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.