Parkinsonism & Related Disorders

Background: Problematic Internet use (PIU) has been scarcely investigated in Parkinson's disease (PD). Objectives: To estimate the prevalence of PIU symptoms in PD using a specific screening instrument and to explore the clinical characteristics of these individuals. Methods: Two-stage observational study in a Movement Disorders clinic. In Evaluation 1, participants with PD were screened by the Brazilian Portuguese Nine-Item Problematic Internet Use Questionnaire-Short Form (BR-PIUQ-SF-9). In Evaluation 2, screening-positive participants underwent an exploratory assessment of Internet use. Results: 16.7% of participants with PD were positive for the BR-PIUQ-SF-9. The median Internet use time among these positive-screened participants was 5.5 hours per day. Most of them had impulsive-compulsive behaviors, and somatic concern, anxiety, and depressive mood were common psychiatric symptoms. Conclusions: Approximately one in six participants screened positive for PIU symptoms. Impulsive-compulsive behaviors and depressive symptoms were frequent among those undergoing subsequent exploratory assessment.

ObjectiveIstradefylline, a selective adenosine A2A receptor antagonist, is indicated in the US and Japan as adjunctive treatment to levodopa/decarboxylase inhibitors in adults with Parkinsons disease (PD) experiencing OFF time. This study aimed to observe patterns of dose escalation of levodopa over time in patients initiated on istradefylline. MethodsUsing Japanese electronic health record data, interrupted time series analyses were used to compare levodopa daily dose (LDD, mg/day) gradients in patients before and after initiation of istradefylline. Data were analyzed by period relative to istradefylline initiation (Month 1): pre-istradefylline (Months -72 to 0), early istradefylline (Months 1 to 24), and late istradefylline (Months 25 to 72). Subgroup analyses included LDD before istradefylline initiation (<400, [&ge;]400 to <600, [&ge;]600 mg/day) and treatment with or without monoamine oxidase-B inhibitors (MAO-BIs), catechol-O-methyltransferase inhibitors (COMTIs), or dopamine agonists before istradefylline initiation. ResultsThe analysis included 4026 patients; mean (SD) baseline LDD was 419.27 mg (174.19). Patients receiving [&ge;]600 mg/day levodopa or not receiving MAO-BIs or COMTIs demonstrated a significant reduction in LDD increase gradient for pre-istradefylline vs late-phase istradefylline ([&ge;]600 mg/day levodopa, -6.259 mg/day each month, p<0.001; no MAO-BIs, -1.819 mg/day each month, p=0.004; no COMTIs, -1.412 mg/day each month, p=0.027). ConclusionsThis real-world analysis of Japanese prescription data indicated that slowing of LDD escalation was observed in patients initiated on istradefylline, particularly in those receiving [&ge;]600 mg/day levodopa, suggesting istradefylline may slow progressive LDD increases. These findings suggest that initiating istradefylline before other levodopa-adjunctive therapies may mitigate LDD increases, potentially reducing occurrence or severity of levodopa-induced complications in long-term istradefylline treatment.

BackgroundADCY5-related dyskinesia is a rare disorder caused by mutations in the ADCY5 gene resulting in abnormal involuntary movements. Currently, there are no standardized guidelines to treat this condition. ObjectivesThe aim of this study is to evaluate the efficacy of theophylline administration in improving symptoms and quality of life in patients with ADCY5-related dyskinesia. MethodsA retrospective study was conducted involving 12 patients (aged 2-34 years) with ADCY5-related dyskinesia. Participants completed a questionnaire about theophylline administration, including dosage, improvement of symptoms, adverse effects, and changes in quality of life. Data were analyzed for reported efficacy and side effects. ResultsTheophylline administration demonstrated substantial efficacy, with 92% (11 out of 12) of patients reporting significant improvements in their movement disorders. The average improvement score was 7.0 ({+/-} 1.9) on a 10-point scale. Notable improvements included reductions in severity and frequency of episodes, improved gait, more independent mobility, psycho-social well-being, and quality of sleep. Adverse effects were reported by 6 patients, including dystonia, speech worsening, headaches, nausea, impaired sleep, and agitation. ConclusionsTheophylline shows substantial promise as a treatment option for ADCY5-related dyskinesia, improving various aspects of patients quality of life and movement disorder symptoms. Further research is needed to optimize dosing, to understand long-term effects, and to explore combinational drug therapies. Despite the small cohort size and the retrospective nature of this study, the results support theophylline administration to decrease dyskinetic movements and enhance overall quality of life in patients.

