Jump to:



Paroxysmal Sympathetic Hyperactivity (PSH) is a syndrome of disproportionate and pathological sympathetic overreaction that can be triggered by nociceptive or environmental stimuli1 which occurs after severe acquired brain injury. It is characterized by episodic, simultaneous tachycardia, hyperthermia, hypertension, tachypnea, and diaphoresis, often accompanied by hypertonia and posturing1. PSH has been referred to by at least 31 separate terms in literature2, including diencephalic or autonomic seizures, brainstem attack, autonomic storming, paroxysmal hyperthermic autonomic dysregulation, and dysautonomia3.  


Paroxysmal Sympathetic Hyperactivity can occur after any brain lesion, from trauma, infection, hemorrhage, infarction, brain tumor, global anoxia-ischemia, autoimmune encephalitis, or degeneration. The clinical presentation does not appear to differ depending on the underlying etiology4.

A review of 349 case reports of PSH published before 2010 found that about 80% occurred after traumatic brain injury (TBI), about 10% occurred after hypoxic brain injury, and about 5% occurred after stroke; the remainder of cases had variable etiologies, including hydrocephalus, tumor, and infection5. It is a different entity from the autonomic dysreflexia that develops in spinal cord injury.

Epidemiology including risk factors and primary prevention

The estimated incidence of PSH in adults with TBI ranges from 8-33%5. The main risk factor for developing PSH after brain injury is increased severity of the injury; individuals with mild brain injuries typically do not develop PSH6.

Individuals who develop PSH tend to be younger in age and male5,7. In a study of 407 pediatric individuals with acquired brain injury, those who developed PSH also tended to be younger in age and male predominant1. In another study, patients with diffuse axonal injury (DAI) and brainstem lesions are at high risks8. Among patients with severe TBI, decreased fractional anisotropy in the splenium of the corpus callosum and posterior limb of the internal capsule is associated with occurrence of PSH9.


The pathophysiology of PSH is still poorly understood. Autopsy studies have not shown insight into an anatomic basis3.

One hypothesis proposes that structural damage sustained after acquired brain injury results in disruption of higher-order autonomic regulatory centers, which may include the brainstem, midbrain, and cortical centers10. This results in unregulated sympathetic activity, thus driving autonomic instability3,10.

Another hypothesis, known as the excitatory:inhibitory (EIR) model, proposes that a lesion in the inhibitory centers in the brainstems and diencephalon reduces tonic descending inhibition to afferent sensory information from spinal cord circuits. This results in the amplifications of normally non-nociceptive afferent sensory information from the periphery and leads to over-excitation of the sympathetic nervous system response3,11.

There is also evidence to support an association between PSH and catecholamine release, which could help account for the exaggerated sympathetic response to non-noxious stimuli12. In one study, catecholamine levels rose 200-300% above baseline during paroxysms in individuals with PSH, with no similar change found in the control group; this was consistent with prior case study data13.   

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Natural History and Trajectory;

  1. Acute (days-weeks)
    PSH usually develops in the acute phase following brain injury14. Symptoms, which are paroxysmal and episodic in nature, first appear as early as the first week after TBI12. In one prospective cohort study, PSH tended to first occur about 6 days post-injury11. Initially, onset of PSH may be difficult to distinguish from other conditions, including acute withdrawal of sedation and sepsis5.

    The majority of episodes, manifested by hypertension, tachycardia, hyperthermia, tachypnea, diaphoresis, and posturing, are provoked by noxious or non-noxious stimuli such as pain, urinary retention, or repositioning12. In one study, episodes were associated with a triggering event in 72% of individuals13.

    Individual episodes vary in intensity and duration but rarely persist for more than several hours. In one prospective cohort study, episodes tended to last about 30 minutes (ranging 15-50 minutes) and occurred an average of 5 times per day11. Other studies have found a wide range in duration of episodes, from 3 minutes to 1-2 hours6.
  1. Chronic/stable (weeks-months)
    The duration of PSH is variable, from less than 2 weeks to several months12. The occurrence of PSH tends to diminish over time. In one study, 24% of individuals had increased autonomic responses at one-week post-injury and 8% were diagnosed with dysautonomia at two weeks post-injury15.

    Spasticity and dystonia may be persistent event after resolution of PSH. It is not clear if residual hypertonia is a true sequela of PSH or rather a consequence of damage to supraspinal motor tracts, which occurs during initial brain injury12.
  1. Pre-terminal
    Autonomic dysfunction may rarely be associated with life-threatening cardiac arrhythmias or myocardial infarction.

