Neurocritical Care

20. Paroxysmal Sympathetic Hyperactivity

A 22-year-old woman rolled over with her car while driving unrestrained on an icy road. She was comatose at the scene, and she was intubated. Initial head CT scan revealed bifrontal contusions and a small subdural hematoma overlying the right cerebral convexity without significant mass effect. She remained comatose with extensor posturing. An intraparenchymal pressure monitor was inserted. Over the subsequent days the intracranial pressures ranged mostly between 15 and 25 mmHg, requiring occasional doses of 20% mannitol and 10% hypertonic saline to keep it under control. Repeat head CT scan on day three showed the expected evolution of the frontal contusions with progression of the surrounding edema.

Seven days after the injury she starts to exhibit recurrent episodes of sinus tachycardia, tachypnea, hypertension, profuse sweating, and extensor posturing, She is also hyperthermic during the episodes. They are not associated with major episodes of oxygen desaturation, and arterial blood gases do not reveal hypoxia. Blood cultures are negative, and serum lactic acid and creatine kinase levels are normal. Electroencephalogram does not demonstrate epileptiform activity during the spells. When severe, these episodes are associated with transient elevations of intracranial pressure beginning after the onset of the changes in vital signs.

What do you do now?

The clinical presentation illustrated by this case is characteristic of paroxysmal sympathetic hyperactivity (PSH). All too frequently PSH remains unrecognized and goes untreated. Physicians who are unfamiliar with this complication may consider these manifestations a mere epiphenomenon of severe brain injury, may obsessively focus on searching for an infectious source or, worse, treat it as seizures with multiple doses of benzodiazepines. PSH can cause major problems in itself. In comatose patients with reduced intracranial compliance, PSH episodes can produce marked rises in intracranial pressure. Also, when PSH is not adequately treated, the severity of the dystonia can result in contractures and make later rehabilitation efforts difficult.

These spells, also known as “sympathetic storms” (or with the misnomer “diencephalic seizures”), are relatively frequent in patients with severe acute brain injury. They are most common in young patients with diffuse axonal traumatic brain injury, but we have also seen them after severe anoxicischemic encephalopathy, large intraparenchymal hemorrhages, subarachnoid hemorrhage, and acute hydrocephalus. Episodes of PSH can begin during the acute phase, often in comatose patients. PSH can also continue into the subacute phase or become first manifest in this later phase and diagnosed by brain rehabilitation specialists.

There is lack of uniformity in the nomenclature and definition of PSH. The denomination PSH includes the three terms that describe the main features. They are rapid and episodic (i.e., paroxysmal) manifestations of excessive sympathetic activity. Patients become tachycardic, hypertensive (with increased pulse pressure), tachypneic, febrile, diaphoretic, and often they develop markedly increased muscle tone, which may result in dystonic postures. Pupillary dilatation, piloerection, and skin flushing can also be seen. Spells of PSH are often provoked by stimulation, but the degree of stimulation necessary to trigger the spells can be minimal in the most sensitive patients, and episodes can also occur without apparent provocation.

Proposed diagnostic criteria for severe episodes of PSH are shown in Table 20.1.

TABLE 20.1 Diagnostic Criteria for Paroxysmal Sympathetic Hyperactivity

Clinical Feature

Diagnostic parameter


Greater than 140 beats per minute


SBP greater than 160 mmHg


Greater than 39 degrees Celsius


Greater than 30 breaths per minute


Markedly increased

Dystonic posturing


SBP, systolic blood pressure

The spells are typical and the diagnosis should be readily apparent to the experienced examiner. However, it is always prudent to consider other causes of sudden, exaggerated sympathetic response. Pulmonary embolism and early sepsis with bacteriemia should come to mind. However, pulmonary embolism is distinctly associated with hypoxia and increased alveolar-arterial oxygen gradient, unlike PSH. Meanwhile, sepsis does not present with hypertension, as PSH does. Other pertinent differential diagnoses are listed in Table 20.2.

There are effective therapies for this condition (Table 20.3) and there are also drugs that should be avoided as they can exacerbate the problem. Acutely, the manifestations of PSH respond best to bolus doses of morphine sulfate (2–8 mg intravenously). This favorable response is not related to the analgesic effect of opiates, but rather to modulation of central pathways responsible for the autonomic dysfunction. The response to morphine is rapid and quite reliable in aborting spells of PSH, but occasionally we have encountered patients who required much larger doses than usual (up to 10–15 mg). In these patients a continuous opiate infusion may be helpful.

