| 1. |
- Keddie, Stephen, et al.
(författare)
-
Peripherin is a biomarker of axonal damage in peripheral nervous system disease
- 2023
-
Ingår i: Brain. - 0006-8950 .- 1460-2156. ; 146:11, s. 4562-4573
-
Tidskriftsartikel (refereegranskat)abstract
- Valid, responsive blood biomarkers specific to peripheral nerve damage would improve management of peripheral nervous system (PNS) diseases. Neurofilament light chain (NfL) is sensitive for detecting axonal pathology but is not specific to PNS damage, as it is expressed throughout the PNS and CNS. Peripherin, another intermediate filament protein, is almost exclusively expressed in peripheral nerve axons. We postulated that peripherin would be a promising blood biomarker of PNS axonal damage. We demonstrated that peripherin is distributed in sciatic nerve, and to a lesser extent spinal cord tissue lysates, but not in brain or extra-neural tissues. In the spinal cord, anti-peripherin antibody bound only to the primary cells of the periphery (anterior horn cells, motor axons and primary afferent sensory axons). In vitro models of antibody-mediated axonal and demyelinating nerve injury showed marked elevation of peripherin levels only in axonal damage and only a minimal rise in demyelination. We developed an immunoassay using single molecule array technology for the detection of serum peripherin as a biomarker for PNS axonal damage. We examined longitudinal serum peripherin and NfL concentrations in individuals with Guillain-Barr © syndrome (GBS, n = 45, 179 time points), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n = 35, 70 time points), multiple sclerosis (n = 30), dementia (as non-inflammatory CNS controls, n = 30) and healthy individuals (n = 24). Peak peripherin levels were higher in GBS than all other groups (median 18.75 pg/ml versus < 6.98 pg/ml, P < 0.0001). Peak NfL was highest in GBS (median 220.8 pg/ml) and lowest in healthy controls (median 5.6 pg/ml), but NfL did not distinguish between CIDP (17.3 pg/ml), multiple sclerosis (21.5 pg/ml) and dementia (29.9 pg/ml). While peak NfL levels were higher with older age (rho = +0.39, P < 0.0001), peak peripherin levels did not vary with age. In GBS, local regression analysis of serial peripherin in the majority of individuals with three or more time points of data (16/25) displayed a rise-and-fall pattern with the highest value within the first week of initial assessment. Similar analysis of serial NfL concentrations showed a later peak at 16 days. Group analysis of serum peripherin and NfL levels in GBS and CIDP patients were not significantly associated with clinical data, but in some individuals with GBS, peripherin levels appeared to better reflect clinical outcome measure improvement. Serum peripherin is a promising new, dynamic and specific biomarker of acute PNS axonal damage.
|
|
| 2. |
- Paterson, Ross W, et al.
(författare)
-
Serum and cerebrospinal fluid biomarker profiles in acute SARS-CoV-2-associated neurological syndromes.
- 2021
-
Ingår i: Brain communications. - : Oxford University Press (OUP). - 2632-1297. ; 3:3
-
Tidskriftsartikel (refereegranskat)abstract
- Preliminary pathological and biomarker data suggest that SARS-CoV-2 infection can damage the nervous system. To understand what, where and how damage occurs, we collected serum and CSF from patients with COVID-19 and characterized neurological syndromes involving the PNS and CNS (n=34). We measured biomarkers of neuronal damage and neuroinflammation, and compared these with non-neurological control groups, which included patients with (n=94) and without (n=24) COVID-19. We detected increased concentrations of neurofilament light, a dynamic biomarker of neuronal damage, in the CSF of those with CNS inflammation (encephalitis and acute disseminated encephalomyelitis) [14800pg/ml (400, 32400)], compared to those with encephalopathy [1410pg/ml (756, 1446)], peripheral syndromes (Guillain-Barré syndrome) [740pg/ml (507, 881)] and controls [872pg/ml (654, 1200)]. Serum neurofilament light levels were elevated across patients hospitalized with COVID-19, irrespective of neurological manifestations. There was not the usual close correlation between CSF and serum neurofilament light, suggesting serum neurofilament light elevation in the non-neurological patients may reflect peripheral nerve damage in response to severe illness. We did not find significantly elevated levels of serum neurofilament light in community cases of COVID-19 arguing against significant neurological damage. Glial fibrillary acidic protein, a marker of astrocytic activation, was not elevated in the CSF or serum of any group, suggesting astrocytic activation is not a major mediator of neuronal damage in COVID-19.
|
|
| 3. |
- Altmann, Patrick, et al.
(författare)
-
Increased serum neurofilament light chain concentration indicates poor outcome in Guillain-Barré syndrome.
