Publications
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Bull, Emilie Meyer; Hofmann, Bjørn Morten; Nærland, Terje; Andreassen, Ole; Quintana, Daniel & Hassel, Bjørnar
(2025).
Ethical and practical concerns of heart rate monitoring: Enabling communication for patients with severe communication difficulties.
Clinical Ethics.
ISSN 1477-7509.
20(3),
p. 170–181.
doi:
10.1177/14777509251361204.
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Monitoring technologies to aid communication in long-term patient care may enhance safety but infringe on privacy. While autonomy is a primary value in bioethics, definitions of autonomy often take for granted a minimum level of communicative ability. This paper explores how contemporary philosophical arguments for using long-term preventative monitoring apply to individuals without the ability to consent to such technologies. Specifically, how do the ethical principles of autonomy, justice, safety, and privacy manifest when implementing technologies such as long-term heart rate monitoring for individuals with severe communication difficulties? While monitoring someone without their consent is ethically problematic, providing heart rate monitoring for individuals with severe communication difficulties may be morally imperative as a necessary means of interaction. Heart rate monitoring enhances their autonomy by offering a form of communication, and it shows promise as safety -inducing through quicker detection of distress. Simultaneously, heart rate monitoring is a form of surveillance, thus potentially violating privacy ; and misinterpretation or over-reliance on such data might undermine the patient's autonomy , lead to unnecessary interventions or result in reduced human interaction. Restricting monitoring based on consent capacity may deepen care disparities and violate the justice principle but so does selectively applying it to disabled individuals. We conclude that heart rate monitoring might greatly benefit this population, but we need to balance potential benefits for the individual with the risks, trained caregivers must integrate data with other cues, and we need data encryption, collaborative decision-making, and regular reassessment.
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Boysen, Elin Sundby; Øderud, Tone; Strisland, Frode; Bull, Emilie Meyer; Dahl, Inger-Lise & Hassel, Bjørnar
[Show all 7 contributors for this article]
(2024).
Using heart rate monitoring to discover pain and discomfort in non-verbal persons with severe intellectual disability: Caregivers’ experiences.
Technology and Disability.
ISSN 1055-4181.
36(4),
p. 161–170.
doi:
10.3233/TAD-230029.
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BACKGROUND Non-verbal persons with intellectual disabilities (ID) may suffer from pain or discomfort, but caregivers may not notice this because of the communication difficulties. Previously, we conducted a study in which professional caregivers used heart rate (HR) monitoring to identify situations that cause acute pain or distress in the everyday life of non-verbal persons with ID. OBJECTIVE To explore professional caregivers’ experience with using HR monitors to better understand non-verbal persons with ID. METHODS Fifteen professional caregivers and 30 final-year students of social education were recruited as informants based on their experience with HR monitoring in non-verbal persons. The informants were interviewed, and they responded to a questionnaire with open-ended questions. The qualitative data were analysed thematically. RESULTS Caregivers reported that HR monitoring provided information about acute pain, acute or prolonged distress, occurrence of epileptic seizures, and the non-verbal persons’ preferences and dislikes. HR data had to be interpreted contextually to be meaningful. Some informants found HR monitoring time-consuming or the interpretation of HR data challenging due to multiple possible causes of increased HR. CONCLUSIONS Caregivers experience HR monitoring as a potentially important source of information that may help them better understand non-verbal persons with ID.
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Rogne, Ane Gretesdatter; Sigurdardottir, Solrun; Raudeberg, Rune; Hassel, Bjørnar & Dahlberg, Daniel
(2024).
Cognitive and everyday functioning after bacterial brain abscess: a prospective study of functional recovery from 8 weeks to 1 year post-treatment.
Brain Injury.
ISSN 0269-9052.
38(10),
p. 787–795.
doi:
10.1080/02699052.2024.2347565.
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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
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Müller, Ebba Gløersen; Dahlberg, Daniel; Hassel, Bjørnar; Rootwelt-Revheim, Mona-Elisabeth & Connelly, James Pattrick
(2024).
Brain Abscess Causes Brain Damage With Long-Lasting Focal Cerebral Hypoactivity that Correlates With Abscess Size: A Cross-Sectional 18F-Fluoro-Deoxyglucose Positron Emission Tomography Study.
Neurosurgery.
ISSN 0148-396X.
doi:
10.1227/neu.0000000000003268.
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BACKGROUND AND OBJECTIVES: Bacterial brain abscesses may have long-term clinical consequences, eg, mental fatigue or epilepsy, but long-term structural consequences to the brain remain underexplored. We asked if brain abscesses damage brain activity long term, if the extent of such damage depends on the size of the abscess, and if the abscess capsule, which is often left in place during neurosurgery, remains a site of inflammation, which could explain long-lasting symptoms in patients with brain abscess. METHODS: 2-[ 18 F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT), electroencephalography, and MRI were performed 2 days to 9 years after neurosurgery for bacterial brain abscess. RESULTS: FDG-PET/CT revealed hypometabolism in the neocortex or cerebellum overlying the previous bacterial abscess in 38 of 40 patients. The larger the abscess, the greater was the extent of the subsequent hypometabolism (r = 0.63; p = 3 × 10 5). In 9 patients, the extent of subsequent hypometabolism seemed to coincide with the extent of peri-abscess edema in the acute phase. Follow-up MRI after ≥1 year in 9 patients showed focal tissue loss and gliosis. In 13 patients with abnormal electroencephalography recordings, abnormalities extended beyond the cerebral lobe affected by the abscess, indicating damage to wider brain networks. The abscess capsule had an FDG signal indicating inflammation only during the first week after neurosurgical pus drainage. CONCLUSION: The bigger a brain abscess is allowed to grow, the more extensive is the long-term focal reduction in brain activity. This finding emphasizes the need for rapid neurosurgical intervention. The abscess capsule does not display long-lasting inflammation and probably does not explain long-term symptoms after brain abscess.
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Hassel, Bjørnar; Sørnes, Kristian; Elsais, Ahmed; Cordero, Patricia Reyes; Frøland, Anne-Sofie & Rise, Frode
(2024).
Glyceraldehyde metabolism in mouse brain and the entry of blood-borne glyceraldehyde into the brain.
Journal of Neurochemistry.
ISSN 0022-3042.
doi:
10.1111/jnc.16158.
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D-Glyceraldehyde, a reactive aldehyde metabolite of fructose and glucose, is neurotoxic in vitro by forming advanced glycation end products (AGEs) with neuronal proteins. In Alzheimer's disease brains, glyceraldehyde-containing AGEs have been detected intracellularly and in extracellular plaques. However, little information exists on how the brain handles D-glyceraldehyde metabolically or if glyceraldehyde crosses the blood–brain barrier from the circulation into the brain. We injected [U-13C]-D-glyceraldehyde intravenously into awake mice and analyzed extracts of serum and brain by 13C nuclear magnetic resonance spectroscopy. 13C-Labeling of brain lactate and glutamate indicated passage of D-glyceraldehyde from blood to brain and glycolytic and oxidative D-glyceraldehyde metabolism in brain cells. 13C-Labeling of serum glucose and lactate through hepatic metabolism of [U-13C]-D-glyceraldehyde could not explain the formation of 13C-labeled lactate and glutamate in the brain. Cerebral glyceraldehyde dehydrogenase and reductase activities, leading to the formation of D-glycerate and glycerol, respectively, were 0.27–0.28 nmol/mg/min; triokinase, which phosphorylates D-glyceraldehyde to D-glyceraldehyde-3-phosphate, has been demonstrated previously at low levels. Thus, D-glyceraldehyde metabolism toward glycolysis could proceed both through D-glycerate, glycerol, and D-glyceraldehyde-3-phosphate. The aldehyde group of D-glyceraldehyde was overwhelmingly hydrated into a diol in aqueous solution, but the diol dehydration rate greatly exceeded glyceraldehyde metabolism and did not restrict it. We conclude that (1) D-glyceraldehyde crosses the blood–brain barrier, and so blood-borne glyceraldehyde could contribute to AGE formation in the brain, (2) glyceraldehyde is taken up and metabolized by brain cells. Metabolism thus constitutes a detoxification mechanism for this reactive aldehyde, a mechanism that may be compromised in disease states.
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Jamali, Ahmed; Kristensen, Erle; Tangeraas, Trine; Arntsen, Vibeke; Sikric, Alma & Kupliauskiene, Guste
[Show all 13 contributors for this article]
(2023).
The spectrum of pyridoxine dependent epilepsy across the age span: A nationwide retrospective observational study.
Epilepsy Research.
ISSN 0920-1211.
190.
doi:
10.1016/j.eplepsyres.2023.107099.
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Background
Pyridoxine-dependent epilepsy (PDE) is a rare seizure disorder usually presenting with neonatal seizures. Most cases are caused by biallelic pathogenic ALDH7A1variants. While anti-seizure medications are ineffective, pyridoxine provides seizure control, and dietary interventions may be of benefit. As the natural history beyond adolescence is insufficiently explored, our study aimed to assess the spectrum of PDE at various ages in Norway.
Methods
Patients were ascertained by contacting all Norwegian paediatric, neurological, and neurohabilitation departments and relevant professional societies. Medical records were collected and reviewed.
Results
We identified 15 patients treated for PDE; 13 had ALDH7A1 variants (PDE-ALDH7A1), one had PNPO deficiency, and in one, aetiology remained obscure. Of those with PDE-ALDH7A1, 12 were alive at time of study; five were > 18 years old and six were 1 h) or uncertain effect. Median delay from first seizure to continuous treatment was 11 days (range 0–42). Nine experienced breakthrough seizures with intercurrent disease or due to pyridoxine discontinuation. Cognitive outcomes ranged from normal to severe intellectual disability. The condition appeared to remain stable in adult life.
