Parkinson Disease: Lyons KE

Pahwa R, Factor SA, Lyons KE, Ondo WG, Gronseth G, Bronte-Stewart H, Hallett M, Miyasaki J, Stevens J, Weiner WJ, Anonymous00045. · University of Kansas Medical Center, Kansas City, USA. · Neurology. · Pubmed #16606909 No free full text.

Abstract: OBJECTIVE: To make evidence-based treatment recommendations for the medical and surgical treatment of patients with Parkinson disease (PD) with levodopa-induced motor fluctuations and dyskinesia. To that end, five questions were addressed. 1. Which medications reduce off time? 2. What is the relative efficacy of medications in reducing off time? 3. Which medications reduce dyskinesia? 4. Does deep brain stimulation (DBS) of the subthalamic nucleus (STN), globus pallidus interna (GPi), or ventral intermediate (VIM) nucleus of the thalamus reduce off time, dyskinesia, and antiparkinsonian medication usage and improve motor function? 5. Which factors predict improvement after DBS? METHODS: A 10-member committee including movement disorder specialists and general neurologists evaluated the available evidence based on a structured literature review including MEDLINE, EMBASE, and Ovid databases from 1965 through June 2004. RESULTS, CONCLUSIONS, AND RECOMMENDATIONS: 1. Entacapone and rasagiline should be offered to reduce off time (Level A). Pergolide, pramipexole, ropinirole, and tolcapone should be considered to reduce off time (Level B). Apomorphine, cabergoline, and selegiline may be considered to reduce off time (Level C). 2. The available evidence does not establish superiority of one medicine over another in reducing off time (Level B). Sustained release carbidopa/levodopa and bromocriptine may be disregarded to reduce off time (Level C). 3. Amantadine may be considered to reduce dyskinesia (Level C). 4. Deep brain stimulation of the STN may be considered to improve motor function and reduce off time, dyskinesia, and medication usage (Level C). There is insufficient evidence to support or refute the efficacy of DBS of the GPi or VIM nucleus of the thalamus in reducing off time, dyskinesia, or medication usage, or to improve motor function. 5. Preoperative response to levodopa predicts better outcome after DBS of the STN (Level B).

Simuni T, Lyons KE, Pahwa R, Hauser RA, Comella C, Elmer L, Weintraub D. · Department of Neurology, Northwestern University, Parkinson's Disease and Movement Disorders Center, Chicago, Ill, USA. · Eur Neurol. · Pubmed #19176961 links to  free full text

Abstract: The management of early Parkinson's disease (PD) involves the treatment of motor symptoms, and, increasingly, non-motor symptoms. Given the fast pace of clinical research in PD, clinicians are faced with the challenge of integrating the latest findings into the ongoing care of individual PD patients. Part 1 of this 2-part article reviews efficacy and safety data for the newest PD treatment options, as well as for established therapies. Part 2 of the article, presented here, reviews key data relevant to the assessment of potential neuroprotective therapies and the treatment of non-motor symptoms.

Simuni T, Lyons KE, Pahwa R, Hauser RA, Comella C, Elmer L, Weintraub D. · Department of Neurology, Northwestern University, Parkinson's Disease and Movement Disorders Center, Chicago, Ill 60611, USA. · Eur Neurol. · Pubmed #19176960 links to  free full text

Abstract: The management of early Parkinson's disease (PD) involves the treatment of motor symptoms and, increasingly, non-motor symptoms. Given the fast pace of clinical research in PD, clinicians are faced with the challenge of integrating the latest findings into the ongoing care of individual PD patients. Part 1 of this 2-part article reviews motor symptom efficacy data for the newest PD treatment options, as well as for established therapies. Safety and tolerability data are also reviewed. Part 2 of the article reviews key findings relevant to the assessment of potential neuroprotective therapies and the treatment of non-motor symptoms.

Kleiner-Fisman G, Herzog J, Fisman DN, Tamma F, Lyons KE, Pahwa R, Lang AE, Deuschl G. · Parkinson's Disease Research Education and Clinical Center, Philadelphia VA Hospital, Philadelphia, Pennsylvania 19104, USA. · Mov Disord. · Pubmed #16892449 No free full text.

