Parkinson Disease: Stebbins GT

Schrag A, Barone P, Brown RG, Leentjens AF, McDonald WM, Starkstein S, Weintraub D, Poewe W, Rascol O, Sampaio C, Stebbins GT, Goetz CG. · University Department of Clinical Neurosciences, Royal Free and University College Medical School, London, UK. · Mov Disord. · Pubmed #17394234 links to  free full text

Abstract: Depression is a common comorbid condition in Parkinson's disease (PD) and a major contributor to poor quality of life and disability. However, depression can be difficult to assess in patients with PD due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired patients. As several rating scales have been used to assess depression in PD (dPD), the Movement Disorder Society commissioned a task force to assess their clinimetric properties and make clinical recommendations regarding their use. A systematic literature review was conducted to explore the use of depression scales in PD and determine which scales should be selected for this review. The scales reviewed were the Beck Depression Inventory (BDI), Hamilton Depression Scale (Ham-D), Hospital Anxiety and Depression Scale (HADS), Zung Self-Rating Depression Scale (SDS), Geriatric Depression Scale (GDS), Montgomery-Asberg Depression Rating Scale (MADRS), Unified Parkinson's Disease Rating Scale (UPDRS) Part I, Cornell Scale for the Assessment of Depression in Dementia (CSDD), and the Center for Epidemiologic Studies Depression Scale (CES-D). Seven clinical researchers with clinical and research experience in the assessment of dPD were assigned to review the scales using a structured format. The most appropriate scale is dependent on the clinical or research goal. However, observer-rated scales are preferred if the study or clinical situation permits. For screening purposes, the HAM-D, BDI, HADS, MADRS, and GDS are valid in dPD. The CES-D and CSDD are alternative instruments that need validation in dPD. For measurement of severity of depressive symptoms, the Ham-D, MADRS, BDI, and SDS scales are recommended. Further studies are needed to validate the CSDD, which could be particularly useful for the assessment of severity of dPD in patients with comorbid dementia. To account for overlapping motor and nonmotor symptoms of depression, adjusted instrument cutoff scores may be needed for dPD, and scales to assess severity of motor symptoms (e.g., UPDRS) should also be included to help adjust for confounding factors. The HADS and the GDS include limited motor symptom assessment and may, therefore, be most useful in rating depression severity across a range of PD severity; however, these scales appear insensitive in severe depression. The complex and time-consuming task of developing a new scale to measure depression specifically for patients with PD is currently not warranted.

Goetz CG, Poewe W, Rascol O, Sampaio C, Stebbins GT, Counsell C, Giladi N, Holloway RG, Moore CG, Wenning GK, Yahr MD, Seidl L, Anonymous00253. · Rush University Medical Center, 1725 W. Harrison Street, Chicago, IL 60612, USA. · Mov Disord. · Pubmed #15372591 links to  free full text

Abstract: The Movement Disorder Society Task Force for Rating Scales for Parkinson's disease (PD) prepared a critique of the Hoehn and Yahr scale (HY). Strengths of the HY scale include its wide utilization and acceptance. Progressively higher stages correlate with neuroimaging studies of dopaminergic loss, and high correlations exist between the HY scale and some standardized scales of motor impairment, disability, and quality of life. Weaknesses include the scale's mixing of impairment and disability and its non-linearity. Because the HY scale is weighted heavily toward postural instability as the primary index of disease severity, it does not capture completely impairments or disability from other motor features of PD and gives no information on nonmotor problems. Direct clinimetric testing of the HY scale has been very limited, but the scale fulfills at least some criteria for reliability and validity, especially for the midranges of the scale (Stages 2-4). Although a "modified HY scale" that includes 0.5 increments has been adopted widely, no clinimetric data are available on this adaptation. The Task Force recommends that: (1) the HY scale be used in its original form for demographic presentation of patient groups; (2) when the HY scale is used for group description, medians and ranges should be reported and analysis of changes should use nonparametric methods; (3) in research settings, the HY scale is useful primarily for defining inclusion/exclusion criteria; (4) to retain simplicity, clinicians should "rate what you see" and therefore incorporate comorbidities when assigning a HY stage; and (5) because of the wide usage of the modified HY scale with 0.5 increments, this adaptation warrants clinimetric testing. Without such testing, however, the original five-point scales should be maintained.

