Background:Essential Tremor (ET) is increasingly recognized as phenotypically heterogeneous disorder, which may encompass alterations in gait, balance and cognitive dysfunction. Disruption in cerebellar-thalamic-cortical circuits results in varying patterns of executive and memory dysfunction and balance disorders. The current study proposed two aims: 1) identify cognitive subtypes within individuals with essential tremor, and 2) examine for a correlation between these subtypes and gait and balance dysfunction. We hypothesize that gait and balance dysfunction are more common in individuals with ET who demonstrate greater cognitive difficulties. Methods:Seventy-one individuals underwent neuropsychological and physical therapy examinations as part of presurgical deep brain stimulation (DBS) evaluations that included measures of gait and balance (Mini-BESTest; Timed Up and Go, SARA). People with ET were categorized into Cognitively Normal (N = 29), Low Executive Function/Processing Speed (N = 17), and Low Memory Multi-domain groups (N = 25). Results:Regression analyses show that scores on the Mini-Balance Evaluation Systems Test and Scale for the Assessment and Rating of Ataxia were worse in the Low Memory and Low Executive Function groups compared to the cognitively normal group; age was also a significant predictor. Scores on the Timed Up and Go were worse for the Low Executive Function compared to the cognitive normal group; age and education were also significant predictors. Medication use was not associated with any of the clinical gait and balance tests. However, medication use and age were significant predictors of reported falls in daily life. Conclusions:A subset of individuals with ET experience cognitive dysfunction that coalesce into processing speed deficits or immediate memory deficits. These cognitive subtypes were associated with greater difficulty in balance and gait as compared to cognitively normal ET patient and this difference could not be accounted for by medications.

Mitochondrial dysfunction is increasingly recognized as a key driver of pathology in patients with Parkinson's disease (PD). Peripheral blood mononuclear cells (PBMCs) have emerged as an accessible way to characterize mitochondrial function in PD. The aim of this study was to conduct a preliminary evaluation of the clinical relevance of PBMC mitochondrial function as a biomarker in early PD. PBMC mitochondrial bioenergetics were measured using the Seahorse XF platform in individuals with de novo, untreated PD (n = 13) and compared to age- and sex-matched healthy controls (n = 15). Correlations between mitochondrial endpoints and clinical outcomes were assessed in the PD group. Basal and ATP-linked respiration were elevated in the PD group (p = 0.002, p = 0.004), while spare capacity, or the cell's ability to handle an unexpected energetic stress, was decreased (p = 0.045), relative to controls. Notably, the variability within basal respiratory measurements was markedly increased in the PD group compared to controls (p = 0.002). Further analyses revealed significant correlations between spare capacity and clinical motor function scores within the PD group. These findings support the potential of PBMC bioenergetics as a biomarker for early-stage PD as well as disease progression.

Background/Objectives: Extracts of the plant Centella asiatica can enhance mitochondrial function, promote antioxidant activity and improve cognitive deficits. Asiatic acid (AA) is one of the constituent triterpene compounds present in the plant. In this study, we explore the effects of AA on brain mitochondrial function, antioxidant response and cognition in a beta-amyloid (Aβ)-overexpressing 5xFAD mouse line. Methods: Six- to seven-month-old 5xFAD mice were treated with 1% AA for 4 weeks. In the last week of treatment, associative memory was assessed along with mitochondrial bioenergetics and the expression of mitochondrial and antioxidant response genes from isolated cortical synaptosomes. The Aβ plaque burden was also evaluated. Results: AA treatment resulted in improvements in associative memory in female 5xFAD mice without altering the Aβ plaque burden. Cortical mitochondrial function and mitochondrial gene expression were increased in the AA-treated female 5xFAD mice, as was the expression of antioxidant genes. More modest effects of AA on cortical mitochondrial function and mitochondrial and antioxidant gene expression were observed in male 5xFAD mice. Conclusions: Oral AA treatment improved cognitive and mitochondrial function and activated antioxidant in Aβ-overexpressing mice. These changes occurred independent of alterations in Aβ plaque burden, suggesting that AA could have translational therapeutic relevance in later-stage AD when plaques are well established.

