Zoltan Mari

Cleveland Clinic · Lou Ruvo Center for Brain Health

Background Mild memory impairment, termed amnestic mild cognitive impairment (aMCI), is associated with rapid progression towards dementia in Parkinson’s disease (PD). Studies have shown hyperactivation of hippocampal DG/CA3 subfields during an episodic memory task as a biomarker of aMCI related to Alzheimer’s disease. This project investigates the...

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that leads to numerous impairments in motor function that compromise the ability to perform activities of daily living. Practical and effective adjunct therapies are needed to complement current treatment approaches in PD. Transcranial direct current stimulation applied to the cer...

Background and purpose: Resting-state functional MRI (rs-fMRI) studies in Parkinson's disease (PD) patients with freezing of gait (FOG) have implicated dysfunctional connectivity over multiple resting-state networks (RSNs). While these findings provided network-specific insights and information related to the aberrant or altered regional functiona...

Digital health technologies can provide continuous monitoring and objective, real-world measures of Parkinson’s disease (PD), but have primarily been evaluated in small, single-site studies. In this 12-month, multicenter observational study, we evaluated whether a smartwatch and smartphone application could measure features of early PD. 82 individu...

Background: Little is known about the impact of the dopamine system on development of cognitive impairment (CI) in Parkinson disease (PD). Objectives: We used data from a multi-site, international, prospective cohort study to explore the impact of dopamine system-related biomarkers on CI in PD. Methods: PD participants were assessed annually f...

Objective: To investigate the subjective phenomenon and the neural underpinnings of tics compared with voluntary movements in patients with tic disorders. Methods: We recorded electroencephalographic and electromyographic data while subjects completed a Libet clock paradigm. Patients and healthy volunteers reported the times of W (willing to mov...

Deep brain stimulation (DBS) to the fornix is an investigational treatment for patients with mild Alzheimer’s Disease. Outcomes from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. This could be explained by variance in electrode placement leading to differential engagement of neur...

Anxiety that occurs in association with on-off dopamine medication fluctuations is a major cause of distress, dysfunction, and lower quality of life in people with Parkinson's disease (PD). However, the association between anxiety and on-off fluctuations is poorly understood and it is difficult to predict which patients will suffer from this atypic...

Introduction: Parkinson's disease (PD) frequently causes communication difficulties due to various voice impairments and there are few treatment options for vocal/communication complaints. We assessed the effects of weekly group singing on PD patients' objective vocal and motoric function, cognition, mood, self-efficacy, and quality of life. Meth...

Deep brain stimulation (DBS) to the fornix is an investigational treatment option for patients with mild Alzheimer's disease. Outcomes from randomised clinical trials have shown that cognitive function improved in some patients but deteriorated in others. One reason could be variance in electrode placement leading to differential engagement of neur...

Introduction: Freezing of gait (FOG) is a highly disabling symptom in Parkinson's Disease (PD) with varying degree of benefits from oral dopaminergic medications and several subtypes that present with different medication states (e.g., off FOG, on FOG, pseudo-on FOG, supra-on FOG). Levodopa-Carbidopa Intestinal Gel (LCIG) greately reduces the vari...

Cerebellar transcranial direct current stimulation (c-tDCS) enhances motor skill acquisition and motor learning in young and old adults. Since the cerebellum is involved in the pathophysiology of Parkinson’s disease (PD), c-tDCS may represent an intervention with potential to improve motor learning in PD. The primary purpose was to determine the in...

[This corrects the article DOI: 10.3389/fneur.2020.571086.].

Resting-state functional MRI (rs-fMRI) studies in Parkinson’s disease (PD) patients with freezing of gait (FOG) have implicated dysfunctional connectivity over multiple resting-state networks. While these findings provided information related to the aberrant or altered regional functional connectivity, whether these alterations have any effect on t...

Resting-state functional MRI (rs-fMRI) studies in Parkinson’s disease (PD) patients with freezing of gait (FOG) have implicated dysfunctional connectivity over multiple resting-state networks. While these findings provided network-specific insights and information related to the aberrant or altered regional functional connectivity, whether these al...

