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John N Caviness

Publications and source records attributed to John N Caviness.

At least 19 recordsLinked to original sources
PubMed2006

Clinical-pathologic study of biomarkers in FTDP-17 (PPND family with N279K tau mutation).

The objective of this clinical-pathologic study was to identify biomarkers for a pallidopontonigral degeneration (PPND) kindred of frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) harboring the N279K tau mutation. Five affected subjects, one at-risk who later became symptomatic, and one at-risk asymptomatic mutation carrier, had abnormal (18)fluorodeoxyglucose PET demonstrating asymmetric temporal lobe hypometabolism. All except the asymptomatic mutation carrier had abnormal brain MRI. Parkinsonism, myoclonus, anosmia, insomnia, speech, and autonomic dysfunction were identified. Autopsy of six affected subjects showed frontotemporal degeneration with extensive tauopathy. Further studies of FTDP-17 patients are needed to replicate these findings.

Adult↗
PubMed2006

Corticomuscular coherence is increased in the small postural tremor of Parkinson's disease.

The mechanisms and electrophysiological characteristics of the postural tremor in Parkinson's disease (PD) have not been defined. We hypothesized that PD subjects with small amplitude postural tremor would show increased corticomuscular coherence at certain frequencies compared to PD subjects without visible tremor. Four groups of participants were studied: (1) Control without postural tremor, (2) Control with small amplitude postural tremor, (3) PD without postural tremor, and (4) PD with small amplitude postural tremor. Accelerometry and electroencephalography-electromyography fast-fourier transform and corticomuscular coherence spectra were generated. Findings showed (1) elevated corticomuscular coherence centered at 12-18 Hz in PD with small amplitude postural tremor; (2) 5-12 Hz accelerometer frequency peaks that did not shift with increasing weight loads in some individuals; and (3) 5-8 Hz accelerometer peaks that shifted frequency with increasing weight loads, consistent with a peripheral-mechanical oscillator in all groups. The small amplitude postural tremor in PD arises from heterogeneous oscillator mechanisms. The discovery of increased corticomuscular coupling shows cortical involvement in the small amplitude postural tremor of PD.

Aged↗
PubMed2006

Speech characteristics of patients with pallido-ponto-nigral degeneration and their application to presymptomatic detection in at-risk relatives.

PURPOSE: This report describes the speech characteristics of individuals with a neurodegenerative syndrome called pallido-ponto-nigral degeneration (PPND) and examines the speech samples of at-risk, but asymptomatic, relatives for possible preclinical detection. METHOD: Speech samples of 9 members of a PPND kindred were subjected to perceptual characterization. Speech deterioration patterns were reported for 2 participants followed longitudinally at 6-month intervals. Cross-sectional findings were reported for 3 participants at various stages of disease. Longitudinal and cross-sectional findings were used to guide the examination of 4 at-risk, but asymptomatic, participants. RESULTS: Results revealed a progressive mixed dysarthria with hypokinetic, spastic, and flaccid features. It was characterized primarily by vocal tremor and high-frequency vocal flutter, speaking rate abnormalities most often in the direction of slowing, and a tendency toward monopitch. Dysarthria progression was marked by exacerbation and increasing severity of early features, progressive decrease in spontaneous speech output, verbal perseverations, and eventual mutism. Results for at-risk participants revealed preclinical speech abnormalities that preceded other motor signs. Speech results were examined in light of available autopsy findings for site of lesion associations. CONCLUSION: The dysarthria of PPND is an early harbinger of disease onset. It has a mixed presentation, with hypokinetic, spastic, and flaccid features.

Cross-Sectional Studies↗
PubMed2006

Analysis of high-frequency electroencephalographic-electromyographic coherence elicited by speech and oral nonspeech tasks in Parkinson's disease.

