Personality and psychopathological characteristics in functional movement disorders.

INTRODUCTION: Aim of the present study was to assess personality and psychopathological characteristics in patients with functional movement disorders (FMDs) compared to patients with other neurological disorders (OND). METHODS: In this cross-sectional study, patients affected by clinically established FMDs and OND who attended the Neurologic Unit of the University-Hospital "Policlinico-San Marco" of Catania from the 1st of December 2021 to the 1st of June 2023 were enrolled. Personality characteristics were assessed with the Rorschach test coded according to Exner's comprehensive system and the Structured Clinical Interview for DSM-5 (SCID-II). RESULTS: Thirty-one patients with FMDs (27 women; age 40.2±15.5 years; education 11.7±3.2 years; disease duration 2.3±2.5 years) and 24 patients affected by OND (18 women; age 35.8±16.3 years; education 11.9±2.9 years; disease duration 3.4±2.8 years) were enrolled. At the Rorschach, FMDs presented a significantly higher frequency of Popular (P) and sum of all Human content codes (SumH>5) responses and avoidant coping than OND. CONCLUSION: FMDs presented "conformity behaviors", excessive interest in others than usual a maladaptive avoidant style of coping and a difficulty in verbalizing emotional distress. These psychopathological characteristics may favor the occurrence of FMDs.

Paroxysmal Dystonic Posturing Mimicking Nocturnal Leg Cramps as a Presenting Sign in an Infant with DCC Mutation, Callosal Agenesis and Mirror Movements.

Background/Objectives: Pathogenic variants in the deleted in colorectal cancer gene (DCC), encoding the Netrin-1 receptor, may lead to mirror movements (MMs) associated with agenesis/dysgenesis of the corpus callosum (ACC) and cognitive and/or neuropsychiatric issues. The clinical phenotype is related to the biological function of DCC in the corpus callosum and corticospinal tract development as Netrin-1 is implicated in the guidance of developing axons toward the midline. We report on a child with a novel inherited, monoallelic, pathogenic variant in the DCC gene. Methods: Standardized measures and clinical scales were used to assess psychomotor development, communication and social skills, emotional and behavioural difficulties. MMs were measured via the Woods and Teuber classification. Exome sequencing was performed on affected and healthy family members. Results: The patient's clinical presentation during infancy consisted of paroxysmal dystonic posturing when asleep, mimicking nocturnal leg cramps. A brain magnetic resonance imaging (MRI) showed complete ACC. He developed typical upper limb MMs during childhood and a progressively evolving neuro-phenotype with global development delay and behavioural problems. We found an intrafamilial clinical variability associated with DCC mutations: the proband's father and uncle shared the same DCC variant, with a milder clinical phenotype. The atypical early clinical presentation of the present patient expands the clinical spectrum associated with DCC variants, especially those in the paediatric age. Conclusions: This study underlines the importance of in-depth genetic investigations in young children with ACC and highlights the need for further detailed analyses of early motor symptoms in infants with DCC mutations.

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.

Can mobile health apps with smartphones and tablets be the new frontier of cognitive rehabilitation in older individuals? A narrative review of a growing field.

INTRODUCTION: A recent interesting field of application of telemedicine/e-health involved smartphone apps. Although research on mHealth began in 2014, there are still few studies using these technologies in healthy elderly and in neurodegenerative disorders. Thus, the aim of the present review was to summarize current evidence on the usability and effectiveness of the use of mHealth in older adults and patients with neurodegenerative disorders. METHODS: This review was conducted by searching for recent peer-reviewed articles published between June 1, 2010 and March 2023 using the following databases: Pubmed, Embase, Cochrane Database, and Web of Science. After duplicate removal, abstract and title screening, 25 articles were included in the full-text assessment. RESULTS: Ten articles assessed the acceptance and usability, and 15 articles evaluated the efficacy of e-health in both older individuals and patients with neurodegenerative disorders. The majority of studies reported that mHealth training was well accepted by the users, and was able to stimulate cognitive abilities, such as processing speed, prospective and episodic memory, and executive functioning, making smartphones and tablets valuable tools to enhance cognitive performances. However, the studies are mainly case series, case-control, and in general small-scale studies and often without follow-up, and only a few RCTs have been published to date. CONCLUSIONS: Despite the great attention paid to mHealth in recent years, the evidence in the literature on their effectiveness is scarce and not comparable. Longitudinal RCTs are needed to evaluate the efficacy of mHealth cognitive rehabilitation in the elderly and in patients with neurodegenerative disorders.

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.

