10

Coma

CONTENTS
Approach to diagnosis, 320
Emergency management,
321
History & examination, 322
Pathophysiologic assessment, 326

Supratentorial structural
lesions, 328
Subtentorial structural
lesions, 332
Diffuse encephalopathies,
333
Seizure or prolonged postictal state, 336

Differential diagnosis, 336

Psychogenic unresponsiveness, 336
Persistent vegetative state,
336
Locked-in syndrome, 337
Brain death, 337

Etiology, 328

KEY CONCEPTS
Coma is produced by disorders that affect both
cerebral hemispheres or the brainstem reticular
activating system.
The possible causes of coma are limited: mass
lesion, metabolic encephalopathy, infection of
the brain (encephalitis) or its coverings (meningitis), and subarachnoid hemorrhage.
The examination of a comatose patient should
be focused and brief: assess whether the pupils
constrict in response to light, whether eye move-

ments can be elicited by rotating the head (dollshead maneuver) or by irrigating the tympanic
membrane with cold water (caloric stimulation),
the nature (especially bilateral symmetry or
asymmetry) of the motor response to a painful
stimulus, and the presence or absence of signs of
meningeal irritation.
Immediately exclude hypoglycemia.
Patients who can open their eyes are not in
coma.

Coma is a sleeplike state in which the patient makes

hemispheres (Figure 101), since these are the brain
reno
purposeful response to the environment and from gions that maintain consciousness.
which he or she cannot be aroused. The eyes are
closed
and do not open spontaneously. The patient does not
APPROACH TO DIAGNOSIS
speak, and there is no purposeful movement of the
face
or limbs. Verbal stimulation produces no response.The approach to diagnosis of the comatose patient
Painful stimulation may produce no response or nonconpurposeful reex movements mediated through sists rst of emergency measures to stabilize the
spinal
patient
cord or brainstem pathways.
and treat presumptively certain life-threatening
Coma results from a disturbance in the func320disorders,
tion of either the brainstem reticular activating
followed by efforts to establish an etiologic diagnosis.
system above the midpons or of both cerebral

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COMA / 321

EMERGENCY MANAGEMENT

Cerebral hemisphere

As summarized in Table 101, emergency

management
of the comatose patient includes the following steps:
1. Ensure patency of the airway and adequacy of
ventilation and circulation. This is accomplished by
rapid visual inspection and by measuring the vital
signs. If the airway is obstructed, the obstruction
should be cleared and the patient intubated. If there
is
evidence of trauma that may have affected the
cervical
spine, however, the neck should not be moved until
spine stability has been established by x-rays of the
cervical spine. If spinal instability is present and intubation is required, tracheostomy should be performed.
Brainstem reticular
Adequacy of ventilation can be established by the abactivating system
sence of cyanosis, a respiratory rate greater than
8/min,
the presence of breath sounds on auscultation of the
chest, and the results of arterial blood gas and pH
studFigure 101. Anatomic basis of coma. Consciousness isies (see below). If any of these suggest inadequate
maintained by the normal functioning of the brainstem ventireticular activating system above the mid pons and its
lation, the patient should be ventilated mechanically.
bilateral projections to the thalamus and cerebral hemiMeasurement of the pulse and blood pressure
spheres. Coma results from lesions that affect either the
provides
reticular activating system or both hemispheres.
a rapid assessment of the status of the circulation.
Circulatory embarrassment should be treated with intravenous uid replacement, pressors, and
antiarrhythmic
drugs, as indicated.
2. Insert an intravenous catheter and withdraw
blood
for laboratory
studies. These studies should inTable 101. Emergency management of the comatose patient.
1
clude measurement of serum glucose and
electrolytes,
Immediately
Next
Later
hepatic and renal function tests, prothrombin time,
partial thromboplastin
time,
Ensure adequacy of airway, ventilation,
If signs of meningeal irritation
are present (Figure
ECG
2 and a complete blood
count.
Extra
tubes
of
blood
should also be obtained
and circulation
3)
for
perform LP to rule out meningitis
Obtain a history if possible
additional studies that may be useful in certain cases,
Draw blood for serum glucose,
Perform detailed general
physical
and
neurologic
Correct
hyper-that
or become
such
as drug
screens,
and
for tests
electrolytes, liver and renal function
examination
hypothermia
necestests, PT, PTT, and CBC
sary as diagnostic evaluation proceeds.
Thalamus

Start IV and administer 25 g of

Order CT scan of head if history or ndings
Correct severe acid-base and
dextrose, 100 mg of thiamine, and
suggest
electrolyte abnormalities
0.41.2 mg of naloxone IV
structural lesion or subarachnoid hemorrhage
Draw blood for arterial blood gas
determinations

Chest x-ray

Treat seizures (see Chapter 8)

Blood and urine toxicology

studies; EEG

1 CBC,

time.

complete blood count; IV, intravenous; LP, lumbar puncture; PT, prothrombin time; PTT, partial thromboplastin

322 / CHAPTER 10
3. Begin an intravenous infusion and administer
1. A sudden onset of coma suggests a vascular
dextrose, thiamine, and naloxone. Every comatose
origin, especially a brainstem stroke or subpaarachnoid hemorrhage.
tient should be given 25 g of dextrose intravenously,
2. Rapid progression from hemispheric signs,
typically as 50 mL of a 50% dextrose solution, to treat such as hemiparesis, hemisensory decit, or
possible hypoglycemic coma. Since administration of aphasia, to coma within minutes to hours is
dextrose alone may precipitate or worsen Wernicke
characteristic of intracerebral hemorrhage.
en3. A more protracted course leading to coma
cephalopathy in thiamine-decient patients, all coma- (days to a week or more) is seen with tumor,
tose patients should also receive 100 mg of thiamine abscess, or chronic subdural hematoma.
by
4. Coma preceded by a confusional state or
the intravenous route. To treat possible opiate
agitated delirium, without lateralizing signs or
overdose,
symptoms, is probably due to a metabolic
the opiate antagonist naloxone, 0.41.2 mg intra- derangement.
venously, should also be administered routinely to
comGeneral Physical Examination
atose patients. The benzodiazepine antagonist
umazeA. SIGNS OF TRAUMA
nil should not be used in coma of unknown cause 1. Inspection of the head may reveal signs of
(see
basilar
p 334).
skull fracture, including the following:
4. Withdraw arterial blood for blood gas and pH a. Raccoon eyesPeriorbital ecchymoses.
determinations. In addition to assisting in the assess-b. Battle signSwelling and discoloration overlying
ment of ventilatory status, these studies can provide
the mastoid bone behind the ear.
clues to metabolic causes of coma (Table 102).
c. HemotympanumBlood behind the tympanic
5. Institute treatment for seizures, if present. Permembrane.
sistent or recurrent seizures in a comatose patient d. Cerebrospinal uid (CSF) rhinorrhea or otorshould
be considered
to represent status epilepticus
rheaLeakage of CSF from the nose or ear. CSF
HISTORY
& EXAMINATION
and
rhinorrhea must be distinguished from other causes
History
treated accordingly, as described in Chapter 8 (seeof rhinorrhea, such as allergic rhinitis. It has been
parsuggested that CSF can be distinguished from nasal
The most crucial aspect of the history is the time over
ticularly Table 86).
which coma develops. In the absence of precise mucus by the higher glucose content of CSF, but this
After these measures have been taken, the history
is not always the case. Beta-2 transferrin is unique
details
(if
about the mode of onset, information about when to
theCSF; its presence documents a CSF source of
available) is obtained and general physical and
rhinorrhea.
patient was last seen in an apparently normal state
neuro2. Palpation of the head may demonstrate a demay
logic examinations are performed.
pressed skull fracture or swelling of soft tissues at the
assist in establishing the time course of the disease
site of trauma.
process.
Table 102. Metabolic coma: Differential
B. BLOOD PRESSURE
diagnosis by acid-base abnormalities.1
Elevation of blood pressure in a comatose patient
may
reect long-standing hypertension, which predisposes
Respiratory acidosis
Metabolic acidosis
to intracerebral hemorrhage or stroke. In the rare
Sedative drug intoxication Diabetic ketoacidosis
conPulmonary encephalopathyUremic encephalopathy
Respiratory alkalosis
Lactic acidosis
dition of hypertensive encephalopathy, the blood
Hepatic encephalopathy Paraldehyde intoxication presSalicylate intoxication
Methanol intoxication
sure is above 250/150 mm Hg in chronically
Sepsis
Ethylene glycol intoxicationhypertenIsoniazid intoxication
sive patients; it may be lower in children or following
Salicylate intoxication
acute elevation of blood pressure in previously norSepsis (terminal)
motensive patients (eg, in acute renal failure).
Metabolic alkalosis
C.
TEMPERATURE
Elevation
Coma unusual
Hypothermia
can occur
in coma
by ethanol
of blood pressure
may also
be a caused
consequence
of theor
sedative
drug
intoxication,
hypoglycemia,
Wernicke
process
causing
the
coma,
as
in
intracerebral
or
sub1
AdaptedfromPlumF,PosnerJB:TheDiagnosis
enarachnoid
hemorrhage
or,
rarely,
brainstem
stroke.
ofStuporandComa,3rded.Vol19of:Contem
cephalopathy, hepatic encephalopathy, and
poraryNeurologySeries.Davis,1980.
myxedema.
Coma with hyperthermia is seen in heat stroke, status

COMA / 323
epilepticus, malignant hyperthermia related to inhalater is a normal nding in 20% of the population; the
tional anesthetics, anticholinergic drug intoxication,
pupils constrict to a similar extent in response to
pontine hemorrhage, and certain hypothalamic
light,
lesions.
and extraocular movements are not impaired. In conD. SIGNS OF MENINGEAL IRRITATION
trast,
a pupil that
constricts less rapidly or to a lesser
EXTRAOCULAR
MOVEMENTS
Signs of meningeal irritation [eg, nuchal rigid-B.
ex1. Pathways testedThe neuronal pathways to be
ity or the Brudzinski sign (see Figure 23)] are
tent
than
its fellow
implies ajunction
structural lesion
tested
begin
at the usually
pontomedullary
of great importance in leading to the promptaffecting
the
midbrain
or
oculomotor
nerve.
[vestibular
diagnosis of meningitis or subarachnoid hemorrhage,
(VIII) nerve and nucleus], synapse in the caudal pons
but they are lost in deep coma.
[horizontal gaze center and abducens (VI) nerve nucleus], ascend through the central core of the
E. OPTIC FUNDI
brainstem
Examination of the optic fundi may reveal
reticular activating system (medial longitudinal
papilledema
or retinal hemorrhages compatible with chronic or fascicuacute hypertension or an elevation in intracranial lus), and arrive at the midbrain level [oculomotor (III)
nucleus and nerve; Figure 103].
pres2. Methods of testingIn the comatose pasure. Subhyaloid (supercial retinal) hemorrhages in
tient, eye movements are tested by stimulating
an
the vestibular system (semicircular canals of
adult
strongly
suggest subarachnoid hemorrhage
Neurologic
Examination
the middle ear) by means of passive head rotation
(FigThe neurologic examination is the key to etio(the
ure 25).
logic diagnosis in the comatose patient. Pupiloculocephalic reex, or dolls-head maneuver) or by
lary size and reactivity, oculocephalic and the stronger stimulus of ice-water irrigation against
A. PUPILS
oculovestibular
reexes, andpupils
the motor
response
1. Normal pupilsNormal
are 34
mm in to
the
pain
diameter
and equal bilaterally; they constrict briskly
tympanic membrane (oculovestibular reex, or coldshould
be evaluated
detail (Figure
102).
and
symmetrically
inin
response
to light.
Normal pupils,
water calorics testing) (see Chapter 3 and Figures 31
however, are larger in children and smaller in the old.
and 103).
2. Thalamic pupilsSlightly smaller reactive pupils3. Normal movementsA comatose patient withare present in the early stages of thalamic
out brainstem involvement will demonstrate full
compression
conjufrom mass lesions, perhaps because of the
gate horizontal eye movements during the dollsinterruption
head
of the descending sympathetic pathways.
maneuver and always exhibits tonic conjugate move3. Fixed dilated pupilsPupils greater than 7 mm
ment of both eyes to the side of the ice-water
in diameter and xed (nonreactive to light) usuallyirrigation
result from compression of the oculomotor (III) cranial
during caloric testing. The presence of full reex eye
nerve anywhere along its course from the midbrain
movements
to
in the comatose patient attests to the inthe orbit but may also be seen in anticholinergic ortegrity of the brainstem from the pontine to the midsympathomimetic drug intoxication. The most combrain level and excludes a mass lesion in the
mon cause of a xed dilated pupil in a comatose brainstem.
patient
4. Abnormal movements
is transtentorial herniation of the medial temporal a. With lesions of the oculomotor nerve or nucleus
lobe
(such as in the rostral-caudal herniation syndrome;
from a supratentorial mass.
Fig4. Fixed midsized pupilsPupils xed at about 5ure 102), oculovestibular testing will reveal failure of
mm in diameter are the result of brainstem damage
ocular adduction with unimpaired contralateral
at
abducthe midbrain level.
tion.
5. Pinpoint pupilsPinpoint pupils (11.5 mm in b. Complete absence of response on
diameter) in a comatose patient usually indicate oculovestibular
C. MOTOR RESPONSE TO PAIN
opioid
testing in a comatose patient implies either a
The motor response to pain is tested by applying
overdose or focal damage at the pontine level. Under
structural
strong
these conditions, the pupils may appear unreactive
lesion
to of the brainstem at the level of the pons or a
pressure on the supraorbital ridge, sternum, or nail
light except when viewed with a magnifying glass.metabolic disorder with a particular predilection for
beds. The response to such stimuli may be helpful in
Pinbrainstem involvement; this is usually caused by
localizing the level of cerebral dysfunction in
point pupils are also caused by organophosphate poisedacomatose
soning, miotic eye drops, and neurosyphilis.
tive drug intoxication.
patients or providing a guide to the depth of coma.
6. Asymmetric pupilsAsymmetry of pupillary sizec. Downward deviation of one or both eyes in re(anisocoria) with a difference of 1 mm or less in sponse to unilateral cold-water irrigation is most sugdiamegestive of sedative drug intoxication.

324
Pupillary
light response

Reflex
eye movement

Motor response to pain

Early
diencephalic

Late
diencephalic

Midbrain

Pons or
upper medulla

Figure 102. Neurologic signs in coma with downward transtentorial herniation. In the early diencephalic phase, the pupils are small (about 2 mm in
diameter) and reactive, reex eye movements are intact, and the motor response to pain is purposeful or semipurposeful (localizing) and often
asymmetric.The late
diencephalic phase is associated with similar ndings, except that painful stimulation results in decorticate (exor) posturing, which may also be
asymmetric.
With midbrain involvement, the pupils are xed and midsized (about 5 mm in diameter), reex adduction of the eyes is impaired, and pain elicits
decerebrate
(extensor) posturing. Progression to involve the pons or medulla also produces xed, midsized pupils, but these are accompanied by loss of reex
abduction
as well as adduction of the eyes and by no motor response or only leg exion upon painful stimulation. Note that although a lesion restricted to the pons
produces pinpoint pupils as a result of the destruction of descending sympathetic (pupillodilator) pathways, downward herniation to the pontine level is
associated with midsized pupils.This happens because herniation also interrupts parasympathetic (pupilloconstrictor) bers in the oculomotor (III) nerve.

COMA / 325

Tonic eye deviation

L

Medial rectus

Lateral rectus

Oculomotor (III) nerve

Oculomotor (III) nucleus

Medial longitudinal fasciculus

Abducens (VI) nerve

Abducens (VI) nucleus
Vestibular (VIII) nucleus

Ice water
irrigation

550

Semicircular canals

Inhibitory

Head
rotation

Vestibular (VIII) nerve

Figure 103. Brainstem pathways mediating reex conjugate horizontal eye movements. In a comatose
patient
with intact brainstem function, irrigation of the tympanic membrane with ice water inhibits the vestibuloocular
pathways shown, resulting in tonic deviation of both eyes toward the irrigated side; head rotation causes eye
deviation away from the direction of rotation.

1. With cerebral dysfunction of only moderate

severity, patients may localize the offending stimulus2. A decorticate response to pain (exion of the
arm
by
reaching toward the site of stimulation. Although at the elbow, adduction at the shoulder, and
extension
semiof the leg and ankle) is classically associated with lepurposeful localizing responses to pain can
sions that involve the thalamus directly or large hemisometimes
be difcult to distinguish from the reex responsesspheric masses that compress it from above.
3. A decerebrate response (extension at the elbow,
deinternal rotation at the shoulder and forearm, and leg
scribed below, movements that involve limb
abduction
are virtually never reexive in nature.

