Alberto J Espay

Alberto J Espay
University of Cincinnati | UC · Department of Neurology

MD, MSc, FAAN, FANA

About

522
Publications
113,973
Reads
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Introduction
My research efforts have focused on the measurement of motor and behavioral phenomena in, and clinical trials for, Parkinson's disease as well as in the understanding and management of functional movement disorders. We have initiated our phenotype-agnostic biomarker study (CCBP) to deploy bioassays aiming at matching available therapies to disease subtypes most suitable to benefit from them, regardless of clinico-pathologic classifications.
Additional affiliations
July 2005 - present
University of Cincinnati
Position
  • Professor (Associate)
July 2005 - present
University of Cincinnati
Position
  • Professor (Associate)
July 2005 - present
University of Cincinnati
Position
  • Professor (Associate)

Publications

Publications (522)
Article
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Past clinical trials of putative neuroprotective therapies have targeted PD as a single pathogenic disease entity. From an Oslerian clinicopathological perspective, the wide complexity of PD converges into Lewy bodies and justifies a reductionist approach to PD: A single-mechanism therapy can affect most of those sharing the classic pathological ha...
Article
Brain proteins function in their soluble, native conformation and cease to function when transformed into insoluble aggregates, also known as amyloids. Biophysically, the soluble-to-insoluble phase transformation represents a process of polymerization, similar to crystallization, dependent on such extrinsic factors as concentration, pH, and a nucle...
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Background: Brain amyloidosis does not invariably predict dementia. We hypothesized that high soluble 42-amino acid b amyloid (Ab42) peptide levels are associated with normal cognition and hippocampal volume despite increasing brain amyloidosis. Methods: This cross-sectional study of 598 amyloid-positive participants in the Alzheimer's Disease Neu...
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Introduction: We sought to examine whether levels of soluble alpha-synuclein (α-syn), amyloid-beta (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau), as measured in cerebrospinal fluid (CSF), are associated with changes in brain volume in Parkinson's disease. Methods: We assessed the 4-year change in total brain volume (n = 99) and baseli...
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Objective To describe a family with primary familial brain calcifications (PFBCs) and leukoencephalopathy associated with a novel variant in PDGFB . Methods We present 3 generations of a family with PFBC associated with a previously unreported variant in PDGFB . Results A 24-year-old woman with migraine, bipolar disorder, and functional neurologi...
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We evaluate the effect of droxidopa on gait and balance measures in nine patients with Parkinson's disease and neurogenic orthostatic hypotension. Computerized gait/balance analysis showed a significant effect of droxidopa in reducing postural sway. Future studies may determine if such effect translates into improvement in postural reflexes and fal...
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Background: The reliability of the Progressive Supranuclear Palsy Rating Scale (PSPRS) using teleneurology has not been assessed. Objectives: To test whether removing items inadequately assessed by video would impact measurement of PSP severity and progression. Methods: We performed secondary analyses of two data sets: the phase 2/3 trial of D...
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Protein aggregation into amyloid fibrils affects many proteins in a variety of diseases, including neurodegenerative disorders, diabetes, and cancer. Physicochemically, amyloid formation is a phase transition process, where soluble proteins are transformed into solid fibrils with the characteristic cross-β conformation responsible for their fibrill...
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Functional tremor is the most common functional movement disorder. It can be diagnosed with clinically definite certainty at the bedside by ascertaining its inconsistent (distractibility, frequency variability) and incongruent features (entrainment, ballistic suppression), requiring no additional neurological investigations except, in selected case...
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Long-read sequencing (LRS) technologies have been recently introduced to overcome intrinsic limitations of widely-used next-generation sequencing (NGS) technologies, namely the sequencing limited to short-read fragments (150–300 base pairs). Since its introduction, LRS has permitted many successes in unraveling hidden mutational mechanisms. One are...
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Background Movement disorders can be associated with anti-neuronal antibodies. Methods We conducted a systematic review of cases with documented anti-neuronal antibodies in serum and/or cerebrospi-nal fluid published in PubMed before April 1, 2020. Only patients with at least one movement disorder were included. We used random forests for variabl...
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Background: The dystonias are phenotypically and etiologically heterogenous disorders. Many proposals and a consensus recommendation have been provided for the diagnosis and classification of the dystonias, but these recommendations serve only as general guidelines. Current diagnosis and classification may still depend on clinical judgment causing...
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Background and Objectives To review the current evidence on the options available for initiating dopaminergic treatment of motor symptoms in early-stage Parkinson disease and provide recommendations to clinicians. Methods A multidisciplinary panel developed practice recommendations, integrating findings from a systematic review and following an In...
