John N Caviness

Mayo Foundation for Medical Education and Research | MMS · Department of Neurology

Myoclonus and other jerky movements form a large heterogeneous group of disorders. Clinical neurophysiology studies can have an important contribution to support diagnosis but also to gain insight in the pathophysiology of different kind of jerks. This review focuses on myoclonus, tics, startle disorders, restless legs syndrome, and periodic leg mo...

Background: The criteria for PD-MCI allow the use of global cognitive tests. Their predictive value for conversion from PD-MCI to PDD, especially compared to comprehensive neuropsychological assessment, is unknown. Methods: The MDS PD-MCI Study Group combined four datasets containing global cognitive tests as well as a comprehensive neuropsychol...

The objective of this study was to characterize network-level changes in nonfluent/agrammatic Primary Progressive Aphasia (agPPA) and Primary Progressive Apraxia of Speech (PPAOS) with graph theory (GT) measures derived from scalp electroencephalography (EEG) recordings. EEGs of 15 agPPA and 7 PPAOS patients were collected during relaxed wakefulnes...

Clinical neurophysiologic testing plays a critical role as a complement to the clinical assessment in patients who are being evaluated for a variety of neurologic symptoms. Many different techniques and methods of assessment can be used to evaluate the function of the nervous system, including electroencephalography, electromyography, evoked potent...

Clinical neurophysiologic testing plays a critical role as a complement to the clinical assessment in patients who are being evaluated for a variety of neurologic symptoms. Many different techniques and methods of assessment can be used to evaluate the function of the nervous system, including electroencephalography, electromyography, evoked potent...

Clinical neurophysiologic testing plays a critical role as a complement to the clinical assessment in patients who are being evaluated for a variety of neurologic symptoms. Many different techniques and methods of assessment can be used to evaluate the function of the nervous system, including electroencephalography, electromyography, evoked potent...

Background Past research has demonstrated that clinical EEG is sensitive to dementia associated with Alzheimer's (AD) and Parkinson’s diseases (PD), and nonfluent/agrammatic Primary Progressive Aphasia (agPPA), but not Primary Progressive Apraxia of Speech (PPAOS). However, clinical EEG studies do not quantify interactions of multiple brain areas,...

Objectives Update data for diagnostic accuracy of a clinical diagnosis of Parkinson’s disease (PD) using neuropathological diagnosis as the gold standard. Methods Data from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) was used to determine the predictive value of a clinical PD diagnosis. Two clinical diagnostic confidence le...

Introduction: There is limited data in the scientific literature using quantitative methods to assess response of golfer's cramp to intervention. The objective of this pilot study was to use quantitative measures to study the effect of propranolol and looking at the hole when putting. Methods: 14 golfers completed 50 10' putts (10 each x 5 condi...

Objective: There are few neuropathological studies on Parkinson's disease with mild cognitive impairment (PD-MCI). Those published reveal coexisting Lewy body and Alzheimer's disease pathology. Our objective is to determine the pathology that underlies PD-MCI. Methods: We used data from the Arizona Study of Aging and Neurodegenerative Disorders,...

Genetically determined myoclonus disorders are a result of a large number of genes. They have wide clinical variation and no systematic nomenclature. With next‐generation sequencing, genetic diagnostics require stringent criteria to associate genes and phenotype. To improve (future) classification and recognition of genetically determined movement...

This study was designed to correlate clinical findings with the extent of pathologic a-synuclein (aSyn) in the brain using the Unified Staging System for Lewy Body disorders (USSLB). Data from 280 cases from the Arizona Study of Aging and Neurodegenerative Disorders are presented. Each case had a complete USSLB staging and at least 1 full research...

Background: Neuropathology has demonstrated a high rate of comorbid pathology in dementia due to Alzheimer's disease (ADD). The most common major comorbidity is Lewy body disease (LBD), either as dementia with Lewy bodies (AD-DLB) or Alzheimer's disease with Lewy bodies (AD-LB), the latter representing subjects with ADD and LBD not meeting neuropa...

Myoclonus is common in neurodegenerative disorders and may be in small or large amplitude. In dementia with Lewy bodies, it occurs as moderately sized jerks in about 1/3 of cases. The combination of dementia, early parkinsonism, hallucinations, cognitive fluctuations, and myoclonus is strongly suggestive of the dementia with Lewy body diagnosis. Th...

