A growing body of evidence supports a prodromal neurodegenerative process preceding the clinical onset of Parkinson's disease (PD). Studies have identified several different prodromal markers that ...may have the potential to predict the conversion from healthy to clinical PD but use considerably different approaches. We systematically reviewed 35 longitudinal studies reporting prodromal PD features and evaluated the methodological quality across 10 different predefined domains. We found limitations in the following domains: PD diagnosis (57% of studies), prodromal marker assessments (51%), temporal information on prodromal markers or PD diagnosis (34%), generalizability of results (17%), statistical methods (accounting for at least age as confounder; 17%), study design (14%), and sample size (9%). However, no limitations regarding drop-out (or bias investigation), or report of inclusion/exclusion criteria or prodromal marker associations were revealed. Lessons learned from these limitations and additional aspects of current prodromal marker studies in PD are discussed to provide a basis for the evaluation of findings and the improvement of future research in prodromal PD. The observed heterogeneity of studies, limitations and analyses might be addressed in future longitudinal studies using a, yet to be established, modular minimal set of assessments improving comparability of findings and enabling data sharing and combined analyses across studies.
Enormous effort is being put into the identification and characterization of symptoms that may be used as predictive and progression markers in Parkinson's disease (PD). An impressive number of PD ...patients and individuals at risk for or in the prodromal stage of PD are currently followed in longitudinal studies; however, there does not exist an overview on the kind of markers evaluated and the assessments used.
Information on the design, sample size, evaluated markers and assessments of 21 studies of the Joint Programme - Neurodegenerative Disease Research BioLoC-PD working group were collected by questionnaire. The studies were classified into at risk/prodromal or clinical PD cohorts. The assessments were grouped into quantitative assessments, investigator-rated assessments, investigator interviews, patient-rated questionnaires and caregiver-rated questionnaires.
Compilation of these data revealed an interesting consensus on evaluated markers, but there was an enormous variability of assessments. Furthermore, there is a remarkable similarity in the markers assessed and evaluation methods applied in the risk/prodromal and clinical PD cohorts.
The inventory of the longitudinal cohorts that are part of the BioLoC-PD consortium reveals that there is a growing consensus on the markers that should be assessed in longitudinal cohort studies in PD. However, controversy still exists on the specific type of assessment. To allow comparison of data and common analyses it will be essential to harmonize scales and assessment outcomes.
Because of the complexity, heterogeneity, and the progressive nature of PD, such predictive and progression markers can only be identified in large cohorts and in studies with a longitudinal design. ......the pivotal combination of data and findings across studies is hampered by the lack of comparability of symptoms/factors that are being assessed and the specific assessments that are being applied. ...a common approach is needed to enable harmonization and combination of data across studies to define and validate predictive and progression markers. ...according to the main research aim of the study, different extension modules can be added. The variability in the choice of the assessments may be explained by a number of different factors: (i) Not all scales/questionnaires are available and validated in all languages. (ii) Study designs vary with regard to outcome variables which influences the choice of assessments. (iii) Some assessments require more resources than others (more time-consuming, more costly or requiring trained staff members), which also influenced the selection and composition of the selected assessment battery. (iv) Advances in knowledge about assessments and biomarkers have led to revision or expansion of assessments after the respective study was initiated. (v) Preference for a specific assessment based on previous experience of the individual researchers involved.
Neonatal hypoxic–ischaemic (HI) brain injury resulting in encephalopathy is a leading cause of morbidity and mortality with no effective treatment. Here we show that caffeic acid phenethyl ester ...(CAPE), an active component of propolis, administered either before or after an HI insult, significantly prevents HI-induced neonatal rat brain damage in the cortex, hippocampus and thalamus. In addition to blocking HI-induced caspase 3 activation, CAPE also inhibits HI-mediated expression of inducible nitric oxide synthase and caspase 1 in vivo and potently blocks nitric oxide-induced neurotoxicity in vitro. Furthermore, CAPE directly inhibits Ca2+-induced cytochrome c release from isolated brain mitochondria. Thus, CAPE induces neuroprotection against HI-induced neuronal death, possibly by blocking HI-induced inflammation and/or directly inhibiting the HI-induced neuronal death pathway. CAPE may therefore be a novel effective therapy for preventing neonatal HI injury.
Neuron-specific enolase (NSE) is a glycolytic isoenzyme which is located in central and peripheral neurons and neuroendocrine cells. Another enolase isoenzyme, non-neuronal enolase (NNE), occurs in ...glial cells. The purpose of this study was to follow any changes in NSE and/or NNE in cranial motor neurons after separation of their cell bodies from their axon terminals. One hypoglossal nerve in the rat and the cynomolgus monkey was thus crushed or cut and, after a given period, the brains were perfusion fixed. Immunocytochemistry, using anti-rat NSE and NNE or anti-human NSE and NNE, was performed on Vibratome-sectioned specimens of the hypoglossal nuclei. In the rat, NSE immunostaining decreased in the affected neurons 2 to 10 days following axonal injury. The change was greatest on the 10th day. Twenty days following nerve crush. NSE staining began to recover on the operated side and by the 45th day had returned to normal levels. NSE changes in the monkey were similar to those in the rat. In rats, where the nerve was cut and the proximal stump was translocated to a normally innervated muscle to inhibit re-formation of synaptic contacts, the NSE remained low for 60 days after nerve injury. As NSE levels fell during degeneration, there was a slight increase in NNE in some of the monkey specimens but not in others; the NNE alterations were, therefore, equivocal. The results demonstrate that the content of NSE in neurons serves as a molecular marker of axon injury, regeneration, and target reinnervation.
Highlights • Prevention of augmentation may be started by considering using medications such as α2δ ligands for initial RLS/WED treatment. • Alternatively, if dopaminergic drugs are elected as ...initial treatment, then the daily dose should be kept as low as possible and not exceed that recommended for RLS/WED treatment. • Patients with low iron stores should be given appropriate iron supplementation. • Treatment of existing augmentation should be initiated with the elimination/correction of extrinsic exacerbating factors (low iron levels, antidepressants, antihistamines, etc.) where possible. • In cases of mild augmentation dopamine agonist therapy can be continued by dividing or advancing the dose, or increasing the dose if there are breakthrough nighttime symptoms. Alternatively, the patient can be switched to an α2δ ligand or rotigotine. • For severe augmentation the patient can be switched either to an α2δ ligand or to rotigotine, noting that rotigotine may also produce augmentation at higher doses with long-term use. In severe cases of augmentation a high-potency opioid may be considered, bypassing α2δ ligands and rotigotine.
The intention of this analysis was to identify patients with treated Wilson disease (WD) and residual neurological symptoms in order to determine whether or not they were undergoing any treatment in ...addition to the common decoppering medication. Moreover, the effects of any symptomatic medication were analyzed. Two samples of WD patients were investigated either by a mailed questionnaire survey (n = 135) or by a retrospective analysis (n = 75). A considerable proportion of patients still suffered from neurological symptoms (n = 106, 50.5%), of whom a relatively small proportion was treated symptomatically (n = 33, 31.1%). The documented effects varied substantially, with anticholinergics and botulinum toxin (against dystonia) and primidone (against tremor) apparently being the most promising compounds. Further studies are required to analyze the symptomatic treatment of WD patients with residual neurological symptoms in more detail.
Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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