Abstract: Subthalamic nucleus (STN) deep brain stimulation (DBS) is currently the most common therapeutic surgical procedure for patients with Parkinson's disease (PD) who have failed medical management. However, a recent summary of clinical evidence on the effectiveness of STN DBS is lacking. We report the results of such a systematic review and meta-analysis. A comprehensive review of the literature using Medline and Ovid databases from 1993 until 2004 was conducted. Estimates of change in absolute Unified Parkinson's Disease Rating Scale (UPDRS) scores after surgery were generated using random-effects models. Sources of heterogeneity were explored with meta-regression models, and the possibility of publication bias was evaluated. Patient demographics, reduction in medication requirements, change in dyskinesia, daily offs, quality of life, and a ratio of postoperative improvement from stimulation compared to preoperative improvement by medication from each study were tabulated and average scores were calculated. Adverse effects from each study were summarized. Thirty-seven cohorts were included in the review. Twenty-two studies with estimates of standard errors were included in the meta-analysis. The estimated decreases in absolute UPDRS II (activities of daily living) and III (motor) scores after surgery in the stimulation ON/medication off state compared to preoperative medication off state were 13.35 (95% CI: 10.85-15.85; 50%) and 27.55 (95% CI: 24.23-30.87; 52%), respectively. Average reduction in L-dopa equivalents following surgery was 55.9% (95% CI: 50%-61.8%). Average reduction in dyskinesia following surgery was 69.1% (95% CI: 62.0%-76.2%). Average reduction in daily off periods was 68.2% (95% CI: 57.6%-78.9%). Average improvement in quality of life using PDQ-39 was 34.5% +/- 15.3%. Univariable regression showed improvements in UPDRS III scores were significantly greater in studies with higher baseline UPDRS III off scores, increasing disease duration prior to surgery, earlier year of publication, and higher baseline L-dopa responsiveness. Average baseline UPDRS III off scores were significantly lower (i.e., suggesting milder disease) in later than in earlier studies. In multivariable regression, L-dopa responsiveness, higher baseline motor scores, and disease duration were independent predictors of greater change in motor score. No evidence of publication bias in the available literature was found. The most common serious adverse event related to surgery was intracranial hemorrhage in 3.9% of patients. Psychiatric sequelae were common. Synthesis of the available literature indicates that STN DBS improves motor activity and activities of daily living in advanced PD. Differences between available studies likely reflect differences in patient populations and follow-up periods. These data provide an estimate of the magnitude of the treatment effects and emphasize the need for controlled and randomized studies.

Pahwa R, Lyons KE, Hauser RA. · Department of Neurology, University of Kansas Medical Center, 3599 Rainbow Blvd, Kansas City, KS 66160, USA. · Expert Rev Neurother. · Pubmed #15853577 No free full text.

Abstract: Ropinirole (Requip, GlaxoSmithKline) is a novel nonergoline dopamine D2 agonist indicated for the treatment of early and advanced Parkinson's disease. It is mainly metabolized by the liver and its elimination half-life is approximately 5.8 h. When used as monotherapy in early Parkinson's disease, ropinirole improves signs and symptoms of the disorder. When used as an adjunct to levodopa in advanced Parkinson's disease patients with motor fluctuations, ropinirole reduces off time and allows a reduction of levodopa dose. The initial use of ropinirole in early Parkinson's disease to which levodopa is added when necessary, has been demonstrated to lead to a lower incidence of dyskinesias compared with treatment with levodopa alone. An 18F-dihydroxyphenylalanine positron emission tomography study suggested the possibility that ropinirole could slow the progression of loss of dopamine neurons compared with treatment with levodopa but this remains to be proven. Side effects of ropinirole include nausea, somnolence, edema, orthostatic hypotension, hallucinations and dyskinesia. A once-daily formulation of ropinirole is currently in development that has the potential for greater convenience, improved tolerability and greater efficacy.

Hauser RA, Lyons KE. · Department of Neurology, University of South Florida and Tampa General Healthcare, Tampa, FL 33606, USA. · Neurol Clin. · Pubmed #15501363 No free full text.

