Modular one-to-many clutchable actuator for a soft elbow exosuit.

Exoskeletons have been developed for a wide range of applications, from the military to the medical field, with the aim of augmenting human performance or compensating for neuromuscular deficiencies. However, to empower the high number of degrees of freedom of the human body, they often employ a high number of motors, increasing the size, weight and power consumption of the system. We hereby present an actuation strategy to empower our elbow exosuit that adopts a single motor to drive multiple, independently actuated, degrees of freedom. This paradigm, known as One-to-many, is achieved using a modular design where each module comprises a clutchable mechanism that allows to convert a single directional motion from the prime mover to a selectable bidirectional output. Moreover, the mechanism has a locking feature that enables the wearer of the exoskeleton to hold a static load with a minimal power consumption. We present a simple controller for the clutchable unit based on a finite-state machine model, and evaluate its performance for varying input velocities. The system is shown to have a bandwidth of 1.5 Hz, sufficient for daily elbow movements, whilst retaining a compact design.

A cross-sectional multicenter study of cognitive and behavioural features in multiple system atrophy patients of the parkinsonian and cerebellar type.

Imaging and neuropathology studies have demonstrated significant abnormalities not only in subcortical, but also in cortical regions of patients with multiple system atrophy (MSA). This raises the possibility that cognitive dysfunction may contribute to the clinical spectrum of this disorder to a greater extent than it is currently not widely appreciated. In this cross-sectional multicenter study from the European multiple system atrophy study group ( http://www.emsa-sg.org ), we applied an extensive neuropsychological test battery in a series of 61 clinically diagnosed probable MSA patients. The results demonstrated that general cognitive decline as assessed by MMSE was uncommon (2 out of 61 patients <24). In contrast, frontal lobe-related functions (as measured by FAB) were impaired in 41 % of patients, with abstract reasoning and sustained attention less compromised. This pattern was similar to our control group of 20 patients with Parkinson's disease (matched for disease duration and age at onset). There was no difference in cognitive performance between MSA patients with the parkinsonian versus the cerebellar variant. Behaviourally, MSA patients had greater depression than PD and in the case of MSA of the cerebellar variant significantly lower anxiety. Our data show that cognitive abnormalities are relatively frequent in multiple system atrophy and this involves primarily frontal-executive functions. Their contribution to clinical disability and disease progression needs to be addressed in larger prospective studies.

Artistic productivity and creative thinking in Parkinson's disease.

BACKGROUND AND PURPOSE: Creative drive and enhanced artistic-like production may emerge in patients with Parkinson's disease (PD) during dopaminergic therapy. However, it has not been described to date whether this artistic-like production results from dopaminergic drugs triggering innate skills or it could be considered as a repeated behavior possibly associated with impulse control disorders (ICDs). METHODS: We investigated creative drive in a cohort of cognitively preserved patients with PD by means of the Torrance Test of Creative Thinking (TTCT). We also investigated a putative association between creative drive and ICDs in 36 PD patients with (PD-c) or without (PD-nc) increased artistic-like production and 36 healthy controls (HC). We considered artistic-like productivity to be enhanced if patients reported working on any form of art more than 2h per day after the introduction of dopaminergic treatment. The TTCT, the Barratt Impulsiveness Scale (BIS-11A), the Minnesota Impulsive Disorders Interview (MIDI), and the Punding Rating Scale were applied. RESULTS: Mean TTCT score of PD-c was found to be similar to HC (169.4±51.6 vs. 170.2±69.7, respectively), and both PD-c and HC had significantly higher TTCT scores than patients with PD-nc (125.4±46.1 P<0.05). TTCT did not correlate with any demographic or clinical data in both PD subgroups. No correlation was found between TTCT, BIS-11A, and MIDI. CONCLUSIONS: Our study suggests that newly acquired artistic-like production in patients with PD is not associated with impulsivity or ICDs. Artistic-like production might represent the emerging of innate skills in a subset of predisposed patients with PD on dopaminergic therapy.

Duodenal levodopa infusion improves quality of life in advanced Parkinson's disease.