Neuropathology has demonstrated a high rate of comorbid pathology in dementia due to Alzheimer disease (ADD). The most common major comorbidity is Lewy body disease (LBD), either as dementia with Lewy bodies (AD-DLB) or Alzheimer disease with Lewy bodies (AD-LB), the latter representing subjects with ADD and LBD not meeting neuropathological distri...

Many studies have been directed at understanding mechanisms of tau aggregation and therapeutics, nearly all focusing on the brain. It is critical to understand the presence of tau in peripheral tissues since this may provide new insights into disease progression and selective vulnerability. The current study sought to determine the presence of sele...

Background: Past research has demonstrated that electroencephalography (EEG) is sensitive to what we now know as Primary Progressive Aphasia (PPA); however, the EEG profiles of patients with Primary Progressive Apraxia of Speech (PPAOS) and PPA, in the context of current consensus criteria, have not been studied. Aims: The primary goal of this stud...

Objective Identify clinical features predictive of Lewy body pathology in AD patients in an ongoing longitudinal clinicopathologic study. Material & Methods We queried the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) database for dementia cases with AD pathology (1997‐2015). Subjects received longitudinal comprehensive clinical...

Purpose: To determine whether quantitative methods could separate golfers with a possible dystonic cause of the "yips" from those that appear to be non-dystonic. Methods: 27 golfers completed 10 two-handed and 10 right hand only putts. Surface EMG assessed forearm muscle co-contraction and motion detectors monitored wrist and putter movements. B...

Inability to accurately diagnose Lewy type alpha-synucleinopathy (LTS) pre-mortem has been a major obstacle to clinical care and research. Probable REM sleep behavior disorder (PRBD) diagnosed with support of instruments such as the Mayo Sleep Questionnaire (MSQ) may provide a cost effective means of predicting LTS. Since 2007, 602 subjects in the...

Background and purpose: Mutations in the glucocerebrosidase (GBA) gene are known to be a risk factor for Parkinson's disease (PD). Data on clinicopathological correlation are limited. The purpose of this study was to determine the clinicopathological findings that might distinguish PD cases with and without mutations in the GBA gene. Methods: Da...

Introduction: Depression and neuropsychiatric disorders in individuals with essential tremor (ET) are not well characterized in the literature. Methods: We compared 104 ET subjects with 481 non-ET controls involved in the Arizona Study of Aging and Neurodegenerative Disorders. An analysis of baseline depression scales and neuropsychiatric invent...

Introduction: The key mechanisms that connect Parkinson's disease pathology with dementia are unclear. We tested the hypothesis that the quantitative spectral electroencephalographic measure, delta bandpower, correlates with Lewy type synucleinopathy on pathological examination in Parkinson's disease. As a corollary hypothesis, we analyzed whether...

Objective: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. Methods: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the Unite...

Background: The aim of this postmortem study was to compare, in Parkinson's disease subjects with and without bilateral subthalamic nucleus deep brain stimulation (STN-DBS), the loss of pigmented neurons within the substantia nigra and pathological alpha-synuclein density within the SN and other brain regions. Methods: PD subjects were identifie...

Background Myoclonus may occur after hypoxia. In 1963, Lance and Adams described persistent myoclonus with other features after hypoxia. However, myoclonus occurring immediately after hypoxia may demonstrate different syndromic features from classic Lance–Adams syndrome (LAS). The aim of this review is to provide up-to-date information about the sp...

Purpose – The purpose of this paper is: first, to present a qualitative descriptive case study of the Mayo Clinic leadership and organization development philosophy and approach; second, to summarize a strategy for using intentional organization design as a foundation for culturally aligned physician leadership development and third, to describe th...

Introduction: Quantitative EEG features have been identified as surrogates and predictors of cognitive decline/dementia, a common feature of progressive PD. The biochemical correlates for altered quantitative EEG features are unknown. Our primary objective was to test the hypothesis that quantitative EEG measures correlate with cortical levels of...

Objectives: To determine what differences exist in graph theory network measures derived from electroencephalography (EEG), between Parkinson's disease (PD) patients who are cognitively normal (PD-CN) and matched healthy controls; and between PD-CN and PD dementia (PD-D). Methods: EEG recordings were analyzed via graph theory network analysis to...

Movement-related cortical potentials (MRCPs) are EEG potentials that occur with movement and are recorded using surface scalp electrodes. A technique termed “EEG-EMG back-averaging” is used to obtain MRCPs. The earliest recordable MRCP is the Bereitschaftspotential or readiness potential. Special EEG averaging techniques may also be used to study t...