This publication has no abstract.

Lyons KE, Pahwa R. · Department of Neurology, University of Kansas Medical Center, 3599 Rainbow Boulevard, Mailstop 2012, Kansas City, KS 66160, USA. · Curr Neurol Neurosci Rep. · Pubmed #15217543 No free full text.

Abstract: Throughout the past decade, there has been a marked increase in surgical therapies, primarily deep brain stimulation (DBS), for the treatment of advanced Parkinson's disease (PD). DBS of the thalamus has been shown to be effective in reducing parkinsonian tremor; however, it is not the treatment of choice for PD given the progression of other symptoms such as rigidity and bradykinesia. Stimulation of the globus pallidus or the subthalamic nucleus is safe and efficacious in the long-term treatment of all cardinal symptoms of PD, and they are currently the surgeries of choice. Serious adverse events with DBS can occur in 1% to 2% of patients, infection in 5% to 8% of patients, and hardware complications in approximately 25% of patients. Complications associated with DBS are related to the experience of the surgical center. Referring physicians and patients should be aware of the number of surgical procedures and complication rates of any prospective surgical center.

Koller WC, Pahwa PR, Lyons KE, Wilkinson SB. · University of Miami Medical Center, Department of Neurology, Florida 33136, USA. · Neurology. · Pubmed #11188972 No free full text.

Abstract: The surgical treatment of tremor has evolved considerably in the past few years. Of the several conditions associated with severe tremor, the most common are Parkinson's disease (PD) and essential tremor (ET). Levodopa therapy reduced drastically the number of patients with PD who require surgery because of inadequate control. However, there remains a small number of "tremor dominant" PD patients for whom surgical treatment is often the best option. The ventralis intermediate nucleus (Vim) of the thalamus has been the preferred surgical target for the treatment of parkinsonian tremor for many years, but this is now challenged by the subthalamic nucleus (STN). Deep brain stimulation (DBS) of either target possesses high therapeutic efficacy against tremor in PD. ET may be difficult to treat pharmacologically. Thalamotomy is an effective surgical procedure for ameliorating ET but may be associated with persistent neurologic deficits. DBS of the thalamus is also a highly effective means of reducing ET. DBS appears to be safer than thalamotomy and is now the recommended surgical procedure.

Koller WC, Pahwa R, Lyons KE, Albanese A. · Department of Neurology, University of Kansas Medical Center, 3901 Rainbow Blvd., Kansas City, KS 66160-7314, USA. · J Neurol Sci. · Pubmed #10500254 No free full text.

Abstract: Stereotaxtic surgery is an effective therapeutic maneuver in the management of advanced Parkinson's disease (PD). Thalamotomy is an effective measure to control tremor but other PD symptoms are not changed. Bilateral operations are associated with a risk of severe speech impairment. Deep brain stimulation (DBS) of the thalamus is as effective as thalamotomy and is associated with fewer side effects. Pallidotomy is effective in reducing contralateral dyskinesias and the cardinal symptoms of PD. Bilateral pallidotomy often results in cognitive dysfunction. Deep brain stimulation of the pallidum replicates the positive effects of pallidotomy and appears to be safer than ablative lesions. Subthalamic DBS is currently under investigation. This procedure may control all PD symptoms, and the dose of levodopa can often be dramatically reduced. Neurotransplantation is a promising surgical approach to PD. However, further investigation is needed to optimize this approach.

