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Michael S Okun

Publications and source records attributed to Michael S Okun.

At least 19 recordsLinked to original sources
PubMed2007

Laterality, region, and type of motor dysfunction correlate with cognitive impairment in Parkinson's disease.

We studied the relationship between two screening cognitive measures and off motor Unified Parkinson's Disease Rating Scale (UPDRS) scores in 108 Parkinson's disease patients. Multiple regressions were conducted to examine the UPDRS subscores' unique contributions to cognitive function. When including bradykinesia, rigidity, and postural/gait instability subscores, only bradykinesia predicted Mini Mental Status Examination (MMSE), normalized beta = -0.57, t(104) = -3.31, P < 0.01, and Dementia Rating Scale-2 (DRS-2), normalized beta = -0.45, t(104) = -2.55, P < 0.05. Tremor was not included in the regression analyses because it did not correlate with cognitive function. When including axial and appendicular subscores, only the axial subscore predicted MMSE, normalized beta = -0.39, t(105) = -3.19, P < 0.01, and DRS-2 scores, normalized beta = -0.40, t(106) = -3.28, P < 0.01. When including left-sided and right-sided subscores, only the right-sided symptoms predicted DRS-2 scores, normalized beta = -0.28, t(105) = -2.45, P < 0.05, and showed a trend toward predicting MMSE scores, normalized beta = -0.22, t(105) = -1.95, P = 0.054. We therefore found that right-sided symptoms (for laterality), axial symptoms (for region), and bradykinesia (for type of symptoms) were the best predictors of cognitive function.

Aged↗
PubMed2006

Deep brain stimulation in the internal capsule and nucleus accumbens region: responses observed during active and sham programming.

BACKGROUND: Recently, anterior limb of the internal capsule and nucleus accumbens deep brain stimulation (DBS) has been used in the treatment of medication-refractory obsessive-compulsive disorder (OCD). This region has been previously explored with lesion therapy, but with the advent of DBS there exists the possibility of monitoring the acute and chronic effects of electrical stimulation. The stimulation-induced benefits and side effects can be reversibly and blindly applied to a variety of locations in this region. OBJECTIVE: To explore the acute effects of DBS in the anterior limb of the internal capsule and nucleus accumbens region. METHODS: Ten total DBS leads in five patients with chronic and severe treatment-refractory OCD were tested. Patients were examined 30 days after DBS placement and received either "sham" testing or actual testing of the acute effects of DBS (the alternative condition tested 30 days later). RESULTS: Pooled responses were reviewed for comparability of distribution using standard descriptive methods, and relationships between the variables of interest were sought using chi2 analysis. A total of 845 stimulation trials across the five patients were recorded and pooled. Of these 16% were elicited from sham stimulation and 17% from placebo (0 V stimulation). A comparison of active to sham trials showed that sham stimulation was not associated with significant side effects or responses from patients. Non-mood-related responses were found to be significantly associated with the ventral lead contacts (0 and 1) (p = 0.001). Responses such as taste, smell and smile were strongly associated with the most ventral lead positions. Similarly, physiological responses--for example, autonomic changes, increased breathing rate, sweating, nausea, cold sensation, heat sensation, fear, panic and panic episodes--were significantly associated with ventral stimulation (p = 0.001). Fear and panic responses appeared clustered around the most ventral electrode (0). Acute stimulation resulted in either improved or worsened mood responses in both the dorsal and ventral regions of the anterior limb of the internal capsule. CONCLUSION: The acute effects of DBS in the region of the anterior limb of the internal capsule and nucleus accumbens, particularly when obtained in a blinded fashion, provide a unique opportunity to localise brain regions and explore circuitry.

Adult↗
PubMed2006

Three-year outcomes in deep brain stimulation for highly resistant obsessive-compulsive disorder.