Significance
We found a much higher prevalence of PDE-ALDH7A1 in children relative to adults, suggesting previous underdiagnosis and early mortality. Perinatal complications are common and can delay diagnosis and initiation of pyridoxine treatment. Lifelong and continuous treatment with pyridoxine is imperative. Due to better diagnostics and survival, the number of adult patients is expected to rise.
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Øderud, Tone; Boysen, Elin Sundby; Strisland, Frode; Dahl, Inger-Lise; Bull, Emilie Meyer & Hassel, Bjørnar
[Show all 7 contributors for this article]
(2023).
Identifying pain and distress in non-verbal persons with intellectual disability: Professional caregivers' and parents' attitudes towards using wearable sensors.
Technology and Disability.
ISSN 1055-4181.
35(3),
p. 207–216.
doi:
10.3233/TAD-220390.
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BACKGROUND: Persons with severe intellectual disability (ID) may be non-verbal and unable to communicate pain or distress. Consequently, painful conditions may go undetected, and non-verbal persons with ID may not receive adequate care and treatment. OBJECTIVE: This study aims to explore how professional caregivers and parents identify pain and distress in non-verbal persons with ID, and their attitudes towards using wearable sensors to identify pain and distress in daily life situations. METHODS: Exploratory, mixed method study. Caregivers (83) answered an online questionnaire, and professional caregivers (18) and parents (7) were interviewed. RESULTS: Professional caregivers and parents recognise pain and distress from observations and behavioural signs that are often equivocal. They experience that this is inadequate to reliably detect pain and distress in non-verbal persons with ID. Professional caregivers and parents’ express frustration and fear that painful conditions may remain untreated. They are positive towards using wearable sensors on condition that sensors do not infringe on user autonomy and privacy. CONCLUSIONS: There is a need for sensors and methods that can objectively identify pain and distress and ensure adequate treatment, that may improve quality of life of non-verbal persons with ID.
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Dahlberg, Daniel; Holm, Sverre; Sagen, Ellen Lund; Michelsen, Annika Elisabet; Stensland, Maria & Souza, Gustavo Antonio De
[Show all 11 contributors for this article]
(2023).
Bacterial Brain Abscesses Expand Despite Effective AntibioticTreatment: A Process Powered by Osmosis Due to NeutrophilCell Death.
Neurosurgery.
ISSN 0148-396X.
doi:
10.1227/neu.0000000000002792.
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BACKGROUND AND OBJECTIVES: A bacterial brain abscess is an emergency and should be drained of pus within24 hours of diagnosis, as recently recommended. In this cross-sectional study, we investigated whether delaying pusdrainage 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: Themedian average increase was 23% per day (range 0%-176%). Abscesses expanded during antibiotic therapy and even ifthe pus did not contain viable bacteria. In a separate patient cohort, we found that brain abscess pus tended to behyperosmolar (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 throughincreased pressure in the abscess cavity. A mechanism likely underlying pus hyperosmolarity was the recruitment ofneutrophils to the abscess cavity with ensuing neutrophil cell death and decomposition of neutrophil proteins and othermacromolecules 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 focalneocortical 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 lastingdamage to surrounding brain tissue. These findings support drainage of brain abscesses within 24 hours of diagnosis.
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Rogne, Ane Gretesdatter & Hassel, Bjørnar
(2022).
Improvement of attention deficit/hyperactivity disorder (ADHD) in three adult men during testosterone treatment: a case series.
Journal of Medical Case Reports.
16(1),
p. 1–7.
doi:
10.1186/s13256-022-03651-w.
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Background Attention deficit/hyperactivity disorder (ADHD) entails inattention, impulsivity, and restlessness at a disabling level. The pharmacological treatment of ADHD rests on the use of centrally acting stimulants, such as methylphenidate and D-amphetamine. In some patients, these drugs cause side effects that preclude their use. Case presentation We present three adult male, Caucasian, ADHD patients (24, 37, and 43 years old) whose ADHD symptoms improved during treatment with testosterone. The first patient experienced loss of libido during treatment with methylphenidate; for this, he was offered a trial of testosterone. Unexpectedly, his ADHD symptoms improved with testosterone treatment, and this effect continued with testosterone as monotherapy. The two other patients, who also had side effects from centrally acting stimulants, received testosterone monotherapy with similar results. The effect has now continued for 4.5–5 years at the same doses: 10–60 mg testosterone/day, administered as a skin gel. Prior to testosterone treatment, the patients had serum levels of testosterone in the low–normal range: 12–16 nmol/L (age-specific reference range: 10.4–32.6 nmol/L). The testosterone/sex hormone-binding globulin ratio was low in two patients (0.32 and 0.34; age-specific reference range: 0.38–1.1), suggesting low free serum levels of testosterone. Serum testosterone levels and testosterone/sex hormone-binding globulin ratios increased with testosterone treatment in all patients, but remained within reference values. Conclusion These cases suggest that a moderately reduced serum level of free testosterone may contribute to the ADHD symptoms of some adult male ADHD patients, and that testosterone treatment may be of value for these patients.
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Kildal, Emilie Smith-Meyer; Hassel, Bjørnar & Bjørnebekk, Astrid
(2022).
ADHD symptoms and use of anabolic androgenic steroids among male weightlifters.
Scientific Reports.
12(1),
p. 1–8.
doi:
10.1038/s41598-022-12977-w.
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Abstract Use of anabolic androgenic steroids (AAS) is associated with adverse health effects. The factors that predispose to AAS use among athletes are poorly understood, but attention deficit/hyperactivity disorder (ADHD), which is known to occur among athletes more often than in the general population, is associated with risk behaviors, including substance abuse. We aimed to see if AAS use in male weightlifters was associated with ADHD symptoms, and test the link between ADHD symptoms and cognitive performance. Hundred and forty male weightlifters, 72 AAS users and 68 weightlifting controls (WLC), completed the Achenbach system of empirically based assessment (ASEBA) for ADHD symptoms and underwent cognitive examination. Self-reported ADHD symptom scores were significantly higher among AAS users compared to WLC, and scores in the range indicating clinically important ADHD was significantly more common in the AAS-using group. Age of onset of AAS use correlated inversely with ADHD scale score (r = − 0.35; p = 0.003). ADHD score correlated inversely with cognitive scores for working memory (r = − 0.25, p < 0.001), processing speed (r = − 0.24, p < 0.001), verbal learning and memory (r = − 0.19, p = 0.03), and problem solving (r = − 0.20, p = 0.02). AAS use among weightlifters is associated with ADHD symptoms and corresponding lower cognitive performance. Recognising a relationship between ADHD symptoms and AAS use may guide drug prevention strategies in sports.
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Svae, Gøril Brevik; Hassel, Bjørnar & Søndenaa, Erik
(2022).
People with intellectual disabilities and harmful sexual behaviour: Professionals' views on the barriers to prevent harm.
JARID: Journal of applied research in intellectual disabilities.
ISSN 1360-2322.
36(1),
p. 176–185.
doi:
10.1111/jar.13048.
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Background
People with intellectual disabilities can be exposed to sexual abuse and they can display harmful sexual behaviour. This study aimed to identify barriers to preventing harmful sexual behaviour in people with intellectual disabilities within the support sector and the justice system.
Method
We conducted focus group interviews with 20 participants from hospital-based habilitation centres, community residences, schools and the criminal justice system.
Results
The interviews identified a lack of education and guidelines for stakeholders or carers on regulating the sexual behaviour of people with intellectual disabilities. The criminal justice system faces challenges related to prioritising, understanding and communicating. People with intellectual disabilities may lack an understanding of the concepts of sexual consent and acceptable sexual behaviour.
Conclusion
There is a need to improve knowledge about intellectual disability and how to prevent harmful sexual behaviour for professional caregivers in the support sector and the criminal justice system.
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Watne, Leiv Otto; Pollmann, Christian Thomas; Neerland, Bjørn Erik; Paulsen, Else Quist; Halaas, Nathalie Bodd & Idland, Ane-Victoria
[Show all 20 contributors for this article]
(2022).
Cerebrospinal fluid quinolinic acid is strongly associated with delirium and mortality in hip-fracture patients.
Journal of Clinical Investigation.
ISSN 0021-9738.
133(2).
doi:
10.1172/JCI163472.
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Background: The kynurenine pathway (KP) has been identified as a potential mediator linking acute illness to cognitive dysfunction by generating neuroactive metabolites in response to inflammation. Delirium (acute confusion) is a common complication of acute illness and is associated with increased risk of dementia and mortality. However, the molecular mechanism underlying delirium, particularly in relation to the KP, remain elusive.
Methods: We undertook a multi-center observational study with 586 hospitalized patients (248 with delirium) and investigated associations between delirium and KP metabolites measured in cerebrospinal fluid (CSF) and serum by targeted metabolomics. We also explored associations between KP metabolites and markers of neuronal damage and one-year mortality.
Results: In delirium, we found concentrations of the neurotoxic metabolite quinolinic acid in CSF (CSF-QA, OR 2.26 [1.78, 2.87], p
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Hassel, Bjørnar; Niehusmann, Pitt; Halvorsen, Bente & Dahlberg, Daniel
(2022).
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.
Frontiers in Oncology.
doi:
10.3389/fonc.2022.846674.
