Clinical trial NCT04938362: Cognitive Function and Fatigue After Brain Abscess
Official title: Cognitive Function and Fatigue After Brain Abscess
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Brain Abscess
Fatigue
Cognitive Dysfunction
Lead sponsor: University of Oslo
Sponsor class: OTHER
Collaborators: name: Oslo University Hospital
name: Sunnaas Rehabilitation Hospital
First posted: 2021-06-24
Enrollment: 50
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients older than 16 years, who have completed treatment for brain abscess and who agree to participate.

Brief summary: Brain abscess is a focal bacterial or fungal infection of the brain. Treatment is neurosurgical drainage of pus followed by long-term antibiotic treatment. In spite of successful treatment of the infection, long-term cognitive problems or mental fatigue may ensue. The reason for this dysfunction may be a continuing inflammatory state or damage to brain tissue caused by the abscess. The investigators will evaluate these possibilities with the use of \[18F\]deoxyglucose-positron emission tomography (FDG-PET) and electroencephalography (EEG) in patients who have been treated for brain abscess and who experience cognitive problems and/or fatigue. FDG-PET may identify both inflammation and altered neuronal activity (the latter indicating damage to brain tissue), and EEG may identify altered neuronal activity, including changes in neuronal network activity.

Detailed description: Brain abscess is a focal bacterial or fungal infection of the brain, which results in a pus-filled cavity within the brain parenchyma. The incidence is approximately 1/100 000 per year, and all age groups are affected. Treatment is neurosurgical drainage of pus followed by long-term antibiotic treatment. Previously, the capsule that surrounds the pus was removed surgically; this is not usually done anymore. In spite of successful treatment of the infection, patients may experience long-lasting cognitive problems or mental fatigue. The reason for this brain dysfunction is not known.

The investigators formulated two hypotheses to explain why some patients experience long-lasting cognitive problems and/or fatigue: 1) The brain abscess caused damage to brain tissue, interrupting neuronal networks underlying cognition or 2) The abscess or the remaining capsule causes a long-lasting inflammatory state of the brain, affecting neurotransmission and cerebral function.

In this prospective study, the investigators evaluate brain abscess patients by cognitive examination by a neuropsychologist at 2 and 12 months after treatment. Participants then undergo \[18F\]deoxyglucose-positron emission tomography (FDG-PET). An inflammatory state in the abscess area would be identified by the FDG-PET signal. Likewise, a change in neuronal (neocortical) function would be detectable from a change in the FDG-PET signal. Participants also undergo EEG investigation to establish whether fatigue is related to alterations in EEG parameters: alpha, theta, and delta activity.

Importantly, brain damage caused by the abscess may be irreversible and functional improvement of the patient would probably have to rely on compensatory strategies, whereas an inflammatory state could probably be modified by anti-inflammatory treatment.

Further, the prognosis for the patients' cognitive problems and fatigue is probably different if the underlying cause is inflammation rather than tissue damage.

Eligibility criteria: Inclusion criteria:

• Patients who have completed treatment for brain abscess and who agree to participate.

Exclusion criteria:

* Patients who cannot undergo neuropsychological investigation due to unconsciousness
* Patients who cannot undergo neuropsychological investigation, being mentally too ill
* Patients who suffer from dementia
* Patients who cannot undergo FDG-PET due to claustrophobia
* Patients who cannot undergo EEG due to panic attacks
* Age under 16.

Primary outcomes:
measure: A change in FDG-PET signal indicating inflammation
timeFrame: When all patients have been followed up for at least 1 year.
measure: A change in FDG-PET signal indicating a change in neuronal activity
timeFrame: When all patients have been followed up for at least 1 year.
measure: A change in EEG activity indicating a change in neuronal activity based on EEG power in alpha, theta, and delta frequencies.
timeFrame: When all patients have been followed up for at least 1 year.
Secondary outcomes:
measure: Fatigue after brain abscess
timeFrame: When all patients have been followed up for at least 1 year.
measure: No fatigue after brain abscess
timeFrame: When all patients have been followed up for at least 1 year.
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: University of Oslo
name: Bjørnar Hassel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Oslo University Hospital
name: Daniel Dahlberg, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rogne AG, Muller EG, Udnaes E, Sigurdardottir S, Raudeberg R, Connelly JP, Revheim ME, Hassel B, Dahlberg D. beta-Amyloid may accumulate in the human brain after focal bacterial infection: An 18 F-flutemetamol positron emission tomography study. Eur J Neurol. 2021 Mar;28(3):877-883. doi: 10.1111/ene.14622. Epub 2020 Nov 27.
citation: Dahlberg D, Holm S, Sagen EML, Michelsen AE, Stensland M, de Souza GA, Muller EG, Connelly JP, Revheim ME, Halvorsen B, Hassel B. Bacterial Brain Abscesses Expand Despite Effective Antibiotic Treatment: A Process Powered by Osmosis Due to Neutrophil Cell Death. Neurosurgery. 2023 Dec 12;94(5):1079-87. doi: 10.1227/neu.0000000000002792. Online ahead of print.
citation: Hassel B, Niehusmann P, Halvorsen B, Dahlberg D. Pro-inflammatory cytokines in cystic glioblastoma: A quantitative study with a comparison with bacterial brain abscesses. With an MRI investigation of displacement and destruction of the brain tissue surrounding a glioblastoma. Front Oncol. 2022 Jul 29;12:846674. doi: 10.3389/fonc.2022.846674. eCollection 2022.