scholarly journals CSF sphingomyelin: a new biomarker of demyelination in the diagnosis and management of CIDP and GBS

2020 ◽  
pp. jnnp-2020-324445
Author(s):  
Giovanna Capodivento ◽  
Chiara De Michelis ◽  
Marinella Carpo ◽  
Roberto Fancellu ◽  
Erika Schirinzi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Neurological Diseases ◽  
High Specificity ◽  
Chronic Inflammatory Demyelinating Polyradiculoneuropathy ◽  
Disease Stage ◽  
Diagnosis And Management ◽  
Protein Levels ◽  
Clinical Scores ◽  
Demyelinating Neuropathies ◽  
Acquired Demyelinating Neuropathies

ObjectiveTo validate sphingomyelin (SM) dosage in the cerebrospinal fluid (CSF) of patients affected by chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Guillain-Barré syndrome (GBS) as a reliably assessable biomarker.MethodsWe prospectively enrolled 184 patients from six Italian referral centres, in whom CSF SM levels were quantified by a fluorescence-based assay optimised and patented in our laboratory.ResultsWe confirmed increased levels of SM in the CSF of patients affected by typical CIDP (n=35), atypical CIDP (n=18) and acute inflammatory demyelinating polyradiculoneuropathy, AIDP (n=12) compared with patients affected by non-demyelinating neurological diseases, used as controls (n=85) (p<0.0001, p=0.0065 and p<0.0001, respectively). In patients with CIDP classified for disease stage, SM was higher in active CIDP compared with both controls and stable CIDP (p<0.0001), applying for a selective tool to treatment tailoring or withdrawal. SM was also increased in AIDP compared with axonal GBS, discerning the demyelinating from axonal variant of the disease. SM did not correlate with CSF protein levels, stratifying patients independently from commonly used CSF indexes, and displaying high specificity to avoid potential misdiagnosis. Finally, SM correlated with the main clinical scores and some neurophysiological parameters in patients with CIDP and AIDP.ConclusionsCSF SM is a diagnostic and staging wet biomarker for acquired demyelinating neuropathies and may effectively improve the management of patients affected by GBS and CIDP.

scholarly journals The Correlation Among the Immunoglobulin G Synthesis Rate, IgG Index and Albumin Quotient in Guillain-Barré Syndrome and Chronic Inflammatory Demyelinating Polyradiculoneuropathy: A Retrospective Case–Control Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Tu ◽  
Xuan Gong ◽  
Yuanyuan Zhang ◽  
Jiewei Peng ◽  
Wenyan Zhuo ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Immunoglobulin G ◽  
High Specificity ◽  
Chronic Inflammatory Demyelinating Polyradiculoneuropathy ◽  
Guillain Barre Syndrome ◽  
Synthesis Rate ◽  
Control Group ◽  
Igg Index ◽  
Positive Rate ◽  
Guillain Barré

Background: The immunoglobulin G synthesis rate (IgG SR) and immunoglobulin G (IgG) index are indicators of abnormal intrathecal humoural immune responses, and the albumin quotient (QALB) is an indicator used to evaluate the completeness of the blood-cerebrospinal fluid barrier (BCB). No systematic reports regarding differences in Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are available. We assessed differences in the IgG SR, IgG index and QALB between GBS and CIDP patients in a Chinese cohort.Methods: A total of 234 patients were retrospectively enrolled in this study, and 167 clinically confirmed GBS and CIDP patients were selected. Meanwhile, 67 non-GBS and non-CIDP patients requiring cerebrospinal fluid (CSF) examination were enrolled as the control group. The IgG SR, IgG index and QALB were calculated using formulas. The relevant clinical data were subjected to statistical analysis.Results: Among the GBS and CIDP study groups and the control group, the QALB had the highest positive rate (80.00%) in the CIDP group (P &lt; 0.01). The QALB stratification analysis showed that the ranges of 10 &lt; QALB ≤ 30 were dominant in the GBS and CIDP groups, and the positive rate of CIDP was higher than that of GBS. Furthermore, a QALB ≤ 7 was dominant in the control group, and a QALB &gt; 30 was dominant in the CIDP group. In receiver operating characteristic (ROC) curve analysis with the CIDP group as the trial group and the GBS group as the control group, the differences in the QALB were statistically significant (P &lt; 0.01). To achieve a high specificity of 98~99%, the diagnostic cut-off value for the QALB was above 57.37 (sensitivity: 9.33%) or below 0.60 (sensitivity: 4.35%). Multivariate logistic regression analysis showed that the CIDP patients had a QALB higher than 57.37, and compared with that in the GBS patients, the difference in the QALB was statistically significant (P &lt; 0.01).Conclusion: QALB elevation was associated with CIDP, while QALB values above 57.37 or below 0.60 had high specificity in differentiating between GBS and CIDP. In CIDP, the BCB is generally moderately to severely damaged; in GBS, the BCB is generally moderately damaged.

