Myelin Basic Protein In Cerebrospinal Fluid Research Articles

Discrepancy in clinical and laboratory profiles of NMOSD patients between AQP4 antibody positive and negative: can NMOSD be diagnosed without AQP4 antibody?

AQP4-IgG has been considered as the pathogenic factor leading to NMOSD. However, about 20-30% of patients lack AQP4-IgG. So far, all therapeutic medicines are ineffective for NMOSD patients without AQP4 IgG. Thus AQP4-IgG is the pathogenic factor of NMOSD has been suspected and challenged. In addition, lack of efficacy of immunotherapy in NMOSD without AQP4 IgG has been a serious problem in the neurology. Identifying the clinical and laboratory characteristics and diversities between NMOSD patients with and without AQP4-IgG can be helpful to further explore the pathogenesis of NMOSD and guide clinical treatment. This is a single-centre retrospective study in The First Hospital of Jilin University, China including 92 patients diagnosed as NMOSD from January 2013 to January 2015. The characteristics of clinic, blood, cerebrospinal fluid (CSF), and image between AQP4-IgG negative (AQP4-IgG-) and AQP4-IgG positive (AQP4-IgG+) NMOSDs were compared. Our results showed that in the AQP4-IgG+ group, the ratio of women to men was 5.55, while in AQP4-IgG- group was 1.54 (P = 0.0092). In the AQP4-IgG+ patients, the expanded disability status scale (EDSS) was from 0 to 8.5, with an average of 5.550 ± 0.25, and the AQP4-IgG- patients had the EDSS score from 0 to 9, with an average of 4.032 ± 0.36 (P = 0.0006), which mainly affected movement system (P < 0.05) and superficial sensory impairment (P < 0.05). In the AQP4-IgG+ group, the blood brain barrier (BBB) permeability (P = 0.0210) and myelin basic protein (MBP) were increased (P = 0.0310) when compared to AQP4-IgG- group. Higher level IL-17 was seen in AQP4-IgG+ group than AQP4-IgG- group (P= 0.0066). Our results demonstrated that the NMOSD with AQP4-IgG more likely occurred in women and presented more severe clinical symptoms as well as significant BBB damage and increased MBP and IL-17 in CSF and blood, respectively compared with NMOSD without AQP4-IgG group. The differences in clinical and laboratory profiles between NMOSD with and without AQP4-IgG indicate the heterogeneity of NMOSD, in which AQP4-IgG may not be the only pathogenic molecule. It is necessary to find more pathogenic factors and to explore the new pathogenesis of NMOSD and therapeutic methods in the future.

Myelin basic protein and index for neuro-Behçet's disease

Neuro-Behçet's disease (NBD) contributes to poor prognosis in BD patients which lacks reliable laboratory biomarkers in assessing intrathecal injury. This study aimed to determine the diagnostic value of myelin basic protein (MBP), an indicator of central nervous system (CNS) myelin damage, in NBD patients and disease controls. Paired samples of cerebrospinal fluid (CSF) and serum MBP were measured using ELISA, while IgG and Alb were routinely examined before the MBP index was developed. CSF and serum MBP in NBD were significantly higher than in NIND, which could distinguish NBD from NIND with a specificity exceeding 90%, moreover, they could also be excellent discriminators for acute NBD and chronic progressive ones. We found positive linkage between MBP index and IgG index. Serial MBP monitoring confirmed serum MBP's sensitive response to disease recurrences and drug effects, whereas MBP index suggests relapses prior to clinical symptoms. MBP has high diagnostic yield for NBD with demyelination and identifies CNS pathogenic processes before imaging or clinical diagnosis.