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Cystic glioblastomas are aggressive primary brain tumors that may both destroy and displace the surrounding brain tissue as they grow. The mechanisms underlying these tumors’ destructive effect could include exposure of brain tissue to tumor-derived cytokines, but quantitative cytokine data are lacking. Here, we provide quantitative data on leukocyte markers and cytokines in the cyst fluid from 21 cystic glioblastomas, which we compare to values in 13 brain abscess pus samples. The concentration of macrophage/microglia markers sCD163 and MCP-1 was higher in glioblastoma cyst fluid than in brain abscess pus; lymphocyte marker sCD25 was similar in cyst fluid and pus, whereas neutrophil marker myeloperoxidase was higher in pus. Median cytokine levels in glioblastoma cyst fluid were high (pg/mL): TNF-α: 32, IL-6: 1064, IL-8: 23585, tissue factor: 28, the chemokine CXCL1: 639. These values were not significantly different from values in pus, pointing to a highly pro-inflammatory glioblastoma environment. In contrast, levels of IFN-γ, IL-1β, IL-2, IL-4, IL-10, IL-12, and IL-13 were higher in pus than in glioblastoma cyst fluid. Based on the quantitative data, we show for the first time that the concentrations of cytokines in glioblastoma cyst fluid correlate with blood leukocyte levels, suggesting an important interaction between glioblastomas and the circulation. Preoperative MRI of the cystic glioblastomas confirmed both destruction and displacement of brain tissue, but none of the cytokine levels correlated with degree of brain tissue displacement or peri-tumoral edema, as could be assessed by MRI. We conclude that cystic glioblastomas are highly pro-inflammatory environments that interact with the circulation and that they both displace and destroy brain tissue. These observations point to the need for neuroprotective strategies in glioblastoma therapy, which could include an anti-inflammatory approach.
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Dahlberg, Daniel; Rummel, Jutta; Distante, Sonia; Souza, Gustavo Antonio De; Stensland, Maria & Mariussen, Espen
[Show all 9 contributors for this article]
(2022).
Glioblastoma microenvironment contains multiple hormonal and non-hormonal growth-stimulating factors.
Fluids and Barriers of the CNS.
19(1).
doi:
10.1186/s12987-022-00333-z.
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BackgroundThe growth of malignant tumors is influenced by their microenvironment. Glioblastoma, an aggressive primary brain tumor, may have cysts containing fluid that represents the tumor microenvironment. The aim of this study was to investigate whether the cyst fluid of cystic glioblastomas contains growth-stimulating factors. Identification of such growth factors may pave the way for the development of targeted anti-glioblastoma therapies.
MethodsWe performed hormone analysis of cyst fluid from 25 cystic glioblastomas and proteomics analysis of cyst fluid from another 12 cystic glioblastomas.
ResultsGlioblastoma cyst fluid contained hormones within wide concentration ranges: Insulin-like growth factor 1 (0–13.7 nmol/L), insulin (1.4–133 pmol/L), erythropoietin (4.7–402 IU/L), growth hormone (0–0.93 µg/L), testosterone (0.2–10.1 nmol/L), estradiol (0–1.0 nmol/L), triiodothyronine (1.0–11.5). Tumor volume correlated with cyst fluid concentrations of growth hormone and testosterone. Survival correlated inversely with cyst fluid concentration of erythropoietin. Several hormones were present at concentrations that have been shown to stimulate glioblastoma growth in vitro. Concentrations of erythropoietin and estradiol (in men) were higher in cyst fluid than in serum, suggesting formation by tumor or brain tissue. Quantitatively, glioblastoma cyst fluid was dominated by serum proteins, illustrating blood–brain barrier leakage. Proteomics identified several proteins that stimulate tumor cell proliferation and invasiveness, others that inhibit apoptosis or mediate adaption to hypoxia and some that induce neovascularization or blood–brain barrier leakage.
ConclusionThe microenvironment of glioblastomas is rich in growth-stimulating factors that may originate from the circulation, the tumor, or the brain. The wide variation in cyst fluid hormone concentrations may differentially influence tumor growth.
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Eide, Per Kristian; Mariussen, Espen; Uggerud, Hilde Thelle; Pripp, Are Hugo; Lashkarivand, Aslan & Hassel, Bjørnar
[Show all 9 contributors for this article]
(2021).
Clinical application of intrathecal gadobutrol for assessment of cerebrospinal fluid tracer clearance to blood.
JCI Insight.
6(9),
p. 1–13.
doi:
10.1172/jci.insight.147063.
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BACKGROUND. Methodology for estimation of cerebrospinal fluid (CSF) tracer clearance could have wide clinical application in predicting excretion of intrathecal drugs and metabolic solutes from brain metabolism and for diagnostic workup of CSF disturbances. METHODS. The MRI contrast agent gadobutrol (Gadovist) was used as a CSF tracer and injected into the lumbar CSF. Gadobutrol is contained outside blood vessels of the CNS and is eliminated along extravascular pathways, analogous to many CNS metabolites and intrathecal drugs. Tracer enrichment was verified and assessed in CSF by MRI at the level of the cisterna magna in parallel with obtaining blood samples through 48 hours. RESULTS. In a reference patient cohort (n = 29), both enrichment within CSF and blood coincided in time. Blood concentration profiles of gadobutrol through 48 hours varied between patients diagnosed with CSF leakage (n = 4), idiopathic normal pressure hydrocephalus dementia (n = 7), pineal cysts (n = 8), and idiopathic intracranial hypertension (n = 4). CONCLUSION. Assessment of CSF tracer clearance is clinically feasible and may provide a way to predict extravascular clearance of intrathecal drugs and endogenous metabolites from the CNS. The peak concentration in blood (at about 10 hours) was preceded by far peak tracer enhancement at MRI in extracranial lymphatic structures (at about 24 hours), as shown in previous studies, indicating a major role of the spinal canal in CSF clearance capacity. FUNDING. The work was supported by the Department of Neurosurgery, Oslo University Hospital; the Norwegian Institute for Air Research; and the University of Oslo.
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Henjum, Kristi; Godang, Kristin; Quist-Paulsen, Else; Idland, Ane-Victoria; Neerland, Bjørn Erik & Sandvig, Heidi Vihovde
[Show all 13 contributors for this article]
(2021).
Cerebrospinal fluid catecholamines in delirium and dementia.
Brain Communications.
3(3),
p. 1–11.
doi:
10.1093/braincomms/fcab121.
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Dopamine and noradrenaline are functionally connected to delirium and have been targets for pharmacological interventions but
the biochemical evidence to support this notion is limited. To study the CSF levels of dopamine, noradrenaline and the third catecholamine
adrenaline in delirium and dementia, these were quantified in three patient cohorts: (i) cognitively normal elderly
patients (n¼122); (ii) hip fracture patients with or without delirium and dementia (n¼118); and (iii) patients with delirium precipitated
by another medical condition (medical delirium, n¼26). Delirium was assessed by the Confusion Assessment Method.
The hip fracture cohort had higher CSF levels of noradrenaline and adrenaline than the two other cohorts (both P<0.001).
Within the hip fracture cohort those with delirium (n¼65) had lower CSF adrenaline and dopamine levels than those without delirium
(n¼52, P¼0.03, P¼0.002). Similarly, the medical delirium patients had lower CSF dopamine levels than the cognitively
normal elderly (P<0.001). Age did not correlate with the CSF catecholamine levels. These findings with lower CSF dopamine levels
in hip fracture- and medical delirium patients challenge the theory of dopamine excess in delirium and question use of antipsychotics
in delirium. The use of alpha-2 agonists with the potential to reduce noradrenaline release needs further examination.
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Raheel, Tayyaba Qureshi; Bjørkmo, Mona; Nordengen, Kaja; Gundersen, Vidar; Utheim, Tor Paaske & Watne, Leiv Otto
[Show all 9 contributors for this article]
(2020).
Slc38a1 Conveys Astroglia-Derived Glutamine into GABAergic Interneurons for Neurotransmitter GABA Synthesis.
Cells.
9(7),
p. 1–12.
doi:
10.3390/cells9071686.
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GABA signaling is involved in a wide range of neuronal functions, such as synchronization of action potential firing, synaptic plasticity and neuronal development. Sustained GABA signaling requires efficient mechanisms for the replenishment of the neurotransmitter pool of GABA. The prevailing theory is that exocytotically released GABA may be transported into perisynaptic astroglia and converted to glutamine, which is then shuttled back to the neurons for resynthesis of GABA—i.e., the glutamate/GABA-glutamine (GGG) cycle. However, an unequivocal demonstration of astroglia-to-nerve terminal transport of glutamine and the contribution of astroglia-derived glutamine to neurotransmitter GABA synthesis is lacking. By genetic inactivation of the amino acid transporter Solute carrier 38 member a1 (Slc38a1)—which is enriched on parvalbumin+ GABAergic neurons—and by intraperitoneal injection of radiolabeled acetate (which is metabolized to glutamine in astroglial cells), we show that Slc38a1 mediates import of astroglia-derived glutamine into GABAergic neurons for synthesis of GABA. In brain slices, we demonstrate the role of Slc38a1 for the uptake of glutamine specifically into GABAergic nerve terminals for the synthesis of GABA depending on demand and glutamine supply. Thus, while leaving room for other pathways, our study demonstrates a key role of Slc38a1 for newly formed GABA, in harmony with the existence of a GGG cycle.
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Sumathipala, Dulika Sanjeewani; Strømme, Petter; Gilissen, Christian; Einarsen, Ingunn Holm; Bjørndalen, Hilde & Server, Andrés
[Show all 11 contributors for this article]
(2020).
Sudden death in epilepsy and ectopic neurohypophysis in Joubert syndrome 23 diagnosed using SNVs/indels and structural variants pipelines on WGS data: a case report.
