Real-world use of Safinamide in motor fluctuating Parkinson's disease patients in Italy.

INTRODUCTION: Safinamide is a recent antiparkinsonian drug that modulates both dopaminergic and glutamatergic systems with positive effects on motor and nonmotor symptoms of Parkinson's disease (PD). Here, we aimed to describe the efficacy and safety of safinamide in the Italian PD patients in real-life conditions. METHODS: We performed a sub-analysis of the Italian cohort of the SYNAPSES study, a multi-country, multi-center, retrospective-prospective cohort observational study, designed to investigate the use of safinamide in routine clinical practice. Patients received for the first time a treatment with safinamide and were followed up for 12 months. The analysis was conducted on the overall population and in subgroups of interest: i) patients > 75 years, ii) patients with relevant comorbidities and iii) patients affected by psychiatric symptoms. RESULTS: Italy enrolled 616/1610 patients in 52 centers, accounting for 38% of the entire SYNAPSES cohort. Of the patients enrolled, 86.0% were evaluable at 12 months, with 23.3% being > 75 years, 42.4% with psychiatric conditions and 67.7% with relevant comorbidities. Safinamide was effective on motor symptoms and fluctuations as measured through the Unified PD rating scale III and IV scores, and on the total score, without safety issues in none of the subgroups considered. CONCLUSION: The SYNAPSES data related to Italian patients confirms the good safety profile of safinamide even in special groups of patients. Motor fluctuations and motor impairment improved at the follow-up suggesting the significant role of safinamide in managing motor symptoms in PD patients.

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.

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.

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.

Subclinical involvement of eye movements detected by video-based eye tracking in myasthenia gravis.

BACKGRO UND: Ocular abnormalities in myasthenia gravis (MG) are characterized by severely limited movements and rapid saccades. Data about eye motility of MG patients whose ocular movements are apparently normal are lacking. Our study assessed the eye movement parameters in MG patients without clinical eye motility dysfunctions and investigated the effects of neostigmine administration on the eye motility in these patients. MATERIALS: In this longitudinal study, we screened all patients diagnosed with MG referring to the Neurologic Clinic of the University of Catania between October 1, 2019, and June 30, 2021. Ten age- and sex-matched healthy controls were enrolled. Patients underwent eye movement recording using the EyeLink1000 Plus® eye tracker at baseline and after 90 min from the intramuscular administration of neostigmine (0.5 mg). RESULTS: A total of 14 MG patients with no clinical signs of ocular motor dysfunction (64.3% men, with a mean age of 50.4 ± 14.4 years) were enrolled. At baseline, saccades in MG patients showed slower velocities and longer latencies compared to controls. Moreover, the fatigue test induced a reduction in saccadic velocity and an increase in latencies. After neostigmine administration, the ocular motility analysis showed shorter saccadic latencies and a significant improvement of velocities. CONCLUSIONS: Eye motility is impaired even in MG patients with no clinical evidence of ocular movement disturbance. Video-based eye tracking may detect subclinical involvement of eye movements in patients with MG.

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.

Executive functioning and serum lipid fractions in Parkinson's disease-a possible sex-effect: the PACOS study.

The association between dyslipidemia and cognitive performance in Parkinson's disease (PD) patients still needs to be clarified. Aim of the study was to evaluate the presence of possible associations between serum lipids fractions and executive dysfunction also exploring the sex-specific contribute of lipids level on cognition. Patients from the PACOS cohort, who underwent a complete serum lipid profile measures (total cholesterol-TC, low-density lipoprotein cholesterol-LDL, high-density lipoprotein cholesterol-HDL and triglycerides-TG) were selected. Adult Treatment Panel III guidelines of the National Cholesterol Education Program were used to classify normal/abnormal lipid fractions. Executive functioning was assessed with the Frontal Assessment Battery (FAB). Logistic regression was performed to assess associations between lipids fractions and FAB score. Correlations between lipids fractions and FAB score were explored. Sex-stratified analysis was performed. Three hundred and forty-eight PD patients (148 women; age 66.5 ± 9.5 years; disease duration 3.9 ± 4.9 years) were enrolled. Women presented significantly higher TC, LDL and HDL than men. In the whole sample, any association between lipid profile measures and FAB score was found. Among women, a positive association between hypertriglyceridemia and FAB score under cutoff was found (OR 3.4; 95%CI 1.29-9.03; p value 0.013). A statistically significant negative correlation was found between the FAB score and triglyceride serum levels (r = - 0.226; p value 0.005). Differently, among men, a statistically significant negative association between hypercholesterolemia and FAB score under cutoff (OR 0.4; 95%CI 0.17-0.84; p value 0.018) and between high LDL levels and FAB score under cutoff (OR 0.4; 95%CI 0.18-0.90; p value 0.027) were found. Our data suggest a sex-specific different role of lipids in executive functioning.

