Parkinson Disease: Rodriguez RL

Hooper AK, Okun MS, Foote KD, Fernandez HH, Jacobson C, Zeilman P, Romrell J, Rodriguez RL. · University of Florida, Movement Disorders Center, Gainesville, FL 32601, USA. · Stereotact Funct Neurosurg. · Pubmed #18334856 No free full text.

Abstract: Deep brain stimulation (DBS) surgery has become the gold standard for treatment of select refractory cases of Parkinson disease and essential tremor. Despite the usefulness of DBS surgery in many cases, there remain situations where lesion therapy (subthalamotomy, pallidotomy or thalamotomy) may provide a reasonable alternative to DBS. We reviewed the University of Florida Institutional Review Board-approved database for movement disorders surgery and identified 286 DBS leads placed in 189 patients as well as 4 additional patients who had lesion therapy. In these 4 cases we reviewed the clinical presentations that resulted in a multidisciplinary team opting for lesion therapy over DBS. Lesion therapy represents a viable alternative and has several important advantages, including a decreased need for access to specialists and clinical follow-up, improved affordability, and a lower infection risk.

Rodriguez RL, Fernandez HH, Haq I, Okun MS. · Department of Neurology, University of Florida Movement Disorders Center, McKnight Brain Institute, Gainesville, Florida, USA. · Neurologist. · Pubmed #17848865 No free full text.

Abstract: BACKGROUND: Deep brain stimulation (DBS) has emerged as an important treatment for medication refractory movement and neuropsychiatric disorders. General neurologists and even general practitioners may be called upon to screen potential candidates for DBS. The patient selection process plays an important role in this procedure. REVIEW SUMMARY: In this article, we discuss "pearls" for the clinician who may be called upon to identify appropriate candidates for DBS. Additionally, we will discuss the important points that should be considered when referring patients for surgical intervention. CONCLUSION: Diagnosis, response to levodopa, cognitive status, psychiatric status, access to care, and patient expectations are all essential elements of the patient selection process for DBS. These areas must be adequately addressed prior to any surgical procedure.

Okun MS, Fernandez HH, Rodriguez RL, Foote KD. · Department of Neurology, University of Florida Movement Disorders Center, McKnight Brain Institute, Gainesville, USA. · Geriatrics. · Pubmed #17489644 No free full text.

Abstract: Deep brain stimulation (DBS) can improve symptoms in well-selected patients with Parkinson's disease. Primary care physicians must take into account many important issues when considering referral for DBS. The Florida Surgical Questionnaire for PD (FLASQ-PD), a 5-section screening tool that can help primary care providers identify appropriate DBS candidates, can be filled out and scored by a general practitioner, advanced clinical nurse practitioner, physician assistant, or trained nurse. Potential candidates who score well on this questionnaire can be referred for presurgical multidisciplinary evaluation at an experienced DBS implanting center.

Skidmore FM, Rodriguez RL, Fernandez HH, Goodman WK, Foote KD, Okun MS. · Department of Neurology, McKnight Brain Institute, University of Florida College of Medicine in Gainesville, 32610, USA. · CNS Spectr. · Pubmed #16816792 links to  free full text

Abstract: 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.

Shapiro MA, Chang YL, Munson SK, Jacobson CE, Rodriguez RL, Skidmore FM, Okun MS, Fernandez HH. · Department of Neurology, Movement Disorders Center, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, FL, USA; · Neuropsychiatr Dis Treat. · Pubmed #19300546 links to  free full text

Abstract: Several studies have related pathological gambling in PD to dopamine agonist therapy. A mail-in survey was sent to PD patients seen at the University of Florida Movement Disorders Center to determine gambling frequency and behavior, and any lifestyle or environmental factors associated with compulsive gambling in PD. 462 surveys were sent and 127 completed surveys were returned, of which ten were from patients who met criteria for compulsive gambling. All ten were taking dopamine agonists coincident with the compulsive gambling. Compulsive gamblers were younger, and psychological distress measures revealed that compulsive gamblers exhibited higher levels of anxiety, anger, and confusion. Thus in this cohort, we have uncovered the several characteristics of the most likely PD compulsive gambler, namely: (young) age, "angry", "anxious", and using a (dopamine) agonist.