Diederich NJ, Goetz CG, Stebbins GT. · Department of Neuroscience, Centre Hospitalier de Luxembourg, Luxembourg. · Mov Disord. · Pubmed #15486924 No free full text.

Abstract: Visual hallucinations (VH) in Parkinson's disease (PD) are a chronic complication in 30 to 60% of treated patients and have a multifaceted phenomenology. Flickering, faultive impressions, and illusionary misperceptions precede the core syndrome of stereotyped, colorful images. The patient variably recognizes these images as hallucinations, being rarely irritated or frightened and more often amused as a bystander. Although studies on VH in PD focus on several research domains, no comprehensive, unified theory has been developed to study their pathophysiology. We have adapted Hobson's work on the states of consciousness and propose a model integrating seemingly disparate data on VH. We suggest that VH should be considered as a dysregulation of the gating and filtering of external perception and internal image production. Contributive elements and anatomical links for the model include poor primary vision, reduced activation of primary visual cortex, aberrant activation of associative visual and frontal cortex, lack of suppression or spontaneous emergence of internally generated imagery through the ponto-geniculo-occipital system, intrusion of rapid eye movement dreaming imagery into wakefulness, errative changes of the brainstem filtering capacities through fluctuating vigilance, and medication-related overactivation of mesolimbic systems. Different etiologies likely produce different phenomenologies and the prognosis may not be uniform. This new conceptual framework permits an anatomical view of VH and suggests new, testable hypotheses regarding their pathophysiology and therapy.

Goetz CG, Leurgans S, Raman R, Stebbins GT. · Department of Neurological Sciences, Rush University, Rush Presbyterian St. Luke's Medical Center, Chicago, IL 60612, USA. · Neurology. · Pubmed #10680808 No free full text.

Abstract: OBJECTIVE: To examine the frequency, temporal development, and stability of objectively derived motor changes during placebo treatment in PD and to define the clinical domains and demographic groups most affected. BACKGROUND: Placebo effects are documented in neurology, but the timing and specific disabilities most susceptible to changes during placebo treatment in PD have not been examined. METHODS: The authors examined the placebo-treated group from a randomized, multicenter, placebo-controlled clinical trial of monotherapy ropinerole in PD patients without motor fluctuations. In 105 patients, they evaluated placebo-associated effects on the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS), dividing the motor examination into four categories: tremor, bradykinesia, rigidity, and gait/balance/midline functions. The motor UPDRS and its subscales were compared over time (at baseline and at 4, 12, and 24 weeks) using Wilcoxon's signed rank test. They applied a rigorous definition of placebo-associated improvement as an improvement over baseline score in motor UPDRS of at least 50% or a change in at least two motor items at any one visit by > or =2 points. RESULTS: During the 6-month study, 16% of subjects improved on placebo treatment. The prevalence of response was steady (8 to 9%) at any one visit without a predominance of an early effect. No patient showed a placebo-associated improvement on all visits. All domains of parkinsonian disability were subject to placebo-associated improvement, with a trend toward more response in bradykinesia and rigidity than in tremor or gait/balance/midline function. Gender, age, disease duration, and baseline disability score did not influence the likelihood of improvement in association with placebo treatment. CONCLUSION: Based on a rigorous definition of placebo-associated improvement, prominent improvements in objective measures of PD disability occur during clinical trials. Because placebo-associated improvements occur throughout a 6-month trial, placebo-controlled studies in PD should be at least 6 months to capture early as well as late improvements.

