Motor associations of iron accumulation in deep grey matter nuclei in Parkinson's disease: a cross-sectional study of iron-related magnetic resonance imaging susceptibility.

BACKGROUND AND PURPOSE: To determine whether iron deposition in deep brain nuclei assessed using high-pass filtered phase imaging plays a role in motor disease severity in Parkinson's disease (PD). METHODS: Seventy patients with mild to moderate PD and 20 age- and gender-matched healthy volunteers (HVs) underwent susceptibility-weighted imaging on a 3 T magnetic resonance imaging scanner. Phase shifts (radians) in deep brain nuclei were derived from high-pass filtered phase images and compared between groups. Analysis of clinical laterality and correlations with motor severity (Unified Parkinson's Disease Rating Scale, Part III, UPDRS-III) were performed. Phase shifts (in radians) were compared between HVs and three PD subgroups divided according to UPDRS-III scores using analysis of covariance, adjusting for age and regional area. RESULTS: Parkinson's disease patients had significantly (P < 0.001) higher radians than HVs bilaterally in the putamen, globus pallidus and substantia nigra (SN). The SN contralateral to the most affected side showed higher radians (P < 0.001) compared to the less affected side. SN radians positively correlated with UPDRS-III and bradykinesia-rigidity subscores, but not with tremor subscores. ancova followed by post hoc Bonferroni-adjusted pairwise comparisons revealed that SN radians were significantly greater in the PD subgroup with higher UPDRS-III scores compared to both lowest UPDRS-III PD and HV groups (P < 0.001). CONCLUSIONS: Increased nigral iron accumulation in PD appears to be stratified according to disease motor severity and correlates with symptoms related to dopaminergic neurodegeneration. This semi-quantitative in vivo iron assessment could prove useful for objectively monitoring PD progression, especially in clinical trials concerning iron chelation therapies.

Memantine and reduced time with dyskinesia in Parkinson's Disease.

OBJECTIVES: The partial glutamate antagonist amantadine is currently used in clinical practice, to reduce dyskinesia developing as a side-effect of levodopa treatment in patients suffering from Parkinson's disease (PD). This study was aimed at evaluating the antidyskinetic effect of another glutamate antagonist, memantine. METHODS AND MATERIALS: We performed a randomized, double-blind and placebo-controlled crossover clinical trial of memantine (20 mg), with a 3-week treatment period, and 15 patients completed the study. RESULTS: The primary outcome measure, a change in observed dyskinesia ratings, did not reach significance. Seven of the 15 patients reduced the L-dopa-induced dyskinesias by 32%, whereas for three patients, they increased by 33%, and for five patients, they did not change. Data from the self-administered diaries, as a secondary outcome measure, did show a significant 35% reduction in the percentage of time of the day spent with dyskinesia, from 25% (placebo) to 16% (memantine). Memantine was well tolerated, without any serious adverse events, or worsening in the parkinsonian motor score. CONCLUSION: The results suggest that memantine may be a useful antidyskinetic drug, and a larger clinical study is warranted.

Interim analysis of long-term intraduodenal levodopa infusion in advanced Parkinson disease.

BACKGROUND: This interim 12-month analysis is a part of an open-label, observational, prospective study on health outcomes and cost impact of levodopa/carbidopa intestinal gel (LCIG, Duodopa) in Parkinson disease (PD). The specific aim was to investigate clinical and health-related quality of life (HRQoL) effects in routine care. METHODS: Unified PD rating scale (UPDRS) was the primary efficacy measurement. PD QoL questionnaire 39 (PDQ-39) assessed HRQoL. Subjects were assessed at baseline, ≥3 months after surgery, and then every 3 months. RESULTS: Twenty-seven treatment-naïve subjects when started with LCIG showed a decrease in UPDRS score that was statistically significant throughout the year: UPDRS total score (mean ± SD), baseline = 52.1 ± 16.1, N = 27, month 0 (first visit; at least 3 months after permanent LCIG) = 43.1 ± 16.7, N = 27, P = 0.003; month 12 = 42.5 ± 22.6, n = 25, P = 0.017. PDQ-39 results also showed a tendency for improvement: PDQ-39 (mean ± SD), baseline = 33.6 ± 10.8, N = 27, month 0 = 27.1 ± 11.8, N = 27, P = 0.001; 12 months = 28.8 ± 12.8, n = 23, P = 0.126. CONCLUSIONS: LCIG provides functional improvement beginning at first visit that is sustained for 12 months.

