Functional connectivity and topology in patients with restless legs syndrome: a case-control resting-state functional magnetic resonance imaging study.

BACKGROUND AND PURPOSE: Functional connectivity studies revealed alterations within thalamic, salience, and default mode networks in restless legs syndrome patients. METHODS: Eighty-two patients with restless legs syndrome (untreated, n = 30; on dopaminergic medication, n = 42; on alpha-2-delta ligands as mono- or polytherapy combined with dopaminergic medication, n = 10), and 82 individually age- and gender-matched healthy controls were studied with resting-state functional magnetic resonance imaging. Connectivity of 12 resting-state networks was investigated with independent component analysis, and network topology was studied with graph methods among 410 brain regions. RESULTS: Patients with restless legs syndrome showed significantly higher connectivity within salience (p = 0.029), executive (p = 0.001), and cerebellar (p = 0.041) networks, as well as significantly lower (p < 0.05) cerebello-frontal communication compared to controls. In addition, they had a significantly higher (p < 0.05) clustering coefficient and local efficiency in motor and frontal regions; lower clustering coefficient in the central sulcus; and lower local efficiency in the central opercular cortex, temporal, parieto-occipital, cuneus, and occipital regions compared to controls. Untreated patients had significantly lower (p < 0.05) cerebello-parietal communication compared to healthy controls. Connectivity between the thalamus and frontal regions was significantly increased (p < 0.05) in patients on dopaminergic medication compared to untreated patients and controls. CONCLUSIONS: Networks with higher intranetwork connectivity (i.e., salience, executive, cerebellar) and lower cerebello-frontal connectivity in the restless legs syndrome patients, as well as lower cerebello-parietal connectivity in untreated patients, correspond to regions associated with attention, response inhibitory control, and processing of sensory information. Intact cerebello-parietal communication and increased thalamic connectivity to the prefrontal regions in patients on dopaminergic medication suggests a treatment effect on thalamus.

Quality of life improvements in patients with cervical dystonia following treatment with a liquid formulation of abobotulinumtoxinA (Dysport® ).

BACKGROUND AND PURPOSE: In patients with cervical dystonia, abobotulinumtoxinA solution for injection (ASI) has been shown to be similarly effective to freeze-dried abobotulinumtoxinA in reducing Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total scores. In this secondary analysis, quality of life data as evaluated with the Cervical Dystonia Impact Profile (CDIP-58) are presented. METHODS: This was a double-blind, randomized, active and placebo-controlled study followed by an open-label extension (NCT01261611). In the double-blind phase, patients were randomized (3:3:1) to one cycle of ASI 500 U (n = 156), abobotulinumtoxinA 500 U (n = 159) or placebo (n = 54). Following the double-blind phase, all patients received open-label ASI for up to four cycles. RESULTS: The CDIP-58 total scores were significantly improved at week 4 of the double-blind phase in both the ASI 500 U and abobotulinumtoxinA 500 U groups versus placebo [least squares mean change from baseline of -9.5 (-11.51, -7.45) and -11.2 (-13.2, -9.26) vs. -0.9 (-4.04, 2.14), respectively; both P < 0.0001 vs. placebo]. All CDIP-58 domains contributed to this improvement and benefits were maintained across open-label treatment. Positive correlations were observed between CDIP-58 total score and all three TWSTRS domains (R = 0.42-0.62) and for all CDIP-58 subscales with the TWSTRS total score and domains (R = 0.23-0.60). CONCLUSIONS: Repeat ASI injections are similarly effective to abobotulinumtoxinA in improving patient-reported outcomes of health-related quality of life. Positive correlations were found between TWSTRS total and domain scores and CDIP-58 total and domain scores.

Burden of non-motor symptoms in Parkinson's disease patients predicts improvement in quality of life during treatment with levodopa-carbidopa intestinal gel.