326 / CHAPTER 10
extension) tends to occur when midbrain function is
Lateral
compromised. Decerebrate posturing generally
ventricles
implies
more severe brain dysfunction than decorticate
posturing, but neither response localizes the site of disease
precisely.
4. Bilateral symmetric posturing may be seen inUncus
both structural and metabolic disorders.
5. Unilateral or asymmetric posturing suggests
structural disease in the contralateral cerebral hemisphere or brainstem.
6. In patients with pontine and medullary lesions,
there is usually no response to pain, but occasionally
some exion at the knee is noted (a spinal reex). Cerebellar tonsil

PATHOPHYSIOLOGIC ASSESSMENT

Supratentorial
mass
1

3
2

Tentorium
cerebelli

Brainstem

The most important step in evaluating the Figure 104. Anatomic basis of herniation syndromes.
An expanding supratentorial mass lesion may cause
comatose patient is to decide whether unconsciousness is the result of a structural brainbrain
le- tissue to be displaced into an adjacent intracranial
compartment, resulting in (1) cingulate herniation under
sion (for which emergency neurosurgical intervention
the falx, (2) downward transtentorial (central) herniation,
may be critical) or is secondary to a diffuse en(3) uncal herniation over the edge of the tentorium, or
cephalopathy caused by metabolic disturbance, (4) cerebellar tonsillar herniation into the foramen magmeninnum. Coma and ultimately death result when (2), (3), or
gitis, or seizures (for which surgical procedures are(4) produces brainstem compression.
unnecessary
and
medical
may be required).
When
coma
is the
resulttreatment
of a supratentorial
mass
The
lesion,
cus) across the cerebellar tentorium (see Figure 10
most
common
dilemma
is tointry
tocourse
the
history
anddiagnostic
physical ndings
early
the
4),
differenusually point to aStructural
hemispheric
disorder. Hemiparesis
Supratentorial
Lesions
thus exerting direct pressure on the rostral
tiate hemisensory
between a supratentorial
(hemispheric)
mass
with
loss is typical.
Aphasia occurs
with
brainstem,
lesion
dominant
(usually left) hemispheric lesions, and agsigns of oculomotor nerve and midbrain compression
and metabolic
encephalopathy.
nosia
(indifference
to or denial of the decit) with injury to the nondominant hemisphere. As the mass such
ex- as ipsilateral pupillary dilatation and impaired
adpands (commonly from associated edema),
duction of the eye (uncal syndrome) may precede
somnolence
loss
supervenes because of the compression of the
of consciousness. As consciousness is lost with
contralatprogreseral hemisphere or downward pressure on the diensive uncal herniation, the fully developed midbrain
cephalon. Stupor progresses to coma, but the
stage
ndings
Subtentorial Structural Lesions
rapidlyofappears,
ipsilateral
pupillary
often remain asymmetric. As rostral-caudal compresComa
sudden with
onsetmarked
with focal
brainstem
signs dilation and supports
loss of reactivity
to light.
treatsion progresses, the thalamus, midbrain, pons, and
strongly
a diagnosis
of a Neurosurgical
subtentorial strucmentlesion.
must be
given early
in the
course
of third-nerve
medulla become sequentially involved, and the tural
Pupillary
function
and
extraocular
moveinvolvement
usefulhelpful
recovery
is to be
neuroments
are theif most
features
of achieved.
the neurologic
logic examination reveals dysfunction at successively
examination, especially if the abnormalities are
lower anatomical levels (see Figure 102). Such segasymmental involvement strongly supports the diagnosis
metric. With focal midbrain lesions, pupillary function
of
is lost: the pupils are midsized (about 5 mm in diamea supratentorial mass with downward transtentorial
ter) and nonreactive to light. Pinpoint pupils are
herniation (Figure 104) and dictates the need for found
neuin pontine hemorrhage and less often in pontine
rosurgical intervention. Once the pontine level is infarcreached, a fatal outcome is inevitable. Even at thetion or pontine compression caused by cerebellar
fully
hemdeveloped midbrain level, chances of survival without
orrhage or infarction. Conjugate gaze deviation away
severe neurologic impairment decrease rapidly, espefrom the side of the lesion and toward the hemiparecially in adults.
sisor disconjugate eye movements, such as internuWhen supratentorial mass lesions produce herniaclear ophthalmoplegia (selective impairment of eye
tion of the medial portion of the temporal lobe (theadunduction)strongly suggests a subtentorial lesion.

COMA / 327
Motor responses are generally not helpful in
A symmetric neurologic examination supports a
separating
metabolic cause of coma. Hepatic encephalopathy,
subtentorial from supratentorial lesions. Ventilatory
hypatterns associated with subtentorial lesions are poglycemia, and hyperosmolar nonketotic hyperabnorglycemia may uncommonly be accompanied by focal
mal but variable and may be ataxic or gasping (Figure
signsespecially hemiparesis, which may alternate
105). Because the fully developed syndrome of from side to side. Asterixis, myoclonus, and tremor
transtentorial herniation from a supratentorial mass
preis
characterized by extensive brainstem dysfunction,ceding
its
coma are important clues that suggest
differentiation from a primary subtentorial processmetabolic
may
disease. Symmetric decorticate or decerebrate
Diffuse Encephalopathies
be impossible except by history.
posturing
Diffuse encephalopathies that result in coma (somecan be seen with hepatic, uremic, anoxic, hypotimes termed metabolic coma) include not only metaglycemic, or sedative-druginduced coma.
bolic disorders such as hypoglycemia and drug intoxiThe nding of reactive pupils in the presence of
cation but other processes that affect the brain
otherwise impaired brainstem function is the halldiffusely,
mark of metabolic encephalopathy. Although coma
such as meningitis, subarachnoid hemorrhage, andwith intact pupillary reactivity is also seen in the early
seizures.
stages of transtentorial herniation (see Figure 102),
The clinical presentation is distinct from that of this
a latter syndrome is associated with asymmetric
mass lesion. There are usually no focal signs, suchneuas
hemiparesis, hemisensory loss, or aphasia, and rologic ndings (hemiparesis). The few metabolic
except
causes of coma that also impair pupillary reexes
in some cases of subarachnoid hemorrhageno include massive barbiturate overdose with apnea and
sudden
hypotension, acute anoxia, marked hypothermia,
loss of consciousness. Instead, the history reveals anticholinergic
a
poisoning (large pupils), and opioid
peoverdose (pinpoint pupils). Even in these condiriod of progressive somnolence or toxic delirium foltions,
however, completely
nonreactive
pupils
The relationship
between neurologic
signs
and are
the
lowed by gradual descent into a stuporous and nally
uncommon.
pathophysiologic basis of coma is summarized in
comatose state.
The respiratory patterns in metabolic coma vary
Table
Normal
widely,
and measurement
of arterial
blood gases
103. Examining
pupillary size
and reactivity
and and
Summary
pH
may
provide
a
further
basis
for
establishing
an
testetioing reex eye movements and the motor response to
logic
diagnosis.
Arterial
blood brain
gas abnormalities
in
pain help
determine
whether
function is disCheyne-Stokes
coma
are
outlined
in
Table
102.
rupted at a discrete anatomic level (structural lesion)
or
in a diffuse manner (metabolic coma).
Central
Supratentorial structural lesions compromise the
hyperventilation
brain in an orderly way, producing dysfunction at progressively lower anatomic levels. In patients with
metabolic coma, such localization is not possible, and scatAtaxic
tered, anatomically inconsistent ndings are noted on
examination. An impressive example of the anatomically discordant ndings characteristic of metabolic
enGasping
cephalopathy is the retention of pupillary reactivity in
the face of otherwise depressed brainstem functions:
paralysis of eye movements, respiratory depression,
Figure 105. Ventilatory patterns in coma. CheyneStokes respiration and central hyperventilation are seenacwith metabolic disturbances and with structural lesions cid muscle tone, and unresponsiveness to painful
at a variety of sites in the brain.They are therefore not stimuseful for anatomic localization of disorders producing uli such as is typical with sedative drug overdose. The
coma. Ataxic and gasping ventilatory patterns are mostsame degree of low brainstem dysfunction produced
commonly seen with pontomedullary lesions.
by
a supratentorial mass lesion would have to rst compromise the more rostrally situated midbrain
structures
that mediate pupillary reactivity before affecting the
lower brainstem centers.

328 / CHAPTER 10
Table 103. Pathophysiologic assessment of the comatose patient.
Supratentorial
Structural Lesion

Subtentorial
Structural Lesion

Diffuse
Encephalopathy/Meningitis

Pupil size and light reaction

Usually normal size (34 mm)Midsized (about 5 mm) and
Usually normal size (34 mm)
and reactive; large (>7 mm) and unreactive with midbrain
and reactive; pinpoint (11.5
unreactive after transtentoriallesions; pinpoint (11.5 mm)
mm) and sometimes
herniationand unreactive with pontine
unreactive with opiates; large
lesion
(>7 mm) and unreactive with
anticholinergics
Reex eye movements

Normal

Impaired adduction with

midbrain lesion; impaired
adduction and abduction
with pontine lesion

Usually normal; impaired by

sedative drugs or Wemickes
encephalopathy

Motor responses

Usually asymmetric; may beAsymmetric (unilateral lesion)

Usually symmetric; may be
symmetric after transtentorial
or symmetric (bilateral lesion)
asymmetric with
herniation
hypoglycemia, hyperosmolar
nonketotic hyperglycemia, or
hepatic encephalopathy

1. SUBDURAL HEMATOMA
Subdural hematoma is a correctable supratentorialTable 104. Clinical features of subdural
mass
hematoma.1
ETIOLOGY
lesion and must be considered in any comatose
patient.
Acute2Subacute3 Chronic 4
It is more common in older patients, since cerebral
(82 Cases) (91 Cases) (216 Cases)
SUPRATENTORIAL
STRUCTURAL
at(%)(%)(%)
LESIONS
rophy makes bridging cortical veins more subject to
laceration from shearing injury or to apparently Symptoms
spontaDepression of
neous rupture.
consciousness
100
88
47
Trauma is the most common cause, and in the Vomiting
24
31
30
Weakness
acute
20
19
22
12
41
37
stage following head injury, focal neurologic decitsConfusion
Headache
11
44
81
are
8
6
often conspicuous. The severity of injury needed to Speech disturbance 6
Seizures
6
3
9
produce a subdural hematoma becomes less with adVertigo
0
4
5
vancing age, so that in perhaps 25% of cases a
Visual disturbance
0
0
12
history
of trauma is not present.
Signs
The most common clinical ndings are headache Depression of
100
88
59
and altered consciousness, but symptoms and signs consciousness
may be absent, nonspecic, or nonlocalizing,
Pupillary inequality 57
27
20
especially
Motor asymmetry
44
37
41
Confusion and
with chronic subdural hematomas that appear
17
21
27
memory loss
months
or years after injury (Table 104). The classic historyAphasia
6
12
11
Papilledema
1
15
22
of
Hemianopia
0
4
3
waxing and waning signs and symptoms is too infre-Facial weakness
0
3
3
quent to be relied on for diagnosis. Hemiparesis,
when
1 Data from McKissock W: Lancet 1960;1:13651370.
present, is contralateral to the lesion in about 70%2 Within
of
3 days of trauma.
cases. Pupillary dilation, when present, is ipsilateral
in days after trauma.
3 420
4 More than 20 days after trauma.
approximately 90% of cases. The frequency of
bilateral
hematomas makes localization of the lesion even
more
difcult, as may coexisting cerebral contusion.
Diagnosis is made by computed tomography (CT)

COMA / 329
scan or magnetic resonance imaging (MRI) (Figure Lumbar puncture is unnecessary and potentially
106).
danTreatment of symptomatic subdural hematoma is
gerous. CT scan or MRI is the diagnostic procedure of
by
choice. In contrast to subdural and epidural
surgical evacuation.
hematomas,
2. EPIDURAL HEMATOMA
4.
INTRACEREBRAL
HEMORRHAGE
cerebral
contusions
are rarely operated upon.
Epidural hematoma typically results from head
Etiology
trauma
associated with a lateral skull fracture and tearingThe
of most common cause of nontraumatic
the
intracerebral
middle meningeal artery and vein. Patients may orhemorrhage is chronic hypertension. This and other
may
causes are discussed in more detail in Chapter 9.
not lose consciousness initially. There is often a lucid
Clinical Findings
interval of several hours before the onset of coma A. SYMPTOMS
Hemorrhage usually occurs when the patient is awake
during
which headache, vomiting, obtundation, seizures, and is not preceded by prodromal symptoms such as
focal neurologic signs may occur. The diagnosis is the transient ischemic attacks often associated with
3.
CEREBRAL CONTUSION
cerebral infarction. Headache occurs in many cases
made
Cerebral
contusion
caused
by
head
trauma
is
by CT scan or MRI (Figure 106), which classically and
associated
shows a radiodense biconvex lens-shaped mass can be moderate to severe. If present, headache may
with
initial unconsciousness from which the patientoverlie the site of hemorrhage or be generalized.
compressreNausea
ing the cerebral hemisphere. Prompt surgical
covers.
Edema surrounding the contusion may cause
and vomiting are common. Hemiparesis is a frequent
evacuation
the
level
of consciousness
to uctuate,
seizures
early symptom because of the proximity of common
of the
hematoma
is essential
to preventand
a fatal
and
hemorrhage sites, such as the basal ganglia and
outcome.
focal neurologic signs may develop. Patients must thalabe
carefully monitored for neurologic deterioration mus, to the internal capsule. Seizures occur in about
related
10% of cases and are often focal. Altered
Left
Right
Left
toRight
progressive edema and herniation.
consciousness

Figure 106. A: Subdural hematoma. Unenhanced CT scan showing a large, high-density crescentic mass over
the
right cerebral hemisphere, with shift of the lateral ventricles across the midline. B: Epidural hematoma.
Unenhanced
CT scan showing a large, high-density lens-shaped mass in the right parietooccipital region. Fracture of the
occipital
bone was seen on bone windows.

330 / CHAPTER 10
is common and may progress steadily to stupor ordangerous hypoperfusion of the brain although
coma over minutes to hours. Neurologic decits doautoregunot
lation is preserved. Once the acute phase is over, the
uctuate spontaneously.
blood pressure should be controlled
B. PHYSICAL EXAMINATION
B. SURGICAL TREATMENT
pharmacologically.
Patients are nearly always hypertensive (blood
Surgical evacuation of the clot would seem
pressure
appropriate,
170/90 mm Hg or higher) even in the late stages of
but because the hematoma is usually deep within the
transtentorial herniation. The funduscopic
brain, surgical results are disappointing. Operation
examination
may
usually shows vascular changes associated with be useful, however, in the cases (approximately 10%)
chronic
in
hypertension. Nuchal rigidity is common, as is conjuwhich
the hemorrhage
located supercially in the
C. TREATMENT
OF CEREBRALis
EDEMA
gate deviation of the eyes toward the side of hemorcerebral
hemisphere
and
produces a mass effect.
C.
INVESTIGATIVE
STUDIEShemisphereand thus away Cerebral edema may be treated with steroids,
rhage
in the cerebral
CT
brain scan without contrast or MRI conrms themannitol,
difrom
or intravenous hypertonic saline (Table 105), but
agnosis,
showingside.
the presence of intraparenchymal
the hemiparetic
such
blood.
measures rarely alter the eventual outcome.

Treatment

Prognosis

Treatment for intracerebral hemorrhage is limited, in

Many patients experience a rapid downhill course
particular because the hemorrhage usually occurs
leadover a
ing to death. Those who do survive may be left with a
brief period and then stops. Bleeding generally does
surprisingly mild decit as the clot resolves over a penot
riod of weeks to months.
recur, but the patients condition worsens because of
5. BRAIN ABSCESS
A.
A
CUTE MANAGEMENT OF BLOOD PRESSURE
cerebral edema.
Brain abscess is an uncommon disorder, accounting
Acute reduction of systemic blood pressure is usually
for
inefonly 2% of intracranial masses.
fective in decreasing edema. In addition, it may result
in
Table 105. Drug therapy for cerebral edema.
Drug
Glucocorticoids
Dexamethasone
Prednisone

Dose

Route

10100 mg, then 4 mg four times Intravenous

daily
or orally
60 mg, then 25 mg four times daily
Orally

Methylprednisone 60 mg, then 25 mg four times daily

Intravenous or orally
Hydrocortisone

300 mg, then 130 mg four times daily

Intravenous or orally

Osmotic diuretic agents

Mannitol1.52 g/kg over 30 minutes to 1 hour
Hypertonic saline 3% continuous infusion
or
23.4% or 29.2% by 20 cc bolus

Indications and Comments

Dexamethasone preferred for
lowest mineralocorticoid effect.
Antacid treatment indicated.
Effective for edema associated
with brain tumor or abscess; not
indicated for intracerebral hemorrhage or infarction

20% Intravenous solution

Effective acutely. Major dehydrating effect on normal tissue;
Intravenously
osmotic effect short-lived, and
more than two intravenous doses
rarely effective. Hypertonic saline
has both osmotic and vasoregulatory effects. Continuous infusion
of 3% hypertonic saline to target
a serum sodium of 145155
mEq/L; boluses of hypertonic
saline may be more effective than
other osmotic agents.

