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Stanley Fahn

Publications and source records attributed to Stanley Fahn.

At least 19 recordsLinked to original sources
PubMed2007

Multiple system atrophy in a patient with the spinocerebellar ataxia 3 gene mutation.

The cerebellar variant of multiple system atrophy (MSA-C) has overlapping clinical features with the hereditary spinocerebellar ataxias (SCAs), but can usually be distinguished on a clinical basis. We describe a patient who developed a sporadic, late-onset, rapidly progressive neurodegenerative disorder consistent with MSA-C. Genetic testing, however, showed an abnormal expansion of one allele of the spinocerebellar ataxia 3 (SCA3) gene. The clinical impression of MSA-C was confirmed by identification of numerous alpha-synuclein-containing glial cytoplasmic inclusions on autopsy. These findings suggest that abnormal expansion of the SCA3 gene may be a risk factor for the development of MSA-C.

Alleles↗
PubMed2007

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (UPDRS), known as the MDS-UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinson's disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS-UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1-day face-to-face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS-UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS-UPDRS in order to increase uniform usage. Multiple language editions are planned. A three-part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS-UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.

Disability Evaluation↗
PubMed2006

A randomized controlled trial of etilevodopa in patients with Parkinson disease who have motor fluctuations.

BACKGROUND: Motor fluctuations are a common complication in patients with Parkinson disease (PD) receiving long-term levodopa therapy. Slowed gastric emptying and poor solubility of levodopa in the gastrointestinal tract may delay the onset of drug benefit after dosing. Etilevodopa is an ethyl-ester prodrug of levodopa that has greater gastric solubility, passes quickly into the small intestine, is rapidly hydrolyzed to levodopa, and has a shortened time to maximum levodopa concentration. OBJECTIVE: To determine the efficacy, safety, and tolerability of etilevodopa in patients with PD who have motor fluctuations. DESIGN: A double-blind, randomized, comparative clinical trial. SETTING: Forty-four sites in the United States and Canada. PATIENTS: Three hundred twenty-seven patients with PD who had a latency of at least 90 minutes total daily time to "on" (TTON) after levodopa dosing. INTERVENTION: Treatment with either etilevodopa-carbidopa or levodopa-carbidopa for 18 weeks. MAIN OUTCOME MEASURE: Change from baseline in total daily TTON as measured using home diaries. RESULTS: The reduction in mean total daily TTON from baseline to treatment was 0.58 hour in the etilevodopa-carbidopa group and 0.79 hour in the levodopa-carbidopa group (P = .24). There was no significant difference between the etilevodopa-carbidopa and levodopa-carbidopa groups in the reduction of response failures (-6.82% vs -4.69%; P = .20). Total daily "off" time improved in the etilevodopa-carbidopa (-0.85 hour) and levodopa-carbidopa (-0.87 hour) groups without an increase in on time with troublesome dyskinesias. CONCLUSION: Despite the theoretical pharmacokinetic advantage of etilevodopa, there was no improvement in TTON, response failures, or off time compared with levodopa.

Aged↗
PubMed2006

Case-control study of the parkin gene in early-onset Parkinson disease.