BACKGROUND AND PURPOSE: GLORIA, a registry conducted with 375 advanced Parkinson's disease patients treated with levodopa-carbidopa intestinal gel (LCIG) for 24 months in routine clinical care, demonstrated significant reductions from baseline in 'off' time and 'on' time with dyskinesia and improvements in the Non-Motor Symptom Scale (NMSS) total and individual domain scores, and in Parkinson's Disease Questionnaire 8 item (PDQ-8) total score. METHODS: Associations between baseline NMSS burden (NMSB), the multi-domain NMSS total score and the PDQ-8 total score were investigated for 233 patients. Baseline NMSB was assigned to five numerical categories defined by the NMSS total cutoff scores (0-20, 21-40, 41-60, 61-80 and >80). Pearson and Spearman correlations were calculated at month 24. RESULTS: The response of LCIG was assessed using validated criteria after 24 months. The proportion of patients decreasing ≥ 30 NMSS score points was 47% in the most affected NMSB category (NMSS total score > 80). A positive association was noted between baseline NMSB and NMSS total score (0.57, P < 0.0001), as well as between NMSS total score and PDQ-8 total score (0.46, P < 0.0001). Associations between improvements of the NMSS domain sleep/fatigue and PDQ-8 total score (0.32, P = 0.0001) as well as between the NMSS domain mood/cognition and PDQ-8 total score (0.37, P < 0.0001) were also shown. CONCLUSIONS: This analysis demonstrated positive associations between NMSS baseline burden and improvements of non-motor symptoms. Improvements of non-motor symptoms were associated with improved quality of life in advanced parkinsonian patients during a 2-year treatment with LCIG and reflect the long-term non-motor efficacy of this treatment.

The neuropsychiatric phenotype in CACNA1A mutations: a retrospective single center study and review of the literature.

BACKGROUND AND PURPOSE: CACNA1A encodes the α1 subunit of the neuronal calcium channel P/Q. CACNA1A mutations underlie three allelic disorders: familial hemiplegic migraine type 1 (FHM1), episodic ataxia type 2 (EA2) and spinocerebellar ataxia type 6 (SCA6). A clear-cut genotype-phenotype correlation is often lacking since clinical manifestations may overlap. Several case reports have described cognitive and behavioral features in CACNA1A disorders, but studies in larger case series are lacking. METHODS: Genetically confirmed CACNA1A cases were retrieved from the database of the ataxia outpatient clinic of the Department of Neurology at Innsbruck Medical University. Clinical charts and neuropsychological test results were retrospectively analyzed. In addition, a review of the literature including only genetically confirmed cases was performed. RESULTS: Forty-four CACNA1A cases were identified in our database. Delayed psychomotor milestones and poor school performance were described in seven (four FHM1, three EA2) and eight (three FHM1, five EA2) patients, respectively. Psychiatric comorbidities were diagnosed in eight patients (two FHM1, six EA2). Neuropsychological testing was available for 23 patients (11 FHM1, 10 EA2, two SCA6). Various cognitive deficits were documented in 21 cases (all patients except one SCA6). Impairments were predominantly seen in figural memory, visuoconstructive abilities and verbal fluency. In the literature, an early psychomotor delay is described in several children with EA2 and FHM1, whilst reports of cognitive and psychiatric findings from adult cases are scarce. CONCLUSIONS: Neuropsychiatric manifestations are common in episodic CACNA1A disorders. In the case of otherwise unexplained developmental delay and a positive family history, CACNA1A mutations should be considered in the differential diagnosis.

Long-term efficacy of opicapone in fluctuating Parkinson's disease patients: a pooled analysis of data from two phase 3 clinical trials and their open-label extensions.

