Publikasjoner
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Bortoli, Alessandro De; Nordøy, Ingvild; Connelly, James Pattrick; Viermyr, Hans-Kittil; Bjerkreim, Randi Haukaas & Broch, Kaspar
[Vis alle 15 forfattere av denne artikkelen]
(2024).
Diagnostics, treatment and outcomes of cardiac sarcoidosis in a Norwegian cohort.
International Journal of Cardiology.
ISSN 0167-5273.
400.
doi:
10.1016/j.ijcard.2024.131809.
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Background Evidence-based guidelines for cardiac sarcoidosis (CS) regarding use of second- and third-line agents, treatment duration, surveillance and prognostic factors are lacking. Objective To analyze the clinical presentation, diagnostics, treatment, monitoring and clinical outcomes in a Norwegian cohort. Methods Using discharge diagnoses between 2017 through 2020 from a large tertiary center, we identified 52 patients with CS. We performed a systematic chart review following a pre-specified checklist. The primary outcome of major cardiovascular events (MACE) was defined as a composite of cardiovascular hospitalization, defibrillator therapy, cardiac transplantation, or death. Results 18-fluorodeoxyglucose positron emission tomography (FDG-PET) showed pathological tracer uptake in 35/36 (97%) of immunosuppression-naïve patients. Immunosuppressive treatment was administered to 49/52 patients (94%) for a median of 43 (IQR 34) months; 69% were treated with second-line (methotrexate, azathioprine, mycophenolate mofetil) and 25% with third-line (rituximab, infliximab) agents, respectively. Rituximab reduced inflammation as assessed by interval FDG-PET imaging and was overall well tolerated. Median duration to first MACE was 6 (IQR 10) months and 17/23 patients (74%) experienced a MACE within 12 months from CS diagnosis. No mortality was recorded and 20% achieved full remission. Age below the median of 53 years at time of diagnosis was associated with an increased risk of a MACE. Conclusion Long-term immunosuppression including a liberal use of non-steroidal agents, appeared essential in treating CS. Although the burden of cardiovascular events was substantial, the survival was excellent in this contemporary cohort. Prospective randomized studies are urgently needed to define the best therapy for these patients.
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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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Bruvoll, Ragnar Bjørn Watte; Blakkisrud, Johan; Mikalsen, Lars Tore Gyland; Connelly, James Pattrick & Stokke, Caroline
(2023).
Correlations between 68Ga]Ga-DOTA-TOC Uptake and Absorbed Dose from [177Lu]Lu-DOTA-TATE.
Cancers.
15(4).
doi:
10.3390/cancers15041134.
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Purpose: The aim of this paper was to investigate correlations between pre- therapeutic [68Ga]Ga-DOTA-TOC uptake and absorbed dose to tumours from therapy with [177Lu]Lu-DOTA- TATE. Methods: This retrospective study included 301 tumours from 54 GEP-NET patients. The tumours were segmented on pre-therapeutic [68Ga]Ga-DOTA-TOC PET/CT, and post-therapy [177Lu]Lu-DOTA-TATE SPECT/CT images, using a fixed 40% threshold. The SPECT/CT images were used for absorbed dose calculations by assuming a linear build-up from time zero to day one, and mono-exponential wash-out after that. Both SUVmean and SUVmax were measured from the PET images. A linear absorbed-dose prediction model was formed with SUVmean as the inde- pendent variable, and the accuracy was tested with a split 70–30 training-test set. Results: Mean SUVmean and SUVmax from [68Ga]Ga-DOTA-TOC PET was 24.0 (3.6–84.4) and 41.0 (6.7–146.5), and the mean absorbed dose from [177Lu]Lu-DOTA-TATE was 26.9 Gy (2.4–101.9). A linear relationship between SUVmean and [177Lu]Lu-DOTA-TATE activity concentration at 24 h post injection was found (R2 = 0.44, p < 0.05). In the prediction model, a root mean squared error and a mean absolute error of 1.77 and 1.33 Gy/GBq, respectively, were found for the test set. Conclusions: There was a high inter- and intra-patient variability in tumour measurements, both for [68Ga]Ga-DOTA-TOC SUVs and absorbed doses from [177Lu]Lu-DOTA-TATE. Depending on the required accuracy, [68Ga]Ga- DOTA-TOC PET imaging may estimate the [177Lu]Lu-DOTA-TATE uptake. However, there could be a high variance between predicted and actual absorbed doses.
