Patients with genetic ion channel diseases develop electrical disturbances in the brain (seizures) and heart (arrhythmias) that can lead to sudden death. Dr. Auerbach explores the mechanisms for multisystem genetic ion channel diseases. During his training at the University of Michigan he showed that in severe genetic forms of epilepsy, in addition to seizures, there are alterations in cardiac electrical function, with a high rate of cardiac arrhythmias. Arrhythmias provide one potential mechanism for the high rate of sudden death in epilepsy.
Now approaching these neuro-cardiac investigations in the opposite direction, he is assessing the co-prevalence and severity of seizures and cardiac arrhythmias in a classically studied cardiac disease, called Long QT Syndrome (LQTS.) LQTS is a genetic disease, characterized by cardiac electrocardiographic pathologies, arrhythmias, and a high risk of sudden death. Mutated genes in LQTS1-3 are expressed in the heart and brain, and seizures have been reported in LQTS patients. Ongoing studies using both LQTS patient registries and animal models of LQTS are being used to establish new clinical and mechanistic insights into this dual system disease, and the potential intricate crosstalk between the brain and heart.
The LQTS registry provides a unique and powerful resource to advance LQTS and epilepsy research. The Rochester-based LQTS Registry is the largest (>18,000 subjects) and most deeply annotated LQTS database in the world. It contains detailed clinical and genetic information from LQTS patients, plus affected and unaffected family members. It offers temporal resolution of the disease progression, including the dates of seizures, syncopes, arrhythmias, start/end of medications, sudden death, and records/results from clinical and genetic tests.
Animals carrying the same mutation as LQTS patients with vs. without seizures, and state of the art in vivo/in vitro techniques (e.g., radiotelemetry ECGs & single cell electrophysiology), provide excellent tools to interrogate direct vs. indirect mechanisms for the neuro-cardiac disease manifestations and progression.