A battery of tools is used to provide neurophysiological characteristics of movement disorders, including EMG, EEG, EEG-EMG with back-averaging, evoked potentials, and long-latency EMG reflexes. Surface EMG forms the foundation of movement neurophysiology and can clarify muscle discharge timing and spatial relationships, as well as frequency inform...

Long latency reflexes (LLRs) are EMG activity occurring during the transition from reflex to voluntary motor activity, which probably arise from a transcortical loop, including afferents within the dorsal column/medial lemniscal system to the sensorimotor cortex and corticospinal tract efferents. Depending upon the site of a lesion and its pathophy...

Objective: To identify a panel of peripheral inflammatory/immune mediators that could discriminate Parkinson disease with dementia (PDD) from Parkinson disease (PD) without dementia. Methods: Plasma samples from 52 patients with PD and 22 patients with PDD were prepared from freshly collected blood following an institutional review board-approve...

Evidence of inflammation has been consistently associated with pathology in Parkinson’s disease (PD)-affected brains, and has been suggested as a causative factor. Dopaminergic neurons in the substantia nigra (SN) pars compacta, whose loss results in the clinical symptoms associated with PD, are particularly susceptible to inflammatory damage and o...

Background: Clinical misdiagnosis, particularly at early disease stages, is a roadblock to finding new therapies for Lewy body disorders. Biopsy of a peripheral site might provide improved diagnostic accuracy. Previously, we reported, from both autopsy and needle biopsy, a high prevalence of submandibular gland synucleinopathy in Parkinson's disea...

Although there are studies investigating the pathologic origins of mild cognitive impairment (MCI), they have revolved around comparisons to normal elderly individuals or those with Alzheimer's disease (AD) or other dementias. There are few studies directly comparing the comprehensive neuropathology of amnestic (aMCI) and nonamnestic (naMCI) MCI. T...

Importance Identifying measures that are associated with the cytosine-adenine-guanine (CAG) expansion in individuals before diagnosis of Huntington disease (HD) has implications for designing clinical trials.Objective To identify the earliest features associated with the motor diagnosis of HD in the Prospective Huntington at Risk Observational St...

Background and purpose: It is believed that progressive Lewy-type synucleinopathy (LTS) is primarily responsible for the worsening of motor and non-motor Parkinson's disease (PD) signs and symptoms. Characterization of quantitative electroencephalography (QEEG) abnormalities across the spectrum of LTS to PD dementia (PD-D) may provide insight into...

Background: In Huntington disease (HD), cognitive changes due to disease-progression or treatment are potentially confounded by "practice effects" (PE) - performance improvement from prior exposure to test materials. Objective: A practice run-in ("dual baseline") was used in an HD cognitive trial to determine if PE could be minimized and evaluat...

Orthostatic tremor (OT) is defined by the presence of a high-frequency (13-18 Hz) tremor of the legs upon standing associated with a feeling of unsteadiness. However, some patients have discharge frequencies of <13 Hz, so-called "slow OT". The aim of this study was to characterize patients with unsteadiness upon standing found to have <13 Hz tremor...

Background Hyposmia is common in Parkinson's disease (PD) and is also observed with normal aging. It can be ascertained through objective testing, but it is unclear whether patients are aware of deficits and whether this has implications for cognitive status.Methods Subjects in the Arizona Study of Aging and Neurodegenerative Disorders were studied...

Dysphagia is common in Parkinson's disease (PD) and causes significant morbidity and mortality. PD dysphagia has usually been explained as dysfunction of central motor control, much like other motor symptoms that are characteristic of the disease. However, PD dysphagia does not correlate with severity of motor symptoms nor does it respond to motor...

The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain-only donations and currently has banked more than 1600 brains. More than 430 whole-body donations have been received since this service was commenced in 2005. The collective academic output of th...

Introduction: The frequency and causes of hypertrophic olivary degeneration (HOD) are unknown. We compared the clinical and radiological characteristics of unilateral HOD and bilateral HOD. Methods: We performed a search of a radiologic report database for patients who were radiologically diagnosed as having HOD. This database includes the patie...

Background: QEEG could provide physiological biomarkers for changes over time in Parkinson's disease (PD) cognitive decline if they track with longitudinal neuropsychological performance. Objective: Our aim was to correlate longitudinal changes in frequency domain quantitative electroencephalography (QEEG) measures with change in neuropsychological...