22q11.2 microdeletion syndrome (22qDS) was recently identified as a risk factor for development of early-onset Parkinsons disease (PD). The classical motor manifestations of this disease are preceded by early signs and symptoms of neurodegeneration. The progression of 22qDS-associated PD is unknown. We aimed to evaluate the presence of prodromal PD in a group of adults with 22qDS using the Movement Disorders Society (MDS) Criteria for Prodromal PD. Thirty-eight persons with 22qDS and 13 age-matched controls participated in the study, and their results were compared using the Mann-Whitney U test. Persons with 22qDS had lower scores on olfaction testing (p=7.42Ex10-5), higher scores on the COMPASS 31 scale for dysautonomia (p=2.28x10-3) and on the motor evaluation using Movement Disorder Society (MDS)-sponsored revision of Unified Parkinsons Disease Rating Scale motor subscore (UPDRS-III) (p=1.84x10-4), compared with healthy controls. Home polysomnogram did not find participants with REM-sleep behavior disorder. Integrity of nigrostriatal dopaminergic system was evaluated by PET-CT imaging of presynaptic dopamine with 18F-PR04.MZ. Patients showed significantly higher specific binding ratios in the striatum, compared to controls (p=9.57x10-3 at the caudate nuclei). Two patients with 22qDS (5.2%) had decreased uptake in the posterior putamen (less than 60% of controls) and one fulfilled MDS criteria for prodromal PD. These results show that patients with 22qDS manifest some signs and symptoms of prodromal PD such as hyposmia, dysautonomia and mild movement alterations. In the majority, this was associated with elevated dopaminergic signaling, suggesting that loss of dopaminergic neurons may not be the cause. A smaller subgroup did show evidence of a decrease in nigrostriatal dopaminergic signaling, as seen in classical prodromal PD. Longitudinal studies are necessary to understand the progression to and risk of PD in persons with 22qDS.

BackgroundIsolated REM sleep behavior disorder (iRBD) is known to be an early feature in some PD patients. Quantitative tools are needed to detect early motor anomalies in iRBD. MethodsA motor battery was used to compare iRBD patients with controls. This included two online keyboard-based tests, the BRadykineisa Akinesia INcoordination (BRAIN) test and the Distal Finger Tapping (DFT) test, a timed handwriting task and two motor assessments (10-meter walking and finger tapping) carried out both alone and during a mental task. This battery was compared with the motor section of the MDS-MDS-UPDRS-III. ROC analyses were used to measure diagnostic accuracy. ResultsWe included 33 patients with video-PSG-confirmed iRBD and 29 age and sex matched controls. The iRBD group performed the BRAIN test and DFT test more slowly (p<0.001, p=0.020 respectively) and erratically (p<0.001, p=0.009 respectively) than controls. Handwriting speed was 10 seconds slower in iRBDs than controls (p=0.004). Unlike controls, under a mental task the iRBD group decreased their walking pace (p<0.001) and had a smaller amplitude (p=0.001) and slower (p=0.007) finger tapping than tasks in isolation. The combination of BRAIN & DFT tests with the effect of mental tasks on walking and finger tapping showed 90.3% sensitivity for 89.3% specificity (AUC 0.94, 95% CI 0.88-0.99), which was higher than the MDS-UPDRS-III (minus action tremor) (69.7% sensitivity, 72.4% specificity; AUC 0.81, 95% CI 0.71-0.91) for detecting motor abnormalities. ConclusionThis study suggests that speed, incoordination, and dual task motor deterioration might be accurate indicators of incipient PD in iRBD.