AbstractExtracts of the plantCentella asiaticacan enhance mitochondrial function, promote antioxidant activity and improve cognitive deficits. Asiatic acid (AA) is one of the constituent triterpene compounds present in the plant. In this study we explore the effects of increasing concentrations of AA on brain mitochondrial function, antioxidant response and cognition in healthy mice and a single concentration of AA in the beta-amyloid overexpressing 5xFAD mouse line. Associative memory and overall activity were assessed. Hippocampal mitochondrial bioenergetics and the expression of mitochondrial and antioxidant response genes was determined. In the 5xFAD line, total beta-amyloid plaque burden after AA treatment was also evaluated. In healthy mice, we report dose responsive effects of increasing concentrations of AA on enhanced associative memory and a dose dependent increase in basal and maximal mitochondrial respiration, mitochondrial gene expression and antioxidant gene expression. Results from the highest AA dose (1% AA) were similar to what was observed with CAW. The high AA dose was then evaluated in the context of Aβ accumulation in 5xFAD mice. Improvements in mitochondrial and antioxidant response genes were favored in females over males without significant alleviation of Aβ plaque burden.

Physical activity and sleep monitoring in daily life provide vital information to track health status and physical fitness. The aim of this study was to establish concurrent validity for the new Opal Actigraphy solution in relation to the widely used ActiGraph GT9X for measuring physical activity from accelerometry epic counts (sedentary to vigorous levels) and sleep periods in daily life. Twenty participants (age 56 + 22 years) wore two wearable devices on each wrist for 7 days and nights, recording 3-D accelerations at 30 Hz. Bland–Altman plots and intraclass correlation coefficients (ICCs) assessed validity (agreement) and test–retest reliability between ActiGraph and Opal Actigraphy sleep durations and activity levels, as well as between the two different versions of the ActiGraph. ICCs showed excellent reliability for physical activity measures and moderate-to-excellent reliability for sleep measures between Opal versus Actigraph GT9X and between GT3X versus GT9X. Bland–Altman plots and mean absolute percentage error (MAPE) also show a comparable performance (within 10%) between Opal and ActiGraph and between the two ActiGraph monitors across activity and sleep measures. In conclusion, physical activity and sleep measures using Opal Actigraphy demonstrate performance comparable to that of ActiGraph, supporting concurrent validation. Opal Actigraphy can be used to quantify activity and monitor sleep patterns in research and clinical studies.

Background:Methods for modulating the cerebellum with transcranial magnetic stimulation (TMS) are well established, and preliminary data from our group and others has shown evidence of transient improvements in balance after cerebellar repetitive transcranial magnetic stimulation (rTMS) in progressive suprancuclear palsy (PSP). This study examines extensive posturography measures before and after 10 sessions of cerebellar rTMS and sham TMS in PSP.Methods:Thirty subjects with PSP and postural instability will undergo cerebellar active and sham rTMS in a single-blind, crossover design with a randomized order of a 10-day intervention. Primary outcomes will be changes in sway area and medio-lateral range of sway with eyes open while standing on a stationary force-plate, and safety, tolerability, and blindedness. Secondary outcomes will include posturography and gait analysis with body-worn, triaxial inertial sensors, clinical balance scales and questionnaires, and a bedside test of vestibular function. Exploratory outcomes are changes in functional near infrared spectroscopy (fNIRS) signal over the prefrontal, supplementary motor, and primary motor cortices while standing and walking, and speech samples for future analysis.Discussion:The C-STIM crossover intervention study adds a longer duration of stimulation and extensive posturography measures to more finely measure the improvements in balance and exploratory functional near-infrared spectroscopy (fNIRS) over the prefronal, supplementary motor, and primary motor cortices during balance assessments before and after 10 sessions of cerebellar rTMS and 10 sessions of sham cerebellar TMS. This project will improve our understanding of the importance of the cerebellum for control of postural stability in PSP.

