Comparing Essential Tremor with and without Soft Dystonic Signs and Tremor Combined with Dystonia: The TITAN Study.

BACKGROUND: Tremor disorders remain as clinical diagnoses and the rate of misdiagnosis between the commonest non-parkinsonian tremors is relatively high. OBJECTIVES: To compare the clinical features of Essential Tremor without other features (pure ET), ET plus soft dystonic signs (ET + DS), and tremor combined with dystonia (TwD). METHODS: We compared the clinical features of patients with pure ET, ET + DS, and TwD enrolled in The ITAlian tremor Network (TITAN). Linear regression models were performed to determine factors associated with health status and quality of life. RESULTS: Three-hundred-eighty-three patients were included. Sex distribution was significantly different between the groups with males being more represented in pure ET and females in TwD. The initial site of tremor was different between the groups with about 40% of TwD having head tremor and ET + DS unilateral upper limb tremor at onset. This pattern mirrored the distribution of overt dystonia and soft dystonic signs at examination. Sensory trick, task-specificity, and position-dependence were more common, but not exclusive, to TwD. Pure ET patients showed the lowest degree of alcohol responsiveness and ET + DS the highest. Midline tremor was more commonly encountered and more severe in TwD than in the other groups. Regression analyses demonstrated that tremor severity, sex, age, and to a lesser degree the variable "group", independently predicted health status and quality of life, suggesting the existence of other determinants beyond tremor. CONCLUSIONS: Pure ET and TwD manifest with a phenotypic overlap, which calls for the identification of diagnostic biomarkers. ET + DS shared features with both syndromes, suggesting intra-group heterogeneity.

Elderly Onset of Functional Motor Disorders: Clinical Correlates from the Italian Registry.

BACKGROUND: Functional motor disorders (FMD) are a frequent neurological condition affecting patients with movement disorders. Commonly described in younger adults, their manifestation can be also associated to an elderly onset. OBJECTIVE: To assess the prevalence and describe the clinical manifestations of FMD with elderly and younger onset and their relationship with demographical and clinical variables. METHODS: We recruited patients with a "clinically definite" diagnosis of FMD from the Italian Registry of FMD. Patients underwent extensive clinical assessments. For elderly onset, we set a chronological cut-off at 65 years or older according to WHO definition. Multivariate regression models were implemented to estimate adjusted odds ratio of elderly FMD onset related to clinical characteristics. RESULTS: Among the 410 patients, 34 (8.2%) experienced elderly-onset FMD, with a mean age at onset of 70.9 years. The most common phenotype was tremor (47.1%), followed by gait disorders, weakness, and dystonia (29.4%, 23.5%, 14.7%, respectively). Eleven elderly patients had a combined phenomenology: 9 exhibited two phenotypes, 2 had three phenotypes. Weakness was isolated in 3/8 patients and combined with another phenotype in 5/8, manifesting as paraplegia (n = 4); upper limb diplegia (n = 2), hemiparesis/hemiplegia (n = 1), and tetraparesis/tetraplegia (n= 1). Non-motor and other functional neurological disorders occurred more frequently in the younger group (89.1%) than the elderly (73.5%). Neurological and non-neurological comorbidities were more prevalent in the elderly group (82.4%) as opposed to the younger (32.7%). In a multivariate regression analysis, elderly-onset FMD was significantly associated with neurological comorbidities, including parkinsonism (OR 6.73) and cerebrovascular diseases (OR 5.48). CONCLUSIONS: These results highlight the importance of achieving an accurate diagnosis of FMD in the elderly, as it is crucial for effectively managing FMD symptoms and addressing neurological comorbidities.

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.

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.

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.

Exploring the knowledge, attitudes, and practices on sexual and gender minorities patients: a survey on Italian Neurologists.

BACKGROUND: Sexual and gender minorities (SGM) encompass individuals identifying as lesbian, gay, bisexual, transgender, and queer (LGBTQ). SGM patients experience difficulties in accessing healthcare and may face discrimination, impacting their overall health outcomes. Enhancing healthcare professionals' knowledge is the initial step in dismantling these barriers. MATERIALS AND METHODS: The study has been conducted on the neurologists of the Italian Society of Neurology (SIN). We utilized a survey instrument comprising 24 Likert-type questions to investigate knowledge, attitudes, and practices concerning sexual orientation and gender identity minorities. Likert scales were assessed with scores 1 and 2 as negative response, 3 as neutral, and 4 and 5 as positive responses. RESULTS: A total of 177 neurologists (103 women; 58.2%) participated, with a mean age of 44.3 ± 14.6 years answered the survey. Over half recognized sexual and gender orientation as social determinants of health, yet only a minority acknowledged the elevated prevalence of physical and mental health issues in SGM populations. Nearly, all respondents felt confident in examining a sexual minority patient, while only half felt the same regarding transgender patients. The majority of neurologists expressed a need for more comprehensive training and supervision in treating SGM patients. CONCLUSION: To enhance healthcare quality for SGM populations, healthcare professionals must receive appropriate training in how to approach, assess, and treat patients within this demographic.