Effectiveness of telerehabilitation plus virtual reality (Tele-RV) in cognitive e social functioning: A randomized clinical study on Parkinson's disease.

INTRODUCTION: Telemedicine could represent an emerging and innovative approach to support cognitive and behavioral rehabilitation reducing the overload of healthcare facilities, favoring home care therapy. The present study aimed to assess the potential efficacy of Tele-VR apps in enhancing cognitive performance and improving social skills in patients with Parkinson's disease (PD). METHODS: Thirty-four patients with PD were included in the study. Patients were assigned to one of the following treatment groups: Experimental Group 1 (EG1) underwent a Tele-VR program using two cognitive rehabilitation applications (app) on smartphones (Neuronation-Brain Training and Train your Brain); Experimental Group 2 (EG2) received a Tele-VR program through one cognitive rehabilitation app (Neuronation-Brain Training) and one socio-cognitive rehabilitation App (The Sims) on smartphones; Active Control Group (aCG) performed a conventional training using pencil and paper exercises (Not-VR). RESULTS: At the end of the study, the aCG and EG1 presented an improvement in the executive, attentional and visuospatial cognitive domains. Mood and subjective memory also improved in the EG1. Moreover, in the EG2 group, a significant improvement was found in all cognitive domains, including social cognition skills (theory of mind). The inter-group comparison showed that both EG1 and EG2 had significantly greater improvements than aCG in MoCA score. Finally, both EG1 and EG2 showed a higher improvement in the FAB score, as compared to the aCG. CONCLUSION: Rehabilitation with smartphone apps could be more useful than conventional rehabilitation in improving cognitive and social cognition skills in patients with PD. Combining cognitive and social cognition training could improve the cognitive and affective domains, also aiding in the long-term maintenance of cognitive outcomes.

Gender differences in non-motor fluctuations in Parkinson's disease.

Non-motor symptoms (NMS) and Non-motor fluctuations (NMF) in Parkinson's Disease (PD) are common, involving several domains and affecting quality of life. Aim of the study is to estimate the burden of NMF in PD patients and to evaluate the possible gender effect. PD patients fulfilling the MDS-PD diagnostic criteria attending the "Parkinson's Disease and Movement Disorders Centre" of the University of Catania were evaluated using the Non-Motor Fluctuations Assessment (NoMoFA) Questionnaire. NoMoFA items were also grouped into the following domains: cognitive, mood, sleep/fatigue, dysautonomia, hallucination/perception and miscellaneous domains were identified. One-hundred and twenty-one patients with PD (67 men, 55.4%; mean age 70.2 ± 8.9 years, disease duration 8.3 ± 4.6 years) were evaluated. All PD patients reported at least one NMS, whereas 87 (71.9%) also reported NMF. "Feel sluggish or had low energy levels" (47.2%) along with "Feel excessively sleepy during the day" (40.0%) were the most common NMF reported in the whole sample. The majority of PD patients reported the presence of NMF during the OFF state (79, 65.3%). At multivariate analysis, NMF were positively associated with the female gender (adjusted OR 3.13; 95%CI 1.21-8.11 p-value 0.01). Women with PD had higher NMF scores especially in depression/anxiety, sleep/fatigue and dysautonomia domains. Our study reported the presence of a gender-related pattern in the frequency of NMS and NMF in PD patients, with female gender associated with a higher risk of developing NMF, highlighting the need for personalized treatment strategies when addressing NMF.

Brain linear measurements for differentiating normal pressure hydrocephalus from Alzheimer's disease: an exploratory study.

BACKGROUND AND PURPOSE: Easy and reliable tools for the differential diagnosis between idiopathic normal pressure hydrocephalus (iNPH) and Alzheimer's disease (AD) are needed. MATERIALS AND METHODS: In this cross-sectional study iNPH and AD patients referred to the Neurology Unit of the University of Catania from 1 January 2020 to 1 December 2022 were enrolled. The following brain linear measurements (BLMs) were calculated: Evan's index (EI), the parieto-occipital ratio (POR) and the temporal ratio (TR). For each index, sensitivity, specificity and the area under the curve (AUC) were calculated. Moreover, a cumulative index, the BLM index, was also considered. RESULTS: Fifty patients (25 iNPH and 25 AD) were enrolled. In differentiating iNPH from AD, EI had the highest AUC (0.956), POR had the highest specificity (100%) whilst TR had the highest sensitivity (92%). The BLM index differentiated iNPH and AD with a sensitivity of 96%, a specificity of 92% and an AUC of 0.963 with an optimal cut-off value of 0.303. CONCLUSION: Evan's index, POR and TR may be useful in the differential diagnosis between iNPH and AD. At an individual level, the BLM index represents a valid and reliable tool to achieve an accurate differentiation between these two conditions.

