Parkinson Disease: Dewey RB

Dewey RB. · University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9036, USA. · Neurol Clin. · Pubmed #18774440 No free full text.

Abstract: Given the magnitude of the problem of motor fluctuations in patients who have Parkinson's disease treated with levodopa, a significant effort has been expended by physicians, researchers, and pharmaceutical manufacturers over the years to find effective treatments. This article briefly reviews the medical options for managing motor fluctuations that are in common use in the United States or that are expected to be available soon.

Dewey RB. · Department of Neurology, University of Texas Southwestern Medical School, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA. · Neurol Clin. · Pubmed #15501361 No free full text.

This publication has no abstract.

Dewey RB. · Department of Neurology, UT Southwestern Medical Center, University of Texas Southwestern Medical School, 5323 Harry Hines Blvd, Dallas, TX 75390-9036, USA. · Neurology. · Pubmed #15037664 No free full text.

Abstract: Motor fluctuations in Parkinson's disease (PD) typically develop after 4-6 years of therapy, and affect approximately half of all patients. The wearing-off effect is the most common type, and "delayed-on," "no-on," and "on-off" effects, as well as dyskinesias, may also develop as the disease progresses. Collectively, motor fluctuations represent a significant source of disability in advanced PD patients, and their mitigation is a major goal of patient management. Adjunctive medications, including dopamine agonists, amantadine, MAO-B inhibitors, and COMT inhibitors, each may reduce the frequency or duration of "off" periods, but none does so completely, and each contributes its own side effects which may limit optimal dosing. Surgery is another strategy to reduce "off" time, and both pallidotomy and deep brain stimulation of the globus pallidus or the subthalamic nucleus have been shown to be highly effective in this regard. However, surgery may be contraindicated in elderly advanced patients who could most benefit from its effect on "off" time. The unmet need for treatment of "off" episodes suggests the potential utility of an agent such as apomorphine injectable, which can reliably trigger an "on" response within 10-15 minutes of injection.

Lacritz LH, Cullum CM, Frol AB, Dewey RB, Giller CA. · University of Texas Southwestern Medical Center at Dallas, 75235-8898, USA. · Brain Cogn. · Pubmed #10753485 No free full text.

Abstract: Neuropsychological functioning was examined at baseline and 2- to 3-month follow-up in 40 subjects with advanced Parkinson's disease (PD) who underwent unilateral posteroventral pallidotomy. Most subjects demonstrated improved verbal learning, visual memory, confrontation naming, and figural fluency at follow-up. Right pallidotomy was associated with decreased cognitive flexibility and increased verbal fluency, whereas Left pallidotomy uniquely resulted in a decline in verbal fluency. Significant motor improvement was demonstrated in both groups. Pallidotomy appears to be an effective treatment for advanced PD, providing a significant improvement in motor functioning, while resulting in few deleterious neurocognitive changes in most cases.

Dewey RB, Hutton JT, LeWitt PA, Factor SA. · Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9036, USA. · Arch Neurol. · Pubmed #11559309 links to  free full text

Abstract: OBJECTIVE: To assess the safety and efficacy of subcutaneous apomorphine hydrochloride administration for off-state (poor motor function) periods in patients with Parkinson disease with motor fluctuations under both inpatient titration and outpatient therapeutic conditions. PATIENTS AND METHODS: Twenty-nine patients had advanced Parkinson disease with 2 hours or more off time despite aggressive oral therapy. Patients randomly received titrated doses of subcutaneous apomorphine hydrochloride (2-10 mg, n = 20) or pH-matched vehicle placebo (n = 9) during an inpatient and 1-month outpatient phase. A change in the United Parkinson Disease Rating Scale motor score 20 minutes after inpatient dosing during a practically defined off-state event and the percentage of injections successfully aborting off-state events were the primary inpatient and outpatient efficacy factors. RESULTS: The average (SEM) levodopa equivalent dose of apomorphine hydrochloride was 5.4 +/- 0.5 mg and the mean placebo dose was 1.0 mL. Mean inpatient United Parkinson Disease Rating Scale motor scores were reduced by 23.9 and 0.1 points (62% and 1%) by apomorphine treatment and placebo, respectively (P<.001). The mean percentage of outpatient injections resulting in successful abortion of off-state events was 95% for apomorphine and 23% for placebo (P<.001). Inpatient response was significantly correlated with and predictive of outpatient efficacy (P<.001). The levodopa dose was not predictive of the apomorphine dose requirement. Frequent adverse events included dyskinesia, yawning, and injection site reactions. CONCLUSION: Apomorphine by intermittent subcutaneous injection is effective and safe for outpatient use to reverse off-state events that occur despite optimized oral therapy.

