PubMed Health⌕ Search

Biomedical subjects

F Stocchi

Publications and source records attributed to F Stocchi.

At least 19 recordsLinked to original sources
PubMed2006

Symptom relief in Parkinson disease by safinamide: Biochemical and clinical evidence of efficacy beyond MAO-B inhibition.

In an open pilot study, doses of safinamide (100, 150, and 200 mg once a day, higher than previously tested) were administered to 13 parkinsonian patients along with a stable dose of dopamine (DA) agonist, causing a significant progressive improvement in motor performance as evaluated by the Unified Parkinson Disease Rating Scale (UPDRS) part III over an 8-week period (4.2 points; P < 0.001). In association with levodopa, the same doses of safinamide in another group of patients (N = 11) induced a significant decrease in motor fluctuations (UPDRS part IV, 2.1 points; P < 0.001), accompanied by a dose-proportional increase of the levodopa AUC, up to 77% from baseline. Because MAO-B was fully inhibited (95%) at all doses tested, we suggest that these biochemical and symptomatic dose-dependent effects must be related to additional mechanisms of action, such as inhibition of glutamate release, increased dopamine release, or inhibition of dopamine re-uptake. These hypotheses are under investigation and will pursue confirmation in controlled clinical trials.

Adult↗
PubMed2006

Rasagiline: defining the role of a novel therapy in the treatment of Parkinson's disease.

Parkinson's disease (PD) is a therapy area with considerable unmet needs. The current key targets for PD treatment include the slowing of disease progression, improved control of motor fluctuations in advanced disease and the treatment of non-motor symptoms. In view of such major requirements, it is important to consider how new drug treatments fit into the context of PD therapy, and the practical advantages that they may offer in the management of PD in clinical practice. Rasagiline is a novel, second-generation, irreversible, selective monoamine oxidase type B inhibitor that is indicated for the treatment of idiopathic PD, either as initial monotherapy or as adjunct therapy (with levodopa) for patients experiencing end-of-dose motor fluctuations. This review assesses the outcome from several large-scale clinical studies that have investigated the use of rasagiline in early and advanced PD patient populations and discusses the role of rasagiline within the current scope of PD therapy.

Delayed-Action Preparations↗
PubMed2005

Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes.

OBJECTIVE: To assess the prevalence, nature, and associated phenotypes of PINK1 gene mutations in a large series of patients with early-onset (<50 years) parkinsonism. METHODS: The authors studied 134 patients (116 sporadic and 18 familial; 77% Italian) and 90 Italian controls. The whole PINK1 coding region was sequenced from genomic DNA; cDNA was analyzed in selected cases. RESULTS: Homozygous pathogenic mutations were identified in 4 of 90 Italian sporadic cases, including the novel Gln456Stop mutation; single heterozygous truncating or missense mutations were found in another 4 Italian sporadic cases, including two novel mutations, Pro196Leu and Gln456Stop. Pathogenic mutations were not identified in the familial cases. Novel (Gln115Leu) and known polymorphisms were identified with similar frequency in cases and controls. In cases carrying single heterozygous mutation, cDNA analysis detected no additional mutations, and revealed a major pathogenic effect at mRNA level for the mutant C1366T/Gln456Stop allele. All patients with homozygous mutations had very early disease onset, slow progression, and excellent response to l-dopa, including, in some, symmetric onset, dystonia at onset, and sleep benefit, resembling parkin-related disease. Phenotype in patients with single heterozygous mutation was similar, but onset was later. CONCLUSIONS: PINK1 homozygous mutations are a relevant cause of disease among Italian sporadic patients with early-onset parkinsonism. The role of mutations found in single heterozygous state is difficult to interpret. Our study suggests that, at least in some patients, these mutations are disease causing, in combination with additional, still unknown factors.

Adolescent↗
PubMed2005

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.

Adult↗
PubMed2004

Improvement of motor function in early Parkinson disease by safinamide.

