Per Julin - Academia.edu (original) (raw)
Papers by Per Julin
Neurology, Nov 16, 2011
We compared the ability of arterial spin labeling (ASL), an MRI method that measures cerebral blo... more We compared the ability of arterial spin labeling (ASL), an MRI method that measures cerebral blood flow (CBF), to that of FDG-PET in distinguishing patients with Alzheimer disease (AD) from healthy, age-matched controls. Fifteen patients with AD (mean age 72 Ϯ 6 years, Mini-Mental State Examination score [MMSE] 20 Ϯ 6) and 19 age-matched controls (mean age 68 Ϯ 6 years, MMSE 29 Ϯ 1) underwent structural MRI. Participants were injected with 5 mCi of FDG during pseudocontinuous ASL scan, which was followed by PET scanning. Statistical parametric mapping and regions of interest (ROI) analysis were used to compare the ability of the 2 modalities in distinguishing patients from controls. Similarity between the 2 modalities was further assessed with linear correlation maps of CBF and metabolism to neuropsychological test scores. Results: Good agreement between hypoperfusion and hypometabolism patterns was observed, with overlap primarily in bilateral angular gyri and posterior cingulate. ROI results showed similar scales of functional deficit between patients and controls in both modalities. Both ASL and FDG-PET were able to distinguish neural networks associated with different neuropsychological tests with good overlap between modalities. Our voxel-wise results indicated that ASL-MRI provides largely overlapping information with FDG-PET. ROI analysis demonstrated that both modalities detected similar degrees of functional deficits in affected areas. Given its ease of acquisition and noninvasiveness, ASL-MRI may be an appealing alternative for AD studies. Neurology ® 2011;77:1977-1985 GLOSSARY A ϭ amyloid-; AD ϭ Alzheimer disease; ADC ϭ Alzheimer's Disease Center; ASL ϭ arterial spin labeling; AUC ϭ area under the curve; BNT ϭ Boston Naming Test; CBF ϭ cerebral blood flow; CDR ϭ Clinical Dementia Rating; DSS ϭ Digit Symbol Substitution; FDG-PET ϭ 18 fluoro-deoxyglucose PET; FWHM ϭ full-width half maximum; GM ϭ gray matter; MCI ϭ mild cognitive impairment; MMSE ϭ Mini-Mental State Examination; MNI ϭ Montreal Neurological Institute; MPRAGE ϭ magnetization-prepared rapid gradient echo; MR ϭ magnetic resonance; NACC ϭ National Alzheimer's Coordinating Center; PSF ϭ point spread functions; PVE ϭ partial volume effects; rCBF ϭ relative cerebral blood flow; rCMRGlc ϭ relative CMRGlc; ROC ϭ receiver operating characteristic; ROI ϭ region of interest; SUV ϭ standardized uptake value; TE ϭ echo time; TIV ϭ total intracranial volume; TR ϭ repetition time; UDS ϭ Uniform Data Set; VBM ϭ voxel-based morphometry; WM ϭ white matter; wsCV ϭ within-subject coefficient of variation.
Dementia and Geriatric Cognitive Disorders, 1996
To examine diagnostic and prognostic potential of quantitative electroencephalography (qEEG) anal... more To examine diagnostic and prognostic potential of quantitative electroencephalography (qEEG) analyzed by the statistical pattern recognition (SPR) method in patients with cognitive impairment. We compared the differential diagnostic ability of SPR to visual EEG analysis. Correlation between SPR findings and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers were evaluated. Methods: It is a multicenter cohort study involving 129 patients, (mild cognitive impairment [MCI], AD, and healthy controls). Standardized EEG was performed at baseline. Patients were continuously clinically evaluated. Results: Receiver Operating Characteristic curves showed a low discriminative ability of SPR and no ability to predict clinical progression in patients with MCI. Moderate correlation between SPR analysis and CSF AD biomarkers was found. Conclusion: The diagnostic and prognostic abilities of qEEG were low. The SPR method was superior to the visual EEG analysis. The qEEG method correlates well to CSF AD biomarkers, suggesting association with pathology in AD.