Giller CA, Liu H, German DC, Kashyap D, Dewey RB. · Baylor Radiosurgery Center, Baylor University Medical Center, Dallas, TX 75246, USA. · J Neurosurg. · Pubmed #19012484 No free full text.

Abstract: OBJECT: The authors previously developed an optical stereotactic probe employing near-infrared (NIR) spectroscopy to provide intraoperative localization by distinguishing gray matter from white matter. In the current study they extend and further validate this technology. METHODS: Near-infrared probes were inserted 203 times during 138 procedures for movement disorders. Detailed validation with postoperative imaging was obtained for 121 of these procedures and with microelectrode recording (MER) for 30 procedures. Probes were constructed to interrogate tissue perpendicular to the probe path and to incorporate hollow channels for microelectrodes, deep brain stimulation (DBS) electrodes, and other payloads. RESULTS: The NIR data were highly correlated to imaging and MER recordings for thalamic targets. The NIR data were highly sensitive but less specific relative to imaging for subthalamic targets, confirming the ability to detect the subthalamic nucleus and to provide warnings of inaccurate localization. The difference between the NIR- and MER-detected midpoints of the subthalamic nucleus along the chosen tracks was 1.1 +/- 1.2 mm (SD). Data obtained during insertion and withdrawal of the NIR probe suggested that DBS electrodes may push their targets ahead of their paths. There was one symptomatic morbidity. Detailed NIR data could be obtained from a 7-cm track in less than 10 minutes. CONCLUSIONS: The NIR probe is a straightforward, quick, and robust tool for intraoperative localization during functional neurosurgery. Potential future applications include localization of targets for epilepsy and psychiatric disorders, and incorporation of NIR guidance into probes designed to convey various payloads.

Singh A, Kandimala G, Dewey RB, O'Suilleabhain P. · Department of Neurology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9036, USA. · J Clin Neurosci. · Pubmed #17720504 No free full text.

Abstract: Three hundred patients with Parkinson's disease taking dopamine agonists were surveyed for the presence of compulsions. Fifty-eight reported active compulsions which had developed after initiation of dopamine agonists. These included 25 with sexual compulsions and 28 with self-described compulsive gambling, of whom 17 met criteria for pathologic gambling. Males were over-represented. Patients with any compulsion and those with pathologic gambling were about 6 years younger than those without compulsions. These behavioral problems were not associated with an individual dopamine agonist, nor dose or duration, nor concomitant levodopa. Follow-up of the pathologic gamblers 1 year after intervention, which was cessation of the dopamine agonist in most cases, found ongoing but controlled gambling in five and complete cessation within 4 months in the remainder.

Dewey RB, Reimold SC, O'Suilleabhain PE. · Department of Neurology and Division of Cardiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390-9036, USA. · Arch Neurol. · Pubmed #17353380 links to  free full text