Do demographic and clinical features and comorbidities affect the risk of spread to an additional body site in functional motor disorders?

The aim of this study is to assess changes in the body distribution and the semeiology of functional motor disorder (FMD) in patients who reported only one or more than one body site affected at FMD onset. Data were obtained from the Italian Registry of Functional Motor Disorders, which included patients with a diagnosis of clinically definite FMDs. The relationship between FMD features and spread to other body sites was estimated by multivariate Cox regression analysis. We identified 201 (49%) patients who reported only one body site affected at FMD onset and 209 (51%) who reported multiple body sites affected at onset. FMD spread from the initial site to another site in 43/201 (21.4%) patients over 5.7 ± 7.1 years in those with only one site affected at FMD onset; FMD spread to an another body site in 29/209 (13.8%) over 5.5 ± 6.5 years. The spread of FMD was associated with non-motor functional symptoms and psychiatric comorbidities only in the patients with one body site affected at FMD onset. Our findings provide novel insight into the natural history of FMD. The number of body sites affected at onset does not seem to have a consistent influence on the risk of spread. Furthermore, our findings suggest that psychiatric comorbidities and non-motor functional symptoms may predict the spread of FMD symptoms, at least in patients with one body site affected at onset.

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.

Parkinsonism in idiopathic normal pressure hydrocephalus: is it time for defining a clinical tetrad?

BACKGROUND: Association between parkinsonism and idiopathic normal pressure hydrocephalus (iNPH) still remains debated. There is already plenty of evidences in the literature suggesting that this clinical sign can be considered as an integral part of the clinical spectrum of iNPH patients. METHODS: We reviewed the possible pitfalls in the core clinical definition of iNPH based on available international diagnostic criteria, phenomenology of parkinsonism in iNPH, and neuroimaging supporting the presence of parkinsonism in iNPH. CONCLUSIONS: We argue that the diagnostic definition of the iNPH "triad" should be possibly reconsidered as a "tetrad" also including parkinsonism.

Reliability of televisits for patients with mild relapsing-remitting multiple sclerosis in the COVID-19 era.

BACKGROUND: Evidence of the cost-effectiveness of telemedicine (TM) for the management of Multiple Sclerosis (MS) has been provided recently. However, some doubts persist about the accuracy of neurological examinations performed remotely. OBJECTIVES: This study investigated the reliability of neurological evaluations performed through TM in mild MS patients as compared with standard in-person visits. METHODS: In total, 76 patients with relapsing-remitting MS and Expanded Disability Status Scale (EDSS) ≤ 3.5 were consecutively recruited. Of them, 40 patients (52.6%) accepted to undergo both in-person and TM evaluations with independent examiners within 48 h. We alternatively asked patients to assure or not the presence of a caregiver during TM visits. A satisfaction questionnaire was administered to all participants. RESULTS: The inter-rater agreement attributed by two independent neurologists during TM visit was high (κ > 0.80) for EDSS and Functional Systems (FS) scores. Moderate agreement between TM and in-person evaluations emerged for pyramidal (κ = 0.57; p < 0.001), brainstem (κ = 0.57; p < 0.001), bowel and bladder (κ = 0.54; p < 0.001) and sensory (κ = 0.51; p < 0.001) FS scores, higher in patients providing the support of a caregiver. A good reliability was reported for EDSS scores computed during remote and in-person visits (ICC = 0.83; 95% CI 0.70-0.91; p < 0.001). CONCLUSIONS: Despite the complexity of neurological examination, TM could be useful in monitoring MS patients with low disability.

Burden of Parkinson's disease in Sicily: a health administrative database study.