Background and Purpose: Resting-state functional MRI (rs-fMRI) studies in Parkinson’s disease (PD) patients with freezing of gait (FOG) have implicated dysfunctional connectivity over multiple resting-state networks. While these findings provided network-specific insights and information related to the aberrant or altered regional functional connec...

Background and Purpose: Resting-state functional MRI (rs-fMRI) studies in Parkinson’s disease (PD) patients with freezing of gait (FOG) have implicated dysfunctional connectivity over multiple resting-state networks. While these findings provided network-specific insights and information related to the aberrant or altered regional functional connec...

Background and Purpose: Resting-state functional MRI (rs-fMRI) studies in Parkinson’s disease (PD) patients with freezing of gait (FOG) have implicated dysfunctional connectivity over multiple resting-state networks. While these findings provided network-specific insights and information related to the aberrant or altered regional functional connec...

In the last half-century, Parkinson's disease (PD) has played a historical role in demonstrating our ability to translate preclinical scientific advances in pathology and pharmacology into highly effective clinical therapies. Yet, as highly efficacious symptomatic treatments were successfully developed and adopted in clinical practice, PD remained...

The field of neurology has experienced a dramatic push towards providing care via telemedicine approaches, triggered by the COVID-19 pandemic. The remote monitoring of movement disorders, including tremor, provides a set of challenges compared to gold-standard in-clinic assessments, but also opens opportunities to assess patients' symptoms in a set...

The Lewy Body Dementia Association (LBDA) held a virtual event, the LBDA Biofluid/Tissue Biomarker Symposium, on January 25, 2021, to present advances in biomarkers for Lewy body dementia (LBD), which includes dementia with Lewy bodies (DLBs) and Parkinson's disease dementia (PDD). The meeting featured eight internationally known scientists from Eu...

Inequalities in mental healthcare and lack of social support during the COVID-19 pandemic have lowered quality of life and increased overall burden of disease in people with Parkinson's (PWP). Although the pandemic has brought attention to these inequalities, they are long standing and will persist unless addressed. Lack of awareness of mental heal...

Background: The use of telemedicine has increased to address the ongoing healthcare needs of patients with movement disorders. Objective: We aimed to describe the technical and basic security features of the most popular telemedicine videoconferencing software. Methods: We conducted a systematic review of articles/websites about “Telemedicine,” “Cy...

Background The initial COVID-19 pandemic shutdown led to the canceling of elective surgeries throughout most of the USA and Canada. Objective This survey was carried out on behalf of the Parkinson Study Group (PSG) to understand the impact of the shutdown on deep brain stimulation (DBS) practices in North America. Methods A survey was distributed...

Importance Urate elevation, despite associations with crystallopathic, cardiovascular, and metabolic disorders, has been pursued as a potential disease-modifying strategy for Parkinson disease (PD) based on convergent biological, epidemiological, and clinical data. Objective To determine whether sustained urate-elevating treatment with the urate p...

Objective: The mechanisms and neuronal networks associated with anxiety in Parkinson's disease (PD) are incompletely understood. One of the best tools for investigating both component function and neuronal networks associated with psychiatric symptoms is functional MRI (fMRI). Unlike structural scans, functional scans, whether task-based or restin...

The use of telemedicine in the management of chronic neurological conditions including movement disorders has expanded over time. In addition to enabling remote access to specialized care, telemedicine has also been shown to reduce caregiver burden and to improve patient satisfaction. With the COVID-19 pandemic, implementation of telehealth for pat...

The present review asks whether magnetic resonance imaging (MRI) studies are able to define neural correlates of episodic memory within the hippocampus in Parkinson's disease (PD). Systematic searches were performed in PubMed, Web of Science, Medline, CINAHL, and EMBASE using search terms related to structural and functional MRI (fMRI), the hippoca...

Due to its involvement in a wide variety of cardiovascular, metabolic, and behavioral functions, the hypothalamus constitutes a potential target for neuromodulation in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. We sought to retrospec...

Introduction Deep brain stimulation (DBS) has become a standard treatment option for select patients with Parkinson’s disease (PD). The selection process and surgical procedures employed have, to date, not been standardized. Methods A comprehensive 58-question web-based survey was developed with a focus on DBS referral practices and peri-operative...

