Levodopa-carbidopa intestinal gel infusion (LCIG) in Parkinson disease with genetic mutations.

BACKGROUND: Levodopa-carbidopa intestinal gel infusion (LCIG) is a therapeutic option for advanced Parkinson disease (PD) patients with troublesome motor complications, unresponsive to conventional oral treatment. There is some evidence to suggest that the genetic background may influence the clinical presentation and rate of progression of PD. Whether the genetic background influences the outcome of device-assisted therapies is currently debated. Some studies have investigated the effectiveness of deep brain stimulation (DBS) in PD patients with different genetic background, while evidence is lacking regarding LCIG. METHODS: A cohort of LCIG patients underwent genetic testing. The motor and neuropsychological outcomes of LCIG were retrospectively analyzed. RESULTS: Fifty-six patients were analyzed, nine of them (15%) had at least one mutation/variant in a PD-associated gene: five GBA1, two SNCA, one LRRK2, one PRKN; 13 (23%) carried the BDNF Val66Met polymorphism. The mean duration of follow-up was 4.9 ± 2.6 years. There were no significant differences in motor or neuropsychological outcomes between patients with and without these gene mutations/variants. No cognitive worsening was observed at follow-up among GBA-PD patients, and they responded well to LCIG in terms of motor symptoms. CONCLUSIONS: Overall, we observed a significant benefit in terms of motor complications in our cohort, including patients carrying genetic mutations/variants. Due to the small sample and limited number of patients carrying genetic mutations/variants, no definitive conclusions can be drawn yet on the genotype impact on LCIG outcome. A careful selection of patients, regardless of the genetic background, is pivotal for an optimal outcome of LCIG.

Increased prevalence of impulse control disorder symptoms in endocrine diseases treated with dopamine agonists: a cross-sectional study.

INTRODUCTION: Impulse control disorders (ICDs) have been described as a side effect of dopamine agonists (DAs) in neurological as well as endocrine conditions. Few studies have evaluated the neuropsychological effect of DAs in hyperprolactinemic patients, and these have reported a relationship between DAs and ICDs. Our objective was to screen for ICD symptoms in individuals with DA-treated endocrine conditions. MATERIALS AND METHODS: A cross-sectional analysis was conducted on 132 patients with pituitary disorders treated with DAs (DA exposed), as well as 58 patients with pituitary disorders and no history of DA exposure (non-DA exposed). Participants responded to the full version of the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's disease (QUIP). RESULTS: Compared with the non-DA-exposed group, a higher prevalence of DA-exposed patients tested positive for symptoms of any ICD or related behavior (52% vs. 31%, p < 0.01), any ICD (46% vs. 24%, p < 0.01), any related behavior (31% vs. 17%, p < 0.05), compulsive sexual behavior (27% vs. 14%, p < 0.04), and punding (20% vs. 7%, p < 0.02) by QUIP. On univariate analysis, DA treatment was associated with a two- to threefold increased risk of any ICD or related behavior [odds ratio (OR) 2.43] and any ICD (OR 2.70). In a multivariate analysis, independent risk factors for any ICD or related behavior were DA use (adjusted OR 2.22) and age (adjusted OR 6.76). Male gender was predictive of the risk of hypersexuality (adjusted OR 3.82). DISCUSSION: Despite the QUIP limitations, a clear sign of increased risk of ICDs emerges in individuals with DA-treated pituitary disorders. Our data contribute to the growing evidence of DA-induced ICDs in endocrine conditions.

Levodopa/carbidopa intestinal gel infusion and weight loss in Parkinson's disease.

