Data from the European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC)
ORPHANET JOURNAL OF RARE DISEASES
Authors: Scalco, Renata S.; Lucia, Alejandro; Santalla, Alfredo; Martinuzzi, Andrea; Vavla, Marinela; Reni, Gianluigi; Toscano, Antonio; Musumeci, Olimpia; Voermans, Nicol C.; Kouwenberg, Carlyn V.; Laforet, Pascal; San-Millan, Beatriz; Vieitez, Irene; Siciliano, Gabriele; Kuhnle, Enrico; Trost, Rebeca; Sacconi, Sabrina; Stemmerik, Mads G.; Durmus, Hacer; Kierdaszuk, Biruta; Wakelin, Andrew; Andreu, Antoni L.; Pinos, Tomas; Marti, Ramon; Quinlivan, Ros; Vissing, John
Background The European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC) was launched to register rare muscle glycogenoses in Europe, to facilitate recruitment for research trials and to learn about the phenotypes and disseminate knowledge about the diseases through workshops and websites. A network of twenty full and collaborating partners from eight European countries and the US contributed data on rare muscle glycogenosis in the EUROMAC registry. After approximately 3 years of data collection, the data in the registry was analysed. Results Of 282 patients with confirmed diagnoses of muscle glycogenosis, 269 had McArdle disease. New phenotypic features of McArdle disease were suggested, including a higher frequency (51.4%) of fixed weakness than reported before, normal CK values in a minority of patients (6.8%), ptosis in 8 patients, body mass index above background population and number of comorbidities with a higher frequency than in the background population (hypothyroidism, coronary heart disease). Conclusions The EUROMAC project and registry have provided insight into new phenotypic features of McArdle disease and the variety of co-comorbidities affecting people with McArdle disease. This should lead to better management of these disorders in the future, including controlling weight, and preventive screening for thyroid and coronary artery diseases, as well as physical examination with attention on occurrence of ptosis and fixed muscle weakness. Normal serum creatine kinase in a minority of patients stresses the need to not discard a diagnosis of McArdle disease even though creatine kinase is normal and episodes of myoglobinuria are absent.
Subthreshold Electrical Stimulation for Controlling Protein-Mediated Impedance Increases in Platinum Cochlear Electrode
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
Authors: Aregueta-Robles, Ulises A.; Enke, Ya Lang; Carter, Paul M.; Green, Rylie A.; Poole-Warren, Laura A.
Objective: This study evaluated subthreshold biphasic stimulation pulses as a strategy to stabilize electrode impedance via control of protein adsorption. Following implantation, cochlear electrodes undergo impedance fluctuations thought to be caused by protein adsorption and/or inflammatory responses. Impedance increases can impact device power consumption, safe charge injection limits, and long-term stability of electrodes. Methods: Protein-mediated changes in polarization impedance (Z(p)) were measured by voltage transient responses to biphasic current pulses and electrochemical impedance spectroscopy, with and without protein solutions. Four subthreshold stimulation regimes were studied to assess their effects on protein adsorption and impedance; (1) symmetric charge-balanced pulses delivered continuously, (2) at 10% duty cycle, (3) at 1% duty cycle, and (4) an asymmetric charge balanced pulse delivered continuously with a cathodic phase twice as long as the anodic phase. Results: The Z(p) of electrodes incubated in protein solutions without stimulation for 2 h increased by between similar to 28% and similar to 55%. Subthreshold stimulation reduced the rate at which impedance increased following exposure to all protein solutions. Decreases in Z(p) were dependent on the type of protein solution and the stimulation regime. Subthreshold stimulation pulses were more effective when delivered continuously compared to 1% and 10% duty cycles. Conclusion: These results support the potential of subthreshold stimulation pulses to mitigate protein-mediated increase in impedance. Significance: This research highlights the potential of clinically translatable stimulation pulses to mitigate perilymph protein adsorption on cochlear electrodes, a key phenomenon precursor of the inflammatory response.