BACKGROUND: Mutations in parkin are estimated to account for as much as 50% of familial Parkinson disease (PD) and 18% of sporadic PD. Single heterozygous mutations in parkin in both familial and sporadic cases may also increase susceptibility to PD. To our knowledge, all previous studies have been restricted to PD cases; this is the first study to systematically screen the parkin coding regions and exon deletions and duplications in controls. OBJECTIVE: To determine the frequency and spectrum of parkin variants in early-onset PD cases (aged < or =50 years) and controls participating in a familial aggregation study. PATIENTS AND METHODS: We sequenced the parkin gene in 101 cases and 105 controls. All cases and controls were also screened for exon deletions and duplications by semiquantitative multiplex polymerase chain reaction. RESULTS: Thirteen (12.9% [95% confidence interval, 7%-21%]) of the 101 cases had a previously described parkin mutation: 1 was homozygous, 11 were heterozygous, and 1 was a compound heterozygote. The mutations Arg42Pro (exon 2) and Arg275Trp (exon 7) were recurrent. The previously reported synonymous substitution Leu261Leu (c.884A>G) was identified in 4 (3.9%) of 101 cases and 2 (2%) of 105 controls (P = .44). Excluding the synonymous substitution Leu261Leu (heterozygotes), 10 (9.9% [95% confidence interval, 4.6%-17.5%]) carried mutations. CONCLUSIONS: The frequency of mutations among cases that were not selected based on family history of PD is similar to what has previously been reported in sporadic PD. The similar frequency of Leu261Leu in cases and controls suggests it is a normal variant rather than a disease-associated mutation. We confirmed that heterozygous parkin mutations may increase susceptibility for early-onset PD.

Age of Onset↗
PubMed2006

Movement disorders fellowship training program at Columbia University Medical Center in 2001-2002.

Data regarding the clinical experience of movement disorders subspecialty training are currently not available. In order to provide information to help design a well-rounded clinical experience, we reviewed the number and types of patients seen by all clinical movement disorders fellows over the course of 1 year at Columbia University Medical Center (CUMC). We conducted a retrospective analysis of all patients seen by four full-time clinical fellows and one part-time fellow during the 2001-2002 academic year, using billing records to tabulate all clinic visits and patient charts to certify diagnosis. One thousand six hundred sixty-two patients (1,132 new and 530 follow-ups) were seen by five fellows. Each full-time fellow evaluated and treated a mean of 263 new patients, 116 follow-up patients, and 15 in-patient consultations. The part-time clinical fellow evaluated and treated 81 new patients and 65 follow-up patients. Approximately half of the new patients had idiopathic Parkinson's disease. Full-time fellows saw equivalent numbers of patients but they evaluated few patients with uncommon movement disorders. Weekly video rounds allowed all fellows to see many more patients, aiding the recognition of movement phenomenology and enhancing understanding of diagnoses and treatment strategies. Thus, CUMC fellows evaluate a large number of patients with a wide range of diagnoses within a 1-year period. Video rounds allow greater exposure to uncommon diagnoses. Similar data from other movement disorder training programs are needed to help create guidelines for formal accreditation and to improve clinical training in this subspecialty.

Academic Medical Centers↗
PubMed2006

Rasagiline improves quality of life in patients with early Parkinson's disease.

The objective of this study was to determine the effects of rasagiline as monotherapy on quality of life (QOL) in patients with early Parkinson's disease (PD). Rasagiline, a potent, second-generation, irreversible, selective monoamine oxidase B inhibitor improves PD symptoms in patients with early PD. Patients with early untreated PD were randomly assigned to once-daily rasagiline 1 mg/day, rasagiline 2 mg/day, or placebo in a 6-month, double-blind trial (n=404). At the end of 6 months, patients entered the preplanned, active-treatment phase in which those receiving 1 mg/day and 2 mg/day of rasagiline continued on their previously assigned dosages and those receiving placebo switched to rasagiline 2 mg/day, while maintaining blinding to treatment assignments. QOL was measured with the Parkinson's Disease Quality of Life questionnaire (PDQUALIF) at 0, 14, 26, and 52 weeks after randomization. Analysis of the change in PDQUALIF scores from baseline to 6 months showed adjusted treatment effects (with 95% confidence interval) favoring rasagiline over placebo of -2.91 units (-5.19, -0.64, P=0.01) for the 1 mg/day group and -2.74 units (-5.02, -0.45, P=0.02) for the 2 mg/day. Subscore analysis attributed most of this benefit to the self-image/sexuality domain. At 12 months (n=266), with all groups receiving rasagiline for at least 6 months, no significant differences in PDQUALIF scores were seen between groups. Rasagiline improved QOL compared with placebo. This QOL improvement appears to be accounted for primarily by the symptomatic benefit of rasagiline.