Pahwa R, Stacy MA, Factor SA, Lyons KE, Stocchi F, Hersh BP, Elmer LW, Truong DD, Earl NL, Anonymous00439. · University of Kansas Medical Center, Kansas City, KS 66160, USA. · Neurology. · Pubmed #17404192 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy of ropinirole 24-hour prolonged release (ropinirole 24-hour) as an adjunct to levodopa in patients with Parkinson disease (PD) and motor fluctuations. METHODS: In a double-blind, placebo-controlled, 24-week study, 393 subjects with PD were randomized to ropinirole 24-hour (n = 202) or placebo (n = 191). The primary outcome measure was reduction in hours of daily "off" time. RESULTS: At week 24, the mean dose of ropinirole 24-hour was 18.8 mg/day with a mean reduction in daily levodopa of 278 mg. There was a mean reduction in daily "off" time of 2.1 hours in the ropinirole 24-hour group and 0.3 hours with placebo. Secondary outcome measures including change in hours and percent of daily "on" time and "on" time without troublesome dyskinesia, Unified PD Rating Scale motor and activities of daily living subscales, Beck Depression Inventory-II, PDQ-39 subscales of mobility, activities of daily living, emotional well-being, stigma and communication, and PD Sleep Scale were significantly improved at week 24 with ropinirole 24-hour. The most common adverse events (AE) with ropinirole 24-hour were dyskinesia, nausea, dizziness, somnolence, hallucinations, and orthostatic hypotension and AEs led to study withdrawal in 5% of both the active and placebo groups. CONCLUSION: Ropinirole 24-hour was effective and well tolerated as adjunct therapy in patients with Parkinson disease (PD) not optimally controlled with levodopa. Ropinirole 24-hour demonstrated an improvement in both motor and non-motor PD symptoms, while permitting a reduction in adjunctive levodopa dose.

Lyons KE, Davis JT, Pahwa R. · University of Kansas Medical Center, Department of Neurology, Kansas City, KS 66160, USA. · Stereotact Funct Neurosurg. · Pubmed #17259749 No free full text.

Abstract: Levodopa responsiveness has been shown to be the best predictor of improvement after subthalamic nucleus (STN) deep brain stimulation (DBS) for Parkinson's disease (PD). The objective of this study was to assess the effect of STN DBS on PD patients intolerant to levodopa due to severe acute side effects such as intolerable nausea. There were 10 patients in the study who received STN DBS for PD. Five patients who were intolerant to levodopa were matched based on age, disease duration, sex and presurgical disease severity to 5 patients taking levodopa and demonstrating a good levodopa response. Both groups had a significant improvement in Unified Parkinson's Disease Rating Scale activities of daily living and motor subscales as well as tremor, rigidity and bradykinesia scores at 3, 6 and 12 months after surgery compared to baseline, and these improvements were equivalent between the two groups. Patient global ratings also indicated significant improvements at all follow-up visits. There were no differences in stimulator settings between the two groups at the 3-, 6- or 12-month follow-up visits. In conclusion, although levodopa responsiveness is the best predictor for outcome after STN DBS, carefully selected PD patients intolerant to levodopa can have significant improvement.

Eng ML, Lyons KE, Greene MS, Pahwa R. · University of Kansas Medical Center, University of Kansas, School of Pharmacy, Department of Pharmacy Practice, Kansas City, KS 66160-7231, USA. · J Altern Complement Med. · Pubmed #16722790 No free full text.

Abstract: OBJECTIVES: This study evaluates the effects of sequential tui na massage, acupuncture, and instrument-delivered qigong for patients with Parkinson disease (PD) over a 6-month period. DESIGN: Patients received weekly treatments, which included tui na massage prior to acupuncture followed by instrument-delivered qigong. Each patient was assessed at baseline and at 6 months. SETTING: The setting was an outpatient research/academic clinic for patients with PD and nonacademic acupuncture clinic. SUBJECTS: Twenty-five (25) patients with idiopathic PD were the subjects. OUTCOME MEASURES: Before and after treatment patients were evaluated with the Unified Parkinson Disease Rating Scale (UPDRS), Hoehn and Yahr Staging (H&Y), Schwab and England Activities of Daily Living (S & E), Beck Depression Inventory (BDI), Parkinson's Disease Questionnaire (PDQ-39) quality of life assessment, and patient global assessments. RESULTS: There were no significant improvements in treatment measures; however, there was a 2.4-point worsening in UPDRS motor scores (24.0 versus 26.4, p = 0.018). There was a 16% improvement in the PDQ- 39 total score (23.2 versus 19.6, p = 0.044) and a 29% improvement in the BDI (9.6 versus 6.8, p = 0.006). Sixteen (16) patients reported moderate to marked improvement. There were no adverse effects. CONCLUSIONS: Acupuncture is safe and well tolerated in patients with PD. Most patients reported subjective improvement. The BDI and PDQ-39 total score, measuring depression and quality of life, demonstrated some improvement, but UPDRS motor scores worsened.