IntroductionSignificant advances have been made in elucidating the pathophysiological mechanisms of Parkinsons disease (PD). Levodopa remains the main therapeutic option -- although it presents heterogeneous clinical benefits among patients. Mutations related to levodopa metabolic pathways have been investigated, but not for mtDNA. Since levodopa metabolism is highly dependent on ionic gradients, endocytosis, and vesicular transport -- all ATP-dependent processes -- the normal function of OXPHOS is essential not only for adequate levodopa metabolism but also for its therapeutic efficacy. This study aimed to analyze levodopa responsiveness profiles considering the mitochondrial genomic component in Brazilian admixed populations. MethodsA total of 49 patients with PD underwent a levodopa challenge test (LCT), followed by whole mitochondrial genome sequencing, pathogenicity prediction of identified variants, and in silico structural analyses. ResultsVariants most frequently affected ND4, ND5, and ND6 subunits in both groups (responsive and non-responsive). Among them, the responsive group presented variants in MT-ND4 (m.12018C>G - T420S) and ND5 (m.13130C>A - P265H) as those with the most significant structural impact, suggesting a loss of the native conformation and alterations in protein efficiency. Additionally, five unique variants were detected only among non-responsive patients, two of which were absent from the dbSNP and ClinVar databases, which indicates the possibility that they are novel variants and potentially population-specific. ConclusionWe provide molecular evidence suggesting that variants in mitochondrial ND4, ND5, and ND6 subunits, in addition to mitochondrial ancestry, may contribute to distinct levodopa responsiveness in PD patients.

BackgroundWhile summarized under the umbrella term "Parkinsonism", several subtypes with different etiologies exist, including Parkinsons Disease, Vascular Parkinsonism and Drug-induced Parkinsonism. However, evidence on their incidence and prevalence remains limited. ObjectivesTo evaluate secular trends of incidence and prevalence of parkinsonism, Parkinsons Disease, Vascular Parkinsonism, and Drug-induced Parkinsonism from 2007 to 2021 in the United Kingdom. MethodsWe used primary care data, Clinical Practice Research Datalink GOLD, from the United Kingdom. Individuals were included if they were registered from January 2007 to December 2021 with at least one year of prior observation. Incidence and prevalence were calculated on a yearly basis with 95% confidence intervals and then stratified by age and sex. ResultsFrom 2007 to 2019, the incidence of parkinsonism and Parkinsons Disease decreased, with Parkinsons Disease incidence dropping from 35.86 (95% confidence interval: 34.22 - 37.56) to 31.40 (29.40 - 33.50) per 100,000 person-years. The prevalence of parkinsonism and Parkinsons Disease increased from 0.22% (0.22% - 0.23%) and 0.21% (0.21% - 0.22%) in 2007 to peak in 2016 with 0.25% (0.25% - 0.26%) and 0.23% (0.23% - 0.24%) respectively. The number of Vascular Parkinsonism diagnoses have increased from 2010, whereas incidence and prevalence of Drug-induced Parkinsonism remained stable. Incidence and prevalence increased with age and were generally higher in males, except for Drug-induced Parkinsonism, which was slightly higher in females. ConclusionsGiven its association with aging, parkinsonism and these subtypes continue to present an increasing challenge to our aging society.

