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Introduction: Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are tauopathic atypical parkinsonisms. Given their overlap in terms of clinical manifestation, there is growing interest in the mechanisms leading to these entities. Materials and methods: In total, 71 patients were included in the study, 19 of whom were clinically diagnosed with CBS, 37 with PSP, and 15 with Parkinson's disease (PD). The mean ages of the participants were 72.8, 72.9, and 64.0 years, respectively, and the disease duration varied from 3 to 6 years. Each individual underwent blood collection. Morphological and biochemical evaluation of blood samples was performed to analyze the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-high-density lipoprotein ratio (NHR). A single-photon emission computed tomography (SPECT) with technetium-99m hexamethylpropyleneamine oxime (99Tc-HMPAO) tracer was used to assess perfusion in two regions of interest (ROI): the thalamus and insula. Using Pearson correlation to assess the linear relationship between NHR and perfusion in the insula and thalamus for CBS, PSP, and PD patients, the authors intended to verify possible correlations between NLR, PLR, and NHR and perfusion in the indicated ROIs. Results: The study revealed a negative linear correlation between NHR and perfusion of both the left (Insula L; R = −0.59) and right (Insula R; R = −0.58) insula regions. Similar to the insula, a linear correlation between NHR and activity in both the left (Thalamus L) and right (Thalamus R) thalamus regions in CBS subjects with a relatively stronger correlation in the right thalamus (R = −0.64 vs. R = −0.58) was found. These observations were not confirmed in PSP and PD patients. Conclusion: Simultaneously using non-specific parameters for peripheral inflammation (NLR, PLR, and NHR) and perfusion, SPECT may be an interesting beginning point for further analysis of inflammatory disease mechanisms. To the best of our knowledge, this is the first study to address the potential correlation between the peripheral neuroinflammatory markers NLR, PLR, and NHR and perfusion disturbances in particular ROIs. [ABSTRACT FROM AUTHOR]

Background/Objectives: Atypical parkinsonian syndromes (APSs) are a group of neurodegenerative disorders that differ from idiopathic Parkinson's disease (IPD) in their clinical presentation, underlying pathology, and response to treatment. APSs include conditions such as multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and dementia with Lewy bodies (DLB). These disorders are characterized by a combination of parkinsonian features and additional symptoms, such as autonomic dysfunction, supranuclear gaze palsy, and asymmetric motor symptoms. Many hypotheses attempt to explain the causes of neurodegeneration in APSs, including interactions between environmental toxins, tau or α-synuclein pathology, oxidative stress, microglial activation, and vascular factors. While extensive research has been conducted on APSs, there is a limited understanding of the symmetry in these diseases, particularly in MSA. Neuroimaging studies have revealed metabolic, structural, and functional abnormalities that contribute to the asymmetry in APSs. The asymmetry in CBS is possibly caused by a variable reduction in striatal D2 receptor binding, as demonstrated in single-photon emission computed tomography (SPECT) examinations, which may explain the disease's asymmetric manifestation and poor response to dopaminergic therapy. In PSP, clinical dysfunction correlates with white matter tract degeneration in the superior cerebellar peduncles and corpus callosum. MSA often involves atrophy in the pons, putamen, and cerebellum, with clinical symmetry potentially depending on the symmetry of the atrophy. The aim of this review is to present the study findings on potential symmetry as a tool for determining potential neuropsychological disturbances and properly diagnosing APSs to lessen the misdiagnosis rate. Methods: A comprehensive review of the academic literature was conducted using the medical literature available in PubMed. Appropriate studies were evaluated and examined based on patient characteristics and clinical and imaging examination outcomes in the context of potential asymmetry. Results: Among over 1000 patients whose data were collected, PSP-RS was symmetrical in approximately 84% ± 3% of cases, with S-CBD showing similar results. PSP-P was symmetrical in about 53–55% of cases, while PSP-CBS was symmetrical in fewer than half of the cases. MSA-C was symmetrical in around 40% of cases. It appears that MSA-P exhibits symmetry in about 15–35% of cases. CBS, according to the criteria, is a disease with an asymmetrical clinical presentation in 90–99% of cases. Similar results were obtained via imaging methods, but transcranial sonography produced different results. Conclusions: Determining neurodegeneration symmetry may help identify functional deficits and improve diagnostic accuracy. Patients with significant asymmetry in neurodegeneration may exhibit different neuropsychological symptoms based on their individual brain lateralization, impacting their cognitive functioning and quality of life. [ABSTRACT FROM AUTHOR]

Background: Epidemiological studies on multisystem atrophy (MSA) are scarce. Our aim has been to analyse 10-year incidence, point prevalence, survival, and the time to diagnosis of MSA in Navarre, a northern Spanish region. Methods: This is a population-based observational retrospective study, from 2012 to 2021, which covered the population of Navarre (followed until 31 December 2021). Data from various sources of health information were reviewed in order to identify all potential diagnoses of MSA, that were validated from medical records. Patients were included if they fulfilled the new Movement Disorder Society criteria. Results: We observed a crude average annual incidence rate (IR) of 0.49/100,000 person-years, with the highest occurring in the age group of 60–69 years. No significant IR differences by sex or subtype were observed. Point prevalence in December 2021 was 2.43/100,000 inhabitants. Joinpoint analysis for global incidence and prevalence experienced stable annual rates during the whole period, showing an upward trend for prevalence without a statistically significant slop. The median age at symptom onset was 65 years (range 47–76). The median time to diagnosis was 36 months, without statistically significant differences between sex, age at diagnosis or subtypes. Median time of survival from clinical onset was 7 years. Age of onset above 70 years and autonomic onset were associated with reduced survival. Conclusions: This is the first population-based epidemiological study on MSA in Spain. It provides detailed incidence and prevalence data for MSA that may be useful for appropriate management of health resources. [ABSTRACT FROM AUTHOR]

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by upper and lower motor neuron signs. There are, however, cases where upper motor neurons (UMNs) are predominantly affected, leading to clinical presentations of UMN‐dominant ALS or primary lateral sclerosis. Furthermore, cases exhibiting an UMN‐predominant pattern of motor neuron disease (MND) presenting with corticobasal syndrome (CBS) have been sparsely reported. This study aims to clarify the clinicopathological features of patients with UMN‐predominant MND. We reviewed 24 patients with UMN‐predominant MND with TDP‐43 pathology in the presence or absence of frontotemporal lobar degeneration. Additionally, we reviewed the medical records of patients with pathologically‐confirmed corticobasal degeneration (CBD) who received a final clinical diagnosis of CBS (n = 10) and patients with pathologically‐confirmed progressive supranuclear palsy (PSP) who received a final clinical diagnosis of PSP syndrome (n = 10). Of 24 UMN‐predominant MND patients, 20 had a clinical diagnosis of an atypical parkinsonian disorder, including CBS (n = 11) and PSP syndrome (n = 8). Only two patients had antemortem diagnoses of motor neuron disease. UMN‐predominant MND patients with CBS less frequently exhibited apraxia than those with CBD, and they were less likely to meet clinical criteria for possible or probable CBS. Similarly, UMN‐predominant MND patients with PSP syndrome less often met clinical criteria for probable PSP than PSP patients with PSP syndrome. Our findings suggest that UMN‐predominant MND can mimic atypical parkinsonism, and should be considered in the differential diagnosis of CBS and PSP syndrome, in particular when criteria are not met. [ABSTRACT FROM AUTHOR]