IC-P-107
Alzheimer's & Dementia, 2006
Frontiers in Immunology, 2019
Scientific Reports, Feb 16, 2016
This study set out to investigate the behavioral correlates of changes in resting-state functiona... more 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.
Alzheimers & Dementia, Oct 24, 2011
BACKGROUND-The utility flourodeoxyglucose PET (FDG-PET) imaging in Alzheimer's Disease (AD) diagn... more BACKGROUND-The utility flourodeoxyglucose PET (FDG-PET) imaging in Alzheimer's Disease (AD) diagnosis is well established. Recently, measurement of cerebral blood flow using arterial spin labeling MRI (ASL-MRI) has shown diagnostic potential in AD, though it has never been directly compared to FDG-PET. METHODS-We employed a novel imaging protocol to obtain FDG-PET and ASL-MRI images concurrently in 17 AD patients and 19 age-matched controls. Paired FDG-PET and ASL-MRI images from 19 controls and 15 AD patients were included for qualitative analysis, while paired images 18 controls and 13 AD patients were suitable for quantitative analyses. RESULTS-The combined imaging protocol was well tolerated. Both modalities revealed very similar regional abnormalities in AD, as well as comparable sensitivity and specificity for the detection of AD following visual review by two expert readers. Interobserver agreement was better for FDG-PET (kappa 0.75, SE 0.12) than ASL-MRI (kappa 0.51, SE 0.15), intermodality agreement was moderate to strong (kappa 0.45-0.61), and readers were more confident of FDG-PET reads. Simple quantitative analysis of global cerebral FDG uptake (FDG-PET) or whole brain cerebral blood flow (ASL-MRI) showed excellent diagnostic accuracy for both modalities, with area under ROC curves of 0.90 for FDG-PET (95% CI 0.79-0.99) and 0.91 for ASL-MRI (95% CI 0.80-1.00). CONCLUSIONS-Our results demonstrate that FDG-PET and ASL-MRI identify similar regional abnormalities and have comparable diagnostic accuracy in a small population of AD patients, and support the further study of ASL-MRI in dementia diagnosis.
Myalgic encephalomyelitis, ME, previously also known as chronic fatigue syndrome (CFS) is a heter... more Myalgic encephalomyelitis, ME, previously also known as chronic fatigue syndrome (CFS) is a heterogeneous, debilitating syndrome of unknown etiology responsible for long-lasting disability in millions of patients worldwide. The most well-known symptom of ME is post-exertional malaise, but many patients also experience autonomic dysregulation, cranial nerve dysfunction and signs of immune system activation. Many patients also report a sudden onset of disease following an infection. The brainstem is a suspected focal point in ME pathogenesis and patients with structural impairment to the brainstem often show ME-like symptoms. The brainstem is also where the vagus nerve originates, a critical neuro-immune interface and mediator of the inflammatory reflex which regulate systemic inflammation. Here we report the results of a randomized, placebo-controlled trial using intranasal mechanical stimulation (INMEST) targeting the vagus nuclei, and higher centers in the brain of ME-patients and ...
Frontiers in Neurology, Sep 21, 2017
Discussion: This study demonstrates that PCASL is a useful technique to investigate neural correl... more 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.
EEG in successful aging
Electroencephalography and Clinical Neurophysiology, 1995
IC-P-107
Alzheimers Dement, 2006
BMC 22002
Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment
Myalgisk encefalomyelit (ME) eller post-viralt trotthetssyndrom, aven kallat Chronic Fatigue Synd... more Myalgisk encefalomyelit (ME) eller post-viralt trotthetssyndrom, aven kallat Chronic Fatigue Syndrome (CFS), ar en sjukdom med okand orsak. ME/CFS karaktariseras av uttalad mental och fysisk utrottbarhet, kognitiv paverkan, somnstorning, symtom fran autonoma nervsystemet, smarta och influensaliknande symtom som forvarras av anstrangning. ME/CFS kan ge upphov till langvariga och stora funktionsnedsattningar. Diagnosen har tidigare varit omstridd da forstaelse for patofysiologin och ocksa biomarkorer for diagnostik har saknats. Internationellt finns nu dock en framvaxande konsensus inom det medicinskt vetenskapliga omradet kring sjukdomens realitet och allvarighetsgrad och det pagar nu flera initiativ bland annat fran National Institutes of Health (NIH) i USA for att undersoka biologiska mekanismer vid ME/CFS. Flera medicinska behandlingsstudier ar ocksa pagaende. Redan nu kan dock sjukvarden gora stor skillnad for ME/CFS-patienterna genom att erbjuda seriosa utredningar, korrekt diag...