Neuron-specific enolase correlates with other prognostic markers after cardiac arrest.

OBJECTIVE: Therapeutic hypothermia (TH) is a recommended treatment for survivors of cardiac arrest. Prognostication is complicated since sedation and muscle relaxation are used and established indicators of a poor prognosis are lacking. This prospective, observational study describes the pattern of commonly used prognostic markers in a hypothermia-treated cohort of cardiac arrest patients with prolonged coma. METHODS: Among 111 consecutive patients, 19 died, 58 recovered, and 34 were in coma 3 days after normothermia (4.5 days after cardiac arrest), defined as prolonged coma. All patients were monitored with continuous amplitude-integrated EEG and repeated samples of neuron-specific enolase (NSE) were collected. In patients with prolonged coma, somatosensory evoked potentials (SSEP) and brain MRI were performed. A postmortem brain investigation was undertaken in patients who died. RESULTS: Six of the 17 patients (35%) with NSE levels <33 µg/L at 48 hours regained the capacity to obey verbal commands. By contrast, all 17 patients with NSE levels >33 failed to recover consciousness. In the >33 NSE group, all 10 studied with MRI had extensive brain injury on diffusion-weighted images, 12/16 lacked cortical responses on SSEP, and all 6 who underwent autopsy had extensive severe histologic damage. NSE levels also correlated with EEG pattern, but less uniformly, since 11/17 with NSE <33 had an electrographic status epilepticus (ESE), only one of whom recovered. A continuous EEG pattern correlated to NSE <33 and awakening. CONCLUSIONS: NSE correlates well with other markers of ischemic brain injury. In patients with no other signs of brain injury, postanoxic ESE may explain a poor outcome.

Tracking the neurodegeneration of parkinsonian disorders--a pilot study.

The purpose of the study was to explore the possibilities of using diffusion tensor imaging (DTI) and tractography (DTT) for the differential diagnosis and monitoring of disease progression in idiopathic Parkinson's disease (IPD), compared with the atypical parkinsonian disorders multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). A 3.0-T MR scanner was used. DTI was acquired using a single-shot EPI sequence with diffusion encoding in 32 directions and a voxel size of 2 x 2 x 2 mm3. DTI data were analysed and DTT was performed using the PRIDE fibre tracking tool supplied by the manufacturer. The fractional anisotropy (FA) and apparent diffusion coefficient (ADC) within each tract were determined. DTI and DTT images in patients with moderate to advanced MSA demonstrated degeneration of the middle cerebellar peduncles and pontine crossing tracts, with decreased FA and increased ADC. This accounted for most of the pontine and cerebellar atrophy characteristic of this disease. In contrast, patients with PSP showed a selective degeneration of the superior cerebellar peduncle. Three-dimensional images of whole-brain white matter tracts demonstrated a reduction of cortical projection fibres in all patients with PSP. Visualization of the selective degeneration of individual fibre tracts, using DTI and DTT, adds qualitative data facilitating the differential diagnosis of parkinsonian disorders. Repeated measurements of FA and ADC values in a whole fibre tract might be used for monitoring disease progression and studying the effect of treatment in neuroprotective trials. The results are preliminary considering the small number of subjects in the study.

The European Multiple System Atrophy-Study Group (EMSA-SG).

