Effects of an information booklet on patient anxiety and satisfaction with information in magnetic resonance imaging: A randomized, single-blind, placebo-controlled trial.

INTRODUCTION: Magnetic resonance imaging (MRI) is an important modality in diagnostics and treatment follow-up. However, MRI can be perceived as unpleasant even though the examination is non-invasive. Patients' knowledge of the MRI procedure is usually scarce, which may enhance patient anxiety at examination. We investigated the effects on anxiety and satisfaction with an information booklet on MRI compared to a placebo booklet delivered to adult patients prior to their first MRI examination. METHODS: This randomized, single-blind, placebo-controlled trial included 197 patients. The intervention group (n = 95) received a booklet about MRI prior to the examination, whereas the control group (n = 102) received a placebo booklet of the same size and layout but containing general information. The State Trait Anxiety Inventory with supplementary questions from the Quality from the Patient's Perspective questionnaire were used as patient-reported outcome measures. RESULTS: Anxiety did not differ between the groups, either prior to MRI or during the examination, but those who received the placebo booklet were at higher risk of experiencing high anxiety prior to the MRI examination (odds ratio 2.64; P = 0.029). The intervention group was more satisfied with the information received (P = 0.044), and a majority of participants in both groups (≥87%) considered it important to obtain information on the MRI procedure. CONCLUSION: Written MRI information decreases the risk of high anxiety levels before MRI and improves patient satisfaction with the information. Further research is needed to investigate whether written information prior to MRI is beneficial not only from the perspective of the patient but may also be cost-effective. IMPLICATIONS FOR PRACTICE: Written MRI information prior to the examination is recommended in radiography care.

Factors associated with life satisfaction in Parkinson's disease.

OBJECTIVES: To identify factors associated with life satisfaction (LS) in people with Parkinson's disease (PD), including a specific focus on those with late-stage PD. MATERIAL AND METHODS: The study included 251 persons with PD (median age 70 years; PD duration 8 years). Analyses involved the total sample and a subsample with late-stage PD, that is Hoehn and Yahr stages IV and V (n=62). LS was assessed with item 1 of the Life Satisfaction Questionnaire (LiSat-11). Simple logistic regression analyses were performed for both the total sample and for the subsample with late-stage PD. For the total sample, a multivariable logistic regression analysis was also performed. RESULTS: In the total sample, 12 of the 20 independent variables were significantly associated with LS: need of help with ADL; walking difficulties; number of non-motor symptoms (NMS); fatigue; depressive symptoms; general self-efficacy; motor symptoms; pain; PD severity; freezing episodes; gender (woman); and fluctuations. When controlling for age and gender in the multivariable logistic regression model, depressive symptoms were negatively associated with high LS and general self-efficacy was positively associated with high LS. In late-stage PD, simple logistic regression analyses (controlling for age and gender) identified the following factors as associated with LS: number of NMS, general self-efficacy, walking difficulties and fatigue. CONCLUSIONS: This study provides new knowledge on factors associated with LS in a PD sample, including those with late-stage PD. As the ultimate goal for PD care should be improvement in LS, the results have direct clinical implication.

Workforce unavailability in Parkinson's disease.

OBJECTIVES: Individuals with Parkinson's disease (PD) become unavailable in the workforce earlier than comparable members of the general population. This may result in significant social insurance expenses, but as workforce participation can be a source for social interaction and a vital part of the personal identity, there are likely to be personal implications extending far beyond the economic aspects. This study aimed to identify aspects that may contribute to workforce unavailability in people with PD. MATERIALS & METHODS: This was a cross-sectional registry study using data from the Swedish national quality registry for PD and included persons with PD in Skåne County, Sweden who were younger than 65 years. Variables were selected from the registry based on earlier studies and clinical experience and were tested for association with unavailability in the workforce: first in a series of simple regression analyses and then in a multiple logistic regression analysis. RESULTS: A total of 99 persons with PD-of whom 59 were available and 40 were unavailable in the workforce-were included in the study. Age (OR per year: 1.47, 95% CI: 1.18-1.85; P < 0.01) and anxiety (OR: 6.81, 95% CI: 1.20-38.67; P = 0.03) were significant contributing factors for unavailability in the workforce. CONCLUSIONS: Based on the findings in this exploratory study, anxiety-a potentially modifiable factor-and age may be contributing factors for workforce unavailability in PD. However, prospective studies are warranted to confirm the findings and the causation of the association between anxiety and workforce unavailability needs to be clarified.