COMA / 331
25500 or more white cells/mm3, depending on the
proximity of the abscess to the ventricular surface
The common conditions predisposing to brain
and
abscess,
its degree of encapsulation; and elevation of protein
in approximate order of frequency, are blood-borne
(45500 mg/dL) in about 60% of patients. CSF culmetastasis from distant systemic (especially
tures are usually negative. Marked clinical
pulmonary)
deterioration
infection; direct extension from parameningeal sites
may follow lumbar puncture in patients with brain ab(otitis, cranial osteomyelitis, sinusitis); an unknown
scess, however, so lumbar puncture should not be
source; infection associated with recent or remoteperhead
Treatment
formed if brain abscess is suspected.
trauma or craniotomy; and infection associated with
Treatment of pyogenic brain abscess can be with
cyanotic congenital heart disease.
antibiThe most common pathogenic agents are aerobic,
anaerobic, and microaerophilic streptococci, and otics alone or combined with surgical drainage.
Surgical
gramtherapy should be strongly considered when there is
negative anaerobes such as bacteroides,
a
fusobacterium,
signicant mass effect or the abscess is near the
and
prevotella.
Staphylococcus aureus, Proteus, and
Clinical
Findings
ventricuother
lar surface, because catastrophic rupture into the
The
course is that
of an
massActinomyces,
lesion, and
gram-negative
bacilli
areexpanding
less common.
venits
Nocardia, and Candida are also found. Multiple organtricular
system may occur. Medical treatment alone is
usual
presentation
is
with
headache
and
focal
signs
in
isms are present in many cases.
indicated for surgically inaccessible, multiple, or early
a
abscesses. If the causal organism is unknown, broad
conscious patient. Coma may develop over days but
rarely over hours. Common presenting signs and coverage with antibiotics is indicated. A suggested
sympregimen
toms are shown in Table 106. Of importance is the
includes penicillin G, 34 million units intravenously
fact that the common correlates of infection may be
every 4 hours, and metronidazole, 7.5 mg/kg intraabvenously or orally every 6 hours. If staphylococcal
sent:
The temperature
Investigative
Studies is within normal limits in 40%
infecof patients, and the peripheral white blood cell count
tion
The
diagnosis
is
strongly
supported
by
the
nding
of is suspected, oxacillin or nafcillin should be
is
added
an
avascular
mass
on
angiography
or
a
lesion
with
a
below 10,000/mm3 in 20% of patients.
at a dose of 3 g intravenously every 6 hours. To cover
contrast-enhanced rim on CT scan or MRI. Examina6.
CEREBRAL INFARCTION
(STROKE
)
staphylococci
and aerobic
gram-negative
bacilli
tion of the CSF reveals an opening pressure greater
Embolic
or
thrombotic
occlusion
of
one
carotid
artery
than 200 mm water in 75% of patients; pleocytosis(trauma
of
does
not
cause
coma
directly,
because
bihemispheric
patients), nafcillin plus cefotaxime or ceftriaxone is
dysfunction
is required for coma to occur. Cerebral
recedema
following
massive hemispheric
ommended.
Glucocorticoids
(see Table infarction,
105) may athowtenuate edema surrounding the abscess. Response to
cantreatment
produce contralateral
hemispheric
Table 106. Brain abscesses: Presenting features ever,
medical
is assessed by
the clinical
compresin 123 cases.
examination
sion
or transtentorial
herniation
that
will result
in
and by
frequent CT scans
or MRIs.
When
medically
coma.
Such
cerebral
swelling
becomes
maximal
treated patients do not improve, needle aspiration of
Headache
55%
within
Disturbed consciousness
48%
the
4872
hours
after thetoinfarct.
the history is of
Fever
58%
abscess
is indicated
identifyThus,
the organisms
the
stroke-like
onset
of
a
focal
neurologic
decit, with
Nuchal rigidity
29%
present.
progression over hours or days to stupor and coma. A
Nausea, vomiting
32%
Seizures
19%
cerebral hemorrhage is excluded by CT scan or MRI.
Visual disturbances
15%
The use of corticosteroids and dehydrating agents
Dysarthria
20%
to
Hemiparesis
48%
7.
BRAIN
TUMOR cerebral edema has produced no
treat
associated
Sepsis
17%
clear
Clinical
Findingsinfarction is discussed in more detail
benet. Cerebral
ModifiedfromLuCHetal:Bacterialbrainaccess:
in Chapter
9.
Primary
or metastatic
tumors of the central nervous

Etiology

Microbiologicalfeatures,epidemiologicaltrends
system (see Chapter 2) rarely present with coma, alandoutcomes.QJMed2002;95:501509.

332 / CHAPTER 10
though they can do so when hemorrhage into the tuTreatment & Prognosis
mor or tumor-induced seizures occur. More often,
Current practice supports anticoagulation for progrescoma occurs late in the clinical course of brain tumor,
sive subtotal basilar artery thrombosis, despite the
and there is a history of headache, focal neurologic
decits, and altered consciousness. Papilledema isaba
sence of clear evidence of efcacy. Anticoagulation
prewill
senting sign in 25% of cases.
reduce the frequency of recurrent cardiac emboli. The
Investigative Studies
prognosis depends directly upon the degree of brain2. PONTINE HEMORRHAGE
stem injury.
If brain tumor is suspected, a CT scan or MRI should
Pontine hemorrhage is essentially restricted to hyperbe
tensive patients and is the least common of the
obtained. It may or may not be possible to determine
hyperthe
tensive intracerebral hemorrhages (6% of cases). The
nature of the tumor by its radiographic appearance
apoplectic onset of coma is the hallmark of this synalone;
drome. Physical examination reveals many of the
biopsy may be required. Chest x-ray is useful,
ndbecause
ings noted in basilar artery infarction, but transient islung carcinoma is the most common source of
Treatment
chemic episodes are not encountered. Features
intracraespecially suggestive of pontine involvement include
In
contrast
to itsand
lackbecause
of therapeutic
effect in
cerebral
nial
metastasis
other tumors
that
ocular
infarction,
corticosteroid treatment (see Table 105)
is bobbing (spontaneous brisk, periodic, mainly
metastasize
conjugate
downward movements of the eyes, with
often
effective
in reducing
tumorto theremarkably
brain commonly
involve
the lungs
rst.
slower
return
to the primary position), pinpoint pupils,
associated
and
loss
of
lateral
eye movements. Hyperthermia
vasogenic brain edema (leaking capillaries) and
[with
improvelevations to 39.5C (103F) or greater]
ing related neurologic decits. Specic approachestemperature
to
occurs in most patients surviving for more than
the treatment of tumors include excision,
several
radiotherapy,
hours. The diagnosis is made by CT scan or MRI. CSF
and chemotherapy, depending on the site and nature
SUBTENTORIAL
STRUCTURAL
LESIONS
is grossly bloody and under increased pressure, but
of
3.
CEREBELLAR
HEMORRHAGE
OR INFARCTION
lumbar
puncture
is not indicated.
There is no
theBlesion.
1.
ASILAR ARTERY THROMBOSIS OR EMBOLIC OCCLUSION
The
clinical
presentation
of
cerebellar
hemorrhage or
effective
These relatively common vascular syndromes
infarction
from
sudden onset
of coma, in
with
treatment.ranges
Pontine
hemorrhage
is considered
(discussed
Clinical Findings
rapid
evolution
to
death,
to
a
progressive
syndrome
greater
in more detail in Chapter 9) produce coma by impairdetail in Chapter 9.
ing blood ow to the brainstem reticular activatingdeveloping over hours or even several days. Acute
sysdeteriotem. Patients are typically middle-aged to elderly and
ration may occur without warning; this emphasizes
often have a history of hypertension, atherosclerotic
the
vascular disease, or transient ischemic attacks (TIAs).
need for careful observation and early treatment of
Thrombosis usually affects the midportion, and emall
bolic occlusion the top, of the basilar artery. Virtually
patients. CT scan or MRI is helpful in conrming the
all patients present with some alteration of consciousdiagnosis.
ness, and 50% of patients are comatose at
Surgical decompression may produce dramatic representation.
duction
of symptoms, and with proper surgical treatFocal signs are present from the outset.
ment,
lethargic
or even stuporous patients may
Pupillary abnormalities vary with the site of the lesurvive
sion and include midsized xed pupils with midbrain
4.
POSTERIOR
with
minimalFOSSA
or noSUBDURAL
residual decits and intact
involvement and pinpoint pupils with pontine lesions.
&
E
PIDURAL
H
EMATOMAS
Vertically skewed deviation of the eyes is common,intellect.
These
very uncommon
lesions have
similar clinical
If the patient
is deeply comatose,
however,
the likeliand
pichood
of
useful
survival
is
small.
Additional
discussion
horizontal eye movements may be absent or
tures
anddisorders
are important
recognize
because
of these
can betofound
in Chapter
9. they
asymmetare
ric during dolls-head or caloric testing. Conjugate
treatable. The history is frequently of occipital trauma
eye
that precedes the onset of brainstem involvement by
deviation, if present, is directed away from the side of
hours to many weeks. Physical ndings are those of
the lesion and toward the hemiparesis. Vertical eye
exmovements may be impaired or intact.
traaxial (extrinsic) compression of the brainstem:
Symmetric or asymmetric long-tract signs, such as
ataxia, nystagmus, vertigo, vomiting, and progressive
hemiparesis, hyperreexia, and Babinski responses,
obtundation. Nuchal rigidity may be present, as may
may
be present. There is no blood in the CSF.

COMA / 333
papilledema in more chronic cases. CT scans of the
2. HYPOGLYCEMIA
skull often reveal a fracture line crossing the
Etiology
transverse
and sigmoid sinuses. The source of the hematomaIn
is most cases, the cause of hypoglycemic
the traumatic tearing of these vessels. Examination
encephalopaof
thy is insulin overdose. Other causes include alcothe CSF is not helpful.
holism, severe liver disease, oral hypoglycemic
Treatment is by surgical decompression.
agents,

DIFFUSE ENCEPHALOPATHIES
1. MENINGEAL IRRITATION

insulin-secreting neoplasms (insulinoma), and large

retroperitoneal
tumors.
Clinical
Findings

As the blood glucose level falls, signs of sympathetic

nervous system hyperactivity (tachycardia, sweating,
Meningitis and encephalitis may be manifested byand
an anxiety) may warn patients of impending hypoglycemia.
These prodromal symptoms may be
acute confusional state or coma, which is
absent,
characteristihowever, in patients with diabetic autonomic
cally associated with fever and headache. In
neuropameningitis,
thy. Neurologic ndings in hypoglycemia include
signs of meningeal irritation are also typically present
and should be sought meticulously so that lumbar seizures, focal signs that may alternate sides,
delirium,
puncture, diagnosis, and treatment are not delayed.
stupor,
and coma.
Progressive hypothermia is
Investigative
Studies
These signs include resistance of the neck to full forcommon
ward exion, knee exion during passive neck exion,
There
no precise correlation between blood levels
duringiscoma.
and exion of the neck or contralateral knee during
of
passive elevation of the extended straight leg (seeglucose and symptoms, so that levels of 30 mg/dL
Figure
can
23). Meningeal signs may be absent in encephalitis
result in coma in one patient, delirium in a second,
without meningeal involvement and in meningitis ocand
curring at the extremes of ageor in patients whohemiparesis with preserved consciousness in a third.
are
Coma, stupor, and confusion have been reported with
deeply comatose or immunosuppressed. The ndings
blood glucose concentrations of 228, 859, and 960
Treatment
on examination are usually symmetric, but focal feamg/dL, respectively.
tures may be seen in certain infections, such as
Permanent brain damage can be avoided if
In
subarachnoid hemorrhage, discussed in detail in
herpes
glucose is rapidly administered, intravenously,
Chapter
2, symptomsorare
suddenmeningitis
in onset and
almost orally, or by nasogastric tube. Because this
simplex encephalitis
bacterial
complialways
include
headache
that is typically,
but not
cated
by
vasculitis.
CSF ndings
and treatment
areincondition is so easily treated and because a delay in
Subarachnoid
Hemorrhage
variably,
severe.
Consciousness
considered
in Chapter
1. If signs is
offrequently
meningeallost,
irritaineither
tion are present, CSF examination should not be destituting therapy may have tragic consequences,
transiently
or permanently,
onset. Decerebrate every
layed in order
to obtain a CTatscan.
pospatient presenting with a syndrome of altered conturing or, rarely, seizures may occur at this time. Besciousness (psychosis, acute confusional state, or
cause bleeding is conned mainly to the
coma)
subarachnoid
should have blood drawn for subsequent glucose
space about the surface of the brain, prominent focal
deterneurologic signs other than oculomotor (III) or ab- Prognosis
mination and immediately receive 50 mL of 50% dexducens (VI) nerve palsies are uncommon, althoughtrose
bi- intravenously. This allows blood to be analyzed
The
duration
of hypoglycemia
that will result in perlateral extensor plantar responses occur frequently.
without
delaying
therapy.
manent
damage
to
the
brain
is
variable.
SubHypoglycemic
arachnoid blood also causes irritation and meningeal
coma may be tolerated for 6090 minutes, but once
signs. Examination of the optic fundi may show acute
the stage of accidity with hyporeexia has been
hemorrhages secondary to suddenly increased
reached, glucose must be administered within 15
intracraminnial pressure or the more classic supercial
utes if recovery is to be expected. If the brain has not
subhyaloid
hemorrhages (see Figure 25). In coma-producing been irreparably damaged, full recovery should occur
within seconds after intravenous administration of
subgluarachnoid hemorrhage, the CSF is bloody and the CT
brain scan shows blood in the subarachnoid spacecose and within 1030 minutes after nasogastric administration. Rapid and complete recovery is the rule,
(see
Figure 26).

