Premotor cortical beta synchronization and the network neuromodulation of externally paced finger tapping in Parkinson's disease.

Parkinson's disease (PD) is characterized by the disruption of repetitive, concurrent and sequential motor actions due to compromised timing-functions principally located in cortex-basal ganglia (BG) circuits. Increasing evidence suggests that motor impairments in untreated PD patients are linked to an excessive synchronization of cortex-BG activity at beta frequencies (13-30 Hz). Levodopa and subthalamic nucleus deep brain stimulation (STN-DBS) suppress pathological beta-band reverberation and improve the motor symptoms in PD. Yet a dynamic tuning of beta oscillations in BG-cortical loops is fundamental for movement-timing and synchronization, and the impact of PD therapies on sensorimotor functions relying on neural transmission in the beta frequency-range remains controversial. Here, we set out to determine the differential effects of network neuromodulation through dopaminergic medication (ON and OFF levodopa) and STN-DBS (ON-DBS, OFF-DBS) on tapping synchronization and accompanying cortical activities. To this end, we conducted a rhythmic finger-tapping study with high-density EEG-recordings in 12 PD patients before and after surgery for STN-DBS and in 12 healthy controls. STN-DBS significantly ameliorated tapping parameters as frequency, amplitude and synchrony to the given auditory rhythms. Aberrant neurophysiologic signatures of sensorimotor feedback in the beta-range were found in PD patients: their neural modulation was weaker, temporally sluggish and less distributed over the right cortex in comparison to controls. Levodopa and STN-DBS boosted the dynamics of beta-band modulation over the right hemisphere, hinting to an improved timing of movements relying on tactile feedback. The strength of the post-event beta rebound over the supplementary motor area correlated significantly with the tapping asynchrony in patients, thus indexing the sensorimotor match between the external auditory pacing signals and the performed taps. PD patients showed an excessive interhemispheric coherence in the beta-frequency range during the finger-tapping task, while under DBS-ON the cortico-cortical connectivity in the beta-band was normalized. Ultimately, therapeutic DBS significantly ameliorated the auditory-motor coupling of PD patients, enhancing the electrophysiological processing of sensorimotor feedback-information related to beta-band activity, and thus allowing a more precise cued-tapping performance.

Factors affecting driving performance in patients with Multiple Sclerosis - still an open question.

Background and objectives: Research on driving ability in people with multiple sclerosis (MS) suggests that they might be at risk for unsafe driving due to MS-related motor, visual, and cognitive impairment. Our first aim was to investigate differences in driving ability and performance between people with MS (PwMS) and those without any neurologic or psychiatric disease ("controls"). Secondly, we determined disease-related factors influencing driving ability in PwMS. Methods: We prospectively compared standardized performance in a driving simulator between 97 persons with early MS [mean (SD) = 6.4 (7.3) years since diagnosis, mean (SD) Expanded Disability Status Scale (EDSS) = 2.5 (1.4)] and 94 group-matched controls. Participants completed an extensive examination comprising questionnaires and assessments regarding driving, cognitive and psychological factors, as well as demographic and disease-related measures. Between-group comparisons of driving-relevant neuropsychological tests and driving performance were done. Correlations were performed to define demographic and disease-related factors on driving performance in MS. Results: In a driving simulator setting, PwMS had more driving accidents [T(188) = 2.762, p = 0.006], reacted slower to hazardous events [T(188) = 2.561, p = 0.011], made more driving errors [T(188) = 2.883, p = 0.004] and had a worse Driving Safety Score (DSS) [T(188) = 3.058, p = 0.003] than controls. The only disease-related measure to be associated with most driving outcomes was the Wechsler Block-Tapping test (WMS-R) backward: number of accidents (r = 0.28, p = 0.01), number of driving errors (r = 0.23, p = 0.05) and DSS (r = -0.23, p = 0.05). Conclusion: Driving performance in a simulator seems to be reduced in PwMS at an early stage of disease compared to controls, as a result of increased erroneous driving, reduced reaction time and higher accident rate. MS-related impairment in mobility, vision, cognition, and in psychological and demographic aspects showed no or only minimal association to driving ability, but impairment in different areas of cognition such as spatial short-term memory, working memory and selective attention correlated with the number of accidents, and might indicate a higher risk for driving errors and worse performance. These results show that driving ability is a complex skill with involvement of many different domains, which need further research.

