Localizing Value of Abnormal
Pupillary Responses in Patients
in Coma
Characteristic pupillary responses are seen
with lesions at specific sites in the neuraxis
(Figure 2–7).
Diencephalic injuries typically result in small,
reactive pupils. Bilateral, small, reactive pupils
are typically seen when there is bilateral dience-
phalic injury or compression, but also are seen
in almost all types of metabolic encephalopathy,
and therefore this finding is also of limited value
in identifying structural causes of coma.
A unilateral, small, reactive pupil accompa-
nied by ipsilateral ptosis is often of great di-
agnostic value. If there is no associated loss of
sweating in the face or the body (even after the
patient is placed under a heating lamp that
causes sweating of the contralateral face), then
the lesion is likely to be along the course of the
internal carotid artery or in the cavernous si-
nus, superior orbital fissure, or the orbit itself
(Raeder’s paratrigeminal syndrome, although
in some cases the Horner’s syndrome is merely
incomplete). If there is a sweating defect con-
fined to the face (peripheral Horner’s syn-
drome), the defect must be extracranial (from
the T1–2 spinal level to the carotid bifurca-
tion). However, if the loss of sweating involves
the entire side of the body (central Horner’s
syndrome), it indicates a lesion involving the
pathway between the hypothalamus and the
spinal cord on the ipsilateral side. Although hy-
pothalamic unilateral injury can produce this
finding, lesions of the lateral brainstem tegmen-
tum are a more common cause.
Midbrain injuries may cause a wide range
of pupillary abnormalities, depending on the
Midbrain:
midposition, fixed
Pons:
pinpoint
Pretectal:
large, "fixed", hippus
Diencephalic:
small, reactive
Diffuse effects of
drugs, metabolic
encephalopathy, etc.:
small, reactive
III nerve (uncall):
dilated, fixed
Figure 2–7. Summary of changes in pupils in patients with lesions at different levels of the brain that cause coma. (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.)
58
Plum and Posner’s Diagnosis of Stupor and Coma
nature of the insult. Bilateral midbrain tegmen-
tal infarction, involving the oculomotor nerves
or nuclei bilaterally, results in fixed pupils,
which are either large (if the descending sym-
pathetic tracts are preserved) or midposition (if
they are not). However, pupils that are fixed
due to midbrain injury may dilate with the
ciliospinal reflex. This response distinguishes
midbrain pupils from cases of brain death. It is
often thought that pupils become fixed and di-
lated in death, but this is only true if there is a
terminal release of adrenal catecholamines. The
dilated pupils found immediately after death
resolve over a few hours to the midposition, as
are seen in patients who are brain dead or who
have midbrain infarction.
More distal injury, after the oculomotor nerve
leaves the brainstem, is typically unilateral. The
oculomotor nerve’s course makes it suscepti-
ble to damage by either the uncus of the tem-
poral lobe as it herniates through the tentorial
opening (see supratentorial causes of coma, page
103) or an aneurysm of the posterior commu-
nicating artery. Either of these lesions may com-
press the oculomotor nerve from the dorsal di-
rection. Because the pupilloconstrictor fibers
lie superficially on the dorsomedial surface of
the nerve at this level,
92
the first sign of im-
pending disaster may be a unilateral enlarged
and poorly reactive pupil. These conditions are
discussed in detail in Chapter 3.
Pontine tegmental injury typically results in
pinpoint pupils. The pupils can often be seen
under magnification to respond to bright light.
However, the simultaneous injury to both the
descending and ascending pupillodilator path-
ways causes near maximal pupillary constric-
tion.
86
The most common cause is pontine
hemorrhage.
Lesions involving the lateral medullary teg-
mentum, such as Wallenberg’s lateral medul-
lary infarction, may cause an ipsilateral central
Horner’s syndrome.
Metabolic and Pharmacologic
Causes of Abnormal
Pupillary Response
Although the foregoing discussion illustrates
the importance of the pupillary light response
in diagnosing structural causes of coma, it
is critical to be able to distinguish structural
causes from metabolic and pharmacologic
causes of pupillary abnormalities. Nearly any
metabolic encephalopathy that causes a sleepy
state may result in small, reactive pupils that
are difficult to differentiate from pupillary re-
sponses caused by diencephalic injuries. How-
ever, the pupillary light reflex is one of the most
resistant brain responses during metabolic en-
cephalopathy. Hence, a comatose patient who
shows other signs of midbrain depression (e.g.,
loss of other oculomotor responses) yet retains
the pupillary light reflex is likely to have a met-
abolic disturbance causing the coma.
During or following seizures, one or both
pupils may transiently (usually for 15 to 20
minutes, and rarely as long as an hour) be large
or react poorly to light. During hypoxia or
global ischemia of the brain such as during a
cardiac arrest, the pupils typically become large
and fixed, due to a combination of systemic
catecholamine release at the onset of the is-
chemia or hypoxia and lack of response by the
metabolically depleted brain. If resuscitation is
successful, the pupils usually return to a small,
reactive state. Pupils that remain enlarged and
nonreactive for more than a few minutes after
otherwise successful resuscitation are indica-
tive of profound brain ischemia and a poor
prognostic sign (see discussion of outcomes
from hypoxic/ischemic coma in Chapter 9).
Although most drugs that impair conscious-
ness cause small, reactive pupils, a few produce
quite different responses that may help to iden-
tify the cause of the coma. Opiates, for exam-
ple, typically produce pinpoint pupils that re-
semble those seen in pontine hemorrhage.
However, administration of an opioid antago-
nist such as naloxone results in rapid reversal
of both the pupillary abnormality and the im-
pairment of consciousness (naloxone must be
given carefully to an opioid-intoxicated patient,
because if the patient is opioid dependent, the
drug may precipitate acute withdrawal). Chap-
ter 7 discusses the use of naloxone. Muscarinic
cholinergic antagonist drugs that cross the
blood-brain barrier, such as scopolamine, may
cause a confused, delirious state, in combina-
tion with large, poorly reactive pupils. Lack of
response to pilocarpine eye drops (see above)
demonstrates the muscarinic blockade. Glu-
tethimide, a sedative-hypnotic drug that was
popular in the 1960s, was notorious for causing
large and poorly reactive pupils. Fortunately, it
is rarely used anymore.
Examination of the Comatose Patient
59