Retinal Thickness in Essential Tremor and Early Parkinson Disease: Exploring Diagnostic Insights.

BACKGROUND: Essential tremor (ET) represents a heterogeneous condition which may overlap with Parkinson disease (PD) even at early stages, by sharing some subtle clinical aspects. Longstanding ET demonstrated also higher risk of developing PD, especially with a Tremor-dominant (TD-PD) phenotype. Therefore, differential diagnosis between ET and early PD could be quite challenging. Optical coherence tomography (OCT) has been recognized as a reliable tool to assess the retina as a proxy of neurodegeneration. We aimed to explore the possible role of retinal assessment in differential diagnosis between ET and early PD. METHODS: Macular layers and peripapillary retinal nerve fiber layer (RNFL) thickness among ET, early PD, and healthy controls (HCs) were assessed using OCT. RESULTS: Forty-two eyes from 23 ET, 41 eyes from 21 early PD, and 33 eyes from 17 HCs were analyzed. Macular RNFL, ganglion cell layer, inner plexiform layer, and inner nuclear layer were thinner in PD as compared with ET and even more in HCs. Differences between ET and PD were more evident when considering the TD-PD subgroup, especially for RNFL. Among ET patients, thickness of the inner macular layers showed negative linear relationship with both age at onset and disease duration. Peripapillary temporal quadrant thinning was found in ET compared with HCs. CONCLUSIONS: Macular inner retina was thinner in patients with ET and early PD compared with HCs. These findings suggest that the retinal assessment may have a utility in the differential diagnosis between ET and PD.

Corticobasal syndrome and Parkinson's disease at the beginning: asymmetrical patterns of MRI and Blink Reflex for early diagnosis.

Differential diagnosis between Parkinson's disease (PD) and corticobasal syndrome (CBS) could be challenging at the early stage, due to the asymmetric onset of both diseases. Despite the clinical overlap, the anatomical circuits involved in these disorders are different. We evaluated R2 Blink Reflex Recovery Cycle (R2BRRC) and cortical thickness (CTh) in drug-naïve PD and CBS patients for characterizing pathophysiological mechanisms underlying these conditions. Patients with a clinically probable diagnosis of PD and possible CBS were recruited. R2BRRC was evaluated bilaterally at interstimulus intervals (ISIs) of 100-150-200-300-400-500-750 ms. Asymmetry index (AI) of R2BRRC for each ISI was computed. Patients underwent a structural brain MRI and hemisphere CTh and AI of MRI was calculated. Fourteen drug-naïve PD patients and 10 patients with early CBS diagnosis were enrolled. R2BRRC of PD patients showed an increased brainstem excitability for less affected side (LAS) stimulation at ISIs of 100 and 150 ms (p < 0.001) compared to most affected side (MAS), whereas no differences between LAS and MAS were found in CBS. AI of R2BRRC at ISI-100 ms showed significant difference, being higher in PD. CTh analysis showed significant differences between groups in hemisphere cortical volume contralateral to MAS, and, conversely, AI of MRI was significantly higher in CBS. PD patients exhibited an asymmetric pattern of brainstem excitability, compared to CBS. Conversely, CBS patients showed an asymmetric pattern of cortical atrophy. This opposite pattern of neurophysiological and structural abnormalities involving cortical and subcortical brain structures could highlight the different pathophysiological mechanisms underlying these disorders.

Epidemiology of Primary Brain Tumors in the Province of Catania during the 2003-2016 Period.

INTRODUCTION: Primary brain tumors (PBTs) account for approximately 2% of all cancers and are associated with significant morbidity and mortality. However, only few epidemiological studies focus on PBTs in Italy. The aim of this study was to evaluate incidence, temporal trend, and survival rate of all PBTs in the province of Catania during the study period. METHODS: All patients diagnosed with PBTs in the province of Catania during the 2003-2016 were identified through the local cancer registry. All cases were classified by histology according to 2007 WHO classification of central nervous system tumors, using the International Classification of Diseases for Oncology, 3rd edition codes. The incidence rate (IR) was calculated for all PBTs and by gender, histology, age-groups, and behavior. Trend analysis was performed using a piecewise log-linear model. RESULTS: A total of 3,819 cases were identified with a female/male ratio of 1.45. The IR for all PBTs was 25.3/100,000 person-years (95% confidence interval 24.5-26.1). Most PBTs were nonmalignant (59.5%, IR = 15.0) with a female predominance. Conversely, malignant tumors (32.4%, IR = 8.2) were more common among men, with a female/male ratio of 0.9. The most frequently reported histology was meningioma (39.0%, IR = 9.8), followed by glioblastoma (11.6%, IR = 2.9). A peak of incidence was found in the 75-84 years age-group, with an IR of 77.6/100,000 person-years. Overall, no increase in incidence was observed along the study period. CONCLUSIONS: The IR of PBTs in the province of Catania is close to incidence reported worldwide. Further studies on risk factors are necessary.