Deep brain stimulation (DBS) of the anterior limb of the internal capsule has been shown to be beneficial in the short term for obsessive-compulsive disorder (OCD) patients who exhaust conventional therapies. Nuttin et al, who published the first DBS for OCD series, found promising results using a capsule target immediately rostral to the anterior commissure extending into adjacent ventral capsule/ventral striatum (VC/VS). Published long-term outcome data are limited to four patients. In this collaborative study, 10 adult OCD patients meeting stringent criteria for severity and treatment resistance had quadripolar stimulating leads implanted bilaterally in the VC/VS. DBS was activated openly 3 weeks later. Eight patients have been followed for at least 36 months. Group Yale-Brown Obsessive Compulsive Scale (YBOCS) scores decreased from 34.6+/-0.6 (mean+/-SEM) at baseline (severe) to 22.3+/-2.1 (moderate) at 36 months (p < 0.001). Four of eight patients had a > or =35% decrease in YBOCS severity at 36 months; in two patients, scores declined between 25 and 35%. Global Assessment of Functioning scores improved from 36.6+/-1.5 at baseline to 53.8+/-2.5 at 36 months (p < 0.001). Depression and anxiety also improved, as did self-care, independent living, and work, school, and social functioning. Surgical adverse effects included an asymptomatic hemorrhage, a single seizure, and a superficial infection. Psychiatric adverse effects included transient hypomanic symptoms, and worsened depression and OCD when DBS was interrupted by stimulator battery depletion. This open study found promising long-term effects of DBS in highly treatment-resistant OCD.

Adult↗
PubMed2006

Hypersexuality and paraphilia induced by selegiline in Parkinson's disease: report of 2 cases.

While hypersexuality and paraphilia are known side effects of anti-Parkinson medications, it is seldom reported. Furthermore, selegiline is rarely implicated in such behaviors. We report two cases of early onset PD who experienced paraphilia and hypersexuality when selegiline was initiated, and later developing obsessive-compulsive and punding behavior with the addition of dopamine agonists. Social repercussions may prohibit patients and/or their families from volunteering such information.

Antiparkinson Agents↗
PubMed2006

Testosterone therapy in men with Parkinson disease: results of the TEST-PD Study.

BACKGROUND: Testosterone deficiency has been reported in patients with Parkinson disease (PD), Alzheimer disease, and Huntington disease. It is not known whether testosterone therapy (TT) in men with borderline hypogonadism and neurodegenerative diseases will be of substantial benefit. Previously, we reported that testosterone deficiency is more common in patients with PD compared with age-matched control subjects, and we also reported in 2 small open-label studies that some nonmotor symptoms responded favorably to TT. OBJECTIVE: To define the effects of TT on nonmotor and motor symptoms in men with PD and probable testosterone deficiency. DESIGN: Double-masked, placebo-controlled, parallel-group, single-center trial. PATIENTS: Two experimental groups: patients with PD who were receiving either TT or placebo. INTERVENTIONS: Participants received either the study drug by intramuscular injection (200 mg/mL of testosterone enanthate every 2 weeks for 8 weeks) or placebo (isotonic sodium chloride solution injections). In patients in each group, the testosterone serum concentration was obtained at each study visit. During 2 study visits, testosterone levels were blindly evaluated and the intramuscular testosterone dose was increased by 200 mg/mL if the free testosterone value failed to double from the baseline value. MAIN OUTCOME MEASURES: The primary outcome variable was the St Louis Testosterone Deficiency Questionnaire, and secondary outcome measures included measures of mood, cognition, fatigue, motor function, and frequency of adverse events. At the end of the double-blind phase, all patients were offered open-label TT and were followed up after 3 and 6 months. RESULTS: Fifteen patients in the placebo group (mean age, 69.9 years), receiving a mean total levodopa equivalent dose of 924 mg/d, had a baseline free testosterone level of 47.91 pg/mL, compared with 15 patients in the TT group (mean age, 66.7 years), receiving an average total levodopa equivalent dose of 734 mg/d, who had a baseline free testosterone level of 63.49 pg/mL. Testosterone was generally well tolerated. More subjects in the TT group experienced lower extremity edema (40% vs 20%). In 2 patients, 1 in each group, prostate-specific antigen levels were elevated from baseline. The improvement in the TT group compared with the placebo group (1.7 vs 1.1) on the St Louis Testosterone Deficiency Scale was not statistically significant. In addition, there were no significant differences in motor and nonmotor features of PD between the 2 groups, although a few subscales showed improvements (Hopkins Verbal Learning Test, P<.04; and Backward Visual Span subtrial, P<.03). However, long-term open-label TT resulted in delayed but sustained improvement in subjects in the TT group who continued to receive treatment (n = 6) compared with subjects in the placebo group who elected not to receive TT (n = 3). CONCLUSIONS: Testosterone therapy was generally well tolerated in elderly men with PD and probable testosterone deficiency. While there was no significant difference in the motor and nonmotor scales between the TT and placebo groups at the end of 8 weeks compared with baseline, this may be due to several study limitations, including small sample size, a strong placebo effect with intramuscular therapy, and short follow-up that did not allow measurement of delayed effects of TT in some subjects. Until more definitive studies are reported, practitioners should be particularly cautious in treatment of low testosterone concentrations in men with PD and borderline testosterone deficiency, and careful consideration should be given to the risks vs the benefits of TT.

