Brain Death and Coma:

Diagnosis and Workup

Adrian J. Goldszmidt, M.D.

Chief, Department of Neurology
Sinai Hospital of Baltimore
Chart #1
 Objectives
 Understand the terms coma and brain
death
 Be familiar with the causes of coma, and
workup of a comatose patient
 Be familiar with mimics of coma
 Understand the criteria for brain death
 Be aware of the hospital’s brain death policy

Chart #2
 Definitions
Coma: “Unarousable unresponsiveness” 1
Eyes closed
No sleep-wake cycles
Brain death: Irreversible loss of function of
the brain, including the brainstem 2

1
Plum and Posner, 1980
2
AAN, 1994
Chart #3
 Coma Mimics
 Stupor: Unresponsiveness from which the patient can be
aroused by vigorous and repeated stimuli
 Persistent Vegetative State: No cognitive function, but
maintains sleep wake cycle; often follows coma
 Locked-in syndrome: “De-efferented state” -- patients
alert and aware but quadriplegic, with lower cranial nerve
palsies; lesion is bilateral ventral pons involving
corticospinal, corticopontine, and corticobulbar tracts. Only
vertical gaze intact
 Abulia: Severe apathy, patient neither moves nor speaks
spontaneously, but aware of environment; cause is bilateral
medial frontal lesion
 Catatonia: Mute with marked decrease in motor activity;
psychiatric; patients usually able to maintain body posture Chart #4
 Coma: Causes 1

 >60% metabolic dysfunction

 Drug poisonings
 Metabolic

 20% supratentorial mass lesions

 Stroke
 Hemorrhage

 15% subtentorial mass lesions

 <2% psychiatric causes of coma
 1 Plum and Posner, 1980

Chart #5
Toxic and Metabolic Causes of Coma
 Toxins:
 Lead, thallium, mushrooms, cyanide, methanol, ethylene
glycol, carbon monoxide
 Drugs:
 Sedatives, barbiturates, tranquilizers, alcohol, opiates,
paraldehyde, salicylates, psychotropics, anticholinergics,
amphetamines, lithium
 Metabolic:
 Hypoxia, hypercapnia,, disorders of sodium, glucose,
calcium, magnesium, Wernicke’s encephalopathy, hepatic
encephalopathy, uremia, Addisonian crisis

Chart #6
 Other Common Nonstructural
Treatable Causes of Coma
 Nonconvulsive status epilepticus
 Meningoencephalitis
 Hypertensive encephalopathy
 Hypothyroidism

Chart #7
 Coma: Exam Pearls: Pupils
Dilation is a sympathetic function: path is from hypothalamus,
down through lateral brainstem to lateral spinal cord to T1, up
through sympathetic chain, then travels with carotid to eye
Constriction is a parasympathetic function: Path is from Edinger
Westphal nucleus (in midbrain tectum) via third nerve to eye

 Large, unreactive pupils seen in midbrain lesions sparing

lateral areas, or with lesions affecting bilateral third
nerves (unopposed sympathetic drive)
 Mid-size, unreactive pupils are seen in large midbrain
lesions (affecting both sympathetic and parasympathetic)
 Small pupils (“pontine pupils”) are seen in lesions below
the midbrain: sympathetic dysfunction only; these pupils
are reactive
Chart #8
 Coma Pearls: Eye Movements
 Because normal ocular motility depends on a
large part of the brain, preservation of normal
ocular motility implies that a large portion of
the brain stem is intact
 Eye movements are mediated by centers
from the vestibular nuclei at the
pontomedullary junction to the rostral
interstitial nuclei in the midbrain
 Voluntary gaze is cortically driven but cannot
be tested in a comatose patient

Chart #9
 Coma Pearls: Eye Movements (II)
 Look at eyes at rest:
 ?Horizontal Deviation
A destructive brainstem lesion drives eyes contralateral
 A destructive cortical lesion will drive the eyes ipsilateral
 ?Vertical Deviation
 Downward deviation seen with pressure/lesion in midbrain
tectum
 Dysconjugacy
 Dysfunction of III, IV, or VI

Chart #10
Coma Pearls: Eye Movements (III)
 Spontaneous movements:
 Nystagmus implies an irritative or epileptic supratentorial
focus
 Ocular bobbing (pontine lesion)
 Ocular dipping (diffuse cerebral damage)

Chart #11
 Coma Pearls: Eye Movements (IV)
 Reflexive movements
 Oculocephalic reflex (“Doll’s eye”)
 Normal response: Eyes move contralateral to
direction of rapid head turn; can be done vertically
and horizontally
 CAUTION: DO NOT ATTEMPT UNLESS NECK
STABILITY HAS BEEN VERIFIED
 Vestibulo-oculogyric reflex (Calorics)
 Everybody knows COWS, but what does it mean???

