| 1. |
- Bergfeldt, Ulla, et al.
(författare)
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Cortical activation changes and improved motor function in stroke patients after focal spasticity therapy- an interventional study applying repeated fMRI.
- 2015
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Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Impaired dominant hand function in stroke patients is a common clinical problem. Functional improvement after focal spasticity therapy is well documented but knowledge about central correlates is sparse. Brain activity was therefore followed during therapy with repeated functional magnetic resonance imaging (fMRI). The purpose was to analyse motor function and central nervous system (CNS) correlates in response to a standardized motor task in stroke patients after a comprehensive focal spasticity therapy.
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| 2. |
- Blomberg, Jonas, et al.
(författare)
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Antibodies to Human Herpesviruses in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients
- 2019
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Ingår i: Frontiers in Immunology. - : FRONTIERS MEDIA SA. - 1664-3224. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Myalgic encephalomyelitis, also referred to as chronic fatigue syndrome (ME/CFS) is a debilitating disease characterized by myalgia and a sometimes severe limitation of physical activity and cognition. It is exacerbated by physical and mental activity. Its cause is unknown, but frequently starts with an infection. The eliciting infection (commonly infectious mononucleosis or an upper respiratory infection) can be more or less well diagnosed. Among the human herpesviruses (HHV-1 -8), HHV-4 (Epstein-Barr virus; EBV), HHV-6 (including HHV-6A and HHV-6B), and HHV-7, have been implicated in the pathogenesis of ME/CFS. It was therefore logical to search for serological evidence of past herpesvirus infection/reactivation in several cohorts of ME/CFS patients (all diagnosed using the Canada criteria). Control samples were from Swedish blood donors. We used whole purified virus, recombinant proteins, and synthetic peptides as antigens in a suspension multiplex immunoassay (SMIA) for immunoglobulin G (IgG). The study on herpesviral peptides based on antigenicity with human sera yielded novel epitope information. Overall, IgG anti-herpes-viral reactivities of ME/CFS patients and controls did not show significant differences. However, the high precision and internally controlled format allowed us to observe minor relative differences between antibody reactivities of some herpesviral antigens in ME/CFS versus controls. ME/CFS samples reacted somewhat differently from controls with whole virus HHV-1 antigens and recombinant EBV EBNA6 and EA antigens. We conclude that ME/CFS samples had similar levels of IgG reactivity as blood donor samples with HHV-1-7 antigens. The subtle serological differences should not be over-interpreted, but they may indicate that the immune system of some ME/CFS patients interact with the ubiquitous herpesviruses in a way different from that of healthy controls.
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| 3. |
- Bynke, Annie, et al.
(författare)
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Autoantibodies to beta-adrenergic and muscarinic cholinergic receptors in Myalgic Encephalomyelitis (ME) patients – A validation study in plasma and cerebrospinal fluid from two Swedish cohorts
- 2020
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Ingår i: Brain, Behavior, and Immunity - Health. - : Elsevier. - 2666-3546. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Myalgic encephalomyelitis (ME) also known as ME/CFS (Chronic Fatigue Syndrome) or ME/SEID (Systemic Exertion Intolerance Disorder), is a disabling and often long-lasting disease that can drastically impair quality of life and physical/social functioning of the patients. Underlying pathological mechanisms are to a large extent unknown, but the presence of autoantibodies, cytokine pattern deviations and the presentation of cognitive and autonomic nervous system related symptoms provide evidence for ME being an immunological disorder with elements of autoimmunity. Increased levels of autoantibodies binding to adrenergic and muscarinic receptors in ME-patients have been reported. It is hypothesized that these autoantibodies have pathological significance and contribute to the ME-specific symptoms, however, these observations need to be validated.This study was designed to investigate potential differences in adrenergic and muscarinic receptor autoantibody levels in plasma and cerebrospinal fluid (CSF) samples between ME patients and gender and age-matched healthy controls, and to correlate the autoantibody levels to disease severity.We collected bodyfluids and health-related questionnaires from two Swedish ME cohorts, plasma and CSF from one of the cohorts (n = 24), only plasma from the second cohort (n = 24) together with plasma samples (n = 24) and CSF (n = 6) from healthy controls.All samples were analysed for IgG autoantibodies directed against Alpha- (α1, α2) and Beta- (β1-3) adrenergic receptors and Muscarinic (M) 1–5 acetylcholine receptors using an ELISA technique. The questionnaires were used as measures of disease severity.Significant increases in autoantibody levels in ME patients compared to controls were found for M3 and M4 -receptors in both cohorts and β1, β2, M3 and M4-receptors in one cohort. No significant correlations were found between autoantibody levels and disease severity. No significant levels of autoantibodies were detected in the CSF samples. These findings support previous findings that there exists a general pattern of increased antibody levels to adrenergic and muscarinic receptors within the ME patient group. However, the role of increased adrenergic and muscarinic receptor autoantibodies in the pathogenesis of ME is still uncertain and further research is needed to evaluate the clinical significance of these findings.