Okun MS, Fernandez HH, Wu SS, Kirsch-Darrow L, Bowers D, Bova F, Suelter M, Jacobson CE, Wang X, Gordon CW, Zeilman P, Romrell J, Martin P, Ward H, Rodriguez RL, Foote KD. · Movement Disorders Center, University of Florida, McKnight Brain Institute, College of Medicine, Department of Neurology, Gainesville, FL 32611, USA. · Ann Neurol. · Pubmed #19288469 No free full text.

Abstract: OBJECTIVE: Our aim was to compare in a prospective blinded study the cognitive and mood effects of subthalamic nucleus (STN) vs. globus pallidus interna (GPi) deep brain stimulation (DBS) in Parkinson disease. METHODS: Fifty-two subjects were randomized to unilateral STN or GPi DBS. The co-primary outcome measures were the Visual Analog Mood Scale, and verbal fluency (semantic and letter) at 7 months post-DBS in the optimal setting compared to pre-DBS. At 7 months post-DBS, subjects were tested in four randomized/counterbalanced conditions (optimal, ventral, dorsal, and off DBS). RESULTS: Forty-five subjects (23 GPi, 22 STN) completed the protocol. The study revealed no difference between STN and GPi DBS in the change of co-primary mood and cognitive outcomes pre- to post-DBS in the optimal setting (Hotelling's T(2) test: p = 0.16 and 0.08 respectively). Subjects in both targets were less "happy", less "energetic" and more "confused" when stimulated ventrally. Comparison of the other 3 DBS conditions to pre-DBS showed a larger deterioration of letter verbal fluency in STN, especially when off DBS. There was no difference in UPDRS motor improvement between targets. INTERPRETATION: There were no significant differences in the co-primary outcome measures (mood and cognition) between STN and GPi in the optimal DBS state. Adverse mood effects occurred ventrally in both targets. A worsening of letter verbal fluency was seen in STN. The persistence of deterioration in verbal fluency in the off STN DBS state was suggestive of a surgical rather than a stimulation-induced effect. Similar motor improvement were observed with both STN and GPi DBS.

Mann JM, Foote KD, Garvan CW, Fernandez HH, Jacobson CE, Rodriguez RL, Haq IU, Siddiqui MS, Malaty IA, Morishita T, Hass CJ, Okun MS. · Department of Neurology, University of Florida College of Medicine/Shands Hospital, Movement Disorders Center, McKnight Brain Institute, Gainesville, Florida 32610, USA. · J Neurol Neurosurg Psychiatry. · Pubmed #19237386 No free full text.

Abstract: OBJECTIVE: To determine how intraoperative microelectrode recordings (MER) and intraoperative lead placement acutely influence tremor, rigidity, and bradykinesia. Secondarily, to evaluate whether the longevity of the MER and lead placement effects were influenced by target location (subthalamic nucleus (STN) or globus pallidus interna (GPi)). BACKGROUND: Currently most groups who perform deep brain stimulation (DBS) for Parkinson disease (PD) use MER, as well as macrostimulation (test stimulation), to refine DBS lead position. Following MER and/or test stimulation, however, there may be a resultant "collision/implantation" or "microlesion" effect, thought to result from disruption of cells and/or fibres within the penetrated region. These effects have not been carefully quantified. METHODS: 47 consecutive patients with PD undergoing unilateral DBS for PD (STN or GPi DBS) were evaluated. Motor function was measured at six time points with a modified motor Unified Parkinson Disease Rating Scale (UPDRS): (1) preoperatively, (2) immediately after MER, (3) immediately after lead implantation/collision, (4) 4 months following surgery-off medications, on DBS (12 h medication washout), (5) 6 months postoperatively-off medication and off DBS (12 h washout) and (6) 6 months-on medication and off DBS (12 h washout). RESULTS: Significant improvements in motor scores (p<0.05) (tremor, rigidity, bradykinesia) were observed as a result of MER and lead placement. The improvements were similar in magnitude to what was observed at 4 and 6 months post-DBS following programming and medication optimisation. When washed out (medications and DBS) for 12 h, UPDRS motor scores were still improved compared with preoperative testing. There was a larger improvement in STN compared with GPi following MER (p<0.05) and a trend for significance following lead placement (p<0.08) but long term outcome was similar. CONCLUSION: This study demonstrated significant acute intraoperative penetration effects resulting from MER and lead placement/collision in PD. Clinicians rating patients in the operating suite should be aware of these effects, and should consider pre- and post-lead placement rating scales prior to activating DBS. The collision/implantation effects were greater intraoperatively with STN compared with GPi, and with greater disease duration there was a larger effect.

