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Maurizio Zibetti,
Aristide Merola,
Valeria Ricchi,
Alice Marchisio,
Carlo Alberto Artusi,
Laura Rizzi,
Elisa Montanaro,
Dario Reggio,
Claudio De Angelis, Mario Rizzone,
Leonardo Lopiano
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ABSTRACT: Duodenal infusion of levodopa/carbidopa gel (Duodopa) is an effective treatment option for advanced Parkinson's disease (PD). Long-term clinical experience up to 16 years suggests that the safety of this procedure is acceptable, while several observational studies showed that Duodopa reduces motor fluctuations and dyskinesias improving patients' quality of life (QoL). The aim of this study is to investigate the long-term motor and cognitive outcome of Duodopa treatment in advanced PD patients and its' impact on the QoL. Twenty-five consecutive PD patients were assessed using the Unified PD rating scale (UPDRS), a battery of neuropsychological tests, and the PD questionnaire (PDQ-39) at baseline and after a mean period of three years of Duodopa treatment. Seventeen out of 25 patients reached the follow-up evaluation; five patients discontinued Duodopa and three patients died of causes unrelated to drug infusion. Duodopa improved motor complications (UPDRS-IV) and quality of life (PDQ-39). A sub-group of subjects (41 %) developed a significant deterioration of cognitive functions over time. The most common adverse events were dislocation and the kinking of the intestinal tube. In conclusion, Duodopa therapy is effective in the long-term treatment of advanced PD patients. Continuous enteral levodopa infusion achieves a reduction of motor fluctuations and dyskinesias improving patients' QoL, despite the progression of PD motor symptoms and a significant decline in cognitive functions in a sub-group of patients.
Journal of Neurology 07/2012; · 3.47 Impact Factor
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Aristide Merola,
Maurizio Zibetti,
Carlo Alberto Artusi,
Alice Marchisio,
Valeria Ricchi,
Laura Rizzi,
Serena Angrisano,
Nichy Arduino,
Michele Lanotte, Mario Rizzone,
Leonardo Lopiano
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ABSTRACT: Patients with young onset Parkinson's disease (YOPD) are often candidates for subthalamic nucleus-deep brain stimulation (STN-DBS). Nevertheless, few data have been reported on the long term STN-DBS clinical outcome of YOPD versus non-young onset Parkinson's disease (n-YOPD) patients.
In this study, the issue of whether YOPD might represent a long term positive predictive factor for STN-DBS was addressed, comparing follow-up data for 20 YOPD and 40 n-YOPD patients (20 treated after <15 years of disease duration and 20 treated after ≥15 years of disease duration).
Mean scores for the Unified Parkinson's Disease Rating Scale (UPDRS) sections were compared 1 year, 5 years and, for 34 patients (12 YOPD and 22 n-YOPD), ≥7 years after surgery. Furthermore, a Cox proportional hazard regression model was used to determine the influence of age at PD onset, clinical phenotype, disease duration and duration of motor complications on the development of stimulation and medication resistant symptoms.
YOPD patients showed a lower incidence of stimulation and medication resistant symptoms and a lower mortality rate; also, the tremor dominant clinical phenotype was associated with a lower risk of developing dementia, hallucinations and constipation. No significant differences in UPDRS scores were observed between n-YOPD patients treated after <15 years of PD and those treated after ≥15 years of PD.
In this series of STN-DBS treated patients, YOPD was associated with a medium to long term lower incidence of stimulation and medication resistant symptoms.
Journal of neurology, neurosurgery, and psychiatry 12/2011; 83(3):251-7. · 4.87 Impact Factor
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Maurizio Zibetti,
Aristide Merola,
Laura Rizzi,
Valeria Ricchi,
Serena Angrisano,
Corrado Azzaro,
Carlo Alberto Artusi,
Nichy Arduino,
Alice Marchisio,
Michele Lanotte, Mario Rizzone,
Leonardo Lopiano
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ABSTRACT: Deep brain stimulation of the subthalamic nucleus is an effective treatment for advanced Parkinson's disease. The benefits of bilateral subthalamic stimulation are well documented, and some studies reported outcomes with a follow-up of 5 to 6 years; nevertheless, few data are available beyond 5 years. We report a long-term prospective evaluation of 14 consecutive parkinsonian patients, treated by bilateral subthalamic stimulation for at least 9 years. Motor symptoms, activity of daily living, and motor complications were evaluated by means of the Unified Parkinson's Disease Rating Scale, while cognition and mood were assessed with a specific neuropsychological test battery; medication intake, stimulation parameters, comorbidity, and adverse events were also recorded. Patients were evaluated before surgery and at 1, 5, and ≥ 9 years after surgery. At last follow-up, deep brain stimulation significantly improved the motor score by 42% compared to baseline, whereas activities of daily living were no longer improved; there was a 39% reduction in the dosage of dopaminergic drugs and a 59% improvement of L-dopa-related motor complications. The neuropsychological assessment showed that 4 patients (29%) developed a significant cognitive decline over the follow-up period. These results indicate a persistent effect of deep brain stimulation of the subthalamic nucleus on the cardinal motor symptoms in advanced Parkinson's disease patients in the long-term; however, a worsening of patients' disability, mainly due to disease progression, was observed.