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| 4. |
- Forsberg, Anton, et al.
(författare)
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Low background and high contrast PET imaging of amyloid-β with [11C]AZD2995 and [11C]AZD2184 in Alzheimer's disease patients
- 2013
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer-Verlag New York. - 1619-7070 .- 1619-7089. ; 40:4, s. 580-593
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The aim of this study was to evaluate AZD2995 side by side with AZD2184 as novel PET radioligands for imaging of amyloid-β in Alzheimer's disease (AD).METHODS: In vitro binding of tritium-labelled AZD2995 and AZD2184 was studied and compared with that of the established amyloid-β PET radioligand PIB. Subsequently, a first-in-human in vivo PET study was performed using [(11)C]AZD2995 and [(11)C]AZD2184 in three healthy control subjects and seven AD patients.RESULTS: AZD2995, AZD2184 and PIB were found to share the same binding site to amyloid-β. [(3)H]AZD2995 had the highest signal-to-background ratio in brain tissue from patients with AD as well as in transgenic mice. However, [(11)C]AZD2184 had superior imaging properties in PET, as shown by larger effect sizes comparing binding potential values in cortical regions of AD patients and healthy controls. Nevertheless, probably due to a lower amount of nonspecific binding, the group separation of the distribution volume ratio values of [(11)C]AZD2995 was greater in areas with lower amyloid-β load, e.g. the hippocampus.CONCLUSION: Both AZD2995 and AZD2184 detect amyloid-β with high affinity and specificity and also display a lower degree of nonspecific binding than that reported for PIB. Overall [(11)C]AZD2184 seems to be an amyloid-β radioligand with higher uptake and better group separation when compared to [(11)C]AZD2995. However, the very low nonspecific binding of [(11)C]AZD2995 makes this radioligand potentially interesting as a tool to study minute levels of amyloid-β. This sensitivity may be important in investigating, for example, early prodromal stages of AD or in the longitudinal study of a disease modifying therapy.
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| 5. |
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| 6. |
- Huang, Chaorui, et al.
(författare)
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Voxel- and VOI-based analysis of SPECT CBF in relation to clinical and psychological heterogeneity of mild cognitive impairment.
- 2003
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Ingår i: NeuroImage. - 1053-8119. ; 19:3, s. 1137-1144
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Tidskriftsartikel (refereegranskat)abstract
- This study aimed to explore the heterogeneity of mild cognitive impairment (MCI) and detect differences in regional cerebral blood flow (rCBF) and cognitive function between progressive mild cognitive impairment (PMCI) and stable mild cognitive impairment (SMCI) in order to identify specific changes useful for early diagnosis of dementia. SPECT was performed in 82 MCI subjects and 20 controls using Tc-99m hexamethylpropyleneamine oxime. Cognitive functions were tested in five domains which included episodic memory, semantic memory, visuospatial function, attention, and general cognitive function. After the initial examination, MCI subjects were clinically followed for an average of 2 years. Twenty-eight subjects progressed to dementia and were defined as PMCI at baseline and 54 subjects remained stable and were defined as SMCI at baseline. The baseline rCBF and cognitive function of PMCI, SMCI, and controls were compared. PMCI had decreased relative rCBF in the parietal lobes and increased relative rCBF in prefrontal cortex compared to SMCI and controls at baseline. The cognitive function of PMCI was more severely impaired compared to SMCI with respect to episodic memory and visuospatial and general cognitive function. Both SPECT and neuropsychological tests had moderate discriminant function between PMCI and SMCI at baseline with the area under the receiver operating characteristic (ROC) curve at 75–77%. The combination of these two methods improved the diagnostic accuracy with the area under the ROC curve at 82–84%. Semantic memory and attention were negatively correlated with left prefrontal relative rCBF among the study population. The results show that the clinical heterogeneity of MCI is reflected in different patterns of psychological and CBF changes. Combined SPECT investigation and neuropsychological testing might predict the future development of dementia in patients with MCI.