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Dahlberg, Daniel; Holm, Sverre; Sagen, Ellen Lund; Michelsen, Annika Elisabet; Stensland, Maria & Souza, Gustavo Antonio De
[Vis alle 11 forfattere av denne artikkelen]
(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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Stokke, Caroline; Nørgaard, Jakob Nordberg; Phillips, Hilde Feiring; Sherwani, Alexander Gul; Nuruddin, Syed Mohammad & Connelly, James Pattrick
[Vis alle 8 forfattere av denne artikkelen]
(2022).
Comparison of [18F]fluciclovine and [18F]FDG PET/CT in Newly Diagnosed Multiple Myeloma Patients.
Molecular Imaging and Biology.
ISSN 1536-1632.
24(5),
s. 842–851.
doi:
10.1007/s11307-022-01734-0.
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Abstract Purpose [ 18 F]FDG PET/CT in multiple myeloma (MM) is currently the best technology to demonstrate patchy and extramedullary disease. However, [ 18 F]FDG PET has some limitations, and imaging with alternative tracers should be explored. In this study, we aimed to evaluate the performance of [ 18 F]fluciclovine PET compared to [ 18 F]FDG PET in newly diagnosed MM patients. Procedures Thirteen newly diagnosed transplant eligible MM patients were imaged both with [ 18 F]FDG PET/CT and [ 18 F]fluciclovine PET/CT within 1 week in a prospective study. The subjects were visually assessed positive or negative for disease. The number of lesions and the SUV max of selected lesions were measured for both tracers. Furthermore, tracer uptake ratios were obtained by dividing lesion SUV max by blood or bone marrow SUV max . Between-group differences and correlations were assessed with paired t -tests and Pearson tests. Bone marrow SUVs were compared to bone marrow plasma cell percentage in biopsy samples. Results Nine subjects were assessed positively by [ 18 F]FDG PET (69%) and 12 positives by [ 18 F]fluciclovine PET (92%). All positive subjects had [ 18 F]fluciclovine scans that were qualitatively scored as easier to interpret visually than the [ 18 F]FDG scans. The number of lesions was also higher; seven of nine subjects with distinct hot spots on [ 18 F]fluciclovine PET had fewer or no visible lesions on [ 18 F]FDG PET. The mean lesion SUV max values were 8.2 and 3.8 for [ 18 F]fluciclovine and [ 18 F]FDG, respectively. The mean tumour to blood values were 6.4 and 2.0 for [ 18 F]fluciclovine and [ 18 F]FDG, and the mean ratios between tumour and bone marrow were 2.1 and 1.5 for [ 18 F]fluciclovine and [ 18 F]FDG. The lesion SUV max and ratios were significantly higher for [ 18 F]fluciclovine (all p < 0.01). Local [ 18 F]fluciclovine SUV max or SUV mean values in os ilium and the percentage of plasma cells in bone marrow biopsies were linearly correlated ( p = 0.048). There were no significant correlations between [ 18 F]FDG SUVs and plasma cells ( p = 0.82). Conclusions Based on this pilot study, [ 18 F]fluciclovine is a promising tracer for MM. The visual and semi-quantitative evaluations indicate that [ 18 F]fluciclovine PET/CT can out-perform [ 18 F]FDG PET/CT at diagnosis.
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Helgebostad, Rasmus; Rootwelt-Revheim, Mona Elisabeth; Johnsrud, Kjersti; Amlie, Kristine; Alavi, Abass & Connelly, James Pattrick
(2022).
Clinical Applications of Somatostatin Receptor (Agonist) PET Tracers beyond Neuroendocrine Tumors.
Diagnostics (Basel).
12(2),
s. 1–19.
doi:
10.3390/diagnostics12020528.
