[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
[show abstract][hide abstract] ABSTRACT: Little is known about the anatomical progression over the body segments of extrapyramidal signs in Parkinson's disease (PD); furthermore a great unmet need is the availability of instruments able to detect disease progression, even in the early phase. The purpose of this study is to demonstrate that assessing topographical distribution of the cardinal motor features of PD may significantly improve the evaluation of disease progression in the early stages. Forty-four drug-naïve PD patients were included in the study. Presence or absence of bradykinesia, rest tremor and rigidity was derived from Unified Parkinson's disease rating scale part III (UPDRS-III) in five different anatomical segments: axial, right and left upper- and lower-limbs. Based on this approach, four new scores were computed evaluating the anatomical spread of the cardinal motor symptoms of PD on the five body segments over a 18-month follow-up period. The four new scores included: the Bradykinesia Segmental Score, the Tremor Segmental Score, the Rigidity Segmental Score, measuring the occurrence of each motor symptom in different segments and the Combined Segmental Score evaluating the occurrence of any motor symptom in different anatomical regions. Data were analyzed using a repeated measures analysis of variance. The Combined Segmental Score showed a significant progression over time whereas the Hoehn and Yahr and the UPDRS-III scores did not. We suggest that a simple approach evaluating the anatomical distribution of motor symptoms and their progression over the body segments may be a useful complement to the classical rating tools to assess progression in early PD.
Parkinsonism & Related Disorders 09/2013; · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gender differences in brain structure and function may lead to differences in the clinical expression of neurological diseases, including Parkinson's disease (PD). Few studies reported gender-related differences in the burden of non-motor symptoms (NMS) in treated PD patients, but this matter has not been previously explored in drug-naïve PD patients. This study is to assess gender differences in the prevalence of NMS in a large sample of early, drug-naïve PD patients compared with age and sex-matched healthy controls. Two hundred early, drug-naïve PD patients and ninety-three age and sex-matched healthy controls were included in the study. Frequency of NMS was evaluated by means of the Non-Motor Symptoms Questionnaire. The difference in gender distribution of NMS was evaluated with the χ (2) exact test; multiple comparisons were corrected with the Benjamini-Hochberg method. Male PD patients complained of problems having sex and taste/smelling difficulties significantly more frequently than female PD patients. Furthermore, men with PD complained more frequently of dribbling, sadness/blues, loss of interest, anxiety, acting during dreams, and taste/smelling difficulties as compared to healthy control men, while female PD patients reported more frequently loss of interest and anxiety as compared with healthy control women. This study shows specific sex-related patterns of NMS in drug-naïve PD. In contrast with previous data, female PD patients did not present higher prevalence of mood symptoms as compared to male PD patients. Comparison with healthy controls showed that some NMS classically present in premotor and early stage of disease (i.e., acting out during dreams, taste/smelling difficulties) are more frequent in male than in female patients.
Journal of Neurology 08/2013; · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND AND PURPOSE: Cognitive impairment is common in Parkinson's disease (PD), even in the early stages. We aimed to assess the relationship between insulin-like growth factor-1 (IGF-1) and cognitive functions in early, drug-naïve patients with PD. METHODS: Serum IGF-1 was measured in 65 early, drug-naïve patients with PD that underwent a complete neuropsychological battery at baseline and after 2 years. Linear regression analysis was used to evaluate the relationships between neuropsychological scores and IGF-1. Repeated-measures anova was applied to assess changes in neuropsychological variables over time. RESULTS: At baseline, IGF-1 levels were related to phonological fluency. At follow-up, IGF-1 levels were associated with the Rey auditory verbal learning test (RAVLT) - immediate and delayed recall, Frontal Assessment Battery, verbal span and Benton judgement of the line orientation test. Patients with low IGF-1 levels at baseline showed a significantly faster decline of performances than patients with high IGF-1 levels on immediate and delayed recall of the RAVLT and interference task of the Stroop test. CONCLUSIONS: Low serum IGF-1 levels are related to poor performance on executive tasks in early, drug-naïve patients with PD, and may predict poor performance on attention/executive and verbal memory tasks after a 2-year follow-up.
