| 1. |
- Mishra, A, et al.
(författare)
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Diminishing benefits of urban living for children and adolescents' growth and development
- 2023
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 615:7954, s. 874-883
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Tidskriftsartikel (refereegranskat)abstract
- Optimal growth and development in childhood and adolescence is crucial for lifelong health and well-being1–6. Here we used data from 2,325 population-based studies, with measurements of height and weight from 71 million participants, to report the height and body-mass index (BMI) of children and adolescents aged 5–19 years on the basis of rural and urban place of residence in 200 countries and territories from 1990 to 2020. In 1990, children and adolescents residing in cities were taller than their rural counterparts in all but a few high-income countries. By 2020, the urban height advantage became smaller in most countries, and in many high-income western countries it reversed into a small urban-based disadvantage. The exception was for boys in most countries in sub-Saharan Africa and in some countries in Oceania, south Asia and the region of central Asia, Middle East and north Africa. In these countries, successive cohorts of boys from rural places either did not gain height or possibly became shorter, and hence fell further behind their urban peers. The difference between the age-standardized mean BMI of children in urban and rural areas was <1.1 kg m–2 in the vast majority of countries. Within this small range, BMI increased slightly more in cities than in rural areas, except in south Asia, sub-Saharan Africa and some countries in central and eastern Europe. Our results show that in much of the world, the growth and developmental advantages of living in cities have diminished in the twenty-first century, whereas in much of sub-Saharan Africa they have amplified.
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| 2. |
- Adli, Erik, et al.
(författare)
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Progress Of The Ess Proton Beam Imaging Systems
- 2022
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Ingår i: LINAC2022. - : ACoW Publishing. ; , s. 395-398
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Konferensbidrag (refereegranskat)abstract
- The ESS Target Proton Beam Imaging Systems has the objective to image the 5 MW ESS proton beam as it entersthe spallation target. The imaging systems has to operate in a harsh radiation environment, leading to a number of challenges : development of radiation hard photon sources, long and aperture-restricted optical paths and fast electronics required to provide rapid information in case of beam anomalies. This paper outlines how main challenges of the imaging systems have been addressed, and the status of deployment as ESS gets closer to beam.
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| 3. |
- Ahlqvist, Emma, et al.
(författare)
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Novel subgroups of adult-onset diabetes and their association with outcomes : a data-driven cluster analysis of six variables
- 2018
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Ingår i: The Lancet Diabetes and Endocrinology. - 2213-8587 .- 2213-8595. ; 6:5, s. 361-369
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundDiabetes is presently classified into two main forms, type 1 and type 2 diabetes, but type 2 diabetes in particular is highly heterogeneous. A refined classification could provide a powerful tool to individualise treatment regimens and identify individuals with increased risk of complications at diagnosis.MethodsWe did data-driven cluster analysis (k-means and hierarchical clustering) in patients with newly diagnosed diabetes (n=8980) from the Swedish All New Diabetics in Scania cohort. Clusters were based on six variables (glutamate decarboxylase antibodies, age at diagnosis, BMI, HbA1c, and homoeostatic model assessment 2 estimates of β-cell function and insulin resistance), and were related to prospective data from patient records on development of complications and prescription of medication. Replication was done in three independent cohorts: the Scania Diabetes Registry (n=1466), All New Diabetics in Uppsala (n=844), and Diabetes Registry Vaasa (n=3485). Cox regression and logistic regression were used to compare time to medication, time to reaching the treatment goal, and risk of diabetic complications and genetic associations.FindingsWe identified five replicable clusters of patients with diabetes, which had significantly different patient characteristics and risk of diabetic complications. In particular, individuals in cluster 3 (most resistant to insulin) had significantly higher risk of diabetic kidney disease than individuals in clusters 4 and 5, but had been prescribed similar diabetes treatment. Cluster 2 (insulin deficient) had the highest risk of retinopathy. In support of the clustering, genetic associations in the clusters differed from those seen in traditional type 2 diabetes.InterpretationWe stratified patients into five subgroups with differing disease progression and risk of diabetic complications. This new substratification might eventually help to tailor and target early treatment to patients who would benefit most, thereby representing a first step towards precision medicine in diabetes.
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| 4. |
- Andersson, Lars-Magnus, 1968, et al.
(författare)
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Normalisation of cerebrospinal fluid biomarkers parallels improvement of neurological symptoms following HAART in HIV dementia--case report.
- 2006
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Ingår i: BMC infectious diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Since the introduction of HAART the incidence of HIV dementia has declined and HAART seems to improve neurocognitive function in patients with HIV dementia. Currently, HIV dementia develops mainly in patients without effective treatment, though it has also been described in patients on HAART and milder HIV-associated neuropsychological impairment is still frequent among HIV-1 infected patients regardless of HAART. Elevated cerebrospinal fluid (CSF) levels of markers of neural injury and immune activation have been found in HIV dementia, but neither of those, nor CSF HIV-1 RNA levels have been proven useful as diagnostic or prognostic pseudomarkers in HIV dementia. CASE PRESENTATION: We report a case of HIV dementia (MSK stage 3) in a 57 year old antiretroviral naïve man who was introduced on zidovudine, lamivudine and ritonavir boosted indinavir, and followed with consecutive lumbar punctures before and after two and 15 months after initiation of HAART. Improvement of neurocognitive function was paralleled by normalisation of CSF neural markers (NFL, Tau and GFAP) levels and a decline in CSF and serum neopterin and CSF and plasma HIV-1 RNA levels. CONCLUSION: The value of these CSF markers as prognostic pseudomarkers of the effect of HAART on neurocognitive impairment in HIV dementia ought to be evaluated in longitudinal studies.
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| 5. |
- Bech, Sara, et al.
(författare)
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Amyloid-related biomarkers and axonal damage proteins in parkinsonian syndromes.
- 2012
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Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; 18:1, s. 69-72
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Tidskriftsartikel (refereegranskat)abstract
- Clinical differentiation between parkinsonian syndromes (PS) remains a challenge despite well-established clinical diagnostic criteria. Specific diagnostic biomarkers have yet to be identified, though in recent years, studies have been published on the aid of certain brain related proteins (BRP) in the diagnosing of PS. We investigated the levels of the light subunit of neurofilament triplet protein (NF-L), total tau and phosphorylated tau, amyloid-β(1-42), and the soluble α- and β-cleaved fragments of amyloid precursor proteins in a cohort of patients with various PS.
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| 6. |
- Blennow, Kaj, 1958, et al.
(författare)
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No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.
- 2011
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Ingår i: Acta neurologica Scandinavica. - : Hindawi Limited. - 1600-0404 .- 0001-6314. ; 123, s. 245-51
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Tidskriftsartikel (refereegranskat)abstract
- Blennow K, Jonsson M, Andreasen N, Rosengren L, Wallin A, Hellström PA, Zetterberg H. No neurochemical evidence of brain injury after blast overpressure by repeated explosions or firing heavy weapons.Acta Neurol Scand: DOI: 10.1111/j.1600-0404.2010.01408.x .(c) 2010 John Wiley & Sons A/S. Background - Psychiatric and neurological symptoms are common among soldiers exposed to blast without suffering a direct head injury. It is not known whether such symptoms are direct consequences of blast overpressure. Objective - To examine if repeated detonating explosions or firing if of heavy weapons is associated with neurochemical evidence of brain damage. Materials and methods - Three controlled experimental studies. In the first, army officers were exposed to repeated firing of a FH77B howitzer or a bazooka. Cerebrospinal fluid (CSF) was taken post-exposure to measure biomarkers for brain damage. In the second, officers were exposed for up to 150 blasts by firing a bazooka, and in the third to 100 charges of detonating explosives of 180 dB. Serial serum samples were taken after exposure. Results were compared with a control group consisting of 19 unexposed age-matched healthy volunteers. Results - The CSF biomarkers for neuronal/axonal damage (tau and neurofilament protein), glial cell injury (GFAP and S-100b), blood-brain barrier damage (CSF/serum albumin ratio) and hemorrhages (hemoglobin and bilirubin) and the serum GFAP and S-100b showed normal and stable levels in all exposed officers. Discussion - Repeated exposure to high-impact blast does not result in any neurochemical evidence of brain damage. These findings are of importance for soldiers regularly exposed to high-impact blast when firing artillery shells or other types of heavy weapons.
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| 7. |
- Constantinescu, Radu, 1966, et al.