scholarly journals Cerebrospinal Fluid Findings Are Poor Predictors of Appropriate FilmArray Meningitis/Encephalitis Panel Utilization in Pediatric Patients

2019 ◽  
Vol 58 (3) ◽  
Author(s):  
Mimi R. Precit ◽  
Rebecca Yee ◽  
Utsav Pandey ◽  
Margil Fahit ◽  
Cheryl Pool ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Pathogen Detection ◽  
Pediatric Patients ◽  
Human Herpesvirus ◽  
High Specificity ◽  
Molecular Testing ◽  
Predictive Values ◽  
Content Type ◽  
Protein Levels ◽  
Missed Diagnostic Opportunities

ABSTRACT Molecular testing of cerebrospinal fluid (CSF) using the BioFire FilmArray meningitis/encephalitis (FA-M/E) panel permits rapid, simultaneous pathogen detection. Due to the broad spectrum of targeted organisms, FA-M/E testing may be restricted to patients with abnormal CSF findings. We sought to determine if restriction is appropriate in our previously healthy and/or immunocompromised pediatric patients. FA-M/E was ordered on 1,025 CSF samples from 948 patients; 121 (11.8%) specimens were FA-M/E positive. Of these, 89 (73.6%) were virus positive, and 30 (24.8%) were bacterium positive. The most common targets detected were enterovirus (n = 38), human herpesvirus 6 (HHV-6) (n = 30), and Streptococcus pneumoniae (n = 14). Pleocytosis with white blood cell (WBC) levels of ≥5 cells/mm3 and ≥10 cells/mm3 were found in 33.1% and 24.3% of all specimens, respectively. Using WBC levels of ≥5 cells/mm3, 63.4% (59/93) of positive specimens exhibited pleocytosis, compared to 29.5% (233/789) of negative specimens. Among positive specimens, 54.4% (37/68) of viral and 87% (20/23) of bacterial cases had pleocytosis. The use of a pleocytosis cutoff of ≥10 cells/mm3 would have missed an additional enterovirus, one cytomegalovirus (CMV), and two HHV-6 diagnoses. CSF glucose and protein levels were normal for 83/116 (75.2%) and 51/116 (44%) positive specimens. Abnormal glucose in combination with WBC levels of ≥10 cells/mm3 showed high specificity (94.5%) and was a better predictor of FA-M/E positivity than abnormal protein. Sensitivity and positive predictive values were <90% for all biomarkers. CSF pleocytosis and abnormal glucose/protein were poor predictors of FA-M/E. Restricting FA-M/E orders based on pleocytosis or other abnormal parameters would have resulted in missed diagnostic opportunities, particularly for the detection of viruses in both previously healthy and immunocompromised patients.

scholarly journals Neuropathies associated with lymphoma†

2015 ◽  
Vol 2 (4) ◽  
pp. 167-178 ◽  
Author(s):  
Wolfgang Grisold ◽  
Anna Grisold ◽  
Christine Marosi ◽  
Stefan Meng ◽  
Chiara Briani
Keyword(s):  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Peripheral Nerve ◽  
Peripheral Nerves ◽  
Chronic Inflammatory Demyelinating Polyradiculoneuropathy ◽  
Proper Treatment ◽  
Intravascular Lymphoma ◽  
Immune Mediated ◽  
Peripheral Nerve Involvement ◽  
Demyelinating Neuropathies