BMC Medical Genetics.
21:96,
p. 1–6.
doi:
10.1186/s12881-020-01024-y.
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Background Joubert syndrome (JBTS) is a genetically heterogeneous group of neurodevelopmental syndromes caused by primary cilia dysfunction. Usually the neurological presentation starts with abnormal neonatal breathing followed by muscular hypotonia, psychomotor delay, and cerebellar ataxia. Cerebral MRI shows mid- and hindbrain anomalies including the molar tooth sign. We report a male patient with atypical presentation of Joubert syndrome type 23, thus expanding the phenotype. Case presentation Clinical features were consistent with JBTS already from infancy, yet the syndrome was not suspected before cerebral MRI later in childhood showed the characteristic molar tooth sign and ectopic neurohypophysis. From age 11 years seizures developed and after few years became increasingly difficult to treat, also related to inadequate compliance to therapy. He died at 23 years of sudden unexpected death in epilepsy (SUDEP). The genetic diagnosis remained elusive for many years, despite extensive genetic testing. We reached the genetic diagnosis by performing whole genome sequencing of the family trio and analyzing the data with the combination of one analysis pipeline for single nucleotide variants (SNVs)/indels and one for structural variants (SVs). This lead to the identification of the most common variant detected in patients with JBTS23 (OMIM# 616490), rs534542684, in compound heterozygosity with a 8.3 kb deletion in KIAA0586, not previously reported. Conclusions We describe for the first time ectopic neurohypophysis and SUDEP in JBTS23, expanding the phenotype of this condition and raising the attention on the possible severity of the epilepsy in this disease. We also highlight the diagnostic power of WGS, which efficiently detects SNVs/indels and in addition allows the identification of SVs.
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Rogne, Ane Gretesdatter; Müller, Ebba Gløersen; Udnæs, Eirin; Sigurdardottir, Solrun; Raudeberg, Rune & Connelly, James Pattrick
[Show all 9 contributors for this article]
(2020).
β-Amyloid may accumulate in the human brain after focal bacterial infection: An 18F-flutemetamol positron emission tomography study.
European Journal of Neurology.
ISSN 1351-5101.
28(3),
p. 877–883.
doi:
10.1111/ene.14622.
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Background and purpose β‐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 β‐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 β‐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 18F‐flutemetamol positron emission tomography on one occasion 1 to 10 months after brain abscess treatment to visualize β‐amyloid accumulation. Results 18F‐flutemetamol uptake was reduced in the edematous brain tissue that surrounded the abscess remains. On this background of reduced 18F‐flutemetamol signal, three out of 17 patients showed a distinctly increased 18F‐flutemetamol uptake in the tissue immediately surrounding the abscess remains, suggesting accumulation of β‐amyloid. These three patients underwent 18F‐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 18F‐flutemetamol signal. Conclusions β‐Amyloid may accumulate locally around the abscess remains in some patients with a brain abscess.
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Zhou, Yun; Eid, Tore; Hassel, Bjørnar & Danbolt, Niels Christian
(2020).
Novel aspects of glutamine synthetase in ammonia homeostasis: Glutamine synthetase and ammonia.
Neurochemistry International.
ISSN 0197-0186.
140,
p. 1–18.
doi:
10.1016/j.neuint.2020.104809.
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Raheel, Tayyaba Qureshi; Sørensen, Christina; Berghuis, Paul; Jensen, Vidar; Dobszay, Marton B. & Farkas, Tamás
[Show all 15 contributors for this article]
(2019).
The glutamine transporter Slc38a1 regulates GABAergic neurotransmission and synaptic plasticity.
Cerebral Cortex.
ISSN 1047-3211.
29(12),
p. 5166–5179.
doi:
10.1093/cercor/bhz055.
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GABA signaling sustains fundamental brain functions, from nervous system development to the synchronization of population activity and synaptic plasticity. Despite these pivotal features, molecular determinants underscoring the rapid and cell-autonomous replenishment of the vesicular neurotransmitter GABA and its impact on synaptic plasticity remain elusive. Here, we show that genetic disruption of the glutamine transporter Slc38a1 in mice hampers GABA synthesis, modifies synaptic vesicle morphology in GABAergic presynapses and impairs critical period plasticity. We demonstrate that Slc38a1-mediated glutamine transport regulates vesicular GABA content, induces high-frequency membrane oscillations and shapes cortical processing and plasticity. Taken together, this work shows that Slc38a1 is not merely a transporter accumulating glutamine for metabolic purposes, but a key component regulating several neuronal functions.
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Holmøy, Anne Katrin; Johannessen, Cecilie Haggag; Hope, Sigrun; Walsem, Marleen Regina Van; Aanonsen, Nils Olav & Hassel, Bjørnar
(2019).
Uncovering health and social care needs among myotonic dystrophy patients: Utility of the Needs and Provisions Complexity Scale.
Acta Neurologica Scandinavica.
ISSN 0001-6314.
139(6),
p. 526–532.
doi:
10.1111/ane.13086.
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Hassel, Bjørnar; Rogne, Ane Gretesdatter & Hope, Sigrun
(2019).
Intellectual disability associated with pyridoxine-responsive epilepsies: The need to protect cognitive development.
Frontiers in Psychiatry.
doi:
10.3389/fpsyt.2019.00116.
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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.
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Zhou, Yun; Hassel, Bjørnar; Eid, Tore & Danbolt, Niels Christian
(2018).
Axon-terminals expressing EAAT2 (GLT-1; Slc1a2) are common in the forebrain and not limited to the hippocampus.
Neurochemistry International.
ISSN 0197-0186.
123,
p. 101–113.
doi:
10.1016/j.neuint.2018.03.006.
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The excitatory amino acid transporter type 2 (EAAT2) represents the major mechanism for removal of extracellular glutamate. In the hippocampus, there is some EAAT2 in axon-terminals, whereas most of the protein is found in astroglia. The functional importance of the neuronal EAAT2 is unknown, and it is debated whether EAAT2-expressing nerve terminals are present in other parts of the brain. Here we selectively deleted the EAAT2 gene in neurons (by crossing EAAT2-flox mice with synapsin 1-Cre mice in the C57B6 background). To reduce interference from astroglial EAAT2, we measured glutamate accumulation in crude tissue homogenates. EAAT2 proteins levels were measured by immunoblotting. Although synapsin 1-Cre mediated gene deletion only reduced the forebrain tissue content of EAAT2 protein to 95.5 ± 3.4% of wild-type (littermate) controls, the glutamate accumulation in homogenates of neocortex, hippocampus, striatum and thalamus were nevertheless diminished to, respectively, 54 ± 4, 46 ± 3, 46 ± 2 and 65 ± 7% of controls (average ± SEM, n = 3 pairs of littermates). GABA uptake was unaffected. After injection of U-13C-glucose, lack of neuronal EAAT2 resulted in higher 13C-labeling of glutamine and GABA in the hippocampus suggesting that neuronal EAAT2 is partly short-circuiting the glutamate-glutamine cycle in wild-type mice. Crossing synapsin 1-Cre mice with Ai9 reporter mice revealed that Cre-mediated excision occurred efficiently in hippocampus CA3, but less efficiently in other regions and hardly at all in the cerebellum. Conclusions: (1) EAAT2 is expressed in nerve terminals in multiple brain regions. (2) The uptake catalyzed by neuronal EAAT2 plays a role in glutamate metabolism, at least in the hippocampus. (3) Synapsin 1-Cre does not delete floxed genes in all neurons, and the contribution of neuronal EAAT2 is therefore likely to be larger than revealed in the present study.
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Zhou, Yun; Dhaher, Roni; Parent, Maxime; Hu, Qiu Xiang; Hassel, Bjørnar & Yee, Siu-Pok
[Show all 10 contributors for this article]
(2018).
Selective deletion of glutamine synthetase in the mouse cerebral cortex induces glial dysfunction and vascular impairment that precede epilepsy and neurodegeneration.
Neurochemistry International.
ISSN 0197-0186.
p. 1–12.
doi:
10.1016/j.neuint.2018.07.009.
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Glutamate-ammonia ligase (glutamine synthetase; Glul) is enriched in astrocytes and serves as the primary enzyme for ammonia detoxification and glutamate inactivation in the brain. Loss of astroglial Glul is reported in hippocampi of epileptic patients, but the mechanism by which Glul deficiency might cause disease remains elusive. Here we created a novel mouse model by selectively deleting Glul in the hippocampus and neocortex. The Glul deficient mice were born without any apparent malformations and behaved unremarkably until postnatal week three. There were reductions in tissue levels of aspartate, glutamate, glutamine and GABA and in mRNA encoding glutamate receptor subunits GRIA1 and GRIN2A as well as in the glutamate transporter proteins EAAT1 and EAAT2. Adult Glul-deficient mice developed progressive neurodegeneration and spontaneous seizures which increased in frequency with age. Importantly, progressive astrogliosis occurred before neurodegeneration and was first noted in astrocytes along cerebral blood vessels. The responses to CO2-provocation were attenuated at four weeks of age and dilated microvessels were observed histologically in sclerotic areas of cKO. Thus, the abnormal glutamate metabolism observed in this model appeared to cause epilepsy by first inducing gliopathy and disrupting the neurovascular coupling.
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Hu, Qiu Xiang; Hansen, Sigrid Ottestad; Holmseth, Silvia; Hassel, Bjørnar; Danbolt, Niels Christian & Zhou, Yun
(2018).
Expression of glutamate transporters in mouse liver, kidney, and intestine.
