DISCUSSION
Neurogenic fever is a diagnosis of exclusion and remains a challenging condition to manage effectively. The traditional approach of supportive care and antipyretic medications often proves inadequate in controlling the underlying dysregulation of the autonomic nervous system. In this case report, we highlight the successful management of neurogenic fever using a combination of baclofen and propranolol.
NF is likely a result of direct pontine destruction or indirect compression. It is characterized by an unchanged setting of the thermoregulatory center so antipyretics have no effects on central hyperthermia.4, 5 The combination of negative cultures; absence of infiltrate on chest radiographs; diagnosis of SAH, intraventricular hemorrhage, or tumor; and onset of fever within 72 hours of admission, predict NF with a probability of 0.90.6
Post-traumatic brain injury-related hyperthermia, also known as neurogenic fever is characterized by the development of hyperthermia, tachycardia, hyperhidrosis, hypertension, and sometimes seizures.7
Traumatic brain injury mechanisms include growth factor deficiency, which reduces sweating capacity and increases the risk of developing hyperthermia; direct injury to the hypothalamic-pituitary area and inflammatory changes within the hypothalamus; and diffuse white matter damage, which causes brain edema, hyperglycemia, leukocytosis, hypotension, and seizure. All of these mechanisms result from autonomic dysfunction. This condition is also known as dysautonomia, paroxysmal sympathetic hyperactivity (PSH), or diencephalic syndrome.8
We hypothesized that baclofen would be effective in this case as it had an effect on central hyperthermia for patients with pontine hemorrhages. Baclofen, a GABA agonist, functions as an inhibitory signal directly acting on the raphe nuclei to suppress BAT activation, which in turn suppresses the body temperatures. Thus, baclofen may control central hyperthermia by replacing neurotransmitters (GABA, glutamate) that were blocked due to the location of hemorrhage.9
We used baclofen at a dosage of 30 mg/day and titrated up to 60 mg/day, resulting in a complete resolution of fever. A study by Lee HC et al. also reports the efficacy of baclofen at a similar dosage to achieve normothermia in patients with central hyperthermia secondary to pontine hemorrhage. They started at a dose of 30 mg/day to a maximum of 60 mg/day with the reduction of fever from >39℃ to 37.5℃.10
Another study done by Huang YS et al successfully treated neurogenic fever with 30 mg/day of baclofen.8
Propranolol, a sympathetic blocking agent that can pass the blood-brain barrier can blunt the sympathetic storming phenomenon resulting in successful control of paroxysmal hyperthermia.11 We expected that combining propranolol with baclofen would have a two-fold effect of lowering his temperature as well as his heart rate in our patient, who also had sinus tachycardia with a heart rate ranging from 120-150.
Meythaler et al. published one of the earliest case reports of three cases of NF in severe TBI patients treated with propranolol.12 Garg M et.al. Stated that propranolol 10 mg thrice daily was effective in alleviating fever and tachycardia for severe traumatic brain injury.13
The Dosages mentioned in both studies were lower than the propranolol dose used in our study. In our patient, 60 mg/day of propranolol combined with 60 mg/day of baclofen provided adequate temperature and heart rate regulation. This dose of nonselective beta blocker has no negative effects.