Spinal cord epidural stimulation for autonomic nervous system control: A focus on improving bladder, bowel, and cardiovascular function

Introduction

Spinal cord injury (SCI) affects nearly 2 million people in the United States ( ) and results in profound neurologic impairment with widespread deficits to sensorimotor and autonomic systems. While the lack of ambulation is most widely recognized, there are many internal systems that are disrupted after SCI due to the critical role of the spinal cord in coordinating bodily functions. As a result, individuals with SCI endure a myriad of complications that result in increased mortality, morbidity, hospitalization, high burden of care and health care costs, and a drastically lowered quality of life ( ).

The autonomic nervous system serves to provide essential regulatory communication between the brain and internal organs, vascular supply, and numerous glands in order to maintain dynamic equilibrium and homeostasis of all systems. Sympathetic and parasympathetic systems (including the enteric system for the gastrointestinal tract) function to integrate complex reflex pathways between the target organ and integration centers within the nervous system ( ). Thus, autonomic disruption extends across multiple systems and drastically impacts overall health and quality of life. Alterations of urogenital and bowel dysfunctions are consistently rated as top consumer priorities for recovery post-SCI ( ; ; ). Acutely post-SCI, bladder dysfunction often manifests as “flaccid paralysis,” resulting in urinary retention necessitating bladder catheterization. Overtime, bladder dysfunction progresses into detrusor hyperreflexia and detrusor-sphincter dyssynergia, resulting in incontinence and incomplete emptying. Gastrointestinal disruptions after SCI are highly prevalent and include a wide-range of symptoms, including delayed gastric emptying, diminished propulsive transit, abdominal distention, pain, constipation, anal fissures, hemorrhoids, rectal prolapse, and sphincter/defecation disturbances ( ). Cardiovascular dysfunction associated with autonomic dysregulation contributes to increased morbidity and is the leading cause of mortality in acute and chronic SCI ( ). The disruption of supraspinal control over sympathetic pathways results in decreased sympathetic tone below the level of injury and impaired autonomic function and blood pressure regulation ( ). One critical complication that occurs in individuals with lesions above T6 is autonomic dysreflexia (AD), an exaggerated sympathetic nervous system response to a noxious stimulus below the level of injury, including bladder/bowel distention, urinary tract infections, fecal impaction, and orgasms ( ). As a result, increased cardiovascular dysregulation has a profound effect on the body as a whole and significantly interferes with motor and autonomic recovery post-injury.

Bladder dysfunction after SCI

Long-term deficits in bladder function after SCI manifest as detrusor hyperreflexia (bladder contractions at low volumes, causing incontinence and smooth muscle hypertrophy), detrusor-sphincter dyssynergia (uncoordinated bladder and external urethral sphincter contractions, causing inefficient emptying and smooth muscle hypertrophy), decreased compliance (unable to store urine under appropriately low pressures) and loss of continence ( Fig. 1 ) requiring lifelong management, maintenance, and health care visits ( ). Major urological concerns contributing to increased morbidity and mortality include repeated lower urinary tract infections that can lead to sepsis, chronic vesico-ureteral reflux and hydronephrosis with progression to renal failure as a result of high-intravesical pressures, and inter-related cardiovascular complications such as AD ( ) that limits bladder storage ( ). Current therapies to improve the efficiency of bladder voiding, management and continence after SCI include catheterization, pharmacologic and surgical interventions, functional electrical stimulation, as well as urethral stents. In particular, neurogenic detrusor overactivity and detrusor sphincter dyssynergia are commonly managed with anti-muscarinic drugs and Botox injections, and while these pharmacotherapy agents do not prevent or reverse the changes, they primarily focus on improving storage outcomes and do not address the emptying phase. Furthermore, anti-muscarinic agents can have unpleasant side effects such as dry mouth and constipation, exacerbating existing bowel dysfunction. The primary goal in managing neurogenic bladder is to protect the upper urinary tract and reduce the incidence of infections, followed by achieving continence. As such, when conservative management fails, surgeries to reduce high bladder pressures and chronic urinary incontinence include urinary diversion and lower urinary tract reconstruction approaches ( ). As urinary complications continue to impact long-term morbidity in this population, additional therapeutic and rehabilitative approaches are needed that aim to improve function by targeting the recovery of underlying impairments.