AbstractNeuropathy occurs with various manifestations as a consequence of lymphoma, and an understanding of the etiology is necessary for proper treatment. Advances in medical imaging have improved the detection of peripheral nerve involvement in lymphoma, yet tissue diagnosis is often equally important. The neoplastic involvement of the peripheral nervous system (PNS) in lymphoma can occur within the cerebrospinal fluid (CSF), inside the dura, or outside of the CSF space, affecting nerve root plexuses and peripheral nerves. The infiltration of either cranial or peripheral nerves in lymphoma is termed neurolymphomatosis (NL). These infiltrations can occur as mononeuropathy, multifocal neuropathy, symmetric neuropathies, or plexopathies. In rare cases, intravascular lymphoma (IL) can affect the PNS and an even rarer condition is the combination of NL and IL. Immune-mediated and paraneoplastic neuropathies are important considerations when treating patients with lymphoma. Demyelinating neuropathies, such as Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy, occur more frequently in non-Hodgkin's lymphoma than in Hodgkin's disease. Paraproteinemic neuropathies can be associated with lymphoma and paraneoplastic neuropathies are rare. While the treatment of lymphomas has improved, a knowledge of neurotoxic, radiotherapy, neoplastic, immune-mediated and paraneoplastic effects are important for patient care.

Neuron-specific enolase and S-100 protein levels in cerebrospinal fluid of patients with various neurological diseases

1983 ◽  
Vol 60 (3) ◽  
pp. 443-451 ◽  
Author(s):  
Kenji Mokuno ◽  
Kanefusa Kato ◽  
Kuniyuki Kawai ◽  
Yukihiko Matsuoka ◽  
Tsutomu Yanagi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Neurological Diseases ◽  
Neuron Specific Enolase ◽  
Protein Levels ◽  
S 100

scholarly journals Alterations of mesenchymal stromal cells in cerebrospinal fluid: insights from transcriptomics and an ALS clinical trial

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ashley A. Krull ◽  
Deborah O. Setter ◽  
Tania F. Gendron ◽  
Sybil C. L. Hrstka ◽  
Michael J. Polzin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cerebrospinal Fluid ◽  
Growth Factors ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Large Scale ◽  
Therapeutic Benefit ◽  
Protein Levels ◽  
Genes Encoding ◽  
Intrathecal Space

Abstract Background Mesenchymal stromal cells (MSCs) have been studied with increasing intensity as clinicians and researchers strive to understand the ability of MSCs to modulate disease progression and promote tissue regeneration. As MSCs are used for diverse applications, it is important to appreciate how specific physiological environments may stimulate changes that alter the phenotype of the cells. One need for neuroregenerative applications is to characterize the spectrum of MSC responses to the cerebrospinal fluid (CSF) environment after their injection into the intrathecal space. Mechanistic understanding of cellular biology in response to the CSF environment may predict the ability of MSCs to promote injury repair or provide neuroprotection in neurodegenerative diseases. Methods In this study, we characterized changes in morphology, metabolism, and gene expression occurring in human adipose-derived MSCs cultured in human (hCSF) or artificial CSF (aCSF) as well as examined relevant protein levels in the CSF of subjects treated with MSCs for amyotrophic lateral sclerosis (ALS). Results Our results demonstrated that, under intrathecal-like conditions, MSCs retained their morphology, though they became quiescent. Large-scale transcriptomic analysis of MSCs revealed a distinct gene expression profile for cells cultured in aCSF. The aCSF culture environment induced expression of genes related to angiogenesis and immunomodulation. In addition, MSCs in aCSF expressed genes encoding nutritional growth factors to expression levels at or above those of control cells. Furthermore, we observed a dose-dependent increase in growth factors and immunomodulatory cytokines in CSF from subjects with ALS treated intrathecally with autologous MSCs. Conclusions Overall, our results suggest that MSCs injected into the intrathecal space in ongoing clinical trials remain viable and may provide a therapeutic benefit to patients.

scholarly journals Cerebrospinal fluid biomarkers of neuroinflammation in children with hydrocephalus and shunt malfunction

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Carolyn A. Harris ◽  
Diego M. Morales ◽  
Rooshan Arshad ◽  
James P. McAllister ◽  
David D. Limbrick
Keyword(s):  
Cerebrospinal Fluid ◽  
Inflammatory Cytokines ◽  
Protein Concentration ◽  
Shunt Revision ◽  
Csf Shunt ◽  
Shunt Failure ◽  
Revision Operation ◽  
Protein Levels ◽  
Anti Inflammatory ◽  
Pro Inflammatory Cytokines