Movement Disorders 11/2011; 26(13):2327-34. · 4.51 Impact Factor
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ABSTRACT: Subthalamic nucleus deep brain stimulation (STN DBS) is an effective therapeutic option for advanced Parkinson's disease (PD). Nevertheless, some patients develop gait disturbances despite a persistent improvement of PD segmental symptoms. Recent studies reported that stimulation of STN with low frequencies produced a positive effect on gait disorders and freezing episodes.
To evaluate the effects of 80 Hz stimulation frequency on gait in PD patients undergoing STN DBS and to determine whether such effects are maintained over time.
We evaluated 11 STN DBS treated PD patients who had developed gait impairment several years after surgery. Gait was assessed by means of the Stand-Walk-Sit (SWS) test. Motor symptoms and activities of daily living were evaluated through the Unified PD Rating Scale (UPDRS). The stimulation frequency was switched from 130 Hz to 80 Hz, adapting the voltage to maintain the same total delivered energy. Patients were assessed at baseline and 3 hours after switching the stimulation frequency to 80 Hz. Follow-up evaluations were carried out after 1, 5, and 15 months. The clinical global improvement scale was rated at every follow-up visit.
A significant improvement of gait (SWS test) was evident immediately after switching the stimulation frequency to 80 Hz, with no deterioration of PD segmental symptoms. However, gait improvement was no longer detectable by the SWS test at follow-up evaluations 1, 5, and 15 months later. Three patients were switched back to 130 Hz because of unsatisfactory control of motor symptoms. Of the eight patients maintained at 80 Hz up to 15 months, five showed a global improvement and three showed no change.
Stimulation frequency at 80 Hz has an immediate positive effect on gait in STN DBS treated patients; however, the objective gait improvement is not maintained over time, limiting the use of this frequency modulation strategy in the clinical setting.
Brain Stimulation 07/2011; 5(3):388-92. · 3.76 Impact Factor
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ABSTRACT: The effects of subthalamic nucleus (STN) stimulation on the spatio-temporal organization of locomotor commands directed to lower limb muscles were studied in subjects with idiopathic Parkinson's Disease (PD) by recording the EMG activity produced during steady-state walking in representative thigh (rectus femoris, RF, and semimembranosus, SM) and leg (gatrocnemius medialis, GAM, and tibialis anterior, TA) muscles, under four experimental conditions: basal stimulation OFF, unilateral (right and left) stimulation ON, and bilateral stimulation ON. Locomotor profiles of all of the muscles tested were found to be substantially affected by STN stimulation, either in terms of restoration/enhancement of the main activity bursts or normalization of recruitment timing thereof. Responses showed relatively higher statistical significance in the distal groups (GAM and TA) and, within them, for the EMG components called into action over the ground-contact (ankle dorsiflexors) and midstance (ankle plantarflexors) phases of the stride cycle. In line with data obtained from clinical rating, unilateral stimulation produced less consistent EMG changes compared with bilateral stimulation. However, at variance with clinical effects, which prevailed on the side of the body contralateral to stimulation, EMG responses to unilateral stimulation were usually symmetrical. Results indicate that the impact of STN stimulation on locomotor activation of lower limb muscles in PD is characterized by: 1) substantial effects exhibiting differential topographical (distal versus proximal) and stride-phase (stance versus swing) consistency and 2) absence of the lateralized actions typically observed for the clinical signs of the disease. Interaction with the activity of functionally different executive systems might account for the observed pattern of responsiveness.
IEEE Transactions on Neural Systems and Rehabilitation Engineering 07/2007; 15(2):182-9. · 3.44 Impact Factor
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Lorenzo Priano,
Gianni Albani,
Andrea Brioschi,
Sara Calderoni,
Leonardo Lopiano, Mario Rizzone,
Roberta Cavalli,
Maria Rosa Gasco,
Francesco Scaglione,
Franco Fraschini,
Bruno Bergamasco,
Alessandro Mauro
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ABSTRACT: We studied absorption, efficacy, and tolerability in Parkinson's disease (PD) of a new preparation of apomorphine included in a microemulsion and administered by transdermal route (Apo-MTD). Twenty-one PD patients were treated with levodopa plus oral dopamine-agonists (T0), with levodopa alone (T1), finally with levodopa plus Apo-MTD (T2). Apo-MTD provided therapeutic plasma levels for many hours, improved Unified Parkinson's Disease Rating Scale III scores, and reduced total duration of off periods compared to T0 and T1. We concluded that Apo-MTD is absorbed and demonstrates clinical efficacy and long action. Therefore, it seems a promising add-on treatment for uncontrolled prolonged off phases in PD patients, but chronic tolerability needs further study.