Over the past three decades, substantial advancements have occurred in non-invasive brain stimulation (NIBS). These developments encompass various non-invasive techniques aimed at modulating brain function. Among the most widely utilized methods today are transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES), which include direct- or alternating-current transcranial stimulation (tDCS/tACS). In addition to these established techniques, newer modalities have emerged, broadening the scope of non-invasive neuromodulation approaches available for research and clinical applications in movement disorders, particularly for Parkinson's disease (PD) and, to a lesser extent, atypical Parkinsonism (AP). All NIBS techniques offer the opportunity to explore a wide range of neurophysiological mechanisms and exert influence over distinct brain regions implicated in the pathophysiology of Parkinsonism. This paper's first aim is to provide a brief overview of the historical background and underlying physiological principles of primary NIBS techniques, focusing on their translational relevance. It aims to shed light on the potential identification of biomarkers for diagnostic and therapeutic purposes, by summarising available experimental data on individuals with Parkinsonism. To date, despite promising findings indicating the potential utility of NIBS techniques in Parkinsonism, their integration into clinical routine for diagnostic or therapeutic protocols remains a subject of ongoing investigation and scientific debate. In this context, this paper addresses current unsolved issues and methodological challenges concerning the use of NIBS, focusing on the importance of future research endeavours for maximizing the efficacy and relevance of NIBS strategies for individuals with Parkinsonism. [ABSTRACT FROM AUTHOR]

We aimed to describe the clinical features of patients with pure autonomic failure (PAF) preceding phenoconversion that could be useful as predictive markers for advancing α-synuclein-associated neurodegeneration of the brain. Patients diagnosed with PAF were evaluated at eight centres (seven US-based and one European) and enrolled in a longitudinal observational cohort study (NCT01799915). Subjects underwent detailed assessments of motor, sleep, olfactory, cognitive and autonomic function and were followed prospectively to determine whether they developed parkinsonism or dementia for up to 10 years. We identified incident cases of Parkinson's disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA) and computed hazard ratios for phenoconversion as functions of clinical features. A total of 209 participants with PAF with a median disease duration of 6 years (IQR: 3–10) were enrolled. Of those, 149 provided follow-up information at an office or telemedicine visit. After a mean follow-up duration of 3 years, 48 (33%) participants phenoconverted (42% to PD, 35% to DLB and 23% to MSA). Faster phenoconversion from study enrolment to any diagnosis was associated with urinary and sexual dysfunction [hazard ratio (HR) 5.9, 95% confidence interval (CI): 1.6–22 and HR: 3.6, 95% CI: 1.1–12] followed by subtle motor signs (HR: 2.7, 95% CI: 1.2–6), trouble swallowing (HR 2.5, 95% CI: 1.4–4.5) and changes in speech (HR:2.4, 95% CI:1.1–4.8) at enrolment. Subjects reporting deterioration of handwriting were more likely to phenoconvert to PD (HR: 2.6, 95% CI: 1.1–5.9) and those reporting difficulty handling utensils were more likely to phenoconvert to DLB (HR: 6.8, 95% CI: 1.2–38). Patients with a younger age of PAF onset (HR: 11, 95% CI: 2.6–46), preserved olfaction (HR: 8.7, 95% CI: 1.7–45), anhidrosis (HR: 1.8, 95% CI: 1–3.1, P = 0.042) and severe urinary problems (HR 1.6, 95% CI: 1–2.5, P = 0.033) were more likely to phenoconvert to MSA. The best autonomic predictor of PD was a blunted heart rate increase during the tilt-table test (HR: 6.1, 95% CI: 1.4–26). Patients with PAF have an estimated 12% (95% CI: 9–15%) per year annual risk following study entry of phenoconverting to a manifest CNS synucleinopathy. [ABSTRACT FROM AUTHOR]

Background: Postural imbalance and falls are an early disabling symptom in patients with progressive supranuclear palsy (PSP) of multifactorial origin that may involve abnormal vestibulospinal reflexes. Low-intensity noisy galvanic vestibular stimulation (nGVS) is a non-invasive treatment to normalize deficient vestibular function and attenuate imbalance in Parkinson's disease. The presumed therapeutic mode of nGVS is stochastic resonance (SR), a mechanism by which weak sensory noise stimulation can enhance sensory information processing. Objective: To examine potential treatment effects of nGVS on postural instability in 16 patients with PSP with a clinically probable and [18F]PI-2620 tau-PET-positive PSP. Methods: Effects of nGVS of varying intensity (0–0.7 mA) on body sway were examined, while patients were standing with eyes closed on a posturographic force plate. We assumed a bell-shaped response curve with maximal sway reductions at intermediate nGVS intensities to be indicative of SR. An established SR-curve model was fitted on individual patient outcomes and three experienced human raters had to judge whether responses to nGVS were consistent with the exhibition of SR. Results: We found nGVS-induced reductions of body sway compatible with SR in 9 patients (56%) with optimal improvements of 31 ± 10%. In eight patients (50%), nGVS-induced sway reductions exceeded the minimal clinically important difference (improvement: 34 ± 5%), indicative of strong SR. Conclusion: nGVS yielded clinically relevant reductions in body sway compatible with the exhibition of SR in vestibular sensorimotor pathways in at least half of the assessed patients. Non-invasive vestibular noise stimulation may be thus a well-tolerated treatment strategy to ameliorate postural symptoms in PSP. [ABSTRACT FROM AUTHOR]

Introduction: Hepcidin is a peptide associated with controlling the distribution of iron in tissues. Growing interest is linked with its impact on neurodegenerative diseases, as disruption of the iron regulation may be considered an initiatory element of pathological protein accumulation. The possible impact of hepcidin was not previously sufficiently explored in progressive supranuclear palsy (PSP). Methods: Twelve patients with PSP–Richardson's syndrome (PSP–RS), 12 with PSP‐Parkinsonism Predominant (PSP‐P), and 12 controls were examined using Unified Parkinson's Disease Rating Scale—III part (UPDRS‐III) in OFF stage and analyzed in the context of hepcidin levels in the serum. Results: The work revealed increased levels of hepcidin in PSP–RS when compared to PSP‐P and controls. Moreover, hepcidin was found to be negatively correlated with UPDRS‐III results in PSP–RS, whereas positively in PSP‐P. Conclusion: The work may suggest a possible impact of hepcidin in PSP, possibly differing depending on its subtype. [ABSTRACT FROM AUTHOR]