Chart #12
 CALORIC TESTING
 COWS refers to the direction of nystagmus seen
during caloric testing in an awake patient with an
intact brainstem
 The nystagmus is driven by the cortex; patients without cortical
activity will not have nystagmus

The use of caloric testing in comatose patients:

Same reflex as VOR’s but effect more long-lasting and
easier to see
Brainstem intact: Eyes slowly deviate to cooled ear
No brainstem activity: Eyes don’t move
Brainstem dysfunction: Findings consistent with
pathological lesion (e.g., in ipsilateral 6th nerve
palsy, only contralateral eye abducts) Chart #13
 COMA PEARLS: Motor
 Decerebrate and decorticate posturing
 May be unilateral or bilateral
 Decerebrate: Bilateral extensor posture with
extension of lower extremities
 Usuallya lesion in the pons or midbrain, but sometimes can
be seen with metabolic encephalopathy or supratentorial
lesions
 Decorticate:bilateral flexion at the elbows with
extension of lower extremities
 Can be a lesion above the brainstem, but less helpful as a
localizing sign

Chart #14
 COMA PEARLS: Motor (II)
 Patients with purposeful movements: not in coma
 Can be difficult to distinguish purposeful from nonpurposeful movement
 Abduction much more likely purposeful than adduction
(especially in the shoulder)
 Reflexive movements include triple flexion response in the
lower extremity; full triple flexion includes dorsiflexion, knee
and hip flexion
 If in doubt, pinch the anterior thigh: purposeful movement here would
be extension of thigh with abduction
 Myoclonus can be seen in post-anoxic coma as well as
hepatic or uremic encephalopathy

Chart #15
 Brain Death
 History:
 First criteria defined in 1968
 Uniform Determination of Death Act defines
death as:
“1)Irreversible cessation of circulatory and respiratory
function, (or) 2)irreversible cessation of all functions of the
entire brain, including the brainstem”
 President’s Commission:
 Cerebral and brainstem functions absent
 Cause of coma established and accounts for loss of brain
function, and possibility of recovery is excluded
 Persistence of cessation persistent for an appropriate period
of time
Chart #16
 Brain Death Criteria

AAN, 1994 available online at

http://aan.com/professionals/practice/pdfs/pdf_1995_thru_1998/1995.45.1012.pdf

Chart #17
 Brain Death Criteria
 Diagnostic Criteria:
 Evidence of an “acute CNS catastrophe” that is
compatible with the clinical diagnosis of brain
death
 Exclusion of complicating medical conditions
that may confound the clinical assessment
 No severe electyrolyte, acid-base, or endocrine disturbance
 No drug intoxication or poisoning
 Core temperature >32 degrees celsius

Practical consideration: Distinguish “brain

death” from “poor prognosis” or “why is Mr.
Smith in a coma?” Chart #18
 Brain Death Criteria
 Three cardinal findings necessary for brain death:
 Coma: no cerebral motor response to pain
centrally or in extremities
 Absent brainstem reflexes
 Pupillaryresponses
 No ocular movement to VOR or caloric testing
 No corneal or jaw reflex
 No grimace to pain
 No gag or cough response

 Absent respiratory drive (including apnea test)

Diagnostic testing is not a
substitute for these criteria Chart #19
 Brain Death Criteria: Apnea Testing
 Numerous prerequisites including temperature,
volume status
 Baseline PCO2 approximately 40
 Pretreat with 100% O2
 Disconnect ventilator for 8+ minutes and WATCH
CLOSELY FOR RESPIRATORY EFFORT
 PCO2 at the end of the test much be >60 OR >20
points above starting to have an interpretable result
 Result is whether there was respiratory effort or not