Meningitis & Encephalitis

334 / CHAPTER 10
but gradual improvement to full normality may take
Table 107. Prognostic signs in coma from global
place over hours to several days. Any lingering signs
cerebral ischemia. Comparison of the ndings in
or
two studies.1,2,3
symptoms suggest irreversible brain damage from
hyProbability of
poglycemia or the presence of an additional neuRecovering
3.
G
LOBAL
C
EREBRAL
I
SCHEMIA
ropathologic process.
Independent
Global cerebral ischemia produces encephalopathy
Function (%)
that
culminates in coma; it most often occurs following
Time Since Onset
carof Coma (Days)
diac arrest. The pupils dilate rapidly, and there may
be
Sign
0
1
3 7
tonic, often opisthotonic, posturing with a few
Data from Levy et al2
seizure13
8
5 6
like tonic-clonic movements. Fecal incontinence is No verbal response
No eye opening
11
6
4 0
common. With prompt reestablishment of cerebral
Unreactive pupils
0
0
0 0
perNo spontaneous eye movements6
5
2 0
fusion, recovery begins at the brainstem level with No caloric responses
5
6
6 0
the
Extensor posturing
18
0
0 0
return of reex eye movements and pupillary
Flexor posturing
14
3
0 0
Absent motor responses
function.
4
3
0 0
Reex motor activity (extensor or exor posturing)
then gives way to purposive movements, and con-Data from Edgren et al3
31
8
0 0
sciousness is regained. The persistence of impairedNo eye opening to pain
25
9
0 0
brainstem function (xed pupils) in adults following Absent or reex motor responses
Unreactive pupils
17
7
0 0
the return of cardiac function makes the outlook
virtu1 It can be seen that there is some variation in the prognosally hopeless. Incomplete recovery may occur,
tic utility of individual signs in the early phase of acute hypoxic encephalopathy.
leading
2 Data from Levy DE et al: Predicting outcome from hyto the return of brainstem function and wakefulness
(ie, eye opening with sleep-wake cycles) without poxic-ischemic coma. JAMA 1985;253:14201426 (N 210).
higher-level intellectual functions. The condition of3 Data from Edgren E et al: Assessment of neurological
prognosis in comatose survivors of cardiac arrest. Lancet
such patientsawake but not awarehas been 1994;343:10551059 (N 131).
Sedative-hypnotic
drug overdose is the most common
termed
cause
of
coma
in
many
series;
and
persistent vegetative state
(seebarbiturates
below). Although
benzodipupillary reactivity, resulting in pupils 23 mm in disuch
azepines
are
the
prototypical
drugs.
Coma
is
that are nonreactive to light. The electroen4.
RUG INTOXICATION
an Doutcome
is possible following other major brainameter
inpreceded
cephalogram
(EEG) may be atand in overdose with
sults such as trauma, bihemispheric stroke, or
by
a
period
of
intoxication
marked
by
prominent
nyslong-acting
barbiturates
may remain isoelectric for at
Sedative-Hypnotic Drugs
subarachtagmus
in
all
directions
of
gaze,
dysarthria,
and
least
24
hoursyet
full
recovery
will occur with supnoid hemorrhage, global ischemia is the most
ataxia.
port
of
cardiopulmonary
function.
Bullous skin erupcommon
Shortly
after
consciousness
is
lost,
the
neurologic
tions
and
hypothermia
are
also
characteristic
of
cause.
exambarbiThe prognosis in anoxic-ischemic encephalopathy
ination
may briey suggest an upper motor neuronturate-induced coma.
is
leTreatment should be supportive, centered upon
related to the rapidity with which central nervous syssion
as
hyperreexia,
ankle
clonus,
extensor
plantar
maintaining
adequate ventilation and circulation. Bartem function returns. Patients without pupillary reacrebiturates
are
dialyzable; however, with the shortertivity within 1 dayor those who fail to regain consponses,
and
(rarely)
decerebrate
or
decorticate
actsciousness within 4 dayshave a poor prognosis for
posturing
The
characteristic
feature of
ing barbiturates, morbidity and mortality rates are
functional appear.
recovery
(Table
107).
sedativeclearly lower in more conservatively managed
hypnotic overdose is the absence of extraocular patients.
moveThe use of benzodiazepine-receptor antagonists such
ments on oculocephalic testing, with preservation as
of
the pupillary light reex. Rarely, concentrations of umazenil (0.20.3 mg intravenously, repeated once,
barthen 0.1-mg intravenous dosing to maximum of 1
biturates or other sedative drugs sufcient to produce
mg)
severe hypotension and respiratory depression
can be used to reverse sedative-hypnotic drug
requiring
intoxicapressors and ventilatory support can also
tion in settings such as conscious sedation. It should
compromise
not be included as standard treatment of coma of un-

COMA / 335
known cause, since in patients with some combined
losis; serum bicarbonate levels are rarely depressed
drug overdoses, eg, with cocaine or a tricyclic agent
bein
low 16 meq/L, however. The CSF is usually normal but
addition to a benzodiazepine, umazenil treatmentmay appear yellow (xanthochromic) in patients with
can
serum bilirubin levels greater than 46 mg/dL. The diprecipitate
status
epilepticus.
agnosis is conrmed by an elevated CSF glutamine
Ethanol
concentration. Coma is usually associated with
Ethanol overdose produces a similar syndrome, al-concenthough nystagmus during wakefulness, early impairtrations above 50 mg/dL but may occur with values
ment of lateral eye movements, and progression to
as
coma are not as common. Peripheral vasodilation is
low as 35 mg/dL. Hepatic encephalopathy is treated
prominent, producing tachycardia, hypotension, and
by
hypothermia. Stupor is typically associated with blood
controlling gastrointestinal bleeding or systemic
ethanol levels of 250300 mg/dL and coma with infeclevels
tion, decreasing protein intake to less than 20 g/d,
of 300400 mg/dL, but alcoholic patients who haveand
developed tolerance to the drug may remain awake
decreasing intracolonic pH with lactulose (30 mg
and
orally
even apparently sober with considerably higher 6.
HYPEROSMOLAR
STATES
Opioids
two
to three times
per day or titrated to produce two
levels.
Coma
with
focal
seizures is a common presentation of
to
Opioid overdose is characterized by pupillary
the
state,daily).
which Abdominal
is most often
fourhyperosmolar
bowel movements
cramping
constricassociated
may
occur
during
the
rst
48
hours
of
lactulose
treattion that is mimicked by miotic eye drops, pontine with nonketotic hyperglycemia. Hyperosmolar nonkement.
Production
of
ammonia
by
colonic
bacteria
may
hemorrhage, Argyll Robertson pupils, and
totic
hyperglycemia
is discussed
in
Chapter
1. or
be
reduced
with
neomycin,
6
g/d
orally
in
three
organophos7.
HYPONATREMIA
four
phate poisoning. The diagnosis of opioid intoxication
Hyponatremia
divided doses. can cause neurologic symptoms if
is
serum
conrmed by rapid pupillary dilation and awakening
sodium levels fall below 120 meq/L, especially when
after intravenous administration of 0.41.2 mg of the
the serum sodium level falls rapidly. Delirium and
narcotic antagonist naloxone. The duration of action
seizures are common presenting features.
8. HYPOTHERMIA
of
Hyponatremia is considered in detail in Chapter 1.
5.
H
EPATIC ENCEPHALOPATHY
All patients with temperatures below 26C (79F) are
naloxone is typically 14 hours. Repeated doses may
comatose, whereas mild hypothermia [temperatures
therefore be necessary, especially following
Clinical Findings
(90F)] does not cause coma. Causes of coma
intoxication
associated
with hypothermia include hypoglycemia,
with long-acting
narcotics(also
suchdiscussed
as methadone.
Hepatic
encephalopathy
in Chapter
1)
leading to coma can occur in patients with severe sedative drug intoxication, Wernicke encephalopathy,
and myxedema. Exposure can also produce hypotherliver
disease, especially those with portacaval shunting.mia, such as may occur when a structural brain lesion
causes acute coma out of doors or in another
Jaununheated
dice need not be present. Coma may be precipitated
area; therefore, such a lesion should not be excluded
by
from consideration in the differential diagnosis of
an acute insult, especially gastrointestinal
coma
hemorrhage,
and the production of ammonia by colonic bacteriawith hypothermia.
may contribute to pathogenesis. Neuronal depressionOn physical examination, the patient is obviously
may result from an increase in inhibitory
cold to the touch but may not be shivering [it ceases
at
tyric acid (GABA)-mediated neurotransmission, perhaps from elevated levels of endogenous benzodi-temperatures below 32.5C (90.5F)]. Neurologic exazepine receptor agonists in the brain. As in other amination shows the patient to be unresponsive to
metabolic encephalopathies, the patient presents pain, with diffusely increased muscle tone. Pupillary
rewith
actions may be sluggish or even absent.
somnolence or delirium. Asterixis may be especially
The electrocardiogram (ECG) may show prolonged
prominent. Muscle tone is often increased, hyperPR,
QRS, and QT intervals; bradycardia; and characreexia
is
common,
and
alternating
hemiparesis
and
Investigative Studies
teristic
J point elevation (Osborn waves). Serum creadecorticate or decerebrate posturing have been deA helpful diagnostic clue is the nearly invariable prestine
phosphokinase
(CPK) may be elevated in the abscribed. Generalized and focal seizures occur but are
ence of hyperventilation with resultant respiratorysence of myocardial infarction, and high levels of
inalkaserum
frequent.
amylase are common. Arterial blood gas values and
pH
must be corrected for temperature; otherwise, falsely

336 / CHAPTER 10
high PO2 and PCO2 and falsely low pH values will berestricted to repetitive movements of part of a single
reported.
limb or one side of the face. Although these signs of
Treatment is aimed at the underlying disease and
seizure activity can be subtle, they must not escape
at
norestoration of normal body temperature. The optimal
tice: status epilepticus requires urgent treatment (see
method and speed of rewarming are controversial,Chapter 8).
but
Coma may also be due to a prolonged postictal
passive rewarming with blankets in a warm room is
state, which is also discussed in Chapter 8.
an
effective and simple treatment. Ventricular brillation
may occur during rewarming. Because warming produces vasodilation and can lead to hypotension, DIFFERENTIAL DIAGNOSIS
intravenous uids may be required.
Coma can be confused with a variety of psychiatric
Most patients who recover from hypothermia doand
so
without neurologic sequelae. Except in myxedemaneurologic disorders.
there is no direct correlation between recorded
PSYCHOGENIC UNRESPONSIVENESS
temperature and survival. Death, when it occurs, is caused
Psychogenic unresponsiveness is a diagnosis of excluby
sion that should be made only on the basis of com9.
YPERTHERMIA
theHunderlying
disease process responsible for
pelling evidence. It may be a manifestation of schizoAt
body temperatures over 4243C (107.6109.4F),
hypotherphrenia (catatonic type), somatoform disorders
the
activitybrillation,
of the central
nervous
mia metabolic
or by ventricular
to which
thesystem
human
(conversion disorder or somatization disorder), or mais
myocardium becomes especially susceptible at
lingering. The general physical examination reveals
unable
to provide for increased energy demands, and
temperano
coma
ensues.
The(86F);
cause of
hyperthermia
in most
tures below
30C
myocardial
sensitivity
is abnormalities; neurologic examination generally
cases
maxreveals
is
exposure
to elevated
environmental temperatures.
imal
below 2124C
(7075F).
symmetrically decreased muscle tone, normal
This is commonly known as heat stroke. Additional
reexes,
causes include status epilepticus, idiosyncratic
and a normal (exor) response to plantar stimulation.
reactions
The pupils are 23 mm in diameter or occasionally
to halogenated inhalational anesthetics (malignant
larger and respond briskly to light. Lateral eye movehyments on oculocephalic (dolls-head) testing may or
perthermia), anticholinergic drugs, hypothalamic
may not be present, since visual xation can
damsuppress
age, and delirium tremens. Patients surviving pontine
this reex. The slow conjugate roving eye movements
hemorrhage for more than a few hours have centrally
of metabolic coma cannot be imitated, however, and,
mediated temperature elevations ranging from 38.5
if
to
present, are incompatible with a diagnosis of psy42.8C (101.3109F). The neurological examination
chogenic unresponsiveness. Likewise, the slow, often
in hyperthermia reveals reactive pupils and a diffuse
asymmetric and incomplete eye closure commonly
inseen
crease in muscle tone as well as coma.
after the eyes of a comatose patient are passively
Treatment is immediate reduction of body
opened
10. OTHER CAUSES
temperacannot be voluntarily reproduced. The patient with
Rare to
causes
coma include
multifocal
disorders
that
ture
39C of
(102.2F)
by sponging
the patient
with
psychogenic unresponsiveness usually exhibits some
present
metabolic
disseminated
ice
waterasand
alcohol coma:
and using
an electric fan or
voluntary muscle tone in the eyelids during passive
intravascular
cooleye
coagulopathy,
sepsis,
vasculitis,
PERSISTENT VEGETATIVE STATE
ing
blanket. Care
mustpancreatitis,
be taken to prevent
opening. A helpful diagnostic test is irrigation of the
thrombotic
overhydraSome
patients
who are
comatose
because
tympanic
membrane
with
cold water.
Brisk of cerebral
thrombocytopenic
purpura,
emboli, hypertensive
tion, since cooling results
in fat
vasoconstriction
that
hypoxia
or ischemiaor structural brain lesions (Fignystagmus
encephalopathy,
and diffuse micrometastases.
may
ure
107)regain
wakefulness
not awareness.
is the
characteristic
response inbut
conscious
patients,AfSEIZURE
OR
PROLONGED
produce pulmonary edema in volume-expanded pater
1 month,
this condition
is termed
persistent
whereas
no
nystagmus
occurs
in
coma.
The
EEG in
POSTICTAL STATE
tients.
vegetapsychogenic unresponsiveness is that of a normal
Status epilepticus should always be considered in tive
the state. Such patients exhibit spontaneous eye
awake
opening
differential diagnosis of coma. Motor activity may be
person. and sleep-wake cycles, which distinguish
them
from patients in coma, and demonstrate intact brain-

COMA / 337

Figure 108. CT brain scan (contrast-enhanced) of a

man with basilar artery occlusion who exhibits the
patient with bilateral middle cerebral artery infarcts,
who is in a persistent vegetative state.The reticular acti-locked-in syndrome.The pontine infarction (arrows) is
below the level of the reticular activating system, allowvating system in the intact midbrain (arrows) allows
ing wakefulness, but the bilateral descending motor
wakefulness, but the bihemispheric lesions preclude
tracts have been effectively transected.
awareness.
Figure 107. CT brain scan (contrast-enhanced) of a

and look at the tip of your nose to elicit such movestem and autonomic function. However, they neither
ments. The EEG is normal. Outcome is variable and
comprehend nor produce language, and they make
related to the underlying cause and the extent of the
no
purposeful motor responses. This condition may brainstem lesion. Mortality, usually from pneumonia,
is
persist
approximately 70% when the cause is a vascular
for years. Recovery of consciousness from
disturnontraumatic
bance and about 40% in nonvascular cases. Survivors
causes
is
rare
after
3
months,
and
from
traumatic
Because
the
portion
of
the
reticular
formation
LOCKED-IN SYNDROME
may recover partially or completely over a period of
causes
responsiweeks to months.
is rare
12 months.
ble
for after
consciousness
lies above the level of the midpons, functional transection of the brainstem below
BRAIN DEATH
this levelby pontine infarction (Figure 108), hemorrhage, central pontine myelinolysis, tumor, or en- Current standards for the determination of brain
death,
cephalitiscan interrupt descending neural pathways
developed by the Presidents Commission for the
to produce an akinetic and mute state, with
Study of
preserved
Ethical Problems in Medicine and Biomedical and Beconsciousness. Such patients appear comatose but
havioral Research (1981), are summarized below.
are
Irreawake and alert although mute and quadriplegic. Decerebrate posturing or exor spasms may be seen.versible cessation of all brain function is required for
a
diCessation
of Brain Function
The
agnosis
of brain death. The diagnosis of brain death
diagnosis is made by noting that voluntary eye openA. UNRESPONSIVENESS
ing, vertical eye movements, ocular convergence, in
or
The
patient
must
be unresponsive
input,
children
under
5 years
of age mustto
besensory
made with
some combination of these volitional midbrain-mediincaution.
ated movements is preserved. During the
cluding pain and speech.
examination
of any apparently comatose patient, the patient
should
be told to open your eyes, look up, look down,

338 / CHAPTER 10
Young GB et al (editors): Coma and Impaired Consciousness: A
B. ABSENT BRAINSTEM REFLEXES
ClinPupillary, corneal, and oropharyngeal responses are
ical Perspective. McGraw-Hill, 1998.
abStructural Lesions
sent, and attempts to elicit eye movements with the
oculocephalic and vestibuloocular maneuvers are unCalfee DP, Wispelwey B: Brain abscess. Semin Neurol 2000;20:
353360.
successful. Respiratory responses are also absent,
Devuyst G et al: Stroke or transient ischemic attacks with basilar
with
artery stenosis or occlusion: clinical patterns and outcome.
no ventilatory effort after the patients PCO2 is permit-Arch Neurol 2002;59:567573.
ted to rise to 60 mm Hg, while oxygenation is mainKoh MS et al: Is decompressive craniectomy for acute cerebral intained by giving 100% oxygen by a cannula inserted farction of any benet? Surg Neurol 2000;53:225230.
Parvizi J, Damasio AR. Neuroanatomical correlates of brainstem
into the endotracheal tube (apnea test).
coma. Brain 2003;126:15241536.
Qureshi AI et al: Spontaneous intracerebral hemorrhage. N Engl J
Med 2001;344:14501460.
The cause of coma must be known; it must be adeServadei F: Prognostic factors in severely head injured adult paquate to explain the clinical picture; and it must be ir-tients with acute subdural haematomas. Acta Neurochir
reversible.
(Wien) 1997;139:279285
Sedative drug intoxication, hypothermia [32.2CSiddique MS, Mendelow AD: Surgical treatment of intracerebral
Br Med Bull 2000;56:444456.
(90F)], neuromuscular blockade, and shock must Wijdicks
be haemorrhage.
EF, St Louis E: Clinical proles predictive of outcome in
ruled out, since these conditions can produce a
pontine hemorrhage. Neurology 1997;49:13421346.

Irreversibility of Brain Dysfunction

clinical
picture that resembles brain death but in which
neurologic recovery may still be possible.