BACKGROUND: A significant percentage of patients with Parkinson's disease (PD) continue to experience motor fluctuations and dyskinesias despite the association of dopamine agonists and levodopa with COMT or MAO-B inhibitors. The use of apomorphine infusion is limited by compliance while deep brain stimulation is feasible only for a small number of patients mostly because of age constraints. OBJECTIVE: To assess prospectively the effectiveness of duodenal levodopa infusion on quality of life as well as motor features in patients with advanced PD. In all but 1 case levodopa infusion was stopped at nighttime. METHODS: We report the outcome of 22 PD patients, followed for up to 2 years, who were on continuous duodenal levodopa/carbidopa infusion through percutaneous endoscopic gastrostomy. RESULTS: We found a significant reduction in 'off' period duration as well as dyskinesia severity (Unified Parkinson's Disease Rating Scale part IV, items 33 and 39). There was significant improvement in the 39-item Parkinson's Disease Quality of Life Questionnaire as well as in the Unified Parkinson's Disease Rating Scale part II up to the 2-year follow-up. Five patients withdrew: 2 for poor compliance and 3 for adverse events (1 was related to percutaneous endoscopic gastrostomy). CONCLUSIONS: These results demonstrate significant clinical improvements in quality of life and activities of daily living consistent with the occurrence of a satisfactory therapeutic response and a reduction in dyskinesia severity.

Striatal dopamine transporter binding in patients with Parkinson's disease and severe occupational hydrocarbon exposure.

We used 123I-Ioflupane SPECT to study striatal dopamine transporter (DAT) binding in 36 Parkinson's disease (PD) patients with history of severe occupational exposure to hydrocarbons. Data were compared with 38 PD patients without exposure history as well as healthy controls. Both PD cohorts showed significant striatal uptake decrements compared with controls. We found significantly lower values in the whole striatum of exposed compared with non-exposed patients (0.83 +/- 0.25 vs. 1.05 +/- 0.39; P = 0.004), more pronounced in the putamen (0.61 +/- 0.24 vs. 0.85 +/- 0.42; P = 0.004). We conclude that severe occupational exposure to hydrocarbons may modify disease course and ultimately accelerate nigro-striatal denervation.

Parkinson's disease, chronic hydrocarbon exposure and striatal neuronal damage: a 1-H MRS study.

Several patients with Parkinson' s disease (PD) reveal an history of chronic exposure to hydrocarbon-solvents. Chronic exposure to hydrocarbon-solvents has been proposed as a risk factor for more severe forms of PD with earlier onset of symptoms and reduced response to dopaminergic therapy. A direct correlation between disease severity and exposure degree has been previously shown. Seven exposed PD patients (two with low degree exposure and five with high degree exposure), 10 unexposed PD patients matched for sex, age and Hoehn and Yahr scale (=3 in the "on" phase), and 10 unexposed PD patients matched for sex, age and l-dopa daily intake instead of disease severity (Hoehn and Yahr scale=3.5 in the "on" phase) were studied. Twenty normal subjects without previous exposure to hydrocarbon-solvents and matched for age and sex with HPD patients were studied for comparison. The purpose of the study was to assess neuronal degeneration in the striatum of exposed vs unexposed PD patients. The authors investigated whether neuronal damage/loss was detectable in the lentiform nucleus measuring N-acetylaspartate (NAA) levels by 1-H MRS. Multiple single voxel MRS water-suppressed spectra were obtained also from the white matter and the occipital lobe. NAA was normal in the lentiform nucleus of patients with low exposure as well as in patients with no exposure whereas it was decreased in PD patients with high degree exposure. White matter and occipital lobe NAA content was normal both in exposed and unexposed PD patients. Clinical expression is more severe in PD patients with previous high degree solvent exposure because of the associated post-synaptic damage of the nigro-striatal pathway.

The G6055A (G2019S) mutation in LRRK2 is frequent in both early and late onset Parkinson's disease and originates from a common ancestor.

