| 1. |
- Bridel, Claire, et al.
(författare)
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Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurology : A Systematic Review and Meta-analysis
- 2019
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Ingår i: JAMA Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:9, s. 1035-1048
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Forskningsöversikt (refereegranskat)abstract
- Importance Neurofilament light protein (NfL) is elevated in cerebrospinal fluid (CSF) of a number of neurological conditions compared with healthy controls (HC) and is a candidate biomarker for neuroaxonal damage. The influence of age and sex is largely unknown, and levels across neurological disorders have not been compared systematically to date.Objectives To assess the associations of age, sex, and diagnosis with NfL in CSF (cNfL) and to evaluate its potential in discriminating clinically similar conditions.Data Sources PubMed was searched for studies published between January 1, 2006, and January 1, 2016, reporting cNfL levels (using the search terms neurofilament light and cerebrospinal fluid) in neurological or psychiatric conditions and/or in HC.Study Selection Studies reporting NfL levels measured in lumbar CSF using a commercially available immunoassay, as well as age and sex.Data Extraction and Synthesis Individual-level data were requested from study authors. Generalized linear mixed-effects models were used to estimate the fixed effects of age, sex, and diagnosis on log-transformed NfL levels, with cohort of origin modeled as a random intercept.Main Outcome and Measure The cNfL levels adjusted for age and sex across diagnoses.Results Data were collected for 10 059 individuals (mean [SD] age, 59.7 [18.8] years; 54.1% female). Thirty-five diagnoses were identified, including inflammatory diseases of the central nervous system (n = 2795), dementias and predementia stages (n = 4284), parkinsonian disorders (n = 984), and HC (n = 1332). The cNfL was elevated compared with HC in a majority of neurological conditions studied. Highest levels were observed in cognitively impaired HIV-positive individuals (iHIV), amyotrophic lateral sclerosis, frontotemporal dementia (FTD), and Huntington disease. In 33.3% of diagnoses, including HC, multiple sclerosis, Alzheimer disease (AD), and Parkinson disease (PD), cNfL was higher in men than women. The cNfL increased with age in HC and a majority of neurological conditions, although the association was strongest in HC. The cNfL overlapped in most clinically similar diagnoses except for FTD and iHIV, which segregated from other dementias, and PD, which segregated from atypical parkinsonian syndromes.Conclusions and Relevance These data support the use of cNfL as a biomarker of neuroaxonal damage and indicate that age-specific and sex-specific (and in some cases disease-specific) reference values may be needed. The cNfL has potential to assist the differentiation of FTD from AD and PD from atypical parkinsonian syndromes.
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| 2. |
- Burkill, Sarah, et al.
(författare)
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Pharmacological Treatments Preceding Diagnosis Of Progressive Multifocal Leukencephalopathy
- 2016
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Ingår i: Pharmacoepidemiology and Drug Safety. - : Wiley-Blackwell. - 1053-8569 .- 1099-1557. ; 25:Suppl. 3, s. 496-497
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Progressive multifocal leukencephalopathy (PML) is a rare, often fatal viral disease, which affects the white matter of the brain. It is caused by John Cunningham (JC) polyomavirus, which is present in most people and is usually harm-less. For immunocompromised persons, such as those who are taking immunosuppressive treatments, the risk of JC virus causing PML is increased, although still rare. As PML diagnosis is not always accurate, epidemiology of PML, including the true incidence and patient characteristics, is incompletely described.Objectives: To identify pharmacological treatments preceding diagnosis of definitive, probable and possible PML, after excluding incorrect PML diagnoses by medical record review.Methods: Patients with a PML diagnosis in Sweden between 1988 and 2013 were identified through the Patient register using ICD 9 code 046D and ICD 10code A81.2 (n = 281). Medical records were reviewed and information on clinical characteristics and pharmacological treatments were collected. Each of the diagnoses was determined as definite PML, possible PML, probable PML or non-PML based on the consensus statement for the AAN neuroinfectious disease section published in 2013. (PMCID: 3662270).Results: Medical records for 251 patients (89%) were available and examined. In total, 84 (33%) of the 251 PML diagnoses were confirmed. For those with a record of being exposed to immunosuppressant drugs, 60 (65%) of the 92 records were confirmed as being definite PML. Among 12 patients exposed to rituximab 11 (92%) had definite and 1 (8%) had probable PML. For the 9 natalizumab users, 8 (89%) had definite PML and 1 (11%) was diagnosed incorrectly.Conclusions: A substantial proportion of PML diagnoses recorded in Sweden are incorrect, however amongst those exposed to immunosuppressants such as rituximab and natalizumab the majority of diagnoses are correct. Assessing immunosuppressive drug history could be an important part of the diagnostic processes for PML.