BACKGROUND AND PURPOSE: Weight loss (WL) is a frequent yet under-recognized complication of levodopa/carbidopa intestinal gel (LCIG) infusion, as well as a milestone of Parkinson's disease (PD) disability progression. The complex association between WL, poor nutritional status, motor complications and PD progression, however, remains unclear. METHODS: Consecutive consenting patients with PD treated with LCIG (n = 44; PD duration, 18.3 ± 6.5 years) were enrolled in an open-label observational study assessing the extent of WL occurring during LCIG treatment. As secondary aims, we correlated the nutritional status, as detected by the Mini Nutritional Assessment, with the severity of motor symptoms [Movement Disorder Society Unified Parkinson's Disease Rating Scale part III], motor complications (Unified Parkinson's Disease Rating Scale part IV), activities of daily living (Schwab and England scale), cognitive impairment (Mini Mental State Examination), depression (Beck Depression Inventory), difficulties in feeding (Edinburgh Feeding Evaluation in Dementia Questionnaire) and levodopa equivalent daily dose (LEDD). RESULTS: There was an average WL of 9.9 ± 10.5% (7.6 ± 7.1 kg) over an LCIG treatment period of 51.6 ± 28.5 months. The extent of WL correlated with the percentage of the waking day spent with dyskinesia (P < 0.05). The nutritional status correlated with motor symptom severity (P < 0.01), dysphagia (P < 0.01) and LEDD (P < 0.01). CONCLUSIONS: Weight loss may occur in patients with PD undergoing LCIG in correlation with the percentage of the waking day spent with dyskinesia. Regardless of the extent of WL, the nutritional status correlated with higher LEDD, as well as with indices of disease progression, such as motor symptom severity and dysphagia.

Sleep improvement with levodopa/carbidopa intestinal gel infusion in Parkinson disease.

BACKGROUND: Sleep disorders are common in patients with advanced Parkinson's disease (PD). Nocturnal akinesia and sleep fragmentation frequently coexist with daytime sleepiness, influencing daytime functioning. Levodopa/carbidopa intestinal gel (LCIG) infusion has been shown to improve motor complications in advanced PD, and preliminary findings suggest that sleep might improve following LCIG infusion. OBJECTIVE: To analyze the impact of LCIG infusion on sleep symptoms and daytime sleepiness in patients with PD. METHODS: Twelve consecutive patients with PD completed the PD-Sleep-Scale-version-2 (PDSS-2) and the Epworth-Sleepiness-Scale (ESS) at baseline and after 2-4 months of LCIG treatment. Activities of daily living, motor symptoms and complications were assessed with the Unified-PD-rating-Scale section II, III, and IV. RESULTS: Nocturnal sleep improved substantially in all patients switched to LCIG infusion. PDSS-2 total score and subscores for 'Disturbed sleep', 'Motor symptoms at night', and 'PD symptoms at night' were significantly reduced. ESS measures of daytime sleepiness also improved. Motor complications and activities of daily living improved significantly with LCIG. CONCLUSION: Subjective measures of sleep quality and daytime sleepiness improve in patients with advanced PD undergoing LCIG infusion. Further studies with a larger number of patients and polysomnographic recordings are needed to confirm the beneficial effect on sleep and clarify the underlying mechanisms.

Single agent epirubicin as first line chemotherapy for metastatic breast cancer patients.

In order to better explore the toxicity and the activity of high dose epirubicin (120 mg/m2, 3 weeks) we analyzed a population of 127 metastatic breast cancer patients, treated in a randomized clinical trial conducted to evaluate the cardioprotective effect of dexrazoxane against epirubicin induced cardiotoxicity. All the patients had a diagnosis of metastatic breast cancer, an ECOG performance status < or = 2 and normal hematologic, renal, hepatic and cardiac function. No prior adjuvant chemotherapy including anthracycline was allowed. Epirubicin was given at the dose of 120 mg/m2 i.v. bolus every 3 weeks. One hundred twenty five patients were evaluable for toxicity and response. Seventeen patients (11%) had a complete response and 47 patients (37%) a partial response, for an overall response rate of 48%. The median progression free and overall survivals were 8.3 months and 18.3 months, respectively. Grade 3 and 4 leukopenia were observed in 8% and 7% of the patients, respectively. The most frequent nonhematological grade 3 toxicities were alopecia (87%), nausea and vomiting (16%), and mucositis (8%). Cardiotoxicity, defined as occurrence of congestive heart failure, decrease in resting left ventricular ejection fraction (L-VEF) to < or = 45%, or 20 EF units decrease from baseline L-VEF, was observed in 19% of the patients, after a median cumulative dose of epirubicin of 720 mg/m2 (range 120-1440). This study confirms in a large series of patients the activity of high dose epirubicin; however, the high incidence of cardiotoxicity requires a careful evaluation of cardiac risk factors before treatment.