(författare)
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Cerebrospinal fluid biomarkers in patients with neurological symptoms but without neurological diseases
- 2019
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elevated levels of the cerebrospinal fluid (CSF) neuronal injury markers (neurofilament light chain [NF-L] and total tau protein [t-tau]) and of the astroglial marker glial fibrillary acidic protein (GFAP) are found in etiologically different neurological disorders affecting the peripheral and the central nervous system. Aims: To explore the role of CSF biomarkers in the clinical management of patients admitted for alarming neurological symptoms, but in whom neurological disorders could be excluded. Methods: Study participants were patients seeking medical attention for neurological symptoms primarily considered to be caused by a neurological diagnosis and investigated according to clinical routine. Demographic, clinical, and CSF data were extracted retrospectively from medical records. Patients with a final neurological diagnosis were excluded. Results: Out of 990 patients, 900 with a neurological diagnosis were excluded leaving 90 patients without a final neurological diagnosis. Sixty-eight (75.6%) were females. Median (range) age at lumbar puncture was 34.7 (16.9-65.1)years. Age-adjusted CSF-NF-L, CSF-t-tau, and CSF-GFAP concentrations were normal in 89 (98.9%), 86 (95.6%), and 87 (96.7%) patients, respectively. Conclusion: In patients with significant neurological symptoms but in whom a neurological diagnosis could not be made, the CSF markers NF-L, t-tau, and GFAP did not indicate signs of neuronal or astroglial cell damage close to symptom onset. Consequently, increased levels of CSF markers are not expected in this patient group and, if present, should raise suspicion of underlying neurological disorders and motivate further investigations. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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| 8. |
- Constantinescu, Radu, 1966, et al.
(författare)
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Cerebrospinal fluid markers of neuronal and glial cell damage in patients with autoimmune neurologic syndromes with and without underlying malignancies.
- 2017
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Ingår i: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 306, s. 25-30
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune neurologic syndromes can be paraneoplastic (associated with malignancies and/or onconeural antibodies), or non-paraneoplastic. Their clinical presentation is often similar. As prognosis is related to malignancy treatment, better biomarkers are needed to identify patients with malignancy. We investigated cerebrospinal fluid (CSF) markers of neuronal (neurofilament light chain, NFL and total tau protein, T-tau) and glial (glial fibrillary acidic protein) damage. CSF-NFL and T-tau were increased in both paraneoplastic and non-paraneoplastic autoimmune syndromes. Patients with manifest malignancies were older, had less epilepsy, more focal central and peripheral neurological signs and symptoms, and worse long-term outcome, than those without malignancy. CSF-NFL-levels predicted long-term outcome but were not diagnostic for malignancy, after age adjustment.
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| 9. |
- Constantinescu, Radu, 1966, et al.
(författare)
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Cerebrospinal fluid markers of neuronal and glial cell damage to monitor disease activity and predict long-term outcome in patients with autoimmune encephalitis
- 2016
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Ingår i: European Journal of Neurology. - : Wiley. - 1351-5101. ; 23:4, s. 796-806
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Tidskriftsartikel (refereegranskat)abstract
- Background and purposeClinical symptoms and long-term outcome of autoimmune encephalitis are variable. Diagnosis requires multiple investigations, and treatment strategies must be individually tailored. Better biomarkers are needed for diagnosis, to monitor disease activity and to predict long-term outcome. The value of cerebrospinal fluid (CSF) markers of neuronal [neurofilament light chain protein (NFL), and total tau protein (T-tau)] and glial cell [glial fibrillary acidic protein (GFAP)] damage in patients with autoimmune encephalitis was investigated. MethodsDemographic, clinical, magnetic resonance imaging, CSF and antibody-related data of 25 patients hospitalized for autoimmune encephalitis and followed for 1 year were retrospectively collected. Correlations between these data and consecutive CSF levels of NFL, T-tau and GFAP were investigated. Disability, assessed by the modified Rankin scale, was used for evaluation of disease activity and long-term outcome. ResultsThe acute stage of autoimmune encephalitis was accompanied by high CSF levels of NFL and T-tau, whereas normal or significantly lower levels were observed after clinical improvement 1 year later. NFL and T-tau reacted in a similar way but at different speeds, with T-tau reacting faster. CSF levels of GFAP were initially moderately increased but did not change significantly later on. Final outcome (disability at 1 year) directly correlated with CSF-NFL and CSF-GFAP levels at all time-points and with CSF-T-tau at 3 1 months. This correlation remained significant after age adjustment for CSF-NFL and T-tau but not for GFAP. ConclusionIn autoimmune encephalitis, CSF levels of neuronal and glial cell damage markers appear to reflect disease activity and long-term disability.
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| 10. |
- Constantinescu, Radu, 1966, et al.
(författare)
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Cerebrospinal fluid neurofilament light and tau protein as mortality biomarkers in parkinsonism
- 2019
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 140:2, s. 147-156
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Tidskriftsartikel (refereegranskat)abstract
- - Background: Mortality is increased in parkinsonian disorders, moderately in Parkinson's disease (PD) but markedly in atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). Still, there are no reliable quantitative biomarkers for mortality. The cerebrospinal fluid (CSF) neurodegeneration biomarkers such as neurofilament light chain (NF-L), total tau (t-tau), and the tau pathology marker phosphorylated tau (p-tau) are related to mortality in other neurological disorders (eg, amyotrophic lateral sclerosis, Alzheimer's disease), but have not been investigated in this respect in parkinsonian disorders. Aims: To investigate the CSF biomarkers' (NF-L, t-tau, and p-tau) relationship to mortality in parkinsonian disorders. Methods: Demographic, mortality, and CSF data were collected from 68 PD and 83 APD patients. Survival analysis was conducted using Cox regression, with age at lumbar puncture, gender, diagnosis, and levels of CSF biomarkers as predictors. Results: NF-L in CSF was associated with increased mortality in synucleinopathies (PD, MSA; HR 3.698 [2.196-6.228, 95% confidence interval (CI)], P<0.001), in PSP (HR 2.767 [1.126-6.802 95% CI], P=0.027), and in the entire cohort (HR 1.661 [1.082-2.55, 95% CI], P=0.02). t-Tau in CSF was associated with increased mortality in PSP (HR 9.587 [1.143-80.418], P=0.037). p-Tau in CSF was associated with decreased mortality in synucleinopathies (HR 0.196 [0.041-0.929, 95% CI], P=0.040). Atypical parkinsonian disorders and tauopathies were associated with higher mortality (HR 8.798 [4.516-17.14, 95% CI] and HR 3.040 [1.904-4.854], respectively, P<0.001). Conclusion: NF-L and tau protein in CSF might be useful for mortality prognosis in patients with parkinsonian disorders and should be investigated in larger studies. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
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| 11. |
- Constantinescu, Radu, 1966, et al.
(författare)
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Cerebrospinal fluid protein markers in PD patients after DBS-STN surgery—A retrospective analysis of patients that underwent surgery between 1993 and 2001
- 2018
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Ingår i: Clinical neurology and neurosurgery. - : Elsevier BV. - 0303-8467. ; 174, s. 174-179
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Tidskriftsartikel (refereegranskat)abstract
- Objective Cerebrospinal fluid (CSF) markers of neurodegeneration [neurofilament light chain (NFL), total Tau (T-Tau)], tau pathology [phosphorylated tau (p-Tau)], glial cell damage or activation [glial fibrillary acidic protein (GFAP)], and brain amyloidosis [β-amyloid 1-42 (Aβ42)] are useful for diagnosis and prognosis in several neurodegenerative disorders. In this paper we investigate these markers and their relationship to key clinical milestones in patients with advanced Parkinson´s disease (PD) operated at our center with subthalamic nucleus deep brain stimulation (STN-DBS) for at least 15 years ago. Patients and methods Retrospective analysis of available cerebrospinal fluid and clinical data in PD-patients, 15 years or more after they underwent STN-DBS surgery. All PD-patients implanted with STN-DBS at Sahlgrenska University Hospital before January 1, 2001, were regularly assessed until January 10, 2018, or until death, or until lost to follow-up. Results Twenty three PD patients were operated with STN-DBS. Sixteen of these (six females and ten males) underwent at least one lumbar puncture (LP) immediately prior to or after STN-DBS. Their age at the latest available LP was 64 (55–75) years [median (range)], PD duration 20 (11–33) years, and Hoehn & Yahr (H&Y) stage 3 (2–4). Time between DBS operation and the last LP was 4.5 (0.3–10.8) years. Time from the last LP to the last follow up was 6 (0.1–18) years, and for the entire cohort 115 person-years. On January 10, 2018, four PD-patients (25%) were still alive. All preoperative CSF marker levels were normal. Between two days and six months after DBS, NFL and GFAP levels increased sharply but they normalized thereafter in most patients, and were normal up to almost 11 years after neurosurgery. Over time, all patients deteriorated slowly. At the last follow up, H&Y was 5 (3–5) and 12/16 were demented. There was no significant correlation between postoperative (> 6 months) CSF NFL, GFAP, T-Tau, p-Tau, β-amyloid levels and the presence of dementia, psychosis, inability to walk or need for nursing home at the time for LP, nor for presence of dementia at the last follow up or for death as of January 10, 2018. Conclusion CSF protein biomarkers remain normal despite long PD duration, severe disability, and chronic STN-DBS. They cannot be used for PD staging or prognostication but may indicate brain damage caused by other pathological factors.