Introduction. The European Multiple System Atrophy-Study Group (EMSA-SG) is an academic network comprising 23 centers across Europe and Israel that has constituted itself already in January 1999. This international forum of established experts under the guidance of the University Hospital of Innsbruck as coordinating center is supported by the 5th framework program of the European Union since March 2001 (QLK6-CT-2000-00661). Objectives. Primary goals of the network include (1) a central Registry for European multiple system atrophy (MSA) patients, (2) a decentralized DNA Bank, (3) the development and validation of the novel Unified MSA Rating Scale (UMSARS), (4) the conduction of a Natural History Study (NHS), and (5) the planning or implementation of interventional therapeutic trials. Methods. The EMSA-SG Registry is a computerized data bank localized at the coordinating centre in Innsbruck collecting diagnostic and therapeutic data of MSA patients. Blood samples of patients and controls are recruited into the DNA Bank. The UMSARS is a novel specific rating instrument that has been developed and validated by the EMSA-SG. The NHS comprises assessments of basic anthropometric data as well as a range of scales including the UMSARS, Unified Parkinson's Disease Rating Scale (UPDRS), measures of global disability, Red Flag list, MMSE (Mini Mental State Examination), quality of live measures, i.e. EuroQoL 5D (EQ-5D) and Medical Outcome Study Short Form (SF-36) as well as the Beck Depression Inventory (BDI). In a subgroup of patients dysautonomic features are recorded in detail using the Queen Square Cardiovascular Autonomic Function Test Battery, the Composite Autonomic Symptom Scale (COMPASS) and measurements of residual urinary volume. Most of these measures are repeated at 6-monthly follow up visits for a total study period of 24 months. Surrogate markers of the disease progression are identified by the EMSA-SG using magnetic resonance and diffusion weighted imaging (MRI and DWI, respectively). Results. 412 patients have been recruited into the Registry so far. Probable MSA-P was the most common diagnosis (49% of cases). 507 patients donated DNA for research. 131 patients have been recruited into the NHS. There was a rapid deterioration of the motor disorder (in particular akinesia) by 26.1% of the UMSARS II, and - to a lesser degree - of activities of daily living by 16.8% of the UMSARS I in relation to the respective baseline scores. Motor progression was associated with low motor or global disability as well as low akinesia or cerebellar subscores at baseline. Mental function did not deteriorate during this short follow up period. Conclusion. For the first time, prospective data concerning disease progression are available. Such data about the natural history and prognosis of MSA as well as surrogate markers of disease process allow planning and implementation of multi-centre phase II/III neuroprotective intervention trials within the next years more effectively. Indeed, a trial on growth hormone in MSA has just been completed, and another on minocycline will be completed by the end of this year.

Treatment of end-of-dose wearing-off in parkinson's disease: stalevo (levodopa/carbidopa/entacapone) and levodopa/DDCI given in combination with Comtess/Comtan (entacapone) provide equivalent improvements in symptom control superior to that of traditional levodopa/DDCI treatment.

The aim of this study was to evaluate the efficacy of the new optimised levodopa, Stalevo (levodopa, carbidopa and entacapone) in patients with Parkinson's disease experiencing end-of-dose wearing-off. Treatment with Stalevo was compared to treatment with traditional immediate-release levodopa and dopa-decarboxylase inhibitor (DDCI) formulations along with adjunct entacapone (Comtess/Comtan). A European, open, parallel-group, active treatment-controlled phase IIIb study evaluating 176 patients randomised to switch from their current regimen of levodopa/DDCI to either an equivalent dose of Stalevo or levodopa/DDCI plus entacapone. After 6 weeks, treatments were assessed using the Clinical Global Impression of Change, the Unified Parkinson's Disease Rating Scale and a Motor Fluctuations Questionnaire. Over 70% of patients in both the Stalevo and adjunct entacapone arms felt that they were clinically improved and over 80% experienced a reduction in fluctuations. Although there was no significant difference between Stalevo and levodopa/DDCI plus entacapone with regard to motor improvement and side effects, 81% of patients stated that they preferred treatment with Stalevo compared with taking two separate tablets (i.e. levodopa/DDCI and entacapone). Stalevo was well tolerated and safe when substituted for levodopa DDCI preparations.

Porcine neural xenografts in rats and mice: donor tissue development and characteristics of rejection.

