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Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment

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A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neurodegenerative Diseases".

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 33657

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Special Issue Editors

Dr. Patricia Martinez-Sanchez

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Guest Editor

1. Department of Neurology and Stroke Centre, Torrecárdenas University Hospital, 04009 Almería, Spain
2. Health Sciences Faculty, University of Almeria, 04120 Almeria, Spain
Interests: stroke prevention; acute stroke treatment; cardioembolic stroke; neurosonology; neuroimaging; neuromodulation; neurorehabilitation

Dr. Francisco Nieto-Escamez

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Guest Editor

Department of Psychology, University of Almeria, 04120 Almeria, Spain
Interests: virtual reality; neurorehabilitation; motor system; neuropsychology; dementia; visual perception
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Special Issue Information

Dear Colleagues,

It is our pleasure to introduce a Special Issue of Brain Science dedicated to basic neuroscience and clinical research about the neurobiology of non-motor symptoms (NMS) of Parkinson’s disease and potential treatment strategies.

Parkinson’s disease (PD) is the second most common neurodegenerative disorder, and although it is usually considered as a disorder that only affects movement, a broad spectrum of NMS can be observed in PD patients. Although the realities of the disease vary enormously from patient to patient, almost all of them have one or more NMS. In fact, a wide range of behavioural, neuropsychiatric and physical symptoms frequently play a primary role for the management of the disorder and constitute a major disease burden for patients and caregivers. Unfortunately, there is very little existing data about NMS, their neurobiology, and their treatment. It is therefore essential that researchers and practitioners comprehensively address the factors related to NMS if we want to achieve the best quality of life for PD patients.

The aim of this Special Issue is to provide an overview of evidence from clinical and basic research perspectives about Parkinson´s NMS. A non-exhaustive list of potential papers may include research involving the use of neurophysiology techniques, genetics, pharmacological therapy, physical therapy, psychological intervention in clinical populations, as well as preclinical studies with animal models.

With regard to the format of papers, we will consider research articles, opinion/perspective articles, and review articles (narrative review, systematic review, meta-analysis).

Dr. Patricia Martinez-Sanchez
Dr. Francisco Nieto-Escamez
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

Parkinson’s disease
Non-motor symptoms
Dementia
Emotional disorder
Cognition disability
Perceptive deficits
Impulse-control
Depression
Apathy
Fatigue
Sleep problems
Neuroanatomy
Neurophysiology
Neuropharmacology
Neurogenetics
Neuroimage
Neuropsychology
Physiotherapy
Clinical models
Animal models
Interdisciplinary approach

Published Papers (12 papers)

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Editorial

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5 pages, 230 KiB

Open AccessEditorial

Unveiling the Hidden Challenges: Non-Motor Disorders in Parkinson’s Disease

by Francisco Nieto-Escamez, Esteban Obrero-Gaitán, Héctor García-López and Irene Cortés-Pérez

Brain Sci. 2023, 13(12), 1710; https://doi.org/10.3390/brainsci13121710 - 12 Dec 2023

Viewed by 879

Abstract

Parkinson’s disease (PD) is not just a motor disorder, it is a complex condition that affects every aspect of a patient’s life, from cognitive impairment and psychiatric disturbances to autonomic dysfunction and sleep disturbances [...] Full article

(This article belongs to the Special Issue Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment)

Research

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12 pages, 2758 KiB

Open AccessArticle

Assessing Anti-Social and Aggressive Behavior in a Zebrafish (Danio rerio) Model of Parkinson’s Disease Chronically Exposed to Rotenone

by Ovidiu-Dumitru Ilie, Raluca Duta, Roxana Jijie, Ilinca-Bianca Nita, Mircea Nicoara, Caterina Faggio, Romeo Dobrin, Ioannis Mavroudis, Alin Ciobica and Bogdan Doroftei

Brain Sci. 2022, 12(7), 898; https://doi.org/10.3390/brainsci12070898 - 08 Jul 2022

