Intrastriatal grafts of embryonic mesencephalic tissue can survive in the brains of patients with Parkinson's disease, but the degree of symptomatic relief is highly variable and some cases develop troublesome dyskinesias. Here we explored, using clinical assessment and 18F-dopa and 11C-raclopride PET, factors which may influence the functional outcome after transplantation. We observed increased 18F-dopa uptake in the grafted putamen, signifying continued survival of the transplanted dopaminergic neurons, in parallel with a progressive reduction of 18F-dopa uptake in non-grafted regions for the whole patient group. The patients with the best functional outcome after transplantation exhibited no dopaminergic denervation in areas outside the grafted areas either preoperatively or at 1 or 2 years post-operatively. In contrast, patients with no or modest clinical benefit showed reduction of 18F-dopa in ventral striatum prior to or following transplantation, which may have limited graft-induced improvement. We obtained no evidence that dyskinesias were caused by abnormal dopamine (DA) release from the grafts. As has been observed for intrinsic dopaminergic neurons, there was a significant correlation between 18F-dopa uptake and methamphetamine-induced change of 11C-raclopride binding (as a measure of DA release) in the putamen containing the graft. Furthermore, we observed no correlation between 11C-raclopride binding in anterior, posterior or entire putamen under basal conditions or after methamphetamine, and dyskinesia severity scores in the contralateral side of the body. Withdrawal of immunosuppression at 29 months after transplantation caused no reduction of 18F-dopa uptake or worsening of UPDRS motor score, indicating continued survival and function of the graft. However, patients showed increased dyskinesia scores, which might have been caused either by growth of the graft or worsening of a low-grade inflammation around the graft. These findings indicate that poor outcome after transplantation is associated with progressive dopaminergic denervation in areas outside the grafts, a process which may have started already before surgery. Also, that the development of dyskinesias after transplantation is not associated with excessive DA release from the grafts. Finally, our data provide evidence that long-term immunosuppression can be withdrawn without interfering with graft survival or the motor recovery induced by transplantation.

We estimated resource use and costs in patients with Parkinson's disease (PD), thereby providing baseline data for future economic evaluations of therapeutic interventions. Data were collected from medical records of a South Swedish cohort of 127 PD patients during 1 year (1996) and a mailed questionnaire inquiring about cost-related consequences and resource use in 1996 and in 2000. Annual costs were calculated based on prevalence and expressed in SEK (monetary value of the year 2000). Direct health care costs averaged approximately SEK 29,000 ( approximately USD 2,900; EUR 3,200) per patient per year, of which drugs were the most costly component. Nonmedical direct costs were higher than direct health care costs, averaging approximately SEK 43,000 ( approximately USD 4,300; EUR 4,800) per patient per year, and costs due to lost production were approximately SEK 52,000 ( approximately USD 5,200; EUR 5,800) per patient per year. The mean total annual cost for PD in our sample approximated SEK 124,000 ( approximately USD 12,400; EUR 13,800) per patient. These findings are roughly within the same range as estimates from other countries and show that PD causes a considerable societal burden. In addition to other outcomes, evaluations of the economic implications of new therapeutic interventions are highly warranted. In this perspective, the present study provides valuable baseline data.

