Multidisciplinary care in Parkinson's disease.

Parkinson's Disease (PD) is a multifaceted and progressive disorder characterized by a diverse range of motor and non-motor symptoms. The complexity of PD necessitates a multidisciplinary approach to manage both motor symptoms, such as bradykinesia, gait disturbances and falls, and non-motor symptoms, including cognitive dysfunction, sleep disturbances, and mood disorders, which significantly affect patients' quality of life. Pharmacotherapy, particularly dopaminergic replacement therapy, has advanced to alleviate many symptoms. However, these medications can also induce side effects or aggravate symptoms like hallucinations or orthostatic dysfunction, highlighting the need for comprehensive patient management. The optimal care for PD patients involves a team of specialists, including neurologists, physical and occupational therapists, speech-language pathologists, psychologists, and other medical professionals, to address the complex and individualized needs of each patient. Here, we illustrate the necessity of such a multidisciplinary approach in four illustrative PD cases with different disease stages and motor and non-motor complications. The patients were treated in different treatment settings (specialized outpatient clinic, day clinic, inpatient care including neurorehabilitation). The biggest challenge lies in organizing and implementing such comprehensive care effectively across different clinical settings.

Dystonia Linked to EIF4A2 Haploinsufficiency: A Disorder of Protein Translation Dysfunction.

BACKGROUND: Protein synthesis is a tightly controlled process, involving a host of translation-initiation factors and microRNA-associated repressors. Variants in the translational regulator EIF2AK2 were first linked to neurodevelopmental-delay phenotypes, followed by their implication in dystonia. Recently, de novo variants in EIF4A2, encoding eukaryotic translation initiation factor 4A isoform 2 (eIF4A2), have been described in pediatric cases with developmental delay and intellectual disability. OBJECTIVE: We sought to characterize the role of EIF4A2 variants in dystonic conditions. METHODS: We undertook an unbiased search for likely deleterious variants in mutation-constrained genes among 1100 families studied with dystonia. Independent cohorts were screened for EIF4A2 variants. Western blotting and immunocytochemical studies were performed in patient-derived fibroblasts. RESULTS: We report the discovery of a novel heterozygous EIF4A2 frameshift deletion (c.896_897del) in seven patients from two unrelated families. The disease was characterized by adolescence- to adulthood-onset dystonia with tremor. In patient-derived fibroblasts, eIF4A2 production amounted to only 50% of the normal quantity. Reduction of eIF4A2 was associated with abnormally increased levels of IMP1, a target of Ccr4-Not, the complex that interacts with eIF4A2 to mediate microRNA-dependent translational repression. By complementing the analyses with fibroblasts bearing EIF4A2 biallelic mutations, we established a correlation between IMP1 expression alterations and eIF4A2 functional dosage. Moreover, eIF4A2 and Ccr4-Not displayed significantly diminished colocalization in dystonia patient cells. Review of international databases identified EIF4A2 deletion variants (c.470_472del, c.1144_1145del) in another two dystonia-affected pedigrees. CONCLUSIONS: Our findings demonstrate that EIF4A2 haploinsufficiency underlies a previously unrecognized dominant dystonia-tremor syndrome. The data imply that translational deregulation is more broadly linked to both early neurodevelopmental phenotypes and later-onset dystonic conditions. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Integrating plant physiology into simulation of fire behavior and effects.

Wildfires are a global crisis, but current fire models fail to capture vegetation response to changing climate. With drought and elevated temperature increasing the importance of vegetation dynamics to fire behavior, and the advent of next generation models capable of capturing increasingly complex physical processes, we provide a renewed focus on representation of woody vegetation in fire models. Currently, the most advanced representations of fire behavior and biophysical fire effects are found in distinct classes of fine-scale models and do not capture variation in live fuel (i.e. living plant) properties. We demonstrate that plant water and carbon dynamics, which influence combustion and heat transfer into the plant and often dictate plant survival, provide the mechanistic linkage between fire behavior and effects. Our conceptual framework linking remotely sensed estimates of plant water and carbon to fine-scale models of fire behavior and effects could be a critical first step toward improving the fidelity of the coarse scale models that are now relied upon for global fire forecasting. This process-based approach will be essential to capturing the influence of physiological responses to drought and warming on live fuel conditions, strengthening the science needed to guide fire managers in an uncertain future.

