Publications by authors named "Mark S Baron"

22 Publications

  • Page 1 of 1

Anticholinergic Medication Burden in Parkinson's Disease Outpatients.

J Parkinsons Dis 2022 ;12(2):599-606

Department of Neurology, Virginia Commonwealth University, Richmond, VA, USA.

Background: Individuals with Parkinson's disease (PD) may be especially vulnerable to future cognitive decline from anticholinergic medications.

Objective: To characterize anticholinergic medication burden, determine the co-occurrence of anticholinergic and cholinesterase inhibitors, and to assess the correlations among anticholinergic burden scales in PD outpatients.

Methods: We studied 670 PD outpatients enrolled in a clinic registry between 2012 and 2020. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden Scale (ACB), Anticholinergic Drug Scale (ADS), Anticholinergic Risk Scale (ARS), and Drug Burden Index-Anticholinergic component (DBI-Ach). Correlations between scales were assessed with weighted kappa coefficients.

Results: Between 31.5 to 46.3% of PD patients were taking medications with anticholinergic properties. Among the scales applied, the ACB produced the highest prevalence of medications with anticholinergic properties (46.3%). Considering only medications with definite anticholinergic activity (scores of 2 or 3 on ACB, ADS, or ARS), the most common anticholinergic drug classes were antiparkinsonian (8.2%), antipsychotic (6.4%), and urological (3.3%) medications. Cholinesterase inhibitors and medications with anticholinergic properties were co-prescribed to 5.4% of the total cohort. The most highly correlated scales were ACB and ADS (κ= 0.71), ACB and ARS (κ= 0.67), and ADS and ARS (κ= 0.55).

Conclusion: A high proportion of PD patients (20%) were either taking antiparkinsonian, urological, or antipsychotic anticholinergic medications or were co-prescribed anticholinergic medications and cholinesterase inhibitors. By virtue of its detection of a high prevalence of anticholinergic medication usage and its high correlation with other scales, our data support use of the ACB scale to assess anticholinergic burden in PD patients.
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http://dx.doi.org/10.3233/JPD-212769DOI Listing
April 2022

Lack of Support for the Use of VMAT-2 Inhibitors for the Treatment of Tics in Tourette Syndrome.

Authors:
Mark S Baron

JAMA Netw Open 2021 10 1;4(10):e2129704. Epub 2021 Oct 1.

Virginia Commonwealth University Parkinson's Movement Disorders Center, Virginia Commonwealth University Health System, Richmond, Virginia.

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http://dx.doi.org/10.1001/jamanetworkopen.2021.29704DOI Listing
October 2021

Parkinsonism and dystonia are differentially induced by modulation of different territories in the basal ganglia.

Neuroscience 2017 06 12;353:42-57. Epub 2017 Apr 12.

Department of Neurology, Virginia Commonwealth University Health System, Richmond, VA, USA; Southeast Veterans Affairs Parkinson's Disease Research, Education and Clinical Center (PADRECC), Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA, USA. Electronic address:

Numerous clinical and experimental observations suggest that deficient neuronal signaling in the globus pallidus externa (GPe) is integral to both Parkinson's disease (PD) and dystonia. In our previous studies in jaundiced dystonic rats, widespread silencing of neurons in GP (rodent equivalent to GPe) preceded and persisted during dystonic motor activity. We therefore hypothesized that on a background of slow and highly irregular and bursty neuronal activity in GP, cortical motor drive produces profound inhibition of GP as the basis for action-induced dystonia in Gunn rats. Presently, the neurotoxin ibotenate was injected locally into the motor territory of GP at one to four sites, over one to two tracts, in 19 normal rats. We found that highly circumscribed dorsal motor territory lesions reproducibly induced parkinsonism, while ventral lesions consistently produced dystonia. Post-lesioning, slow neuronal burst oscillations in the entopeduncular nucleus distinguished parkinsonian from dystonic rats. Next, we compared the deep brain stimulation contact sites in the GP internus used to treat patients with PD (n=21 implants in 12 successive patients) versus dystonia (n=16 implants in nine patients) and found the efficacious territory for ameliorating PD to be located chiefly dorsal to that for dystonia. The comparative distribution for treating PD versus dystonia was therefore anatomically consistent with that for inducing these features via GP lesions in rodents. Our collective findings thus suggest that dystonia and parkinsonism are differentially produced by pathological silencing of GPe neurons along distinct motor sub-circuits, resulting in disparate pathological basal ganglia output signaling.
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http://dx.doi.org/10.1016/j.neuroscience.2017.03.063DOI Listing
June 2017

Antipsychotics and Increased Mortality: Are We Sure?