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Epilepsia partialis continua manifests as low-frequency, rhythmic involuntary movements of a focal body part. We report a young man, HIV-positive and with syphilis, who developed right-hand epilepsia partialis continua associated with a small left-sided cortico-subcortical frontal lesion. A pen and paper test provided ‘mechanographic’ data on frequ...
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We examined the role of the cerebellum in patients with tremor-dominant cervical dystonia by measuring the adaptive capacity of rapid reflexive eye movements (saccades). We chose the saccade adaptation paradigm because, unlike other motor learning paradigms, the real-time modification of saccades cannot “wait” for the sensory (visual) feedback. Ins...
Article
The occurrence of Functional Neurological Disorder (FND) and Somatic Symptom Disorder (SSD) in PD was not commonly accepted until recently, despite some evidence that emerged in the pre and early L-Dopa era. More recently, the recognition of FND and SSD were noted to be relevant for the management of PD. FND and SSD appear early in the course of PD...
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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...
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Background: Continuous, subcutaneous (SC) levodopa/carbidopa infusion with ND0612 is under development as a treatment for patients with Parkinson's disease (PD) and motor fluctuations. Objective: Evaluate 1-year safety data. Methods: BeyoND is an open-label study evaluating the long-term safety of two ND0612 dosing regimens. Results: Of the...
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Background Postural instability is a disease milestone signaling advanced disease.Objectives To estimate the onset of postural instability in monogenic parkinsonisms.Methods We systematically reviewed studies (PubMed 1996–2017) in SNCA, PRKN, PINK1, DJ-1, LRRK2, ATP13A2, FBXO7, VPS35, DNAJC6, or SYNJ1-related monogenic parkinsonisms, with documente...
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Background: Patients with bipolar spectrum disorders (BSDs) exhibit an increased risk of Parkinson's disease (PD). Objective: The aim is to investigate whether a previous diagnosis of BSDs influences the phenotype of PD. Methods: Of 2660 PD patients followed for at least 6 years (6-27), 250 (BSD-PD) had BSDs, 6-20 years before PD diagnosis; 48...
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Introduction Otological symptoms contribute to the disability of established Parkinson’s disease (PD). We sought to evaluate whether prodromal onset may affect PD progression. Methods A retrospective cohort design was used to compare time to advanced disease, defined as a Hoehn & Yahr stage ≥ 3 in consecutive PD patients with history of auditory a...
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Background Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. Objectives 1) To develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; 2) to evaluate whether presence of tremor associated with dystonia influences model pr...
Article
Purpose of Review Dopa-responsive dystonia (DRD) encompasses a group of phenotypically and genetically heterogeneous neurochemical disorders. Classic GTP cyclohydrolase 1 ( GCH-1 )-associated DRD consists of early-onset lower limb asymetrical dystonia, with sleep benefit, diurnal variation, and excellent and sustained response to low L-dopa doses....
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The gold standard for classification of neurodegenerative diseases is postmortem histopathology; however, the diagnostic odyssey of this case challenges such a clinicopathologic model. We evaluated a 60-year-old woman with a 7-year history of a progressive dystonia–ataxia syndrome with supranuclear gaze palsy, suspected to represent Niemann–Pick di...
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Background: Several monogenic causes for isolated dystonia have been identified, but they collectively account for only a small proportion of cases. Two genome-wide association studies have reported a few potential dystonia risk loci; but conclusions have been limited by small sample sizes, partial coverage of genetic variants, or poor reproducibi...
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The use of artificial intelligence (AI) to help diagnose and manage disease is of increasing interest to researchers and clinicians. Volumes of health data are generated from smartphones and ubiquitous inexpensive sensors. By using these data, AI can offer otherwise unobtainable insights about disease burden and patient status in a free-living envi...
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Objective To evaluate whether orthostatic hypotension (OH) or supine hypertension (SH) is associated with brain atrophy and white matter hyperintensities (WMH), we analyzed clinical and radiological data from a large multicenter consortium of patients with Parkinson’s disease (PD) and dementia with Lewy bodies (DLB). Methods Supine and orthostatic...
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The objective of this study is to examine the role of the cerebellum in the tremor-dominant subtype of cervical dystonia (CD). CD patients with head tremor at onset (Tr-CD) were age- and sex-matched to CD patients without head tremor at onset (nTr-CD). All patients were evaluated for cerebellar disability using the Scale for the Assessment and Rati...
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Introduction neurofilament light chain (NfL) levels have been proposed as reliable biomarkers of neurodegeneration in Parkinson’s disease (PD) but the relationship between plasma NfL, clinical subtypes of PD and motor progression is still debated. Methods plasma NfL concentration was measured in 45 healthy controls and consecutive 92 PD patients w...