Therapeutic use of medical Cannabis in neurological diseases: a clinical update.

The use of medical Cannabis has increased in recent years due to changing legal circumstances in many countries. Approval exists only for a few neurological conditions such as rare forms of epilepsy or spasticity in multiple sclerosis. Beyond that, however, medical Cannabis is used for a wide range of neurological conditions and symptoms. In Germany, in parallel with new legislation that has simplified the prescription of medical Cannabis, an accompanying survey has been implemented for which initial data are now available. In this context, our review provides an overview of the evidence for the therapeutic use of medical Cannabis in neurology, the potential benefits, and side effects.

Automatic covariance pattern analysis outperforms visual reading of 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) in variant progressive supranuclear palsy.

BACKGROUND: To date, studies on positron emission tomography (PET) with 18 F-fluorodeoxyglucose (FDG) in progressive supranuclear palsy (PSP) usually included PSP cohorts overrepresenting patients with Richardson's syndrome (PSP-RS). OBJECTIVES: To evaluate FDG-PET in a patient sample representing the broad phenotypic PSP spectrum typically encountered in routine clinical practice. METHODS: This retrospective, multicenter study included 41 PSP patients, 21 (51%) with RS and 20 (49%) with non-RS variants of PSP (vPSP), and 46 age-matched healthy controls. Two state-of-the art methods for the interpretation of FDG-PET were compared: visual analysis supported by voxel-based statistical testing (five readers) and automatic covariance pattern analysis using a predefined PSP-related pattern. RESULTS: Sensitivity and specificity of the majority visual read for the detection of PSP in the whole cohort were 74% and 72%, respectively. The percentage of false-negative cases was 10% in the PSP-RS subsample and 43% in the vPSP subsample. Automatic covariance pattern analysis provided sensitivity and specificity of 93% and 83% in the whole cohort. The percentage of false-negative cases was 0% in the PSP-RS subsample and 15% in the vPSP subsample. CONCLUSIONS: Visual interpretation of FDG-PET supported by voxel-based testing provides good accuracy for the detection of PSP-RS, but only fair sensitivity for vPSP. Automatic covariance pattern analysis outperforms visual interpretation in the detection of PSP-RS, provides clinically useful sensitivity for vPSP, and reduces the rate of false-positive findings. Thus, pattern expression analysis is clinically useful to complement visual reading and voxel-based testing of FDG-PET in suspected PSP. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Brain MRI in Progressive Supranuclear Palsy with Richardson's Syndrome and Variant Phenotypes.

BACKGROUND: Brain magnetic resonance imaging (MRI) is used to support the diagnosis of progressive supranuclear palsy (PSP). However, the value of visual descriptive, manual planimetric, automatic volumetric MRI markers and fully automatic categorization is unclear, particularly regarding PSP predominance types other than Richardson's syndrome (RS). OBJECTIVES: To compare different visual reading strategies and automatic classification of T1-weighted MRI for detection of PSP in a typical clinical cohort including PSP-RS and (non-RS) variant PSP (vPSP) patients. METHODS: Forty-one patients (21 RS, 20 vPSP) and 46 healthy controls were included. Three readers using three strategies performed MRI analysis: exclusively visual reading using descriptive signs (hummingbird, morning-glory, Mickey-Mouse), visual reading supported by manual planimetry measures, and visual reading supported by automatic volumetry. Fully automatic classification was performed using a pre-trained support vector machine (SVM) on the results of atlas-based volumetry. RESULTS: All tested methods achieved higher specificity than sensitivity. Limited sensitivity was driven to large extent by false negative vPSP cases. Support by automatic volumetry resulted in the highest accuracy (75.1% ± 3.5%) among the visual strategies, but performed not better than the midbrain area (75.9%), the best single planimetric measure. Automatic classification by SVM clearly outperformed all other methods (accuracy, 87.4%), representing the only method to provide clinically useful sensitivity also in vPSP (70.0%). CONCLUSIONS: Fully automatic classification of volumetric MRI measures using machine learning methods outperforms visual MRI analysis without and with planimetry or volumetry support, particularly regarding diagnosis of vPSP, suggesting the use in settings with a broad phenotypic PSP spectrum. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Prospective controlled study on the effects of deep brain stimulation on driving in Parkinson's disease.