Authors:
Mark S Baron

JAMA Neurol 2016 05;73(5):502-4

Department of Neurology, Virginia Commonwealth University Health System, Richmond2Southeast Parkinson's Disease Research, Education, and Clinical Center, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia.

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http://dx.doi.org/10.1001/jamaneurol.2016.0213DOI Listing
May 2016

Preserved dichotomy but highly irregular and burst discharge in the basal ganglia in alert dystonic rats at rest.

Brain Res 2015 Oct 23;1624:297-313. Epub 2015 Jul 23.

Southeast Parkinson's Disease Research, Education and Clinical Center (PADRECC), Hunter Holmes McGuire Veterans Affairs Medical Center, 1201 Broad Rock Blvd, Richmond, VA 23249, USA; Department of Neurology, Virginia Commonwealth University Health System, Richmond, VA 23298, USA. Electronic address:

Despite its prevalence, the underlying pathophysiology of dystonia remains poorly understood. Using our novel tri-component classification algorithm, extracellular neuronal activity in the globus pallidus (GP), STN, and the entopeduncular nucleus (EP) was characterized in 34 normal and 25 jaundiced dystonic Gunn rats with their heads restrained while at rest. In normal rats, neurons in each nucleus were similarly characterized by two physiologically distinct types: regular tonic with moderate discharge frequencies (mean rates in GP, STN and EP ranging from 35-41 spikes/s) or irregular at slower frequencies (17-20 spikes/s), with a paucity of burst activity. In dystonic rats, these nuclei were also characterized by two distinct principal neuronal patterns. However, in marked difference, in the dystonic rats, neurons were primarily slow and highly irregular (12-15 spikes/s) or burst predominant (14-17 spikes/s), with maintained modest differences between nuclei. In GP and EP, with increasing severity of dystonia, burstiness was moderately further increased, irregularity mildly further increased, and discharge rates mildly further reduced. In contrast, these features did not appreciably change in STN with worsening dystonia. Findings of a lack of bursting in GP, STN and EP in normal rats in an alert resting state and prominent bursting in dystonic Gunn rats suggest that cortical or other external drive is normally required for bursting in these nuclei and that spontaneous bursting, as seen in dystonia and Parkinson's disease, is reflective of an underlying pathophysiological state. Moreover, the extent of burstiness appears to most closely correlate with the severity of the dystonia.
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http://dx.doi.org/10.1016/j.brainres.2015.07.018DOI Listing
October 2015

Scientific data support that ocular tremor is genuine and unrelated to head movement.

Parkinsonism Relat Disord 2014 Dec 8;20(12):1449-50. Epub 2014 Oct 8.

Virginia Commonwealth University, Department of Biomedical Engineering, United States.

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http://dx.doi.org/10.1016/j.parkreldis.2014.09.032DOI Listing
December 2014

A novel tri-component scheme for classifying neuronal discharge patterns.

J Neurosci Methods 2015 Jan 23;239:148-61. Epub 2014 Sep 23.

McGuire Research Institute, Hunter Holmes McGuire Veteran Affairs Medical Center, Richmond, VA, USA; Southeast Parkinson's Disease Research, Education and Clinical Center (PADRECC), Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA, USA; Department of Neurology, Virginia Commonwealth University, Richmond, VA, USA. Electronic address:

Background: Neuronal discharge patterns can be described by three principle patterns, namely, regular, irregular, and bursty.

New Method: Available discrimination metrics, including global ISI metrics (e.g., coefficient of variation (CV), asymmetric index), local variables (CV2, CV for a sequence of two ISIs; IR, difference of log of two adjacent ISIs; LVr, local variation with refractory period), Fano factor (FF) and Allan factor (AF), and three new burst metrics, 'burst percentage' (BP), 'burst tendency' (BT) and 'burst entropy' (BE), were extensively tested on representative simulated spike trains. Upon verifying that individual metrics could not by themselves reliably classify the diverse simulation patterns, a novel tri-component classification algorithm was developed. Inadequate metrics were rejected and the remaining selected metrics were grouped and weighted using multiple metric optimization to form three proxy metrics: 'regularity' (combining local variables), 'burstiness' (combining BP, BT and BE), and 'corruption' (combining FF and AF).