Specific secondary or associated conditions and complications

Resting energy expenditure during episodes of PSH is as high as three times of norm, therefore adequate nutrition is important to prevent severe weight loss16. Body weight losses of 25% have been reported during the acute period in individuals with PSH5.

Individuals with PSH are at increased risk of developing heterotopic ossifications5. It has also been suggested that prolonged sympathetic hyperactivity associated with PSH may lead to cardiac damage, nutritional deficiencies, and skin breakdown3.  Furthermore, patients with PSH were found to have a longer hospital stay and higher hospital cost; they were also found to have a higher rate of complications, and made less neurological recovery in acute care after brain injury17,18.



Paroxysmal sympathetic hyperactivity (PSH) presents with non-specific findings and is therefore a diagnosis of exclusion. History of repeated episodes of rapid-onset tachycardia, hypertension, tachypnea, fever, diaphoresis, and rigidity with dystonic posturing is most common. These features do not and typically are not present in all episodes. However, several features must be observed simultaneously for PSH to be considered.

When assessing for PSH, clinicians should first consider other conditions that could present similarly, such as systemic inflammatory response syndrome, infection, noxious stimuli causing discomfort (consider fractures, heterotopic ossification, pressure wounds, constipation), seizures, intracranial hypertension, hydrocephalus, medication or substance withdrawal, serotonin syndrome and neuroleptic malignant syndrome3. Neuroleptic malignant syndrome may present very similarly and should be especially considered in the setting of recent antipsychotic use.

History should look for possible triggers, which can be painful or non-painful, such as touching, passive movement, turning, and endotracheal tube suctioning2. Episodes can occur spontaneously as well. Persistently elevated blood pressure, respiratory rate, heart rate, and temperature are less likely to be consistent with PSH and other diagnoses should be excluded first.  Significant gastroesophageal reflux can be one of noxious stimuli escalating dystonic posturing, and vice versa. High dose of anti-reflux medications can improve symptoms of PSH.

Physical examination

Patients with PSH may have paroxysmal increases in heart rate, respiratory rate, blood pressure, and temperature with return to baseline vital signs in between episodes. During episodes, they may have worsened level of consciousness, dilated pupils, and diaphoresis. Episodes are also associated with dystonia, muscle rigidity, and posturing2,4,11. This may include decorticate or decerebrate rigidity, bruxism, and opisthotonos.

Patients should have a thorough physical exam to assess for other causes of vital sign changes such as infection. They should also be assessed for potential consequences of PSH such as skin breakdown and heterotopic ossification.

Clinical functional assessment

These patients often have more severe brain injuries, in disorders of consciousness, and are dependent for care. It is important to perform passive range of motion testing of al joints to evaluate for residual spasticity6. If there is spasticity, the patient may benefit from resting hand or ankle splints to provide stretch.

Laboratory studies

PSH cannot be diagnosed based on laboratory studies. However, certain studies may be useful in evaluating for other conditions that present similar to PSH. A complete blood cell count along with blood, urine, or sputum cultures as indicated can assess for infection. A comprehensive metabolic panel can evaluate for electrolyte abnormalities or gastroenterological pathology that may be causing pain. Patients should also be assessed for nutritional deficiencies as a result of increased energy expenditure during episodes of PSH.


Imaging is not diagnostic for PSH. However, diffuse brain damage and injury to the deep brain structures, including the periventricular white matter, corpus callosum, diencephalon or the brainstem are associated with PSH8,11.

Imaging may be useful to evaluate for other intracranial pathology including infection or hydrocephalus.

Supplemental assessment tools

In 2014, a consensus on diagnostic criteria was developed by an international, multidisciplinary group to aid in the diagnosis of PSH. The Paroxysmal Sympathetic Hyperactivity – Assessment Measure (Figure 1) helps to determine PSH diagnostic likelihood. First section, the Diagnostic Likelihood Tool, assesses the presence of PSH features and the second portion, the Clinical Feature Scale, measures the severity of PSH features. The PSH-AM is designed for serial use with maximum values from the prior 24-hour period documented. It can be used to monitor clinical trends and aid in treatment2.

Table 1

Evaluation to rule out other causes of paroxysmal symptoms (e.g. seizures, thyroid storm, medication withdrawal) is indicated based on clinical considerations.

Early predictions of outcomes

PSH has been associated with worse clinical outcomes including more time on mechanical ventilation, more infection, tracheostomy placement, longer ICU stays, and longer total hospitalization11,17. Duration of PSH may also have an effect on outcome with persistent episodes possibly having worse outcomes12.