Genetic overlap between dystonia and other neurologic disorders: A study of 1,100 exomes.

INTRODUCTION: Although shared genetic factors have been previously reported between dystonia and other neurologic conditions, no sequencing study exploring such links is available. In a large dystonic cohort, we aimed at analyzing the proportions of causative variants in genes associated with disease categories other than dystonia. METHODS: Gene findings related to whole-exome sequencing-derived diagnoses in 1100 dystonia index cases were compared with expert-curated molecular testing panels for ataxia, parkinsonism, spastic paraplegia, neuropathy, epilepsy, and intellectual disability. RESULTS: Among 220 diagnosed patients, 21% had variants in ataxia-linked genes; 15% in parkinsonism-linked genes; 15% in spastic-paraplegia-linked genes; 12% in neuropathy-linked genes; 32% in epilepsy-linked genes; and 65% in intellectual-disability-linked genes. Most diagnosed presentations (80%) were related to genes listed in ≥1 studied panel; 71% of the involved loci were found in the non-dystonia panels but not in an expert-curated gene list for dystonia. CONCLUSIONS: Our study indicates a convergence in the genetics of dystonia and other neurologic phenotypes, informing diagnostic evaluation strategies and pathophysiological considerations.

Individual Response to Botulinum Toxin Therapy in Movement Disorders: A Time Series Analysis Approach.

On a group level, satisfaction with botulinum neurotoxin (BoNT) treatment in neurological indications is high. However, it is well known that a relevant amount of patients may not respond as expected. The aim of this study is to evaluate the BoNT treatment outcome on an individual level using a statistical single-case analysis as an adjunct to traditional group statistics. The course of the daily perceived severity of symptoms across a BoNT cycle was analyzed in 20 cervical dystonia (CD) and 15 hemifacial spasm (HFS) patients. A parametric single-case autoregressive integrated moving average (ARIMA) time series analysis was used to detect individual responsiveness to BoNT treatment. Overall, both CD and HFS patients significantly responded to BoNT treatment with a gradual worsening of symptom intensities towards BoNT reinjection. However, only 8/20 CD patients (40%) and 5/15 HFS patients (33.3%) displayed the expected U-shaped curve of BoNT efficacy across a single treatment cycle. CD (but not HFS) patients who followed the expected outcome course had longer BoNT injection intervals, showed a better match to objective symptom assessments, and were characterized by a stronger certainty to control their somatic symptoms (i.e., internal medical locus of control). In addition to standard evaluation procedures, patients should be identified who do not follow the mean course-of-treatment effect. Thus, the ARIMA single-case time series analysis seems to be an appropriate addition to clinical treatment studies in order to detect individual courses of subjective symptom intensities.

[Hallucinations in Patients with Idiopathic Parkinson's Disease]. / Halluzinationen bei Patienten mit idiopathischem Parkinson-Syndrom.

Patients with idiopathic Parkinson's disease develop symptoms of the hallucination-psychosis spectrum in more than 20%. Most common are visual hallucinations. The pathogenesis of hallucinations mainly depends on disease duration, the distribution and extent of alpha-synuclein pathology, and modulating effects of the dopaminergic therapy. When managing PD hallucinations both anti-delirogenic actions and medication management are important. However, decrease in dopaminergic medication may lead to critical worsening of akinesia. If appropriate neuroleptic medication - essentially quetiapin or clozapin - can be considered. Instead, anti-dopaminergic neuroleptics should not be used owing to their pro-akinetic side-effects. Here, we provide therapy recommendations to manage PD hallucinations based on an up-to-date targeted review of the literature and expert-based empirical evidence.

Blood DNA methylation provides an accurate biomarker of KMT2B-related dystonia and predicts onset.