BACKGROUND: The standard of care for respiratory support of preterm infants is nasal continuous positive airway pressure (CPAP), yet practices are not standardized. Our aim was to survey CPAP practices in infants < 32 weeks gestation among the American Academy of Pediatrics Neonatal-Perinatal section. METHODS: A US, web-based survey inquired about the initiation, management, and discontinuation of CPAP, and chinstrap use and oral feedings on CPAP. RESULTS: 857 providers consented. Regarding criteria to discontinue/wean CPAP: 69% use specific respiratory stability criteria; 22% a specific post-menstrual age; 8% responded other. 64% did not have guidelines for CPAP discontinuation; 54% did not have guidelines for CPAP initiation. 66% believe chinstraps improve CPAP efficacy; however, 11% routinely apply a chinstrap. 22% allow oral feeds on CPAP in certain circumstances. CONCLUSION: There are meaningful variabilities in CPAP practices among neonatal providers across the US. Given the potential long-term implications this can have on the growth and development of the preterm lung, further evidence-based research is needed in relation to respiratory outcomes to optimize and standardize CPAP strategies.

Objective This study aimed to evaluate the effect of deep brain stimulation (DBS) on anticholinergic burden in Parkinson's disease (PD) and the association of anticholinergic burden with cognition. Materials and Methods A retrospective chart review in patients with PD who underwent bilateral subthalamic nucleus (STN) or globus pallidus internus (GPi) DBS from 2010 to 2020 reviewed medications with anticholinergic burden at baseline, six months, and one year (N = 216) after surgery. The cumulative anticholinergic burden at each visit was calculated using the Anticholinergic Risk Scale (ARS). Results ARS scores were significantly lower for patients six months and one year after surgery than at baseline (z = 6.58, p < 0.0001; z = 6.99, p < 0.0001). Change in ARS scores at both six months and one year were driven by down-titration of PD medications (z = 9.35, p < 0.0001; z = 8.61, p < 0.0001), rather than changes in pain, psychiatric, or urinary medications with anticholinergic effects. There was no significant difference in change in ARS scores at one year between targets (t = 0.41, p = 0.68). In addition, there was no significant association between anticholinergic burden and cognitive performance. Conclusion GPi and STN DBS are associated with decreased anticholinergic burden due to PD medications in the first year after surgery.

The plant Centella asiatica can enhance mitochondrial function, promote antioxidant activity and improve cognitive deficits in mouse models of aging and Alzheimer’s disease. Asiatic acid (AA) is one of the constituent triterpene compounds present in the plant. In this study we explore the effects of increasing concentrations of AA on mitochondrial function and antioxidant response in healthy mice and investigate whether high doses of AA can elicit beneficial effects on mitochondrial function, antioxidant response and cognitive function in the 5xFAD mouse model of beta-amyloid accumulation. Nine month old female CF1 mice were treated with 0, 5mg, 50mg or 1000 mg of AA per 1kg of AIN-93M diet for four weeks. Toxicity was also monitored. Hippocampal mitochondrial bioenergetics and the expression of mitochondrial and antioxidant response genes was determined. Results were compared to animals treated with 1000mg/kg of a water extract of Centella asiatica (CAW) incorporated into their diet. Additionally, six month old male and female 5xFAD mice were treated with 0 or 1000 mg/kg AA in their diet for four weeks. In the third week mice underwent cognitive testing. Hippocampal mitochondrial bioenergetics and expression of synaptic, mitochondrial and antioxidant response genes was assessed. In the healthy mice increasing concentrations of AA resulted in a dose dependent increase in basal and maximal mitochondrial respiration, mitochondrial gene expression and antioxidant gene expression. Results from the 1000mg/kg AA dose were similar to what was observed with CAW. No evidence of toxicity was observed at any concentration of AA. In the 5xFAD mice 1000mg/kg AA attenuated deficits in cognitive and mitochondrial function and induced the expression of antioxidant genes. Interestingly, there was not a consistent effect of AA on mitochondrial or synaptic gene expression. These data show that high concentrations of AA can improve mitochondrial function and antioxidant response in the brains of treated animals. Consistent with the fact that mitochondrial dysfunction and oxidative stress are known to contribute to cognitive impairments this improvement was accompanied by improved cognitive function in the 5xFAD mice. Taken together these results suggest that AA is a promising cognitive enhancing therapy to develop for use in AD.