Inflammation, långvarig trötthet och värk – uppdatering av kunskapsläget
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
Brain, Behavior, & Immunity - Health, 2020
Myalgic encephalomyelitis (ME) also known as ME/CFS (Chronic Fatigue Syndrome) or ME/SEID (System... more 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.
Frontiers in Immunology, 2019
Frontiers in Neurology, 2017
Discussion: This study demonstrates that PCASL is a useful technique to investigate neural correl... more 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.
MRI and SPECT neuroimaging in mild cognitive impairment and Alzheimer's disease
Scientific Reports, 2016
This study set out to investigate the behavioral correlates of changes in resting-state functiona... more 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.
Fibromyalgia Syndrome or Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Factors Influencing Work Disability in Women
Handbooks in Health, Work, and Disability, 2016
Fibromyalgia is a complex chronic pain syndrome characterized by widespread muscle pain, tenderne... more Fibromyalgia is a complex chronic pain syndrome characterized by widespread muscle pain, tenderness, and fatigue. Women with fibromyalgia report that symptoms limiting their work ability include pain, tiredness, muscle weakness, and memory and concentration difficulties. Work tasks perceived as “difficult” for women with fibromyalgia are repetitive movements, static muscle work as when holding, standing, or sitting in the same positions for fairly long periods, heavy work, working above shoulder level, power gripping, and frequent carrying and lifting. These difficulties reflect the fibromyalgia pathophysiology. To be able to remain at work, women with fibromyalgia need workplaces, which are flexible and adjustable. They need to be able to change and alternate positions and tasks, take short breaks, and, in many cases, reduce working hours. With appropriate support and adaptation, most are able to continue working to some extent.
NeuroImage, 2013
Introduction: Perfusion measurement by arterial spin labeling (ASL) techniques is well suited for... more Introduction: Perfusion measurement by arterial spin labeling (ASL) techniques is well suited for pharmaceutical magnetic resonance imaging (phMRI) studies to investigate how drugs change the cerebral perfusion status and further, neuronal activity. Materials and method: Twelve healthy normal male volunteers participated in the study which was based on a double blinded design. Six subjects were randomly selected to receive a single oral dose of 20 mg D-amphetamine and six were given placebo. Perfusion measurements by pseudo-continuous ASL (pCASL) technique were repeatedly performed at 10 different time points with a 3T clinical MRI scanner during a 10 hour period after dose together with physiologic data and blood sample collections. The dynamic changes in cerebral perfusion in response to the plasma concentration variations of D-amphetamine were analyzed at voxel-level and for regions of interest. Results: Compared to the placebo group a 20% reduction in cerebral blood flow (CBF) was observed in gray matter for the subjects that received D-amphetamine. The most significant reduction of regional CBF (rCBF) was detected in the basal ganglia, frontal region and insular cortex using voxel based analysis. A relation between D-amphetamine exposure and CBF response was found using PK/PD modeling, which predicted on average a 15% decrease of the CBF in gray matter at a plasma concentration of 30 ng/ml. Conclusion: In this study we have demonstrated that repeated perfusion measurements by pCASL technique was sufficiently robust to differentiate the neurological response between the groups that received D-amphetamine and placebo. Quantitative and repetitive CBF measurements can be used for PK/PD modeling of CNS drug responses in humans.