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| 7. |
- Julin, Per
(författare)
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MRI and SPECT neuroimaging in mild cognitive impairment and Alzheimer's disease
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis concerns measurements of regional brain volumes using Magnetic Resonance Imaging (MRI) and of regional cerebral blood flow (CBF) using Single Photon Emission Computed Tomography (SPECT) in patients investigated for suspected dementia. In the first study (I), visually rated MRI-, SPECT and EEG-pathology were compared between patients with Alzheimer's disease (AD) and patients with Frontal Lobe Dementia (FLD). Patients with AD had predominantly parietal lobe atrophy and blood flow reduction whereas patients with FLD had a more pronounced frontal lobe hypoperfusion without a corresponding atrophy. A measure of the difference between frontal and parietal hypoperfusion gave the best separation between AD and FLD patients. This indicates that hypoperfusion preceeds atrophy in FLD and consequently that SPECT imaging of CBF is a better method than MRI to support the clinical separation of AD and FLD. In the second study (II), a method for quantitative measurements of regional brain volumes from 3-dimensionally reconstructed MRI was implemented and evaluated. The accuracy of the method was +1.5% and the intra-operator error in repeated scanning was less than 5% for all tissues and regions studied. In the third study (III), we evaluated a methodology for MRI-guided SPECT measurements of CBF based on computer software that supported manual alignment of MRI and SPECT image sets. The accuracy and reliability of the method allowed the detection of both atrophy and hypoperfusion of the medial temporal lobes in patients with AD. In study IV, the previously evaluated methods were used to investigate brain atrophy and hypoperfusion in patients with familial AD caused by the Swedish APP mutation. The results showed that a reduction of lateral temporal CBF, preceeding atrophy, was related to the early stage of AD in this family. In study V, automatic co-registration of MRI and SPECT brain image sets using the uniformity index method was found to have high accuracy. Changes of medial temporal and temporo-parietal regions were evaluated in patients with mild cognitive impairment (MCI) and AD. AD patients had atrophy and CBF reduction of both regions, although the most significant change was found in the CBF of the temporo-parietal region. MCI patients showed a significant reduction only of CBF in the temporo-parietal region. To summarize, these studies show that combined analysis of MRI and SPECT based on automatic co-registration has high accuracy and reliability. The results also indicate that reduction of CBF preceeds atrophy, both in FLD and AD. In FLD, changes are largly confined to the frontal lobes and in AD the earliest changes seem to be in the temporo-parietal and not in the medial temporal regions. Future longitudinal studies have the possibility to examine if this method for combined MRI and SPECT imaging of the brain can have predictive value regarding progression of cognitive decline and development of AD in patients with MCI.
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| 8. |
- Möller, Marika C, et al.
(författare)
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Fatigue and Cognitive Fatigability in Mild Traumatic Brain Injury are Correlated with Altered Neural Activity during Vigilance Test Performance.
