[Show abstract][Hide abstract] ABSTRACT: Background. The early detection of wearing-off in Parkinson disease (DEEP) observational study demonstrated that women with Parkinson’s disease (PD) carry an increased risk (80.1%) for wearing-off (WO). This post hoc analysis of DEEP study evaluates gender differences on WO and associated phenomena. Methods. Patients on dopaminergic treatment for ≥1 year were included in this multicenter observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as the use of the 19-item wearing-off questionnaire (WOQ-19); WO was defined for scores ≥2. Post hoc analyses were conducted to investigate gender difference for demographic and clinical features with respect to WO. Results. Of 617 patients enrolled, 236 were women and 381 were men. Prevalence of WO was higher among women, according to both neurologists’ judgment (61.9% versus 53.8%, ) and the WOQ-19 analysis (72.5% versus 64.0%, ). In patients with WO (WOQ-19), women experienced ≥1 motor symptom in 72.5% versus 64.0% in men and ≥1 nonmotor symptom in 44.5% versus 36.7%, in men. Conclusions. Our results suggest WO as more common among women, for both motor and nonmotor symptoms. Prospective studies are warranted to investigate this potential gender-effect
The Scientific World Journal 01/2015; · 1.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess over a period of 9 months in a sample of Italian Parkinson’s disease (PD) patients reasons leading the neurologist to modify dopaminergic treatment and patients’ causes of dissatisfaction with ongoing therapy. To evaluate the influence of disease severity on therapy persistence. A disease severity balanced sample of PD patients with stable anti-parkinsonian drugs (APD) treatment was enrolled and evaluated every 3 months. Patients requiring APD treatment modifications were discontinued from the study. The probability to modify APD treatment is greater for higher motor (UPDRS scores) and non-motor symptoms (NMSS score) severity. Both from neurologist’s and patient’s perspective, motor symptoms were the main determinants underlying APD treatment modifications. Non-motor symptoms were cause of dissatisfaction with ongoing APD treatment for 52 % of the patients, while only 36 % of the neurologists considered these as valid reasons for therapy change. REASON is the first study in PD patients that prospectively examined reasons driving APD treatment changes. Results show that the disease severity significantly increases the probability of APD treatment change. Patients attribute greater relevance than neurologists to non-motor symptoms as reason requiring treatment changes. This confirms that patient and neurologist perceptions only partially overlap.
[Show abstract][Hide abstract] ABSTRACT: Movement disorders (MDs) are frequently associated with sensory abnormalities. In particular, proprioceptive deficits have been largely documented in both hypokinetic (Parkinson's disease) and hyperkinetic conditions (dystonia), suggesting a possible role in their pathophysiology. Proprioceptive feedback is a fundamental component of sensorimotor integration allowing effective planning and execution of voluntary movements. Rehabilitation has become an essential element in the management of patients with MDs, and there is a strong rationale to include proprioceptive training in rehabilitation protocols focused on mobility problems of the upper limbs. Proprioceptive training is aimed at improving the integration of proprioceptive signals using "task-intrinsic" or "augmented feedback." This perspective article reviews the available evidence on the effects of proprioceptive stimulation in improving upper limb mobility in patients with MDs and highlights the emerging innovative approaches targeted to maximizing the benefits of exercise by means of enhanced proprioception.
Frontiers in Human Neuroscience 11/2014; 8:961. · 2.90 Impact Factor
[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: 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 06/2014; · 4.13 Impact Factor
[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; · 3.67 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. · 4.13 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: Spasticity is the velocity-dependent increase in muscle tone due to the exaggeration of stretch reflex. It is only one of the several components of the upper motor neuron syndrome (UMNS). The central lesion causing the UMNS disrupts the balance of supraspinal inhibitory and excitatory inputs directed to the spinal cord, leading to a state of disinhibition of the stretch reflex. However, the delay between the acute neurological insult (trauma or stroke) and the appearance of spasticity argues against it simply being a release phenomenon and suggests some sort of plastic changes, occurring in the spinal cord and also in the brain. An important plastic change in the spinal cord could be the progressive reduction of postactivation depression due to limb immobilization. As well as hyperexcitable stretch reflexes, secondary soft tissue changes in the paretic limbs enhance muscle resistance to passive displacements. Therefore, in patients with UMNS, hypertonia can be divided into two components: hypertonia mediated by the stretch reflex, which corresponds to spasticity, and hypertonia due to soft tissue changes, which is often referred as nonreflex hypertonia or intrinsic hypertonia. Compelling evidences state that limb mobilisation in patients with UMNS is essential to prevent and treat both spasticity and intrinsic hypertonia.
BioMed Research International 01/2014; 2014:354906. · 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; · 4.13 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; · 4.62 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.