Results: The accuracy of the proxy metrics was verified on a large set of neuronal spike trains extracellularly recorded from multiple regions of the brain in unsedated normal and dystonic rats. Cross-validation of the tri-component classifier against meticulous subjective classification of these data demonstrated an agreement of 95.9%, with a high discriminatory power of 2.6.

Comparison With Existing Methods: The tri-component classifier was demonstrated to well outperform individual metrics on all aspects of pattern and corruption discrimination.

Conclusions: The tri-component classifier provides a novel, reliable algorithm to differentiate highly diverse neuronal discharge patterns and discriminate natural or erroneous corruption in the signal.
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http://dx.doi.org/10.1016/j.jneumeth.2014.09.015DOI Listing
January 2015

Experimental support that ocular tremor in Parkinson's disease does not originate from head movement.

Parkinsonism Relat Disord 2014 Jul 8;20(7):743-7. Epub 2014 Apr 8.

Southeast Parkinson's Disease Research, Education, and Clinical Center (PADRECC), Hunter-Holmes McGuire Veterans Affairs Medical Center, Richmond, VA, USA; Virginia Commonwealth University, Department of Neurology, Richmond, VA, USA. Electronic address:

Introduction: Our recent report of ocular tremor in Parkinson's disease (PD) has raised considerable controversy as to the origin of the tremor. Using an infrared based eye tracker and a magnetic head tracker, we reported that ocular tremor was recordable in PD subjects with no apparent head tremor. However, other investigators suggest that the ocular tremor may represent either transmitted appendicular tremor or subclinical head tremor inducing the vestibulo-ocular reflex (VOR). The present study aimed to further investigate the origin of ocular tremor in PD.

Methods: Eye movements were recorded in 8 PD subjects both head free, and with full head restraint by means of a head holding device and a dental impression bite plate. Head movements were recorded independently using both a high sensitivity tri-axial accelerometer and a magnetic tracking system, each synchronized to the eye tracker.

Results: Ocular tremor was observed in all 8 PD subjects and was not influenced by head free and head fixed conditions. Both magnetic tracking and accelerometer recordings supported that the ocular tremor was fully independent of head position.

Conclusion: The present study findings support our initial findings that ocular tremor is a fundamental feature of PD unrelated to head movements. Although the utility of ocular tremor for diagnostic purposes requires validation, current findings in large cohorts of PD subjects suggest its potential as a reliable clinical biomarker.
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http://dx.doi.org/10.1016/j.parkreldis.2014.03.028DOI Listing
July 2014

Slowed saccades and increased square wave jerks in essential tremor.

Tremor Other Hyperkinet Mov (N Y) 2013 3;3. Epub 2013 Sep 3.

Southeast Parkinson's Disease Research, Education, and Clinical Center (PADRECC), Hunter-Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia, United States of America ; Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, Virginia, USA.

Background: Eye movements in essential tremor (ET) are poorly described and may present useful information on the underlying pathophysiology of the disorder.

Methods: Sixty patients with ET, including 15 de novo untreated patients, and 60 age-matched controls constitute the study population. A video-based eye tracker was used to assess binocular eye position. Oculomotor function was assessed while subjects followed random horizontally and vertically step-displaced targets.

Results: For all reflexive saccades, latencies were increased in ET subjects by a mean of 16.3% (p<0.01). Saccades showed reduced peak velocities with a lengthy, wavering velocity plateau, followed by slowed decelerations. For larger 30°+ saccades, peak velocities were decreased by a mean of 25.2% (p<0.01) and durations increased by 31.8% (p<0.01). The frequency of square wave jerks (SWJs) in patients was more than triple that of controls (p<0.0001). Despite frequent interruptions by SWJs, fixations were otherwise stable and indistinguishable from controls (root mean square [RMS] velocity, p = 0.324). The abnormal eye movement parameters were independent of disease duration, tremor severity, and medication therapy.