Avoid known triggers for episodes and overstimulation12. It is important to minimize noise and to promote a normal sleep-wake cycle.

Social role and social support system

PSH can be distressing for family members, friends, and healthcare providers. Clinicians should provide education about PSH, including prognosis. Informed family members and staff can help by reducing overstimulation and identifying triggers.

Professional Issues

Patients with more severe brain injuries often require life sustaining treatment including mechanical ventilation and surgeries. These treatments may pose ethical dilemmas. Clinicians should be mindful of such situations when caring for patients consider ethics consultation when appropriate.


Available or current treatment guidelines

Paroxysmal Sympathetic Hyperactivity treatment should include 1) minimizing avoidable stimulation, 2) aborting paroxysms with medication, and 3) preventing further episodes. First step is avoidance of overstimulation and reduction of noxious stimuli. As for pharmacological treatment, all treatment trials are empirical but are supported by clinical experience3,12,19-23.

Table 2. Medications for Paroxysmal Sympathetic Hyperactivity24,25:

MedicationMechanismDoseClinical EffectSide Effects
PropranololNoncardioselective beta-blockerStart: 10 mg tid by enteral route Max: 320 mg/dayPreventive; effective for tachycardia, hypertension, and diaphoresis Less effective for feverBradycardia, hypotension, sleep disturbance Contraindicated: asthma, heart-block
LabetalolNoncardioselective beta-blocker; selective α(1)-adrenergic receptor antagonistStart: 50 mg bid by enteral route (IV option available)Preventive; effective for tachycardia and hypertensionBradycardia, hypotension Contraindicated: asthma, heart-block
GabapentinInteracts with α2δ subunit of voltage-gated calcium channels in brain and spinal cordStart: 100-300 mg tid by enteral route Max: up to 3600-4800 mg/dayPreventive; improves most featuresSedation
ClonidineCentral α2-adrenergic receptor agonistStart: 0.1-0.3 mg bid by enteral route Max: 2.4 mg/dayAbortive and preventive; mostly improves tachycardia and hypertensionBradycardia, hypotension, sedation
BromocriptineDopamine D2 receptor agonistStart: 1.25-2.5 mg every 12 hours by enteral route Max: 20-40 mg/dayPreventive; effect tends to be modest and delayedConfusion, agitation, dyskinesia, nausea/emesis, orthostatic hypotension, could reduce seizure threshold
DantroleneInhibits calcium release from sarcoplasmic reticulumStart: 0.5-2 mg/kg/IV every 6-12 hours or 25 mg daily by enteral route Max: 10 mg/kg/IV or 400 mg qid by enteral routeAbortive; improves hypertonicity and dystoniaHepatotoxicity (can be severe), respiratory depression, muscle weakness
BaclofenGABAB agonistStart: 5 mg every 8 hours by enteral route Max: 80 mg/dayPreventive; improves hypertonicity and dystoniaSedation, muscle weakness
MorphineOpioid agonist2-8 mg IV bolusAbortive; improves most featuresRespiratory depression, sedation, hypotension, ileus, emesis, histamine release, developing of tolerance

Some studies have found that antipsychotics/dopamine antagonists such as haloperidol are not useful and may even worsen PSH26. For severe dystonia or rigidity, treatment with intrathecal baclofen and botulinum toxin injection have also been used with benefit.

At different disease stages

New onset/acute

  1. Potential curative interventions
    Identify and address precipitating causes. If possible, replace medications that can cause malignant neuroleptic-like syndrome (e.g., metochlopramide). Correct electrolyte imbalance. Remove or reduce noxious stimulation.
  2. Symptom relief
    Medication trial with titration should be initiated. Treatment is empirical and may require switching or addition of a different category, if one medication is not effective. Botulinum toxin injection is considered in case of significant bruxism, opisthotonus, or abnormal posturing. In case of significant bruxism, initiate dental consultation for mouth piece to protect teeth.
  3. Rehabilitation strategies intended to stabilize or optimize function or prepare for further interventions at later disease stages. Resting splint and passive range of motion for prevention of joint contractures. Frequent position changes for prevention of decubitus ulcer. Control over or prevention of noxious stimulation in the environment.


