Search

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

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

According to the hygiene hypothesis, parasites could have a protective role in the development of Multiple Sclerosis (MS). Our aim was to assess the association between presence of anti-Toxoplasma gondii antibodies and MS. MS patients were randomly selected from a population-based incident cohort of MS patients in the city of Catania. Age and sex-matched controls were randomly selected from the general population. Clinical and sociodemographic variables were recorded with a structured questionnaire and a blood sample was taken for serological analysis. Specific T. gondii IgG have been detected with a commercial kit. Adjusted Odds Ratios (ORs) were estimated using unconditional logistic regression. 129 MS subjects (66.7% women with a mean age 44.7 ± 11.0 years) and 287 controls (67.3% women with a mean age 48.1 ± 15.6 years) have been enrolled in the study. Anti-T. gondii antibodies were found in 38 cases (29.5%) and 130 controls (45.4%) giving an adjusted OR of 0.56 (95%CI 0.34–0.93). History of mononucleosis and high educational level were significantly associated with MS (adjOR 2.22 and 1.70 respectively) while an inverse association was found between high educational level and T. gondii seropositivity (adjOR 0.42). Our results further support the protective role of parasitic infections in MS.

Mild cognitive impairment (MCI) is a very common non-motor feature of Parkinson’s disease (PD) and the non-amnestic single-domain is the most frequent subtype. Transcranial random noise stimulation (tRNS) is a non-invasive technique, which is capable of enhancing cortical excitability. As the main contributor to voluntary movement control, the primary motor cortex (M1) has been recently reported to be involved in higher cognitive functioning. The aim of this study is to evaluate the effects of tRNS applied over M1 in PD-MCI patients in cognitive and motor tasks. Ten PD-MCI patients, diagnosed according to the Movement Disorder Society, Level II criteria for MCI, underwent active (real) and placebo (sham) tRNS single sessions, at least 1 week apart. Patients underwent cognitive (Digit Span Forward and Backward, Digit Symbol, Visual Search, Letter Fluency, Stroop Test) and motor assessments (Unified Parkinson’s Disease Rating Scale [UPDRS-ME], specific timed trials for bradykinesia, 10-m walk and Timed up and go tests) before and after each session. A significant improvement in motor ability (UPDRS-ME and lateralized scores, ps from 0.049 to 0.003) was observed after real versus sham tRNS. On the contrary, no significant differences were found in other motor tasks and cognitive assessment both after real and sham stimulations. These results confirm that tRNS is a safe and effective tool for improving motor functioning in PD-MCI. Future studies using a multisession tRNS applied over multitargeted brain areas (i.e., dorsolateral prefrontal cortex and M1) are required to clarify the role of tRNS regarding rehabilitative intervention in PD.

Background Vascular risk factors (VRFs) may be associated with cognitive decline in early Parkinson’s disease (PD) but results are inconclusive. The identification of modifiable risk factors is relevant for prevention and treatment. Methods Parkinson’s disease (PD) patients of the PACOS cohort who underwent a baseline and follow-up neuropsychological evaluation were enrolled in the study. PD with Mild Cognitive Impairment (MCI) and dementia (PDD) were diagnosed according to the MDS criteria. A Baseline 1.5 T brain MRI was used to calculate the white matter lesions (WMLs) burden using the Wahlund visual scale. Laboratory data, presence of hypertension, diabetes and use of anti-hypertensive drugs were collected and the Framingham Risk (FR) score was calculated. VRFs predicting PD-MCI and PDD were evaluated using Cox proportional hazard regression model. Results Out of 139 enrolled patients, 84 (60.4%) were classified as normal cognition (NC) and 55 (39.6%) as MCI at baseline. At follow-up 28 (33.3%) PD-NC developed MCI and 4 (4.8%) PDD (follow-up time 23.5 ± 10.3 months). Out of 55 PD-MCI patients at baseline, 14 (25.4%) converted to PDD. At multivariate analysis among PD-NC a systolic blood pressure (SBP) > 140 mmHg was the stronger predictor of MCI (adjHR 4.04; 95% CI 1.41–11.3) while the presence of MCI at baseline (adj HR 7.55; 95% CI 1.76–32.3) and a severe WMLs burden (adj HR 2.80; 95% CI 0.86–9.04) were the strongest predictors of PDD, even if this latter association has a trend towards significance. Conclusion Hypertension represents the most important modifiable risk factor for PD-MCI in the PACOS cohort, increasing the risk of about four times.