Abstract: BACKGROUND: Although most studies have suggested an increased risk of valvulopathy (primarily regurgitation) with pergolide mesylate use, one study suggested that this problem may also occur with use of the non-ergot-derived dopamine agonists pramipexole dihydrochloride and ropinirole hydrochloride. OBJECTIVE: To determine if cardiac valve regurgitation occurs more commonly in patients with Parkinson disease (PD) treated with pergolide than in those treated with nonergot agonists at a comparable dose. DESIGN: A case-control study of echocardiographic findings of valve function in patients receiving dopamine agonists for PD. SETTING: University-based referral center. Patients Thirty-six patients with idiopathic PD taking pergolide were compared with a matched control group of patients taking nonergot agonists with regard to the frequency and severity of cardiac valve regurgitation. Main Outcome Measure Valve scores (1 indicates trace; 2, mild; 3, moderate; and 4, severe) for the pergolide group were compared with those for the nonergot agonist control group. RESULTS: The mean +/- SD valve regurgitation scores in the matched pergolide group compared with the nonergot group were as follows: aortic, 0.83 +/- 1.23 vs 0.19 +/- 0.53 (P = .01); mitral, 1.42 +/- 1.0 vs 0.39 +/- 0.65 (P<.001); and tricuspid, 1.43 +/- 1.0 vs 0.19 +/- 0.53 (P<.001). Lifetime exposure to a dopamine agonist was not statistically different between the pergolide and nonergot agonist groups (P = .18). CONCLUSIONS: These data strengthen the conclusion that pergolide contributes to cardiac valve regurgitation when used in the long term as a treatment for PD. There appears to be low risk of cardiac valve regurgitation when using non-ergot-derived dopamine agonists.

O'Suilleabhain PE, Oberle R, Bartis C, Dewey RB, Bottiglieri T, Diaz-Arrastia R. · Department of Neurology, Southwestern Medical Center at Dallas, University of Texas, 5323 Harry Hines Boulevard, Dallas, TX 75390-9036, USA. · Parkinsonism Relat Disord. · Pubmed #16368256 No free full text.

Abstract: Elevated homocysteine (Hcy), prevalent in Parkinson's disease (PD), is potentially a modifiable risk factor for neurologic deterioration. We measured cognitive, affective and motor changes over 2 years in a cohort of people with early PD. Subjects whose Hcy had been elevated (>14 micromol/L, n = 31) at baseline were compared with the rest (n = 66). Overall progression in 2 years did not significantly differ (p = 0.20). Four subjects with elevated and one with normal Hcy had died (p = 0.03). We conclude that hyperhomocysteinemia does not predict significantly worse progression over 2 years in early PD. The data raised the possibility of higher mortality, but the number of deaths was small.

O'Suilleabhain PE, Bottiglieri T, Dewey RB, Sharma S, Diaz-Arrastia R. · Department of Neurology, University of Texas Southwestern Medical School, Dallas, Texas, USA. · Mov Disord. · Pubmed #15390053 No free full text.

Abstract: Levodopa, typically ingested chronically at high daily doses, is predictably methylated by means of a series of reactions using B vitamins, which convert methionine to homocysteine. Elevated total plasma homocysteine (tHcy), a risk factor for dementia, has been found in PD patients using levodopa. We prospectively measured the effects on plasma tHcy and B vitamins of levodopa initiation, and measured the effects of dose changes and of treatment with dopamine agonists and entacapone. We collected paired plasma samples, at baseline and again after several months treatment, from patients initiating levodopa (n = 30), from patients whose levodopa dose was doubled (n = 15), halved or stopped (n = 14), from patients starting or stopping entacapone (n = 15) and from patients initiating or doubling dopamine agonist monotherapy (n = 16). Vitamin B12, folate, and tHcy concentrations were measured. Baseline tHcy concentration of 8.7 (2.8) micromol/L increased to 10.1 (3.1) micromol/L (P = 0.004) an average of 94 (range 36 to 200) days after initiation of 604 (240 to 1050) mg/day of L-dopa. Average concentration of vitamin B12 fell from 380 to 291 pmol/ L (P = 0.01). Patients who doubled their daily levodopa dose experienced tHcy elevations from 9.5 to 11.1 micromol/L (P = 0.05). Levodopa reduction, agonist treatment, and entacapone treatment did not have significant effects. Levodopa elevates tHcy and lowers vitamin B12 concentration to modest degrees. The clinical implications, if any, have not yet been determined.

Baseman DG, O'Suilleabhain PE, Reimold SC, Laskar SR, Baseman JG, Dewey RB. · University of Texas Southwestern Medical School, University of Texas Southwestern Medical Center, Dallas, TX 75390-9036, USA. · Neurology. · Pubmed #15277624 No free full text.

