Parkinson-Klinik Ortenau

BackgroundIn Germany, the approach to treatment optimization for patients with advanced Parkinson's disease (PD) is considered somewhat conservative. The MANAGE-PD tool (www.managepd.eu) was developed to help identify patients with advanced PD and to facilitate treatment decision making and appropriate allocation of patients to device-aided therapies (DAT). This prospective, non-interventional study aimed to investigate the real-world disease burden of PD and treatment optimization after MANAGE-PD implementation.MethodsAdult PD patients (N = 278) visited specialist clinics and neurologist’s practices in Germany in 2022. Disease burden was assessed using the Unified PD rating scale (UPDRS parts II-IV), the non-motor symptoms scale (NMSS) and the 8-item Parkinson’s disease Questionnaire (PDQ-8). Data on planned treatment changes were collected. Data were analyzed by disease control categories according to the MANAGE-PD tool.ResultsMean scores for motor and non-motor symptoms, quality of life, and comorbidity burden were worse in patients with lower disease control measured by MANAGE-PD. For 52.8% of patients in Category 2 (inadequately controlled—might benefit from oral optimization), no change in oral treatment was planned. No change in oral treatment and no DAT initiation was planned for 37.9% and 65.0% of patients in Category 3 (inadequately controlled—might benefit from DAT). Patient refusal and needing more time to decide were the most common reasons for not making treatment changes.ConclusionsThis study supports the validity of MANAGE-PD by showing its high association with disease burden and emphasizes the importance of timely provision of necessary information to enable informed decisions about treatment optimization.

A striatal toe is a misalignment of the hallux in dorsal flexion that frequently presents as a symptom of Parkinson’s disease and also atypical Parkinson syndromes. It can negatively impact patients during activities such as walking, putting on socks and shoes, and particularly while wearing shoes. It causes pain and thus induces a loss of quality of life. But, to date, we have few data on the topics of the prevalence, genesis, and therapy of striatal toe. Publications available on botulinum neurotoxin (BoNT) have demonstrated a positive effect in the treatment of striatal toe, although the current study data are also rather limited in this area. Commensurate approval studies have not yet been performed. We will introduce our contemporary data on therapy for striatal toe with BoNT and we will also discuss possible questions open for further study.

Botulinum neurotoxin (BoNT) has been in use since the 1970's. Its effect is reached mainly by inhibiting the release of acetylcholine in the synaptic gap of motor neurons or at the motor end plate and the parasympathetic ganglia. In the case of Parkinson's disease, it is used to treat several motor and non-motor symptoms. Within recent years increasingly numerous possible fields of application of BoNT have been found for the treatment of Parkinson's disease, and for some specific symptoms it has in fact become the therapy of choice, while for others it is but one of the therapeutic options that come into consideration when others are not sufficiently effective. In the following, we intend to outline the indications, the possible side effects and also the approvals for therapies with botulinum toxin in the primary and secondary symptoms of Parkinson's disease.

Parkinson's disease (PD) is a chronic disease, which at diagnosis has already been active for years. The degenerative process progresses continually and the motor and non-motor symptoms increase and become worse over time. It begins insidiously and continues to advance slowly, but neither in clear stages nor in sudden intermittent flare-ups. As a result, it is impossible to delineate the course of the disease into specific phases. Nonetheless, the Hoehn and Yahr has been well established over many years now as a scaling instrument, using stages which are decidedly not sharply delineated but rather merge into one another gradually with more or less overlapping. Funding agencies also place importance in just such staging to enable classifications and to restrict costs when approving new therapeutics, and, of course, we as attending physician are thankful for just such characterizations. The need for and the usefulness of such staging are obvious, but do we have to be satisfied with insufficient remedies? In PD, we make frequent use of other segmentations such as "early and late stage". Defining an "early stage" was particularly useful when introducing MAO-B inhibitors and the dopamine agonists, and has stood the test of time ever since. It was also ideally suited for recognizing a stage when a neuroprotective therapy might be possible. Unfortunately, the other concept, "late stage", has taken on a negative connotation. Yet another term, "advanced stage", has found widespread use although it is not sharply defined, neither in its exact definition nor in its timeframe: Might it be an as-yet undefined phase between the early and the late stage. But just when do we speak of "advanced"? The interpretations here are quite diverse, depending on one's personal perspective: as patient, family member, physician or a representative of the health insurance company. Shakespeare would have asked: Advanced, or Not Advanced, that is the question.