Sex and gender differences in Alzheimer's disease, Parkinson's disease, and Amyotrophic Lateral Sclerosis: A narrative review.

Neurodegenerative diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), exhibit high phenotypic variability and they are very common in the general population. These diseases are associated with poor prognosis and a significant burden on patients and their caregivers. Although increasing evidence suggests that biological sex is an important factor for the development and phenotypical expression of some NDs, the role of sex and gender in the diagnosis and prognosis of NDs has been poorly explored. Current knowledge relating to sex- and gender-related differences in the epidemiology, clinical features, biomarkers, and treatment of AD, PD, and ALS will be summarized in this narrative review. The cumulative evidence hitherto collected suggests that sex and gender are factors to be considered in explaining the heterogeneity of these NDs. Clarifying the role of sex and gender in AD, PD, and ALS is a key topic in precision medicine, which will facilitate sex-specific prevention and treatment strategies to be implemented in the near future.

Influence of RBD onset on the clinical characteristics of Parkinson's disease patients: a retrospective study.

INTRODUCTION: In Parkinson's disease (PD), rapid eye movement (REM) sleep behavior disorder (RBD) might either precede the appearance of motor symptoms, or develop during the disease course. PD patients with RBD are characterized by a higher burden of cognitive impairment and hallucinations. However, few studies have analyzed the clinical characteristics of PD patients according to the timeline of RBD onset. METHODS: PD patients have been retrospectively enrolled. Presence and onset of probable RBD (pRBD) has been evaluated using RBD Screening Questionnaire (score ≥ 6). Presence of Mild Cognitive Impairment (MCI) at baseline has been evaluated using the MDS criteria level II. Presence of motor complications and hallucinations has been evaluated at a 5-year follow-up. RESULTS: A total of 115 PD patients (65 men, 56.5%; mean age 62.5 ± 9.7 years; mean disease duration 3.7 ± 3.9 years) have been enrolled. Out of these, 63 fulfilled the diagnosis of pRBD (54.8%) with 21 (33.3%) reporting the RBD onset before the onset of the motor symptoms (PD-RBDpre), and 42 (66.7%) after the motor symptoms (PD-RBDpost). At enrolment presence of MCI was associated with PD-RBDpre patients (OR 5.04; 95% CI 1.33-19.05; p value 0.02). At follow-up, a higher risk of developing hallucinations was also associated with PD-RBDpre (OR 4.68; 95% CI 1.24-17.63; p = 0.022). CONCLUSIONS: PD patients with RBD occurring before the onset of motor symptoms represent a subgroup of patients with a more severe cognitive phenotype and with a higher risk of developing hallucinations along the disease course, with significant implications in terms of prognostic stratification and therapeutic approach.

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.

Verbal Reasoning Impairment in Parkinson's Disease.

Background: The aim of this study was to assess verbal reasoning (VR) functioning in patients with Parkinson's disease (PD) and healthy controls (HCs). Methods: The non-demented PD patients and HCs matched by age and global cognition were enrolled in this study. VR was assessed with the verbal reasoning test (VRT), total score, and subsets. Results: Eighty-seven PD patients (51 men; mean age 63.8 ± 7.9 years) and 87 HCs (46 men; mean age 63.7 ± 8.0 years) were enrolled. At univariate analysis, PD patients presented a significantly lower score in the VRT subset classification (12.3 ± 2.1) than HCs (12.9 ± 1.7) with an odds ratio (OR) of 0.8 (95% confidence interval [CI] 0.70-0.98; p = 0.003). The strength of association was also confirmed at multivariate analysis (OR = 0.8, 95% CI 0.70-0.98; p = 0.003). Moreover, in PD patients, a statistically significant positive correlation was found between VRT-classification and MoCA scores (r = 0.330; p = 0.002). Conclusions: PD patients presented lower VR performance than HCs.

Data-driven clustering of combined Functional Motor Disorders based on the Italian registry.

