Post Head Injury Autonomic Complications 

Updated: Mar 29, 2019
Author: Stephen Kishner, MD, MHA; Chief Editor: Consuelo T Lorenzo, MD 



Autonomic dysfunction syndrome (ADS) is reported in cases of traumatic brain injury (TBI), hydrocephalus, brain tumors, subarachnoid hemorrhage, and intracerebral hemorrhage. ADS is rarely reported without an identified cause. In ADS, altered autonomic activity results in hypertension, fever, tachycardia, tachypnea, pupillary dilation, and extensor posturing. In an effort to more precisely characterize this syndrome, two other terms for it—paroxysmal autonomic instability with dystonia (PAID) and paroxysmal sympathetic hyperactivity—have come into use.

PAID occurs as a result of severe brain injury (Rancho level ≤IV) from multiple causes, including TBI, hydrocephalus, brain tumors, subarachnoid hemorrhage, and intracerebral hemorrhage. PAID is a syndrome attributed to altered autonomic activity. Clinical manifestations consist of a temperature of 38.5º C, hypertension, a pulse rate of at least 130 beats per minute, a respiratory rate of at least 140 breaths per minute, intermittent agitation, and diaphoresis; these are accompanied by dystonia (rigidity or decerebrate posturing for a duration of at least 1 cycle per d for at least 3 d).

Other issues that can occur because of autonomic dysregulation are electrocardiographic alterations, arrhythmias, increased intracranial pressure (ICP), hypohidrosis, subnormal temperature in flaccid limbs, and neurogenic lung disease. Usually episodic, PAID first appears in the intensive care setting but may persist into the rehabilitation phase for weeks to months after injury in individuals who remain in a low-response state.

Although migraine has also been associated with autonomic dysfunction, a study by Howard et al, using the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire, reported that, in comparison with migraine sufferers, such dysfunction was greater in individuals with persistent posttraumatic headaches (PPTHs) caused by mild TBI. The study also found evidence that in persons with PPTHs, the number of TBIs are positively correlated with total weighted COMPASS-31 scores, while years lived with headache and headache frequency were positively associated with the questionnaire’s vasomotor domain subscores.[1]

See also the following related Medscape Drugs & Diseases topics:

  • Head Trauma

  • Classification and Complications of Traumatic Brain Injury

  • Post Head Injury Endocrine Complications

  • Traumatic Brain Injury: Definition, Epidemiology, Pathophysiology

See also the related Medscape resource Trauma.


The cause of ADS is dysregulation of the autonomic nervous system (ANS) due to injury to 1 or more parts of the brain that contribute to the ANS.[2, 3, 4] Cortical areas that influence the activity of the hypothalamus include the orbitofrontal, anterior temporal, and insular regions. Subcortical areas that influence the hypothalamus include the amygdala (particularly the central nucleus), the peri-aqueductal gray, the nucleus of the tractus solitarius, the cerebellar uvula, and the cerebellar vermis. Damage to these areas releases control of vegetative functions and results in dysregulation of overall autonomic balance. The complex interaction of these regions is illustrated by the control of temperature and blood pressure.

The pre-optic area of the hypothalamus contains heat-sensitive neurons. Temperature elevation is met with cooling measures: sympathetic activation of sweat glands is augmented, and sympathetic vasoconstriction is inhibited. Increased antidiuretic hormone (ADH) secretion causes water retention and greater sweating.

Cold is detected by two mechanisms; initially, a decreased rate of firing of the pre-optic heat-sensitive neurons is interpreted as a sensation of cold, and activation of specific cold receptors also ensues. Sensations of cold are carried to the posterior hypothalamus by the spinothalamic tract, and the sympathetic nervous system is then stimulated to produce increases in body temperature. This occurs through shivering, vasoconstriction, pilo-erection, and inhibition of sympathetically induced sweating. Integration of cold sensory input and the warm sensory input from the anterior hypothalamus occurs in the posterior hypothalamus. Pyrogens alter the set point of the hypothalamic control, and raising it promotes fever.

Isolated impairment of thermoregulation after extremely severe brain injury has been reported. In this reported case, episodic elevations in temperature during the summer months were reported. Upon controlled manipulation of the environment, failure to manage temperature elevations was documented. Even paradoxical responses to temperature decreases were noted. Other features of dysautonomia were not described in this case.

The anterior and the posterior hypothalamus interact with the brainstem through multiple feedback loops. The midbrain tegmentum gives rise to descending pathways that inhibit a thermogenic drive from the brainstem. Decerebrating lesions result in hyperthermia in rats. Fever in patients with brain injury is most often due to infection. Less frequently, fever is due to deep venous thrombosis (DVT) or is caused by medications, and even less frequently, fever results from impaired autonomic regulation due to the injury.