Psychometric properties of the General Self-Efficacy Scale in Parkinson's disease.

OBJECTIVE: This study aimed to investigate the psychometric properties of the General Self-Efficacy Scale (GSE) in people with Parkinson's disease (PD). More specifically, we investigated data completeness, scaling assumptions, targeting, reliability, and construct validity. MATERIALS AND METHODS: This study involves data available from two different projects that included people diagnosed with PD for at least 1 year, yielding two samples (1 and 2). The combined total sample (N=346; 60% men) had a mean (SD) age and PD duration of 71 (8.9) and 9 years (6.3), respectively. Both samples received a self-administered survey by mail, which was administered twice in sample 2. Additional data (e.g., clinical assessments) were available for Sample 1. RESULTS: Total GSE scores were computable for 336 participants (97%). Corrected item-total correlations exceeded 0.4. Principal component analyses identified one component (the eigenvalue of the first component extracted was 6.9), explaining 69% of the total variance. Floor and ceiling effects were <6%. Internal consistency (coefficient alpha) was 0.95. Analyses of test-retest reliability yielded (ICC) values from 0.69 to 0.80. The highest value refers to those (n=47) with identical self-ratings of mobility (in the on condition) at both tests; the standard error of measurement was 3.1 points. Construct validity was further supported by correlations in accordance with a priori expectations. CONCLUSIONS: This study provides support for the validity and reliability of GSE scores in people with PD; the GSE can thus serve as a valuable outcome measurement in clinical practice and research.

Is excessive daytime sleepiness a separate manifestation in Parkinson's disease?

BACKGROUND: Excessive daytime sleepiness (EDS) is common in Parkinson's disease (PD), but its role and relation to other PD features is less well understood. OBJECTIVE: To investigate potential predictors of EDS in PD and to explore how EDS relates to other motor and non-motor PD features. METHODS: 118 consecutive persons with PD (54% men; mean age, 64) were assessed regarding EDS using the Epworth Sleepiness Scale (ESS) and a range of motor and non-motor symptoms. Variables significantly associated with ESS scores in bivariate analyses were used in multiple regression analyses with ESS scores as the dependent variable. Principal component analysis (PCA) was conducted to explore the interrelationships between ESS scores and other motor and non-motor PD aspects. RESULTS: Among 114 persons with complete ESS data, significant independent associations were found between ESS scores and axial/postural/gait impairment, depressive symptoms, and pain (R2, 0.199). ESS scores did not load significantly together with any other PD features in the PCA. CONCLUSIONS: Only a limited proportion of the variation in EDS could be accounted for by other symptoms, and EDS did not cluster together with any other PD features in PCAs. This suggests that EDS is a separate manifestation differing from, for example, poor sleep quality and fatigue.

Malnutrition and risk of falling among elderly without home-help service--a cross sectional study.