BACKGROUND AND PURPOSE: The aim was to evaluate the efficacy of the catechol-O-methyltransferase inhibitor opicapone (25 and 50 mg) as adjunct therapy to levodopa in a pooled population of Parkinson's disease patients who participated in the pivotal double-blind trials of opicapone and their 1-year open-label extensions. METHODS: Data (placebo, opicapone 25 mg and opicapone 50 mg) from the BIPARK-1 and BIPARK-2 double-blind and open-label studies were combined. The studies had similar designs, eligibility criteria and assessment methods. The primary efficacy variable in both double-blind studies was the change from baseline in absolute OFF time based on patient diaries. RESULTS: Double-blind treatment with opicapone (25 and 50 mg) significantly reduced absolute daily OFF time from a baseline of 6.1-6.6 h. The mean (and 95% confidence interval) treatment effect versus placebo was -35.1 (-62.1, -8.2) min (P = 0.0106) for the 25 mg dose and -58.1 (-84.5, -31.7) min (P < 0.0001) for the 50 mg dose. Reductions in OFF time were mirrored by significant increases in ON time without troublesome dyskinesia (P < 0.05 and P < 0.0001 for the 25 and 50 mg doses, respectively). No significant differences were observed for ON time with troublesome dyskinesia. Patient diary results from the open-label phase indicated a maintenance of effect for patients previously treated with opicapone 50 mg. The group previously treated with the 25 mg dose benefitted with further optimization of therapy during the open-label phase, whilst switching from placebo to opicapone led to significant reductions in OFF time and increased ON time. CONCLUSIONS: Over at least 1 year of open-label therapy, opicapone consistently reduced OFF time and increased ON time without increasing the frequency of troublesome dyskinesia.

Past, present, and future of Parkinson's disease: A special essay on the 200th Anniversary of the Shaking Palsy.

This article reviews and summarizes 200 years of Parkinson's disease. It comprises a relevant history of Dr. James Parkinson's himself and what he described accurately and what he missed from today's perspective. Parkinson's disease today is understood as a multietiological condition with uncertain etiopathogenesis. Many advances have occurred regarding pathophysiology and symptomatic treatments, but critically important issues are still pending resolution. Among the latter, the need to modify disease progression is undoubtedly a priority. In sum, this multiple-author article, prepared to commemorate the bicentenary of the shaking palsy, provides a historical state-of-the-art account of what has been achieved, the current situation, and how to progress toward resolving Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

New insights into orthostatic hypotension in multiple system atrophy: a European multicentre cohort study.

OBJECTIVES: Orthostatic hypotension (OH) is a key feature of multiple system atrophy (MSA), a fatal progressive neurodegenerative disorder associated with autonomic failure, parkinsonism and ataxia. This study aims (1) to determine the clinical spectrum of OH in a large European cohort of patients with MSA and (2) to investigate whether a prolonged postural challenge increases the sensitivity to detect OH in MSA. METHODS: Assessment of OH during a 10 min orthostatic test in 349 patients with MSA from seven centres of the European MSA-Study Group (age: 63.6 ± 8.8 years; disease duration: 4.2 ± 2.6 years). Assessment of a possible relationship between OH and MSA subtype (P with predominant parkinsonism or C with predominant cerebellar ataxia), Unified MSA Rating Scale (UMSARS) scores and drug intake. RESULTS: 187 patients (54%) had moderate (> 20 mm Hg (systolic blood pressure (SBP)) and/or > 10 mm Hg (diastolic blood pressure (DBP)) or severe OH (> 30 mm Hg (SBP) and/or > 15 mm Hg (DBP)) within 3 min and 250 patients (72%) within 10 min. OH magnitude was significantly associated with disease severity (UMSARS I, II and IV), orthostatic symptoms (UMSARS I) and supine hypertension. OH severity was not associated with MSA subtype. Drug intake did not differ according to OH magnitude except for antihypertensive drugs being less frequently, and antihypotensive drugs more frequently, prescribed in severe OH. CONCLUSIONS: This is the largest study of OH in patients with MSA. Our data suggest that the sensitivity to pick up OH increases substantially by a prolonged 10 min orthostatic challenge. These results will help to improve OH management and the design of future clinical trials.

[Predictors of mental and physical quality of life in Huntington's disease]. / Prädiktoren der psychischen und physischen Lebensqualität beim Morbus Huntington.