Abstract: OBJECTIVE: To determine if pergolide injures heart valves, by comparing echocardiographic findings in pergolide-treated patients with those of a historical control group. METHODS: Letters were sent to all patients in the authors' practice believed to be taking pergolide, and those responders who wished to continue it were urged to undergo echocardiography. Echocardiograms were obtained on 46 patients, and scores for valvular regurgitation were compared with those from an age-matched control group derived from the Framingham Study. The composite valve regurgitation score was modeled as a linear function of total milligrams lifetime use of pergolide, controlling for age. RESULTS: Eighty-nine percent of pergolide-treated patients had some degree of valvular insufficiency. For each of the three valves for which there are control data, we found an approximately 2- to 3-fold increased risk of abnormal valves in the pergolide patients (odds ratio [OR] approximately 3) and an estimated 14-fold increased risk of concerning tricuspid regurgitation (OR = 18.4). The composite valve score (the sum of valve scores for each of the four valves) was a function of lifetime pergolide use. CONCLUSION: Pergolide may injure cardiac valves, resulting most commonly in tricuspid regurgitation.

O'Suilleabhain PE, Sung V, Hernandez C, Lacritz L, Dewey RB, Bottiglieri T, Diaz-Arrastia R. · Department of Neurology, The University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. · Arch Neurol. · Pubmed #15210523 links to  free full text

Abstract: BACKGROUND: An elevated plasma homocysteine (Hcy) level has been prospectively associated with an increased risk of vascular and degenerative dementias. An Hcy elevation is prevalent in patients with Parkinson disease (PD) in part because levodopa metabolism produces Hcy. The clinical relevance of an elevated Hcy level in patients with PD is unknown. OBJECTIVE: To determine if hyperhomocysteinemia in patients with PD is associated with depression or with cognitive or physical impairments. DESIGN: Ninety-seven people with a mean (SD) PD duration of 3.6 (1.6) years completed the Beck Depression Inventory, a battery of 11 cognitive tests, and the motor and function components of the Unified Parkinson's Disease Rating Scale. Normalized scores for the affective, cognitive, and physical measures were compared between those with a normal Hcy level (n = 66) and those with hyperhomocysteinemia (n = 31) (Hcy level, >1.89 mg/L [>14 micro mol/L]), controlling for age, sex, disease duration, and treatment. RESULTS: Subjects with an elevated Hcy level were slightly older (68 vs 62 years), but had similar plasma concentrations of vitamin B(12) and folate. Hyperhomocysteinemic patients were more depressed (P =.02) and had worse cognition (P<.01), but the physical measure did not differ. CONCLUSIONS: Patients with PD and hyperhomocysteinemia are more likely to be depressed and to perform worse on neuropsychometric tasks compared with normohomocysteinemic patients. Further research is warranted to see if hyperhomocysteinemia is a reversible risk factor for neuropsychiatric burden in patients with PD.

Defreitas GA, Lemack GE, Zimmern PE, Dewey RB, Roehrborn CG, O'Suilleabhain PE. · Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9110, USA. · Urology. · Pubmed #14550436 No free full text.

Abstract: OBJECTIVES: To examine the urodynamic (UDS) attributes of detrusor overactivity (DO) in patients with Parkinson's disease in comparison to DO in men without neurologic disease, in whom DO is presumably outlet obstruction induced. METHODS: The UDS database was reviewed for three groups of patients: group 1, men with lower urinary tract symptoms (LUTS) and no known neurologic condition with DO (n = 22); group 2, men with Parkinson's disease and LUTS (n = 39); and group 3, women with Parkinson's disease and LUTS (n = 18). Statistical analysis was used to compare the UDS parameters and diagnoses among the groups and to test for associations between Parkinson's disease duration, Hoehn and Yahr score, and UDS findings. RESULTS: Patients with Parkinson's disease had a significantly lower median volume at first detrusor contraction than those with non-neurogenic DO. The percentage of group 1 patients with urge incontinence was significantly lower than that found in the other two groups (9.1% versus 53.8% and 55.6%, P <0.001 and 0.002, respectively). No statistically significant correlation between the duration or severity of Parkinson's disease and UDS parameters was found. CONCLUSIONS: Men with non-neurogenic LUTS are less likely to have urge incontinence on UDS than either men or women with Parkinson's disease. DO owing to Parkinson's disease occurs earlier during filling compared with non-neurogenic DO, especially in women. The duration and severity of Parkinson's disease are not predictive of the nature or severity of UDS abnormalities.

