anatomy and pathophysiology of each of these
processes is critical in evaluating patients in
coma.
COMPRESSIVE LESIONS
MAY DIRECTLY DISTORT
THE AROUSAL SYSTEM
Compression at key levels of the brain may
cause coma by exerting pressure upon the struc-
tures of the arousal system. The mechanism by
which local pressure may impair neuronal func-
tion is not entirely understood. However, neu-
rons are dependent upon axonal transport to
supply critical proteins and mitochondria to
their terminals, and to transport used or dam-
aged cellular components back to the cell body
for destruction and disposal. Even a loose lig-
ature around an axon causes damming of axon
contents on both sides of the stricture, due to
impairment of both anterograde and retrograde
axonal flow, and results in impairment of axonal
function. Perhaps the clearest example of this
relationship is provided by the optic nerve in
patients with papilledema (see section on in-
creased ICP, page 91). When a compressive
lesion results in displacement of the structures
of the arousal system, consciousness may be-
come impaired, as described in the sections
below.
Compression at Different Levels
of the Central Nervous System
Presents in Distinct Ways
When a cerebral hemisphere is compressed by
a lesion such as a subdural hematoma, tumor,
or abscess that grows slowly over a long period
of time, it may reach a relatively large size with
little in the way of local signs that can help
identify the diagnosis. The tissue in the cerebral
hemispheres can absorb a surprising amount of
distortion and stretching, as long as the growth
of the mass can be compensated for by dis-
placing cerebrospinal fluid (CSF) from the
ventricles in that hemisphere. However, when
there is no further room in the hemisphere
to expand, even a small amount of growth can
only be accommodated by compressing the di-
encephalon and midbrain either laterally across
the midline or downward. In such patients, the
impairment of consciousness correlates with
the displacement of the diencephalon and up-
per brainstem in a lateral or caudal direction.
1
Hence, when a patient with a hemispheric le-
sion reaches the point of impairment of con-
sciousness, there is very little time left to in-
tervene before the brain is irreparably injured.
The diencephalon may also be compressed
by a mass lesion in the thalamus itself (gener-
ally a tumor or a hemorrhage) or a mass in the
suprasellar cistern (typically a craniopharyngi-
oma, a germ cell tumor, or suprasellar exten-
sion of a pituitary adenoma; see Chapter 4). In
addition to causing impairment of conscious-
ness, suprasellar tumors typically cause visual
field deficits, classically a bitemporal hemia-
nopsia, although a wide range of optic nerve or
tract injuries may also occur. If a suprasellar
tumor extends into the cavernous sinus, there
may be injury to the cranial nerves that supply
the ocular muscles (III, IV, VI) and the oph-
thalmic division of the trigeminal nerve (V1).
On occasion, these tumors may also cause en-
docrine dysfunction. If they damage the pitui-
tary stalk, they may cause diabetes insipidus or
panhypopituitarism. In women, the presence
of a pituitary tumor is often heralded by ga-
lactorrhea and amenorrhea, as prolactin is the
sole anterior pituitary hormone under negative
regulation, and it is typically elevated when
the pituitary stalk is damaged.
The dorsal midbrain may be compressed by
a tumor in the pineal region. Pineal mass lesions
may be suprasellar germinomas or other germ
cell tumors (embryonal cell carcinoma, terato-
carcinoma) that occur along the midline, or
pineal masses including pinealcytoma or pineal
astrocytoma. Pineal masses compress the pre-
tectal area as well. Thus, in addition to causing
impairment of consciousness, they produce di-
agnostic neuro-ophthalmologic signs including
fixed, slightly enlarged pupils; impairment of vol-
untary vertical eye movements (typically eleva-
tion is impaired earlier and more severely than
depression) and convergence; and convergence
nystagmus and sometimes retractory nystagmus
(Parinaud’s syndrome; see page 110).
2
Hem-
orrhage into the pulvinar of the thalamus, which
overlies the pretectal area and dorsal midbrain,
may sometimes produce a similar constellation
of signs.
Posterior fossa compressive lesions most often
originate in the cerebellum, including tumors,
hemorrhages, infarctions, or abscesses, although
90
Plum and Posner’s Diagnosis of Stupor and Coma
occasionally extra-axial lesions, such as a sub-
dural or epidural hematoma, may have a sim-
ilar effect. Tumors of the cerebellum include
the full range of primary and metastatic brain
tumors (Chapter 4), as well as juvenile pilocytic
astrocytomas and medulloblastomas in children
and hemangioblastoma in patients with von
Hippel-Lindau syndrome.