BackgroundPatients with Parkinsons disease (PD) often have cold hands and experience frostbite. The diagnostic criteria for multiple system atrophy (MSA) also describe cold and discolored hands, but in our clinical experience we have noticed that the hands are relatively warm. These symptoms are thought to be caused by autonomic dysfunction; however, the detailed mechanisms and differences in cold hands between MSA and PD remain unclear. ObjectivesTo identify an appropriate cold stimulation test to differentiate patients with PD and MSA using finger surface temperature (FST). MethodsWe included 27 and seven patients diagnosed with PD and MSA, respectively, at least 5 years after disease onset. After 15 minutes in a room with constant temperature and humidity, the patients hand was placed in cold water at 4{degrees}C for 10 seconds as the cold water stress test (10sec-CWST). FST was captured using a thermal imaging camera every minute for 15 minutes, and the recovery of FST was analyzed. The association between the clinical characteristics of each patient and the degree of FST recovery was examined. ResultsAll patients completed the 10sec-CWST without adverse events. Patients with PD showed a significantly slower recovery of FST after 7 minutes than that of those with MSA, with a maximum difference at 11 minutes (PD: 8.1{+/-}0.6{degrees}C; MSA: 10.5{+/-}0.3{degrees}C; p<0.01). FST recovery at 11 minutes was negatively correlated with the degree of resting hand tremor (r=-0.585, p<0.01). ConclusionsFST after 10sec-CWST may be safe and efficient test to differentiate PD and MSA.

BackgroundThe prodromal phase of Parkinsons disease (PD), much like the disease itself, displays marked heterogeneity, with varied rates of progression and symptom severities. A detailed clinical characterization of prodromal subgroups may provide useful insights for both clinical and research settings. ObjectivesTo compare clinical assessments in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) and those with isolated hyposmia. MethodsA cross-sectional study was conducted on 191 patients with iRBD, 213 patients with isolated hyposmia and 150 healthy controls recruited in the Parkinsons Progression Markers Initiative. The earliest available assessment for each participant was selected. Our analysis investigated and compared the Montreal Cognitive Assessment, Scales for Outcomes in Parkinsons Disease Autonomic Dysfunction (SCOPA-AUT) and Movement Disorder Society Unified Parkinsons Disease Rating Scale (MDS-UPDRS) Parts I, II and III scores across the three groups. To assess differences, after adjusting for age and sex, we employed permutations testing. We further investigated the specific question items that contributed most significantly to the observed variations between the groups. ResultsWe found significant differences between the healthy control group and a combined prodromal group across all assessment categories, with prodromal participants displaying poorer scores. For between prodromal groups comparison, significant differences emerged in SCOPA-AUT and MDS-UPDRS Part I scores, with the iRBD group presenting with more severe scores. ConclusionOur study highlights that even in the premotor stage of PD, clinical distinctions exist in terms of autonomic burden between individuals with iRBD and those with isolated hyposmia.

BackgroundAccess to levodopa remains limited in many low- and middle-income countries. Brazils Popular Pharmacy Program dispenses subsidized levodopa nationwide. ObjectivesTo assess levodopa dispensing and geographic coverage of Popular Pharmacy units in Brazil. MethodsNationwide ecological study. We extracted numbers of levodopa/benserazide and carbidopa/levodopa tablets dispensed from 2020 to 2024, and derived absolute/percent change, annualized growth, and 2024 patient-equivalents of people with PD. Popular Pharmacy coverage was mapped. ResultsIn 2024, the Popular Pharmacy Program dispensed levodopa to approximately 15% of Brazilians with PD. There is a North-South gradient for levodopa dispensing through the program, with higher concentrations in the South/Southeast regions and a significant number of municipalities not dispensing levodopa in the North. ConclusionsThe Popular Pharmacy Program is consistent with increased accessibility to levodopa, yet coverage is limited and uneven. These results may guide other countries to elaborate similar health policies to increase accessibility to levodopa.

