To report the results of a national survey aimed at quantifying the current level of diffusion of Levodopa/carbidopa intestinal gel (LCIG) in Italy. Sixty Parkinson's Disease (PD) specialists in Italy were invited to complete a survey... more
To report the results of a national survey aimed at quantifying the current level of diffusion of Levodopa/carbidopa intestinal gel (LCIG) in Italy. Sixty Parkinson's Disease (PD) specialists in Italy were invited to complete a survey covering issues on clinical and practical aspects of LCIG therapy. Clinical features of 905 patients were collected retrospectively. The majority of centres reported the use of a multidisciplinary team, biochemistry testing, neurophysiological and neuropsychological tests before and after treatment, in addition to caregivers' training and patient's follow as outpatients. Most centres (60%) used internal guidelines for patient selection. The overall rate of adverse events was 55.1%. Weight loss, chronic polyneuropathy and stoma infection were the most frequently reported. 40% of centres used replacement therapy with Vitamin B12 and Folic acid from the start of LCIG and continued this for the duration of treatment. The rate of discontinuation...
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L-dopa-induced dyskinesias (LID) is a common motor side effect of levodopa therapy of Parkinson's disease (PD). The identified predictors may only partially account for the risk of developing LID and genetic factors may contribute to... more
L-dopa-induced dyskinesias (LID) is a common motor side effect of levodopa therapy of Parkinson's disease (PD). The identified predictors may only partially account for the risk of developing LID and genetic factors may contribute to this variability. The present study is aimed to investigate whether polymorphisms in the dopamine transporter gene (DAT) are associated with the risk of developing LID. Genotyping of the 40-bp VNTR (rs28363170) and rs393795 (A/C) polymorphisms of the DAT gene was performed in a well-characterized cohort of 181 Italian PD patients in treatment with L-DOPA for 3 years or more. The results of our study show that there is no difference in dyskinesias prevalence among carriers of the two DAT gene polymorphisms. However, the combination of the two genotypes 10R/10R (rs28363170) and A carrier (rs393795) of the DAT gene reduces the risk of LID occurrence during long-term therapy with l-DOPA with respect to the PD subjects who did not carry these alleles (OR...
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Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the... more
Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the development of these disorders. Our study was done in three stages. First, we did genome-wide linkage analysis of an Italian family with dominantly inherited Parkinson's disease to identify the disease locus. Second, we sequenced the candidate gene in an international multicentre series of unrelated probands who were diagnosed either clinically or pathologically with Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. As a control, we used gene sequencing data from individuals with abdominal aortic aneurysms (who were not examined neurologically). Third, we enrolled an independent series of patients diagnosed clinically with Parkinson's disease and controls with no signs or family history of Parkinson's dis...
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The clinical presentation of Parkinson's disease (PD) includes a wide spectrum of non-motor features, including cardiovascular autonomic failure. To evaluate cardiovascular autonomic status and cardiac functional capacity in... more
The clinical presentation of Parkinson's disease (PD) includes a wide spectrum of non-motor features, including cardiovascular autonomic failure. To evaluate cardiovascular autonomic status and cardiac functional capacity in drug-naïve PD patients. 18 newly-diagnosed PD patients underwent laboratory cardiovascular autonomic function tests using power spectral analysis of the R-R interval, blood pressure (BP) short-term variability and non-invasive baroreflex sensitivity (BRS). A two-dimensional (2D) transthoracic echocardiogram, spirometry and cardiopulmonary exercise test (CPET) were also performed. Thirteen patients underwent myocardial scintigraphy with [I] metaiodobenzylguanidine (MIBG). At rest, total power spectral analysis of heart rate variability was lower in PD patients than in controls. BRS decreased during sympathetic activation in both patients and controls. While echocardiography and spirometry were normal, a mild degree of exercise intolerance was observed at the CPET in PD patients (mean V'O: 83% of predicted; mean W: 80% of predicted). The heart-to-mediastinum (H/M) ratio of MIBG uptake was pathologically impaired in 9 patients, one of whom displayed a definite cardiovascular dysautonomic pattern. Our results confirm that subclinical to overt cardiovascular autonomic failure may occur from the early stages of PD. The less efficient adaptive response to physical stimuli during the CPET and postural changes observed in untreated PD patients possibly reflect cardiac sympathetic denervation, although the involvement of PD-related motor impairment in physical deconditioning cannot be excluded.