OBJECTIVES: The aim of this study was to explore the frequency of malnutrition risk and associated risk of falling, social and mental factors among elderly without home-help service. The aim was also to explore factors associated with risk of falling. DESIGN: A cross-sectional design was used. SETTING: Elderly persons own homes. PARTICIPANTS: Data were collected during preventive home visits to 565 elderly (age range 73-90 years) without home-help service. Those with complete SCREEN II forms were included in the study (n = 465). MEASUREMENTS: MEASUREMENTS included rating scales regarding malnutrition risk (SCREEN II) and risk of falling (Downton). In addition, single-items: general health, satisfaction with life, tiredness, low-spiritedness, worries/anxiety and sleeping were used. RESULTS: According to the SCREEN II, 35% of the sample had no malnutrition risk, 35% had moderate risk and 30% had high malnutrition risk. In an ordinal regression analysis, increased malnutrition risk was associated with being a woman living alone (OR 4.63), male living alone (OR 6.23), lower age (OR 0.86), poorer general health (OR 2.03-5.01), often/always feeling tired (OR 2.38), and an increased risk of falling (OR 1.21). In a linear regression analysis, risk of falling was associated with higher age (B 0.020), not shopping independently (B 0.162), and low meat consumption (B 0.138). CONCLUSION: There are complex associations between malnutrition risk and the gender-cohabitation interaction, age, general health, tiredness, and risk of falling. In clinical practice comprehensive assessments to identify those at risk of malnutrition including associated factors are needed. These have to be followed by individual nutritional interventions using a holistic perspective which may also contribute to reducing the risk of falling.

Danish translation and psychometric testing of the Rivermead Mobility Index.

OBJECTIVES: The Rivermead Mobility Index (RMI) is widely used in several neurological conditions including multiple sclerosis (MS), but its psychometric properties have not been documented in Scandinavia. Therefore, the aim of the study was to translate RMI from UK English into Danish and conduct an initial psychometric testing of the Danish RMI. MATERIALS AND METHODS: The Danish translation conducted by the forward-backward method was first field-tested regarding user-friendliness and relevance. It was then psychometrically tested among 40 outpatients with MS regarding unidimensionality (corrected item-total correlations, adherence to an assumed Guttman response pattern), reliability, and construct validity. RESULTS: Field testing found the Danish RMI relevant and user-friendly. Corrected item-total correlations were ≥0.47 and item responses fitted the Guttman pattern. There was a 47.5% ceiling effect, and reliability was 0.91. Correlations supported construct validity. CONCLUSION: The Danish RMI is user-friendly, unidimensional, reliable, and valid. The results correspond to those previously reported with the original UK RMI version. Ceiling effects are limiting but sample related. Larger samples representing a wider variety of MS severities are needed for firmer evaluation of the Danish RMI.

Stability of rating scale response category interpretations in neurological disorders.

OBJECTIVES: Unambiguous use and interpretation of rating scale data assume that response categories are interpreted and work as intended. This study investigated the stability of interpretations of commonly used patient-reported rating scale response categories among people with neurological disorders. MATERIALS AND METHODS: Forty-six people with neurological disorders (26 men; mean age, 57; Parkinson's disease, 50%; multiple sclerosis, 41%) indicated their interpretation of 21 response categories (representing frequencies, intensities and levels of agreement) on 100-mm visual analog scales (VAS) at two occasions, ≥2 weeks apart. Data were analyzed using intraclass correlation and weighted Kappa (ICC/Κw ; should be >0.4), mean/median differences, percentages agreement (PA), and the standard error of measurement (SEM). RESULTS: Most response categories had ICC/Κw values <0.4. The overall average ICC/Κw was 0.279/0.294 (frequencies, 0.224/0.255; intensities, 0.265/0.251; levels of agreement, 0.362/0.376). The mean/median difference between time points across all 21 categories was 0.43/0.5 mm (mean/median absolute difference, 3.36/9 mm). The overall average PA and SEM were 6.5% and 16.1 mm, respectively. CONCLUSIONS: Stabilities in interpretations of patient-reported rating scale response categories among people with neurological disorders were generally low. Categories expressing levels of agreement showed best results, suggesting that these may be preferable when appropriate with respect to the scale and its items. Future studies should consider response category interpretations in relation to various contexts. These observations suggest caution when interpreting raw rating scale data and argue for the use of modern rating scale methodologies such as the Rasch measurement model.

A Swedish version of the 16-item Parkinson fatigue scale (PFS-16).