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| 12. |
- Constantinescu, Radu, 1966, et al.
(författare)
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Proteomic profiling of cerebrospinal fluid in parkinsonian disorders.
- 2010
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Ingår i: Parkinsonism & related disorders. - : Elsevier BV. - 1873-5126 .- 1353-8020. ; :16, s. 545-49
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) and atypical parkinsonian disorders (APD), including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), are a group of neurodegenerative diseases sharing many similar signs and symptoms but distinguished by their particular clinical features, treatment response, prognosis and mortality. The differential diagnosis may be challenging, especially in early disease stages. Considering the importance of an accurate diagnosis both for clinical management and for research, new diagnostic tools are needed. In this study, we investigated 56 PD, 42 MSA, 39 PSP, 9 CBD patients, and 24 healthy controls. After screening the cerebrospinal fluid (CSF) proteome using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS), we identified 4 proteins (ubiquitin [mass-to-charge ratio (m/z) 8590], beta2-microglobulin [m/z 11730], and 2 secretogranin 1 [chromogranin B] fragments [m/z 7260 and m/z 6250]) that differentiated healthy controls and PD patients from patients with APD. However, they could not differentiate PD patients from controls. As none of these changes were APD subgroup-specific, they most likely reflect the intensity and/or extent of the neurodegenerative process in general.
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| 13. |
- Eriksson, Hanna, et al.
(författare)
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Acute symptomatic seizures and epilepsy after mechanical thrombectomy
- 2020
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Ingår i: Epilepsy and Behavior. - : Elsevier BV. - 1525-5050 .- 1525-5069. ; 104
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: The purpose of this study was to assess the incidence of acute symptomatic seizures and poststroke epilepsy (PSE) in a well-characterized cohort of patients treated with mechanical thrombectomy. In addition, we aimed to describe the dynamics of blood markers of brain injury in patients that developed PSE. Methods: Participants of the prospective AnStroke Trial of anesthesia method during mechanical thrombectomy were included and acute symptomatic seizures and PSE ascertained by medical records review. Blood markers neurofilament light (NFL), tau, glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B), and neuron-specific enolase (NSE) were assessed. Results: A total of 90 patients with acute anterior ischemic stroke were included. Median National Institutes of Health Stroke Scale (NIHSS) at admission to hospital was 18 (IQR 15–22). Recanalization was achieved in 90%. No patients had epilepsy prior to the ischemic stroke. Four patients (4.4%) had acute symptomatic seizures and four patients (4.4%) developed PSE during the follow-up time (to death or last medical records review) of 0–4.5 years (median follow-up 1070 days IQR 777–1306), resulting in a two-year estimated PSE risk of 5.3% (95%CI: 0.2–10.4%). Blood markers of brain injury (NFL, tau, GFAP, S100B, and NSE) were generally above the cohort median in patients that developed PSE. Conclusions: The incidence of PSE after mechanical thrombectomy was low in our cohort. All blood biomarkers displayed interesting sensitivity and specificity. However, the number of PSE cases was small and more studies are needed on risk factors for PSE after mechanical thrombectomy. The potential of blood markers of brain injury markers to contribute to assessment of PSE risk should be explored further. This article is part of the Special Issue "Seizures & Stroke".
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| 14. |
- Gavhed, Desiree, et al.
(författare)
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Biomarkers in the Cerebrospinal Fluid and Neurodegeneration in Langerhans Cell Histiocytosis
- 2009
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 53:7, s. 1264-1270
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Tidskriftsartikel (refereegranskat)abstract
- Background. Progressive neurodegeneration may result in potentially severe cognitive and motor dysfunctions as a complication of Langerhans cell histiocytosis (LCH), a suggested IL-17A-associated inflammatory condition. To detect this complication (CNS-LCH) early and to evaluate the potential efficacy of therapeutic interventions, biomarkers detecting and measuring ongoing neurodegeneration Would be valuable. We evaluated cerebrospinal fluid (CSF) biomarkers of ongoing neurodegeneration in CNS-LCH patients. Procedure. Nine patients with endocrine, neuromotor, cognitive or/and behavioral abnormalities as well as neuroradiological evidence of CNS-LCH were evaluated 4-12 years after LCH diagnosis for CSF levels of neurofilament protein light chain (NF-L), glial fibrillary acid protein (GFAp), and total tau protein (TAU). Two patients were analyzed longitudinally. One hundred ten children with newly diagnosed acute lymphoblastic leukemia (ALL) served as controls. Results. NF-L, TAU, and GFAp levels were elevated in four, six, and eight of nine patients studied, respectively. NF-L (P < 0.001) and GFAp (P < 0.001) were higher in patients than in controls (TAU not analyzed in controls). The patient with most severe clinical and neuroradiological CNS-LCH displayed the highest levels of NF-L and GFAp whereas three patients without signs of systemic disease had low TAU levels and normal/slightly elevated NF-L. NF-L tended to be higher at radiological progression of neurodegeneration than at Status quo (P = 0.07). Notably, we experienced frequent lumbar puncture complications in these patients. Conclusions. CSF levels of NF-L, TAU, and GFAp appear to be elevated in CNS-LCH. It would be valuable if these markers were validated in order to serve as markers for early CNS-LCH, to monitor disease progression and to evaluate various treatment attempts for CNS-LCH. Pediatr Blood Cancer 2009;53:1264-1270. (C) 2009 Wiley-Liss, Inc.
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| 15. |
- Gisslén, Magnus, 1962, et al.
(författare)
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Amyloid and tau cerebrospinal fluid biomarkers in HIV infection.
- 2009
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Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Because of the emerging intersections of HIV infection and Alzheimer's disease, we examined cerebrospinal fluid (CSF) biomarkers related of amyloid and tau metabolism in HIV-infected patients. METHODS: In this cross-sectional study we measured soluble amyloid precursor proteins alpha and beta (sAPPalpha and sAPPbeta), amyloid beta fragment 1-42 (Abeta1-42), and total and hyperphosphorylated tau (t-tau and p-tau) in CSF of 86 HIV-infected (HIV+) subjects, including 21 with AIDS dementia complex (ADC), 25 with central nervous system (CNS) opportunistic infections and 40 without neurological symptoms and signs. We also measured these CSF biomarkers in 64 uninfected (HIV-) subjects, including 21 with Alzheimer's disease, and both younger and older controls without neurological disease. RESULTS: CSF sAPPalpha and sAPPbeta concentrations were highly correlated and reduced in patients with ADC and opportunistic infections compared to the other groups. The opportunistic infection group but not the ADC patients had lower CSF Abeta1-42 in comparison to the other HIV+ subjects. CSF t-tau levels were high in some ADC patients, but did not differ significantly from the HIV+ neuroasymptomatic group, while CSF p-tau was not increased in any of the HIV+ groups. Together, CSF amyloid and tau markers segregated the ADC patients from both HIV+ and HIV- neuroasymptomatics and from Alzheimer's disease patients, but not from those with opportunistic infections. CONCLUSIONS: Parallel reductions of CSF sAPPalpha and sAPPbeta in ADC and CNS opportunistic infections suggest an effect of CNS immune activation or inflammation on neuronal amyloid synthesis or processing. Elevation of CSF t-tau in some ADC and CNS infection patients without concomitant increase in p-tau indicates neural injury without preferential accumulation of hyperphosphorylated tau as found in Alzheimer's disease. These biomarker changes define pathogenetic pathways to brain injury in ADC that differ from those of Alzheimer's disease.
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| 16. |
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| 17. |
- Gottfries, Johan, et al.
