| 41. |
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| 42. |
- Anckarsäter, Henrik, 1966, et al.
(author)
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Increased CSF/serum albumin ratio: a recurrent finding in violent offenders.
- 2005
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In: Acta neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 112:1, s. 48-50
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To test the hypothesis that cerebrospinal fluid (CSF)/ serum albumin ratios are increased in violent offenders. SUBJECTS AND METHODS: In a previous study of violent offenders, we found significantly higher CSF/serum album ratios (as a sign of increased blood-brain barrier permeability) in violent offenders than in healthy controls. For the present replication study, we recruited a new group of 28 violent offenders, aged 45 years or younger, and 20 new control subjects. RESULTS: The albumin ratio was again significantly higher in the offender group (mean 6.2) than in the control group (mean 4.6) (P = 0.012). Substance abuse or current medication did not appear to explain this finding. CONCLUSION: Increased CSF/serum albumin ratios are an unspecific sign of neurological dysfunction in subgroups of violent offenders.
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| 43. |
- Anckarsäter, Rolf, 1956, et al.
(author)
-
Association between thyroid hormone levels and monoaminergic neurotransmission during surgery.
- 2007
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In: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 32:8-10, s. 1138-43
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Human studies assessing thyroid hormone metabolism in relation to brain monoaminergic activity in vivo are scarce. The few studies that do exist suggest significant associations between thyroid function and monoaminergic activity, but the cause-and-effect relationships are far from elucidated. METHODS: We simultaneously collected cerebrospinal fluid (CSF) and serum samples from 35 patients undergoing orthopaedic surgery before, 3h after and the morning after interventions and performed analyses for thyroid hormones and monoamine metabolites. RESULTS: At baseline, the CSF 3-methoxy-4-hydroxyphenylglycol concentrations were significantly correlated to the serum T(3)/T(4) ratio (rho=0.41, p=0.017). During surgery, serum thyroid hormones and the T(3)/T(4) ratio decreased (p<0.0001), while the CSF T(3)/T(4) ratio increased (p=0.0009). There were no correlations between serum and CSF levels of T(3) and T(4) at any of the samplings. Strong correlations were noted between baseline CSF thyroid hormone concentrations and subsequent increases in CSF 5-hydroxyindoleacetic acid (5-HIAA), and homovanillinic acid (HVA), but not vice versa. CONCLUSIONS: Thyroid hormone levels in serum and CSF during stress seem to be distinctly regulated. Baseline thyroid hormone activity may facilitate changes in brain monoaminergic neurotransmission in response to stress.
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| 44. |
- Anckarsäter, Rolf, 1956, et al.
(author)
-
Cerebrospinal fluid protein reactions during non-neurological surgery.
- 2007
-
In: Acta neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 115:4, s. 254-9
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To study changes in cerebrospinal fluid (CSF) protein markers of blood-CSF barrier integrity and immunological reactions during surgical stress. SUBJECTS AND METHODS: Thirty-five patients without neurological or psychiatric disorders undergoing knee replacements had CSF and serum samples drawn from spinal and arterial catheters before, 3 h after and the morning after surgery. RESULTS: Serum albumin decreased during surgery and CSF albumin decreased during and after surgery, and, as a consequence, the CSF/serum albumin ratio decreased significantly during the study period, especially after the intervention. In contrast, CSF concentrations of beta-2-microglobuline (beta2M) increased significantly during surgery and remained high. The CSF general marker beta-trace protein (betaTP) remained unchanged. CONCLUSIONS: Central nervous system protein reactions to a non-neurological surgical intervention include sharply decreased permeability of albumin into the CSF and signs of intrathecal inflammatory activity.
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| 45. |
- Anckarsäter, Rolf, 1956, et al.
(author)
-
Non-neurological surgery and cerebrospinal fluid biomarkers for neuronal and astroglial integrity.
- 2014
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In: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 121:6, s. 649-653
-
Journal article (peer-reviewed)abstract
- Non-neurological surgery has both acute and long-term effects on the brain. Markers for Alzheimer pathology may be used to study surgically induced neurological changes relevant for postoperative confusion, asthenia or cognitive decline. Inflammatory biomarkers, total tau (T-tau) and phosphorylated tau (P-tau) were recently shown to increase progressively in the cerebrospinal fluid (CSF) during surgery for nasal CSF leak, suggesting a neuroinflammatory response with signs of neuronal damage. We used a study group of 35 patients, undergoing knee arthroplasty with a spinal blockade and propofol sedation, to replicate this finding. Five CSF biomarkers were analyzed before, 3h after and on the morning after the interventions: T-tau and P-tau for cortical axonal integrity and tangle pathology, respectively, the 42 amino acids form of amyloid β (Aβ42) for plaque formation, neurofilament light (NFL) for the integrity of large-caliber myelinated axons and glial fibrillary acidic protein (GFAp) for astroglial cell integrity. CSF T-tau concentrations increased significantly during and after surgery (p=0.028) and were significantly correlated with the administered doses of bupivacaine. P-tau, Aβ42 and NFL remained unchanged, while the mean GFAp concentration increased with a large standard deviation. CSF T-tau and P-tau correlated significantly with the CSF/serum albumin ratios as an indicator of blood-brain barrier permeability. Findings from earlier studies showing a significant increase in biomarkers for Alzheimer's pathology during surgery were partly replicated, as neurochemical signs of impaired cortical axonal integrity during non-neurological surgery were detected. Bupivacaine may be involved in these reactions.