- 2020
-
Ingår i: Journal of neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 17:1
-
Tidskriftsartikel (refereegranskat)abstract
- Guillain-Barré syndrome (GBS) is an autoimmune disease that results in demyelination and axonal damage. Five percent of patients die and 20% remain significantly disabled on recovery. Recovery is slow in most cases and eventual disability is difficult to predict, especially early in the disease. Blood or cerebrospinal fluid (CSF) biomarkers that could help identify patients at risk of poor outcome are required. We measured serum neurofilament light chain (sNfL) concentrations from blood taken upon admission and investigated a correlation between sNfL and clinical outcome.Baseline sNfL levels in 27 GBS patients were compared with a control group of 22 patients with diagnoses not suggestive of any axonal damage. Clinical outcome parameters for GBS patients included (i) the Hughes Functional Score (HFS) at admission, nadir, and discharge; (ii) the number of days hospitalised; and (iii) whether intensive care was necessary.The median sNfL concentration in our GBS sample on admission was 85.5pg/ml versus 9.1pg/ml in controls. A twofold increase in sNfL concentration at baseline was associated with an HFS increase of 0.6 at nadir and reduced the likelihood of discharge with favourable outcome by a factor of almost three. Higher sNfL levels upon admission correlated well with hospitalisation time (rs=0.69, p<0.0001), during which transfer to intensive care occurred more frequently at an odds ratio of 2.4. Patients with baseline sNfL levels below 85.5pg/ml had a 93% chance of being discharged with an unimpaired walking ability.sNfL levels measured at hospital admission correlated with clinical outcome in GBS patients. These results represent amounts of acute axonal damage and reflect mechanisms resulting in disability in GBS. Thus, sNfL may serve as a convenient blood-borne biomarker to personalise patient care by identifying those at higher risk of poor outcome.
|
|
| 4. |
- Appleton, Jason Philip, et al.
(författare)
-
Improving the likelihood of neurology patients being examined using patient feedback
- 2015
-
Ingår i: BMJ Quality Improvement Reports. - : BMJ. - 2050-1315. ; 4:1
-
Tidskriftsartikel (refereegranskat)abstract
- We aimed to establish whether recall of elements of the neurological examination can be improved by use of a simple patient assessment score. In a previous study we demonstrated that in-patients referred to neurology at two United Kingdom (UK) hospitals were not fully examined prior to referral; we therefore designed a larger quality improvement report with 80% power to detect a 10% increase in tendon hammer or ophthalmoscope use following an educational intervention. In-patients referred to neurology over a four month period (in hospitals in the UK (10), Jordan (1), Sweden (2), and the United Arab Emirates (1)) were asked whether they recalled being examined with a tendon hammer (T), ophthalmoscope (O), and stethoscope (S) since admission. The results were disseminated to local medical teams using various techniques (including Grand Round presentations, email, posters, discounted equipment). Data were then collected for a further four month period post-intervention. Pre-intervention and post-intervention data were available for 11 centres with 407 & 391 patients in each arm respectively. Median age of patients was 51 (range 13-100) and 49 (range 16-95) years respectively, with 44.72% and 44.76% being male in each group. 264 patients (64.86%) recalled being examined with a tendon hammer in the pre-intervention arm, which significantly improved to 298 (76.21%) (p<0.001). Only 119 patients (29.24%) recollected examination with an ophthalmoscope pre-intervention, which significantly improved to 149 (38.11%)(p=0.009). The majority of patients (321 (78.87%)) pre-intervention recalled examination with a stethoscope, which significantly improved to 330 (84.4%) to a lesser extent (p=0.045). Results indicate that most patients are not fully examined prior to neurology referral yet a simple assessment score and educational intervention can improve recall of elements of the neurological examination and thus the likelihood of patients being examined neurologically. This is the largest and - to our knowledge - only study to assess this issue. This has implications for national neurological educators.
|
|
| 5. |
- Banerjee, Gargi, et al.
(författare)
-
Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy.