European Journal of Neurology 03/2013; · 4.16 Impact Factor
[show abstract][hide abstract] ABSTRACT: Much pre-clinical evidence show that insulin-like growth factor 1 (IGF-1) provides protection against loss of dopaminergic neurons. Recently, IGF-1 has been proposed as a possible biomarker for early diagnosis of Parkinson's disease (PD). We aimed to assess the relationship between serum IGF-1 levels and progression of motor symptoms in a cohort of drug-naïve PD patients. Serum IGF-1 was measured at baseline in 37 early, drug-naive PD patients; subsequently, patients were evaluated "on drug" by means of UPDRS-III, UPDRS dopa-resistant score and dopaminergic score at 12, 18 and 24 month follow-up. Repeated measures ANOVA was used both to evaluate progression of motor scores within time and differences between serum IGF-1 quartiles, age at onset and motor phenotype. Patients at the highest IGF-1 quartile were found to have significantly higher UPDRS-III (p < 0.001) and dopaminergic score (p < 0.001), as compared to patients at other quartiles. Mean serum IGF-1 level was moderately increased in PD as compared to healthy controls (p < 0.011). IGF-1 levels are related to those symptoms predominantly responsive to dopaminergic treatment. This is the first study to demonstrate a relationship between serum IGF-1 and progression of motor symptoms in the early stage of disease.
Journal of Neurology 02/2013; · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: The variability in the clinical phenotype of Parkinson's disease seems to suggest the existence of several subtypes of the disease. To test this hypothesis we performed a cluster analysis using data assessing both motor and non-motor symptoms in a large cohort of newly diagnosed untreated PD patients.
We collected data on demographic, motor, and the whole complex of non-motor symptoms from 100 consecutive newly diagnosed untreated outpatients. Statistical cluster analysis allowed the identification of different subgroups, which have been subsequently explored.
THE DATA DRIVEN APPROACH IDENTIFIED FOUR DISTINCT GROUPS OF PATIENTS, WE HAVE LABELED: 1) Benign Pure Motor; 2) Benign mixed Motor-Non-Motor; 3) Non-Motor Dominant; and 4) Motor Dominant.
Our results confirmed the existence of different subgroups of early PD patients. Cluster analysis revealed the presence of distinct subtypes of patients profiled according to the relevance of both motor and non-motor symptoms. Identification of such subtypes may have important implications for generating pathogenetic hypotheses and therapeutic strategies.
PLoS ONE 01/2013; 8(8):e70244. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: A relation between the side of motor onset and cognitive impairment in early PD has been reported, suggesting that the asymmetric degeneration affecting subcortical regions may play a pivotal role in lateralized cognitive function. However, evidences are controversial and all previous studies were performed on treated patients, though it is known that dopaminergic therapy can affect cognition in PD. METHODS: Sixty-nine early untreated PD patients underwent an extensive neuropsychological battery exploring memory, visuospatial and attention/executive functions. Patients were divided with respect of the side of onset (right vs. left) and further grouped according to motor phenotype (tremor vs. rigidity-bradykinesia). Multivariate analysis of variance has been carried out to compare clinical and neuropsychological data between subgroups. RESULTS: There were no differences in any neuropsychological task between right-sided and left-sided onset subgroups, irrespective of tremor dominant or rigid-bradykinetic phenotype. Age at onset was significantly higher in patients with any cognitive impairment as compared with patients without (66.7 ± 3.2 vs. 56.3 ± 6.8 years, p = 0.001). CONCLUSION: Side of motor onset is not a major determinant for developing lateralized cognitive deficits in newly diagnosed untreated PD patients.
Parkinsonism & Related Disorders 11/2012; · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Non-motor symptoms are very common among patients with Parkinson's disease since the earliest stage, but little is known about their progression and their relationship with dopaminergic replacement therapy. METHODS: We studied non-motor symptoms before and after 2 years from dopaminergic therapy introduction in ninety-one newly diagnosed previously untreated PD patients. RESULTS: At baseline, nearly all patients (97.8%) referred at least one non-motor symptom. At follow-up, only few non-motor symptoms significantly changed. Particularly, depression and concentration became less frequent, while weight change significantly increased after introduction of dopamine agonists. CONCLUSIONS: We reported for the first time a 2-year prospective study on non-motor symptoms before and after starting therapy in newly diagnosed PD patients. Even if non-motor symptoms are very frequent in early stage, they tend to remain stable during the early phase of disease, being only few non-motor symptoms affected from dopaminergic therapy and, specifically, by the use of dopamine agonists.