Persistence of Brain Dysfunction

Diffuse Encephalopathies
Brust JC: Acute neurologic complications of drug and alcohol

The criteria for brain death described above must

abuse. Neurol Clin 1998;16:503519.
perBouchama A, Knochel JP: Heat stroke. N Engl J Med 2002;346:
19781988.
sist for an appropriate length of time, as follows:
Edgren
E et al: Assessment of neurological prognosis in comatose
1. Six hours with a conrmatory isoelectric (at)
survivors of cardiac arrest. Lancet 1994;343:10551059.
EEG, performed according to the technical standards
Fischbeck KH, Simon RP: Neurological manifestations of accidenof the American Electroencephalographic Society.
tal hypothermia. Ann Neurol 1981;10:384387.
2. Twelve hours without a conrmatory isoelectric
Hart SP, Frier BM: Causes, management and morbidity of acute
hypoglycaemia in adults requiring hospital admission. Q J
EEG.
3. Twenty-four hours for anoxic brain injury with- Med 1998;91:505510.
Levy DE et al: Predicting outcome from hypoxic-ischemic coma.
out a conrmatory isoelectric EEG.
JAMA 1985;253:14201426.
Lowenstein DH, Simon RP: Acute drug intoxication. Pages
302336 in: Principles of Drug Therapy in Neurology. Johnston MV, Macdonald RL, Young AB (editors). Vol 37 of:
Demonstration of the absence of cerebral blood ow Contemporary Neurology Series. Davis, 1992.
conrms brain death without a waiting period. CereWeinbroum A et al: Use of umazenil in the treatment of drug
overdose: a double-blind and open clinical study in 110 pabral angiography provides the most unequivocal
tients. Crit Care Med 1996;24:199206.
assessWilson JX, Young GB. Progress in clinical neurosciences: sepsis-asment; Doppler techniques and technetium imaging sociated encephalopathy: evolving concepts. Can J Neurol Sci
are
2003;30:98105.

Additional Conrmatory Tests

used in some centers.

REFERENCES
General

Persistent Vegetative State

Buettner UW, Zee DS: Vestibular testing in comatose patients.

Arch Neurol 1989;46:561563.
Giacino JT et al: The minimally conscious state: denition and diFisher CM: The neurological examination of the comatose patient.agnostic criteria. Neurology 2002;58:349353.
Acta Neurol Scand 1969;45(Suppl 36):156.
Jennett B: The vegetative state. J Neurol Neurosurg Psychiatry
Fisher CM: Brain herniation: a revision of classical concepts. Can J2002;73:355357.
Neurol Sci 1995;22:8391.
Plum F, Posner JB: The Diagnosis of Stupor and Coma, 3rd ed. Vol
Locked-In Syndrome
19 of: Contemporary Neurology Series. Davis, 1980.
Simon RP: Coma. Pages 151 in: Clinical Neurology. Joynt RJ,
Katz RT et al: Long-term survival, prognosis, and life-care planning
Griggs RC (editors). Lippincott Raven, 1997.
for 29 patients with chronic locked-in syndrome. Arch Phys
Rehabil 1992;73:403408.

COMA / 339
Leon-Carrion J et al: The locked-in syndrome: a syndrome looking
Halevy A, Brody B: Brain death: reconciling denitions, criteria,
for a therapy. Brain Inj 2002;16:555569.
and tests. Ann Intern Med 1993;119:519525.
Wijdicks EFM: The diagnosis of brain death. N Engl J Med
2001;344:12151221.

Brain Death

de Tourtchaninoff M et al: Brain death diagnosis in misleading

conditions. Q J Med 1999;92:407414.

11

Neurologic
Investigations
CONTENTS
Lumbar puncture, 340
Electrophysiologic
studies, 344
Electroencephalography, 344
Evoked potentials, 345
Electromyography & nerve
conduction studies, 346
F-response studies, 347
Repetitive nerve stimulation,
347
Cranial imaging studies, 348
Plain x-rays, 348
Computed tomography, 348
Magnetic resonance imaging, 349

Diffusion-weighted magnetic resonance imaging,

352
Perfusion-weighted magnetic resonance imaging, 352
Positron emission tomography, 352
Single-photon emission
computed tomography,
353
Functional magnetic resonance imaging, 353
Magnetic resonance spectroscopy, 353
Arteriography, 353
Magnetic resonance angiography, 354

Computed tomographic
angiography, 354
Spinal imaging studies, 354
Plain x-rays, 354
Myelography, 354
Computed tomography, 355
Magnetic resonance imaging, 355
Ultrasonography, 355
Biopsies, 356
Brain biopsy, 356
Muscle biopsy, 356
Nerve biopsy, 356
Artery biopsy, 356

KEY CONCEPTS
The investigations that are performed in a particular case depend on the clinical context and
the likely diagnosis.

Investigations are performed not only to suggest

or conrm the diagnosis but also to exclude
other diagnostic possibilities, aid prognostica-

tion, provide a guide to further management,

and follow disease progression.
Physiologic studies evaluate function and are
complementary to imaging studies, which evaluate structure.
The results of investigations need to be interpreted in the context in which they were obtained.

1. Diagnosis of meningitis and other infective or inammatory disorders, subarachnoid hemorrhage, heLUMBAR PUNCTURE
patic encephalopathy, meningeal malignancies,
paraneoplastic disorders, or suspected abnormalities of
Indications
intracranial pressure.
Lumbar puncture is indicated for the following pur- 2. Assessment of the response to therapy in
poses:
meningitis and other infective or inammatory disorders.
340
Copyright 2005, 2002 by The McGraw-Hill Companies, Inc. Click here for terms of use.

NEUROLOGIC INVESTIGATIONS / 341

3. Administration of intrathecal medications or radiologic contrast media.
4. Rarely, to reduce cerebrospinal uid (CSF) pressure.

4. Drapes.
5. Lidocaine (1%).
6. Syringe (5 mL).
7. Needles (22- and 25-gauge).
8. Spinal needles (preferably 22-gauge) with
stylets.
Contraindications
9. Three-way stopcock.
1. Suspected intracranial mass lesion. In this situa-10. Manometer.
tion, performing a lumbar puncture can hasten incipi-11. Collection tubes.
ent transtentorial herniation.
12. Adhesive bandage.
2. Local infection overlying the site of puncture.C. POSITIONING
Under this circumstance, cervical or cisternal
Lumbar puncture is usually performed with the
puncture
patient
should be performed instead.
in the lateral decubitus position (Figure 111), lying at
3. Coagulopathy. Clotting-factor deciencies andthe edge of the bed and facing away from the person
thrombocytopenia (below 20,000/mm3 or rapidly performing the procedure. The patients lumbar spine
falling platelet counts) should be corrected before should be maximally exed to open the intervertebral
lumspaces. The spine should be parallel to the surface of
bar puncture is undertaken, to reduce the risk of the bed and the hips and shoulders should be aligned
hemin the vertical plane.
orrhage.
Occasionally, it is desirable to perform lumbar
4. Suspected spinal cord mass lesion. Lumbar puncture with the patient seated. In this case, the papuncture in this case should be performed only in tient is seated on the side of the bed, bent over a
assopillow
Preparation
ciation with myelography, which is used to determine
that rests on a bedside table, while the physician
A.
thePERSONNEL
presence and level of structural spinal pathology.
reaches over the bed from the opposite side to
With a cooperative patient, lumbar puncture can genD.
SITE OF PUNCTURE
perform
erally be performed by one person. An assistant can
The
usual practice is to enter the L34 or L45 interthe procedure.
be
space, since the spinal cord (conus medullaris) termihelpful in positioning the patient and handling CSFnates at about the L12 level in adults. Thus, the prosamples, of course, especially if the patient is
cedure is performed without danger of puncturing the
uncoopercord. The L34 interspace is located at the level of
B.
EQUIPMENT
AND SUPPLIES
ative
or frightened.
the
The following items, which are usually included in posterior iliac crests.
preassembled lumbar puncture trays, are required. AllProcedure
must be sterile.
1. If a comparison between blood and CSF glucose
1. Gloves.
levels is planned, venous blood is drawn for glucose
2. Iodine-containing solution for sterilizing the skin.
de3. Sponges.
termination. Ideally, blood and CSF glucose levels
Level of the iliac crests

L34 interspace

Figure 111. Lateral decubitus position for lumbar puncture.

should be measured in samples obtained simultaneously after the patient has fasted for at least 4 hours.
2. The necessary equipment and supplies are
placed
342 / CHAPTER 11
within easy reach.
3. Sterile gloves are worn by the person performing
13. It has been customary to have the patient lie
the procedure.
prone or supine for 1 or 2 hours after the procedure
4. A wide area surrounding the interspace to be ento
tered is sterilized, using iodine-containing solution apreduce the risk of post-lumbar-puncture headache.
plied to sponges; the solution is then wiped off with
Current evidence suggests this is unnecessary.
clean sponges.
5. The area surrounding the sterile eld may beComplications
draped.
A. UNSUCCESSFUL TAP
6. The skin overlying the puncture site is anes- A variety of conditions, including marked obesity, dethetized using lidocaine, a 5-mL syringe, and a 25-generative disease of the spine, previous spinal
gauge needle. A 22-gauge needle is then substituted
surgery,
to
recent lumbar puncture, and dehydration, can make
anesthetize the underlying tissues.
it
7. With the stylet in place, the spinal needle is indifcult to perform lumbar puncture in the convenserted at the midpoint of the chosen interspace. The
tional manner. When puncture in the lateral decubitus
needle should be parallel to the surface of the bedposition is impossible, the procedure should be atand
tempted with the patient in a sitting position. If the
angled slightly cephalad, or toward the umbilicus. tap
The
is again unsuccessful, alternative methods include
bevel of the needle should face upward, toward the
lumface
bar puncture by an oblique approach or guided by
of the person performing the procedure.
uo8. The needle is advanced slowly until a pop, from
B.
ARTERIAL
OR VENOUS
PUNCTURE
roscopy;
lateral
cervical
puncture; or cisternal
penetration of the ligamentum avum, is felt. The If
the needle enters a blood vessel rather than the
puncture.
stylet is withdrawn to determine whether the CSF spinal
These procedures should be undertaken by a neurolospace has been entered, which is indicated by owsubarachnoid
of neurosurgeon,
space,orit neuroradiologist
should be withdrawn
and a
gist,
experienced
CSF through the needle. If no CSF appears, the stylet
new
in
is replaced and the needle advanced a short
needle
usedthem.
to attempt the tap at a different level.
performing
distance;
Pathis is continued until CSF is obtained. If at some tients who have coagulopathy or are receiving aspirin
point the needle cannot be advanced, it is likely that
or
bone has been encountered. The needle is withdrawn
C.
POST-LUMBAR-Pshould
UNCTURE
anticoagulants
beHEADACHE
observed with particular
partway, maintained parallel to the surface of the A
mild headache, worse in the upright position but recare
bed,
lieved
by of
recumbency,
is not uncommon
for signs
spinal cord compression
(see following
Chapter 5)
and advanced again at a slightly different angle. lumbar
puncture
and or
will
resolvehematoma.
spontaneously over
from spinal
subdural
epidural
9. When CSF is obtained, the stylet is reinserted.
a
The patient is asked to straighten his or her legs, and
period of hours to days. Frequency is directly related
the stopcock and manometer are attached to the to
neethe size of the spinal needle. Vigorous hydration or
dle. The stopcock is turned to allow CSF to enter the
keeping the patient in bed for 1 or 2 hours after the
manometer to measure the opening pressure. Theprocedure apparently does not reduce the likelihood
presof
sure should uctuate with the phases of respiration.
such headache. The headache usually responds to
10. The stopcock is turned to allow the CSF to be
noncollected, and the appearance (clarity and color) of
steroidal antiinammatory drugs or caffeine (see
the
ChapAnalysis
of Results
A.
PPEARANCE
uid is noted. The amount obtained and the number
terA2).
Severe
and protracted headache can be
The
clarity and color of the CSF should be observed
of
treated
as
tubes required varies, depending on the tests to be
by an autologous blood clot patch, which should be
it
leaves the spinal needle, and any changes in the
perapapformed. Typically, 12 mL is collected in each of ve
plied by experienced personnel.
pearance of uid during the course of the procedure
tubes for cell count, glucose and protein
should be noted. CSF is normally clear and colorless.
determination,
It
VDRL, Gram stain, and cultures. Additional specimens
may appear cloudy or turbid with white blood cell
may be collected for other tests, such as oligoclonal
counts that exceed about 200/L, but counts as low
bands and glutamine, and for cytologic study. If the
as
CSF appears to contain blood, additional uid should
be obtained so that the cell count can be repeatedabout
on 50/L can be detected by holding the tube up
to
the specimen in the last tube collected. Cytologic
direct sunlight and observing the light-scattering
stud(Tynies, if desired, require at least 10 mL of CSF.

NEUROLOGIC INVESTIGATIONS / 343

dall) effect of suspended cells. Color can be imparted
Table 111. Pigmentation of the CSF following
to
subarachnoid hemorrhage.
the CSF by hemoglobin (pink), bilirubin (yellow), or,
rarely, melanin (black).
Appearance Maximum Disappearance
B. PRESSURE
With the patient in the lateral decubitus position, CSF
Oxyhemoglobin 0.54
2435
710
pressure in the lumbar region does not normally
(pink)
hours
hours
days
exceed
812
24
23
180200 mm water. When lumbar puncture is per-Bilirubin
hours
days
weeks
formed with patients in the sitting position, patients(yellow)
should assume a lateral decubitus posture before CSF
pressure is measured. Increased CSF pressure may
result
days. In addition, blood related to traumatic puncture
from obesity, agitation, or increased intraabdominal
does not clot, whereas clotting may occur with subpressure related to position; the latter factor may be
arachnoid hemorrhage. Crenation (shriveling) of red
eliminated by having the patient extend the legs and
back once the CSF space has been entered and blood cells, however, is of no diagnostic value.
In addition to breakdown of hemoglobin from red
before
blood
cells, other causes of CSF xanthochromia
the opening pressure is recorded. Pathologic
include
conditions
C.
MICROSCOPIC
EXAMINATION
associated
with
increased CSF pressure include in-jaundice with serum bilirubin levels above 46 mg/dL,
CSF protein concentrations greater than 150 mg/dL,
This
may
be
performed
by the person who pertracranial mass lesions, either
meningoencephalitis,
and, rarely, the presence of carotene pigments.
formed
the
lumbar
puncture
or
by
a
technician
at
the
subarachWhite blood cells seen in the CSF early after subclinical
laboratory;
it
always
includes
a
cell
count
and
noid hemorrhage, and pseudotumor cerebri.
arachnoid
hemorrhage or with traumatic lumbar
differential. Gram stain for bacteria, acid-fast stain for
puncmycobacteria, an India ink preparation for Cryptococcus, and cytologic examination for tumor cells mayture result from leakage of circulating whole blood. If
the hematocrit and peripheral white blood cell count
also
be indicated. The CSF normally contains up to veare within normal limits, there is approximately one
white blood cell for each 1000 red cells. If the periphmononuclear leukocytes (lymphocytes or monocytes)
per microliter, no polymorphonuclear cells, and noeral white cell count is elevated, a proportionate increase in this ratio should be expected. In addition,
ery1000 red cells present in CSF will increase the
throcytes. Erythrocytes may be present, however, every
if
CSF
protein
concentration by about 1 mg/dL.
D.
Procedure Notes
theBLOODY CSF
If
the lumbar
puncture
yields bloody
CSF, itNormal
is crucial
lumbar
puncture
is traumatic
(see below).
Whenever a lumbar puncture is performed, notes deto
distinguish between central nervous system
CSF
scribing the procedure should be recorded in the pahemoris sterile, so that in the absence of central nervous
tients chart. These notes should provide the
rhage
sys- and a traumatic tap. The uid should be
following
watched
tem infection, no organisms should be observed with
information:
as
leaves stains
the spinal
needle
to determine whether1. Date and time performed.
theitvarious
listed
above.
the
2. Name of person or persons performing the proceblood clears, which suggests a traumatic tap. This dure.
can
3. Indication.
be established with greater accuracy by comparing4. Position of patient.
cell
5. Anesthetic used.
counts in the rst and last tubes of CSF obtained; a6. Interspace entered.
marked decrease in the number of red cells supports
7. Opening pressure.
a
8. Appearance of CSF, including changes in appeartraumatic cause. The specimen should be centrifuged
ance during the course of the procedure.
promptly and the supernatant examined. With a trau9. Amount of uid removed.
matic lumbar puncture, the supernatant is colorless.
10. Closing pressure.
In
11. Tests ordered, eg:
contrast, following central nervous system
Tube #1 (1 mL), cell count.
hemorrhage,
Tube #2 (1 mL), glucose and protein levels.
enzymatic degradation of hemoglobin to bilirubin in
situ renders the supernatant yellow (xanthochromic).
The time course of changes in CSF color following
subarachnoid hemorrhage is outlined in Table 111.
Blood in the CSF following a traumatic lumbar puncture usually clears within 24 hours; blood is usually
present after subarachnoid hemorrhage for at least 6

