of the neck). Nevertheless, it is imperative to
identify infection as early as possible to allow
the administration of antibiotics or antiviral
agents.
Patient 2–2
A 73-year-old woman who was on 10 mg/day of
prednisone for her ulcerative colitis had a 2-day
history of presumed gastroenteritis, with fever,
nausea, and vomiting. She awoke on the third
day and found it difficult to walk to the bath-
room. By the afternoon she had difficulty swal-
lowing, her voice was hoarse, and her left limbs
were clumsy. She was brought to the hospital by
ambulance, and examination in the emergency
department disclosed a lethargic patient who
could be easily wakened. Pupils were equal and
constricted from 3 to 2 mm with light, but the left
eye was lower than the right, she complained of
skewed diplopia, and there was difficulty main-
taining gaze to the left. There was left-sided facial
numbness and lower motor neuron facial weak-
ness. Hearing was intact, but her voice was hoarse.
The tongue deviated to the right and there was
distal weakness in her arms, and the left limbs
were clumsy on fine motor tasks and showed
dysmetria.
MRI scan showed a left pontomedullary le-
sion surrounded by edema, which was bright on
diffusion-weighted imaging, and she was diag-
nosed as having a brainstem infarct. However,
despite normal MRA of the vertebrobasilar system,
her deficits progressed over the next day. A se-
nior neuroradiologist noticed some enhancement
at the periphery of the lesion on review of the MRI
scan, and suggested an abscess. Lumbar puncture
disclosed 47 white blood cells/mm
3
and elevated
protein, and she recovered after being treated for
Listeria monocytogenes. An MRI scan much later
in her course, disclosing a multioculated abscess,
is shown in Figure 4–13.
Comment. This case demonstrates the impor-
tance of examining the spinal fluid, even when a
presumptive diagnosis of vascular disease is en-
tertained. This is particularly true in patients with
fever, elevated white blood cell count, or stiff neck,
where infectious disease is a consideration. How-
ever, every patient with an undetermined cause of
coma requires lumbar puncture as part of the rou-
tine evaluation.
The timing of lumbar puncture with respect
to CT scanning is discussed in Chapters 4 and
5. However, in some circumstances, scanning
may not be not immediately available. In these
cases it is common to give antibiotics imme-
diately and then do imaging and lumbar punc-
ture up to a few hours later. However, once the
antibiotics have penetrated the CSF, the abil-
ity to grow a bacterial pathogen and identify its
susceptibilities may be permanently compro-
mised. Hence, deferring lumbar puncture in
such cases until after the scanning procedure
may do the patient harm. For this reason, when
the evidence for meningitis is compelling, it
may be necessary to do the lumbar puncture
without benefit of prior imaging. As discussed
in Chapters 4 and 5, the danger of this pro-
cedure is greatly overestimated. If the exami-
nation is nonfocal, and there is no evidence of
papilledema on funduscopy, it is extremely
rare to precipitate brain herniation by lumbar
puncture. The benefit of establishing the exact
microbial diagnosis far outweighs the risk of
herniation.
A critical but often overlooked component
of the lumbar puncture is to measure and re-
cord the opening pressure. Elevated pressure
may be a key sign that leads to diagnosis of
venous sinus thrombosis, cerebral edema, or
other serious conditions that can cause coma.
In addition to the routine cell count, protein,
and glucose, CSF should be obtained for full
cultures, including tuberculosis and fungal
agents; serology and polymerase chain reaction
(PCR) for specific agents such as syphilis,
Lyme disease, and herpes encephalitis; and cy-
tology, as cancer or leukemia sometimes may
present with meningeal and subarachnoid in-
filtration. It is a good practice to set aside sev-
eral milliliters of refrigerated CSF in case ad-
ditional studies become necessary. This entire
group of tests typically requires about 20 mL
of CSF, an amount that the choroid plexus in
the brain restores within about an hour.
One common problem is that the lumbar
tap may be traumatic, yielding bloody CSF.