Introduction: The approval of 9-δ-tetrahydocannabinol (THC)+cannabidiol (CBD) oromucosal spray (Sativex®) in Italy as an add-on medication for the management of moderate to severe spasticity in multiple sclerosis (MS) has provided a new opportunity for MS patients with drug-resistant spasticity. We aimed to investigate the improvement of MS spasticity-related symptoms in a large cohort of patients with moderate to severe spasticity in daily clinical practice. Materials and methods: MS patients with drug-resistant spasticity were recruited from 30 Italian MS centers. All patients were eligible for THC:CBD treatment according to the approved label: ≥ 18 years of age, at least moderate spasticity (MS spasticity numerical rating scale [NRS] score ≥ 4) and not responding to the common antispastic drugs. Patients were evaluated at baseline (T0) and after 4 weeks of treatment (T1) with the spasticity NRS scale and were also asked about meaningful improvements in 6 key spasticity-related symptoms. Results: Out of 1615 enrolled patients, 1432 reached the end of the first month trial period (T1). Of these, 1010 patients (70.5%) reached a ≥ 20% NRS score reduction compared with baseline (initial responders; IR). We found that 627 (43.8% of 1432) patients showed an improvement in at least one spasticity-related symptom (SRSr group), 543 (86.6%) of them belonging to the IR group and 84 (13.4%) to the spasticity NRS non-responders group. Conclusion: Our study confirmed that the therapeutic benefit of cannabinoids may extend beyond spasticity, improving spasticity-related symptoms even in non-NRS responder patients. © 2020, Fondazione Società Italiana di Neurologia.

An innovative approach to identify new conformational antigens of Aβ1–42 recognized by IgG autoantibodies as biomarkers of state and stage in Alzheimer’s disease (AD) patients is described. In particular, through the use of bioinformatics modeling, conformational similarities between several Aβ1–42 forms and other amyloid-like proteins with F1 capsular antigen (Caf1) of Yersinia pestis were first found. pVIII M13 phage display libraries were then screened against YPF19, anti-Caf1 monoclonal antibody, and IgGs of AD patients, in alternate biopanning cycles of a so-called “double binding” selection. From the selected phage clones, one, termed 12III1, was found to be able to prevent in vitro Aβ1–42-induced cytotoxicity in SH-SY5Y cells, as well as to promote disaggregation of preformed fibrils, to a greater extent with respect to wild-type phage (pC89). IgG levels detected by 12III1 provided a significant level of discrimination between diseased and nondemented subjects, as well as a good correlation with the state progression of the disease. These results give significant impact in AD state and stage diagnosis, paving the way for the development not only for an innovative blood diagnostic assay for AD precise diagnosis, progressive clinical assessment, and screening but also for new effective treatments.

Background Functional neurological disorders (FND) are disabling medical conditions commonly seen in neurological practice. Neurologists play an essential role in managing FND, from establishing a diagnosis to coordination of multidisciplinary team-based treatment for patients. With this study, we investigated the knowledge and the clinical experience of Italian neurologists in managing patients with FND. Methods Members of the Italian Society of Neurology were invited via e-mail to participate in this ad hoc online survey; 492 questionnaires were returned completed. Results The term “Functional neurological disorders” in reference to FND was used more frequently than other psychological (e.g., psychogenic or conversion), or descriptive terms (e.g., non-organic or stress-related). When speaking with patients, the respondents stated that they preferred explaining symptoms based on abnormal functioning of the nervous system than discussing mental illness and that they would refer their patient to a psychologist rather than to a psychiatrist. Few considered that physiotherapy and psychiatric interventions are useful approaches to treating FND. Some believed that patients simulate their symptoms. Conclusions Overall, the responses suggest that knowledge about scientific advances in FND is somewhat sparse. A psychiatric-centered view of FND opens the way to an approach in which neurobiological and psychological aspects constitute essential factors of the condition. In this context, professional education could improve understanding of FND and optimize patient management.

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. 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. 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). 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.

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.