Dystonia is a prevalent, heterogeneous movement disorder characterized by involuntarily abnormal postures. Biomarkers of dystonia are notoriously lacking. Here, a biomarker is reported for histone lysine methyltransferase (KMT2B)-deficient dystonia, a leading subtype among the individually rare monogenic dystonias. It was derived by applying a support vector machine to an episignature of 113 DNA CpG sites, which, in blood cells, showed significant epigenome-wide association with KMT2B deficiency and at least 1× log-fold change of methylation. This classifier was accurate both when tested on the general population and on samples with various other deficiencies of the epigenetic machinery, thus allowing for definitive evaluation of variants of uncertain significance and identifying patients who may profit from deep brain stimulation, a highly successful treatment in KMT2B-deficient dystonia. Methylation was increased in KMT2B deficiency at all 113 CpG sites. The coefficients of variation of the normalized methylation levels at these sites also perfectly classified the samples with KMT2B-deficient dystonia. Moreover, the mean of the normalized methylation levels correlated well with the age at onset of dystonia (P = 0.003)-being lower in samples with late or incomplete penetrance-thus serving as a predictor of disease onset and severity. Similarly, it may also function in monitoring the recently envisioned treatment of KMT2B deficiency by inhibition of DNA methylation.

Multimodal assessment of autonomic dysfunction in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder with predominant progressive degeneration of motor neurons and motor deficits, but non-motor symptoms (NMS) such as cognitive and behavioural deficits are frequent and underestimated in current diagnostic pathways. Autonomic dysfunction has occasionally been described, although its frequency and relevance are unclear. The aim of this study was to investigate the role of the autonomic nervous system in ALS using a multimodal approach. METHODS: Thirty-seven ALS patients and 40 healthy sex- and age-matched controls were included. NMS were studied with the NMS assessment scale for Parkinson's disease and an autonomic subscale was calculated. Cardioautonomic innervation at rest and whilst standing was assessed by different parameters of heart rate variability. Morphological changes (cross-sectional area) of the vagus and median nerves for control were measured with high-resolution ultrasound. RESULTS: Non-motor symptoms in general were more frequent in ALS patients and correlated inversely with the ALS Functional Rating Scale whereas the autonomic subscore of the NMS assessment scale for Parkinson's disease did not differ between the two groups and was not related to functional impairment. Cardioautonomic assessment solely revealed an increased heart rate at rest in ALS patients, whereas the other heart rate variability parameters did not differ from controls. Structural sonographic investigation of the vagus and median nerves was similar in both groups. CONCLUSIONS: Using a multimodal approach evidence was found for a rather mild cardio-sympathetic overactivity in ALS patients. Overall, autonomic dysfunction seems to be subtle and is not related to the functional state of ALS patients.

Differentiating neurodegenerative parkinsonian syndromes using vestibular evoked myogenic potentials and balance assessment.

OBJECTIVE: Vestibular evoked myogenic potentials (VEMP) were investigated to differentiate between parkinsonian syndromes. We correlated balance and VEMP parameters to investigate the VEMP brainstem circuits as possible origin for postural instability. METHODS: We assessed clinical status, ocular and cervical VEMP (oVEMP, cVEMP) and conducted a balance assessment (posturography, Activities-specific Balance Confidence Scale, Berg Balance Scale, modified Barthel Index) in 76 subjects: 30 with Parkinson's disease (PD), 16 with atypical parkinsonism (AP) and 30 healthy controls. VEMP were elicited by using a mini-shaker on the forehead. RESULTS: Patients with PD had a prolonged oVEMP n10 in comparison to controls and prolonged p15 compared to controls and AP. Patients with AP showed reduced oVEMP amplitudes compared to PD and controls. CVEMP did not differ between groups. Postural impairment was higher in AP compared to controls and PD, particularly in the rating scales. No correlations between VEMP and posturography were found. A support vector machine classifier was able to automatically classify controls and patient subgroups with moderate to good accuracy based on oVEMP latencies and balance questionnaires. CONCLUSIONS: Both oVEMP and posturography, but not cVEMP, may be differentially affected in PD and AP. We did not find evidence that impairment of the cVEMP or oVEMP pathways is directly related to postural impairment. SIGNIFICANCE: OVEMP and balance assessment could be implemented in the differential diagnostic work-up of parkinsonian syndromes.

Scoring Algorithm-Based Genomic Testing in Dystonia: A Prospective Validation Study.

