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1.	Floderus, Johan, 1721-1789 (författare) Dissertatio gradualis, de præcipuis veteris comoediæ scriptoribus Græcis, quam consensu ampl. fac. phil. Ups. praeside mag. Johanne Flodero ... publice ventilandam sistit Johannes Wikström, Gestricius. In auditorio Carol. maj. d. [tomrum] Junii a. MDCCLXXIII. H. a. m. s. 1773 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
2.	Murberg, Johan, 1734-1805 (författare) Commentatio philologica, de suppliciis Persarum, ex occasione Ctesiae Cnidii [persikōn]. Quam ... Bonorum examini modeste offerunt Johannes Murberg ... et Johannes Wikström, Gestricii. In audit. Carol. maj. d. XXII. Dec. MDCCLXX. Horis ante meridiem solitis. 1770 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)
3.	Bergman, Lina, 1982- (författare) Cerebral biomarkers in women with preeclampsia 2017 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Preeclampsia and eclampsia are among the most common causes of maternal and fetal mortality and morbidity worldwide. There are no reliable means to predict eclampsia or cerebral edema in women with preeclampsia and knowledge of the brain involvement in preeclampsia is still limited. S100B and neuron specific enolase (NSE) are two cerebral biomarkers of glial- and neuronal origin respectively. They are used as predictors for neurological outcome after traumatic brain injuries and cardiac arrest but have not yet been investigated in preeclampsia.This thesis is based on one longitudinal cohort study of pregnant women (n=469, Paper I and III), one cross sectional study of women with preeclampsia and women with normal pregnancies (n=53 and 58 respectively, Paper II and IV) and one experimental animal study of eclampsia (Paper V).In Paper I and III, plasma concentrations of S100B and NSE were investigated throughout pregnancy in women developing preeclampsia (n=16) and in women with normal pregnancies (n=36) in a nested case control study. Plasma concentrations were increased in women developing preeclampsia in gestational week 33 and 37 for S100B and in gestational week 37 for NSE compared to women with normal pregnancies.In Paper II and IV, increased plasma concentrations of S100B and NSE were confirmed among women with preeclampsia compared to women with normal pregnancies. Furthermore, increased plasma concentrations of S100B correlated to visual disturbances among women with preeclampsia (Paper II) and plasma concentrations of S100B and NSE remained increased among women with preeclampsia one year after delivery (Paper IV).In Paper V, an experimental rat model of preeclampsia and eclampsia demonstrated increased serum concentrations of S100B after seizures in normal pregnancy (n=5) and a tendency towards increased plasma concentrations of S100B in preeclampsia (n=5) compared to normal pregnancy (n=5) without seizures. Furthermore, after seizures, animals with magnesium sulphate treatment demonstrated increased serum concentrations of S100B and NSE compared to no treatment.In conclusion; plasma concentrations of S100B and NSE are increased in preeclampsia during late pregnancy and postpartum and S100B correlates to visual disturbances in women with preeclampsia. The findings are partly confirmed in an animal model of eclampsia.
4.	Bergman, Lina, et al. (författare) Investigating Maternal Brain Alterations in Preeclampsia : the Need for a Multidisciplinary Effort 2019 Ingår i: Current Hypertension Reports. - : Springer Science and Business Media LLC. - 1522-6417 .- 1534-3111. ; 21:9 Tidskriftsartikel (refereegranskat)abstract PURPOSE OF REVIEW: To provide insight into the mechanisms underlying cerebral pathophysiology and to highlight possible methods for evaluation, screening, and surveillance of cerebral complications in preeclampsia.RECENT FINDINGS: The pathophysiology of eclampsia remains enigmatic. Animal studies show that the cerebral circulation in pregnancy and preeclampsia might be affected with increased permeability over the blood-brain barrier and altered cerebral blood flow due to impaired cerebral autoregulation. The increased blood pressure cannot be the only underlying cause of eclampsia and cerebral edema, since some cases of eclampsia arise without simultaneous hypertension. Findings from animal studies need to be confirmed in human tissues. Evaluation of brain alterations in preeclampsia and eclampsia is challenging and demands a multidisciplinary collaboration, since no single method can accurately and fully describe how preeclampsia affects the brain. Cerebral complications of preeclampsia are significant factors in maternal morbidity and mortality worldwide. No single method can accurately describe the full picture of how preeclampsia affects the brain vasculature and parenchyma. We recommend an international and multidisciplinary effort not only to overcome the issue of limited sample availability but also to optimize the quality of research.
5.	Bergman, Lina, et al. (författare) Plasma Levels of S100B in Preeclampsia and Association With Possible Central Nervous System Effects 2014 Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 27:8, s. 1105-1111 Tidskriftsartikel (refereegranskat)abstract BACKGROUND:S100B is supposed to be a peripheral biomarker of central nervous system (CNS) injury. The purpose of this study was to compare levels of S100B in women with preeclampsia with levels in healthy pregnant control subjects and furthermore to analyze levels of S100B in relation to possible CNS effects.METHODS:A cross-sectional case-control study in antenatal care centers in Uppsala, Sweden, was performed. Fifty-three women with preeclampsia and 58 healthy pregnant women were recruited at similar gestational length; women with preeclampsia were recruited at time of diagnosis, and control subjects were recruited during their routine visit to an antenatal clinic. Plasma samples were collected, and levels of S100B were analyzed with an enzyme-linked immunosorbent assay. Information about demographic and clinical characteristics, including symptoms related to CNS affection, was collected from the medical records. The main outcome measures were plasma levels of S100B and possible CNS effects.RESULTS:Levels of S100B were significantly higher among women with preeclampsia than among control subjects (0.12 µg/L vs. 0.07 µg/L; P < 0.001). In preeclampsia, there was a significant association between high levels of S100B and visual disturbances (P < 0.05).CONCLUSIONS:S100B is increased among women with preeclampsia, and high levels of S100B associate with visual disturbances, which might reflect CNS affection in women with preeclampsia.
6.	Bergman, Lina, et al. (författare) Preeclampsia and Increased Permeability Over the Blood–Brain Barrier : A Role of Vascular Endothelial Growth Receptor 2 2021 Ingår i: American Journal of Hypertension. - : Oxford University Press. - 0895-7061 .- 1941-7225. ; 34:1, s. 73-81 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Cerebral complications in preeclampsia are leading causes of maternal mortality worldwide but the underlying pathophysiology is largely unknown and a challenge to study. Using an in vitro model of the human blood brain barrier (BBB), we explored the role of vascular endothelial growth factor receptor 2 (VEGFR2) in preeclampsia.METHODS: The human brain endothelial cell line (hCMEC/D3) cultured on Tranwells insert were exposed (12 h) to plasma from women with preeclampsia (n=28), normal pregnancy (n=28) and non-pregnant (n=16) controls. Transendothelial electrical resistance (TEER) and permeability to 70 kDa FITC-dextran were measured for assessment of BBB integrity. We explored possible underlying mechanisms, with focus on expression of tight junction proteins and phosphorylation of two tyrosine residues of VEGFR2, associated with vascular permeability and migration (pY951) and cell proliferation (pY1175). Plasma concentrations of soluble FMS like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) were measured in order to establish correlations with in vitro results.RESULTS: hCMEC/D3 exposed to plasma from women with preeclampsia exhibited reduced TEER and increased permeability to 70 kDa FITC-dextran. Further, these cells up-regulated the mRNA levels of VEGFR2, as well as pY951-VEGFR2; but reduced pY1175-VEGFR2 (p&0.05 in all cases). No difference in mRNA expression of tight junction protein was observed between gruops. There was no correlation between angiogenic biomarkers and BBB permeability.CONCLUSION: We present a promising in vitro model of the BBB in preeclampsia. Selective tyrosine phosphorylation of VEGFR2 may participate in the increased BBB permeability in preeclampsia irrespective of plasma concentrations of angiogenic biomarkers.
7.	Casar Borota, Olivera, et al. (författare) Serotonin, ATRX, and DAXX Expression in Pituitary Adenomas : Markers in the Differential Diagnosis of Neuroendocrine Tumors of the Sellar Region. 2017 Ingår i: American Journal of Surgical Pathology. - 0147-5185 .- 1532-0979. ; 41:9, s. 1238-1246 Tidskriftsartikel (refereegranskat)abstract Differential diagnosis based on morphology and immunohistochemistry between a clinically nonfunctioning pituitary neuroendocrine tumor (NET)/pituitary adenoma and a primary or secondary NET of nonpituitary origin in the sellar region may be difficult. Serotonin, a frequently expressed marker in the NETs, has not been systematically evaluated in pituitary NETs. Although mutations in ATRX or DAXX have been reported in a significant proportion of pancreatic NETs, the mutational status of ATRX and DAXX and their possible pathogenetic role in pituitary NETs are unknown. Facing a difficult diagnostic case of an invasive serotonin and adrenocorticotroph hormone immunoreactive NET in the sellar region, we explored the immunohistochemical expression of serotonin, ATRX, and DAXX in a large series of pituitary endocrine tumors of different types from 246 patients and in 2 corticotroph carcinomas. None of the pituitary tumors expressed serotonin, suggesting that serotonin immunoreactive sellar tumors represent primary or secondary NETs of nonpituitary origin. Normal expression of ATRX and DAXX in pituitary tumors suggests that ATRX and DAXX do not play a role in the pathogenesis of pituitary endocrine tumors that remain localized to the sellar and perisellar region. A lack of ATRX or DAXX in a sellar NET suggests a nonpituitary NET, probably of pancreatic origin. One of the 2 examined corticotroph carcinomas, however, demonstrated negative ATRX immunolabeling due to an ATRX gene mutation. Further studies on a larger cohort of pituitary carcinomas are needed to clarify whether ATRX mutations may contribute to the metastatic potential in a subset of pituitary NETs.