(författare)
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Proteomics for drug target discovery
- 2004
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Ingår i: Chemometrics and Intelligent Laboratory Systems. - : Elsevier B.V.. - 0169-7439. ; 73:1, s. 47-53
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Tidskriftsartikel (refereegranskat)abstract
- Proteomics, genomics and metabonomics have, during the last decade, provided researchers with huge amounts of data. The choice of transformation of such data into useful information is dependent on the study aims and objectives. In the present study, projection methods (i.e., Principal Components Analysis [PCA] and Partial List Squares-Discriminant Analysis [PLS-DA]) were used to overview results from two-dimensional (2D) protein gel separations. The aim was to unravel possibilities for target discovery options via an in-depth understanding of quantified alterations in tissue or body fluid sample protein levels related to diseases. Two examples will be included comprising (1) data measured in cerebrospinal fluid (CSF) samples from diagnosed dementia patients and healthy volunteers, and (2) data from liver samples of drug-treated animals (i.e., Rosigltazone and Wy14643). The examples reveal clear clustering, using the protein levels as input, coinciding with the clinical diagnoses in example 1 and by treatment group in example 2.
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| 18. |
- Gudmundsson, Pia, 1978, et al.
(författare)
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Is there a CSF biomarker profile related to depression in elderly women?
- 2010
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Ingår i: Psychiatry Research. - 0165-1781. ; 176:2-3, s. 174-178
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Tidskriftsartikel (refereegranskat)abstract
- In light of our previous observation of higher levels of cerebrospinal fluid (CSF) amyloid beta-42 (Aβ42) and CSF/serum albumin ratio in major depressive disorder (MDD), we analyzed two additional CSF biomarkers reflecting neurodegeneration—neurofilament protein light (NFL) and glial fibrillary acidic protein (GFAp)—in relationship to prevalent geriatric depression. Neuropsychiatric, physical, and lumbar puncture examinations, with DSM-III-R-based depression diagnoses and measurement of CSF levels of NFL and GFAp, were evaluated among a population-based sample of 78 elderly women (mean age, 73.9±3.2 years) without dementia for at least 10 years after CSF collection. Eleven (13.1%) women had MDD, and higher levels of NFL compared with women without depression. A multivariate model including age, NFL, Aβ42 and the CSF/serum albumin ratio showed that each biomarker was independently and positively associated with MDD, and that this biomarker profile explained more variation in the model compared with single or combined biomarkers. A CSF profile with higher levels of NFL, Aβ42, and CSF/serum albumin ratio may indicate neuropathological and vascular events in depression etiology. This contrasts with the well-characterized pattern of low Aβ42, higher CSF/serum albumin ratio, and higher NFL in Alzheimer's disease.
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| 19. |
- Gudmundsson, Pia, 1978, et al.
(författare)
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The relationship between cerebrospinal fluid biomarkers and depression in elderly women.
- 2007
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Ingår i: The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry. - 1064-7481. ; 15:10, s. 832-8
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Cerebrospinal fluid (CSF) biomarkers including the 42 amino-acid form of beta-amyloid (Abeta42), total tau protein (T-tau), and the CSF/serum albumin ratio are markers of brain pathology and metabolism. Abeta42 and T-tau are sometimes used to discriminate geriatric depression from mild forms of Alzheimer disease (AD) in clinical studies. However, studies focusing on the relationship between these CSF biomarkers and geriatric depression are lacking. METHODS: This was a cross-sectional study with a population-based sample of 84 nondemented elderly women in Sweden. Measurements included neuropsychiatric, physical, and lumbar puncture examinations, with Diagnostic and Statistical Manual of Mental Disorders, Third Revision-based depression diagnoses and measurement of CSF levels of Abeta42, T-tau, albumin, and serum albumin. RESULTS: Fourteen women (mean age: 72.6 years) had any depression (11 with major depressive disorder [MDD]). Compared to women without depression, women with MDD had higher levels of Abeta42 and the CSF/serum albumin ratio. The CSF/serum albumin ratio was also higher in women with any depression. No differences in T-tau were observed; however, T-tau increased with age. CONCLUSION: Higher levels of CSF Abeta42 were observed among elderly depressed women, in contrast to lower levels usually observed in AD, indicating potential neuropathological differences between the two disorders. Higher CSF/serum albumin ratios observed in depressed women point to potential vascular processes.
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| 20. |
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| 21. |
- Gustafson, Deborah, 1966, et al.
(författare)
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Cerebrospinal fluid beta-amyloid 1-42 concentration may predict cognitive decline in older women.
- 2007
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 1468-330X .- 0022-3050. ; 78:5, s. 461-4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Low levels of cerebrospinal fluid (CSF) beta-amyloid 1-42 (Abeta42) and high total tau (T-tau) are diagnostic for manifest Alzheimer's disease. It is not known, however, whether these biomarkers may be risk indicators for cognitive decline in otherwise healthy older people. METHODS: The longitudinal relationship between CSF markers, Abeta42 and T-tau, measured in 1992, and change in Mini-Mental State Examination (deltaMMSE) score between 1992 and 2002 were investigated in 55 women (aged 70-84 years, mean (SD) MMSE score = 28.3 (1.5)), who were participants in the Prospective Population Study of Women in Gothenburg, Sweden. These women did not have dementia when they experienced lumbar puncture in 1992-3. RESULTS: Over the 8-year follow-up period, deltaMMSE (range = +3 to -21 points) was correlated with Abeta42 (Spearman's r = 0.40, p = 0.002), such that lower levels of Abeta42 were related to greater decline. This was also observed after excluding 4 women who developed dementia between 1992 and 2002 (Spearman's r = 0.34, p = 0.019). A multivariate logistic regression model predicting a decline of > or = 5 points on the MMSE (observed in six women), or a risk of developing dementia over the 8-year follow-up period (observed in four women), including age, education, Abeta42 and T-tau as covariates, showed that Abeta42 was the sole predictor of significant cognitive decline or dementia (OR per 100 pg/ml Abeta42 = 2.24, 95% CI 1.19 to 4.22, p = 0.013). CONCLUSIONS: Low levels of CSF Abeta42 may predict cognitive decline among older women without dementia.
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| 22. |
- Gustafson, Deborah, 1966, et al.
(författare)
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Mid-life adiposity factors relate to blood-brain barrier integrity in late life.
- 2007
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Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 262:6, s. 643-50
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We explored the relationship between adiposity factors measured during mid-life and blood-brain barrier (BBB) integrity measured via the cerebrospinal fluid/serum (CSF/S) albumin ratio in late life. Adiposity factors included body mass index and blood levels of sex hormone binding globulin (SHBG) and leptin. Design. Retrospective analyses over 24 years within a longitudinal study. SETTING: Population-based sample. Subjects. Eighty-one women. MAIN OUTCOME MEASURES: CSF/S albumin ratio. RESULTS: The CSF/S albumin ratio measured at age 70-84 years was higher amongst women who were overweight or obese (6.50 +/- 2.79 vs. 5.23 +/- 1.61, age-adjusted P = 0.012), and was inversely correlated with SHBG (age-adjusted r = -0.321, P < 0.005) at age 46-60 years. In stepwise regression models, SHBG predicted the CSF/S albumin ratio (beta = -0.017, R2 = 0.107, P = 0.007). The best model (R2 = 0.187) predicting CSF/S albumin ratio included SHBG, age group (age 46 years versus >46), overweight or obesity, and an age group by SHBG interaction. CONCLUSIONS: Lower levels of SHBG in mid-life were related to worse BBB integrity in women after 24 years in late life, even considering other adiposity factors. SHBG may be important for understanding sex hormone-mediated mechanisms in brain health or as an independent marker of adipose tissue, the largest endocrine organ.
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| 23. |
- Johansson, Lena, 1972, et al.
(författare)
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Midlife Stress in Relation to Late-Life Cerebrospinal Fluid Biomarkers of Alzheimer's Disease: A 25-Year Follow-Up Study
- 2018
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Ingår i: Dementia and geriatric cognitive disorders. - : S. Karger AG. - 1421-9824 .- 1420-8008. ; 46:1-2, s. 90-99
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background/Aims:</i></b> Psychological stress has previously been associated with higher risk of developing late-life dementia, especially Alzheimer’s disease (AD). This study tested whether longstanding midlife stress is related to cerebrospinal fluid (CSF) biomarkers of late-life AD, such as tau protein and amyloid beta (Aβ). <b><i>Methods:</i></b> The study included 79 nondemented females from the Prospective Population Study of Women in Gothenburg, Sweden, who responded to a standardized stress question at baseline (mean age 49 years) and underwent a lumbar puncture at follow-up 25 years later. Multiple linear regression models analyzed the relationships between midlife psychological stress and late-life CSF measures of total tau (t-tau), phosphorylated tau (p-tau), Aβ40, and Aβ42. <b><i>Results:</i></b> Longstanding stress in midlife was associated with higher levels of CSF t-tau (β = 0.64, <i>p</i> = 0.01) and Aβ40 (β = 0.60, <i>p</i> = 0.02) in late life. No associations were found between midlife stress and levels of p-tau or Aβ42. <b><i>Conclusion:</i></b> The findings suggest that longstanding stress stimulates unspecific neurodegenerative processes, but not the core processes of AD, at least not in the early phase of the disease. The association with higher concentration of CSF t-tau may reflect neural degeneration and the association with higher Aβ40 may be an early sign of Aβ overproduction or cerebrovascular processes in the brain.