Lyons KE, Pahwa R. · Department of Neurology, University of Kansas Medical Center, Kansas City, 66160, USA. · Clin Neuropharmacol. · Pubmed #16614538 No free full text.

Abstract: OBJECTIVES: This study was performed to determine if conversion from sustained release carbidopa/levodopa (SR-CL) with or without entacapone to carbidopa/levodopa/entacapone (CLE; Stalevo) improves motor functioning and quality of life in Parkinson disease (PD) patients and to assess patient tolerance and drug preference. METHODS: PD patients reporting suboptimal symptom control with SR-CL were converted to CLE. The basic conversion was 1 SR-CL 25/100 to 1 25/100/200 CLE and 1 SR-CL 50/200 to 1 37.5/150/200 CLE with additional changes as necessary. RESULTS: There were 62 patients with an average age of 68 years and an average disease duration of 11 years. CLE was preferred by 42 patients and SR-CL was preferred by 20 patients. In those that preferred CLE, Unified Parkinson Disease Rating Scale (UPDRS) mentation and motor subscores, Parkinson Disease Questionnaire-39 (PDQ-39) quality-of-life activities of daily living (ADL) and bodily discomfort subscores, and Epworth Sleepiness Scale (ESS) scores were significantly improved. There were no significant changes in any measures in the group that preferred SR-CL. Common adverse effects in the group that preferred CLE included nausea, vomiting, increased dyskinesia or off time, dizziness, and somnolence. The most common adverse events in the group preferring SR-CL were increased off time or dyskinesia, nausea, and vomiting. CONCLUSIONS: A majority of patients suboptimally controlled on SR-CL can be successfully converted to CLE with improvements in motor function, quality of life, and sleepiness. Older patients, with longer disease duration not previously exposed to entacapone, may better tolerate CLE after the addition of entacapone.

Liu W, McIntire K, Kim SH, Zhang J, Dascalos S, Lyons KE, Pahwa R. · Department of Physical Therapy and Rehabilitation Sciences, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160-7601, USA. · Parkinsonism Relat Disord. · Pubmed #16157502 No free full text.

Abstract: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective for the treatment of advanced Parkinson's disease. Most studies have evaluated the effectiveness of DBS of the STN using clinical motor scores or simple timed tests of motor function. There have been few studies that quantitatively assessed the outcome of STN DBS using multiple testing paradigms. In the current study, 11 patients who had bilateral STN DBS were quantitatively evaluated under four conditions using gait, postural control, and gait initiation. The four conditions included the medication on/stimulation on (M_on/S_on), medication on/stimulation off (M_on/S_off), medication off/stimulation on (M_off/S_on), and medication off/stimulation off (M_off/S_off) conditions. DBS of the STN significantly increased walking speed with and without levodopa, but had no influence on the cadence. The addition of levodopa had a minimal additional effect on walking speed. The effect of STN DBS on gait initiation approached the significant level. The mean values of lateral body sway during quiet standing increased moderately with medication and/or DBS, but the changes were not statistically significant. Future studies need to determine whether or not there is a potential negative effect of STN DBS on the postural control.

Koller WC, Lyons KE, Truly W. · Department of Neurology, The Mount Sinai School of Medicine, New York, NY, USA. · Neurology. · Pubmed #15007122 No free full text.

Abstract: BACKGROUND: Manganese is known to cause a parkinsonian syndrome similar clinically to Parkinson disease (PD). L-Dopa responsiveness is a hallmark of PD; however, L-dopa's effect on manganese-induced parkinsonism is not well defined. OBJECTIVE: To access the efficacy and safety of L-dopa therapy in a double-blind, randomized, placebo-controlled trial. METHODS: Thirteen patients with manganese-induced parkinsonism were evaluated in a cross-over study with a modified Unified PD Rating Scale (UPDRS), timed walk test, tapping, and global clinical impression scores. Adverse reactions were assessed. RESULTS: There was no significant difference between placebo and L-dopa for any measure: motor UPDRS, 27.4 vs 28.8; walk time, 16.6 seconds vs 17.7 seconds; tapping right hand, 69.5 vs 64.7; and tapping left hand, 66.8 vs 64.4. There were no differences in the global impression scores. Adverse reactions occurred similarly in the two groups, including headaches, drowsiness, and diarrhea. CONCLUSIONS: L-Dopa therapy is not effective for the management of parkinsonism in welders. L-dopa unresponsiveness may be useful to distinguish manganese-induced parkinsonism from Parkinson disease.