Stebbins GT, Gabrieli JD, Masciari F, Monti L, Goetz CG. · Department of Neurological Sciences, Rush Medical College, Chicago, IL 60612, USA. · Neuropsychologia. · Pubmed #10215097 No free full text.

Abstract: Immediate and delayed recognition memory for words was examined in a sample of 16 non-demented patients with Parkinson's disease and 16 normal control participants of equivalent age and educational attainment. The patients, relative to control participants, had intact immediate but impaired delayed recognition memory performance. Patients were also impaired on tests of free and cued recall, working memory and a measure of psychomotor processing speed. Processing speed was a significant covariate for delayed recognition, free and cued recall and working memory performance, but not for immediate recognition performance. These results suggest that the same cognitive processes which support performance on tests of recall and working memory also support performance on tests of delayed recognition.

Goetz CG, Blasucci L, Stebbins GT. · Department of Neurological Sciences, Rush University/Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA. · Neurology. · Pubmed #10214748 No free full text.

Abstract: BACKGROUND: New dopamine agonists are available, but no study has examined safe and effective ways to switch from one agonist to another. OBJECTIVE: To compare rapid- versus slow-titration schedules for starting a new dopamine agonist in patients already on chronic agonist therapy for Parkinson's disease. METHODS: Sixteen patients on stable carbidopa/levodopa and a dopamine agonist (bromocriptine or pergolide) switched to pramipexole using a conversion calculation of 1:1 for pergolide dose and 10:1 for bromocriptine dose. Patients were randomized to two titration schedules-either slow titration, following the package insert and taking up to 8 weeks to reach their equivalent dosage (8 patients), or rapid titration, receiving the full converted dose the day after stopping the former agonist (8 patients) with subsequent weekly dose adjustments. Using a blinded observer, the primary outcome variable was the time required to a Unified Parkinson's Disease Rating Scale (UPDRS) motor score superior to baseline without increased adverse effects. RESULTS: Both groups showed equivalent and statistically significant improvement after switching to the new agonist. The mean time to reach a UPDRS score that was superior to baseline without increased adverse effects was significantly shorter in the rapid-titration group (mean 2.1 weeks versus 5.3 weeks). Furthermore, with slow titration two patients experienced enhanced parkinsonian serious adverse effects requiring hospitalization (two falls with fractures). CONCLUSION: The switchover from one agonist to another can be safely and successfully accomplished with a rapid titration based on an equivalency dose calculation.

Goetz CG, Tilley BC, Shaftman SR, Stebbins GT, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stern MB, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, van Hilten JJ, LaPelle N, Anonymous00025. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA. · Mov Disord. · Pubmed #19025984 links to  free full text

Abstract: We present a clinimetric assessment of the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS). The MDS-UDPRS Task Force revised and expanded the UPDRS using recommendations from a published critique. The MDS-UPDRS has four parts, namely, I: Non-motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver. Item-specific instructions and an appendix of complementary additional scales are provided. Movement disorder specialists and study coordinators administered the UPDRS (55 items) and MDS-UPDRS (65 items) to 877 English speaking (78% non-Latino Caucasian) patients with Parkinson's disease from 39 sites. We compared the two scales using correlative techniques and factor analysis. The MDS-UPDRS showed high internal consistency (Cronbach's alpha = 0.79-0.93 across parts) and correlated with the original UPDRS (rho = 0.96). MDS-UPDRS across-part correlations ranged from 0.22 to 0.66. Reliable factor structures for each part were obtained (comparative fit index > 0.90 for each part), which support the use of sum scores for each part in preference to a total score of all parts. The combined clinimetric results of this study support the validity of the MDS-UPDRS for rating PD.

Goetz CG, Nutt JG, Stebbins GT. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA. · Mov Disord. · Pubmed #19025759 No free full text.