BackgroundHandwriting changes, such as micrographia, are recognised as an early manifestation of Parkinsons disease (PD). Whilst isolated rapid eye movement sleep behaviour disorder (iRBD) is strongly associated with future PD diagnosis, changes in handwriting remain under-explored. ObjectiveTo assess the handwriting of people with iRBD and develop a rating scale for detection of early disease clinical hallmarks. MethodsThis is a cross-sectional study involving 33 people with polysomnography (PSG)- confirmed iRBD and 29 healthy controls. Participants copied a standard sentence using a pen and paper. A graphologist analysed each handwriting script blindly and designed a scale based on observed abnormal patterns which included: micrographia, sentence slope, hidden tremor, retracing, resting marks, irregular shape, excessive pen pressure, and inconsistent word spacing. Each item was scored 0/1 based on their absence/presence. Separately, three blinded movement disorders experts assessed the scripts based on their global clinical impression as well as using the developed rating scale. ResultsPeople with iRBD were slower to complete the task than controls (76.70s (SD = 30.39) vs 61s (SD = 10.71); p=0.004). Hidden tremor was the most common feature amongst the iRBD group (72.0% vs 34.5%; p=0.005), followed by sentence slope (60% vs 24% p=0.005) and pen pressure (48% vs 14%; p=0.006). Micrographia was equally observed in both groups (iRBD 45.4%, controls 41.4% p=0.801). Classification accuracy of the scale for iRBD was higher than expert global assessment (AUC 0.76 vs AUC 0.62, p = 0.029). ConclusionsWriting speed, tremor, pen pressure and sentence slope are handwriting features that warrant further investigation to define early patterns in people with iRBD.

BackgroundPsychosis affects over half of people with Parkinsons disease (PD) over the disease course and severely worsens quality of life. Clinicians often face a trade-off between reducing dopaminergic therapies to control hallucinations/delusions and maintaining motor function. Multiple atypical antipsychotics are used, but their comparative efficacy and safety remain uncertain. MethodsWe conducted a prespecified systematic review and network meta-analysis (NMA) following PRISMA 2020 and registered in PROSPERO (CRD420251143957). PubMed, Embase, Scopus, and CENTRAL were searched to August 2025 without language restrictions. Randomized controlled trials evaluating atypical antipsychotics for PD psychosis were eligible. Two reviewers independently screened studies, extracted data, and assessed risk of bias (RoB 2); certainty was appraised with GRADE. Continuous outcomes (BPRS, CGI-S, UPDRS-II) were synthesized as mean differences; binary outcomes (adverse events, discontinuation, mortality, cardiovascular events) as risk ratios in a random-effects NMA, with placebo as the common comparator. ResultsA total of 22 trials with 2,047 participants (mean age 70.6 {+/-} 12 years; 1,038 males and 997 females) were included, with a mean follow-up of 2.73 {+/-} 1.0 months. Across treatment arms, 1,091 patients received active interventions and 1,036 placebo. The active groups included clozapine (n=139), olanzapine (n=111), pimavanserin (n=746), quetiapine (n=126), risperidone (n=5), and ziprasidone (n=8). None of the drugs demonstrated consistent or statistically significant superiority over placebo in reducing psychosis severity as measured by BPRS or CGI-S, although clozapine and quetiapine showed trends toward improvement and risperidone suggested possible benefit with very wide intervals due to small samples. Motor and daily living outcomes assessed with UPDRS-II revealed no significant changes across treatments, with pooled effects for clozapine, olanzapine, quetiapine, pimavanserin, risperidone, and ziprasidone all overlapping the null. Safety analyses indicated no meaningful increase in risk of PD worsening, insomnia, cardiovascular events, or mortality compared with placebo, with overall pooled risk ratios approximating unity and showing no heterogeneity. SUCRA rankings suggested risperidone and clozapine as potentially more efficacious on BPRS, olanzapine as higher on CGI-S, and ziprasidone on UPDRS-II, though none achieved robust statistical significance. ConclusionsNo antipsychotic showed clear superiority over placebo; clozapine and pimavanserin remain the most relevant options, but stronger evidence is needed.

