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.

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.

Incidence, survival and geoepidemiological analysis of meningiomas and glioblastomas in the province of Catania during the 2003-2016 period.

BACKGROUND: Meningiomas are the most common primary brain tumors, followed by glioblastomas. Nevertheless, no previous studies have been conducted to evaluate the epidemiology of meningiomas and glioblastomas in the southern region of Italy. Thus, the aim of our study was to evaluate incidence, temporal trend and survival rate of meningiomas and glioblastomas in the province of Catania during the study period. Moreover, a geoepidemiological analysis was performed in order to identify possible geographical and temporal clusters. METHODS: All subjects with meningiomas and glioblastomas diagnosed from 2003 to 2016 in the province of Catania were collected, using the local cancer registry. Incidence rate (IR) was calculated by gender, age-groups and tumor behavior. Temporal changes in incidence trend were assessed using a Joinpoint regression analysis while survival analysis was performed using Kaplan-Meier method. Cluster analysis was performed using Kulldorff's spatial scan statistic. RESULTS: In the province of Catania, a total of 1488 cases of meningiomas and 443 cases of glioblastomas were identified from 2003 to 2016, with an IR of 9.8/100,000 person-years (95%CI 9.3-10.3) and 2.9/100,000 person-years (95%CI 2.7-3.2), respectively. Meningiomas were more common among women (p-value<0.0001), while glioblastomas among men (p-value<0.0001). IR progressively increased over the ages, reaching a peak in the 75-84 and 65-74 years-old group in, respectively, meningiomas and glioblastomas. Mean survival was higher in subjects diagnosed with meningiomas as compared to those with glioblastomas (10.7 years and 15.8 months, respectively), with age as the strongest risk factor for death. Spatial and space-time cluster of high incidence of meningiomas was detected in a small community on the eastern flank of the Mt. Etna volcano. CONCLUSIONS: Epidemiology of meningioma and glioblastoma in the province of Catania is close to that reported worldwide. Spatial and space-time cluster of meningiomas were found in Pedara. Further studies on risks factor are necessary.

Incidence of multiple sclerosis in the province of Catania. A geo-epidemiological study.

BACKGROUND: An increasing incidence of MS in the city of Catania was reported during 1975-2004, with a higher incidence along the south-eastern flank of the Mt.Etna. We evaluated the incidence of MS in the entire province of Catania during 2005-2015 and the spatial distribution of MS-cases using a cluster analysis. METHODS: Patients were considered as incident MS-cases if they fulfilled the revised McDonald criteria for MS during 2005-2015 and were residents in the province of Catania at the time of disease onset. Cluster analysis was performed using both LISA and Kulldorff's spatial scan statistic. Residence address at disease onset was considered for each case. Communalities were assessed considering the centroid of their inhabited area. RESULTS: A total of 973 MS-cases were identified. Mean annual incidence risk was 8.2/100,000 person-years (95%CI 7.7-8.7), significantly higher among women (10.5/100,000 versus 5.7/100,000). LISA identified a spatial aggregation of MS-cases in the eastern side of the province of Catania and Kulldorff's statistics confirmed the existence of a statistically significant spatial cluster in this area (SIR 1.23,95%CI 1.08-1.23, p-value 0.04). CONCLUSIONS: Our study confirms a high incidence of MS in the province of Catania and the presence of a spatial cluster along the eastern side of the province. This area is considered the most exposed to volcanogenic ashes due to the prevailing westerly to north-westerly trade winds. Even if such distribution could be related with a greater exposure to volcanogenic metals, further studies are needed to explore possible alternative hypotheses.

Validation of the Italian version of the PSP Quality of Life questionnaire.

BACKGROUND: Progressive supranuclear palsy (PSP) is a rare rapidly progressive, neurodegenerative disease characterized by falls and ocular movement disturbances. The use of health-related quality of life (HR-QoL) measures allows assessing changes in health status induced by therapeutic interventions or disease progress in neurodegenerative diseases. The PSP-QoL is a 45-item, self-administered questionnaire designed to evaluate HR-QoL in PSP. METHODS AND RESULTS: Here, the PSP-QoL was translated into Italian and validated in 190 PSP (96 women and 94 men; mean age ± standard deviation, 72 ± 6.5; mean disease duration, 4.2 ± 2.3) patients diagnosed according to the Movement Disorder Society criteria and recruited in 16 third level movement disorders centers participating in the Neurecanet project. The mean PSP-QoL total score was 77.8 ± 37 (physical subscore, 46.5 ± 18.7; mental subscore, 33.6 ± 19.2). The internal consistency was high (Cronbach's alpha = 0.954); corrected item-total correlation was > 0.40 for the majority of items. The significant and moderate correlation of the PSP-QoL with other HR-QoL measures as well as with motor and disability assessments indicated adequate convergent validity of the scale. Gender and geographic location presented a significant impact on the PSP-QoL in our sample with women and patients from the South of Italy scoring higher than their counterparts. CONCLUSION: In conclusion, the Italian version of the PSP-QoL is an easy, reliable and valid tool for assessment of HR-QoL in PSP.