To explore the influence of bilateral subthalamic deep brain stimulation (STN-DBS) on car driving ability in patients with Parkinson's disease (PD), we prospectively examined two age-matched, actively driving PD patient groups: one group undergone DBS-surgery (PD-DBS, n = 23) and one group that was eligible for DBS but did not undergo surgery (PD-nDBS, n = 29). In PD-DBS patients, investigation at Baseline was done just prior and at Follow-up 6-12 month after DBS-surgery. In PD-nDBS patients, time interval between Baseline and Follow-up was aimed to be comparable. To assess the general PD driving level, driving was assessed once in 33 age-matched healthy controls at Baseline. As results, clinical and driving characteristics of PD-DBS, PD-nDBS and controls did not differ at Baseline. At Follow-up, PD-DBS patients drove unsafer than PD-nDBS patients. This effect was strongly driven by two single PD-DBS participants (9%) with poor Baseline and disastrous Follow-up driving performance. Retrospectively, we could not identify any of the assessed motor and non-motor clinical Baseline characteristics as predictive for this driving-deterioration at Follow-up. Excluding these two outliers, comparable driving performance between PD-DBS and PD-nDBS patients not only at Baseline but also at Follow-up was demonstrated. Age, disease duration and severity as well as Baseline driving insecurity were associated with poorer driving performance at Follow-up. This first prospective study on driving safety in PD after DBS surgery indicates that DBS usually does not alter driving safety but might increase the risk for driving deterioration, especially in single subjects with already unsafe driving prior to DBS surgery.

Device-Aided Therapies in Parkinson's Disease-Results from the German Care4PD Study.

Data on the use of device-aided therapies (DATs) in people with Parkinson's disease (PwP) are scarce. Analyzing data from the Care4PD patient survey, we (1) evaluated application frequency and type of DAT in a larger, nationwide, cross-sectoral PwP sample in Germany; (2) analyzed the frequency of symptoms indicative for advanced PD (aPD) and need for DAT amongst the remaining patients and (3) compared the most bothersome symptoms and need for professional long-term care (LTC) of patients with and without suspected aPD. Data from 1269 PwP were analyzed. In total, 153 PwP (12%) received DAT, mainly deep brain stimulation (DBS). Of the remaining 1116 PwP without DAT, >50% fulfilled at least one aPD criterion. Akinesia/rigidity and autonomic problems were most bothersome for PwP with and without suspected aPD, with more tremor in the non-aPD and more motor fluctuations and falls in the aPD group. To recapitulate, the German DAT application rate is rather low, although a large proportion of PwP fulfills aPD criteria indicating a need for intensified treatment strategies. Many reported bothersome symptoms could be overcome with DAT with benefits even for LTC patients. Thus, precise and early identification of aPD symptoms (and therapy-resistant tremor) should be implemented in future DAT preselection tools and educational trainings.

Blood neurofilament light chain in Parkinson's disease.

Blood neurofilament light chain (NfL) is an easily accessible, highly sensitive and reliable biomarker for neuroaxonal damage. Currently, its role in Parkinson's disease (PD) remains unclear. Here, we demonstrate that blood NfL can distinguish idiopathic PD from atypical parkinsonian syndromes (APS) with high sensitivity and specificity. In cross-sectional studies, some found significant correlations between blood NfL with motor and cognitive function, whereas others did not. In contrast, prospective studies reported very consistent associations between baseline blood NfL with motor progression and cognitive worsening. Amongst PD subtypes, especially postural instability and gait disorder (PIGD) subtype, symptoms and scores are reliably linked with blood NfL. Different non-motor PD comorbidities have also been associated with high blood NfL levels suggesting that the neuroaxonal damage of the autonomic nervous system as well as serotonergic, cholinergic and noradrenergic neurons is quantifiable. Numerous absolute NfL cutoff levels have been suggested in different cohort studies; however, validation across cohorts remains weak. However, age-adjusted percentiles and intra-individual blood NfL changes might represent more valid and consistent parameters compared with absolute NfL concentrations. In summary, blood NfL has the potential as biomarker in PD patients to be used in clinical practice for prediction of disease severity and especially progression.

Combined Short-Pulse and Directional Deep Brain Stimulation of the Thalamic Ventral Intermediate Area for Essential Tremor.