In addition, dystonia leads to a hypermetabolic state and further temperature elevations. The proposed mechanism for this occurs when lesions in the midbrain block interfere with normal inhibitory signals to the pontine and vestibular nuclei, thus making them tonically active. A facilitation signal is then transmitted to the spinal cord control circuits. This results in a hyperexcitable spinal reflex that can be evoked by sensory input signals that have thresholds below those required for motor excitation.

Blood pressure is controlled by the interaction of the following cortical and subcortical areas of the brain:

  • Hypothalamus

  • Thalamus

  • Amygdala

  • Orbitofrontal cortex

  • Nucleus ambiguus

  • Nucleus tractus solitarius

The orbitofrontal cortex is believed to promote parasympathetic activity and to inhibit sympathetic activity. Dysregulation occurs when these areas are damaged; it causes a cortically provoked release of adrenomedullary catecholamines during ADS episodes, resulting in increased blood pressure, tachycardia, and tachypnea. The previous cases of episodic elevations of blood pressure after TBI contrast with the more constant and persistent hypertension that frequently develops but remains consistent with ADS. The fluctuations have been found early in the course of the episodic cases (the second day). In a study by Blackman and colleagues, it was noted that plasma catecholamines were elevated at the time of the blood pressure fluctuations.[5]

In experimentally induced brain trauma, an elevation of catecholamine and acetylcholine levels have occurred. Hypotension, cardiac arrhythmias, or hypertension can result. Milder brain injuries yield an elevation of acetylcholine levels. More severe injuries yield an elevation of catecholamine levels in magnitudes that are proportional to the severity of injury. (A study by Fernandez-Ortega et al showed a rise in catecholamine levels of 200-300% during paroxysms in patients with ADS, with adrenocortical hormone levels also increasing, but to a lesser degree.[6] ) Coincidentally, the catecholamine levels are inversely proportional to the Glasgow Coma Scale (GCS; see the Glasgow Coma Scale calculator) scores soon after TBI.




Following brain injury, about 15-33% of patients acutely develop ADS.[7] Within the population of individuals with severe TBI, dysautonomia syndrome is not more common for any particular subset of GCS scores, nor does the frequency increase according to age, sex, or mode of injury. Neuroimaging has revealed more frequent evidence of diffuse axonal injury (DAI) and brainstem injury in persons who develop dysautonomia.


Autonomic dysfunction is associated with increased morbidity. Although the length of stay in acute services is not different from that of persons without ADS, the length of stay in rehabilitation services is longer on the average. The risk of myocardial infarction (MI) and secondary injury due to hemorrhage or elevated intracerebral temperature is of concern. ADS is also associated with less favorable functional outcomes.[8]




ADS usually occurs in the setting of severe TBI associated with DAI. ADS must be distinguished from other syndromes presenting similarly; a diagnosis of ADS is one of exclusion, because there are no pathognomonic tests or findings.

The other syndromes to consider include neuroleptic malignant syndrome, serotonin syndrome, malignant hyperthermia, and thyroid storm.[3, 9]

The use of neuroleptics generally is contraindicated in patients with brain injuries, and so classic neuroleptic malignant syndrome is unlikely to be encountered in these patients. However, withdrawal of premorbidly used dopaminergic agents or the use of metoclopramide can precipitate neuroleptic malignant syndrome, so this condition must be considered.

The use of serotonergic agents is common in persons with brain injury; consideration of serotonin syndrome is therefore essential.

Malignant hyperthermia mainly occurs after surgery during which there was exposure to anesthetic agents, particularly succinylcholine. Malignant hyperthermia in the rehabilitation setting most often is seen in patients with spinal cord injury, because of their increased susceptibility.

Thyroid storm is a potential complication of trauma to the neck, if excess thyroid hormone is released from the injured thyroid gland.

An observational study by Hinson et al indicated that early fever following a TBI, particularly within the initial 24 hours, may predict the onset of ADS.[10]


Patients with ADS present with a combination of typical physical findings. The elevation of temperature may vary in severity from low-grade to high fever. Fever frequently and justifiably prompts a detailed search for infectious etiologies. The individual's temperature may vary from being elevated to being within the reference range, or it may stay elevated. One important aspect of elevated temperature in persons with TBI is that intracerebral temperature may significantly exceed measured body temperature due to impaired blood flow in the injured area. Thus, temperature control should be prompt and aggressive in individuals with TBI. Cephalosporins, ibuprofen, and H2 blockers help to reduce the fever and/or help to treat the cause of fever; therefore, they frequently are used in patients with TBI.

Findings of ADS, which may be prominent during the intensive care stages of the case, include the following:

  • Hypertension

  • Fever

  • Tachycardia

  • Tachypnea

  • Pupillary dilation

  • Extensor posturing

  • Diaphoresis

The combination of all findings does not always occur. Tachycardia, fever, and hypertension often are the main presenting signs.