Validation of the Italian version of carers' quality-of-life questionnaire for parkinsonism (PQoL Carer) in progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is a rare, rapidly progressive, neurodegenerative disease characterized by falls and ocular movement disturbances. Caring for a partner or relative who suffers from PSP entails a strenuous and demanding task, usually lasting for years that affects carers' everyday life routines and emotional and social well-being. The 26-item Parkinsonism Carers QoL (PQoL Carer) is a self-administered, concise instrument evaluating the quality of life of caregivers of patients with atypical parkinsonism (both PSP and multiple system atrophy). Here, the PQoL Carer was translated into Italian and validated in 162 carers of PSP patients (54.3% women; mean age (standard deviation), 62.4 (15.4)) diagnosed according to the Movement Disorder Society criteria and recruited in 16 third-level movement disorders centers participating in the Neurecanet project. The mean PQoL total score was 40.66 ± 19.46. The internal consistency was excellent (Cronbach's alpha = 0.941); corrected item-total correlation was > 0.40 for all the items. A correlation with other health-related quality of life measures as well as with behavioral assessments was shown suggesting adequate convergent validity of the scale. PQoL also correlated with patients' severity of disease. The discriminant validity of the scale was evidenced by its capacity to differentiate between carers with varying levels of self-reported health (p < 0.001). In conclusion, the Italian version of the PQoL Carer is an easy, consistent, and valid tool for the assessment of the quality of life in carers of PSP patients.

Obsessive-compulsive personality disorder in rapid eye movement sleep behavior disorder.

Rapid eye movement sleep behavior disorder (RBD) is a common prodromic non-motor symptom of Parkinson's disease (PD). Only few studies have evaluated the personality of RBD patients with conflicting results. Aim of the study was to evaluate the frequency of Personality Disorders (PeDs)in RBD. RBD patients, PD patients and healthy controls (HC) were enrolled. All the enrolled subjects underwent a full neurological examination. Motor symptoms were evaluated with the UPDRS-Motor Examination. PeDs were assessed with the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II). Twenty-nine RBD patients [14 men (48.3%); mean age 55.6 ± 11.1], 30 PD patients [17 men (56.7%); mean age 65.7 ± 10.7] and 30 HC [12 men (40%); mean age 65.7 ± 5.4] were enrolled in the study. PD patients had a disease duration of 4.5 ± 4.6 and presented a mean UPDRS-ME score of 26.7 ± 9.4. The most frequent PeDs was the Obsessive-Compulsive one (OCPeD); OCPeD was significantly more frequent in RBD (55.2%) patients than HC (13.3%; p-value < 0.001). No significant differences were found comparing the frequency of OCPeD in RBD patients to that in PD. In the present study, the prevalence of OCPeD in RBD patients was close to that reported in PD patients. Our data could suggest the existence of a common disease-specific RBD-PD personality profile.

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.

Does an association between cigarette smoking and Parkinson's Disease-related psychosis exist? Insights from a large non-demented cohort.

BACKGROUND: Parkinson's Disease-related Psychosis (PDP) encompasses a spectrum of symptoms ranging from "minor" hallucinations to formed hallucinations and delusions. Notably, cognitive impairment has been recognized as the strongest risk factor for PDP. Several evidences suggest a possible role of cigarette smoking in both cognition and psychotic syndromes. OBJECTIVES: To evaluate the possible independent association between cigarette smoking and PDP in a large cohort of non-demented PD patients. METHODS: A cohort of non-demented PD patients was selected from the FRAGAMP study population. All participants underwent a standardised structured questionnaire to assess demographic, clinical and environmental exposure data. Clinical features were assessed using UPDRS, HY stage, AIMS, MMSE and Hamilton Rating Scale for Depression. Presence of psychotic symptoms was assessed using UPDRS-I.2 score. Diagnosis of PDP was made according to NINDS/NIMH criteria. RESULTS: Four hundred eighty-five non-demented PD patients were enrolled [292 men (60.2%); mean age ± SD 65.6 ± 9.8]. Among them, 28 (5.8%) had PDP. Multivariate analysis, adjusting by HY stage, MMSE and LED, shown an independent association between PDP and "nightmares-abnormal movements during sleep" and current smoking [adjOR 7.39 (95%CI 1.45-37.69; P-value 0.016)]. CONCLUSIONS: Our findings provide interesting insights about the possible role of current smoking in facilitating the occurrence of psychotic symptoms in PD.