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Research Interests: Humans, Female, Male, Clinical Sciences, Aged, and 4 moreMiddle Aged, Adult, Parkinson Disease, and Cohort Studies
Excessive daytime sleepiness (EDS) in Parkinson's disease (PD) is due to either treatment-related factors or the disease itself. The study of this disturbing phenomenon in de novo... more
Excessive daytime sleepiness (EDS) in Parkinson's disease (PD) is due to either treatment-related factors or the disease itself. The study of this disturbing phenomenon in de novo parkinsonian patients may contribute to a better understanding of its pathophysiology. We conducted a case control study in which we compared 25 PD patients who had never been treated before with dopaminergic drugs (de novo PD), 50 PD patients being treated with dopaminergic drugs (treated PD), and 25 healthy control subjects, all of whom were matched for age and gender. EDS was measured by means of the Epworth Sleepiness Scale (ESS) and quality of sleep by means of the Pittsburgh Sleep Quality Index (PSQI). ESS and PSQI scores were not statistically different between de novo PD patients and controls, whereas they were significantly higher in treated PD. Differences in ESS score variability were best explained by the treatment effect, whereas there was no clear correlation between PSQI and any of the clinical variables considered.
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Parkinsonism death rates in Italy were analysed for the period 1969-1987. Crude death rates increased markedly in the above period for both sexes. Age-specific rates underwent important changes during these twenty years. In the years... more
Parkinsonism death rates in Italy were analysed for the period 1969-1987. Crude death rates increased markedly in the above period for both sexes. Age-specific rates underwent important changes during these twenty years. In the years 1969-71 the age-specific death rates reach their maximum values at ages 80-84, after which they decline. In the years 1983-87 the rates continue to increase until the 80-84 age group, when they reach a plateau. Moreover, in the more recent years the age-specific rates for ages < 70-75 are lower, whereas those for the older ages are approximately twice as high as the values in the earlier years. The age-adjusted death rates (1981 Italian population) increased slightly in the period studied for both sexes. Rates for males exceed those for females in all the previous analyses. Minor differences appeared in death distribution between the five large areas Italy was divided into. The observed changes in death rates are likely to reflect: changes in age composition of the population over time, greater attention to parkinsonian patients and especially increased duration of this disease following the discovery of its neurochemical basis and effective medical treatment.
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... Members of the Study Group on Atypical Parkinsonisms include Michele De Mari, MD, AngeloMoramarco, MD, and Paolo Lamberti, MD ... D'Antonio, MD, Stefania Salvetti, MD, and Ubaldo Bonuccelli, MD, Institute of Neurology,... more
... Members of the Study Group on Atypical Parkinsonisms include Michele De Mari, MD, AngeloMoramarco, MD, and Paolo Lamberti, MD ... D'Antonio, MD, Stefania Salvetti, MD, and Ubaldo Bonuccelli, MD, Institute of Neurology, University of Pisa, Pisa, Italy; Vincenzo Bonifati, MD ...
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Acute high dose treatment with cocaine in planaria has been shown to produce hyperkinesia followed by immobilization, thus suggesting progressive neuronal dopamine (DA) depletion. On the contrary, treatment with low doses of cocaine... more
Acute high dose treatment with cocaine in planaria has been shown to produce hyperkinesia followed by immobilization, thus suggesting progressive neuronal dopamine (DA) depletion. On the contrary, treatment with low doses of cocaine inhibits motor activity in planaria, without producing hyperkinesias. Here we investigated the morpho-functional changes of the DA presynaptic terminals following cocaine treatment in planaria (acute high dose and chronic low dose). Neuronal DA content was determined by means of histochemical methods, and nerve cell ultrastructure was examined by electron microscopy. The effects of cocaine were compared to those of L-dopa, reserpine (used as positive and negative controls, respectively) and normal untreated specimens. Presynaptic vesicles and DA content were significantly reduced by chronic low-dose cocaine treatment. These effects were even more robust when the drug was acutely administered at high dose. Thus, depletion of DA vesicles is produced by coc...
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A double-blind crossover trial was carried out on the sleep-inducing activity of a new preparation (oral drops) of lormetazepam versus placebo. Twenty patients were included and requested to subjectively evaluate their sleep, both by... more
A double-blind crossover trial was carried out on the sleep-inducing activity of a new preparation (oral drops) of lormetazepam versus placebo. Twenty patients were included and requested to subjectively evaluate their sleep, both by analogue scales and semiquantitative ratings, during 2-night administration of the two products. Also, the usual parameters, sleep duration, sleep latency and number of awakenings were evaluated. Lormetazepam drops appeared to exert the same actions as the capsules' preparation, being significantly different from those of the placebo.