Epilepsy and neurocysticercosis in rural areas of the Bolivian Chaco: What has changed during the last 30 years?

OBJECTIVE: Neurocysticercosis (NCC) is considered the major cause of epilepsy in endemic regions. In the rural areas of the Bolivian Chaco prevalence of NCC among people with epilepsy (PWE) was 27.4%, according to a population-based survey carried out in 1994. The aim of the study was to estimate the prevalence of Epilepsy Associated with Tonic-Clonic Seizures (EATCS) and to evaluate the prevalence of NCC among PWE in the rural communities of the Bolivian Chaco after 30 years. METHODS: Twenty-two rural communities (total population 12 852) were involved in the study. PWE in the study area were ascertained by multiple sources and the diagnosis was confirmed by a neurologist. All PWE identified were invited to undergo brain CT scan examination and diagnosis of NCC was sought according to the revised Del Brutto criteria. RESULTS: Seventy-eight PWE (30 men, 38.4%; mean age at onset was 12.7 ± 13.2 years) with EATCS were identified giving a crude prevalence of 6.1/1000 (95% CI: 4.7-7.3). Due to the COVID-19 lockdown, the study was interrupted in 2020 and only 36 PWE (46%) of the whole sample underwent CT scan examination. Of these, 8 (22.2%) fulfilled the criteria for NCC of whom 6 (75%) presented only single or multiple calcifications. SIGNIFICANCE: This is the first study reassessing the prevalence of NCC among PWE after 30 years, in the same rural area and using a population-based design. T. solium is still endemic in the Bolivian Chaco where more than 20% of EATCS may be attributable to NCC. Our findings show a substantially unchanged prevalence of NCC over the past 30 years despite improved knowledge, underlining the need for active intervention programs to control T. solium transmission in this area. PLAIN LANGUAGE SUMMARY: Neurocysticercosis is still endemic in the Bolivian Chaco. The proportion of epilepsy attributable to neurocysticercosis is about 22%. Systematic efforts towards elimination of neurocysticercosis in these areas should be implemented.

Clinical correlates of "pure" essential tremor: the TITAN study.

Background: To date, there are no large studies delineating the clinical correlates of "pure" essential tremor (ET) according to its new definition. Methods: From the ITAlian tremor Network (TITAN) database, we extracted data from patients with a diagnosis of "pure" ET and excluded those with other tremor classifications, including ET-plus, focal, and task-specific tremor, which were formerly considered parts of the ET spectrum. Results: Out of 653 subjects recruited in the TITAN study by January 2022, the data of 208 (31.8%) "pure" ET patients (86M/122F) were analyzed. The distribution of age at onset was found to be bimodal. The proportion of familial cases by the age-at-onset class of 20 years showed significant differences, with sporadic cases representing the large majority of the class with an age at onset above 60 years. Patients with a positive family history of tremor had a younger onset and were more likely to have leg involvement than sporadic patients despite a similar disease duration. Early-onset and late-onset cases were different in terms of tremor distribution at onset and tremor severity, likely as a function of longer disease duration, yet without differences in terms of quality of life, which suggests a relatively benign progression. Treatment patterns and outcomes revealed that up to 40% of the sample was unsatisfied with the current pharmacological options. Discussion: The findings reported in the study provide new insights, especially with regard to a possible inversed sex distribution, and to the genetic backgrounds of "pure" ET, given that familial cases were evenly distributed across age-at-onset classes of 20 years. Deep clinical profiling of "pure" ET, for instance, according to age at onset, might increase the clinical value of this syndrome in identifying pathogenetic hypotheses and therapeutic strategies.

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.

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.

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.

Progression of clinical markers in prodromal Parkinson's disease and dementia with Lewy bodies: a multicentre study.