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| 24. |
- Jonsson, Michael, 1955, et al.
(författare)
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Cerebrospinal fluid biomarkers of white matter lesions - cross-sectional results from the LADIS study.
- 2010
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Ingår i: European journal of neurology. - : Wiley. - 1468-1331 .- 1351-5101. ; 17:3, s. 377-382
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: White matter lesions (WMLs) caused by small vessel disease are common in elderly people and contribute to cognitive impairment. There are no established biochemical markers for WMLs. We aimed to study the relation between degree of WMLs rated on magnetic resonance imaging of the brain and cerebrospinal fluid (CSF) levels of structural biomarkers associated with Alzheimer's disease (AD) and subcortical vascular dementia. Methods: Fifty-three non-demented elderly individuals with WMLs were subjected to lumbar puncture. Degree of WMLs was rated using the Fazekas scale. Volumetric assessment of WMLs was performed. CSF samples were analyzed for the 40 and 42 amino acid fragments of amyloid beta, alpha- and beta-cleaved soluble amyloid precursor protein, total tau (T-tau), hyperphosphorylated tau (P-tau(181)), neurofilament light protein (NFL), sulfatide and CSF/Serum-albumin ratio. Results: Fifteen subjects had mild, 23 had moderate and 15 had severe degree of WMLs. CSF-NFL levels differed between the groups (P < 0.001) and correlated with the volume of WMLs (r = 0.477, P < 0.001). CSF sulfatide concentration displayed similar changes but less strongly. T-tau, P-tau(181) and the different amyloid markers as well as CSF/S-albumin ratio did not differ significantly between the groups. Conclusions: The association of increased CSF-NFL levels with increasing severity of WMLs in non-demented subjects suggests that NFL is a marker for axonal damage in response to small vessel disease in the brain. This manifestation may be distinct from or earlier than the neurodegenerative process seen in AD, as reflected by the lack of association between WMLs and AD biomarkers.
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| 25. |
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| 26. |
- Kern, Silke, et al.
(författare)
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Lower CSF interleukin-6 predicts future depression in a population-based sample of older women followed for 17 years
- 2013
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Ingår i: Brain Behavior and Immunity. - : Elsevier BV. - 0889-1591. ; 32, s. 153-158
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Tidskriftsartikel (refereegranskat)abstract
- Objective The literature regarding cerebrospinal fluid (CSF) cytokines in geriatric depression is sparse. The aim of this study was to examine associations between CSF interleukin-6 (IL-6) and related proinflammatory cytokines and current and future depression in a population-based sample of older women who were followed for 17 years. Methods 83 non-demented women aged 70–84 years who participated in the Prospective Population Study of Women in Gothenburg, Sweden took part in a lumbar puncture in 1992–3. CSF- IL-6, interleukin-1β (IL-1β), interleukin- 8 (IL-8) and tumor necrosis factor-α (TNF-α) were measured. Psychiatric symptoms were rated with the Comprehensive Psychopathological Rating Scale at baseline and at three subsequent face-to-face examinations. Depression (major or minor) was diagnosed in accordance with DSM-IV/DSM-IV research criteria. Results At baseline, women with ongoing depression had lower levels of IL-6 (p < 0.04), IL-8 (p < 0.05) and TNF-α (p < 0.05) compared with those without depression. In women without depression at baseline, lower CSF IL-6 levels predicted depression at one or more follow-up examination (p < 0.03). Results from the generalized linear mixed logistic model using all baseline and follow-up data on depression status and Mini Mental State Examination score showed a significant relationship between IL-6 and depression (p = 0.005 OR 0.370 CI [0.184–0.744]). Conclusion Lower levels of CSF IL-6 were associated with current depression and with future depression during a follow-up of almost two decades. Our findings suggest that lower levels of CSF IL-6 may be related to depression vulnerability in later life.
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| 27. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Elevated cerebrospinal fluid F2-isoprostane levels indicating oxidative stress in healthy siblings of multiple sclerosis patients.
- 2007
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Ingår i: Neuroscience letters. - : Elsevier BV. - 0304-3940. ; 414:3, s. 233-6
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Tidskriftsartikel (refereegranskat)abstract
- Lipid peroxidation has been implicated in the pathogenesis of multiple sclerosis (MS). Isoprostanes, isomers of prostaglandins, are produced by free radical-mediated peroxidation of fatty acids in vivo and can be quantified in biological fluids. This study examines the levels of cerebrospinal fluid (CSF) F2-isoprostanes (F2-iPs) in MS patients (n=46), their healthy siblings (n=46) and unrelated controls (n=50). The median CSF F2-iP concentration (range) was significantly higher in siblings of MS patients, as compared to healthy controls (40.0 [7.1-68.7] and 29.1 [6.4-60.3] pg/mL, respectively, p=0.031). MS patients demonstrated F2-iP levels intermediate between siblings and controls. F2-iP levels in MS patients and siblings correlated significantly (R=0.360, p=0.012). These results suggest that siblings of MS patients have an increased oxidative stress response to environmental and/or genetic factors that may be involved in MS pathogenesis.
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| 28. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Elevated cerebrospinal fluid levels of prostaglandin E2 and 15-(S)-hydroxyeicosatetraenoic acid in multiple sclerosis.
- 2009
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Ingår i: Journal of internal medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 265:4, s. 459-64
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To test the hypothesis that the arachodinic acid metabolites prostaglandin E2 (PGE2) and 15-(S)-hydroxyeicosatetraenoic acid (15(S)-HETE) in cerebrospinal fluid (CSF) are elevated and reflect neuroinflammation and degenerative changes in multiple sclerosis (MS). PATIENTS AND METHODS: We measured PGE2 and 15(S)-HETE concentrations, as well as markers of axonal and astroglial injury in CSF from 46 MS patients, 46 healthy siblings and 50 controls. RESULTS: We found elevated levels of both PGE2 and 15(S)-HETE in MS compared with the control and sibling groups. Siblings had lower PGE2 levels and higher 15(S)-HETE levels than controls. There were no correlations between either PGE2 or 15(S)-HETE and clinical scores of MS severity or biochemical markers of axonal or astroglial injury. CONCLUSION: These data suggest no direct involvement of PGE2 and 15(S)-HETE in the MS disease process. Rather, the elevated levels reflect a general up-regulation of arachidonic acid metabolism and neuroinflammation.
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| 29. |
- Mattsson, Niklas, 1979, et al.
(författare)
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Novel cerebrospinal fluid biomarkers of axonal degeneration in frontotemporal dementia.
- 2008
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Ingår i: Molecular medicine reports. - : Spandidos Publications. - 1791-2997. ; 1:5, s. 757-61
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a heterogeneous disease with substantial interpersonal variance in aggressiveness. Novel biomarkers for rapidly progressive FTD could improve diagnosis and provide clues regarding its pathogenesis. In this study, surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry (MS) was used to analyze peptide profiles in cerebrospinal fluid (CSF) from 24 FTD patients. Thirteen patients had rapidly progressive FTD with distinct pathology in a brain MRI after less than 3 years of disease duration. Eleven patients had slowly progressive FTD with a normal brain MRI, but had abnormal findings in SPECT/PET after more than 5 years of disease duration. The axonal damage marker CSF neurofilament light-chain (NF-L) was measured in all subjects to evaluate the amount of axonal degeneration. A CSF NF-L level of 150 ng/l was used as a cut-off point for high NF-L expression. SELDI-TOF analysis of peptides in the range of 2000-20000 m/z revealed one peak with m/z of 6378 that was expressed at a significantly different level (p<0.01) when rapidly versus slowly progressive cases of FTD were compared. Eleven peaks were expressed at different levels when high versus low CSF NF-L were compared. Using chromatographic purification followed by tandem mass spectrometric analysis, five of these peaks were identified as follows: C-terminal fragment of neuroendocrine protein 7B2 (3512.84 Da), C-terminal fragment of osteopontin (7658.19 Da) as well as its mono- and diphosphorylated forms (7738.16 Da and 7818.13 Da, respectively) and pancreatic ribonuclease (14566.33 Da). The peak intensity of pancreatic ribonuclease was higher in patients with low NF-L expression, while the other peptides had a lower peak intensity in this group. Altered levels of these peptides have also been described in other neurodegenerative diseases. Taken together, these data suggest that differentially-expressed peptides are general markers of axonal degeneration. Further studies are needed to verify their prognostic value in FTD.