BACKGROUND: The PFS-16 is a 16-item fatigue scale for Parkinson's disease (PD) developed in the UK. However, documented translations and psychometric evaluations are sparse. AIM: To translate the PFS-16 into Swedish and conduct initial testing of its psychometric properties. METHODS: Following translation, the PFS-16 was administered twice (2 weeks apart) to 30 people with PD (18 men; mean age/PD duration, 60/6.4 years). The PFS-16 uses five response categories (1 = strongly disagree, 5 = strongly agree), and the total score is the mean over item scores (1-5; 5 = more fatigue). An alternative, dichotomised scoring method has also been suggested (total score, 0-16; 16 = more fatigue). Scaling assumptions, floor/ceiling effects, reliability, and correlations with other variables including the generic fatigue scale Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-F) were tested. RESULTS: Scaling assumptions were generally supported for the original scoring [range of mean (SD) item scores, 2.1-3.3 (1-1.4); corrected item-total correlations, ≥0.40], but not for dichotomised scoring [range of mean (SD) item scores, 0.1-0.6 (0.3-0.5); corrected item-total correlations, ≥0.16]. Reliabilities were ≥0.88. Floor effects were absent (original scoring) and >23% (dichotomised scoring); there were no ceiling effects. Correlations with other variables followed expectations (e.g. -0.88 with FACIT-F scores). CONCLUSIONS: These observations support the psychometric properties of the Swedish PFS-16, but cautions against dichotomised scoring.

Freezing of Gait Questionnaire: validity and reliability of the Swedish version.

BACKGROUND: Patient-reported assessments of freezing of gait (FOG) in Parkinson's disease (PD), such as the FOG questionnaire (FOGQ), are needed because FOG is difficult to assess objectively. However, the measurement properties of the FOGQ have been sparsely assessed. AIM: To assess the measurement properties of the Swedish FOGQ, and to explore relationships between FOGQ scores and other aspects of PD. Methods - Thirty-seven people with PD were assessed with the FOGQ, Unified PD Rating Scale (UPDRS), Hoehn and Yahr (HY), Falls-Efficacy Scale [FES(S)], timed gait tests, and the SF-36 physical functioning (PF) scale. RESULTS: Mean (SD) FOGQ item scores ranged between 1.3 and 2.1 (1.2-1.5); corrected item-total correlations ranged between 0.80 and 0.94. Reliability was 0.95. Mean (SD) and median (q1-q3) FOGQ scores were 9.6 (7.4) and 10 (2-15). Floor and ceiling effects were < or =5.4%. FOGQ correlated strongest with UPDRS part II (ADL), UPDRS item 14 (freezing), and HY (r(S) 0.65-0.66). FOGQ scores correlated with PD duration, the Timed Up and Go test, dyskinesia, motor fluctuations, FES(S), and PF scores (r(S) 0.40-0.62). Fallers had higher FOGQ scores than non-fallers (median 12.5 vs 5.0). CONCLUSION: Data support the measurement properties of the Swedish FOGQ by replicating and extending previous psychometric reports.

Towards an understanding of fatigue in Parkinson disease.

OBJECTIVES: To gain an improved understanding of fatigue in Parkinson disease (PD) by exploring possible predictors among a wide range of motor and non-motor aspects of PD. METHODS: 118 consecutive PD patients (54% men; mean age 64 years) were assessed regarding fatigue, demographics and a range of non-motor and motor symptoms. Variables significantly associated with fatigue scores in bivariate analyses were used in multiple regression analyses with fatigue as the dependent variable. RESULTS: Fatigue was associated with increasing Hoehn & Yahr stages, specifically the transition from stages I-II to stages III-V. Regression analysis identified five significant independent variables explaining 48% of the variance in fatigue scores: anxiety, depression, lack of motivation, Unified PD Rating Scale (UPDRS) motor score and pain. Gender, age, body mass index, PD duration, motor fluctuations, dyskinesias, symptomatic orthostatism, thought disorder, cognition, drug treatment, sleep quality and daytime sleepiness were not significantly associated with fatigue scores. When considering individual motor symptom clusters instead of the UPDRS motor score, only axial/postural/gait impairment was associated with fatigue. CONCLUSIONS: This study found fatigue to be primarily associated with symptoms of depression and anxiety, and with compromised motivation, parkinsonism (particularly axial/postural/gait impairment) and pain. These results are in agreement with findings in other disorders and imply that fatigue should be considered a separate PD entity differing from, for example, excessive daytime sleepiness. Fatigue may have a distinguished neurobiological background, possibly related to neuroinflammatory mechanisms. This implies that novel treatment options, including anti-inflammatory therapies, could be effective.