Neurology, Nov 16, 2011
We compared the ability of arterial spin labeling (ASL), an MRI method that measures cerebral blo... more We compared the ability of arterial spin labeling (ASL), an MRI method that measures cerebral blood flow (CBF), to that of FDG-PET in distinguishing patients with Alzheimer disease (AD) from healthy, age-matched controls. Fifteen patients with AD (mean age 72 Ϯ 6 years, Mini-Mental State Examination score [MMSE] 20 Ϯ 6) and 19 age-matched controls (mean age 68 Ϯ 6 years, MMSE 29 Ϯ 1) underwent structural MRI. Participants were injected with 5 mCi of FDG during pseudocontinuous ASL scan, which was followed by PET scanning. Statistical parametric mapping and regions of interest (ROI) analysis were used to compare the ability of the 2 modalities in distinguishing patients from controls. Similarity between the 2 modalities was further assessed with linear correlation maps of CBF and metabolism to neuropsychological test scores. Results: Good agreement between hypoperfusion and hypometabolism patterns was observed, with overlap primarily in bilateral angular gyri and posterior cingulate. ROI results showed similar scales of functional deficit between patients and controls in both modalities. Both ASL and FDG-PET were able to distinguish neural networks associated with different neuropsychological tests with good overlap between modalities. Our voxel-wise results indicated that ASL-MRI provides largely overlapping information with FDG-PET. ROI analysis demonstrated that both modalities detected similar degrees of functional deficits in affected areas. Given its ease of acquisition and noninvasiveness, ASL-MRI may be an appealing alternative for AD studies. Neurology ® 2011;77:1977-1985 GLOSSARY A ϭ amyloid-; AD ϭ Alzheimer disease; ADC ϭ Alzheimer's Disease Center; ASL ϭ arterial spin labeling; AUC ϭ area under the curve; BNT ϭ Boston Naming Test; CBF ϭ cerebral blood flow; CDR ϭ Clinical Dementia Rating; DSS ϭ Digit Symbol Substitution; FDG-PET ϭ 18 fluoro-deoxyglucose PET; FWHM ϭ full-width half maximum; GM ϭ gray matter; MCI ϭ mild cognitive impairment; MMSE ϭ Mini-Mental State Examination; MNI ϭ Montreal Neurological Institute; MPRAGE ϭ magnetization-prepared rapid gradient echo; MR ϭ magnetic resonance; NACC ϭ National Alzheimer's Coordinating Center; PSF ϭ point spread functions; PVE ϭ partial volume effects; rCBF ϭ relative cerebral blood flow; rCMRGlc ϭ relative CMRGlc; ROC ϭ receiver operating characteristic; ROI ϭ region of interest; SUV ϭ standardized uptake value; TE ϭ echo time; TIV ϭ total intracranial volume; TR ϭ repetition time; UDS ϭ Uniform Data Set; VBM ϭ voxel-based morphometry; WM ϭ white matter; wsCV ϭ within-subject coefficient of variation.
Dementia and Geriatric Cognitive Disorders, 1996
To examine diagnostic and prognostic potential of quantitative electroencephalography (qEEG) anal... more To examine diagnostic and prognostic potential of quantitative electroencephalography (qEEG) analyzed by the statistical pattern recognition (SPR) method in patients with cognitive impairment. We compared the differential diagnostic ability of SPR to visual EEG analysis. Correlation between SPR findings and cerebrospinal fluid (CSF) Alzheimer disease (AD) biomarkers were evaluated. Methods: It is a multicenter cohort study involving 129 patients, (mild cognitive impairment [MCI], AD, and healthy controls). Standardized EEG was performed at baseline. Patients were continuously clinically evaluated. Results: Receiver Operating Characteristic curves showed a low discriminative ability of SPR and no ability to predict clinical progression in patients with MCI. Moderate correlation between SPR analysis and CSF AD biomarkers was found. Conclusion: The diagnostic and prognostic abilities of qEEG were low. The SPR method was superior to the visual EEG analysis. The qEEG method correlates well to CSF AD biomarkers, suggesting association with pathology in AD.
