[Show abstract][Hide abstract] ABSTRACT: Tremor dominant (TD) and akinetic-rigid type (ART) are two motor subtypes of Parkinson's disease associated with different disease progression and neurochemical/neuropathological features. The role of presynaptic nigrostriatal dopaminergic damage is still controversial, poorly explored, and only assessed in medicated patients. In this study, we investigated with FP-CIT SPECT the striatal dopamine transporter (DAT) availability in drug-naïve PD patients with ART and TD phenotypes. Fifty-one de novo, drug-naïve patients with PD underwent FP-CIT SPECT studies. Patients were evaluated with Unified Parkinson's Disease Rating Scale (UPDRS) part III and Hoehn and Yahr scale (H&Y) and divided into ART (24/51) and TD (27/51) according to UPDRS part III. ART and TD patients were not different with regard to age, gender, and disease duration. However, compared to TD, ART patients presented higher UPDRS part III (p = 0.01) and H&Y (p = 0.02) and lower DAT availability in affected and unaffected putamen (p = 0.008 and p = 0.007, respectively), whereas no differences were found in caudate. Moreover, in the whole group of patients, rigidity and bradykinesia, but not tremor scores of UPDRS part III were significantly related to FP-CIT binding in the putamen. These results suggest that in newly diagnosed drug-naïve PD patients DAT availability might be different between ART and TD in relation to different disease severity.
[Show abstract][Hide abstract] ABSTRACT: Background and purposeUric acid (UA) has been studied extensively as a valuable biomarker of Parkinson's disease (PD), but its relationship with non-motor symptoms (NMS) in de novo PD has been poorly investigated. Our aim was to evaluate the usefulness of baseline serum UA as a marker of NMS progression in newly diagnosed PD.Methods
Sixty-nine newly diagnosed PD patients were enrolled. At baseline, all patients completed the NMS questionnaire (NMSQuest), and serum UA levels were measured. After 2 years, the NMSQuest was completed again and patients were categorized into four groups: NMS improvement (domain involvement at baseline but not at 2-year follow-up visit), NMS absence (domain not involved at baseline or 2-year follow-up visits), NMS presence (domain involvement both at baseline and 2-year follow-up visits) and NMS worsening (domain not involved at baseline but involved at 2-year follow-up).Resultsanova with post hoc Bonferroni correction showed that patients with NMS absence presented significantly higher UA values than patients with NMS presence with regard to the attention/memory (P = 0.023), depression/anxiety (P = 0.028) and cardiovascular domains (P = 0.002), whilst no differences were found with regard to both the NMS improvement and worsening groups. In addition, multinomial regression analysis showed that the lowest tertile of NMS progression presented higher UA levels (P = 0.023; odds ratio 0.488) compared with patients with greater NMS progression.Conclusions
This is the first report of a relationship between serum UA and presence/progression of multiple NMS in de novo PD, providing additional evidence of the reliability of UA as a biomarker of PD and opening new insights on PD neuroprotection.
European Journal of Neurology 08/2014; · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: SYNJ1 has been recently identified by two independent groups as the gene defective in a novel form of autosomal recessive, early-onset atypical parkinsonism (PARK20). Two consanguineous families were initially reported (one of Sicilian and one of Iranian origins), with the same SYNJ1 homozygous mutation (c.773G > A, p.Arg258Gln) segregating with a similar phenotype of early-onset parkinsonism and additional atypical features. Here, we report the identification of the same SYNJ1 homozygous mutation in two affected siblings of a third pedigree. Both siblings had mild developmental psychomotor delay, followed, during the third decade of life, by progressive parkinsonism, dystonia, and mild cognitive impairment. One sibling suffered one episode of generalized seizures. Neuroimaging studies revealed severe nigrostriatal dopaminergic defects, mild striatal and very mild cortical hypometabolism. Treatment with dopamine agonists and anticholinergics resulted in partial improvements. Genetic analyses revealed in both siblings the SYNJ1 homozygous c.773G > A (p.Arg258Gln) mutation. Haplotype analysis suggests that the mutation has arisen independently in this family and the Sicilian PARK20 family previously described by us, in keeping with the hypothesis of a mutational hot spot. This is the third reported family with autosomal recessive, early-onset parkinsonism associated with the SYNJ1 p.Arg258Gln mutation. This work contributes to the definition of the genetic and clinical aspects of PARK20. This newly recognized form must be considered in the diagnostic work-up of patients with early-onset atypical parkinsonism. The presence of seizures might represent a red flag to suspect PARK20.