Risk factors and prevention among patients with hospital-acquired and pre-existing pressure ulcers in an acute care hospital.

AIMS AND OBJECTIVES: This study aimed to describe and identify risk factors associated with hospital-acquired pressure ulcers among adults in an acute care hospital compared with patients with pre-existing pressure ulcers present on admission. A further aim was to identify the preventive measures performed with both groups respectively. BACKGROUND: Pressure ulcers occur most often in older and immobile persons with severe acute illness and neurological deficits. However, few studies have addressed risk factors that are associated with hospital-acquired pressure ulcers compared with patients with pre-existing pressure ulcers. DESIGN: A point prevalence study with a cross-sectional survey design was conducted at a Swedish university hospital. METHOD: Data on 535 patients were recorded using a modified version of the protocol developed and tested by the European Pressure Ulcer Advisory Panel, including the Braden scale for risk assessment. RESULTS: The prevalence of pressure ulcers was 27% (95% confidence interval, 23-31%). Higher age and a total Braden score below 17 were significantly associated with the presence of pressure ulcers. Among individual risk factors higher age, limited activity level and friction and shear while seated or lying down were associated with hospital-acquired pressure ulcers, whereas only higher age and friction and shear were associated with the presence of pressure ulcers in the overall sample. There was an overall sparse use of preventive measures to relieve pressure. CONCLUSION: The findings of the present study revealed that pressure ulcers and the insufficient use of preventive measure to relieve pressure is still a problem in acute care settings. A continued focus must be placed on staff training in identifying patients at risk for pressure ulcers development. RELEVANCE TO CLINICAL PRACTICE: Increasing the ability to identify patients who are at risk for pressure ulcer development can assist in preventing unnecessary complications and suffering as well as reduce costs.

Testing the SF-36 in Parkinson's disease. Implications for reporting rating scale data.

Rating scales are increasingly the primary outcome measures in clinical trials. However, clinically meaningful interpretation of such outcomes requires that the scales used satisfy basic requirements (scaling assumptions) within the data. These are rarely tested. The SF-36 is the most widely used patient-reported rating scale. Its scaling assumptions have been challenged in neurological disorders but remain untested in Parkinson's disease (PD). We therefore tested these by analyzing SF-36 data from 202 PD patients (54% men; mean age 70) to determine if it was legitimate to report scores for the eight SF-36 scales and its two summary measures of physical and mental health, and if those scores were reliable and valid. Results supported generation of the eight SF-36 scale scores and their reliabilities were generally good (> or = 0.74 in all but one instance). However, we found limitations that question the meaningfulness of four scales and other limitations that restrict the ability of four scales to detect change in clinical trials (floor/ceiling effects, 19.6-46.2 %). The two SF-36 summary measures were not found to be valid indicators of physical and mental health. This study demonstrates important limitations of the SF-36 and provides the first evidence-based guidelines for its use in PD. The limitations of the SF-36 demonstrated here may explain some unexpected findings in previous studies. However, the main implication is a general one for the clinical research community regarding requirements for reporting rating scale endpoints. Specifically, investigators should routinely provide scale evaluations based on data from within major clinical trials.

Respondent burden and patient-perceived validity of the PDQ-39.