This may make it difficult to determine the
underlying numbers of both red and white
blood cells in the CSF. If the cells come from
the blood (rather than the white cells being
elevated within the CSF, e.g., due to infection),
the proportion of the red and white cells should
remain the same as in the blood (usually
Examination of the Comatose Patient
81
500 to 1,000 red cells per one white cell). If the
tap is bloody, many clinicians send fluid from
both tubes 1 and 4 for cell count. A falling
count indicates that the tap was traumatic, but
it does not tell you what the underlying CSF
counts were compared with the count in tube
4. Nor does lack of a falling cell count indicate
that the blood was there before the tap (the tip
of the needle may be partially within or ad-
jacent to a bleeding vein). An alternative ap-
proach is to examine the CSF for xantho-
chromia. However, CSF may be stained yellow
due to high protein or bilirubin. Examination of
the red blood cells under the microscope im-
mediately after the tap may be helpful. Fresh
red cells have the typical doughnut-shaped
morphology, whereas crenelated cells indicate
that they have been in the extravascular space
for some time. Similarly, if the CSF sample is
spun in a centrifuge until there are no red
blood cells in the supernatant, the fluid can
be tested for blood products with a urine dip-
stick. A positive test indicates breakdown of
red blood cells, which typically takes at least
6 hours to occur after a subarachnoid hemor-
rhage, and demonstrates that the blood was
there before the tap.
Electroencephalography and
Evoked Potentials
Electroencephalography (EEG) is useful as an
objective electrophysiologic assay of cortical
function in patients who do not respond to
normal sensory stimuli. A typical waking EEG
is dominated anteriorly by low-voltage beta
activity (faster than 13 Hz). During periods of
quiet wakefulness, the EEG may slow into the
alpha range (8 to 13 Hz) and the wave activity
may be more rhythmic and symmetric. As the
patient becomes more drowsy, higher voltage
theta rhythms (4 to 7 Hz) become dominant;
delta activity (1 to 3 Hz) predominates in pa-
tients who are deeply asleep or comatose. The
EEG provides a rough but fairly accurate es-
timate of the degree to which a patient who is
unresponsive may be simply uncooperative.
On the other hand, occasional patients with
coma due to brainstem injury show an alpha
EEG pattern. The alpha activity in such pa-
tients is usually more regular and less variable
than in an awake patient, and it is not inhibited
by opening the eyes.
163
It may be possible to
drive the EEG by photic stimulation in alpha
coma. Certain types of metabolic encephalop-
athy may also have characteristic EEG chan-
ges. For example, triphasic waves are often seen
in patients with hepatic encephalopathy, but
can be seen in other metabolic disorders that
cause coma.
163,164
The EEG is most helpful in diagnosing im-
pairment of consciousness due to non-
convulsive status epilepticus.
165
Such patients
may lack the usual behavioral signs of com-
plex partial seizures, such as lip smacking or
blinking, and may present as merely confused,
drowsy, or even stuporous or comatose. Some
patients may demonstrate twitching move-
ments of the eyelids or extremities, but others
give no external sign of epileptic activity. In
one series, 8% of comatose patients were found
to be suffering from nonconvulsive status epi-
lepticus.
166
When the EEG shows continuous
epileptic activity, the diagnosis is easy and an-
ticonvulsants are required. However, noncon-
vulsive status epilepticus may occur in patients
without characteristic EEG changes,
167
prob-
ably because the seizure activity is mainly in
areas such as the medial temporal lobes that
are not sampled by the surface electrodes. Ac-
cordingly, if one suspects that the patient’s loss
of consciousness is a result of nonconvulsive
status epilepticus, it is probably wise to admin-
ister a short-acting benzodiazepine and observe
the patient’s response. If the patient improves,
antiepileptic drugs should be administered. Un-
fortunately, some patients with a clinical and
electroencephalographic diagnosis of noncon-
vulsive status epilepticus do not respond to an-
ticonvulsant drugs, because the underlying pro-
cess causing the seizure activity is too severe
to be suppressed by routine doses of drugs.
Such patients are sometimes treated by large
intravenous doses of gamma-aminobutyric acid
agonist drugs, such as barbiturates or propofol,
which at sufficiently high dosage can suppress
all brain activity. However, unless the underly-
ing brain process can be reversed, the prognosis
of patients with nonconvulsive status epilepticus
who do not awaken after anticonvulsant treat-
ment is poor
168
(see also Seizures in Chapter 5).
Evoked potentials may also be used to test
the integrity of brainstem and forebrain path-
ways in comatose patients. Although they do
not provide reliable information on the loca-
tion of a lesion in the brainstem, both auditory-
and somatosensory-evoked potentials, and cor-
82
Plum and Posner’s Diagnosis of Stupor and Coma