BACKGROUND: The assessment of health-related quality of life (hrQoL) is an important tool in therapy studies and in the treatment of patients with Huntington's disease (HD). In the absence of causal interventions, HD therapy targets the alleviation of symptoms aiming to improve impaired hrQoL. The aim of this study was to determine the impact of disease characteristics on hrQoL in HD. METHODS: A total of 80 genetically confirmed HD patients underwent an assessment using the Unified Huntington's Disease Rating Scale, the Beck Depression Inventory, the Hamilton Rating Scale and the SF-36, a scale for the assessment of physical and mental QoL. RESULTS: Multiple regression analysis revealed that health-related physical and mental QoL was considerably influenced by the functional capacity. The mental QoL also correlated with the degree of depressive symptoms, age and the number of CAG repeats. However, there was no statistical relation between QoL and motor and cognitive abilities. DISCUSSION: This study underlines the relationship between function capacity and depressive symptoms with mental and physical QoL. This is the first time that hrQoL has been investigated in a German speaking cohort. The results are in accordance with previous studies of hrQoL in HD.

Long-term safety and sustained efficacy of extended-release pramipexole in early and advanced Parkinson's disease.

BACKGROUND AND PURPOSE: To assess the long-term safety and efficacy of pramipexole as a once-daily (q.d.) extended-release oral formulation in early or advanced Parkinson's disease (PD). METHODS: In two double-blind (DB) studies of early PD and one of advanced PD,active-treatment arms received pramipexole immediate release (IR) or extended release (ER), with exposure lasting up to 33 weeks. In open-label (OL) extensions that followed immediately, subjects took ER q.d. for up to 80 weeks, with dosage adjustment permitted (range 0.375-4.5 mg q.d.). RESULTS: Of 590 subjects completing an early-PD DB study, 511 entered the early-PD OL extension; 408 completed it. Reported adverse events (AEs) with incidence ≥10.0% were somnolence (15.1%), peripheral edema (11.7%) and back pain (10.6%). Of 465 subjects completing the advanced-PD DB study, 391 entered the advanced-PD OL extension; 329 completed it. Reported AEs with incidence ≥10.0%were dyskinesia (27.4%) and somnolence (13.6%). Impulse control disorders were identified by semi-structured interview in 13 subjects (1.4% of 902). In exploratory analyses, adjusted mean Unified Parkinson's Disease Rating Scale (UPDRS) PartsII + III scores (excluding ex-placebo recipients) remained substantially improved from DB baseline scores prior to pramipexole introduction, at -6.6 and -6.3 points amongst ex-DB-ER and ex-DB-IR recipients after 113 weeks of pramipexole (33 DB plus 80 OL) in early PD, and -11.5 and -9.1 after up to 113 weeks (up to 33 DB plus 80 OL) in advanced PD. CONCLUSIONS: These results support the long-term safety and efficacy of pramipexole ER in early and advanced PD. AEs were typical for dopaminergic medications, and UPDRS scores suggested sustained symptomatic benefit.

A cross-sectional multicenter study of cognitive and behavioural features in multiple system atrophy patients of the parkinsonian and cerebellar type.

Imaging and neuropathology studies have demonstrated significant abnormalities not only in subcortical, but also in cortical regions of patients with multiple system atrophy (MSA). This raises the possibility that cognitive dysfunction may contribute to the clinical spectrum of this disorder to a greater extent than it is currently not widely appreciated. In this cross-sectional multicenter study from the European multiple system atrophy study group ( http://www.emsa-sg.org ), we applied an extensive neuropsychological test battery in a series of 61 clinically diagnosed probable MSA patients. The results demonstrated that general cognitive decline as assessed by MMSE was uncommon (2 out of 61 patients <24). In contrast, frontal lobe-related functions (as measured by FAB) were impaired in 41 % of patients, with abstract reasoning and sustained attention less compromised. This pattern was similar to our control group of 20 patients with Parkinson's disease (matched for disease duration and age at onset). There was no difference in cognitive performance between MSA patients with the parkinsonian versus the cerebellar variant. Behaviourally, MSA patients had greater depression than PD and in the case of MSA of the cerebellar variant significantly lower anxiety. Our data show that cognitive abnormalities are relatively frequent in multiple system atrophy and this involves primarily frontal-executive functions. Their contribution to clinical disability and disease progression needs to be addressed in larger prospective studies.