8.	Correia de Verdier, Maria, 1983-, et al. (författare) Effect of MRI acquisition parameters on accuracy and precision of phase-contrast measurements in a small-lumen vessel phantom 2024 Ingår i: European radiology experimental. - : Springer. ; 8 Tidskriftsartikel (refereegranskat)abstract BackgroundPhase-contrast magnetic resonance imaging (PC-MRI) quantifies blood flow and velocity noninvasively. Challenges arise in neurovascular disorders due to small vessels. We evaluated the impact of voxel size, number of signal averages (NSA), and velocity encoding (VENC) on PC-MRI measurement accuracy and precision in a small-lumen vessel phantom.MethodsWe constructed an in vitro model with a constant flow rate using a 2.2-mm inner diameter plastic tube. A reservoir with a weight scale and timer was used as standard reference. Gradient-echo T1 weighted PC-MRI sequence was performed on a 3-T scanner with varying voxel size (2.5, 5.0, 7.5 mm3), NSA (1, 2, 3), and VENC (200, 300, 400 cm/s). We repeated measurements nine times per setting, calculating mean flow rate, maximum velocity, and least detectable difference (LDD).ResultsPC-MRI flow measurements were higher than standard reference values (mean ranging from 7.3 to 9.5 mL/s compared with 6.6 mL/s). Decreased voxel size improved accuracy, reducing flow rate measurements from 9.5 to 7.3 mL/s. The LDD for flow rate and velocity varied between 1 and 5%. The LDD for flow rate decreased with increased voxel size and NSA (p = 0.033 and 0.042). The LDD for velocity decreased with increased voxel size (p < 10-16). No change was observed when VENC varied.ConclusionsPC-MRI overestimated flow. However, it has high precision in a small-vessel phantom with constant flow rate. Improved accuracy was obtained with increasing spatial resolution (smaller voxels). Improved precision was obtained with increasing signal-to-noise ratio (larger voxels and/or higher NSA).
9.	Correia de Verdier, Maria, 1983- (författare) Evaluation of Intracranial Arteriovenous Malformations with Magnetic Resonance Imaging 2022 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Intracranial arteriovenous malformations (AVMs) are characterized by feeding arteries, a tangle of abnormal vessels (nidus) and draining veins. Radiological evaluation methods are used in diagnosing AVMs, treatment planning, post-treatment evaluation and monitoring stability. The general aim of our studies reviewed in this thesis was to develop and evaluate magnetic resonance imaging (MRI) techniques for the evaluation of AVMs. MethodsPaper I – In 30 patients treated with proton radiation therapy, radiation-induced MRI changes (vasogenic edema, contrast enhancement and cavitation) and their association with development of neurological symptoms and nidus obliteration were assessed. Paper II – We evaluated the effect of acquisition parameters (voxel size, number of signal averages and velocity encoding) on the accuracy and precision of phase-contrast MRI (PC-MRI)-measured flow and velocity in a small-lumen vessel phantom with constant flow. Paper III – Normal ranges and test-retest reproducibility of flow and velocity in the anterior, middle and posterior cerebral arteries were measured with PC-MRI in 30 healthy volunteers.Paper IV – We studied PC-MRI-measured flow and velocity in feeding arteries in 10 patients with AVMs and compared the values obtained with the results from paper III. We also assessed post-treatment changes in flow and velocity in three patients. Results Paper I – Radiation-induced MRI changes were found in 87% of patients after proton radiation treatment of AVMs. MRI changes were associated with neurological symptoms but not with nidus obliteration. Paper II – PC-MRI overestimated flow in a small-lumen vessel phantom. Accuracy for flow measurements improved by decreasing voxel size. Precision for both flow and velocity measurements improved by increasing voxel size. Precision for flow measurements improved by increasing the number of signal averages.Paper III – We reported normal ranges and test-retest reproducibility for PC-MRI-measured flow and velocity in the main intracranial arteries. Reproducibility was overall quite low, but higher for the middle cerebral arteries than for the anterior and posterior cerebral arteries.Paper IV – Patients with a large nidus have increased velocity measured with PC-MRI in feeding arteries compared to intracranial arteries in healthy individuals. There is a reduction in PC-MRI-measured flow and velocity after treatment. ConclusionRadiation-induced MRI changes are common after proton radiation treatment of AVMs. The accuracy and precision of PC-MRI measurements in a phantom depend on acquisition parameter settings. In patients with AVMs with a large nidus, increased velocity is observed in feeding arteries, and a decrease in flow and velocity is observed after treatment. PC-MRI can potentially be used as a clinical tool to aid treatment planning and post-treatment evaluation.
10.	Engelbrektsson, Johan, 1976, et al. (författare) The impact of Mexican hat and dual-tree complex wavelet transforms on multivariate evaluation of image texture properties 2010 Ingår i: Journal of Chemometrics. Tidskriftsartikel (refereegranskat)
11.	Fahlström, Markus, et al. (författare) A mathematical model for temporal cerebral blood flow response to acetazolamide evaluated in patients with Moyamoya disease 2024 Ingår i: Magnetic Resonance Imaging. - : Elsevier. - 0730-725X .- 1873-5894. ; 110, s. 35-42 Tidskriftsartikel (refereegranskat)abstract Background: Paired cerebral blood flow (CBF) measurement is usually acquired before and after vasoactive stimulus to estimate cerebrovascular reserve (CVR). However, CVR may be confounded because of variations in time-to-maximum CBF response (tmax) following acetazolamide injection. With a mathematical model, CVR can be calculated insensitive to variations in tmax, and a model offers the possibility to calculate additional model-derived parameters. A model that describes the temporal CBF response following a vasodilating acetazolamide injection is proposed and evaluated.Methods: A bi-exponential model was adopted and fitted to four CBF measurements acquired using arterial spin labelling before and initialised at 5, 15 and 25 min after acetazolamide injection in a total of fifteen patients with Moyamoya disease. Curve fitting was performed using a non-linear least squares method with a priori constraints based on simulations.Results: Goodness of fit (mean absolute error) varied between 0.30 and 0.62 ml·100 g-1·min-1. Model-derived CVR was significantly higher compared to static CVR measures. Maximum CBF increase occurred earlier in healthy- compared to diseased vascular regions.Conclusions: The proposed mathematical model offers the possibility to calculate CVR insensitive to variations in time to maximum CBF response which gives a more detailed characterisation of CVR compared to static CVR measures. Although the mathematical model adapts generally well to this dataset of patients with MMD it should be considered as experimental; hence, further studies in healthy populations and other patient cohorts are warranted.
12.	Fällmar, David, et al. (författare) The extent of neuroradiological findings in COVID-19 shows correlation with blood biomarkers, Glasgow coma scale score and days in intensive care 2022 Ingår i: Journal of neuroradiology. - : Elsevier. - 0150-9861 .- 1773-0406. ; 49:6, s. 421-427 Tidskriftsartikel (refereegranskat)abstract Background and purposeA wide range of neuroradiological findings has been reported in patients with coronavirus disease 2019 (COVID-19), ranging from subcortical white matter changes to infarcts, haemorrhages and focal contrast media enhancement. These have been descriptively but inconsistently reported and correlations with clinical findings and biomarkers have been difficult to extract from the literature. The purpose of this study was to quantify the extents of neuroradiological findings in a cohort of patients with COVID-19 and neurological symptoms, and to investigate correlations with clinical findings, duration of intensive care and biomarkers in blood.Material and methodsPatients with positive SARS-CoV-2 and at least one new-onset neurological symptom were included from April until July 2020. Nineteen patients were examined regarding clinical symptoms, biomarkers in blood and MRI of the brain. In order to quantify the MRI findings, a semi-quantitative neuroradiological severity scale was constructed a priori, and applied to the MR images by two specialists in neuroradiology.Results and conclusionsThe score from the severity scale correlated significantly with blood biomarkers of CNS injury (glial fibrillary acidic protein, total-tau, ubiquitin carboxyl-terminal hydrolase L1) and inflammation (C-reactive protein), Glasgow Coma Scale score, and the number of days spent in intensive care. The underlying radiological assessments had inter-rater agreements of 90.5%/86% (for assessments with 2/3 alternatives). Total intraclass correlation was 0.80.Previously reported neuroradiological findings in COVID-19 have been diverse and heterogenous. In this study, the extent of findings in MRI examination of the brain, quantified using a structured report, shows correlation with relevant biomarkers.