- 2017
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Ingår i: Frontiers in Neurology. - : Frontiers Media SA. - 1664-2295. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Fatigue is the most frequently reported persistent symptom following a mild traumatic brain injury (mTBI), but the explanations for the persisting fatigue symptoms in mTBI remain controversial. In this study, we investigated the change of cerebral blood flow during the performance of a psychomotor vigilance task (PVT) by using pseudo-continuous arterial spin labeling (PCASL) MRI technique to better understand the relationship between fatigability and brain activity in mTBI.MATERIAL AND METHODS: Ten patients (mean age: 37.5 ± 11.2 years) with persistent complaints of fatigue after mTBI and 10 healthy controls (mean age 36.9 ± 11.0 years) were studied. Both groups completed a 20-min long PVT inside a clinical MRI scanner during simultaneous measurements of reaction time and regional cerebral blood flow (rCBF) with PCASL technique. Cognitive fatigability and neural activity during PVT were analyzed by dividing the performance and rCBF data into quintiles in addition to the assessment of self-rated fatigue before and after the PVT.RESULTS: The patients showed significant fatigability during the PVT while the controls had a stable performance. The variability in performance was also significantly higher among the patients, indicating monitoring difficulty. A three-way ANOVA, modeling of the rCBF data demonstrated that there was a significant interaction effect between the subject group and performance time during PVT in a mainly frontal/thalamic network, indicating that the pattern of rCBF change for the mTBI patients differed significantly from that of healthy controls. In the mTBI patients, fatigability at the end of the PVT was related to increased rCBF in the right middle frontal gyrus, while self-rated fatigue was related to increased rCBF in left medial frontal and anterior cingulate gyri and decreases of rCBF in a frontal/thalamic network during this period.DISCUSSION: This study demonstrates that PCASL is a useful technique to investigate neural correlates of fatigability and fatigue in mTBI patients. Patients suffering from fatigue after mTBI used different brain networks compared to healthy controls during a vigilance task and in mTBI, there was a distinction between rCBF changes related to fatigability vs. perceived fatigue. Whether networks for fatigability and self-rated fatigue are different, needs to be investigated in future studies.
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| 9. |
- Nordin, Love Engstrom, et al.
(författare)
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Post mTBI fatigue is associated with abnormal brain functional connectivity
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- This study set out to investigate the behavioral correlates of changes in resting-state functional connectivity before and after performing a 20 minute continuous psychomotor vigilance task (PVT) for patients with chronic post-concussion syndrome. Ten patients in chronic phase after mild traumatic brain injury (mTBI) with persisting symptoms of fatigue and ten matched healthy controls participated in the study. We assessed the participants' fatigue levels and conducted resting-state fMRI before and after a sustained PVT. We evaluated the changes in brain functional connectivity indices in relation to the subject's fatigue behavior using a quantitative data-driven analysis approach. We found that the PVT invoked significant mental fatigue and specific functional connectivity changes in mTBI patients. Furthermore, we found a significant linear correlation between self-reported fatigue and functional connectivity in the thalamus and middle frontal cortex. Our findings indicate that resting-state fMRI measurements may be a useful indicator of performance potential and a marker of fatigue level in the neural attentional system.
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| 10. |
- Nyberg, Svante, et al.
(författare)
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Detection of amyloid in Alzheimer's disease with positron emission tomography using [11C]AZD2184
- 2009
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer. - 1619-7070 .- 1619-7089. ; 36:11, s. 1859-1863
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Current positron emission tomography (PET) radioligands for detection of Aβ amyloid in Alzheimer's disease (AD) are not ideal for quantification. To improve the signal to noise ratio we have developed the radioligand [11C]AZD2184 and report here the first clinical evaluation.METHODS: Eight AD patients and four younger control subjects underwent 93-min PET measurements with [11C]AZD2184. A ratio approach using the cerebellum as reference region was applied to determine binding parameters.RESULTS: Brain uptake of [11C]AZD2184 peaked within 1 min at 3-4% of injected radioactivity. AD patients had high radioactivity in cortical regions while controls had uniformly low radioactivity uptake. Specific binding peaked within 30 min at which time standardized uptake value ratios (SUVR) ranged between 1.19 and 2.57.CONCLUSION: [11C]AZD2184 is a promising radioligand for detailed mapping of Aβ amyloid depositions in Alzheimer's disease, due to low non-specific binding, high signal to background ratio and reversible binding as evident from early peak equilibrium.
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