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Biomedical subjects

Laura Vacca

Publications and source records attributed to Laura Vacca.

9 recordsLinked to original sources
PubMed2005

Intermittent vs continuous levodopa administration in patients with advanced Parkinson disease: a clinical and pharmacokinetic study.

BACKGROUND: Levodopa-related motor complications can be an important source of disability for patients with advanced Parkinson disease. Current evidence suggests that these motor complications are related to the relatively short half-life of levodopa and its potential to induce pulsatile stimulation of striatal dopamine receptors. Motor complications can be diminished with a continuous infusion of levodopa. OBJECTIVE: To investigate the specific pharmacokinetic changes associated with the benefits of levodopa infusion. DESIGN: We performed an open-label study in 6 patients with Parkinson disease who experienced severe motor complications while receiving standard oral formulations of levodopa/carbidopa. Patients were subsequently treated for 6 months with continuous daytime intraintestinal infusions of levodopa methyl ester. Levodopa pharmacokinetic studies were performed at baseline and 6 months in 3 of these patients. RESULTS: Compared with treatment with intermittent doses of a standard oral formulation of levodopa, continuous infusion provided significant improvement in both "off periods" and dyskinesia. Results of plasma pharmacokinetic studies demonstrated that compared with oral administration, continuous levodopa infusion was associated with a significant increase in the levodopa area under the curve and avoided the low plasma trough levels seen with oral drug administration. CONCLUSIONS: This study confirms that a continuous levodopa infusion is associated with reduced motor complications compared with the standard oral formulation of the drug in patients with advanced PD. Pharmacokinetic studies demonstrate that reduced motor complications are associated with avoiding low plasma levodopa trough levels and are not adversely affected by relatively high plasma levodopa concentrations. We propose that if levodopa/carbidopa could be administered orally in a manner that mirrors the pharmacokinetic pattern of the infusion, it might lead to a similar reduction in motor complications.

Administration, Oral↗
PubMed2005

A novel family with an unusual early-onset generalized dystonia.

We report on an Italian family in which three brothers and their maternal grandfather had a generalized early-onset dystonia with mild parkinsonian signs. Genetic testing excluded the rapid-onset dystonia-parkinsonism locus (DYT12; OMIM*128235), autosomal recessive Parkin locus (PARK2; OMIM *602544), and DYT1 dystonia. Three affected siblings were found to share an identical haplotype at the X-linked dystonia-parkinsonism locus (XDP; Lubag; OMIM*314250). This haplotype differed from the haplotype observed in Filipino patients, ruling out the hypothesis of a common underlying mutation. In addition, direct sequencing analysis of the putative disease causing changes observed in Filipino patients were not found in the Italian patients. The condition we describe could be a newly recognized dystonia syndrome with parkinsonism.

Adult↗
PubMed2005

Relationship between eye symptoms and blepharospasm: a multicenter case-control study.

Although patients with primary blepharospasm (BSP) commonly report experiencing ocular symptoms before the onset of orbicular spasms, the precise frequency and pathogenic role of this subjective ocular discomfort are poorly understood. We conducted a multicenter case-control study to investigate symptoms related to disorders of the anterior segment of the eye, administering a questionnaire to 165 patients with BSP and 180 age- and gender-matched control patients with hemifacial spasm. On a validation sample, our questionnaire yielded high accuracy in detecting eye diseases (predominantly, dry eye syndrome) using detailed ophthalmological examination as the criterion. Logistic regression analysis indicated a significant association between ocular symptoms at disease onset and BSP. Ocular symptoms starting in the year preceding disease onset (short-latency symptoms) showed a stronger association with BSP than ocular symptoms occurring earlier in time (long-latency symptoms). The association was stronger when short-latency symptoms developed from 40 to 59 years of age, whereas this was not observed for long-latency symptoms. Our findings support the view that eye symptoms associated with BSP result from eye diseases and may be involved in the pathogenesis of BSP. The differential risk of developing BSP, based on age at onset of ocular symptoms, suggests that age and eye diseases may interact in giving rise to BSP.

Age of Onset↗
PubMed2003

Dual dopamine agonist treatment in Parkinson's disease.

We studied the effectiveness of cabergoline as an adjunct in patients with early Parkinson's disease receiving another dopamine agonist (pramipexole or ropinirole), at the maximal permitted dose. The study enrolled 47 patients: 35 had motor fluctuations and were receiving a dopamine agonist with levodopa; and 12, without motor fluctuations, were receiving a dopamine agonist without levodopa. These medications had in all cases failed to achieve adequate symptom control. In the 35 patients with motor fluctuations, when cabergoline was added to therapy, the time spent in the OFF period decreased by 65.6% (from 3.14+/-1.11 to 1.08+/-1.07 hours p<0.0001); and the Unified Parkinson's Disease Rating Scale (UPDRS) motor score decreased by 19.24% (from 41.68+/-12.6 to 33.66+/-10.22; (p<0.0001) during the OFF condition, and by 7.11% (from 17.01+/-6.63 to 15.8+/-7.22; p<0.001) during the ON condition. Nocturnal akinesia improved in all the patients except one. In the 12 patients without motor fluctuations, when cabergoline was added, the UPDRS score improved by 34.4% (from 23.5+/-5.3 to 15.5+/-4.7). This open study shows that dual dopamine agonist therapy can be useful in the symptomatic treatment of patients with early or more advanced Parkinson's disease receiving therapy with or without levodopa.