Discussion: In contrast to normally swift onset and efficient acceleration/deceleration movements, saccades in ET are characterized by abnormally prolonged latencies and slowed velocity profiles. Although ET subjects maintain highly stable fixations, they are interrupted by increased numbers of SWJs. This study reveals novel oculomotor deficits in ET, which are distinct from the eye movement dysfunction of other movement disorders, supporting a role for eye tracking to assist in the differential diagnoses of not only atypical, but also more common movement disorders.
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http://dx.doi.org/10.7916/D8251GXNDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3779821PMC
October 2013

Pervasive ocular tremor in patients with Parkinson disease.

Arch Neurol 2012 Aug;69(8):1011-7

Southeast Parkinson's Disease Research, Education, and Clinical Center, Richmond, VA, USA.

Objective: To further assess oculomotor control of patients with Parkinson disease (PD) during fixation and with movement.

Design: Case-control study.

Setting: A Parkinson disease research, education, and clinical center. PATIENTS One hundred twelve patients with PD, including 18 de novo untreated patients, and 60 age-matched controls.

Intervention: Modern, precise eye tracking technology was used to assess oculomotor parameters. Oculomotor function was compared between groups during fixation and while tracking a randomly displaced target on a PC monitor.

Main Outcome Measures: Fixation stability and saccadic parameters.

Results: All patients with PD and 2 of 60 control subjects showed oscillatory fixation instability (ocular tremor), with an average fundamental frequency of 5.7 Hz and average magnitude of 0.27°. Saccadic parameters and occurrences of square wave jerks did not differ between subjects with PD and controls. The amplitude and frequency of fixation instability did not correlate with disease duration, clinical Unified Parkinson's Disease Rating Scale scores, or dopa-equivalent dosing. No differences in oculomotor parameters were found between medicated and unmedicated patients with PD.

Conclusions: All patients with PD exhibited persistent ocular tremor that prevented stability during fixation. The pervasiveness and specificity of this feature suggest that modern, precise oculomotor testing could provide a valuable early physiological biomarker for diagnosing PD.
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http://dx.doi.org/10.1001/archneurol.2012.70DOI Listing
August 2012

Multi-neuronal recordings in the Basal Ganglia in normal and dystonic rats.

Front Syst Neurosci 2011 31;5:67. Epub 2011 Aug 31.

Department of Neurology, Virginia Commonwealth University Richmond, VA, USA.

Classical rate-based pathway models are invaluable for conceptualizing direct/indirect basal ganglia pathways, but cannot account for many aspects of normal and abnormal motor control. To better understand the contribution of patterned basal ganglia signaling to normal and pathological motor control, we simultaneously recorded multi-neuronal and EMG activity in normal and dystonic rats. We used the jaundiced Gunn rat model of kernicterus as our experimental model of dystonia. Stainless steel head fixtures were implanted on the skulls and EMG wires were inserted into antagonistic hip muscles in nine dystonic and nine control rats. Under awake, head-restrained conditions, neuronal activity was collected from up to three microelectrodes inserted in the principal motor regions of the globus pallidus (GP), subthalamic nucleus, and entopeduncular nucleus (EP). In normal animals, most neurons discharged in regular or irregular patterns, without appreciable bursting. In contrast, in dystonic animals, neurons discharged in slow bursty or irregular, less bursty patterns. In normal rats, a subset of neurons showed brief discharge bursts coinciding with individual agonist or antagonist EMG bursts. In contrast, in dystonics, movement related discharges were characterized by more prolonged bursts which persist over multiple dystonic co-contraction epics. The pattern of movement related decreases in discharge activity however did not differ in dystonics compared to controls. In severely dystonic rats, exclusively, simultaneously recorded units often showed abnormally synchronized movement related pauses in GP and bursts in EP. In conclusion, our findings support that slow, abnormally patterned neuronal signaling is a fundamental pathophysiological feature of intrinsic basal ganglia nuclei in dystonia. Moreover, from our findings, we suggest that excessive movement related silencing of neuronal signaling in GP profoundly disinhibits EP and in turn contributes to sustained, unfocused dystonic muscle contractions.
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http://dx.doi.org/10.3389/fnsys.2011.00067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3171071PMC
November 2011

A novel stereotaxic apparatus for neuronal recordings in awake head-restrained rats.

J Neurosci Methods 2011 May 15;198(1):29-35. Epub 2011 Mar 15.

Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23298-0599, USA.

A novel technique for neuronal recordings in awake head-restrained animals is presented. Our setup allows (1) daily repeat microelectrode studies in rats without use of anesthesia, (2) excellent stabilization of head using an eight point fixation, (3) painless head-restraint of the animal, (4) accurate stereotaxic localization during multiple sessions of recording, (5) to considerably reduced surgical time, (6) quick repositioning during chronic recording sessions and (7) high quality stabilized neuronal recordings during periods of rest and active movements.
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http://dx.doi.org/10.1016/j.jneumeth.2011.02.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3098765PMC
May 2011

Pharmacological management of psychosis in elderly patients with parkinsonism.

Am J Med 2009 Jul;122(7):614-22

Department of Psychiatry, Western Regional Integrated Health Authority, Sir Thomas Roddick Hospital, Stephenville, Newfoundland, Canada.

Parkinsonism is a characteristic feature of Parkinson's disease and dementia with Lewy bodies and is commonly seen in Alzheimer's disease. Psychosis commonly appears during the course of these illnesses. Treatment of parkinsonism with antiparkinsonian medications constitutes an additional risk factor for the appearance or worsening of psychosis. Conversely, treatment of psychosis with antipsychotic drugs in patients with parkinsonism might worsen the underlying movement disorder, especially in the elderly. In this article, we review parkinsonian conditions in the elderly and offer guidelines to assess and manage comorbid psychosis. We focus on the pharmacologic management of psychosis with atypical antipsychotic medications and briefly review the role of acetylcholinesterase inhibitors.
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http://dx.doi.org/10.1016/j.amjmed.2009.01.025DOI Listing
July 2009

Quantification of gait in dystonic Gunn rats.

J Neurosci Methods 2009 Jun 6;180(2):273-7. Epub 2009 Apr 6.

Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA 23298-0599, USA.

Spontaneously jaundiced Gunn rats exposed to sulfadimethoxine develop bilirubin encephalopathy (kernicterus) with hearing loss and dystonia, closely resembling the human syndrome. We recently characterized the electromyographic activity in this animal model supporting our clinical impression of dystonia. The objective of this study was to develop a simple, non-invasive method to quantify the motor deficits in dystonic rodents. On postnatal day 16, Gunn rats were treated with 100mg/kg of sulfadimethoxine or saline. On postnatal day 31, the ventral view of the animals was videotaped while the animals walked inside a Plexiglas chamber. Individual video frames were reviewed and specific gait parameters including hindlimb spread, step length ratio variability, stance/swing ratio and walking speed were compared between dystonic and non-dystonic jaundiced and non-jaundiced littermates. Data analysis demonstrated statistically significant increases in hindlimb spread and step length ratio variability and decreases in walking speed in dystonic animals as compared to controls. This study demonstrates a valuable technique to objectively characterize dystonia in Gunn rats, which could have wide use for other experimental movement disorders as well.
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http://dx.doi.org/10.1016/j.jneumeth.2009.03.023DOI Listing
June 2009

A comparison of computerized dynamic posturography therapy to standard balance physical therapy in individuals with Parkinson's disease: a pilot study.

NeuroRehabilitation 2007 ;22(4):261-5

Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, VA, USA.

Postural instability is a common impairment in idiopathic Parkinson's disease (PD). People with PD are prone to balance and walking difficulties. This study analyzed the feasibility of a prospective investigation of Computerized Dynamic Posturography (CDP) and standard Physical Therapy (PT) treatments in individuals with mild-moderate PD. Treatment took place at two sites: 1) CDP therapy at the Southeast Parkinson's Disease Research Education and Clinical Center (PADRECC) within a Veterans Affairs Medical Center and 2) standard physical therapy at a community outpatient rehabilitation center. Final analysis compared 15 patients randomly assigned for therapy to either the CDP or PT treatments. Therapy time was eight weeks (four weeks of CPD or PT followed by home therapy for four weeks). The CDP therapy included gradually intensified closed chain and mobility training. Standard PT consisted of upright, mat, and theraball exercises and gait training. The home exercise phase was identical for both groups. The pilot data demonstrated treatment was tolerated by 68 percent of the sample despite the occurrence of a progressive neurological condition and medical comorbidities. While results failed to reveal any differences between treatment groups, both groups demonstrated improvement on selected outcome measures. An expanded prospective study with methodological improvements appears warranted.
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February 2008

Caregiver distress in parkinsonism.

