Bacterial Brain Abscesses Expand Despite Effective Antibiotic Treatment: A Process Powered by Osmosis Due to Neutrophil Cell Death

Daniel Dahlberg; Sverre Holm; Ellen Margaret Lund Sagen; Annika Elisabet Michelsen; Maria Stensland; Gustavo Antonio de Souza; Ebba Gløersen Müller; James Patrick Connelly; Mona-Elisabeth Revheim; Bente Halvorsen; Bjørnar Hassel

doi:10.1227/neu.0000000000002792

Bacterial Brain Abscesses Expand Despite Effective Antibiotic Treatment: A Process Powered by Osmosis Due to Neutrophil Cell Death

Neurosurgery. 2023 Dec 12;94(5):1079-1087. doi: 10.1227/neu.0000000000002792. Online ahead of print.

Authors

Daniel Dahlberg¹, Sverre Holm², Ellen Margaret Lund Sagen^{2

3}, Annika Elisabet Michelsen^{2

3}, Maria Stensland⁴, Gustavo Antonio de Souza^{4

5}, Ebba Gløersen Müller^{3

6}, James Patrick Connelly⁶, Mona-Elisabeth Revheim^{3

6

7}, Bente Halvorsen^{2

3}, Bjørnar Hassel^{3

8

9}

Affiliations

¹ Department of Neurosurgery, Oslo University Hospital, Oslo, Norway.
² Research Institute of Internal Medicine, Oslo University Hospital, Oslo, Norway.
³ Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁴ Institute of Immunology and Centre for Immune Regulation, Oslo University Hospital, Oslo, Norway.
⁵ Department of Biochemistry, Universidade Federal Do Rio Grande Do Norte, Natal, Brazil.
⁶ Division of Radiology and Nuclear Medicine, Department of Nuclear Medicine, Oslo University Hospital, Oslo, Norway.
⁷ The Intervention Centre, Oslo University Hospital, Oslo, Norway.
⁸ Department of Neurohabilitation, Oslo University Hospital, Oslo, Norway.
⁹ Norwegian Defence Research Establishment (FFI), Kjeller, Norway.

PMID: 38084989
PMCID: PMC10990409 (available on 2024-12-12)
DOI: 10.1227/neu.0000000000002792

Abstract

Background and objectives: A bacterial brain abscess is an emergency and should be drained of pus within 24 hours of diagnosis, as recently recommended. In this cross-sectional study, we investigated whether delaying pus drainage entails brain abscess expansion and what the underlying mechanism might be.

Methods: Repeated brain MRI of 47 patients who did not undergo immediate pus drainage, pus osmolarity measurements, immunocytochemistry, proteomics, and 18F-fluorodeoxyglucose positron emission tomography.

Results: Time from first to last MRI before neurosurgery was 1 to 14 days. Abscesses expanded in all but 2 patients: The median average increase was 23% per day (range 0%-176%). Abscesses expanded during antibiotic therapy and even if the pus did not contain viable bacteria. In a separate patient cohort, we found that brain abscess pus tended to be hyperosmolar (median value 360 mOsm; range 266-497; n = 14; normal cerebrospinal fluid osmolarity is ∼290 mOsm). Hyperosmolarity would draw water into the abscess cavity, causing abscess expansion in a ballooning manner through increased pressure in the abscess cavity. A mechanism likely underlying pus hyperosmolarity was the recruitment of neutrophils to the abscess cavity with ensuing neutrophil cell death and decomposition of neutrophil proteins and other macromolecules to osmolytes: Pus analysis showed the presence of neutrophil proteins (protein-arginine deiminases, citrullinated histone, myeloperoxidase, elastase, cathelicidin). Previous studies have shown very high levels of osmolytes (ammonia, amino acids) in brain abscess pus. 18F-fluorodeoxyglucose positron emission tomography showed focal neocortical hypometabolism 1 to 8 years after brain abscess, indicating long-lasting damage to brain tissue.

Conclusion: Brain abscesses expand despite effective antibiotic treatment. Furthermore, brain abscesses cause lasting damage to surrounding brain tissue. These findings support drainage of brain abscesses within 24 hours of diagnosis.