Affect↗
PubMed2006

Deep brain stimulation of the internal segment of the globus pallidus in delayed runaway dyskinesia.

BACKGROUND: Dyskinesias that occur during a period without medication after embryonic cell transplantation have been commonly reported in double-blind trials; however, to date, they have not been reported in the few patients who participated in open-label pilot studies. DESIGN: Single case observation with preoperative and postoperative data, and intraoperative single-cell physiology. PATIENT: A patient who underwent embryonic cell transplantation in 1993 as part of the University of South Florida open-label study was referred for evaluation of intractable dyskinesia of the right arm. The dyskinesia was present during evaluation of the patient after a 12-hour period without medication and was clinically disabling. It was manifested as a severe groping movement of the hand. Intraoperative physiologic evaluation revealed decreased firing rates in the internal segment of the globus pallidus. RESULTS: Deep brain stimulation of the internal segment of the globus pallidus resulted in resolution of the dyskinesia. CONCLUSION: This case highlights the delayed development of runaway dyskinesia after a period without medication as an important potential long-term adverse effect of embryonic cell transplantation in patients with Parkinson disease.

Deep Brain Stimulation↗
PubMed2006

Genome-wide genotyping in Parkinson's disease and neurologically normal controls: first stage analysis and public release of data.

BACKGROUND: Several genes underlying rare monogenic forms of Parkinson's disease have been identified over the past decade. Despite evidence for a role for genetics in sporadic Parkinson's disease, few common genetic variants have been unequivocally linked to this disorder. We sought to identify any common genetic variability exerting a large effect in risk for Parkinson's disease in a population cohort and to produce publicly available genome-wide genotype data that can be openly mined by interested researchers and readily augmented by genotyping of additional repository subjects. METHODS: We did genome-wide, single-nucleotide-polymorphism (SNP) genotyping of publicly available samples from a cohort of Parkinson's disease patients (n=267) and neurologically normal controls (n=270). More than 408,000 unique SNPs were used from the Illumina Infinium I and HumanHap300 assays. FINDINGS: We have produced around 220 million genotypes in 537 participants. This raw genotype data has been and as such is the first publicly accessible high-density SNP data outside of the International HapMap Project. We also provide here the results of genotype and allele association tests. INTERPRETATION: We generated publicly available genotype data for Parkinson's disease patients and controls so that these data can be mined and augmented by other researchers to identify common genetic variability that results in minor and moderate risk for disease.

Aged↗
PubMed2006

Lessons learned in deep brain stimulation for movement and neuropsychiatric disorders.

The introduction of deep brain stimulation (DBS) as a treatment for medication-refractory essential tremor in the late 1980s revealed, for the first time, that "chronically" implanted brain hardware had the potential to modulate neurologic function with surprisingly low morbidity. Over time, the therapeutic promise of DBS has become evident in Parkinson's disease and dystonia. In some experienced centers, complex tremor disorders, such as posttraumatic Holmes tremor and the tremor of multiple sclerosis, are being increasingly targeted. More recently, other indications, including obsessive-compulsive disorder, Tourette's syndrome, major depression, and chronic pain, have been proposed. As the field has expanded, our knowledge about potential cognitive side effects of DBS has also expanded. This article reviews the current knowledge regarding the impact of stimulation of the subthalamic nucleus, globus pallidus internus, and ventralis intermedius nucleus of the thalamus on symptoms in essential tremor, Parkinson's disease, and dystonia. Also discussed are the emerging targets, what is known about the cognitive sequelae of DBS, and what has been learned about the complications and therapeutic failures.