Background The pathological hallmarks of Parkinson's disease include intraneuronal Lewy bodies, neuronal loss, and gliosis. We aim to correlate Parkinson's disease neuropsychiatric symptoms, (e.g., depression, psychosis, and anxiety) with the severity of neuropathology in the substantia nigra and locus coeruleus. Methods The brains of 175 particip...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Freezing of gait (FoG) is a disabling symptom characterized as a brief inability to step or by short steps, which occurs when initiating gait or while turning, affecting over half the population with advanced Parkinson's disease (PD). Several non-competing hypotheses have been proposed to explain the pathophysiology and mechanism behind FoG. Yet, d...

Transcranial direct current stimulation of the cerebellum (c-tDCS) improves motor performance in young and old adults. Based on the cerebellar involvement in Parkinson's disease (PD), c-tDCS could have potential to improve motor function in PD. The purpose was to determine the effects of c-tDCS on motor performance in PD while participants were on...

Objective To assess the clinical manifestations and predictors of different types of tremors in a individuals with different types of isolated dystonia. Methods Clinical manifestations of tremor were assessed in a multicenter, international cross-sectional, cohort study of 2362 individuals with all types of isolated dystonia (focal, segmental, mul...

Schizophrenic patients often do not have the sense that they direct their own movements or author their own thoughts (passivity phenomena). As willing must precede movement to be causal and thus generate the sense of agency, it is possible that the timing between the senses of willing and movement is shortened in schizophrenia. We tested the subjec...

There remains a significant mismatch between the complexity and variability of symptoms and disabilities in Parkinson's disease (PD), and the capabilities of existing validated assessment tools to objectively measure and monitor them. However, with the advances of circuit and sensor technologies, it is now possible to apply the concept of digital p...

Background The COVID‐19 pandemic restricted usual healthcare management for movement‐disorders patients, with a consequent upsurge in telemedicine to bridge the gap. Objective To assess global telemedicine usage in the context of the pandemic. Methods The MDS Telemedicine Study Group surveyed telemedicine experts from 40 countries across all cont...

Parkinson disease (PD) is a neurodegenerative disorder characterized by rest tremor, rigidity, bradykinesia, and postural instability. While most cases of PD are sporadic in nature, cases secondary to genetic mutations have been identified. These are typically monogenic and often present as early-onset or juvenile-onset PD. While rare, individuals...

Objective: To investigate the topographic arrangement and strength of whole-brain white matter (WM) structural connectivity in patients with early-stage, drug-naive Parkinson disease (PD). Methods: We employed a model-free data-driven approach for computing whole-brain WM topologic arrangement and connectivity strength between brain regions by u...

Anxiety is a severe problem for at least one-third of people living with Parkinson’s disease (PD). Anxiety appears to have a greater adverse impact on quality of life than motor impairment. Despite its high prevalence and impact on daily life, anxiety is often undiagnosed and untreated. To better address anxiety in PD, future research must improve...

Objective: To determine the minimal clinically important change (MCIC) on Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) scores using data from Cervical Dystonia Patient Registry for Observation of OnabotulinumtoxinA Efficacy (CD PROBE), which captured real-world practices and outcomes. Methods: Changes in the baseline TWSTRS scores...

Introduction: Deep brain stimulation (DBS) is an established treatment for Parkinson's Disease (PD). Despite the improvement of motor symptoms in most patients by sub-thalamic nucleus (STN) DBS and its widespread use, the neurobiological mechanisms are not completely understood. The objective of the present study was to elucidate the effects of su...

Parkinson disease (PD) is a progressive neurodegenerative disease with a higher prevalence of neuropsychiatric symptoms compared with the general population. Symptoms such as anxiety, depression, psychosis, impulse control disorders, and cognitive impairment cause a greater worsening of quality of life than even the motor symptoms that define PD. D...

Objective: To investigate whether self-report, clinical, and physical therapy (PT) assessments differ in identifying freezing of gait (FOG) in Parkinson's disease (PD).

Objective: To assess the effect of levodopa on dual-tasking in situations triggering freezing of gait (FOG) in Parkinson's disease (PD).