Abstract Background Approximately 30% of cerebrospinal fluid (CSF) shunt systems for hydrocephalus fail within the first year and 98% of all patients will have shunt failure in their lifetime. Obstruction remains the most common reason for shunt failure. Previous evidence suggests elevated pro-inflammatory cytokines in CSF are associated with worsening clinical outcomes in neuroinflammatory diseases. The aim of this study was to determine whether cytokines and matrix metalloproteinases (MMPs) contribute towards shunt failure in hydrocephalus. Methods Using multiplex ELISA, this study examined shunt failure through the CSF protein concentration profiles of select pro-inflammatory and anti-inflammatory cytokines, as well as select MMPs. Interdependencies such as the past number of previous revisions, length of time implanted, patient age, and obstruction or non-obstruction revision were examined. The pro-inflammatory cytokines were IL-1β, IL-2, IL-5, IL-6, IL-8, IL-12, IL-17, TNF-α, GM-CSF, IFN-γ. The anti-inflammatory cytokines were IL-4 and IL-10, and the MMPs were MMP-2, MMP-3, MMP-7, MMP-9. Protein concentration is reported as pg/mL for each analyte. Results Patient CSF was obtained at the time of shunt revision operation; all pediatric (< 18), totaling n = 38. IL-10, IL-6, IL-8 and MMP-7 demonstrated significantly increased concentrations in patient CSF for the non-obstructed subgroup. Etiological examination revealed IL-6 was increased in both obstructed and non-obstructed cases for PHH and congenital hydrocephalic patients, while IL-8 was higher only in PHH patients. In terms of number of past revisions, IL-10, IL-6, IL-8, MMP-7 and MMP-9 progressively increased from zero to two past revisions and then remained low for subsequent revisions. This presentation was notably absent in the obstruction subgroup. Shunts implanted for three months or less showed significantly increased concentrations of IL-6, IL-8, and MMP-7 in the obstruction subgroup. Lastly, only patients aged six months or less presented with significantly increased concentration of IL-8 and MMP-7. Conclusion Non-obstructive cases are reported here to accompany significantly higher CSF cytokine and MMP protein levels compared to obstructive cases for IL-10, IL-6, IL-8, MMP-7 and MMP-9. A closer examination of the definition of obstruction and the role neuroinflammation plays in creating shunt obstruction in hydrocephalic patients is suggested.

scholarly journals Cerebrospinal Fluid Parameters in Antisense Oligonucleotide-Treated Adult 5q-Spinal Muscular Atrophy Patients

2021 ◽  
Vol 11 (3) ◽  
pp. 296
Author(s):  
Lars Hendrik Müschen ◽  
Alma Osmanovic ◽  
Camilla Binz ◽  
Konstantin F. Jendretzky ◽  
Gresa Ranxha ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Spinal Muscular Atrophy ◽  
Total Protein ◽  
Antisense Oligonucleotide ◽  
Muscular Atrophy ◽  
Neurological Diseases ◽  
Clinical Signs ◽  
Central Nervous System Disease ◽  
Oligoclonal Bands ◽  
System Disease

Approval of nusinersen, an intrathecally administered antisense oligonucleotide, for the treatment of 5q-spinal muscular atrophy (SMA) marked the beginning of a new therapeutic era in neurological diseases. Changes in routine cerebrospinal fluid (CSF) parameters under nusinersen have only recently been described in adult SMA patients. We aimed to explore these findings in a real-world setting and to identify clinical and procedure-associated features that might impact CSF parameters. Routinely collected CSF parameters (leukocyte count, lactate, total protein, CSF/serum albumin quotient (QAlbumin), oligoclonal bands) of 28 adult SMA patients were examined for up to 22 months of nusinersen treatment. Total protein and QAlbumin values significantly increased in the first 10 months, independent of the administration procedure. By month 14, no further increases were detected. Two patients developed transient pleocytosis. In two cases, positive oligoclonal bands were found in the beginning and in four patients throughout the whole observation period. No clinical signs of inflammatory central nervous system disease were apparent. Our data confirm elevated CSF total protein and QAlbumin during nusinersen treatment. These alterations may be caused by both repeated lumbar punctures and the interval between procedures rather than by the medication itself. Generally, there were no severe alterations of CSF routine parameters. These results further underline the safety of nusinersen therapy.

