Might We Consider Placing More Emphasis on the Relationship Between Autonomic Dysfunction and Stroke?

Sir, Following a stroke, the autonomic nervous system can become dysregulated in 25–76% of cases, which may lead to myocardial injury, leading to arrhythmias. Myocardial stunning in stroke may be caused by microvascular dysfunction due to impaired regulation of coronary microcirculation mediated by neurons of the brain stem. The incidence of sudden death due to arrhythmic causes in acute stroke patients is reported to be around 6%.1 How to identify these susceptible patients? Firstly, we should consider whether in the background the patients are having autonomic dysfunction: Diabetes with autonomic neuropathy, atypical Parkinson’s disease, amyloidosis, autoimmune diseases like Sjögren’s syndrome, systemic lupus erythematosus (lupus), rheumatoid arthritis, spinal cord injuries (especially at T6 or above), multiple sclerosis, and amyloidosis. Commonly used drugs that can worsen or cause autonomic dysfunction include diuretics, nitroglycerin, hydralazine, clonidine, propranolol, verapamil, diltiazem, lisinopril, valsartan, paroxetine, trazodone, amitriptyline, chlorpromazine, olanzapine, risperidone, quetiapine, alfuzosin, terazosin, and cancer chemotherapeutics like taxanes, bortezomib, etc., However, rare inherited disorders such as familial dysautonomia and Fabry disease, along with viral infections like COVID-19, may worsen autonomic dysfunction. Poor nutrition and chronic alcoholism are other risk factors and it is essential to conduct a thorough history taking. Secondly, we need to consider whether stroke has affected potential anatomical sites for autonomic abnormalities (central autonomic structures mainly include the insular cortex, anterior cingulate cortex, amygdala, hypothalamus, nucleus of the solitary tract, ventrolateral medulla, dorsal motor nucleus of the vagus, nucleus ambiguus, parabrachial nucleus, and periaqueductal grey). Thirdly, seriously take into account the history of cardiac patients with arrhythmias, dilated cardiomyopathy, coronary artery disease, and heart failure who are susceptible to having a cardiac event with minimal autonomic dysfunction. Fourthly, consider other points that are recorded to be associated with autonomic dysregulation after stroke: High National Institutes of Health Stroke Scale (NIHSS), presence of intraventricular hemorrhage, hydrocephalus, and high catecholamine level post stroke. Fifthly, we can also identify the susceptible patients with autonomic tests (perform safe tests only) in acute stroke patients. For example, Ewing battery test can be safely utilized in such patients to determine the extent of autonomic dysfunction.2 Sixthly, continuous cardiac monitoring may be utilized: In the time domain analysis, the intervals between adjacent normal R waves in ECG (NN intervals) are measured over the period of recording (24 hours). SDANN (the standard deviation of the average NN interval) calculated over short periods, usually five minutes, which is an estimate of the changes in heart rate due to cycles longer than five minutes, suggests an overall reduction in heart rate variability, indicating poorer autonomic nervous system (ANS) control and a diminished ability to adapt to stress and poor outcome.3 However, an increase in pNN50 (the percentage of intervals >50 ms different from the preceding interval), a measure of parasympathetic activity, would contradict this finding, as it typically points to a higher degree of parasympathetic influence.3 Similarly, patients with lower deceleration capacity, or DC (a noninvasive measure of cardiac autonomic function derived from ECG), of ≤4.5 milliseconds had significantly been associated with worse functional outcomes.4 Finally, the presence of endothelial dysfunction may be detected by a low reactive hyperemia index as assessed by peripheral arterial tonometry (indicates impaired vasodilation) and is linked to an increased risk of adverse cardiovascular events. Thus, this assessment may help channelize safe management of acute stroke patients by remaining extra cautious about this entity (which is quite often overlooked)—not only in the acute stroke condition but also in the rehabilitative phase. We should seriously avoid drugs with arrhythmogenic potential while selecting favorable drugs like carvedilol (with additional vasodilative effect, also proposed due to its anti-inflammatory properties), ACE inhibitors, angiotensin-receptor blockers (ARBs), and statins, which have been shown to improve the sympathovagal balance and BRS (baroreceptor sensitivity). These will prevent unnecessary blood pressure surges in stroke patients, decrease the risk of stroke recurrence, and enhance patient survival. More research is required to reliably establish other medical and surgical options not only to prevent autonomic dysfunction-related catastrophe but also to contribute toward post stroke rehabilitation. As an example, VNS (vagal nerve stimulation) has been indicated to regulate immune cells and reduce proinflammatory cytokines through the cholinergic anti-inflammatory pathway, thus exerting neuro-immunomodulatory effects.5 Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.