Abstract: We developed and tested a rating scale aimed to capture the essential features of dyskinesia in Parkinson's disease (PD). Although several scales assess selected attributes of PD-dyskinesias, no comprehensive rating tool exists. Available rating scales were evaluated by the investigators and patient focus groups. Modifications were finalized into the Unified Dyskinesia Rating Scale (UDysRS). The UDysRS has four parts: I: Historical Disability (patient perceptions) of On-Dyskinesia impact (maximum 44 points); II: Historical Disability (patient perceptions) of Off-Dystonia impact (maximum 16 points); III: Objective Impairment (dyskinesia severity, anatomical distribution over seven body regions, and type (choreic or dystonic) based on four activities observed or video-recorded (28 points); IV: Objective Disability based on Part III activities (maximum 16 points). For clinimetric testing, 70 PD patients with all severities of dyskinesia were interviewed and videotaped. Twenty movement disorder experts rated the videotapes with the UDysRS. Internal consistency was examined with Cronbach's alpha. Inter- and intra-rater reliability was evaluated with generalized weighted and nonweighted Kappa coefficients, and intraclass correlation coefficients. Both subjective (Sections I and II) and objective (Sections III and IV) demonstrated high internal consistency (alpha: 0.915, 0.971). Interrater reliability for the objective sections was acceptable for all items and likewise for intrarater reliability except for right leg. Reliable factor structures were found for both subjective (six factors) and objective sections (five factors). The UDysRS is a clinimetrically sound rating scale for dyskinesia in PD, demonstrating acceptable levels of internal consistency and inter- and intra-rater reliability. Testing scale responsivity to treatment interventions is planned.

Leentjens AF, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, Starkstein SE, Weintraub D, Sampaio C, Poewe W, Rascol O, Stebbins GT, Goetz CG. · Department of Psychiatry, Maastricht University Hospital, Maastricht, the Netherlands. · Mov Disord. · Pubmed #18792121 links to  free full text

Abstract: Anxiety syndromes are common in patients with Parkinson's disease (PD) with up to 30% suffering from panic disorder, and up to 11% from generalized anxiety disorder (GAD). Anxiety is associated with increased subjective motor symptoms, more severe gait problems, dyskinesias, freezing, and on/off fluctuations. Anxiety has a negative impact on health related quality of life and is strongly associated with depressive syndromes. Since a variety of anxiety scales have been used in PD patients, the Movement Disorder Society commissioned a task force to assess the clinimetric properties of these scales in PD. A systematic review was conducted to identify anxiety scales that have either been validated or used in patients with PD. Six anxiety rating scales were identified. These were the Beck anxiety inventory, the hospital anxiety and depression scale, the Zung self-rating anxiety scale and anxiety status inventory, the Spielberger state trait anxiety inventory, and the Hamilton anxiety rating scale. In addition, Item 5 (anxiety) of the neuropsychiatric inventory was included in the review. No scales met the criteria to be "recommended," and all scales were classified as "suggested." Essential clinimetric information is missing for all scales. Because several scales exist and have been used in PD, the task force recommends further studies of these instruments. If these studies show that the clinimetric properties of existing scales are inadequate, development of a new scale to assess anxiety in PD should be considered.

Leentjens AF, Dujardin K, Marsh L, Martinez-Martin P, Richard IH, Starkstein SE, Weintraub D, Sampaio C, Poewe W, Rascol O, Stebbins GT, Goetz CG. · Department of Psychiatry, Maastricht University Hospital, Maastricht, The Netherlands. · Mov Disord. · Pubmed #18709683 links to  free full text