BACKGROUND: Mutations in the gene Leucine-Rich Repeat Kinase 2 (LRRK2) were recently identified as the cause of PARK8 linked autosomal dominant Parkinson's disease. OBJECTIVE: To study recurrent LRRK2 mutations in a large sample of patients from Italy, including early (<50 years) and late onset familial and sporadic Parkinson's disease. RESULTS: Among 629 probands, 13 (2.1%) were heterozygous carriers of the G2019S mutation. The mutation frequency was higher among familial (5.1%, 9/177) than among sporadic probands (0.9%, 4/452) (p<0.002), and highest among probands with one affected parent (8.7%, 6/69) (p<0.001). There was no difference in the frequency of the G2019S mutation in probands with early v late onset disease. Among 600 probands, one heterozygous R1441C but no R1441G or Y1699C mutations were detected. None of the four mutations was found in Italian controls. Haplotype analysis in families from five countries suggested that the G2019S mutation originated from a single ancient founder. The G2019S mutation was associated with the classical Parkinson's disease phenotype and a broad range of onset age (34 to 73 years). CONCLUSIONS: G2019S is the most common genetic determinant of Parkinson's disease identified so far. It is especially frequent among cases with familial Parkinson's disease of both early and late onset, but less common among sporadic cases. These findings have important implications for diagnosis and genetic counselling in Parkinson's disease.

An overview of parkinsonian syndromes: data from the literature and from an Italian data-base.

Recent molecular biology research on neurodegenerative diseases, including parkinsonisms, has identified mutations in the genes that code for the proteins alpha-synuclein and tau, which have been used to classify them into synucleinopathies and tauopathies. The synucleinopathies include, besides the most common and well studied Parkinson's disease (PD), dementia with Lewy bodies, which accounts for approximately 20% of all cases of dementia in the elderly, and multiple system atrophy, whereas the tauopathies include rare and rapidly progressive syndromes, such as progressive supranuclear palsy and corticobasal degeneration. Data we collected at our center in over 2900 parkinsonian patients show that PD accounts for no more than 70% of parkinsonisms. The various syndromes have many features in common that make the differential diagnosis difficult in the early stages of disease. Our data are consistent with the findings reported in the international literature and provide additional information useful for differential diagnosis.

123I-Ioflupane/SPECT binding to striatal dopamine transporter (DAT) uptake in patients with Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy.

We used SPECT and the tracer (123)I-Ioflupane to measure dopamine transporter (DAT) binding in the caudate nucleus and the putamen of 70 patients with Parkinson's disease (PD), 10 with multiple system atrophy (MSA-P type), and 10 with progressive supranuclear palsy (PSP). Data were compared with 12 age-matched control subjects. We found significant reductions in mean striatal values in all three forms of parkinsonism. However, decrements were significantly greater in PSP (0.51+/-0.39, p<0.01) compared with MSA-P (0.70+/-0.33) and PD (0.95+/-0.38). No differences were found between MSA and PD. Putamen/caudate ratios were greater in PSP (0.83+/-0.12, p<0.01) than in PD (0.51+/-0.11), suggesting a more-uniform involvement of dopamine nerve terminals in both caudate nucleus and putamen. Our results confirm that DAT binding can provide an accurate and highly sensitive measure of dopamine degeneration. PSP patients may show a different pattern of neuronal loss compared with MSA and PD.

Poor metabolization of n-hexane in Parkinson's disease.

Although genomic screening studies have identified several genes associated with Parkinson's disease (PD), there is evidence that environmental factors are also involved in the pathogenesis of the disease and that hydrocarbon-solvents may be one of them. The genetic component is less evident in late-onset PD. To assess whether age and PD may affect the catabolism of the hydrocarbon n-hexane, a two-part study was performed. In the first part the urinary levels of its main metabolites, 2,5-hexanedione and 2,5-dimethylpyrroles, were measured in 108 patients and 108 healthy controls, matched by age and sex. Metabolite urinary excretion was significantly reduced in PD patients as compared with controls and was inversely related to age in both groups. In the second part the same comparison was made between 24 non-smoking and 10 smoking patients, matched to controls, after smoking of a hydrocarbon-rich cigarette. In these subjects also n-hexane and 2,5-hexanedione blood levels were measured. There was no appreciable difference in n-hexane blood levels between patients and controls in non-smokers, whereas there was a significant increase in patients over controls in smokers (p < 0.01). 2,5-hexanedione blood levels were significantly lower in patients than in healthy controls, both in non-smokers and in smokers, but the reduction was more pronounced in smokers (-46.3 % versus -10.7 %). The same was true for 2,5-hexanedione and 2,5-dimethylpyrrole urinary levels. This study suggests that aging and PD may be associated with a reduction in the capacity to eliminate the hydrocarbon n-hexane. This metabolic alteration may play a role in the pathogenesis of PD.