Movement Disorders 09/2004; 19(8):937-42. · 4.51 Impact Factor
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Lorenzo Priano MD,
Gianni Albani MD,
Andrea Brioschi MD,
Sara Calderoni,
PhD Leonardo Lopiano MD,
Mario Rizzone MD,
Roberta Cavalli PhD,
Maria Rosa Gasco PhD,
PhD Francesco Scaglione MD,
Franco Fraschini PhD, [......],
Gianni Albani,
Andrea Brioschi,
Leonardo Lopiano, Mario Rizzone,
Roberta Cavalli,
Maria Rosa Gasco,
Francesco Scaglione,
Franco Fraschini,
Bruno Bergamasco,
Alessandro Mauro
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[hide abstract]
ABSTRACT: We studied absorption, efficacy, and tolerability in Parkinson's disease (PD) of a new preparation of apomorphine included in a microemulsion and administered by transdermal route (Apo-MTD). Twenty-one PD patients were treated with levodopa plus oral dopamine-agonists (T0), with levodopa alone (T1), finally with levodopa plus Apo-MTD (T2). Apo-MTD provided therapeutic plasma levels for many hours, improved Unified Parkinson's Disease Rating Scale III scores, and reduced total duration of off periods compared to T0 and T1. We concluded that Apo-MTD is absorbed and demonstrates clinical efficacy and long action. Therefore, it seems a promising add-on treatment for uncontrolled prolonged off phases in PD patients, but chronic tolerability needs further study. © 2004 Movement Disorder Society
Movement Disorders 07/2004; 19(8):937 - 942. · 4.51 Impact Factor
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ABSTRACT: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a very effective therapy for the advanced phase of Parkinson's disease (PD). The functional inhibition of this nucleus is responsible for a significant improvement of cardinal motor symptoms of PD. The aim of the study was the assessment of the effectiveness of STN DBS on bradykinesia by the analysis of movement time (MT) in 2 conditions: with the stimulators turned on ('stim-on') or off ('stim-off').
After pharmacological wash-out, 10 patients submitted to bilateral STN DBS were studied with an MT analyser in 3 phases: stim-on, stim-off and stim-on again, in order to establish the time course of MT lengthening, the posteffect duration and the latency of the effect of STN DBS. MT data were then compared with the UPDRS motor scores.
After turning off the stimulators, MT progressively increases, reaching a plateau after about 30 min, which then lasts for the subsequent observation time (2 h). A significant elongation is achieved after the first 5 min. Upon pulse generator activation, MT shows a dramatic shortening, already significant after 2 min. Moreover, we observed a significant correlation between MT and the severity of PD, higher with bradykinesia than with rigidity or tremor.
Our findings show a relevant effect of STN DBS on MT, a parameter strongly related to bradykinesia. This study confirms the effectiveness of STN inhibition on the whole parkinsonian triad, suggesting that this target can be considered a proper choice for the surgical treatment of advanced PD.
European Neurology 02/2003; 50(2):94-9. · 1.81 Impact Factor
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ABSTRACT: Expectations about future events are known to trigger neural mechanisms that affect both perception and action. Here we report that different and opposite expectations of bad and good motor performance modulate the therapeutic effects of subthalamic nucleus stimulation in Parkinsonian patients who had undergone chronic implantation of electrodes for deep brain stimulation. By analyzing the effects of subthalamic stimulation on the velocity of movement of the right hand, we found hand movement to be faster when the patients expected a good motor performance. The expectation of good performance was induced through a placebo-like procedure, thus indicating that placebo-induced expectations have influence on the treatment outcome. All these effects occurred within minutes, suggesting that expectations induce neural changes very quickly.
Neuroreport 09/2002; 13(11):1383-6. · 1.66 Impact Factor
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ABSTRACT: Deep Brain Stimulation (DBS) of the Subthalamic Nucleus (STN) represents a proper choice for the treatment of advanced Parkinson's disease (PD). A correct selection of the patients as candidates for the surgery is essential for a good outcome. In this study, we analyzed the exclusion causes of a series of PD patients hospitalized for the selection protocol.
Ninety-eight PD patients as potential candidates for the STN DBS were studied. All patients were hospitalized and underwent a clinical evaluation of the PD stage, a levodopa challenge, a MR of the brain and a neuropsychological assessment.
The percentage of subjects considered not suitable for the surgery was 29.6%. A single cause of exclusion was present in 65.5% of not suitable patients, while multiple causes were present in 34.5%. The most frequent cause of exclusion was the finding of neuropsychological or psychic disorders (48.3%); in 37.9% of the patients, the motor disability was not severe enough to justify the surgery, while in 31%, we found relevant abnormalities at the brain MR. Three patients (10.3%) were poorly motivated for the surgery, while in three others (10.3%), we found a significant illness other than PD.
The finding that about 30% of the PD patients potentially suitable for STN DBS presents some exclusion causes underlines the importance of a careful selection of the candidates for this surgery.
Journal of the Neurological Sciences 04/2002; 195(2):167-70. · 2.35 Impact Factor
