On cerebrospinal fluid immunoglobulin-G (IgG) quotients in multiple sclerosis and other diseases : A review and a new formula to estimate the amount of IgG synthesized per day by the central nervous system
TL;DR: Other diseases which induce the CNS to become an immunological organ, i.e. to produce IgG, are clinically infrequent and are easily differentiated on clinical grounds from MS; thus the elevated CSF IgG quotient found in over two-thirds of the cases of MS becomes of value in supporting the diagnosis of MS.
About: This article is published in Journal of the Neurological Sciences.The article was published on 1970-03-01 and is currently open access. It has received 246 citations till now. The article focuses on the topics: CSF albumin & Cerebrospinal fluid.
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TL;DR: A proposed graphical presentation of CSF/S albumin and IgG-index may facilitate the interpretation of these parameters in routine clinical work.
Abstract: Protein parameters in CSF and serum have been studied in ninety-three reference subjects. CSF/S albumin ratio is proposed to be superior to CSF-protein or CSF-albumin as a test of the blood-brain barrier function, while IgG-index = (CSF/S IgG ratio)/(CSF/S albumin ratio) is superior to CSF IgG/protein ratio or CSF/albumin ratio for the demonstration of IgG elevation in CSF due to synthesis within CNS. The two quotients recommended correct for variations of albumin and IgG concentrations in serum. When the serum proteins are within reference range, the CSF protein concentrations are mainly regulated by the permeability of the blood-brain barrier, while the influence of S-albumin and S-IgG is only secondarily. The CSF/S albumin ratio is age dependent, while IgG-index is not. A proposed graphical presentation of CSF/S albumin and IgG-index may facilitate the interpretation of these parameters in routine clinical work.
952 citations
TL;DR: Recent work in mice that are genetically deficient for different cytokines (MCSF, IL1, IL6, TNFalpha, TGFbeta1) has begun to shed light on the molecular signals that regulate this cellular response.
861 citations
TL;DR: This new view of the immunoreactivity of the normal brain is based on an active and highly-regulated communication between the brain and the central immune organs and the blood-brain barrier, which contributes to the regulation of immunoregulatory cells and molecules in the brain cell microenvironment.
646 citations
TL;DR: 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.
638 citations
TL;DR: Quantification of the connection to lymph in rabbit, cat and sheep, using radiolabeled albumin as a marker of flow, indicates that a minimum of 14 to 47% of protein injected into different regions of brain or cerebrospinal fluid passes through lymph.
Abstract: Cerebral extracellular fluids drain from brain to blood across the arachnoid villi and to lymph along certain cranial nerves (primarily olfactory) and spinal nerve root ganglia. Quantification of the connection to lymph in rabbit, cat and sheep, using radiolabeled albumin as a marker of flow, indicates that a minimum of 14 to 47% of protein injected into different regions of brain or cerebrospinal fluid passes through lymph. The magnitude of the outflow to lymph is at variance with the general assumption that the absence of conventional lymphatics from the brain interrupts the afferent arm of the immune response to brain antigens. The immune response to antigens (albumin or myelin basic protein) introduced into the central nervous system (CNS) has been analysed using a rat model with normal brain barrier permeability. The micro-injection of antigen into brain or cerebrospinal fluid elicits a humoral immune response, with antibody production in cervical lymph nodes and spleen, and also affects cell-mediated immunity. Furthermore, antigen may be more immunogenic when administered into the CNS than into conventional extracerebral sites. Clearly, the afferent arm of the immune response to antigens, within the CNS, is intact. Modern studies suggest that the efferent arm is also intact with passage of activated lymphocytes into the brain. Results support a new view of CNS immunology which incorporates continuous and highly regulated communication between the brain and the immune system in both health and disease.
393 citations
References
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Journal Article•
TL;DR: Procedures are described for measuring protein in solution or after precipitation with acids or other agents, and for the determination of as little as 0.2 gamma of protein.