The pathologic changes of Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP) have been reported to coexist, but whether PSP pathology modifies the clinical course of those individuals is unknown. The aim of this study was to determine whether clinical features of pathologically confirmed PD subjects with concomitant PSP pathology dif...

Objective Previous research has linked complex or formed visual hallucinations (VH) to Lewy-type alpha-synucleinopathy (LTS) in neocortical and limbic areas. As Alzheimer’s disease pathology often co-occurs with LTS, we questioned whether this pathology - amyloid plaques and neurofibrillary tangles - might also be linked to VH. Methods We performe...

Background: Olfactory dysfunction in Parkinson's disease (PD) is well-established and may represent one of the earliest signs of the disease. Objective & methods: The objective of this study was to evaluate the relationship of olfactory dysfunction, using the University of Pennsylvania Smell Identification Test (UPSIT), to clinical and pathologi...

Background: "Practice effects" (PE), or performance improvements due to prior exposure to testing, are known to confound cognitive test results, particularly when short intervals occur between two test sessions. Objective: We examined two subsamples with short or long re-test intervals from a recent clinical trial. Methods: Thirty-four non-dep...

Objectives: Determine diagnostic accuracy of a clinical diagnosis of Parkinson disease (PD) using neuropathologic diagnosis as the gold standard. Methods: Data from the Arizona Study of Aging and Neurodegenerative Disorders were used to determine the predictive value of a clinical PD diagnosis, using 2 clinical diagnostic confidence levels, Poss...

Introduction Many clinicopathological studies do not specify the presence of other pathologies located within the brain, so disease heterogeneity may be under appreciated. Objective The purpose of this study was to determine the frequencies of concomitant pathologies among parkinsonian disorders. Methods Data from the Arizona Study of Aging and N...

The objective of this study was to evaluate citalopram for executive functioning in Huntington's disease (HD). The study was randomized, double-blind, and placebo-controlled. Thirty-three adults with HD, cognitive complaints, and no depression (Hamilton Depression [HAM-D] rating scale ≤12) were administered citalopram 20 mg or placebo (7 visits, 20...

Advancements in neuroscience have uncovered an amazing complexity of connectivity between nuclei sites and circuits within the brain. Moreover, clinical and neuropathological study has revealed diffuse involvement of the nervous system in Parkinson's disease associated with early and/or significant clinical symptoms. Behavior manifestations in Park...

Existing reports on the frequencies of neurodegenerative diseases are typically based on clinical diagnoses. We sought to determine these frequencies in a prospectively assessed, community-based autopsy series. Included subjects had normal cognitive and movement disorder assessments at study entry. Of the 119 cases meeting these criteria, 52% were...

Synucleinopathies are a broad class of neurodegenerative disorders characterized by the presence of intracellular protein aggregates containing α-synuclein protein. The aggregated α-synuclein protein is hyperphosphorylated on serine 129 (S129) compared to the unaggregated form of the protein. While the precise functional consequences of S129 hyperp...

Data regarding autonomic function in restless legs syndrome (RLS) are limited to heart rate and blood pressure changes in cases with periodic limb movements (PLMS). We compared autonomic symptoms of 49 subjects with RLS vs 291 control subjects using the Scales for Outcome in Parkinson disease-Autonomic (SCOPA-AUT) questionnaire, consisting of 23 it...

Myoclonus creates significant disability for patients. This symptom or sign can have many different etiologies, presentations, and pathophysiological mechanisms. A thorough evaluation for the myoclonus etiology is critical for developing a treatment strategy. The best etiological classification scheme is a modified version from that proposed by Mar...

The etiology and natural history of Parkinson's disease (PD) are not well understood. Some non-motor symptoms such as hyposmia, rapid eye movement sleep behavior disorder, and constipation may develop during the prodromal stage of PD and precede PD diagnosis by years. To discuss the promise and pitfalls of research on pre-motor symptoms of PD and t...

Background Hippocampal sclerosis (HS) is a neuropathological finding that frequently occurs with pathologies, such as Alzheimer's disease (AD). Prevalence estimates of HS in autopsy-confirmed dementia samples have varied between 0.4% and 24.5%. However, the prevalence of HS within other pathologic groups has not been well characterized. Methods Ut...

Dysphagia is very common in patients with Parkinson disease (PD) and often leads to aspiration pneumonia, the most common cause of death in PD. Current therapies are largely ineffective for dysphagia. Because pharyngeal sensation normally triggers the swallowing reflex, we examined pharyngeal sensory nerves in PD patients for Lewy pathology.Sensory...