13.	Giordanetto, Fabrizio, et al. (författare) Design of Selective sPLA2-X Inhibitor (-)-2-{2-[Carbamoyl-6-(trifluoromethoxy)-1 H-indol-1-yl]pyridine-2-yl}propanoic Acid 2018 Ingår i: ACS Medicinal Chemistry Letters. - : American Chemical Society. - 1948-5875. ; 9:7, s. 600-605 Tidskriftsartikel (refereegranskat)abstract A lead generation campaign identified indole-based sPLA2-X inhibitors with a promising selectivity profile against other sPLA2 isoforms. Further optimization of sPLA2 selectivity and metabolic stability resulted in the design of (-)-17, a novel, potent, and selective sPLA2-X inhibitor with an exquisite pharmacokinetic profile characterized by high absorption and low clearance, and low toxicological risk. Compound (-)-17 was tested in an ApoE-/- murine model of atherosclerosis to evaluate the effect of reversible, pharmacological sPLA2-X inhibition on atherosclerosis development. Despite being well tolerated and achieving adequate systemic exposure of mechanistic relevance, (-)-17 did not significantly affect circulating lipid and lipoprotein biomarkers and had no effect on coronary function or histological markers of atherosclerosis.
14.	Nelander, Maria, et al. (författare) Assessment of cerebral perfusion and edema in preeclampsia with intravoxel incoherent motion MRI 2018 Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 97:10, s. 1212-1218 Tidskriftsartikel (refereegranskat)abstract BackgroundCerebral complications are the main reasons for morbidity and mortality in preeclampsia and eclampsia. Still we do not know if the pathophysiology entails hypo- or hyperperfusion of the brain, or how and when edema emerges, due to the difficulty to examine the cerebral circulation.Material and methodsWe have used a non-invasive diffusion weighted magnetic resonance imaging (MRI) technique, intravoxel incoherent motion, to study cerebral perfusion on the capillary level and cerebral edema in women with preeclampsia (n=30), normal pregnancy (n=32) and non-pregnant women (n=16). Estimates of cerebral blood volume, blood flow and edema were measured in five different regions. These points were chosen to represent blood supply areas of both the carotid and vertebrobasilar arteries, and to include both white and grey matter.ResultsExcept for the caudate nucleus, we did not detect any differences in cerebral perfusion measures on a group level. In the caudate nucleus we found lower cerebral blood volume and lower blood flow in preeclampsia compared to both normal pregnancy (p=0.01 and p=0.03, respectively) and non-pregnant women (both p=0.02). No differences in edema were detected between study groups.ConclusionThe cerebral perfusion measures were comparable between the study groups, except for a portion of the basal ganglia where hypoperfusion was detected in preeclampsia compared to normal pregnancy and non-pregnant women.
15.	Nelander, Maria, et al. (författare) Cerebral Magnesium Levels in Preeclampsia; A Phosphorus Magnetic Resonance Spectroscopy Study 2017 Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 30:7, s. 667-672 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Magnesium sulfate (MgSO4) is used as a prophylaxis for eclamptic seizures. The exact mechanism of action is not fully established. We used phosphorus magnetic resonance spectroscopy (31P-MRS) to investigate if cerebral magnesium (Mg2+) levels differ between women with preeclampsia, normal pregnant, and nonpregnant women.METHODS: This cross-sectional study comprised 28 women with preeclampsia, 30 women with normal pregnancies in corresponding gestational week (range: 23-41 weeks) and 11 nonpregnant healthy controls. All women underwent 31P-MRS from the parieto-occipital region of the brain and were interviewed about cerebral symptoms. Differences between groups were assessed by analysis of variance and Tukey's post-hoc test. Correlations between Mg2+ levels and specific neurological symptoms were estimated with Spearman's rank test.RESULTS: Mean maternal cerebral Mg2+ levels were lower in women with preeclampsia (0.12 mM ± 0.02) compared to normal pregnant controls (0.14 mM ± 0.03) (P = 0.04). Nonpregnant and normal pregnant women did not differ in Mg2+ levels. Among women with preeclampsia, lower Mg2+ levels correlated with presence of visual disturbances (P = 0.04). Plasma levels of Mg2+ did not differ between preeclampsia and normal pregnancy.CONCLUSIONS: Women with preeclampsia have reduced cerebral Mg2+ levels, which could explain the potent antiseizure prophylactic properties of MgSO4. Within the preeclampsia group, women with visual disturbances have lower levels of Mg2+ than those without such symptoms.
16.	Nelander, Maria, 1974-, et al. (författare) Cerebral osmolytes and plasma osmolality in pregnancy and preeclampsia : a proton magnetic resonance spectroscopy study 2018 Ingår i: American Journal of Hypertension. - : Oxford University Press (OUP). - 0895-7061 .- 1941-7225. ; 31:7, s. 847-853 Tidskriftsartikel (refereegranskat)abstract Background: Cerebral complications contribute substantially to mortality in preeclampsia. Pregnancy calls for extensive maternal adaptations, some associated with increased propensity for seizures, but the pathophysiology behind the eclamptic seizures is not fully understood. Plasma osmolality and sodium levels are lowered in pregnancy. This could result in extrusion of cerebral organic osmolytes, including the excitatory neurotransmitter glutamate, but this remains to be determined. The hypothesis of this study was that cerebral levels of organic osmolytes are decreased during pregnancy, and that this decrease is even more pronounced in women with preeclampsia.Method: We used proton magnetic resonance spectroscopy to compare levels of cerebral organic osmolytes, in women with preeclampsia (n=30), normal pregnancy (n=32) and non-pregnant controls (n=16). Cerebral levels organic osmolytes were further correlated to plasma osmolality, and plasma levels of glutamate and sodium.Results: Compared to non-pregnant women, women with normal pregnancy and preeclampsia had lower levels of the cerebral osmolytes myo-inositol, choline and creatine (p=0.001 or less), and all these metabolites correlated with each other (p<0.05). Women with normal pregnancies and preeclampsia had similar levels of osmolytes, except for glutamate, which was significantly lower in preeclampsia. Cerebral and plasma glutamate levels were negatively correlated with each other (p<0.008), and cerebral myo-inositol, choline and creatine levels were all positively correlated with both plasma osmolality and sodium levels (p<0.05).Conclusion: Our results indicate that pregnancy is associated with extrusion of cerebral organic osmolytes. This includes the excitatory neurotransmitter glutamate, which may be involved in the pathophysiology of seizures in preeclampsia.
17.	Nelander, Maria, 1974- (författare) Preeclampsia and the Brain : Epidemiological and Magnetic Resonance Studies 2018 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract Preeclampsia is a pregnancy specific syndrome that causes substantial maternal and fetal morbidity and mortality. One major contributor to maternal deaths is eclampsia, i.e. when seizures arise in the context of preeclampsia. The pathophysiology of eclampsia is still incompletely chartered and the long-term cerebral consequences of preeclampsia are also largely unknown.This thesis consists of a register based cohort study (n=3232, study I), and a cross-sectional neuroimaging study of pregnant women with and without preeclampsia (n=78, studies II-IV).In paper I, we compared the incidence of dementia and cardiovascular disease (CVD) between women ≥65 years with a self-reported history of hypertensive pregnancy, and women with a normotensive pregnancy. No difference was found regarding dementia, but an increased risk of CVD persisted among these elderly women.In paper II, we used phosphorus magnetic resonance spectroscopy to measure cerebral magnesium levels (Mg2+). We found lower levels of Mg2+ in women with preeclampsia than in women with normal pregnancy and non-pregnant women. Further, which was novel, we showed that lower cerebral Mg2+levels correlated with visual disturbances. The findings are interesting, since magnesium sulfate is the most effective treatment and prophylaxis for eclampsia, but with a largely unknown mechanism of action.In paper III, we measured cerebral organic osmolytes with proton magnetic resonance spectroscopy and found lower levels of osmolytes in pregnancy. Cerebral osmolytes were positively correlated with a decreased plasma osmolality, indicating that there is a joint biological mechanism. The only osmolyte that differed between women with preeclampsia and healthy pregnant women was glutamate. Glutamate is an excitatory neurotransmitter, which also functions as an osmolyte. Thus, lower cerebral glutamate levels could have implications on the pathophysiology of seizures.In paper IV, cerebral perfusion and edema were assessed with magnetic resonance imaging using intravoxel incoherent motion technique. A reduced perfusion fraction was found in a part of the basal ganglia in women with preeclampsia. No difference in edema was detected.Our findings indicate Mg2+ metabolism, plasma hypoosmolality and possibly cerebral hypoperfusion to be involved in the pathophysiology of cerebral affection in preeclampsia.
