Csf Protein Levels Multiple Sclerosis

What Abnormal Results Mean

CSF testing

An abnormal protein level in the CSF suggests a problem in the central nervous system.

Increased protein level may be a sign of a tumor, bleeding, nerve inflammation, or injury. A blockage in the flow of spinal fluid can cause the rapid buildup of protein in the lower spinal area.

A decrease in protein level can mean your body is rapidly producing spinal fluid or you have a more generalized protein deficiency.

Determination Of Csf Chi3l1 Levels In A Second Validation Cohort Of Patients With Cis

Finally, in a second validation phase, CSF levels of CHI3L1 were also determined by ELISA in a totally independent validation cohort comprised of 52 new CIS patients classified based on conversion to multiple sclerosis, as described in the Materials and methods section. Sixteen individuals with inflammatory neurological disorders were also included as a control group. Similar to the findings observed in the first validation cohort, CSF CHI3L1 levels were found to be significantly increased in CIS patients who later converted to multiple sclerosis compared with patients who remained as CIS . Although CSF levels of CHI3L1 were also higher in patients who converted to multiple sclerosis compared with controls with other inflammatory neurological disorders, the difference did not reach statistical significance . These results reinforce the potential of CHI3L1 to discriminate between CIS patients who convert to multiple sclerosis and patients who remain as CIS.

CSF levels of CHI3L1 in CIS patients and controls included in the second validation phase of the study. Levels of CHI3L1 were measured by ELISA in CSF samples from a second independent validation cohort comprised of CIS patients who did not convert to multiple sclerosis , CIS patients who converted to multiple sclerosis , and controls with inflammatory neurological disorders . CSF CHI3L1 levels were significantly increased in Group 2 compared with Group 1 .

Csf Chi3l1 Levels Are Associated With Brain Mri Abnormalities At Baseline And Disability Progression During Follow

We next investigated whether levels of CHI3L1 in CSF correlated with brain MRI-derived metrics in patients with CIS at the time of disease onset. As shown in , baseline CSF CHI3L1 levels significantly correlated with the number of gadolinium enhancing lesions and the number of T2 lesions observed in brain MRI scans performed at baseline.

To determine whether baseline CSF CHI3L1 levels are associated with MRI abnormalities and disability progression during follow-up, analysis was restricted to those patients who will convert to multiple sclerosis . As shown in , significant correlations between baseline CSF CHI3L1 levels and brain MRI findings were lost at 1- and 5-year follow-up, most likely reflecting the small number of patients from whom MRI data were available. Of note, baseline CSF CHI3L1 levels were associated with disability progression at follow-up, as reflected by the statistically significant correlations observed between CSF CHI3L1 levels and Expanded Disability Status Scale during Years 1 through 4 .

These results indicate that CSF levels of CHI3L1 at the time of a CIS event are associated with the amount of CNS inflammation and T2 lesion burden, and more interestingly, that CHI3L1 may be used as a prognostic marker for disability progression in patients who will later convert to clinically definite multiple sclerosis.

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Csf Sampling And Pooling Strategy

CSF samples were collected at baseline by lumbar puncture and centrifuged for 5 min at 1500 rpm to remove cells. Samples were subsequently used for routine CSF diagnostics that included biochemistry and determination of IgG oligoclonal bands by agarose isoelectric focusing combined with immunoblotting and immunoperoxidase staining. The remaining volume of the samples was aliquoted and conserved at 80°C until used. CSF characteristics of patients included in Groups 1 and 2 are shown in .

A CSF pooling strategy was designed in the screening phase to identify proteins differentially expressed between patients belonging to Groups 1 and 2. Twelve CSF pools were created, six per group, each pool containing CSF from five different patients, and each patient contributing with 300 µl to a final volume of 1.5 ml. Pools between groups were sex- and age-matched, and patients between pools were different. An illustration of the pooling design is depicted in Supplementary Fig. S1.

Csf Protein And Glucose Concentration

Investigating Chemokines and Chemokine Receptors in Patients With ...