Abstract: Apathy is a common condition in Parkinson's disease (PD) and is generally defined as a lack of motivation. It is associated with more severe cognitive dysfunction and a decrease in activities of daily living (ADL) performance. Anhedonia, the inability to experience pleasure, can be a symptom of both depressive and apathetic syndromes. The Movement Disorder Society (MDS) commissioned a task force to assess the clinimetric properties of apathy and anhedonia scales in PD patients. A systematic literature review was conducted to identify scales that have either been validated or used in PD patients. Apathy scales identified for review include the Apathy Evaluation Scale (AES), the Apathy Scale (AS), the Apathy Inventory (AI), and the Lille Apathy Rating Scale (LARS). In addition, item 4 (motivation/initiative) of the Unified Parkinson's Disease Rating Scale (UPDRS) and item 7 (apathy) of the Neuropsychiatric Inventory (NPI) were included. Anhedonia scales identified for review were the Snaith-Hamilton Pleasure Scale (SHAPS) and the Chapman scales for physical and social anhedonia. Only the AS is classified as "recommended" to assess apathy in PD. Although item 4 of the UPDRS also meets the criteria to be classified as recommended, it should be considered for screening only because of the obvious limitations of a single item construct. For the assessment of anhedonia, only the SHAPS meets the criteria of "Suggested." Information on the validity of apathy and anhedonia scales is limited because of the lack of consensus on diagnostic criteria for these conditions.

Fernandez HH, Aarsland D, Fénelon G, Friedman JH, Marsh L, Tröster AI, Poewe W, Rascol O, Sampaio C, Stebbins GT, Goetz CG. · Department of Neurology, McKnight Brain Institute/University of Florida, Gainesville, Florida 32611, USA. · Mov Disord. · Pubmed #18175343 links to  free full text

Abstract: Psychotic symptoms are a frequent occurrence in Parkinson's disease (PD), affecting up to 50% of patients. The Movement Disorder Society established a Task Force on Rating Scales in PD, and this critique applies to published, peer-reviewed rating psychosis scales used in PD psychosis studies. Twelve psychosis scales/questionnaires were reviewed. None of the reviewed scales adequately captured the entire phenomenology of PD psychosis. While the Task Force has labeled some scales as "recommended" or "suggested" based on the fulfilling-defined criteria, none of the current scales contained all the basic content, mechanistic and psychometric properties needed to capture PD psychotic phenomena and to measure clinical response over time. Different scales may be better for some settings versus others. Since one scale may not be able to serve all needs, a scale used to measure clinical response and change over time [such as the Clinical Global Impression Scale (CGIS)] may need to be combined with another scale better at cataloging specific features [such as the Neuropsychiatric Inventory (NPI) or Schedule for Assessment of Positive Symptoms (SAPS)]. At the present time, for clinical trials on PD psychosis assessing new treatments, the following are recommended primary outcome scales: NPI (for the cognitively impaired PD population or when a caregiver is required), SAPS, Positive and Negative Syndrome Scale (PANSS), or Brief Psychiatric Rating Scale (BPRS) (for the cognitively intact PD population or when the patient is the sole informant). The CGIS is suggested as a secondary outcome scale to measure change and response to treatment over time.

Goetz CG, Fahn S, Martinez-Martin P, Poewe W, Sampaio C, Stebbins GT, Stern MB, Tilley BC, Dodel R, Dubois B, Holloway R, Jankovic J, Kulisevsky J, Lang AE, Lees A, Leurgans S, LeWitt PA, Nyenhuis D, Olanow CW, Rascol O, Schrag A, Teresi JA, Van Hilten JJ, LaPelle N. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA. · Mov Disord. · Pubmed #17115387 links to  free full text

Abstract: 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.

Kroonenberg PM, Oort FJ, Stebbins GT, Leurgans SE, Cubo E, Goetz CG. · Department of Education and Child Study, Wassenaarseweg 52, Leiden University, Leiden, The Netherlands. · BMC Med Res Methodol. · Pubmed #16772027 links to  free full text