Estimation of Myelin Basic Protein Levels in Natural Cases of Canine Distemper Encephalomyelitis

Background: Canine distemper virus (CDV) affects both white and grey matter in the central nervous system (CNS). It causes demyelination of white matter tracts, which releases myelin basic protein (MBP) into the cerebrospinal fluid (CSF). MBP levels in CSF could therefore indirectly indicate the extent of white matter damage. The objective of this study was to determine MBP levels in the CSF of dogs infected with natural cases of neurologic distemper. Methods: In this study samples from healthy dogs, clinical cases of CDV and stray dogs from in and around the institute were collected for investigation. The infection of the CNS was established by estimating the albumin quotient and, for 16 cases, by histopathology. CSF biochemical parameters were analysed for 35 sero-positive clinical cases of neurologic distemper. MBP levels in samples were estimated by quantitative ELISA. Stray dogs (6 cases) were also screened for this purpose. Result: MBP levels in CSF were significantly (p≤0.05) increased in natural cases of distemper encephalomyelitis and stray dogs relative to controls. Three of the neurologic distemper cases clinically recovered despite high MBP levels, and two stray dogs also had higher MBP concentrations. High CSF MBP may therefore not be a useful marker for predicting the outcome of neurologic distemper.

A rare case of bilateral optic neuritis and acute disseminated encephalomyelitis post mycoplasma pneumoniae infection

A case of a 4-year-old boy who developed acute disseminated encephalomyelitis (ADEM) and optic neuritis (ON) following Mycoplasma pneumoniae infection is reported. His symptoms, including excessive sleepiness, frontal headache, bilateral vision impairment, retro-auricular pain and unbalanced gait, were resolved after methylprednisolone pulse therapy, intravenous immunoglobulin (IVIG) and ciprofloxacin. Cerebrospinal fluid myelin basic protein (MBP) and Mycoplasma serology IgM were detected in our patient. This is the first report of a child with ADEM and ON associated with mastoditis caused by M. pneumoniae infection. Combined immunomodulatory therapy (pulse steroids and immunoglobulin) with anti- mycoplasma microbial therapy resulted in favorable visual recovery. Bilateral isolated optic neuritis as the first presenting feature in childhood ADEM is rare and requires proper evaluation and early therapeutic management. This case highlights the need for physician awareness of the association of mycoplasma infection with optic neuritis and ADEM.

Myelin basic protein and its diagnostic value in HIV-infected individuals with 4th clinical stage and neuroinfections

It was shown that in HIV-infected patients, pathomorphological changes in the white matter in the form of demyelinization are already observed in the early stages of the disease. The most studied marker of this process is myelin basic protein that can be detected in cerebrospinal fluid or serum immediately after acute myelin breakdown.&#x0D; The aim. To assess the diagnostic value of myelin basic protein content in serum and cerebrospinal fluid of HIV-infected individuals with 4th clinical stage and central nervous system opportunistic infections.&#x0D; Materials and methods. Using ELISA with diagnostic kit “MBP ELISA” (Ansh Labs, USA), we studied the myelin basic protein content in serum and cerebrospinal fluid of 53 HIV-infected patients with 4th clinical stage and central nervous system opportunistic infections depending on its etiology, the outcome of the diseases and according to Glasgow coma scale score. As well correlation analysis with some laboratory and clinical indicators was performed.&#x0D; Results. We found significantly increased myelin basic protein content in both cerebrospinal fluid and serum of HIV-infected patients 4th clinical stage with central nervous system opportunistic infections compared to control (p˂0.01), which indicate the presence of active demyelinization in central nervous system. The highest cerebrospinal fluid myelin basic protein was registered in patients with an unfavourable outcome of the disease, as death or residual neurologic deficit, and patients with cerebral toxoplasmosis. The cerebrospinal fluid myelin basic protein had an association with the size of white matter lesions on magnetic resonance imaging and serum myelin basic protein content.&#x0D; Conclusions. Myelin basic protein detection in cerebrospinal fluid as well as in serum can serve as an additional quantitative marker of myelin disruption, which can be used along with magnetic resonance imaging for the diagnosis improvement and prognosis of central nervous system opportunistic infections in HIV-infected individuals with 4th clinical stage