Pahwa R, Wilkinson SB, Overman J, Lyons KE. · Department of Neurology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. · J Neurosurg. · Pubmed #12854747 No free full text.

Abstract: OBJECT: Bilateral subthalamic nucleus (STN) stimulation is increasingly used in patients with advanced Parkinson disease (PD). This study was performed to evaluate the long-term efficacy and safety of bilateral STN stimulation in cases of PD. METHODS: The authors performed a prospective, open-label study in patients with PD who underwent bilateral STN stimulation. The authors compared motor scores and activities of daily living (ADL) scores based on the Unified PD Rating Scale (UPDRS) obtained before surgery while patients were in the medication-off state with scores obtained at follow-up evaluations of these patients while in the medication-off/stimulator-on state. Data contained in patient diaries were also compared. Thirty-three patients with PD were evaluated 12 months postoperatively and 19 were evaluated at a mean follow-up time of 28 months. A comparison between UPDRS scores obtained in patients in the medication-off/stimulator-on state and those obtained when patients were in the baseline medication-off state showed a 27% improvement in ADL scores and a 28% improvement in motor scores after surgery. There was a 57% reduction in the use of levodopa-equivalent medication doses. The percentage of the waking day that patients were in the medication-on state increased from 38 to 72%. Surgical complications included seizures (three patients), confusion (five patients), hemiballismus (one patient), and visual disturbance (one patient). Stimulation-related adverse effects were mild. Device-related events included nine lead replacements, seven lead revisions, six extension replacements, and 12 implantable pulse generator (IPG) replacements; one IPG was cleaned and one IPG was placed in a pocket because of the presence of a shunt. CONCLUSIONS: Bilateral STN simulation is associated with a significant improvement in the motor features of PD. Device-related events were common in the first 20 patients who underwent surgery, often requiring repeated surgeries.

Woods SP, Fields JA, Lyons KE, Koller WC, Wilkinson SB, Pahwa R, Tröster AI. · Department of Psychiatry & Behavioral Sciences, University of Washington School of Medicine, Seattle, Washington 98195, USA. · Acta Neurochir (Wien). · Pubmed #11810392 No free full text.

Abstract: BACKGROUND: The long-term neuropsychological and quality of life (QOL) outcomes of unilateral thalamic deep brain stimulation (DBS) in patients with intractable Parkinson's disease (PD) have not heretofore been described. METHOD: Six patients diagnosed with PD underwent unilateral DBS implantation into a verified thalamic VIM nucleus target. Participants completed presurgical neuropsychological evaluation and follow-up assessment at approximately one year postsurgery. FINDINGS: Compared to their presurgical scores, PD patients exhibited significant improvement on measures of conceptualization, verbal memory, emotional adjustment, and QOL at one-year follow-up. A few nominal declines were observed across the battery of tests. INTERPRETATION: These data provide preliminary support for the long-term neurocognitive safety and QOL improvements following thalamic stimulation in patients with PD.

Muniz AS, Nobre FF, Liu H, Lyons KE, Pahwa R, Liu W, Nadal J. · Biomedical Engineering Program, COPPE, Federal University of Rio de Janeiro, Brazil P.O. Box 68.510, 21941-972 - BRAZIL. · Conf Proc IEEE Eng Med Biol Soc. · Pubmed #19163765 No free full text.