  1. Secondary prevention and disease management strategies
    Continue passive range of motion and position changes to prevent decubitus ulcer, deep vein thrombosis, joint contractures and heterotopic ossification. When medications fail to ameliorate symptoms, intrathecal baclofen can be considered.
  2. Symptom relief: as above.
  3. Rehabilitation strategies intended to optimize function:
    As long as vital signs are unstable, only minimal rehabilitative intervention is feasible, with monitoring of vital signs. Passive range of motion should be continued.


  1. Continue treatment as in subacute phase. As vital signs stabilize, increase mobility; from simple activity (sitting up, standing at tilt table) with monitoring of vital signs. Initiate aggressive treatment for joint contractures or dystonia.

Coordination of care

Close interdisciplinary communication that includes the acute intensive care physician is crucial for optimizing management.

Patient & family education

Family education is important to decrease noxious stimulation and help with maintaining good positioning to prevent joint contractures and decubitus ulcers.

Measurement of Patient Outcomes

Most evidence suggest that PSH is associated with worse short and long-term outcomes after TBI1,8,12,17, including longer hospital stay or higher rate of tracheostomy11. The outcomes measured by GOS (Glasgow outcome scale) at 6 and 12 months after brain injury reported poor as well8,27.

Translation into practice

Early treatment with medication that can prevent or abort these features can be effective. Given the significant disturbances of care from PSH, treatment will be beneficial.


Cutting edge concepts and practice

For focal dystonia (bruxism or opisthotonus), botulinum toxin injection is indicated. For bruxism, key target muscles are bilateral masseter and temporalis (if approachable, pterygoid muscles are to be targeted). For severe opisthotonus, key target muscles are paraspinal muscles.


Gaps in the evidence-based knowledge

There is still a paucity of evidence in pharmacological treatment and understanding of pathophysiology. More research in this field is necessary. At this time, it is important to makes sure that the awareness of PSH grows to help lead to better definition and treatment.


