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Paroxysmal sympathetic hyperactivity (PSH) is a syndrome that causes episodes of increased activity of the sympathetic nervous system. Hyperactivity of the sympathetic nervous system can be seen by an increased heart rate, increased respiration, increased blood pressure, diaphoresis, and hyperthermia. Previously this syndrome has previously been identified as general dysautonomia, but now is considered a specific form of it. It has also been referred to as paroxysmal sympathetic instability with dystonia, or PAID, and sympathetic storm. Recently, however, studies have adopted the name paroxysmal sympathetic hyperactivity to ensure specificity. PSH is observed more in younger patients. It is also seen more commonly in men than women. There is no known rational reason why this is the case, although it is suspected pathophysiological links may exist. In patients surviving traumatic brain injury, the occurrence of these episodes reaches one in every three. PSH can also be associated with severe anoxia, subarachnoid and intracerebral hemorrhage, and hydrocephalus.

Symptoms

Characteristics of paroxysmal sympathetic hyperactivity include:

• fever
• tachycardia
• hypertension
• tachypnea
• hyperhidrosis or diaphoresis
• dystonic posturing
• pupillary dilation
• flushing

In cases where PSH episodes develop post-injury, specifically TBI, symptoms typically develop relatively quickly, usually within a week. One study found that the mean onset of symptoms was 5.9 days. Episodes vary in duration and occurrence. Episodes can last as little as a few minutes or as long as ten hours, and they can occur multiple times a day. The same study aforementioned found the mean of episode duration to be 30.8 minutes occurring fie to six times a day. Episodes can occur natural or can arise from external triggers. Some common triggers include pain, body turning or movements, and bladder distention (observed in patients in intensive care units with the use of catheters). The symptoms of this syndrome can last from weeks to years. As episodes persist over time, they have been found to become less frequent in occurrence, but occur for prolonged periods.

Causes/Pathophysiology

The causes of PSH are numerous. Traumatic brain injury, hypoxia, stroke, anti-NMDA receptor encephalitis (although further association are being explored), injury of the spinal cord, and many other forms of brain injury can cause onset of PSH. One case study recorded a one year old girl who developed paroxysmal sympathetic hyperactivity from intracranial tuberculoma and also hydrocephalus. It is observed that these injuries cause PSH, but the pathophysiology is not very well understood.

A considerable number of theories exist as to the pathophysiology of PSH:

• Epileptiform discharges in the diencephalon or the interbrain is a potential theory for PSH. These discharges can be identified using electroencephalography.
• Increased intracranial pressure is another. Currently, this theories seems to be less likely than the others, at least not in all cases. There have been many cases where intercranial pressure had no correlation to PSH episodes.
• Disconnection via lesions of the inhibitory efferent pathways from cortical and subcortical areas is a potential theory. This theory deals with inhibitory pathways being ablated or malfunctioning post-injury, meaning that sympathetic pathways from the cortical and subcortical areas is less controlled resulting in a 'sympathetic storm'.
• Excitatory-inhibitory models suggest that lesion in mesencephalic area lessens inhibition pathways from the brain. This is thought to lead to pathways that are usually non-nociceptive becoming nociceptive which results in the peripheral sympathetic nervous system being over activated.
• Another theory deals with malfunction of the brain stem, specifically, excitatory centers in the brain stem. In this case, rather than inhibition pathways malfunctioning and allowing sympathetic pathways to propagate unhindered, excitatory centers are up-regulated increasing sympathetic activity.

