Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 26 Cerebrospinal Fluid
Oligoclonal bands are associated with disease and are seen
in a high percentage of people with multiple sclerosis or
encephalitis. These bands, readily identifiable against the
low background of normal polyclonal IgG in the CSF, are
thought to represent the products of a limited number of
plasma cell clones. Oligoclonal bands unique to CSF (i.e.,
not present in serum) indicate intrathecal synthesis of
immunoglobulin and may be more sensitive than the IgG
index in detecting this synthesis. People with multiple
sclerosis may have a normal IgG index yet have CSF oligoclonal
banding; thus, the demonstration of these bands
is considered by some to be the single most useful test in
the diagnosis of multiple sclerosis ( Kjeldsberg and Knight,
1993 ). Oligoclonal bands are also seen in patients with
inflammatory diseases and in some patients with neoplasia
( Fishman, 1992 ). Occasionally, a single (monoclonal) band
is identified in the CSF electrophoretic pattern of people.
Monoclonal bands have been seen in neurologically normal
people as well as in patients with neurological disease
( Kjeldsberg and Knight, 1993 ).
8 . Other CSF Proteins
Numerous attempts have been made to correlate specific
CSF proteins, particularly “ brain-specific ” proteins, with
specific diseases. Proteins such as C-reactive protein, interferon,
myelin basic protein, and S-100 are increased in
the CSF associated with neurological disease, but these
increases are found in many heterogeneous conditions. This
nonspecificity limits the clinical utility of many of these specific
protein assays. However, the measurement of some of
these proteins is thought to be useful as a screening procedure
for neurological disease or as an indication of prognosis
(Fishman, 1992 ; Kjeldsberg and Knight, 1993 ; Lowenthal
et al. , 1984 ). Immunoassay detection in the CSF of the brainderived
protein 14-3-3 appears to be helpful for the diagnosis
of transmissible spongiform encephalopathies in both
animals and people ( Hsich et al. , 1996 ; Sanchez-Juan et al. ,
2006 ). An autoantibody against canine glial fibrillary acidic
protein present in astrocytes has been detected in the CSF of
two pug dogs affected with necrotizing encephalitis ( Uchida
et al. , 1999 ). However, it is unknown if the presence of this
antibody is a primary or secondary phenomenon.
9 . Plasma Proteins in the CSF
Alterations in plasma proteins may be reflected in the CSF.
For example, in people, the serum protein monoclonal gammopathy
of multiple myeloma may be evident in the CSF.
Bence Jones proteins are also readily seen in the CSF. The
high molecular weight paraproteins do not cross the normal
blood-brain barrier, however. Serum protein electrophoresis
is indicated in patients with elevated CSF globulins to clarify
the source of the globulins ( Fishman, 1992 ).
D . Antibody Titers
The CSF antibody titer can be measured for a number of
diseases (Dubey, 1990b; Greene, 1990 ). Interpretation
of the results is confounded by the need to differentiate
among titers caused by vaccination, exposure to the antigen
without development of the disease, and actual disease.
Interpretation of CSF antibody titers could be aided by an
accurate vaccination history, comparison of CSF and serum
titers, assessment of blood-brain/CSF barrier function, and
intrathecal immunoglobulin production by determination of
albumin and immunoglobulin indices, determination of CSF
IgM levels, and analysis of acute and convalescent samples
(Chrisman, 1992 ; Green et al. , 1993 ; Porter et al. , 2004 ).
E . Glucose
Increased CSF glucose usually reflects hyperglycemia.
Decreased CSF glucose occurs with several disorders of the
nervous system, particularly acute, bacterial, fungal, amebic,
or tuberculous meningitis. In people, low CSF glucose is also
characteristic of diffuse carcinomatous meningitis, meningeal
cysticercosis or trichinosis, and syphilitic meningitis.
The major factors responsible for low CSF glucose levels are
inhibition of the entry of glucose because of the alteration of
membrane glucose transport and increased anaerobic glycolysis
by neural tissue. As noted previously, hyperglycemia
elevates the CSF glucose, which may mask a decreased CSF
level. Therefore, calculation of a CSF/serum glucose ratio
has been recommended to identify pathologically low CSF
glucose levels ( Deisenhammer et al. , 2006 ; Kjeldsberg and
Knight, 1993 ). A CSF/serum glucose ratio less than 0.4 to 0.5
is considered to be pathological in people ( Deisenhammer
et al. , 2006 ). A low CSF glucose level in the absence of hypoglycemia
indicates a diffuse, meningeal disorder, rather than
focal disease ( Fishman, 1992 ; Kjeldsberg and Knight, 1993 ).
Decreased CSF glucose classically has been associated with
bacterial meningitis, but many human patients with bacterial
meningitis have normal CSF glucose levels. Therefore, the
recommendation has been made that CSF glucose need be
measured only if the opening CSF pressure, cell count, cytospin
differential, and protein are inconclusive ( Hayward et al. ,
1987 ). CSF glucose concentration and CSF/serum glucose
ratio are not routinely measured in veterinary medicine, possibly
because of the lack of specificity and availability of more
specific tests in most instances.
F . Enzymes
Numerous enzymes have been assayed in the CSF of animals
( Furr and Tyler, 1990 ; Jackson et al. , 1996 ; Rand et al. ,
1994b ; Wilson, 1977 ). Of these, creatine kinase has received
the most attention, and opinions of its usefulness are conflicting.
Although Furr and Tyler confirmed previous observations
that CSF creatine kinase activity was elevated in