Effect and safety of duodenal levodopa infusion in advanced Parkinson's disease: a retrospective multicenter outcome assessment in patient routine care.

Duodenal levodopa infusion represents an effective strategy to manage motor and non-motor complications in patients with advanced Parkinson's disease (PD). However, most published clinical series regard small numbers of patients and do not exceed 1 year follow-up. In this multi-national observational cohort study conducted in seven specialised PD clinics and university hospitals we assessed long-term safety and outcome of chronic treatment with intra-duodenal levodopa infusions in a large population of patients with advanced PD. The starting population consisted of 98 treated patients (safety population). We report clinical outcomes of 73 patients with subsequent efficacy assessment(s) (efficacy population) over a follow-up period up to 2 years. Follow-up periods and collection of clinical observations varied based on individual routine care program. At last follow-up there was a significant (p ≤ 0.05) reduction in duration of "Off" periods as well as dyskinesia duration and severity that was associated with an improvement of quality of life. Twenty three patients (25.3 % of the safety population) withdraw, due to adverse drug reaction (5), procedure and device related events (7), compliance (3) and lack of efficacy (8). The mean duration for last value reported after baseline (LV) was 608 ± 292 days (median: 697 days). Our results demonstrate significant and sustained benefit over a long observation period in motor complications and in quality of life following a change from oral pulsatile to continuous levodopa delivery. The relatively large number of withdrawals reflects the current use of duodenal levodopa infusion in very advanced PD patients.

Patient-reported convenience of once-daily versus three-times-daily dosing during long-term studies of pramipexole in early and advanced Parkinson's disease.

BACKGROUND AND PURPOSE: In chronic diseases including Parkinson's disease (PD), complex pharmacotherapy dosing schedules are reported to reduce adherence, perhaps leading to less-effective symptom control and, in PD, more erratic stimulation of dopamine receptors. However, blinded clinical-trial designs preclude direct comparisons of adherence to various schedules. METHODS: In two double-blind (DB) studies of early PD and one of advanced PD, subjects received three-times-daily (t.i.d.) pramipexole or placebo. In open-label (OL) extensions, subjects took extended-release, once-daily (q.d.) pramipexole. At 24 or 32 OL weeks, q.d. versus t.i.d. dosing preference was surveyed by questionnaire. RESULTS: Of 590 DB-trial completers with early PD, 511 entered the OL extension. Of 374 survey respondents, 94.4% preferred q.d. dosing (72.2% of them found it 'very much more convenient' and 27.8%'more convenient'), 2.7% preferred t.i.d., and 2.9% chose 'no difference'. Of 465 DB-trial completers with advanced PD, 391 entered its OL extension. Of 334 survey respondents, 88.9% preferred q.d. dosing (59.9% of them found it 'very much more convenient' and 40.1%'more convenient'), 5.7% preferred t.i.d., and 5.4% chose 'no difference'. Results excluding DB-placebo recipients were highly similar. CONCLUSIONS: In this first direct comparison of patient preference for q.d. versus t.i.d. dopamine-agonist dosing, patients with early or advanced PD had a strong preference for q.d. rather than t.i.d. pramipexole. The high proportion of advanced-PD patients declaring this preference indicates that it does not depend on whether a patient is taking concomitant PD medications dosed more frequently than q.d.

Success rate, efficacy, and safety/tolerability of overnight switching from immediate- to extended-release pramipexole in advanced Parkinson's disease.