Embryonic ventral mesencephalic tissue from the pig is a potential alternative donor tissue for neural transplantation to Parkinson's disease patients. For stable graft survival, the host immune response has to be prevented. This study was performed in order to analyze the mechanisms and dynamics of neural xenograft rejection, as well as neurobiological properties of the donor tissue. Adult normal mice and rats, and cyclosporin A-treated rats, received intrastriatal transplants of dissociated embryonic ventral mesencephalic pig tissue that was 27 or 29 embryonic days of age (E27 and E29). The animals were perfused at 2, 4, 6, and 12 weeks after grafting and the brains were processed for immunohistochemistry of dopaminergic (tyrosine hydroxylase positive) neurons, CD4(+) and CD8(+) lymphocytes, natural killer cells, macrophages, microglia, and astrocytes. Thirty-five rats received daily injections of BrdU for 5 consecutive days at different time points after transplantation and were perfused at 6 weeks. These animals were analyzed for proliferation of cells in the donor tissue, both in healthy and in rejecting grafts. No tyrosine hydroxylase-positive cells proliferated after grafting. Our results demonstrated that E27 was superior to E29 donor tissue for neurobiological reasons. Cyclosporin A immunosuppression was protective only during the first weeks and failed to protect the grafts in a long-term perspective. Grafts in mice were invariably rejected between 2 and 4 weeks after transplantation, while occasional grafts in untreated rats survived up to 12 weeks without signs of an ongoing rejection process. CD8(+) lymphocytes and microglia cells are most likely important effector cells in the late, cyclosporin A-resistant rejection process.

Enhanced survival of porcine neural xenografts in mice lacking CD1d1, but no effect of NK1.1 depletion.

Transplantation of embryonic porcine neurons may restore neurological function in patients with Parkinson's disease, if immunological rejection could be prevented. This study was performed to investigate the role of natural killer cells (NK cells) and NK1.1+ T cells (NK T cells) in the rejection of neural xenografts. A cell suspension was prepared from the ventral mesencephalon of 26-27-day-old pig embryos, and 2 microl was implanted in the right striata of mutant CD1d1 null (CD1.1-/-) mice, NK1.1-depleted mice, and controls. The CD1.1-/- mice are deficient in NK T cells and the antigen-presenting molecule CD1d1. Graft survival and host responses were determined immunohistochemically using markers for dopamine neurons, CD4-, CD8- cells, microglia, and macrophages. At 2 weeks, the grafts were significantly larger in CD1.1-/- mice, 0.09 +/- 0.02 microl (mean +/- SEM), compared with controls, 0.05 +/- 0.01 microl. There was no significant difference between NK1.1-depleted mice, 0.02 +/- 0.01 microl, and controls. At 5 weeks, two grafts were still present in the CD1-/- mice, whereas only scars remained in the controls and in the NK1.1-depleted mice. Immune reactions were strong at 2 weeks and less pronounced at 5 weeks in all groups. Microglial activation was lower in NK-depleted mice than in the controls at 2 weeks. In contrast to organ xenografting, NK1.1+ cells do not seem to be important mediators of the rejection of discordant cellular neural xenografts. However, our results suggest that the antigen-presenting molecule CD1d1 may be involved in the rejection process.

Effects of immunosuppressive treatment on host responses against intracerebral porcine neural tissue xenografts in rats.

BACKGROUND: Embryonic xenogeneic neural tissue is an alternative for transplantation in Parkinson's disease, but immune responses limit the application. The aims of this study were to enhance the in vitro viability rates by donor tissue pretreatment; to compare the efficacy of cyclosporine A (CsA) and tacrolimus (FK) in inhibiting xenograft rejection in rats; to evaluate additional inductive therapy with prednisolone (PRE) or mycophenolate mofetil (MMF). METHODS: Tirilazad (a lipid peroxidase inhibitor) or FK and acYVAD-cmk (a caspase inhibitor), were added to embryonic porcine ventral mesencephalic tissue and viability was assessed in vitro. Tirilazad-treated tissue was grafted to the striatum of rats that were either left untreated or immunosuppressed with FK (1 mg/kg) or CsA (15 mg/kg) alone or in combination with a 2-week PRE (20 mg/kg) or MMF (40 mg/kg) induction course. Xenograft survival and host responses were determined using immunohistochemistry. RESULTS: Pretreatment with tirilazad enhanced tissue survival in vitro. After transplantation into untreated controls, there was no graft survival at twelve weeks. Neural cell counts were significantly improved in immunosuppressed recipients, but there were no differences between the treatment groups. Additional inductive treatment reduced the infiltration with CD4+ and CD8+ cells, and macrophage infiltration was reduced compared with animals given CsA or FK alone. CONCLUSION: Pretreatment of the donor tissue with free-radical scavengers reduces cell loss caused by tissue trauma. Porcine neural tissue xenografts survive significantly better in animals immunosuppressed with either FK or CsA. Additional inductive treatment with PRE or MMF reduced the infiltration of host cells into the xenografts.