OBJECTIVE: Novel deep brain stimulation (DBS) systems allow directional and short-pulse stimulation to potentially improve symptoms and reduce side effects. The aim of this study was to investigate the effect of short-pulse and directional stimulation, in addition to a combination of both, in the ventral intermediate thalamus (VIM)/posterior subthalamic area (PSA) on tremor and stimulation-induced side effects in patients with essential tremor. MATERIALS AND METHODS: We recruited 11 patients with essential tremor and VIM/PSA-DBS. Tremor severity (Fahn-Tolosa-Marin), ataxia (International Cooperative Ataxia Rating Scale), and paresthesia (visual analog scale) were assessed with conventional omnidirectional and directional stimulation with pulse width of 60 µs and 30 µs. RESULTS: All stimulation conditions reduced tremor. The best directional stimulation with 60 µs reduced more tremor than did most other stimulation settings. The best directional stimulation, regardless of pulse width, effectively reduced stimulation-induced ataxia compared with the conventional stimulation (ring 60 µs) or worst directional stimulation with 60 µs. All new stimulation modes reduced occurrence of paresthesia, but only the best directional stimulation with 30 µs attenuated paresthesia compared with the conventional stimulation (ring 60 µs) or worst directional stimulation with 60 µs. The best directional stimulation with 30 µs reduced tremor, ataxia, and paresthesia compared with conventional stimulation in most patients. Correlation analyses indicated that more anterior stimulation sites are associated with stronger ataxia reduction with directional 30 µs than with conventional 60 µs stimulation. CONCLUSION: Directional and short-pulse stimulation, and a combination of both, revealed beneficial effects on stimulation-induced adverse effects.

Botulinum neurotoxin type A in the interdisciplinary treatment of sialorrhea in adults and children-update and practice recommendations.

Sialorrhea is defined as a chronic excessive flow of saliva from the mouth, often with adverse consequences for health and quality of life of patients. In addition to currently used non-drug treatment and systemic drugs, intraglandular Botulinum Neurotoxin A (BoNT/A) injections have been examined in case studies, controlled trials and clinical practice. Two pivotal Phase III trials recently led to market approval in the USA and EU for IncobotulinumtoxinA [Xeomin®, IncoBoNT/A, Clostridium botulinum neurotoxin type A (150 kD), free from complexing proteins, Merz Pharmaceuticals GmbH] for treatment of chronic sialorrhea in adults and pediatric patients. This review provides a multidisciplinary approach to discuss the current state of sialorrhea therapy as well as benefits and current limitations of BoNT/A injections. A consensus regarding treatment recommendations made available to physicians in Germany in 2022 has now been updated here for presentation to an international audience. This review provides a framework including a flow chart for patient selection, recommendations for dosing and the injection process, as well as a discussion of therapeutic goals, long-term benefits and safety aspects. This review is aimed at supporting physicians in developing multidisciplinary and individualized treatment approaches to achieve optimal benefits for patients.

Driving ability and predictors for driving performance in Multiple Sclerosis: A systematic review.

Objective: To provide an overview of the evidence on driving ability in persons with multiple sclerosis (PwMS), specifically to (i) study the impact of MS impairment on driving ability and (ii) evaluate predictors for driving performance in MS. Methods: To identify relevant studies, different electronic databases were screened in accordance with PRISMA guidelines; this includes reference lists of review articles, primary studies, and trial registers for protocols. Furthermore, experts in the field were contacted. Two reviewers independently screened titles, abstracts, and full-texts to identify relevant articles targeting driving in people with MS that investigated driving-related issues with a formal driving assessment (defined as either an on-road driving assessment; or naturalistic driving in a car equipped with video cameras to record the driving; or a driving simulator with a steering wheel, a brake pedal, and an accelerator). Results: Twenty-four publications, with 15 unique samples (n = 806 PwMS), were identified. To assess driving ability, on-road tests (14 papers) and driving simulators (10 papers) were used. All studies showed moderate to high study quality in the CASP assessment. About 6 to 38% of PwMS failed the on-road tests, showing difficulties in different areas of driving. Similarly, PwMS showed several problems in driving simulations. Cognitive and visual impairment appeared to most impact driving ability, but the evidence was insufficient and inconsistent. Conclusion: There is an urgent need for more research and standardized guidelines for clinicians as one in five PwMS might not be able to drive safely. On-road tests may be the gold standard in assessing driving ability, but on-road protocols are heterogeneous and not infallible. Driving simulators assess driving ability in a standardized way, but without standardized routes and driving outcomes, comparability between studies is difficult. Different aspects, such as cognitive impairment or vision problems, impact driving ability negatively and should be taken into consideration when making decisions about recommending driving cessation. Systematic review registration: Identifier [10.17605/OSF.IO/WTG9J].

