The Association of Autonomic Nervous System Function With Ischemic Stroke, and Treatment Strategies

Abstract

Acute ischemic stroke, especially minor stroke, and transient ischemic attack have high risks of recurrence and exacerbation into severe ischemic strokes. It remains challenging to perform risk stratification and screen high-risk groups for initiation of early treatment in these patients. Moreover, with the growing population of patients with chronic small vessel disease, the mechanisms and clinical implications require further investigation. Traditional tools such as the ABCD2 score (age, blood pressure, clinical features, duration of symptoms, diabetes) have only moderate predictive value in patients with transient ischemic attack or minor stroke. By contrast, measurement of changes in heart rate variability (HRV) is an important and novel tool for risk stratification and outcome prediction in patients with cardiovascular diseases, as it reflects the overall level of autonomic nervous system dysfunction. Thus, abnormal HRV may be useful for prognosis and improve stratification of stroke patients with diverse risks. HRV may also partially explain autonomic nervous dysfunction and other manifestations during the process of chronic cerebral small vessel disease. In summary, measurement of HRV may contribute to early initiation of interventions in acute or chronic stroke patients using novel treatments involving rebalancing of autonomic nervous system function.

Keywords: autonomic nervous system function; heart rate variability; intervention; outcome; risk stratification; stroke.

Figure 1

Hypertension, diabetes, smoking, and other risk factors of stroke, as well as acute ischemic stroke (AIS) and cerebral small vessel disease (CSVD), may have a negative influence on the body. Regulated by the autonomic nervous system (ANS), the body initiates the stress response to these various stressors perceived by the brain, in an attempt to neutralize the effects of the stressors and regain homeostasis. When demands for re-establishment exceed the adaptive capacity, impaired ANS attributed to altered sympathetic-vagal balance may provide inaccurate responses or progressively lead to a delayed reactivity. This eventually evolves into stress-related disorders as secondary stresses, such as arrhythmia, myocardial infarction, dyslipidemia, and other complications. These secondary stressors increase the incidence of recurrent ischemic stroke. These pathways can form a vicious cycle, while targeting sympathetic-vagal imbalance maybe an efficient interventional strategy.

Figure 2

Hypertension, obstructive sleep apnea (OSA), smoking, and other risk factors are significantly associated with AIS. Studies found several pathologic changes after AIS onset, including transient changes in cardiac electrophysiology, blood pressure (BP) variation, and a higher probability of extensive infarction and in-hospital cardiovascular complications. These post-stroke deteriorations attributed to ANS dysfunction (i.e., sympathetic over-activity) may lead to poor clinical outcomes. Hypertension, OSA, and white matter lesions (WMLs) are considered independent risk factors of cerebral small vessel disease (CSVD). Some CSVD lesions present with acute stroke symptoms, while others are asymptomatic. A possible mechanism for these silent lesions may relate to locations in the motor or sensory tracts such as the internal capsule. Some studies suggest that dysregulation of heart rate variability (HRV), especially over-activation of sympathetic tone, may be a pathophysiologic mechanism underlying the development of WMLs in OSA patients. Failed autonomic control of the cerebral circulation can predispose patients to CSVD, leading to cognitive impairment, in which sympathetic activation may have a major role. Further studies examining the underlying pathogenesis of CSVD are required.