- 2020
-
Ingår i: Journal of Alzheimer's disease : JAD. - 1875-8908. ; 74:4, s. 1189-1201
-
Tidskriftsartikel (refereegranskat)abstract
- There is limited data on cerebrospinal fluid (CSF) biomarkers in sporadic amyloid-β (Aβ) cerebral amyloid angiopathy (CAA).To determine the profile of biomarkers relevant to neurodegenerative disease in the CSF of patients with CAA.We performed a detailed comparison of CSF markers, comparing patients with CAA, Alzheimer's disease (AD), and control (CS) participants, recruited from the Biomarkers and Outcomes in CAA (BOCAA) study, and a Specialist Cognitive Disorders Service.We included 10 CAA, 20 AD, and 10 CS participants (mean age 68.6, 62.5, and 62.2 years, respectively). In unadjusted analyses, CAA patients had a distinctive CSF biomarker profile, with significantly lower (p<0.01) median concentrations of Aβ38, Aβ40, Aβ42, sAβPPα, and sAβPPβ. CAA patients had higher levels of neurofilament light (NFL) than the CS group (p<0.01), but there were no significant differences in CSF total tau, phospho-tau, soluble TREM2 (sTREM2), or neurogranin concentrations. AD patients had higher total tau, phospho-tau and neurogranin than CS and CAA groups. In age-adjusted analyses, differences for the CAA group remained for Aβ38, Aβ40, Aβ42, and sAβPPβ. Comparing CAA patients with amyloid-PET positive (n=5) and negative (n=5) scans, PET positive individuals had lower (p<0.05) concentrations of CSF Aβ42, and higher total tau, phospho-tau, NFL, and neurogranin concentrations, consistent with an "AD-like" profile.CAA has a characteristic biomarker profile, suggestive of a global, rather than selective, accumulation of amyloid species; we also provide evidence of different phenotypes according to amyloid-PET positivity. Further replication and validation of these preliminary findings in larger cohorts is needed.
|
|
| 6. |
- Benjamin, L. A., et al.
(författare)
-
Antiphospholipid antibodies and neurological manifestations in acute COVID-19: A single-centre cross-sectional study
- 2021
-
Ingår i: Eclinicalmedicine. - : Elsevier BV. - 2589-5370. ; 39
-
Tidskriftsartikel (refereegranskat)abstract
- Background: A high prevalence of antiphospholipid antibodies has been reported in case series of patients with neurological manifestations and COVID-19; however, the pathogenicity of antiphospholipid antibodies in COVID-19 neurology remains unclear. Methods: This single-centre cross-sectional study included 106 adult patients: 30 hospitalised COVID-neurological cases, 47 non-neurological COVID-hospitalised controls, and 29 COVID-non-hospitalised controls, recruited between March and July 2020. We evaluated nine antiphospholipid antibodies: anticardiolipin antibodies [aCL] IgA, IgM, IgG; anti-beta-2 glycoprotein-1 [a beta(2)GPI] IgA, IgM, IgG; anti-phosphatidylserine/prothrombin [aPS/PT] IgM, IgG; and anti-domain I b2GPI (aD1 beta 2GPI) IgG. Findings: There was a high prevalence of antiphospholipid antibodies in the COVID-neurological (73.3%) and non-neurological COVID-hospitalised controls (76.6%) in contrast to the COVID-non-hospitalised controls (48.2%). aPS/PT IgG titres were significantly higher in the COVID-neurological group compared to both control groups (p < 0.001). Moderate-high titre of aPS/PT IgG was found in 2 out of 3 (67%) patients with acute disseminated encephalomyelitis [ADEM]. aPS/PT IgG titres negatively correlated with oxygen requirement (FiO(2) R=-0.15 p = 0.040) and was associated with venous thromboembolism (p = 0.043). In contrast, aCL IgA (p < 0.001) and IgG (p < 0.001) was associated with non-neurological COVID-hospitalised controls compared to the other groups and correlated positively with D-dimer and creatinine but negatively with FiO(2). Interpretation: Our findings show that aPS/PT IgG is associated with COVID-19-associated ADEM. In contrast, aCL IgA and IgG are seen much more frequently in non-neurological hospitalised patients with COVID-19. Characterisation of antiphospholipid antibody persistence and potential longitudinal clinical impact are required to guide appropriate management. (C) 2021 The Author(s). Published by Elsevier Ltd.
|
|
| 7. |
- Clark, Kristen D., et al.
(författare)
-
State-Level Policy Environments, Discrimination, and Victimization among Sexual and Gender Minority People
- 2022
-
Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 19:16
-
Tidskriftsartikel (refereegranskat)abstract
- Legislation has been passed in some states to reduce discrimination and victimization toward sexual and gender minority people (SGM; people who are not solely heterosexual and/or whose gender identity is not equal to what is socially associated with sex assigned at birth). The purpose of these analyses is to test whether state-level policy environments are associated with past-year discrimination and victimization among SGM people. Cross-sectional data from The Population Research in Identity and Disparities for Equality (PRIDE) Study annual questionnaire (collected 2018–2019), a national study of the health of SGM adults in the USA, were used for these analyses. Measures included related to discrimination, victimization, and demographic characteristics. State-level policy environments were measured using data from the Movement Advancement Project. Logistic regression analyses evaluated state-level policy environment scores and past-year discrimination and victimization among gender identity categories. In this sample, 7044 people (gender minority n = 2530) were included. Cisgender sexual minority (odds ratio [OR] = 1.007, p = 0.041) and the gender expansive subgroup of gender minority people (OR = 1.010, p = 0.047) in states with more protective policy environments had greater odds of discrimination. The gender expansive subgroup was found to have greater odds of victimization in states with more protective policy environments (OR = 1.003, p < 0.05). There was no relationship between state-level policy environments and victimization among any other study groups. SGM people may experience increased risk for discrimination and victimization despite legislative protections, posing continued risks for poor health outcomes and marginalization. Evaluation of factors (e.g., implementation strategies, systems of accountability) that influence the effectiveness of state-level polices on the reported experiences of discrimination and victimization among SGM people is needed.