Progressive supranuclear palsy (PSP) is an atypical form of parkinsonism characterized by tauopathy, manifesting as oculomotor dysfunction, postural instability, akinesia, and cognitive/language impairments. The diagnosis and examination of PSP can be challenging, primarily due to the unclear and underexplored pathomechanisms involved, alongside absence of effective treatments. Clinical variants of PSP is the second most common form of neurodegenerative parkinsonism after Parkinson’s disease (PD). It is defined by a symmetrical akinetic-rigid syndrome (atypical parkinsonism) and vertical supranuclear gaze palsy. In contrast to PD, PSP often presents with gait instability, backward falls, and cognitive and behavioral changes at early disease stages. The classification of PSP has evolved since Richardson, Steele, and Olszewski’s initial reporting of the condition in 1963, which included a cohort of nine patients. Over the years, the definition of this disorder has evolved to encapsulate a group of patients with distinct clinical variants, notably the classical Richardson syndrome (RS) and several atypical phenotypes, each with significant implications for disease progression and quality of life (QoL). The 2017 Movement Disorder Society Diagnostic Criteria by Hoglinger et al., improved the sensitivity for detecting early and variant PSP presentations and provided more specific differential diagnoses for conditions such as PD and other forms of atypical parkinsonian syndromes. Owing to the growing interest in the disease’s progression, evaluating the QoL for patients with PSP has become crucial. This review emphasizes the significance of QoL evaluation and its feasibility for practical implications, serving as an initial foundation for future research focused on the well-being of individuals affected by PSP. Progressive supranuclear palsy (PSP) is an atypical form of parkinsonism characterized by tauopathy, manifesting as oculomotor dysfunction, postural instability, akinesia, and cognitive/language impairments. Diagnosing PSP is challenging owing to the lack of tools for differential examination. Additionally, the pathomechanism of this disease is not sufficiently understood, and no treatment is currently available. Owing to the growing interest in the disease’s progression, evaluating the quality of life (QoL) for patients with PSP has become crucial. This review emphasizes the significance of QoL evaluation and its feasibility for practical implications, serving as an initial foundation for future research focused on the well-being of individuals affected by PSP.

IntroductionProgressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are tauopathic atypical parkinsonisms. Given their overlap in terms of clinical manifestation, there is growing interest in the mechanisms leading to these entities.Materials and methodsIn total, 71 patients were included in the study, 19 of whom were clinically diagnosed with CBS, 37 with PSP, and 15 with Parkinson's disease (PD). The mean ages of the participants were 72.8, 72.9, and 64.0 years, respectively, and the disease duration varied from 3 to 6 years. Each individual underwent blood collection. Morphological and biochemical evaluation of blood samples was performed to analyze the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-high-density lipoprotein ratio (NHR). A single-photon emission computed tomography (SPECT) with technetium-99m hexamethylpropyleneamine oxime (99Tc-HMPAO) tracer was used to assess perfusion in two regions of interest (ROI): the thalamus and insula. Using Pearson correlation to assess the linear relationship between NHR and perfusion in the insula and thalamus for CBS, PSP, and PD patients, the authors intended to verify possible correlations between NLR, PLR, and NHR and perfusion in the indicated ROIs.ResultsThe study revealed a negative linear correlation between NHR and perfusion of both the left (Insula L; R = −0.59) and right (Insula R; R = −0.58) insula regions. Similar to the insula, a linear correlation between NHR and activity in both the left (Thalamus L) and right (Thalamus R) thalamus regions in CBS subjects with a relatively stronger correlation in the right thalamus (R = −0.64 vs. R = −0.58) was found. These observations were not confirmed in PSP and PD patients.ConclusionSimultaneously using non-specific parameters for peripheral inflammation (NLR, PLR, and NHR) and perfusion, SPECT may be an interesting beginning point for further analysis of inflammatory disease mechanisms. To the best of our knowledge, this is the first study to address the potential correlation between the peripheral neuroinflammatory markers NLR, PLR, and NHR and perfusion disturbances in particular ROIs.

Atypical parkinsonism (AP) is a group of complex neurodegenerative disorders with marked clinical and pathophysiological heterogeneity. The use of systems biology tools may contribute to the characterization of hub-bottleneck genes, and the identification of its biological pathways to broaden the understanding of the bases of these disorders. A systematic search was performed on the DisGeNET database, which integrates data from expert curated repositories, GWAS catalogues, animal models and the scientific literature. The tools STRING 11.0 and Cytoscape 3.8.2 were used for analysis of protein-protein interaction (PPI) network. The PPI network topography analyses were performed using the CytoHubba 0.1 plugin for Cytoscape. The hub and bottleneck genes were inserted into 4 different sets on the InteractiveVenn. Additional functional enrichment analyses were performed to identify Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and gene ontology for a described set of genes. The systematic search in the DisGeNET database identified 485 genes involved with Atypical Parkinsonism. Superimposing these genes, we detected a total of 31 hub-bottleneck genes. Moreover, our functional enrichment analyses demonstrated the involvement of these hub-bottleneck genes in 3 major KEGG pathways. We identified 31 highly interconnected hub-bottleneck genes through a systems biology approach, which may play a key role in the pathogenesis of atypical parkinsonism. The functional enrichment analyses showed that these genes are involved in several biological processes and pathways, such as the glial cell development, glial cell activation and cognition, pathways were related to Alzheimer disease and Parkinson disease. As a hypothesis, we highlight as possible key genes for AP the MAPT (microtubule associated protein tau), APOE (apolipoprotein E), SNCA (synuclein alpha) and APP (amyloid beta precursor protein) genes. [ABSTRACT FROM AUTHOR]

Background: Advanced imaging techniques have been studied for differential diagnosis between PD, MSA, and PSP. Objectives: This study aims to validate the utility of individual voxel‐based morphometry techniques for atypical parkinsonism in a blinded fashion. Methods: Forty‐eight healthy controls (HC) T1‐WI were used to develop a referential dataset and fit a general linear model after segmentation into gray matter (GM) and white matter (WM) compartments. Segmented GM and WM with PD (n = 96), MSA (n = 18), and PSP (n = 20) were transformed into z‐scores using the statistics of referential HC and individual voxel‐based z‐score maps were generated. An imaging diagnosis was assigned by two independent raters (trained and untrained) blinded to clinical information and final diagnosis. Furthermore, we developed an observer‐independent index for ROI‐based automated differentiation. Results: The diagnostic performance using voxel‐based z‐score maps by rater 1 and rater 2 for MSA yielded sensitivities: 0.89, 0.94 (95% CI: 0.74–1.00, 0.84–1.00), specificities: 0.94, 0.80 (0.90–0.98, 0.73–0.87); for PSP, sensitivities: 0.85, 0.90 (0.69–1.00, 0.77–1.00), specificities: 0.98, 0.94 (0.96–1.00, 0.90–0.98). Interrater agreement was good for MSA (Cohen's kappa: 0.61), and excellent for PSP (0.84). Receiver operating characteristic analysis using the ROI‐based new index showed an area under the curve (AUC): 0.89 (0.77–1.00) for MSA, and 0.99 (0.98–1.00) for PSP. Conclusions: These evaluations provide support for the utility of this imaging technique in the differential diagnosis of atypical parkinsonism demonstrating a remarkably high differentiation accuracy for PSP, suggesting potential use in clinical settings in the future. [ABSTRACT FROM AUTHOR]