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Somatostatin receptor (SSTR) agonist tracers used in nuclear medicine scans are classically used for neuroendocrine tumor diagnosis and staging. SSTR are however, expressed more widely in a variety of cells as seen in the distribution of physiological tracer uptake during whole body scans. This provides opportunities for using these tracers for applications other than NETs and meningiomas. In this qualitative systematic review, novel diagnostics in SSTR-PET imaging are reviewed. A total of 70 studies comprised of 543 patients were qualitatively reviewed. Sarcoidosis, atherosclerosis and phosphaturic mesenchymal tumors represent the most studied applications currently with promising results. Other applications remain in progress where there are many case reports but a relative dearth of cohort studies. [18F]FDG PET provides the main comparative method in many cases but represents a well-established general PET technique that may be difficult to replace, without prospective clinical studies.
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Rogne, Ane Gretesdatter; Müller, Ebba Gløersen; Udnæs, Eirin; Sigurdardottir, Solrun; Raudeberg, Rune & Connelly, James Pattrick
[Vis alle 9 forfattere av denne artikkelen]
(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),
s. 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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Skogseid, Inger Marie; Røsby, Oddveig; Konglund, Ane; Connelly, James Pattrick; Nedregaard, Bård & Jablonski, Greg Eigner
[Vis alle 9 forfattere av denne artikkelen]
(2018).
Dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity shows striatal dopaminergic dysfunction and response to pallidal stimulation.
Journal of Neurodevelopmental Disorders.
10(17),
s. 1–8.
doi:
10.1186/s11689-018-9235-z.
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Background Dystonia-deafness syndrome is a well-known clinical entity, with sensorineural deafness typically manifesting earlier than dystonia. ACTB p.Arg183Trp heterozygosity has been reported in six patients to cause combined infant-onset deafness and dystonia manifesting in adolescence or young adulthood. Three of these have received beneficial pallidal stimulation. Brain imaging to assess striatal function has not been reported previously, however. Nor has a comprehensive hypothesis been presented for how the pleiotropic manifestations of this specific beta-actin gene mutation originate developmentally. Case presentation A 19-year-old girl with congenital mild dysmorphic facial features, cochlear implants for infant-onset deafness, and mild cognitive and emotional disability, presented with an adolescent-onset, severe generalized dystonia. Brain MRI and multiple single gene sequencing were inconclusive. Due to life-threatening dystonia, we implanted a neurostimulation device, targeting the postero-ventral internal pallidum bilaterally. The Burke-Fahn-Marsden Dystonia Rating Scale motor/disability scores improved from 87/25 to 21/13 at 2.5 months postoperatively, 26/14 at 3 years, and 30/14 at 4 years. Subsequent whole exome sequencing identified heterozygosity for the ACTB p.Arg183Trp variant. Brain imaging included 123I-ioflupane single photon emission computed tomography (Dopamine Transporter-SPECT), SPECT with 123I-epidepride (binds to dopamine type 2-receptors) and 18 Fluoro-Deoxy-Glucose (FDG)–PET. Both Epidepride-SPECT and FDG-PET showed reduced tracer uptake in the striatum bilaterally, particularly in the putamen. DaT-SPECT was slightly abnormal. Conclusions In this patient with dystonia-deafness syndrome caused by ACTB p.Arg183Trp heterozygosity, unprecedented brain imaging findings strongly indicate striatal neuronal/dopaminergic dysfunction as the underlying cause of the dystonia. Pallidal stimulation provided a substantial improvement of the severe generalized dystonia, which is largely sustained at 4-year follow-up, and we advise this treatment to be considered in such patients. We hypothesize that the pleiotropic manifestations of the dystonia-deafness syndrome caused by this mutation derive from diverse developmental functions of beta-actin in neural crest migration and proliferation (facial dysmorphogenesis), hair cell stereocilia function (infant-onset deafness), and altered synaptic activity patterns associated with pubertal changes in striatal function (adolescent-onset dystonia). The temporal differences in developmental onset are likely due to varying degrees of susceptibility and of compensatory upregulation of other actin variants in the affected structures.
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1. okt. 2025 12:42
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1. okt. 2025 12:42