Cited by 6 | Viewed by 2947

Abstract

Background: Rotenone (ROT) is currently being used in various research fields, especially neuroscience. Separated from other neurotoxins, ROT induces a Parkinson’s disease (PD)-related phenotype that mimics the associated clinical spectrum by directly entering the central nervous system (CNS). It easily crosses through the blood–brain barrier (BBB) and accumulates in mitochondria. Unfortunately, most of the existing data focus on locomotion. This is why the present study aimed to bring novel evidence on how ROT alone or in combination with different potential ant(agonists) might influence the social and aggressive behavior using the counterclockwise rotation as a neurological pointer. Material and Methods: Thus, we exposed zebrafish to ROT—2.5 µg/L, valproic acid (VPA)—0.5 mg/mL, anti-parkinsonian drugs (LEV/CARB)—250 mg + 25 mg, and probiotics (PROBIO)—3 g for 32 days by assessing the anti-social profile and mirror tests and counterclockwise rotation every 4 days to avoid chronic stress. Results: We observed an abnormal pattern in the counterclockwise rotation only in the (a) CONTROL, (c) LEV/CARB, and (d) PROBIO groups, from both the top and side views, this indicating a reaction to medication and supplements administered or a normal intrinsic feature due to high levels of stress/anxiety (p < 0.05). Four out of eight studied groups—(b) VPA, (c) LEV/CARB, (e) ROT, and (f) ROT + VPA—displayed an impaired, often antithetical behavior demonstrated by long periods of time on distinct days spent on the right and the central arm (p < 0.05, 0.005, and 0.0005). Interestingly, groups (d) PROBIO, (g) ROT + LEV/CARB, and (h) ROT + PROBIO registered fluctuations but not significant ones in contrast with the above groups (p > 0.05). Except for groups (a) CONTROL and (d) PROBIO, where a normalized trend in terms of behavior was noted, the rest of the experimental groups exhibited exacerbated levels of aggression (p < 0.05, 0.005, and 0.001) not only near the mirror but as an overall reaction (p < 0.05, 0.005, and 0.001). Conclusions: The (d) PROBIO group showed a significant improvement compared with (b) VPA, (c) LEV/CARB, and ROT-treated zebrafish (e–h). Independently of the aggressive-like reactions and fluctuations among the testing day(s) and groups, ROT disrupted the social behavior, while VPA promoted a specific typology in contrast with LEV/CARB. Full article

(This article belongs to the Special Issue Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment)

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14 pages, 1393 KiB

Open AccessEditor’s ChoiceArticle

Opicapone Improves Global Non-Motor Symptoms Burden in Parkinson’s Disease: An Open-Label Prospective Study

by Diego Santos García, Gustavo Fernández Pajarín, Juan Manuel Oropesa-Ruiz, Francisco Escamilla Sevilla, Raúl Rashid Abdul Rahim López and José Guillermo Muñoz Enríquez

Brain Sci. 2022, 12(3), 383; https://doi.org/10.3390/brainsci12030383 - 12 Mar 2022

Cited by 8 | Viewed by 3267

Abstract

Patients with Parkinson’s disease (PD) can improve some non-motor symptoms (NMS) after starting treatment with opicapone. The aim of this study was to analyze the effectiveness of opicapone on global NMS burden in PD. OPEN-PD (Opicapone Effectiveness on Non-motor symptoms in Parkinson’s Disease) is a prospective open-label single-arm study conducted in 5 centers from Spain. The primary efficacy outcome was the change from baseline (V0) to the end of the observational period (6 months ± 30 days) (V2) in the Non-Motor Symptoms Scale (NMSS) total score. Different scales were used for analyzing the change in motor, NMS, quality of life (QoL), and disability. Thirty-three patients were included between JUL/2019 and JUN/2021 (age 63.3 ± 7.91; 60.6% males; 7.48 ± 4.22 years from symptoms onset). At 6 months, 30 patients completed the follow-up (90.9%). The NMSS total score was reduced by 27.3% (from 71.67 ± 37.12 at V0 to 52.1 ± 34.76 at V2; Cohen’s effect size = −0.97; p = 0.002). By domains, improvement was observed in sleep/fatigue (−40.1%; p < 0.0001), mood/apathy (−46.6%; p = 0.001), gastrointestinal symptoms (−20.7%; p = 0.029), and miscellaneous (−44.94%; p = 0.021). QoL also improved with a 18.4% reduction in the 39-item Parkinson’s Disease Quality of Life Questionnaire Summary Index (from 26.67 ± 17.61 at V0 to 21.75 ± 14.9 at V2; p = 0.001). A total of 13 adverse events in 11 patients (33.3%) were reported, 1 of which was severe (not related to opicapone). Dyskinesias and nausea were the most frequent (6.1%). Opicapone is well tolerated and improves global NMS burden and QoL in PD patients at 6 months. Full article