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Background: In Parkinson’s disease (PD), there is heterogeneity in the clinical presentation and underlying biology. Research on PD subtypes aims to understand this heterogeneity with potential contribution for the knowledge of disease pathophysiology, natural history and therapeutic development. There have been many studies of PD subtypes but thei...
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Objective: We sought to test the hypothesis that technology could predict the risk of falls in Parkinson's disease (PD) patients with orthostatic hypotension (OH) with greater accuracy than in-clinic assessment. Methods: Twenty-six consecutive PD patients with OH underwent clinical (including home-like assessments of activities of daily living)...
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The Trial of Parkinson’s And Zoledronic acid (TOPAZ, https://clinicaltrials.gov/ct2/show/NCT03924414) is a unique collaboration between experts in movement disorders and osteoporosis to test the efficacy of zoledronic acid, an FDA-approved parenteral treatment for osteoporosis, for fracture prevention in people with neurodegenerative parkinsonism....
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Functional neurological (conversion) disorder (FND) was of great interest to early clinical neuroscience leaders. During the 20th century, neurology and psychiatry grew apart - leaving FND a borderland condition. Fortunately, a renaissance has occurred in the last two decades, fostered by increased recognition that FND is prevalent and diagnosed us...
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Background: Although the β-blocker propranolol is considered one of the most effective tremor treatments and other β-blockers are often prescribed to patients with tremor, those with partial β-agonist activity on β-adrenoreceptors can theoretically induce or exacerbate tremor. Here we report 2 patients with tremor induced or worsened by such β-blo...
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Background: In patients with Parkinson's disease (PD), sleep, mood, cognitive, autonomic, and other non-motor symptoms may fluctuate in a manner similar to motor symptoms. Objectives: To validate a final version of a patient-rated questionnaire that captures the presence and severity of non-motor fluctuations in levodopa-treated PD patients (NoM...
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Background: Urinary dysfunction and constipation, manifestations of pelvic floor dysfunction are common sources of disability and impaired quality of life in women with Parkinson's disease (PD). Objective: We sought to evaluate the pelvic floor health amongst women with PD and their reporting of bladder and bowel symptoms. Methods: We surveyed...
Article
Objective To evaluate the relationship between health-related quality of life (HR-QoL) and both physical and psychiatric factors in a large, international, multicentre cohort of patients with isolated dystonia, the Dystonia Coalition. Methods Natural history data from 603 patients with isolated dystonia (median age 57 years (IQR: 48 to 64 years),...
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Objective To evaluated three cases illustrating a rarely recognized phenotype of Parkinson disease (PD), namely biphasic levodopa-induced respiratory dysfunction manifesting as dyspnea. Methods To appreciate the nature of the fluctuations of respiratory function in response to levodopa, we measured changes in respiratory muscle control before and...
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Objective The expanding power and accessibility of personal technology provide an opportunity to reduce burdens and costs of traditional clinical site‐centric therapeutic trials in Parkinson’s disease and generate novel insights. The value of this approach has never been more evident than during the current COVID‐19 pandemic. We sought to (1) estab...
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Background: Copulatory or pelvic thrusting dyskinesia is a subtype of tardive dyskinesia (TD) which is caused by exposure to dopamine blocking agents. Phenomenology shown: A man exhibiting rhythmic, stereotypical pelvic thrusting movements. Educational value: Recognition of copulatory dyskinesia as a distinctive iatrogenic disorder helps preve...
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- New dopa-responsive phenotype expands the spectrum of GlyR antibody-associated PERM syndrome. - Appendicular rigidity with axial hypotonia and oculomotor abnormalities suggested hypodopaminergic tone. -Downstream effects GlyR antibody may interfere with the dopamine network.
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Many disease symptoms restrict the quality of life of the affected. This usually occurs indirectly, at least in most neurological diseases. Here, impaired daily function is interposed between the symptoms and the reduced quality of life. This is reflected in the International Classification of Function, Disability and Health model published by the...
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Genes associated with parkinsonism may also be implicated in carcinogenesis, but their interplay remains unclear. We systematically reviewed studies (PubMed 1967–2019) reporting gene variants associated with both parkinsonism and cancer. Somatic variants were examined in cancer samples, whereas germline variants were examined in cancer patients wit...
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Background: ND0612 is a continuous, subcutaneous levodopa/carbidopa delivery system in development for patients with Parkinson's disease (PD) experiencing motor fluctuationsObjective:Evaluate the efficacy and safety of two ND0612 dosing regimens in patients with PD. Methods: This was a 28-day open-label study (NCT02577523) in PD patients with ≥2...