A median safinamide (SAF) dose of 70 mg/day (range 40 to 90 mg/day) increased the percentage of parkinsonian patients improving their motor scores by > or =30% from baseline (responders) after 3 months from 21.4% (placebo) to 37.5% (p < 0.05, calculated by logistic regression analysis). In a subgroup of 101 patients under stable treatment with a single dopamine agonist, addition of SAF magnified the response (47.1% responders, mean 4.7-point motor score decrease; p > or = 0.05). These results suggest that doses of SAF exerting ion channel block and glutamate release inhibition add to its symptomatic effect and warrant exploration of higher doses.

Adult↗
PubMed2004

Entacapone improves the pharmacokinetic and therapeutic response of controlled release levodopa/carbidopa in Parkinson's patients.

The aim of this trial was to evaluate the effects of the COMT inhibitor entacapone on both the pharmacokinetic profile and clinical efficacy of controlled release levodopa in Parkinson's disease (PD) patients. Twelve PD patients experiencing "end-of-dose" type motor fluctuations were evaluated in this single-blind, randomized cross-over study. A single dose of either entacapone (200 mg) or placebo was co-administered with controlled release levodopa. Blood samples were taken every 30 minutes for 3 hours, and in 6 patients, sampling was continued for a further 3 hours. The clinical response to treatment was evaluated using the Unified Parkinson's Disease Rating Scale motor score. Addition of entacapone to levodopa treatment prolonged the "on" phase of the PD patients by 37% (p<0.05). This increased duration of 'on' time was concomitant with a significant increase in levodopa bioavailability (AUC). These data confirm the ability of entacapone to enhance the clinical efficacy of controlled release levodopa formulations, and provide further evidence that entacapone is of value in extending the benefits of levodopa in PD patients experiencing motor fluctuations.

Aged↗
PubMed2004

Continuous apomorphine infusion (CAI) and neuropsychiatric disorders in patients with advanced Parkinson's disease: a follow-up of two years.

This study was performed to assess whether patients with Parkinson's disease (PD)develop cognitive and psychiatric impairments more frequently during therapy with continuous subcutaneous apomorphine infusion (CAI) compared to the standard oral treatment. Thirty consecutive PD patients with severe motor fluctuations were included. Of them, 12 patients received the CAI treatment, while the remaining 18 continued the treatment with oral dopaminergic drugs. The two groups were evaluated with neuropsychological,psychiatric and motor tests at baseline and after two years. The off-awake daily duration and the levodopa dosage were significantly reduced in the patients infused with apomorphine.In comparison with the baseline evaluation, the neuropsychiatric assessment did not change in either of groups at the follow-up, except for a significant improvement of mood in the CAI treated group.

Antiemetics↗
PubMed2003

Continuous apomorphine infusion and neuropsychiatric disorders: a controlled study in patients with advanced Parkinson's disease.

The aim of this study was to assess whether patients with Parkinson's disease (PD) develop cognitive and psychiatric complications more frequently during prolonged therapy with continuous apomorphine infusion compared with standard oral treatment. Thirty consecutive PD patients with severe motor fluctuations were included in the study. Twelve patients accepted the treatment with subcutaneous continuous apomorphine infusion, while the remaining 18 preferred to continue with oral dopaminergic therapy. The two groups were evaluated with neuropsychological, psychiatric, and motor tests at baseline and after 1 year. The off daily duration and the levodopa dosage were significantly reduced in infused patients. The neuropsychiatric assessment did not change in both groups compared with baseline, except for a significant improvement of mood in the apomorphine group.

Aged↗
PubMed2002

A six-month multicentre, double-blind, bromocriptine-controlled study of the safety and efficacy of ropinirole in the treatment of patients with Parkinson's disease not optimally controlled by L-dopa.