Background and ObjectivesIsolated Rapid Eye Movement (REM) sleep behavior disorder (iRBD) is a sleep disorder associated with neurodegenerative diseases such as Parkinsons disease and dementia with Lewy bodies. Predicting which iRBD patients will phenoconvert to neurodegenerative diseases is crucial for prognosis and management. The objective of this study is to develop a machine learning model using clinical markers to predict phenoconversion in patients with RBD. MethodsAnalyzing a cohort of 178 iRBD patients over a median follow-up period of 3.6 years, during which 30 patients converted to neurodegenerative conditions, we leveraged an comprehensive dataset encompassing demographics, medication history, cognitive assessments, sleep quality, autonomic symptoms, and parkinsonian signs. We explored a variety of feature selection methods and survival models. Additionally, separate models to predict the subtype of photoconversion--whether motor-first or cognition-first--were developed. ResultsThe extreme gradient boosting survival embeddings-Kaplan neighbors (XGBSE-KN) model demonstrated the best performance, achieving a concordance index of 0.823 and integrated Brier score of 0.123 on 10-fold cross-validation. Explainable AI methods provided insights into prediction rationales and key risk factors including age, RBDQ-KR factor 2 (behavioral factors), weight, antidepressant, coffee use, and UPDRS III excluding tremor score. For subtype classification, the RandomForestClassifier utilizing three features (PSQI-TST, MoCA, and age), emerged as the most effective, achieving a Matthews Correlation Coefficient of 0.697 in 100 repeated 5-fold cross-validations. These models have been deployed on a server for physician access. DiscussionThese models can aid prognosis and enable personalized management in RBD patients, potentially improving patient care and outcomes. While these findings are promising, further external validation of the models is necessary to confirm their efficacy and reliability in clinical settings. Future research should focus on incorporating additional biomarkers and exploring the models performance in larger, diverse cohorts.

Transcranial temporal interference stimulation (tTIS) is a non-invasive method designed to target deep brain regions, such as the basal ganglia, without affecting overlying cortical areas. This study investigated intermittent theta-burst (iTBS) tTIS effects on symptom severity in Parkinsons disease (PD) and motor learning behavior, a condition associated with - among others - basal ganglia dysfunction. We hypothesized that iTBS-tTIS applied to the right putamen would alleviate PD symptoms and improve motor learning expressed by the contra-lateral hand. This randomized, double-blinded, crossover trial included 19 PD patients (mean age 64 years, 14 males) and 19 age- and sex-matched healthy controls (mean age 68.6 years). Structural MRI data were obtained for each participant, and individualized electric field simulations were performed to predict field strength in the right putamen. The motor part of the Movement Disorder Societys Unified Parkinsons Disease Rating Scale (MDS-UPDRS III) served as a primary outcome parameter, an alternating finger tapping task (aFTT) and Motor learning assessed through a sequential finger-tapping tasks (sFTT) were secondary outcome parameters. ITBS-tTIS significantly reduced MDS-UPDRS motor scores in PD patients and the stimulation induced changes in motor performance correlated with the electric field strength in the targeted putamen region. No significant effects were found for motor performance or motor learning in either group. These findings indicate that iTBS-tTIS in general holds potential as a non-invasive approach for deep brain stimulation in PD.

BackgroundDeep brain stimulation (DBS) is an effective surgical procedure for the treatment of Parkinsons disease (PD) and other movement disorders. Immediate and delayed complications after DBS surgery have been described. Peri-lead edema (PLE) is a DBS-related complication whose etiology is still unknown. Moreover, PLE frequency and long-term effects are subjects of ongoing debate. ObjectivesTo elucidate the long-term clinical and neuropsychological effects of PLE and to find possible etiological correlates. MethodsWe retrospectively collected clinical and neuropsychological data from 51 PD patients before and one year after DBS. PLE visualized on FLAIR MRI sequence was manually segmented. Using appropriate statistical tests, continuous and categorical variables were compared between patients with and without PLE. A multivariate regression model was employed to analyze the contribution of clinical variables to edema volume changes. Results68.62% of patients presented PLE at the immediate postoperative MRI. Patients with PLE were significantly older (p<0.001) and had more frequent postoperative confusion episodes (p=0.025). Furthermore, more MER (microelectrode recording) tracks (p<0.001) were used in patients with PLE. Multiple MER tracks were directly correlated with edema volume and were the only significant predictors of edema volume changes in a multivariate regression model. No differences were found in other clinical and neuropsychological variables. ConclusionsPLE is a frequent post-surgical event and may cause transient postoperative confusion. It seems linked to older age and multiple MER tracks. Although it does not influence global motor and neuropsychological outcomes, PLE contributes to postoperative confusion episodes. To avoid PLE sequelae, using multiple MER tracks in older patients should be discouraged.