PURPOSE: Corticomuscular electroencephalographic-electromyographic (EEG-EMG) coherence elicited by speech and nonspeech oromotor tasks in healthy participants and those with Parkinson's disease (PD) was examined. Hypotheses were the following: (a) corticomuscular coherence is demonstrable between orbicularis oris (OO) muscles' EMG and scalp EEG recording; (b) the presence, location, and magnitude of coherence is task specific; (c) differences in corticomuscular coherence patterns exist between healthy and PD participants; and (d) differences will manifest as either increased or decreased coherence values in certain frequency bands, with EEG localization at primary sensorimotor cortex and/or supplementary motor area (SMA). METHOD: Simultaneous EEG, EMG (OO), and speech samples were recorded on 20 healthy and 20 PD participants during speech and nonspeech tasks. Fast Fourier transform and coherence analysis was performed with Neuroscan software on 1,000 randomly generated epochs per task per group. Corticomuscular coherence was analyzed between each EEG electrode and right and left superior and inferior OO muscles up to 200 Hz. Significant coherence peaks exceeded 95% confidence limits (.003). RESULTS: Corticomuscular coherence existed for both groups and for all tasks, but to varying degrees in primary sensorimotor cortex and SMA. CONCLUSIONS: Results support task specificity for both groups and, in PD, a diminished modulation flexibility linked to the sensorimotor area and reduced corticomuscular coherence at the SMA.

Acoustic Stimulation↗
PubMed2005

Increased tau burden in the cortices of progressive supranuclear palsy presenting with corticobasal syndrome.

The objective of this study is to better define the pathological characteristics of pathologically proven progressive supranuclear palsy (PSP) presenting with the corticobasal syndrome (CBS). PSP is characterized by early falls, vertical supranuclear ophthalmoplegia, and axial rigidity, whereas asymmetric limb features, including rigidity, bradykinesia, apraxia, alien limb phenomena, and cortical sensory loss are characteristic of CBS. We investigated clinicopathological characteristics of 5 cases of PSP that presented with CBS (CBS-PSP). Comprehensive pathological analysis was undertaken to determine the presence of concomitant pathological processes as well as quantitative tau burden in cortical regions of CBS-PSP, compared with 8 typical PSP cases (Typ-PSP). The clinical features in the CBS-PSP cases included asymmetrical features, apraxia, alien limb phenomena, and progressive aphasia. All cases had Parkinsonism, and vertical supranuclear ophthalmoplegia was noted in all but 1 case of CBS-PSP. Secondary neuropathological diagnoses included argyrophilic grain disease (AGD) in 1 of the 8 cases of Typ-PSP, whereas Alzheimer's disease (AD), Lewy body disease, AGD, and vascular disease was found in 3 cases of CBS-PSP. Image analysis of cortical tau burden performed in 8 Typ-PSP and 3 CBS-PSP cases revealed a significant increased tau burden in mid-frontal and inferior-parietal cortices in the CBS-PSP cases. This study demonstrates that when PSP presents as CBS, it is most likely due to either a concurrent cortical pathology from a secondary process such as AD or from the primary pathology of PSP extending into cortical areas that are primarily and commonly affected in CBD.

Aged↗
PubMed2004

Botulinum toxin type A for treating voice tremor.

BACKGROUND: Voice tremor, like spasmodic dysphonia and other tremor disorders, may respond to botulinum toxin type A injections. OBJECTIVE: To evaluate the safety and efficacy of botulinum toxin type A injections as treatment for voice tremor. DESIGN: A randomized study of 3 doses of botulinum toxin type A with 6 weeks of follow-up. SETTING: A single-site tertiary care center. PARTICIPANTS AND METHODS: Thirteen subjects (11 women, 2 men; mean age, 73 years) with voice tremor and no spasmodic dysphonia or head, mouth, jaw, or facial tremor were entered into this study. Patients received 1.25 U (n = 5), 2.5 U (n = 5), or 3.75 U (n = 3) of botulinum toxin type A in each vocal cord. All patients were evaluated at baseline and postinjection at weeks 2, 4, and 6. MAIN OUTCOME MEASURES: The primary outcome measure was the patient tremor rating scale, with secondary measures including patient-rated functional disability, response rating scale, independent randomized tremor ratings, and acoustical measures. RESULTS: All patients at all dose levels noted an effect from the injection. The mean time to onset of effect was 2.3 days (range, 1-7 days). For all patients combined, mean tremor severity scale scores (rated by patients on a 5-point scale) improved 1.4 points at week 2, 1.6 points at week 4, and 1.7 points at week 6. Measures of functional disability, measures of the effect of injection, independent ratings of videotaped speech, and acoustic measures of tremor also showed improvement. The main adverse effects at all doses were breathiness and dysphagia. CONCLUSION: Voice tremor improves following injections of botulinum toxin type A.