Ellis TM, Foote KD, Fernandez HH, Sudhyadhom A, Rodriguez RL, Zeilman P, Jacobson CE, Okun MS. · Department of Neurology, Movement Disorders Center, University of Florida, McKnight Brain Institute, Gainesville, Florida, USA. · Neurosurgery. · Pubmed #18981887 No free full text.

Abstract: OBJECTIVE: To examine a case series of reoperations for deep brain stimulation (DBS) leads in which clinical scenarios revealed suboptimal outcome from a previous operation. Suboptimally placed DBS leads are one potential reason for unsatisfactory results after surgery for Parkinson's disease (PD), essential tremor (ET), or dystonia. In a previous study of patients who experienced suboptimal results, 19 of 41 patients had misplaced leads. Similarly, another report commented that lead placement beyond a 2- to 3-mm window resulted in inadequate clinical benefit, and, in 1 patient, revision improved outcome. The goal of the current study was to perform an unblinded retrospective chart review of DBS patients with unsatisfactory outcomes who presented for reoperation. METHODS: Patients who had DBS lead replacements after reoperation were assessed with the use of a retrospective review of an institutional review board-approved movement disorders database. Cases of reoperation for suboptimal clinical benefit were included, and cases of replacement of DBS leads caused by infection or hardware malfunction were excluded. Data points studied included age, disease duration, diagnosis, motor outcomes (the Unified Parkinson Disease Rating Scale III in PD, the Tremor Rating Scale in ET, and the Unified Dystonia Rating Scale in dystonia), quality of life (Parkinson's Disease Questionnaire-39 in PD), and the Clinician Global Impression scale. The data from before and after reoperation were examined to determine the estimated impact of repeat surgery. RESULTS: There were 11 patients with PD, 7 with ET, and 4 with dystonia. The average age of the PD group was 52 years, the disease duration was 10 years, and the average vector distance of the location of the active DBS contact was adjusted 5.5 mm. Six patients (54%) with PD had preoperative off medication on DBS Unified Parkinson Disease Rating Scale scores that could be compared with postoperative off medication on DBS scores. The average improvement across this group of patients was 24.4%. The Parkinson's Disease Questionnaire-39 improved in the areas of mobility (28.18), activities of daily living (14.77), emotion (14.72), stigma (17.61), and discomfort (17.42). The average age of the ET group was 66 years, the disease duration was 29 years, and the average adjusted distance was 6.1 mm. Five ET patients (83.3%) in the cohort had a prereplacement on DBS Tremor Rating Scale and a postreplacement on DBS Tremor Rating Scale with the average improvement of 60.4%. The average age of the dystonia group was 39 years, the average disease duration was 7 years, and the average adjusted lead distance was 6.7 mm. Three patients (75%) with dystonia had prereplacement on DBS Unified Dystonia Rating Scale and postreplacement on DBS Unified Dystonia Rating Scale scores. Across these 3 dystonia patients, the improvement was 12.8%. Clinician Global Impression scale scores (1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; 7, very much worse) after replacement revealed the following results in patients with PD: 1, 7 patients; 2, 3 patients; 3, 1 patient); with ET (1, 4 patients; 2, 3 patients); and with dystonia (1, 1 patient; 2, 2 patients; 3, 1 patient). The latency from original lead placement to reoperation (repositioning/revision) overall was 28.9 months (range, 2-104 mo); however, in leads referred from outside institutions (n = 11 patients), this latency was 48 months (range, 12-104 mo) compared with leads implanted by surgeons from the University of Florida (n = 11 patients), which was 9.7 months (range, 2-19 mo). The most common clinical history was failure to achieve a perceived outcome; however, history of an asymmetric benefit was present in 4 (18.2%) of 22 patients, and lead migration was present in 3 (13.6%) of 22 patients. CONCLUSION: There are many potential causes of suboptimal benefit after DBS. Timely identification of suboptimal lead placements followed by reoperation and repositioning/replacement in a subset of patients may improve outcomes.