Journal of neurology, neurosurgery, and psychiatry 09/2012; · 4.87 Impact Factor
[show abstract][hide abstract] ABSTRACT: Epidermal growth factor (EGF) has been proposed as a candidate biomarker for cognitive impairment in Parkinson's disease (PD). We aimed to assess the relationship between serum EGF and cognitive functions in early, drug-naive PD patients and evaluate the predictive value of EGF on cognitive functions in a 2-year follow-up study. Serum EGF was measured in 65 early, drug-naive PD patients, that underwent a comprehensive neuropsychological battery. Motor symptoms were assessed by means of the Unified Parkinson's Disease Rating Scale, Part III (UPDRS-III). Neuropsychological evaluation was repeated after 2 years. Spearman's rank correlation was used to assess the relationship between serum EGF levels and neuropsychological variables. Linear regression analysis was used to evaluate the relationship between EGF and neuropsychological scores as well as other variables (age, gender, UPDRS-III, levodopa equivalent dose, and type of treatment at follow-up) potentially affecting cognitive performance. Variation over time in cognitive scores was analyzed using repeated-measures ANOVA. At baseline, EGF was the only significant variable associated with performance on semantic fluency (R (2) = 0.131; p = 0.005). EGF levels (p = 0.025), together with UPDRS-III (p = 0.009) and age (p = 0.011), were associated with performance on frontal assessment battery (R (2) = 0.260). At 2-year follow-up, EGF was the only significant variable to predict performance on semantic fluency (R (2) = 0.147; p = 0.025) and color naming task of Stroop color-word test (R (2) = 0.121; p = 0.044). Serum EGF levels are related to frontal and temporal cognitive functions in early, drug-naive PD patients and predict performance on frontal and posterior cognitive functions at 2-year follow-up. EGF is proposed as a potential serum biomarker for early cognitive impairment in PD.
Journal of Neurology 08/2012; · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Anxiety is a common non-motor symptom among patients with Parkinson's disease (PD). Although the etiology of anxiety in PD is likely to be multifactorial, a dysfunction in the dopaminergic system might be implicated in its pathogenesis. The aim of our study was to investigate a possible dopaminergic mechanism involved in anxiety in newly diagnosed never-medicated PD patients using SPECT and (123)I-FP-CIT as the dopamine transporter ligand. METHODS: Thirty-four newly diagnosed, untreated PD patients with asymmetric motor symptoms were included in the study: 17 patients with right- and 17 with left-motor onset, matched for age, disease duration and motor disability constituted the group. They were all evaluated for anxiety and depression and underwent an SPECT with (123)I-FP-CIT. Dopamine transporter (DAT) availability values for right and left caudate and putamen were calculated and compared between patients with and without anxiety. Regression analyses were also performed in order to correlate DAT availability with the severity of the anxiety symptoms. RESULTS: Comparison between PD patients with and those without anxiety revealed significant differences of DAT availability in all the examined regions except the right putamen. In the group of patients considered as a whole, a significant correlation was found between increased anxiety severity and decreased DAT availability in right caudate. CONCLUSIONS: We reported an association between nigrostriatal DAT availability deficits and anxiety symptoms in newly diagnosed, untreated PD patients. Our results suggest that hypofunction of the nigrostriatal dopaminergic system may represent one of the functional anomalies involved in anxiety in PD from the earliest stages of disease and irrespective of any therapy.
Parkinsonism & Related Disorders 07/2012; · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Little is known about the relationship between cognitive dysfunctions and the non-motor complex in subjects with newly diagnosed untreated Parkinson's disease (PD). The aim of this study was to explore the association between non-motor symptoms (NMS) and cognitive dysfunctions in an incident cohort of de novo, drug-naive, PD patients. Sixty-six non-demented, early, untreated PD patients completed a semi-structured interview on NMS and a battery of neuropsychological tests that assess verbal memory, visuospatial abilities, and attention/executive functions. Scores were age- and education-corrected. Patients who failed at least two tests for each cognitive domain were diagnosed as having mild cognitive impairment (MCI). All but three (95.4%) PD patients complained of at least one NMS. A total of 37.8% was diagnosed with MCI. There was a relationship between sleep-NMS and cognitive dysfunctions. Specifically, both REM behavioral sleep disorders (RBD) and insomnia were associated with lower scores on several cognitive tests. Moreover, RBD was closely related to MCI. NMS and MCI are very common even in the early phase of PD, before patients are treated. Given the correlation between sleep disturbances and cognitive impairment, it is possible that sleep symptoms in PD patients might be considered as an early marker of dementia.
