Effectiveness of AbobotulinumtoxinA in Post-stroke Upper Limb Spasticity in Relation to Timing of Treatment.

Background: Recent studies of botulinum toxin for post-stroke spasticity indicate potential benefits of early treatment (i. e., first 6 months) in terms of developing hypertonicity, pain and passive function limitations. This non-interventional, longitudinal study aimed to assess the impact of disease duration on the effectiveness of abobotulinumtoxinA treatment for upper limb spasticity. Methods: The early-BIRD study (NCT01840475) was conducted between February 2013 and 2018 in 43 centers across Germany, France, Austria, Netherlands and Switzerland. Adult patients with post-stroke upper limb spasticity undergoing routine abobotulinumtoxinA treatment were followed for up to four treatment cycles. Patients were categorized by time from stroke event to first botulinum toxin-A treatment in the study (as defined by the 1st and 3rd quartiles time distribution) into early-, medium- and late- start groups. We hypothesized that the early-start group would show a larger benefit (decrease) as assessed by the modified Ashworth scale (MAS, primary endpoint) on elbow plus wrist flexors compared with the late-start group. Results: Of the 303 patients enrolled, 292 (96.4%) received ≥1 treatment and 186 (61.4%) received 4 injection cycles and completed the study. Patients in all groups showed a reduction in MAS scores from baseline over the consecutive injection visits (i.e., at end of each cycle). Although reductions in MAS scores descriptively favored the early treatment group, the difference compared to the late group did not reach statistical significance at the last study visit (ANCOVA: difference in adjusted means of 0.15, p = 0.546). Conclusions: In this observational, routine-practice study, patients in all groups displayed a benefit from abobotulinumtoxinA treatment, supporting the effectiveness of treatment for patients at various disease stages. Although the data revealed some trends in favor of early vs. late treatment, we did not find strong evidence for a significant benefit of early vs. late start of treatment in terms of reduction in MAS scores.

[Epidemiology of Parkinson's Disease and Current Concepts of Outpatient Care in Germany]. / Epidemiologie der Parkinsonerkrankung und aktuelle ambulante Versorgungskonzepte in Deutschland.

The ambulatory care of patients with Parkinson's disease (PD) in Germany has been established for a long time. As the prevalence of Parkinson's disease continues to increase, the outpatient neurological sector is becoming more and more important and needs to adapt itself to current needs. This includes an optimization of the care structures for Parkinson's patients as well as adequate concepts for the execution of differentiated diagnostics and therapy. For many patients care is provided by non-specialized neurological practices or general practitioners, without exchange of views with neurologists or a specialized university outpatient clinic for movement disorders. A connective link between these care structures could be provided by a "practice with focus on Parkinson's disease", whose idea and conception is presented in this article. In addition to the necessity and usefulness of such an institution, structural prerequisites and basic principles for the treatment of Parkinsonian patients in a disease state-centered manner will be presented but also current limitations of the concept are pointed out. This article presents the results of an expert workshop on Parkinson's disease, which took place in Frankfurt am Main on 21 November 2015.

A botulinum toxin A treatment algorithm for de novo management of torticollis and laterocollis.

OBJECTIVES: Few studies have investigated the injection patterns for botulinum toxin type A for the treatment of heterogeneous forms of cervical dystonia (CD). This large, prospective, open-label, multicentre study aimed to evaluate the effectiveness and safety of 500 U botulinum toxin A for the initial treatment according to a standardised algorithm of the two most frequent forms of CD, predominantly torticollis and laterocollis. DESIGN: Patients (aged ≥ 18 years) with CD not previously treated with botulinum neurotoxin therapy were given one treatment with 500 U Dysport, according to a defined intramuscular injection algorithm based on clinical assessment of direction of head deviation, occurrence of shoulder elevation, occurrence of tremor (all evaluated using the Tsui rating scale) and hypertrophy of the sternocleidomastoid muscle. RESULTS: In this study, 516 patients were enrolled, the majority of whom (95.0%) completed treatment. Most patients had torticollis (78.1%). At week 4, mean Tsui scores had significantly decreased by -4.01, -3.76 and -4.09 points in the total, torticollis and laterocollis populations, respectively. Symptom improvement was equally effective between groups. Tsui scores remained significantly below baseline at week 12 in both groups. Treatment was well tolerated; the most frequent adverse events were muscular weakness (13.8%), dysphagia (9.9%) and neck pain (6.6%). CONCLUSIONS: Dysport 500 U is effective and well tolerated for the de novo management of a range of heterogeneous forms of CD, when using a standardised regimen that allows tailored dosing based on individual symptom assessment. Clinical trials information (NCT00447772; clinicaltrials.gov).