Cerebrospinal fluid myelin basic protein is elevated in multiple system atrophy

IntroductionParkinson's disease (PD) and multiple system atrophy (MSA) have overlapping symptoms, challenging an early diagnosis. Diagnostic accuracy is important because PD and MSA have a different prognosis and response to treatment. Here, we aimed to evaluate the diagnostic value of brain-specific structural proteins in cerebrospinal fluid (CSF) of PD and MSA patients, as well as their association with cognitive decline. MethodsCSF samples were collected from patients with clear signs of parkinsonism, but with uncertain diagnosis at the time of inclusion. Clinical diagnoses of PD (n = 55) and MSA (n = 22) were established after 3 and 10 years of follow-up and re-evaluated after 12 years, according to the most updated clinical criteria. CSF from controls (n = 118) was studied for comparison. Neuron-specific enolase (NSE), glial fibrillary acidic protein (GFAP), S100 calcium-binding protein B (S100B) and myelin basic protein (MBP) levels in CSF were measured using ELISA. Protein levels were also correlated with cognitive decline, i.e. worsening of the mini mental state examination (MMSE) over a period of three years. ResultsMBP concentrations were increased in MSA compared to PD and controls (p < 0.005) and could differentiate MSA and PD with high accuracy (AUC = 0.781; p < 0.001). Concentrations of MPB, GFAP and S100B, but not NSE, were significantly elevated in PD patients compared to controls (p = 0.05). None of the brain-specific structural proteins correlated with MMSE progression. ConclusionsOur results demonstrate that MBP differentiates PD from MSA at early stages of the disease, indicating that demyelination and axonal damage may already occur in early stages of MSA.

Abstract TMP26: Extracellular Vesicles and Myelin Plasticity After Cortical Injury in Non-Human Primates

Introduction: Our laboratory demonstrated that monkeys treated after cortical injury with extracellular vesicles (EVs) derived from Mesenchymal Stem Cell (MSC) had enhanced recovery compared to controls. To identify the EV-mediated neuroplastic changes involved in improved recovery, we assessed markers of myelin damage and plasticity in brain and cerebrospinal fluid (CSF) of monkeys treated with EVs or vehicle. Hypothesis: MSC derived EVs enhance behavioral plasticity by reducing the post injury cascade of myelin damage and stimulating remyelination. Methods: Monkeys were given a unilateral cortical injury in the hand representation of M1. EVs were delivered IV 24 hours and 14 days later. Monkeys were tested on motor tasks for 14 weeks, and brains were harvested at completion. To quantify myelinated axons, we first used Spectral Confocal Reflectance (SCoRe) microscopy. To assess myelin damage, we measured accumulation of Myelin Basic Protein (MBP) in CSF from 24 hours to 14 weeks after injury. To assess myelin related gene expression changes, we used qPCR to assess MBP, BCAS1 as a marker of oligodendroglia engaged in new myelination, and Myelin Regulatory Factor (MyRF) a marker of oligodendrocyte regulation and differentiation. Additionally, we used IHC and stereology to quantify densities of BCAS1 and CC1 positive oligodendroglia. Results: Preliminary results show that EV treatment is associated with greater density of myelinated axons. In addition, longitudinal MBP levels in CSF gradually declined over 6 weeks, suggesting that EV treatment limited ongoing damage . PCR studies of perilesional brain tissue demonstrated a 4-fold increase in MyRF, as well as a 1.5-fold increase for BCAS1 and MBP in EV-treated monkeys relative to vehicle. Finally, increased densities of CC1+ and BCAS1+ cells approached significance in EV treated subjects. Conclusions and Future Directions: Our data suggests that MSC-EVs likely reduce the post injury cascade of myelin damage and promote remyelination, thus enhancing plasticity. (Supported by R21-NS102991 &amp; R21-NS111174).

Sudden onset of sleep caused by hypothalamic infarction: a case report

BackgroundHypothalamic lesions, such as tumors and demyelinating diseases, reportedly cause abnormal sleepiness. However, stroke involving the hypothalamus has rarely been described. Here, we report a patient with infarction restricted to the hypothalamus who presented with sudden onset of sleep.Case presentationA 42-year-old woman with a history of migraine without aura presented with irresistible sleepiness and developed several episodes of sudden onset of sleep. Neurological examinations were unremarkable except for partial left Horner syndrome. Brain magnetic resonance imaging (MRI) revealed a high-intensity lesion restricted to the left hypothalamus on diffusion-weighted and fluid-attenuated inversion recovery MRI images. Cerebrospinal fluid (CSF) orexin-A levels obtained on hospital day 3 after her sleepiness had resolved were normal (337 pg/mL; normal > 200 pg/mL). Serum anti-nuclear and anti-aquaporin 4 (AQP4) antibodies and CSF myelin basic protein and oligoclonal band were negative. A small hypothalamic infarction was suspected, and the patient was treated with intravenous edaravone and argatroban, as well as oral clopidogrel. Three months later, there had been no clinical relapse, and the hypothalamic lesion had almost disappeared on follow-up MRI. No new lesion suggestive of demyelinating disease or tumor was observed.ConclusionHypothalamic stroke should be considered a cause of sudden onset of sleep.