Abstract: BACKGROUND: In order to better understand the similarities and differences in the motor behaviour of different groups of patients, their scores on the Motor Examination section of the Unified Parkinson's Disease Rating Scale (UPDRS) were analysed simultaneously. The three groups consisted, respectively, of patients with Parkinson's disease (PD) on medication, patients with Parkinson's disease withdrawn from anti-parkinsonian medication for at least 12 hours, and patients diagnosed with a specific Parkinsonism syndrome: Progressive Supranuclear Palsy (PSP). METHODS: A total of 669 consecutively sampled patients from three separate hospital-based clinics participated (294 PD on medication; 200 PD off medication: 175 PSP). The Motor Examination section of the UPDRS was administered by neurologists at the three participating clinics. The patient scores on each item were recorded. To assess similarities and differences among the components of the UPDRS in these samples, we performed simultaneous or multigroup factor analysis on the covariance matrices of the three groups. In addition, it was investigated whether a single model for the Motor Examination section of the UPDRS could be developed which would be valid for all three groups at the same time. RESULTS: A single six-dimensional factor solution was found that fitted all groups, although this was not straightforward due to differences between the tremor-at-rest variables. The factors were identified as Tremor-at-rest, Postural Tremor, Axial Dysfunctioning, Rigidity, Left Bradykinesia and Right Bradykinesia. The analysis also pointed to a somewhat lower lateralization in bradykinesia for PSP patients. The groups differed in intensity of motor impairment, especially with respect to Tremor-at-Rest, but the overall relationships between the variables were shared by the three groups. In addition, apart from the common factor structure evidence of differences in body part-specific and motor-specific variances was found. CONCLUSION: From a clinical point of view, the analyses showed that using the Motor Examination section of the UPDRS is also appropriate for patients with PSP, because the correlational structure of the items is directly comparable to that of Parkinson's patients. Methodologically, the analysis of all groups together showed that it is possible to evaluate similarities and differences between factor structures in great detail.

Goetz CG, Fan W, Leurgans S, Bernard B, Stebbins GT. · Department of Neurological Sciences, Rush University Medical Center, 1725 W. Harrison Street, Chicago, IL 60612, USA. · Arch Neurol. · Pubmed #16682540 links to  free full text

Abstract: OBJECTIVE: To monitor progression of "benign hallucinations" in Parkinson disease (PD). METHODS: We searched our data repository for subjects with PD with 3 sets of neuropsychological testing during 3 years and Unified Parkinson's Disease Rating Scale thought disorder scores taken at 4- to 12-month intervals during this period. We found 48 patients with benign hallucinations, defined as a thought disorder score of 2 (benign hallucinations, insight retained), receiving no treatment for hallucinations. We followed up thought disorder scores under best medical management for at least 3 years or until a thought disorder score of 3 (loss of insight) or 4 (delusions) occurred. In subjects whose thought disorder scores remained at 2, we assessed neuroleptic use and decreases in PD medications to abate hallucinations. RESULTS: Most subjects (81%) progressed to thought disorder scores of 3 or 4. In 7 (78%) of 9 subjects who retained a thought disorder score of 2, PD medications were reduced to treat hallucinations, and 3 subjects (33%) also received neuroleptics. If the composite end point (any of the criteria) was used, 96% of subjects progressed, with only 2 subjects continuing with stable, untreated benign hallucinations. CONCLUSIONS: Because hallucinations progress, the concept of benign hallucinations is prognostically misleading. Though hallucinations with retained insight may be "benign" for the moment, they portend serious consequences. The term benign hallucinations of PD should be considered generally unsound and dropped from operative vocabulary.

Stebbins GT, Goetz CG, Carrillo MC, Bangen KJ, Turner DA, Glover GH, Gabrieli JD. · Department of Neurological Sciences, Rush University Medical Center, 1725 West Harrison Street, Suite 309, Chicago, IL 60612, USA. · Neurology. · Pubmed #15505157 No free full text.