Brain↗
PubMed2006

Long-term habituation of the smile response with deep brain stimulation.

Human and animal research has shown that the ventral striatum, including the nucleus accumbens, may play a critical role in mediating positive emotions. Recently we described a subject with obsessive-compulsive disorder who intra-operatively exhibited the acute onset of an asymmetric smile and acute positive emotional change with contralateral deep brain stimulation (DBS) in either the right or left nucleus accumbens and anterior limb of the internal capsule region. The purpose of the present study was to examine the stability of the stimulation-induced smile(s) over a 12-month period. Custom computer software objectively quantified left and right facial movement during DBS. Although stimulation-induced smiles were elicited at one and two months post-surgery, they were no longer present from 3-12 months following chronic high frequency DBS. The smiles could not be elicited even with long washout periods. These findings imply potential long-term habituation and changes in the neural chemistry (possibly neuroplasticity) induced by chronic DBS.

Adult↗
PubMed2006

Dual electrode thalamic deep brain stimulation for the treatment of posttraumatic and multiple sclerosis tremor.

OBJECTIVE: To report the results of ventralis intermedius nucleus/ventralis oralis posterior nucleus (VIM) plus ventralis oralis anterior (VOA)/ventralis oralis posterior (VOP) thalamic deep brain stimulation (DBS) for the treatment of posttraumatic and multiple sclerosis tremor. OBJECTIVE: The treatment of posttraumatic tremor and multiple sclerosis tremor, by either medication or surgery, has proven difficult. Lesions and DBS have had mixed and somewhat disappointing results. Previously, we reported the use of two DBS electrodes (one at the VIM/VOP border and one at the VOA/VOP border) as effective for the treatment of posttraumatic tremor in a single patient. In this study, we report the results of this technique on four patients. METHODS: Four patients with either posttraumatic tremor (n = 3) or multiple sclerosis tremor (n = 1) underwent placement of two DBS electrodes (one at the VIM/VOP border and one at the VOA/VOP border). Patients underwent preoperative testing and testing at a minimum of 6 months after implantation in four conditions: On VIM DBS/On VOA/VOP DBS; On VIM DBS/Off VOA VOP DBS (5 h DBS washout); Off VIM DBS/Off VOA/VOP DBS (12 h overnight washout); and Off VIM DBS/On VOA/VOP DBS (5 h DBS washout). RESULTS: Each of the patients showed improvements in all four conditions when compared with the baseline. All of the improvements were maintained with chronic DBS, without tremor rebound. An analysis was performed to determine whether each condition was associated with symptom reduction (percentage change). The percentage reduction was significant for each condition and measure, despite the small number of participants. For the total tremor rating scale score, the Off VIM/Off VOA/VOP condition yielded less symptom reduction than the On VIM condition or the On VOA/VOP condition. The On VIM and On VOA/VOP conditions did not differ significantly from each other in terms of contralateral upper extremity symptoms or total clinical score. Activation of both the VIM and VOA/VOP electrodes was associated with the greatest symptom reduction. CONCLUSION: Tremors, such as those examined in this study, that are refractory to medications and have a poor response to VIM DBS monotherapy, may respond favorably to VIM plus VOA/VOP DBS. Two electrodes may be better than one for the treatment of certain disorders; however, more study will be required to confirm this hypothesis.

Adolescent↗
PubMed2006

Tutorial on maximum inspiratory and expiratory mouth pressures in individuals with idiopathic Parkinson disease (IPD) and the preliminary results of an expiratory muscle strength training program.

