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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.

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

In der vorliegenden Ubersicht soll deutlich gemacht werden, dass ein vaskulares Parkinson-Syndrom (VPS) im engeren Sinne eine seltene und klinisch nicht immer von der idiopathischen Parkinson abgrenzbare Erkrankung ist. Im klinischen Sprachgebrauch wird der Terminus VPS allerdings auch fur andere Storungsbilder verwendet, die nicht zuletzt aufgrund der unterschiedlichen therapeutischen Implikationen von einem VPS differenziert werden sollten. Die Differenzialdiagnose des VPS umfasst in erster Linie die subkortikale arteriosklerotische Enzephalopathie, bei der eine Parkinson-artige Gangstorung nicht mit weiteren Kardinalsymptomen eines Parkinson-Syndroms verbunden ist sowie die Koexistenz eines neurodegenerativen Parkinson-Syndroms mit einer subkortikalen vaskularen Enzephalopathie. Ein akutes oder subakutes VPS entsteht in der Regel kontralateral zu Hirninfarkten, die den externen Teil des Globus pallidus, den ventrolateralen Teil des Thalamus und (seltener) die Substantia nigra betreffen. Chronische VPS mit schleichendem Beginn entstehen auf dem Boden bilateraler lakunarer subkortikaler Infarkte mit Beeintrachtigung thalamokortikaler Projektionen. Progressionsneigung und Dopa-Responsivitat kommen bei akuten und chronischen VPS vor und erschweren die Differenzialdiagnose zu einem degenerativen Parkinson-Syndrom.

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.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.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.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.

The evaluation of cortical evoked potentials after stimulation of the vesicourethral junction shows accurate and reproducible results and offers an elegant technique for evaluation of the viscerosensory pathways in patients with lower urinary tract dysfunction. The results must be considered in context with the results of simultaneously investigated pudendal somatosensory evoked potentials and the clinical symptomatology. They are of great help (1) in differentiating between intraspinal and extraspinal lesions of the afferent pathways of the detrusor if the etiology is unknown, (2) in differentiating between neurogenic and myogenic damage to the urinary bladder, and (3) in selecting patients not suitable for intravesical electrotherapy for bladder rehabilitation.

OBJECTIVES—Botulinum toxin injections have become a first line therapeutic approach in cervical dystonia. Nevertheless, published dosing schedules, responder rates, and frequency of adverse events vary widely. The present prospective multicentre placebo controlled double blind dose ranging study was performed in a homogenous group of previously untreated patients with rotational torticollis to obtain objective data on dose-response relations. METHODS—Seventy five patients were randomly assigned to receive treatment with placebo or total doses of 250, 500, and 1000 Dysport® units divided between one splenius capitis (0, 175, 350, 700 units) and the contralateral sternocleidomastoid (0, 75, 150, 300 units) muscle. Assessments were obtained at baseline and weeks 2, 4,and 8 after treatment and comprised a modified Tsui scale, a four point pain scale, a checklist of adverse events, global assessment of improvement, and a global rating taking into account efficacy and adverse events. At week 8 the need for retreatment was assessed and then the code was unblinded. For those still responding, there was an open follow up until retreatment to assess the duration of effect. RESULTS—seventy nine per cent reported subjective improvement at one or more follow up visits. Decreases in the modified Tsui score were significant at week 4 for the 500 and 1000 unit groups versus placebo (p

This paper deals with signs, symptoms and course in spasmodic torticollis (ST). Two hundred and fifty-six patients were included in the study, 59.3% women, 40.7% men. The mean age was 49.1 years. Rotating torticollis out-numbered latero- and antero-retrocollis. A family history of ST occurred in 3.1% of the total sample. First degree relatives were affected in 2.3%. Thirty-four per cent of the patients had additional dystonic symptoms. Most frequently these affected the upper extremities (13%), and less often the legs. Of the patients 19.1% had experienced a period of complete remission. The correlations between the severity of the signs and the neurological symptoms are surprisingly weak.

Psychosocial changes in spasmodic torticollis (ST) affect predominantly social life, professional life and psychological well-being. Concerning social life, 84.6% of the patients felt that they attracted considerable public attention due to their neurological illness and 65% had reduced participation in social events. A substantial number of patients had retired from professional activities; others felt severely impaired in their working capacity. The psychosocial sequelae in ST, however, seemed to depend less on the neurological signs per se than on the physical symptoms and on coping. Depressive coping in particular emerged as a predictor of psychosocial distress.

The GSI (General Symptom Index) of the Symptom Checklist 90 R (SCL 90 R) (as a global indicator of the severity of psychiatric symptoms) of 27% of the spasmodic torticollis (ST) sample fell outside the 95% range of the normal control group (two standard deviations). Patients with a higher GSI were younger, more functionally disabled and subject to higher psychosocial stress due to the illness. The highest scores were reached on the subscales of somatization, interpersonal sensitivity and depression. On the depression scale, 23% of the patients' scores were abnormal. This scale correlated significantly with the neurological signs, particularly the TSUI-index and laterocollis. A statistically significant correlation also existed between psychiatric morbidity and a family history of mental disorder. More than 50% of the patients reported that stressful life events had triggered their illness. In order of frequency, a death came first, followed by marital strife, changes in employment and family arguments. The data suggest that psychopathology in ST should generally be considered as a result of a variety of interacting factors, biological, psychological and social.