BackgroundHuntingtons disease (HD) is a monogenic neurodegenerative disorder typically characterized by chorea, a hyperkinetic motor feature. Historical data suggest that hypokinetic features, like rigidity and bradykinesia, become more prominent in later stages of HD. No evidence-based analysis has confirmed this observation. Additionally, several motor features of the disease are not clearly defined as hypokinetic or hyperkinetic. ObjectivesThis study aimed to 1) elucidate the trajectory of hyperkinetic and hypokinetic features across the disease course and 2) to classify vague motor features as following a hyperkinetic or hypokinetic trajectory. MethodsData from 13,475 motor-manifest HD patients from the Enroll-HD platform were analyzed. Linear mixed-effects models were constructed for each of the 31 Unified Huntingtons Disease Rating Scale (UHDRS) motor subscales, with disease burden as the primary predictor. The models were used to generate the trajectories of features known to represent hyperkinesis and hypokinesis, with the same being done for vague subscales. Dynamic time warping (DTW) was then used to classify said subscales as having a hyperkinetic or hypokinetic trajectory. ResultsHyperkinetic features rise initially and diminish in middle disease, while hypokinetic features continually increase across the disease course. All non-choreiform features demonstrated a hypokinetic-like trajectory. ConclusionsHD is generally considered a hyperkinetic movement disorder, but the middle and late stages of the disease are predominated by hypokinesis. These findings suggest that hypokinetic features may be a larger contributor to the overall motor burden of HD. This has significant implications for clinical trial design, motor phenotype clustering, and pharmacotherapy.

PurposeDespite advances in recent years, genetic testing for Parkinsons disease (PD) is still underutilized in clinical practice. A 2019 questionnaire of movement disorder specialists found low rates of genetic testing in PD and barriers such as cost and insurance coverage. Since that time, PD GENEration as well as several international programs have broadly increased access to genetic testing and counseling for people with PD. A new survey sent out in 2024 examined how genetic testing for PD has changed over the past 5 years. MethodsBetween October 2024-January 2025, 621 movement disorders specialists from the Parkinsons Study Group (PSG) were invited by email to complete a questionnaire assessing knowledge, attitudes, and barriers to genetic testing in PD based on the 2019 survey. Results119 total PSG clinicians from the United States and Canada responded to the questionnaire. When compared to results from 2019, 2024 survey respondents reported increased comfort and willingness to order genetic testing, including reduced fears of negative repercussions. PD GENEration-affiliated sites reported significantly higher genetic testing volume and patients with known genetic variants. Conclusions2024 survey respondents report greater comfort with genetic testing in PD compared to 2019, concurrent with the launch of PD GENEration.