18.	Nelander, Maria, et al. (författare) Pregnancy hypertensive disease and risk of dementia and cardiovascular disease in women aged 65 years or older : a cohort study 2016 Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 6:1 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: The primary aim was to study pregnancy hypertensive disease and subsequent risk of dementia. The second aim was to study if the increased risks of cardiovascular disease (CVD) and stroke after pregnancy hypertensive disease persist in an elderly population.DESIGN: Cohort study.SETTING: Sweden.POPULATION OR SAMPLE: 3232 women 65 years or older (mean 71 years) at inclusion.METHODS: Cox proportional hazards regression analyses were used to calculate risks of dementia, CVD and/or stroke for women exposed to pregnancy hypertensive disease. Exposure data were collected from an interview at inclusion during the years 1998-2002. Outcome data were collected from the National Patient Register and Cause of Death Register from the year of inclusion until the end of 2010. Age at inclusion was set as a time-dependent variable, and adjustments were made for body mass index, education and smoking.MAIN OUTCOME MEASURES: Dementia, CVD, stroke.RESULTS: During the years of follow-up, 7.6% of the women exposed to pregnancy hypertensive disease received a diagnosis of dementia, compared with 7.4% among unexposed women (HR 1.19; 95% CI 0.79 to 1.73). The corresponding rates for CVD were 22.9% for exposed women and 19.0% for unexposed women (HR 1.29; 95% CI 1.02 to 1.61), and for stroke 13.4% for exposed women and 10.7% for unexposed women (HR 1.36; 95% CI 1.00 to 1.81).CONCLUSIONS: There was no increased risk of dementia after self-reported pregnancy hypertensive disease in our cohort. We found that the previously reported increased risk of CVD and stroke after pregnancy hypertensive disease persists in an older population.
19.	Nylander, Ruta, et al. (författare) Relation between cardiovascular disease risk markers and brain infarcts detected by magnetic resonance imaging in an elderly population 2015 Ingår i: Journal of Stroke & Cerebrovascular Diseases. - : Elsevier BV. - 1052-3057 .- 1532-8511. ; 24:2, s. 312-318 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Established cardiovascular risk markers, such as hypertension, are associated with increased risk of brain infarcts. The newer markers N-terminal pro-brain natriuretic peptide, troponin I, C-reactive protein, and cystatin C may affect the risk of cardiovascular events and potentially, thereby, also stroke. We investigated the association between established and new risk markers for cardiovascular disease and brain infarcts detected by magnetic resonance imaging (MRI) at age 75.METHODS: Four hundred six randomly selected subjects from the Prospective Investigation of the Vasculature in Uppsala Seniors study were examined with MRI of the brain at age 75. Blood samples, measurements, and dedicated questionnaires at age 70 were used for analysis of risk markers. A history of diseases had been obtained at age 70 and 75. MRI was evaluated regarding lacunar and cortical infarcts. Univariate associations between outcomes and risk markers were assessed with logistic regression models.RESULTS: One or more infarcts were seen in 23% of the subjects (20% had only lacunar infarcts, 1% had only cortical infarcts, and 2% had both). Hypertension (odds ratio [OR] 2.6, 95% confidence interval [CI] 1.4, 4.7) and obesity (OR 1.3; CI 1.0, 1.8) were significantly associated with increased risk of brain infarction. The newer risk markers were not significantly associated with the brain infarcts.CONCLUSIONS: The new markers were not associated with the predominantly lacunar infarcts in our 75-year-old population, why troponin I and NT-proBNP may be associated mainly with cardioembolic infarcts as shown recently.
20.	Sohlberg, Sara, 1977-, et al. (författare) In vivo(31)P-MR spectroscopy in normal pregnancy, early and late preeclampsia : A study of placental metabolism 2014 Ingår i: Placenta. - : Elsevier BV. - 0143-4004 .- 1532-3102. ; 35:5, s. 318-323 Tidskriftsartikel (refereegranskat)abstract INTRODUCTION: Preeclampsia affects about 3% of pregnancies and the placenta is believed to play a major role in its pathophysiology. Lately, the role of the placenta has been hypothesised to be more pronounced in preeclampsia of early (<34 weeks) rather than late (≥34 weeks) onset. (31)P Magnetic Resonance Spectroscopy (MRS) enables non-invasive, in vivo studies of placental metabolism. Our aim was to study placental energy and membrane metabolism in women with normal pregnancies and those with early and late onset preeclampsia.METHODS: The study population included fourteen women with preeclampsia (five with early onset and nine with late onset preeclampsia) and sixteen women with normal pregnancy (seven with early and nine with late pregnancy). All women underwent a (31)P-MRS examination of the placenta.RESULTS: The phosphodiester (PDE) spectral intensity fraction of the total (31)P signal and the phosphodiester/phosphomonoester (PDE/PME) spectral intensity ratio was higher in early onset preeclampsia than in early normal pregnancy (p = 0.03 and p = 0.02). In normal pregnancy the PDE spectral intensity fraction and the PDE/PME spectral intensity ratio increased with increasing gestational age (p = 0.006 and p = 0.001).DISCUSSION: Since PDE and PME are related to cell membrane degradation and formation, respectively, our findings indicate increased cell degradation and maybe also decreased cell proliferation in early onset preeclampsia compared to early normal pregnancy, and with increasing gestational age in normal pregnancy.CONCLUSIONS: Our findings could be explained by increased apoptosis due to ischaemia in early onset preeclampsia and also increased apoptosis with increasing gestational age in normal pregnancy.
21.	Sohlberg, Sara, 1977-, et al. (författare) MRI estimated placental perfusion in fetal growth assessment 2015 Ingår i: Ultrasound in Obstetrics and Gynecology. - : Wiley. - 0960-7692 .- 1469-0705. ; 46:6, s. 700-705 Tidskriftsartikel (refereegranskat)abstract ObjectiveThis study aimed to evaluate placental perfusion fraction estimated by magnetic resonance imaging (MRI) in vivo as a marker of placental function.MethodsThe study population included 35 pregnant women, of whom 13 had preeclampsia, examined at gestational weeks 22 to 40. Each woman underwent, within a 24 hour period: a MRI diffusion-weighted sequence (from which we calculated the placental perfusion fraction); venous blood sampling; and an ultrasound examination including estimation of fetal weight, amniotic fluid index and Doppler velocity measurements. We compared the perfusion fraction in pregnancies with and without fetal growth restriction and estimated correlations between the perfusion fraction and ultrasound estimates and plasma markers with linear regression. The associations between the placental perfusion fraction and ultrasound estimates were modified by the presence of preeclampsia (p < 0.05) and therefore we included an interaction term between preeclampsia and the covariates in the models.ResultsThe median placental perfusion fraction in pregnancies with and without fetal growth restriction was 21% and 32%, respectively (p = 0.005). The correlations between the placental perfusion fraction and ultrasound estimates and plasma markers were highly significant (p-values 0.002 to 0.0001). The highest coefficient of determination (R2= 0.56) for placental perfusion fraction was found for a model including pulsatility index in ductus venosus, plasma level of sFlt1, estimated fetal weight and presence of preeclampsia.ConclusionThe placental perfusion fraction has potential to contribute to the clinical assessment in cases of placental insufficiency.
22.	Sohlberg, Sara, 1977-, et al. (författare) Placental perfusion in normal pregnancy and early and late preeclampsia : A magnetic resonance imaging study. 2014 Ingår i: Placenta. - : Elsevier BV. - 0143-4004 .- 1532-3102. ; 35:3, s. 202-206 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: Our primary aim was to investigate if women with early or late preeclampsia have different placental perfusion compared with normal pregnancies. A secondary aim was to investigate if placental perfusion changes with increasing gestational age in normal pregnancy.METHODS: The study population included thirteen women with preeclampsia (five with early and eight with late preeclampsia) and nineteen women with normal pregnancy (ten with early and nine with late pregnancy). Early was defined as <34 weeks and late as ≥34 weeks gestation. All women underwent a magnetic resonance imaging (MRI) examination including a diffusion weighted sequence at 1.5 T. The perfusion fraction was calculated.RESULTS: Women with early preeclampsia had a smaller placental perfusion fraction (p = 0.001) and women with late preeclampsia had a larger placental perfusion fraction (p = 0.011), compared to women with normal pregnancies at the corresponding gestational age. The placental perfusion fraction decreased with increasing gestational age in normal pregnancies (p = 0.001).CONCLUSION: Both early and late preeclampsia differ in placental perfusion from normal pregnant women. Observed differences are however in the opposite direction, suggesting differences in pathophysiology. Placental perfusion decreases with increasing gestational age in normal pregnancy.