PurposeVarious MRI-based techniques were tested for the differentiation of neurodegenerative Parkinson syndromes (NPS); the value of these techniques in direct comparison and combination is uncertain. We thus compared the diagnostic performance of macrostructural, single compartmental, and multicompartmental MRI in the differentiation of NPS.MethodsWe retrospectively included patients with NPS, including 136 Parkinson’s disease (PD), 41 multiple system atrophy (MSA) and 32 progressive supranuclear palsy (PSP) and 27 healthy controls (HC). Macrostructural tissue probability values (TPV) were obtained by CAT12. The microstructure was assessed using a mesoscopic approach by diffusion tensor imaging (DTI), neurite orientation dispersion and density imaging (NODDI), and diffusion microstructure imaging (DMI). After an atlas-based read-out, a linear support vector machine (SVM) was trained on a training set (n = 196) and validated in an independent test cohort (n = 40). The diagnostic performance of the SVM was compared for different inputs individually and in combination.ResultsRegarding the inputs separately, we observed the best diagnostic performance for DMI. Overall, the combination of DMI and TPV performed best and correctly classified 88% of the patients. The corresponding area under the receiver operating characteristic curve was 0.87 for HC, 0.97 for PD, 1.0 for MSA, and 0.99 for PSP.ConclusionWe were able to demonstrate that (1) MRI parameters that approximate the microstructure provided substantial added value over conventional macrostructural imaging, (2) multicompartmental biophysically motivated models performed better than the single compartmental DTI and (3) combining macrostructural and microstructural information classified NPS and HC with satisfactory performance, thus suggesting a complementary value of both approaches.Supplementary InformationThe online version of this article (10.1007/s00062-023-01377-w) contains supplementary material, which is available to authorized users.

Multiple system atrophy (MSA) clinically manifests with either predominant nigrostriatal or cerebellopontine degeneration. This corresponds to two different phenotypes, one with predominant Parkinson's symptoms (MSA-P [multiple system atrophy-parkinsonian subtype]) and one with predominant cerebellar deficits (MSA-C [multiple system atrophy-cerebellar subtype]). Both nigrostriatal and cerebellar degeneration can lead to impaired dexterity, which is a frequent cause of disability in MSA. The aim was to disentangle the contribution of nigrostriatal and cerebellar degeneration to impaired dexterity in both subtypes of MSA. We thus investigated nigrostriatal and cerebellopontine integrity using diffusion microstructure imaging in 47 patients with MSA-P and 17 patients with MSA-C compared to 31 healthy controls (HC). Dexterity was assessed using the 9-Hole Peg Board (9HPB) performance. Nigrostriatal degeneration, represented by the loss of cells and neurites, leading to a larger free-fluid compartment, was present in MSA-P and MSA-C when compared to HCs. Whereas no intergroup differences were observed between the MSAs in the substantia nigra, MSA-P showed more pronounced putaminal degeneration than MSA-C. In contrast, a cerebellopontine axonal degeneration was observed in MSA-P and MSA-C, with stronger effects in MSA-C. Interestingly, the degeneration of cerebellopontine fibers is associated with impaired dexterity in both subtypes, whereas no association was observed with nigrostriatal degeneration. Cerebellar dysfunction contributes to impaired dexterity not only in MSA-C but also in MSA-P and may be a promising biomarker for disease staging. In contrast, no significant association was observed with nigrostriatal dysfunction. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Background Parkinson’s Disease (PD) is a common progressive neurodegenerative disorder that leads to an imbalance of various neurotransmitters and affects cognitive, motor and non-motor function. Safinamide inhibits monoamine oxidase B in a highly selective and reversible manner and beyond that has anti-glutamatergic properties, with positive effects on motor and non-motor symptoms. The aim of the study was to obtain data about the effectiveness and tolerability of safinamide under routine clinical practice conditions in unselected patients with Parkinson’s disease (PD). Methods A post-hoc analysis of the German cohort of the European SYNAPSES study (a non-interventional cohort study). Patients were treated with safinamide as an add-on to levodopa and followed-up for 12 months. Analyses were done in the total cohort and in clinically relevant subgroups (patients older than 75 years; with relevant comorbidities; with psychiatric conditions). Results 181 PD patients were eligible for analysis. Motor symptoms included bradykinesia (76.8%), rigidity (77.3%), tremor (58.6%), and postural instability (27.1%). Non-motor symptoms were reported in 161 patients (89.0%), mainly psychiatric symptoms (43.1%), sleep disorders (35.9%), fatigue (30.9%), and pain (27.6%). 28.7% of patients were aged 75 years or older, 84.5% had relevant comorbidities, and 38.1% had psychiatric conditions. During treatment, the rate of motor complications decreased from 100.0% to 71.1%. UPDRS scores improved under safinamide, with a clinically important effect in 50% in the total score and 45% in the motor score. The positive effect on motor complications occurred already at the 4-month visit and was maintained over 12 months. At least one adverse event (AE)/adverse drug reaction (ADR) was reported by 62.4%/25.4% of patients, AEs were generally mild or moderate, and completely resolved. Only 5 (1.5%) AEs had a definite relationship to safinamide. Conclusions The benefit-risk profile of safinamide was favourable and consistent with the total cohort of the SYNAPSES study. In the subgroups, findings were congruent with the total population, which allows the clinical utilisation of safinamide also in more vulnerable patient groups.