Second edition

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34 Diagnostic assessment
almost superfluous. Appropriate cultures should also be
requested, whether bacterial, tubercular, or fungal.
Tests for syphilis
It is good practice to always request a CSF-VDRL test with
titer. Furthermore, in cases where the clinical picture is consistent
with neurosyphilis but the CSF-VDRL is negative it is
entirely appropriate to obtain a CSF-FTA, given that the
CSF-FTA is a far more sensitive test than the CSF-VDRL
(Davis and Schmitt 1989; Timmermans and Carr 2004).
Opening pressure
Measurement of the opening pressure, although once considered
standard, is rarely required in modern practice: one
exception consists of cases of suspected benign intracranial
hypertension. The normal opening pressure ranges from
6 to 20 cm of water; values of below 5 cm may be seen with
systemic dehydration, subarachnoid block, or following a
prior lumbar puncture. Elevations of over 20 cm are seen
in cases of benign intracranial hypertension, meningitis,
cerebral venous occlusion, and with mass lesions, hemorrhages,
or acute infarctions.
Other determinations
Other determinations are requested depending on one’s
diagnostic suspicions, and may include PCR assay and testing
for various antibodies and antigens: in these regards,
consultation with an infectious disease specialist, if not
already in the works, is always appropriate, given the rapid
advances made in these fields. Other tests to consider
include the immunoglobulin G (IgG) index, oligoclonal
bands, myelin basic protein and the 14-3-3 protein.
Polymerase chain reaction assay represents a rapid, sensitive,
and specific means for detecting various infections.
Viruses detected include herpes simplex, varicella zoster,
Epstein-Barr, JC virus, HIV, and cytomegalovirus (CMV)
(Steiner et al. 2005). Furthermore, almost all bacteria may
also be identified (Poppert et al. 2005). Fungal and tubercular
infections may also be detected.
Antibodies to arboviruses, rabies virus, Borrelia burgdorferi
and Coccidioides immitis may be tested for, as may
antigens specific for Cryptococcus and Histoplasma, and
these should be ordered in the appropriate clinical setting.
The IgG index provides a reliable measure of increased
production of IgG within the CNS. Elevations of total
IgG itself may represent a false-positive, given that the
immunoglobulin level in the CSF reflects not only
intrathecal synthesis of globulin, but also transfer of globulins
from the systemic circulation. Consequently, it is necessary
to correct the CSF level by obtaining what is known as
the ‘IgG index’. The IgG index � (IgG[CSF]/IgG[serum])/
(albumin[CSF]/albumin[serum]). IgG index values above
0.65 indicate intrathecal synthesis. To calculate this, of
course, one must also obtain blood for a serum protein
electrophoresis, and this should be done just before the
lumbar puncture.
Oligoclonal bands, that is to say anywhere from three to
five bands seen on electrophoresis, are seen in a number of
conditions, including multiple sclerosis, lupus, Behçet’s
syndrome, neurosarcoidosis, and infections, whether viral,
bacterial, or fungal.
Myelin basic protein is found in diseases characterized
by myelin breakdown, such as multiple sclerosis. An
increased myelin basic protein, however, is certainly not
specific for multiple sclerosis, being found in various other
conditions, such as encephalitis, lupus, vasculitidies, and
recent infarction.
The 14-3-3 protein should be tested for in suspected
cases of Creutzfeldt–Jakob disease. Although this is very
sensitive for Creutzfeldt–Jakob disease, false-positives have
been noted in large number of conditions such as encephalitis,
recent infarction, multiple sclerosis, Hashimoto’s
encephalopathy, paraneoplastic limbic encephalitis, astrocytoma,
and even degenerative disorders such as Alzheimer’s
disease, diffuse Lewy body disease, and amyotrophic lateral
scelerosis (Lemstra et al. 2000; Martinez-Yelamos et al. 2001;
Van Everbroeck et al. 2005).
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