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| 30. |
- Mehlig, Kirsten, 1964, et al.
(författare)
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The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism.
- 2013
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Ingår i: Heart (British Cardiac Society). - : BMJ. - 1468-201X .- 1355-6037. ; 99:23, s. 1761-1765
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Tidskriftsartikel (refereegranskat)abstract
- An elevated level of total plasma homocysteine (tHcy) has been associated with risk of coronary heart disease (CHD). The level of tHcy is affected by lifestyle, in addition to genetic predisposition. The methylene tetrahydrofolate reductase (MTHFR) 677C>T polymorphism (rs1801133) is among the strongest genetic predictors of tHcy. We examined whether the association between tHcy and CHD is modified by the MTHFR 677C>T polymorphism.
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| 31. |
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| 32. |
- Mörtberg, Erik, et al.
(författare)
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S-100B is superior to NSE, BDNF and GFAP in predicting outcome of resuscitation from cardiac arrest with hypothermia treatment
- 2011
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 82:1, s. 26-31
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To conduct a pilot study to evaluate the blood levels of brain derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), neuron specific enolase (NSE) and S-100B as prognostic markers for neurological outcome 6 months after hypothermia treatment following resuscitation from cardiac arrest. Design: Prospective observational study. Setting: One intensive care unit at Uppsala University Hospital. Patients: Thirty-one unconscious patients resuscitated after cardiac arrest. Interventions: None. Measurements and main results: Unconscious patients after cardiac arrest with restoration of spontaneous circulation (ROSC) were treated with mild hypothermia to 32-34 °C for 26. h. Time from cardiac arrest to target temperature was measured. Blood samples were collected at intervals of 1-108. h after ROSC. Neurological outcome was assessed with Glasgow-Pittsburgh cerebral performance category (CPC) scale at discharge from intensive care and again 6 months later, when 15/31 patients were alive, of whom 14 had a good outcome (CPC 1-2). Among the predictive biomarkers, S-100B at 24. h after ROSC was the best, predicting poor outcome (CPC 3-5) with a sensitivity of 87% and a specificity of 100%. NSE at 96. h after ROSC predicted poor outcome, with sensitivity of 57% and specificity of 93%. BDNF and GFAP levels did not predict outcome. The time from cardiac arrest to target temperature was shorter for those with poor outcome. Conclusions: The blood concentration of S-100B at 24. h after ROSC is highly predictive of outcome in patients treated with mild hypothermia after cardiac arrest.
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| 33. |
- Nylén, Karin, 1961, et al.
(författare)
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CSF -neurofilament correlates with outcome after aneurysmal subarachnoid hemorrhage.
- 2006
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Ingår i: Neurosci Lett. - : Elsevier BV. - 0304-3940. ; 404:1-2, s. 132-6
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Tidskriftsartikel (refereegranskat)abstract
- Aneurysmal subarachnoid hemorrhage (aSAH) is a devastating event. Following the bleeding, a number of pathophysiological changes and clinical factors determine outcome. Not surprisingly, attempts to predict outcome based on a single factor have failed. The neurological status graded at admission to hospital and distributions of the blood on CT are the strongest predictors. There is evidence that cerebrospinal fluid (CSF) proteins may serve as markers of the extent of brain damage. The present study is focused on the light unit of neurofilament protein (NFL), previously not evaluated in aSAH. Lumbar puncture (LP), neurological grading according to World Federation of Neurological Surgeons (WFNS) and neurological examination according to the National Institute of Health Stroke Scale (NIHSS) were performed in 48 consecutive patients with aSAH 10-14 days after the hemorrhage. CSF-NFL concentrations were analyzed using an ELISA. Outcome was assessed after 1 year and categorised according to the extended Glasgow Outcome Scale (GOSE). A significant correlation between CSF-NFL and GOSE was detected at follow up after 1 year. CSF-NFL also correlated with WFNS and NIHSS on the day of the lumbar puncture. CSF-NFL is a biochemical marker of brain damage correlating to neurological status and long-term outcome after aneurysmal subarachnoid hemorrhage.
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| 34. |
- Nylen, K, et al.
(författare)
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Increased serum-GFAP in patients with severe traumatic brain injury is related to outcome
- 2006
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Ingår i: J Neurol Sci. - : Elsevier BV. - 0022-510X. ; 240:1-2, s. 85-91
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Several studies have established the relevance of S-100 in blood as a marker of brain damage after traumatic brain injury. However, a more specific marker is required and glial fibrillary acidic protein (GFAP) is considered to be a good candidate. METHODS: In order to assess the increase of GFAP in serum (s-GFAP) after a severe traumatic brain injury (TBI) we collected daily serum samples from 59 patients with severe TBI starting on the day of the trauma. S-GFAP was measured using a sandwich ELISA. The Glasgow outcome scale (GOS) assessed outcome after 1 year. RESULTS: All but one patient had maximal s-GFAP values above the laboratory reference value (median increased 10-fold). The highest detected levels were seen during the first days after TBI and then decreased gradually. Patients with unfavourable outcome had significantly (p<0.001) higher maximal s-GFAP values in the acute phase compared with patients with favourable outcome. All patients (n=5) with s-GFAP>15.04 microg /L died (reference level<0.15 microg/L). We found no significant difference in the maximal s-GFAP levels of patients with isolated brain injury in comparison with patients with multiple traumas. CONCLUSION: Serum-GFAP is increased during the first days after a severe traumatic brain injury and related to clinical outcome.
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| 35. |
- Nylén, Karin, 1961, et al.
(författare)
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Serum glial fibrillary acidic protein is related to focal brain injury and outcome after aneurysmal subarachnoid hemorrhage.
- 2007
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Ingår i: Stroke. - 1524-4628. ; 38:5, s. 1489-94
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND PURPOSE: Aneurysmal subarachnoid hemorrhage (aSAH) stands out from other subtypes of stroke because of the high early mortality and the risk of complications. Serum glial fibrillary acidic protein (s-GFAP) concentrations are increased after stroke. The aim of this study was to investigate whether s-GFAP could be used as a marker of brain damage and outcome after aSAH. METHODS: Serum samples were obtained on a regular basis from 116 adults during a 2-week period after aSAH and analyzed using an enzyme-linked immunosorbent assay. The World Federation of Neurological Surgeons scale was used for neurological evaluation. Outcome was assessed after 1 year and categorized according to the Extended Glasgow Outcome Scale. RESULTS: Increased s-GFAP levels were seen in 81 of the 116 patients. Maximum s-GFAP correlated with World Federation of Neurological Surgeons scale on arrival and on days 10 to 15 (r=0.37, P<0.001 and r=0.47, P<0.001, respectively). Furthermore, maximum s-GFAP levels were increased in the patient group with radiological signs of focal lesions acute or at 1 year, compared with the group without focal lesions (P<0.001 in both comparisons). Patients with secondary events (re-bleeding or ischemia) reached maximum levels later in the series and both maximum and final s-GFAP levels increased compared with the levels in patients without secondary events (P<0.001 in all 3 comparisons). Finally, maximum s-GFAP correlated with outcome (r=-0.48, P<0.001) and s-GFAP was an independent predictor of dichotomized outcome. CONCLUSIONS: s-GFAP provides information about brain injury severity and outcome after aSAH, which can be useful as a complement to clinical data.
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| 36. |
- Nylén, Karin, 1961, et al.
(författare)
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Serum levels of S100B, S100A1B and S100BB are all related to outcome after severe traumatic brain injury.
- 2008
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Ingår i: Acta neurochirurgica. - : Springer Science and Business Media LLC. - 0942-0940 .- 0001-6268. ; 150:3
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: S100B is an established marker of brain damage. Used in the context as a biochemical marker, S100B denotes a measurement of all S100 proteins, including at least one S100B monomer, i.e. the sum of the two dimers S100A1B and S100BB. Almost all published studies are based on this "sum concentration". However, the brain specificity of S100B has been questioned and increased serum levels have also been reported after trauma without head injury. Since the S100B monomer dominates in the brain, we hypothesised that the S100BB dimer should be better related to outcome after severe traumatic brain injury than S100A1B or the "sum concentration". METHODS: Daily serum samples were collected from 59 patients with severe traumatic brain injury. Three different ELISA methods were used for measurements of S100B, S100A1B and S100BB respectively. Outcome was assessed after one year and categorised according to the Glasgow Outcome Scale. RESULTS: Serum levels of S100B, S100A1B and S100BB followed the same temporal course, with early maximum and rapidly decreasing values over the first days after the trauma. Maximum serum concentrations of each of the parameters were increased in the patient group with an unfavourable outcome compared with those with a favourable outcome (p = 0.01, 0.006 and 0.004, respectively). CONCLUSION: Both S100A1B and S100BB were related to outcome after severe traumatic brain injury. Even though this study is small, it seems unlikely that separate analyses of the dimers are of any advantage compared with measuring S100B alone.