IC-P-107
Alzheimer's & Dementia, 2006
Frontiers in Immunology, 2019
Scientific Reports, Feb 16, 2016
This study set out to investigate the behavioral correlates of changes in resting-state functiona... more 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.
Alzheimers & Dementia, Oct 24, 2011
BACKGROUND-The utility flourodeoxyglucose PET (FDG-PET) imaging in Alzheimer's Disease (AD) diagn... more BACKGROUND-The utility flourodeoxyglucose PET (FDG-PET) imaging in Alzheimer's Disease (AD) diagnosis is well established. Recently, measurement of cerebral blood flow using arterial spin labeling MRI (ASL-MRI) has shown diagnostic potential in AD, though it has never been directly compared to FDG-PET. METHODS-We employed a novel imaging protocol to obtain FDG-PET and ASL-MRI images concurrently in 17 AD patients and 19 age-matched controls. Paired FDG-PET and ASL-MRI images from 19 controls and 15 AD patients were included for qualitative analysis, while paired images 18 controls and 13 AD patients were suitable for quantitative analyses. RESULTS-The combined imaging protocol was well tolerated. Both modalities revealed very similar regional abnormalities in AD, as well as comparable sensitivity and specificity for the detection of AD following visual review by two expert readers. Interobserver agreement was better for FDG-PET (kappa 0.75, SE 0.12) than ASL-MRI (kappa 0.51, SE 0.15), intermodality agreement was moderate to strong (kappa 0.45-0.61), and readers were more confident of FDG-PET reads. Simple quantitative analysis of global cerebral FDG uptake (FDG-PET) or whole brain cerebral blood flow (ASL-MRI) showed excellent diagnostic accuracy for both modalities, with area under ROC curves of 0.90 for FDG-PET (95% CI 0.79-0.99) and 0.91 for ASL-MRI (95% CI 0.80-1.00). CONCLUSIONS-Our results demonstrate that FDG-PET and ASL-MRI identify similar regional abnormalities and have comparable diagnostic accuracy in a small population of AD patients, and support the further study of ASL-MRI in dementia diagnosis.
Myalgic encephalomyelitis, ME, previously also known as chronic fatigue syndrome (CFS) is a heter... more Myalgic encephalomyelitis, ME, previously also known as chronic fatigue syndrome (CFS) is a heterogeneous, debilitating syndrome of unknown etiology responsible for long-lasting disability in millions of patients worldwide. The most well-known symptom of ME is post-exertional malaise, but many patients also experience autonomic dysregulation, cranial nerve dysfunction and signs of immune system activation. Many patients also report a sudden onset of disease following an infection. The brainstem is a suspected focal point in ME pathogenesis and patients with structural impairment to the brainstem often show ME-like symptoms. The brainstem is also where the vagus nerve originates, a critical neuro-immune interface and mediator of the inflammatory reflex which regulate systemic inflammation. Here we report the results of a randomized, placebo-controlled trial using intranasal mechanical stimulation (INMEST) targeting the vagus nuclei, and higher centers in the brain of ME-patients and ...
Frontiers in Neurology, Sep 21, 2017
Discussion: This study demonstrates that PCASL is a useful technique to investigate neural correl... more 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.
EEG in successful aging
Electroencephalography and Clinical Neurophysiology, 1995
IC-P-107
Alzheimers Dement, 2006
BMC 22002
Cingulate cortex hypoperfusion predicts Alzheimer's disease in mild cognitive impairment
Myalgisk encefalomyelit (ME) eller post-viralt trotthetssyndrom, aven kallat Chronic Fatigue Synd... more Myalgisk encefalomyelit (ME) eller post-viralt trotthetssyndrom, aven kallat Chronic Fatigue Syndrome (CFS), ar en sjukdom med okand orsak. ME/CFS karaktariseras av uttalad mental och fysisk utrottbarhet, kognitiv paverkan, somnstorning, symtom fran autonoma nervsystemet, smarta och influensaliknande symtom som forvarras av anstrangning. ME/CFS kan ge upphov till langvariga och stora funktionsnedsattningar. Diagnosen har tidigare varit omstridd da forstaelse for patofysiologin och ocksa biomarkorer for diagnostik har saknats. Internationellt finns nu dock en framvaxande konsensus inom det medicinskt vetenskapliga omradet kring sjukdomens realitet och allvarighetsgrad och det pagar nu flera initiativ bland annat fran National Institutes of Health (NIH) i USA for att undersoka biologiska mekanismer vid ME/CFS. Flera medicinska behandlingsstudier ar ocksa pagaende. Redan nu kan dock sjukvarden gora stor skillnad for ME/CFS-patienterna genom att erbjuda seriosa utredningar, korrekt diag...
