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

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Chapter | 26 Cerebrospinal Fluid
positive cases had normal cell counts. The Kölmel technique
results in a higher cell yield than cytocentrifugation,
which may be partly responsible for the increased incidence
of neoplastic cell observation in the CSF. Despite
the low yield of cytospin slides, the presence of neoplastic
cells in cytospin CSF slides from animals with CNS tumors
other than lymphoma has been reported in cats with intracranial
oligodendroglioma, dogs with CNS histiocytic sarcoma,
and dogs with choroid plexus carcinoma ( Dickinson
et al., 2000 ; Zimmerman et al., 2006 ). 3, 5
A large number of studies assess the prevalence of
neoplastic cells in the CSF of people with central nervous
system neoplasia. Overall sensitivities that are frequently
quoted are 70% for CNS leukemia, 20% to 60% for metastatic
meningeal carcinoma, and approximately 30%
for primary CNS tumors ( Kjeldsberg and Knight, 1993 ),
regardless of the technique utilized. The detection rate of
malignant cells in the CSF is improved by the collection
of multiple samples ( Olson et al., 1974 ). These figures are
supported by one study utilizing cytocentrifugation in 117
cases of histopathologically confirmed central nervous system
neoplasia ( Glass et al., 1979 ). Overall, 26% (31/117)
were positive. However, if only those people with leptomeningeal
involvement were considered, the prevalence
increased to 59%. Conversely, of 66 cases in which the
tumor did not reach the leptomeninges, only a single sample
was positive. In another study, only 13.9% of all gliomas
had a positive CSF cytology ( Balhuizen et al., 1978 ).
This low prevalence is likely because the majority of gliomas
does not extend into the subarachnoid space ( Balhuizen
et al. , 1978 ). As a result of these studies, the following generalizations
are frequently made in human medicine: (1) a
positive CSF cytology is a reliable indicator of central nervous
system malignancy and almost always reflects a leptomeningeal
tumor (or one involving the ventricular system),
and (2) a negative cytology does not exclude the presence
of an intracerebral tumor, particularly a deep parenchymal
mass that does not breach the pia or the ventricular system.
Controlled studies are required in veterinary medicine to
determine the prevalence of positive CSF cytology in confirmed
cases of different types of central nervous system
neoplasias, and also to compare the sensitivities of different
preparative methods. These studies may be hampered by the
general lack of experience at identifying cells derived from
central nervous system neoplasms. Tumor cells can be erroneously
identified as normal ependymal or choroid plexus
cells. Solitary tumor cells from metastatic carcinomas can
be mistaken for lymphocytes or monocytes ( Kjeldsberg and
Knight, 1993 ). The need for the above type of study has
been somewhat decreased by the advent of more routine
access to advanced imaging and biopsy techniques ( Koblik
et al., 1999 ; Vernau et al., 2001 ).
5
Westworth, D., in preparation.
C . Protein
1 . Changes in CSF Total Protein Content
An increase in the total protein content of CSF is the single
most useful alteration in the chemical composition of the
fluid ( Fishman, 1992 ). However, this alteration accompanies
many diseases and is therefore nonspecific. Increased total
protein may be caused by (1) increased permeability of the
blood-brain/spinal cord/CSF barriers allowing passage of
serum proteins into the CSF, (2) intrathecal globulin production,
and (3) interruption of CSF flow or absorption.
Particular emphasis has been put on CSF flow rate as a
major factor in CSF protein content ( Reiber, 1994 ). In many
diseases, two or all three of these mechanisms are at work.
In complete spinal subarachnoid space blockage (e.g., by a
compressive lesion or arachnoiditis), CSF withdrawn caudal
to the block may clot when aspirated. In people, this
phenomenon is called Froin’s syndrome and results from
very high CSF protein levels caused by the defective flow
and absorption and blood-spinal cord barrier breakdown
(Fishman, 1992 ; Kjeldsberg and Knight, 1993 ).
Decreased total protein is much less common.
Theoretically, low levels of CSF protein could result from
decreased entry of protein into the CSF or increased removal.
No evidence exists to support the first mechanism. Increased
removal can occur, however, if intracranial pressure is
increased while the barriers to serum protein remain normal.
In this situation, bulk flow absorption of CSF is increased,
whereas entrance of protein into the CSF remains normal.
Protein content of fluid collected from the lumbar site could
be decreased if large volumes are removed or if ongoing
leakage of CSF from the lumbar area is occurring. In these
situations, lumbar CSF is replaced more quickly than normal
by ventricular CSF, which has a lower protein content than
lumbar CSF ( Fishman, 1992 ; Kjeldsberg and Knight, 1993 ).
Low CSF protein has also occurred in people with hyperthyroidism,
leukemia, or water intoxication ( Fishman, 1992 ;
Kjeldsberg and Knight, 1993 ).
2 . Albuminocytological Dissociation
In many disease processes, the CSF cell count and CSF
total protein increase in rough parallel. In some disorders,
the cell count remains normal, whereas the total protein is
notably increased, a phenomenon termed albuminocytological
dissociation. Some degenerative disorders, ischemia/
infarction, immune-mediated diseases (e.g., polyradiculoneuritis),
tumors, and neural compression produce albuminocytological
dissociation ( Laterre, 1996 ).
3 . Increased CSF Albumin and Albumin Index
Elevation of CSF albumin (which originates in the serum),
and consequently an increased albumin index, indicates
dysfunction of the blood-brain/spinal cord/CSF barriers or