Neuroprosthetic interventions for orthostatic hypotension in neurological diseases

Neurological diseases such as Multiple System Atrophy (MSA), Parkinson's disease, Lewy Body Dementia, and Pure Autonomic Failure lead to severe dysfunctions of the autonomic nervous system, resulting in neurogenic orthostatic hypotension. Current treatments remain limited, and certain therapies, such as dopamine replacement, may worsen symptoms. Our recent research revealed how a neuroprosthetic intervention such as epidural electrical stimulation (EES) of the thoracic spinal cord regulates blood pressure, leading to the development of a neuroprosthetic baroreflex effective across multiple species, including humans with spinal cord injury (SCI). SCI and neurodegenerative disorders disrupt communication between brainstem cardiovascular centers and spinal cord neurons, prompting our hypothesis that EES could alleviate orthostatic hypotension in MSA patients. As expected, EES reduced symptoms in one human participant.However, uncertainties persist regarding which patient populations benefit from EES, its mechanisms on sympathetic neurons, and the long-term effects of this therapy. To address these questions, we established rodent models mimicking neurodegenerative conditions causing orthostatic hypotension, and found that EES restores stability only under specific neuronal loss patterns. Future studies will explore the correlation between these patterns and patient populations for clinical trials, alongside assessing long-term effects of targeted EES on hemodynamic stability.