Because the syndrome includes features in common with acute infection, ruling out infection is paramount.


The cause of ADS is dysregulation of the ANS due to injury to 1 or more parts of the brain that contribute to the ANS. (See Pathophysiology.)



Diagnostic Considerations

These include the following:

  • Lethal catatonia

  • Malignant hyperthermia

  • Infection

  • Serotonin syndrome

Differential Diagnoses



Laboratory Studies

Appropriate lab studies include the following:

  • Complete blood count (CBC) - To reveal potential infection (Elevated white blood cell and/or platelet counts may signal infection.)

  • Blood cultures - To rule out sepsis

  • Sputum cultures - To rule out pneumonia

  • Urine cultures and urinalysis - To rule out urinary tract infection

  • Sputum Gram stain - To rule out infection

  • Plasma catecholamine levels - May be of interest acutely but are not required for the diagnosis

  • Thyroid panel - To rule out thyroid storm

  • Random chemistry panel - To rule out neuroleptic malignant syndrome

  • Plasma creatine kinase and troponin levels - To rule out acute MI, neuroleptic malignant syndrome, and serotonin syndrome

Imaging Studies

Appropriate imaging studies include the following:

  • Chest radiograph - To rule out pneumonia and atelectasis

  • Duplex ultrasonogram - To rule out DVT

  • Electrocardiogram (ECG) - To rule out MI

  • Head computed tomography (CT) or magnetic resonance imaging (MRI) scan - To rule out abscess, encephalitis, or hydrocephalus


Lumbar puncture may be performed to rule out meningitis.



Rehabilitation Program

Physical Therapy

Severe episodes of ADS may preclude or delay any of the components of a contemporary, multidisciplinary rehabilitation program. Physical therapy sessions may have to be held episodically because labile blood pressure, ICP, heart rate, and temperature may preclude participation. Of course, it is preferable to continue not only with passive range of motion (PROM) but also with as much of the functional program as possible; monitor these symptoms during therapy.

Occupational Therapy

Continue occupational therapy as regularly as possible, with the same considerations as for physical therapy.

Speech Therapy

Patients with ADS usually have severe impairment of alertness. Thus, speech therapy may not yet be appropriate.

Medical Issues/Complications

Severe muscle rigidity can result in muscle rupture or in rhabdomyolysis. Fever is viewed as a source of secondary injury in individuals with TBI, because marginal cerebral blood flow fails to provide for normal brain cooling. This may result in a brain temperature that is higher than the measured core temperature. The resulting increase in metabolic demand may not be met by increasing blood flow, so local areas of hypoxia and further neuronal dysfunction and death ensue.

Hypertension and tachycardia could theoretically increase the risk of developing hemorrhage from injured blood vessels. Prolonged, severe diaphoresis may result in dehydration and in electrolyte abnormalities.

Surgical Intervention

Surgery is not part of the treatment for ADS.


Consultation from infectious disease experts is appropriate, but it is not always necessary in this context.



Medication Summary

Because a wide array of neurotransmitters are involved in the pathways of autonomic control, a wide array of medications exert an influence on this system.[4, 11, 12, 13]

The effectiveness of chlorpromazine and bromocriptine (a dopamine antagonist and a dopamine agonist, respectively) in the treatment of ADS illustrates the complexity of the neurotransmitter regulation pathways and the variability of the lesions that can cause the syndrome.

Propranolol, a lipophilic beta blocker, has successfully been used to control ADS.[14] Beta blockade has been shown to decrease hypertension and hemodynamic abnormalities. Beta blockade does not alter diaphoresis, which is mediated via sympathetic cholinergic neurons. As with all beta blockers, use caution when using in patients with diabetes and asthma.

Clonidine has been effective in normalizing plasma epinephrine and in reducing plasma norepinephrine levels, effectively decreasing blood pressure. Alpha-adrenergic and beta-adrenergic blockers prevent electrocardiographic changes and cardiac arrhythmias associated with TBI. However, clonidine is known to cause sedation.

Bromocriptine has been used to help combat the hyperthermia and diaphoresis that occur with ADS.[15, 16]

Dantrolene has been a useful treatment for extensor posturing but has shown minimal effect against other components of ADS.[15]

Morphine has been effective in abolishing ADS, as has naltrexone. Gabapentin has been found to be effective in controlling the autonomic symptoms and the dystonic posturing of ADS.[13]

Beta blockers

Class Summary

May block effect of vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing the membrane, and increasing the release of oxygen to tissues.

Propranolol (Inderal)

Beta blockers oppose the multisystemic effects of excessive adrenergic tone.

Dopamine agonists

Class Summary

Inhibit noxious input to spinal cord.

Bromocriptine (Parlodel)

Central dopamine excess and central dopamine insufficiency are viewed as contributing to dysregulation of autonomic pathways. Agonists or antagonists may be helpful in treating ADS.

