The differential diagnosis of Parkinson syndromes remains a major challenge. Quantitative MR imaging can aid in this classification, but it is unclear which of the proposed techniques is best suited ...for this task. We, therefore, conducted a head-to-head study with different quantitative MR imaging measurements in patients with IPS, MSA-type Parkinson, PSP, and healthy elderly controls.
Thirty-one patients and 13 controls underwent a comprehensive quantitative MR imaging protocol including R2*-, R2- and R1-mapping, magnetization transfer, and DTI with manual region-of-interest measurements in basal ganglia regions. Group differences were assessed with a post hoc ANOVA with a Bonferroni error correction and an ROC.
The best separation of MSA from IPS in patients and controls could be achieved with R2*-mapping in the PU, with an ROC AUC of ≤0.96, resulting in a sensitivity of 77.8% (with a specificity 100%). MD was increased in patients with PSP compared with controls and to a lesser extent compared with those with IPS and MSA in the SN.
Among the applied quantitative MR imaging methods, R2*-mapping seems to have the best predictive power to separate patients with MSA from those with IPS, and DTI for identifying PSP.
The MDS-Unified Parkinson's disease (PD) Rating Scale (MDS-UPDRS) is the most used scale in clinical trials. Little is known about the predictive potential of its single items.
To systematically ...dissect MDS-UPDRS to predict PD progression.
574 de novo PD patients and 305 healthy controls were investigated at baseline (BL) in the single-center DeNoPa (6-year follow-up) and multi-center PPMI (8-year follow-up) cohorts. We calculated cumulative link mixed models of single MDS-UPDRS items for odds ratios (OR) for class change within the scale. Models were adjusted for age, sex, time, and levodopa equivalent daily dose. Annual change and progression of the square roots of the MDS-UDPRS subscores and Total Score were estimated by linear mixed modeling.
Baseline demographics revealed more common tremor dominant subtype in DeNoPa and postural instability and gait disorders-subtype and multiethnicity in PPMI. Subscore progression estimates were higher in PPMI but showed similar slopes and progression in both cohorts. Increased ORs for faster progression were found from BL subscores I and II (activities of daily living; ADL) most marked for subscore III (rigidity of neck/lower extremities, agility of the legs, gait, hands, and global spontaneity of movements). Tremor items showed low ORs/negative values.
Higher scores at baseline for ADL, freezing, and rigidity were predictors of faster deterioration in both cohorts. Precision and predictability of the MDS-UPDRS were higher in the single-center setting, indicating the need for rigorous training and/or video documentation to improve its use in multi-center cohorts, for example, clinical trials.
Polypharmacy is common in geriatric Parkinson's disease (PD) patients in advanced disease stages with multiple comorbidities, bearing multiple risks for drug safety in theory.
The aim of this study ...was to empirically identify the most frequent and relevant contraindications and drug interactions actually occurring and compromising drug safety in PD in real life.
We conducted a prospective observational study in a multimorbid cohort of PD patients with polypharmacy admitted to a specialized hospital. Inclusion criteria were the presence of at least one comorbidity requiring pharmacotherapy and at least five different drugs in the discharge prescription. Hoehn and Yahr stage during the 'on' state, therapeutic problems related to motor and non-motor PD symptoms, comorbidities, and drug regimens on admission and discharge were analyzed for contraindications and interactions.
Overall, 127 patients were included (medium Hoehn and Yahr stage = IV, range II-V). Interactions with the anti-PD medication were mainly caused by other central nervous system (CNS)-active substances, cytochrome P450-metabolized substances, and QT-time prolonging substances. Contraindications against the anti-PD medication mainly occurred from internal, haematopoietic, neurologic and psychiatric diseases, and QT-time prolonging drugs. The highest frequency of interactions and contraindications were identified with levodopa (n = 119 at admission/n = 126 at discharge), entacapone (n = 46/42), pramipexole (n = 44/24), and amantadine (n = 32/30).
Several medically relevant risk factors (interactions and contraindications) frequently occurred in advanced PD patients. These findings provide a basis for developing programmes for awareness, education, monitoring, and preventive interventions to avoid adverse incidents. Future studies will need to evaluate preventive efficacy of structured drug safety programmes.
Background
Multiple system atrophy (MSA) is a complex and fatal neurodegenerative movement disorder. Understanding the comorbidities and drug therapy is crucial for MSA patients’ safety and ...management.
Objectives
To investigate the pattern of comorbidities and aspects of drug therapy in MSA patients.