J Rehabil Res Dev 2006 Jul-Aug;43(4):499-508

Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA, USA.

This study examined the frequency and degree of caregiver burden in persons with parkinsonism, a group of disorders with four primary symptoms that include tremor, rigidity, postural instability, and bradykinesia. We assessed associations between perceived caregiver burden and physical, cognitive, and functional impairments using well-established tools for persons with parkinsonism. The 49 individuals with parkinsonism ranged in age from 61 to 87 (mean = 75), while their caregivers (N = 49) ranged in age from 48 to 83 (mean = 70). The caregivers were predominantly either wives (82%) or daughters (6%), with other family members, friends, and/or neighbors (12%) making up the rest. The caregivers reported a relatively high ability for coping (mean scores = 4.6/6). Caregiver burden was significantly negatively associated with activities of daily living and motoric difficulties as measured on the Unified Parkinson's Disease Rating Scale (UPDRS). Likewise, caregiver burden was negatively associated with caregiver self-reported sleep and coping ability. Results did not demonstrate an association on the UPDRS among mentation, behavior, and mood. We found a significant negative correlation for mentation between the Folstein Mini-Mental Status Examination and caregiver burden measures; however, we did not find this association with the Dementia Rating Scale-2. Patient's self-reported pain and caregiver burden were not associated.
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http://dx.doi.org/10.1682/jrrd.2005.08.1365DOI Listing
October 2007

Deep brain stimulation for dystonia: a meta-analysis.

Neuromodulation 2006 Oct;9(4):253-61

The South-eastern Parkinson's Disease Research, Education and Clinical Care (PADRECC) Center of Excellence at McGuire VAMC, and the Departments of Neurosurgery, Neurology, Psychology, Physical Medicine and Rehabilitation, and Biostatistics at the Medical College of Virginia Hospital of Virginia Commonwealth University, Richmond, VA, USA.

Objective.  To use a meta-analysis on all reported cases of deep brain stimulation (DBS) for dystonia to determine which factors significantly influence outcome. The Burke-Fahn-Marsden (BFM) movement scale, the most reported measure, was chosen as the primary outcome measure for this analysis. Methods.  A MEDLINE search identified 137 patients who underwent DBS for dystonia in 24 studies that had individual BFM scores. Individual patient data, including age at onset of dystonia, age at surgery, gender, distribution of dystonia, etiology of dystonia, presence of associated features, abnormality of preoperative imaging, prior stereotactic surgeries, nucleus stimulated, type of anesthesia used, use of physiologic monitoring, type of imaging used for localization, stimulation parameters used, time of response to stimulation, and timing of outcome assessment were entered into an SPSS database for statistical analysis. Results.  The mean BFM percentage change (improvement in postoperative score from baseline) was 51.8% (range -34% to 100%). Significantly better outcomes were achieved with stimulation of the globus pallidus internus (GPi) than with stimulation of the posterior portion of the ventral lateral (VLp) nucleus of the thalamus (p = 0.0001). The etiology of the dystonia also had a significant effect on outcomes. Statistically significant improvements in outcomes were seen for all etiologic categories, except encephalitis. Dystonia due to birth injury and encephalitis had significantly worse outcomes when compared to other etiologies. However, there were no significant differences in the outcomes of patients who were DYT1 (DYT1 is the gene associated with the disorder Dystonia Musculorum Deformans) gene positive, DYT1 gene negative, or had pantothenate kinase-associated neurodegeneration (PKAN), tardive dyskinesia, and idiopathic and posttraumatic dystonias. Longer duration of dystonia symptoms correlated negatively with surgical outcome. A regression model using the three variables-stimulation site, etiology of dystonia, and duration of dystonia symptoms-explained 51% of the variance in outcomes. Conclusion.  Deep brain stimulation of the GPi provides significant improvement in BFM scores in a variety of dystonic conditions.
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http://dx.doi.org/10.1111/j.1525-1403.2006.00067.xDOI Listing
October 2006

Restricted ablative lesions in motor portions of GPi in primates produce extensive loss of motor-related neurons and degeneration of the lenticular fasciculus.