STUDY OBJECTIVES: Few studies have analyzed the prevalence of isolated rapid eye movement sleep behavior disorder (RBD) giving different estimates. Aim of the study was to estimate the prevalence of isolated RBD in the city of Catania. METHODS: A 3-stage design was adopted. Participants attending the offices of general practitioners in the city of Catania were screened with the RBD Single Question Screen questionnaire (Stage I). Positive participants were interviewed by phone and, if suspected of RBD, were invited for clinical examination by a movement disorders specialist and a sleep specialist (Stage II). After the clinical examination, patients diagnosed as probable isolated RBD (pRBD) were invited to undergo a video polysomnography (Stage III) to confirm the diagnosis of definite RBD. RESULTS: A total of 1,524 participants were screened. Of these, 220 (14.4%) screened positive. One hundred forty-three of them were further screened by phone, of whom 75 were suspected RBD. Thirty-six patients were diagnosed as pRBD, giving a prevalence of 2.36% (95% confidence interval, 1.71–3.25). Twelve pRBD agreed to a video polysomnography and, of these, 4 were diagnosed as definite RBD, giving a prevalence of 0.26% (95% confidence interval, 0.07–0.67). Prevalence adjusted by nonparticipants was 3.48% (95% confidence interval, 2.67–4.52) and 1.18% (95% confidence interval, 0.45–1.37) for pRBD and definite RBD, respectively. CONCLUSIONS: Prevalence of both pRBD and definite RBD in Italy is comparable to the estimates reported in literature, confirming that isolated RBD has a low prevalence in the general population. CITATION: Cicero CE, Giuliano L, Sgroi R, et al. Prevalence of isolated RBD in the city of Catania, Italy: a population-based study. J Clin Sleep Med. 2021;17(11):2241–2248.

Objective\ud We aimed to describe the prevalence and clinical-demographical features of patients with functional gait disorders (FGDs) and to compare them to patients with functional motor disorders (FMDs) without FGDs (No-FGDs).\ud \ud Methods\ud In this multicenter observational study, we enrolled patients with a clinically definite diagnosis of FMDs in 25 tertiary movement disorders centers in Italy. Each subject with FMDs underwent a comprehensive clinical assessment, including screening for different subtypes of functional gait disorders. Multivariate regression models were implemented in order to estimate the adjusted odds ratio (OR; 95% confidence interval) of having FGDs in relation to sociodemographic and clinical characteristics.\ud \ud Results\ud Out of 410 FMDs, 26.6% (n = 109) of patients exhibited FGDs. The most frequent FGDs were slow gait (n = 43, 39.4%), astasia-abasia (n = 26, 23.8%), and knee buckling (n = 24, 22%). They exhibited single FGDs in 51.4% (n = 56) or complex FGDs (more than one type of FGDs) in 48.6% (n = 53) of cases. On multivariate regression analysis, the presence of FGDs was more likely associated with older age (OR 1.03, 95% CI 1.01–1.04), functional visual symptoms (OR 2.19, 95% CI 1.08–4.45), and the diagnosis of somatic symptoms disorder (OR 2.97, 95% CI 1.08–8.17). FGDs were also more likely to undergo physiotherapy (OR 1.81, 95% CI 1.08–3.03).\ud \ud Conclusions\ud People with FMDs may present with different and overlapping types of FGDs, which may occur in older age. The association of FGDs with functional visual symptoms and somatic symptoms disorder opens up to new avenues to the understanding of the neural mechanisms of these disorders.

Subjective memory complaints (SMC) may represent the preclinical phase of mild cognitive impairment (MCI) due to Alzheimer's disease. Dementia/MCI have been described with a high prevalence in Parkinson's disease (PD), but whether SMC may predict the development of cognitive impairment has been barely explored. To evaluate the frequency and clinical correlates of isolated SMC (PD-SMC) or within the construct of MCI in subjects with PD, 147 PD patients from the PArkinson's disease COgnitive impairment Study (PACOS) were consecutively recruited for the study. This is a multicenter study involving two Movement Disorder Centers in south Italy. All subjects underwent comprehensive neuropsychological evaluation and PD-MCI was diagnosed according to Litvan's criteria. The Memory Assessment Clinics Questionnaire was used to assess SMC. Logistic regression analysis, adjusted for demographics and significant covariates, was used to evaluate clinical differences between groups. Forty-two (28.6%) individuals presented with PD without SMC and/or MCI (PDw), 40 (27,2%) with PD-SMC, 48 (32,6%) PD-SMC-MCI, and 17 (11,6%) PD-MCI without SMC (PD-MCI). When compared to PDw, PD-SMC was significantly associated with anxiety (OR = 3.93, 95% CI = 1.18-13.03), while PD-SMC-MCI related to motor progression (OR = 5.29, 95% CI = 1.12-24.86), and instrumental disability (OR = 6.98, 95% CI = 2.08-23.38). About 60% of patients showed SMC, in isolation or within the MCI frame. The role of SMC in PD seems to have a different etiology depending on the presence/absence of MCI. In particular, PD-SMC would represent a subjective reaction to the disease, while PD-SMC-MCI would depict motor progression and disability.

