination threshold values induced by KinesioTaping. CONCLUSIONS: These preliminary results suggest that KinesioTaping may be useful in treating pain in patients with dystonia.
Neurorehabilitation and neural repair 06/2013; · 4.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Information about patients' adherence to therapy represents a primary issue in Parkinson's disease (PD) management. To perform the linguistic validation of the Italian version of the self-rated 8-Item Morisky Medical Adherence Scale (MMAS-8) and to describe in a sample of Italian patients affected by PD the adherence to anti-Parkinson drug therapy and the association between adherence and some socio-demographic and clinical features. MMAS-8 was translated into Italian language by two independent Italian mother-tongue translators. The consensus version was then back-translated by an English mother-tongue translator. This translation process was followed by a consensus meeting between the authors of translation and investigators and then by two comprehension tests. The translated version of the MMAS-8 scale was then administered at the baseline visit of the "REASON" study (Italian Study on the Therapy Management in Parkinson's disease: Motor, Non-Motor, Adherence and Quality Of Life Factors) in a large sample of PD patients. The final version of the MMAS-8 was easily understood. Mean ± SD MMAS-8 score was 6.1 ± 1.2. There were no differences in adherence to therapy in relationship to disease severity, gender, educational level or decision to change therapy. The Italian version of MMAS-8, the key tool of the REASON study to assess the adherence to therapy, has shown to be understandable to patients with PD. Patients enrolled in the REASON study showed medium therapy adherence.
[Show abstract][Hide abstract] ABSTRACT: Short-term upper limb disuse induces a hemispheric unbalance between the primary motor cortices (M1s). However, it is still unclear whether these changes are mainly attributable to the absence of voluntary movements or to the reduction of proprioceptive information. The goal of this work was to investigate the role of proprioception in modulating hemispheric balance during a short-term right arm immobilization. We evaluated the 2 M1s excitability and the interhemispheric inhibition (IHI) between M1s in 3 groups of healthy subjects. Two groups received during the immobilization a proprioceptive (P-VIB, 80 Hz) and tactile (T-VIB, 30 Hz) vibration to the right hand, respectively. Another group did not receive any conditioning sensory inputs (No-VIB). We found that in the No-VIB and in the T-VIB groups immobilization induced a decrease of left M1 excitability and IHI from left to right hemisphere and an increase of right M1 excitability and IHI from right to left hemisphere. Differently, only a partial decrease in left M1 excitability, no change in right M1 excitability and in IHI was observed in the P-VIB group. Our findings demonstrate that the maintenance of dynamic proprioceptive inputs in an immobilized arm through muscle vibration can prevent the hemispheric unbalance induced by short-term limb disuse.
[Show abstract][Hide abstract] ABSTRACT: Postactivation depression is decreased in patients with spasticity and partially restored by physical exercise in spinal cord injured patients. Up until now, the possibility to modulate postactivation depression with motor training has never been explored in subjects with spasticity following brain lesions. Postactivation depression, assessed as frequency related depression of soleus H-reflex, was investigated before and after robotic-assisted gait training in a group of seven subjects with spastic hemiparesis following hemispheric stroke. Patients received three sessions per week of robotic-assisted gait training for a period of 4 weeks (12 sessions in total). Postactivation depression was measured before the treatment (T0), after the first session (T1) and after the last session (T2). Postactivation depression was quantified as the ratio between H-reflex amplitude at 1Hz and at 0.1Hz. The greater the 1Hz/0.1Hz ratio, the smaller the postactivation depression. Following robotic-assisted gait training, the 1Hz/0.1Hz ratio decreased from 0.79±0.26 at T0 to 0.56±0.18 at T1 and 0.58±0.13 at T2. Post hoc analysis showed a significant difference between T0 and T1 and between T0 and T2, stating an increase of postactivation depression. No significant differences were found between T1 and T2. This study provides the first demonstration that physical exercise can determine a partial normalization of postactivation depression in hemiparetic patients with spasticity following unilateral hemispheric stroke.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: . Action observation influences motor performance in healthy subjects and persons with motor impairments. OBJECTIVE: . To understand the effects of action observation on the spontaneous rate of finger movements in patients with Parkinson disease (PD). METHODS: . Participants, 20 with PD and 14 healthy controls, were randomly divided into 2 groups. Those in the VIDEO group watched video clips showing repetitive finger movements paced at 3 Hz, whereas those in the ACOUSTIC group listened to an acoustic cue paced at 3 Hz. All participants performed a finger sequence at their spontaneous pace at different intervals (before, at the end of, 45 minutes after, and 2 days after training); 8 participants with PD were recruited for a sham intervention, watching a 6-minute video representing a static hand. Finally, 10 patients participated in the same protocol used for the VIDEO group but were tested in the on and off medication states. RESULTS: . Both VIDEO and ACOUSTIC training increased the spontaneous rate in all participants. VIDEO intervention showed a greater effect over time, improving the spontaneous rate and reducing the intertapping interval to a larger extent than ACOUSTIC 45 minutes and 2 days after training. Action observation significantly influenced movement rate in on and off conditions, but 45 minutes after training, the effect was still present only in the on condition. No effect was observed after sham intervention. CONCLUSIONS: . These findings suggest that the dopaminergic state contributes to the effects of action observation, and this training may be a promising approach in the rehabilitation of bradykinesia in PD.
Neurorehabilitation and neural repair 02/2013; · 4.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Recent work has demonstrated that fall risk can be attributed to cognitive as well as motor deficits. Indeed, everyday walking in complex environments utilizes executive function, dual tasking, planning and scanning, all while walking forward. Pilot studies suggest that a multi-modal intervention that combines treadmill training to target motor function and a virtual reality obstacle course to address the cognitive components of fall risk may be used to successfully address the motor-cognitive interactions that are fundamental for fall risk reduction. The proposed randomized controlled trial will evaluate the effects of treadmill training augmented with virtual reality on fall risk. METHODS: Three hundred older adults with a history of falls will be recruited to participate in this study. This will include older adults (n=100), patients with mild cognitive impairment (n=100), and patients with Parkinson's disease (n=100). These three sub-groups will be recruited in order to evaluate the effects of the intervention in people with a range of motor and cognitive deficits. Subjects will be randomly assigned to the intervention group (treadmill training with virtual reality) or to the active-control group (treadmill training without virtual reality). Each person will participate in a training program set in an outpatient setting 3 times per week for 6 weeks. Assessments will take place before, after, and 1 month and 6 months after the completion of the training. A falls calendar will be kept by each participant for 6 months after completing the training to assess fall incidence (i.e., the number of falls, multiple falls and falls rate). In addition, we will measure gait under usual and dual task conditions, balance, community mobility, health related quality of life, user satisfaction and cognitive function. DISCUSSION: This randomized controlled trial will demonstrate the extent to which an intervention that combines treadmill training augmented by virtual reality reduces fall risk, improves mobility and enhances cognitive function in a diverse group of older adults. In addition, the comparison to an active control group that undergoes treadmill training without virtual reality will provide evidence as to the added value of addressing motor cognitive interactions as an integrated unit.Trial Registration: NIH NCT01732653.