OBJECTIVES: To evaluate the respondent burden and patient-perceived content validity of the Parkinson's disease (PD)-specific health status questionnaire PDQ-39, and the linguistic validity of its revised Swedish version. MATERIALS AND METHODS: Eighteen PD patients completed the revised Swedish version of the PDQ-39. Respondent burden was assessed by recording the time taken to complete the questionnaire. Content and linguistic validity was evaluated qualitatively. RESULTS: Patients with mild, moderate and advanced PD needed a mean time of 9.5, 11.3 and 20.1 min, respectively, to complete the PDQ-39. One-third of the patients identified irrelevant items and 50% identified important health-related areas that were missing. Revisions had eliminated previous linguistic problems with the Swedish PDQ-39. CONCLUSIONS: Undue respondent burden challenged the appropriateness of the PDQ-39 among patients with more advanced disease. Overall content validity was acceptable but compromised by lack of important content areas. Observations supported the linguistic validity of the revised Swedish PDQ-39.

Use and interpretation of on/off diaries in Parkinson's disease.

OBJECTIVE: To explore the use and interpretation of self reported on/off diary data for assessment of daily motor fluctuations in Parkinson's disease. METHODS: 26 consecutive non-demented patients with fluctuating Parkinson's disease received standardised training on how to fill out the four category CAPSIT-PD on/off diary, followed by four hours of clinical observation and four weeks of daytime on/off diaries every 30 minutes at home. RESULTS: Overall patient-clinician agreement in diary entries was good (kappa = 0.62; weighted kappa = 0.84). Agreement for individual diary categories was good for "off" and "on with dyskinesias" (kappa = > or =0.72), but moderate for "partial off" and "on" (kappa = 0.49). The overall validity of patient kept diaries was supported by expected symptom severity variability across diary categories, as assessed in the clinic. One day's home diary data failed to predict outcomes from the full four weeks for all diary categories, and data from three days failed to yield good prediction (predefined as R(2) = > or =approximately 0.7) for the time spent in "off" and "partial off". Data from one week yielded good prediction (R(2) = > or =0.74) in all instances except "partial off", which could not be well predicted even when two weeks' home diary data were considered (R(2) = 0.52). CONCLUSIONS: The data provide support for the overall accuracy and validity of the four category CAPSIT-PD on/off diary, but suggest that a three category diary format may improve accuracy and validity. Interpretation of diary data beyond the assessed time frame should be made with caution unless diaries have been kept for sufficiently long periods.

Cell survival and clinical outcome following intrastriatal transplantation in Parkinson disease.

Intrastriatal transplantation of embryonic dopaminergic neurons is currently explored as a restorative cell therapy for Parkinson disease (PD). Clinical results have varied, probably due to differences in transplantation methodology and patient selection. In this review, we assess clinical trials and autopsy findings in grafted PD patients and suggest that a minimum number of surviving dopaminergic neurons is required for a favorable outcome. Restoration of [18F]-fluorodopa uptake in the putamen to about 50% of the normal mean seems necessary for moderate to marked clinical benefit to occur. Some studies indicate that this may require mesencephalic tissue from 3-5 human embryos implanted into each hemisphere. The volume, density and pattern of fiber outgrowth and reinnervation, as well as functional integration and dopamine release. are postulated as additional important factors for an optimal clinical outcome. For neural transplantation to become a feasible therapeutic alternative in PD, graft survival must be increased and the need for multiple donors of human embryonic tissue substantially decreased or alternate sources of donor tissue developed. Donor cells derived from alternative sources should demonstrate features comparable to those associated with successful implantation of human embryonic tissue before clinical trials are considered.

Cell therapy and transplantation in Parkinson's disease.