Children with chronic kidney disease (CKD) are at risk for neurocognitive deficits while simultaneously being at risk for chronic school absenteeism (≥ 18 school days per school year). Chronic school absenteeism compounds the negative impacts of CKD on academic achievement. In this study, we examined patient- and caregiver-reported factors associated with school absenteeism in children with non-dialysis- or transplant-dependent CKD in order to help identify which factors could be modifiable and ultimately improve school attendance. We utilized a combination of chart review and questionnaires distributed in person to patients and caregivers at a pediatric nephrology clinic between November 2018 and August 2019 to gather data. We used descriptive statistics to illustrate clinical characteristics of the children included in the study, caregiver characteristics, and examined reported reasons for missing school. Twenty-one percent of participants (10/48) missed 18 full days of school or more, categorizing them as chronically absent. The top three reasons for missing school were doctor appointments, feeling sick, and being bullied. More specific sequelae of CKD were not highly reported as reasons for missing school. Chronic absenteeism is a highly reported phenomenon among children with pediatric CKD. Given that missing school for doctor appointments was a top reason for absenteeism, this data suggests alternative appointment hours and virtual appointments may reduce chronic school absenteeism in children, and by extension improve their health, behavioral, and academic outcomes.

PURPOSE:Measuring persistent imbalance after mTBI is challenging and may include subjective symptom-reporting as well as clinical scales. Clinical assessments for quantifying balance following mTBI have focused on sensory orientation. It is theorized that balance control goes beyond sensory orientation and also includes subdomains of anticipatory postural adjustments, reactive postural control, and dynamic gait. The Mini Balance Evaluation Systems Test (Mini-BESTest) is a validated balance test that measures balance according to these subdomains for a more comprehensive assessment. The purpose of this study was to compare Mini-BESTest total and subdomain scores after subacute mTBI with healthy controls. METHODS:Symptomatic mTBI (n = 90, 20 % male, age=36.0 ± 12.0, 46.3.4 ± 22.1 days since injury) and healthy control (n = 45, 20 % male, age=35.4 ± 12.5) participants completed the Mini-BESTest for balance. Mini-BESTest between-group differences were evaluated using Wilcoxon rank-sum tests. RESULTS:The mTBI group (Median[minimum,maximum]) had a significantly worse Mini-BESTest total score than the healthy controls (24[18,28] vs 27[23-28], p < 0.001). The mTBI group performed significantly worse in 3 of the 4 subdomains compared to the healthy controls: reactive postural control: 5[2-6] vs 6[3-6], p = 0.003; sensory orientation: 6[5,6] vs 6[6], p = 0.005; dynamic gait: 8[5-10] vs 9[8-10], p < 0.001. There was no significance difference between groups in the anticipatory postural adjustments domain (5[3-6] vs 5[3-6], p = 0.12). CONCLUSIONS:The Mini-BESTest identified deficits in people with subacute mTBI in the total score and 3 out of 4 subdomains, suggesting it may be helpful to use in the clinic to identify balance subdomain deficits in the subacute mTBI population. In combination with self-reported assessments, the mini-BESTest may identify balance domain deficits in the subacute mTBI population and help guide treatment for this population.

BACKGROUND:Instrumented measures of balance and gait measure more specific balance and gait impairments than clinical rating scales. No prior studies have used objective balance/gait measures to examine associations with ventricular and brain volumes in people with Parkinson's disease (PD). OBJECTIVE:To test the hypothesis that larger ventricular and smaller cortical and subcortical volumes are associated with impaired balance and gait in people with PD. METHODS:Regional volumes from structural brain images were included from 96 PD and 50 control subjects. Wearable inertial sensors quantified gait, anticipatory postural adjustments prior to step initiation (APAs), postural responses to a manual push, and standing postural sway on a foam surface. Multiple linear regression models assessed the relationship between brain volumes and balance/gait and their interactions in PD and controls, controlling for sex, age and corrected for multiple comparisons. RESULTS:Smaller brainstem and subcortical gray matter volumes were associated with larger sway area in people with PD, but not healthy controls. In contrast, larger ventricle volume was associated with smaller APAs in healthy controls, but not in people with PD. A sub-analysis in PD showed significant interactions between freezers and non-freezers, in several subcortical areas with stride time variability, gait speed and step initiation. CONCLUSION:Our models indicate that smaller subcortical and brainstem volumes may be indicators of standing balance dysfunction in people with PD whereas enlarged ventricles may be related to step initiation difficulties in healthy aging. Also, multiple subcortical region atrophy may be associated with freezing of gait in PD.