Zahodne LB, Okun MS, Foote KD, Fernandez HH, Rodriguez RL, Kirsch-Darrow L, Bowers D. · Clinical and Health Psychology, University of Florida, Gainesville, FL 32610-0165, USA. · Clin Neuropsychol. · Pubmed #18821180 No free full text.

Abstract: Conflicting research suggests that deep brain stimulation surgery, an effective treatment for medication-refractory Parkinson's disease (PD), may lead to selective cognitive declines. We compared cognitive performance of 22 PD patients who underwent unilateral DBS to the GPi or STN to that of 19 PD controls at baseline and 12 months. We hypothesized that compared to PD controls, DBS patients would decline on tasks involving dorsolateral prefrontal cortex circuitry (letter fluency, semantic fluency, and Digit Span Backward) but not on other tasks (Vocabulary, Boston Naming Test), and that a greater proportion of DBS patients would fall below Reliable Change Indexes (RCIs). Compared to controls, DBS patients declined only on the fluency tasks. Analyses classified 50% of DBS patients as decliners, compared to 11% of controls. Decliners experienced less motor improvement than non-decliners. The present study adds to the literature through its hypothesis-driven method of task selection, inclusion of a disease control group, longer-term follow-up and use of Reliable Change. Our findings provide evidence that unilateral DBS surgery is associated with verbal fluency declines and indicate that while these changes may not be systematically related to age, cognitive or depression status at baseline, semantic fluency declines may be more common after left-sided surgery. Finally, use of Reliable Change highlights the impact of individual variability and indicates that fluency declines likely reflect significant changes in a subset of patients who demonstrate a poorer surgical outcome overall.

Cooper CA, Mikos AE, Wood MF, Kirsch-Darrow L, Jacobson CE, Okun MS, Rodriguez RL, Bowers D, Fernandez HH. · Department of Neurology, University of Florida, PO Box 100236, Gainesville, FL 32610, USA. · Parkinsonism Relat Disord. · Pubmed #18793864 No free full text.

Abstract: This cross-sectional study investigates the relationship between severity of right- and left-sided motor symptoms and deficits in global cognitive function as well as individual cognitive domains in 117 Parkinson disease patients. Items of the Unified Parkinson Disease Rating Scale Part III were divided into right- and left-sided total scores. Composite scores in verbal fluency, verbal memory, executive function, and visuoperceptual skills were obtained from a full neuropsychological battery. We observed a significant association between right-sided motor impairment and verbal memory, visuoperceptual skills, and verbal fluency, but not executive function. The relationship between right symptoms and verbal fluency was fully mediated by cognitive status, while the relationship between right symptoms and verbal memory as well as visuoperceptual skills was not. Left-sided motor symptoms were not significantly related to any composite cognitive domain. When patients were divided into groups based on the side of predominant symptoms, no group differences were found in performance on the specific cognitive domains. This suggests that the degree of right-sided symptoms is more correlated to specific cognitive domains than is group classification of laterality.

Okun MS, Rodriguez RL, Mikos A, Miller K, Kellison I, Kirsch-Darrow L, Wint DP, Springer U, Fernandez HH, Foote KD, Crucian G, Bowers D. · Department of Neurology, Movement Disorders Center, University of Florida, Gainesville, FL 32610, USA. · Clin Neuropsychol. · Pubmed #17366283 No free full text.

Abstract: Deep brain stimulation (DBS) now plays an important role in the treatment of Parkinson's disease, tremor, and dystonia. DBS may also have a role in the treatment of other disorders such as obsessive-compulsive disorder, Tourette's syndrome, and depression. The neuropsychologist plays a crucial role in patient selection, follow-up, and management of intra-operative and post-operative effects (Pillon, 2002; Saint-Cyr & Trepanier, 2000). There is now emerging evidence that DBS can induce mood, cognitive, and behavioral changes. These changes can have dramatic effects on patient outcome. There have been methodological problems with many of the studies of DBS on mood, cognition, and behavior. The neuropsychologist needs to be aware of these issues when following up patients, and constructing future studies. Additionally, this article will review all aspects of the DBS procedure that can result in mood, cognitive, and behavioral effects and what role(s) the neuropsychologist should play in screening and follow-up.