BACKGROUND: Despite the established value of genomic testing strategies, practice guidelines for their use do not exist in many indications. OBJECTIVES: We sought to validate a recently introduced scoring algorithm for dystonia, predicting the diagnostic utility of whole-exome sequencing (WES) based on individual phenotypic aspects (age-at-onset, body distribution, presenting comorbidity). METHODS: We prospectively enrolled a set of 209 dystonia-affected families and obtained summary scores (0-5 points) according to the algorithm. Singleton (N = 146), duo (N = 11), and trio (N = 52) WES data were generated to identify genetic diagnoses. RESULTS: Diagnostic yield was highest (51%) among individuals with a summary score of 5, corresponding to a manifestation of early-onset segmental or generalized dystonia with coexisting non-movement disorder-related neurological symptoms. Sensitivity and specificity at the previously suggested threshold for implementation of WES (3 points) was 96% and 52%, with area under the curve of 0.81. CONCLUSIONS: The algorithm is a useful predictive tool and could be integrated into dystonia routine diagnostic protocols. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson Movement Disorder Society.

Striatal dopamine transporter availability and individual clinical course within the 1-year follow-up of deep brain stimulation of the subthalamic nucleus in patients with Parkinson's disease.

OBJECTIVE: Degeneration of dopaminergic neurons in the substantia nigra projecting to the striatum is responsible for the motor symptoms in Parkinson's disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established procedure to alleviate these symptoms in advanced PD. Yet the mechanism of action, especially the effects of STN-DBS on the availability of striatal dopamine transporter (DAT) as a marker of nigrostriatal nerve cell function, remains largely unknown. The aim of this study was therefore to evaluate whether 1) DAT availability changes within 1 year of STN-DBS and 2) the clinical outcome can be predicted based on preoperative DAT availability. METHODS: Twenty-seven PD patients (mean age 62.7 ± 8.9 years; mean duration of illness 13.0 ± 4.9 years; PD subtypes: akinetic-rigid, n = 11; equivalence, n = 13; and tremor-dominant, n = 3) underwent [123I]FP-CIT SPECT preoperatively and after 1 year of STN-DBS. DAT availability as determined by the specific binding ratio (SBR) was assessed by volume of interest (VOI) analysis of the caudate nucleus and the putamen ipsilateral and contralateral to the clinically more affected side. RESULTS: Unified Parkinson's Disease Rating Scale (UPDRS) III scores improved significantly (mean preoperative on medication 25.6 ± 12.3, preoperative off medication 42.3 ± 15.2, postoperative on medication/off stimulation 41.4 ± 13.2, and postoperative on medication/on stimulation 16.1 ± 9.4; preoperative on medication vs postoperative on medication/on stimulation, p = 0.006), while the levodopa-equivalent daily dose was reduced (mean preoperative 957 ± 440 mg vs postoperative 313 ± 189 mg, p < 0.001). The SBR did not differ significantly before and 1 year after DBS, regardless of PD subtype. Preoperative DAT availability was not related to the change in UPDRS III score, but the change in DAT availability was significantly correlated with the change in UPDRS III score (contralateral head of the caudate VOI, p = 0.014; contralateral putamen VOI, p = 0.018). CONCLUSIONS: Overall, DAT availability did not change significantly after 1 year of STN-DBS. However, on an individual basis, the improvement in UPDRS III score was associated with an increase in DAT availability, whereas DAT availability before STN-DBS surgery did not predict the clinical outcome. Whether a subtype-specific pattern of preoperative DAT availability can become a reliable predictor of successful STN-DBS must be evaluated in larger study cohorts.

Subjective versus objective symptom intensities ratings in cervical dystonia and hemifacial spasm across a botulinum neurotoxin cycle.

BACKGROUND: Subjective symptom complaints often do not match the expert's ratings in focal dystonia. Nonetheless, perceived symptom intensities drive compliance and outcome of botulinum neurotoxin (BoNT) treatment. METHODS: Perception of symptom development across a BoNT cycle was obtained in 21 cervical dystonia (CD) and 15 hemifacial spasm (HFS) patients at four time points during a BoNT cycle. Subjective assessments were recorded by means of a quality-of-life questionnaire and a patient diary containing items related to subjective severity of disease, mood, pain, social impairment, and quality of life. Medical investigation used the Tsui score and TWSTRS, and a HFS rating score, respectively. RESULTS: In both patient groups, subjective intensities were strongly associated with psychological variables. Only in CD did objective assessment moderately correlate with subjective ratings solely at the beginning and the end of the BoNT cycle. Overall, the beneficial effects of BoNT treatment were only loosely associated with subjective experiences in both groups. CONCLUSION: The emotional situation should be assessed regularly in patients undergoing BoNT therapy.

Compositional data analysis of smoke emissions from debris piles with low-density polyethylene.