Journal of Histochemistry and Cytochemistry.
ISSN 0022-1554.
66(3),
p. 189–202.
doi:
10.1369/0022155417749828.
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Glutamate transport activities have been identified not only in the brain, but also in the liver, kidney, and intestine. Although glutamate transporter distributions in the central nervous system are fairly well known, there are still uncertainties with respect to the distribution of these transporters in peripheral organs. Quantitative information is mostly lacking, and few of the studies have included genetically modified animals as specificity controls. The present study provides validated qualitative and semi-quantitative data on the excitatory amino acid transporter (EAAT)1-3 subtypes in the mouse liver, kidney, and intestine. In agreement with the current view, we found high EAAT3 protein levels in the brush borders of both the distal small intestine and the renal proximal tubules. Neither EAAT1 nor EAAT2 was detected at significant levels in murine kidney or intestine. In contrast, the liver only expressed EAAT2 (but 2 C-terminal splice variants). EAAT2 was detected in the plasma membranes of perivenous hepatocytes. These cells also expressed glutamine synthetase. Conditional deletion of hepatic EAAT2 did neither lead to overt neurological disturbances nor development of fatty liver.
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Morland, Cecilie; Frøland, Anne-Sofie; Nguyen, Mi Mong Tran; Storm-Mathisen, Jon; Gundersen, Vidar & Rise, Frode
[Show all 7 contributors for this article]
(2018).
Propionate enters GABAergic neurons, inhibits GABA transaminase, causes GABA accumulation and lethargy in a model of propionic acidemia.
Biochemical Journal.
ISSN 0264-6021.
doi:
10.1042/BCJ20170814.
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Propionic acidemia is the accumulation of propionate in blood due to dysfunction of propionyl-CoA carboxylase. The condition causes lethargy and striatal degeneration with motor impairment in humans. How propionate exerts its toxic effect is unclear. Here, we show that intravenous administration of propionate causes dose-dependent propionate accumulation in the brain and transient lethargy in mice. Propionate, an inhibitor of histone deacetylase, entered GABAergic neurons, as could be seen from increased neuronal histone H4 acetylation in the striatum and neocortex. Propionate caused an increase in GABA (γ-amino butyric acid) levels in the brain, suggesting inhibition of GABA breakdown. In vitro propionate inhibited GABA transaminase with a Ki of ∼1 mmol/l. In isolated nerve endings, propionate caused increased release of GABA to the extracellular fluid. In vivo, propionate reduced cerebral glucose metabolism in both striatum and neocortex. We conclude that propionate-induced inhibition of GABA transaminase causes accumulation of GABA in the brain, leading to increased extracellular GABA concentration, which inhibits neuronal activity and causes lethargy. Propionate-mediated inhibition of neuronal GABA transaminase, an enzyme of the inner mitochondrial membrane, indicates entry of propionate into neuronal mitochondria. However, previous work has shown that neurons are unable to metabolize propionate oxidatively, leading us to conclude that propionyl-CoA synthetase is probably absent from neuronal mitochondria. Propionate-induced inhibition of energy metabolism in GABAergic neurons may render the striatum, in which >90% of the neurons are GABAergic, particularly vulnerable to degeneration in propionic acidemia.
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Hassel, Bjørnar; Souza, Gustavo Antonio De; Stensland, Maria; Ivanovic, Jugoslav; Voie, Øyvind Albert & Dahlberg, Daniel
(2017).
The proteome of pus from human brain abscesses: Host-derived neurotoxic proteins and the cell-type diversity of CNS pus.
Journal of Neurosurgery.
ISSN 0022-3085.
129(3),
p. 829–837.
doi:
10.3171/2017.4.JNS17284.
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OBJECTIVE What determines the extent of tissue destruction during brain abscess formation is not known. Pyogenic brain infections cause destruction of brain tissue that greatly exceeds the area occupied by microbes, as seen in experimental studies, pointing to cytotoxic factors other than microbes in pus. This study examined whether brain abscess pus contains cytotoxic proteins that might explain the extent of tissue destruction. METHODS Pus proteins from 20 human brain abscesses and, for comparison, 7 subdural empyemas were analyzed by proteomics mass spectrometry. Tissue destruction was determined from brain abscess volumes as measured by MRI. RESULTS Brain abscess volume correlated with extracellular pus levels of antibacterial proteins from neutrophils and macrophages: myeloperoxidase (r = 0.64), azurocidin (r = 0.61), lactotransferrin (r = 0.57), and cathelicidin (r = 0.52) (p values 0.002-0.018), suggesting an association between leukocytic activity and tissue damage. In contrast, perfringolysin O, a cytotoxic protein from Streptococcus intermedius that was detected in 16 patients, did not correlate with abscess volume (r = 0.12, p = 0.66). The median number of proteins identified in each pus sample was 870 (range 643-1094). Antibiotic or steroid treatment prior to pus evacuation did not reduce the number or levels of pus proteins. Some of the identified proteins have well-known neurotoxic effects, e.g., eosinophil cationic protein and nonsecretory ribonuclease (also known as eosinophil-derived neurotoxin). The cellular response to brain infection was highly complex, as reflected by the presence of proteins that were specific for neutrophils, eosinophils, macrophages, platelets, fibroblasts, or mast cells in addition to plasma and erythrocytic proteins. Other proteins (neurofilaments, myelin basic protein, and glial fibrillary acidic protein) were specific for brain cells and reflected damage to neurons, oligodendrocytes, and astrocytes, respectively. Pus from subdural empyemas had significantly higher levels of plasma proteins and lower levels of leukocytic proteins than pus from intracerebral abscesses, suggesting greater turnover of the extracellular fluid of empyemas and washout of pus constituents. CONCLUSIONS Brain abscess pus contains leukocytic proteins that are neurotoxic and likely participate actively in the excessive tissue destruction inherent in brain abscess formation. These findings underscore the importance of rapid evacuation of brain abscess pus.
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Dahlberg, Daniel; Struys, Eduard A.; Janssen, EE; Mørkrid, Lars; Midttun, Øivind & Hassel, Bjørnar
(2017).
Cyst Fluid From Cystic, Malignant Brain Tumors: A Reservoir of Nutrients, Including Growth Factor-Like Nutrients, for Tumor Cells.
Neurosurgery.
ISSN 0148-396X.
80(6),
p. 917–924.
doi:
10.1093/neuros/nyw101.
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BACKGROUND: Brain tumors may have cysts, whose content of nutrients could influence tumor cell microenvironment and growth.
OBJECTIVE: To measure nutrients in cyst fluid from glioblastoma multiforme (GBM) and metastatic brain tumors.
METHODS: Quantification of nutrients in cyst fluid from 12 to 18 GBMs and 4 to 10 metastatic brain tumors.
RESULTS: GBM cysts contained glucose at 2.2 mmol/L (median value; range <0.8-3.5) and glutamine at 1.04 mmol/L (0.17-4.2). Lactate was 7.1 mmol/L (2.4-12.5) and correlated inversely with glucose level (r = -0.77; P < .001). Amino acids, including glutamate, varied greatly, but median values were similar to previously published serum values. Ammonia was 75 μmol/L (11-241). B vitamins were present at previously published serum values, and riboflavin, nicotinamide, pyridoxal 5΄-phosphate, and cobalamin were higher in cyst fluid than in cerebrospinal fluid. Inorganic phosphate was 1.25 mmol/L (0.34-3.44), which was >3 times higher than in ventricular cerebrospinal fluid: 0.35 mmol/L (0.22-0.66; P < .001). Tricarboxylic acid cycle intermediates were in the low micromolar range, except for citrate, which was 240 μmol/L (140-590). In cystic metastatic malignant melanomas and lung tumors values were similar to those in GBMs.
CONCLUSION: Tumor cysts may be a nutrient reservoir for brain tumors, securing tumor energy metabolism and synthesis of cell constituents. Serum is one likely source of cyst fluid nutrients. Nutrient levels in tumor cyst fluid are highly variable, which could differentially stimulate tumor growth. Cyst fluid glutamate, lactate, and phosphate may act as tumor growth factors; these compounds have previously been shown to stimulate tumor growth at concentrations found in tumor cyst fluid.
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Idland, Ane-Victoria; Wyller, Torgeir Bruun; Støen, Randi; Dahl, Gry Torsæter; Frihagen, Frede Jon & Brækhus, Anne
[Show all 8 contributors for this article]
(2017).
Cerebrospinal Fluid Phosphate in Delirium after Hip Fracture.
Dementia and Geriatric Cognitive Disorders Extra.
doi:
10.1159/000478723.
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Aims: Phosphate is essential for neuronal activity. We aimed to investigate whether delirium is associated with altered phosphate concentrations in cerebrospinal fluid (CSF) and serum. Methods: Seventy-seven patients with hip fracture were assessed for delirium before and after acute surgery. Prefracture dementia was diagnosed by an expert panel. Phosphate was measured in CSF obtained immediately before spinal anesthesia (n = 77) and in serum (n = 47). CSF from 23 cognitively healthy elderly patients undergoing spinal anesthesia was also analyzed. Results: Hip fracture patients with prevalent delirium had higher CSF phosphate concentrations than those without delirium (median 0.63 vs. 0.55 mmol/L, p = 0.001). In analyses stratified on dementia status, this difference was only significant in patients with dementia. Serum phosphate was ∼1 mmol/L; there was no association between serum phosphate concentration and delirium status. CSF phosphate did not correlate with serum levels. Conclusion: Patients with delirium superimposed on dementia have elevated phosphate levels.