Guidelines for the Management of Pediatric Severe Traumatic Brain Injury, Third Edition: Update of the Brain Trauma Foundation Guidelines.

Severe Traumatic Brain Injury in Infants, Children, and Adolescents in 2019: Some Overdue Progress, Many Remaining Questions, and Exciting Ongoing Work in the Field of Traumatic Brain Injury ResearchIn this Supplement to Pediatric Critical Care Medicine, we are pleased to present the Third Edition o

Longstanding psychological stress in relation to biomarkers of neuronal dysfunction in cerebrospinal fluid: a 25-year follow-up study in women

Longstanding psychological stress has been associated with increased risk of neurodegenerative disorders, such as dementia and Alzheimer’s disease. In a prospective population study of women (n = 81), we tested if midlife stress (mean age 49 years) was associated with late-life biomarkers of neurodegeneration in cerebrospinal fluid (CSF) (mean age 74 years) in linear regression models. It was found that women who report of stress at baseline (n = 20) had higher levels of CSF visinin-like protein-1 (VILIP-1) (age adjusted β = 0.113, p = 0.017) and CSF myelin basic protein (β = 0.060, p = 0.030) compared with women without midlife stress (n = 61). There was also a trend observed for higher CSF neurofilament light (β = 0.133, p = 0.056). In addition, longer periods of stress (i.e., stress at 2–3 midlife examinations) were associated with higher levels of CSF VILIP-1. The results suggest that longstanding stress might be associated with neurodegenerative processes in the brain, as CSF VILIP-1 is an unspecific marker for neuronal injury and CSF myelin basic protein reflects neuroaxonal demyelination.

Abstract TP141: Mesenchymal Stem Cell Derived Exosomes as a Modulator of Neuroinflammation Following Cortical Injury

In this study, we tested Mesenchymal Stem Cell derived exosomes as a therapeutic to enhance recovery in our established nonhuman primate model of cortical injury. After pretraining monkeys on fine motor hand task,10 aged female monkeys were randomly assigned to an exosome treatment group (n=5) or a vehicle control (PBS) group (n=5). Then, in a single surgery, monkeys received a lesion in the hand representation of M1. One day and 14 days after injury, monkeys were given 4x10 11 exosomes/kg or PBS intravenously. Fifteen days after surgery, motor assessments were resumed for 12 weeks. The five treated monkeys all returned to pre-operative latencies to retrieve on motor tasks while none of the control monkeys returned to pre-operative latencies. To assess recovery mechanisms, cerebrospinal fluid (CSF) collected across the post-injury recovery period and terminal brain tissue were analyzed for markers of neuroinflammation. Preliminary ELISA results in both groups showed a trend towards increased Myelin Basic Protein (MBP) in CSF 24 hours after cortical injury followed by a gradual decline over 6 weeks. Interestingly, MBP levels declined more rapidly in exosome-treated animals, suggesting a potential reduction in damage. Scholl analysis of microglia branching in perilesional grey matter showed that exosomes increased ramification length, branching complexity, and convex hull 3D coverage volume. These findings suggest an increase in the surveying capacity of microglia in treated monkeys that may serve to promote repair after injury. Further, optical density analyses of microglial markers revealed a lower expression in treated monkeys of IBA1/P2RY12 and the MHCII antigen-presenting marker, LN3. This is consistent with decreased microglial activation associated with exosome treatment. These results provide evidence for the translational potential of exosomes as a treatment for human stroke.

Diagnostic significance of the determination of myelin basic protein in cerebrospinal fluid in HIV-associated neurological diseases.

