Fatigue and depression at 8 weeks and 1 year after bacterial brain abscess and their relationship with cognitive status.

A bacterial brain abscess (BA) is a focal brain infection with largely unknown long-term implications. This prospective study assessed the frequency of fatigue and symptoms of depression at 8 weeks and 1 year after BA and examined the relationship between fatigue, depressive symptoms, and cognitive status. Twenty BA-patients (age 17-73; 45% female) were assessed for fatigue, depression, memory, and executive functions. Fatigue rates were 40-65% at 8 weeks and 25-33% at 1 year on various fatigue questionnaires. Patient Health Questionnaire indicated symptoms of depression in 10% at the 8-week follow-up only. Relevant comorbidities and vocational outcomes were not associated with fatigue or symptoms of depression. Mean fatigue scores improved significantly between the two-time points. Greater fatigue was related to subjective problems with working memory, inhibition, self-monitoring, and emotional control and worse objective verbal memory performance. Symptoms of depression were associated with one out of two fatigue measures. We conclude that fatigue is common in the first year after BA, and higher levels of fatigue are related to more cognitive problems. Symptoms of clinical depression were rare. These findings underscore fatigue as an important consequence of BA and emphasize the necessity for targeted rehabilitation interventions.

Cognitive and everyday functioning after bacterial brain abscess: a prospective study of functional recovery from 8 weeks to 1 year post-treatment.

OBJECTIVE: A bacterial brain abscess may damage surrounding brain tissue by mass effect, inflammatory processes, and bacterial toxins. The aim of this study was to examine cognitive and functional outcomes at 8 weeks and 1 year following acute treatment. METHODS: Prospective study of 20 patients with bacterial brain abscess (aged 17-73 years; 45% females) with neuropsychological assessment at 8 weeks and 1 year post-treatment. Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) and Patient Competence Rating Scale (PCRS) were used to assess everyday functioning and administered to patients and informants. RESULTS: Cognitive impairment was found in 30% of patients at 8 weeks and 22% at 1 year. Significant improvements were seen on tests of perceptual reasoning, attention, verbal fluency, and motor abilities (p < 0.05). At 1 year, 45% had returned to full-time employment. Nevertheless, patients and their informants obtained scores within the normal range on measures of everyday functioning (PCRS and BRIEF-A) at 8 weeks and 1 year. No significant improvements on these measures emerged over time. CONCLUSION: Residual long-term cognitive impairment and diminished work ability affected 22% and 45% of patients one year after BA. Persistent cognitive impairment emphasizes the importance of prompt acute treatment and cognitive rehabilitation.

ß-Amyloid may accumulate in the human brain after focal bacterial infection: An 18 F-flutemetamol positron emission tomography study.

BACKGROUND AND PURPOSE: ß-Amyloid formation has been suggested to form part of the brain's response to bacterial infection. This hypothesis has been based on experimental animal studies and autopsy studies in humans. We asked if ß-amyloid accumulates locally around a bacterial brain abscess in living human patients. Furthermore, because brain abscess patients may suffer from chronic cognitive symptoms after abscess treatment, we also asked if a brain abscess precipitates accumulation of ß-amyloid in the neocortex in a manner that could explain abscess-related cognitive complaints. METHODS: In a prospective study, we investigated 17 brain abscess patients (age 24-72 years) with 18 F-flutemetamol positron emission tomography on one occasion 1 to 10 months after brain abscess treatment to visualize ß-amyloid accumulation. RESULTS: 18 F-flutemetamol uptake was reduced in the edematous brain tissue that surrounded the abscess remains. On this background of reduced 18 F-flutemetamol signal, three out of 17 patients showed a distinctly increased 18 F-flutemetamol uptake in the tissue immediately surrounding the abscess remains, suggesting accumulation of ß-amyloid. These three patients underwent 18 F-flutemetamol positron emission tomography significantly earlier after neurosurgical treatment (p = 0.042), and they had larger abscesses (p = 0.027) than the rest of the patients. All 17 patients suffered from mental fatigue or some subjective cognitive symptom, such as attention difficulties or memory problems, but in none of the patients was there an increase in neocortical 18 F-flutemetamol signal. CONCLUSIONS: ß-Amyloid may accumulate locally around the abscess remains in some patients with a brain abscess.

Intellectual Disability Associated With Pyridoxine-Responsive Epilepsies: The Need to Protect Cognitive Development.

Pyridoxine (vitamin B6)-responsive epilepsies are severe forms of epilepsy that manifest as seizures immediately after birth, sometimes in utero, sometimes months, or years after birth. Seizures may be treated efficiently by life-long supplementation with pyridoxine or its biologically active form, pyridoxal phosphate, but even so patients may become intellectually disabled, for which there currently is no effective treatment. The condition may be caused by mutations in several genes (TNSALP, PIGV, PIGL, PIGO, PNPO, PROSC, ALDH7A1, MOCS2, or ALDH4A1). Mutations in ALDH7A1, MOCS2, and ALDH4A1 entail build-up of reactive aldehydes (α-aminoadipic semialdehyde, γ-glutamic semialdehyde) that may react non-enzymatically with macromolecules of brain cells. Such reactions may alter the function of macromolecules, and they may produce "advanced glycation end products" (AGEs). AGEs trigger inflammation in the brain. This understanding points to aldehyde-quenching, anti-AGE, or anti-inflammatory therapies as possible strategies to protect cognitive development and prevent intellectual disability in affected children. Studies on how aldehydes traverse cell membranes and how they affect brain function could further the development of therapies for patients with pyridoxine-responsive epilepsies.