Background Parkinson’s disease (PD) is a neurodegenerative disorder characterized by a combination of motor and non-motor dysfunction. Dysphagia is a common symptom in PD, though it is still too frequently underdiagnosed. Consensus is lacking on screening, diagnosis, and prognosis of dysphagia in PD. Objective To systematically review the literature and to define consensus statements on the screening and the diagnosis of dysphagia in PD, as well as on the impact of dysphagia on the prognosis and quality of life (QoL) of PD patients. Methods A multinational group of experts in the field of neurogenic dysphagia and/or PD conducted a systematic revision of the literature published since January 1990 to February 2021 and reported the results according to PRISMA guidelines. The output of the research was then analyzed and discussed in a consensus conference convened in Pavia, Italy, where the consensus statements were drafted. The final version of statements was subsequently achieved by e-mail consensus. Results Eighty-five papers were used to inform the Panel’s statements even though most of them were of Class IV quality. The statements tackled four main areas: (1) screening of dysphagia: timing and tools; (2) diagnosis of dysphagia: clinical and instrumental detection, severity assessment; (3) dysphagia and QoL: impact and assessment; (4) prognostic value of dysphagia; impact on the outcome and role of associated conditions. Conclusions The statements elaborated by the Consensus Panel provide a framework to guide the neurologist in the timely detection and accurate diagnosis of dysphagia in PD.

Levodopa is the standard long-term dopamine replacement therapy to treat Parkinson’s disease (PD) symptoms. With time, levodopa may induce debilitating dyskinesias (LID), the treatment of which represents a large clinically unmet need. However, time-to-LID onset varies between patients, reflecting a possible genetic component. We performed an hypothesis-free whole-exome sequencing (WES)-based screening of time-to-LID onset and attempted replication of previously published candidate gene studies. A WES association analysis was carried out in 134 PD patients in a meta-analytical framework. Replication was attempted in an independent study of 97 PD patients. Variants from previously reported candidate genes (OPRM1, COMT, BDNF) were also specifically examined. We significantly replicated, for the first time, an association of variant rs1799971 in the OPRM1 gene with time-to-LID onset. Furthermore, we identified two novel potentially functional variants, in the MAD2L2 (rs2233019) and MAP7 (rs35350783) genes, which were significantly associated at the discovery stage. In the replication study, the two variants showed direction-consistent effects but did not achieve the replication significance threshold. Our study provides the first WES results for time-to-LID onset, where we replicate association at OPRM1, and suggest new variants in MAD2L2 and MAP7 genes that are significant in discovery, but require larger datasets for replication. The results are being made publicly available to allow for independent external validation.

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

Introduction Parkinson's Disease (PD) is frequently associated with cognitive dysfunction ranging from Mild Cognitive Impairment (PD-MCI) to dementia. Few electrophysiological studies are available evaluating potential pathogenetic mechanisms linked to cognitive impairment in PD since its initial phases. The objective of the study is to analyze electrocortical networks related with cognitive decline in PD-MCI for identifying possible early electrophysiological markers of cognitive impairment in PD. Methods From the PaCoS (Parkinson's disease Cognitive impairment Study) cohort, a sample of 102 subjects including 46 PD-MCI and 56 PD with normal cognition (PD-NC) was selected based on the presence of a neuropsychological assessment and at least one EEG recording. EEG signal epochs were analysed using Independent Component Analysis LORETA and spectral analysis by computing the Power Spectral Density (PSD) of site-specific signal epochs. Results LORETA analysis revealed significant differences in PD-MCI patients compared to PD-NC, with a decreased network involving alpha activity over the occipital lobe, an increased network involving beta activity over the frontal lobe associated with a reduction over the parietal lobe, an increased network involving theta and delta activity over the frontal lobe and a reduction of networks involving theta and delta activity in the parietal lobe. Quantitative EEG analysis showed a significant decrease of alpha PSD over the occipital regions and an increase of delta PSD over the left temporal region in PD-MCI as compared to PD-NC. Conclusion Electrocortical abnormalities detected in PD-MCI patients may represent the instrumental counterpart of early cognitive decline in PD.