Thirteen patients with idiopathic Parkinson's disease of recent onset (mean age 63·2 years) and a group of 10 young healthy volunteers (mean age 26·1 years) underwent a series of neuropsychological tests for assessment of memory, learning ability and mental processing speed before and during treatment with trihexyphenidyl. Retesting after anticholinergic exposure (mean of 2 weeks for patients and 1 week for controls) revealed in young healthy controls the same pattern and magnitude of decline in memory function as in Parkinson patients. Non-demented subjects with Parkinson's disease of recent onset thus do riot seem to be selectively vulnerable to cognitive side-effects of anticholinergic treatment.

PURPOSE To define characteristic MR-findings in patients with clinically typical extrapyramidal movement disorders. METHODS 15 patients with Parkinson's disease (PD), 9 with multisystem atrophy (MSA), and 6 with progressive supranuclear palsy (PSP) underwent MRI using a 1.5 T. Magnetom unit. Two investigators analysed the images with special regard to global and/or focal atrophy and to changes in signal intensity of the CNS in the consensus mode. Normal images of 10 subjects served as controls to patient's images. RESULTS In all patients with PSP and MSA characteristic pathological findings on MRI were observed including regional changes within the extrapyramidal nuclei. In contrast all patients with PD had an unremarkable MRI study of the CNS. CONCLUSION MRI enables us to define characteristic morphological changes of the brain in patients with extrapyramidal movement disorders. Early recognition of these findings avoids misdiagnoses in patients who are difficult to diagnose.

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.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.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.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.

ZusammenfassungZiel der Studie war die Darstellung der striatalen Dopamin-D2-Rezeptordichte bei 6 Patienten mit Morbus Parkinson und bei 3 gesunden Probanden mit Hilfe der 123I-Lisurid-SPECT. Im weiteren sollte die Möglichkeit von Rezeptorverdrängungs-Untersuchungen mit Hilfe der Kombination aus 123I-Lisurid mit nichtmarkiertem Lisurid geprüft werden. Entsprechend der Verteilung der Dopaminrezep-toren und in Übereinstimmung mit anderen Studien zeigte sich bei Patienten und bei Probanden die höchste zerebrale Anreicherung von 123I-Lisurid im Striatum. Bei 2 Patienten konnte eine spezifische Rezeptorverdrängung des Radioliganden 123I-Lisurid durch nichtmarkiertes Lisurid dokumentiert werden. Die 123I-Lisurid-SPECT ist zur Darstellung der Striatalen Dopamin-D2-Rezeptordichte in vivo geeignet. Inwieweit Rezeptorverdrängungs-Untersuchungen für die Beurteilung dynamischer Veränderungen der Rezeptoraffinität sowie für die Abschätzung der Anzahl belegter bzw. freier Bindungsstellen geeignet sind, muß durch weitere Studien mit größeren Fallzahlen verifiziert werden.

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. 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. 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. 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.

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.

The aim of our study was to compare the striatal dopamine D2-receptor density as measured by 123I-IBZM-SPECT with the results of the apomorphine-test. 30 patients were studied; 21 with idiopathic Parkinson's disease (IPD), 9 with Parkinson plus syndromes (PPS). Patients with IPD showed a significantly higher striatal IBZM binding as compared to patients with PPS (p = 0.006). A good correlation between IBZM binding and outcome of the apomorphine-test was found (p = 0.006). Low striatal IBZM binding indicates reduced dopamine D2-receptor density. This compromises successful dopaminergic medical therapy and is indicative of non-IPD disease. 123I-IBZM-SPECT could be diagnostic aid in the work-up of patients with extrapyramidal movement disorders. The response to dopaminergic drug treatment might be precluded by IBZM-SPECT in patients with Parkinsonian syndromes.

Oral levodopa treatment remains the most efficacious treatment of Parkinson's disease, but the majority of patients treated with a levodopa monotherapy for more than 5 years will develop fluctuations and/or dyskinesias. Important pathophysiological mechanisms are peripheral factors resulting in fluctuating levodopa blood concentrations and central pharmacodynamic changes, possibly due to chronic pulsatile stimulation of dopamine receptors. Continuous dopaminergic stimulation is able to smooth out a fluctuating response to oral levodopa and reduce 'off period' dystonia and the intensity of 'peak dose' dyskinesias. New drug delivery techniques include 'slow release' levodopa preparations and subcutaneous infusions of apomorphine. Future methods of transcutaneous or intramuscular application of dopamine agonists are under development. These methods may help to improve the results of long-term levodopa treatment of parkinsonian patients.