Background: Constipation is a prodromal feature of Parkinson's disease (PD) and the gastrointestinal (GI) tract is implicated in the pathogenesis of PD. However, no studies have demonstrated ante-mortem relationships between nigrostriatal dysfunction and GI dysautonomia in PD. Methods: The Scale for Outcomes in Parkinson's disease for Autonomic...

Activation of microglia by classical inflammatory mediators can convert astrocytes into a neurotoxic A1 phenotype in a variety of neurological diseases1,2. Development of agents that could inhibit the formation of A1 reactive astrocytes could be used to treat these diseases for which there are no disease-modifying therapies. Glucagon-like peptide-1...

Background: Given recent challenges in developing new treatments for Alzheimer dementia (AD), it is vital to explore alternate treatment targets, such as neuromodulation for circuit dysfunction. We previously reported an exploratory Phase IIb double-blind trial of deep brain stimulation targeting the fornix (DBS-f) in mild AD (the ADvance trial)....

Background: We undertook this study to identify patients with Parkinson disease (PD) with no or rare falls who may progress to frequent falling by their next annual follow-up visit. Methods: We analyzed data in the National Parkinson Foundation Quality Improvement Initiative database to identify factors predicting which patients with PD with no...

Purpose of review: Advances in technology have expanded telemedicine opportunities covering medical practice, research, and education. This is of particular importance in movement disorders (MDs), where the combination of disease progression, mobility limitations, and the sparse distribution of MD specialists increase the difficulty to access. In...

Background: Telemedicine is increasingly used to care for patients with movement disorders, but data regarding its global use are limited. Introduction: To obtain baseline international data about telemedicine use among movement disorder clinicians. Methods: An online survey was sent to all 6,056 Movement Disorder Society members in 2015. Scop...

A highly sensitive method was developed to measure putrescine by micellar electrokinetic chromatography with laser induced fluorescence detection with excellent linearity in the 1 nM to 3 μM range. The technique was tested on a drop of blood from Parkinson's disease patients obtained by finger prick. The results showed a statistically significant i...

Objective: On/off motor fluctuations in Parkinson disease (PD) can be associated with extreme mood fluctuations and severe dysphoria. The impact of these affective symptoms may be overlooked in the treatment of motor fluctuations. Our goal was to examine the relationship between motor fluctuations, their treatment status, and suicidality in PD par...

Importance Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome. Objective To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome. Design, Setting, and Participants The prospective International Deep Brain Stimulation Database and R...

Heat has been reported to exert variable effects on people with Gilles de la Tourette syndrome (TS). At age 24 years, a 32-year-old right-handed man with TS experienced a marked reduction in tics for two years after undergoing dehydration by entering a hot tub at 103°F (39.4°C) to 104°F (40.0°C) for 3 to 4 hours. On the Yale Global Tic Severity Sca...

Introduction: Dopaminergic therapy in Parkinson's disease (PD) can be associated with both motoric (e.g., dyskinesias) and neuropsychiatric adverse effects. Examples of the latter include Dopamine Dysregulation Syndrome (DDS) and impulse control disorder (ICD), which are separate but related behavioral/psychiatric complications of treatment in PD....

Over the past decade technological advances have created entirely new opportunities for studying and understanding neural circuits and brain activities. Meanwhile the expansion of therapeutic scope of Deep Brain Stimulation has continuously happened together with the improvement in precision of stimulation and neurosurgical implantation techniques....

The last one to make it to the operating room (OR) after surgery and anesthesia, intraoperative neuromonitoring (IONM) has now matured into a standard-of-care addition to most surgeries on parts of the central and peripheral nervous system that involve monitorable structures (such as sensory and motor pathways) and/or subject to elicitable response...

Objective: To determine whether providing remote neurologic care into the homes of people with Parkinson disease (PD) is feasible, beneficial, and valuable. Methods: In a 1-year randomized controlled trial, we compared usual care to usual care supplemented by 4 virtual visits via video conferencing from a remote specialist into patients' homes....

No disease modifying therapies for Parkinson's disease (PD) have been found effective to date. To properly power clinical trials for discovery of such therapies