BackgroundThe 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.MethodsWe 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.ResultsThe 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.ConclusionOur 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.

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.

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.

The objective of this study was to evaluate hearing impairment in patients affected by Parkinson's disease compared with hearing scores observed in normal age- and sex-matched controls. One hundred eighteen consecutive patients with a clinical diagnosis of Parkinson's disease were screened. Severity of motor symptoms and staging were measured with the Unified Parkinson's Disease Rating Scale (section III) and the Hoehn and Yahr scale. Audiometric evaluation consisted of a comprehensive audiologic case history and questionnaire, visual otoscopic examination, acoustic immittance measures (tympanogram and acoustic reflexes), pure tone audiometry, and measurement of brain stem auditory-evoked potentials. Healthy age- and sex-matched subjects were selected as the control group. One hundred six of 118 patients were enrolled. Pure tone audiometry revealed age-dependent high-frequency hearing loss in patients with Parkinson's disease compared with both normative values and values for healthy age- and sex-matched controls (75/106 [71%], χ(2) = 5.959, P = .02; 92/106 [86.8%] vs 60/106 [56.6%], χ(2) = 23.804, P < .001, respectively). Pure tone audiometry scores correlated with Hoehn and Yahr scale scores (P < .05). Brain stem auditory-evoked potentials were normal in all patients. Our patients with Parkinson's disease showed age-dependent peripheral, unilateral, or bilateral hearing impairment. Whether these auditory deficits are intrinsic to Parkinson's disease or secondary to a more complex impaired processing of sensorial inputs occurring over the course of illness remains to be determined. Because α-synuclein is located predominately in the efferent neuronal system within the inner ear, it could affect susceptibility to noise-induced hearing loss or presbycusis. It is feasible that the natural aging process combined with neurodegenerative changes intrinsic to Parkinson's disease might interfere with cochlear transduction mechanisms, thus anticipating presbycusis.

Hyposmia is a common finding in Parkinson's disease (PD). The 40-item University of Pennsylvania Smell Identification Test (UPSIT-40) has been adapted and administered in several countries as a diagnostic tool in the diagnosis of PD. We have developed a culturally adapted version of the UPSIT-40 and applied it to 61 nondemented Italian controls and to 68 PD patients. Multiple linear regression analysis was performed to assess the factors that independently influence UPSIT-40 and logistic regression analysis was employed to study the usefulness of UPSIT-40 to predict PD diagnosis. Multiple linear regression analysis showed that PD diagnosis (p< 0.001), age (p = 0.006), gender (p = 0.003) and smoking status (p = 0.03) were significant independent predictors of the UPSIT-40 total score. Using diagnosis as dependent variable, logistic regression analysis showed that UPSIT-40 total score (p < 0.001) was an independent predictor of PD. Using a score ≤ 21/40 as a cut-off point for assigning subjects to PD group, the UPSIT-40 total score differentiated PD and control subjects with 82 % sensitivity and 88.2 % specificity. The adapted version of UPSIT-40 may be useful in addition to clinical examination to improve accuracy of diagnosis of PD in Italian population.