Purpose of review: This review describes the current approaches to the diagnosis and management of progressive supranuclear palsy (PSP) Recent findings: PSP is an atypical parkinsonian disorder associated with the accumulation of abnormal 4-repeat tau protein in the brain. Initially, the recognized clinical phenotype included a progressive disorder with vertical supranuclear gaze palsy and prominent postural instability leading to early falls. However, the current PSP diagnostic criteria recognize a broader range of clinical PSP presentations and define eight clinical PSP variants according to the levels of diagnostic certainty. While definite PSP remains a neuropathological diagnosis, imaging modalities including brain magnetic resonance imaging (MRI), dopamine transporter (DAT), and tau positron emission tomography (PET) scans may aid in the diagnosis. In the future, new tau PET ligands and CSF and genetic biomarkers may improve diagnostic accuracy. There is no disease-modifying therapy currently available for PSP. However, there are many pharmacological and non-pharmacological treatment options for symptomatic management. Because PSP is a multisystem disease, optimal management requires a coordinated multidisciplinary team approach. Summary: PSP is a fatal multisystem disease that can be challenging to diagnose and manage. However, improved clinical diagnostic criteria, emerging biomarkers, and availability of useful therapeutic approaches provide cause for optimism. [ABSTRACT FROM AUTHOR]

Background: Multiple system atrophy (MSA) is a primary oligodendroglial synucleinopathy, characterized by elevated iron burden in early-affected subcortical nuclei. Although neurotoxic effects of brain iron deposition and its relationship with α-synuclein pathology have been demonstrated, the exact role of iron dysregulation in MSA pathogenesis is unknown. Therefore, advancing the understanding of iron dysregulation at the cellular level is critical, especially in relation to α-synuclein cytopathology. Methods: Iron burden in subcortical and brainstem regions were histologically mapped in human post-mortem brains of 4 MSA-parkinsonian (MSA-P), 4 MSA-cerebellar (MSA-C), and 1 MSA case with both parkinsonian and cerebellar features. We then performed the first cell type-specific evaluation of pathological iron deposition in α-synuclein-affected and -unaffected cells of the globus pallidus, putamen, and the substantia nigra, regions of highest iron concentration, using a combination of iron staining with immunolabelling. Selective regional and cellular vulnerability patterns of iron deposition were compared between disease subtypes. In 7 MSA cases, expression of key iron- and closely related oxygen-homeostatic genes were examined. Results: MSA-P and MSA-C showed different patterns of regional iron burden across the pathology-related systems. We identified subcortical microglia to predominantly accumulate iron, which was more distinct in MSA-P. MSA-C showed relatively heterogenous iron accumulation, with greater or similar deposition in astroglia. Iron deposition was also found outside cellular bodies. Cellular iron burden associated with oligodendrocytic, and not neuronal, α-synuclein cytopathology. Gene expression analysis revealed dysregulation of oxygen homeostatic genes, rather than of cellular iron. Importantly, hierarchal cluster analysis revealed the pattern of cellular vulnerability to iron accumulation, distinctly to α-synuclein pathology load in the subtype-related systems, to distinguish MSA subtypes. Conclusions: Our comprehensive evaluation of iron deposition in MSA brains identified distinct regional, and for the first time, cellular distribution of iron deposition in MSA-P and MSA-C and revealed cellular vulnerability patterns to iron deposition as a novel neuropathological characteristic that predicts MSA clinical subtypes. Our findings suggest distinct iron-related pathomechanisms in MSA clinical subtypes that are therefore not a consequence of a uniform down-stream pathway to α-synuclein pathology, and inform current efforts in iron chelation therapies at the disease and cellular-specific levels.

Abstract Introduction Hepcidin is a peptide associated with controlling the distribution of iron in tissues. Growing interest is linked with its impact on neurodegenerative diseases, as disruption of the iron regulation may be considered an initiatory element of pathological protein accumulation. The possible impact of hepcidin was not previously sufficiently explored in progressive supranuclear palsy (PSP). Methods Twelve patients with PSP–Richardson's syndrome (PSP–RS), 12 with PSP‐Parkinsonism Predominant (PSP‐P), and 12 controls were examined using Unified Parkinson's Disease Rating Scale—III part (UPDRS‐III) in OFF stage and analyzed in the context of hepcidin levels in the serum. Results The work revealed increased levels of hepcidin in PSP–RS when compared to PSP‐P and controls. Moreover, hepcidin was found to be negatively correlated with UPDRS‐III results in PSP–RS, whereas positively in PSP‐P. Conclusion The work may suggest a possible impact of hepcidin in PSP, possibly differing depending on its subtype.

Atypical Parkinsonian syndromes are a subset of progressive neurodegenerative disorders that present with signs of Parkinson's disease. However, due to multisystem degeneration, the atypical Parkinsonian syndromes have additional symptoms that are often referred to as Parkinson-plus syndromes. The most well-studied subsets include progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and Lewy body dementia. Specifically, progressive supranuclear palsy is a tauopathy neurodegenerative disorder that presents with parkinsonism symptoms along with postural instability, vertical saccade, and vertical gaze palsy. Here, we present a case of PSP and provide a brief review of the literature.

Amyotrophic Lateral Sclerosis (ALS) is a heterogeneous disorder and the phenotypic variability goes far beyond the used clinical stratification parameter. Evidence has emerged that ALS may coexist with distinct neurodegenerative diseases in single cases. We aim to study the clinical features of two familial cases of ALS carriers of two distinct variants harbored in the Optineurin (OPTN) gene. We included definite familial ALS followed up in the Department of Neurology of Razi University Hospital, Tunisia, and selected according to Byrne criteria. Preliminary screening for the four main ALS genes (SOD1, C9ORF72, TARDBP, FUS) was conducted. Given the negative results, we proceeded to NGS target-re-sequencing with a custom panel including genes associated with ALS-FTD, Alzheimer's, and Parkinson's diseases. Both families are carriers of two different OPTN variants and they present very different ALS clinical features. The first family comprises two siblings diagnosed with ALS and Corticobasal syndrome (ALS-CBS) at an early age of onset and carriers of OPTN p.E135X in the homozygous state. The proband for the second family was diagnosed with ALS at an early age of onset presenting as progressive muscular atrophy with rapid progression. Genetic analysis revealed the presence of the homozygous variant p.R520H. Our findings highlight the peculiarity of genetic Tunisian drift. Indeed, genes with a recessive mode of inheritance may explain part of ALS diversity in clinical features. Therefore, the screening of the OPTN gene is highly recommended among inbreeding populations such as the Tunisian one. [ABSTRACT FROM AUTHOR]

