Paroxysmal sympathetic hyperactivity (PSH) is a well-recognized but frequently underdiagnosed complication of severe acquired brain injury, particularly in patients with traumatic brain injury (TBI) (Baguley et al., 2014; Perkes et al., 2010). It is characterized by episodic and simultaneous increases in sympathetic and motor activity, manifesting as tachycardia, hypertension, hyperthermia, tachypnea, diaphoresis, and abnormal posturing (Perkes et al., 2010; Rabinstein, 2007). These paroxysmal episodes are typically triggered by external or internal stimuli and can significantly complicate the clinical course of critically ill neurotrauma patients.

Diffuse axonal injury (DAI), a common pathological substrate in high-velocity neurotrauma, is often associated with the development of PSH (Meyfroidt et al., 2017; Dolce et al., 2008). The shearing forces involved in DAI lead to widespread disruption of white matter tracts, particularly affecting the diencephalon, brainstem, and cortical-subcortical connections that regulate autonomic function (Meyfroidt et al., 2017). This structural disconnection is believed to result in loss of inhibitory control over sympathetic centers, giving rise to the exaggerated autonomic responses observed in PSH.

The reported incidence of PSH varies widely, ranging from 8% to 33% among patients with severe TBI, with higher rates observed in those with DAI (Perkes et al., 2010; Fernandez-Ortega et al., 2006). Young patients appear to be particularly susceptible, possibly due to higher exposure to high-impact trauma and differing neurophysiological responses. Despite its clinical significance, PSH remains under recognized, often misdiagnosed as sepsis, withdrawal syndromes, or uncontrolled pain, leading to delays in appropriate management (Godoy & Rabinstein, 2015; Hinson & Sheth, 2012).

Given the clinical burden and diagnostic challenges associated with PSH, especially in young patients with DAI, there is a need for better characterization of its clinical profile, triggers, treatment response, and outcomes. This case series, along with systematic review of the literature, aims to enhance understanding of PSH in this specific population and contribute to improved recognition and management strategies in neurocritical care settings.

CASE 1

15 years male patient having history of road traffic accident presented in ER with GCS E2V2M4. NCCT brain (fig 1) did not reveal any major intracranial injury. Supportive managements were started in line with diffuse axonal injury. On Day 3^rd of injury he started to develop episodic hypertension, tachycardia, spasticity of limbs associated with profuse sweating. He also had persistent low grade fever with episodic spikes of temperature. After excluding other reasons and considering PSH, he was started on broad spectrum beta blocker (Propranolol 20 mg twice daily) in addition to all other ongoing supportive cares. PSH episodes kept on increasing in initial 3 days thereafter started to decline and became only occasional by day 12^th of injury. GCS also gradually improved with control in PSH incidences. He was discharged to home care on day 15^th of injury at full GCS and hemodynamic stable conditions. Propranolol was gradually tapered off over next 15 days in follow up care.

Fig 1 NCCT brain of case 1

CASE 2

19 years male patient was admitted in neuro-intensive care unit in altered sensorium state with history of RTA 11 hours ago. At admission GCS were E2V2M5 and blood pressure was on lower side. NCCT brain (fig 2) was not suggestive of any surgically correctable lesion and was not corresponding to his current sensorium. Conservative cares were tailored towards DAI management. Hemodynamics were improved on fluid correction. He started following commands on day 3^rd of admission but again sensorium declined on day 4 with occurrence of frequent tachycardia, hypertension and limb spasticity. After ruling out seizures, sepsis and pain, propranolol 10 mg twice daily was added to the treatment regime considering PSH syndromes. Sympathetic episodes kept on increasing in spite of beta blocker, so infusion fentanyl at the rate of 30 mcg/hour was added on day 5^th. Symptoms started to settle down by day 7^th and became nil bothering by day 11^th. Fentanyl was withdrawn on day 8^th and beta blocker gradually stopped on day 25^th of starting. He was discharged at GCS 15 on day 17^th of admission.

Fig 2: NCCT brain of case 2

CASE 3

26 years male patient was admitted in neuro ICU with alleged history of RTA 1 day ago with low GCS (E1V1M4) and pupils bilateral equal and reactive to light. After securing airway and stabilizing hemodynamic conditions, NCCT brain (fig 3) was done which showed right intra-ventricular bleed without hydrocephalus and small right deep temporal contusions. NCCT brain findings could not explain the decline in sensorium so, patient was kept on supportive cares keeping DAI as differential. Patient started regaining consciousness on day 3^rd of injury (E2VtM5) but remained non progressive till day 5^th. On day 5^th he started to trigger paroxysmal episodes of hypertension, tachycardia, tachypnea and bilateral upper limb straitening. Considering PSH, he was started on Propranolol 20 mg twice daily and supplemented with infusion dexmedetomidine 4 mcg/kg/hour for 48 hours taking refractory nature of PSH into account. Sympathetic episodes started to decrease by day 9^th and almost vanished by day 14^th. Sensorium was restored to E4VtM6 on day 9th^th and was weaned from ventilation followed by extubation of endotracheal tube on day 10^th. He was sent for home care on days 17^th at full GCS and hemodynamic stable conditions. Propranolol was tapered and stop gradually by day 29^th of injury.

Fig 3: NCCT brain of case 3

DISCUSSION

Paroxysmal sympathetic hyperactivity (PSH) remains a challenging and often under recognized complication in patients with severe traumatic brain injury (TBI), particularly those with diffuse axonal injury (DAI). In the present case series focusing on young neurotrauma patients, PSH was observed as a significant contributor to secondary morbidity, consistent with prior literature (Baguley et al., 2014; Perkes et al., 2010).

Clinically, PSH is characterized by recurrent episodes of tachycardia, hypertension, hyperthermia, tachypnea, diaphoresis, and dystonic posturing. These features were consistently observed, often triggered by ICU stimuli. Diagnostic challenges persist due to overlap with sepsis and other conditions.

The pathophysiology of PSH is best explained by the “disconnection theory,” which postulates an imbalance between excitatory and inhibitory autonomic pathways following brain injury. Loss of descending inhibitory control from cortical and subcortical centers leads to unchecked sympathetic outflow from hypothalamic and brainstem centers. Alternative hypotheses, including the excitatory:inhibitory ratio (EIR) model, further support this concept by emphasizing the role of impaired modulation of spinal and supraspinal reflexes.

In 2014, an international consensus group proposed standardized diagnostic criteria and the PSH Assessment Measure (PSH-AM), which includes a Clinical Feature Scale (CFS) and Diagnosis Likelihood Tool (DLT), significantly improving diagnostic consistency (Baguley et al., 2014). Early recognition and targeted management are crucial, as PSH is associated with prolonged mechanical ventilation, increased intensive care unit (ICU) stay, higher healthcare costs, and poorer neurological outcomes (Lv et al., 2010; Zheng et al., 2020).

Management of PSH remains largely supportive and symptomatic, involving multimodal pharmacotherapy aimed at reducing sympathetic overactivity. Commonly used agents include opioids, beta-blockers (e.g., propranolol), alpha-2 agonists (e.g., clonidine, dexmedetomidine), benzodiazepines, and gabapentin. However, there is no universally accepted treatment protocol, and current practices are largely based on observational studies and expert consensus. non-pharmacological strategies such as minimizing triggers and ensuring adequate analgesia are also important. Early recognition improves outcomes.

CONCLUSION

PSH in not very uncommon in young neurotrauma patients having DAI. This impairs the clinical improvement and increase the ICU/hospital stay of patients. Early clinical diagnosis and prompt management of sympathetic response along with primary injury remains the cornerstone of good patient outcome.

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