23.	Thorgeirsdottir, Lilja, et al. (författare) Study protocol: establishment of a multicentre pre-eclampsia database and biobank in Sweden: GO PROVE and UP MOST, a prospective cohort study 2021 Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 11:11 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Introduction Pre-eclampsia, a multisystem disorder in pregnancy, is one of the most common causes of maternal morbidity and mortality worldwide. However, we lack methods for objective assessment of organ function in pre-eclampsia and predictors of organ impairment during and after pre-eclampsia. The women’s and their partners’ experiences of pre-eclampsia have not been studied in detail. To phenotype different subtypes of the disorder is of importance for prediction, prevention, surveillance, treatment and follow-up of pre-eclampsia.The aim of this study is to set up a multicentre database and biobank for pre-eclampsia in order to contribute to a safer and more individualised treatment and care.Methods and analysis This is a multicentre cohort study. Prospectively recruited pregnant women ≥18 years, diagnosed with pre-eclampsia presenting at Sahlgrenska University Hospital, Uppsala University Hospital and at Södra Älvsborgs Hospital, Sweden, as well as normotensive controls are eligible for participation. At inclusion and at 1-year follow-up, the participants donate biosamples that are stored in a biobank and they are also asked to participate in various organ-specific evaluations. In addition, questionnaires and interviews regarding the women’s and partner’s experiences are distributed at follow-up.Ethics and dissemination By creating a database and biobank, we will provide the means to explore the disorder in a broader sense and allow clinical and laboratory discoveries that can be translated to clinical trials aiming at improved care of women with pre-eclampsia. Further, to evaluate experiences and the psychological impact of being affected by pre-eclampsia can improve the care of pregnant women and their partners. In case of incidental pathological findings during examinations performed, they will be handled in accordance with clinical routine. Data are stored in a secure online database. Biobank samples are identified through the women’s personal identification number and pseudonymised after identification in the biobank before analysis.This study was approved by the regional ethical review board in Gothenburg on 28 December 2018 (approval number 955-18) and by the Swedish Ethical Review Authority on 27 February 2019 (approval number 2019-00309).
24.	Virhammar, Johan, et al. (författare) Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid 2020 Ingår i: Neurology. - 0028-3878 .- 1526-632X. ; 95:10, s. 445-449 Tidskriftsartikel (refereegranskat)abstract Here, we report a case of COVID-19–related acute necrotizing encephalopathy where SARS-CoV-2 RNA was found in CSF 19 days after symptom onset after testing negative twice. Although monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurologic function deteriorated into coma. MRI of the brain showed pathologic signal symmetrically in central thalami, subinsular regions, medial temporal lobes, and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein, were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received IV immunoglobulins and plasma exchange. Her neurologic status improved, and she was extubated 4 weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected COVID-19 and neurologic symptoms.
25.	Wikström, Anna-Karin, et al. (författare) Plasma levels of S100B during pregnancy in women developing pre-eclampsia. 2012 Ingår i: Pregnancy hypertension. - : Elsevier BV. - 2210-7789 .- 2210-7797. ; 2:4, s. 398-402 Tidskriftsartikel (refereegranskat)abstract S100B is suggested to be a peripheral biomarker of central nervous system injury with increased blood-brain barrier permeability. The aim of this study was to investigate if there is a difference in plasma levels of S100B throughout pregnancy between women developing pre-eclampsia and those who did not.A nested case-control study within a longitudinal study cohort was performed. Healthy pregnant women were enrolled and plasma samples were collected at gestational weeks 10, 25, 28, 33 and 37. Levels of S100B throughout pregnancy were analyzed with an ELISA assay.The levels of S100B did not change between gestational weeks 10 and 37 (0.047 vs. 0.052; p=0.71) in the healthy controls, but the S100B levels increased between corresponding weeks in women who developed pre-eclampsia (0.052 vs. 0.075; p<0.05). In gestational weeks 33 and 37 women who developed pre-eclampsia had higher levels of S100B than the controls (p=0.047 and p=0.010, respectively).S100B levels increase during pregnancy in women who develop pre-eclampsia and there is an increased S100B level in women who develop pre-eclampsia compared with healthy pregnancies several weeks before clinical symptoms of the disease. The increased amount of plasma S100B in women developing pre-eclampsia might be secondary to cerebral vascular damage and S100B is a potential peripheral biomarker reflecting cerebral involvement in pre-eclampsia.
26.	Wikström, Anna-Karin, et al. (författare) Random albumin/creatinine ratio for quantification of proteinuria in manifest pre-eclampsia 2006 Ingår i: BJOG. - 1470-0328. ; 113:8, s. 930-934 Tidskriftsartikel (refereegranskat)
27.	Wikström, Anna-Karin, et al. (författare) Random albumin/creatinine ratio for quantification of proteinuria in manifest pre-eclampsia - Reply 2007 Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 114:1, s. 120-120 Tidskriftsartikel (refereegranskat)
28.	Wikström, Anna-Karin, et al. (författare) Random albumin/creatinine ratio for quantification of proteinuria in manifest pre-eclampsia - Reply 2007 Ingår i: British Journal of Obstetrics and Gynecology. - : Wiley. - 1470-0328 .- 1471-0528. ; 114:1, s. 119-119 Tidskriftsartikel (refereegranskat)
29.	Wissman, Jörgen, et al. (författare) Hur kan landsbygdsprogrammets miljöersättningar förbättras : Erfarenheter från andra länder 2012 Rapport (övrigt vetenskapligt/konstnärligt)
30.	Abdellah, Tebani, et al. (författare) Annotation of pituitary neuroendocrine tumors with genome-wide expression analysis 2021 Ingår i: Acta neuropathologica communications. - : BioMed Central (BMC). - 2051-5960. ; 9:1 Tidskriftsartikel (refereegranskat)abstract Pituitary neuroendocrine tumors (PitNETs) are common, generally benign tumors with complex clinical characteristics related to hormone hypersecretion and/or growing sellar tumor mass. PitNETs can be classified based on the expression pattern of anterior pituitary hormones and three main transcriptions factors (TF), SF1, PIT1 and TPIT that regulate differentiation of adenohypophysial cells. Here, we have extended this classification based on the global transcriptomics landscape using tumor tissue from a well-defined cohort comprising 51 PitNETs of different clinical and histological types. The molecular profiles were compared with current classification schemes based on immunohistochemistry. Our results identified three main clusters of PitNETs that were aligned with the main pituitary TFs expression patterns. Our analyses enabled further identification of specific genes and expression patterns, including both known and unknown genes, that could distinguish the three different classes of PitNETs. We conclude that the current classification of PitNETs based on the expression of SF1, PIT1 and TPIT reflects three distinct subtypes of PitNETs with different underlying biology and partly independent from the expression of corresponding hormones. The transcriptomic analysis reveals several potentially targetable tumor-driving genes with previously unknown role in pituitary tumorigenesis.
31.	Abu Hamdeh, Sami, et al. (författare) Extended anatomical grading in diffuse axonal injury using MRI : Hemorrhagic lesions in the substantia nigra and mesencephalic tegmentum indicate poor long-term outcome 2017 Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 0897-7151 .- 1557-9042. ; 5:34, s. 341-352 Tidskriftsartikel (refereegranskat)abstract Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. In this study, three magnetic resonance imaging (MRI) sequences were used to quantify the anatomical distribution of lesions, to grade DAI according to the Adams grading system, and to evaluate the value of lesion localization in combination with clinical prognostic factors to improve outcome prediction. Thirty patients (mean 31.2 years ±14.3 standard deviation) with severe DAI (Glasgow Motor Score [GMS] <6) examined with MRI within 1 week post-injury were included. Diffusion-weighted (DW), T2*-weighted gradient echo and susceptibility-weighted (SWI) sequences were used. Extended Glasgow outcome score was assessed after 6 months. Number of DW lesions in the thalamus, basal ganglia, and internal capsule and number of SWI lesions in the mesencephalon correlated significantly with outcome in univariate analysis. Age, GMS at admission, GMS at discharge, and low proportion of good monitoring time with cerebral perfusion pressure <60 mm Hg correlated significantly with outcome in univariate analysis. Multivariate analysis revealed an independent relation with poor outcome for age (p = 0.005) and lesions in the mesencephalic region corresponding to substantia nigra and tegmentum on SWI (p = 0.008). We conclude that higher age and lesions in substantia nigra and mesencephalic tegmentum indicate poor long-term outcome in DAI. We propose an extended MRI classification system based on four stages (stage I—hemispheric lesions, stage II—corpus callosum lesions, stage III—brainstem lesions, and stage IV—substantia nigra or mesencephalic tegmentum lesions); all are subdivided by age (≥/<30 years).