OBJECTIVES: To compare the safety and efficacy of ropinirole and bromocriptine as adjunct therapy in patients with Parkinson's disease (PD) not optimally controlled by L-dopa. METHODS: A randomised, double-blind trial in which 555 patients were assigned to three treatment groups according to the level of daily dosage of L-dopa, presence of motor fluctuations, and use of dopamine agonist before study entry. Patient response was defined as at least a 20% reduction in daily L-dopa dose plus: for patients with no prior treatment and no motor fluctuations, a 20% reduction in UPDRS motor score; for patients with motor fluctuations, a 20% reduction in time spent "off"; and for patients already taking an agonist, an improvement on the CGI scale. RESULTS: Safety assessments showed no significant differences in the two treatment groups for patients without prior dopamine-agonist therapy. In the group of patients with prior dopamine-agonist therapy, more patients reported adverse events in the ropinirole group (90% versus 79%, p < 0.001). The proportions of responders tended to be higher in ropinirole groups compared with bromocriptine groups and, in the subgroup with motor fluctuations, this difference was statistically significant (9.1% versus 0.0%, respectively; p < 0.05). CONCLUSIONS: Both drugs were well tolerated. In patients receiving a relatively high dose of L-dopa and requiring the addition of a dopamine agonist to control motor fluctuations or dyskinesias, ropinirole was significantly more effective than bromocriptine.

Adult↗
PubMed2002

Autosomal recessive early onset parkinsonism is linked to three loci: PARK2, PARK6, and PARK7.

Autosomal recessive, early onset parkinsonism (AREP) is genetically heterogeneous. Mutations in the parkin gene (PARK2 locus, chromosome 6q) account for up to 50% of AREP families. The parkin protein displays ubiquitin-ligase activity for different targets, which accumulate in the brain of patients with parkin defect and might cause neurodegeneration. Two new AREP loci (PARK6 and PARK7) have been recently mapped on chromosome 1p and confirmed in independent datasets, suggesting that both might be frequent. The three AREP forms display similar clinical phenotypes. Recruiting new families will help cloning the defective genes at PARK6 and PARK7 loci. This will contribute to unraveling the pathogenesis of AREP, and it is also expected to foster our understanding of molecular events underlying classic Parkinson's disease.

Age of Onset↗
PubMed2002

Modification of respiratory function parameters in patients with severe Parkinson's disease.

Respiratory dysfunction remains one of the most common causes of death in patients with complicated Parkinson's disease (PD). The aim of this study was to investigate pulmonary function in fluctuating PD patients during "on" and "off" states of the disease. We studied 12 fluctuating, non-smoking PD patients (H&Y stages 3-5) without a history of lung or cardiovascular disease; all patients underwent Hoehn and Yahr scale (H&Y) and Unified Parkinson Disease Rating Scale (UPDRS items 18-31) to evaluate extrapyramidal impairment, as well as pulmonary function tests (PFT) and arterial blood gas analyses to assess respiratory function. All evaluations were performed during a stable on state of disease and in an off state produced by 12 hours of therapy withdrawal. A restrictive pattern of flow-volume loop was observed both in on and off states of disease. In the off state, we found a significant worsening in both FEV1 and FVC; the FEV1/FVC ratio was unmodified. These results suggest a restrictive pattern of flow-volume loop in these patients.

Aged↗
PubMed2002

Combination of two different dopamine agonists in the management of Parkinson's disease.

An alternative approach to the symptomatic treatment of parkinsonian patients with and without motor fluctuations is to use dual dopamine agonists. The aim of this study was to investigate the symptomatic effect of administrating a second dopamine agonist to parkinsonian patients already assuming pramipexole or ropinirole. As the second dopamine agonist we chose cabergoline, a drug with a long half life, whose pharmacological profile differs from that of the newer non-ergot-derived dopamine-receptor agonists. In this pilot study we enrolled 27 patients: 21 patients had motor fluctuations and were receiving levodopa plus a dopamine agonist, and 6 patients without motor fluctuations were receiving a dopamine agonist without levodopa. This open study shows that dual dopamine agonist therapy (cabergoline plus pramipexole or ropinirole) may be used in the symptomatic treatment of patients with Parkinson's disease receiving therapy with or without levodopa.