High CSF protein concentration has been reported to be significantly and independently associated with an unfavorable outcome in patients with PCNSL . In this study, a prognostic score including CSF protein concentration, as well as patient age, performance status, serum lactate dehydrogenase level, and involvement of deep structures of the brain has been proposed for distinguishing different risk groups in PCNSL. However, CSF protein concentration failed to correlate with meningeal involvement in a series of 116 immunocompetent patients with PCNSL .

CSF glucose levels are often low relative to serum glucose levels in patients with PCNSL.

Matthew Koenig, Eric M. Aldrich, in, 2009

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How Can A Lumbar Puncture Can Help Diagnose Ms

The CSF of people with MS usually contains elevated levels of IgG antibodies as well as a specific group of proteins called oligoclonal bands. Occasionally there are also certain proteins that are the breakdown products of myelin. These findings indicate an abnormal autoimmune response within the central nervous system, meaning that the body is producing an immune response against itself. Analysis of cerebrospinal fluid in the diagnosis of MS is looking for:

  • White blood cells the number of white cells in cerebrospinal fluid of people with multiple sclerosis is usually up to seven times higher than normal. If the count is even higher than this, it is probably due to an infection of some sort, such as Lymes Disease, and not MS.
  • Oligoclonal bands the immune system produces antibodies to fight infection. In MS, antibodies cross the blood-brain barrier and attack the myelin surrounding nerves. As a result, the level of antibodies in the cerebrospinal fluid of someone with MS is higher than it should be and is higher than the level in the blood, a sample of which is also analysed.

High Protein Count In My Csf

If your doctor orders a lumbar puncture test for you, he does so based on your symptoms. Something has led him to believe you have a disease or condition in your brain or spinal column. An examination of the cerebral spinal fluid reveals enough information to make a diagnosis and implement a treatment plan.

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Determination Of Serpina3n And S100a4 Expression Levels In Cns By Qpcr

mRNA expression levels for Serpina3n and S100A4 were determined in CNS samples from 4 EAE and 4 control animals at days 8, 16, 36, 50, and 90 pi. Total RNA was taken from the same samples that had been used for the microarrays, and complementary DNA synthesized using the High capacity cDNA Archive kit . Serpina3n and S100A4 transcripts were determined with TaqMan gene expression assays . Obtained values were normalized according to the level of expression of the housekeeping gene glyceraldehyde-3-phosphate dehydrogenase. Assays were run on the ABI PRISM® 7900HT system , and data were analyzed with the 2-CT method.7 Results were expressed as fold change in gene expression in EAE mice compared with controls .5

Screening Phase: Clinical Information And Csf Characteristics

A metabolic perspective on CSF-mediated neurodegeneration in multiple sclerosis

A schematic flow chart summarizing the main steps performed in study design is represented in . At baseline, demographic and clinical characteristics were comparable between CIS patients who did not convert to clinically definite multiple sclerosis and CIS patients who converted to clinically definite multiple sclerosis . A higher number of CIS patients presenting with optic neuritis was observed in Group 1 compared with Group 2, although overall differences in clinical presentation were not statistically significant. As shown in , the median time between the CIS event and CSF collection was similar between Groups 1 and 2 . Comparisons of CSF characteristics between groups only revealed a statistically significantly higher IgG concentration in Group 2 patients, which is associated with the IgG oligoclonal bands that are present in these patients.

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Are There Any Risks To Having A Csf Protein Test

ââSerious risks are rare with the procedure, but you may have more minor side effects.

These can include:

  • âHeadaches called âpost-lumbar headaches,â which can last for a few hours to a week
  • âPain or tenderness where the needle went in
  • âSlight bleeding at the wound site

Rarely, you may get more serious side effects like infections, inflammation, or severe bleeding. Speak to your doctor or head to an emergency room immediately if you feel unwell.