INTRODUCTION: Prevalence of Parkinson's disease (PD) increases with the advanced ages, representing a relevant health burden. Accurate prevalence estimates are of fundamental need in order to adjust the supply of health services for these patients. The availability of administrative health data from the National Health System provides a useful resource to assess the burden of diseases. Our aim was to evaluate the prevalence of PD through the use of administrative data in the Sicily region. METHODS: We have identified all the subjects affected by PD in Sicily in 2017 by gathering data from three regional health administrative databases: the hospital discharge records, the medical exemption databases, and the pharmacological prescription database. Prevalence rates and 95% confidence intervals (CI) have been calculated across 5-year age classes. RESULTS: PD patients identified through database searching were 24,674, giving a prevalence of 488/100,000 (95%CI 481.9-494.1) inhabitants. Prevalence was higher among men (514.5/100,000; 95%CI 505.6-523.6) and reached a peak in the 85-89 age class (3203.8/100,000; 95%CI 3095.2-3315.1). DISCUSSION: Our prevalence estimates of PD were higher when compared to previous epidemiological surveys conducted in Sicily. These findings are, however, comparable to other studies conducted in Italy that identified cases through administrative databases. Using health databases is a feasible strategy to assess the burden of PD.

Pure sensitive chronic inflammatory axonal polyneuropathy following Pfizer COVID-19 vaccine.

BACKGROUND: During the worldwide mass vaccination campaign against SARS-CoV-2, multiple side effects have been observed. We described the case of a patient who developed pure sensitive chronic inflammatory axonal polyneuropathy (CIAP) in a close temporal relationship with the administration of the BNT162b2 (Pfizer®) vaccine. CASE REPORT: An 82-year-old woman developed lower limb sensory loss and "pricking" associated with marked gait imbalance after she had received her second dose of Pfizer-BioNTech COVID-19 vaccine. At the electroneurographic examination, the motor nerves conduction study was normal. Median, ulnar, and sural nerves sensory compound nerve action potential (CNAP) were bilaterally absent. Somatosensory evoked potentials (SSEPs) were not recordable. Spine MRI demonstrated roots enhancement from C3 to Th2 and diffuse enhancement of cauda equina nerve roots. She was treated with IV methylprednisolone whit benefit. A follow-up visit was made 4 months after the disease onset; a diagnosis of pure sensitive CIAP has been made. DISCUSSION: To the best of our knowledge, this is the first description of CIAP occurring in a close temporal relationship with the administration of Pfizer-BioNTech COVID-19 vaccine.

Diagnostic and therapeutic recommendations in adult dystonia: a joint document by the Italian Society of Neurology, the Italian Academy for the Study of Parkinson's Disease and Movement Disorders, and the Italian Network on Botulinum Toxin.

The diagnostic framework and the therapeutic management of patients with adult dystonia can represent a challenge for clinical neurologists. The objective of the present paper is to delineate diagnostic and therapeutic recommendations for dystonia provided by a panel of Italian experts afferent to the Italian Society of Neurology, the Italian Academy for the Study of Parkinson's Disease and Movement Disorders, and the Italian Network on Botulinum Toxin. We first discuss the clinical approach and the instrumental assessment useful for diagnostic purpose. Then, we analyze the pharmacological, surgical, and rehabilitative therapeutic options for adult dystonia. Finally, we propose a hospital-territory network model for adult dystonia management.

A Comparison among Different Strategies to Detect Potential Unstable Behaviors in Postural Sway.

Assistive Technology helps to assess the daily living and safety of frail people, with particular regards to the detection and prevention of falls. In this paper, a comparison is provided among different strategies to analyze postural sway, with the aim of detecting unstable postural status in standing condition as precursors of potential falls. Three approaches are considered: (i) a time-based features threshold algorithm, (ii) a time-based features Neuro-Fuzzy inference system, and (iii) a Neuro-Fuzzy inference fed by Discrete-Wavelet-Transform-based features. The analysis was performed across a wide dataset and exploited performance indexes aimed at assessing the accuracy and the reliability of predictions provided by the above-mentioned strategies. The results obtained demonstrate valuable performances of the three considered strategies in correctly distinguishing among stable and unstable postural status. However, the analysis of robustness against noisy data highlights better performance of Neuro-Fuzzy inference systems with respect to the threshold-based algorithm.

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.

Functional motor disorders associated with other neurological diseases: Beyond the boundaries of "organic" neurology.