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| 46. |
- Anckarsäter, Rolf, 1956, et al.
(author)
-
Non-neurological surgery results in a neurochemical stress response.
- 2008
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In: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 115:3, s. 397-9
-
Journal article (peer-reviewed)abstract
- There is a paucity of studies assessing changes in measures of human neurotransmission during stressful events, such as surgery. Thirty-five patients without any neurological disorders undergoing knee replacements with spinal bupivacaine anaesthesia and propofol sedation had cerebrospinal fluid (CSF) drawn from a spinal catheter before, three hours after and the morning after surgery. The CSF concentrations of the dopamine metabolite homovanillinic acid (HVA) and the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), which are related to the activity of the dopaminergic and serotonergic systems of the brain, increased sharply during surgery and reached 188% and 166% of their initial concentrations on the morning after the intervention (p < 0.0001). The CSF concentrations of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglucol (MHPG) increased modestly (non-significantly) during and after surgery. The HVA/5-HIAA ratios initially increased but returned to the initial level during the night after surgery. We conclude that non-neurological surgery, in this case to the lower limb, is accompanied by a marked central nervous stress response in spite of a spinal blockade.
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| 47. |
- Anderson, Albert M, et al.
(author)
-
Cerebrospinal fluid CXCL10 is associated with the presence of low level CSF HIV during suppressive antiretroviral therapy.
- 2021
-
In: Journal of neuroimmunology. - : Elsevier BV. - 1872-8421 .- 0165-5728. ; 353
-
Journal article (peer-reviewed)abstract
- Surrogate markers of HIV central nervous system (CNS) persistence are needed because direct HIV measurements from the CNS require specialized protocols and are not always detectable or quantifiable. We analyzed paired plasma and CSF samples from people with HIV (PWH) on suppressive therapy (ART) with a validated HIV single copy RNA assay. Two potential markers of CNS persistence were measured (CXCL10 and sCD30). We then examined associations with CSF HIV RNA positivity in univariable and multivariable analyses. Among 66 individuals, 18.2% had detectable CSF HIV. Individuals who had detectable HIV in CSF had higher CSF CXCL10 concentrations (median 514pg/ml versus median 317pg/ml, p=0.019), but did not have significantly different CSF sCD30 concentrations (median 7.5ng/ml versus median 7.6ng/ml, p=0.78). In the multiple logistic analysis, both higher CSF CXCL10 (p=0.038) and plasma HIV detectability (p=0.035) were significantly associated with detectable CSF HIV. Both sCD30 and CXCL10 correlated positively with NfL and NSE, two neuronal markers. This study demonstrates that CSF CXCL10 concentrations reflect low level HIV CNS persistence despite virologic suppression on ART. Given that it is readily detectable and quantifiable, this chemokine may be a promising biomarker to evaluate HIV eradication therapies that target the CNS.
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| 48. |
- Anderson, Albert M., et al.
(author)
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Cerebrospinal fluid interferon alpha levels correlate with neurocognitive impairment in ambulatory HIV-Infected individuals
- 2017
-
In: Journal of NeuroVirology. - : Springer Science and Business Media LLC. - 1355-0284 .- 1538-2443. ; 23, s. 106-112
-
Journal article (peer-reviewed)abstract
- © 2016, Journal of NeuroVirology, Inc. HIV-associated neurocognitive disorders (HANDs) continue to be common and are associated with increased morbidity and mortality. However, the underlying mechanisms in the combination antiretroviral therapy (cART) era are not fully understood. Interferon alpha (IFNα) is an antiviral cytokine found to be elevated in the cerebrospinal fluid (CSF) of individuals with advanced HIV-associated dementia in the pre-cART era. In this cross-sectional study, we investigated the association between IFNα and neurocognitive performance in ambulatory HIV-infected individuals with milder impairment. An eight-test neuropsychological battery representing six cognitive domains was administered. Individual scores were adjusted for demographic characteristics, and a composite neuropsychological score (NPT-8) was calculated. IFNα and CSF neurofilament light chain (NFL) levels were measured using enzyme-linked immunosorbent assay (ELISA). There were 15 chronically infected participants with a history of significant immunocompromise (median nadir CD4+ of 49 cells/μl). Most participants were neurocognitively impaired (mean global deficit score of 0.86). CSF IFNα negatively correlated with three individual tests (Trailmaking A, Trailmaking B, and Stroop Color-Word) as well as the composite NPT-8 score (r=−0.67, p=0.006). These negative correlations persisted in multivariable analyses adjusting for chronic hepatitis B and C. Additionally, CSF IFNα correlated strongly with CSF NFL, a marker of neuronal damage (rho=0.748, p=0.0013). These results extend findings from individuals with severe HIV-associated dementia in the pre-cART era and suggest that IFNα may continue to play a role in HAND pathogenesis during the cART era. Further investigation into the role of IFNα is indicated.