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Watne, Leiv Otto; Idland, Ane-Victoria; Fekkes, Durk; Ræder, Johan; Frihagen, Frede Jon & Ranhoff, Anette Hylen
[Show all 10 contributors for this article]
(2016).
Increased CSF levels of aromatic amino acids in hip fracture patients with delirium suggests higher monoaminergic activity.
BMC Geriatrics.
doi:
10.1186/s12877-016-0324-0.
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Background
To examine whether delirium in hip fracture patients was associated with changes in the levels of amino acids and/or monoamine metabolites in cerebrospinal fluid (CSF) and serum.Methods
In this prospective cohort study, 77 patients admitted with an acute hip fracture to Oslo University Hospital, Norway, were studied. The concentrations of amino acids in CSF and serum were determined by high performance liquid chromatography. The patients were assessed daily for delirium by the Confusion Assessment Method (pre-operatively and post-operative day 1–5 (all) or until discharge (delirious patients)). Pre-fracture dementia status was decided by an expert panel. Serum was collected pre-operatively and CSF immediately before spinal anesthesia.Results
Fifty-three (71 %) hip fracture patients developed delirium. In hip fracture patients without dementia (n = 39), those with delirium had significantly higher CSF levels of tryptophan (40 % higher), tyrosine (60 % higher), phenylalanine (59 % higher) and the monoamine metabolite 5-hydroxyindoleacetate (23 % higher) compared to those without delirium. The same amino acids were also higher in CSF in delirious patients with dementia (n = 38). The correlations between serum and CSF amino acid levels were poor.Conclusion
Higher CSF levels of monoamine precursors in hip fracture patients with delirium suggest a higher monoaminergic activity in the central nervous system during delirium in this patient group.
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Morland, Cecilie; Pettersen, Mi Nguyen & Hassel, Bjørnar
(2016).
Hyperosmolar sodium chloride is toxic to cultured neurons and causes reduction of glucose metabolism and ATP levels, an increase in glutamate uptake, and a reduction in cytosolic calcium.
Neurotoxicology.
ISSN 0161-813X.
doi:
10.1016/j.neuro.2016.03.005.
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Elevation of serum sodium, hypernatremia, which may occur during dehydration or treatment with sodium chloride, may cause brain dysfunction and damage, but toxic mechanisms are poorly understood. We found that exposure to excess NaCl, 10–100 mmol/L, for 20 h caused cell death in cultured cerebellar granule cells (neurons). Toxicity was due to Na+, since substituting excess Na+ with choline reduced cell death to control levels, whereas gluconate instead of excess Cl− did not. Prior to cell death from hyperosmolar NaCl, glucose consumption and lactate formation were reduced, and intracellular aspartate levels were elevated, consistent with reduced glycolysis or glucose uptake. Concomitantly, the level of ATP became reduced. Pyruvate, 10 mmol/L, reduced NaCl-induced cell death. The extracellular levels of glutamate, taurine, and GABA were concentration-dependently reduced by excess NaCl; high-affinity glutamate uptake increased. High extracellular [Na+] caused reduction in intracellular free [Ca2+], but a similar effect was seen with mannitol, which was not neurotoxic. We suggest that inhibition of glucose metabolism with ensuing loss of ATP is a neurotoxic mechanism of hyperosmolar sodium, whereas increased uptake of extracellular neuroactive amino acids and reduced intracellular [Ca2+] may, if they occur in vivo, contribute to the cerebral dysfunction and delirium described in hypernatremia.
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Dahlberg, Daniel; Ivanovic, Jugoslav; Mariussen, Espen & Hassel, Bjørnar
(2015).
High extracellular levels of potassium and trace metals in human brain abscess.
Neurochemistry International.
ISSN 0197-0186.
82,
p. 28–32.
doi:
10.1016/j.neuint.2015.02.003.
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Solyga, Volker; Western, Elin; Solheim, Hanne; Hassel, Bjørnar & Kerty, Emilia
(2015).
Posterior kortikal atrofi.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
135(10),
p. 949–952.
doi:
10.4045/tidsskr.14.1127.
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Dahlberg, Daniel; Ivanovic, Jugoslav & Hassel, Bjørnar
(2014).
High extracellular concentration of excitatory amino acids glutamate and aspartate in human brain abscess.
Neurochemistry International.
ISSN 0197-0186.
69(1),
p. 41–47.
doi:
10.1016/j.neuint.2014.03.001.
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Hassel, Bjørnar; Dahlberg, Daniel; Mariussen, Espen; Goverud, Ingeborg Løstegaard; Antal, Ellen-Ann & Tonjum, Tone
[Show all 7 contributors for this article]
(2014).
Brain infection with Staphylococcus aureus leads to high extracellular levels of glutamate, aspartate, γ-aminobutyric acid, and zinc.
Journal of Neuroscience Research.
ISSN 0360-4012.
doi:
10.1002/jnr.23444.
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Staphylococcal brain infections may cause mental deterioration and epileptic seizures, suggesting interference with normal neurotransmission in the brain. We injected Staphylococcus aureus into rat striatum and found an initial 76% reduction in the extracellular level of glutamate as detected by microdialysis at 2 hr after staphylococcal infection. At 8 hr after staphylococcal infection, however, the extracellular level of glutamate had increased 12-fold, and at 20 hr it had increased >30-fold. The extracellular level of aspartate and γ-aminobutyric acid (GABA) also increased greatly. Extracellular Zn2+ , which was estimated at ∼2.6 µmol/liter in the control situation, was increased by 330% 1-2.5 hr after staphylococcal infection and by 100% at 8 and 20 hr. The increase in extracellular glutamate, aspartate, and GABA appeared to reflect the degree of tissue damage. The area of tissue damage greatly exceeded the area of staphylococcal infiltration, pointing to soluble factors being responsible for cell death. However, the N-methyl-D-aspartate receptor antagonist MK-801 ameliorated neither tissue damage nor the increase in extracellular neuroactive amino acids, suggesting the presence of neurotoxic factors other than glutamate and aspartate. In vitro staphylococci incubated with glutamine and glucose formed glutamate, so bacteria could be an additional source of infection-related glutamate. We conclude that the dramatic increase in the extracellular concentration of neuroactive amino acids and zinc could interfere with neurotransmission in the surrounding brain tissue, contributing to mental deterioration and a predisposition to epileptic seizures, which are often seen in brain abscess patients.
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Madslien, Elisabeth Henie; Rønning, Helene; Lindback, Toril; Hassel, Bjørnar; Andersson, M.A. & Granum, Per Einar
(2013).
Lichenysin is produced by most Bacillus licheniformis strains.
Journal of Applied Microbiology.
ISSN 1364-5072.
115(4),
p. 1068–1080.
doi:
10.1111/jam.12299.
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Hassel, Bjørnar
(2013).
Tetanus: Pathophysiology, Treatment, and the Possibility of Using Botulinum Toxin against Tetanus-Induced Rigidity and Spasms.
Toxins.
doi:
10.3390/toxins5010073.
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Tetanus toxin, the product of Clostridium tetani, is the cause of tetanus symptoms. Tetanus toxin is taken up into terminals of lower motor neurons and transported axonally to the spinal cord and/or brainstem. Here the toxin moves trans-synaptically into inhibitory nerve terminals, where vesicular release of inhibitory neurotransmitters becomes blocked, leading to disinhibition of lower motor neurons. Muscle rigidity and spasms ensue, often manifesting as trismus/lockjaw, dysphagia, opistotonus, or rigidity and spasms of respiratory, laryngeal, and abdominal muscles, which may cause respiratory failure. Botulinum toxin, in contrast, largely remains in lower motor neuron terminals, inhibiting acetylcholine release and muscle activity. Therefore, botulinum toxin may reduce tetanus symptoms. Trismus may be treated with botulinum toxin injections into the masseter and temporalis muscles. This should probably be done early in the course of tetanus to reduce the risk of pulmonary aspiration, involuntary tongue biting, anorexia and dental caries. Other muscle groups are also amenable to botulinum toxin treatment. Six tetanus patients have been successfully treated with botulinum toxin A. This review discusses the use of botulinum toxin for tetanus in the context of the pathophysiology, symptomatology, and medical treatment of Clostridium tetani infection.
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Hassel, Bjørnar
(2012).
Hans (Hansemann) Tønnesen, en diagnostisk gåte fra Amalie Skram [A description of early hydrocephalus with macrocephaly, cerebral palsy, epilepsy, intellectual disability, and growth retardation by Norwegian novelist Amalie Skram (1846-1905)].
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
132,
p. 2632–2635.
doi:
10.4045/tidsskr.12.0912.
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Hassel, Bjørnar
(2012).
13C Magnetic Resonance Spectroscopy in
Neurobiology - Its Use in Monitoring Brain
Energy Metabolism and in Identifying Novel
Metabolic Substrates and Metabolic Pathways.
InTech.
ISSN 0192-303X.
http://cdn.intechopen.com/pdfs-wm/30447.pdf.
doi:
10.5772/33095.
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Zhou, Yun; Holmseth, Silvia; Guo, C; Hassel, Bjørnar; Höfner, G & Huitfeldt, Henrik
[Show all 8 contributors for this article]
(2012).
Deletion of the γ-aminobutyric acid transporter 2 (GAT2 and SLC6A13) gene in mice leads to changes in liver and brain taurine contents.
Journal of Biological Chemistry.
ISSN 0021-9258.
doi:
10.1074/jbc.M112.368175.