289,852 citations
Book•
01 Jan 1967
TL;DR: A summary of the structure and function of the cerebrospinal fluid is presented, by Hugh Davson, DSc, with 171 illustrations.
Abstract: Cerebrospinal Fluid. By Hugh Davson, DSc. Price, $22.50. Pp 456, with 171 illustrations. Little, Brown & Company, 34 Beacon St, Boston 02106, 1967. This book presents a summary of the structure and function of the cerebrospinal fluid. The author has performed a great service by compiling vast amounts of information in an orderly fashion in a single volume. This monograph is an invaluable refer-
627 citations
"On cerebrospinal fluid immunoglobul..." refers background in this paper
...1968; DAVSON 1967) this rapid turnover of CSF lgG was largely the result of drainage and corresponded to a renewal rate of 0.1 ~o per rain....
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TL;DR: The present study was undertaken to determine with some precision the position and relative frequency of plaques seen macroscopically in the cerebral hemispheres in a series of necropsied cases of multiple sclerosis.
Abstract: One of the fundamental problems posed by multiple sclerosis is concerned with the distribution of the pathological lesions called plaques. The literature concerning the histopathology of this disease is immense but a recent review by Lumsden (1955) did not refer to any paper in which the position of plaques in the cerebrum had been determined with any exactitude although such an exact study was made on the spinal cord of eight cases by Fog (1950), who found that spinal plaques occurred consistently in certain regions. This work was based on histological sections cut transversely through the spinal cord, a technique also applicable to the brain-stem but not essential in the cerebrum where the position of plaques can be seen sufficiently well by the naked eye. The present study was undertaken to determine with some precision the position and relative frequency of plaques seen macroscopically in the cerebral hemispheres in a series of necropsied cases of multiple sclerosis.
521 citations
June1
TL;DR: My own approach to the study of epilepsy, and through it to the functional anatomy of the human brain, was a long journey---blind in the beginning but somewhat inevitable; I shall dcscrihe my journey as a Pilgrim's Progress and hope you will forgive me if it seems no more than a wandering tale of personal adventure in the outset.
Abstract: My own approach to the study of epilepsy, and through it to the functional anatomy of the human brain, was a long journey---blind in the beginning but somewhat inevitable. I shall dcscrihe my journey as a Pilgrim’s Progress and hope you will forgive me if it seems no more than a wandering tale of personal adventure in the outset. We are told that Martin Luther was willing to ‘‘bet’’ (drum wohlte ich schier wettcn) that St. Valentine was thought to bc the patron saint of the falling disease simply because, to the German ear, St. Valcntine sounded like “der Fallenden Sucht”]. Luther himself, it is clear, had a fatal wcakncss for “heresies”. His heresics changed the history of Christendom. Rut in this case I remain unconvinced and orthodox. I prefer to believe in St. Valentine. God knows the vast army of innocent Inen and women and childrcn who suffer from cpilepsy in its many form4 has always had need of a powerful patron saint. Many cpileptics in that army arc my friends. I owe them a wonderful debt of gratitude. For this reason I have comc to Copenhagen--to pay tribute to St. Valcntine before this distinguished Society that honours him. Sir Charles Sherrington was Professor of Physiology a t Oxford whcn I was a medical student. He was always the student of function in the nervous system, always speculating on the “how” of integration. In his laboratory, questions were put to the experimental “preparation” for authoritative answer. Later, during my hospital service in Boston, 1 watched Harvey Cushing in his surgical clinic a t the Peter Bent Brigham Hospital. He was then demonstrating that neurosurgery could be made a rcspcctablc specialty with a low’ mortality rate. But, a t that time, it was almost exclusively the surgery of tuinours and of pain. For me, the great
469 citations
453 citations
"On cerebrospinal fluid immunoglobul..." refers methods in this paper
...Normally, 18.5 mg of tgG per day come from the blood [normal CSF IgG concentration is 3.7 mg/100 ml (ToURTELLOTTE 1970)] and 500 ml of CSF are formed and absorbed per day according to CUTLER et al. (1968)....
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