Journal of Neurology 02/2012; 259(9):1808-13. · 3.58 Impact Factor
[show abstract][hide abstract] ABSTRACT: To characterize brain metabolic changes associated with mild cognitive impairment (MCI) in drug-naive patients with Parkinson disease (PD) using (18)F-fluorodeoxyglucose (FDG) and PET (FDG-PET).
This cross-sectional study included newly diagnosed patients with PD with MCI in single or multiple domain (PD-MCI; n =12) and without MCI (PD-nMCI; n =12), and healthy controls (n =12). The groups were matched for age. Moreover, the patient groups were matched for motor disability. All subjects underwent a FDG-PET study. Cerebral regional relative metabolic maps were compared in PD-MCI, PD-nMCI, and controls using regions of interest analysis (ROIs) and voxel-based analysis with statistical parametric mapping.
ROIs and voxel-based analyses revealed significant relative hypometabolism in the prefrontal, superior/inferior parietal, and associative occipital cortices as well as in the striatum in patients with PD-MCI relative to controls (p < 0.05) and to a lesser extent in patients with PD-nMCI. In contrast, patients with PD-nMCI did not show significant metabolic changes as compared to controls.
MCI in patients with PD is associated with cortical hypometabolism since the earliest stage, independent of therapy or motor disability. The early involvement of posterior cortical region, a pattern shared by advanced stages of PD-MCI and PD with dementia, could represent an early marker of dementia. The relevance of this pattern in predicting prodromal dementia has to be evaluated in longitudinal studies.
[show abstract][hide abstract] ABSTRACT: The "eye of the tiger" is a neuroradiologic sign due to iron deposition in the globus pallidus: it appears as diffuse low signal intensity with a central area of high signal intensity confined to the globus pallidus. The "eye of the tiger" sign has been associated with neurodegeneration with brain iron accumulation type 1 (NBIA1), a condition caused by mutations in the gene encoding pantothenate kinase 2 (PANK2). However, the specificity of this neuroradiologic sign has been already challenged and it has been described in other neurodegenerative diseases. Here, we report the first case of a patient suffering from pure akinesia with gait freezing with the "eye of the tiger" sign in T2-weighted MRI sequences. All clinical, laboratory and radiologic data excluded other diagnosis and genetic testing excluded PANK2 mutations suggesting that the "eye of the tiger" is not specific for NBIA1 and may also occur in other movement disorders.
[show abstract][hide abstract] ABSTRACT: Lateral trunk flexion is a very common clinical observation in patients affected by Parkinson's disease. Postural control is known to depend on vestibular, visual, and somatosensory information. The aim of this study was to investigate whether impairment of vestibular function can account for the postural alterations observed in parkinsonian patients with lateral trunk flexion. We evaluated vestibular function in 11 parkinsonian patients with lateral trunk flexion and in 11 age-, sex-, and disease duration-matched patients without lateral trunk flexion. The following vestibular tests were performed: infrared videonystagmography including fast and slow ocular movements, spontaneous-positional and evoked nystagmus search with and without visual fixation, fast positioning maneuvers, the bithermal caloric test, and the vibration test. A peripheral, unilateral vestibular hypofunction was identified in all patients with lateral trunk flexion. The vestibular hypofunction was ipsilateral to the leaning side and contralateral to the most affected parkinsonian side in all patients. In the control group, 7 subjects had no vestibular signs; 4 subjects had unilateral vestibular hypofunction without clinically evident lateral trunk flexion. Two of the latter patients subsequently developed lateral trunk flexion ipsilateral to the vestibular deficit and contralateral to the side most affected by Parkinson's disease. The processing of vestibular information was impaired in parkinsonian patients affected by lateral trunk flexion. The impairment was at least in part responsible for the patients' postural abnormality. We propose that the acronym PISA (Postural Imbalance Syndrome with vestibular Alterations) be used to describe the specific postural change observed in parkinsonian patients affected by a vestibular defect and lateral trunk flexion.