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The GABA transporters (GAT1, GAT2, GAT3, and BGT1) have mostly been discussed in relation to their potential roles in controlling the action of transmitter GABA in the nervous system. We have generated the first mice lacking the GAT2 (slc6a13) gene. Deletion of GAT2 (both mRNA and protein) neither affected growth, fertility, nor life span under nonchallenging rearing conditions. Immunocytochemistry showed that the GAT2 protein was predominantly expressed in the plasma membranes of periportal hepatocytes and in the basolateral membranes of proximal tubules in the renal cortex. This was validated by processing tissue from wild-type and knockout mice in parallel. Deletion of GAT2 reduced liver taurine levels by 50%, without affecting the expression of the taurine transporter TAUT. These results suggest an important role for GAT2 in taurine uptake from portal blood into liver. In support of this notion, GAT2-transfected HEK293 cells transported [3H]taurine. Furthermore, most of the uptake of [3H]GABA by cultured rat hepatocytes was due to GAT2, and this uptake was inhibited by taurine. GAT2 was not detected in brain parenchyma proper, excluding a role in GABA inactivation. It was, however, expressed in the leptomeninges and in a subpopulation of brain blood vessels. Deletion of GAT2 increased brain taurine levels by 20%, suggesting a taurine-exporting role for GAT2 in the brain.
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Hassel, Bjørnar; Taubøll, Erik; Shaw, Renee; Gjerstad, Leif & Dingledine, Ray
(2010).
Region-specific changes in gene expression in rat brain after chronic treatment with levetiracetam or phenytoin.
Epilepsia.
ISSN 0013-9580.
51(9),
p. 1714–1720.
doi:
10.1111/j.1528-1167.2010.02545.x.
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Hassel, Bjørnar; Tessler, S.; Faull, R. L. M. & Emson, P. C.
(2008).
Glutamate uptake is reduced in prefrontal cortex in Huntington's disease.
Neurochemical Research.
ISSN 0364-3190.
33,
p. 232–237.
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Herrman, Helle; Brækhus, Anne; Aaserud, Olaf; Aukrust, Pål; Stubhaug, Audun & Hassel, Bjørnar
(2008).
Early treatment of tetanus-induced trismus with botulinum toxin A.
Anesthesia and Analgesia.
ISSN 0003-2999.
106,
p. 1591–1591.
doi:
10.1213/ANE.0b013e31816a30f0.
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Hassel, Bjørnar; Solyga, Volker & Lossius, Andreas
(2008).
High-affinity choline uptake and acetylcholine-metabolizing enzymes in CNS white matter. A quantitative study.
Neurochemistry International.
ISSN 0197-0186.
53,
p. 193–198.
doi:
10.1016/j.neuint.2008.06.008.
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Nguyen, Nga H. T.; Gonzalez, Susan Villa & Hassel, Bjørnar
(2007).
Formation of glycerol from glucose in rat brain and cultured brain cells. Augmentation with kainate or ischemia.
Journal of Neurochemistry.
ISSN 0022-3042.
101,
p. 1694–1700.
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Bough, Kristopher J.; Paquet, Maryse; Pare, Jean-Francois; Hassel, Bjørnar; Smith, Youland & Hall, Randy A.
[Show all 7 contributors for this article]
(2007).
Evidence against enhanced glutamate transport in the anticonvulsant mechanism of the ketogenic diet.
Epilepsy Research.
ISSN 0920-1211.
74(2-3),
p. 232–236.
doi:
10.1016/j.eplepsyres.2007.03.002.
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Excessive glutamatergic neurotransmission is considered an underlying factor of epilepsy. Energy-dependent glutamate transporters clear extracellular glutamate to limit neuronal excitability. Evidence suggests that reduced expression and/or activity of glutamate transporters contribute to hyperexcitability and progressive seizure activity in rats. By comparison, treatment with the anticonvulsant ketogenic diet (KD) results in increased mRNA expression of the neuronal glutamate transporter EAAC1, elevated energy reserves, and an increased resistance to seizures in rats. The goal of the current study was to determine whether the expression and/or re-uptake activity of glutamate transporters were elevated in hippocampal tissue of rats after KD treatment. Rats were fed either a ketogenic- or control diet for 4-5 weeks. Western blot analysis showed that protein levels of EAAC1, GLT-1 and GLAST glutamate transporters were not changed in hippocampus, cerebral cortex, or cerebellum after KID. Electron microscopic evidence indicated that the KD did not affect hippocampal EAAC1 distribution. In addition, the re-uptake activity of H-3-glutamate into hippocampal proteoliposomes was similar in both KID and control tissue extracts. These multiple studies suggest that the anticonvulsant nature of the KID does not stem from enhanced glutamate re-uptake. (C) 2007 Elsevier B.V. All rights reserved.
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Nguyen, Nga H. T.; Gonzalez, Susana Villa; Rise, Frode & Hassel, Bjørnar
(2007).
Cerebral metabolism of glucose and pyruvate in soman poisoning. A 13C nuclear magnetic resonance spectroscopic study.
Neurotoxicology.
ISSN 0161-813X.
doi:
10.1016/j.neuro.2006.09.007.
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Morland, Cecilie; Henjum, Solveig; Iversen, Evy Grini; Skrede, Knut Kristian & Hassel, Bjørnar
(2007).
Evidence for a higher glycolytic than oxidative metabolic activity in white matter of rat brain.
Neurochemistry International.
ISSN 0197-0186.
doi:
10.1016/j.neuint.2007.01.003.
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Henjum, Solveig & Hassel, Bjørnar
(2007).
High-affinity GABA uptake and GABA-metabolizing enzymes in pig forebrain white matter: A quantitative study.
Neurochemistry International.
ISSN 0197-0186.
50(2),
p. 365–370.
doi:
10.1016/j.neuint.2006.09.004.
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GABA receptor activation in central nervous white matter may be protective during white matter hypoxia in the adult, and it may modify axonal conduction, especially in the developing brain. GABA uptake is important for the shaping of the GABA signal, but quantitative data are lacking for GABA uptake and GABA-metabolizing enzymes in central nervous white matter. We report that high-affinity uptake of GABA in adult pig corpus callosum, fimbria, subcortical pyramidal tracts, and occipital white matter is similar to 20% of that in temporal cortex gray matter. Tiagabine (0.1 mu M), an antiepileptic drug that specifically inhibits the GAT-I GABA transporter inhibited GABA uptake 50% in temporal cortex and 60-68% in white structures. This finding indicates that GAT-1 is an important GABA transporter in white matter and suggests that white matter GABA uptake is inhibited during tiagabine therapy. GABA transaminase activity in white structures was similar to 20% of neocortical values. Glutamate decarboxylase (GAD) activity in white structures was only 4% of that in neocortex (7-12 pmol/mg tissue x min(-1) versus similar to 200 pmol/mg tissue x min-1). Since white matter activity of citrate synthase of the tricarboxylic acid cycle was similar to 25% of neocortical values (similar to 0.4 nmol/mg tissue x min(-1) versus similar to 1.5 nmol/mg tissue x min(-1)), the low GAD activity suggests a slower metabolic turnover of GABA in white than in gray matter. (c) 2006 Elsevier Ltd. All rights reserved.
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Henjum, Solveig & Hassel, Bjørnar
(2007).
High-affinity glycine and glutamate transport in pig forebrain white and gray matter: A quantitative study.
Neurochemistry International.
ISSN 0197-0186.
50(5),
p. 696–702.
doi:
10.1016/j.neuint.2007.01.002.
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High-affinity uptake of glycine and glutamate modulates glutamatergic neurotransmission in gray matter. N-Methyl-D-aspartate (NMDA) receptors were recently described on white matter oligodendrocytes, therefore uptake of glutamate and glycine in white matter may also modulate NMDA receptor function. We found that glycine uptake in white structures of pig forebrain (corpus callosum, fimbria, subcortical pyramidal tracts, and occipital subcortical white matter) was similar to that in gray structures (frontal and temporal cortices and hippocampus), and that it was sensitive to sarcosine, a GLYT1 inhibitor (IC50 15 mu M). Glutamate uptake in white matter was similar to 10% of that in gray; it was sensitive to dihydrokainate, an EAAT2 inhibitor. The levels of glycine and its precursor serine were similar in white and gray matter: approximately 2 and 1 nmol/mg tissue, respectively. The white matter level of glutamate was similar to 7.6 nmol/mg tissue, or similar to 74% of gray matter levels. The activity of serine hydroxymethyl transferase, which converts serine into glycine, was similar in white and gray matter (11-18 pmol/(mg tissue) min), whereas the white matter activity of phosphate-activated glutaminase, which converts glutamine into glutamate, was similar to 100 pmol/(mg tissue) min, or similar to 34% of gray matter activity. The white matter activity of glutamine synthetase, the glial enzyme that converts glutamate into glutamine, was 20-40 nmol/ (mg tissue) min in neocortex and 5-6 nmol/(mg tissue) min in white matter. The data show that forebrain white matter is equipped to regulate extracellular levels of glycine and glutamate, functions that may modulate white matter NMDA receptor function. (c) 2007 Elsevier Ltd. All rights reserved.
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Morland, Cecilie; Henjum, Solveig; Iversen, Evy Grini; Skrede, Knut Kristian & Hassel, Bjørnar
(2007).
Evidence for a higher glycolytic than oxidative metabolic activity in white matter of rat brain.
Neurochemistry International.
ISSN 0197-0186.
50(5),
p. 703–709.
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Morland, Cecilie; Boldingh, Karen A; Iversen, Evy Grini & Hassel, Bjørnar
(2004).
Valproate is neuroprotective against malonate toxicity in rat striatum: an association with augmentation of high-affinity glutamate uptake.
Journal of Cerebral Blood Flow and Metabolism.