Data describing the composition of smoke are inherently multivariate and always non-negative parts of a whole. The data are relative and the information is contained in the ratios between parts of the composition. A prior analysis of smoke emissions produced from the burning of manzanita wood mixed with low-density polyethylene plastic applied traditional statistical methods to the compositional data and found no effect. The current paper applies compositional data techniques to these smoke emissions to determine if the prior analysis was accurate. Analysis of variance of the isometric log-ratios showed that LDPE significantly affected the CO2 emission ratio for 8 of the 191 trace gases; this analysis showed none of the gases identified in the previous analysis were affected by LDPE. LDPE did not affect the CO2 emission ratios for the alkanes, alkenes, alkynes, aldehydes, cycloalkanes, cycloalkenes, diolefins, ketones, MAHs, and PAHs. Compositional data analysis should be used to analyze smoke emissions data. Burning contaminant-free LDPE should produce emissions like wood. Implications Reanalysis of impact of burning LDPE plastic in silvicultural debris piles using appropriate statistical techniques confirmed previously published results from inappropriate techniques that LDPE did not change the composition of the smoke emissions. Being able to dispose of these LDPE-covered forest debris by burning can save thousands of dollars in labor costs annually. Disposal of pesticide-free agricultural LDPE plastic by burning should only produce wood-like smoke emissions. This applies to LDPE/total mass ratios of 0.25- 2.5% as studied.

Correlation between sonographic morphology and function of the cervical vagus nerves.

The heart receives parasympathetic and to a lesser degree sympathetic input via the vagus nerve. Here, we investigated whether morphological changes of the cervical vagus nerves (VN) as assessed by high-resolution ultrasound (HRUS) correlated with the autonomic cardiac innervation. Measurement of heart rate variability (HRV) and HRUS of the VNs were performed in 88 healthy subjects (50 female; mean age 56 ±â€¯18 years). HRV parameters and the cross-sectional area (CSA) of the VNs correlated both inversely with age. We also found an inverse correlation between the left VN-CSA and HRV as well as parasympathetic parameters. The results imply an asymmetric parasympathetic (vagal) innervation of the heart.

Dual-Site Transcranial Magnetic Stimulation for the Treatment of Parkinson's Disease.

Abnormal oscillatory activity in the subthalamic nucleus (STN) may be relevant for motor symptoms in Parkinson's disease (PD). Apart from deep brain stimulation, transcranial magnetic stimulation (TMS) may be suitable for altering these oscillations. We speculated that TMS to different cortical areas (primary motor cortex, M1, and dorsal premotor cortex, PMd) may activate neuronal subpopulations within the STN via corticofugal neurons projecting directly to the nucleus. We hypothesized that PD symptoms can be ameliorated by a lasting decoupling of STN neurons by associative dual-site repetitive TMS (rTMS). Associative dual-site rTMS (1 Hz) directed to PMd and M1 ("ADS-rTMS") was employed in 20 PD patients treated in a blinded, placebo-controlled cross-over design. Results: No adverse events were noted. We found no significant improvement in clinical outcome parameters (videography of MDS-UPDRS-III, finger tapping, spectral tremor power). Variation of the premotor stimulation site did not induce beneficial effects either. A single session of ADS-rTMS was tolerated well, but did not produce a clinically meaningful benefit on Parkinsonian motor symptoms. Successful treatment using TMS targeting subcortical nuclei may require an intervention over several days or more detailed physiological information about the individual brain state and stimulation-induced subcortical effects.

Assessing blink reflex circuits by three different afferent routes in Parkinson's disease.

OBJECTIVE: Degeneration of nuclei of the brainstem, especially parts of the vagal nuclei complex and the reticular formation, in Parkinson's disease (PD) may in part be responsible for nonmotor signs like obstipation, cardiac dysfunction and rapid eye movement sleep behavior disorder (RBD). The aim of the study was to establish a new blink reflex (BR) variant involving the vagal nuclei complex and the reticular formation and to investigate BR comprehensively using 3 different afferent routes in PD. METHODS: In this cross-sectional observational study in 30 PD patients and 30 age and sex matched healthy controls, BR was elicited by stimulation of the auricular branch of the vagus nerve (ABVN) and compared to conventional BR variants evoked by the trigeminal and median nerve. RESULTS: BRs could be elicited reliably by stimulation of ABVN in both groups. In none of the three BR variants, latencies or amplitudes differed between PD patients and controls. In PD, BR parameters were not related to cognition or presence of RBD. CONCLUSION: The present study did not provide evidence for malfunctioning of neural circuits subserving BRs elicited by three different afferents in PD. SIGNIFICANCE: Brainstem circuits mediating these BR variants may be spared from neurodegeneration in PD.