344 / CHAPTER 11
Tube #3 (1 mL), microbiologic stains.
seizures there may be abnormal rhythmic activity of
Tube #4 (1 mL), bacterial, fungal, and mycobac-variable frequency with a localized or generalized
terial cultures.
distri12. Results of any studies, such as microbiologic bution, or, in some instances, there may be no
stains,
electroperformed by the operator.
graphic correlates. The presence of a focal or
13. Complications, if any.
lateralized
epileptogenic
source
is of particular
importance if surAssessment &
Prognosis
of Seizures
gical treatment is under consideration.
The EEG ndings may provide a guide to prognosis
ELECTROPHYSIOLOGIC STUDIES
and have been used to follow the course of seizure
disorders. A normal EEG implies a more favorable progELECTROENCEPHALOGRAPHY
nosis for seizure control, whereas an abnormal backThe electrical activity of the brain can be recordedground or profuse epileptiform activity implies a poor
prognosis. The EEG ndings do not, however, provide
nona reliable guide to the subsequent development of
invasively from electrodes placed on the scalp. Elecseizures in patients with head injuries, stroke, or
troencephalography (EEG) is easy to perform, is relabrain
tively inexpensive, and is helpful in several different
tumors. Some physicians have used the
clinical contexts.
electrophysioEvaluation of Suspected Epilepsy
logic ndings to determine whether anticonvulsant
EEG is useful in evaluating patients with suspectedmedication can be discontinued in patients who have
epilepsy. The presence of electrographic seizure been free of seizures for several years. Although
activity
patients
(abnormal, rhythmic electrocerebral activity of abrupt
are more likely to be weaned successfully if the EEG
onset and termination) during a behavioral
is
disturbance
normal, the ndings provide only a general guide,
that could represent a seizure, but about which there
and
Management of Status Epilepticus
is
patients can certainly have further seizures, despite a
The
EEGEEG,
is ofafter
littlewithdrawal
help in managing
tonic-clonicmedclinical uncertainty, establishes the diagnosis beyond
normal
of anticonvulsant
doubt. Because seizures occur unpredictably, it is status
ication. Conversely, they may have no further
epilepticus
unless patients have received
often
seizures
not possible to obtain an EEG during a seizure. De-neuromuscular
despite a continuing EEG disturbance.
blocking agents and are in a coma induced by
spite that, the EEG ndings may be abnormal interictally (at times when the patient is not experiencingmedication. In this case, the electrophysiologic ndings are
clinical attacks) and are therefore still useful for diagusenostic purposes. The interictal presence of
ful in indicating the level of anesthesia and
epileptiform
activity (abnormal paroxysmal activity containing determining
whether the seizures are continuing. The status itself
some
is
spike discharges) is of particular help in this regard.
characterized by repeated electrographic seizures or
Such activity is occasionally encountered in patients
conwho have never had a seizure, but its prevalence is
tinuous epileptiform (spike-and-wave) activity.
greater in patients with epilepsy than in normal subNonconjects. Epileptiform
activity in
the EEG of a patient with
Classication
of Seizure
Disorders
vulsive status
may follow Brain
controlLesions
of convulsive status.
an episodic behavioral disturbance that could on cliniDetection
of Structural
In
epileptics,
the EEG ndings
may help
in Electroencephalography
has been used as a
In
calknown
grounds
be a manifestation
of seizures
markedly
classifying
the seizure disorder and thus in selecting
noninvasive
patients with nonconvulsive status epilepticus, the
inapof detecting focal structural abnormalities,
EEG
creases the likelihood that the attacks are indeed means
propriate
in
ndings
provide the only means of making the
epilep- anticonvulsant medication. For example,such
patients
with the typical
absences
of petitdiagnosis.
mal
as
brain tumors. There may be a focal slow-wave
diagnosis
tic, thus providing
support
for the clinical
epilepsy
disturwith condence and in distinguishing the two main
(see Chapter 8) the EEG is characterized both ictally
bance,
a localized
loss ofepilepticus,
electrocerebral
activity, or a
types. In
absence status
continuous
and interictally by episodic generalized spike-and- more
spike-generalized EEG disturbance that probably
wave
relates
and-wave activity is seen, whereas repetitive electroactivity (Figure 83). In contrast, in patients with in
part to
an altered
graphic
seizures
are level
foundofinarousal.
complexNoninvasive
partial status.
episodes of impaired external awareness caused by
imagcoming procedures such as computed tomography (CT)
plex partial seizures, the EEG may be normal or show
and magnetic resonance imaging (MRI) have supfocal epileptiform discharges interictally. During the
planted the use of EEG in this context.

NEUROLOGIC INVESTIGATIONS / 345

noted. Although its amplitude can also be measured,
alCertain neurologic disorders produce characteristicterations in amplitude are far less helpful in
but
recognizing
nonspecic abnormalities in the EEG. Their presence
B.
AUDITORY
pathology.
is
Monaural stimulation with repetitive clicks is used to
helpful in suggesting, establishing, or supporting the
elicit brainstem auditory evoked potentials, which are
diagnosis. In patients presenting with an acute disturrecorded at the vertex of the scalp. A series of
bance of cerebral function, for example, the presence
potentials
of
are evoked in the rst 10 ms after the auditory stimurepetitive slow-wave complexes over one or both lus; these represent the sequential activation of
temvarious
poral lobes suggests a diagnosis of herpes simplexstructures in the subcortical auditory pathway. For
enclincephalitis.
Similarly,
the
presence
of
periodic
ical purposes, attention is directed at the presence,
Evaluation of Altered Consciousness
C.
complexes
la- SOMATOSENSORY
The
EEG tends
become
slower as consciousness
is
Electrical
of a peripheral
is used
to
in a patient
withtoan
acute dementing
disorder
tency,
andstimulation
interpeak intervals
of the nerve
rst ve
positive
depressed,
but
the
ndings
depend
at
least
in
part
elicit
the
somatosensory
evoked
potentials,
which
are
suggests
potentials recorded at the vertex.
upon
recorded over the scalp and spine. The conguration
a diagnosis of Creutzfeldt-Jakob disease or subacute
the
etiology
of
the
clinical
disorder.
The
ndings,
such
and latency of the responses depend on the nerve
sclerosing panencephalitis.
as the presence of electrographic seizure activity, that
can
suggest diagnostic possibilities that might otherwise
is stimulated.
be
Indications for Use
overlooked. Serial records permit the prognosis and
course of the disorder to be followed. The EEG re- A.
DETECTION
OF LESIONS
IN Mare
ULTIPLE
SCLEROSIS
Evoked
potential
studies
useful
in several clinical
sponse to external stimulation is an important
Evoked
potentials have been used to detect and
contexts.
diagnoslocalize
tic and prognostic guide: electrocerebral
lesions in the central nervous system. This is particuresponsiveness
larly important in multiple sclerosis, where the
implies a lighter level of coma. Electrocerebral silence
diagnoin a technically adequate record implies neocortical
sis depends upon detecting lesions in several regions
death, in the absence of hypothermia or drug
of
overdose.
the central nervous system. When patients present
In some patients who appear to be comatose, con-with
sciousness is, in fact, preserved. Although there is clinical evidence of a lesion at only one site, electroquadphysiologic recognition of abnormalities in other locaEVOKED POTENTIALS
riplegia and a supranuclear paralysis of the facial and
tions helps to establish the diagnosis. When patients
The
spinal
or cerebral
potentials
evoked
byin such with
bulbar
muscles,
the EEG
is usually
normal
pa- suspected multiple sclerosis present with ill-denoninvasive
tients with locked-in syndrome (see Chapter 10) and
ned complaints, electrophysiologic abnormalities in
stimulation
of specic
pathways are an the appropriate afferent pathways are helpful in
helps in indicating
the afferent
correct diagnosis.
imporindicattant means of monitoring the functional integrity of
ing the organic basis of the symptoms. Although nonthese pathways. They do not, however, indicate the
invasive imaging studies such as MRI are also useful
nafor
ture of any lesion that may involve these pathways.
detecting lesions, they should be used to
The
complement
responses are very small compared with the
evoked potential studies rather than as a
background
replacement.
EEG
activity
(noise),
which has no relationship to the
Types
of Evoked
Potentials
Evoked potential studies monitor the functional status
time of stimulation. The responses to a number of rather than anatomic integrity of the afferent
A.
VISUAL
stimuli
are therefore recorded and averaged (with pathways
a
Monocular
stimulation
with a noise.
checkerboard patcomputer) visual
to eliminate
the random
and can sometimes reveal abnormalities that are not
tern is used to elicit visual evoked potentials, which
deare
B. DETECTION OF LESIONS IN OTHER CENTRAL NERVOUS
tected by MRI (and the reverse also holds true). Their
recorded from the midoccipital region of the scalp.SYSTEM DISORDERS
cost is also considerably lower than MRI. In patients
The
Evoked potential abnormalities are encountered in
with established multiple sclerosis, the evoked
most clinically relevant component is the P100 re- dispotential
sponse, a positive peak with a latency of
orders other than multiple sclerosis; multimodal
ndings are sometimes used to follow the course of
approximately
evoked
the
100 ms. The presence and latency of the response
disorder or monitor the response to novel forms of
are
treatment, but their value in this regard is unclear.

Diagnosis of Neurologic Disorders

346 / CHAPTER 11
potential abnormalities may be encountered in
A. ACTIVITY AT REST
certain
Relaxed muscle normally shows no spontaneous
spinocerebellar degenerations, familial spastic
electriparaplecal activity except in the end-plate region where
gia, Lyme disease, acquired immunodeciency synneurodrome (AIDS), neurosyphilis, and vitamin E or B12 demuscular junctions are located, but various types of
ciency. The diagnostic value of electrophysiologicababnormalities therefore depends upon the contextnormal
in
activity occur spontaneously in diseased
which they are found. Although the ndings may permuscle. Fibrillation potentials and positive sharp
mit lesions to be localized within broad areas of the
waves (which reect muscle ber irritability) are typicentral nervous system, precise localization may not
cally found in denervated muscle; they are not invaribe
ably present, however. They are sometimes also
C.
ASSESSMENT
AND PROGNOSIS FOLLOWING CENTRAL
possible
because
the generators of many of the found
N
ERVOUS SYSTEM TRAUMA OR HYPOXIA
recorded
in myopathic disorders, especially inammatory disorEvoked
potentials
studies can provide information ders
of such as polymyositis. Although fasciculation pocomponents
are unknown.
prognostic relevance. In posttraumatic or postanoxic
tentialswhich reect the spontaneous activation of
coma, for example, the bilateral absence of cortically
individual motor unitsare occasionally encountered
generated components of the somatosensory evoked
in normal muscle, they are characteristic of
potential implies that cognition will not be recovered;
neuropathic
the prognosis is more optimistic when cortical re- disorders, especially those with primary involvement
sponses are present on one or both sides. Such of
studies
anterior horn cells (eg, amyotrophic lateral sclerosis).
may be particularly useful in patients with suspected
Myotonic discharges (high-frequency discharges of
brain death. Somatosensory evoked potentials have
poalso
B.
ACTIVITY
DURING
VOLUNTARY
USCLE
CONTRACTION
tentials
from
muscle
bers M
that
wax
and wane in
been used to determine the completeness of a
A
slight voluntary contraction of a muscle activates a
amplitraumatic
small
number
of motor
potentials
tude and
frequency)
areunits.
foundThe
most
commonly in discord lesion; the presence or early return of a
generated
orders such as myotonic dystrophy or myotonia
response
by
the muscle
of individual
units within
the decongenita
and bers
occasionally
in polymyositis
or other,
D.
INTRAOPERATIVE
MONITORING
following
stimulation
of a nerve below the level of tection
the
range
of
the
needle
electrode
can
be
rarer disorders. Other types of abnormal spontaneous
Evoked
potentials
arethat
alsothe
used
to monitor
the funccord injury
indicates
lesion
is incomplete
and
recorded.
activity also occur.
tional
integrityaofbetter
certain
neural structures during Normal motor-unit potentials have clearly dened limthus suggests
prognosis.
operits of duration, amplitude, conguration, and ring
ative procedures, in an attempt to permit the earlyrates. These limits depend, in part, on the muscle unrecognition of any dysfunction and thereby minimize
der study, and the number of units activated for a
damage. When the dysfunction relates to a surgical
specmaied degree of voluntary activity is known within
neuver, it may be possible to prevent or diminish any
broad
prominent neurologic decit by reversing the maneulimits. In many myopathic disorders, there is an inE.
EVALUATION OF VISUAL OR AUDITORY ACUITY
ver.
creased incidence of small, short-duration, polyphasic
Visual and auditory acuity may be evaluated through
motor units in affected muscles, and an excessive
evoked potential studies in patients who are unable
numto
ber of units may be activated for a specied degree
cooperate with behavioral testing because of age or
of
abvoluntary activity. There is a loss of motor units in
normal mental state.
ELECTROMYOGRAPHY & NERVE
neuropathic disorders, so that the number of units actiCONDUCTION STUDIES
vated during a maximal contraction will be reduced,
Electromyography
and units will re at a faster rate than normal. In
The electrical activity within a discrete region of anC. CLINICAL UTILITY
addiacLesions
involve theand
neural
or muscle
tion, thecan
conguration
dimensions
of component
the potencessible muscle can be recorded by inserting a
of
tials may be abnormal, depending on the acuteness
needle
the
of motor unit, or the neuromuscular junction. When
electrode into it. The pattern of electrical activity in
the neural
component
is and
affected,
the pathologic
neuropathic
process
on whether
muscle (electromyogram) both at rest and during process can be either at the level of the anterior horn
reinnervation
activcells
or at some
point along
length of the
axon
is occurring.
Variations
in thethe
conguration
and
sizeas
ity has been characterized, and abnormalities have
it
of
been
traverses
nerve root,
limb plexus,
and peripheralof
individual amotor-unit
potentials
are characteristic
correlated with disorders at different levels of the nerve
disorders of neuromuscular transmission.
motor
unit.

NEUROLOGIC INVESTIGATIONS / 347

before branching into its terminal arborizations. Elec3. Determining the site of a focal lesion and providtromyography can detect disorders of the motor units
ing a guide to prognosis in patients with a mononeuand can indicate the site of the underlying lesion. The
ropathy.
technique also permits neuromuscular disorders to be
4. Distinguishing between a polyneuropathy and a
recognized when clinical examination is unrewarding
mononeuropathy multiplex. This distinction may not
because the disease is still at a mild stageor
be possible clinically, but it is important because the
because
causes of these conditions differ.
poor cooperation on the part of the patient or the 5. Clarifying the extent to which the disabilities expresperienced by patients with polyneuropathy relate to
ence of other symptoms such as pain makes clinical
suevaluation difcult. Note that the electromyographic
perimposed compressive focal neuropathieswhich
ndings do not, of themselves, permit an etiologicare
diagnosis to be reached, and the electrophysiologic common complications.
nd6. Following the progression of peripheral nerve disings must be correlated with the clinical ndings and
orders and their response to treatment.
the results of other laboratory studies.
7. Indicating the predominant pathologic change in
The electromyographic ndings may provide a peripheral nerve disorders. In demyelinating neuguide to prognosis. For example, in patients with an
ropathies, conduction velocity is often markedly
acute disorder of a peripheral or cranial nerve (eg,slowed
a
pressure palsy of the radial nerve or a Bell palsy) and conduction block may occur; in axonal neuelecropathies, conduction velocity is usually normal or
tromyographic evidence of denervation implies a slowed only mildly, sensory nerve action potentials
poorer prognosis for recovery than when denervation
are
has not occurred.
small or absent, and electromyography shows
In contrast to needle electromyography, the
evidence
Nerve
Conduction Studies
clinical
of
denervation STUDIES
in affected muscles.
F-RESPONSE
utility
of
surface-recorded
electromyography
is
not
8.
Detecting
hereditary
disorders of the peripheral
A. MOTOR NERVE CONDUCTION STUDIES
When
a
stimulus
is
applied
toina genetic
motor nerve,
established.
nerves
at
a
subclinical
stage
and epidemioThese studies are performed by recording the
impulses
logic
studies.
electrical
travel antidromically (toward the spinal cord) as well
response of a muscle to stimulation of its motor nerve
as
at two or more points along its course. This permits
orthodromically (toward the nerve terminals) and
conduction velocity to be determined in the fastestlead
conducting motor bers between the points of
to the discharge of a few anterior horn cells. This prostimuladuces a small motor response that occurs
B. SENSORY NERVE CONDUCTION STUDIES
tion.
considerably
These are performed by analogous means, by
later than the direct muscle response elicited by
determinnerve
ing the conduction velocity and amplitude of action
potentials in sensory bers when these bers are stimulation. The F wave so elicited is sometimes
abnorstimuREPETITIVE NERVE STIMULATION
mal
lated
at
one
point
and
their
responses
are
recorded
at in patients with lesions of the proximal portions
C. INDICATIONS FOR USE
Description
of
another
point
along
the
course
of
the
nerve.
Nerve conduction studies provide a means of conrmperipheral nervous system, such as the nerve
ing the presence and extent of peripheral nerve the
The size of the electrical response of a muscle to
roots.
damage.
supraThese studies may be helpful in detecting
Such studies are particularly helpful when clinical exmaximal electrical stimulation of its motor nerve deabnormalities
amination is difcult (eg, in children). Nerve conducpends on a number of factors but correlates with the
conventional nerve conduction studies are
tion studies are particularly helpful in the followingwhen
number of activated muscle bers. Neuromuscular
normal.
contexts.
transmission can be tested by recording (with surface
1. Determining whether sensory symptoms are electrodes) the response of a muscle to
caused by a lesion proximal or distal to the dorsal supramaximal
root
stimulation of its motor nerve either repetitively or by
ganglia (in the latter case, sensory conduction
single shocks or trains of shocks at selected intervals
studies of
afNormal Response
the involved bers will be abnormal) and whether ter a maximal voluntary contraction.
In normal subjects, there is little or no change in the
neuromuscular dysfunction relates to peripheral nerve size of the compound muscle action potential
following
disease.
2. Detecting subclinical involvement of other peripheral nerves in patients who present with a
mononeuropathy.