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Setoperone (R 52245), a serotonin S2 and dopamine D2 receptor blocker, was tested on eight healthy male volunteers, receiving 5 or 40 mg orally, in order to assess the modifications of plasma prolactin levels, as an index of receptor... more
Setoperone (R 52245), a serotonin S2 and dopamine D2 receptor blocker, was tested on eight healthy male volunteers, receiving 5 or 40 mg orally, in order to assess the modifications of plasma prolactin levels, as an index of receptor blocking activity. Both doses significantly increased plasma levels, confirming the dopamine blocking activity. In vitro and in vivo studies have shown serotonin S2 receptor blockade and lysergic acid diethylamide antagonist activity. Setoperone is proposed as a possible new neuroleptic drug.
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Research Interests: Movement disorders, Brain, Amines, Animals, Amphetamine, and 4 moreLevodopa, Rats, S-Adenosylmethionine, and Apomorphine
On the basis of a reassessment of the aetiopathogenetic problem and the neuroendocrine implications, the therapeutic effectiveness of a prolactin inhibitor, 2-alpha-Br-ergocryptine (CB 154), in Parkinson's disease is assessed. Five... more
On the basis of a reassessment of the aetiopathogenetic problem and the neuroendocrine implications, the therapeutic effectiveness of a prolactin inhibitor, 2-alpha-Br-ergocryptine (CB 154), in Parkinson's disease is assessed. Five patients were treated for a total of two weeks using doses between 10 and 15 mg/die. CB 154 was found to act as a dopaminergic receptor agonist at nigro-striatal level, considerably improving tremor and rigidity and to a lesser extent bradykinesia and total disability.
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To study the frequency, clinical features and clinical genetics of familial Parkinson's disease (PD). Family history for PD and tremors was studied in 100 consecutive PD cases. Spouses served as controls. Clinical features were... more
To study the frequency, clinical features and clinical genetics of familial Parkinson's disease (PD). Family history for PD and tremors was studied in 100 consecutive PD cases. Spouses served as controls. Clinical features were compared between personally verified familial and sporadic PD cases, from the same consecutive clinical series. Clinical genetic analysis was performed in a larger group of non-consecutive multicase PD families. Family history for PD was positive in 24% of consecutive PD cases and in 6% of spouse controls (p < 0.001). When family history for isolated tremor is also considered, the number of positive cases rises to 43% compared with 9% in controls (p < 0.001). Nine of the consecutive cases had at least one living affected relative, for a total of 20 familial PD cases. These familial cases showed an earlier onset age when compared with sporadic ones from the same consecutive series. Within 22 non-consecutive PD families with at least two living and pe...
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The aim of our study was to investigate the efficacy of pramipexole in advanced parkinsonian patients by means of an acute stimulation test. We studied the motor effects of pramipexole in fluctuating parkinsonian patients by comparing the... more
The aim of our study was to investigate the efficacy of pramipexole in advanced parkinsonian patients by means of an acute stimulation test. We studied the motor effects of pramipexole in fluctuating parkinsonian patients by comparing the response to acute levodopa with the response to levodopa + pramipexole. The adjunct of pramipexole to levodopa increased the time spent on from 136 +/- 22.3 to 186 +/- 20.6 minutes (p<0.01), while it did not change the latency to on, the magnitude of the motor improvement, or the duration and severity of dyskinesias. The main effect of pramipexole in fluctuating parkinsonian patients is an increased duration of the on phase.
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Freezing of gait (FOG) is as a brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk. Structural neuroimaging studies on FOG in PD using volumetric techniques yielded variable and... more
Freezing of gait (FOG) is as a brief, episodic absence or marked reduction of forward progression of the feet despite the intention to walk. Structural neuroimaging studies on FOG in PD using volumetric techniques yielded variable and partially conflicting findings, probably reflecting the heterogeneity and complexity of the phenomenon. The aim of this study was to further explore the differences in local gray matter (GM) volume in patients with PD with and without FOG by using Voxel-Based Morphometry (VBM). We enrolled 26 patients (7 women and 19 men) with a diagnosis of PD in stable treatment with dopaminergic therapy. Thirteen patients classified as FOG+ were matched with thirteen non-freezer (FOG-) PD patients. All 26 participants underwent a detailed neuropsychological assessment as well as a VBM analysis derived from T1 weighted 3T MRI. The patient groups did not significantly differ for age, disease duration, H&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;Y stage, UPDRS part-III or educational attainment. No significant differences of cognitive profile emerged. PD-FOG+ patients showed a pattern of relative GM atrophy in left posterior parietal gyrus compared with PD-FOG-. Our results suggest that a specific pattern of cortical volume reduction involving posterior parietal cortex contributes to the occurrence of FOG in PD. These data agree with the growing body of evidence considering the parietal posterior cortex as an associative area involved in spatial control of motor behavior, par-taking in response selection to sensory evaluation.