(This article belongs to the Special Issue Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment)

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11 pages, 294 KiB

Open AccessArticle

Naturalistic Study of Depression Associated with Parkinson’s Disease in a National Public Neurological Referral Center in Mexico

by Reinhard Janssen-Aguilar, Patricia Rojas, Elizabeth Ruiz-Sánchez, Mayela Rodriguez-Violante, Yessica M. Alcántara-Flores, Daniel Crail-Meléndez, Amin Cervantes-Arriaga, Óscar Sánchez-Escandón and Ángel A. Ruiz-Chow

Brain Sci. 2022, 12(3), 326; https://doi.org/10.3390/brainsci12030326 - 28 Feb 2022

Cited by 1 | Viewed by 2025

Abstract

Major depressive disorder (MDD) is a major health problem in Parkinson’s disease (PD) patients. We described the clinical and sociodemographic factors of MDD among patients with PD at a national neurological referral center in Mexico. One hundred patients with PD + MDD were included in the study. All the patients were evaluated during the “ON” treatment phase of PD. Clinical scales for cognition (MMSE and MoCA) and MDD (MADRS) were applied. The mean age was 58.49 ± 11.02 years, and 57% of the sample was male. The most frequent symptom of PD was tremor (67%), and onset was more frequent on the right side (57%). Additionally, 49% of the patients with PD had moderate to severe (M/S) MDD. Selective serotonin reuptake inhibitors were the most frequent antidepressant treatment (69%). The scores of the scales were MADRS 21.33 ± 5.49, MoCA 21.06 ± 4.65, and MMSE 26.67 ± 1.20. The females had lower MMSE scores compared to the males (p = 0.043). The patients with M/S MDD had more rigidity at the beginning of PD (p = 0.005), fewer march alterations (p = 0.023), and a greater prevalence of left-side initial disease (p = 0.037). Rigidity was associated with M/S MDD (OR 3.75 p = 0.013). MDD was slightly more frequent in the males than in the females. The MDD symptoms and cognitive impairment were worse in the female population. Full article

(This article belongs to the Special Issue Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment)

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10 pages, 1485 KiB

Open AccessCommunication

Zonisamide Ameliorates Microglial Mitochondriopathy in Parkinson’s Disease Models

by Satoshi Tada, Mohammed E. Choudhury, Madoka Kubo, Rina Ando, Junya Tanaka and Masahiro Nagai

Brain Sci. 2022, 12(2), 268; https://doi.org/10.3390/brainsci12020268 - 14 Feb 2022

Cited by 7 | Viewed by 2869

Abstract

Mitochondrial dysfunction and exacerbated neuroinflammation are critical factors in the pathogenesis of both familial and non-familial forms of Parkinson’s disease (PD). This study aims to understand the possible ameliorative effects of zonisamide on microglial mitochondrial dysfunction in PD. We prepared 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and lipopolysaccharide (LPS) co-treated mouse models of PD to investigate the effects of zonisamide on mitochondrial reactive oxygen species generation in microglial cells. Consequently, we utilised a mouse BV2 cell line that is commonly used for microglial studies to determine whether zonisamide could ameliorate LPS-treated mitochondrial dysfunction in microglia. Flow cytometry assay indicated that zonisamide abolished microglial reactive oxygen species (ROS) generation in PD models. Extracellular flux assays showed that LPS exposure to BV2 cells at 1 μg/mL drastically reduced the mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Zonisamide overcame the inhibitory effects of LPS on mitochondrial OCR. Our present data provide novel evidence on the ameliorative effect of zonisamide against microglial mitochondrial dysfunction and support its clinical use as an antiparkinsonian drug. Full article