Basic science in Parkinson's disease: its impact on clinical practice.

Failures in clinical studies that were aimed to prove disease-modifying effects of treatments in Parkinson's disease (PD) raise the question as to whether basic sciences have had an impact in clinical practice. This question implies that despite well-publicized results obtained by intensive genetic and pathogenetic research, e.g. the identification of mutations and cellular biochemical pathways that underlie Parkinson-specific neurodegeneration, no relevant disease-modifying treatment options have been developed. This view neglects the fact that today there are plenty of dopaminergic and non-dopaminergic and surgical treatment options, and that PD was not treatable 50 years ago. This progress was made possible only by basic science. In this review, we underline the success of previous basic science for daily practice in PD and its impact for the understanding and development of an early diagnosis. Early, even pre-symptomatic diagnosis might be key to successfully establish disease-modifying treatments.

Initial experience with ropinirole PR (prolonged release).

Ropinirole is a non-ergolinic dopamine agonist, which has been used for over 10 years for the treatment of Parkinson's disease. A new formulation (PR = prolonged release) has been developed, which allows the drug to be released slowly (continuously) so that it only has to be given once daily. Switching from the previous ropinirole immediate release ( ropinirole IR) to the prolonged release (ropinirole PR) formulation at the nearest equivalent total daily dose, can take place overnight and the acceptance and tolerability are good. The advantages are once-daily dosing, faster titration with good tolerability and more stable plasma levels. The new formulation is regarded as valuable addition to the currently available medications.

Scales in Parkinson's disease.

The search for valid instruments to measure different domains of health disturbances becomes increasingly important for the assessment of Parkinson's disease. The most widely used tool is the Unified Parkinson's Disease Rating Scale (UPDRS) which was introduced in 1987 and is currently awaiting revision. In addition, a variety of instruments have been used to capture non-motor aspects of Parkinson's disease but only a minority of these instruments has been validated for this particular disease condition. Measurements of quality of life are being incorporated into an increasing number of studies in order to reflect a more integral view of health and have contributed to a better understanding of the impact of disease and interventions. The International Classification of Functioning, Disability and Health introduced by the WHO in 2001 offers a multidimensional approach to human functioning and participation that can also be applied to the assessment of health status in PD. This workshop report will focus on the present state of clinimetry in PD and discuss future perspectives.

The Adaptive Digit Ordering Test: clinical application, reliability, and validity of a verbal working memory test.

In the face of ample experimental evidence on the importance of working memory capacity for everyday life, there is a growing need for measures suited for clinical assessment of working memory. For this purpose, the Adaptive Digit Ordering Test (DOT-A), a new version of a digit ordering test introduced by Cooper et al. [Brain 114 (1991) 2095], was developed in analogy to the Digit spans. In Study 1, we investigated DOT-A performance in patients with Parkinson's disease (PD) and patients with frontal lobe damage, as these groups often exhibit working memory impairments within the framework of executive dysfunctions. In comparison with matched controls, both patient groups showed reduced performance in DOT-A but not in Digit span performance. This pattern was found to be particularly sensitive for patients with PD. In Study 2, DOT-A performance was assessed in 50 healthy subjects carefully selected according to demographic criteria in order to ensure representativity. Parallel test and split-half correlations indicated sufficient reliability of the DOT-A. Concurrent validity was confirmed by significant correlation with a well-established working memory test (two-back task). We conclude that DOT-A is a promising diagnostic instrument, and its economy and direct comparability to the Wechsler Digit spans and high sensitivity for patient populations make it especially well-suited for assessment in clinical practice.