The aetiology of Parkinsons disease (PD) has been linked to the aggregation and spread of misfolded alpha-synuclein via the gut-brain axis. We previously reported the effects of a biological response modifier, beta-glucan, produced by the AFO-202 strain of Aureobasidium Pullulans, which improves clinical symptoms and controls gut Enterobacteriaceae associated with curli and amyloid-alpha-synuclein production. In this study, we report the effects of beta-glucan on PD. Eight patients with PD were recruited, five of whom completed the study. Each participant was administered 3 g of AFO-202 B-glucan orally daily for 90 days in addition to their regular prescription drugs. Pre- and post-study comparison revealed that the mean UPDRS decreased from 43.25 {+/-} 13.75 at baseline to 40 {+/-} 13.65 post intervention. Improvements in cognition, walking and balance, postural stability, and constipation scales were observed. The mean constipation severity score decreased from 3 {+/-} 1.73 to 1.75 {+/-} 0.43 post intervention. The serum creatinine kinase levels decreased and the blood glucose and lipid levels normalised. The MRI Parkinsons index (MRPI) improved in one patient. This safe AFO-202 B-glucan produced beneficial disease-modifying improvements in the UPDRS and MRI that were clinically significant in the short timeframe of 90 days. Further validation in larger, longer-term clinical trials will help confirm the use of beta-glucan as a potential adjuvant treatment for PD which may pave way for future evaluations of these beta-glucans in other synculeinopathies as well Lewy-body related pathogenesis.

Background The global burden of Parkinson's disease (PD) has increased substantially over recent decades, driven by population ageing and rising age-standardized prevalence. In Africa, accurate estimates remain limited due to a lack of recent, methodologically robust population-based studies. Objectives To determine the current age-standardized and sex-specific prevalence rates of PD in Nigeria. Methods We conducted a 2-stage, cross-sectional population-based door-to-door survey among adults aged [&ge;]18 years in two densely populated urban local government areas in Lagos State, Nigeria, between April 1, 2024 and January 31, 2025. The first stage involved a household census and screening for parkinsonism using a standardized screening tool. The second stage consisted of in-person clinical assessment and diagnostic confirmation by physicians using established clinical diagnostic criteria. Crude and age-standardized prevalence rates (to the World Health Organization World Standard and European Standard Populations) were calculated. Results 31,009 individuals (52.7% female) from 13,222 households were surveyed, and 70 persons were diagnosed with PD. The crude prevalence ratio was 225.7 per 100,000, with higher prevalence in males (53/14658, 361.6) than females (17/16,351, 104.0). The age-standardized prevalence rate (95% confidence interval) was 193 per 100,000 (150 -- 245) (females: 86 (50 -- 137); males: 277 (207 -- 362)), and increased with advancing age. The diagnostic gap (previously undiagnosed) was 60.0% (42/70). Treatment gap (never treated) was 44/70 (62.9%). Conclusions The age-standardized prevalence of PD is higher than previously reported in sub-Saharan Africa. These findings provide contemporary data to inform updated estimates of disease burden and support health systems planning.

BackgroundAlthough levodopa remains the gold standard treatment for Parkinsons disease (PD), its chronic use is associated with levodopa-induced dyskinesia (LID), a motor complication that impacts prognosis, quality of life, and treatment costs. Most known LID-associated factors have been identified in European-descendant populations. ObjectivesTo describe the epidemiology of LID in Latin American and Caribbean (LATAM) countries and assess the relevance of known and novel LID-associated factors in this population. MethodsWe conducted a cross-sectional study using data from the Latin American Research consortium on the Genetics of Parkinsons Disease (LARGE-PD). We included PD patients with information on LID status and levodopa use from eight LATAM countries. LID prevalence was calculated overall and by country. Countries were compared on demographic and clinical variables. Logistic regression was used to identify associations with LID. ResultsA total of 3,695 PD patients (58.8% male) were included. Overall LID prevalence was 25.4% [95% CI: 24.06-26.87], ranging from 9.3% in Colombia to 45.1% in Puerto Rico. Prevalence increased progressively with longer disease duration. Country comparisons showed that not all known LID-associated factors explained prevalence differences. In logistic regression, fast disease progression was significantly associated with LID (OR: 1.55, 95%CI: 1.16-2.07), while sex was not (OR: 1.02, 95%CI: 0.87-1.18). ConclusionsThis is the largest study on LID epidemiology in LATAM. While some known risk factors remain relevant, others, like sex, do not, underscoring the need for population-specific studies. Future work should integrate environmental, clinical, and genetic data to better understand LID mechanisms.