Trivedi JR, Wolfe GI, Nations SP, Burns DK, Bryan WW, Dewey RB. · Department of Neurology, University of Texas Southwestern Medical Center, Dallas, 75390, USA. · Arch Neurol. · Pubmed #12756142 links to  free full text

Abstract: BACKGROUND: Adult polyglucosan body disease (PGBD) is rare and typically presents with upper and lower motor neuron involvement and neurogenic bladder. Extrapyramidal features are unusual in PGBD and are presumed secondary to widespread pathology that includes the basal ganglia. There are no prior reports of Lewy bodies in PGBD. OBJECTIVE: To report a unique finding of Lewy bodies in a patient with PGBD. REPORT OF A CASE A 46-year-old woman initially presented with a 4-year history of resting tremor. The tremor responded to levodopa therapy. Several months later, she developed upper and lower motor neuron involvement and other clinical features of PGBD. A sural nerve biopsy specimen revealed intra-axonal polyglucosan bodies that confirmed the clinical diagnosis. Bulbar and limb weakness progressed, and she developed dementia. She died 6 years after onset. At autopsy, extensive polyglucosan body formation was found in many regions of the central nervous system. In addition, numerous alpha-synuclein staining Lewy bodies were observed in the substantia nigra, accompanied by marked neuron depopulation. CONCLUSIONS: To our knowledge, this is the first report of adult PGBD associated with Lewy bodies and levodopa-responsive tremor. Although polyglucosan bodies were seen in substantia nigra, it is most likely that our patient had coexisting Parkinson disease.

O'Suilleabhain PE, Dewey RB. · Clinical Center for Movement Disorders, Department of Neurology, University of Texas Southwestern Medical School, Dallas, TX, USA. · Arch Neurol. · Pubmed #12056935 links to  free full text

Abstract: BACKGROUND: Excessive daytime somnolence is a common report among patients who have Parkinson disease (PD). The relative contributions of disease severity and of the various dopaminergic drugs are unclear. OBJECTIVE: To separate and quantify the contributions of disease markers and drug doses. METHODS: Patients seen during a 7-month period at a center for movement disorders completed the Epworth Sleepiness Scale. Treatment subgroups were compared. The relationship to sedation of age; dopaminergic drug classes and doses; Hoehn and Yahr stage; duration of disease; total score on the motor subsection of the Unified Parkinson Disease Rating Scale; and the presence or absence of dementia, depression, or hallucinations was calculated using simple and multiple regression and t tests. RESULTS: The Epworth Sleepiness Scale scores were higher among patients with PD (mean [SD], 10.8 [5.3]; n = 368) compared with patients with other neurological disorders (mean, 8.5 [5.1]; n = 243; P<.001). A model containing the Hoehn and Yahr stage, levodopa dose, and use of a dopamine agonist was the best at predicting the total score of Epworth Sleepiness Scale in patients who have PD, but accounted for only 9% of the interindividual variance. The parameter estimates (SE) corresponded to a 1.02 (0.03)-point increase per Hoehn and Yahr stage, a 0.14 (0.06)-point increase per 100-mg increase in levodopa dose over 24 hours, and a 2.33 (0.57)-point increase with use of an agonist. There was no statistically significant dose response for agonists. No statistically significant difference in sedation among the commonly used dopamine agonists was found. CONCLUSIONS: Somnolence in patients with PD, which is on average 25% higher than in other neurological diseases, is related to PD stage, levodopa dose, and the use of a dopamine agonist. However, most of the variability in sedation levels in patients with PD as well as in controls is the result of, as yet, unidentified factors.