Background Simultaneous measurement of gastrointestinal transit time (GITT) and plasma levodopa concentration (PLC) is crucial to understanding the effect of dysfunctional motility on levodopa response in patients with Parkinson's disease (PwPD). Objective The aim is to determine if altered segmental GITT correlates with clinical response and PLC variability in PwPD. Methods Ten typical and 10 erratic responders ingested the SmartPill (SP) wireless motility capsule. Serial PLC and finger tapping, obtained every 30 minutes for 3 hours after SP/levodopa ingestion, evaluated the correlation between GITT, clinical response, and PLC. Glucose breath testing assessed small intestinal bacterial overgrowth (SIBO). Results GITT was not significantly different in "typical" and "erratic" responders. SIBO was positive in half of the erratic and negative in most typical responders. Conclusion SP is a feasible technology for assessing GITT in PwPD. A larger study may be able to significantly differentiate/correlate GITT in different segments of the GI tract with response to levodopa. (c) 2022 International Parkinson and Movement Disorder Society.

ObjectiveThe purpose of this study was to determine the sensitivity and specificity of α‐synuclein seed amplification assay (αSyn‐SAA) in antemortem and postmortem cerebrospinal fluid (CSF) of autopsy‐confirmed patients with different distributions of pathological αSyn, co‐pathologies, and clinical diagnoses.MethodsThe αSyn‐SAA was used to test antemortem CSF samples from 119 subjects with a variety of clinical syndromes and standardized neuropathological examinations from Oregon Health and Science University (OHSU) and University of California San Diego (UCSD; 56 additional postmortem CSF samples available). The αSyn‐SAA was also applied to frontal cortex and amygdala homogenates. Sensitivity and specificity were compared across distributions of αSyn pathology. Clinical data and co‐pathologies were compared across αSyn‐SAA positive and negative groups.ResultsFifty‐three individuals without and 66 with αSyn‐pathology (neocortical [n = 38], limbic [n = 7], and amygdala‐predominant [n = 21]) were included. There was a sensitivity of 97.8% and specificity of 98.1% of the αSyn‐SAA to identify patients with limbic/neocortical pathology from antemortem CSF. Sensitivity to detect amygdala‐predominant pathology was only 14.3%. Postmortem CSF and brain tissue αSyn‐SAA analyses also showed higher assay positivity in samples from limbic/neocortical cases.InterpretationCSF αSyn‐SAA reliably identifies αSyn seeds in patients with diffuse αSyn pathology in the context of co‐pathology and non‐Lewy body disease (LBD) diagnoses. The analysis of brain homogenates suggests that pathological αSyn in the amygdala might differ from pathological αSyn in the frontal cortex. The αSyn‐SAA might facilitate the differential diagnosis of dementias with mixed pathologies. ANN NEUROL 2022;92:650–662