Phonemic Verbal Fluency and Midbrain Atrophy in Progressive Supranuclear Palsy.

BACKGROUND: The neuropsychological profile of progressive supranuclear palsy (PSP) patients is mainly characterized by executive dysfunction, but the relationship between the latter and midbrain atrophy is still unclear. OBJECTIVE: The aims of the study were to investigate which test evaluating executive functioning is more frequently impaired in PSP patients and to evaluate the relationship between midbrain-based MRI morphometric measures and executive dysfunction. METHODS: PSP patients who had undergone a neuropsychological battery assessing executive functioning with the Frontal Assessment Battery (FAB), the phonemic verbal fluency F-A-S, the Raven's Progressive Colored Matrix, and the Stroop word colors test (time and errors) were enrolled in the study. A group of Parkinson's disease (PD) patients matched by age, sex, education, and global cognitive status was selected. All the enrolled patients also underwent a volumetric T1-3D brain MRI. RESULTS: Thirty-five PSP patients and 35 PD patients were enrolled. Patients with PSP as compared to patients with PD showed a significant greater impairment in verbal fluency (16.0±7.9 and 23.4±8.7 words/180 s; p < 0.001) and a significant lower score at the FAB total score (11.5±3.8 and 13.7±3.4; p = 0.013). Midbrain area was significantly smaller in PSP patients than in PD patients (83.9±20.1 and 134.5±19.9 mm2; p < 0.001). In PSP patients, a significant positive correlation between verbal fluency and the midbrain area (r = 0.421; p = 0.028) was observed. CONCLUSION: Our findings suggest that the phonemic verbal fluency is among the most frequently impaired executive functions in PSP patients and is strongly correlated to midbrain atrophy.

Retinal thickness and microvascular pathway in Idiopathic Rapid eye movement sleep behaviour disorder and Parkinson's disease.

INTRODUCTION: Retinal impairment has previously been described in Parkinson's Disease (PD), also in early stage of disease. Idiopathic Rapid-eye-movement sleep Behavior Disorder (iRBD) is considered the strongest marker in the diagnosis of "Prodromal PD". Thus, we evaluated the thickness of retinal layers and the microvascular retinal pattern in a group of iRBD patients compared to PD and healthy subjects (HCs). METHODS: retinal layer's thickness and microvascular pattern among PD, iRBD and HCs were assessed using Spectral-Density Optical Coherence Tomography (SD-OCT) and OCT-Angiography (OCT-A), respectively. RESULTS: Forty-one eyes from 21 PD, 37 eyes from 19 iRBD and 33 eyes from 17 HCs were analysed. Peripapillary Retinal Nerve Fiber Layer (RNFL) was thinner in PD and RBD compared to HCs. All macular retinal layers, except for retinal pigment epithelium, resulted to be significantly thinner in iRBD and in PD compared to HCs, also adjusting by age, sex and hypertension. Macular RNFL and ganglionic cell layer were thinner in PD compared to iRBD. Moreover, in iRBD, a peculiar microvascular pattern was found, characterized by a higher vascularization of the deep capillary plexus with respect both PD patients and HCs. CONCLUSION: in PD and iRBD patients retina was thinner than HCs, and values of iRBD were between PD and HCs. Moreover, in iRBD, a peculiar microvascular pattern has been found, characterized by a higher vascularization of the deep capillary plexus. Our findings suggest that retina might be considered a biomarker of neurodegeneration in iRBD, easily estimable using non-invasive tool such as OCT and OCT-A.

Clinical-Instrumental patterns of neurodegeneration in Essential Tremor: A data-driven approach.

INTRODUCTION: Essential Tremor (ET) is increasingly recognized as a complex disorder with additional clinical signs other than tremor. It is still unknown whether a unique pathophysiologic or neurodegenerative process underlies progression and prognosis of the disease. The aim of the study was to identify ET phenotypes through a clinical-instrumental data-driven approach and to characterize possible patterns of neurodegeneration. METHODS: ET patients were categorized using spatio-temporal and kinematic variables related to mobility and dynamic stability processed by motion transducers. Differences between the identified groups in clinical-demographic variables, neuropsychological performances and retinal parameters by Optical Coherence Tomography (OCT) segmentation analysis were tested. RESULTS: Twenty-five ET patients were studied. Based on clustering of kinematic and spatio-temporal gait parameters, two independent groups were identified: cluster "A" (N = 15) and cluster "B" (N = 10). Compared to group A, group B had overall worse performance in mobility, especially on turning tasks. Identified clusters did not differ in terms of age, age at onset and disease duration. Patients in group B had more head tremor and more severe action tremor in the upper limbs as compared to group A, demonstrating also worse performances on cognitive assessments. Based on OCT analysis, group B presented a reduced thickness of the retinal inner layer as compared to group A, suggesting underlying neurodegenerative processes. CONCLUSIONS: The presence of gait and mobility impairment, associated with midline tremor, cognitive decline and retinal degeneration suggests a subtype of ET associated with neurodegeneration.