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| 37. |
- Olsson, Annika, et al.
(författare)
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Marked increase of beta-amyloid(1-42) and amyloid precursor protein in ventricular cerebrospinal fluid after severe traumatic brain injury.
- 2004
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Ingår i: Journal of neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 251:7, s. 870-6
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Tidskriftsartikel (refereegranskat)abstract
- Severe traumatic brain injury (TBI) may result in widespread damage to axons, termed diffuse axonal injury. Alzheimer's disease (AD) is characterised by synaptic and axonal degeneration together with senile plaques (SP). SP are mainly composed of aggregated beta-amyloid (Abeta), which are peptides derived from the amyloid precursor protein (APP). Apart from TBI in itself being considered a risk factor for AD, severe head injury seems to initiate a cascade of molecular events that are also associated with AD. We have therefore analysed the 42 amino acid forms of Abeta (Abeta1-42) and two soluble forms of APP (alpha-sAPP and ss-sAPP) in ventricular cerebrospinal fluid (VCSF) and Abeta(1-42) in plasma from 28 patients in a serial samples 0-11 days after TBI. The levels of alpha-sAPP, ss-sAPP and Abeta(1-42) were determined using ELISA assays. After TBI, there was a significant stepwise increase in VCSF-Abeta(1-42) up to 1173 % from day 0-1 to day 5-6 and in VCSF-beta-sAPP up to 2033 % increase from day 0-1 to day 7-11. There was also a slight but significant increase of VCSF-beta-sAPP from day 0-1 to day 5-6 and day 7-11. By contrast, the plasma- Abeta(1-42) level is unchanged after injury. The marked increase in VCSFAbeta(1-42) implies that increased Abeta expression may occur as a secondary phenomenon after TBI with axonal damage. The unchanged level of plasma-Abeta(1-42) in contrast to the marked increase in VCSF-Abeta(1-42) after severe TBI, supports the suggestion that plasma Abeta(1-42) does not reflect Abeta metabolism in the central nervous system (CNS).
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| 38. |
- Pedersen, Annie, 1981, et al.
(författare)
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Circulating neurofilament light in ischemic stroke: temporal profile and outcome prediction
- 2019
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Ingår i: Journal of Neurology. - : Springer Science and Business Media LLC. - 0340-5354 .- 1432-1459. ; 266:11, s. 2796-2806
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose Neurofilament light chain (NfL) is a marker of neuroaxonal damage. We aimed to study associations between serum NfL (sNfL) concentrations at different time points after ischemic stroke and outcomes. Methods We prospectively included ischemic stroke cases (n=595, mean age 59 years, 64% males) and assessed outcomes by both the modified Rankin Scale (mRS) and the NIH stroke scale (NIHSS) at 3 months and by mRS at 2 years. In a subsample, long-term (7-year) outcomes were also assessed by both mRS and NIHSS. We used the ultrasensitive single-molecule array assay to measure sNfL in the acute phase (range 1–14, median 4 days), after 3 months and 7 years in cases and once in controls (n=595). Results Acute-phase sNfL increased by the time to blood-draw and highest concentrations were observed at 3 months post-stroke. High sNfL associated to stroke severity and poor outcomes, and both associations were strongest for 3-month sNfL. After adjusting for age, previous stroke, stroke severity, and day of blood draw, 3-month sNfL was significantly associated to both outcomes at all time points (p<0.01 throughout). For all main etiological subtypes, both acute phase and 3-month sNfL were significantly higher than in controls, but the dynamics of sNfL differed by stroke subtype. Conclusions The results from this study inform on sNfL in ischemic stroke and subtypes over time, and show that sNfL predicts short- and long-term neurological and functional outcomes. Our findings suggest a potential utility of sNfL in ischemic stroke outcome prediction.
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| 39. |
- Pielberg, Gerli Rosengren, et al.
(författare)
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A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 40:8, s. 1004-1009
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Tidskriftsartikel (refereegranskat)abstract
- In horses, graying with age is an autosomal dominant trait associated with a high incidence of melanoma and vitiligo-like depigmentation. Here we show that the Gray phenotype is caused by a 4.6-kb duplication in intron 6 of STX17 (syntaxin-17) that constitutes a cis-acting regulatory mutation. Both STX17 and the neighboring NR4A3 gene are overexpressed in melanomas from Gray horses. Gray horses carrying a loss-of-function mutation in ASIP (agouti signaling protein) had a higher incidence of melanoma, implying that increased melanocortin-1 receptor signaling promotes melanoma development in Gray horses. The Gray horse provides a notable example of how humans have cherry-picked mutations with favorable phenotypic effects in domestic animals.
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| 40. |
- Rosén, Christoffer, 1986, et al.
(författare)
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Cerebrospinal fluid biomarkers in cardiac arrest survivors.
- 2014
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Ingår i: Resuscitation. - : Elsevier BV. - 1873-1570 .- 0300-9572. ; 85:2, s. 227-232
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to investigate the levels of various cerebrospinal fluid (CSF) biomarkers related to neuronal damage, inflammation and amyloid β (Aβ) metabolism in patients resuscitated after an out-of-hospital cardiac arrest (CA).
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| 41. |
- Sandelius, Anna Stina, 1952, et al.
(författare)
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Transient increase in CSF GAP-43 concentration after ischemic stroke.
- 2018
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Ingår i: BMC neurology. - : Springer Science and Business Media LLC. - 1471-2377. ; 18:1
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Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers reflect ongoing processes in the brain. Growth-associated protein 43 (GAP-43) is highly upregulated in brain tissue shortly after experimental ischemia suggesting the CSF GAP-43 concentration may be altered in ischemic brain disorders. CSF GAP-43 concentration is elevated in Alzheimer's disease patients; however, patients suffering from stroke have not been studied previously.The concentration of GAP-43 was measured in longitudinal CSF samples from 28 stroke patients prospectively collected on days 0-1, 2-4, 7-9, 3weeks, and 3-5months after ischemia and cross-sectionally in 19 controls. The stroke patients were clinically evaluated using a stroke severity score system. The extent of the brain lesion, including injury size and degrees of white matter lesions and atrophy were evaluated by CT and magnetic resonance imaging.Increased GAP-43 concentration was detected from day 7-9 to 3weeks after stroke, compared to day 1-4 and to levels in the control group (P=0.02 and P=0.007). At 3-5months after stroke GAP-43 returned to admission levels. The initial increase in GAP-43 during the nine first days was associated to stroke severity, the degree of white matter lesions and atrophy and correlated positively with infarct size (rs=0.65, P=0.001).The transient increase of CSF GAP-43 is important to take into account when used as a biomarker for other neurodegenerative diseases such as Alzheimer's disease. Furthermore, GAP-43 may be a marker of neuronal responses after stroke and additional studies confirming the potential of CSF GAP-43 to reflect severity and outcome of stroke in larger cohorts are warranted.
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| 42. |
- Selnes, Per, et al.