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.

Neural tissue xenografting.

Neural transplantation may become an important treatment alternative for focal brain disorders. To date, the most successful grafts have been obtained in patients with Parkinson's disease. Completely normalized dopamine production and reduction of Parkinsonian symptoms have been demonstrated 10 years after grafting. However, the allogeneic donor tissue has to be obtained from induced abortions, and there are logistical difficulties, risks of infection, and ethical constraints limiting a wider clinical use. Xenografting is an alternative that could bridge these limitations if immunological rejection could be prevented. Pig embryonic neural tissue has been grafted to patients with Parkinson's disease, but no functional benefits have clinically been proven so far. The immune reactions to neural xenografts were incompletely characterized at the time of these early clinical trials, and it is likely that the treatments used were insufficient and that the grafts were rejected. In this article we will review new experiments addressing the immune responses against porcine neural tissue grafted to the adult brain, including the role of antibodies, complement, natural killer (NK) cells, lymphocytes, as well as the effects of immunosuppressive drugs and donor tissue modifications.

Xenotransplantation for CNS repair: immunological barriers and strategies to overcome them.

Neural transplantation holds promise for focal CNS repair. Owing to the shortage of human donor material, which is derived from aborted embryos, and ethical concerns over its use, animal donor tissue is now considered an appropriate alternative. In the USA, individuals suffering from Parkinson's disease, Huntington's disease, focal epilepsy or stroke have already received neural grafts from pig embryos. However, in animal models, neural tissue transplanted between species is usually promptly rejected, even when implanted in the brain. Some of the immunological mechanisms that underlie neural xenograft rejection have recently been elucidated, but others remain to be determined and controlled before individuals with neurological disorders can benefit from xenotransplantation.

Bilateral caudate and putamen grafts of embryonic mesencephalic tissue treated with lazaroids in Parkinson's disease.

Five parkinsonian patients were transplanted bilaterally into the putamen and caudate nucleus with human embryonic mesencephalic tissue from between seven and nine donors. To increase graft survival, the lipid peroxidation inhibitor tirilazad mesylate was administered to the tissue before implantation and intravenously to the patients for 3 days thereafter. During the second postoperative year, the mean daily L-dopa dose was reduced by 54% and the UPDRS (Unified Parkinson's Disease Rating Scale) motor score in 'off' phase was reduced by a mean of 40%. At 10-23 months after grafting, PET showed a mean 61% increase of 6-L-[(18)F]fluorodopa uptake in the putamen, and 24% increase in the caudate nucleus, compared with preoperative values. No obvious differences in the pattern of motor recovery were observed between these and other previously studied cases with putamen grafts alone. The amount of mesencephalic tissue implanted in each putamen and caudate nucleus was 42 and 50% lower, respectively, compared with previously transplanted patients from our centre. Despite this reduction in grafted tissue, the magnitudes of symptomatic relief and graft survival were very similar. These findings suggest that tirilazad mesylate may improve survival of grafted dopamine neurons in patients, which is in agreement with observations in experimental animals.

[Patients' attitudes to xenotransplantation: "I'll do anything, I don't want to die!"]. / Patientröster om xenotransplantation: "jag skulle göra allt, för jag vill inte dö!"

Transplantation of neural tissue is an effective therapeutical approach in Parkinson's disease, but the method is constrained by the lack of suitable donor material. Embryonic neural tissue from pigs, xenografts, is considered as an alternative source of donor tissue. The attitudes towards neural tissue grafting in general and xenografts in particular were investigated by interviewing a group of patients with Parkinson's disease. The analysis revealed an ambivalence regarding xenografts. A pragmatic view, with priority placed on survival over ethical and other reservations, became apparent.