Is underweightness still a major problem in Parkinson's disease patients?

OBJECTIVE: To evaluate the current rate of underweightness amongst Parkinson's disease (PD) patients at an Italian referral centre. DESIGN: Epidemiological study on consecutive patients presenting for the first time in a 16-month period. SETTING: Nutritional service of PD referral centre in Milan, Italy. SUBJECTS: Three-hundred and sixty-four PD patients diagnosed according to CAPIT criteria. METHODS: Anthropometric assessments: BMI and waist-to-hip ratio; evaluation of therapeutic physical activity (h/week). RESULTS: Three-hundred and sixty-four patients were included (180 female, 184 male), mean (s.d.) age 65.9 (8.9) y, mean (s.d.) duration of PD 10.6 (5.3) y; 134 patients (37%) were overweight and 92 (25%) were obese; 11 (3%) were underweight; 127 (35%) had normal BMI. No important differences in BMI according to sex and smoking status were observed. There was highly significant inverse correlation between duration of disease and BMI (P<0.001): mean (s.d.) duration of disease was 9.7 (4.7) y in overweight+obese patients, 11.1 (5.5) y in patients with normal BMI and 14.1 (7.2) y in underweight patients (P=0.0059). The waist-to-hip ratio was a cardiovascular risk factor in 47.7% of men and 73.8% of women. Mean (s.d.) therapeutic physical activity was 1.07 (1.59) h/week in overweight and obese patients vs 1.61 (2.04) h/week in patients with normal BMI (50.5% increase; P=0.03). CONCLUSIONS: At present underweightness is uncommon in PD patients in Italy; this may be due to the increase in the prevalence of overweightness in the Italian population and to modern antiparkinsonian therapy.

Tolerability of paroxetine in Parkinson's disease: a prospective study.

Depression is a common finding in patients with Parkinson's disease (PD). Traditionally, depression has been treated with tricyclic antidepressants, which are often associated with undesirable side effects that may limit their use in PD. Few studies have been performed with selective serotonin reuptake inhibitors (SSRIs) in these patients. We assessed the tolerability of the SSRI antidepressant paroxetine (10-20 mg once per day) in 65 outpatients with PD and depression for a period of at least 3 months. Treatment was continued for 125.3+/-89.6 days (mean +/- standard deviation) in 52 patients. In these subjects the Hamilton Disease Rating Scale improved from 21.7+/-6.4 to 13.8+/-5.8 (p <0.001). Overall, 13 patients stopped paroxetine after 9.6+/-10.6 days because of adverse reactions. Two patients reported increased "off" time and tremor that reversed after treatment was stopped. No risk factors for intolerance were identified. Paroxetine is a safe and effective drug to treat depression in PD.

Hydrocarbon exposure and Parkinson's disease.