Do Impulse Control Disorders Impair Car Driving Performance in Patients with Parkinson's Disease?

BACKGROUND: Based on data regarding the prevalence of Parkinson's disease (PD), the prevalence of impulsive control disorders (ICD) in PD, and the percentage of PD patients driving a car, it has to be assumed that at least 50,000 PD patients with ICD in Germany actively drive a car. However, these patients might be at risk for unsafe driving due to ICD-related dysfunctions such as failure to resist an impulse or temptation, to control an act or other altered neurobehavioral processes. OBJECTIVE: This study determines the influence of ICD on driving ability in PD. METHODS: We prospectively compared driving simulator performance of 23 PD patients with and 23 matched patients without ICD. ICD had to be socially compensated and presence was defined clinically for primary and questionnaire-based (QUIP-RS) for post-hoc analyses. Furthermore, between-group comparisons of driving-relevant neuropsychological tests were executed. RESULTS: Except from a lower blinking frequency when changing lanes, overall driving safety of patients with ICD did not differ significantly from those without-regardless of the clinical or QUIP-RS-based ICD definition. ICD severity did not correlate with driving performance, but the latter correlated significantly with mean reaction times and certain neuropsychiatric tests (MoCA, TMT-A, TAP-M "flexibility" and DBQ "error"). CONCLUSION: Clinically compensated ICD does not seem to impair driving safety in PD patients. Rather, cognitive and attentional deficits appear to be clinical markers for driving uncertainty.

Short pulse and directional thalamic deep brain stimulation have differential effects in parkinsonian and essential tremor.

The aim of this study was to assess the effects of novel stimulation algorithms of deep brain stimulation (short pulse and directional stimulation) in the ventrointermediate thalamus and posterior subthalamic area (VIM/PSA-DBS) on tremor in Parkinson's disease (PD) and to compare the effects with those in essential tremor (ET). We recruited six PD patients (70.8 ± 10.4 years) and seven ET patients (64.4 ± 9.9 years) with implanted VIM/PSA-DBS in a stable treatment condition (> 3 months postoperatively). Tremor severity and ataxia were assessed in four different stimulation conditions in a randomized order: DBS switched off (STIM OFF), omnidirectional stimulation with 60 µs (oDBS60), omnidirectional stimulation with 30 µs (oDBS30), directional stimulation at the best segment with 60 µs (dDBS60). In both patient groups, all three DBS stimulation modes reduced the total tremor score compared to STIM OFF, whereas stimulation-induced ataxia was reduced by oDBS30 and partially by dDBS60 compared to oDBS60. Tremor reduction was more pronounced in PD than in ET due to a limited DBS effect on intention and action-specific drawing tremor in ET. In PD and ET tremor, short pulse or directional VIM/PSA-DBS is an effective and well tolerated therapeutic option.Trial registration: The study was registered in the DRKS (ID DRKS00025329, 18.05.2021, German Clinical Trials Register, DRKS-Deutsches Register Klinischer Studien).

[Treatment of Sialorrhea with Botulinum Neurotoxin Type A - Consensus Practice Recommendations for Children and Adults]. / Behandlung der Sialorrhoe mit Botulinum Neurotoxin Typ A ­ Konsentierte Praxisempfehlungen für Kinder und Erwachsene.

Sialorrhea, uncontrolled, excessive drooling, accompanies different, mostly neurological disorders from childhood to adulthood. With incobotulinumtoxinA (Xeomin, IncoBoNT/A, Merz Pharmaceuticals GmbH), an approved medication for the treatment of sialorrhea has been available since 2019. Patient selection, possible therapy goals, treatment and the management of specific treatment situations build the focus of this interdisciplinary expert consensus recommendations with the intent to facilitate access to treatment and to contribute to qualified botulinum toxin therapy.

Diabetes, Glycated Hemoglobin (HbA1c), and Neuroaxonal Damage in Parkinson's Disease (MARK-PD Study).