BACKGROUND AND PURPOSE: For Parkinson's disease (PD), an extended-release (ER) pramipexole formulation taken once daily, has shown efficacy, safety, and tolerability resembling those of immediate-release (IR) pramipexole taken three times daily. The present study assessed, in advanced PD, the success of an overnight switch from adjunctive IR to ER. METHODS: Levodopa users experiencing motor fluctuations were randomized to adjunctive double-blind (DB) placebo, IR, or ER. Amongst completers of ≥18 weeks, ER recipients were kept on DB ER, whilst IR recipients were switched overnight to DB ER at unchanged daily dosage. After a DB week, switch success was assessed. During the next 5 weeks, all patients underwent ER titration to optimal open-label maintenance dosage. RESULTS: One week post-switch, 86.2% of 123 IR-to-ER and 83.8% of 105 ER-to-ER patients had ≤15% (or ≤3-point, for pre-switch scores ≤20) increase on UPDRS Parts II + III, and 77.9% (of 122) and 70.2% (of 104) had ≤1-h increase in daily OFF-time. At 32 weeks, the groups showed comparable improvements from DB baseline (pramipexole inception), including, on UPDRS II + III, adjusted mean (SE) changes of -14.8 (1.5) for IR-to-ER and -13.3 (1.6) for ER-to-ER. Rates of premature discontinuation owing to adverse events were 6.5% for IR-to-ER and 4.9% for ER-to-ER. CONCLUSIONS: By OFF-time and UPDRS criteria, majorities of patients with advanced PD were successfully switched overnight from pramipexole IR to ER at unchanged daily dosage. During subsequent maintenance, pramipexole showed sustained efficacy, safety, and tolerability, regardless of formulation (IR or ER) in the preceding DB trial.

The PRIPS study: screening battery for subjects at risk for Parkinson's disease.

BACKGROUND AND PURPOSE: Screening batteries to narrow down a target-at-risk population are essential for trials testing neuroprotective compounds aiming to delay or prevent onset of Parkinson's disease (PD). METHODS: The PRIPS study focuses on early detection of incident PD in 1847 at baseline PD-free subjects, and assessed age, male gender, positive family history, hyposmia, subtle motor impairment and enlarged substantia nigra hyperechogenicity (SN+). RESULTS: After 3 years follow-up 11 subjects had developed PD. In this analysis of the secondary outcome parameters, sensitivity and specificity of baseline markers for incident PD were calculated in 1352 subjects with complete datasets (10 PD patients). The best approach for prediction of incident PD comprised three steps: (i) prescreening for age, (ii) primary screening for positive family history and/or hyposmia, and (iii) secondary screening for SN+. CONCLUSION: With this approach, one out of 16 positively screened participants developed PD compared to one out of 135 in the original cohort. This corresponds to a sensitivity of 80.0%, a specificity of 90.6% and a positive predictive value of 6.1%. These values are higher than for any single screening instrument but still too low for a feasible and cost-effective screening strategy which might require longer follow-up intervals and application of additional instruments.

Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease.

OBJECTIVE: To summarize the 2010 EFNS/MDS-ES evidence-based treatment recommendations for the management of Parkinson's disease (PD). This summary includes the treatment recommendations for early and late PD. METHODS: For the 2010 publication, a literature search was undertaken for articles published up to September 2009. For this summary, an additional literature search was undertaken up to December 2010. Classification of scientific evidence and the rating of recommendations were made according to the EFNS guidance. In cases where there was insufficient scientific evidence, a consensus statement ('good practice point') is made. RESULTS AND CONCLUSIONS: For each clinical indication, a list of therapeutic interventions is provided, including classification of evidence.

EFNS/MDS-ES/ENS [corrected] recommendations for the diagnosis of Parkinson's disease.