Abstract: OBJECTIVE: To compare fMRI activation during two visual stimulation paradigms in Parkinson disease (PD) subjects with chronic visual hallucinations vs PD patients who had never hallucinated. METHODS: Twelve pairs of PD subjects, matched for age, PD duration, and dopaminergic drug exposure duration, participated in this study. The authors examined group differences in activation during stroboscopic (flashing) vs no visual stimulation and kinematic (apparent motion) vs stationary visual stimulation. RESULTS: During stroboscopic stimulation, non-hallucinating PD subjects showed significantly greater activation in the parietal lobe and cingulate gyrus compared to hallucinating PD subjects. In contrast, the hallucinating subjects showed significantly greater activation in the inferior frontal gyrus and the caudate nucleus. During kinematic stimulation, non-hallucinating PD subjects showed significantly greater activation in area V5/MT, parietal lobe, and cingulate gyrus compared to hallucinating PD subjects. Hallucinating PD subjects showed significantly greater activation in the superior frontal gyrus. CONCLUSIONS: PD patients with chronic visual hallucinations respond to visual stimuli with greater frontal and subcortical activation and less visual cortical activation than non-hallucinating PD subjects. Shifting visual circuitry from posterior to anterior regions associated primarily with attention processes suggests altered network organization may play a role in the pathophysiology of visual hallucinations in PD.

Goetz CG, Stebbins GT. · Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois 60612, USA. · Mov Disord. · Pubmed #15389981 No free full text.

Abstract: We assessed rates of successful certification on the motor section of the Unified Parkinson's Disease Rating Scale (UPDRSm) after training with the UPDRS Teaching Tape. The most frequently used clinical scale for PD is the UPDRS, and most clinical trials rely on the motor examination as the primary outcome measure. Whereas the Movement Disorder Society's UPDRS Teaching Tape has been used widely as a training format, outcome data are lacking. We examined data sets from four multicenter studies that required raters to pass the certification exercise of the UPDRS Teaching Tape. Raters viewed the Teaching Tape showing examples of all rating levels for all items (38 minutes), and then took the certification exercise, rating 4 subjects with PD (20 minutes). Certification required scores on all 4 subjects that fit within the 95% confidence interval range established by three experts. We calculated the numbers of raters successfully certified after one or more rating attempts. Only one-half of 226 raters that participated successfully completed certification on their first attempt, but all completed by the third attempt. North American raters scored better than Europeans raters. The most difficult case to rate was the subject with the least impairment. Standardized methods for training UPDRSm application are essential to ensure that raters use the scale uniformly. Raters have the greatest difficulty with the mildest impairment, making training especially important to studies of early PD.

Goetz CG, Stebbins GT, Blasucci LM. · Department of Neurological Sciences, Rush Presbyterian St. Luke's Medical Center, Chicago, Illinois 60612, USA. · Mov Disord. · Pubmed #10830412 No free full text.

Abstract: OBJECTIVE: To monitor comparative progression of clinical impairment over 4 years in patients with Parkinson's disease (PD) who present on levodopa at two different levels of Hoehn and Yahr (HY) stages, II and III. BACKGROUND: The rate of clinical impairment progression in patients with PD being treated with levodopa has not been studied in detail using current, standardized assessment tools. Sample size estimates for all levodopa adjunctive treatment studies and proper definition of study groups require a solid estimate of longitudinal motor impairment progression. DESIGN/METHODS: From our computer database, we identified two groups of patients with PD being treated with levodopa based on their initial HY stage at presentation to our center (II or III). Fifty randomly selected subjects in each stage were monitored in the ON state with annual Unified Parkinson's Disease Rating Scale (UPDRS) motor scores, dyskinesia ratings, and antiparkinsonian medication doses using a repeated measures analysis of variance. RESULTS: The stage II and stage III subjects had similar disease duration. In stage II subjects, parkinsonian impairment was maintained without progression over 4 years, but in association with significantly higher dyskinesia scores and dopaminergic medication doses. In stage III subjects, UPDRS motor scores deteriorated despite more medication and increased dyskinesias. Of the established six factors comprising the UPDRS motor scale, bradykinesia accounted for the increased impairment. Initial UPDRS motor score and disease duration did not influence progression of motor impairment. CONCLUSION: In subjects with similar disease duration, progression of PD motor impairment differs significantly between stage II and stage III subjects over 4 years. Whereas in stage II subjects, parkinsonian impairment can be stabilized at the expense of increased dyskinesia and dopaminergic drugs, once subjects reach stage III, motor impairment progresses. Power estimates and sample size calculations for these groups of patients should be calculated separately.