scholarly journals Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1210
Author(s):  
Júlia Costa ◽  
Marta Gromicho ◽  
Ana Pronto-Laborinho ◽  
Conceição Almeida ◽  
Ricardo A. Gomes ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Cerebrospinal Fluid ◽  
Motor Neurons ◽  
Neurological Diseases ◽  
Disease Diagnosis ◽  
Enzyme Linked Immunosorbent Assay ◽  
Progression Rate ◽  
Therapeutic Trials ◽  
Als Patients ◽  
Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease that affects motor neurons controlling voluntary muscles. Survival is usually 2–5 years after onset, and death occurs due to respiratory failure. The identification of biomarkers would be very useful to help in disease diagnosis and for patient stratification based on, e.g., progression rate, with implications in therapeutic trials. Neurofilaments constitute already-promising markers for ALS and, recently, chitinases have emerged as novel marker targets for the disease. Here, we investigated cerebrospinal fluid (CSF) chitinases as potential markers for ALS. Chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), chitinase-3-like protein 2 (CHI3L2) and the benchmark marker phosphoneurofilament heavy chain (pNFH) were quantified by an enzyme-linked immunosorbent assay (ELISA) from the CSF of 34 ALS patients and 24 control patients with other neurological diseases. CSF was also analyzed by UHPLC-mass spectrometry. All three chitinases, as well as pNFH, were found to correlate with disease progression rate. Furthermore, CHIT1 was elevated in ALS patients with high diagnostic performance, as was pNFH. On the other hand, CHIT1 correlated with forced vital capacity (FVC). The three chitinases correlated with pNFH, indicating a relation between degeneration and neuroinflammation. In conclusion, our results supported the value of CHIT1 as a diagnostic and progression rate biomarker, and its potential as respiratory function marker. The results opened novel perspectives to explore chitinases as biomarkers and their functional relevance in ALS.

scholarly journals Cerebrospinal fluid neurofilament light chain in multiple sclerosis and its subtypes: a meta-analysis of case–control studies

2019 ◽  
Vol 90 (9) ◽  
pp. 1059-1067 ◽  
Author(s):  
Sarah-Jane Martin ◽  
Sarah McGlasson ◽  
David Hunt ◽  
James Overell
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Light Chain ◽  
Meta Analysis ◽  
Grey Literature ◽  
Case Control ◽  
Disease Stage ◽  
Case Control Studies ◽  
Neurofilament Light Chain ◽  
Neurofilament Light

ObjectiveNeurofilament is a biomarker of axonal injury proposed as a useful adjunct in the monitoring of patients with multiple sclerosis (MS). We conducted a systematic review and meta-analysis of case–control studies that have measured neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of people with MS (pwMS), in order to determine whether, and to what degree, CSF NfL levels differentiate MS from controls, or the subtypes or stages of MS from each other.MethodsGuidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. Electronic databases were searched for published and ‘grey’ literature, with 151 hits. Of 51 full articles screened, 20 were included in qualitative analysis, and 14 in meta-analysis.ResultsCSF NfL was higher in 746 pwMS than 435 (healthy and disease) controls, with a moderate effect size of 0.61 (p < 0.00001). Mean CSF NfL levels were significantly higher in 176 pwMS with relapsing disease than 92 with progressive disease (2124.8 ng/L, SD 3348.9 vs 1121.4 ng/L, SD 947.7, p = 0.0108). CSF NfL in 138 pwMS in relapse (irrespective of MS subtype) was double that seen in 268 pwMS in remission (3080.6 ng/L, SD 4715.9 vs 1541.7 ng/L, SD 2406.5, p < 0.0001).ConclusionsCSF NfL correlates with MS activity throughout the course of MS, reflecting the axonal damage in pwMS. Relapse is more strongly associated with elevated CSF NfL levels than the development of progression, and NfL may be most useful as a marker of disease ‘activity’ rather than as a marker of disability or disease stage.

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