32.	Abu Hamdeh, Sami, et al. (författare) Intracranial pressure elevations in diffuse axonal injury : association with nonhemorrhagic MR lesions in central mesencephalic structures 2019 Ingår i: Journal of Neurosurgery. - 0022-3085 .- 1933-0693. ; 131:2, s. 604-611 Tidskriftsartikel (refereegranskat)abstract Objective: Increased intracranial pressure (ICP) in patients with severe traumatic brain injury (TBI) with diffuse axonal injury (DAI) is not well defined. This study investigated the occurrence of increased ICP and whether clinical factors and lesion localization on MRI were associated with increased ICP in patients with DAI.Methods: Fifty-two patients with severe TBI (median age 24 years, range 9–61 years), who had undergone ICP monitoring and had DAI on MRI, as determined using T2-weighted gradient echo, susceptibility-weighted imaging, and diffusion-weighted imaging (DWI) sequences, were enrolled. The proportion of good monitoring time (GMT) with ICP > 20 mm Hg during the first 120 hours postinjury was calculated and associations with clinical and MRI-related factors were evaluated using linear regression.Results: All patients had episodes of ICP > 20 mm Hg. The mean proportion of GMT with ICP > 20 mm Hg was 5%, and 27% of the patients (14/52) spent more than 5% of GMT with ICP > 20 mm Hg. The Glasgow Coma Scale motor score at admission (p = 0.04) and lesions on DWI sequences in the substantia nigra and mesencephalic tegmentum (SN-T, p = 0.001) were associated with the proportion of GMT with ICP > 20 mm Hg. In multivariable linear regression, lesions on DWI sequences in SN-T (8% of GMT with ICP > 20 mm Hg, 95% CI 3%–13%, p = 0.004) and young age (−0.2% of GMT with ICP > 20 mm Hg, 95% CI −0.07% to −0.3%, p = 0.002) were associated with increased ICP.Conclusions: Increased ICP occurs in approximately one-third of patients with severe TBI who have DAI. Age and lesions on DWI sequences in the central mesencephalon (i.e., SN-T) are associated with elevated ICP. These findings suggest that MR lesion localization may aid prediction of increased ICP in patients with DAI.Abbreviations: ADC = apparent diffusion coefficient; CPP = cerebral perfusion pressure; DAI = diffuse axonal injury; DWI = diffusion-weighted imaging; EVD = external ventricular drain; GCS = Glasgow Coma Scale; GMT = good monitoring time; GOSE = Glasgow Outcome Scale–Extended; ICC = intraclass correlation coefficient; ICP = intracranial pressure; MAP = mean arterial blood pressure; NICU = neurointensive care unit; SN-T = substantia nigra and mesencephalic tegmentum; SWI = susceptibility-weighted imaging; TBI = traumatic brain injury; T2GRE = T2*-weighted gradient echo.
33.	Abu Hamdeh, Sami, et al. (författare) Intracranial pressure elevations in diffuse axonal injury are associated with non-hemorrhagic MR lesions in central mesencephalic structures Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract Objective: Increased intracranial pressure (ICP) in severe traumatic brain injury (TBI) patients with diffuse axonal injury (DAI) is not well defined. This study investigated the occurrence of increased ICP and whether clinical factors and lesion localization on MRI were associated with increased ICP in DAI patients.Methods: Fifty-two severe TBI patients (median 24, range 9-61 years), with ICP-monitoring and DAI on MRI, using T2*-weighted gradient echo, susceptibility-weighted and diffusion-weighted (DW) sequences, were enrolled. Proportion of good monitoring time (GMT) with ICP>20 mmHg during the first 120 hours post-injury was calculated and associations with clinical and MRI-related factors were evaluated using linear regression. Results: All patients had episodes of ICP>20 mmHg. The mean proportion of GMT with ICP>20 mmHg was 5% and 27% of the patients (14/52) had more than 5% of GMT with ICP>20 mmHg. Glasgow Coma Scale motor score at admission (P=0.04) and lesions on DW images in the substantia nigra and mesencephalic tegmentum (SN-T, P=0.001) were associated with the proportion of GMT with ICP>20 mmHg. In multivariate linear regression, lesions on DW images in SN-T (8% of GMT with ICP>20 mmHg, 95% CI 3–13%, P=0.004) and young age (-0.2% of GMT with ICP>20 mmHg, 95% CI -0.07–-0.3%, P=0.0008) were associated with increased ICP. Conclusions: Increased ICP occurs in ~1/3 of severe TBI patients with DAI. Age and lesions on DW images in the central mesencephalon (SN-T) associate with elevated ICP. These findings suggest that MR lesion localization may aid prediction of increased ICP in DAI patients.
34.	Abu Hamdeh, Sami, et al. (författare) MRI analysis of diffuse axonal injury - Hemorrhagic lesions in the mesencephalon idicate poor long-term outcome 2016 Ingår i: MRI analysis of diffuse axonal injury - Hemorrhagic lesions in the mesencephalon idicate poor long-term outcome. - : Springer. Konferensbidrag (refereegranskat)abstract Purpose: Clinical outcome after traumatic diffuse axonal injury (DAI) is difficult to predict. Three MRI techniques were compared in demonstrating acute brain lesions. Relationship of the anatomical distribution of the lesions in combination with clinical prognostic factors to outcome after 6 months was evaluated. Methods and Materials: Thirty patients, aged 16-60 years (mean 31.2 years) with severe DAI (Glasgow Motor Score = GMS < 6) were examined with MRI at 1.5T within one week after the injury. A diffusion-weighted (DW) sequence (SE-EPI, b value 1000 s/mm2), a T2-weighted gradient echo (T2GRE) sequence and a susceptibility-weighted (SWI) sequence were evaluated by two independent reviewers with short and long neuroradiological experiences. Clinical outcome was assessed with Extended Glasgow Outcome Score (GOSE) after ≥ 6 months.Results: Interreviewer agreement for DAI classification was very good (ҡ 0.82 – 0.91) with all three sequences. SWI visualized more lesions than the T2*GRE or DW sequence. In univariate analysis, number of DW lesions in the deep gray matter area including the internal capsules, number of SWI lesions in the mesencephalon, age, and GMS at admission and discharge correlated significantly with poor outcome. Multivariate analysis only revealed an independent relation with poor outcome for age (p = 0.011) and lesions in the mesencephalic region including crura cerebri, substantia nigra and tegmentum on SWI (p = 0.032).Conclusion: SWI is the most sensitive technique to visualize lesions in DAI. Age over 30 years and hemorrhagic mesencephalic lesions anterior to the tectum are indicators of poor long-term outcome in DAI.
35.	Achterberg, A., et al. (författare) Five years of searches for point sources of astrophysical neutrinos with the AMANDA-II neutrino telescope 2007 Ingår i: Physical Review D. Particles, fields, gravitation, and cosmology. - 1550-7998. ; 75:10, s. 102001- Tidskriftsartikel (refereegranskat)abstract We report the results of a five-year survey of the northern sky to search for point sources of high energy neutrinos. The search was performed on the data collected with the AMANDA-II neutrino telescope in the years 2000 to 2004, with a live time of 1001 days. The sample of selected events consists of 4282 upward going muon tracks with high reconstruction quality and an energy larger than about 100 GeV. We found no indication of point sources of neutrinos and set 90% confidence level flux upper limits for an all-sky search and also for a catalog of 32 selected sources. For the all-sky search, our average (over declination and right ascension) experimentally observed upper limit Phi0=((E/(1 TeV)))gamma·((d Phi)/dE) to a point source flux of muon and tau neutrino (detected as muons arising from taus) is Phinu[sub mu] + [overline nu ][sub mu]0+Phinu[sub tau] + [overline nu ][sub tau]0=11.1× 10-11 TeV-1 cm-2 s-1, in the energy range between 1.6 TeV and 2.5 PeV for a flavor ratio Phinu[sub mu] + [overline nu ][sub mu]0/Phinu[sub tau] + [overline nu ][sub tau]0=1 and assuming a spectral index gamma=2. It should be noticed that this is the first time we set upper limits to the flux of muon and tau neutrinos. In previous papers we provided muon neutrino upper limits only neglecting the sensitivity to a signal from tau neutrinos, which improves the limits by 10% to 16%. The value of the average upper limit presented in this work corresponds to twice the limit on the muon neutrino flux Phinu[sub mu] + [overline nu ][sub mu]0=5.5×10-11 TeV-1 cm-2 s-1. A stacking analysis for preselected active galactic nuclei and a search based on the angular separation of the events were also performed. We report the most stringent flux upper limits to date, including the results of a detailed assessment of systematic uncertainties.
36.	Adlitzer, Helena, et al. (författare) Palliativ vård i livets slutskede : Nationellt vårdprogram 2016 Rapport (övrigt vetenskapligt/konstnärligt)
37.	Ahnström, Ulrika, et al. (författare) Detection and direction-finding of spread spectrum signals using correlation and narrowband interference rejection 2003 Ingår i: Nordic Matlab Conference 2003. Konferensbidrag (refereegranskat)abstract An algorithm for correlation-based detection of direct sequence spread spectrum signals with direction finding, including direction-filtering and narrow-band interference rejection, is implemented and evaluated in MATLAB. An analog noise-free signal is generated and sampled by a test-bed system. Numerical simulations are run based on data corrupted by mutually uncorrelated white Gaussian noise sequences, and also with recorded noise from two spatially separated HF radio receivers. The simulations and measurements show promising results for detection and direction-finding of covert wideband signals in low SNR and in presence of narrowband interferers. Direction filtering is shown to improve the results.