Absence Of Markers For Remyelination

Remyelination is not the primary mechanism of recovery of function in multiple sclerosis. In fact, most lesions remain demyelinated at the time when return of function occurs. This is best seen in optic neuritis where the optic nerves, which are commonly affected, show severe demyelination at the site of the original optic neuritis at autopsy, although during life, the patient reported normal or near-normal vision. Often, this is the sentinel event that led to the future occurrence of MS, an event that may have occurred some 3050 years prior to death. Many patients have trouble remembering which eye was affected during the sentinel optic neuritis although return of myelin did not occur. In the nonhuman primate model of demyelination with lysolecithin, remyelination was found to be slow in the optic nerve as compared to the spinal cord. Although shadow plaques occur in multiple sclerosis, remyelination is the exception rather than the rule in the evolution of most lesions of multiple sclerosis. There are no good markers for remyelination that allow the detection of shadow plaques in patients during life. Voxel-based magnetization transfer imaging attempts to define parameters for remyelination in MS, but the utility of this technique has remained a research tool. This inability to detect remyelination has hampered the identification of markers in the CSF that correlate with remyelination. At this time, there are no markers for detection of remyelination in the CSF.

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Csf Analysis And Multiple Sclerosis

CSF analysis may also be used to help diagnose multiple sclerosis . MS is a chronic condition in which your immune system destroys the protective covering of your nerves, which is called myelin. People with MS may have a variety of symptoms that are constant or come and go. They include numbness or pain in their arms and legs, vision problems, and trouble walking.

CSF analysis may be done to rule out other medical conditions that have symptoms similar to MS. The fluid may also show signs that your immune system isnt functioning normally. This can include high levels of IgG and the presence of certain proteins that form when myelin breaks down. About 85 to 90 percent of people with MS have these abnormalities in their cerebral spinal fluid.

Some types of MS progress quickly and can be life-threatening within weeks or months. Looking at the proteins in CSF may enable doctors to develop keys called biomarkers. Biomarkers can help identify the type of MS you have earlier and more easily. Early diagnosis could allow you to get treatment that could extend your life if you have a form of MS thats rapidly progressing.

The following are often measured in CSF analysis:

  • white blood cell count

What Is A Csf Protein Test

Multiple sclerosis imaging

âA CSF protein test is a medical test that takes a sample of your cerebrospinal fluid. It runs the sample through a series of steps to see how much protein you have in your spinal fluid. This test â also known as immunofixation and protein electrophoresis CSF and CSF protein electrophoresis â uses an electrical current on the fluid sample after it has been removed from your spine.â

The current passes through the fluid in the tube and separates the two main types of protein â immunoglobulin and albumin. Healthy fluid has barely any immunoglobulin. Immunoglobulin is often known as IgG.â

Usually, your cerebrospinal fluid has 0 milligrams to 4.5 milligrams per deciliter of IgG and 5 milligrams to 34 milligrams per deciliter of albumin. â

Altogether, healthy spinal fluid has anywhere from 15 milligrams to 45 milligrams per deciliter of protein. If you have more protein in your cerebrospinal fluid â especially IgG â you may have a health condition that needs treatment.

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Interpretation Of Csf Results From Lumbar Puncture

  • The outline below gives basic indication of patterns of disease to look for in CSF. However, note that CSF results should always be interpreted with the clinical picture in mind.
  • Reference ranges may vary between labs
  • Normal cell counts do not rule out meningitis or any other pathology
  • Glucose level: > 60% of serum glucose
  • Protein level: < 45 mg/dL
  • Consider additional tests: CSF culture, others depending on clinical findings
    • Appearance: Clear, cloudy, or purulent
    • Opening pressure: Usually elevated
    • WBC count: > 100 cells/µL
    • Partially treated cases may have as low as 1 WBC/µL
  • Glucose level: Low
  • Protein level: Elevated
  • Additional tests: CSF Gram stain and cultures, blood cultures, CSF bacterial antigens, CSF polymerase chain reaction for common viruses
    • Opening pressure: Normal or elevated
    • WBC count: 10-1000 cells/µL
    • Classically lymphocytes but may be PMN early
  • Glucose level: > 60% serum glucose
  • Protein level: Elevated
  • Consider additional tests: CSF Gram stain and cultures, blood cultures, CSF bacterial antigens, CSF PCR for herpes simplex virus , varicella-zoster virus and other common virus such as adenovirus or enterovirus depending on area
  • What Happens During A Csf Igg Index