ISSN 0271-678X.
doi:
10.1097/01.WCB.0000138666.25305.A7.
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The antiepileptic drug valproate (VPA) may be neuroprotective. We treated rats with VPA for 14 days (300 mg/kg twice daily) before intrastriatal injection of 1.5 μmol (1 M) of the succinate dehydrogenase inhibitor malonate. VPA-treated animals developed smaller lesions than control animals: 10 ± 2 mm3 versus 26 ± 8 mm3 (means ± SD; P = 10−4). Injection of NaCl that was equiosmolar with 1 M malonate caused lesions of only 1.2 ± 0.4 mm3 in control animals, whereas physiologic saline produced no lesion. VPA pretreatment reduced the malonate-induced extracellular accumulation of glutamate. This effect paralleled an increase in the striatal level of the glutamate transporter GLT, which augmented high-affinity glutamate uptake by 25%, as determined from the uptake of [3H] glutamate into striatal proteoliposomes. Malonate caused a 76% reduction in striatal adenosine triphosphate (ATP) content, but the glial, ATP-dependent formation of glutamine from radiolabeled glucose or glutamate was intact, indicating that glial ATP production supported uptake of glutamate. Striatal levels of HSP-70 and fos were reduced, and the levels of bcl-2 and phosphorylated extracellular signal-regulated kinase remained unaffected, but histone acetylation was increased by VPA treatment. The results suggest that augmentation of glutamate uptake may contribute importantly to VPA-mediated neuroprotection in striatum.
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Hassel, Bjørnar; Boldingh, Karen Astrid; Morland, Cecilie; Iversen, Evy Grini & Skrede, Knut Kristian
(2003).
Glutamate transport, glutamine synthetase and phosphate-activated glutaminase in rat CNS white matter. A quantitative study.
Journal of Neurochemistry.
ISSN 0022-3042.
doi:
10.1046/j.1471-4159.2003.01984.x.
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Pettersen, Nga Huynh Tran Nguyen; Bråthe, Anders & Hassel, Bjørnar
(2003).
Neuronal uptake and metabolism of glycerol and the neuronal expression of mitochondrial glycerol-3-phosphate dehydrogenase.
Journal of Neurochemistry.
ISSN 0022-3042.
doi:
10.1046/j.1471-4159.2003.01762.x.
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Hassel, Bjørnar & Sawcer, Stephen
(1998).
Neuralgic amyotrophy.
Tidsskrift for Den norske legeforening (Tidsskriftet).
ISSN 0029-2001.
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Hassel, Bjørnar; Landmark, Cecilie Johannessen; Sonnewald, Ursula & Fonnum, Frode
(1998).
Quantification of the GABA shunt and the importance of the GABA shunt versus the 2-oxoglutarate dehydrogenase pathway in GABAergic neurons.
Journal of Neurochemistry.
ISSN 0022-3042.
doi:
10.1046/j.1471-4159.1998.71041511.x.
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Emhjellen, Petter Espeseth; Starrfelt, Randi; Raudeberg, Rune & Hassel, Bjørnar
(2025).
Assessment of Developmental Prosopagnosia in an Individual with Tourette Syndrome and Attention Deficit Hyperactivity Disorder: A Case Report.
doi:
10.3390/brainsci15010056.
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Background/Objectives: Prosopagnosia is the inability to recognize people by their faces. Developmental prosopagnosia is the hereditary or congenital variant of the condition. The aim of this study was to demonstrate the assessment of developmental prosopagnosia in a clinical context, using a combination of commercially available clinical assessment tools and experimental tools described in the research literature. Methods: We conducted a comprehensive neuropsychological assessment of a man with Tourette syndrome and attention deficit hyperactivity disorder (ADHD). The patient (ON) had experienced difficulties with face identity recognition throughout his life but believed they were caused by a lack of interest in others. Results: The neuropsychological assessment revealed varying degrees of difficulties primarily related to executive functions, attention, reaction time, and memory processes, as expected in a person with Tourette’s syndrome and ADHD. In addition, ON reported severe problems with face recognition on a prosopagnosia questionnaire and demonstrated severely impaired performance on tests of face memory and face perception commonly used to diagnose prosopagnosia. Interestingly, he reported familial face recognition problems on the maternal side of the family, while tics and ADHD symptoms occurred on the paternal side. This suggests that, in this case, the conditions were likely inherited through different genetic pathways. Conclusions: Proper assessment of face recognition problems, which includes a broad spectrum of clinical assessment tools, could help patients develop awareness and acceptance of themselves and their difficulties, and could serve as a basis for the development of clinical interventions. While ON’s DP, Tourette syndrome, and ADHD may have distinct genetic origins, impairment in face identity recognition has been observed across several neurodevelopmental conditions and is likely more common than currently thought.
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Hassel, Bjørnar
(2024).
"...dei treffest kysser eta saman han sit og drikk båt og hund må ein ha" - Ordsalat på julaftan som nevrologisk symptom i Jon Fosses "Septologien".
Axonet.
ISSN 0805-4916.
axonet_2024_3.pdf(3),
p. 36–38.
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Kildal, Emilie Smith-Meyer; Quintana, Daniel; Szabo, Attila; Tronstad, Christian; Andreassen, Ole & Nærland, Terje
[Show all 7 contributors for this article]
(2023).
Heart rate monitoring to detect acute pain in non-verbal patients: a study protocol for a randomized controlled clinical trial.
BMC Psychiatry.
23(1).
doi:
10.1186/s12888-023-04757-1.
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Background Autism entails reduced communicative abilities. Approximately 30% of individuals with autism have intellectual disability (ID). Some people with autism and ID are virtually non-communicative and unable to notify their caregivers when they are in pain. In a pilot study, we showed that heart rate (HR) monitoring may identify painful situations in this patient group, as HR increases in acutely painful situations. Objectives This study aims to generate knowledge to reduce the number of painful episodes in non-communicative patients’ everyday lives. We will 1) assess the effectiveness of HR as a tool for identifying potentially painful care procedures, 2) test the effect of HR-informed changes in potentially painful care procedures on biomarkers of pain, and 3) assess how six weeks of communication through HR affects the quality of communication between patient and caregiver. Methods We will recruit 38 non-communicative patients with autism and ID residing in care homes. Assessments: HR is measured continuously to identify acutely painful situations. HR variability and pain-related cytokines (MCP-1, IL-1RA, IL-8, TGFβ1, and IL-17) are collected as measures of long-term pain. Caregivers will be asked to what degree they observe pain in their patients and how well they believe they understand their patient’s expressions of emotion and pain. Pre-intervention: HR is measured 8 h/day over 2 weeks to identify potentially painful situations across four settings: physiotherapy, cast use, lifting, and personal hygiene. Intervention: Changes in procedures for identified painful situations are in the form of changes in 1) physiotherapy techniques, 2) preparations for putting on casts, 3) lifting techniques or 4) personal hygiene procedures. Design: Nineteen patients will start intervention in week 3 while 19 patients will continue data collection for another 2 weeks before procedure changes are introduced. This is done to distinguish between specific effects of changes in procedures and non-specific effects, such as caregivers increased attention. Discussion This study will advance the field of wearable physiological sensor use in patient care. Trial registration Registered prospectively at ClinicalTrials.gov (NCT05738278).
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Hassel, Bjørnar & Strisland, Frode
(2019).
Forstå hvordan jeg har det. Sensorteknologi for personer med sterkt begrensende kommunikasjonsevner.
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Mennesker med alvorlig grad av utviklingshemming eller andre omfattende funksjonsnedsettelser kan ha sterkt reduserte eller manglende evner til å uttrykke seg verbalt eller på andre måter. De kan derfor ha problemer med å uttrykke smerte eller andre ubehag, og de kan reagere med selvskadende eller aggressiv atferd uten at bakenforliggende årsak blir kjent. Kan enkle fysiologiske målinger, slik som pulsmåling, brukes som en ekstra indikator for å hjelpe tjenestene tolke hva som foregår?
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Rogne, Ane G.; Dahlberg, Daniel; Udnæs, Eirin; Raudeberg, Rune; Sigurdardottir, Solrun & Hassel, Bjørnar
(2019).
Cognitive dysfunction in brain abscess patients is not attributable to beta-amyloid deposition.
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Zhou, Yun; Hassel, Bjørnar; Eid, Tore & Danbolt, Niels Christian
(2018).
Axon-terminals expressing EAAT2 (GLT-1; slc1a2) are common in the forebrain and not limited to the hippocampus.
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Hassel, Bjørnar
(2018).
Religiøs anatomi i hofteregionen.
In Frich, Jan C; Brean, Are & Dietrichs, Espen (Ed.),
Hjernen og historien.
Michael.
ISSN 9788292871843.
p. 95–97.
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Hassel, Bjørnar
(2018).
Michelangelos David - et syndrome for fremtiden?
In Frich, Jan C; Brean, Are & Dietrichs, Espen (Ed.),
Hjernen og historien.
Michael.
ISSN 9788292871843.
p. 107–113.
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Hassel, Bjørnar
(2018).
Jakobs delirium og overbevisningens nevrobiologi.
In Frich, Jan C; Brean, Are & Dietrichs, Espen (Ed.),
Hjernen og historien.
Michael.
ISSN 9788292871843.
p. 87–94.
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Aarønæs, Lars; Hassel, Bjørnar; Rogne, Ane & Dahlberg, Daniel
(2018).
Puss kan gi hjerneskade.
[Internet].
Forskning.no.
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Published
Oct. 15, 2015 2:48 PM
- Last modified
Oct. 10, 2023 1:56 PM