Abstract: This study aims at applying an artificial neural network for the evaluation of the effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) on Parkinson disease (PD) patients with and without medication. A sample of 15 PD patients who have undergone STN DBS were evaluated under four test conditions: medication off and stimulation off (mof-sof), medication off and stimulation on (mof-son), medication on and stimulation off (mon-sof) and medication on and stimulation on (mon-son). A control group with 30 subjects was also evaluated. Principal component analysis (PCA) was applied on vertical ground reaction force (vGRF) and the first six principal component scores (PC score) were obtained in both groups. Those PCs scores were used as input in a probabilistic neural network (PNN). PNN presented satisfactory classification performance in the separation of controls and PD with 90.1% accuracy, 69.2% sensitivity and 100% specificity. The stimulation mof-son and mon-son conditions presented better results compared to mon-sof. In the mof-son condition, 41.7% were classified as normal, while further enhancement (63.3%) was given by the mon-son condition. These results indicated the potentiality of PNN to quantitatively evaluate treatment effects. Furthermore, STN DBS shows improvement on vGRF pattern in PD patients, most substantially when used with medication.

LeWitt PA, Lyons KE, Pahwa R, Anonymous00261. · Clinical Neuroscience Center, Southfield, MI 48034, USA. · Neurology. · Pubmed #17438216 No free full text.

Abstract: BACKGROUND: In patients experiencing motor fluctuations, a major treatment challenge is the reduction of "off" time, particularly upon awakening. Rotigotine (Neupro) is a novel dopaminergic agonist with 24-hour transdermal delivery. METHODS: A randomized, double-blind, placebo-controlled trial (PREFER Study) was performed to assess efficacy and safety with two targeted transdermal doses of rotigotine in subjects with advanced Parkinson disease with > or =2.5 hours of daily "off" time. Subjects were randomized to receive placebo patches (n = 120) or rotigotine up to either 8 mg/24 hours (n = 120) or 12 mg/24 hours (n = 111). The primary efficacy measures compared changes from baseline to the end of week 24 in the number of daily hours "off" and responder rates for subjects achieving > or =30% reduction in "off" time. RESULTS: Compared to placebo, there were significant decreases in mean "off" time of 1.8 hours/day for the rotigotine 8 mg/24 hours group and 1.2 hours/day for the 12 mg/24 hours group. For rotigotine 8 and 12 mg/24 hours groups, > or =30% responder rates were 56.6% and 55.1% compared to the 34.5% placebo response. "On" time without dyskinesia after awakening was more than doubled in both rotigotine treatment groups vs placebo. Drug-related adverse effects included typical dopaminergic side effects, which were generally mild/moderate in intensity. Patch application site reactions including erythema and pruritus were mild to moderate and transient in the majority of instances. CONCLUSIONS: Transdermal rotigotine significantly improved "off" time in subjects with Parkinson disease not optimally controlled with levodopa and was safe and well tolerated, with typical dopaminergic side effects and occasional application site reactions.

Eng ML, Lyons KE, Pahwa R. · No affiliation provided · Mov Disord. · Pubmed #17044065 No free full text.

This publication has no abstract.

Lyons KE, Pahwa R. · Parkinson's Disease and Movement Disorder Center, Department of Neurology, University of Kansas Medical Center, 3599 Rainbow Blvd, Mailstop 2012, Kansas City, KS 66160, USA. · Parkinsonism Relat Disord. · Pubmed #16920380 No free full text.

Abstract: Parkinson's disease (PD) studies often measure daily motor function with paper diaries resulting in issues of compliance and reliability. The feasibility and compliance of PD patients using electronic diaries were examined. Twelve patients completed diaries for 7 consecutive days. Diaries recorded motor function, time and date of each half-hour entry and had an alarm as notification of missed entries. Entry compliance was 99.98% within 24h and average response time during awake hours was 63 min. Electronic diaries could be operated by PD patients, provided valuable information about response patterns and resulted in average response compliance of approximately 1h.

Benabid AL, Deuschl G, Lang AE, Lyons KE, Rezai AR. · Grenoble, France. · Mov Disord. · Pubmed #16810721 No free full text.

This publication has no abstract.

Deuschl G, Herzog J, Kleiner-Fisman G, Kubu C, Lozano AM, Lyons KE, Rodriguez-Oroz MC, Tamma F, Tröster AI, Vitek JL, Volkmann J, Voon V. · Department of Neurology, Christian-Albrechts-Universität Kiel, Kiel, Germany. · Mov Disord. · Pubmed #16810719 No free full text.