Background and purpose: Levodopa (LD) is the main treatment for parkinsonism, but its use may be limited by a potential hypotensive effect. Methods: We evaluated the cardiovascular effect of LD performing head‐up tilt test (HUTT) before and 60 min after 100/25 mg LD/dopa‐decarboxylase inhibitor (pre‐LD vs. post‐LD HUTT) in 164 patients with parkinsonism on chronic LD treatment. Features predictive of LD‐induced orthostatic hypotension (OH) were assessed by logistic regression analysis. Results: Basal supine blood pressure (BP) and heart rate (HR) decreased after LD. During post‐LD HUTT, BP drop and HR increase were significantly greater than at pre‐LD HUTT. Thirty‐eight percent of patients had OH at post‐LD HUTT compared to 22% of patients presenting OH at pre‐LD HUTT (p < 0.001). Risk factors for LD‐induced/worsened OH were pre‐LD OH (odds ratio [OR] = 36, 95% confidence interval [CI] = 10–131), absence of overshoot at Valsalva maneuver (OR = 9, 95% CI = 4–20), and pathological Valsalva ratio (OR = 6, 95% CI = 2–15). Conclusions: LD administration caused/worsened hypotension in both supine and orthostatic conditions. Patients with cardiovascular autonomic failure had a higher risk of developing LD‐induced OH. In clinical practice, LD‐induced OH could represent a red flag for cardiovascular autonomic failure. [ABSTRACT FROM AUTHOR]

Differentiating multiple system atrophy (MSA) from related neurodegenerative movement disorders (NMD) is challenging. MRI is widely available and automated decision-tree analysis is simple, transparent, and resistant to overfitting. Using a retrospective cohort of heterogeneous clinical MRIs broadly sourced from a tertiary hospital system, we aimed to develop readily translatable and fully automated volumetric diagnostic decision-trees to facilitate early and accurate differential diagnosis of NMDs. 3DT1 MRI from 171 NMD patients (72 MSA, 49 PSP, 50 PD) and 171 matched healthy subjects were automatically segmented using Freesurfer6.0 with brainstem module. Decision trees employing substructure volumes and a novel volumetric pons-to-midbrain ratio (3D-PMR) were produced and tenfold cross-validation performed. The optimal tree separating NMD from healthy subjects selected cerebellar white matter, thalamus, putamen, striatum, and midbrain volumes as nodes. Its sensitivity was 84%, specificity 94%, accuracy 84%, and kappa 0.69 in cross-validation. The optimal tree restricted to NMD patients selected 3D-PMR, thalamus, superior cerebellar peduncle (SCP), midbrain, pons, and putamen as nodes. It yielded sensitivities/specificities of 94/84% for MSA, 72/96% for PSP, and 73/92% PD, with 79% accuracy and 0.62 kappa. There was correct classification of 16/17 MSA, 5/8 PSP, 6/8 PD autopsy-confirmed patients, and 6/8 MRIs that preceded motor symptom onset. Fully automated decision trees utilizing volumetric MRI data distinguished NMD patients from healthy subjects and MSA from other NMDs with promising accuracy, including autopsy-confirmed and pre-symptomatic subsets. Our open-source methodology is well-suited for widespread clinical translation. Assessment in even more heterogeneous retrospective and prospective cohorts is indicated. [ABSTRACT FROM AUTHOR]

Multiple system atrophy (MSA) is generally a sporadic neurodegenerative disease which ranks among atypical Parkinson's syndromes. The main clinical manifestation is a combination of autonomic dysfunction and parkinsonism and/or cerebellar disability. The disease may resemble other Parkinsonian syndromes, such as Parkinson's disease (PD) or progressive supranuclear palsy (PSP), from which MSA could be hardly distinguishable during the first years of progression. Due to the lack of a reliable and easily accessible biomarker, the diagnosis is still based primarily on the clinical picture. Recently, reduced levels of coenzyme Q10 (CoQ10) were described in MSA in various tissues, including the central nervous system. The aim of our study was to verify whether the level of CoQ10 in plasma and lymphocytes could serve as an easily available diagnostic biomarker of MSA. The study reported significantly lower levels of CoQ10 in the lymphocytes of patients with MSA compared to patients with PD and controls. The reduction in CoQ10 levels in lymphocytes correlated with the increasing degree of clinical involvement of patients with MSA. CoQ10 levels in lymphocytes seem to be a potential biomarker of disease progression. [ABSTRACT FROM AUTHOR]

Purpose: First, to investigate the patterns of [18F]-FDOPA positron emission tomography imaging in corticobasal syndrome using visual and semi-quantitative analysis and to compare them with patterns found in Parkinson's disease and progressive supranuclear palsy. Then, to search for correlations with clinical features and [18F]-FDG positron emission tomography imaging. Methods: 27 corticobasal syndrome patients who underwent [18F]-FDOPA positron emission tomography imaging were retrospectively studied. They were compared to 27 matched Parkinson's disease patients, 12 progressive supranuclear palsy patients and 53 normal controls. Scans were visually assigned to one of the following patterns: normal; unilateral homogeneous striatal uptake reduction; putamen uptake reduction with putamen-caudate gradient. A semi-quantitative analysis of striatal regional uptake and asymmetry was performed and correlated to clinical features and [18F]-FDG positron emission tomography patterns. Results: [18F]-FDOPA positron emission tomography appeared visually abnormal in only 33.5% of corticobasal syndrome patients. However, semi-quantitative analysis found putaminal asymmetry in 63%. Striatal uptake was homogeneously reduced in both putamen and caudate nucleus in corticobasal syndrome patients unlike in Parkinson's disease and progressive supranuclear palsy. No correlation was found between [18F]-FDOPA positron emission tomography and clinical features. Half of corticobasal syndrome patients presented a corticobasal degeneration pattern on [18F]-FDG positron emission tomography. Conclusion: [18F]-FDOPA positron emission tomography can often be normal in corticobasal syndrome patients. Semi-quantitative analysis is useful to unmask a significant asymmetry in many of them. Homogeneous striatal uptake reduction contralateral to the clinical signs is highly suggestive of corticobasal syndrome. This finding can be helpful to better characterize this syndrome with respect to Parkinson's disease and progressive supranuclear palsy. [ABSTRACT FROM AUTHOR]

Over the past three decades, substantial advancements have occurred in non-invasive brain stimulation (NIBS). These developments encompass various non-invasive techniques aimed at modulating brain function. Among the most widely utilized methods today are transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES), which include direct- or alternating-current transcranial stimulation (tDCS/tACS). In addition to these established techniques, newer modalities have emerged, broadening the scope of non-invasive neuromodulation approaches available for research and clinical applications in movement disorders, particularly for Parkinson’s disease (PD) and, to a lesser extent, atypical Parkinsonism (AP). All NIBS techniques offer the opportunity to explore a wide range of neurophysiological mechanisms and exert influence over distinct brain regions implicated in the pathophysiology of Parkinsonism. This paper’s first aim is to provide a brief overview of the historical background and underlying physiological principles of primary NIBS techniques, focusing on their translational relevance. It aims to shed light on the potential identification of biomarkers for diagnostic and therapeutic purposes, by summarising available experimental data on individuals with Parkinsonism. To date, despite promising findings indicating the potential utility of NIBS techniques in Parkinsonism, their integration into clinical routine for diagnostic or therapeutic protocols remains a subject of ongoing investigation and scientific debate. In this context, this paper addresses current unsolved issues and methodological challenges concerning the use of NIBS, focusing on the importance of future research endeavours for maximizing the efficacy and relevance of NIBS strategies for individuals with Parkinsonism.

