The Importance and Utility of Cerebrospinal Fluid Evaluation in the Diagnosis of Central Demyelinating Diseases

Author(s):  
Mark S. Freedman ◽  
Mohammad Abdoli

This chapter aims to highlight the diagnostic and prognostic value of cerebrospinal fluid (CSF) findings in multiple sclerosis with a special consideration of distinguishing it from neuromyelitis optica (NMO) and NMO spectrum disorder. Interpretation of CSF findings in daily clinical practice in patients with MS is thoroughly explained. New advances in CSF analysis and recently identified biomarkers may be helpful for diagnosis, help elucidate disease subtype and activity, or aid in prognosis and monitoring of the response to treatment. Characteristics of CSF changes in different subtypes of multiple sclerosis, clinically isolated syndrome (CIS), and radiologically isolated syndrome (RIS) are discussed. CSF findings in NMO spectrum disease as a diagnostic and differentiating marker are explained separately.

2016 ◽  
Vol 74 (4) ◽  
pp. 337-350 ◽  
Author(s):  
Hansotto Reiber

ABSTRACT The analysis of intrathecal IgG, IgA and IgM synthesis in cerebrospinal fluid (CSF) and evaluation in combined quotient diagrams provides disease-related patterns. The compilation with complementary parameters (barrier function, i.e., CSF flow rate, cytology, lactate, antibodies) in a cumulative CSF data report allows a knowledge-based interpretation and provides analytical and medical plausibility for the quality assessment in CSF laboratories. The diagnostic relevance is described for neurological and psychiatric diseases, for which CSF analysis can’t be replaced by other diagnostic methods without loss of information. Dominance of intrathecal IgM, IgA or three class immune responses give a systematic approach for Facial nerve palsy, Neurotrypanosomiasis, Opportunistic diseases, lymphoma, Neurotuberculosis, Adrenoleucodystrophy or tumor metastases. Particular applications consider the diagnostic power of the polyspecific antibody response (MRZ-antibodies) in multiple sclerosis, a CSF-related systematic view on differential diagnostic of psychiatric diseases and the dynamics of brain- derived compared to blood-derived molecules in CSF for localization of paracytes.


Author(s):  
Fay Probert ◽  
Tianrong Yeo ◽  
Yifan Zhou ◽  
Megan Sealey ◽  
Siddharth Arora ◽  
...  

Abstract Eighty-five percent of multiple sclerosis cases begin with a discrete attack termed clinically isolated syndrome, but 37% of clinically isolated syndrome patients do not experience a relapse within 20 years of onset. Thus, the identification of biomarkers able to differentiate between individuals who are most likely to have a second clinical attack from those who remain in the clinically isolated syndrome stage is essential to apply a personalised medicine approach. We sought to identify biomarkers from biochemical, metabolic, and proteomic screens that predict clinically defined conversion from clinically isolated syndrome to multiple sclerosis and generate a multi-omics-based algorithm with higher prognostic accuracy than any currently available test. An integrative multi-variate approach was applied to the analysis of cerebrospinal fluid samples taken from 54 individuals at the point of clinically isolated syndrome with 2–10 years of subsequent follow-up enabling stratification into clinical converters and non-converters. Leukocyte counts were significantly elevated at onset in the clinical converters and predict occurrence of a second attack with 70% accuracy. Myo-inositol levels were significantly increased in clinical converters while glucose levels were decreased, predicting transition to multiple sclerosis with accuracies of 72% and 63%, respectively. Proteomics analysis identified 89 novel gene products related to conversion. The identified biochemical and protein biomarkers were combined to produce an algorithm with predictive accuracy of 83% for the transition to clinically defined multiple sclerosis, outperforming any individual biomarker in isolation including oligoclonal bands. The identified protein biomarkers are consistent with an exaggerated immune response, perturbed energy metabolism, and multiple sclerosis pathology in the clinical converter group. The new biomarkers presented provide novel insight into the molecular pathways promoting disease while the multi-omics algorithm provides a means to more accurately predict whether an individual is likely to convert to clinically defined multiple sclerosis.


2004 ◽  
Vol 10 (4) ◽  
pp. 469-471 ◽  
Author(s):  
Magnus Vrethem ◽  
Ingrid Fernlund ◽  
Jan Ernerudh ◽  
Sten Öhman

IgA antibodies do not activate complement and may compete with and protect against myelin degradation caused by IgM and IgG in multiple sclerosis (MS). We retrospectively evaluated cerebrospinal fluid (CSF) IgA and IgG (as indices and extended indices) from 1980 to 1988 in 68 patients with definitive MS. Sixty-one of them had survived since the time of sampling (11- 19 years). IgA Extended Index was significantly higher for surviving patients (median 0.65) than for the dead patients (median 0.33). CSF IgA or IgG indices did not correlate with disability, walking distance, or time from onset of symptoms to the need of walking aid. The retrospective experimental design allowed an unusually long follow-up time, but it also had the disadvantages of such a study. Thus the results warrant a prospective study to verify the prognostic vale of CSF IgA in MS.


