After surviving acute brain injury, patients can develop paroxysmal sympathetic hyperactivity (PSH), a syndrome of episodic physiologic hyperactivation manifesting in fevers, diaphoresis, tachycardia, tachypnea, hypertension, and dystonic posturing. Since the first description in 1929 by Wilder Penfield, numerous terms have been used to describe this syndrome: episodic autonomic instability, dysautonomia, autonomic dysregulation, central autonomic dysfunction, paroxysmal autonomic instability with dystonia (PAID), sympathetic storming, autonomic storming, dysautonomic crises, and diencephalic fits. First believed to be epileptic in nature and now believed to be a syndrome caused by a disconnection of inhibitory pathways, the etiology of PSH is still not well understood. The unifying principle describing this syndrome is the episodic nature of the dysregulation of the autonomic nervous system, manifesting as episodic sympathetic hyperactivity.

PSH can develop abruptly and last a short time period but can also be prolonged and a main driver of complications after acute brain injury. Delayed recognition leading to unnecessary workup and medications can further prolong hospitalization with potentially harmful results to patients. Additionally, uncontrolled symptoms can lead to secondary brain injury from hypertension, hyperthermia, cardiac damage, and even death.

The absence of a unified diagnostic criterion, the unclear etiology, and the multiple different causes of PSH has hindered the study of the syndrome. There are widely differing estimates of prevalence of PSH from 8% to 33% of patients admitted to the intensive care unit (ICU), reflecting the differences in population of patients.

The cause of brain injury is an important risk factor for the development of PSH. Most reported cases of PSH result from traumatic brain injury (TBI) (80%), followed by hypoxic brain injury (10%) and stroke (5.4%). The main risk factor for developing PSH after acute brain injury is the severity of the initial brain injury, younger age, and male gender. Although TBI may be the etiology for most cases of PSH, patients with other diseases may actually be at a higher risk for PSH. For instance, N-methyl-D-aspartate (NMDA) receptor-associated encephalitis is characterized by an aggressive and difficult to treat PSH-like syndrome.

Most believe PSH is caused by a functional disconnection leading to unbalanced activation of brain stem systems controlling the autonomic nervous system. Brain regions implicated range from the cerebral cortex to the anterior hypothalamus to the medulla and the connections in between. Regardless of the lesion location, the final common pathway is an imbalance of adrenergic outflow.

The Excitatory-to-Inhibitory Ratio (EIR) Model has been used to explain the pathophysiology of PSH and it takes into account the hypersensitive, overreactive nature of the responses to normal stimuli. Autonomic efferents at the level of the spinal cord are modulated centrally by a balance of sympathetic and parasympathetic inputs from higher brain stem nuclei. Afferents from the spinal cord can modulate this balance in response to stimuli from the environment. The EIR model proposes that the afferent stimuli from the spine have an allodynic tendency, which is normally controlled by tonic inhibitory drive from diencephalic centers. Damage to these inhibitory centers or their inhibitory processes down to the mesencephalon releases the inhibition of the allodynic tendency. Once the tonically inhibitory cycle is broken, there is a positive feedback loop that produces sympathetic overactivity to any afferent stimuli. This model explains how a normally nonnoxious stimulus can become a very noxious stimulus associated with an uncontrolled sympathetic response.

Imaging studies have shown that injury to the deep brain structures, periventricular white matter, corpus callosum, diencephalon, or brain stem may be associated with the development of PSH. PSH is associated with an increased number of lesions in the midbrain and upper pons compared with number of lesions in cerebral cortex, subcortex, corpus callosum, and diencephalon. Bilateral diencephalic lesions have also been attributed to PSH in hypoxic-ischemic encephalopathy. The evidence from imaging studies showing damage to brain stem structures emphasizes the importance of the diencephalic and mesencephalic regions to the pathophysiology of PSH.

PSH usually occurs, or at least is noticed, once patients are being weaned off of continuous intravenous sedation and they begin to awaken. Usually, it occurs in patients with a depressed mental status and episodes are associated with worsening mental status. The clinical manifestation of PSH define the syndrome: Episodic increases in heart rate, blood pressure, respiratory rate, temperature, diaphoresis, at times with pupillary dilatation, and motor hyperactivity manifested in abnormal posturing and dystonic movements. Episodes of exacerbation may last from minutes to hours and can occur several times a day or in refractory cases nearly continuously. PSH can be difficult to differentiate from opiate withdrawal or agitation from mechanical ventilation. It may persist into the rehabilitation phase and last weeks to months after the injury. In severe cases, it may persist for a year.