Multiple sclerosis (MS) is an acquired demyelinating disease of the central nervous system (CNS) that traditionally has been considered to be mediated primarily by T cells. Increasing evidence, however, suggests the fundamental role of B cells in the pathogenesis and development of the disease. Recently, anti-CD20 B cell-based therapies have demonstrated impressive and somewhat surprising results in MS, showing profound anti-inflammatory effects with a favorable risk-benefit ratio. Moreover, for the first time in the MS therapeutic scenario, the anti-CD20 monoclonal antibody ocrelizumab has been granted for the treatment of the primary progressive form of the disease. In this review, we provide a brief overview about anti-CD20 B cell-based therapies in MS, in the perspective of their influence on the future management of the disease, and of their possible positioning in a new wider therapeutic scenario.

Summary The majority of the screening questionnaires for epilepsy have been validated in hospital settings. We previously developed and used for field validation a screening tool to detect generalized tonic‐clonic seizures (GTCS) in the rural communities of the Chaco region of Bolivia. The objective of the present study was to perform a hospital‐based validation of the same questionnaire and to compare the levels of accuracy obtained when validated in the field or in a hospital‐based context. We carried out a hospital‐based validation in the Hospital Hernandez Vera of Santa Cruz, Bolivia, where we enrolled patients affected by epilepsy with GTCS and controls. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) were calculated. One hundred twenty questionnaires were administered to 59 patients (27 men [45.8%]; mean age ± SD = 32.4 ± 14.2 years) and 61 controls (27 men [44.3%]; mean age ± SD = 32.6 ± 14.3 years). We obtained levels of accuracy of 100%. Sensitivity and PPV were significantly higher than the estimates obtained in the field‐validation study (sensitivity 100% vs 76.3%; PPV 100% vs 69.0%). Our screening questionnaire showed a significantly lower level of sensitivity when validated in the field, confirming that hospital‐based validation can lead to an overestimation of sensitivity.

Background Although various motor manifestations can be seen in patients with cerebrospinal fluid (CSF) disorders, such as hydrocephalus or intracranial hypotension, the clinical presentation with parkinsonism is not clearly elucidated. Methods We searched the literature for studies describing the occurrence of parkinsonism in subjects with normal pressure hydrocephalus (NPH), obstructive hydrocephalus, and intracranial hypotension. We analyzed the clinical presentation (particularly with respect to bradykinesia, rigidity, rest tremor, and gait disturbance/postural instability) as well as the response to treatment. Results Parkinsonism was most commonly reported in NPH patients. Although gait disturbance/postural instability is a well-known motor symptom of NPH, other cardinal signs include upper limb involvement or asymmetric presentation. As for obstructive hydrocephalus, parkinsonism was mainly observed in subjects with aqueductal stenosis and more often after shunt surgery. Patients with NPH or obstructive hydrocephalus rarely improved with levodopa therapy, while most subjects only improved with shunt surgery. Although the mechanism is still controversial, a functional involvement of nigrostriatal pathway has been hypothesized based on imaging studies and case reports. Brain imaging is also helpful for atypical cases of intracranial hypotension presenting with parkinsonism. Parkinsonism improved after treatment in such cases as well. Conclusions Studies exploring the relationship between CSF disorders and parkinsonism are mainly descriptive and their quality is generally poor. However, considering that these disorders can be treated, clinicians' awareness of the differential diagnosis is important and future studies better exploring the underlying pathophysiological mechanisms are warranted. This article is part of the Special Issue "Parkinsonism across the spectrum of movement disorders and beyond" edited by Joseph Jankovic, Daniel D. Truong and Matteo Bologna.

