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To date, the diagnoses of Parkinson syndromes are based on clinical examination. Therefore, these specific diagnoses are made, when the neuropathological process is already advanced. However, disease modification or neuroprotection, is considered to be most effective before marked neurodegeneration has occurred. In recent years, early clinical or prodromal stages of Parkinson syndromes came into focus. Moreover, subtypes of distinct diseases will allow predictions of the individual course of the diseases more precisely. Thereby, patients will be enrolled into clinical trials with more specific disease entities and endpoints. Furthermore, novel fluid and imaging biomarkers that allow biochemical diagnoses are under development. These will lead to earlier diagnoses and earlier therapy in the future as consequence. Furthermore, therapeutic approaches will take the underlying neuropathological process of neurodegenerative Parkinson syndromes more specific into account. Specifically, future therapies will target the aggregation of aggregation-prone proteins such as alpha-synuclein and tau, the degradation of pathological aggregates, and the spreading of pathological protein aggregates throughout the brain. Many of these approaches are already in (pre)clinical development. In addition, anti-inflammatory approaches are in development. Furthermore, drug-repurposing is a feasible approach to shorten the developmental process of new drugs. [ABSTRACT FROM AUTHOR]

However, CTA was unremarkable, except for an aberrant right vertebral artery (VA) entering the C4 foramen transversarium (aVA-C4). In contrast to the first CTA, the superior cornu of the thyroid cartilage was in close proximity to aVA-C4 anterior to the C5 transverse process (Fig. To our knowledge, this is the first report of a patient treated surgically that did not show luminal abnormalities in angiography or VA compression on dynamic imaging. [Extracted from the article]

Dopamine agonists are an important component of Parkinson's therapy. When weighing up the various therapy options, therapy with levodopa has recently been increasingly preferred due to its stronger efficacy and the ostensibly lower rate of side effects. The advantage of the lower incidence of motor complications during therapy with dopamine agonists was neglected. The occurrence of side effects can be explained by the different receptor affinity to the individual dopaminergic and non-dopaminergic receptors of the individual dopamine agonists. However, the different affinity to individual receptors also explains the different effect on individual Parkinson symptoms and can, therefore, contribute to a targeted use of the different dopamine agonists. Since comparative studies on the differential effect of dopamine agonists have only been conducted for individual substances, empirical knowledge of the differential effect is of great importance. Therefore, the guidelines for the treatment of Parkinson's disease do not consider the differential effect of the dopamine agonists. The historical consideration of dopamine agonists within Parkinson's therapy deserves special attention to be able to classify the current discussion about the significance of dopamine agonists. [ABSTRACT FROM AUTHOR]

This correction notice is for an article titled "Role of dopamine agonists in Parkinson's disease therapy" published in the Journal of Neural Transmission. The notice provides corrected details for two sections of the article. In the introduction section, it clarifies the use of nonergoline agents in Parkinson's disease therapy. In the section on therapy development, it corrects the timeline of the approval of certain dopamine agonists. Additionally, it corrects the values for Tmax of piribedil in table 2 and the elimination process of apomorphine in table 3. The notice concludes with a statement from the publisher. [Extracted from the article]

To reduce potentially inappropriate medications, the FORTA (Fit fOR The Aged) concept classifies drugs in terms of their suitability for geriatric patients with different labels, namely A (indispensable), B (beneficial), C (questionable), and D (avoid). The aims of our study were to assess the medication appropriateness in PD inpatients applying the FORTA list and drug-drug interaction software, further to assess the adequacy of FORTA list for patients with PD. We retrospectively collected demographic data, comorbidities, laboratory values, and the medication from the discharge letters of 123 geriatric inpatients with PD at the university hospital of Hannover Medical School. Patients suffered on average from 8.2 comorbidities. The majority of the medication was labeled A (60.6% of PD-specific and 40.9% of other medication) or B (22.3% of PD-specific and 26.9% of other medication). Administered drugs labeled with D were amantadine, clozapine, oxazepam, lorazepam, amitriptyline, and clonidine. Overall, 545 interactions were identified, thereof 11.9% severe interactions, and 1.7% contraindicated combinations. 81.3% of patients had at least one moderate or severe interaction. The FORTA list gives rational recommendations for PD-specific and other medication, especially for general practitioners. Considering the demographic characteristics and the common multimorbidity of geriatric PD patients, this study underlines the importance of awareness, education, and preventive interventions to increase drug safety. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a chronic progressive movement disorder with severe reduction in patients' health-related quality of life (HR-QoL). Motor and cognitive symptoms are especially linked with decreased PD patients' HR-QoL. However, the relationship of these symptoms to caregiver burden is relatively unclear. Influence of the Montreal Cognitive Assessment scale (MoCA) as a cognitive screening tool and Movement Disorders Society Unified Parkinson's disease Rating Scale MDS-UPDRS symptoms in relation to patients' HR-QoL and caregivers' burden was analyzed. PD patients (n = 124) completed MDS-UPDRS, MoCA, and the PD questionnaire 8 (PDQ-8) as a measure of quality of life. Caregivers (n = 78) were assessed by the PD caregiver burden inventory (PDCB). PDQ-8 and PDCB scores were regressed on MDS-UPDRS subscales and MoCA subscores. PDQ-8 correlated with attention (R2 0.1282; p < 0.001) and executive (R2 0.0882; p 0.001) MoCA subscores and all parts of the MDS-UPDRS. PDCB correlated most strongly with MDS-UPDRS part III motor symptoms (R2 0.2070; p < 0.001) and the MoCA attention subscore (R2 0.1815; p < 0.001). While all facets of PD symptoms assessed by the MDS-UPDRS relate to PD patients' quality of life, motor symptoms are the most relevant factor for the prediction of caregiver burden. In addition, patients' attentional symptoms seem to affect not only them, but also their caregivers. These findings show the potential of a detailed analysis of MDS-UPDRS and MoCA performance in PD patients. [ABSTRACT FROM AUTHOR]