Respiratory symptoms are recognized as sequelae of motor dysfunction in idiopathic Parkinson's disease (IPD) and these symptoms have the potential to cause problems with swallow, cough, voice and speech. Specifically, maneuvers that require rapid activation and coordination of upper airway and chest wall musculature become progressively impaired as motor dysfunction progresses during the natural course of the disease. This study reports on the maximum inspiratory and expiratory pressures produced by 28 participants (average age 64) diagnosed with moderate to severe IPD (average stage 2.5 with a range of 2.0-3.0). All measures were collected during the "medication on" state. Outcomes of a specific respiratory muscle strength training technique for improving maximum expiratory pressure are reported for three of the patients in this study. Techniques that focus on strengthening the respiratory muscles in patients with IPD (other than with low load breathing exercises), have not been previously reported. The results of this pilot study demonstrate that respiratory muscle weakness may be an important factor in the respiratory complications in IPD and that respiratory muscle strength training has the potential to improve expiratory muscle strength for this population. This improvement has the potential to positively impact high forced respiratory activities, such as forced breathing maneuvers, swallow, cough and speech functions that require greater magnitude and duration of expiration.

Adult↗
PubMed2005

The human prion gene M129V polymorphism is not associated with idiopathic Parkinson's disease in three distinct populations.

Coexistence of prion disease and idiopathic Parkinson's disease (IPD) has been previously described. It remains unclear whether this relationship may reflect the high incidence of IPD or whether both prion and IPD share common pathogenetic mechanisms. For this reason, we investigated the genotype distribution of the M129V polymorphism of the human prion gene for association with IPD (controls: n = 398, IPD cases: n = 400). No association between genotypes in codon 129 and IPD was detected in three distinct populations, suggesting that this PRNP polymorphism has no direct influence on the susceptibility to IPD.

Adult↗
PubMed2005

Management of referred deep brain stimulation failures: a retrospective analysis from 2 movement disorders centers.

BACKGROUND: Since the Food and Drug Administration approved DBS, there has been a surge in the number of centers providing the procedure. There is currently no consensus regarding appropriate screening procedures, necessary training of individuals providing the therapy, the need for an interdisciplinary team, or guidelines for the management of complications. An increasing number of patients come to experienced DBS centers after unsatisfactory results from DBS surgery. An attempt is made herein to evaluate the reasons for DBS failure in a series of such patients and to make recommendations to improve overall DBS outcomes. OBJECTIVE: To improve outcomes of deep brain stimulation (DBS) surgery by analyzing a series of patients who had suboptimal results from DBS. METHODS: Forty-one consecutive patients complaining of suboptimal results from DBS surgery came to the University of Florida Movement Disorders Center, or to Beth Israel Movement Disorders Center, over a 24-month period. All patients had undergone implantation of DBS devices at outside medical centers. Each patient was evaluated by a movement disorders neurologist, and the complete medical record was reviewed. The DBS device for each patient was interrogated for adverse effects and programmed for maximal benefit. Postoperative imaging studies were evaluated whenever possible. RESULTS: The average age of patients was 63.4 years (range, 49-84 years). The indication for surgery (by record review) included 9 patients with essential tremor, 31 with Parkinson disease, and 1 with dystonia. The diagnoses after referral examination included 5 with essential tremor, 26 with Parkinson disease, 3 with Parkinson disease and dementia, 1 with Parkinson disease and essential tremor, 1 with corticobasal degeneration, 1 with dystonia, 2 with multiple system atrophy, 1 with progressive supranuclear palsy, and 1 with myoclonus. Issues related to inadequate preoperative screening: Thirty (73%) of 41 patients saw a movement disorders specialist prior to DBS implantation. Fourteen (34%) patients had neuropsychological testing, 4 (10%) did not have testing, and in 23 cases (56%), it could not be determined whether or not they were tested. Five (12%) of 41 patients had an inadequate medication trial, and 5 patients (12%) had significant cognitive dysfunction prior to their DBS implantation. Surgical and device-related complications: Nineteen (46%) of 41 patients had suboptimally placed electrodes. Seven electrodes (17%) were replaced with improvement. Three patients' devices had failed due to end of battery life, 2 had infections, and 1 had a fractured lead. Programming and medication adjustments: Seven (17%) of 41 patients had no or poor access to programming. Two patients (5%) moved, and 2 physicians (5%) moved, creating issues with access to care. Eight patients (20%) required local follow-up (they flew to remote centers to have the surgery performed). Fifteen patients (37%) were inadequately programmed and improved significantly with reprogramming. Six patients (15%) experienced partial improvement with reprogramming, and 21 patients (51%) failed to improve despite extensive reprogramming. Thirty patients (73%) benefited from medication changes, 4 (10%) had antidepressants added to their regimens, and 1 (2%) had donepezil hydrochloride added. One patient's carbidopa/levodopa (2%) was restarted after complete discontinuation. OUTCOMES: With the various postoperative interventions described, 21 (51%) of 41 patients had good outcomes, 6 (15%) had modest clinical improvement, and 14 (34%) did not improve. CONCLUSIONS: With appropriate intervention, 51% of patients who complained of "failed" DBS procedures ultimately had good outcomes. Thirty-four percent of these patients had persistently poor outcomes despite maximal intervention. This case series provides important insights into reasons for "DBS failure" and proposes strategies to manage patients with DBS more effectively.