BACKGROUND AND PURPOSE: The aims of this study were to describe the clinical manifestations of functional motor disorders (FMDs) coexisting with other neurological diseases ("comorbid FMDs"), and to compare comorbid FMDs with FMDs not overlapping with other neurological diseases ("pure FMDs"). METHODS: For this multicenter observational study, we enrolled outpatients with a definite FMD diagnosis attending 25 tertiary movement disorder centers in Italy. Each patient with FMDs underwent a detailed clinical assessment including screening for other associated neurological conditions. Group comparisons (comorbid FMDs vs. pure FMDs) were performed in order to compare demographic and clinical variables. Logistic regression models were created to estimate the adjusted odds ratios (95% confidence intervals) of comorbid FMDs (dependent variable) in relation to sociodemographic and clinical characteristics (independent variables). RESULTS: Out of 410 FMDs, 21.7% of patients (n = 89) had comorbid FMDs. The most frequent coexisting neurological diseases were migraine, cerebrovascular disease and parkinsonism. In the majority of cases (86.5%), FMDs appeared after the diagnosis of a neurological disease. Patients with comorbid FMDs were older, and more frequently had tremor, non-neurological comorbidities, paroxysmal non-epileptic seizures, major depressive disorders, and benzodiazepine intake. Multivariate regression analysis showed that diagnosis of comorbid FMDs was more likely associated with longer time lag until the final diagnosis of FMD, presence of tremor and non-neurological comorbidities. CONCLUSIONS: Our findings highlight the need for prompt diagnosis of FMDs, given the relatively high frequency of associated neurological and non-neurological diseases.

The impact of COVID-19 pandemic on frail health systems of low- and middle-income countries: The case of epilepsy in the rural areas of the Bolivian Chaco.

INTRODUCTION: The Coronavirus disease 2019 (COVID-19) has put some health systems under pressure, especially in low- and middle-income countries. We aimed at evaluating the impact of COVID-19 emergency on the management of people with epilepsy (PWE) living in the rural communities of the Gran Chaco area of the Plurinational State of Bolivia. MATERIALS AND METHODS: We selected a sample of PWE living in the rural communities of the Bolivian Chaco. A standardized questionnaire was developed, consisting of six questions addressing drug availability, drug discontinuation, personnel responsible for drug retrieval during the lockdown, and the presence of seizures in the two months preceding the interview. Questionnaires were administered by community health workers of the rural health centers in September 2020. RESULTS: Seventy PWE (38 men, 54.3%; mean age 26.9 ±â€¯16.7) were interviewed. During the lockdown the large majority of them (n = 51, 73.9%) reported an irregular medication intake mainly due to the lack of antiseizure medications in the local health posts, leading to an increase in seizure frequency. CONCLUSION: The COVID-19 pandemic has unmasked the frailty of the Bolivian health system, especially for the management of chronic diseases such as epilepsy in the rural communities.

Usefulness of a smartphone application for the diagnosis of epilepsy: Validation study in high-income and rural low-income countries.

INTRODUCTION: In low- and middle-income countries (LMIC), the diagnosis of epilepsy should be made by Non-Physician Health Workers (NPHW) who are widely available in these settings. Recently a smartphone app (Epilepsy Diagnosis Aid) has been developed and validated to be used by NPHW, in order to confirm the diagnosis of epilepsy. The aim of our study was to perform a validation of the app in two different contexts: a hospital-based setting of a high-income country (HIC) and a population-based setting of the rural communities of a LMIC. MATERIAL AND METHODS: For the hospital-based setting, the app was administered to a sample of patients with epilepsy (PWE) and to a sample of subjects affected by syncope attending the epilepsy center of the University of Catania. For the population-based setting, performed in the rural communities of the Gran Chaco region in Bolivia,the app was administered by NPHW to a sample of PWE previously identified. Sensitivity and specificity were calculated for the diagnosis of epilepsy. RESULTS: In the hospital-setting, the app was administered to 100 PWE and 20 syncopes. A probability score > 80 showed a sensitivity of 76% (95%CI 66.4-84) and a specificity of 100% (95%CI 83.2-100) for the diagnosis of epilepsy; higher values were found for active epilepsy with tonic-clonic seizures. In the rural-setting, the app was administered to 38 PWE, giving a sensitivity of 92.1% (95%CI 78.6-98.3). CONCLUSION: The app for epilepsy could represent a valuable instrument, which can be easily employed by trained NPHW to diagnose epilepsy in primary health-care settings of LMIC.