Hintergrund: Die Aggregation des mikrotubuliassoziierten Proteins Tau in Nervenzellen definiert eine Gruppe neurodegenerativer Krankheiten, welche Tauopathien genannt werden.Ziel der Arbeit: Erstellung eines aktuellen Übersichtsartikels zum Stand der klinischen Forschung auf dem Gebiet der Tauopathien.Material und Methoden: Systematischer Review über die Literatur der letzten 10 Jahre.Ergebnis: Tau wird vermehrt als hochvariables Protein wahrgenommen, welches ein Spektrum von Erkrankungen molekular definiert. Das klinische Bild der Tauopathien reicht von Demenzen bis zu hypokinetischen Bewegungsstörungen. Genetische Variation am Tau-Lokus kann Krankheiten auslösen oder das Krankheitsrisiko verändern. Modifikationen im Tau-Protein können Nervenzellen schädigen und die Krankheitsprozesse durch das Gehirn propagieren. Daher kann Tau sowohl als serologischer als auch als bildgebender Biomarker verwendet werden. Tau bietet auch ein breites Spektrum an rationalen therapeutischen Interventionsmöglichkeiten, um die Krankheitsprogression zu modifizieren. Diese Erkenntnisse haben zu modernen klinischen Prüfungen geführt.Diskussion: Das Feld der Tauopathien ist in raschem und dynamischem Fortschritt begriffen, der eine intensive interdisziplinäre Kooperation voraussetzt. [ABSTRACT FROM AUTHOR]

Background: This overview focuses on the aspects of the pharmacotherapy of Parkinson's disease, which is one of the most common disorders of the nervous system. This article presents the complexity of the pharmacotherapy of geriatric patients with neurological diseases. Objectives: Information about the potential risk factors and aspects of drug safety in the pharmacotherapy of Parkinson's disease. Materials and methods: Selective literature search using PubMed and the scientific-clinical experience of the authors. Results: Patients with Parkinson's disease are usually geriatric patients with concomitant diseases. As a result they are often treated with comedication which leads to a complex medication regime with more than five drugs. Such polypharmacy increases the risk of adverse drug events due to the rising number of possible interactions and contraindications. To control this risk and maintain a safe therapy, certain measures should be considered. This implies additional need for educational work in order to create awareness regarding potential adverse drug events. In certain cases of diagnosed comorbidities or relevant drug prescriptions in the medication regime, follow-up examinations should be conducted. Conclusion: Specific parameters of Parkinson's disease, the health-related quality of life of affected patients and the quality of pharmacotherapeutic drug safety can be improved by targeted monitoring of the medication regime. As a result, the overall drug safety can be increased. [ABSTRACT FROM AUTHOR]

Progressive supranuclear palsy (PSP) is a tauopathy, presenting clinically most often with a symmetrical akinetic-rigid syndrome, postural instability, supranuclear gaze palsy and frontal dementia. In the absence of reliably validated biomarkers, the diagnosis of PSP in vivo is presently based on clinical criteria, which to date do not include supporting imaging findings, as is accepted for other neurodegenerative diseases. However, data from conventional magnetic resonance imaging (MRI) and various advanced MRI techniques including magnetic resonance volumetry, voxel-based morphometry, diffusion-weighted and diffusion-tensor imaging, magnetization transfer imaging and proton resonance spectroscopy suggest that MRI can contribute valuable information for the differential diagnosis of PSP. We review here the presently published literature concerning MRI in PSP and discuss the potential role of MRI in differentiating PSP from other parkinsonian syndromes. [ABSTRACT FROM AUTHOR]