Chlorpromazine (Thorazine)

Mechanisms include blocking postsynaptic mesolimbic dopamine receptors, anticholinergic effects, and depression of RAS. Blocks alpha-adrenergic receptors and depresses release of hypophyseal and hypothalamic hormones. As a rule, however, dopamine antagonists are avoided in patients with TBI

Muscle relaxants

Class Summary

Modulate muscle contractions.

Dantrolene (Dantrium)

Stimulates muscle relaxation by modulating skeletal muscle contractions at a site beyond the myoneural junction and by acting directly on muscle itself. Most patients respond to 400 mg/d or less.


Class Summary

Pain control is essential to quality patient care. Analgesics such as opioids ensure patient comfort, promote pulmonary toilet, and have sedating properties, which are beneficial for patients who have sustained trauma or injuries.

Morphine (Duramorph, Astramorph, MS Contin, MSIR, Oramorph)

Opioid receptor system is involved in the regulation of central autonomic pathways. ADS has been found to be responsive to narcotics. As a rule, however, narcotics and other sedating medications are avoided in patients with TBI.

Naltrexone (ReVia)

Cyclopropyl derivative of oxymorphone that acts as a competitive antagonist at opioid receptors. ADS has been found to be responsive to naltrexone.


Class Summary

These agents terminate clinical and electrical seizure activity of the brain.

Gabapentin (Neurontin)

Membrane stabilizer, a structural analogue of inhibitory neurotransmitter gamma-amino butyric acid (GABA), which paradoxically is thought not to exert effect on GABA receptors. Appears to exert action via the alpha(2)delta1 and alpha(2)delta2 auxiliary subunits of voltage-gaited calcium channels.



Further Outpatient Care

The outpatient setting is rarely the context for ADS to present.

The usual outpatient therapy programs and the typical concerns regarding family functioning and community re-integration issues pertain to outpatient care.

Rarely, continued medication use is required long term. Thus, monitoring for common side effects and minimizing medications that impair cognition are required.

Further Inpatient Care

The length of stay in rehabilitation is usually reported as being longer for those patients who experience ADS. Other than this observation, no specific alterations from a typical multidisciplinary, acute inpatient rehabilitation program are expected in this population.

If actual myocardial damage is identified as a result of the syndrome, observe appropriate cardiac rehabilitation principles during the head injury rehabilitation program.


Transfer to the neurosurgery service or an ICU setting is rarely necessary for patients with ADS, although it is conceivable in the event of dangerously high blood pressure and tachycardia.


Increased sensitivity of neurons to elevated temperature occurs during the acute phase of TBI. In animals, functional differences are discernible between those with temperatures in excess of 38 º C and those whose temperature is maintained below 38 º C. In one study, 73% of patients with dysautonomia had temperatures above 38 º C for 2 weeks after injury, contrasted with only 18% of patients without dysautonomia.[8]

Posturing increases energy expenditure by 150-250%.[8] These features increase the risk that persons with dysautonomia will sustain secondary injury to the brain.


Although patients who have dysautonomia can make functional gains, their outcomes—as measured by Glasgow Outcome Scale (GOS) and Functional Independence Measure (FIM) scores—have been found to be poorer than those of patients without dysautonomia.[17] Individuals with dysautonomia also have more difficulty with memory and experience longer periods of posttraumatic amnesia (PTA) than do patients without dysautonomia. Research has found that for patients with dysautonomia, the duration of ICU stay is the same as that recorded for controls but that the length of rehabilitation stay is greater. On average, the duration of the dysautonomia (as measured by cessation of sweating) has been found to be about 75 days.

A study by Hendén et al suggested that measurement of heart rate variability and baroreflex sensitivity can predict late neurologic outcomes in patients with isolated TBI. The study involved 19 patients with TBI who required mechanical ventilation, sedation, and analgesia. The investigators found that those with significantly depressed measures of heart rate variability and baroreflex sensitivity tended after 1 year to demonstrate poor scores (< 5) on the Glasgow Outcome Scale-Extended (GOSE), with the difference being unrelated to the severity of TBI at admission or the extent of sedative or analgesic drug use.[18]

A retrospective study by Pozzi et al indicated that in pediatric patients with acquired brain injury, the length of coma and the mortality rate are greater in those experiencing paroxysmal sympathetic hyperactivity (also known as paroxysmal autonomic instability with dystonia [PAID]). The study involved 407 pediatric patients with postacute acquired brain injury, including 26 with paroxysmal sympathetic hyperactivity.[19]

Patient Education

Explaining ADS to the patient is rarely an issue, because patients are usually cognitively compromised at the time of manifestation of the syndrome. However, reducing the fear of family members is important. The family should understand that this syndrome is seen in persons with brain injury, that it is almost always controllable with medications, and that it does not usually remain a long-term problem.