|
|
| 8. |
- Cunningham, Emma L, et al.
(författare)
-
CSF Beta-amyloid 1-42 Concentration Predicts Delirium Following Elective Arthroplasty Surgery in an Observational Cohort Study.
- 2019
-
Ingår i: Annals of surgery. - 1528-1140. ; 269:6, s. 1200-1205
-
Tidskriftsartikel (refereegranskat)abstract
- To test the hypothesis that APOE ε4 status and cerebrospinal fluid (CSF) Aβ42, T-tau and P-tau would independently predict the risk of postoperative delirium.Delirium following surgery is common and associated with adverse outcomes. Age and cognitive impairment are consistent risk factors for postoperative delirium.This observational cohort study recruited 282 participants aged 65 years or older, without a diagnosis of dementia, admitted for primary elective hip or knee arthroplasty. Cognitive tests were undertaken preoperatively, blood and CSF were sampled at the time of spinal anesthesia, and participants were assessed daily postoperatively for delirium.Increasing age (P = 0.04), preoperative comorbidity (P = 0.03), type of surgery (P = 0.05), intravenous opioid usage (P = 0.04), and low CSF Aβ42 (P < 0.01) were independent predictors of postoperative delirium.This study is the first to show an independent association between CSF Aβ42 and delirium incidence in an elective surgical population, suggesting that postoperative delirium may indicate incipient Alzheimer disease.
|
|
| 9. |
- Keshavan, Ashvini, et al.
(författare)
-
CSF biomarkers for dementia.
- 2022
-
Ingår i: Practical neurology. - : BMJ. - 1474-7766 .- 1474-7758. ; 22:4, s. 285-294
-
Tidskriftsartikel (refereegranskat)abstract
- Although cerebrospinal fluid (CSF) biomarker testing is incorporated into some current guidelines for the diagnosis of dementia (such as England's National Institute for Health and Care Excellence (NICE)), it is not widely accessible for most patients for whom biomarkers could potentially change management. Here we share our experience of running a clinical cognitive CSF service and discuss recent developments in laboratory testing including the use of the CSF amyloid-β 42/40 ratio and automated assay platforms. We highlight the importance of collaborative working between clinicians and laboratory staff, of preanalytical sample handling, and discuss the various factors influencing interpretation of the results in appropriate clinical contexts. We advocate for broadening access to CSF biomarkers by sharing clinical expertise, protocols and interpretation with colleagues working in psychiatry and elderly care, especially when access to CSF may be part of a pathway to disease-modifying treatments for Alzheimer's disease and other forms of dementia.
|
|
| 10. |
- Mattsson, Niklas, 1979, et al.
(författare)
-
Reference measurement procedures for Alzheimer's disease cerebrospinal fluid biomarkers: definitions and approaches with focus on amyloid β42.
- 2012
-
Ingår i: Biomarkers in medicine. - : Future Medicine Ltd. - 1752-0371 .- 1752-0363. ; 6:4, s. 409-17
-
Tidskriftsartikel (refereegranskat)abstract
- Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) are increasingly used in clinical settings, research and drug trials. However, their broad-scale use on different technology platforms is hampered by the lack of standardization at the level of sample handling, determination of concentrations of analytes and the absence of well-defined performance criteria for in vitro diagnostic or companion diagnostic assays, which influences the apparent concentration of the analytes measured and the subsequent interpretation of the data. There is a need for harmonization of CSF AD biomarker assays that can reliably, across centers, quantitate CSF biomarkers with high analytical precision, selectivity and stability over long time periods. In this position paper, we discuss reference procedures for the measurement of CSF AD biomarkers, especially amyloid β42 and tau. We describe possible technical approaches, focusing on a selected reaction monitoring mass spectrometry assay as a candidate reference method for quantification of CSF amyloid β42.
|
|