Aged↗
PubMed2001

Long-duration effect and the postsynaptic compartment: study using a dopamine agonist with a short half-life.

A possible reason why levodopa induces a sustained, stable motor benefit during the first months to years of therapy may be its long duration of action. This long-duration effect may be due either to a presynaptic storage mechanism or to postsynaptic pharmacodynamic changes. We previously reported that the dopamine agonist ropinirole induced a long-duration response (LDR) in levodopa-naive patients with Parkinson's disease. In this study, we investigated motor responses to the short half-life dopamine agonist lisuride in a group of levodopa naive parkinsonian patients. Once lisuride reached its maximum effect, it was substituted, in randomized order, with placebo. Neither investigators nor patients knew when the active drug was switched to placebo. When patients were switched from lisuride to placebo, their Unified Parkinson's Disease Rating Scale (UPDRS) motor scores and tapping test and screw scores declined to baseline values within a mean 9.0 +/- 1.9 days. The results confirmed that, like ropinirole and levodopa, the short-acting dopamine agonist lisuride induces a long-duration response, probably due to postsynaptic changes.

Adult↗
PubMed2001

Subcutaneous continuous apomorphine infusion in fluctuating patients with Parkinson's disease: long-term results.

Fluctuations in motor disability and dyskinesias are the major problem in the long-term treatment of Parkinson's disease (PD). Many authors and ourselves have shown that by giving patients a continuous infusion of levodopa it is possible to control motor fluctuations. Levodopa can be administered continuously only by intravenous, intragastric or intrajejunal delivery. Continuous dopaminergic stimulation can be achieved more easily by infusing dopamine agonists subcutaneously. Apomorphine is a potent water-soluble dopamine receptor agonist that has been shown to successfully control motor fluctuation when subcutaneously infused in complicated parkinsonian patients. We report the clinical data of 30 PD patients having at least five years of treatment with subcutaneous continuous apomorphine infusion.

Aged↗
PubMed2001

Epidemiology of multiple system atrophy. ESGAP Consortium. European Study Group on Atypical Parkinsonisms.

Multiple system atrophy (MSA) is a form of atypical parkinsonism with unknown etiology. The epidemiological studies conducted up to now on this disease are scarce. The incidence rate is about 0.6 cases per 100,000 persons per year. The prevalence rates show 4-5 cases per 100,000 persons. In Italy, about 4,900 prevalent cases have been estimated. The mean onset age is about 54 years; the median survival is 7-9 years. Only one case-control study has been performed on this disease. This study showed an increased risk of MSA associated with occupational exposure to organic solvents, plastic monomers and additives, pesticides and metals. Smoking habits seem to be less frequent in MSA cases (as in Parkinson's disease cases) than in healthy controls. Quinn's clinical criteria and those of the Consensus Conference promoted by the American Academy of Neurology are in fair agreement. We have performed a case-control study on 73 MSA cases, 146 hospital controls and 73 population controls.

Age of Onset↗
PubMed2001

Epidemiology of progressive supranuclear palsy. ESGAP Consortium. European Study Group on Atypical Parkinsonisms.

Progressive supranuclear palsy (PSP) is a rare form of parkinsonism. The incidence rates are about 0.3-1.1 cases per 100,000 persons. The only two case-control studies performed up to now show conflictual results as regards education and residence in rural areas. Recently, a cluster of PSP and atypical parkinsonism has been observed in French Antilles. The hypothesis is that a consumption of both tropical fruit and herbal tea may be associated with PSP onset. Some PSP families with a probably autosomal dominant transmission have been described. A high frequency of a tau haplotype (H1/H1) associated with PSP is reported by some authors. The significance of this association is still not clear. We have performed a case-control study on 58 PSP cases, 116 hospital controls and 58 population controls.

Age of Onset↗