Transplanted human fetal dopamine neurons can reinnervate the striatum in patients with Parkinson's disease (PD). Recent findings using positron emission tomography indicate that the grafts are functionally integrated and restore dopamine release in the patient's striatum. The grafts can exhibit long-term survival without immunological rejection and despite an ongoing disease process and continuous antiparkinsonian drug treatment. In the most successful cases, patients have been able to withdraw L-dopa treatment after transplantation and resume an independent life. About two-thirds of grafted patients have shown clinically useful, partial recovery of motor function. The major obstacle for the further development of this cell replacement strategy is that large amounts of human fetal mesencephalic tissue are needed for therapeutic effects. Stem cells hold promise as a virtually unlimited source of self-renewing progenitors for transplantation. The possibility to generate dopamine neurons from such cells is now being explored using different approaches. However, so far the generated neurons have survived poorly after transplantation in animals.

Apomorphine in the treatment of Parkinson's disease.

Apomorphine is a potent, nonselective, direct-acting dopamine-receptor agonist. Given subcutaneously, it has a rapid onset of antiparkinsonian action qualitatively comparable to that of levodopa. Despite its long history, it was not until peripheral dopaminergic side effects could be controlled by oral domperidone that the clinical usefulness of apomorphine in Parkinson's disease began to be investigated thoroughly in the mid-1980s. Although several routes have been tried, subcutaneous administration, either as intermittent injections or continuous infusion, is so far the best and most applied in the treatment of advanced, fluctuating Parkinson's disease. Clinical trials have shown stable efficacy with markedly reduced time spent in "off" phases as well as, for infusion therapy, reduced levodopa requirements. In the most successful cases, motor fluctuations disappear and the need for oral medication is eliminated. Adverse events are usually mild and dominated by cutaneous reactions. Neuropsychiatric side effects occur, but the influence of apomorphine on these remains controversial. Controlled long-term clinical trials are highly warranted to reveal the full potentials of this treatment. Careful patient selection and follow-up, where the specialized movement disorder nurse has a crucial role, are paramount for a successful long-term outcome. Apomorphine warrants a wider application in the treatment of advanced Parkinson's disease and should be tried before more invasive interventions are considered.

Delayed recovery of movement-related cortical function in Parkinson's disease after striatal dopaminergic grafts.

Intrastriatal transplantation of dopaminergic neurones aims to repair the selective loss of nigrostriatal projections and the consequent dysfunction of striatocortical circuitries in Parkinson's disease (PD). Here, we have studied the effects of bilateral human embryonic dopaminergic grafts on the movement-related activation of frontal cortical areas in 4 PD patients using H2 15O positron emission tomography and a joystick movement task. At 6.5 months after transplantation, mean striatal dopamine storage capacity as measured by 18F-dopa positron emission tomography was already significantly elevated in these patients. This was associated with a modest clinical improvement on the Unified Parkinson's Disease Rating Scale, whereas the impaired cortical activation was unchanged. At 18 months after surgery, there was further significant clinical improvement in the absence of any additional increase in striatal 18F-dopa uptake. Rostral supplementary motor and dorsal prefrontal cortical activation during performance of joystick movements had significantly improved, however. Our data suggest that the function of the graft goes beyond that of a simple dopamine delivery system and that functional integration of the grafted neurones within the host brain is necessary to produce substantial clinical recovery in PD.

Restorative neurology in movement disorders.

Cell replacement for restoration of neurological functions in patients with movement disorders has been investigated for more than 15 years. Initial attempts used autologous adrenal medulla grafts implanted into the denervated striatum of patients with Parkinson's disease (PD). This approach was soon abandoned in favor of intrastriatal implantation of human embryonic mesencephalic tissue, rich in dopaminergic neurons. Available data from grafted PD patients show long-term (up to 10 years) graft survival and clinical benefits. The pattern and magnitude of symptomatic relief following transplantation, however, are incomplete and the outcome varies among patients. The need for large amounts of human embryonic tissue has to be circumvented and a better understanding of the relationship between graft placement and symptomatic recovery is necessary before this procedure can be offered to larger groups of patients. Clinical trials in Huntington's disease have so far shown inconclusive results. Neural cell replacement therapy is still an experimental procedure, but has the potential to become a future restorative treatment in PD and other movement disorders.