Paroxysmal sympathetic hyperactivity (PSH) is a syndrome of excessive and pathological
adrenergic output to nociceptive or non-nociceptive (including environmental) stimuli.
It is observed as a complication of various acute brain insults such as traumatic
brain injury (TBI), stroke, anoxic brain injury, tumors, infections, autoimmune encephalitis,
and acute hydrocephalus. It can manifest as a constellation of episodic, simultaneous
symptoms such as tachycardia, hyperthermia, hypertension, tachypnea, and diaphoresis,
often accompanied by dystonia and even motor posturing.[1] Onset of these symptoms is usually fast, but resolution is slow, unless terminated
by medication.
Since the first description of this syndrome by Penfield,[2] many names have been ascribed to it which has created puzzlement in its diagnosis
as well as understanding of its pathophysiology. Some of the names associated with
this condition over the years are “autonomic storm,” “sympathetic storm,” “hypothalamic
dysregulation syndrome,” and “paroxysmal autonomic instability with dystonia.” In
2014, the International Brain Injury Association proposed the term “paroxysmal sympathetic
hyperactivity.”[3] Its overall incidence is 18% among various cohorts of patients admitted in neurocritical
care with an incidence of 33% in severe TBI patients.[4] According to Perkes et al, 80% of cases of PSH are observed after TBI, and the remaining
20% following other cerebral pathologies.[5] The most consistent observation is that patients with PSH are frequently young and
comatose. Pediatric patients appear more prone to develop PSH after anoxic–ischemic
insults and with non-bacterial encephalitis.[6] It is common that patients with PSH are erroneously suspected of having other diagnoses,
and this may lead to unnecessary testing and sometimes inappropriate treatments, making
an early and accurate diagnosis important.[7] PSH may persist for weeks or months, and has been associated with worse clinical
outcomes such as increased time of mechanical ventilation, infection, malnutrition,
dehydration, tracheostomy, longer hospitalization longer intensive care unit (ICU)
stays, contractures, and heterotopic ossification.
PSH remains an under-recognized condition that is difficult to diagnose. A high index
of suspicion is key to early diagnosis. The first step in diagnosis is to exclude
conditions with similar symptoms, such as infection, sedation withdrawal, seizures,
and pulmonary embolism. Clinical diagnostic tools (PSH assessment measure) have been
proposed to assist clinicians in the reliable identification of PSH.[8] Such tools incorporate a clinical feature scale that categorizes the severity of
sympathetic signs during episodes and a diagnostic tool that gauges the likelihood
of diagnosis of PSH based on the presence of characteristic features. These two components
are combined in a score that reflects the degree of confidence in diagnosis of PSH.
The feasibility and reliability of these tools have been recently validated by van
Eijck et al.[9] There is evidence that they may reduce the chances of misdiagnosis and favorably
impact hospital length of stay and costs of hospitalization.[10]
The pathophysiology of PSH is poorly understood and the dominant theory suggests the
failure of the central autonomic network. Disruption of descending pathways releases
sympathetic responses from their normal inhibitory modulation. The consequence is
that sympathetic responses to internal or external stimuli become exaggerated.[11] The interruption of descending inhibitory modulation might also produce maladaptive
changes in the spinal cord leading to excitatory interneuronal activity.[12] These changes could help explain how non-noxious stimuli are perceived as noxious
by brain.[12]
While formal evidence on treatment is scant and lacks methodological quality, PSH
is a disorder that can be treated.[13]
Can episodes be prevented with pharmacological intervention? There is at least one retrospective study that claims so. Tang et al asserted that
dexmedetomidine infusion has preventive effect on PSH in severe TBI patients who have
undergone surgery.[14] Treatment revolves around meticulous general care and pharmacological therapy with
abortive (morphine) and preventive medication (propranolol). Many other drugs have
been used with varying success rates. Drug combinations are frequently used and chosen
based on individual preference rather than objective evidence. Avoidance of triggering
stimuli is critical in its management.
While there are numerous published studies from various countries to unravel the epidemiology,
pathophysiology, and management of this serious but treatable condition, in India,
neurocritical care specialists are still under-recognizing/under-reporting this complication.
Failure to recognize the condition can adversely impact outcomes of these patients.
Literature search in Indian context revealed a few case reports but only one small
study on PSH incidence in 57 patients admitted in neurological ICU by Verma et al
in 2015, in which the authors reported 10.53% incidence of PSH.[15] In this issue of Journal of Neuroanesthesiology and Critical Care, Bhardwaj et al have published a retrospective study in a relatively large population
of 257 patients with TBI, and have observed PSH in 30.8% of patients.[16] This study focuses only on patients with TBI, which raises questions regarding the
true incidence of PSH in other varieties of critical neurological diseases. Hence,
to validate their reported incidence of PSH, there is a crucial need for conducting
prospective multicenter studies in the whole gamut of neurocritical care patients.
This would expand the understanding of this condition among neurocritical care specialists
with proper management and improved outcomes. A greater effort should also be devoted
to discover pharmacological agents that can either prevent this dangerous syndrome
or at least mitigate its detrimental effects. Simultaneously, another vital area of
research could be to predict which patient is likely to develop this complication,
through use of certain predictive clinical features and/or blood biomarkers unique
to these vulnerable patients.