Parkinson disease (PD) is a neurodegenerative disease primarily characterized by cardinal motor manifestations and CNS pathology. Current drug therapies can often stabilize these cardinal motor symptoms, and attention has shifted to the other motor and nonmotor symptoms of PD that are resistant to drug therapy. Dysphagia in PD is perhaps the most i...

Modifications of α-synuclein resulting in changes in its conformation are considered to be key pathological events for Lewy body diseases (LBD), which include Parkinson's disease (PD) and dementia with Lewy bodies (DLB). We have previously described a histopathological Unified Staging System for LBD that classifies the spread of α-synuclein phospho...

Dementia is a frequent complication of Parkinson's disease (PD). About half of PD dementia (PDD) is hypothesized to be due to progression of the underlying Lewy body pathology into limbic regions and the cerebral cortex while the other half is thought to be due to coexistent Alzheimer's disease. Clinically, however, these are indistinguishable. The...

Objective: To compare autonomic function of subjects with Parkinson's disease (PD) and essential tremor (ET) relative to controls. Background: It has been reported that patients with PD have autonomic dysfunction while no literature exists regarding autonomic function in ET. Methods: Subjects with PD, ET, and controls had autonomic function me...

Dysphagia (impaired swallowing) is common in patients with Parkinson disease (PD) and is related to aspiration pneumonia, the primary cause of death in PD. Therapies that ameliorate the limb motor symptoms of PD are ineffective for dysphagia. This suggests that the pathophysiology of PD dysphagia may differ from that affecting limb muscles, but lit...

High-density electroencephalography (EEG) was used to evaluate cortical activity patterns during the auditory processing of speech presented at various levels of degradation in a sentence verification task. 25 healthy participants listened to true-false sentences produced with one of 3 channel levels (1, 6, 16), ranging from unintelligible, moderat...

A key component in Lewy body (LB) pathology in LB disorders is α-synuclein phosphorylated at serine 129 (pαsyn). However, it is not known if increase in the level of biochemically measurable pαsyn precedes the presence of histologically identified Lewy-type synucleinopathy (LTS). To gain sights into possible temporal sequence, we measured levels of...

Segmental myoclonus is defined as rhythmic or semi-rhythmic involuntary contractions of muscle groups supplied by one or more contiguous segments of the brainstem and/or spinal cord. This movement is caused by a central nervous system generator which arises from circumscribed interneuron pools along the craniospinal neuraxis that are normally conce...

Orthostatic tremor (OT) is a disabling movement disorder manifested by postural and gait disturbance. Primarily a condition of elderly people, it can be progressive in up to 15% of patients. The primary treatments are medications that are often ineffective. A 75-year-old male presented with a 10-year history of progressive and disabling OT. He had...

There is a growing interest in presymptomatic diagnosis of Parkinson's disease (PD), but the best and most practical method to screen and confirm asymptomatic individuals for PD needs further study. The Banner-Sun Health Brain and Body Donation program in Sun City, Arizona has studied primarily PD and Alzheimer's disease. Enrollees receive annual p...

The pathology of essential tremor is increasingly being studied; however, there are limited studies of biochemical changes in this condition. We studied several candidate biochemical/anatomical systems in the brain stem, striatum, and cerebellum of 23 essential tremor subjects who came to autopsy, comparing them with a control population. Striatal...

Myoclonus can be classified as physiologic, essential, epileptic, and symptomatic. Animal models of myoclonus include DDT and posthypoxic myoclonus in the rat. 5-Hydrotryptophan, clonazepam, and valproic acid suppress myoclonus induced by posthypoxia. The diagnostic evaluation of myoclonus is complex and involves an extensive work-up including basi...

Special EEG averaging techniques may be used to study the cortical processes underlying movement and cognition. Movement-related potentials and contingent negative variation are observed before a voluntary movement occurs. The P300 and other event-related potentials provide electrophysiologic correlates of perception and cognition.

LLRs and the silent period are EMG phenomena that reflect the complex interplay of spinal, brain stem, and cortical influences in motor control. These techniques have been applied to the study of disorders of motor control such as Parkinson’s disease, Huntington’s disease, and dystonia. Abnormalities of these reflexes may help to detect lesions of...

Surface EMG, EEG, and elicited response results provide a simple and noninvasive means of studying movement disorders. These techniques are particularly helpful in classifying involuntary movements such as tremor and myoclonus. In addition, EMG can assist with designing and performing botulinum toxin injections.