[Show abstract][Hide abstract] ABSTRACT: To assess the long-term safety and efficacy of pramipexole as a once-daily (q.d.) extended-release oral formulation in early or advanced Parkinson's disease (PD).
In two double-blind (DB) studies of early PD and one of advanced PD,active-treatment arms received pramipexole immediate release (IR) or extended release (ER), with exposure lasting up to 33 weeks. In open-label (OL) extensions that followed immediately, subjects took ER q.d. for up to 80 weeks, with dosage adjustment permitted (range 0.375-4.5 mg q.d.).
Of 590 subjects completing an early-PD DB study, 511 entered the early-PD OL extension; 408 completed it. Reported adverse events (AEs) with incidence ≥10.0% were somnolence (15.1%), peripheral edema (11.7%) and back pain (10.6%). Of 465 subjects completing the advanced-PD DB study, 391 entered the advanced-PD OL extension; 329 completed it. Reported AEs with incidence ≥10.0%were dyskinesia (27.4%) and somnolence (13.6%). Impulse control disorders were identified by semi-structured interview in 13 subjects (1.4% of 902). In exploratory analyses, adjusted mean Unified Parkinson's Disease Rating Scale (UPDRS) PartsII + III scores (excluding ex-placebo recipients) remained substantially improved from DB baseline scores prior to pramipexole introduction, at -6.6 and -6.3 points amongst ex-DB-ER and ex-DB-IR recipients after 113 weeks of pramipexole (33 DB plus 80 OL) in early PD, and -11.5 and -9.1 after up to 113 weeks (up to 33 DB plus 80 OL) in advanced PD.
These results support the long-term safety and efficacy of pramipexole ER in early and advanced PD. AEs were typical for dopaminergic medications, and UPDRS scores suggested sustained symptomatic benefit.
European Journal of Neurology 05/2014; 21(5):736-43. · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background and purposeApathy may be either a symptom of major depression or a behavioral disturbance occurring in concomitance with depression or alone in Parkinson's disease (PD). The aim of the present study was to determine the progression of cognitive impairment in drug-naïve untreated PD patients with or without clinically significant apathy.Methods
Sixty-two PD patients with a disease duration <2 years and without history of present or past therapy with pro-dopaminergic agents were included and underwent the Apathy Evaluation Scale (S-AES), a clinical interview based on diagnostic criteria for apathy and a comprehensive neuropsychological battery to assess memory, frontal functions and visuospatial functions. Two years after the first assessment, all patients were re-evaluated on the S-AES, a clinical interview and neuropsychological tests.ResultsAccording to the cut-off value of the S-AES and diagnostic criteria for apathy, eight patients experienced apathy at both baseline and follow-up (A+A+), nine patients had apathy only at follow-up (A−A+), 37 patients never experienced apathy (A−A−) and eight patients showed apathy at the baseline only (A+A−). Cognitive performance significantly declined in all four groups. At both baseline and follow-up A+A+ performed worse than A−A− on visuospatial and frontal tests; A−A+ had lower scores than A−A− on the interference task of the Stroop test (IT-ST). Regression analysis showed that poor performance on the IT-ST at baseline was the only independent predictor of onset of apathy at follow-up.Conclusions
The results indicated a relationship between apathy and dysexecutive syndrome in early PD. Reduced scores on the IT-ST may predict development of apathy in PD patients.
European Journal of Neurology 05/2014; · 4.16 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Longitudinal studies on healthy participants have shown that subjective memory impairment (defined as subjective cognitive complaints with normal cognitive objective performance) might be a strong predictor of mild cognitive impairment (MCI). Parkinson disease (PD) also manifests cognitive disturbances, but whether subjective memory complaints may predict the development of MCI in PD has not yet been explored.
We prospectively screened newly diagnosed, untreated patients with PD in order to evaluate whether subjective memory complaints may predict development of MCI over a 2-year follow-up evaluation.