Introduction: Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) manifest with variable clinical features. We initiated a multicenter prospective registry study—the Japanese Longitudinal Biomarker Study in PSP and CBD—in November 2014 at 45 Japanese institutions to collect clinical information and biological samples to elucidate the natural courses and diagnostic biomarkers of PSP/CBD. Methods: Initial symptoms, clinical features, and scores (Progressive Supranuclear Palsy Rating Scale [PSPRS], Barthel Index, Mini-Mental State Examination, and Frontal Assessment Battery) of patients clinically diagnosed with PSP/corticobasal syndrome (CBS) at the first registration were analyzed. PSPRS score progression in the initial 8 years and predictive factors were examined. Results: As of October 2022, first registration had been conducted for 349 patients—57 with probable/possible Richardson’s syndrome (RS), 133 with possible CBS, 41 with overlapping CBS and PSP criteria (RS/CBS group), 20 with PSP subtypes other than RS, and 98 who did not fulfill the PSP or CBS criteria. Among the RS, CBS, and RS/CBS groups, the RS group exhibited the best scores. Initial symptoms of personality change and asymmetric onset were correlated with the total PSPRS score. The average PSPRS score increment by the second registration (n = 116 patients) was 11.8 in all three groups, and progression was correlated with cognitive dysfunction. Seventy patients died during the study period. The 5-year survival rate from onset was approximately 90 %. Conclusion: There were fewer severe clinical features in the RS group than in the CBS group. Cognitive dysfunction may be important in predicting clinical severity and disease progression.

Introduction: Progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA) are rare neurodegenerative diseases associated with rapid decline and require complex symptom management. Caregiving responsibilities significantly increase with progression of these atypical Parkinsonian syndromes, yet care burden in these syndromes has not been researched extensively to date. Methods: The Zarit Burden Interview (ZBI) was used to assess burden in care partners of patients clinically diagnosed with PSP, CBS, or MSA seen in specialty interdisciplinary clinics at two academic movement disorders centers. Univariable and multivariable regression analyses were performed to evaluate cross-sectional demographic and clinical determinants of care partner burden. Results: A total of 139 care partners completed the ZBI (59.0% PSP, 28.1% MSA, 12.9% CBS). Cohorts at both medical centers were similar across all variables. Female gender of both patients and care partners was independently associated with higher ZBI scores. Additionally, MSA-Parkinsonian type was significantly associated with lower total care partner burden compared to PSP and CBS. Conclusion: Several determinants of higher care partner burden in atypical Parkinsonian syndromes were identified, particularly female gender and diagnosis. Healthcare professionals can consider this information when assessing individualized needs of patients and care partners and referring to disease-specific resources. Additionally, this study’s methods and results highlight the potential to further explore interdisciplinary care as a means of comprehensive evaluation and support for those with atypical Parkinsonism.

Background: New diagnostic criteria of Progressive Supranuclear Palsy (PSP) have highlighted the interest of Eye Movement Records (EMR) at the early stage of the disease. Objectives: To investigate the metabolic brain correlates of ocular motor dysfunction using [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in early PSP. Methods: Retrospective observational descriptive study on longitudinal data with patients who underwent EMR and FDG-PET at the stage of suggestive and possible PSP according to Movement Disorders Society criteria. Longitudinal follow-up enables to confirm diagnosis of probable PSP. Using the Statistical Parametric Mapping software, we performed whole-brain voxel-based correlations between oculomotor variables and FDG-PET metabolism. Results: Thirty-seven patients with early PSP who fulfilled criteria of probable PSP during the follow-up were included. Decrease in the gain of vertical saccades correlated with reduced metabolism in Superior Colliculi (SC). We also found a positive correlation between mean velocity of horizontal saccades and SC metabolism as well as dorsal nuclei in the pons. Finally, increase in horizontal saccades latencies correlated with decrease of posterior parietal metabolism. Conclusions: These findings suggest the early involvement of SC in saccadic dysfunction in the course of PSP. [ABSTRACT FROM AUTHOR]

Objective: To study the neurological manifestations of glutamic acid decarboxylase (GAD 65) autoimmunity in Indian patients. Methods: Retrospective study conducted in a tertiary care referral hospital in South India. Patients who tested positive for GAD 65 antibodies from February 2013 to July 2019 were included. Results: We identified 922 patients who underwent GAD 65 testing, of which 81 tested positive (8.78%) [mean age 55.42 years (SD 17.39, range 9-86 years, median age 57 years)]. Males (n = 47) outnumbered the females (n = 34). All the GAD values measured were <5000 IU/ml. There were 34 cases (42%) of atypical parkinsonism (16/34, 47% fulfilled the diagnostic criteria for autoimmune atypical parkinsonism) in our series forming the most common group with GAD 65 positivity, followed by autoimmune encephalitis (8 cases, 9.88%). Men were more affected with atypical parkinsonism (22/34; 64.70%), stiff person syndrome (2/3; 66.66%), and neuropathy (4/7; 57.1%) while women were more with autoimmune encephalitis (6/8; 75%). Eighteen (22.6%) had underlying autoimmunity (three had type 1 diabetes mellitus). Six (7.4%) had underlying neoplasm. Thirty three out of 43 patients responded to immunotherapy (76.74%). Five had spontaneous improvement. Conclusion: Glutamic acid decarboxylase65 antibody values were much lower in our study population. Male dominant autoimmunity was seen unlike that in Western literature. The most striking was the high preponderance of atypical parkinsonism in GAD 65 positive patients. We also found that GAD 65 positivity is a useful marker for a positive response to immunotherapy in suspected autoimmune neurological syndromes irrespective of their titers. [ABSTRACT FROM AUTHOR]

Among people with Parkinson's disease (PD), non-motor symptoms (NMS) are a well-recognised cause of significant morbidity and poor quality of life. Yet, it is only more recently that NMS have been recognised to affect the lives of patients with atypical parkinsonian syndromes in a similar fashion. The aim of this article is to highlight and compare the relative prevalence of NMS among patients with atypical parkinsonian syndromes in the published literature, which largely remain underreported and unaddressed in routine clinical practice. All NMS that are recognised to occur in PD are also found to commonly occur in atypical parkinsonian syndromes. In particular, excessive daytime sleepiness is more prevalent among atypical parkinsonian syndromes (94.3%) compared to PD (33.9%) or normal controls (10.5%) (p < 0.001). Urinary dysfunction (not limited to urinary incontinence) is not only found to occur in MSA (79.7%) and PD (79.9%), but has also been reported in nearly half of the patients with PSP (49.3%), DLB (42%) and CBD (53.8%) (p < 0.001). Apathy is significantly more common among the atypical parkinsonian syndromes [PSP (56%), MSA (48%), DLB (44%), CBD (43%)] compared to PD (35%) (p = 0.029). Early recognition and addressing of NMS among atypical parkinsonian syndromes may help improve the holistic patient care provided and may encompass a range of conservative and pharmacotherapeutic treatments to address these symptoms. [ABSTRACT FROM AUTHOR]