Adult↗
PubMed2002

Botulinum toxin A treatment for primary hemifacial spasm: a 10-year multicenter study.

BACKGROUND: Botulinum toxin A (BTX) is the currently preferred symptomatic treatment for primary hemifacial spasm (HFS), but its long-term efficacy and safety are not known. OBJECTIVE: To assess the long-term effectiveness and safety of BTX in the treatment of primary HFS. DESIGN: Retrospective review of medical records of the 1st and 10th years of treatment. SETTING: Outpatient clinics of 4 Italian university centers in the Italian Movement Disorders Study Group. PARTICIPANTS: A series of 65 patients with primary HFS who had received BTX injections regularly for at least 10 years. MAIN OUTCOME MEASURES: Mean duration of improvement and quality of the effect induced by the preceding treatment (measured using a patient self-evaluation scale) and occurrence and duration of adverse effects in the 1st and 10th years of treatment. RESULTS: Using a mean BTX dose per treatment session similar to that used by others, we obtained a 95% response rate and an overall mean duration of improvement of 12.6 weeks during year 1. The effectiveness of BTX in relieving the symptoms of primary HFS, as measured by the response rate and average duration of improvement, remained unchanged in the 1st and 10th years. Patients needed statistically similar BTX doses in the 1st and 10th years. The rate of local adverse effects (including upper lid ptosis, facial weakness, and diplopia) diminished significantly in the 10th year of treatment. CONCLUSION: Treatment with BTX effectively induces sustained relief from symptoms of HFS in the long term, with only minimal and transient adverse reactions.

Adult↗
PubMed2002

Prospective randomized trial of lisuride infusion versus oral levodopa in patients with Parkinson's disease.

Motor complications are a major source of disability for patients with advanced Parkinson's disease. Surgical therapies provide benefit to some, but these treatments are expensive and associated with adverse effects. Current research indicates that motor complications are associated with abnormal, intermittent, pulsatile stimulation of denervated dopamine receptors using short acting dopaminergic agents such as levodopa. Retrospective studies suggest that the use of longer-acting more continuous dopaminergic therapies can improve both motor fluctuations and dyskinesia. We performed a prospective, long-term (4-year) trial comparing patients randomized to receive subcutaneous infusion of the dopamine agonist lisuride versus conventional therapy with oral levodopa and dopamine agonists. We demonstrate that patients receiving lisuride infusions experienced a significant reduction in both motor fluctuations and dyskinesia compared with patients receiving standard dopaminergic therapies. Benefits persisted for the 4-year duration of the study. Mean Unified Parkinson's Disease Rating Scale scores in "ON" and "OFF" states did not significantly change between baseline and 4 years for patients in the lisuride group, but deteriorated in patients in the levodopa group. This study indicates that continuous lisuride infusion can be beneficial for patients with advanced Parkinson's disease and reverse established motor fluctuations and dyskinesia.

Administration, Oral↗
PubMedDate not supplied

A frequent LRRK2 gene mutation associated with autosomal dominant Parkinson's disease.

Mutations in the LRRK2 gene have been identified in families with autosomal dominant parkinsonism. We amplified and sequenced the coding region of LRRK2 from genomic DNA by PCR, and identified a heterozygous mutation (Gly2019 ser) present in four of 61 (6.6%) unrelated families with Parkinson's disease and autosomal dominant inheritance. The families originated from Italy, Portugal, and Brazil, indicating the presence of the mutation in different populations. The associated phenotype was broad, including early and late disease onset. These findings confirm the association of LRRK2 with neurodegeneration, and identify a common mutation associated with dominantly inherited Parkinson's disease.

Adult↗
PubMedDate not supplied

Apomorphine infusion and the long-duration response to levodopa in advanced Parkinson's disease.

The authors investigated the long-duration response to levodopa in advanced Parkinson's disease. Eight patients with advanced Parkinson's disease disabled by severe ON/OFF fluctuations treated by chronic daytime subcutaneous apomorphine infusion with supplemental oral levodopa were studied. On day 1, oral levodopa was withdrawn at 4:00 pm and on the following morning subcutaneous apomorphine infusion was continued at the same rate without levodopa therapy. While receiving apomorphine alone, seven of the eight patients turned ON, and their usual dyskinesias returned. The ON phase persisted for 60 to 100 minutes (mean, 185.7 minutes) but then, despite continued, constant-rate apomorphine infusion to stabilize plasma levels, switched to an OFF phase. The authors conclude that the clinical effect of apomorphine is sustained by levodopa long-duration response. This effect is probably the result of postsynaptic mechanisms. In patients with advanced Parkinson's disease, the long-duration response to levodopa is present although slightly diminished.

Administration, Oral↗