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Background: The cerebrospinal fluid total protein level (CSF-TP) is commonly used as a potential marker of infectious or immune disease of the CNS and PNS. Recent laboratory reference studies indicate that the antiquated single upper reference limit of 0.45 g/L commonly used by hospital laboratories and widely quoted in medical literature is a significant underestimation., Methods: We distributed worldwide a web-based survey comprised of three questions: 1. What is the CSF-TP upper limit used at your institution? 2. What is the source of this upper limit? 3. Do you adjust your upper limit according to age?, Results: A total of 473 unique responses were obtained from North America (37.5%), South America (5.5%), Europe (29.4%), Africa (4%), Asia (21.6%) and Oceania (1.7%). A strong preponderance (86.8%) of institutions reported an upper limit of 0.45 g/L or less. Only 4% reported making age-partitioned adjustments., Conclusions: Worldwide, a strong majority of hospital laboratories presently use an underestimation of CSF-TP upper reference value, particularly for older adults. Recent well powered laboratory reference studies support higher values with age adjustment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Our study examined the prognostic role of increased cerebrospinal fluid protein and motor conduction studies on outcome and nerve ultrasound changes in Guillain-Barré syndrome (GBS)., Methods: Fifty post-GBS patients underwent clinical and nerve ultrasound examination, with a mean of 3.4 years (SD=2.8) after disease onset. Outcome was measured using the Medical Research Council Sum Score (MRC), the Rasch-built Overall Disability Scale (R-ODS) and the Rasch-built fatigue severity scale (R-FSS). Ιn addition, the results of the motor conduction studies and cerebrospinal fluid (CSF) examination at disease onset were retrospectively evaluated., Results: No significant changes in outcome were noted between patients with (p-CSF) and without increased CSF protein (n-CSF). The p-CSF group showed significant lower cross-sectional area (CSA) values of the radial nerve in spiral groove (p<0.001) and higher values of the internerve-CSA variability (p<0.001) compared to n-CSF patients. GBS patients with axonal affection in motor studies (GBS-a) showed significantly lower values of the R-ODS and MRC sum scores (p>0.001), but not of the R-FSS Score (p=0.018). Sonographically the GBS-a patients showed significant lower values of the median and ulnar nerve in the upper arm (p<0.001)., Discussion: Axonal affection in motor studies, but not increased CSF protein at disease onset, seems to be an infavourable prognostic factor for outcome in GBS. Both axonal affection and increased CSF protein have a minor prognostic role in the development of nerve ultrasound changes., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Neuromyelitis optica (NMO, Devic disease) is a severely disabling autoimmune disorder of the CNS, which was considered a subtype of multiple sclerosis (MS) for many decades. Recently, however, highly specific serum autoantibodies (termed NMO-IgG or AQP4-Ab) have been discovered in a subset (60-80%) of patients with NMO. These antibodies were subsequently shown to be directly involved in the pathogenesis of the condition. AQP4-Ab positive NMO is now considered an immunopathogenetically distinct disease in its own right. However, to date little is known about the cerebrospinal fluid (CSF) in AQP4-Ab positive NMO., Objective: To describe systematically the CSF profile of AQP4-Ab positive patients with NMO or its formes frustes, longitudinally extensive myelitis and optic neuritis., Material and Methods: Cytological and protein biochemical results from 211 lumbar punctures in 89 AQP4-Ab positive patients of mostly Caucasian origin with neuromyelitis optica spectrum disorders (NMOSD) were analysed retrospectively., Results: CSF-restricted oligoclonal IgG bands, a hallmark of MS, were absent in most patients. If present, intrathecal IgG (and, more rarely, IgM) synthesis was low, transient, and, importantly, restricted to acute relapses. CSF pleocytosis was present in around 50% of samples, was mainly mild (median, 19 cells/μl; range 6-380), and frequently included neutrophils, eosinophils, activated lymphocytes, and/or plasma cells. Albumin CSF/serum ratios, total protein and CSF L-lactate levels correlated significantly with disease activity as well as with the length of the spinal cord lesions in patients with acute myelitis. CSF findings differed significantly between patients with acute myelitis and patients with acute optic neuritis at the time of LP. Pleocytosis and blood CSF barrier dysfunction were also present during remission in some patients, possibly indicating sustained subclinical disease activity., Conclusion: AQP4-Ab positive NMOSD is characterized by CSF features that are distinct from those in MS. Our findings are important for the differential diagnosis of MS and NMOSD and add to our understanding of the immunopathogenesis of this devastating condition., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Cerebrospinal fluid (CSF) analysis is a basic tool for diagnosis of neurological diseases. Knowledge regarding blood-CSF barrier function (molecular flux/CSF flow theory) and neuroimmunology is reviewed to aid understanding and evaluation of CSF data. Disease-related immunoglobulin patterns (IgG, IgA, IgM with reference to albumin) are described in CSF/serum quotient diagrams with the hyperbolic reference range for blood-derived protein fractions in CSF. Clinical relevance of complementary analyses (cytology, PCR, oligoclonal IgG, antibody detection and brain-derived proteins) is briefly discussed. Integrated CSF data reports are shown with numerical and graphical data representation, reference range-related interpretation and diagnosis-related comments. The principles and rationale of general CSF analysis reported in this review should enable the reader to accurately interpret CSF data profiles, and to plan a proper evaluation of new brain- or blood-derived analytes in CSF.

A high alkaline fraction with a pI of 9.2 is sometimes seen on isoelectric focusing patterns of cerebrospinal fluid. The appearance of this fraction mainly depends on the type of concentrators used to prepare the cerebrospinal fluid samples, prior to isoelectric focusing. The amino acid sequence of the high alkaline fraction showed sequence identity to cystatin C, a cysteine protease inhibitor with a pI of 9.2-9.3 and a molecular mass of 13.4 kDa. In addition, on Western blot the high alkaline fraction was recognized by an antibody, directed against cystatin C. Taken together, the present findings demonstrate that the high alkaline fraction is cystatin C.

Levels of the proteinase inhibitors alpha 2-macroglobulin (alpha 2-m) and alpha 1-antitrypsin (alpha 1-at), and total protein, IgG and transferrin were measured in cerebrospinal fluid (CSF) from patients with multiple sclerosis (MS) and other neurological diseases. All groups except that termed "meningitis" had similar alpha 2-m levels, but alpha 1-at and transferrin were significantly depressed in MS. Total protein levels were normal and IgG levels were elevated in MS. Serum levels of alpha 1-at were normal so the decreases observed in the CSF in MS were not due to impaired systemic production. In view of previous reports that proteinase activity is high in MS plaques and CSF, the inhibitory capacity of alpha 2-m and alpha 1-at in CSF was measured. As any decreases in inhibitory capacity noted in MS were slight, they could only be important in the local environment of a plaque where enzyme levels may be critically high.