BACKGROUND: A Task Force was convened by the EFNS/MDS-ES Scientist Panel on Parkinson's disease (PD) and other movement disorders to systemically review relevant publications on the diagnosis of PD. METHODS: Following the EFNS instruction for the preparation of neurological diagnostic guidelines, recommendation levels have been generated for diagnostic criteria and investigations. RESULTS: For the clinical diagnosis, we recommend the use of the Queen Square Brain Bank criteria (Level B). Genetic testing for specific mutations is recommended on an individual basis (Level B), taking into account specific features (i.e. family history and age of onset). We recommend olfactory testing to differentiate PD from other parkinsonian disorders including recessive forms (Level A). Screening for pre-motor PD with olfactory testing requires additional tests due to limited specificity. Drug challenge tests are not recommended for the diagnosis in de novo parkinsonian patients. There is an insufficient evidence to support their role in the differential diagnosis between PD and other parkinsonian syndromes. We recommend an assessment of cognition and a screening for REM sleep behaviour disorder, psychotic manifestations and severe depression in the initial evaluation of suspected PD cases (Level A). Transcranial sonography is recommended for the differentiation of PD from atypical and secondary parkinsonian disorders (Level A), for the early diagnosis of PD and in the detection of subjects at risk for PD (Level A), although the technique is so far not universally used and requires some expertise. Because specificity of TCS for the development of PD is limited, TCS should be used in conjunction with other screening tests. Conventional magnetic resonance imaging and diffusion-weighted imaging at 1.5 T are recommended as neuroimaging tools that can support a diagnosis of multiple system atrophy (MSA) or progressive supranuclear palsy versus PD on the basis of regional atrophy and signal change as well as diffusivity patterns (Level A). DaTscan SPECT is registered in Europe and the United States for the differential diagnosis between degenerative parkinsonisms and essential tremor (Level A). More specifically, DaTscan is indicated in the presence of significant diagnostic uncertainty such as parkinsonism associated with neuroleptic exposure and atypical tremor manifestations such as isolated unilateral postural tremor. Studies of [(123) I]MIBG/SPECT cardiac uptake may be used to identify patients with PD versus controls and MSA patients (Level A). All other SPECT imaging studies do not fulfil registration standards and cannot be recommended for routine clinical use. At the moment, no conclusion can be drawn as to diagnostic efficacy of autonomic function tests, neurophysiological tests and positron emission tomography imaging in PD. CONCLUSIONS: The diagnosis of PD is still largely based on the correct identification of its clinical features. Selected investigations (genetic, olfactory, and neuroimaging studies) have an ancillary role in confirming the diagnosis, and some of them could be possibly used in the near future to identify subjects in a pre-symptomatic phase of the disease.

[MSA-QoL: disease-specific questionnaire to assess health-related quality of life in multiple system atrophy: validation of the German translation]. / MSA-QoL: spezifisches Bewertungsinstrument zur Erfassung der Lebensqualität bei Multisystematrophie : Validierung der deutschsprachigen Übersetzung.

BACKGROUND: Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disorder which causes early sustained disability and quality of life impairment. Recently, a self-reported questionnaire focusing on MSA-specific symptoms (Multiple System Atrophy Quality of Life questionnaire, MSA-QoL) was developed in the English language. This article reports the validation of the German translation of the MSA-QoL. METHODS: Translation of the MSA-QoL was implemented in a 3-tiered approach including a forward translation, a back translation and an independent review. For the validation study 38 consecutive patients with MSA according to the consensus criteria were recruited by the participating centers in a German-Austrian cohort. Data were analyzed using standard psychometric procedures. RESULTS: As determined by the independent review, the German translation of the MSA-QoL was classified as fully equivalent to the English version. The validation study confirmed good psychometric properties of the rating scale. CONCLUSION: The German translation of the MSA-QoL was shown to be a reliable patient-reported rating scale to determine health-related quality of life in MSA patients.

[Atypical Parkinson syndromes--recent advances in diagnosis and therapy]. / Atypische Parkinson-Syndrome - Aktuelles aus Diagnostik und Therapie.

The term "atypical Parkinson syndromes" usually encompasses the following diseases: multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). The differential diagnosis is still a challenge even for a movement disorders specialist, not least because of the distinct therapeutic approaches and disease prognosis. The aim of this review is to provide an overview of current diagnostic criteria and therapeutic approaches and to cite recent findings from clinical and experimental studies.