(This article belongs to the Special Issue Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment)

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Review

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23 pages, 1247 KiB

Open AccessReview

Visual Dysfunction in Parkinson’s Disease

by Francisco Nieto-Escamez, Esteban Obrero-Gaitán and Irene Cortés-Pérez

Brain Sci. 2023, 13(8), 1173; https://doi.org/10.3390/brainsci13081173 - 07 Aug 2023

Cited by 4 | Viewed by 1824

Abstract

Non-motor symptoms in Parkinson’s disease (PD) include ocular, visuoperceptive, and visuospatial impairments, which can occur as a result of the underlying neurodegenerative process. Ocular impairments can affect various aspects of vision and eye movement. Thus, patients can show dry eyes, blepharospasm, reduced blink rate, saccadic eye movement abnormalities, smooth pursuit deficits, and impaired voluntary and reflexive eye movements. Furthermore, visuoperceptive impairments affect the ability to perceive and recognize visual stimuli accurately, including impaired contrast sensitivity and reduced visual acuity, color discrimination, and object recognition. Visuospatial impairments are also remarkable, including difficulties perceiving and interpreting spatial relationships between objects and difficulties judging distances or navigating through the environment. Moreover, PD patients can present visuospatial attention problems, with difficulties attending to visual stimuli in a spatially organized manner. Moreover, PD patients also show perceptual disturbances affecting their ability to interpret and determine meaning from visual stimuli. And, for instance, visual hallucinations are common in PD patients. Nevertheless, the neurobiological bases of visual-related disorders in PD are complex and not fully understood. This review intends to provide a comprehensive description of visual disturbances in PD, from sensory to perceptual alterations, addressing their neuroanatomical, functional, and neurochemical correlates. Structural changes, particularly in posterior cortical regions, are described, as well as functional alterations, both in cortical and subcortical regions, which are shown in relation to specific neuropsychological results. Similarly, although the involvement of different neurotransmitter systems is controversial, data about neurochemical alterations related to visual impairments are presented, especially dopaminergic, cholinergic, and serotoninergic systems. Full article

(This article belongs to the Special Issue Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment)

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19 pages, 904 KiB

Open AccessReview

Apathy in Parkinson’s Disease: Defining the Park Apathy Subtype

by Ségolène De Waele, Patrick Cras and David Crosiers

Brain Sci. 2022, 12(7), 923; https://doi.org/10.3390/brainsci12070923 - 14 Jul 2022

Cited by 7 | Viewed by 2809

Abstract

Apathy is a neurobehavioural symptom affecting Parkinson’s disease patients of all disease stages. Apathy seems to be associated with a specific underlying non-motor disease subtype and reflects dysfunction of separate neural networks with distinct neurotransmitter systems. Due to the complicated neuropsychiatric aetiology of apathy, clinical assessment of this invalidating non-motor symptom remains challenging. We aim to summarize the current findings on apathy in Parkinson’s disease and highlight knowledge gaps. We will discuss the prevalence rates across the different disease stages and suggest screening tools for clinically relevant apathetic symptoms. We will approach the fundamental knowledge on the neural networks implicated in apathy in a practical manner and formulate recommendations on patient-tailored treatment. We will discuss the Park apathy phenotype in detail, shedding light on different clinical manifestations and implications for prognosis. With this review, we strive to distil the vast available theoretical knowledge into a clinical and patient-oriented perspective. Full article

(This article belongs to the Special Issue Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment)

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10 pages, 294 KiB

Open AccessReview

Gastroparesis in Parkinson Disease: Pathophysiology, and Clinical Management

by Heithem Soliman, Benoit Coffin and Guillaume Gourcerol

Brain Sci. 2021, 11(7), 831; https://doi.org/10.3390/brainsci11070831 - 23 Jun 2021