BACKGROUND: Single cases of parkinsonism have been associated with hydrocarbon solvents. OBJECTIVE: To determine whether exposure to hydrocarbon solvents is related to PD. METHODS: Cohort study of 990 patients with PD according to Core Assessment Program for Intracerebral Transplantations (CAPIT) criteria, selected from 1455 consecutive subjects presenting at a referral center; case-control study assessing Unified PD Rating Scale scores (motor score as primary endpoint) in all subjects with positive history of hydrocarbon solvent exposure (n = 188), matched for duration of disease and gender to 188 subjects selected from the remaining 802 with a negative history. Two subgroups in the case-control study included the following: 1) response to apomorphine (n = 26); 2) brain MRI (n = 15). PET imaging (n = 9) was compared with that of historic controls. RESULTS: Exposed patients were younger (61.0 +/- 9.4 versus 64.7 +/- 9.4 years, p = 0.002), predominantly male (76.4% versus 45.2%, p = 0.0001), less educated (8.4 +/- 4.2 versus 10.1 +/- 4.4 years, p = 0.0001), and younger at onset of disease (55.2 +/- 9.8 versus 58.6 +/- 10 years, p = 0.014). Exposure to hydrocarbon solvents directly correlated to disease severity (r = 0. 311) and inversely correlated to latency period (r = -0.252). Nine blue-collar occupations accounted for 91.1% of exposures. CONCLUSIONS: Occupations involving the use of hydrocarbon solvents are a risk factor for earlier onset of symptoms of PD and more severe disease throughout its course. Hydrocarbon solvents may be involved in the etiopathogenesis of PD, which does not have a major genetic component.

An overnight switch to ropinirole therapy in patients with Parkinson's disease. Short communication.

Patients with Parkinson's disease (n = 68) switched from pergolide or bromocriptine to ropinirole overnight (dose equivalence ratios 1:6 and 10:6, respectively). The activities of daily living score for the Unified Parkinson's Disease Rating Scale (UPDRS) was significantly improved 4 weeks after the bromocriptine-ropinirole switch. All other UPDRS scores, including that for the side-effect component, were not significantly different after either switch. Overnight switching may be a safe therapeutic approach that may reduce hospitalisation and related socio-economic costs.

T1 and T2 in the brain of healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy: relation to iron content.

PURPOSE: To investigate the potential of magnetic resonance imaging for identification and quantification of brain iron in healthy subjects, patients with Parkinson disease, and patients with multiple system atrophy. MATERIALS AND METHODS: Forty-nine subjects were studied at 1.5 T. Regional T1 and T2 values were compared among groups and also with histopathologic estimates of iron concentration. RESULTS: In healthy subjects, interregional T1 and T2 differences in the cortex and basal ganglia showed a good correlation with reported values for iron concentration, and intraregional variations were generally consistent with reported variability of iron concentration. Patients with multiple system atrophy had T1 and T2 shortening in the globus pallidus consistent with reported increases in ferritin-bound iron and changes in the putamen consistent with accumulation of hemosiderin (posterior portion) and neuromelanin (remainder). Both groups of patients had changes in the cortex that are consistent with decreased ferritin concentration and T2 changes in white matter consistent with demyelination. Patients with Parkinson disease also had a (nonsignificant) T2 shortening in the substantia nigra that was suggestive of iron accumulation. CONCLUSION: Most of the T1 and T2 findings appear to be related to changes in iron content and form and may possibly be used as indicators of such changes.

n-Hexane-induced parkinsonism: pathogenetic hypotheses.

n-Hexane, similar hydrocarbons, and derivatives are common environmental pollutants and by-products of lipid peroxidation, and they may have a nigrotoxic effect like that of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. This report describes our second case of parkinsonism in a subject exposed to n-hexane. Positron emission tomography studies demonstrated regional striatal abnormalities of the nigrostriatal dopaminergic system and of glucose metabolism that were different from those found in idiopathic Parkinson's disease.

Pergolide mesylate in Parkinson's disease treatment.

In the past 15 years, clinical data of over 1,500 patients treated with pergolide mesylate have been published. Pergolide is a dopamine agonist with a potent stimulating effect on D2 and also on D1 receptors. This pharmacodynamic characteristic seems the most effective in increasing the motility in Parkinson's disease. Pergolide has been used almost exclusively as an adjunct to levodopa treatment. Its positive effects seems to be related to its long plasma half life, about 27 hours, and 5-6 hours of clinical activity; it has shown to be effective on all parkinsonian symptoms except for the reduction of postural reflexes, it reduces off periods and compared to bromocriptine, it considerably improves the activities of daily living. Adverse reactions are, for the most part, mild and reversible, they mostly include nausea and gastroenteric disturbances.