Aged↗
PubMed2006

Effects of tyramine administration in Parkinson's disease patients treated with selective MAO-B inhibitor rasagiline.

Rasagiline is a novel, potent, and selective MAO-B inhibitor shown to be effective for Parkinson's disease. Traditional nonselective MAO inhibitors have been associated with dietary tyramine interactions that can induce hypertensive reactions. To test safety, tyramine challenges (50-75 mg) were performed in 72 rasagiline-treated and 38 placebo-treated Parkinson's disease (PD) patients at the end of two double-blind placebo-controlled trials of rasagiline. An abnormal pressor response was prespecified as three consecutive measurements of systolic blood pressure (BP) increases of >or= 30 mm Hg and/or bradycardia of < 40 beats/min. In the first study involving 55 patients with early PD on rasagiline monotherapy, no patients randomized to rasagiline (1 mg/2 mg; n = 38) or placebo (n = 17) developed systolic BP (SBP) or heart rate changes indicative of a tyramine reaction. In the second trial involving 55 levodopa-treated patients, 3 of 22 subjects on rasagiline 0.5 mg/day and 1 of 21 subjects on placebo developed asymptomatic, self-limiting SBP elevations >or= 30 mm Hg on three measurements. No subject on 1 mg/day rasagiline (0/12) experienced significant BP or heart rate changes following tyramine ingestion. These data demonstrate that rasagiline 0.5 to 2 mg daily is not associated with clinically significant tyramine reactions and can be used as monotherapy or adjunct to levodopa in PD patients without specific dietary tyramine restriction.

Administration, Oral↗
PubMed2005

Contribution of aging to the severity of different motor signs in Parkinson disease.

BACKGROUND: Evidence does not support the view that Parkinson disease (PD) represents an accelerated aging process; however, the additional contribution of aging to the severity of different motor signs in patients with PD is not known. This knowledge may have implications for clinical trials of neuroprotective agents in PD. OBJECTIVE: To investigate the contribution of aging to the severity of the different motor signs of idiopathic PD. SETTING: Center for Parkinson Disease and Other Movement Disorders of the Columbia University Medical Center and a neurology clinic that primarily served individuals from the Washington Heights-Inwood community in New York City. PATIENTS: Sample of patients with a wide range of disease duration and age. DESIGN: Cross-sectional clinic-based study. Patients with PD were evaluated using the Unified Parkinson Disease Rating Scale (UPDRS). The total UPDRS motor score was divided into 6 motor domains (tremor, rigidity, bradykinesia, facial expression, speech, and axial impairment) and 2 subscores that represented predominantly dopaminergic (subscore A: tremor, rigidity, bradykinesia, and facial expression) and nondopaminergic (subscore B: speech and axial impairment) deficiency. Analyses were performed using linear regression models with the UPDRS motor domains and subscores as the outcomes. The variation (adjusted R(2)) of the outcome variables explained by the inclusion of disease duration in the models, adjusting for sex, years of education, levodopa dosage, and use of other antiparkinsonian medications, was calculated. The additional variation explained by adding age at examination to the models was used to gauge the contribution of aging to each motor domain and subscore of the UPDRS. RESULTS: A total of 451 patients participated in the study. Mean age at examination was 62.0 years (SD, 12.6 years; median, 62.0 years; range, 18-93 years), and mean disease duration was 7.2 years (SD, 5.9 years; median, 5.6 years; range, 0.1-41.6 years). The additional variation of the outcome variable explained by including age in the models was higher for subscore B (14.3%; 95% confidence interval [CI], 9.9%-20.4%) than subscore A (4.7%; 95% CI, 2.0%-9.1%). Among the 6 motor domains, the additional variation of the outcome variable explained by including age in the models was highest for axial impairment (13.6%; 95% CI, 9.4%-19.6%). CONCLUSION: Axial (gait and postural) impairment in PD may result from the combined effect of the disease and the aging process on nondopaminergic subcortical structures.