Neural tissue xenotransplantation: what is needed prior to clinical trials in Parkinson's disease? Neural Tissue Xenografting Project.

Embryonic allografted human tissue in patients with Parkinson's disease has been shown to survive and ameliorate many of the symptoms of this disease. Despite this success, the practical problems of using this tissue coupled to the ethical restrictions of using aborted human fetal tissue have lead to an exploration for alternative sources of suitable material for grafting, including xenogeneic embryonic dopaminergic-rich neural tissue. Nevertheless, xenografted neural tissue itself generates a number of practical, ethical, safety, and immunological issues that have to be addressed prior to any clinical xenotransplant program. In this article we review these critical issues and set out the criteria that we consider need to be met in the development of our clinical xenotransplantation research programs. We advocate that these, or similar, criteria should be adopted and made explicit by other centers contemplating similar clinical trials.

Intrastriatal ventral mesencephalic xenografts of porcine tissue in rats: immune responses and functional effects.

Transplantation of neural tissue from other species has the potential to improve function in patients with neurodegenerative disorders. We investigated the functional effects of embryonic porcine dopaminergic neurons transplanted in a rat model of Parkinson's disease and the immune responses to the grafts in immunosuppressed and nonimmunosuppressed hosts. Twenty-three rats with unilateral 6-hydroxydopamine lesions received dissociated, 27-day-old embryonic porcine ventral mesencephalic tissue in the right striatum. Eighteen rats received cyclosporine (10 mg/kg, IP, daily) during the whole period of 14 weeks, in combination with prednisolone (20 mg/kg, IP, daily) the first 4 days. Five rats served as nonimmunosuppressed controls. All rats were tested for amphetamine-induced rotational behavior at 3-week intervals. Two immunosuppressed rats were excluded due to severe side effects of the treatment. Functional recovery was seen in 9 of 16 immunosuppressed rats at 12 weeks. Six animals remained functionally recovered at 14 weeks and contained an average of 5750+/-1450 (SEM) dopaminergic neurons. Between 9 and 14 weeks, three immunosuppressed rats rejected their grafts, based on rotation scores and immunohistochemical demonstration of cell infiltrates. One additional immunosuppressed rat showed evidence of ongoing rejection at 14 weeks. The striata in animals with ongoing or recent rejection contained large numbers of CD4- and CD8-positive lymphocytes, NK cells, macrophages, and microglia cells, whereas scar tissue was found in rats with grafts rejected at earlier time points (n = 11). Embryonic porcine ventral mesencephalic tissue matures in the adult rat striatum, reinnervates the host brain, and restores behavioral defects. Immunosuppressive treatment was necessary for long-term graft survival and functional recovery, but did not sufficiently protect from rejection mechanisms. Porcine neural tissue is an interesting alternative to embryonic human tissue for intracerebral transplantation in neurodegenerative diseases. However, to achieve stable graft survival in discordant xenogeneic combinations, an appropriate immunosuppressive treatment or donor tissue modifications are needed.

Health-related quality of life following bilateral intrastriatal transplantation in Parkinson's disease.

Intrastriatal transplantation of embryonic dopaminergic tissue is a new, experimental approach for the treatment of Parkinson's disease (PD). Clinical trials have shown longterm graft survival and therapeutically valuable improvements with decreased L-dopa dose and time spent in the "off"-phase, and reduced rigidity and hypokinesia. We have measured health-related quality of life (HRQoL) using the Nottingham Health Profile (NHP) in five patients subjected to bilateral transplantation in the caudate and putamen to explore the influence of intrastriatal grafts on HRQoL and the value of such measures in trials of restorative therapies. The results demonstrate improved HRQoL following transplantation, with individual patients showing striking improvements within different dimensions of the NHP as well as the NHP distress index (NHPD). The most pronounced improvements after grafting were observed for physical mobility along with emotional reactions and energy. These results indicate that intrastriatal transplantation of embryonic dopaminergic tissue can give rise to improvements within most areas of HRQoL, and that HRQoL measurements provide important information additional to that obtained by traditional, symptom-oriented assessment protocols. However, the optimal approach to HRQoL measurement in PD remains to be determined.