The neurodegenerative synucleinopathies, including Parkinson's disease and dementia with Lewy bodies, are characterized by a typically lengthy prodromal period of progressive subclinical motor and non-motor manifestations. Among these, idiopathic REM sleep behaviour disorder is a powerful early predictor of eventual phenoconversion, and therefore represents a critical opportunity to intervene with neuroprotective therapy. To inform the design of randomized trials, it is essential to study the natural progression of clinical markers during the prodromal stages of disease in order to establish optimal clinical end points. In this study, we combined prospective follow-up data from 28 centres of the International REM Sleep Behavior Disorder Study Group representing 12 countries. Polysomnogram-confirmed REM sleep behaviour disorder subjects were assessed for prodromal Parkinson's disease using the Movement Disorder Society criteria and underwent periodic structured sleep, motor, cognitive, autonomic and olfactory testing. We used linear mixed-effect modelling to estimate annual rates of clinical marker progression stratified by disease subtype, including prodromal Parkinson's disease and prodromal dementia with Lewy bodies. In addition, we calculated sample size requirements to demonstrate slowing of progression under different anticipated treatment effects. Overall, 1160 subjects were followed over an average of 3.3 ± 2.2 years. Among clinical variables assessed continuously, motor variables tended to progress faster and required the lowest sample sizes, ranging from 151 to 560 per group (at 50% drug efficacy and 2-year follow-up). By contrast, cognitive, olfactory and autonomic variables showed modest progression with higher variability, resulting in high sample sizes. The most efficient design was a time-to-event analysis using combined milestones of motor and cognitive decline, estimating 117 per group at 50% drug efficacy and 2-year trial duration. Finally, while phenoconverters showed overall greater progression than non-converters in motor, olfactory, cognitive and certain autonomic markers, the only robust difference in progression between Parkinson's disease and dementia with Lewy bodies phenoconverters was in cognitive testing. This large multicentre study demonstrates the evolution of motor and non-motor manifestations in prodromal synucleinopathy. These findings provide optimized clinical end points and sample size estimates to inform future neuroprotective trials.

Long-Duration Response to Levodopa, Motor Learning, and Neuroplasticity in Early Parkinson's Disease.

BACKGROUND: Long-duration response (LDR) to levodopa and motor learning could be involved in changes in neuroplasticity of cortical excitability in Parkinson's disease (PD). P300, motor evoked potentials (MEPs), and Bereitschaftspotential (BP) are neurophysiological surrogate markers of neuroplasticity. OBJECTIVE: We aimed to define in PD the effects of LDR and motor learning on neurophysiological parameters involved in neuroplasticity. METHODS: Drug-naive PD patients underwent a 15-day treatment with levodopa/carbidopa 250/25 mg daily. Achievement of LDR was assessed on the 15th day of treatment (T15). Patients were grouped based on the achievement of a sustained LDR (LDR+) or no LDR (LDR-) and to the assignment of a learning motor exercise (LME) or no motor exercise (NME). Patients underwent clinical and neurophysiological (P300, MEPs, and BP) assessments at baseline (T0) and on T15. RESULTS: Forty-one PD patients and 24 age- and sex-matched normal controls (NCs) were enrolled. Neurophysiological parameters differed between untreated PD patients and NCs. Four groups of patients were obtained at the end of treatments: trained patients with a sustained LDR (LDR + LME group), untrained patients with a sustained LDR (LDR + NME group), trained patients without LDR (LDR-LME group), and untrained patients without LDR (LDR-NME group). At baseline, no differences in clinical and neurophysiological parameters were evident among the groups. After the treatments, significant improvements in neurophysiological parameters were observed in the LDR + LME group. No modifications were found in the groups without LDR. CONCLUSIONS: The achievement of a sustained LDR may act synergistically with motor learning to induce adaptive changes in neuroplasticity in basal ganglia and cortical networks. Our findings support LDR as a pharmacological outcome possibly facilitating the action of motor learning on neuroplasticity in early PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Prevalence of epilepsy in the rural area of the Bolivian Gran Chaco: Usefulness of telemedicine and impact of awareness campaigns.

OBJECTIVE: The objective of this study is to estimate the prevalence of epilepsy with Tonic-Clonic (TC) seizures in rural areas of the Bolivian Gran Chaco and to evaluate the usefulness of telemedicine in this context. METHODS: The study was carried out in the Isozo Area, southern-eastern Bolivia. Twenty-five rural communities with a population of 8258 inhabitants were included in the survey. Trained community-health workers administered a validated single screening question to the householders (stage I). A second face-to-face questionnaire was administered to each positive subject (stage II). At stage II subjects were also screened using the smartphone app "Epilepsy Diagnosis Aid". Subjects screened positive at stage II underwent a complete neurological examination to confirm the diagnosis (stage III). Due to the COVID-19 lockdown, some subjects have been evaluated through a digital platform (Zoom®). RESULTS: One-thousand two-hundred and thirteen interviews were performed at stage I, corresponding to a total screened population of 6692 inhabitants. Thirty-eight screened positive were identified at stage I and II and of these, 28 people with epilepsy were identified, giving an overall prevalence of 4.2/1000 (95% CI 2.6-5.7). Prevalence rate steeply increased with age reaching a peak of 7.9/1000 in the population aged 20-29 years without significant differences between women and men. For almost 50% of the screened positive subjects, confirmation of epilepsy by a neurologist at stage III was achieved through simple videoconsultation. After a simultaneous awareness campaign, 22 self-reported PWE requested a consultation and, among them, 11 had a diagnosis of epilepsy confirmed. SIGNIFICANCE: This study shows a prevalence estimate close to those reported for LMIC. Simple videoconsultation and specific apps may be valuable tools in epidemiological research. Awareness campaigns are important allies for a full case identification, particularly in contexts where higher rates of stigma are recorded.

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.

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.