Movement Disorders 04/2011; 26(8):1458-63. · 4.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: Parkinson's disease (PD) is a common neurodegenerative disorder with a progressive disabling course. Health-related quality of life (HrQoL) in Italian patients with PD has not been evaluated. The objective of this study was to evaluate HrQol of an Italian cohort of PD patients and to provide a comprehensive analysis of HrQoL determinants. We performed a cross-sectional survey of 70 outpatients with idiopathic PD recruited in the department of Neurology, Napoli University, Italy. Clinical data included the Unified PD Rating Scale (UPDRS), motor and non-motor symptoms. The generic instrument EuroQol (EQ-5D and EQ-VAS) was used to evaluate HrQol. Factors influencing HrQol were assessed by multivariate regression analysis. Severe problems in at least one dimension of the EQ-5D were experienced by 60% of PD patients versus 4.7% in general Italian population. The dimensions most affected were mobility, pain/discomfort and anxiety/depression with only 17.4%, 18.8% and 17.4% of patients, respectively, reporting no problems in these dimensions. The mean EQ-VAS score was 54.20 ± 18.38. Independent determinants of reduced HrQoL were increased UPDRS scores, motor fluctuations, dyskinesias, depression and dementia. PD strongly affects HrQol in Italian patients. The results of this study should be considered in the development of national healthcare programmes aimed at improvement of the HrQoL in Italian patients with PD. In particular, these programmes should concentrate not only on motor but also on non-motor manifestations of PD.
Parkinsonism & Related Disorders 02/2011; 17(4):265-9. · 3.27 Impact Factor
[show abstract][hide abstract] ABSTRACT: Insulin-like growth factors (IGF-I and IGF-II) have been shown to have several neurotrophic actions and IGF system may be impaired in neurodegenerative disorders. The aim of this study was to investigate the IGF system in patients with MSA and to evaluate correlations between this endocrine system and clinical features of the disease. Serum levels of IGF-I, IGF-II, insulin, IGF-binding protein 1 (BP1), and IGF-binding protein 3 (BP3) were measured in 25 patients with probable MSA and 25 age, sex and BMI-matched healthy controls. Clinical status of each patient was evaluated with the Unified Multiple System Atrophy Rating Scale (UMSARS) Part II and the Hoehn and Yahr rating scale. IGF-I levels were significantly higher in MSA (164.1 + 66.2 μg/L) than in healthy controls (111.7 + 60.3 μg/L; p = 0.001). Insulin levels were significantly higher in MSA patients (21.9 ± 14.4 μU/mL) than in healthy controls (13.3 ± 5.1 μU/mL, p = 0.048). No significant difference was found in serum IGF-II, IGF-BP1, and IGF- BP3 levels between patients with MSA and healthy controls. There was a trend toward significantly higher IGF-II levels in MSA patients with UMSARS score <26 (1026.3 ± 442.6 μg/L) than MSA patients with UMSARS score >26 (796.1 ± 234 μg/L, p = 0.055). The results of this study demonstrated that IGF system is altered in MSA. The degenerative process in MSA could lead to a compensatory increase in IGF-I and insulin in an attempt to provide additional support to degenerating neurons.
Movement Disorders 11/2010; 25(15):2621-6. · 4.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: Antiparkinsonian pharmacotherapy is costly and the determinants of drug costs in Parkinson's disease (PD) have been poorly investigated. The objective of this study was to investigate the costs of PD and antiparkinsonian drugs in an Italian cohort of patients and identify cost-driving factors of drug therapy.
Seventy outpatients with idiopathic PD were recruited in the Department of Neurology, Napoli University, Italy. Data on resource utilization were collected for 6 months using a bottom-up approach. Clinical status was evaluated using the Unified Parkinson's Disease Rating Scale. Direct and indirect costs were calculated from the societal perspective (figures of year 2009). Independent determinants of total costs and costs of antiparkinsonian drugs were identified using multivariate regression analysis.
The total costs of PD were EUR 8,640 (95% CI: EUR 6,700-11,240) per patient over a 6-month period. Direct costs accounted for 70% of the total costs. Antiparkinsonian drugs (EUR 1,450; 95% CI: EUR 1,220-1,760) were the primary component of costs paid by the health insurance (39.6%) and one of the most expensive components of the direct costs (24.0%). The highest copayments made by patients were for antiparkinsonian drugs and medical equipment (58%). Independent determinants of the increased costs of antiparkinsonian pharmacotherapy were younger age and occurrence of motor fluctuations.
Antiparkinsonian pharmacotherapy is one of the major cost components of PD-related costs for health insurance. It imposes a considerable economic burden on patients and their families as well.