Progressive Supranuclear Palsy and Multiple-System Atrophy are entities within the spectrum of atypical parkinsonism. The role of imaging methods in the diagnosis and differentiation between PSP and MSA is limited and Magnetic Resonance Imaging (MRI) is currently used as a reference modality. In this study, the authors examined a group of patients with atypical parkinsonism using a 1.5 T MRI system and aimed to find simple and repeatable measurements that may be useful to distinguish between these diseases. The results of the study indicate that the maximal width of the frontal horns of the lateral ventricles and Evans' Index may, to some extent, be useful as basic and simple measurements in the diagnostic imaging of patients with atypical parkinsonism. [ABSTRACT FROM AUTHOR]

Gastrointestinal (GI) dysfunction is a common nonmotor symptom in Parkinson's disease (PD) as well as other parkinsonian syndromes and may precede the onset of motor symptoms by decades. Involvement of all segments of the GI tract can lead to altered responses to medications and worsened quality of life for patients. While some GI symptoms occur in isolation, others overlap. Therefore, understanding the changes in different segments of the GI tract and how they relate to altered responses to PD treatment can guide both diagnostic and pharmacological interventions. Gut microbiota plays a critical role in immune activity and modulation of the enteric and central nervous systems. Understanding this bidirectional relationship helps to elucidate the pathogenesis of neurodegeneration. This review will describe the current understanding of how GI dysfunction develops in parkinsonian syndromes, common symptoms in PD and related disorders, and available treatments. [ABSTRACT FROM AUTHOR]

Background and purpose: Clinical correlates of fear of falling (FoF) are scarcely studied in patients with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). This study was undertaken to evaluate the clinical correlates of FoF in PSP and MSA. Methods: This cross‐sectional study features motor, cognitive, and psychiatric assessment and longitudinal evaluation of falls and FoF at 6‐month follow‐up. Results: Twenty‐one patients with PSP‐parkinsonism, 22 patients with MSA (13 parkinsonian type and nine cerebellar type), and 22 healthy controls were evaluated; 76.2% of patients with PSP and 86.4% of patients with MSA had FoF regardless of falls. Berg Balance Scale (p < 0.001), Tinetti Mobility Test (p < 0.01), Beck Anxiety Inventory (p = 0.001), and Beck Depression Inventory‐II (p = 0.01) correlated with FoF in patients with PSP and MSA, whereas Timed Up and Go test (p = 0.01) and Starkstein Apathy Scale correlated only in MSA (p = 0.04). Conclusions: Mobility, balance, and gait performance as well as anxiety and depression in PSP and MSA, and apathy in MSA, were determinants of FoF. These findings underline the importance of a multidisciplinary approach to FoF in neurodegenerative atypical parkinsonism. [ABSTRACT FROM AUTHOR]

Atypical Parkinsonism (AP) syndromes are characterized by a wide spectrum of non-motor symptoms including prominent attentional and executive deficits. However, the cognitive profile of AP and its differences and similarities with that of Parkinson's Disease (PD) are still a matter of debate. The present meta-analysis aimed at identifying patterns of cognitive impairment in AP by comparing global cognitive functioning, memory, executive functions, visuospatial abilities, language, non-verbal reasoning, and processing speed test performances of patients with AP relative to healthy controls and patients with PD. All investigated cognitive domains showed a substantial impairment in patients with AP compared to healthy controls. When AP syndromes were considered separately, their cognitive functioning was distributed along a continuum from Multiple Systemic Atrophy at one extreme, with the least impaired cognitive profile (similar to that observed in PD) to Progressive Supranuclear Palsy, with the greatest decline in global cognitive and executive functioning (similar to Corticobasal Syndrome). These findings indicate that widespread cognitive impairment could represent an important clinical indicator to distinguish AP from other movement disorders. [ABSTRACT FROM AUTHOR]

Four-repeat tauopathies are a neurodegenerative disease characterized by brain parenchymal accumulation of a specific isoform of the protein tau, which gives rise to a wide breadth of clinical syndromes encompassing diverse symptomatology, with the most common syndromes being progressive supranuclear palsy-Richardson's and corticobasal syndrome. Despite the lack of effective disease-modifying therapies, targeted treatment of symptoms can improve quality of life for patients with 4-repeat tauopathies. However, managing these symptoms can be a daunting task, even for those familiar with the diseases, as they span motor, sensory, cognitive, affective, autonomic, and behavioral domains. This review describes current approaches to symptomatic management of common clinical symptoms in 4-repeat tauopathies with a focus on practical patient management, including pharmacologic and nonpharmacologic strategies, and concludes with a discussion of the history and future of disease-modifying therapeutics and clinical trials in this population.

Objective: To study the neurological manifestations of glutamic acid decarboxylase (GAD 65) autoimmunity in Indian patients. Methods: Retrospective study conducted in a tertiary care referral hospital in South India. Patients who tested positive for GAD 65 antibodies from February 2013 to July 2019 were included. Results: We identified 922 patients who underwent GAD 65 testing, of which 81 tested positive (8.78%) [mean age 55.42 years (SD 17.39, range 9–86 years, median age 57 years)]. Males (n = 47) outnumbered the females (n = 34). All the GAD values measured were

Multiple system atrophy (MSA) is generally a sporadic neurodegenerative disease which ranks among atypical Parkinson’s syndromes. The main clinical manifestation is a combination of autonomic dysfunction and parkinsonism and/or cerebellar disability. The disease may resemble other Parkinsonian syndromes, such as Parkinson’s disease (PD) or progressive supranuclear palsy (PSP), from which MSA could be hardly distinguishable during the first years of progression. Due to the lack of a reliable and easily accessible biomarker, the diagnosis is still based primarily on the clinical picture. Recently, reduced levels of coenzyme Q10 (CoQ10) were described in MSA in various tissues, including the central nervous system. The aim of our study was to verify whether the level of CoQ10 in plasma and lymphocytes could serve as an easily available diagnostic biomarker of MSA. The study reported significantly lower levels of CoQ10 in the lymphocytes of patients with MSA compared to patients with PD and controls. The reduction in CoQ10 levels in lymphocytes correlated with the increasing degree of clinical involvement of patients with MSA. CoQ10 levels in lymphocytes seem to be a potential biomarker of disease progression.

Osmotic demyelination syndrome (ODS) is a condition which occurs due to rapid osmotic changes which result in myelinolysis of the nervous system. Uncommonly the myelinolysis could involve areas beyond the pons resulting in extrapontine myelinolysis (EPM). We report a 70-year-old gentleman who presented with a 2-week history of reduced interaction and altered behavior with parkinsonism following oral correction of severe hyponatraemia. Magnetic resonance imaging (MRI) of the brain revealed hyperintensities in the T2-weighted FLAIR images involving the pontine region with no involvement of basal ganglia. This case illustrates the significance of adhering to recommended protocols when correcting hyponatraemia and the importance of timing brain imaging in ODS.