Neuroanatomical changes in early Parkinson's disease with mild cognitive impairment: a VBM study; the Parkinson's Disease Cognitive Impairment Study (PaCoS).

INTRODUCTION: Mild cognitive impairment (MCI) is common in Parkinson's disease (PD), but the underlying pathological mechanism has not been fully understood. Voxel-based morphometry could be used to evaluate regional atrophy and its relationship with cognitive performances in early PD-MCI. PATIENTS AND METHODS: One hundred and six patients with PD were recruited from a larger cohort of patients, the Parkinson's Disease Cognitive Impairment Study (PaCoS). Subject underwent a T1-3D MRI and a complete clinical and neuropsychological evaluation. Patients were divided into PD with normal cognition (PD-NC) and PD-MCI according to the MDS level II criteria-modified for PD-MCI. A subgroup of early patients with short disease duration (≤ 2 years) was also identified. VBM analysis between PD-NC and PD-MCI and between early PD-NC and PD-MCI was performed using two-sample t tests with whole-brain statistical threshold of p < 0.001 uncorrected in the entire PD group and p < 0.05 FWE inside ROIs, in the early PD. RESULTS: Forty patients were diagnosed with MCI and 66 were PD-NC. PD-MCI patients showed significant gray matter (GM) reduction in several brain regions, including frontal gyrus, precuneus, angular gyrus, temporal lobe, and cerebellum. Early PD-MCI showed reduction in GM density in superior frontal gyrus and cerebellum. Moreover, correlation analysis between neuropsychological performances and GM volume of early PD-MCI patients showed associations between performances of Raven and superior frontal gyrus volume, Stroop time and inferior frontal gyrus volume, accuracy of Barrage and volume of precuneus. CONCLUSION: The detection of frontal and cerebellar atrophy, even at an early stage, could be used as an early marker of PD-related cognitive impairment.

Neuroanatomical findings in isolated REM sleep behavior disorder and early Parkinson's disease: a Voxel-based morphometry study.

Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is a parasomnia characterized by loss of physiological atonia of skeletal muscles with abnormal behaviors arising during REM sleep. RBD is often the early manifestation of neurodegenerative diseases, particularly alpha-synucleinopathies, such as Parkinson's disease (PD). Both structural and functional neuroimaging studies suggest that iRBD might share, or even precede, some of the features commonly found in PD, although without a definitive conclusion. Aim of the study is to evaluate the presence of structural abnormalities involving cortical and subcortical areas in PD patients with RBD and iRBD. Patients with video-polysomnographic (VPSG)-confirmed iRBD, and patients with a diagnosis of PD were recruited. In all PD patients, the presence of probable RBD was assessed during the follow-up visits (PD/pRBD). A group of healthy controls (HC) subjects was also recruited. Each subject underwent a structural brain MRI using a 3-D T1-weighted spoiled gradient echo sequence. Twenty-three patients with iRBD, 24 PD/pRBD, and 26 HC were enrolled. Voxel-based morphometry-AnCOVA analysis revealed clusters of grey matter changes in iRBD and PD/pRBD compared to HC in several regions, involving mainly the frontal and temporal regions. The involvement of cortical brain structures associated to the control of sleep cycle and REM stage both in PD/pRBD and iRBD might suggest the presence of a common structural platform linking iRBD and PD, although this pattern may not underlie exclusively RBD-related features. Further longitudinal studies are needed to clarify the patterns of changes occurring at different time points of RBD-related neurodegeneration.

Turning and Sitting in Early Parkinsonism: Differences Between Idiopathic Normal Pressure Hydrocephalus Associated with Parkinsonism and Parkinson's Disease.