Aged↗
PubMed2004

Myoclonus: current concepts and recent advances.

Myoclonus presents as a sudden brief jerk caused by involuntary muscle activity. An organisational framework is crucial for determining the medical significance of the myoclonus as well as for its treatment. Clinical presentations of myoclonus are divided into physiological, essential, epileptic, and symptomatic. Most causes of myoclonus are symptomatic and include posthypoxia, toxic-metabolic disorders, reactions to drugs, storage disease, and neurodegenerative disorders. The assessment of myoclonus includes an initial screening for those causes that are common or easily corrected. If needed, further testing may include clinical neurophysiological techniques, enzyme activities, tissue biopsy, and genetic testing. The motor cortex is the most commonly shown myoclonus source, but origins from subcortical areas, brainstem, spinal, and peripheral nervous system also occur. If treatment of the underlying disorder is not possible, treatment of symptoms is worthwhile, although limited by side-effects and a lack of controlled evidence.

Animals↗
PubMed2003

Cortical myoclonus during lithium exposure.

BACKGROUND: Myoclonus can occur in association with lithium therapy at toxic and therapeutic dosages, and can be a predominant and disabling adverse effect. Moreover, myoclonus has been reported when lithium has been combined with cyclic antidepressants and with the neuroleptic clozapine. Although clinical case reports exist, no electrophysiologic data are available that provide a source or a neurophysiological mechanism for the myoclonus seen in lithium therapy. OBJECTIVE: To describe the electrophysiologic characteristics and source of the myoclonus associated with lithium therapy. DESIGN AND METHODS: We retrospectively analyzed 5 cases of myoclonus during lithium therapy. We reviewed the clinical features and results of previous electrophysiologic testing. Four patients received lithium monotherapy; and 1, sertraline hydrochloride and nefazodone hydrochloride in addition to lithium. The electrophysiologic data that had been gathered included multichannel surface electromyographic (EMG) recordings with simultaneous electroencephalography (EEG), somatosensory evoked potentials, and elicitation of long-latency EMG reflexes to median and digital nerve stimulation. RESULTS: All 5 patients showed multifocal action myoclonus without reflex activation and only rare occurrence at rest. In each case, back-averaging created a focal EEG transient over the contralateral sensorimotor area preceding the myoclonus EMG discharge. In 2 of the patients receiving lithium monotherapy, the therapy was discontinued and the myoclonus disappeared. CONCLUSIONS: Lithium, by itself, can be associated with prominent clinical myoclonus, short-duration (<50-millisecond) myoclonus EMG discharges and cortical action myoclonus without the presence of epileptiform abnormalities on the routine EEG. This myoclonus is different from the most common form that is well documented to occur with tricyclic antidepressant therapy by clinical and electrophysiologic means.

Adult↗
PubMed2003

Randomized trial of modafinil for treating subjective daytime sleepiness in patients with Parkinson's disease.

We assessed the safety and efficacy of modafinil for the treatment of excessive daytime sleepiness in patients with Parkinson's disease (PD). This was a single-site, randomized, double-blind, placebo-controlled crossover study of 21 PD patients having an Epworth Sleepiness Scale (ESS) score > or =10. They received either placebo or modafinil 200 mg/day for 3 weeks, followed by a washout week, then the alternate treatment for 3 weeks. The ESS data demonstrated a carryover effect, so the changes from baseline ESS scores were compared between the two treatments for period 1 only. The ESS scores for the placebo group went from 16.0 +/- 4.2 (mean +/- SD) to 17.0 +/- 5.1 and for the modafinil group went from 17.8 +/- 4.2 to 14.4 +/- 5.7 (P = 0.039). There was no significant carryover effect for any other measure. The patient Clinical Global Impression of Change (+3 to -3) improved by 0.75 on modafinil compared with 0.15 for placebo (P = 0.07). A total of 7 of 20 (35%) of the patients reported some improvement on modafinil but not placebo. There was no significant improvement or worsening of the UPDRS subscores I-III, Timed Tap test, or time on. Vital signs, electrocardiograms, and lab tests were unchanged. Modafinil was very well tolerated. Our data demonstrate that, in a small sample size, administration of 200 mg/day of modafinil was associated with few side effects and was modestly effective for the treatment of excessive daytime sleepiness in patients with PD.