Adolescent↗
PubMed2005

Pilot association study of the beta-glucocerebrosidase N370S allele and Parkinson's disease in subjects of Jewish ethnicity.

Mutations in the beta-glucocerebrosidase gene cause Gaucher's disease, one of the most common lysosomal lipid storage diseases in the Ashkenazi Jewish population. The occurrence of parkinsonism in patients with Type 1 Gaucher's disease has been noted previously. In this pilot study, we evaluated a possible association between Parkinson's disease (PD) and the beta-glucocerebrosidase gene N370S allele (nt.1226 A>G) in 160 Parkinson's disease patients and 92 controls of Jewish ethnicity. We observed a higher frequency of the N370S genotype in PD cases (NS and SS, 10.7%) compared to controls (NS and SS 4.3%); however, the difference was not statistically significant (chi(2) = 3.4, P = 0.2). A total of 17 PD cases carry the N370S allele, including 2 homozygotes and 15 heterozygotes. The N370S allele (nt.1226 A>G) may be associated with PD in patients of Jewish ethnicity and should be examined in a larger study.

Aged↗
PubMed2005

Does levodopa slow or hasten the rate of progression of Parkinson's disease?

UNLABELLED: Levodopa therapy, as originally established by George Cotzias [2, 3], is the most powerful treatment for Parkinson's disease (PD). Levodopa's toxicity to neurons in vitro has raised concerns if it might hasten the progression of PD, although in vivo animal studies suggest it may be neuroprotective. OBJECTIVE: To discuss the results of the ELLDOPA trial that was carried out to determine if levodopa therapy influences the rate of progression of Parkinson's disease (PD). DESIGN: ELLDOPA was a multicenter, parallel-group, double-blind, dosage-ranging, randomized, controlled clinical trial. SETTING: Academic movement disorders clinics at 38 sites in the United States and Canada. PATIENTS: Three hundred and sixty-one patients with early PD of less than 2 years' duration who did not require symptomatic therapy. INTERVENTIONS: Subjects were randomly assigned to one of four treatment groups: carbidopa/levodopa 12.5/50 mg t. i. d. (N=92), 25/100 mg t. i. d. (N=88), 50/200 mg t. i. d. (N=91), or matching placebo (N=90). The dosage was gradually escalated over 9 weeks and then maintained until Week 40, at which time active treatment was withdrawn over 3 days. After 2 weeks without active treatment (Week 42), a final assessment of PD severity was obtained. OUTCOME MEASURES: The prespecified primary clinical outcome was the change in the total Unified Parkinson's Disease Rating Scale (UPDRS) between baseline and Week 42, comparing the four treatment groups. The primary neuroimaging component of the study in a subgroup of 142 subjects was the percent change in striatal (123)iodine 2-beta-carboxymethoxy-3-beta-(4-iodophe nyl)tropane (beta-CIT) uptake between baseline and Week 40 visits. The neuroimaging substudy utilized single photon emission computed tomography (SPECT) of the dopamine transporter. RESULTS: All dosages of levodopa exerted clinical benefit compared to placebo on the UPDRS scores throughout the study, including 2 weeks after discontinuing levodopa. The UPDRS scores at Week 42 failed to reach the level encountered in the placebo group (change of 7.8+/-9.0, 1.9+/-6.0, 1.9+/-6.9, and -1.4+/-7.8, for placebo, 150 mg/day, 300 mg/ day, and 600 mg/day, respectively, p<0.0001). Nausea (p=0.001) and dyskinesias (p=0.0001) were more common in the levodopa groups, especially with the higher dosages. Freezing appeared around the same time, but was more common in the placebo (14 %) and 150 mg/day group (10 %). The percent decline of beta-CIT uptake in the striatum was significantly more pronounced in the levodopa groups than the placebo group (-7.2%, -4%, -6%, and -1.4% in 600 mg/day, 300 mg/day, 150 mg/day, and placebo, respectively; p=0.035). CONCLUSIONS: The clinical outcomes not only indicate that levodopa is effective in a dose-dependent manner in overcoming the signs and symptoms of PD, they also support the concept that the drug does not hasten the disease progression, but rather may slow down the rate of the disease. The clinical study failed to demonstrate any evidence of levodopa worsening early PD. However, the beta-CIT SPECT substudy indicates the opposite effect, namely that levodopa causes a more rapid decline in the integrity of the dopamine transporter located in the nigrostriatal nerve terminals in the striatum. These contradictory findings warrant further investigation into the effect of levodopa on PD. OTHER OBSERVATIONS: The ELLDOPA study was the first levodopa dose-response study ever conducted. It showed that dose is a factor in the cause of producing motor complications of dyskinesias and wearing-off, and that these can develop as early as 5 to 6 months. On the other hand, freezing of gait could be delayed or its occurrence reduced by high dosage levodopa, compared to placebo or low-dose levodopa. Withdrawal of levodopa over a 3-day step-down can be safely carried out without inducing the neuroleptic-like syndrome. The UPDRS was shown to be a reliable linear marker for disease progression. The ELLDOPA study also called into question the interpretation of beta-CIT SPECT in the presence of dopaminergic agents. Neuroimaging in ELLDOPA also showed that some people diagnosed with early PD do not have a dopaminergic deficit, calling into question how difficult the correct diagnosis may be in people with early symptoms of PD.

