Continuous subcutaneous apomorphine monotherapy in Parkinson’s disease

Introduction and objective. Continuous subcutaneous apomorphine (APO) treatment is one of the 3 therapeutic options for advanced Parkinson’s disease (PD), in addition to deep brain stimulation (DBS) and intrajejunal levodopa. Data from previously performed studies show that few PD patients can achieve APO infusion as monotherapy. The current pilot study presents the authors’ experience in achieving APO monotherapy. Materials and method. During the last 2 years, 9 patients with APO were treated in the Department of Neurology of the Medical University of Lublin; each patient was offered a 5-day duration APO treatment as monotherapy. The main indication for the APO therapy was advanced PD with motor fluctuations and the patient’s non-agreement for DBS therapy. Mean age of treated patients – 65.11 years, mean disease duration – 7.67 years, mean Hoehn-Yahr – 2.67, mean L-dopa equivalent before APO treatment – 1751.11 mg, mean daily dose of apomorphine as monotherapy – 106.11 ± 14.09 mg. Results. All treated patients managed to achieve APO monotherapy. A statistically significant reduction was found in the duration of the ‘off’ states in the observed PD patients on APO monotherapy (p<0.05). No significant improvement was observed in the III motor score of the UPDRS on APO treatment, compared to optimized oral therapy used before APO treatment. Conclusions. APO monotherapy can be achieved in advanced PD, and seems to be a good therapeutic option for this group of patients, especially in that it allows a significant reduction in the off-time which significantly simplifies the drug regime. Nevertheless, hospital admission with experienced neurologist supervision is recommended when establishing a PD patient’s APO monotherapy

Neurofilament ELISA validation

Background: Neurofilament proteins (Nf) are highly specific biomarkers for neuronal death and axonal degeneration. As these markers become more widely used, an inter-laboratory validation study is required to identify assay criteria for high quality performance. Methods: The UmanDiagnostics NF-light ®enzyme-linked immunoabsorbent assays (ELISA) for the neurofilament light chain (NfL, 68 kDa) was used to test the intra-assay and inter-laboratory coefficient of variation (CV) between 35 laboratories worldwide on 15 cerebrospinal fluid (CSF) samples. Critical factors, such as sample transport and storage, analytical delays, reaction temperature and time, the laboratories&apos; accuracy and preparation of standards were documented and used for the statistical analyses. Results: The intra-laboratory CV averaged 3.3% and the inter-laboratory CV 59%. The results from the test laboratories correlated with those from the reference laboratory (R = 0.60, p &lt; 0.0001). Correcting for critical factors improved the strength of the correlation. Differences in the accuracy of standard preparation were identified as the most critical factor. Correcting for the error introduced by variation in the protein standards improved the correlation to R = 0.98, p &lt; 0.0001 with an averaged inter-laboratory CV of 14%. The corrected overall inter-rater agreement was subtantial (0.6) according to Fleiss&apos; multi-rater kappa and Gwet&apos;s AC1 statistics. Conclusion: This multi-center validation study identified the lack of preparation of accurate and consistent protein standards as the main reason for a poor inter-laboratory CV. This issue is also relevant to other protein biomarkers based on this type of assay and will need to be solved in order to achieve an acceptable level of analytical accuracy. The raw data of this study is available online. © 2009 Elsevier B.V