Chart #20
 Brain Death Criteria: Apnea Testing
 Numerous prerequisites including temperature,
volume status
 Baseline PCO2 approximately 40
 Pretreat with 100% O2
 Disconnect ventilator for 8+ minutes and WATCH
CLOSELY FOR RESPIRATORY EFFORT
 PCO2 at the end of the test much be >60 OR >20
points above starting to have an interpretable result
 Result is whether there was respiratory effort or not

Chart #21
 Brain Death Criteria: 2nd Exam
 Clinical evaluation 6 hours later
recommended by AAN to confirm
“irreversibility”
 Timing is somewhat arbitrary but should
be adhered to, especially in cases
where there is some uncertainty as to
clinical situation
e.g., after cardiac arrest

Chart #22
 Brain Death Criteria: Diagnostic
Testing
 Not necessary to establish brain death in the vast
majority of cases
 Not a substitute for clinical exam
 Tests not 100% sensitive or specific
 Reserve for cases where entire exam can’t be
done, for example:
 Severe trauma including face
 Preexisting pupillary abnormalities

Chart #23
 Diagnostic Testing for Brain Death
 Cerebral angiography
 EEG
 TCD
 Technecium scan
 SSEP’s

Chart #24
 Sinai Hospital’s Brain Death Policy
 Mirrors AAN brain death policy
 Exceptions:
 Both physicians examining patient must be attendings
 One physician must be a neurologist or a neurosurgeon
 Criteria under which second exam may be done less
than six hours after the first
 Policy can be viewed on the Sinai intranet by
clicking “Sinai” under “Choose a Facility”, then
clicking on “policies and procedures,” then
searching for “brain death”
 Form available to make sure all steps followed
Chart #25
 CASES: 1
 A 52-year old man is in the ICU following
colorectal surgery and subsequent
chemotherapy for adenocarcinoma. He is off
paralytics and sedatives. He is unresponsive.
The right eye is abducted and the pupil is 8mm.
The left pupil is 4 mm and reacts. The most
likely cause of coma is:
 1. Boredom
 2. Residual effects of propofol received yesterday
 3. Nonconvulsive status epilepticus
 4. Large right cerebral hemorrhage
 5. None of the above Chart #26
 CASES: 2
 A 68-year old man is intubated in the ED after
being found at the bottom of the stairs. He
withdraws all four limbs properly, but is
unresponsive with persistent right gaze
preference. Appropriate initial steps in workup
for his unresponsiveness include all of the
following except:
 1. Imaging (CT)
 2. EEG
 3. MRI if the CT is negative
 4. Vestibulo-ocular reflex testing (“Doll’s Eye”)
 5. Vestibulo-oculogyric testing (“Calorics”) Chart #27
 CASES: 3
 A 70-year old obese man with a tracheostomy
is increasingly unarousable over a period of
hours. His BP is 100/60. O2 saturation is 99%
by pulse oximetry on FiO2 of 50%. Which of the
following is the appropriate first diagnostic step:
 1. Imaging (CT)
 2. Neuro consult
 3. EEG
 4. Blood gas
 5.

Chart #28
 CASES: 4
 A 60-year old woman has been unresponsive
after cardiac arrest for 10 days. There is no
movement to pain, and pupillary, corneal, gag,
and caloric responses are absent. Episodic
facial grimacing is noted. An EEG is isoelectric
(no brain activity). Which of the following is true:
 1. The patient meets criteria for brain death
 2. A brain flow study is needed to confirm brain death.
 3. An apnea test is needed to confirm brain death.
 4. A second exam is needed to confirm brain death.
 5. None of the above.

Chart #29
 CASES: 5
 A 70-year old man has absent motor
movements, pupillary, corneal, gag, and caloric
responses after massive brain hemorrhage.
Apnea testing was tried, but unsuccessful due
to hypotension. The appropriate next step is:
 1. Hang dopamine then repeat the apnea test
 2. Cannot declare the patient brain dead; proceed to
PEG and tracheostomy
 3. Obtain brain flow study
 4. Obtain EEG
 5. Choices 1 and 4 are correct
Chart #30