38.	Ali, Zafar, et al. (författare) Homozygous GRID2 missense mutation predicts a shift in the D-serine binding domain of GluD2 in a case with generalized brain atrophy and unusual clinical features 2017 Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 18:1 Tidskriftsartikel (refereegranskat)abstract BACKGROUND: Spinocerebellar ataxias comprise a large and heterogeneous group of disorders that may present with isolated ataxia, or ataxia in combination with other neurologic or non-neurologic symptoms. Monoallelic or biallelic GRID2 mutations were recently reported in rare cases with cerebellar syndrome and variable degree of ataxia, ocular symptoms, hypotonia and developmental delay.CASE PRESENTATION: We report on a consanguineous family with autosomal recessive childhood onset of slowly progressive cerebellar ataxia and delayed psychomotor development in three siblings. MRI of an adult and affected family member revealed slightly widened cerebral and cerebellar sulci, suggesting generalized brain atrophy, and mild cerebellar atrophy. Using whole exome sequencing we identified a novel homozygous missense variant [c.2128C > T, p.(Arg710Trp)] in GRID2 that segregates with the disease. The missense variant is located in a conserved region encoding the extracellular serine-binding domain of the GluD2 protein and predicts a change in conformation of the protein.CONCLUSION: The widespread supratentorial brain abnormalities, absence of oculomotor symptoms, increased peripheral muscle tone and the novel missense mutation add to the clinical and genetic variability in GRID2 associated cerebellar syndrome. The neuroradiological findings in our family indicate a generalized neurodegenerative process to be taken into account in other families segregating complex clinical features and GRID2 mutations.
39.	Almby, Kristina E., et al. (författare) Effects of Gastric Bypass Surgery on the Brain : Simultaneous Assessment of Glucose Uptake, Blood Flow, Neural Activity, and Cognitive Function During Normo- and Hypoglycemia 2021 Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 70:6, s. 1265-1277 Tidskriftsartikel (refereegranskat)abstract While Roux-en-Y gastric bypass (RYGB) surgery in obese individuals typically improves glycemic control and prevents diabetes, it also frequently causes asymptomatic hypoglycemia. Previous work showed attenuated counterregulatory responses following RYGB. The underlying mechanisms as well as the clinical consequences are unclear. In this study, 11 subjects without diabetes with severe obesity were investigated pre- and post-RYGB during hyperinsulinemic normo-hypoglycemic clamps. Assessments were made of hormones, cognitive function, cerebral blood flow by arterial spin labeling, brain glucose metabolism by F-18-fluorodeoxyglucose (FDG) positron emission tomography, and activation of brain networks by functional MRI. Post- versus presurgery, we found a general increase of cerebral blood flow but a decrease of total brain FDG uptake during normoglycemia. During hypoglycemia, there was a marked increase in total brain FDG uptake, and this was similar for post- and presurgery, whereas hypothalamic FDG uptake was reduced during hypoglycemia. During hypoglycemia, attenuated responses of counterregulatory hormones and improvements in cognitive function were seen postsurgery. In early hypoglycemia, there was increased activation post- versus presurgery of neural networks in brain regions implicated in glucose regulation, such as the thalamus and hypothalamus. The results suggest adaptive responses of the brain that contribute to lowering of glycemia following RYGB, and the underlying mechanisms should be further elucidated.
40.	Almqvist Terán, Nicolas, et al. (författare) In Reply to the Letter to the Editor Regarding "Posterior Fossa Volume and Dimensions : Relation to Pathophysiology and Surgical Outcomes in Classical Trigeminal Neuralgia" 2023 Ingår i: World Neurosurgery. - : Elsevier. - 1878-8750 .- 1878-8769. ; 180 Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
41.	Almqvist Téran, Nicolas, et al. (författare) Posterior Fossa Volume and Dimensions : Relation to Pathophysiology and Surgical Outcomes in Classic Trigeminal Neuralgia 2023 Ingår i: World Neurosurgery. - : Elsevier. - 1878-8750 .- 1878-8769. ; 179, s. e397-e403 Tidskriftsartikel (refereegranskat)abstract OBJECTIVE: A small posterior fossa (PF) has been hypothesized to explain the increased incidence of trigeminal neuralgia (TN) in females and could make microvascular decompression (MVD) more challenging. The aim of this study was to investigate the association between the PF volume and dimensions in relation to biological sex, type of neurovascular conflict (NVC), and outcome after MVD in classic TN.METHODS: In this observational study, 84 patients with TN operated on with MVD with a preoperative head computed tomography(CT) scan were included. Eighty-two adults without TN who had undergone head CT for other reasons were included as controls. PF volume and dimensions (x-axis, y-axis, and z-axis) were evaluated on the CT scans. For the patients with TN, Barrow Neurological Institute (BNI) grade was evaluated 6 months after MVD.RESULTS: There was no difference in PF volume or dimensions between the patients with TN and controls. Women showed a smaller volume and narrower (x-axis) PF than men, but these differences did not manifest when comparing patients with TN and controls within each sex. Patients with an NVC involving the superior cerebellar artery had a narrower (x-axis) and shorter (y-axis) PF than did patients with an NVC resulting from other arteries. PF volume or dimensions were not associated with BNI grade after MVD.CONCLUSIONS: PF anatomy was related to the NVC type but did not differ between patients with TN and controls and was not related to the surgical outcome after MVD.
42.	Amini, Hashem (författare) Fetal Anomalies : Surveillance and Diagnostic Accuracy of Ultrasound and Magnetic Resonance Imaging 2010 Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract The aims were to investigate the accuracy of ultrasound in diagnosis of structural fetal anomalies with special focus on false positive findings (I), to evaluate the additional value of second trimester fetal MRI on pregnancy management (II-III) and to estimate the ascertainment in the Swedish Birth Defects Registry and incidence of spina bifida and cleft lip/palate (IV). Retrospectively, 328 fetal autopsies were identified where pregnancies were terminated due to ultrasonographically diagnosed fetal anomalies. In 175 (53.4 %) cases ultrasound and fetal autopsy were identical, in 124 (37.8 %) ultrasound was almost correct, in 23 (7.0 %) ultrasound diagnoses could not be verified, but fetal autopsy showed other anomalies with at least the same prognostic value and in six (1.8 %) ultrasound diagnosis could not be verified and autopsy showed no or less severe anomalies (I). Prospectively, 29 pregnancies with CNS- (II) and 63 with non-CNS-anomalies (III) were included. In the CNS study MRI provided no additional information in 18 fetuses (62 %), additional information without changing the management in 8 (28 %) and additional information altering the pregnancy management in 3 (10%). In the non-CNS study the corresponding figures were 43 (68 %), 17 (27 %) and three (5 %), respectively. MRI in the second trimester might be a clinically valuable adjunct to ultrasound for the evaluation of CNS anomalies, especially when the ultrasound is inconclusive due to maternal obesity (II) and in non-CNS anomalies in cases of diaphragmatic hernia or oligohydramnios (III). In newborns, the ascertainments of birth defects are relatively high and assessable, but in pregnancy terminations they are lower or unknown. The incidence of newborns with spina bifida has decreased because of an increased rate of pregnancy terminations (>60%). There is room for improvement concerning the reporting of anomalies from terminated pregnancies (IV).
43.	Amini, Hashem, et al. (författare) Second trimester fetal magnetic resonance imaging improves diagnosis of non-central nervous system anomalies 2011 Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 90:4, s. 380-389 Tidskriftsartikel (refereegranskat)abstract Objectives. To evaluate the additional information of second trimester magnetic resonance imaging (MRI) compared to ultrasound in fetuses with identified or suspected non-CNS anomalies and to study the clinical impact of the MRI information on pregnancy management. Design. Prospective study during 2003-2007. The fetal MRI examination was planned to be performed within three days after the ultrasound. Setting. Uppsala University hospital. Material and methods. Sixty-three women, where the second trimester ultrasound identified or raised suspicion of fetal anomalies were included. Ultrasound was compared to MRI in relation to the final diagnosis, which was based on the assessment of all available data including post-partum clinical follow-up and autopsy results. Main outcome measures. Evaluation of the additional information gained from MRI and the consequences it had on pregnancy management. Results. The mean interval between ultrasound and MRI was 2.6 days (range 0-15). In 42 (67%) cases MRI was performed within three days. All MRI examinations were assessable. In 43 (68%) fetuses MRI provided no additional information, in 17 (27%) MRI added information without changing the management and in three (5%) MRI provided additional information which changed the management. All these three cases had oligohydramnios. In all six cases of diaphragmatic hernia MRI provided additional information. Conclusions. Fetal MRI of non-CNS anomalies in the second trimester seems to be a valuable adjunct to ultrasound diagnosis of non-CNS anomalies, especially in cases of oligohydramnios and diaphragmatic hernia.