A cerebellar mass causes coma by direct com-
pression of the brainstem, which may also cause
the brainstem to herniate upward through the
tentorial notch. As the patient loses conscious-
ness, there is a pattern of pontine level dysfunc-
tion, with small reactive pupils, impairment of
vestibulo-ocular responses (which may be asym-
metric), and decerebrate motor responses.
3,4
Because the base of the pons is farthest from
the cerebellum, motor signs (e.g., upgoing toes)
are usually a relatively late finding, and suggest
instead an intrinsic brainstem mass. With up-
ward pressure on the midbrain, the pupils be-
come asymmetric or unreactive. If vestibulo-
ocular responses were not previously impaired
by pontine compression, vertical eye movements
may be lost.
Cerebellar mass lesions may also cause coma
by compressing the fourth ventricle to the point
where it impairs flow of CSF. This causes acute
hydrocephalus and rapidly increasing ICP (see
page 147). The onset of obstruction of the
fourth ventricle is typically heralded by nau-
sea and sometimes sudden, projectile vomiting.
There may also be a history of ataxia, vertigo,
neck stiffness, and eventually respiratory arrest
as the cerebellar tonsils are impacted upon the
lip of the foramen magnum. If the compression
develops slowly (i.e., over more than 12 hours),
there may also be papilledema. Because cere-
bellar masses may cause acute obstruction of
the fourth ventricle by expanding by only a few
millimeters in diameter, they are potentially very
dangerous.
On occasion, impairment of consciousness
may occur as a result of a mass lesion directly
compressing the brainstem. These are more
commonly intrinsic masses, such as an abscess
or a hemorrhage, in which case it is difficult to
determine how much of the impairment is due
to compression as opposed to destruction. Oc-
casionally, a mass lesion of the cerebellopon-
tine angle, such as a vestibular schwannoma,
meningioma, or cholesteatoma, may compress
the brainstem. However, these are usually slow
processes and the mass may reach a very large
size and often causes signs of local injury be-
fore consciousness is impaired.
The Role of Increased Intracranial
Pressure in Coma
A key and often misunderstood point is that
increases in ICP are withstood remarkably well
by the brain, as long as they progress relatively
slowly. In patients with chronic elevation of CSF
pressure, such as those with pseudotumor cer-
ebri, there is little evidence of brain dysfunction,
even when CSF pressures reach 600 mm of wa-
ter or greater. The chief problems induced by
increased ICP are papilledema and headache,
until the pressure gets high enough to impair
cerebral blood flow.
Papilledema is due to the pressure differen-
tial applied to the optic nerve by the increase in
ICP. Retinal ganglion cells within the eye are
subject to intraocular pressure, typically in the
same range as normal CSF pressure. Their axons
leave the eye through the optic disk and travel
to the brain via the optic nerve. Axoplasm flows
from the retinal ganglion cell bodies in the
eye, down the axon and through the optic disc.
Similarly, the retinal veins within the eye are
subject to intraocular pressure. They also leave
through the optic disc and run along the optic
nerve. The optic nerve in turn is surrounded by
a dural and arachnoid sleeve, which contains
CSF that communicates with the CSF in the
subarachnoid space around the brain.
5
The op-
tic disk itself is composed of a dense fibrous net-
work forming a cribriform (from the Latin for
sieve) plate that acts as a pressure fitting, so that
the optic nerve and retinal vein are exposed to
intraocular pressure on one side of the disk and
to ICP on the other side.
Normally, axonal transport proceeds unim-
peded and the retinal veins show normal venous
pulsations, as there is little, if any, pressure dif-
ferential between the two compartments. As
ICP rises above systemic venous pressure, ret-
inal venous pulsations are damped or elimi-
nated as an early feature of papilledema. The
retinal veins become larger and more numer-
ous appearing, because increased venous pres-
sure causes smaller veins to become more no-
ticeable on funduscopy. Thus, the presence of
retinal venous pulsations is a good but not
invariable sign of normal ICP, and engorge-
ment of retinal veins is a reliable early sign of
Structural Causes of Stupor and Coma
91