Sympathetic Skin Response Detects Paroxysmal Sympathetic Hyperactivity in Consciousness Disorders

A simple electrical test that measures how the skin reacts to a burst of stimulation may offer clinicians a faster, more objective way to detect a dangerous and often hidden complication of severe brain injury, according to new research published in the journal Neurocritical Care. The study, led by Juanjuan Fu and colleagues at Zhongda Hospital of Southeast University and the Affiliated Jiangning Hospital of Nanjing Medical University in China, found that a measurement known as the sympathetic skin response amplitude difference strongly distinguishes patients with paroxysmal sympathetic hyperactivity from those without the condition among people living with prolonged disorders of consciousness.

Paroxysmal sympathetic hyperactivity, commonly abbreviated PSH, is a devastating autonomic disturbance that can follow traumatic brain injury, stroke, and other forms of acquired brain damage. In affected patients, the sympathetic nervous system, the branch of the autonomic system responsible for the fight-or-flight response, erupts into sudden, repeated storms of overactivity. During these paroxysms, patients may develop fever-like elevations in body temperature, rapid heart rate, surging blood pressure, profuse sweating, and abnormally fast breathing, along with episodes of muscle posturing and rigidity. The episodes can easily be mistaken for sepsis, pain, or other medical crises, delaying appropriate treatment and exposing patients to unnecessary interventions. Beyond the immediate danger, PSH has been linked to worse functional outcomes and a slower, more complicated rehabilitation course.

Diagnosing PSH in patients with prolonged disorders of consciousness, a population that includes people in unresponsive wakefulness and minimally conscious states, is particularly challenging. These patients cannot report symptoms, and their behavioral fluctuations make clinical scoring scales, such as the PSH Assessment Method used in this study, difficult to apply reliably. Prolonged disorders of consciousness already present a diagnostic and prognostic puzzle, and medical comorbidities, including autonomic dysregulation, can complicate both care and recovery. Clinicians have long sought biomarkers that could supplement behavioral observation, and the new study suggests that a well-established electrophysiological technique may fill this gap.

The sympathetic skin response is a noninvasive test that has been used for decades, originally described in the 1980s as a method for assessing unmyelinated axon dysfunction in peripheral neuropathies. When an unexpected stimulus is delivered, typically a mild electrical pulse, sympathetic cholinergic fibers trigger a change in the electrical conductance of the skin through activation of sweat glands. Electrodes placed on the palms and soles record this transient voltage shift. The resulting waveform has two principal characteristics that clinicians measure: the latency, or the time between the stimulus and the onset of the response, and the amplitude, which reflects the size of the electrical deflection and is thought to correlate with the intensity of sympathetic outflow. The response has previously been applied in research on diabetes-related autonomic neuropathy, Parkinson’s disease, multiple system atrophy, and outcome prediction after intracerebral hemorrhage, but its role in identifying PSH in disorders of consciousness had not been systematically examined.

To investigate this question, the research team conducted a retrospective observational study of 124 consecutive patients with prolonged disorders of consciousness treated between March 2022 and March 2024. Using the consensus-based PSH Assessment Method, which scores clinical features such as fever, tachycardia, hypertension, tachypnea, and sweating, the patients were divided into a PSH-positive group of 43 individuals and a PSH-negative group of 81 individuals. Each patient underwent sympathetic skin response testing, and the researchers compared elicitation rates, latencies, amplitudes, and the difference in amplitude between the two sides of the body.

The results were striking. The rate at which a response could be elicited did not differ significantly between the groups, and neither did the latency, suggesting that the basic sympathetic pathway remained intact in both. What set the groups apart was the magnitude of the response. Both the absolute amplitude and the amplitude difference between the left and right sides were significantly elevated in the PSH-positive group, with P values below 0.001. Among the 75 patients in whom a response was elicitable, the researchers built a multivariable logistic regression model that simultaneously accounted for age, score on the Coma Recovery Scale-Revised, right and left amplitudes, and the amplitude difference, confirming that the model suffered from no significant multicollinearity. In that analysis, only the amplitude difference remained independently associated with PSH, with an odds ratio of 2.08 for every 0.1 millivolt increase and a 95 percent confidence interval spanning 1.49 to 3.45.

The diagnostic performance was even more impressive. Receiver operating characteristic analysis, a standard method for evaluating how well a continuous measure separates two groups, showed that the amplitude difference alone achieved an area under the curve of 0.96, with a confidence interval of 0.93 to 0.998, a level the authors describe as excellent. In practical terms, a test with an area under the curve of 0.96 distinguishes affected from unaffected individuals with near-perfect accuracy, approaching the performance of an ideal classifier.

The researchers also performed a sensitivity analysis designed to include all 124 patients rather than only the subset with elicitable responses, coding the absence of a response as an amplitude of zero. This more conservative analysis told a somewhat different but complementary story. In this broader cohort, younger age, lower Coma Recovery Scale-Revised scores, and the amplitude difference were each independently associated with PSH, with the amplitude difference carrying an odds ratio of 1.47 per 0.1 millivolt. The amplitude difference alone yielded good diagnostic accuracy, with an area under the curve of 0.77. Notably, combining age, consciousness scale score, and the amplitude difference produced the highest accuracy of any model tested, with an area under the curve of 0.888. This suggests that the electrical measurement is most powerful when integrated with established clinical variables, particularly in settings where the response cannot be reliably elicited.

The findings carry important implications for the management of this vulnerable population. Because PSH episodes drive metabolic demand, raise intracranial pressure, and can hamper neurorehabilitation, early identification matters. A tool that requires only surface electrodes, a stimulator, and a few minutes of recording time could be performed at the bedside without transporting patients or exposing them to radiation. It could also help resolve the frequent diagnostic uncertainty in which PSH is confused with infection or other complications, a confusion that previous studies have documented even in patients with brainstem stroke. Moreover, the involvement of hypothalamic and brainstem circuitry in PSH pathophysiology, supported by diffusion tensor imaging and lesion-mapping studies, fits with the idea that sympathetic outflow measured at the skin could serve as a window onto central autonomic dysregulation.

The authors caution, as their study design demands, that the work is retrospective and observational. Causality cannot be established, and the coding of absent responses as zero millivolts in the sensitivity analysis represents an assumption that future prospective studies should refine. The population studied was drawn from a single rehabilitation setting in Nanjing, and validation in independent, multi-center cohorts will be needed before the amplitude difference can be adopted as a routine diagnostic threshold. Questions also remain about whether the measure tracks PSH severity over time or predicts response to treatment, avenues the researchers and others may pursue next.

Nevertheless, the study adds a compelling piece to a growing body of evidence that peripheral electrophysiology can illuminate central autonomic dysfunction. For families and clinicians navigating the long and uncertain road of disorders of consciousness, a reproducible, inexpensive marker that flags paroxysmal sympathetic hyperactivity could translate into earlier treatment, better-controlled episodes, and potentially improved rehabilitation outcomes. The work was supported by the National Key Research and Development Program of China and several Jiangsu Province research programs, and the authors report no conflicts of interest. If validated prospectively, the sympathetic skin response amplitude difference may become a standard component of the autonomic assessment in patients who cannot speak for themselves but whose nervous systems, as this research shows, still broadcast unmistakable signals.