Background: The neuropsychological profile of progressive supranuclear palsy (PSP) patients is mainly characterized by executive dysfunction, but the relationship between the latter and midbrain atrophy is still unclear. Objective: The aims of the study were to investigate which test evaluating executive functioning is more frequently impaired in PSP patients and to evaluate the relationship between midbrain-based MRI morphometric measures and executive dysfunction. Methods: PSP patients who had undergone a neuropsychological battery assessing executive functioning with the Frontal Assessment Battery (FAB), the phonemic verbal fluency F-A-S, the Raven’s Progressive Colored Matrix, and the Stroop word colors test (time and errors) were enrolled in the study. A group of Parkinson’s disease (PD) patients matched by age, sex, education, and global cognitive status was selected. All the enrolled patients also underwent a volumetric T1-3D brain MRI. Results: Thirty-five PSP patients and 35 PD patients were enrolled. Patients with PSP as compared to patients with PD showed a significant greater impairment in verbal fluency (16.0±7.9 and 23.4±8.7 words/180 s; p

Eyelid myoclonia with absences (EMA) shares some clinical characteristics with juvenile myoclonic epilepsy (JME), in which impulsivity traits have been described. Aim of the study was to evaluate whether EMA patients could present a peculiar behavioural profile.Patients with EMA, JME and healthy controls (HCs) were enrolled. Subjects with intellectual quotient80 were excluded from the study. All the enrolled subjects underwent the Italian version of the Barratt Impulsiveness Scale (BIS-11) and the three dimensions of impulsivity (motor, attentional-cognitive and nonplanning impulsivity) were considered.Seventeen patients with EMA (12 females [70.6%], age 30.8±10 years), 29 patients with JME (17 females [58.6%], age 29.1±9.7 years) and 31 HCs (15 females [48.4%], age 27.6±5.8 years) were enrolled. Both EMA and JME patients presented a borderline significantly higher BIS total score than HCs (p=0.064). EMA patients presented a significantly higher BIS nonplanning subscore than JME patients and HCs (p=0.001).The study showed the presence of peculiar behavioral characteristics in EMA patients, slightly different from patients with JME.

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 ± 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.

Aim of the study was to evaluate possible associations between cognitive dysfunctions and development of Levodopa Induced Dyskinesia (LID). PD patients from the Parkinson’s disease Cognitive impairment Study cohort who underwent a baseline and follow-up neuropsychological evaluations were enrolled. Mild Cognitive Impairment (PD-MCI) was diagnosed according to MDS level II criteria. The following cognitive domains were evaluated: episodic memory, attention, executive function, visuo-spatial function and language. A domain was considered as impaired when the subject scored 2 standard deviation below normality cut-off values in at least one test for each domain. Levodopa equivalent dose, UPDRS-ME and LID were recorded at baseline and follow-up. To identify possible neuropsychological predictors associated with the probability of LID development at follow-up, Cox proportional-hazards regression model was used. Out of 139 PD patients enrolled (87 men, mean age 65.7 ± 9.4), 18 (12.9%) were dyskinetic at baseline. Out of 121 patients non-dyskinetic at baseline, 22 (18.1%) developed LID at follow-up. The impairment of the attention and executive domains strongly predicted the development of LID (HR 4.45;95%CI 1.49–13.23 and HR 3.46; 95%CI 1.26–9.48 respectively). Impairment of the attention and executive domains increased the risk of dyskinesia reflecting the alteration of common cortical network.

Purpose Idiopathic intracranial hypertension (IIH) is a rare disorder characterised by raised intracranial pressure. The underlying pathophysiology is mostly unknown and effective treatment is an unmet clinical need in this disease. This review evaluates key emerging themes regarding disease characteristics, mechanisms contributing to raised intracranial pressure and advances in potential therapeutic targets. Findings IIH is becoming more common, with the incidence rising in parallel with the global obesity epidemic. Current medical management remains centred around weight management, which is challenging. Metabolic investigations of patients have identified specific androgen profiles in cerebrospinal fluid (CSF), which suggest an endocrine dysfunction impacting CSF secretion in IIH. Glucagon-like peptide-1 (GLP-1) and 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have been found to play a role in CSF dynamics in IIH and have formed the basis of the first clinical trials looking at new treatments. Conclusions Identification of novel molecular targets thought to underlie IIH pathology is now being translated to clinical trials.