Methods
Cross-sectional data of MSA patients according to Gilman et al. (2008) diagnostic criteria and control patients without neurodegenerative diseases (non-ND) were collected from German, multicenter cohorts. The prevalence of comorbidities according to WHO ICD-10 classification and drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were identified using AiDKlinik®.
Results
The analysis included 254 MSA and 363 age- and sex-matched non-ND control patients. MSA patients exhibited a significantly higher burden of comorbidities, in particular diseases of the genitourinary system. Also, more medications were prescribed MSA patients, resulting in a higher prevalence of polypharmacy. Importantly, the risk of potential drug-drug interactions, including severe interactions and contraindicated combinations, was elevated in MSA patients. When comparing MSA-P and MSA-C subtypes, MSA-P patients suffered more frequently from diseases of the genitourinary system and diseases of the musculoskeletal system and connective tissue.
Conclusions
MSA patients face a substantial burden of comorbidities, notably in the genitourinary system. This, coupled with increased polypharmacy and potential drug interactions, highlights the complexity of managing MSA patients. Clinicians should carefully consider these factors when devising treatment strategies for MSA patients.
Abstract Introduction Cognitive impairment is a common and disabling non-motor symptom in Parkinson's disease (PD). The apolipoprotein E (APOE) allele ε4 is a known risk factor for Alzheimer's ...disease and has also been suggested to be a risk factor for dementia in PD and even a predictor of impairment in certain cognitive domains. Methods A total of 447 PD patients (PD patients without cognitive impairment: n = 187; PD patients with mild cognitive impairment: n = 188; PD patients with dementia: n = 72) were included from an ongoing observational German multicenter cohort study (LANDSCAPE study). All patients underwent an extensive neuropsychological test battery, including assessments of memory, visuospatial functioning, attention, language, and executive function. APOE genotype was determined by an allelic discrimination assay. Linear regression analysis was used to explore the associations between APOE-ε4 and cognitive performance. Results The APOE-ε4 allele was not associated with a diagnosis of cognitive impairment in PD (PD with mild cognitive impairment and PD with dementia) or with deficits in specific neuropsychological domains in our study cohort. Conclusion Our data question the relevance of the APOE-ε4 allele as a predictor of cognitive impairment in PD.
Several studies demonstrated reduced CSF alpha-synuclein values in patients with advanced Parkinson's disease (PD). Values in drug-naieve PD subjects and healthy controls (HC) have not yet been ...reported. We measured CSF values including alpha-synuclein in a cohort of 78 previously untreated PD patients and 48 HC subjects. Measurements of total alpha-synuclein concentrations were performed using two independently operated immunoassays, i.e., one academia-based and previously validated (ELISA 1), the other industry-based, renewable and commercially available (ELISA 2). Mean values for CSF alpha-synuclein were significantly lower in de novo PD patients when compared to HC subjects, as demonstrated by both assays (ELISA 1, p = 0.049; ELISA 2, p = 0.005; combined, p = 0.002). Using the renewable ELISA 2, CSF alpha-synuclein concentrations of 1884.31 pg/ml or less showed a sensitivity of 0.91 and a specificity of 0.25 for the diagnosis of Parkinson's disease. The corresponding area-under-the-curve value was 0.65 (confidence interval, 0.554a0.750), which was statistically significant (p = 0.004). Total CSF alpha-synuclein is reduced early in the course of Parkinson's disease, as measured by two independent ELISA platforms at the time of enrolment, and this reduction appears independent from drug treatment. Follow-up investigations will determine the usefulness of CSF alpha-synuclein values as markers of progression in individual subjects.
A solitary histone H3 gene encoding a novel H3 protein sequence has been isolated. This H3 gene maps to chromosome 1 (1q42), whereas we have shown previously that the majority of the human histone ...genes form a large cluster on chromosome 6 (6p21.3). In addition, a small cluster has been described at 1q21. The clustered histone genes are expressed during the S-phase of the cell cycle, hence their definition as replication-dependent histone genes. In contrast, expression of replacement histone genes is essentially cell-cycle independent; they are solitary genes and map outside the major clusters. The newly described H3 gene maps outside all known histone gene clusters and varies by four amino acid residues from the consensus mammalian H3 structure. In contrast to other solitary histone genes, this human H3 gene shows the consensus promoter and 3' flanking portions that are typical for replication-dependent genes.
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![Total CSF [alpha]-synuclein...](http://api.summon.serialssolutions.com/2.0.0/image/issn/XR4PS5YY4K/0304-3940/small "Total CSF [alpha]-synuclein is lower in de novo Parkinson patients than in healthy subjects")