Diagnosis

Diagnosing PSH can be very difficult due to the lack of common terminology in circulation and a lack of diagnostic criteria. Dysautonomia, central autonomic dysfunction, paroxysmal autonomic instability with dystonia, autonomic storming, dysautonomic crisis, and autonomic dysregulation are all examples of terms that are used and referred to professionally. Each of those terms have varying diagnostic criteria as well. Paroxysmal sympathetic hyperactivity and mixed autonomic hyperactivity are confused and variable across the literature. Standardization is needed to be able to accurately diagnosis and treat patients universally. Different systems for diagnosis have been proposed, but a universal system has not been embraced. One example of a posed systems confirms diagnosis following observation of four of the six following symptoms: fever greater than 38.3 degrees Celsius, tachycardia classified as a heart rate of 120 bpm or higher, hypertension classified as a systolic pressure higher than 160 mmHg or a pulse pressure higher than 80 mmHg, tachypnea classified as respiration rate higher than 30 breaths per minute, excess sweating, and severe dystonia. Ruling out other diseases or syndromes that show similar symptoms is also imperative because PSH shows no radiological features. Sepsis, encephalitis, neuroleptic malignant syndrome, malignant hyperthermia, lethal catatonia, spinal cord injury (not associated with PSH), seizures, and hydrocephalus (although this can cause PSH episodes, it is not the reason PSH occurs) are examples of diagnoses that should be considered.

Prognosis

Patients who develop PSH after traumatic injury have longer hospitalization and longer durations in intensive care. They often are more vulnerable to infections and spend longer times on ventilators, which can lead to an increased risk of lung diseases. PSH does not effect mortality rate, but it effects the length of time in which the patient can recover form injury. It often takes patients who develop PSH longer to reach similar levels of brain activity compared to patients who do not develop PSH, although they do eventually reach the same levels.

Treatment/Management

Various methods are used to treat PSH. Medications are used to end episodes or prevent their occurrence. Hyperbaric oxygen treatment has been explored as well. Many other treatments have been used, but their success is measured on a case-by-case basis. It is difficult to find successful treatments with qualitative results or efficacy that are non-case studies.

Pharmacological Intervention

The two most common pharmaceuticals used in the treatment of paroxysmal sympathetic hyperactivity are morphine sulfate and beta-blockers. Morphine is useful in helping halt episodes that have started to occur. Beta-blockers are helpful in preventing the occurrence of 'sympathetic storms'. Other drugs that used and have in some cases been helpful are dopamine agonists, opiates, benzodiazepines, clondine, and balcofen. Chlorpromazine and Halopridol, both dopamine agonists, in some cases have worsen PSH symptoms. These drugs are in use currently for treatment, although the exact pathways and helpfulness are speculative.

Morphine

Morphine has been found to most effective in aborting episodes; sometimes it is the only medication that can combat the sympathetic response. Morphine helps lower respiration rates and hypertension. It is given in doses of two milligrams to eight milligrams but can be administered up to twenty milligrams. Nausea and vomiting are common side effects. Withdrawal is sometimes seen in patients.

Beta-blockers

Non-selective beta-blockers are the most effective in reducing the frequency and severity of PSH episodes. They help decrease the effect of circulating catecholamines and lower metabolic rates, which are high in patients during episodes. Beta-blockers also help in reducing fever, diaphoresis, and in some cases dystonia. Propanolol is a common beta-blocker administered due to the fact that it penetrates the blood-brain barrier relatively well. Typically it is administered in twenty milligrams to sixty milligrams every four to six hours.

Other Medications

Clonidine is an alpha receptor agonist that helps reduces sympathetic activity leaving the hypothalamus and reduces circulating catecholamines. It is helpful in lowing blood pressure and heart rate, but it does not show much effect on other symptoms. It may also increase sympathetic inhibition in the brain stem. Bromocriptine is a dopamine agonist that helps lower blood pressure. Its effects are modest, but they are not well understood. Baclofen is a GABA agonist that helps control muscle spasms, so it is helpful in treating dystonia. Benzodiazepines bind to GABA receptors and work as muscle relaxants. Benzodiazepines combat high blood pressure and respiratory rates. However, benzodiazepines are associated with glaucoma. Gabapentin inhibits neurotransmitter release in the dorsal horn and various areas of the central nervous system. It helps treat mild symptoms and can be tolerated for longer periods of time. Dantrolene helps combat dystonia and fever by effecting muscle contraction and relaxation cycles. It hinders the release of calcium from the sarcoplasmic reticulum. It causes decreases in respiration, but it can be very dangerous for the liver. Again, these treatments are usually only seen case by case, and their efficacy is speculative.

External Links

• Dysautonomia International
• Dysautonomia Information Network
• Dysautonomia Foundation