Cognitive Function and Fatigue After Brain Abscess

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.

Study Overview

• Status: Recruiting
• Conditions: Fatigue; Cognitive Dysfunction; Brain Abscess
• Intervention / Treatment: Other: FDG-PET; Other: EEG

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.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Peder H Utne; Phone Number: +4723066023; Email: pedutn@ous-hf.no

Study Locations

• Norway
  • Oslo, Norway, 0450
    • Recruiting
    • Oslo University Hospital
    • Contact: Bjørnar Hassel, MD, PhD; Phone Number: +4722118080; Email: bjornar.hassel@medisin.uio.no
    • Contact: Daniel Dahlberg, MD, PhD; Phone Number: +4723070000; Email: danieldahlberg@gmail.com
    • Sub-Investigator: Ane G Rogne, Psychol.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients older than 16 years, who have completed treatment for brain abscess and who agree to participate.

Description

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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Brain abscess patients with cognitive dysfunction and/or fatigue; This group of patients experience cognitive dysfunction and/or fatigue after brain abscess.	Other: FDG-PET; [18F]Deoxyglucose-positron emission tomography at 0-10 years after brain abscess; Other: EEG; Electroencephalography (EEG) at 0-10 years after brain abscess
Brain abscess patients without cognitive dysfunction and/or fatigue; This group of patients does not experience cognitive dysfunction and/or fatigue after brain abscess.	Other: FDG-PET; [18F]Deoxyglucose-positron emission tomography at 0-10 years after brain abscess; Other: EEG; Electroencephalography (EEG) at 0-10 years after brain abscess

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A change in FDG-PET signal indicating inflammation	The FDG-PET signal indicates inflammation of brain tissue or the brain abscess capsule.	When all patients have been followed up for at least 1 year.
A change in FDG-PET signal indicating a change in neuronal activity	A change neocortical FDG-PET signal indicates a change in neuronal activity caused by brain tissue damage by the brain abscess.	When all patients have been followed up for at least 1 year.
A change in EEG activity indicating a change in neuronal activity based on EEG power in alpha, theta, and delta frequencies.	A change neocortical EEG activity indicates a change in neuronal activity caused by brain tissue damage by the brain abscess evident as changes in EEG power in alpha, theta, and delta frequencies..	When all patients have been followed up for at least 1 year.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue after brain abscess	Neuropsychological investigation with the use of Chalder's fatigue questionnaire. Degree of fatigue is determined from the answers to 11 questions. The answer "Better than before" gives a score of 0, "Same as before" gives a score of 1, "Worse than before" gives a score of 2, and "Much worse than before" gives a score of 3. Thus, a maximum fatigue score is 33, meaning a very high degree of fatigue.	When all patients have been followed up for at least 1 year.
No fatigue after brain abscess	Neuropsychological investigation with the use of Chalder's fatigue questionnaire. Degree of fatigue is determined from the answers to 11 questions. The answer "Better than before" gives a score of 0, "Same as before" gives a score of 1, "Worse than before" gives a score of 2, and "Much worse than before" gives a score of 3. Thus, a maximum fatigue score is 33, meaning a very high degree of fatigue.	When all patients have been followed up for at least 1 year.

Collaborators and Investigators

• Sponsor: University of Oslo
• Collaborators: Oslo University Hospital; Sunnaas Rehabilitation Hospital
• Investigators: Principal Investigator: Bjørnar Hassel, MD, PhD, University of Oslo; Principal Investigator: Daniel Dahlberg, MD, PhD, Oslo University Hospital

Publications and helpful links

General Publications

• 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.
• 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. doi: 10.1227/neu.0000000000002792. Online ahead of print.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2020
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: June 13, 2021
• First Submitted That Met QC Criteria: June 23, 2021
• First Posted (Actual): June 24, 2021

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 19, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Infections; Inflammation; Neurocognitive Disorders; Central Nervous System Infections; Cognition Disorders; Suppuration; Fatigue; Cognitive Dysfunction; Abscess; Brain Abscess
• Other Study ID Numbers: Cognition/fatigue/brainabscess

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Patient data will be published on a group basis without identifiable characteristics. Publication will be in an international, peer-reviewed medical journal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No