44.	Amini, Hashem, 1960-, et al. (författare) The Clinical Impact of Fetal Magnetic Resonance Imaging on Management of CNS Anomalies in the Second Trimester of Pregnancy 2010 Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 89:12, s. 1571-1581 Tidskriftsartikel (refereegranskat)abstract Objectives: To evaluate the additional information of second trimester magnetic resonance imaging (MRI) compared to ultrasound in fetuses with identified or suspected CNS anomalies and to study the clinical impact of the information on pregnancy management. Design: Prospective study during 2004-2007. The fetal MRI examination was planned to be performed within three days after the ultrasound. Setting: Uppsala University hospital. Subjects: Twenty-nine pregnant women where second trimester ultrasound identified or suspected fetal CNS anomalies. Main outcome measures: Evaluation of the additional information gained from MRI and the consequence it had on pregnancy management. Results: The mean interval between ultrasound and MRI was 1.6 days (range 0 –7). In 18 fetuses (62 %) MRI verified the ultrasound diagnosis but provided no additional information, while in 8 (28 %) MRI gave additional information without changing the management. In 3 (10 %), MRI provided additional information that changed the management of the pregnancy. Two of these women were obese. Conclusions: Fetal MRI in the second trimester might be a clinically valuable adjunct to ultrasound for the evaluation of CNS anomalies, especially when ultrasound is inconclusive due to maternal obesity.
45.	Amini, Hashem, 1960-, et al. (författare) The Clinical Impact of Fetal Magnetic Resonance Imaging on Management of Non-CNS Anomalies in the Second Trimester of Pregnancy Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Objectives: To evaluate the additional information of second trimester MRI compared to ultrasound in fetuses with identified or suspected non-CNS anomalies and to study the clinical impact of the MRI information on pregnancy management. Methods: Sixty-three women were included, where the second trimester ultrasound identified or raised suspicion of fetal anomalies. Ultrasound was compared to MRI in relation to the final diagnosis, fetal autopsy if performed or postnatal diagnosis. The additional information of MRI and effect on pregnancy management was estimated in consensus. Results: The mean gestational age at the last ultrasound before MRI was 18+1 weeks (range 13+0-21+5). The mean interval between ultrasound and MRI was 2.6 days (range 0-15). In 42 (67 %) cases MRI was performed within three days. All MRI examinations were assessable. In 43 (68 %) fetuses MRI provided no additional information, in 17 (27 %) MRI added information without changing the management and in three (5 %) MRI provided additional information which changed the management. These three cases had all oligohydramnios. In all six cases of diaphragmatic hernia MRI provided additional information. Conclusions: Fetal MRI of non-CNS anomalies is feasible in the second trimester and gives additional information in nearly a third of cases. It may provide a clinically valuable adjunct to ultrasound especially in cases of diaphragmatic hernia or oligohydramnios.
46.	Andersson, Jacob, et al. (författare) Differences in head circumference and neuroimaging characteristics : what can they tell about the aetiologies of infant subdural haematoma? Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Background Acute (ASDH) and chronic subdural haematoma (CSDH) in infants have been regarded as highly specific for abuse. A recent study showed different risk factors for ASDH and CSDH, indicating that CSDH in many cases was related to external hydrocephalus. Purpose To investigate to what extent external hydrocephalus may explain findings and symptoms interpreted as signs of abusive head trauma. Material and methods Eighty-five infants with ASDH (n=16) and CSDH (n=69) were reviewed with regard to cranio-cortical- (CCW), sino-cortical- (SCW), frontal interhemispheric-(IHW), subarachnoid space width (SSW) and head circumference (HC). In infants with unilateral SDH, the correlation between the contralateral SSW and the ipsilateral CCW and SDH width was calculated. A correlation would imply that the CSDH replaces an already existing extracerebral space.Results Infants with CSDH had significantly higher CCW, SCW, IHW and SSW than infants with ASDH (p < 0.05). The ipsilateral CCW (R = 0.92, p < 0.001) and SDH width (R = 0.81, p < 0.01) were correlated to the contralateral SSW. Increased HC was more prevalent in Infants with CSDH (71%) than in infants with ASDH (14%) (p < 0.01). Forty-two infants, all with CSDH, had at least one of CCW, SCW or IHW ≥ 95th percentile. Twenty infants, all with CSDH, had CCW, SCW and IHW > 5 mm and increased HC. Conclusion A significant proportion of infants with CSDH may have external hydrocephalus as an underlying cause and that parts of the widened subarachnoid space in some infants is replaced by a CSDH.
47.	Andersson, Jacob, et al. (författare) Different vulnerability profiles in acute compared to chronic subdural haematoma amongst infants with suspected abusive head trauma Annan publikation (övrigt vetenskapligt/konstnärligt)abstract Background: In a register study based on ICD 10 coding, there was a similar vulnerability profile (male sex, preterm and small for gestational age) in infants diagnosed with non-traumatic subdural haematoma (SDH) and infants having SDH with abuse diagnosis. However, ICD-10 does not separate between acute (ASDH) and chronic subdural haematoma (CSDH). Purpose: To determine the vulnerability profile in infants having CSDH and ASDH, respectively. Material and methods: A descriptive review of infants with SDH/hygroma examined by the Swedish National Board of Forensic Medicine between 1994 and 2018. Included cases (n=85) were analysed with regard to possible vulnerability factors. Results: Type of subdural fluid could be determined in 85 of 96 cases. Sixteen infants had ASDH and 69 CSDH. Infants with ASDH had the peak incidence during the first month of life, 56% were male, 6% were premature, 13% were twins and 44% died. In infants with CSDH, the peak incidence occurred during the third month of life, 69% were male, 34% were premature, 12% were twins and 4% died. Conclusion: CSDH, but not ASDH, is associated with factors suggesting non-traumatic pathogenesis, for which reason CSDH and ASDH should be analysed separately to extend the knowledge regarding the aetiology of SDH during infancy.
48.	Andersson, Jacob, et al. (författare) External Hydrocephalus as a Cause of Infant Subdural Hematoma : Epidemiological and Radiological Investigations of Infants Suspected of Being Abused 2022 Ingår i: Pediatric Neurology. - : Elsevier. - 0887-8994 .- 1873-5150. ; 126, s. 26-34 Tidskriftsartikel (refereegranskat)abstract Background: Acute subdural hematoma (ASDH) and chronic subdural hematoma (CSDH) in infants have been regarded as highly specific for abuse. Other causes of CSDH have not been investigated in a large population.Purpose: The purpose of this study was to investigate to what extent external hydrocephalus is present in infants with ASDH and CSDH undergoing evaluation for abuse.Material and methods: Eighty-five infants suspected of being abused, with ASDH (n = 16) or CSDH (n = 69), were reviewed regarding age, risk factor profiles, craniocortical width (CCW), sinocortical width (SCW), frontal interhemispheric width (IHW), subarachnoid space width (SSW), and head circumference (HC). In infants with unilateral subdural hematoma (SDH), correlations between contralateral SSW and ipsilateral CCW and SDH width were investigated.Results: Infants with CSDH had significantly lower mortality, were more often premature and male, and had significantly higher CCW, SCW, IHW, and SSW than infants with ASDH (P < 0.05). Ipsilateral CCW (R = 0.92, P < 0.001) and SDH width (R = 0.81, P < 0.01) correlated with contralateral SSW. Increased HC was more prevalent in infants with CSDH (71%) than in infants with ASDH (14%) (P < 0.01). Forty-two infants, all with CSDH, had at least one of CCW, SCW, or IHW ≥95th percentile. Twenty infants, all with CSDH, had CCW, SCW, and IHW >5 mm, in addition to increased HC.Conclusion: A substantial proportion of infants with CSDH who had been suspected of being abused had findings suggesting external hydrocephalus.
49.	Aronsson, Thomas, 1963-, et al. (författare) Regional income growth and net migration in Sweden, 1970-1995 2001 Ingår i: Regional studies. - : Taylor & Francis Group. - 0034-3404 .- 1360-0591. ; 35:9, s. 823-830 Tidskriftsartikel (refereegranskat)abstract This paper concerns the regional growth pattern in Sweden, and the purpose is to analyse what factors determine the growth rate of average income and the net migration at the regional level. We find a negative relationship between the initial level of regional average income and subsequent income growth. The results also imply that the initial endowment of human capital (measured as the percentage of the population with higher education) has a positive effect on the subsequent net migration. Other determinants of regional income growth and population movements are 'fixed endowments' (related to geography and climate) and regional labour market characteristics.
50.	Aronsson, Thomas, 1963-, et al. (författare) The Impact of regional public expenditures on the local decision to spend 2000 Ingår i: Regional Science and Urban Economics. - 0166-0462 .- 1879-2308. ; 30:2, s. 185-202 Tidskriftsartikel (refereegranskat)abstract This paper studies the hypothesis that local (municipal) expenditures in part can be explained by the expenditures of the regional (county) government. To accomplish this task, we derive and estimate a model of local public (municipal) spending that is defined conditional on the level of regional public expenditures. The empirical analysis is based on panel data from the Swedish local public sector for the time period 1981–1986. Among the results, we find that the hypothesis that regional expenditures are weakly separable from local expenditures can be rejected. However, we cannot reject the hypothesis that the regional expenditures are weakly exogenous in the local expenditure equation.

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