We investigated retinal structure changes in patients with Parkinson's disease (PD), multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and controls, and explored the value of this method in differential diagnosis. Spectral domain optical coherence tomography (SD-OCT) was used to measure peripapillary retinal nerve fiber layer (pRNFL) thickness, and macular thickness and volume. PSP patients showed higher temporal pRNFL thickness than PD and MSA patients. Peripapillary RNFL thickness could be used for discriminating PSP from MSA and PD. PD and MSA patients showed retinal thinning in the foveal center circle and nasal inner sectors compared to controls. Macular thickness and volume could be used for discriminating MSA from PD. There were negative correlations between disease duration and OCT parameters in PD, MSA, and PSP, independent of age, sex ratio, and the side of the eye. PD and atypical parkinsonism correlate with specific patterns of retina alterations. OCT could be a biomarker for differential diagnosis and progression evaluation of parkinsonian syndrome. [ABSTRACT FROM AUTHOR]

In this manuscript, we review the epidemiology of movement disorders including Parkinson's disease (PD), atypical parkinsonism, essential tremor, dystonia, functional movement disorders, tic disorders, chorea, and ataxias. We emphasize age-, sex-, and geography-based incidence and prevalence, as well as notable trends including the rising incidence and prevalence of PD. Given the growing global interest in refining clinical diagnostic skills in recognizing movement disorders, we highlight some key epidemiological findings that may be of interest to clinicians and health systems tasked with diagnosing and managing the health of patients with movement disorders. [ABSTRACT FROM AUTHOR]

Neuroimaging is an important adjunct to the clinical assessment of Parkinson disease (PD). Parkinsonism can be challenging to differentiate, especially in early disease stages, when it mimics other movement disorders or when there is a poor response to dopaminergic therapies. There is also a discrepancy between the phenotypic presentation of degenerative parkinsonism and the pathological outcome. The emergence of more sophisticated and accessible neuroimaging can identify molecular mechanisms of PD, the variation between clinical phenotypes, and the compensatory mechanisms that occur with disease progression. Ultra-high-field imaging techniques have improved spatial resolution and contrast that can detect microstructural changes, disruptions in neural pathways, and metabolic and blood flow alterations. We highlight the imaging modalities that can be accessed in clinical practice and recommend an approach to the diagnosis of clinically uncertain parkinsonism. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) and atypical parkinsonism (AP), including progressive supranuclear palsy (PSP) and multiple system atrophy (MSA), share similar nonmotor symptoms. Quantitative electroencephalography (QEEG) can be used to examine the nonmotor symptoms. This study aimed to characterize the patterns of QEEG and functional connectivity (FC) that differentiate PD from PSP or MSA, and explore the correlation between the differential QEEG indices and nonmotor dysfunctions in PD and AP. We enrolled 52 patients with PD, 31 with MSA, 22 with PSP, and 50 age-matched health controls to compare QEEG indices among specific brain regions. One-way analysis of variance was applied to assess QEEG indices between groups; Spearman's correlations were used to examine the relationship between QEEG indices and nonmotor symptoms scale (NMSS) and mini-mental state examination (MMSE). FCs using weighted phase lag index were compared between patients with PD and those with MSA/PSP. Patients with PSP revealed higher scores on the NMSS and lower MMSE scores than those with PD and MSA, with similar disease duration. The delta and theta powers revealed a significant increase in PSP, followed by PD and MSA. Patients with PD presented a significantly lower slow-to-fast ratio than those with PSP in the frontal region, while patients with PD presented significantly higher EEG-slowing indices than patients with MSA. The frontal slow-to-fast ratio showed a negative correlation with MMSE scores in patients with PD and PSP, and a positive correlation with NMSS in the perception and mood domain in patients with PSP but not in those with PD. Compared to PD, MSA presented enhanced FC in theta and delta bands in the posterior region, while PSP revealed decreased FC in the delta band within the frontaltemporal cortex. These findings suggest that QEEG might be a useful tool for evaluating the nonmotor dysfunctions in PD and AP. Our QEEG results suggested that with similar disease duration, the cortical neurodegenerative process was likely exacerbated in patients with PSP, followed by those with PD, and lastly in patients with MSA. [ABSTRACT FROM AUTHOR]

Objectives: The classic triad of idiopathic normal pressure hydrocephalus (NPH) encompass gait disturbance, cognitive impairment, and urinary incontinence. These symptoms overlap with parkinsonism but with distinct treatment. Lacking applicable differentiation also hampers the prediction to therapeutic response. Here, we try to clarify this issue among different Parkinsonian syndromes and propose some innovative thinking while approaching a patient with parkinsonism and hydrocephalus concomitantly. Methods: Twenty‐four patients with clinical probable multiple system atrophy (MSA), 34 with probable progressive supranuclear palsy (PSP), and 58 with sex‐ and age‐matched Parkinson's disease (PD) were enrolled. Evans' index (EI), callosal angle (CA), antero‐posterior (AP) diameter of the midbrain, length of the midbrain tegmentum diameter (MBTegm), and disproportionately enlarged subarachnoid space hydrocephalus (DESH) were evaluated using the conventional MRI. Logistic regression was applied to identify the independent variables in hydrocephalus. Results: Patients with PSP had higher mean EI than those with MSA and PD. Around 38.2% of patients with PSP had accompanied hydrocephalus (EI > 0.3). Parkinsonism subtypes (PD, MSA, or PSP), AP diameter of the midbrain, and MBTegm were significantly different among patients with and without hydrocephalus. After regression analysis, parkinsonism subtype stood out to be the most key risk factor of hydrocephalus. The comparison between patients with PSP with and without hydrocephalus did not disclose specific clinical characteristics or risk factors. Conclusions: This study demonstrates that the presence of NPH‐like MRI features is much higher in PSP patients, and this tendency is decided upon the determination of parkinsonism subtype. Sharing pathophysiological characteristics in these two diseases is implied. More diagnostic tools are needed to better differentiate the two diseases and decide the treatment. To closely observe hydrocephalic parkinsonism patients and well inform the possible limited shunting benefits if PSP core features appear, will be more pivotal and practical at present clinical practice. [ABSTRACT FROM AUTHOR]

Accurate and timely diagnosis of atypical parkinsonian syndromes (APS) remains a challenge. Especially early in the disease course, the clinical manifestations of the APS overlap with each other and with those of idiopathic Parkinson's disease (PD). Recent advances in magnetic resonance imaging (MRI) technology have introduced promising imaging modalities to aid in the diagnosis of APS. Some of these MRI modalities are also included in the updated diagnostic criteria of APS. Importantly, MRI is safe for repeated use and more affordable and accessible compared to nuclear imaging. These advantages make MRI tools more appealing for diagnostic purposes. As the MRI field continues to advance, the diagnostic use of these techniques in APS, alone or in combination, are expected to become commonplace in clinical practice. [ABSTRACT FROM AUTHOR]