Central Effects of Botulinum Neurotoxin-Evidence from Human Studies.

For more than three decades, Botulinum neurotoxin (BoNT) has been used to treat a variety of clinical conditions such as spastic or dystonic disorders by inducing a temporary paralysis of the injected muscle as the desired clinical effect. BoNT is known to primarily act at the neuromuscular junction resulting in a biochemical denervation of the treated muscle. However, recent evidence suggests that BoNT's pharmacological properties may not only be limited to local muscular denervation at the injection site but may also include additional central effects. In this review, we report and discuss the current evidence for BoNT's central effects based on clinical observations, neurophysiological investigations and neuroimaging studies in humans. Collectively, these data strongly point to indirect mechanisms via changes to sensory afferents that may be primarily responsible for the marked plastic effects of BoNT on the central nervous system. Importantly, BoNT-related central effects and consecutive modulation and/or reorganization of the brain may not solely be considered "side-effects" but rather an additional therapeutic impact responsible for a number of clinical observations that cannot be explained by merely peripheral actions.

Early after Administration [11C]PiB PET Images Correlate with Cognitive Dysfunction Measured by the CERAD Test Battery.

BACKGROUND: Amyloid-ß (Aß) and [18F]FDG PET are established as amyloid pathology and neuronal injury biomarkers. Early after administration Aß PET images have the potential to replace [18F]FDG PET images allowing dual biomarker delivery by the administration of a single tracer. For [18F]FDG PET data, a correlation with cognitive performance is known. OBJECTIVE: The aim of this study was to investigate whether early after administration [11C]PiB PET data also correlate with cognitive performance. METHODS: The early after administration [11C]PiB PET data of 31 patients with cognitive impairment were evaluated. CERAD subtests were summarized to five cognitive domains. The resulting z scores were correlated with the PET data on a voxel- and VOI-based approach. Additional subgroup analyses (MCI versus dementia, Aß-positive versus Aß-negative subjects) were performed. RESULTS: Significant correlations between cognitive performance and early after administration [11C]PiB PET data were found between left temporo-parietal SUVR and language domain, bilateral occipital as well as left temporal SUVR and executive function, left pre- and postcentral SUVRs, and visuospatial abilities. For the episodic and immediate memory domains, the analysis at the high significance level did not show any correlated cluster, however, the exploratory analysis did. CONCLUSION: Our study revealed correlations between deficits in different cognitive domains and regional early after administration [11C]PiB PET data similar to those known from [18F]FDG PET studies. Thus, our data support the assumption that early [11C]PiB PET data have a potential as neuronal injury biomarker. Head-to-head double-tracer studies of larger cohorts are needed to confirm this assumption.

Axonal Degeneration of the Vagus Nerve in Parkinson's Disease-A High-Resolution Ultrasound Study.

Background: Recent histopathological studies revealed degeneration of the dorsal motor nucleus early in the course of Parkinson's disease (PD). Degeneration of the vagus nerve (VN) axons following neurodegeneration of brainstem vagal nuclei should be detectable by high-resolution ultrasound (HRUS) as a thinning of the VNs. Methods: We measured both VNs cross-sectional area (VN-CSA) of 35 patients with PD and 35 age- and sex-matched healthy controls at the level of the thyroid gland using HRUS. Results: On both sides, the VN-CSA was significantly smaller in PD patients than in controls (right: 2.1 ± 0.4 vs. 2.3 ± 0.5 mm2, left 1.5 ± 0.4 vs. 1.8 ± 0.4 mm2; both p < 0.05). There was no correlation between the right or left VN-CSA and age, the Hoehn & Yahr stage, disease duration, the motor part of the Unified Parkinson's Disease Rating Scale score, the Montreal Cognitive Assessment score, or the Non-motor Symptoms Questionnaire, and Scale for Parkinson's disease score including its gastrointestinal domain. Conclusions: These findings provide evidencethat atrophy of the VNs in PD patients can be detected in-vivo by HRUS.