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| 3. |
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| 4. |
- Iacobaeus, Ellen, et al.
(författare)
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The national incidence of PML in Sweden, 1988-2013
- 2018
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Ingår i: Neurology. - : Lippincott Williams & Wilkins. - 0028-3878 .- 1526-632X. ; 90:6, s. E498-E506
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate the incidence of progressive multifocal leukoencephalopathy (PML) and patient characteristics in Sweden between 1988 and 2013.Methods: All PML diagnoses in Sweden between 1988 and 2013 were identified in the National Patient Register. Information to validate the diagnosis and patient characteristics was obtained from medical records.Results: Medical record review classified 108 out of 250 patients (43%) as definite (n = 84), probable (n = 4), or possible (n = 20) PML according to diagnostic criteria. Accurate diagnoses were more common in records obtained from neurology departments (82% of patients seen in neurology departments) compared with other departments (31%) (p < 0.001). The incidence of PML increased from a largely stable level at 0.026 (95% confidence interval [CI] 0.021-0.031) per 100,000 individuals per year during 1988-2010 to 0.11 (95% CI 083-0.137) during 2011-2013, during which time there was a notable increase (p < 0.001). Hematologic malignancies (n = 34), HIV/AIDS (n = 33), and autoimmune disease (n = 23) were the most common underlying diseases. Treatment with a monoclonal antibody prior to PML diagnosis was identified in 26 patients.Conclusion: An increased incidence of PML in Sweden was observed and coincided with the prior use of monoclonal antibody treatment. The high level of misdiagnosis emphasizes the importance of immediate contact with a neurology center upon suspicion of PML.
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| 5. |
- Yeung, Maggie S. Y., et al.
(författare)
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Dynamics of oligodendrocyte generation in multiple sclerosis
- 2019
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 566:7745, s. 538-
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Tidskriftsartikel (refereegranskat)abstract
- Oligodendrocytes wrap nerve fibres in the central nervous system with layers of specialized cell membrane to form myelin sheaths(1). Myelin is destroyed by the immune system in multiple sclerosis, but myelin is thought to regenerate and neurological function can be recovered. In animal models of demyelinating disease, myelin is regenerated by newly generated oligodendrocytes, and remaining mature oligodendrocytes do not seem to contribute to this process(2-4). Given the major differences in the dynamics of oligodendrocyte generation and adaptive myelination between rodents and humans(5-9), it is not clear how well experimental animal models reflect the situation in multiple sclerosis. Here, by measuring the integration of C-14 derived from nuclear testing in genomic DNA(10), we assess the dynamics of oligodendrocyte generation in patients with multiple sclerosis. The generation of new oligodendrocytes was increased several-fold in normal-appearing white matter in a subset of individuals with very aggressive multiple sclerosis, but not in most subjects with the disease, demonstrating an inherent potential to substantially increase oligodendrocyte generation that fails in most patients. Oligodendrocytes in shadow plaques-thinly myelinated lesions that are thought to represent remyelinated areas-were old in patients with multiple sclerosis. The absence of new oligodendrocytes in shadow plaques suggests that remyelination of lesions occurs transiently or not at all, or that myelin is regenerated by pre-existing, and not new, oligodendrocytes in multiple sclerosis. We report unexpected oligodendrocyte generation dynamics in multiple sclerosis, and this should guide the use of current, and the development of new, therapies.
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