Stebbins GT, Gabrieli JD, Shannon KM, Penn RD, Goetz CG. · Department of Neurological Sciences, Rush Medical College, Chicago, IL 60612, USA. · Brain Cogn. · Pubmed #10753484 No free full text.

Abstract: We investigated the long-term effects of posteroventral pallidotomy on tests sensitive to the functional integrity of frontostriatal neural systems in a sample of 11 patients with advanced Parkinson's disease (PD). Patients were assessed within 1 month prior to surgery and at 12 months following pallidotomy. Changes in outcome measures were compared to a control sample of equally performing PD patients receiving nonsurgical medical management assessed over a 12-month period. Measures of cognitive abilities sensitive to frontostriatal functional integrity tested psychomotor processing speed, executive components of working memory, and reasoning. Additional tests of general mental status and semantic memory ability were utilized to assess the specificity of the effect of pallidotomy on cognitive function. Significant declines in performance on all measures sensitive to frontostriatal integrity were found for the surgery group but not the PD control group. No significant changes in performance were found on the measures of general mental status or semantic memory for either the surgery or PD control samples. These results suggest that the posteroventral pallidotomy selectively impairs performance on tests of frontostriatal cognitive abilities.

Cubo E, Stebbins GT, Golbe LI, Nieves A, Leurgans S, Goetz CG, Kompoliti K. · Department of Neurological Sciences, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA. · Mov Disord. · Pubmed #10752576 No free full text.

Abstract: An important criterion in scale validation is the demonstration of a stable factor structure. The Unified Parkinson's Disease Rating Scale (UPDRS) is widely used to assess Parkinson's disease (PD). The reliability and applicability of the motor subscale of the UPDRS (UPDRSm) when applied to patients diagnosed with progressive supranuclear palsy (PSP) is unknown. In a sample of 175 patients with PSP, factor analysis revealed five clinically distinct factors: two independent bradykinesia factors (axial/gait and extremities), one rigidity factor, and two independent tremor factors (rest and action). Two items (posture and rest head tremor) did not reach criteria for factor loadings. There was a high degree of internal consistency. These results suggest that UPDRSm is a reliable and applicable scale for assessing most aspects of PSP function as well as severity measures of five clinical disability domains.

Stebbins GT, Goetz CG, Lang AE, Cubo E. · Department of Neurological Sciences, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA. · Mov Disord. · Pubmed #10435494 No free full text.

Abstract: Determination of a scale's factor structure requires a two-part process: (1) an initial examination of the factor structure using a sample of individuals with the condition of interest, and (2) repeated examinations of the factor structure using the same analytic methods but applied to independent samples of individuals with the condition of interest who contribute unique variability to the scale measurement. In a previous study, we performed an initial investigation of the factor structure of the Motor Examination section of the Unified Parkinson's Disease Rating Scale (UPDRS). We used a sample of 294 consecutive patients with idiopathic Parkinson's disease (PD) assessed while in the on-state and identified six clinically distinct factors. In the present study, we performed a confirmatory investigation of the factor structure and analysis of the internal consistency of the UPDRS in a new sample of 200 consecutive PD patients who were assessed while in the off-state. Factor analysis again revealed six factors with identical item loadings as those obtained from examinations of patients in the on-state. Estimates of internal consistency were comparable in the off- and on-state examinations. These results indicate that the Motor Examination section of the UPDRS has a stable factor structure and high internal consistency across off- and on-state examinations.