Antiparkinson Agents↗
PubMed2005

Treatment issues in psychogenic-neuropsychiatric movement disorders.

Patients with PNMDs pose a fascinating challenge to clinicians at the neurology-psychiatry interface. We have outlined a diagnostic and therapeutic approach to these complex disorders. Patients with PNMDs typically manifest abnormal movements and postures that do not fit expected patterns of movement disorder phenomenology. The first goal of neurologic consultation is to make an accurate diagnosis, with a view to either ruling out or defining the extent of any organic substrate. The next task is an effective referral to a psychiatrist capable of diagnosing relevant psychopathology and collaborating in a treatment plan. A supportive explanation of the diagnosis, one that is sensitive to the patient's intellectual capacity, conception of the illness, and self-esteem, appears to be a crucial determinant that influences the patient's capacity to be engaged effectively in treatment. The treatment for each patient with PNMD is individualized and may include psychotherapy, hypnosis, pharmacotherapy, physical therapy, and other approaches. To date, no treatment approach has been shown to be superior, and very few long-term outcome data are available. Although many factors influence response to treatment, those of particular importance are the effectiveness of communication among the neurologist, the psychiatrist, and the patient; the nature, severity, and chronicity of relevant psychopathology and environmental stressors; and the quality of external support and intrinsic resources available to the patient.

Humans↗
PubMed2004

Levodopa and the progression of Parkinson's disease.

