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

VII. General Characteristics of CSF in Disease
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several neurological diseases, they concluded that the greater
frequency of elevation in the CSF of horses with protozoal
myelitis versus horses with cervical compressive myelopathy
indicated this enzyme assay was useful in differentiating
these two diseases ( Furr and Tyler, 1990 ). This conclusion
was disputed by Jackson et al. (1996) , who did not find the
sensitivity or specificity of creatine kinase measurement
sufficient for diagnosis of a specific disease. Jackson et al.
(1996) also concluded that contamination of the CSF sample
with epidural fat or dura mater may contribute to previously
unexplained elevations in CSF creatine kinase activity.
Their conclusion regarding this enzyme’s lack of sensitivity
and specificity reflects the current situation with all of the
enzymes in CSF studied to date—none has sufficient specificity
to warrant its routine use as diagnostic test ( Fishman,
1992 ; Indrieri et al., 1980 ; Jackson et al. , 1996 ; Kjeldsberg
and Knight, 1993 ; Rand et al. , 1994b ). The site of CSF collection
with respect to the location of the lesion may be
responsible for some of the lack of diagnostic significance
in CSF enzyme analysis. Cerebellomedullary fluid may be
less affected than lumbar fluid in animals with spinal disease
(Indrieri et al. , 1980 ). Measurement of enzyme isomers may
increase the specificity ( Kjeldsberg and Knight, 1993 ).
To date, none of the enzyme assays are sufficiently sensitive
or specific to warrant routine use in clinical practice
( Fishman, 1992 ; Indrieri et al. , 1980 ; Jackson et al. , 1996 ;
Kjeldsberg and Knight, 1993 ; Rand et al. , 1994a ).
G . Other Constituents
1 . Interferon
Interferon is increased in the CSF in a large percentage of
people with viral encephalitis-meningitis. This finding is
not specific, however, as increases are also found in patients
with bacterial meningitis ( Glimaker et al. , 1994 ) or multiple
sclerosis and occasionally in patients with noninflammatory
neurological disease (Brooks et al. , 1983). In an experimental
study of canine distemper, interferon appeared to be a
valid marker for persistence of the virus in the central nervous
system ( Tsai et al. , 1982 ).
2 . Neurotransmitters
Gamma-aminobutyric acid (GABA) is a major inhibitory
neurotransmitter, whose dysfunction has been suggested
to play a role in experimental ( Griffith et al. , 1991 ) and
clinical seizure disorders. Conversely, glutamate (GLU) is a
major excitatory neurotransmitter in the CNS that plays an
important role in the initiation, spread, and maintenance of
epileptic activity in people ( Meldrum, 1994 ). Increased extracellular
concentrations of glutamate in the CNS may also
mediate secondary tissue damage and cell death ( Meldrum,
2000 ). A study of epileptic dogs found the average CSF
concentration of GABA to be significantly reduced, a situation
similar to that in people ( Loscher and Schwartz-Porsche,
1986 ). Inhibitory and excitatory neurotransmitters have been
assayed in the CSF of epileptic dogs ( Ellenberger et al. ,
2004 ; Podell and Hadjiconstantinou, 1997 ). In one study, epileptic
dogs were found to have lower levels of CSF GABA
and higher levels of CSF glutamate than normal dogs ( Podell
and Hadjiconstantinou, 1997 ). In another study, CSF GABA
was also found to be decreased in epileptic Labradors, but in
contrast to the former report, these dogs had lower levels of
CSF glutamate than normal dogs or epileptic non-Labradors
(Ellenberger et al. , 2004 ). CSF neurotransmitters have also
been assayed in dogs with portosystemic shunts (PSS) and
clinical signs of hepatic encephalopathy ( Holt et al. , 2002 ).
Dogs with PSS had significantly higher levels of glutamine,
tryptophan, and 5-hydroxyindoleacetic acid. These alterations
may play a role in the neurological abnormalities associated
with hepatic encephalopathy ( Holt et al. , 2002 ). Because of
its potential role in secondary tissue damage, glutamate concentrations
in lumbar CSF have been measured in dogs with
intervertebral disk herniation and acute and chronic compressive
spinal cord lesions ( Olby et al. , 1999 ). Dogs with severe,
acute thoracolumbar disk herniations have two- to ten-fold
increases in their lumbar CSF 12 h or more after injury. The
severity of the clinical signs appeared to be related to the
lumbar CSF glutamate concentration ( Olby et al. , 1999 ).
Dogs with chronic compressive thoracolumbar lesions have
a two-fold elevation of lumbar CSF glutamate concentration.
However, focal spinal cord injuries did not alter glutamate
concentrations in cisternal CSF ( Olby et al. , 1999 ).
Increased CSF levels of the biogenic amine neurotransmitter
metabolites homovanillic acid and 5-hydroxyindoleacetic
acid were found in 2 of 10 collies experimentally
given ivermectin (Vaughn et al. , 1989 ). Both of these collies
had severe neurological deficits. Neurotransmitter metabolite
concentrations were also elevated in the CSF of goats
demonstrating neurological abnormalities after experimental
boron toxicosis ( Sisk et al. , 1990 ). Significant differences
in neurotransmitter concentrations were found
between the CSF of normal dogs and narcoleptic dogs
(Faull et al. , 1982 ). Hyopocretins are neuropeptides that
bind to the G-protein coupled hypocretin receptors Hcrtr
1 and Hcrtr 2. Hypocretins are undetectable in the CSF of
sporadic narcoleptic dogs but are normal in familial narcoleptic
dogs that have mutations in the hypocretin receptor 2
gene ( Ripley et al. , 2001 ).
3 . Quinolinic Acid
Quinolinic acid is a neuroexcitotoxic metabolite of
L-tryptophan and an agonist of N-methyl- d -aspartate
receptors. Increased levels have been found in people with
a variety of neurological diseases including AIDS ( Heyes
et al. , 1992 ) and macaques infected with simian immunodeficiency
virus ( Smith, 1995 ). Quinolinic acid levels