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| 49. |
- Anderson, Albert M, et al.
(author)
-
Cognitive and Neuronal Link With Inflammation: A Longitudinal Study in People With and Without HIV Infection.
- 2020
-
In: Journal of acquired immune deficiency syndromes. - 1944-7884. ; 85:5, s. 617-625
-
Journal article (peer-reviewed)abstract
- Across many settings, lack of virologic control remains common in people with HIV (PWH) because of late presentation and lack of retention in care. This contributes to neuronal damage and neurocognitive impairment, which remains prevalent. More evidence is needed to understand these outcomes in both PWH and people without HIV (PWOH).We recruited PWH initiating antiretroviral therapy and PWOH at 2 sites in the United States. One hundred eight adults were enrolled (56 PWOH and 52 PWH), most of whom had a second assessment at least 24 weeks later (193 total assessments). Tumor necrosis factor alpha, monocyte chemotactic protein-1 (MCP-1), neopterin, soluble CD14, and neurofilament light chain protein (NFL) were measured in plasma and cerebrospinal fluid (CSF). Using multivariate models including Bayesian model averaging, we analyzed factors associated with global neuropsychological performance (NPT-9) and CSF NFL at baseline and over time.At baseline, higher CSF MCP-1 and plasma sCD14 were associated with worse NPT-9 in PWH, while CSF HIV RNA decrease was the only marker associated with improved NPT-9 over time. Among PWH, higher CSF neopterin was most closely associated with higher NFL. Among PWOH, higher CSF MCP-1 was most closely associated with higher NFL. After antiretroviral therapy initiation, decrease in CSF MCP-1 was most closely associated with NFL decrease.Monocyte-associated CSF biomarkers are highly associated with neuronal damage in both PWH and PWOH. More research is needed to evaluate whether therapies targeting monocyte-associated inflammation may ameliorate HIV-associated neurobehavioral diseases.
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| 50. |
- Anderson, Albert M, et al.
(author)
-
Neurofilament light chain in blood is negatively associated with neuropsychological performance in HIV-infected adults and declines with initiation of antiretroviral therapy.
- 2018
-
In: Journal of neurovirology. - : Springer Science and Business Media LLC. - 1538-2443 .- 1355-0284. ; 24:6, s. 695-701
-
Journal article (peer-reviewed)abstract
- HIV-associated neurocognitive disorder (HAND) persists in the combination antiretroviral therapy (cART) era and is associated with diminished quality of life. The disorder remains challenging to diagnose given the requirement for comprehensive neuropsychological testing. Blood biomarkers are needed to facilitate the diagnosis of HAND and to gauge neurological response to antiretroviral therapy. We performed a study of plasma neurofilament light chain (NFL) that included 37 HIV-infected and 54 HIV-negative adults. In the univariate mixed-effect model involving HIV-infected participants, there was a statistically significant linear relationship between composite neuropsychological score (NPT-11) and plasma NFL (slope=-9.9, standard error=3.0 with 95% confidence interval -3.2 to -16.6 and p=0.008 when testing slope=0). Similarly, in the multivariate mixed-effect model, higher plasma NFL was significantly associated with worse NPT-11 (slope=-11.5, standard error=3.3 with 95% confidence interval -3.7 to -19.0 and p=0.01 when testing slope=0). The association between NPT-11 and NFL appeared to be driven by the group of individuals off cART. In a subset of participants who had visits before and after 24weeks on cART (n=11), plasma NFL declined over time (median=22.7 versus 13.4pg/ml, p=0.02). In contrast, plasma NFL tended to increase over time among HIV-negative participants (median 10.3 versus 12.6pg/ml, p=0.065, n=54). Plasma NFL therefore shows promise as a marker of neuropsychological performance during HIV. Larger studies are needed to determine if NFL could serve as a diagnostic tool for HAND during suppressive cART.
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