Aged↗
PubMed2005

Stimulation of the subthalamic nucleus in a patient with Parkinson disease and essential tremor.

BACKGROUND: The preferred surgical target for the treatment of Parkinson disease (PD) is either the internal globus pallidus or the subthalamic nucleus (STN); the target for treatment of essential tremor (ET) is the thalamic subnucleus ventralis intermedius (Vim). Some patients with PD have coexistent ET, and the identification of a single surgical target to treat both parkinsonian motor symptoms and ET would be of practical importance. OBJECTIVE: To describe the use of the STN target in deep brain stimulator (DBS) surgery to treat PD motor symptoms and the action-postural tremor of ET. DESIGN: Case report. PATIENT: A 62-year-old man had a greater than 30-year history of action-postural tremor in both hands, well controlled with beta-blockers for more than 20 years. He developed resting tremor, bradykinesia, and rigidity on his right side that progressed to his left side during the past 10 years. Dopaminergic medication improved his rigidity and bradykinesia, with only mild improvement of his resting tremor and no effect on his action-postural tremor. INTERVENTIONS: Left pallidotomy followed by placement of a left DBS in the Vim and subsequent placement of a right STN DBS. MAIN OUTCOME MEASURES: Control of symptoms of PD and ET. RESULTS: The left pallidotomy controlled the patient's parkinsonian motor symptoms on the right side of his body, but did not affect the action-postural component of his tremor. The symptoms on the left side of the body, including both an action-postural and a resting tremor (as well as the rigidity and bradykinesia), improved after placement of a single right STN DBS. CONCLUSION: Placement of an STN DBS should be considered as the procedure of choice for surgical treatment of patients with a combination of PD and ET.

Deep Brain Stimulation↗
PubMed2005

Rebound psychosis: effect of discontinuation of antipsychotics in Parkinson's disease.

To determine whether psychiatrically stable patients with a history of drug-induced psychosis could be successfully weaned off their antipsychotic drug, we offered consecutive Parkinson disease (PD) patients on quetiapine or clozapine, who were free of any on-going psychosis, to be slowly weaned off their antipsychotic drug. Before the study was aborted 6 PD patients (mean age, 78 years) with an average antipsychotic exposure of 20 months (5 on quetiapine, 1 on clozapine) were enrolled. After the antipsychotic agent was discontinued, psychosis recurred in 5 of 6 patients. In 3 patients the "rebound psychosis" was worse than the original psychotic episode and required subsequent higher antipsychotic medication doses.

Aged↗
PubMed2005

Paraneoplastic chorea with leukoencephalopathy presenting with obsessive-compulsive and behavioral disorder.

Chorea is a rare manifestation of paraneoplastic disease and is associated with CV2/CRMP-5 antibodies. Obsessive-compulsive disorder and large-scale white matter abnormalities on MRI have not been previously reported in association with these antibodies. We report on a case of CV2 paraneoplastic syndrome with obsessive-compulsive behavior preceding the motor manifestations of chorea with associated leukoencephalopathy on MRI. The literature on paraneoplastic chorea is reviewed.

Aged↗