48 patients aged from 21 to 54 years, infected with human immunodeficiency virus (HIV) and presence of diseases of the central nervous system (CNS) were examined. CNS diseases included cerebral tuberculosis, viral encephalitis (caused by Epstein-Barr Virus (EBV), cytomegalovirus (CMV), herpes simplex virus (HSV)), encephalitis of unspecified etiology, cerebral toxoplasmosis, fungal meningitis. 29 (60.4%) of the patients were discharged from the hospital with a clinical improvement, and 19 (39.6%) of the patients died as a result of CNS disease. Significant differences in the content of the myelin basic protein (MBP) in the cerebrospinal fluid (CSF), depending on the outcome of the disease, were determined. The Median of MBP in deceased patients was 2.9 times higher than in the survived patients - 4.00 (1.90-7.70) ng/ml vs. 1.40 (0.99-2.00) ng/ml (p=0.002 U). An inverse correlation between the content of MBP in the CSF and the time from the determination of the HIV status to the manifestation of neurologic symptoms (rs=-0.30, p&lt;0.05) was found. According to the results of the ROC analysis, the high risk of unfavorable course of HIV-associated CNS diseases is predicted when the concentration of MBP in the cerebrospinal fluid increases by more than 2 ng/ml (68.4% sensitivity, 75.9% specificity, 72.9% accuracy). The highest level of this protein was observed in patients with fungal lesions of the central nervous system (6.6 (1.9-7.8) ng/ml), and the lowest MBP level – in the group of patients with unspecified encephalitis (0.99 (0.9-1.1) ng/ml), which correlated to more favorable outcomes of the disease. The MBP in cerebrospinal fluid can be an important diagnostic and prognostic marker of HIV-associated neurological diseases.

Defining active progressive multiple sclerosis

Background: It is unknown whether disease activity according to consensus criteria (magnetic resonance imaging activity or clinical relapses) associate with cerebrospinal fluid (CSF) changes in progressive multiple sclerosis (MS). Objective: To compare CSF biomarkers in active and inactive progressive MS according to consensus criteria. Methods: Neurofilament light chain (NFL), myelin basic protein (MBP), IgG-index, chitinase-3-like-1 (CHI3L1), matrix metalloproteinase-9 (MMP-9), chemokine CXCL13, terminal complement complex, leukocyte counts and nitric oxide metabolites were measured in primary (n = 26) and secondary progressive MS (n = 26) and healthy controls (n = 24). Results: Progressive MS patients had higher CSF cell counts, IgG-index, CHI3L1, MMP-9, CXCL13, NFL and MBP concentrations. Active patients were younger and had higher NFL, CXCL13 and MMP-9 concentrations than inactive patients. Patients with active disease according to consensus criteria or detectable CXCL13 or MMP-9 in CSF were defined as having combined active progressive MS. These patients had increased CSF cell counts, IgG-index and MBP, NFL and CHI3L1 concentrations. Combined inactive patients only had increased IgG-index and MBP concentrations. Conclusion: Patients with combined active progressive MS show evidence of inflammation, demyelination and neuronal/axonal damage, whereas the remaining patients mainly show evidence of active demyelination. This challenges the idea that neurodegeneration independent of inflammation is crucial in disease progression.

Is myelin basic protein a potential biomarker of brain cancer?

Myelin basic protein is a potential biomarker for the central nervous system diseases in which the myelin sheath is destroyed. Using pseudo-selected reaction monitoring and the method of standard additions, we have measured the myelin basic protein level in the cerebrospinal fluid of patients with neurotrauma (n = 6), chronic neurodegenerative diseases (n = 2) and brain cancer (n = 5). Myelin basic protein was detected only in four out of five cerebrospinal fluid samples of patients with brain cancer. The cerebrospinal fluid myelin basic protein level ranged from 3.7 to 8.8 ng ml-1. We suggest that monitoring of myelin basic protein in cerebrospinal fluid can serve as a diagnostic test for the brain cancer.