(författare)
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Effects of cerebrovascular disease on amyloid precursor protein metabolites in cerebrospinal fluid
- 2010
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Ingår i: Fluids and Barriers of the CNS. - : Springer Science and Business Media LLC. - 2045-8118. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Background Alzheimer's disease (AD) and cerebrovascular disease (CVD) including chronic small vessel disease of the brain (SVD) are the most frequent causes of dementia. AD is associated with metabolism of amyloid precursor protein (APP) and low levels of amyloid-β peptide (Aβ) X-42 in the cerebrospinal fluid (CSF). CVD and SVD are established risk factors for AD, brain white matter lesions (WML) are established surrogate markers for SVD and are also associated with reduced CSF AβX-42. A cohort survey was performed to examine whether SVD or acute CVD affects APP metabolism and to explore a potential association between WML and APP metabolism in two groups; cognitively impaired patients, subjective and mild (SCI and MCI) and stroke patients. Through measurements of CSF APP metabolite levels in patients with a wide range of WML volumes, this study aimed to determine how SVD influences APP metabolism. Methods Sixty-three patients were included: 37 with subjective cognitive impairment (SCI) or mild cognitive impairment (MCI) without stroke, and 26 after acute stroke. Chronic and acute WML volume and infarct volume were determined by magnetic resonance imaging (MRI) post-scan processing, and CSF levels of α- and β-cleaved soluble APP (sAPP-α and sAPP-β, AβX-38, AβX-40 and AβX-42) were determined. The Mann-Whitney test was used to compare the patient groups. Chronic and acute WML volumes, infarct volume, age, and sex were used as predictors for CSF biomarker levels in linear regression analysis. Results CSF levels of sAPP-α and sAPP-β were strongly correlated (r = 0.95, p < 0.001) and lower levels of these biomarkers were found in the stroke group than in the SCI/MCI group; median sAPP-α 499.5 vs. 698.0 ng/mL (p < 0.001), sAPP-β 258.0 vs. 329.0 ng/mL (p < 0.005). CSF levels of sAPP-α, sAPP-β, AβX-38, AβX-40 and AβX-42 were inversely correlated with chronic WML volume (p ≤ 0.005; p ≤ 0.01; p ≤ 0.01; p ≤ 0.05; p ≤ 0.05 respectively), but not with acute WML or infarct volumes. Conclusions Lower CSF levels of sAPP-α and sAPP-β in the stroke group than in the SCI/MCI group and an inverse correlation with chronic WML indicate that ischemia lowers the levels of CSF sAPP metabolites and suggests that APP axonal transport or metabolism may be affected in SVD of the brain.
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| 43. |
- Sjögren, Magnus, et al.
(författare)
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Neurofilament protein in cerebrospinal fluid: a marker of white matter changes.
- 2001
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Ingår i: Journal of neuroscience research. - : Wiley. - 0360-4012. ; 66:3, s. 510-6
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to compare cerebrospinal fluid (CSF) levels of the light subtype of the neurofilament proteins (NFL), tau, and beta-amyloid42 (Abeta42) in individuals with moderate or severe white matter changes (WMC) and in those with mild or no WMC. Twenty-two patients with Alzheimer's disease (AD), nine patients with subcortical vascular dementia (SVD), and 20 normal controls were included in the study. The occurrence of WMC was evaluated by a neuroradiologist using the Blennow-Wallin scale. Thirty-seven subjects had no or only punctate WMC; 14 had moderate to severe WMC. Both diagnostic group and WMC, but not gender or apolipoproteinE E4 inheritance, contributed to the variance in the CSF levels of tau, NFL, and Abeta42. In patients with moderate to severe WMC, CSF NFL (P < 0.01), but not CSF tau or CSF Abeta42, was increased also after correction for age, gender, and degree of cognitive impairment. A comparison between patients and controls with any signs of WMC and those without such signs yielded a similar result: CSF NFL (P < 0.001) was increased in the group with signs of WMC. As in numerous previous studies, we found that CSF tau was increased in AD (P < 0.001) compared with controls. Furthermore, CSF NFL was increased in both AD and SVD compared with controls (P < 0.001 for both). Although diagnostic group seems to be a stronger predictor of the variance found in CSF NFL, a clear association between the presence of WMC and increased CSF NFL was found. Because NFL is located mainly in large myelinated axons, increased CSF NFL in individuals with WMC probably reflects axonal degeneration.
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| 44. |
- Skillbäck, Tobias, et al.
(författare)
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CSF neurofilament light differs in neurodegenerative diseases and predicts severity and survival.
- 2014
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Ingår i: Neurology. - 1526-632X .- 0028-3878. ; 83:21, s. 1945-53
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Tidskriftsartikel (refereegranskat)abstract
- We hypothesized that CSF neurofilament light (NFL) levels would be elevated in dementias with subcortical involvement, including vascular dementia (VaD), but less elevated in dementias primarily affecting gray matter structures, such as Alzheimer disease (AD), and that elevated CSF NFL would correlate with disease severity and shorter survival time irrespective of clinical diagnosis.
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| 45. |
- Tullberg, Mats, 1965, et al.
(författare)
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CSF sulfatide distinguishes between normal pressure hydrocephalus and subcortical arteriosclerotic encephalopathy.
- 2000
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Ingår i: Journal of neurology, neurosurgery, and psychiatry. - : BMJ. - 0022-3050. ; 69:1, s. 74-81
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Tidskriftsartikel (refereegranskat)abstract
- To examine the CSF concentrations of molecules reflecting demyelination, neuronal and axonal degeneration, gliosis, monoaminergic neuronal function, and aminergic and peptidergic neurotransmission in a large series of patients with normal pressure hydrocephalus (NPH) or subcortical arteriosclerotic encephalopathy (SAE), to elucidate pathogenic, diagnostic, and prognostic features.CSF concentrations of glycosphingolipid (sulfatide), proteins (neurofilament triplet protein (NFL), glial fibrillary acidic protein (GFAP)), neuropeptides (vasoactive intestinal peptide (VIP), 4-aminobutyric acid (GABA)), and monoamines (homovanillic acid (HVA), 5-hydroxy-indoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenylglycol (HMPG)) were analysed in 43 patients with NPH and 19 patients with SAE. The diagnoses of NPH and SAE were based on strict criteria and patients with NPH were subsequently operated on. Twelve clinical variables, psychometric tests measuring perceptual speed, accuracy, learning, and memory and a psychiatric evaluation were performed in all patients and before and after a shunt operation in patients with NPH.The CSF sulfatide concentration was markedly increased in patients with SAE (mean 766, range 300-3800 nmol/l) compared with patients with NPH (mean 206, range 50-400 nmol/l) (p<0.001). 5-HIAA, GABA, and VIP in CSF were higher in patients with SAE than in patients with NPH. The patients with NPH with cerebrovascular aetiology had higher sulfatide concentrations and a poorer outcome after shunt surgery than patients with NPH with other aetiologies.The pathogenesis of the white matter changes in NPH and SAE is different and ischaemic white matter changes can be a part of the NPH state. The markedly increased CSF sulfatide concentrations in patients with SAE indicate ongoing demyelination as an important pathophysiological feature of SAE. The CSF sulfatide concentration distinguished between patients with SAE and those with NPH with a sensitivity of 74% and a specificity of 94%, making it an important diagnostic marker.
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| 46. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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Association of APOE with age at onset of sporadic amyotrophic lateral sclerosis.
- 2008
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Ingår i: Journal of the neurological sciences. - : Elsevier BV. - 0022-510X .- 1878-5883. ; 273:1-2, s. 67-9
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Tidskriftsartikel (refereegranskat)abstract
- Amyotrophic lateral sclerosis (ALS) is a neurodegenerative syndrome with familial and sporadic forms. We conducted a study including 60 sporadic and 19 familial ALS patients, 206 reference patients with other neurological disorders and 1265 neurologically healthy controls to assess the Alzheimer-associated apolipoprotein E (APOE) epsilon4 gene variant as a possible risk factor for ALS. While no major influence of APOE epsilon4 on disease risk was detected, a gene dose-dependent effect with lower age at onset of sporadic ALS in epsilon4 carriers was found (p=0.027). These data support APOE epsilon4 as a subordinate contributing factor in ALS.
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| 47. |
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| 48. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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Neurochemical aftermath of amateur boxing
- 2006
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Ingår i: ARCHIVES OF NEUROLOGY. - : American Medical Association (AMA). - 0003-9942. ; 63:9, s. 1277-1280
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Tidskriftsartikel (refereegranskat)
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| 49. |
- Zetterberg, Henrik, 1973, et al.
(författare)
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No neurochemical evidence for brain injury caused by heading in soccer.
- 2007
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Ingår i: British journal of sports medicine. - : BMJ. - 1473-0480 .- 0306-3674. ; 41:9, s. 574-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The possible injurious effect to the brain of heading in soccer is a matter of discussion. OBJECTIVE: To determine whether standardised headings in soccer are associated with increased levels of biochemical markers for neuronal injury in cerebrospinal fluid (CSF) and serum. METHODS: 23 male amateur soccer players took part in a heading training session involving heading a ball kicked from a distance of 30 m at least 10 m forward. Ten players performed 10 and 13 players performed 20 approved headings. The players underwent lumbar puncture and serum sampling 7-10 days after the headings. The study also included 10 healthy male non-athletic control subjects. CSF was analysed for neurofilament light protein, total tau, glial fibrillary acidic protein, S-100B and albumin concentrations. Serum was analysed for S-100B and albumin. RESULTS: None of the biomarker levels were abnormal and there were no significant differences between any of the three groups, except for a slightly increased CSF S-100B concentration in controls compared with headers. Biomarker levels did not correlate with the number of headings performed. CONCLUSION: Repeated low-severity head impacts due to heading in soccer are not associated with any neurochemical signs of injury to the brain.
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| 50. |
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