2014 ◽  
Vol 92 ◽  
pp. 0-0
Author(s):  
A MOUALLEM ◽  
V TOUITOU ◽  
B BODAGHI ◽  
E CHAMPION ◽  
A DARUGAR ◽  
...  

2018 ◽  
Vol 9 (2) ◽  
pp. 58-64 ◽  
Author(s):  
Colin A. Ellis ◽  
Andrew C. McClelland ◽  
Suyash Mohan ◽  
Emory Kuo ◽  
Scott E. Kasner ◽  
...  

Background and Purpose: Patients with posterior reversible encephalopathy syndrome (PRES) sometimes undergo analysis of cerebrospinal fluid (CSF) to exclude alternative diagnoses. This study’s objectives were to describe the CSF characteristics in patients with PRES and to identify clinical and radiologic findings associated with distinct CSF abnormalities. Methods: We identified a retrospective cohort of patients with PRES. We compared clinical and radiographic characteristics of those who did versus did not undergo lumbar puncture, described the observed range of CSF findings, and analyzed clinical and radiographic features associated with specific CSF abnormalities. Results: A total of 188 patients were included. Patients with (n = 77) and without (n = 111) CSF analysis had similar clinical and radiographic characteristics. Cerebrospinal fluid protein was elevated in 46 (60%) of 77, with median CSF protein 53 mg/dL (upper limit of normal 45 mg/dL). Protein elevation was significantly associated with radiographic severity ( P = .0058) but not with seizure, time from symptom onset, radiographic evidence of diffusion restriction, or contrast enhancement. Five (7%) patients had elevated CSF white blood cells, all of whom had infarction and/or hemorrhage on neuroimaging, and 4 of whom had eclampsia. Conclusion: The CSF of most patients with PRES shows a mild protein elevation commensurate with radiographic severity. Cerebrospinal fluid pleocytosis may mark a distinct subtype of PRES with predisposition toward infarction and/or hemorrhage. These findings help clinicians interpret CSF findings in these patients and generate new hypotheses about the pathophysiology of this syndrome.


2015 ◽  
Vol 134 (4) ◽  
pp. 748-755 ◽  
Author(s):  
Roubina Ch. Antonelou ◽  
Evangelia Emmanouilidou ◽  
Gerasimos Gasparinatos ◽  
Theodora Velona ◽  
Konstantinos I. Voumvourakis ◽  
...  

2000 ◽  
pp. 809-816 ◽  
Author(s):  
U Michel ◽  
S Ebert ◽  
O Schneider ◽  
Y Shintani ◽  
S Bunkowski ◽  
...  

OBJECTIVE: Follistatin (FS) is the specific binding protein of activin and expression of both factors is regulated by inflammatory agents. Therefore, FS concentrations were determined in cerebrospinal fluid (CSF) of patients with bacterial and viral meningitis or multiple sclerosis (MS), as well as in the CSF of patients without meningial inflammation or autoimmune diseases. Furthermore, a mouse pneumococcal meningitis model was used to localise the cellular sources of FS in brains of normal and meningitic mice. METHODS: FS concentrations in CSF were determined by ELISA; FS in mice was localised by in situ hybridisation and immunohistochemistry. RESULTS: FS concentrations were > or =0.4 microg/l in 22 of 66 CSF samples of meningitis patients versus 2 of 27 CSF samples from patients with multiple sclerosis (P<0.05) and 2 of 41 CSF specimen from patients without neuroinflammatory diseases (P<0.01). In the CSF of patients with meningitis, the concentration of FS was correlated with total protein (P<0.005) and lactate concentrations (P<0.05), but not with leukocyte counts, interval between onset of disease and CSF analysis, or clinical outcome. The CSF-to-serum ratios of FS and albumin also correlated significantly (P<0.0005). In some patients with meningitis the CSF-to-serum ratios suggested that the elevated FS in CSF did not originate from serum alone. FS was localised in mice brains to neurones of the hippocampus, dentate gyrus, neocortex, and to the choroid plexus. Analyses of brains and other organs from uninfected and infected animals sacrificed 6-36 h after infection did not reveal any obvious differences in the distribution and intensity of FS mRNA and protein expression. CONCLUSIONS: The concentration of FS in humans is elevated during meningitis. In some patients the increase is caused by a release of FS from brain into CSF. Data from the mouse meningitis model suggest that increased CSF concentrations of FS in meningitis appear not to be accompanied by an elevated number of cells containing FS mRNA or protein in the brain.


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