Cited by 22 | Viewed by 4073

Abstract

Patients with Parkinson disease (PD) experience a range of non-motor symptoms, including gastrointestinal symptoms. These symptoms can be present in the prodromal phase of the disease. Recent advances in pathophysiology reveal that α-synuclein aggregates that form Lewy bodies and neurites, the hallmark of PD, are present in the enteric nervous system and may precede motor symptoms. Gastroparesis is one of the gastrointestinal involvements of PD and is characterized by delayed gastric emptying of solid food in the absence of mechanical obstruction. Gastroparesis has been reported in nearly 45% of PD. The cardinal symptoms include early satiety, postprandial fullness, nausea, and vomiting. The diagnosis requires an appropriate test to confirm delayed gastric emptying, such as gastric scintigraphy, or breath test. Gastroparesis can lead to malnutrition and impairment of quality of life. Moreover, it might interfere with the absorption of antiparkinsonian drugs. The treatment includes dietary modifications, and pharmacologic agents both to accelerate gastric emptying and relieve symptoms. Alternative treatments have been recently developed in the management of gastroparesis, and their use in patients with PD will be reported in this review. Full article

(This article belongs to the Special Issue Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment)

Other

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17 pages, 2104 KiB

Open AccessSystematic Review

Clinical Evaluation of Sleep Disorders in Parkinson’s Disease

by Fulvio Lauretani, Crescenzo Testa, Marco Salvi, Irene Zucchini, Francesco Giallauria and Marcello Maggio

Brain Sci. 2023, 13(4), 609; https://doi.org/10.3390/brainsci13040609 - 03 Apr 2023

Cited by 1 | Viewed by 2084

Abstract

The paradigm of the framing of Parkinson’s disease (PD) has undergone significant revision in recent years, making this neurodegenerative disease a multi-behavioral disorder rather than a purely motor disease. PD affects not only the “classic” substantia nigra at the subthalamic nuclei level but also the nerve nuclei, which are responsible for sleep regulation. Sleep disturbances are the clinical manifestations of Parkinson’s disease that most negatively affect the quality of life of patients and their caregivers. First-choice treatments for Parkinson’s disease determine amazing effects on improving motor functions. However, it is still little known whether they can affect the quantity and quality of sleep in these patients. In this perspective article, we will analyze the treatments available for this specific clinical setting, hypothesizing a therapeutic approach in relation to neurodegenerative disease state. Full article

(This article belongs to the Special Issue Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment)

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17 pages, 1213 KiB

Open AccessSystematic Review

Treatment of Vascular Parkinsonism: A Systematic Review

by Cristina del Toro-Pérez, Eva Guevara-Sánchez and Patricia Martínez-Sánchez

Brain Sci. 2023, 13(3), 489; https://doi.org/10.3390/brainsci13030489 - 14 Mar 2023

Cited by 2 | Viewed by 3141

Abstract

Background and aims: Although the distinction between vascular parkinsonism (VP) and idiopathic Parkinson’s disease (IPD) is widely described, it is not uncommon to find parkinsonisms with overlapping clinical and neuroimaging features even in response to levodopa treatment. In addition, several treatments have been described as possible adjuvants in VP. This study aims to update and analyze the different treatments and their efficacy in VP. Methods: A literature search was performed in PubMed, Scopus and Web of Science for studies published in the last 15 years until April 2022. A systematic review was performed. No meta-analysis was performed as no new studies on response to levodopa in VP were found since the last systematic review and meta-analysis in 2017, and insufficient studies on other treatments were located to conduct it in another treatment subgroup. Results: Databases and other sources yielded 59 publications after eliminating duplicates, and a total of 12 original studies were finally included in the systematic review. The treatments evaluated included levodopa, vitamin D, repetitive transcranial magnetic stimulation (rTMS) and intracerebral transcatheter laser photobiomodulation therapy (PBMT). The response to levodopa was lower in patients with VP with respect to IPD. Despite this, there has been described a subgroup of patients with good response, it being possible to identify them by means of neuroimaging techniques and the olfactory identification test. Other therapies showed encouraging results in studies with some risk of bias. Conclusions: The response of VP to different therapeutic strategies is modest. However, there is evidence that a subgroup of patients can be identified as more responsive to L-dopa based on clinical and neuroimaging criteria. This subgroup should be treated with L-dopa at appropriate doses. New therapies such as vitamin D, rTMS and PBMT warrant further studies to demonstrate their efficacy. Full article