O'Suilleabhain P, Bullard J, Dewey RB. · Department of Neurology, University of Texas, Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9036, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #11606670 links to  free full text

Abstract: OBJECTIVES: Impaired proprioception has been previously reported in patients with Parkinson's disease. It was hypothesised that dopaminergic medications transiently depress proprioception, with amplification of adventitious movements as a result. This study tested for effects on proprioception of dopaminergic drugs, and for associations between such effects and drug induced dyskinesias. METHODS: In 17 patients with Parkinson's disease, arm proprioception was tested in the practically defined "off" state, and retested 1 hour after taking levodopa or dopamine agonist. Testing consisted of side to side comparison of elbow angle, matching the contralateral elbow angle, and spatial recall of an unrestrained arm. RESULTS: Proprioception deteriorated as hypothesised, reaching significance by one tailed t test for each of the three tasks. The relative deterioration (and the 95% lower confidence bound for estimated deterioration) was 31% (4%) for side to side elbow comparison, was 27% (11%) for accuracy in matching the contralateral elbow angle, and was 11% (0%) for spatial recall. Dyskinetic (n=6) and non-dyskinetic (n=11) patients did not differ significantly in these effects on proprioception. Control subjects (n=6) and untreated parkinsonian subjects (n=5) did not significantly differ from the parkinsonian patients in the off state. CONCLUSIONS: Administration of levodopa and dopamine agonists were associated with a modest acute suppression in central responsiveness to joint position. It is speculated that compensatory exaggerated movement could account in part for the phenomenon of drug induced dyskinesias.

O'Suilleabhain PE, Dewey RB. · Department of Neurology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9036, USA. · Mov Disord. · Pubmed #11295779 No free full text.

Abstract: An electromagnetic tracking system was used to record arm motion in subjects with Parkinson's disease (n = 23), essential tremor (n = 28) or without neurological disease (n = 4). Tremor magnitude was calculated by averaging the three-dimensional displacement of individual tremor bursts. Tremor magnitude calculated in this manner was quite closely correlated with a clinician's estimate (r = 0.88 and 0.86 for Parkinsonian and essential tremors, respectively) and was reproducible (r = 0.93 for repeated recordings). The accuracy of the device and algorithm was confirmed by mechanically generating oscillations of known magnitudes and frequencies. This device is adaptable for quantifying different types of tremors and its accuracy is easy to verify. Because position rather than acceleration is tracked, tremor amplitude can be stated in readily comprehensible units.

Dewey RB, O'Suilleabhain PE. · Clinical Center for Movement Disorders, Department of Neurology, University of Texas Southwestern Medical Center, Dallas, USA. · Neurology. · Pubmed #11113242 No free full text.

This publication has no abstract.

Lemack GE, Dewey RB, Roehrborn CG, O'Suilleabhain PE, Zimmern PE. · Department of Urology, University of Texas-Southwestern Medical Center, Dallas, Texas 75235-9110, USA. · Urology. · Pubmed #10925088 No free full text.

Abstract: OBJECTIVES: To assess the lower urinary tract symptoms (LUTS) in men and women with mild to moderate Parkinson's disease (PD) using validated symptom questionnaires. METHODS: Eighty men and 39 women with mild to moderate PD (Hoehn and Yahr score less than 3) were mailed LUTS questionnaires to complete and return. Men received the American Urological Association Symptom Index and women received the Urogenital Distress Inventory-6. Patients not responding by mail were called and asked to complete the survey over the telephone. Control populations of both symptomatic and asymptomatic men and women (without PD) were identified for comparison. RESULTS: The overall response rate was 78%. Men with early-stage PD had higher American Urological Association Symptom Index scores than age-matched controls (total score of 12.0 versus 7.7, P <0.05) and scores similar to those reported for men with symptomatic benign prostatic hyperplasia (12.5). Specific items noted to be higher among the men with PD included questions regarding frequency and urgency. Women with PD had higher scores on the Urogenital Distress Inventory-6 than non-age-matched controls (total score of 4.8 versus 2.1, P <0.05), but lower scores than an age-matched group of neurologically intact women presenting for urologic evaluation of LUTS (6.9, P <0.05). CONCLUSIONS: On the basis of the responses to the validated symptom indexes, the development of LUTS appears to occur at an earlier stage of PD than was once appreciated. Prompt evaluation and treatment of patients with lower urinary tract complaints in the setting of PD may identify bladder dysfunction at an earlier, more treatable stage.