Standardized Autonomic Testing in Patients With Probable Radiation-Induced Afferent Baroreflex Failure

Injury of the afferent limb of the baroreflex from neck radiation causes radiation-induced afferent baroreflex failure (R-ABF). Identification and management of R-ABF is challenging. We aimed to investigate the pattern of autonomic dysfunction on standardized autonomic testing in patients with probable R-ABF. We retrospectively analyzed all autonomic reflex screens performed at Mayo Clinic in Rochester, MN, between 2000 and 2020 in patients with probable R-ABF. Additional tests reviewed included ambulatory blood pressure monitoring, plasma norepinephrine, and thermoregulatory sweat test. We identified 90 patients with probable R-ABF. Median total composite autonomic severity score (range, 0–10) was 7 (interquartile range, 6–7). Cardiovascular adrenergic impairment was seen in 85 patients (94.4%), increased blood pressure recovery time after Valsalva maneuver in 71 patients (78.9%; median 17.4 seconds), and orthostatic hypotension in 68 patients (75.6%). Cardiovagal impairment was demonstrated by abnormal heart rate responses to deep breathing (79.5%), Valsalva ratio (87.2%), and vagal baroreflex sensitivity (57.9%). Plasma norepinephrine was elevated and rose appropriately upon standing (722–1207 pg/mL). Ambulatory blood pressure monitoring revealed hypertension, postural hypotension, hypertensive surges, tachycardia, and absence of nocturnal dipping. Blood pressure lability correlated with impaired vagal baroreflex function. Postganglionic sympathetic sudomotor function was normal in most cases; the most frequent thermoregulatory sweat test finding was focal neck anhidrosis (78.9%). Standardized autonomic testing in R-ABF demonstrates cardiovascular adrenergic impairment with orthostatic hypotension, blood pressure lability, and elevated plasma norepinephrine. Cardiovagal impairment is common, while sudomotor deficits are limited to direct radiation effects.

Sudomotor Dysfunction

Disorders of sudomotor function are common and diverse in their presentations. Hyperhidrosis or hypohidrosis in generalized or regional neuroanatomical patterns can provide clues to neurologic localization and inform neurologic diagnosis. Conditions that impair sudomotor function include small fiber peripheral neuropathy, sudomotor neuropathy, myelopathy, α-synucleinopathies, autoimmune autonomic ganglionopathy, antibody-mediated hyperexcitability syndromes, and a host of medications. Particularly relevant to neurologic practice is the detection of postganglionic sudomotor deficits as a diagnostic marker of small fiber neuropathies. Extensive anhidrosis is important to recognize, as it not only correlates with symptoms of heat intolerance but may also place the patient at risk for heat stroke when under conditions of heat stress. Methods for assessing sudomotor dysfunction include the thermoregulatory sweat test, the quantitative sudomotor axon reflex test, silicone impressions, and the sympathetic skin response.

Novel methods of imaging and analysis for the thermoregulatory sweat test

The thermoregulatory sweat test (TST) can be central to the identification and management of disorders affecting sudomotor function and small sensory and autonomic nerve fibers, but the cumbersome nature of the standard testing protocol has prevented its widespread adoption. A high-resolution, quantitative, clean and simple assay of sweating could significantly improve identification and management of these disorders. Images from 89 clinical TSTs were analyzed retrospectively using two novel techniques. First, using the standard indicator powder, skin surface sweat distributions were determined algorithmically for each patient. Second, a fundamentally novel method using thermal imaging of forced evaporative cooling was evaluated through comparison with the standard technique. Correlation and receiver operating characteristic analyses were used to determine the degree of match between these methods, and the potential limits of thermal imaging were examined through cumulative analysis of all studied patients. Algorithmic encoding of sweating and nonsweating regions produces a more objective analysis for clinical decision-making. Additionally, results from the forced cooling method correspond well with those from indicator powder imaging, with a correlation across spatial regions of −0.78 (confidence interval: −0.84 to −0.71). The method works similarly across body regions, and frame-by-frame analysis suggests the ability to identify sweating regions within ~1 s of imaging. Although algorithmic encoding can enhance the standard sweat testing protocol, thermal imaging with forced evaporative cooling can dramatically improve the TST by making it less time consuming and more patient friendly than the current approach. NEW & NOTEWORTHY The thermoregulatory sweat test (TST) can be central to the identification and management of several common neurological disorders, but the cumbersome nature of the standard testing protocol has prevented its widespread adoption. In this study, images from 89 clinical TSTs were analyzed retrospectively using two novel techniques. Our results suggest that these improved methods could make sweat testing more reliable and acceptable for screening and management of a range of neurological disorders.

Thermoregulatory Sweat Test

The thermoregulatory sweat test (TST) consists of giving a controlled heat and humidity stimulus to produce a generalized sweat response. The TST assesses the integrity of efferent sympathetic sudomotor pathways. The entire anterior body surface is tested for both pre- and post-ganglionic lesions. The TST can evaluate patients with symptoms of small-fiber neuropathy and demonstrate autonomic involvement in disorders such as multiple system atrophy, hyperhidrosis, and some skin disorders. An indicator powder placed on the body surface before heating provides visualization of sweating and non-sweating skin. The patient’s weight (before and after heating) and height allows calculation of total body sweat rate, and the slope of the core temperature rise with time provides an estimate of heat tolerance. Normal and abnormal TST patterns, report generation, and difficulties and pitfalls in test interpretation are described.

Thermoregulatory Sweat Test

The TST assesses the integrity of central and peripheral efferent sympathetic sudomotor neural pathways. A controlled heat and humidity stimulus is given to produce a generalized sweating response in all skin areas capable of sweating. Sweating is visualized by placing an indicator powder on the skin beforehand. The entire anterior body surface can be examined and abnormalities can usually be detected at a glance.