We enrolled 76 de novo untreated patients with PD. Of the 76 patients, 23 (30.3%) complained memory issues. Among the patients cognitively unimpaired at baseline, those with subjective complaints were more likely to develop MCI at follow-up. The regression model confirmed that presence of subjective memory complaints at baseline was an independent predictor of development of MCI at follow-up.
This is the first prospective study to explore the relationship between subjective and objective cognitive deficits in newly diagnosed, untreated patients. Our results provide preliminary evidence that subjective memory complaints might predict future development of MCI.
Journal of Geriatric Psychiatry and Neurology 04/2014; · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background: PARK8 is the most common known mendelian form of Parkinson's Disease (PD). It is due to mutations in the leucine-rich repeat kinase 2 (LRRK2) gene and G2019S is considered the most frequent mutation in the Caucasian population, in particular in the Southern Europe and Mediterranean countries. Objective: We assessed the frequency of the G2019S and R1441C/H/G mutations in 513 (311 M and 202 F) unrelated PD patients from Campania, in Southern Italy. Methods: Three hundreds and thirty-six patients presented a sporadic disease, and 177 had a familial history of PD or tremor. Three hundreds and eighty cases originated from the province of Naples. We compared our LRRK2 mutation carriers to idiopathic PD patients matched for recruiting center, gender, age and age at onset. Results: Thirteen patients (8 M and 5 F) carried the R1441C mutation and 4 (3 M and 1 F) the G2019S mutation, all in heterozygous state. All carriers originated from the province of Naples. No carriers of the R1441H or R1441G mutations were found. The LRRK2 mutation carriers were clinically similar to idiopathic PD patients. The R1441C and G2019S mutations are not rare causes of PD in Campania, especially in the province of Naples and among the familial cases, where the overall mutation prevalence is 6.8%. Conclusions: The R1441C prevalence was higher than that of G2019S (2.5% vs 0.8%), underlining the importance of the geographical differencies in LRRK2 mutation frequency for molecular screening and genetic counseling of PD patients.
[Show abstract][Hide abstract] ABSTRACT: Background
Low serum uric acid (UA) has been consistently shown to be associated with increased risk of PD, and to predict faster motor and cognitive decline in established PD. The aim of the present study is to evaluate the relationship between serum UA and non-motor symptoms (NMS) de novo PD.
Serum UA was measured in consecutively recruited, early drug-naïve PD patients. Exclusion criteria were: treatment with UA modifying drugs; current smoking status; metabolic or cardiac morbidity. All patients completed the NMS Questionnaire (NMSQuest). The relationship between UA levels and NMSQuest domains was explored by logistic regression, subsequently adjusted for age, gender, disease duration (months since reported motor onset) UPDRS part III, H&Y scale, and MMSE. Regression analysis studied the overall relationship between UA levels and total NMS score, and subsequently adjusted for age, gender, disease duration UPDRS part III, H&Y scale and MMSE.
Eighty PD patients were recruited. At logistic regression, higher UA levels were related to lower involvement of Attention/Memory (p=0.004), Cardiovascular (0.009) and Sleep (p=0.028) domains of NMSQuest. UA levels showed a significant negative correlation with total NMSQuest score at regression analysis (p=0.001; Adjusted R-squared=0.319).
The present study investigated, for the first time, the relation between NMSQuest and UA in de novo PD. Lower UA was related to higher NMSQuest total score and in particular to Attention/Memory, Cardiovascular and Sleep domains. Thus, UA seems to be a major candidate to be a valuable biomarker of such early features of PD as NMS.
Parkinsonism & Related Disorders 01/2014; · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
We recently showed specific sex-related patterns of non motor symptoms (NMS) in early, drug-naïve PD patients. However, to date studies investigating gender-related effects of dopaminergic treatment on NMS in early PD are lacking.
In the present study, we first report a prospective assessment of gender-related differences in the spectrum of NMS before (baseline) and after starting dopaminergic therapy (2-year follow-up) in a large cohort of newly diagnosed PD patients. Differences in NMS frequency between baseline and follow-up were evaluated by McNemar test. Spearman's rank test was employed to explore interactions between NMS and drug treatment.