Other effective medications for the treatment of PSH include noncardioselective beta-blockers (such as propranolol), clonidine (a central alpha 2-receptor agonist), dexmedetomidine (another central alpha 2 receptor agonist), bromocriptine (a dopamine D2-receptor agonist), baclofen (a GABAB receptor agonist), benzodiazepines (GABAA receptor agonist), and gabapentin (which binds GABA receptors and voltage-gated calcium channels in the dorsal horn of the spinal cord). In our experience, beta-blockers and clonidine are useful in controlling the tachycardia and hypertension, but less so for the dystonia. Baclofen and benzodiazepines (especially diazepam) do cause muscle relaxation, but may not improve the other hypersympathetic features. We have seen dramatic improvement in the frequency and severity of spells within days of starting gabapentin, which has become our first choice for the longer-term control of this disorder. We have not been impressed by the efficacy of bromocriptine. Antidopaminergic drugs, such as haloperidol, and sympathetic agonists need to be avoided.

TABLE 20.2 Differential Diagnosis of Paroxysmal Sympathetic Hyperactivity

To rule out

You should check

Pulmonary embolism

Arterial blood gases
CT angiogram of the chest


White blood cell count
Blood cultures
Serum lactic acid



Neuroleptic malignant syndrome

History of neuroleptic exposure
Serum creatine kinase
Response to dantrolene

Serotonin syndrome

History of use of proserotonin drugs
Serum creatine kinase
Response to cyproheptadine

Alcohol withdrawal

History of alcohol abuse
Response to benzodiazepines

Cushing response

Brain imaging

Autonomic dysreflexia from spinal cord injury **

Spinal cord imaging


Cerebrospinal fluid

Aneurysmal rebleeding in subarachnoid hemorrhage

Repeat brain imaging

*Typically associated with hypotension rather than hypertension

**Typically associated with bradycardia rather than tachycardia

Choosing the right medication to treat the spells is not enough, and other aspects of management are equally important. These patients sweat profusely and fluid intake should be adjusted to compensate for this marked increase in insensible losses and to prevent volume contraction. Fever must be aggressively treated with cooling measures as it has a negative impact on the acutely injured brain. It is best to minimize patient stimulation.

TABLE 20.3 Pharmacological Options for the Treatment of Paroxysmal Sympathetic Hyperactivity


ICP, intracranial pressure; IV intravenous

*Intrathecal baclofen can be useful in refractory cases with extreme dystonia.

How did we manage our patient? We treated her acutely with boluses of morphine, and she responded well. Her tachycardia and hypertension improved on low doses of propranolol. We also started her on gabapentin with a target dose of 1,800 mg per day. Ten days later her episodes of PSH had become much milder and infrequent and they were no longer manifested with dystonia.

PSH is often associated with poor neurologic outcome but not invariably so. The manifestations excessively increase the metabolic demand, risk increase in intracranial pressure, and may cause long-term complications. Because it is a relatively common and treatable complication in comatose patients, physicians need to be aware of it and be prepared to initiate effective therapy.


· PSH is not uncommon, especially in young patients with severe traumatic brain injury.

· The differential diagnosis is broad, but can be sorted out quickly by a focused evaluation. When the clinical signs are not characteristic consider pulmonary embolism, early sepsis, and seizures.

· Lack of recognition of PSH can lead to major complications, such as intracranial hypertension, dehydration, refractory fever, refractory surges of hypertension, and muscle contractures.

· Boluses of morphine sulfate are effective in aborting the episodes, propranolol and clonidine can help control the tachycardia and hypertension, baclofen and diazepam can improve the increased muscle tone.

· Gabapentin is very useful to achieve control of the sympathetic dysfunction in the long-term.

Further Reading

Baguley IJ, Heriseanu RE, Cameron ID, Nott MT, Slewa-Younan S. A critical review of the pathophysiology of dysautonomia following traumatic brain injury. Neurocrit Care 2008; 8:293–300.

Baguley IJ, Heriseanu RE, Gurka JA, Nordenbo A, Cameron ID. Gabapentin in the management of dysautonomia following severe traumatic brain injury: a case series. J Neurol Neurosurg Psychiatry 2007; 78:539–541.

Blackman JA, Patrick PD, Buck ML, Rust RS Jr. Paroxysmal autonomic instability with dystonia after brain injury. Arch Neurol 2004; 61:321–328.

Boeve BF, Wijdicks EF, Benarroch EE, Schmidt KD. Paroxysmal sympathetic storms (“diencephalic seizures”) after severe diffuse axonal head injury. Mayo Clin Proc 1998; 73:148–152.

Perkes I, Baguley IJ, Nott MT, Menon DK. A review of paroxysmal sympathetic hyperactivity after acquired brain injury. Ann Neurol 2010; 68,126–135.

Rabinstein AA. Paroxysmal sympathetic hyperactivity in the neurological intensive care unit. Neurol Res 2007; 29:680–682.

Rabinstein AA, Benarroch EE. Treatment of paroxysmal sympathetic hyperactivity. Curr Treat Options Neurol 2008; 10:151–157.