BACKGROUND: Diabetes is associated with incidence and prevalence of Parkinson's disease (PD). Furthermore, glycated hemoglobin (HbA1c) levels have been linked with motor function and progression. OBJECTIVES: We evaluated the relationship between prevalent diabetes and HbA1c levels with serum neurofilament light chain (NfL) levels as marker of neuroaxonal damage. METHODS: NfL concentrations were analyzed with Simoa in serum of 195 PD patients with available HbA1c values. Motor (MDS-UPDRS III, Hoehn & Yahr [H&Y]) and cognitive (Montreal Cognitive Assessment [MoCA]) function was assessed and vascular comorbidities were documented from medical records. RESULTS: PD patients with prevalent diabetes had higher serum NfL levels and lower MoCA scores independent of age, body mass index (BMI), and vascular risk factors. Furthermore, diabetes was associated with higher H&Y stages in unadjusted and age/BMI-adjusted models. Higher HbA1c levels were associated with increased NfL in unadjusted and age/BMI-adjusted models. CONCLUSIONS: In PD patients, diabetes and high HbA1c are associated with increased neuroaxonal damage and cognitive impairment. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Prevalence, clinical presentations and impact on relationship of sexual dysfunction in Parkinson's Disease

Sexual dysfunction is one of the commonest non-motor symptoms in Parkinson's disease (PD) and has been found about twice as high in PD patients compared to age-matched controls. The quality of sexual life is reduced in PD patients compared to healthy peers and impairment affects wide aspects of physical sexual function as well as sexual desire, sexual satisfaction and sexual partnership. Overall, male PD patients are more frequently affected by sexual disorders than females and seem to suffer more from sexual impairment. The reported frequencies and presentations of various sexual dysfunctions vary widely in the literature, which is likely related to the patient cohorts examined, in particular with regard to age and gender, duration and severity of disease and applied measurement instruments. This chapter gives an overview of the prevalence, phenotype and clinical presentation of sexual dysfunction in PD and its influence on the partnership.

Comparison of Montreal cognitive assessment and Mattis dementia rating scale in the preoperative evaluation of subthalamic stimulation in Parkinson's disease.

INTRODUCTION: The preoperative evaluation of Parkinson's Disease (PD) patients for subthalamic nucleus deep brain stimulation (STN-DBS) includes the assessment of the neuropsychological status of the patient. A widely used preoperative test is the Mattis Dementia rating scale (MDRS). However, the Montreal cognitive assessment (MoCA) has also been proven to be a sensitive, time-sparing tool with high diagnostic validity in PD. We evaluate the utility of the MoCA as a preoperative screening test for PD patients undergoing bilateral STN-DBS. METHODS: In this single-centre, retrospective study, we analysed pre- and postoperative assessments of MoCA, MDRS, Movement disorder society-Unified PD Rating Scale-motor examination, PD Questionnaire-39 and levodopa equivalent daily dose. Longitudinal outcome changes were analysed using paired t-test, Pearson's correlation coefficient, linear regression and CHAID (chi-square automatic interaction detector) regression tree model. RESULTS: Clinical motor and cognitive scores of 59 patients (61.05±7.73 years, 24 females) were analysed. The MoCA, but not the MDRS, identified significant postoperative cognitive decline in PD patients undergoing STN-DBS. The preoperative MoCA score correlated with postoperative quality of life improvement, whereas the MDRS did not. PD patients with a MoCA score ≤ 23 points had a significant decline of quality of life after DBS surgery compared to patients > 23 points. CONCLUSION: This study identifies the MoCA as an alternative test within the preoperative evaluation of PD patients for the detection of neuropsychological deficits and prediction of the postoperative improvement of quality of life.

Blood-based biomarker in Parkinson's disease: potential for future applications in clinical research and practice.

The clinical presentation of Parkinson's disease (PD) is both complex and heterogeneous, and its precise classification often requires an intensive work-up. The differential diagnosis, assessment of disease progression, evaluation of therapeutic responses, or identification of PD subtypes frequently remains uncertain from a clinical point of view. Various tissue- and fluid-based biomarkers are currently being investigated to improve the description of PD. From a clinician's perspective, signatures from blood that are relatively easy to obtain would have great potential for use in clinical practice if they fulfill the necessary requirements as PD biomarker. In this review article, we summarize the knowledge on blood-based PD biomarkers and present both a researcher's and a clinician's perspective on recent developments and potential future applications.