Abstract: Numerous factors need to be taken into account when managing a patient with Parkinson's disease (PD) after deep brain stimulation (DBS). Questions such as when to begin programming, how to conduct a programming screen, how to assess the effects of programming, and how to titrate stimulation and medication for each of the targeted sites need to be addressed. Follow-up care should be determined, including patient adjustments of stimulation, timing of follow-up visits and telephone contact with the patient, and stimulation and medication conditions during the follow-up assessments. A management plan for problems that can arise after DBS such as weight gain, dyskinesia, axial symptoms, speech dysfunction, muscle contractions, paresthesia, eyelid, ocular and visual disturbances, and behavioral and cognitive problems should be developed. Long-term complications such as infection or erosion, loss of effect, intermittent stimulation, tolerance, and pain or discomfort can develop and need to be managed. Other factors that need consideration are social and job-related factors, development of dementia, general medical issues, and lifestyle changes. This report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society, outlines answers to a series of questions developed to address all aspects of DBS postoperative management and decision-making with a systematic overview of the literature (until mid-2004) and by the expert opinion of the authors. The report has been endorsed by the Scientific Issues Committee of the Movement Disorder Society and the American Society of Stereotactic and Functional Neurosurgery.

Lang AE, Houeto JL, Krack P, Kubu C, Lyons KE, Moro E, Ondo W, Pahwa R, Poewe W, Tröster AI, Uitti R, Voon V. · Department of Neurology, Toronto Western Hospital, Toronto, Ontario, Canada. · Mov Disord. · Pubmed #16810718 No free full text.

Abstract: Numerous factors need to be taken into account in deciding whether a patient with Parkinson's disease (PD) is a candidate for deep brain stimulation. Patient-related personal factors including age and the presence of other comorbid disorders need to be considered. Neuropsychological and neuropsychiatric concerns relate both to the presurgical status of the patient and to the potential for surgery to result in new problems postoperatively. A number of factors related to the underlying PD need to be considered, including the specific parkinsonian motor indications (e.g., tremor, bradykinesia, gait dysfunction), previous medical therapies, including benefit from current therapy and adverse effects, and past surgical treatments. Definable causes of Parkinsonism, particularly atypical Parkinsonisms, should be considered. Finally, methods of evaluating outcomes should be defined and formalized. This is a report from the Consensus on Deep Brain Stimulation for Parkinson's Disease, a project commissioned by the Congress of Neurological Surgeons and the Movement Disorder Society (MDS). The report has been endorsed by the Scientific Issues Committee of the MDS and the American Society of Stereotactic and Functional Neurosurgery. It outlines answers to a series of questions developed to address all aspects of deep brain stimulation preoperative decision-making.

Lyons KE, Pahwa R. · Department of Neurology, University of Kansas Medical Center, Kansas City, 66160, USA. · Clin Neuropharmacol. · Pubmed #16772814 No free full text.

Abstract: OBJECTIVES: This open-label study was performed to evaluate the efficacy and tolerability of levetiracetam for levodopa-induced dyskinesia and its effect on motor functioning and quality of life in Parkinson disease (PD) patients. METHODS: PD patients with moderate to severe dyskinesia were enrolled in the study. PD medications were unchanged during the study, and levetiracetam was slowly titrated up to a maximum dosage of 3,000 mg/d over a 2-month period. RESULTS: There were 9 patients with a mean age of 65 years and mean disease duration of 13 years. Forty-four percent of the subjects withdrew before the end of the study due to adverse events, primarily worsening of PD symptoms and sleepiness. Of the remaining 5 subjects, 1 subject continued levetiracetam after the study with mild improvement in dyskinesia and 4 discontinued levetiracetam due to worsening of PD symptoms and sleepiness. CONCLUSIONS: Levetiracetam is not well tolerated in PD patients with levodopa-induced dyskinesia resulting in worsening of PD symptoms, intolerable somnolence, and worsening of dyskinesia in most patients.