  1. Pozzi M, Conti V, Locatelli F, Galbiati S, Radice S, Citerio G, et al. Paroxysmal Sympathetic Hyperactivity in Pediatric Rehabilitation: Clinical Factors and Acute Pharmacological Management. J Head Trauma Rehabil. 2015;30(5):357–63.
  2. Baguley IJ, Perkes IE, Fernandez-Ortega JF, Rabinstein AA, Dolce G, Hendricks HT. Paroxysmal sympathetic hyperactivity after acquired brain injury: consensus on conceptual definition, nomenclature, and diagnostic criteria. J Neurotrauma. 2014;31(17):1515–20.
  3. Lump D, Moyer M. Paroxysmal sympathetic hyperactivity after severe brain injury. Vol. 14, Current Neurology and Neuroscience Reports. 2014. p. 1–7.
  4. I.E. P, D.K. M, M.T. N, I.J. B. Paroxysmal sympathetic hyperactivity after acquired brain injury: A review of diagnostic criteria [Internet]. Vol. 25, Brain Injury. 2011. p. 925–32. Available from: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=emed10&NEWS=N&AN=2011433189
  5. Perkes I, Baguley IJ, Nott MT, Menon DK. A review of paroxysmal sympathetic hyperactivity after acquired brain injury. Ann Neurol. 2010;68(2):126–35.
  6. Choi HA, Jeon SB, Samuel S, Allison T, Lee K. Paroxysmal sympathetic hyperactivity after acute brain injury. Curr Neurol Neurosci Rep. 2013;13(8).
  7. Zafonte RD. Traumatic brain injury: an enduring challenge. Lancet Neurol [Internet]. 2017;16(10):766–8. Available from: http://dx.doi.org/10.1016/S1474-4422(17)30300-9
  8. Lv LQ, Hou LJ, Yu MK, Qi XQ, Chen HR, Chen JX, et al. Prognostic influence and magnetic resonance imaging findings in paroxysmal sympathetic hyperactivity after severe traumatic brain injury. J Neurotrauma. 2010;27(11):1945–50.
  9. Hinson HE, Puybasset L, Weiss N, Perlbarg V, Benali H, Galanaud D, et al. Neuroanatomical basis of paroxysmal sympathetic hyperactivity: A diffusion tensor imaging analysis. Brain Inj. 2015;29(4):455–61.
  10. Letzkus L, Keim-Malpass J, Kennedy C. Paroxysmal sympathetic hyperactivity: Autonomic instability and muscle over-activity following severe brain injury. Brain Inj. 2016;30(10):1181–5.
  11. Fernandez-Ortega JF, Prieto-Palomino MA, Garcia-Caballero M, Galeas-Lopez JL, Quesada-Garcia G, Baguley IJ. Paroxysmal sympathetic hyperactivity after traumatic brain injury: Clinical and prognostic implications. J Neurotrauma. 2012;29(7):1364–70.
  12. Meyfroidt G, Baguley IJ, Menon DK. Paroxysmal sympathetic hyperactivity: the storm after acute brain injury. Lancet Neurol [Internet]. 2017;16(9):721–9. Available from: http://dx.doi.org/10.1016/S1474-4422(17)30259-4
  13. Fernandez-Ortega JF, Baguley IJ, Gates TA, Garcia-Caballero M, Quesada-Garcia JG, Prieto-Palomino MA. Catecholamines and paroxysmal sympathetic hyperactivity after traumatic brain injury. J Neurotrauma. 2017;34(1):109–14.
  14. Hughes JD, Rabinstein AA. Early diagnosis of paroxysmal sympathetic hyperactivity in the ICU. Neurocrit Care. 2014;20(3):454–9.
  15. Baguley IJ, Slewa-Younan S, Heriseanu RE, Nott MT, Mudaliar Y, Nayyar V. The incidence of dysautonomia and its relationship with autonomic arousal following traumatic brain injury. Brain Inj. 2007;21(11):1175–81.
  16. Mehta NM, Bechard LJ, Leavitt K, Duggan C. Severe weight loss and hypermetabolic paroxysmal dysautonomia following hypoxic ischemic brain injury: The role of indirect calorimetry in the intensive care unit. J Parenter Enter Nutr. 2008;32(3):281–4.
  17. Fernández-Ortega JF, Prieto-Palomino MA, Muñoz-López A, Lebron-Gallardo M, Cabrera-Ortiz H, Quesada-García G. Prognostic influence and computed tomography findings in dysautonomic crises after traumatic brain injury. J Trauma – Inj Infect Crit Care. 2006;61(5):1129–33.
  18. Baguley IJ. Autonomic complications following central nervous system injury. Semin Neurol. 2008;28(5):716–25.
  19. Rabinstein AA, Sandhu K. Non-infectious fever in the neurological intensive care unit: Incidence, causes and predictors. J Neurol Neurosurg Psychiatry. 2007;78(11):1278–80.
  20. Rabinstein AA, Benarroch EE. Treatment of Paroxysmal Sympathetic Hyperactivity. Curr Treat Options Neurol. 2008;10(2):151–7.
  21. Ley EJ, Leonard SD, Barmparas G, Dhillon NK, Inaba K, Salim A, et al. Beta blockers in critically ill patients with traumatic brain injury: Results from a multicenter, prospective, observational American Association for the Surgery of Trauma study. J Trauma Acute Care Surg. 2018;84(2):234–44.
  22. Thomas A, Greenwald BD. Paroxysmal sympathetic hyperactivity and clinical considerations for patients with acquired brain injuries: A narrative review. Am J Phys Med Rehabil. 2019;98(1):65–72.
  23. Patel MB, McKenna JW, Alvarez JAM, Sugiura A, Jenkins JM, Guillamondegui OD, et al. Decreasing adrenergic or sympathetic hyperactivity after severe traumatic brain injury using propranolol and clonidine (DASH After TBI Study): study protocol for a randomized controlled trial. Trials [Internet]. 2012;13(1):1. Available from: Trials
  24. Rabinstein AA. Autonomic Hyperactivity. Contin Lifelong Learn Neurol. 2020;26(1):138–53.
  25. Ripley D, Driver S, Stork R, Maneyapanda M. Pharmacologic Management of the Patient with Traumatic Brain Injury. In: Eapen B, Cifu DX, editors. Rehabilitation after Traumatic Brain Injury. Elsevier; 2018. p. 154.
  26. Baguley IJ, Camerons ID, Green AM, Slewa-Younan S, Marosszeky JE, Gurka JA. Pharmacological management of dysautonomia following traumatic brain injury. Brain Inj. 2004;18(5):409–17.
  27. Hendricks HT, Heeren AH, Vos PE. Dysautonomia after severe traumatic brain injury. Eur J Neurol. 2010;17(9):1172–7.

Original Version of Topic

Chong Tae Kim, MD. Cerebrally Mediated Autonomic Dysfunction. 11/10/2011.

Previous Revision(s) of the Topic

Chong Tae Kim, MD. Cerebrally Mediated Autonomic Dysfunction. 9/17/2015.

Author Disclosure

Kayli Gimarc, MD,
Nothing to Disclose

Lesleay Abraham, MD,
Nothing to Disclose

Cherry Junn, MD
Nothing to Disclose