(This article belongs to the Special Issue Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment)

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14 pages, 586 KiB

Open AccessSystematic Review

Non-Immersive Virtual Reality to Improve Balance and Reduce Risk of Falls in People Diagnosed with Parkinson’s Disease: A Systematic Review

by Héctor García-López, Esteban Obrero-Gaitán, Adelaida María Castro-Sánchez, Inmaculada Carmen Lara-Palomo, Francisco Antonio Nieto-Escamez and Irene Cortés-Pérez

Brain Sci. 2021, 11(11), 1435; https://doi.org/10.3390/brainsci11111435 - 28 Oct 2021

Cited by 13 | Viewed by 3102

Abstract

(1) Objective: To evaluate the effectiveness of non-immersive virtual reality in reducing falls and improving balance in patients diagnosed with Parkinson’s disease. (2) Methods: The following databases were searched: PUBMED, PEDro, Scielo, CINAHL, Web of Science, Dialnet, Scopus and MEDLINE. These databases were searched for randomized controlled trials published using relevant keywords in various combinations. The methodological quality of the articles was evaluated using the PEDro scale. (3) Results: A total of 10 studies with a total of 537 subjects, 58.7% of which (n = 315) were men, have been included in the review. The age of the participants in these studies ranged between 55 and 80 years. Each session lasted between 30 and 75 min, and the interventions lasted between 5 and 12 weeks. These studies showed that non-immersive virtual reality is effective in reducing the number of falls and improving both static and dynamic balance in patients diagnosed with Parkinson’s disease. Results after non-immersive virtual reality intervention showed an improvement in balance and a decrease in the number and the risk of falls. However, no significant differences were found between the intervention groups and the control groups for all the included studies regarding balance. (4) Conclusions: There is evidence that non-immersive virtual reality can improve balance and reduce the risk and number of falls, being therefore beneficial for people diagnosed with Parkinson’s disease. Full article

(This article belongs to the Special Issue Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment)

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16 pages, 1366 KiB

Open AccessSystematic Review

Neurosonological Findings Related to Non-Motor Features of Parkinson’s Disease: A Systematic Review

by Cristina del Toro Pérez, Laura Amaya Pascasio, Antonio Arjona Padillo, Jesús Olivares Romero, María Victoria Mejías Olmedo, Javier Fernández Pérez, Manuel Payán Ortiz and Patricia Martínez-Sánchez

Brain Sci. 2021, 11(6), 776; https://doi.org/10.3390/brainsci11060776 - 11 Jun 2021

Cited by 3 | Viewed by 2706

Abstract

Non-motor symptoms (NMS) in Parkinson’s disease (PD), including neuropsychiatric or dysautonomic complaints, fatigue, or pain, are frequent and have a high impact on the patient’s quality of life. They are often poorly recognized and inadequately treated. In the recent years, the growing awareness of NMS has favored the development of techniques that complement the clinician’s diagnosis. This review provides an overview of the most important ultrasonographic findings related to the presence of various NMS. Literature research was conducted in PubMed, Scopus, and Web of Science from inception until January 2021, retrieving 23 prospective observational studies evaluating transcranial and cervical ultrasound in depression, dementia, dysautonomic symptoms, psychosis, and restless leg syndrome. Overall, the eligible articles showed good or fair quality according to the QUADAS-2 assessment. Brainstem raphe hypoechogenicity was related to the presence of depression in PD and also in depressed patients without PD, as well as to overactive bladder. Substantia nigra hyperechogenicity was frequent in patients with visual hallucinations, and larger intracranial ventricles correlated with dementia. Evaluation of the vagus nerve showed contradictory findings. The results of this systematic review demonstrated that transcranial ultrasound can be a useful complementary tool in the evaluation of NMS in PD. Full article

(This article belongs to the Special Issue Non-motor Disorders in Parkinson Disease: Basic Science and Advances in Treatment)

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