Miller KM, Okun MS, Fernandez HF, Jacobson CE, Rodriguez RL, Bowers D. · Department of Clinical and Health Psychology, College of Public Health and Health Professions, University of Florida, Gainesville, FL 32608, USA. · Mov Disord. · Pubmed #17266084 No free full text.

Abstract: Depression is common in Parkinson's disease (PD) and affects 30 to 50% of all patients. In contrast to the wealth of research on depression in PD, little is known about the occurrence of depression in other movement disorders. The primary objective of the current study was to determine whether the high prevalence of depression symptoms seen in PD is also found in other movement disorders, by directly comparing rates of specific depression symptoms and depression severity across PD, dystonia, and essential tremor (ET). Three hundred and fifty-four patients with PD, 83 patients with dystonia, and 53 patients with ET completed the Beck Depression Inventory (BDI). We found no significant between-groups differences for depression severity, frequency, or endorsement of specific depression symptoms. Forty-eight percent of PD patients, 37.3% of dystonia patients, and 34% of ET patients were found to be at least mildly depressed (BDI score of 10 or higher). The most commonly endorsed symptoms were fatigability, difficulty with work, anhedonia, and sleep disturbance. Clinicians should be aware that depression is a frequent problem in dystonia and ET, in addition to PD, and inquire about depression symptoms in these patients so that they can be appropriately treated.

Scholz S, Mandel RJ, Fernandez HH, Foote KD, Rodriguez RL, Barton E, Munson S, Singleton A, Okun MS. · Molecular Genetics Unit, National Institute on Aging, National Institutes of Health, Bethsda, MD, USA. · Eur J Neurol. · Pubmed #17116211 No free full text.

Abstract: In the last decade, major breakthroughs in the understanding of genetic contributions to Parkinson's disease (PD) have been achieved. Recently, mutations in LRRK2, encoding dardarin, have been found to be responsible for an autosomal dominant parkinsonism (OMIM 607060). We screened 311 subjects (cases: n = 202, controls: n = 109) for the three previously reported LRRK2 mutations. Our investigation revealed a sporadic case of PD with a heterozygous mutation G2019S (c.6055G>A). Here, we present the clinical phenotype of this patient and discuss the implications of genetic testing for the G2019S mutation in patients with sporadic PD.

Williams LN, Seignourel P, Crucian GP, Okun MS, Rodriguez RL, Skidmore FM, Foster PS, Jacobson CE, Romrell J, Bowers D, Fernandez HH. · Department of Neurology, University of Florida College of Medicine, Gainesville, Florida 32610, USA. · Mov Disord. · Pubmed #17089386 No free full text.

Abstract: 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.

Graff-Radford J, Foote KD, Rodriguez RL, Fernandez HH, Hauser RA, Sudhyadhom A, Rosado CA, Sanchez JC, Okun MS. · Department of Neurology, University of Florida Movement Disorders Center, University of Florida, Gainesville, FL, USA. · Arch Neurol. · Pubmed #16908749 links to  free full text

Abstract: 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.

Okun MS, Fernandez HH, Rodriguez RL, Romrell J, Suelter M, Munson S, Louis ED, Mulligan T, Foster PS, Shenal BV, Armaghani SJ, Jacobson C, Wu S, Crucian G. · Department of Neurology, University of Florida Movement Disorders Center, McKnight Brain Institute, Gainesville, FL 32610, USA. · Arch Neurol. · Pubmed #16682542 links to  free full text

Abstract: 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.

Okun MS, Tagliati M, Pourfar M, Fernandez HH, Rodriguez RL, Alterman RL, Foote KD. · Department of Neurology, University of Florida, Movement Disorders Center, McKnight Brain Institute, Gainesville, FL 32610, USA. · Arch Neurol. · Pubmed #15956104 No free full text.

Abstract: 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.