Asymmetry index of Blink Reflex Recovery Cycle differentiates Parkinson's disease from atypical Parkinsonian syndromes.

BACKGROUND: Differential diagnosis between Parkinson's disease (PD) and atypical Parkinsonian syndromes (APS), such as multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), is often difficult because of overlap of common clinical features. We evaluated R2 Blink Reflex Recovery Cycle (R2BRRC) in drug-naive PD patients and in MSA and PSP patients to differentiate early PD from APS. METHODS: We investigated 43 patients: 15 drug-naive PD patients, 16 MSA patients, and 12 PSP patients. R2BRRC was evaluated bilaterally at interstimulus intervals (ISIs) of 100, 150, 200, 300, 400, 500, and 750 ms. An asymmetry index (AI) of R2BRRC for each ISI was computed. RESULTS: R2BRRC of PD patients showed an increased brainstem excitability for less affected side (LAS) stimulation at ISIs of 100, 150, 200 (p < 0.001), and 300 ms (p = 0.03) compared to more affected side (MAS) stimulation, whereas no differences between LAS and MAS stimulation were found in APS. AI of 0.87 at ISI of 100 ms differentiated PD from MSA with a sensitivity of 86.7% and a specificity of 100%, whereas AI of 0.78 at ISI of 100 ms permitted to discriminate PD from PSP with a sensitivity of 86.7% and a specificity of 91.7%. CONCLUSION: AI of R2BRRC may represent a reliable tool in differentiating PD from APS, especially at the early stage of the disease.

Retinal Thickness and Microvascular Pattern in Early Parkinson's Disease.

A thinning of intraretinal layers has been previously described in Parkinson's disease (PD) patients compared to healthy controls (HCs). Few studies evaluated the possible correlation between retinal thickness and retinal microvascularization. Thus, here we assessed the thickness of retinal layers and microvascular pattern in early PD patients and HCs, using, respectively, spectral-domain optical coherence tomography (SD-OCT) and SD-OCT-angiography (SD-OCT-A), and more interestingly, we evaluated a possible correlation between retinal thickness and microvascular pattern. Patients fulfilling criteria for clinically established/clinically probable PD and HCs were enrolled. Exclusion criteria were any ocular, retinal, and systemic disease impairing the visual system. Retinal vascularization was analyzed using SD-OCT-A, and retinal layer thickness was assessed using SD-OCT. Forty-one eyes from 21 PD patients and 33 eyes from 17 HCs were evaluated. Peripapillary retinal nerve fiber layer (RNFL) and macular RNFL, ganglionic cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL), resulted to be thinner in PD compared to HCs. Among PD patients, a positive correlation between RNFL, GCL, and IPL thickness and microvascular density was found in the foveal region, also adjusting by age, sex, and, especially, hypertension. Such findings were already present in the early stage of disease and were irrespective of dopaminergic treatment. Thus, the retina might be considered a biomarker of PD and could be a useful instrument for onset and disease progression.

Seroprevalence of Toxocara Canis in the city of Catania, Italy.

Toxocariasis is one of the most common helminthiases worldwide. However, there is a lack of data regarding Southern Italy. We have evaluated the seroprevalence and associated environmental factors of toxocariasis in a sample of adults living in the city of Catania. Presence of anti-Toxocara canis IgG antibodies was searched using an ELISA test using excretory/secretory antigens. Environmental risk factors have been evaluated with a face-to-face questionnaire. Two hundred eighty-seven subjects (193 [67.3%] women, mean age 48.1±15.6 years) were enrolled, and presence of anti T. canis antibodies was found in 23 participants, of whom 18 (78.3%) were women with a mean age of 51.1±14.0 years, giving a seroprevalence of 8.0% (95%CI 5.4-11.7). At multivariate analysis, a positive association for subjects with more than three siblings (adjOR 3.17; 95%CI 1.09-9.25) was recorded. Our study confirms that exposition to T. canis is frequent also in urban areas of western countries.