348 / CHAPTER 11
repetitive stimulation of a motor nerve at 10 Hz orgressive accumulation of calcium in the motor nerve
less,
terminal.
or with a single stimulus or a train of stimuli delivered
at intervals after a voluntary muscle contraction of
about 10 seconds. This lack of change is the case
even
CRANIAL IMAGING STUDIES
though preceding activity in the junctional region inuences the amount of acetylcholine released and
thus
PLAIN X-RAYS
the size of the end-plate potentials elicited by the
Abnormalities of bone may be visualized by plain xstimrays
uli. Although the amount of acetylcholine released is
of the skull. Such abnormalities include metastatic
increased briey after maximal voluntary activity and
deis
posits, fractures, and the changes associated with
then reduced,
more acetylcholine is normally
Response
in Disorders
Paget
released
of Neuromuscular Transmission
disease or brous dysplasia. In addition, plain lms
than is required to bring the motor end-plate
can
A.
MYASTHENIA GRAVIS
potentials
show areas of abnormal intracranial calcication,
In
gravis,
depletionmuscle-ber
of postsynaptic
to myasthenia
the threshold
for generating
action
alteracetylpotentials.
choline receptors at the neuromuscular junction ations in size of the sella turcica, and inammatory
disCOMPUTED TOMOGRAPHY
makes
ease of the paranasal sinuses. The advent of
it impossible to compensate for the reduced release
Computed
Description
computed tomographic (CT) scanning is a noninvaof
sive computer-assisted
radiologic
means
of
scanning (which
permits
visualization
of
acetylcholine that follows repetitive ring of the tomographic
examining
cerebral
tissue
as
well
as
bone)
has
led
to
a
marked
motor
anatomic
structures (Figure 112). It permits the
deneuron. Accordingly, repetitive stimulation,
deteccline in the use of plain lms.
particularly
tion of structural intracranial abnormalities with precibetween 2 and 5 Hz, may lead to a depression of neusion, speed, and facility. It is thus of particular use in
romuscular transmission, with a decrement in the evaluating
size
patients with progressive neurologic disorof the compound muscle action potential recordedders or focal neurologic decits in whom a structural
from an affected muscle. Similarly, an electrical lesion is suspected as well as patients with dementia
stimuor
lus of the motor nerve immediately after a 10-second
increased intracranial pressure. It is particularly
period of maximal voluntary activity may elicit a musimporcle
that is slightly larger than before,
B. Mresponse
YASTHENIC SYNDROME AND BOTULISM
tant in the evaluation of patients with suspected
indicatIn Lambert-Eaton myasthenic syndrome, in which stroke
ing
that more muscle bers are responding. This or with head injuries. Intravenous administration of
there
postactivation
facilitation
of neuromuscular
is a defective release
of acetylcholine
at thetransmisan
sion
is
followed
by
a
longer-lasting
period
of
neuromuscuiodinated contrast agent improves the ability of CT to
depression
lar junction, the compound muscle action potentialdetect and dene lesions, such as tumors and
that
is maximal
from
24 minutes
after the
conditionelicited
by a single
stimulus
is generally
very
small.
abscesses,
ing
period
and
lasts
up
to
10
minutes
or
so.
Duringassociated with a disturbance of the blood-brain
With
this
period,
the compound
muscle
is
repetitive
stimulation
at rates
of upaction
to 10 potential
Hz, the rst
barrier.
reduced
in
size.
few responses may decline in size, but subsequentBecause the contrast agents may have an adverse
re-Decrementing responses to repetitive stimulation
effect
at
sponses increase and their amplitude is eventuallyon the kidneys, they should be used with discrimina25
sev-Hz can also occur in congenital myasthenic tion. Other adverse effects of the contrast agents in
syndromes.
eral times larger than the initial response. Patientscommon use are pain, nausea, thermal sensations,
with
and
forreactions
Use
botulism exhibit a similar response to repetitive Indications
anaphylactoid
that include bronchospasm
stimulaand
A. STROKE
tion, but the ndings are somewhat more variable death.
Contrast-enhanced
may provide
CT is particularly
helpful inscans
evaluating
strokes more
and
inbecause
not all muscles are affected. Incremental responses
formation
in distinguish
than that
obtained
by unenhanced
scans in
it can
infarction
from
intracranial hemorLambert-Eaton syndrome and botulism are more conpatients with known or suspected primary or
rhage; it is particularly sensitive in detecting
spicuous with high rates of stimulation and may secondary
intracereresult
brain tumors, arteriovenous malformations (AVMs),
from the facilitation of acetylcholine release by thecerebral abscesses, chronic isodense subdural
prohematomas, infarcts, or hydrocephalus.

NEUROLOGIC INVESTIGATIONS / 349

Figure 112. Contrast-enhanced CT brain scans from a 62-year-old man, showing the normal anatomy. Images
at
the level of the mid-brain and lateral ventricles are illustrated (same patient as Figure 113).

bral hematomas, and the location of such lesions may

E. SUBARACHNOID HEMORRHAGE
provide a guide to their cause. Moreover, the CT scan
In patients with subarachnoid hemorrhage, the CT
occasionally demonstrates a nonvascular cause ofscan generally indicates the presence of blood in the
the
subarachnoid space and may even suggest the
patients clinical decit, such as a tumor or abscess.
source of
B. TUMOR
the bleeding. If the CT ndings are normal despite
CT scans can indicate the site of a brain tumor, theclinical ndings suggestive of subarachnoid hemorexrhage, the CSF should be examined to exclude
tent of any surrounding edema, whether the lesionhemoris
cystic or solid, and whether it has displaced midline
rhage or meningitis. CT angiography (discussed on p
or
354) may demonstrate an underlying vascular malforother normal anatomic structures. It also
mation or aneurysm.
C.
TRAUMA
demonstrates
The
CT scan is ancomponent.
important means of evaluating paMAGNETIC RESONANCE IMAGING
any hemorrhagic
tients following head injuryin particular for detectDescription
ing traumatic subarachnoid or intracerebral hemorrhage and bony injuries. It also provides a more Magnetic resonance imaging (MRI) is an imaging proprecise
cedure that involves no radiation. The patient lies
delineation of associated fractures than do plain x-within a large magnet that aligns some of the protons
D.
DEMENTIA
rays.
in the body along the magnets axis. The protons resIn patients with dementia, CT scan may indicate the
onate when stimulated with radio-frequency energy,
presence of a tumor or of hydrocephalus (enlargedproducing a tiny echo that is strong enough to be deventected. The position and intensity of these radio-fretricles), with or without accompanying cerebral atroquency emissions are recorded and mapped by a
phy. The occurrence of hydrocephalus without
comcerebral
puter. The signal intensity depends upon the
atrophy in demented patients suggests normal
concentration of mobile hydrogen nuclei (or nuclearpressure
spin density) of the tissues. Spin-lattice (T1) and spinor communicating hydrocephalus. Cerebral atrophy
can occur in demented or normal elderly subjects.

350 / CHAPTER 11
spin (T2) relaxation times are mainly responsible for
sary to dene their anatomic features and plan
the relative differences in signal intensity of the effective
various
treatment. In cases of unexplained hematoma, a
soft tissues; these parameters are sensitive to thefollowstate of
up MRI obtained 3 months later may reveal the
water in biologic tissues. Pulse sequences with
underB. TUMOR
varying
lying cause, which is sometimes unmasked as the
Both CT scans and MRI are very useful in detecting
dependence on T1 and T2 selectively alter the
hematoma resolves.
brain tumors, but the absence of bone artifacts
contrast
makes
between soft tissues (Figure 113).
MRI superior for visualizing tumors at the vertex or in
The soft-tissue contrast available with MRI makes it
the posterior fossa and for detecting acoustic
more sensitive than CT scanning in detecting certain
neuromas.
structural lesions. MRI provides better contrast than
Secondary effects of tumors, such as cerebral herniadoes CT between the gray and white matter of the
tion, can be seen with either MRI or CT scan, but
brain; it is superior for visualizing abnormalities in the
MRI provides more anatomic information. Neither
posterior fossa and spinal cord and for detecting
technique, however, permits the nature of the
lesions
underlyassociated with multiple sclerosis or those that cause
ing tumor to be determined with any certainty. Pituseizures. In addition to its greater sensitivity, it is also
itary tumors are often visualized more easily by MRI
free of bony artifact and permits multiplane (axial,C. TRAUMA
than CT because of the absence of bone or dental
sagittal, and coronal) imaging with no need to
In
the artifacts.
acute phase following head injury, CT scan is
metal
manipupreferable to MRI because it requires less time, is
late the position of the patient. Because there are supeno
known hazardous effects, MRI studies can be
rior for detecting intracranial hemorrhage, and may
repeated
rein
serial manner if necessary. Occasional patients
A. a
STROKE
veal bony injuries. Similarly, spinal MRI should not be
canWithin a few hours of vascular occlusion, it may beused in the initial evaluation of patients with spinal
not
tolerate
the procedure
because
of claustrophobia,
possible
to detect
and localize
cerebral
infarcts byinbut
sedation
usually
alleviates
this
problem.
MRI.
juries because nondisplaced fractures are often not
Gadopentetate
dimeglumine
is stable,
wellBreakdown
in the blood-brain
barrier
(which
occursvisutolerated
D.
DEMENTIA
Indications
Useonset
& Comparison
with CT
several hoursfor
after
of cerebral ischemia)
alized.
For follow-up purposes, however, MRI is
intravenously,
and
an
effective
enhancing
MRI
agent
In
patients
with dementia, either CT or MRI can help
permits
helpful
that
is
useful
in
identifying
small
tumors
that,
in
demonstrating
treatable pathology
structural causes,
but MRI
the intravascular content to be extravasated into the
for detecting parenchymal
of the brain
or
because
appears
to
be
more
sensitive
in
demonstrating
abnorexspinal cord.
of
their similar
relaxation
to normal
tis- white matter signal and associated atrophy.
mal
tracellular
space.
This cantimes
be detected
by cerebral
T2sue,
may
be
missed
on
unenhanced
MRI.
It
also
helps
weighted
to
separate
from surrounding
edema, identify
E. MULTIPLE SCLEROSIS
imaging
andtumor
uid-attenuated
inversion-recovery
In patients with multiple sclerosis, it is often possible
leptomeningeal
disease,
and
provide
information
(FLAIR) sequences. Diffusion-weighted MRI also has
about
to
an important role in the early assessment of stroke,
detect lesions in the cerebral white matter or the
the
blood-brain
barrier.
as is
discussed in a later section. CT scans, on the othercervihand, may be unrevealing for up to 48 hours. Aftercal cord by MRI, even though such lesions may not be
that period, there is less advantage to MRI over CTvisualized on CT scans. The demyelinating lesions descanning except for the formers ability to detect tected by MRI may have signal characteristics resembling those of ischemic changes, however, and
smaller
lesions and its superior imaging of the posterior clinical
correlation is therefore always necessary. Gadoliniumfossa.
enhanced MRI permits lesions of different ages to be
Nevertheless, CT scanning without contrast is usually
the preferred initial study in patients with acute distinguished. This ability facilitates the diagnosis of
multiple sclerosis: the presence of lesions of different
stroke,
in order to determine whether hemorrhage has oc-ages suggests a multiphasic disease, whereas lesions
F.
of INFECTIONS
curred. Intracranial hemorrhage is not easily detected
MRI
is very
detecting white-matter
edema
similar
age sensitive
suggest ainmonophasic
disorder, such
as
by MRI within the rst 36 hours, and CT scan is more
and
probably
permits
earlier
recognition
of
focal
acute
disseminated
encephalomyelitis.
reliable for this purpose. Hematomas of more than 2
areas
3
of cerebritis and abscess formation than is possible
days duration, however, are better visualized by MRI.
with
Although MRI is very effective in detecting and
CT.
localizing vascular malformations, angiography is still
neces-

NEUROLOGIC INVESTIGATIONS / 351

Figure 113. Brain MR images from a 62-year-old man, showing the normal anatomy. Left panels: gadoliniumenhanced T1-weighted (CSF dark) images; right panels: T2-weighted (CSF white) images. Images are at the level
of
the lateral ventricles (top panels) and midbrain (lower panels). Midsagittal T1-weighted image on following page.
Brain images from same patient as Figure 112. (continued)

352 / CHAPTER 11
Diffusion-weighted MRI permits reliable identication of acute cerebral ischemia during the rst few
hours after onset, before it is detectable on standard
MRI. This is important because it reveals infarcts
early
enough for treatment with thrombolytic agents. When
more than one infarct is found on routine MRI, diffusion-weighted imaging permits the discrimination of
acute from older infarcts by the relative increase in
signal
intensity of the former. MAGNETIC
PERFUSION-WEIGHTED

RESONANCE IMAGING
Perfusion-weighted imaging measures relative blood
ow through the brain by either an injected contrast
medium (eg, gadolinium) or an endogenous technique (in which the patients own blood provides the
contrast). It allows cerebral blood-ow abnormalities
to
be
recognized
andtomography
can conrm (PET)
the early
Positron
emission
is anreperfusion
imaging
of
technique that uses positron-emitting
tissues
after treatment. Cerebral ischemia may be deradiopharmaceutected
very
soon
after clinical onset.
Comparison
ticals, such as
18F-uoro-2-deoxyD-glucose
or 18F-of
Lthe to map brain biochemistry and physiology. PET
dopa,
ndings
from diffusion-weighted
perfusionthus
complements
other imagingand
methods
that
weighted MRI may have a prognostic role and is
provide
Figure 113. (continued)
currently anatomic
under study.
The distinction
of CT
reversible
primarily
information,
such as
and MRI,
from
irreversible
ischemic
damage
is
important
in this
and
may
demonstrate
functional
brain
abnormalities
POSITRON EMISSION TOMOGRAPHY
regard.
before structural abnormalities are detectable.
Although
Contraindications
its availability is currently limited, PET has proved
Contraindications to MRI include the presence of inusetracranial clips, metallic foreign bodies in the eye or
ful in several clinical settings. When patients with
elsewhere, pacemakers, cochlear implants, and medcondiically refractory epilepsy are being considered for
tions requiring close monitoring of patients. Furthersurgimore, it can be difcult to image patients with
cal treatment, PET can help identify focal areas of
claustrohypometabolism in the temporal lobe as likely sites of
phobia, gross obesity, uncontrolled movement
the origin of seizures. PET can also be useful in the
disorders, or respiratory disorders that require
difassisted
ferential diagnosis of dementia, since common
ventilation or carry any risk of apnea. Advances indementMRI-compatible mechanical ventilators and monitoring disorders such as Alzheimer disease and multiining
equipment now allow even
critically ill patientsfarct
to dementia exhibit different patterns of abnormal
DIFFUSION-WEIGHTED
MAGNETIC
be scanned safely.
cerebral metabolism. PET can help distinguish
RESONANCE IMAGING
between
This technique, in which contrast within the imageclinically
is
similar movement disorders, such as Parkinbased on the microscopic motion of water protonsson
in disease and progressive supranuclear palsy, and
tissue, provides information that is not available on
can
standard MRI. It is particularly important in the
provide conrmatory evidence of early Huntington
assessdisment of stroke because it can discriminate cytotoxic
ease. PET may also be of value in grading gliomas,
edema (which occurs in strokes) from vasogenic seedema
lecting tumor biopsy sites, and distinguishing
(found with other types of cerebral lesion) and thus
recurrent
reveals cerebral ischemia early and with high
tumors from radiation-induced brain necrosis. It has
specicity.
also been an important tool with which to investigate
It has rapidly and widely been adopted into clinicalthe functional involvement of different cerebral areas
practice.
in
behavioral and cognitive tasks.