Altered white matter metabolism in delayed neurologic sequelae after carbon monoxide poisoning: A proton magnetic resonance spectroscopic study

Proton magnetic resonance spectroscopy (1H-MRS) was recently used to examine altered metabolism in the white matter (WM) of patients experiencing carbon monoxide (CO) poisoning; however, only a small number of patients with delayed neurologic sequelae (DNS) were analyzed. We aimed to detect altered metabolism in the WM of patients with DNS using 1H-MRS; to explore its clinical relevance in the management of patients experiencing CO poisoning. Patients experiencing acute CO poisoning underwent 1H-MRS and cerebrospinal fluid (CSF) examination within 1week and at 1month after acute poisoning. Metabolites including choline-containing compounds (Cho), creatine (Cr), N-acetylaspartate (NAA), and lactate were measured from the periventricular WM. Myelin basic protein (MBP) concentrations were measured in CSF. Fifty-two patients experiencing acute CO poisoning (15 with DNS, 37 without DNS; median age, 49years; 65% males) underwent 1H-MRS. Within 1week, NAA/Cr ratios, reflecting neuroaxonal viability, were lower in patients with DNS than in those without DNS (P<0.05). At 1month, when 9 of 15 patients (60%) developed DNS, Cho/Cr ratios were higher, and NAA/Cr and NAA/Cho ratios lower in patients with DNS (P=0.0001, <0.0001, and <0.0001, respectively), indicating increased membrane metabolism and decreased neuroaxonal viability. 1H-MRS parameter abnormalities correlated with the elevation of MBP in CSF. The presence of a lactate peak was a predictor for a poor long-term outcome. 1H-MRS within 1week may be useful for predicting DNS development; 1H-MRS at 1month may be useful for discriminating patients with DNS and predicting long-term outcomes.

Cerebrovascular Biomarker Profile Is Related to White Matter Disease and Ventricular Dilation in a LADIS Substudy

Background: Small vessel disease (SVD) represents a common often progressive condition in elderly people contributing to cognitive disability. The relationship between cerebrospinal fluid (CSF) biomarkers and imaging correlates of SVD was investigated, and the findings were hypothesized to be associated with a neuropsychological profile of SVD. Methods: CSF SVD-related biomarkers [neurofilament light (NF-L), myelin basic protein (MBP), soluble amyloid precursor protein-β (sAPPβ), matrix metalloproteinases (MMPs), and tissue inhibitor of metalloproteinase (TIMP)] were analysed in 46 non-demented elderly with imaging findings of SVD. We assessed the relationship between the CSF biomarkers and white matter hyperintensity (WMH) volume, diffusion-weighted imaging and atrophy as well as their association with neuropsychological profiles. Results: The WMH volume correlated with ventricular dilation, which was associated with executive function and speed and attention. Increased WMH and ventricular dilation were related to increased CSF levels of TIMP-1, NF-L and MBP and to decreased sAPPβ. A positive correlation was found between the CSF biomarker MMP-9 and WMH progression. Conclusions: The link between progressive WMH and MMP-9 suggests an involvement of the enzyme in white matter degeneration. CSF TIMP-1, NF-L, MBP and sAPPβ may function as biological markers of white matter damage.

Serum uric acid levels and their correlation with clinical and cerebrospinal fluid parameters in patients with neuromyelitis optica

Although uric acid (UA) concentration has been considered a surrogate marker for monitoring the progression of multiple sclerosis (MS), less is known about the relationship between UA and the progression of neuromyelitis optica (NMO). We therefore investigated the correlations between serum UA concentrations and the clinical and cerebrospinal fluid (CSF) parameters in patients with NMO. Factors assessed in patients with NMO included gender, disease duration, disease disability, CSF white blood cell (WBC) counts, oligoclonal bands (OB), 24hour immunoglobulin (Ig)G index, and myelin basic protein (MBP) concentration. Mean serum UA concentrations were compared in patients with NMO and in a control group of patients with cerebral infarction (CI). We found that mean serum UA concentrations were significantly lower in patients with NMO compared to those with CI (206.81 compared to 274.00μmol/L, p=0.00). Serum UA concentration was correlated directly with NMO duration (p=0.013) and was inversely correlated with the Expanded Disability Status Scale score (p=0.021). Patients with NMO with lower serum UA concentrations tended to be positive for OB, to have higher CSF protein and MBP concentrations, and to have higher WBC counts and 24hour IgG index, but no correlation was statistically significant. UA may be a useful surrogate marker for monitoring NMO activity.

