Cerebrospinal Fluid Brain Injury Biomarkers in Children: A Multicenter Study

Shahim, Pashtun; Darín, Niklas; Andréasson, Ulf; Blennow, Kaj; Jennions, Elizabeth; Lundgren, Johan; Månsson, Jan‐Eric; Naess, K; Törnhage, Carl-Johan; Zetterberg, Henrik; Mattsson, Niklas

doi:10.1016/j.pediatrneurol.2013.02.015

Cited by 35 publications

(39 citation statements)

References 36 publications

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“…T-tau concentrations were significantly elevated, with decreasing concentrations by increasing age. These findings are consistent with Shahim et al (7) who demonstrated increased concentrations of T-tau, GFAp and NFLp, in children, aged 0-16 years, with different CNS disorders, including lysosomal storage disorders. Numerous mechanisms including neuronal damage can cause disturbance of T-tau metabolism (7).…”

Section: Discussionsupporting

confidence: 92%

Alpha‐mannosidosis: characterization of CNS pathology and correlation between CNS pathology and cognitive function

et al. 2015

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Alpha-mannosidosis (AM) (OMIM 248500) is a rare lysosomal storage disease. The understanding of the central nervous system (CNS) pathology is limited. This study is the first describing the CNS pathology and the correlation between the CNS pathology and intellectual disabilities in human AM. Thirty-four patients, aged 6-35 years, with AM were included. Data from 13 healthy controls were included in the analysis of the magnetic resonance spectroscopy (MRS). Measurements of CNS neurodegeneration biomarkers in cerebrospinal fluid (CSF), CSF-oligosaccharides, and performance of cerebral magnetic resonance imaging (MRI) and MRS were carried out. On MRI, 5 of 10 patients had occipital white matter (WM) signal abnormalities, and 6 of 10 patients had age-inappropriate myelination. MRS demonstrated significantly elevated mannose complex in gray matter and WM. We found elevated concentrations of tau-protein, glial fibrillary acidic protein and neurofilament light protein in 97 patients, 74% and 41% of CSF samples, respectively. A negative correlation between CSF-biomarkers and cognitive function and CSF-oligosaccharides and cognitive function was found. The combination of MRS/MRI changes, elevated concentrations of CSF-biomarkers and CSF-oligosaccharides suggests gliosis and reduced myelination, as part of the CNS pathology in AM. Our data demonstrate early neuropathological changes, which may be taken into consideration when planning initiation of treatment.

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Section: Discussionsupporting

confidence: 92%

Alpha‐mannosidosis: characterization of CNS pathology and correlation between CNS pathology and cognitive function

et al. 2015

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“…TBI involves a primary injury, causing in the release of intracellular contents as a result of the disruption of cell membranes and the blood-brain barrier, as well as a secondary injury, which involves a cascade of molecular events resulting in cell death (19). As a part of this cascade, certain biomarkers promote cell survival (NSE and S100B), synaptic regeneration (sNCAM), and immune response in the microcirculation (sE-selectin) eventually promoting repair mechanisms (31)(32)(33)(34)(35).…”

Section: Discussionmentioning

confidence: 99%

“…There are a number of different classes of serum biomarkers that are being investigated as potential biomarkers in pediatric TBI. We measured NSE, phosphorylated neurofilament heavy protein and S100B because they have previously been shown to be associated with global neurological function and Pediatric Critical Care Medicine www.pccmjournal.org 3 cognitive outcomes in children with TBI (21,(27)(28)(29)(30)(31). There may also be biological rationale for the measurement of these biomarkers based on cell death, regeneration, and repair mechanisms.…”

Section: Serum Biomarkersmentioning

confidence: 99%

Serum Biomarkers Help Predict Attention Problems in Critically Ill Children With Traumatic Brain Injury

Wilkinson

Simić

Frndova

et al. 2016

Pediatric Critical Care Medicine

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“…CSF T-tau levels were also increased in patients with lysosomal diseases in another survey of pediatric neurological diseases (Shahim et al, 2013). There was no association of CSF T-tau levels with disease severity, but patients with longer disease duration (N6 years) had lower CSF T-tau levels (Mattsson et al, 2011), which may indicate a less intense neurodegenerative process in this subgroup.…”

Section: Interestingly Although Purkinje Cells Are the Most Prominenmentioning

confidence: 92%

Bidirectional links between Alzheimer's disease and Niemann–Pick type C disease

Malnar

Hečimović

Mattsson

et al. 2014

Neurobiology of Disease

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Alzheimer's disease (AD) and Niemann-Pick type C (NPC) disease are progressive neurodegenerative diseases with very different epidemiology and etiology. AD is a common cause of dementia with a complex polyfactorial etiology, including both genetic and environmental risk factors, while NPC is a very rare autosomal recessive disease. However, the diseases share some disease-related molecular pathways, including abnormal cholesterol metabolism, and involvement of amyloid-β (Aβ) and tau pathology. Here we review recent studies on these pathological traits, focusing on studies of Aβ and tau pathology in NPC, and the importance of the NPC1 gene in AD. Further studies of similarities and differences between AD and NPC may be useful to increase the understanding of both these devastating neurological diseases.

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Cerebrospinal Fluid Brain Injury Biomarkers in Children: A Multicenter Study

Cited by 35 publications

References 36 publications

Alpha‐mannosidosis: characterization of CNS pathology and correlation between CNS pathology and cognitive function

Alpha‐mannosidosis: characterization of CNS pathology and correlation between CNS pathology and cognitive function

Serum Biomarkers Help Predict Attention Problems in Critically Ill Children With Traumatic Brain Injury

Bidirectional links between Alzheimer's disease and Niemann–Pick type C disease

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