NEUROLOGIC INVESTIGATIONS / 353

The major problems associated with PET are its expense, the requirement that radioactive isotopes are
produced near the site of imaging, and the exposure
of
subjects to radiation.

SINGLE-PHOTON EMISSION COMPUTED

TOMOGRAPHY
Single-photon emission computed tomography
(SPECT) involves the administration intravenously or
by inhalation of chemicals containing isotopes that
emit single photons in order to image the brain.
SPECT has been used, in particular, for perfusion
studies, the investigation of receptor distribution, and the
detection of areas of increased metabolism such as
occurs with seizures. At present the technique is more
of
academic interest than of clinical relevance, but it is
considerably
cheaper
than PET
and the isotopes inFigure 114. A functional MR brain image obtained
FUNCTIONAL
MAGNETIC
RESONANCE
use
from a patient during rapid nger tapping of the left
IMAGING
do not have to be produced near the site of imaging.
hand. An increase in relative blood ow in the region of
Functional MRI (fMRI) involves the intravenous ad-the right motorstrip is imaged (arrow) and superimministration of contrast material that lowers signalposed
in- intracranial
upon a T1-weighted
MRis
scan.
(FromWaxman
The
circulation
visualized
most
SG:CorrelativeNeuroanatomy,23rded.,
tensity on MRI in relation to blood ow as the
satisfacto1996.)
material
rily by arteriography, a technique in which the major
passes through the cerebral vasculature. Studies are
vespersels to the head are opacied and radiographed. A
formed with the subject at rest and then after an ARTERIOGRAPHY
catheter is introduced into the femoral or brachial
activaDescription
artery
tion procedure, so that the change in signal intensity
and passed into one of the major cervical vessels. A
reects the effect of the activation procedure on local
racerebral blood ow (Figure 114). An alternative apdiopaque contrast material is then injected through
proach involves pulse sequences that show changes
the
in
catheter, allowing the vessel (or its origin) to be
signal intensity from regional changes in the oxygen
visualconcentration
of venous
bloodfocal
cerebral activity
Magnetic
resonance
spectroscopy
is an
ized. The technique, generally performed after
leads to regional increases in the concentration of noninvainvestigational
oxy- available in some centers; it provides information
tool
sive imaging by CT scanning or MRI, has a denite
genated
These
techniquesofpermit
about
theblood.
chemical
composition
tissue.changes
Proton in
(apsigmagproximately 1%) morbidity and mortality associated
nal
to
be
related
to
underlying
activity
and
thus
allow
netic
resonance
spectroscopy
(
1
H-MRS)
may
be
used
with it and involves considerable exposure to
MAGNETIC RESONANCE SPECTROSCOPY
functional processes to be localized within the brain.
to
radiation.
At
determine levels of N-acetylaspartate exclusive toIt is contraindicated in patients with a stroke in evolupresent,
neurons fMRI is an important investigative tool, but
tion (progressing stroke) and in patients who are
its
or choline creatinine and lactate (glia and neurons).
allergic
role
Mea-in the clinical evaluation of patients remains to
to the contrast medium. Stroke may result as a
be
surements of brain concentration may be useful incomplicaestablished.
detecttion of arteriography. Moreover, at the conclusion of
ing specic tissue loss in diseases such as Alzheimer
the
disprocedure, bleeding may occur at the puncture site
ease or hypoxic-ischemic encephalopathy, or to and
classify
occlusion of the
catheterized artery (usually the
Indications
for Use
brain tumors or lateralize temporal lobe epilepsy. femoral
The
major
indications
for arteriography
include the
Phosartery)
may
lead to distal
ischemic complications.
phorus magnetic resonance spectroscopy (31P-MRS)
The
may
puncture site and the distal circulation must therefore
be useful in the evaluation of metabolic muscle be
diseases.
monitored with these complications in mind.

354 / CHAPTER 11
following:
the vascular ow void.
1. Diagnosis of intracranial aneurysms, arteriovenous malformations, or stulas. Although these COMPUTED TOMOGRAPHIC
lesions
ANGIOGRAPHY
can be visualized by CT scan or MRI, their detailed
anatomy and the vessels that feed, drain, or are Spiral CT angiography is a minimally invasive proceotherdure that requires the CT scanner to be capable of
wise implicated in them cannot reliably be denedrapby
these other means. Moreover, arteriography is stillidly
re- acquiring numerous thin, overlapping sections
quired for interventional procedures such as
after
embolizaintravenous injection of a bolus of contrast material.
tion, the injection of occlusive polymers, or the placeIt
ment of detachable balloons to treat certain vascular
can be performed within minutes, and is less likely to
anomalies.
be
2. Detection and denition of the underlying lesion
affected by patient movement than MR angiography.
in patients with subarachnoid hemorrhage who areA
considered good operative candidates (see Table 2
wide range of vessels can be imaged with the
2).
technique.
3. Localization of vascular lesions in patients with CT angiography of the carotid bifurcation is being
transient cerebral ischemic attacks if surgical
used increasingly, but it cannot reliably distinguish
treatment
beis
being
considered.
tween moderate (5069%) and severe (7099%)
Several imaging techniques that have been used to
4.
Evaluation
of
small
vessels,
such
as
when
a
vasstenovisuculitis
is
under
consideration.
sis, which is an important limitation. It can also be
alize blood vessels by MRI depend upon certain physi5.
Diagnosis
of
cerebral
venous
sinus
thrombosis.
cal properties of blood to generate contrast. Theseused for intracranial imaging and can detect stenotic
6. Evaluation
of the
space-occupying
le-or
properties
include
rate at which intracranial
blood is supplied
sions,
particularly
when
CT
scanning
or
MRI
is
unaneurysmal lesions. However, sensitivity is reduced
to the imaged area, its velocity and relaxation time,
available.
There
may
be
displacement
of
the
normal
for
and
vasculature,
and
in
some
tumors
neovasculature
may
the absence RESONANCE
of turbulent ow.
MR angiography is aaneurysms less than 5 mm, and the method cannot
MAGNETIC
ANGIOGRAPHY
produce
a
blush
or
stain
on
the
Meninnoninvasive technique that has angiogram.
a reduced cost
andadgiomas
can
be
recognized
by
their
blood
supply
from
equately dene aneurysmal morphology in the
rethe
external
carotid
circulation.
preoperduced risks compared with conventional angiography.
It has been most useful in visualizing the carotid ative evaluation of patients. It is sensitive in
visualizing
arterthe anatomy in the circle of Willis, the vasculature of
ies and proximal portions of the intracranial circulation, where ow is relatively fast. The images are the anterior and posterior circulations, and
intracranial
SPINAL IMAGING STUDIES
used
vasoocclusive lesions, but it may not reveal plaque
to screen for stenosis or occlusion of vessels and for
large atheromatous lesions. It has particular utilityulin
PLAIN X-RAYS
screening for venous sinus occlusion. Resolution isceration. It is a reliable alternative to MR
angiography,
infePlain x-rays of the spine can reveal congenital, trauboth
techniques are
less sensitive
rior to that of conventional angiography and, in but
matic,
degenerative
or neoplastic
bonythan
abnormalities,
conventional
vessels
or narrowing (stenosis) of the spinal canal. Degeneraangiography
this regard.
with slow ow, it may be difcult to recognize
tive changes in
become
increasingly common with adIn patients
withtheir
acute
stroke,relevance
CT angiography
occlusive
vancing
age, and
clinical
dependsproon
vides
important
information
complementary
to condisease. Moreover, intracranial MR angiograms may
the
ventional
studies,
and length of
be
context inCT
which
they revealing
are found.the
In site
patients
vascular
occlusion
and
the
contrast-enhanced
marred by irregular or discontinuous signal intensity
presenting
arteries
in
with neck or low back pain, a plain lm is usually the
distal
to the occlusion
as a reection
of collateral
vessels close to the skull base. Although current techrst
radiologic
investigation
undertaken.
MYELOGRAPHY
blood
niques allow visualization of arteriovenous malformaow.
Injecting radiopaque contrast medium into the subtions and aneurysms greater than 3 mm in diameter,
arachnoid space permits visualization of part or all of
conventional angiography remains the gold
the spinal subarachnoid system. The cord and nerve
standard
in this context. Finally, MR angiography may revealroots, which are silhouetted by the contrast material
dissection of major vessels: narrowing is producedinby
the subarachnoid space, are visualized indirectly. The
the dissection and cross-sectional images reveal the
false
lumen as a crescent of abnormal signal intensity next
to

NEUROLOGIC INVESTIGATIONS / 355

procedure is invasive and carries the risks of
In many instances, the information obtained by myelheadache,
ography can now be obtained more simply by MRI of
low back pain, confusion, arachnoiditis, inadvertent
the spine. Imaging of the spinal canal by MRI is direct
inand noninvasive, and it permits differentiation of solid
travenous injection of contrast material, and
from cystic intramedullary lesions. MRI is therefore
vasovagal
bereactions. Rarely, traumatic herniated intervertebral
ing used increasingly in place of myelography. In sydisks have occurred because of poor technique, asringomyelia, for example, MRI is the preferred
has
imaging
damage to nerve roots.
method for visualizing cord cavitation and detecting
Water-soluble agents (such as iohexol) have now
any associated abnormalities at the craniocervical
rejuncplaced oil-based formulations (pantopaque) as thetion. Congenital abnormalities associated with spinal
predysraphism are also easily visualized by MRI. In paferred contrast medium. The dye is absorbed fromtients with degenerative disk disease, MRI is probably
the
more
accurate
than myelography
forreected
detecting
cord
In B-mode
ultrasonography,
echoes
from
CSF and excreted by the kidneys, with approximately
or
anatomic structures are plotted on an oscilloscope
75% eliminated over the rst 24 hours. Unlike pan-root
compression
(Figure 115).
However,
abnormalat
screen
in two dimensions.
The resulting
brightness
topaque, iohexol does not produce signicant arachMRI
ndings
in
the
lumbar
spine
are
common
each point reects the density of the imaged in
noiditis, but tonic-clonic seizures have been reported
asymptomatic
subjects, especially in middle or later
structure.
in
life,
The technique has been used to image the carotid
some instances when contrast entered the
and
care must therefore be exercised in attributing
artery
intracranial
symptoms
such as in
back
anatomic evaluation
and its bifurcation
the pain
neck,topermitting
cavity. Other complications include headaches,
abnormalities
of
nausea
that
may be
When a spinal
AVM
is susthe
extent
ofcoincidental.
extracranial vascular
disease.
Blood
ULTRASONOGRAPHY
and vomiting, and CSF leak. Contrast myelographypected
the
myelogram
is
the
most
sensitive
owing
may be followed by a CT scan of the spine while the
screening
within an artery does not reect sound, and the
medium is still in place. This shows the soft tissue technique.
lumen
structures in or about the spinal cord and providesofin-the vessels therefore appears black. The arterial
formation complementary to that obtained by the wall
myecan be seen, however, and atherosclerotic lesions can
logram (see below).
be
Myelography is indicated in the investigation of detected.
paNote that with severe stenosis or complete
COMPUTED
TOMOGRAPHY
tients with suspected spinal cord or nerve root comocpression
or structural
anomalieshas
in the
foramen
magCT
scanning
after myelography
become
a routine
clusion of the internal carotid artery, it may not be
num region,
particularly
in patients
spinal
procedure
but
is particularly
helpful with
when
the myeloposhardware
precluding
usefulany
MRIabnormality
studies. It isorhelpful
in to visualize the carotid artery bifurcation.
gram
either
fails to reveal
sible
detecting both extradural and intradural lesions and The velocity of blood ow through an artery can be
provides
in
poor
visualization of the area of interest. The myelomeasured by Doppler ultrasonography. Sound waves
providing
of an
gram
mayevidence
be normal,
for intramedullary
example, whenabnormality.
there is awithin a certain frequency range are reected off red
Although it remains a powerful diagnostic tool, noninlatblood cells, and the frequency of the echo provides a
vasiveplaced
CT scanning
and MRI have
reduced
the need
erally
disk protrusion;
in such
circumstances,
guide to the velocity of the ow. Any shift in
for
a its use.
frequency
contrast-enhanced CT scan may reveal the lesion. is
It proportional to the velocity of the red cells and the
is
angle of the beam of sound waves. When the arterial
also useful in visualizing more fully the area abovelumen
or
is narrowed, the velocity of ow increases; inbelow an almost complete block in the subarachnoid
creased frequencies are therefore recorded by
space and in providing further information in patients
Doppler
with cord tumors.
ultrasonography. Spectral analysis of Doppler
CT scan is also helpful in dening the bony
frequenanatomy of the spine. CT scanning may show osteocies is also used to evaluate the anatomic status of
phytic narrowing of neural foramina or the spinal the
canal
carotid artery. Transcranial Doppler studies are now
in patients with cervical spondylosis and may showused routinely in many centers to detect intracranial
spinal stenosis or disk protrusions in patients with arMAGNETIC
RESONANCE IMAGING
neuterial lesions or vasospasm (eg, after subarachnoid
rogenic claudication. In patients with neurologic hemdecits, however, MRI is generally preferred as it proorrhage) and to assess the hemodynamic
vides more useful information.
consequences
of extracranial disease of the carotid arteries.

356 / CHAPTER 11
when less invasive methods, such as imaging studies,
fail to provide a diagnosis. Brain lesions most
amenable
to biopsy are those that can be localized by imaging
studies; are situated in supercial, surgically
1
accessible
sites; and do not involve critical brain regions, such
as
the brainstem or the areas of cerebral cortex involved
2
in
language or motor function. Cerebral disorders that
can be diagnosed by biopsy include primary and
metastatic brain tumors, infectious disorders such as
3
herpes simplex encephalitis or brain abscess, and
MUSCLE
BIOPSY
certain degenerative
diseases such
Creutzfeldt-Jakob
Histopathologic
examination
of aas
biopsy
specimen of
disease.
a
4
weak muscle can indicate whether the underlying
weakness is neurogenic or myopathic in origin. In
neurogenic disorders, atrophied bers occur in groups,
5
with adjacent groups of larger uninvolved bers. In
myopathies, atrophy occurs in a random pattern; the nuclei of muscle cells may be centrally situated, rather
than in their normal peripheral location; and brosis
or
fatty inltration may also be found. Examination of a
muscle biopsy specimen may also permit certain inammatory diseases of muscle, such as polymyositis,
Figure 115. Disk herniation at the L3L4 level
to
(arrows).
be recognized and treated.
In some patients with a suspected myopathy, althe electromyographic ndings are normal,
Duplex instruments, which are now widely usedthough
for
exvascular ultrasound, perform a combination of both
amination of a muscle biopsy specimen reveals the
Bnature of the underlying disorder. Conversely, electromode imaging and Doppler ultrasonography, thereby
providing information at the same time about bothmyographic abnormalities suggestive of a myopathy
NERVE BIOPSY
structure and the hemodynamics of the circulationare
in
sometimes
found intopatients
in whom
histologic
It
is not necessary
undertake
nerve the
biopsy
to
a
or
color-coded format. The technique is being increasestablish
histochemical
failneuropathy.
to establish The
a diagnosis
of
a diagnosis of studies
peripheral
nature of
ingly used to evaluate patients with suspected
myatheroany
opathy. The two approaches
arecan
therefore
neuropathologic
abnormalities
be important,
matous lesions of the carotid artery in the neck. Such
complemensonographic screening has been helpful in identifying
howtary. in suggesting the underlying disorder of
ever,
patients who require arteriography, thereby
increasing
peripheral
In particular, evidence may be found of metathe yield of the latter and reducing the number of nerves.
unnecessary arteriograms. When sonography shows bolic storage disease (eg, Fabry disease, Tangier
disease),
significant disease that may require operative treatment,
infection (eg, leprosy), inammatory change,
BIOPSIES
vasculitis,
anARTERY BIOPSY
giography is required to provide an overview of the
or neoplastic involvement. The ndings are not
patients with suspected giant cell arteritis,
always
vasculature and aid in the planning of treatment. In
BRAIN BIOPSY
temporal
of diagnostic relevance, however, and nerve biopsy
artery
Biopsy of brain tissue can be useful in certain cases
itself biopsy may help to conrm the diagnosis, but
the
abnormalities
are usually
patchy
can pathologic
be performed
only on accessible
nerves.
It isin
disrarely
undertaken on more than a single occasion.

NEUROLOGIC INVESTIGATIONS / 357

tribution. Therefore, a normal study should not ex- ology 1995;195:445449.
Knauth M et al: Potential of CT angiography in acute ischemic
clude the diagnosis or lead to withdrawal of
stroke. AJNR Am J Neuroradiol 1997;18:10011010.
treatment.
Laughlin S, Montanera W: Central nervous system imaging. When

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