BACKGROUND: Despite the known benefit of levodopa in reducing the symptoms of Parkinson's disease, concern has been expressed that its use might hasten neurodegeneration. This study assessed the effect of levodopa on the rate of progression of Parkinson's disease. METHODS: In this randomized, double-blind, placebo-controlled trial, we evaluated 361 patients with early Parkinson's disease who were assigned to receive carbidopa-levodopa at a daily dose of 37.5 and 150 mg, 75 and 300 mg, or 150 and 600 mg, respectively, or a matching placebo for a period of 40 weeks, and then to undergo withdrawal of treatment for 2 weeks. The primary outcome was a change in scores on the Unified Parkinson's Disease Rating Scale (UPDRS) between baseline and 42 weeks. Neuroimaging studies of 142 subjects were performed at baseline and at week 40 to assess striatal dopamine-transporter density with the use of iodine-123-labeled 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT) uptake. RESULTS: The severity of parkinsonism increased more in the placebo group than in all the groups receiving levodopa: the mean difference between the total score on the UPDRS at baseline and at 42 weeks was 7.8 units in the placebo group, 1.9 units in the group receiving levodopa at a dose of 150 mg daily, 1.9 in those receiving 300 mg daily, and -1.4 in those receiving 600 mg daily (P<0.001). In contrast, in a substudy of 116 patients the mean percent decline in the [123I]beta-CIT uptake was significantly greater with levodopa than placebo (-6 percent among those receiving levodopa at 150 mg daily, -4 percent in those receiving it at 300 mg daily, and -7.2 percent among those receiving it at 600 mg daily, as compared with -1.4 percent among those receiving placebo; 19 patients with no dopaminergic deficits on the baseline scans were excluded from the analysis) (P=0.036). The subjects receiving the highest dose of levodopa had significantly more dyskinesia, hypertonia, infection, headache, and nausea than those receiving placebo. CONCLUSIONS: The clinical data suggest that levodopa either slows the progression of Parkinson's disease or has a prolonged effect on the symptoms of the disease. In contrast, the neuroimaging data suggest either that levodopa accelerates the loss of nigrostriatal dopamine nerve terminals or that its pharmacologic effects modify the dopamine transporter. The potential long-term effects of levodopa on Parkinson's disease remain uncertain.

Aged↗
PubMed2004

Reaction time and movement time after embryonic cell implantation in Parkinson disease.

BACKGROUND: Embryonic nigral cell implants are a novel treatment for Parkinson disease (PD). Reaction time (RT) and movement time (MT) analysis, validated quantitative measures of premovement neural processing and motor execution, can be used as objective physiological markers of motor performance in PD. OBJECTIVES: To gauge the change in motor performance in patients with PD who received implants, and to determine whether the physiological findings correlate with clinical outcome measures after transplantation. DESIGN: Double-blind, placebo-controlled trial. Patients Forty patients with levodopa-responsive, Hoehn and Yahr stage III or greater PD. INTERVENTIONS: Random assignment to embryonic tissue implants or placebo (sham) operation. MAIN OUTCOME MEASURES: Combined RT + MT scores measured preoperatively and at 4 and 12 months postoperatively in the "off" state. RESULTS: The difference in mean RT + MT scores between the sham and implant groups was statistically significant (P =.005) and was greatest in those 60 years or older (P =.003). Changes correlated with Unified Parkinson's Disease Rating Scale off scores at 4 (r = 0.87, P =.001) and 12 (r = 0.75, P =.01) months in those younger than 60 years. There was a significant deterioration in the sham surgery group at 12 months (P =.03) that was thought to be due to worsening in subjects 60 years and older (P<.001). CONCLUSIONS: The physiological measures detected significant changes in patients undergoing embryonic nigral cell implants and correlated directly with clinical outcome measures. Comprehensive analyses of RT paradigms can document subtle changes in motor performance over time, making them useful outcome measures in therapeutic trials of PD. These findings support further research into nigral cell implantation for PD.

Adult↗
PubMed2004

Lack of familial aggregation of Parkinson disease and Alzheimer disease.

OBJECTIVE: To investigate the risk of Alzheimer disease (AD) in first-degree relatives of patients with Parkinson disease (PD) compared with first-degree relatives of controls. DESIGN: Case-control study, family history method, and reconstructed cohort approach. METHODS: Probands with PD without dementia and control probands, matched by age strata, sex, and ethnicity, were examined in person and enrolled without knowledge of family history of PD and other neurological disorders. Disease status in first-degree relatives of probands with PD and control probands was ascertained through a structured family history interview administered to the proband and a second informant (self-report or another informant). Cox proportional hazards models with double-censoring techniques for missing information on age of onset of AD were used to analyze the risk of AD in first-degree relatives of patients with PD compared with first-degree relatives of controls. RESULTS: Four hundred eighty-seven probands with PD and 409 control probands provided family history information on 4819 first-degree relatives older than 30 years (2534 relatives of probands with PD and 2285 relatives of control probands). One hundred thirteen first-degree relatives (2.3%; 61 relatives [2.4%] of patients with PD and 52 relatives [2.3%] of controls) were diagnosed with AD. The risk of AD was not increased in relatives of patients with PD compared with relatives of controls (hazard ratio, 1.1; 95% confidence interval, 0.7-1.6; P =.65). Similarly, no significantly increased risk of AD was observed when comparing relatives of patients with early-onset (< or =50 years) and late-onset (>50 years) PD with relatives of controls. CONCLUSION: The lack of familial aggregation of PD and AD does not support the hypothesis of major shared genetic contributions to the etiology of the 2 most common neurodegenerative disorders.