Introduction: Functional Motor Disorders (FMDs) represent nosological entities with no clear phenotypic characterization, especially in patients with multiple (combined FMDs) motor manifestations. A data-driven approach using cluster analysis of clinical data has been proposed as an analytic method to obtain non-hierarchical unbiased classifications. The study aimed to identify clinical subtypes of combined FMDs using a data-driven approach to overcome possible limits related to "a priori" classifications and clinical overlapping. Methods: Data were obtained by the Italian Registry of Functional Motor Disorders. Patients identified with multiple or "combined" FMDs by standardized clinical assessments were selected to be analyzed. Non-hierarchical cluster analysis was performed based on FMDs phenomenology. Multivariate analysis was then performed after adjustment for principal confounding variables. Results: From a study population of n = 410 subjects with FMDs, we selected n = 188 subjects [women: 133 (70.7%); age: 47.9 ± 14.4 years; disease duration: 6.4 ± 7.7 years] presenting combined FMDs to be analyzed. Based on motor phenotype, two independent clusters were identified: Cluster C1 (n = 82; 43.6%) and Cluster C2 (n = 106; 56.4%). Cluster C1 was characterized by functional tremor plus parkinsonism as the main clinical phenotype. Cluster C2 mainly included subjects with functional weakness. Cluster C1 included older subjects suffering from anxiety who were more treated with botulinum toxin and antiepileptics. Cluster C2 included younger subjects referring to different associated symptoms, such as pain, headache, and visual disturbances, who were more treated with antidepressants. Conclusion: Using a data-driven approach of clinical data from the Italian registry, we differentiated clinical subtypes among combined FMDs to be validated by prospective studies.

Feasibility and usability of a non-immersive virtual reality tele-cognitive app in cognitive rehabilitation of patients affected by Parkinson's disease.

BACKGROUND: Cognitive impairment is one of the most common non-motor features of Parkinson's disease (PD). The aim of the present study was to evaluate the feasibility and acceptability/usability of a protocol using a non-immersive virtual reality tele-cognitive app, performed remotely in a sample of Italian patients with PD. METHODS: Non-demented patients with mild PD were included in the study. Patients performed the cognitive rehabilitation in a remote way, at home (three training sessions lasting 20 min/week for 6 weeks) using the NeuroNation app, downloaded for free on the patients' smartphones. The usability and feasibility of the tele-cognitive rehabilitation program were assessed with the System Usability Scale (SUS) and the Goal Attainment Scaling (GAS). RESULTS: Sixteen patients (9 men and 7 women; mean age 58.4 ± 8.3 years; mean disease duration 4.6 ± 2.1 years) were included in the study. At the end of the study, the mean SUS was 83.4 ± 11.5. The GAS score recorded at the end of the study (65.6 ± 4.2) was significantly higher than at baseline (38.5 ± 2.4; P-value <0.001). CONCLUSION: In our sample, good feasibility and usability were observed for a 6-week cognitive rehabilitation protocol based on the non-immersive virtual reality tele-cognitive app NeuroNation. Our data support the usefulness of cognitive rehabilitation performed in a remote way in PD patients.

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.

Morphometric magnetic resonance imaging cortico-subcortical features in Parkinson's disease with mild cognitive impairment.

BACKGROUND AND PURPOSE: Parkinson's disease (PD) patients with cognitive impairment undergo progressive atrophy of several cortical and subcortical areas. The aim was to study the magnetic resonance imaging (MRI) morphometric features of PD patients with mild cognitive impairment (MCI). METHODS: Patients from the Parkinson's Disease Cognitive Impairment Study (PACOS) cohort with an available structural volumetric brain MRI and morphometric measurements of the midbrain and pons areas, middle cerebellar peduncle, superior cerebellar peduncle width and midbrain anteroposterior diameter (A-Pdiam) were included. MCI was diagnosed according to the Movement Disorder Society level II criteria. Additionally, cortical thickness analysis was performed and correlated with morphometric brainstem measurements. RESULTS: Morphometric measurements were available for 168 subjects, of whom 67 (39.9%) were diagnosed with PD-MCI. The mean age (± standard deviation) of the sample was 64.2 ± 9.8. Amongst patients, 84 (50%) were men with a disease duration of 5.2 ± 5.4 years and a Unified Parkinson's Disease Rating Scale-Motor Examination score of 32.1 ± 12.9. In the univariate and multivariate analysis, after adjusting for age, sex, years of schooling and disease duration, MCI was associated with midbrain area (odds ratio 0.98; 95% confidence interval 0.96-0.99; p = 0.048) and A-Pdiam (odds ratio 0.63; 95% confidence interval 0.46-0.86; p = 0.005). Furthermore, 121 PD patients underwent cortical thickness analysis, which showed the presence of cortical thinning in lateral orbitofrontal regions of patients with PD-MCI. No correlation was found between cortical thickness and brainstem morphometric measurements. CONCLUSIONS: A mild midbrain atrophy and the presence of frontal cortical thickness reduction might be considered a structural MRI feature of PD patients with MCI.