Increased CSF Concentrations of Myelin Basic Protein After TBI in Infants and Children: Absence of Significant Effect of Therapeutic Hypothermia

The objectives of this study were to determine effects of severe traumatic brain injury (TBI) on cerebrospinal fluid (CSF) concentrations of myelin basic protein (MBP) and to assess relationships between clinical variables and CSF MBP concentrations. We measured serial CSF MBP concentrations in children enrolled in a randomized controlled trial evaluating therapeutic hypothermia (TH) after severe pediatric TBI. Control CSF was obtained from children evaluated, but found not to be having CNS infection. Generalized estimating equation models and Wilcoxon Rank-Sum test were used for comparisons of MBP concentrations. There were 27 TBI cases and 57 controls. Overall mean (± SEM) TBI case MBP concentrations for 5 days after injury were markedly greater than controls (50.49 ± 6.97 vs. 0.11 ± 0.01 ng/ml, p < 0.01). Mean MBP concentrations were lower in TBI patients <1 year versus >1 year (9.18 ± 1.67 vs. 60.22 ± 8.26 ng/ml, p = 0.03), as well as in cases with abusive head trauma (AHT) versus non-abusive TBI (14.46 ± 3.15 vs. 61.17 ± 8.65 ng/ml, p = 0.03). TH did not affect MBP concentrations. Mean CSF MBP increases markedly after severe pediatric TBI, but is not affected by TH. Infancy and AHT are associated with low MBP concentrations, suggesting that age-dependent myelination influences MBP concentrations after injury. Given the magnitude of MBP increases, axonal injury likely represents an important therapeutic target in pediatric TBI.

Cerebrospinal Fluid Myelin Basic Protein Is Frequently Ordered but Has Little Value

Diagnosis of multiple sclerosis (MS) is facilitated by analyzing biochemical properties of cerebrospinal fluid (CSF). Oligoclonal bands (OCBs) and immunoglobulin G (IgG) index are well-established markers for evaluating patients suspected of having MS. Myelin basic protein (MBP) is also ordered frequently, but its usefulness remains questionable. OCB, IgG index, and MBP were measured in 16,690 consecutive CSF samples. Samples were divided into 2 groups based on MS status known (n = 71) or unknown (n = 16,118). Medical charts of the MS status known group were reviewed to determine their MS status. OCBs have a stronger association to IgG index results than does MBP. Importantly, MBP does not add a statistically significant increase in diagnostic sensitivity or specificity when used in combination with OCB and/or IgG index. The data indicate that MBP is an unnecessary and overused test.

Optimisation of the quantification of glutamine synthetase and myelin basic protein in cerebrospinal fluid by a combined acidification and neutralisation protocol

The measurement of proteins in cerebrospinal fluid (CSF) by enzyme-linked immunosorbent assays (ELISAs) is becoming increasingly important in the diagnosis of many neurodegenerative diseases such as Alzheimer's Disease. However, detection of proteins in these immunoassays can be hampered by confounding factors either present in the sample matrix or inherent to the protein of interest. These confounding factors may, for example, include protein aggregation or binding to other proteins resulting in epitope masking. Furthermore, the pH of CSF may vary considerably amongst different samples which may limit standardisation of CSF analysis. Pre-treatment of CSF to liberate epitopes or optimise conditions for antibody binding may enhance protein detection. In the current study we investigated whether CSF acidification followed by neutralisation (in short: AFBN) or neutralisation alone prior to measurement might improve the detection of a panel of brain-specific proteins. We demonstrate that the AFBN pre-treatment protocol for CSF significantly enhances the measurement of glutamine synthetase (GS) and myelin basic protein (MBP) in CSF but does not affect detection of glial fibrillary protein (GFAP), amyloid β 42 (Aβ42), total tau (t-tau) or phosphorylated tau (p-tau). Neutralisation alone did not improve detection of any of the proteins tested. Based on our results, we suggest including the AFBN protocol in the evaluation of new biomarker development protocols to avoid confounders such as CSF pH or epitope-masking of the target protein.