Adult↗
PubMed2003

Abnormal corticomuscular coherence is associated with the small amplitude cortical myoclonus in Parkinson's disease.

Coherence is the degree of time-locked correlation between two signals as a function of frequency. The purpose of this study was to test the following hypotheses: (1) corticomuscular coherence is abnormally increased in those Parkinson's disease (PD) patients with small amplitude cortical myoclonus, and (2) corticomuscular coherence peaks around the time of the myoclonus electromyographic (EMG) discharge. We studied Parkinson's disease patients with and without myoclonus and controls. The data were digitally collected and processed off-line with EMG rectification, creation of 511-msec epochs, Fast-Fourier transform, and coherence analysis. In the 12 to 30 Hz frequency band, but not at 30 to 60 Hz or above, coherence peaks were observed in the PD subjects with myoclonus that were significantly greater than in the control subjects (P < 0.001) and in PD subjects without myoclonus (P < 0.001). The abnormal coherence values are evidence for abnormal rhythmic activity in cortical motor areas in those Parkinson's disease patients with myoclonus. In combination with previous findings on back-averaging, our results show that this myoclonus occurs when neuronal populations are driven to an extreme amount of synchronous activity with higher corticomuscular coherence values. These results have mechanistic implications for cortical dysfunction in Parkinson's disease and for cortical myoclonus in general.

Aged↗
PubMed2003

Clinical-electrophysiological correlation of tremor and myoclonus in a kindred with the N279K tau mutation.

We used electrophysiological methods to study the hyperkinetic movement disorders in a pallido-ponto-nigral degeneration (PPND) family, which harbors the N279K tau gene mutation. Our purpose was to: (1). characterize the tremor patterns, (2). characterize the myoclonus physiology, (3). determine whether electrophysiology can detect abnormalities in asymptomatic cases. In PPND, we found that the activation tremors correlated with a semi-rhythmic 6-10 Hz electromyography (EMG) pattern, and the rest tremors showed a reciprocal 4-6 Hz pattern. At least two different myoclonus physiology patterns exist in PPND, most notably contrasted by the presence or absence of a demonstrable electroencephalography (EEG) correlate. Electrophysiology yielded remarkable findings in those asymptomatic at-risk individuals that carried the N279K tau mutation.

Electromyography↗
PubMed2003

Myoclonus and neurodegenerative disease--what's in a name?

Myoclonus is a clinical symptom (or sign) defined as sudden, brief, shock-like, involuntary movements caused by muscular contractions or inhibitions. It may be classified by examination findings, etiology, or physiological characteristics. The main physiological categories for myocolonus are cortical, cortical-subcortical, subcortical, segmental, and peripheral. Neurodegenerative syndromes are potential causes of symptomatic myoclonus. Such syndromes include multiple system atrophy, corticobasal degeneration, progressive supranuclear palsy, frontotemporal dementia and parkinsonism linked to chromosome 17, Huntington's disease, dentato-rubro-pallido-luysian atrophy, Alzheimer's disease, and Parkinson's disease, and other Lewy body disorders. Each neurodegenerative syndrome can have overlapping as well as distinctive clinical neurophysiological properties. However, claims of differentiating between neurodegenerative disorders by using the presence or absence of small amplitude distal action myclonus appear unwarranted. When the myoclonus is small and repetitive, it may not be possible to distinguish it from tremor by phenotypic appearance alone. In this case, clinical neurophysiological offers an opportunity to provide greater differentiation of the phenomenon. More study of the myoclonus in neurodegenerative disease will lead to a better understanding of the processes that cause phenotypic variability among these disorders.

Humans↗
PubMed2003

Case studies in movement disorders.

Six cases representing the most commonly encountered movement disorders-restless legs syndrome with periodic limb movements, tics, myoclonus, chorea, essential tremor, and cervical dystonia-are presented. Discussion of each case focuses on a practical approach to recognizing the important clinical features of each movement disorder as well as the current therapeutic options. A detailed discussion of botulinum toxin follows the case on cervical dystonia, focusing on its mechanism of action, clinical indications, side effects, and dosing.

Adolescent↗
PubMed2002

Small-amplitude cortical myoclonus in Parkinson's disease: physiology and clinical observations.