Study Objectives To provide an overall estimate of the prevalence of idiopathic REM Sleep Behavior Disorder (iRBD). Methods Two investigators have independently searched the PubMed and Scopus databases for population-based studies assessing the prevalence of iRBD. Data about type of diagnosis (polysomnographic diagnosis, defined iRBD [dRBD]; clinical diagnosis, probable RBD [pRBD]), continent, age range of the screened population, quality of the studies, sample size, screening questionnaires, and strategies have been gathered. A random-effect model was used to estimate the pooled prevalence. Heterogeneity was investigated with subgroup analysis and meta-regression. Results From 857 articles found in the databases, 19 articles were selected for the systematic review and meta-analysis. According to the type of diagnosis, five studies identified dRBD cases given a pooled prevalence of 0.68% (95% confidence interval [CI] 0.38–1.05) without significant heterogeneity (Cochran’s Q p = 0.11; I2 = 46.43%). Fourteen studies assessed the prevalence of pRBD with a pooled estimate of 5.65% (95% CI 4.29–7.18) and a significant heterogeneity among the studies (Cochran’s Q p < 0.001; I2 = 98.21%). At the subgroup analysis, significant differences in terms of prevalence were present according to the quality of the studies and, after removing two outlaying studies, according to the continents and the screening questionnaire used. Meta-regression did not identify any significant effect of the covariates on the pooled estimates. Conclusion Prevalence estimates of iRBD are significantly impacted by diagnostic level of certainty. Variations in pRBD prevalence are due to methodological differences in study design and screening questionnaires employed.

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

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.

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

Objective To perform the genetic characterization of a cohort with familial parkinsonism and cognitive-behavioral syndrome. Methods A Next Generation Sequencing – based targeted sequencing of 32 genes associated to various neurodegenerative phenotypes, plus a screening for SNCA Copy Number Variations and C9orf72 repeat expansion, was applied in a cohort of 85 Italian patients presenting with parkinsonism and cognitive and/or behavioral syndrome and a positive familial history for any neurodegenerative disorder (i.e., dementia, movement disorders, amyotrophic lateral sclerosis). Results Through this combined genetic approach, we detected potentially relevant genetic variants in 25.8% of patients with familial parkinsonism and cognitive and/or behavioral syndrome. Peculiar phenotypes are described (Cortico-basal syndrome with APP, Posterior Cortical Atrophy with GBA, Progressive Supranuclear Palsy-like with GRN, Multiple System Atrophy with TARDBP). The majority of patients presented a rigid-bradykinetic parkinsonian syndrome, while rest tremor was less common. Myoclonic jerks, pyramidal signs, dystonic postures and vertical gaze disturbances were more frequently associated with the presence of a pathogenic variant in one of the tested genes. Conclusions Given the syndromic approach adopted in our study, we were able to provide a detailed clinical description of patients beyond the boundaries of specific clinical diagnoses and describe peculiar phenotypes. This observation further supports the knowledge that genetic disorders present phenotypic overlaps across different neurodegenerative syndromes, highlighting the limitations of current clinical diagnostic criteria defining sharp boundaries between distinct conditions.

Introduction Functional motor disorders (FMDs) are usually categorized according to the predominant phenomenology; however, it is unclear whether this phenotypic classification mirrors the underlying pathophysiologic mechanisms. Objective To compare the characteristics of patients with different FMDs phenotypes and without co-morbid neurological disorders, aiming to answer the question of whether they represent different expressions of the same disorder or reflect distinct entities. Methods Consecutive outpatients with a clinically definite diagnosis of FMDs were included in the Italian registry of functional motor disorders (IRFMD), a multicenter data collection platform gathering several clinical and demographic variables. To the aim of the current work, data of patients with isolated FMDs were extracted. Results A total of 176 patients were included: 58 with weakness, 40 with tremor, 38 with dystonia, 23 with jerks/facial FMDs, and 17 with gait disorders. Patients with tremor and gait disorders were older than the others. Patients with functional weakness had more commonly an acute onset (87.9%) than patients with tremor and gait disorders, a shorter time lag from symptoms onset and FMDs diagnosis (2.9 ± 3.5 years) than patients with dystonia, and had more frequently associated functional sensory symptoms (51.7%) than patients with tremor, dystonia and gait disorders. Patients with dystonia complained more often of associated pain (47.4%) than patients with tremor. No other differences were noted between groups in terms of other variables including associated functional neurological symptoms, psychiatric comorbidities, and predisposing or precipitating factors. Conclusions Our data support the evidence of a large overlap between FMD phenotypes.