This study evaluated and compared the measurement properties of the 13-item FACITFatigue Scale (FACIT-F) and the 9-item Fatigue Severity Scale (FSS) in 118 consecutive Parkinson's disease (PD) patients, using traditional and Rasch measurement methodologies.Both questionnaires exhibited excellent data quality and reliability (coefficient alpha ≥0.9), acceptable rating scale functionality, and discriminated between fatigued and non-fatigued patients. Factor and Rasch analyses provided general support for unidimensionality of both the FACIT-F and FSS, although they do not appear to measure identical aspects of fatigue.No signs of differential item functioning (DIF) were found for the FACIT-F whereas potential age DIF was detected for 2 FSS items. These results support the measurement validity of both questionnaires in PD, although the FACIT-F displayed better measurement precision and modest psychometric advantages over the FSS. Availability of psychometrically sound fatigue measures that are applicable across disorders provides a sound basis for advancing the understanding of this common and distressing complaint. Fatigue can be defined as an overwhelming sense of tiredness, lack of energy, and feeling of exhaustion (1) and is a common complaint in a range of medical conditions, including many neurological disorders (1-3). In a clinical context, fatigue is considered to be a multidimensional concept with physical, emotional, cognitive, and social aspects. This can pose a challenge to measurement. In Parkinson's disease (PD), fatigue has been reported in 40-65% of patients and although many consider it to be one of their most disabling symptoms, it often remains undetected in clinical practice (4)(5)(6)(7)(8). Its cause remains unclear. For example, while some reports suggest an association between fatigue and the underlying parkinsonism (5, 9), others do not (10, 11).One reason for such mixed results may relate to how fatigue has been assessed. Studies have tended to use fatigue scales from generic health status questionnaires or approaches not validated in [10][11][12]. Although generic health status questionnaires have been validated broadly, their subscales are brief and often lack sufficient detail for accurately measuring individuals. For example, the Energy subscale of the Nottingham Health Profile (NHP-EN) (13) has been found to be only a coarse measure of fatigue (14). Other employed instruments have been validated in other patient groups but remain untested in terms of their measurement properties in PD. This is a limitation because traditional psychometric properties are sample dependent. Thus their performance in specific applications is important to consider in the context of accumulated experience with an instrument (15). There is thus a need for fatigue measures with documented reliability and validity in specific patient populations, such as PD, that also allow for comparisons with other patient groups and healthy control populations (3).We therefore sought to identify and validate an availa...

A de novo α-synuclein A53T (p.Ala53Thr; c.209G>A) mutation has been identified in a Swedish family with autosomal dominant Parkinson's disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria, and cognitive decline. Longitudinal clinical follow-up, EEG, SPECT and CSF biomarker examinations suggested an underlying encephalopathy with cortical involvement. The mutated allele (c.209A) was present within a haplotype different from that shared among mutation carriers in the Italian (Contursi) and the Greek-American Family H kindreds. One unaffected family member carried the mutation haplotype without the c.209A mutation, strongly suggesting its de novo occurrence within this family. Furthermore, a novel mutation c.488G>A (p.Arg163His; R163H) in the presenilin-2 (PSEN2) gene was detected, but was not associated with disease state.

A long-term cost-effectiveness model for early decision-making and estimation of outcomes of novel therapeutic procedures for Parkinson's disease (PD) was developed based on the Hoehn and Yahr (HY) stages of PD. Results provided support for model validity. Model application to a future dopamine cell replacement therapy indicated long-term cost offsets and gains in quality-adjusted life years in early onset PD (HY III-IV), as compared to standard drug therapy. The maximum price premium (i.e., profit or compensation for developmental costs) for the intervention to remain cost-effective was estimated to €12 000-€64 000 according to cost-per-QALY thresholds of €38 000-€70 000 and depending on whether all or only medical direct costs are considered. The study illustrates the value of early health economic modeling and the described model shows promise as a means to estimate outcomes and aid decision-making regarding novel interventions for PD.3

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We demonstrate how rather hydrophilic surfactants can be used for solubilizing simultaneously water and alkane. The required hydrophilic−lipophilic balance can be achieved by the addition of a medium-chain alcohol, that is, a hydrophobic cosurfactant. Specifically, the phase behavior of the quaternary water−n-octane−n-octyl β-d-glucopyranoside (C8G1)−n-octanol (C8E0) system has been investigated. Sugar surfactants, in general, are hydrophilic and, because of the comparatively large number of hydroxyl groups, much less temperature-sensitive than the well-known alkylpolyglycolether (C i E j ) surfactants. Therefore, one has to resort to tuning the phase behavior by mixing with a hydrophobic cosurfactant. Once this is done, the phase behavior mimics that of water−alkane−C i E j microemulsions. To show this, the trajectory of the middle-phase is determined as the phase inversion is passed. A scaling of the trajectory onto the trajectories of conventional temperature-sensitive ternary microemulsions is possible after the composition (i.e. the fraction of n-octanol) of the mixed amphiphilic film is determined from phase behavior and density measurements.

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