Apoptosis-inducing factor (AIF) has important supportive as well as potentially lethal roles in neurons. Under normal physiological conditions, AIF is a vital redox-active mitochondrial enzyme, whereas in pathological situations, it translocates from mitochondria to the nuclei of injured neurons and mediates apoptotic chromatin condensation and cell death. In this study, we reveal the existence of a brain-specific isoform of AIF, AIF2, whose expression increases as neuronal precursor cells differentiate. AIF2 arises from the utilization of the alternative exon 2b, yet uses the same remaining 15 exons as the ubiquitous AIF1 isoform. AIF1 and AIF2 are similarly imported to mitochondria in which they anchor to the inner membrane facing the intermembrane space. However, the mitochondrial inner membrane sorting signal encoded in the exon 2b of AIF2 is more hydrophobic than that of AIF1, indicating a stronger membrane anchorage of AIF2 than AIF1. AIF2 is more difficult to be desorbed from mitochondria than AIF1 on exposure to non-ionic detergents or basic pH. Furthermore, AIF2 dimerizes with AIF1, thereby preventing its release from mitochondria. Conversely, it is conceivable that a neuron-specific AIF isoform, AIF2, may have been ‘designed’ to be retained in mitochondria and to minimize its potential neurotoxic activity. [ABSTRACT FROM AUTHOR]

Tauopathies with parkinsonism represent a spectrum of disease entities unified by the pathologic accumulation of hyperphosphorylated tau protein fragments within the central nervous system. These pathologic characteristics suggest shared pathogenetic pathways and possible molecular targets for disease-modifying therapeutic interventions. Natural history studies, for instance, in progressive supranuclear palsy, frontotemporal dementia with parkinsonism linked to chromosome 17, corticobasal degeneration, and Niemann-Pick disease type C as well as in amyotrophic lateral sclerosis/Parkinson–dementia complex permit clinical characterization of the disease phenotypes and are crucial to the development and validation of biological markers for differential diagnostics and disease monitoring, for example, by use of neuroimaging or proteomic approaches. The wide pathologic and clinical spectrum of the tauopathies with parkinsonism is reviewed in this article, and perspectives on future advances in the understanding of the pathogenesis are given, together with potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

Regulated intramembrane proteolysis by γ-secretase cleaves proteins in their transmembrane domain and is involved in important signaling pathways. At least four different γ-secretase complexes have been identified, but little is known about their biological role and specificity. Previous work has demonstrated the involvement of the Aph1A-γ-secretase complex in Notch signaling, but no specific function could be assigned to Aph1B/C-γ-secretase. We demonstrate here that the Aph1B/C-γ-secretase complex is expressed in brain areas relevant to schizophrenia pathogenesis and that Aph1B/C deficiency causes pharmacological and behavioral abnormalities that can be reversed by antipsychotic drugs. At the molecular level we find accumulation of Nrg1 fragments in the brain of Aph1BC-/- mice. Our observations gain clinical relevance by the demonstration that a Val-to-Leu mutation in the Nrg1 transmembrane domain, associated with increased risk for schizophrenia, affects γ-secretase cleavage of Nrg1. This finding suggests that dysregulation of intramembrane proteolysis of Nrg1 could increase risk for schizophrenia and related disorders. [ABSTRACT FROM AUTHOR]

Aim To investigate the natural course of progression of ocular motor signs in patients with progressive supranuclear palsy (PSP). Methods 114 patients with a possible or probable PSP following NINDS-SPSP criteria seen at the Department of Neurology and the German Center for Vertigo and Balance Disorders (LMU, Munich) were included in this retrospective study. All patients underwent a structured neuro-ophthalmological testing by a orthoptist at initial diagnostic evaluation, 35 patients several times during their course of disease. The following ocular motor signs were extracted from the charts: Saccadic slowing (with normal range of movement) and saccadic paresis (loss of saccade initiation or severe saccadic hypometria) in vertical and horizontal direction, range of up- and downward as well as horizontal ocular motility during smooth pursuit in mm, presence of square wave jerks, function of the vestibulo-ocular reflex on head impulse testing. Clinical ocular motor signs were analysed in all patients in relation to the duration of disease at the time of examination (based on the medical history of the first sign indicative for PSP) or longitudinally during the course of disease in a subgroup of 35 patients. Results In the whole group of PSP patients saccadic abnormalities showed the following distribution over time: at 1 year of disease duration 10% showed only saccadic slowing on upgaze, 40% on up- and downgaze, 21% saccadic paresis on upgaze and 29% complete vertical saccade paresis; at 2 years the proportion of vertical saccade paresis was 32%, at 3 years 65% and at 4 years 82%. Progression of horizontal saccade paresis was slower (year 1: 6%, year 2: 9%, year 3: 21%, year 4: 41%). The subgroup of patients with longitudinal follow up showed a similar tendency. Ocular motility in this group decrease by a mean of 1.5 mm/a on upgaze, 1.6 mm/a on downgaze and 1.4 mm/a on horizontal gaze. The degree of motility loss on up- and downgaze over time showed a good correlation (R2 = 0.71). Conclusion Ocular motor examination can be used as a robust marker of disease progression. Variability between patients however is considerable. Prospective clinical and apparative quantification of ocular motor markers in well-characterized cohorts of PSP patients is needed. [ABSTRACT FROM AUTHOR]