Exp Neurol 2006 Nov 30;202(1):67-75. Epub 2006 Jun 30.

Southeast Parkinson's Disease Research, Education, and Clinical Center, Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, VA 23249, USA.

Deep brain stimulation (DBS) of the internal pallidum (GPi) and the subthalamic nucleus and to a lesser extent, ablative lesioning, are broadly utilized to treat patients with medically intractable Parkinson's disease and other movement disorders. Beneficial outcomes however are not uniform and adverse cognitive and behavioral are significant risks. Surgical outcomes of GPi surgeries might be improved by approaches that better account for the course of motor and non-motor pallidothalamic projections. Although several studies, including our own tracer investigations, suggest that motor projections from GPi principally form the lenticular fasciculus and non-motor projections primarily contribute to the ansa lenticularis, other schemes have perpetuated. Presently, to corroborate the course of pallidothalamic projections and to assess the feasibility of selectively targeting the motor circuit of GPi, radiofrequency lesions were placed in the motor portion of GPi in monkeys. Degenerating pallidothalamic fibers were visualized with amino cupric staining techniques and regional cell counts in GPi were compared with control hemispheres. Lesions restricted to posterior motor portions of GPi produced selective degeneration of LF and only damaged AL if the lesions extended more anteriorly. Marked secondary neuronal loss occurred well beyond the principal lesions but was mainly confined to the posterolateral motor region of GPi. These findings corroborate the original pallidothalamic outflow scheme proposed by Ranson and Ranson. Conceivably, a restrictive lesion or a DBS probe could be placed in the centroposterior portion of GPi to selectively target both local motor-related neurons and traversing pallidothalamic fibers originating from more posterior and lateral motor regions.
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http://dx.doi.org/10.1016/j.expneurol.2006.05.014DOI Listing
November 2006

Movement disorders in the older patient: differential diagnosis and general management.

Authors:
Mark S Baron

Cleve Clin J Med 2005 Oct;72 Suppl 3:S38-51

Virginia Commonwealth University School of Medicine, Richmond, VA, USA.

Movement disorders are especially prevalent in the elderly, and some are highly treatable. Because reduced agility and slowing of gait are associated with numerous movement disorders as well as with the normal aging process, the differential diagnosis of movement disorders in the elderly can be challenging. Many of these disorders share features of parkinsonism-hypokinesia, tremor, and muscular rigidity. This article reviews common and less common movement disorders in the elderly from a primary care perspective, with an emphasis on the presenting features and the differential diagnosis. It also provides general management recommendations with advice for tailoring treatment to elderly patients.
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http://dx.doi.org/10.3949/ccjm.72.suppl_3.s38DOI Listing
October 2005

Effects of transient focal inactivation of the basal ganglia in parkinsonian primates.

J Neurosci 2002 Jan;22(2):592-9

Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.

Ablative and chronic stimulation procedures targeting the internal pallidum (GPi) and the subthalamic nucleus (STN) have led to major advancements in the treatment of Parkinson's disease and other movement disorders. Although these procedures have evolved to primarily target the posterior ventrolateral sensorimotor portion of GPi and to less selectively target STN, centrally, the ideal targets within these structures remain to be fully established. In this study, we sought to identify the optimal targeting sites in GPi and STN for reversal of parkinsonian signs through a series of reversible injections of the GABA(A) agonist muscimol in these nuclei in parkinsonian primates. Akinesia and bradykinesia were strongly ameliorated by discrete inactivation within the centromedial extent of the sensorimotor territory in GPi and the lateral portion of the sensorimotor territory in STN. This suggests that akinesia and bradykinesia might, in fact, originate from abnormalities in the same, or at least overlapping, motor circuits in the parkinsonian state. Inactivation of areas outside of the motor territories did not improve parkinsonism but induced circling and behavioral abnormalities. The segregation of basal ganglia-thalamocortical circuits appears to be therefore maintained, at least to a large extent, in the parkinsonian state. These results underscore that inactivation of discrete regions in the central territory of GPi and the lateral portion of STN are sufficient to ameliorate parkinsonian motor signs and that extension of lesions into nonmotor territories may be deleterious. Surgical outcomes might therefore be optimized by placing more discrete lesions and by restricting the extent of chronic stimulation.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6758679PMC
January 2002
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