Adult↗
PubMed2004

Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial.

BACKGROUND: The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear. OBJECTIVE: To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes. DESIGN: Multicenter, parallel-group, double-blind, randomized controlled trial. SETTING: Academic movement disorders clinics at 22 sites in the United States and Canada. PATIENTS: Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001. INTERVENTION: Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n = 150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability. MAIN OUTCOME MEASURES: Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-of-life scales; and adverse events. RESULTS: Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval [CI], 0.25-0.56; P<.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months was greater in the levodopa group than in the pramipexole group (2 +/- 15.4 points vs -3.2 +/- 17.3 points, P =.003). Somnolence (36% vs 21%, P =.005) and edema (42% vs 15%, P<.001) were more common in pramipexole-treated subjects than in levodopa-treated subjects. Mean changes in quality-of-life scores did not differ between the groups. CONCLUSIONS: Initial treatment with pramipexole resulted in lower incidences of dyskinesias and wearing off compared with initial treatment with levodopa. Initial treatment with levodopa resulted in lower incidences of freezing, somnolence, and edema and provided for better symptomatic control, as measured by the Unified Parkinson's Disease Rating Scale, compared with initial treatment with pramipexole. Both options resulted in similar quality of life. Levodopa and pramipexole both appear to be reasonable options as initial dopaminergic therapy for Parkinson disease, but they are associated with different efficacy and adverse-effect profiles.

Aged↗
PubMed2004

Effects of perceived treatment on quality of life and medical outcomes in a double-blind placebo surgery trial.

CONTEXT: This study was part of a large double-blind sham surgery-controlled trial designed to determine the effectiveness of transplantation of human embryonic dopamine neurons into the brains of persons with advanced Parkinson's disease. This portion of the study investigated the quality of life (QOL) of participants during the 1 year of double-blind follow-up. OBJECTIVES: To determine whether QOL improved more in the transplant group than in the sham surgery group and to investigate outcomes at 1 year based on perceived treatment (the type of surgery patients thought they received). DESIGN: Participants were randomly assigned to receive either the transplant or sham surgery. Reported results are from the 1-year double-blind period. SETTING: Participants were recruited from across the United States and Canada. Assessment and surgery were conducted at 2 separate university medical centers. PARTICIPANTS: A volunteer sample of 40 persons with idiopathic Parkinson's disease participated in the transplant ("parent") study, and 30 agreed to participate in the related QOL study: 12 received the transplant and 18 received sham surgery. INTERVENTIONS: Interventions in the parent study were transplantation and sham brain surgery. Assessments of QOL were made at baseline and 4, 8, and 12 months after surgery. MAIN OUTCOME MEASURES: Comparison of the actual transplant and sham surgery groups and the perceived treatment groups on QOL and medical outcomes. We also investigated change over time. RESULTS: There were 2 differences or changes over time in the transplant and sham surgery groups. Based on perceived treatment, or treatment patients thought they received, there were numerous differences and changes over time. In all cases, those who thought they received the transplant reported better scores. Blind ratings by medical staff showed similar results. CONCLUSIONS: The placebo effect was very strong in this study, demonstrating the value of placebo-controlled surgical trials.

Aged↗