The Blood Pressure Pendulum following Spinal Cord Injury: Implications for Vascular Cognitive Impairment

Abstract

Cognitive impairment following spinal cord injury (SCI) has received considerable attention in recent years. Among the various systemic effects of SCI that contribute towards cognitive decline in this population, cardiovascular dysfunction is arguably one of the most significant. The majority of individuals with a cervical or upper-thoracic SCI commonly experience conditions called orthostatic hypotension and autonomic dysreflexia, which are characterized by dangerous fluctuations in systemic blood pressure (BP). Herein, we review the potential impact of extreme BP lability on vascular cognitive impairment (VCI) in individuals with SCI. Albeit preliminary in the SCI population, there is convincing evidence that chronic hypotension and hypertension in able-bodied individuals results in devastating impairments in cerebrovascular health, leading to VCI. We discuss the pertinent literature, and while drawing mechanistic comparisons between able-bodied cohorts and individuals with SCI, we emphasize the need for additional research to elucidate the mechanisms of cognitive impairment specific to the SCI population. Lastly, we highlight the current and potential future therapies to manage and treat BP instability, thereby possibly mitigating VCI in the SCI population.

Keywords: autonomic dysreflexia; cerebrovascular health; orthostatic hypotension; spinal cord injury; vascular cognitive impairment.

Figure 1

An overview of spinal cord injury (SCI), autonomic cardiovascular innervation, blood pressure (BP) instability, and cerebral autoregulation. The schematic diagram in the middle demonstrates autonomic control of the cardiovascular system. Parasympathetic control of the heart (dashed line), mediated by the vagus nerve, usually remains intact following SCI. Neurons within the brainstem provide sympathetic tonic control to spinal sympathetic preganglionic neurons. Heart and upper-body blood vessels are innervated via spinal segments T1–T5, whereas the trunk and lower extremity vasculature receive innervation from T6–L2. The splanchnic bed (liver, spleen, and intestines) is densely innervated, highly compliant, and contains approximately one-quarter of the total blood volume at rest, making it the primary capacitance bed. An SCI disrupting the sympathetic control of these vessels (i.e., at or above T6) makes them highly vulnerable to vasodilation and extreme constriction, leading to BP instability. Orthostatic hypotension (shown on the left): cardiovascular changes in a participant with a motor-complete cervical SCI (C5, American Spinal Injury Association Impairment Scale (AIS) A) during a head-up-tilt assessment. Beat-by-beat BP is shown in grey, and heart rate is shown in blue. BP plummeted immediately upon initiation of 60° upright tilt from the supine position and the tilt was terminated after 2 min. Mean arterial pressure was recorded as 25 mmHg at its lowest, well below the lower limit of cerebral autoregulation (top middle inset). Rebound hypertension was also apparent when the participant was returned to the supine position, further emphasizing the instability in blood pressure regulation. Autonomic dysreflexia (shown on the right): cardiovascular changes in a male with motor-incomplete SCI (C6, AIS C) during a sperm retrieval procedure with penile vibrostimulation (PVS), which is a visceral/somatic trigger originating below the spinal lesion. The dashed lines indicate each time the PVS is applied and is followed by significant and rapid increases in BP. * indicates ejaculation. In this case, systolic BP almost triples and mean arterial pressure is ~250 mmHg, well above the upper limit of cerebral autoregulation (top Figure). Cerebral autoregulation curve (shown on the top): cerebral blood flow (CBF) is shown in relation to cerebral artery lumen diameter and mean arterial pressure. The dashed lines represent the lower and upper limits of CBF autoregulation, which are exceeded by our clinical orthostatic and autonomic dysreflexia examples. Red circles represent the cerebral arteries (either vasodilating or vasoconstricting to counteract changes in systemic blood pressure), and the blue solid line represents cerebral blood flow.

Figure 2

Ambulatory BP monitoring data collected from a research participant with a motor-complete cervical SCI (C5, AIS B). These data demonstrate transient, pendulum-like shifts in BP (in grey) in response to various stimuli throughout a normal day. Multiple episodes of autonomic dysreflexia (n = 25) and orthostatic hypotension (n = 33) were observed in this case, with systolic BP ranging from 71 to 180 mmHg (mean arterial pressure: 53 to 132 mmHg). Triggers for these conditions are annotated on the figure. The bowel routine in particular demonstrates aberrant BP changes, in both directions, in response to suppository insertion, digital stimulation, and pressure applied to the abdomen (autonomic dysreflexia) and transferring to and from the commode (orthostatic hypotension). Heart rate is represented by the blue solid line.