    Your cerebrospinal fluid will be collected through a procedure called a spinal tap, also known as a lumbar puncture. A spinal tap is usually done in a hospital. During the procedure:

    • You will lie on your side or sit on an exam table.
    • A health care provider will clean your back and inject an anesthetic into your skin, so you won’t feel pain during the procedure. Your provider may put a numbing cream on your back before this injection.
    • Once the area on your back is completely numb, your provider will insert a thin, hollow needle between two vertebrae in your lower spine. Vertebrae are the small backbones that make up your spine.
    • Your provider will withdraw a small amount of cerebrospinal fluid for testing. This will take about five minutes.
    • You’ll need to stay very still while the fluid is being withdrawn.
    • Your provider may ask you to lie on your back for an hour or two after the procedure. This may prevent you from getting a headache afterward.

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    Additional File : Table S1

    Detailed information on used studies. Table S2. Detailed information on used studies from FinnGen consortium. Table S3. Associations of CSF sTREM2 with neurological diseases and subtypes in inverse-variance weighted method, as well as weighted median method and MR-Egger method. Table S4. Effects of genetic liability to MS on CSF sTREM2 levels in reverse Mendelian randomization analysis. Figure S1. Leave-one-SNP-out sensitivity analyze for CSF sTREM2 levels on MS.

    Statistical Analyses For Selection Of Proteins

    Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Guillain-Barre Syndrome, Myasthenia Gravis

    Proteome Discoverer software was used to process the raw mass spectrometry files, identify the proteins and generate quantitative data which was further processed by three parallel approaches.

    ANOVA-based

    For each peptide, ANOVA was performed with the lmPerm R package to determine difference between groups. Afterwards, to determine which pairs of groups showed most differences, the Tukey’s HSD test was performed as post-hoc analysis.

    Limma-based

    Linear regression and analysis of variance were performed with the limma R package. The ratios of a specific protein between two compared groups were log2 transformed, normalized to the median, and the 3 replicates merged into one, and proteins were significant according to q-values . The resulting data were visualized in volcano plots and heatmaps using Perseus.

    Complementary analysis of the three replicates

    Using the PD software, for each of the three sets the coefficient of variation CV of proteins within the set as well as the ratio of the mean abundance between the sets were calculated. A protein was selected for further analyses, if the ratio was larger than 1+2xCV . Subsequently, the PD software calculated a global ratio for a protein based on data from the three sets compared to healthy samples . Proteins were finally selected, if the protein expression was larger than 1+2xCV at least between two different conditions, and was consistently altered in a minimum of two of the three sets.

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    The Cerebrospinal Fluid In Multiple Sclerosis

    • 1Department of Neurology, Innsbruck Medical University, Innsbruck, Austria
    • 2Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
    • 3Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden
    • 4Department of Neurodegenerative Disease, UCL Institute of Neurology, London, United Kingdom
    • 5The Fluid Biomarker Laboratory, UK Dementia Research Institute at UCL, London, United Kingdom
    • 6Division of Neuroimmunology, Department of Neurology, University Medicine Rostock, Rostock, Germany

    Investigation of cerebrospinal fluid in the diagnostic work-up in suspected multiple sclerosis patients has regained attention in the latest version of the diagnostic criteria due to its good diagnostic accuracy and increasing issues with misdiagnosis of MS based on over interpretation of neuroimaging results. The hallmark of MS-specific changes in CSF is the detection of oligoclonal bands which occur in the vast majority of MS patients. Lack of OCB has a very high negative predictive value indicating a red flag during the diagnostic work-up, and alternative diagnoses should be considered in such patients. Additional molecules of CSF can help to support the diagnosis of MS, improve the differential diagnosis of MS subtypes and predict the course of the disease, thus selecting the optimal therapy for each patient.

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