One-hundred and thirty four PD patients (86M and 48W) were included in the present study. At 2-year follow-up, Sadness/blues presented a significant percentage reduction as compared to baseline in both sexes, while Urgency, Daytime sleepiness, Weight change and Sex drive presented a significant percentage increase only in men. At follow up men complained of a greater number of NMS as compared to women. Occurrence of Weight change was related to therapy in both sexes. Male gender was found to be a risk factor for developing Dribbling and Nocturia, irrespective of therapy and clinical features.
In conclusion, our study showed that mood symptoms improved after the introduction of therapy in both sexes, while men appeared to be more prone to develop some NMS possibly linked to dopaminergic treatment.
Parkinsonism & Related Disorders 01/2014; · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Szewczyk-Krolikowski and colleagues recently investigated the influence of age and gender on motor and non-motor features in early Parkinson's disease. We recently published the results of a study specifically designed to assess gender differences in the spectrum of non-motor features in a large number of early, drug-naïve PD patients compared to an age- and sex-matched healthy control group. This letter briefly outlines comparisons between Szewczyk-Krolikowski and colleagues results and ours on this topic
Parkinsonism & Related Disorders 01/2014; · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study investigated the long-term safety of rivastigmine (12 mg/d capsules, 9.5 mg/24 h patch) and effects on motor symptoms in patients with mild-to-moderately severe Parkinson disease dementia.
This was a 76-week, prospective, open-label, randomized study in patients aged 50 to 85 years. Primary outcomes included incidence of, and discontinuation due to, predefined adverse events (AEs) potentially arising from worsening of Parkinson disease motor symptoms with capsules. Secondary outcomes included frequency of AEs/serious AEs. Efficacy outcomes included Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL), Neuropsychiatric Inventory (NPI-10), and Mattis Dementia Rating Scale (MDRS).
Five hundred eighty-three patients were randomized to rivastigmine capsules (n = 295) or patch (n = 288). Incidence of predefined AEs was 36.1% for capsules, 31.9% for patch; discontinuation due to worsening of motor symptoms was 4.4% and 2.4%, respectively. Most common AEs were nausea (capsules, 40.5%; patch, 8.3%), tremor (24.5%; 9.7%), fall (17.0%; 20.1%), vomiting (15.3%; 2.8%), and application site erythema (0%; 13.9%). Significant efficacy in favor of capsules was observed at weeks 24 to 76 on MDRS; 24 and 76 on NPI-10; weeks 52 and 76 on ADCS-ADL. In patients with Mini-Mental State Examination (MMSE) greater than 21, no differences in efficacy on MDRS and ADCS-ADL were observed at any time point; significant differences in favor of capsules were maintained in patients with MMSE less than or equal to 21.
This study supports the long-term safety of rivastigmine in Parkinson disease dementia. The rate of worsening of motor symptoms was in the range expected due to the natural progression of Parkinson disease, no new or unexpected safety issues emerged in the long-term.
[Show abstract][Hide abstract] ABSTRACT: Objective
Assessing the frequency of Wearing-Off (WO) in Parkinson's disease (PD) patients, and its impact on Quality of Life (QoL).
Consecutive ambulatory patients, who were on dopaminergic treatment for ≥1 year, were included in this multicentre, observational cross-sectional study. In a single visit, WO was diagnosed based on neurologist assessment as well as using the validated Italian version of a patient self-rated 19-question Wearing-Off Questionnaire (WOQ-19); WO was defined for scores ≥ 2. QoL was evaluated by the 8-item Parkinson's Disease Questionnaire (PDQ-8).
617 subjects were included, with a mean anti-Parkinson treatment duration of 6.6 ± 4.6 years, 87.2% were on levodopa treatment. Neurologists identified presence of WO in 351 subjects (56.9%), whereas 415 subjects (67.3%) were identified by the self-administered WOQ-19. In patients with a <2.5 years disease duration, WO was diagnosed in 12 subjects (21.8%) by neurologists and in 23 subjects (41.8%) by the WOQ-19. The most frequent WO symptoms, as identified by WOQ-19, were “slowness of movements” (55.8%) and “reduced dexterity” (48.8%). Younger age, female gender, Unified Parkinson's Disease Rating Scale (UPDRS) part II score and duration of anti-Parkinson treatment were found significantly associated with WO. The number of motor (p < 0.0001) and non-motor (p < 0.0001) WO symptoms correlated with PDQ-8 total score.