We studied the occurrence of small-amplitude myo- clonus in 20 idiopathic Parkinson's disease patients who had no evidence of dementia as defined by criteria in the Diagnostic and Statistical Manual of Mental Disorders, fourth edition. Parkinson's disease was diagnosed by United Kingdom Brain Bank criteria, and clinical assessment was performed with the Unified Parkinson's Disease Rating Scale motor score, Hoehn and Yahr staging, and the Mini-Mental State Examination. Clinical assessment showed a range of mild-to-moderate disease severity. All patients underwent polygraphic electro-encephalographic-electromyographic (EMG) recording with back-averaging, somatosensory evoked potential testing, and attempted elicitation of long-latency EMG responses. Multichannel surface EMG recording during muscle activation showed irregular, multifocal, brief (<50 msec) myoclonus EMG discharges. Back-averaging consistently showed a focal, short-latency, electroencephalographic transient prior to the myoclonus EMG discharge. Cortical somatosensory evoked potential waves were not enlarged, and long-latency EMG responses at rest were not present. The small-amplitude myoclonus in such cases arises from an abnormal discharge from the sensorimotor cortex. The mechanism of this cortical myoclonus in Parkinson's disease has differences from the more common "cortical reflex myoclonus" physiology. Advanced parkinsonism is not a requirement for manifestation of this myoclonus type. Although the myoclonus occurred without dementia in these cases, its relationship to the subsequent development of cognitive impairment remains to be defined.

Aged↗
PubMed2002

Motor impairment in normal aging, clinically possible Parkinson's disease, and clinically probable Parkinson's disease: longitudinal evaluation of a cohort of prospective brain donors.

This study presents data on the antemortem evaluations of a cohort of individuals registered in a brain donation program. Clinical evaluation determined that many individuals were unaware they had clinical signs of Parkinson's disease (PD) (rest tremor, bradykinesia, rigidity). Quantitative motor testing (timed tapping test and Purdue pegboard test) revealed a graded reduction in performance in those clinically found to have clinically possible and clinically probable PD. Longitudinal examinations over 4 years revealed some individuals progressed from control to clinically possible PD and clinically possible PD to clinically probable PD. This study underscores the importance of longitudinal antemortem testing of prospective brain donors as well as the potential value of quantitative motor testing.

Adult↗
PubMed2002

The effects of familiarization on intelligibility and lexical segmentation in hypokinetic and ataxic dysarthria.

This study is the third in a series that has explored the source of intelligibility decrement in dysarthria by jointly considering signal characteristics and the cognitive-perceptual processes employed by listeners. A paradigm of lexical boundary error analysis was used to examine this interface by manipulating listener constraints with a brief familiarization procedure. If familiarization allows listeners to extract relevant segmental and suprasegmental information from dysarthric speech, they should obtain higher intelligibility scores than nonfamiliarized listeners, and their lexical boundary error patterns should approximate those obtained in misperceptions of normal speech. Listeners transcribed phrases produced by speakers with either hypokinetic or ataxic dysarthria after being familiarized with other phrases produced by these speakers. Data were compared to those of nonfamiliarized listeners [Liss et al., J. Acoust. Soc. Am. 107, 3415-3424 (2000)]. The familiarized groups obtained higher intelligibility scores than nonfamiliarized groups, and the effects were greater when the dysarthria type of the familiarization procedure matched the dysarthria type of the transcription task. Remarkably, no differences in lexical boundary error patterns were discovered between the familiarized and nonfamiliarized groups. Transcribers of the ataxic speech appeared to have difficulty distinguishing strong and weak syllables in spite of the familiarization. Results suggest that intelligibility decrements arise from the perceptual challenges posed by the degraded segmental and suprasegmental aspects of the signal, but that this type of familiarization process may differentially facilitate mapping segmental information onto existing phonological categories.

Adult↗
PubMed2002

Epidemiology of myoclonus.

All studies that attempt to evaluate the general occurrence of myoclonus have various biases. Even so, myoclonus has been demonstrated to be an important cause of abnormal movement control when compared to other movement disorders. Clearly, posthypoxia etiology, neurodegenerative disease, and epilepsy syndromes are important individual causes of myoclonus. The epidemiology of myoclonus is worthy of further study in other defined populations.

Adolescent↗