One aspect of the present disclosure relates to a closed-loop therapy system for treating autonomic instability or a medical condition associated therewith in a subject. The therapy delivery system can include a sensing component, a delivery component, and a controller. The sensing component can be configured to detect at least one physiological parameter associated with autonomic instability or a medical condition associated therewith. The delivery component can be configured for implantation on or about an autonomic nervous tissue target or a spinal nervous tissue target. The controller can be configured to automatically coordinate operation of the sensing and delivery components. The controller can also be configured to deliver an electrical signal to the delivery component to modulate activity at the autonomic nervous tissue target or a spinal nervous tissue target and effectively treat autonomic instability or a medical condition associated therewith.