Background: Differential diagnosis between idiopathic normal pressure hydrocephalus (iNPH) associated with parkinsonism (iNPH-P) and Parkinson's disease (PD) may prove difficult when evaluating patients with early parkinsonism. The objective of this study was to evaluate differences in mobility during standardized tasks between iNPH-P and PD. Methods: We selected 21 iNPH-P and 21 pharmacologically untreated PD patients. They all performed the instrumented Timed Up and Go test at the time of diagnosis. Results: Turning tasks showed longer duration and lower speed in iNPH-P than in PD. Vertical variation in acceleration during the sit-to-stand phase was lower in iNPH-P patients, whereas the duration of the stand-to-sit phase was longer. On walking, iNPH-P showed smaller stride length and a longer gait cycle duration. In multivariate analysis adjusting for age and cognitive status as potential confounders, average angular speed on turning before sitting was the discriminating parameter between the two groups. Conclusions: Patients with iNPH-P showed specific abnormal mobility performances with respect to untreated PD, specifically during the turning-to-sitting transition.

Gender Differences in Levodopa Pharmacokinetics in Levodopa-Naïve Patients With Parkinson's Disease.

Background: Levodopa (LD) is the most effective drug in the treatment of Parkinson's disease (PD). Unfortunately, prolonged use of LD leads to complications, mainly motor/non-motor fluctuations (MNMF) and dyskinesias (DYS). Women seem more prone to develop such LD-related complications. Nonetheless, there is a paucity of prospective studies examining gender-related predictors of MNMF and DYS. Among several factors, which concur with a very complex scenario, changes in LD pharmacokinetics influence the drug's effectiveness. The present study aimed to assess gender-related differences in LD pharmacokinetics in patients with PD at their first-ever intake of LD. Materials and Methods: This is a multicentric study enrolling patients with PD, who were LD-naïve and received a single dose of LD/benserazide (100/25 mg) formulation. All participants gave their written informed consent, and the study was approved by the local Ethics Committees. To measure plasma LD concentrations and pharmacokinetic parameters (AUC, Cmax, Tmax, t 1/2), fasting blood samples were collected before drug intake and then at 8-time points until 260 min. LD concentrations were measured by ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS). Multiple linear regression analyses were performed to identify the predictors of the parameters. Results: Thirty-five patients (16 women and 19 men) were consecutively enrolled. Area under curve (AUC) and maximum plasma concentration (Cmax) were significantly higher in women than men (p = 0.0006 and p = 0.0014, respectively). No statistically significant difference was found regarding Tmax and t 1/2. Multiple linear regression analyses revealed that female sex (ß = 1.559116, 95% CI 0.8314479 2.286785; p < 0.0001) and body mass index (BMI) (ß = -0.0970631, 95% CI -0.1733004 -0.0208258; p = 0.014) significantly predicted AUC. Only female sex significantly predicted Cmax (ß = 1,582.499, 95% CI 731.581 2,433.417; p = 0.001). Moreover, only BMI significantly predicted t 1/2 (ß = 0.0756267, 95% CI 0.0143407 0.1369126; p = 0.017). Stratifying by gender, BMI was confirmed to significantly predict t 1/2 in women (ß = 0.1300486, 95% CI 0.0172322 0.242865; p = 0.027), but not in men. Conclusion: This study provides novel insights on gender differences in LD pharmacokinetics, possibly contributing to the later development of motor complications and dyskinesia in PD.

Structural MRI substrate of long-duration response to levodopa in Parkinson's disease: an exploratory study.

OBJECTIVE: The long-duration response (LDR) to L-dopa is a sustained benefit deriving from chronic administration of therapy to patients with Parkinson's disease (PD). Almost all patients with early PD may develop the LDR to L-dopa, even if some patients could not at given dosages of the drug. Aim of this exploratory study is to investigate whether a neuroanatomical substrate may underlie the development of the of LDR using structural magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) analysis. METHODS: Twenty-four drug-naïve PD patients were enrolled and underwent a baseline 3D T1-weighted structural brain MRI. Then, a treatment with 250/25 mg of L-dopa/carbidopa every 24 h was started and, after 2 weeks, LDR was evaluated by movement time recordings. RESULTS: After 2 weeks of continuative therapy, 15 patients (62.5%) showed a sustained LDR (LDR +), while nine patients (37.5%) did not develop a sustained LDR (LDR -). VBM analysis on MRI executed before treatment showed changes of gray matter in precentral and middle frontal gyri in patients subsequently developing a sustained LDR with respect to those patients who will not achieve LDR. CONCLUSIONS: Parkinsonian patients who will develop a LDR to L-dopa may present, before starting treatment, peculiar structural conditions in cortical areas involved in motor control. Our exploratory study suggests that some cortical structural changes may predispose individual patients for developing the LDR to L-dopa.