WO is common already at the early stages of PD and is underestimated by routine neurological clinical evaluation. The number of WO symptoms, both motor and non motor, increases along with disease duration and has a negative impact on patients QoL.
Parkinsonism & Related Disorders 01/2014; 20(2):204–211. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Smoke-induced upper airway damage and Parkinson’s disease (PD) can be considered independent risk factors for smell impairment. Interestingly, cigarette smoking has been strongly associated with reduced risk of PD and, therefore, has been suggested to have neuroprotective effects. Our pilot study aimed to evaluate relationship between smoking and olfaction in PD patients and matched controls.
Sixty-eight PD patients and 61 healthy controls were categorized in relation to PD diagnosis and current smoking status, and evaluated by means of the Italian version of University of Pennsylvania 40-item Smell Identification Test (UPSIT-40).
ANOVA analysis with post-hoc Bonferroni correction showed that non-smoker controls presented a higher UPSIT-40 total score than smoker controls (p < 0,001), non-smoker PD patients (p < 0,001) and smoker PD patients (p < 0,001). In this view, smoking seems to affect olfaction in controls but not in PD patients, and no significant differences were found when comparing smoker controls, smoker PD patients and non-smoker PD patients.
Several epidemiological studies showed a negative effect of smoking on olfaction in the general population. Otherwise the sense of smell is similar in smoker and non-smoker PD patients. These results suggest that PD and smoking are not independent risk factors for impairment of sense of smell, but they might variably interact.
Journal of the neurological sciences 01/2014; · 2.32 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background. The minimal clinically important difference (MCID) is the smallest change in an outcome measure that is meaningful for patients. Objectives. To calculate the MCID for Unified Parkinson's Disease Rating Scale (UPDRS) scores in early Parkinson's disease (EPD) and for UPDRS scores and "OFF" time in advanced Parkinson's disease (APD). Methods. We analyzed data from two pivotal, double-blind, parallel-group trials of pramipexole ER that included pramipexole immediate release (IR) as an active comparator. We calculated MCID as the mean change in subjects who received active treatment and rated themselves "a little better" on patient global impression of improvement (PGI-I) minus the mean change in subjects who received placebo and rated themselves unchanged. Results. MCIDs in EPD (pramipexole ER, pramipexole IR) for UPDRS II were -1.8 and -2.0, for UPDRS III -6.2 and -6.1, and for UPDRS II + III -8.0 and -8.1. MCIDs in APD for UPDRS II were -1.8 and -2.3, for UPDRS III -5.2 and -6.5, and for UPDRS II + III -7.1 and -8.8. MCID for "OFF" time (pramipexole ER, pramipexole IR) was -1.0 and -1.3 hours. Conclusions. A range of MCIDs is emerging in the PD literature that provides the basis for power calculations and interpretation of clinical trials.
[Show abstract][Hide abstract] ABSTRACT: 1)Detecting olfaction impairment may support the diagnosis of many ENT and Neurological diseases. The 40-item University of Pennsylvania Smell Identification test is one of the most frequently used identification test evaluating olfaction worldwide. 2)Smell identification tests can be significantly conditioned by age, gender and cultural background. Therefore, cultural adaptations and normative data are needed. 3)The 40-item University of Pennsylvania Smell Identification test was culturally adapted for Italian population and then administered with the help of a physician to 128 control subjects of different ages. 4)A correction grid for the 40-item University of Pennsylvania Smell Identification test raw scores was built according to age groups and gender. The cut-off value distinguishing between normal and pathological performances was fixed at 18.80, corresponding to the inner tolerance limit on the 5th centile. 5)The present data may implement the use of 40-item University of Pennsylvania Smell Identification test administered with the help of a physician in Italian population in both ENT and Neurology settings. This article is protected by copyright. All rights reserved.
Clinical otolaryngology: official journal of ENT-UK; official journal of Netherlands Society for Oto-Rhino-Laryngology & Cervico-Facial Surgery 12/2013; · 1.87 Impact Factor