and it can induce a vomiting reflex.
78
The area
postrema contains both dopaminergic and se-
rotoninergic neurons, and the latter produce
emesis primarily by means of contacting 5HT
3
receptors.
77
Hence, drugs that block dopamine
D
2
receptors (e.g., chlorpromazine, metoclo-
pramide) or serotonin 5HT
3
receptors (ondan-
setron) are effective antiemetics.
PUPILLARY RESPONSES
The pupillary light reflex is one of the most ba-
sic and easily tested nervous system responses.
It is controlled by a complex balance of sym-
pathetic (pupillodilator) and parasympathetic
(pupilloconstrictor) pathways (see Figure 2–
6). The anatomy of these pathways is closely
intertwined with the components of the as-
cending arousal system. In addition, the pupil-
lary pathways are among the most resistant to
metabolic insult. Hence, abnormalities of pu-
pillary responses are of great localizing value
in diagnosing the cause of stupor and coma,
and the pupillary light reflex is the single most
important physical sign in differentiating met-
abolic from structural coma.
Examine the Pupils and
Their Responses
If possible, inquire if the patient has suffered
eye disease or uses eyedrops. Observe the pu-
pils in ambient light; if room lights are bright
and pupils are small, dimming the light may
make it easier to see the pupillary responses.
They should be equal in size and about the
same size as those of normal individuals in the
same light (8% to 18% of normal individuals
have anisocoria greater than 0.4 mm). Unequal
pupils can result from sympathetic paralysis
making the pupil smaller or parasympathetic
paralysis making the pupil larger. If one sus-
pects sympathetic paralysis (see Horner’s syn-
drome, page 58), dim the lights in the room,
allowing the normal pupil to dilate and thus
bringing out the pupillary inequality. Unless
there is specific damage to the pupillary sys-
tem, pupils of stuporous or comatose patients
are usually smaller than normal pupils in awake
subjects. Pupillary responses must be exam-
ined with a bright light. The eyelids can be held
open while the light from a bright flashlight
illuminates each pupil. Shining the light into
one pupil should cause both pupils to react
briskly and equally. Because the pupils are of-
ten small in stuporous or comatose patients and
the light reflex may be through a small range,
one may want to view the pupil through the
bright light of an ophthalmoscope using a plus
20 lens or through the lens of an otoscope.
Most pupillary responses are brisk, but a tonic
pupil may react slowly, so the light should il-
luminate the eye for at least 10 seconds. Moving
the light from one eye to the other may result
in constriction of both pupils when the light
is shined into the first eye, but paradoxically
pupillary dilation when the light is shined in
the other eye. This aberrant pupillary response
results from damage to the retina or optic
nerve on the side on which the pupil dilates
(relative afferent pupillary defect [RAPD]).
79
One of the most ominous signs in neurology
is a unilateral dilated and unreactive pupil. In a
comatose patient, this usually indicates oculo-
motor nerve compromise either by a posterior
communicating artery aneurysm or by tempo-
ral lobe herniation (see oculomotor responses,
page 60). However, the same finding can be
mimicked by unilateral instillation of atropine-
like eye drops. Occasionally this happens by
accident, as when a patient who is using a sco-
polamine patch to avert motion sickness in-
advertently gets some scopolamine onto a finger
when handling the patch, and then rubs the
eye; however, it is also seen in cases of facti-
tious presentation. Still other times, unilateral
pupillary dilation may occur in the setting of
ciliary ganglion dysfunction from head or facial
trauma. In most of these cases there is a frac-
ture in the posterior floor of the orbit that in-
terrupts the fibers of the inferior division of the
oculomotor nerve.
80
Injury to the third nerve
can be distinguished from atropinic blockade at
the bedside by instilling a dilute solution of pi-
locarpine into the eye (see pharmacology, page
56). The denervated pupil will respond briskly,
whereas the one that is blocked by atropine
will not.
81
Once both the ipsilateral and consensual
pupillary light reflexes have been noted, the
next step is to induce a ciliospinal reflex.
10
This
can be done by pinching the skin of the neck or
the face. The pupils should dilate 1 to 2 mm
bilaterally. This reflex is an example of a spin-
obulbospinal response (i.e., the pain stimulus
54
Plum and Posner’s Diagnosis of Stupor and Coma
arises from the trigeminal or spinal dorsal horn,
must ascend to brainstem autonomic control
areas, and then descend again to the C8-T2
sympathetic preganglionic neurons). A normal
ciliospinal response ensures integrity of these
circuits from the lower brainstem to the spinal
cord, thus usually placing the lesion in the
rostral pons or higher.
Pathophysiology of Pupillary
Responses: Peripheral Anatomy
of the Pupillomotor System
The pupil is a hole in the iris; thus, change in
pupillary diameter occurs when the iris con-
tracts or expands. The pupillodilator muscle is
a set of radially oriented muscle fibers, running
from the edge of the pupil to the limbus (outer
edge) of the iris. When these muscles contract,
they open the pupil in much the way a draw-
string pulls up a curtain. The pupillodilator
muscles are innervated by sympathetic ganglion
cells in the superior cervical ganglion. These
axons pass along the internal carotid artery,
joining the ophthalmic division of the trigem-
inal nerve in the cavernous sinus and accom-
panying it through the superior orbital fissure,
into the orbit. Sympathetic input to the lid re-
tractor muscle takes a similar course, but sym-
pathetic fibers from the superior cervical gan-
glion that control facial sweating travel along
the external carotid artery. Hence, lesions of
the ascending cervical sympathetic chain up
to the superior cervical ganglion typically give
rise to Horner’s syndrome (ptosis, miosis, and
facial anhydrosis). However, lesions along the
course of the internal carotid artery may give
only the first two components of this syndrome
(Raeder’s paratrigeminal syndrome). The sym-
pathetic preganglionic neurons for pupillary
control are found in the intermediolateral col-
umn of the first three thoracic segments. Hence,
lesions of those roots, or of the ascending sym-
pathetic trunk between T1 and the superior
cervical ganglion, may also cause a Horner’s
syndrome with, depending on the exact site of
the lesion, anhydrosis of the ipsilateral face or
the face and arm.
B
A
Retinal
ganglion cell
Pupilloconstrictor
muscle in the iris
Ciliary
ganglia
III
nerve
LGN
MLF
Olivary pretectal
nucleus
Edinger-Westphal
nucleus
T
3
T
2
T
1
Superior
cervical
sympathetic
ganglion
3rd
neuron
Internal
carotid
artery
Ophthalmic
division
trigeminal
nerve
Long
ciliary nerve
Hypothalamus
Pupillodilator
muscle in the iris
Short
ciliary
nerve
Ciliary
ganglion
Figure 2–6. Two summary drawings indicating the (A) parasympathetic pupilloconstrictor pathways and (B) sympathetic
pupillodilator pathways. LGN, lateral geniculate nucleus; MLF, medial longitudinal fasciculus. (From Saper, C. Brain stem
modulation of sensation, movement, and consciousness. Chapter 45 in: Kandel, ER, Schwartz, JH, Jessel, TM. Principles of
Neural Science. 4th ed. McGraw-Hill, New York, 2000, pp. 871–909. By permission of McGraw-Hill.)
Examination of the Comatose Patient
55