Central Hyperthermia

Central Hyperthermia

1. Ade Wijaya , MD - July 2019 - Central Hyperthermia

2. Outline: Introduction Clinical Manifestation Pathogenesis Diagnosis Management Summary

3. Introduction Fever occurs in 23% of stroke patients Fever in CNS disorders without evidence of infection Poor response to antipyretics 33 % of fever in stroke patients 90 % occur during first 3 days of stroke Morales-Ortiz A, Jiménez-Pascual M, Pérez -Vicente JA, Monge-Arguiles A, Bautista- Prados J. Fever of central origin during stroke. Rev Neurol. 2001;32(12):1111–1114 Sung CY, Lee TH, Chu NS. Central hyperthermia in acute stroke. Eur Neurol. 2009;62(2):86–92

4. Clinical Manifestation Schwarz S, Häfner K, Aschoff A, Schwab S. Incidence and prognostic significance of fever following intracerebral hemorrhage . Neurology. 2000;54(2):354–361. Sung CY, Lee TH, Chu NS. Central hyperthermia in acute stroke. Eur Neurol. 2009;62(2):86–92 Morales-Ortiz A, Jiménez-Pascual M, Pérez -Vicente JA, Monge-Arguiles A, Bautista- Prados J. Fever of central origin during stroke. Rev Neurol. 2001;32(12):1111–1114

5. Pathogenesis Damage or dysfunction to central fever control centers , such as at the level of the diencephalon Selective loss of warm-sensitive neurons, the osmotic changes detected by the organum vasculosum laminae terminalis (OVLT), or the humoral changes (progesterone, prostaglandin) modifying the firing rate of heat sensitive neurons in the medial preoptic nucleus (MPO) – hypothalamus Brainstem; brown adipose thermogenesis (BAT) C. B. Saper , J. Lu, T. C. Chou, and J. Gooley , “The hypothalamic integrator for circadian rhythms,” Trends in Neurosciences, vol. 28, no. 3, pp. 152–157, 2005 M. R. Crompton, “Hypothalamic lesions following closed head injury,” Brain, vol. 94, no. 1, pp. 165–172, 1971. View at Publisher M. Rango , A. Arighi , L. Airaghi , and N. Bresolin , “Central hyperthermia, brain hyperthermia and low hypothalamus temperature,” Clinical Autonomic Research, vol. 22, no. 6, pp. 299–301, 2012. Sung CY, Lee TH, Chu NS. Central hyperthermia in acute stroke. Eur Neurol. 2009;62(2):86–92 N. Samudra and S. Figueroa, “Intractable central hyperthermia in the setting of brainstem hemorrhage ,” Therapeutic Hypothermia and Temperature Management, vol. 6, no. 2, pp. 98–101, 2016.

6. Diagnosis (a) High fever with temperatures > 39°C within 24 hours after onset of stroke (b ) No prior infections or fevers at least 1 week prior to onset of stroke (c ) Negative workup for fever of infectious origin H. C. Lee, J. M. Kim, J. K. Lim, Y. S. Jo, and S. K. Kim, “Central hyperthermia treated with baclofen for patient with pontine hemorrhage ,” Annals of Rehabilitation Medicine, vol. 38, no. 2, pp. 269–272, 2014.

7. Management Multimodal approach Medications like bromocriptine or baclofen Intravascular cooling devices Antipyretic Natteru , P., George, P., Bell, R., Nattanmai , P., & Newey , C. R. (2017). Central Hyperthermia Treated with Bromocriptine . Case reports in neurological medicine , 2017 .

8. Bromocriptine Dopamine D2 agonist that acts on the corpus striatum and the hypothalamus 0.025 mg/kg twice daily and gradually increased to 0.05 mg/kg thrice daily Russo RN, O’Flaherty S. Bromocriptine for the management of autonomic dysfunction after severe traumatic brain injury. J Paediatr Child Health. 2000;36(3):283–285. Kang SH, Kim MJ, Shin IY, Park DW, Sohn JW, Yoon YK. Bromocriptine for control of hyperthermia in a patient with mixed autonomic hyperactivity after neurosurgery: a case report. J Korean Med Sci. 2012;27(8):965–968

9. Baclofen GABA agonist Acts on the raphe nuclei and inhibits BAT which in turn can suppress the core body temperature Side effects: drowsiness, tiredness, and muscle weakness of the affected or unaffected limbs Dose: 30-60 mg / day Y.-S. Huang, M.-C. Hsiao, M. Lee, Y.-C. Huang, and J.-D. Lee, “ Baclofen successfully abolished prolonged central hyperthermia in a patient with basilar artery occlusion,” Acta Neurologica Taiwanica , vol. 18, no. 2, pp. 118–122, 2009 A. Hulme , W. J. MacLennan, R. T. Ritchie, V. A. John, and P. A. Shotton , “ Baclofen in the elderly stroke patient its side-effects and pharmacokinetics,” European Journal of Clinical Pharmacology, vol. 29, no. 4, pp. 467–469, 1985. Lee, H. C., Kim, J. M., Lim, J. K., Jo, Y. S., & Kim, S. K. (2014). Central hyperthermia treated with baclofen for patient with pontine hemorrhage . Annals of rehabilitation medicine , 38 (2), 269.

10. Summary Fever often occurs in CNS injury Mostly due to infections Central hyperthermia  rule out infection Hypothalamus; brainstem Multimodal approach Bromocriptine & baclofen