Objective To determine the sensitivity and specificity of α-synuclein seed amplification assay (αSyn-SAA) in antemortem and postmortem CSF and brain homogenate samples of autopsy-confirmed patients with a spectrum of Lewy-related pathology (LRP).Methods Antemortem CSF samples were examined from 119 subjects with standardized neuropathological examinations from OHSU and UCSD (56 additional postmortem CSF samples available). The assay was also applied to frontal cortex and amygdala tissue to determine if the results could be explained by a regional variation in the propensity for seed aggregation. Sensitivity, specificity, and assay kinetics were compared across pathology groups and clinical data was compared across αSyn-SAA positive and negative groups.Results Fifty-three LRP-individuals and 66 LRP+ individuals (neocortical (n=38), limbic (n=7), and amygdala-predominant (n=21)) were included. There was a sensitivity of 97.8% and specificity of 98.1% of the αSyn-SAA to identify patients with limbic/neocortical pathology from antemortem CSF. Sensitivity to detect amygdala-predominant pathology was only 14.3%. Postmortem CSF and brain tissue αSyn-SAA analyses showed a similar detection pattern, with higher positivity in samples from limbic/neocortical cases. Kinetic parameters of aggregation were significantly slower in amygdala-predominant cases compared to limbic and neocortical cases.Interpretation In this multicenter study of autopsy-confirmed subjects with a spectrum of Lewy-related pathology, we confirm that the αSyn-SAA using CSF and brain tissue reliably identifies α-synuclein seeds in patients with diffuse pathology and related cognitive symptoms. Pathological α-synuclein in the amygdala appears less likely to form detectable seeds, which may result from differences in abundance, conformation, or strains of α-synuclein.Summary for Social Media If Published 1. Twitter handles of the authors: none2. Alpha-synuclein seed amplification assays have shown high sensitivity and specificity in clinically defined DLB and PD cohorts3. It is less well known how well these assays detect synuclein seeds across a pathologically defined spectrum of Lewy body disease. Here we examine the ability of the αSyn-SAA to detect alpha-synuclein seeds in a multicenter cohort of autopsy-validated cases with a spectrum of Lewy body related pathology.4. High sensitivity and specificity of the αSyn-SAA is confirmed in detecting alpha-synuclein seeds in spinal fluid and brain tissue in limbic and neocortical stage Lewy body stage pathology, but markedly decreased sensitivity is observed in detecting alpha-synuclein seeds in both spinal fluid and brain tissue in amygdala-predominant type Lewy body related pathology. A small number of these cases showed seeding capability from the amygdala that was not present in the frontal cortex, suggesting a topographic spread of alpha-synuclein seeds.5. The current generation of αSyn-SAAs have a high sensitivity and specificity for detecting the most clinically relevant forms of Lewy body related pathology. Further study is needed to understand the differences in Lewy body related pathology between limbic/neocortical cases and amygdala-predominant cases that result in this difference in seeding capability.### Competing Interest StatementDr. Concha, Ms. Farris, and Mr. Ma are inventors on several patents related to PMCA technology (SAA) and are associated to Amprion Inc, a biotech company focused on the commercial utilization of SAA for diagnosis. All other authors have no conflicts of interest to disclose.### Funding StatementThis study was funded in part by the Alzheimer Disease Center Clinical Core at Oregon Health and Science University (PI: Kaye, eIRB 725, supported by NIH P30 AG008017, P30 AG066518) as well as the National Center for Advancing Translational Sciences (National Institutes of Health, Grant Award Number UL1TR002369). Amprion's efforts were funded in part by the Alzheimer's Drug Discovery Foundation (ADDF) Diagnostics Accelerator, as well as by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (Award Number U44NS111672). Moriah R. Arnold is funded through the Medical Scientist Training Program of Oregon Health & Science University (T32 GM 109835). Dr. Coughlin is funded by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health (Award Number NS120038) and the National Institute on Aging (Award Number AG062429). Dr. Galasko is funded by the UCSD Shiley-Marcos ADRC (AG062429), and by the DLB Research Center of Excellence award from the Lewy Body Dementia Association. The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data, preparation, review of approval of the manuscript, and decision to submit the manuscript for publication.### Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:eIRB 725 of Oregon Health and Science University ADRC gave ethical approval for this work. IRB 170957 of University of California San Diego ADRC gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data produced in the present study are available upon reasonable request to the authors.

Oral lichen planus (OLP) and oral lichenoid contact lesions (OLCL) are chronic inflammatory mucocutaneous reactions with a risk of malignant transformation that alter the epithelium. OLP and OLCL have similar clinical and histopathological features and it is difficult to distinguish one from the other. Metallic restorations are suspected to generate OLCLs. Trace metal analysis of OLCL specimens may facilitate the discrimination of symptoms and identification of causative metallic restorations. The purpose of this study was to assess OLCL tissue samples for the prevalence of metallic elements derived from dental restorations and to discriminate OLCL from OLP by using synchrotron radiation-excited X-ray fluorescence analysis (SR-XRF), particle-induced X-ray emission (PIXE) and X-ray absorption fine structure (XAFS). Typical elements of dental materials were detected in the OLCL, whereas no obvious element accumulation was detected in OLP and negative control specimens. The origin of the detected metallic elements was presumed to be dental alloys through erosion. Therefore, our findings support the feasibility of providing supporting information to distinguish OLCL from OLP by using elemental analysis.