Inflammation, långvarig trötthet och värk – uppdatering av kunskapsläget
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
Brain, Behavior, & Immunity - Health, 2020
Myalgic encephalomyelitis (ME) also known as ME/CFS (Chronic Fatigue Syndrome) or ME/SEID (System... more 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.
Frontiers in Immunology, 2019
Frontiers in Neurology, 2017
Discussion: This study demonstrates that PCASL is a useful technique to investigate neural correl... more 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.
MRI and SPECT neuroimaging in mild cognitive impairment and Alzheimer's disease
Scientific Reports, 2016
This study set out to investigate the behavioral correlates of changes in resting-state functiona... more 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.
Fibromyalgia Syndrome or Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and Factors Influencing Work Disability in Women
Handbooks in Health, Work, and Disability, 2016
Fibromyalgia is a complex chronic pain syndrome characterized by widespread muscle pain, tenderne... more Fibromyalgia is a complex chronic pain syndrome characterized by widespread muscle pain, tenderness, and fatigue. Women with fibromyalgia report that symptoms limiting their work ability include pain, tiredness, muscle weakness, and memory and concentration difficulties. Work tasks perceived as “difficult” for women with fibromyalgia are repetitive movements, static muscle work as when holding, standing, or sitting in the same positions for fairly long periods, heavy work, working above shoulder level, power gripping, and frequent carrying and lifting. These difficulties reflect the fibromyalgia pathophysiology. To be able to remain at work, women with fibromyalgia need workplaces, which are flexible and adjustable. They need to be able to change and alternate positions and tasks, take short breaks, and, in many cases, reduce working hours. With appropriate support and adaptation, most are able to continue working to some extent.
NeuroImage, 2013
Introduction: Perfusion measurement by arterial spin labeling (ASL) techniques is well suited for... more Introduction: Perfusion measurement by arterial spin labeling (ASL) techniques is well suited for pharmaceutical magnetic resonance imaging (phMRI) studies to investigate how drugs change the cerebral perfusion status and further, neuronal activity. Materials and method: Twelve healthy normal male volunteers participated in the study which was based on a double blinded design. Six subjects were randomly selected to receive a single oral dose of 20 mg D-amphetamine and six were given placebo. Perfusion measurements by pseudo-continuous ASL (pCASL) technique were repeatedly performed at 10 different time points with a 3T clinical MRI scanner during a 10 hour period after dose together with physiologic data and blood sample collections. The dynamic changes in cerebral perfusion in response to the plasma concentration variations of D-amphetamine were analyzed at voxel-level and for regions of interest. Results: Compared to the placebo group a 20% reduction in cerebral blood flow (CBF) was observed in gray matter for the subjects that received D-amphetamine. The most significant reduction of regional CBF (rCBF) was detected in the basal ganglia, frontal region and insular cortex using voxel based analysis. A relation between D-amphetamine exposure and CBF response was found using PK/PD modeling, which predicted on average a 15% decrease of the CBF in gray matter at a plasma concentration of 30 ng/ml. Conclusion: In this study we have demonstrated that repeated perfusion measurements by pCASL technique was sufficiently robust to differentiate the neurological response between the groups that received D-amphetamine and placebo. Quantitative and repetitive CBF measurements can be used for PK/PD modeling of CNS drug responses in humans.