Confusion, Stupor and Coma

Disorders of consciousness are common; these always signify a disorder of the

nervous system. Assessment should determine whether there is a change in level

of consciousness (drowsy, stuporous, comatose) and/or content of consciousness

(confusion, perseveration, hallucinations). Confusion is a lack of clarity in

thinking with inattentiveness; stupor, a state in which vigorous stimuli are

needed to elicit a response; coma, a condition of unresponsiveness. Patients in

suchstates are usually seriously ill, and etiologic factors must be assessed (Table

17-1).

Table 17-1

Differential Diagnosis of Coma

1. Diseases that cause no focal or lateralizing neurologic signs, usually with

normal brainstem functions; CT scan and cellular content of the CSF are

normal

a. Intoxications: alcohol, sedative drugs, opiates, etc.

b. Metabolic disturbances: anoxia, hyponatremia, hypernatremia, hypercalcemia,

diabetic acidosis, nonketotic hyperosmolar hyperglycemia, hypoglycemia,

uremia, hepatic coma, hypercarbia, addisonian crisis, hypo- and

hyperthyroid states, profound nutritional deficiency

c. Severe systemic infections: pneumonia, septicemia, typhoid fever, malaria,

Waterhouse-Friderichsen syndrome

d. Shock from any cause

e. Postseizure states, status epilepticus, subclinical epilepsy

f. Hypertensive encephalopathy, eclampsia

g. Severe hyperthermia, hypothermia

h. Concussion

i. Acute hydrocephalus

2. Diseases that cause meningeal irritation with or without fever, and with an

excess of WBCs or RBCs in the CSF, usually without focal or lateralizing

cerebral or brainstem signs; CT or MRI shows no mass lesion

a. Subarachnoid hemorrhage from ruptured aneurysm, arteriovenous malformation,

trauma

b. Acute bacterial meningitis

c. Viral encephalitis

d. Miscellaneous: Fat embolism, cholesterol embolism, carcinomatous and

lymphomatous meningitis, etc.

3. Diseases that cause focal brainstem or lateralizing cerebral signs, with or

without changes in the CSF; CT and MRI are abnormal

a. Hemispheral hemorrhage (basal ganglionic, thalamic) or infarction (large

middle cerebral artery territory) withsecondary brainstem compression

b. Brainstem infarction due to basilar artery thrombosis or embolism

c. Brain abscess, subdural empyema

d. Epidural and subdural hemorrhage, brain contusion

e. Brain tumor withsurrounding edema

f. Cerebellar and pontine hemorrhage and infarction

g. Widespread traumatic brain injury

h. Metabolic coma (see above) with preexisting focal damage

i. Miscellaneous: cortical vein thrombosis, herpes simplex encephalitis,

multiple cerebral emboli due to bacterial endocarditis, acute hemorrhagic

leukoencephalitis, acute disseminated (postinfectious) encephalomyelitis,

thrombotic thrombocytopenic purpura, cerebral vasculitis, gliomatosis

cerebri, pituitary apoplexy, intravascular lymphoma, etc.

Approach to the Patient

1. Support vital functions.

2. Administer glucose, thiamine, and naloxone if etiology is not clear.

3. Utilize history, examination, and laboratory and radiologic information to

rapidly establish the cause of the disorder.

Urgent lumbar puncture indicated if meningitis suspected (fever, headache,

meningismus).

5. Provide appropriate medical and surgical treatment.

History

The pt should be aroused, if possible, and questioned regarding use of insulin,

narcotics, anticoagulants, other prescription drugs, suicidal intent, recent

trauma, headache, epilepsy, significant medical problems, and preceding symptoms.

Witnesses and family members should be interviewed, often by phone.

History of sudden headache followed by loss of consciousness suggests intracranial hemorrhage; preceding vertigo, nausea, diplopia, ataxia, hemisensory

disorder suggest basilar insufficiency; chest pain, palpitations, and faintness

suggest cardiovascular cause.

Immediate Assessment

Vital signs should be evaluated, and appropriate support initiated. Blood should

be drawn for glucose, electrolytes, calcium, and renal (BUN) and hepatic (ammonia,

transaminases) function; also screen for presence of alcohol and other

toxins if these are possibilities. Arterial blood-gas analysis is helpful in pts with

lung disease and acid-base disorders. Fever, especially with petechial rash, suggests meningitis. Examination of CSF is essential in diagnosis of meningitis

and encephalitis; lumbar puncture should not be deferred if meningitis is a

possibility. Fever with dry skin suggests heat shock or intoxication with anticholinergics.

Hypothermia suggests myxedema, intoxication, sepsis, exposure,

or hypoglycemia. Marked hypertension occurs with increased intracranial pressure

(ICP) and hypertensive encephalopathy.

Neurologic Evaluation

Focus on establishing pt’s best level of function and uncovering signs that enable

a specific diagnosis. Although confused states may occur with unilateral

cerebral lesions, stupor and coma are signs of bihemispheral dysfunction or

damage to midbrain-tegmentum (reticular activating system). Lack of movement

on one side suggests hemiplegia; multifocal myoclonus indicates that a

metabolic disorder is likely; intermittent twitching may be the only sign of a

seizure.

Responsiveness Stimuli of increasing intensity are applied to gauge the

degree of unresponsiveness and any asymmetry in sensory or motor function.

Motor responses may be purposeful or reflexive. Spontaneous flexion of elbows

withleg extension, termed decortication, accompanies severe damage to contralateral hemisphere above midbrain. Internal rotation of the arms with extension of elbows, wrists, and legs, termed decerebration, suggests damage to

midbrain or diencephalon. These postural reflexes occur in profound encephalopathic states.

Pupils In comatose pts, equal, round, reactive pupils exclude midbrain

damage as cause and suggest a metabolic abnormality. Pinpoint pupils occur in

narcotic overdose (except meperidine, which causes midsize pupils), with pontine

damage, hydrocephalus, or thalamic hemorrhage; the response to naloxone

and presence of reflex eye movements can distinguishth ese. A unilateral, enlarged,

often oval, poorly reactive pupil is caused by midbrain lesions or compression of third cranial nerve, as occurs in transtentorial herniation. Bilaterally

dilated, unreactive pupils indicate severe bilateral midbrain damage, anticholinergic overdose, or ocular trauma.

Eye Movements Examine spontaneous and reflex eye movements. Intermittent

horizontal divergence is common in drowsiness. Slow, to-and-fro horizontal

movements suggest bihemispheric dysfunction. Conjugate eye deviation

to one side indicates damage to the pons on the opposite side or a lesion in the

frontal lobe on the same side (“The eyes look toward a hemispheral lesion and

away from a brainstem lesion”). An adducted eye at rest withimpaired ability

to turn eye laterally indicates an abducens (VI) nerve palsy, common in raised

ICP or pontine damage. The eye with a dilated, unreactive pupil is often abducted

at rest and cannot adduct fully due to third nerve dysfunction, as occurs

withtranstentorial herniation. Vertical separation of ocular axes (skew deviation)

occurs in pontine or cerebellar lesions. Doll’s head maneuver (oculocephalic

reflex) and cold caloric–induced eye movements allow diagnosis of gaze

or cranial nerve palsies in pts who do not move their eyes purposefully. Doll’s

head maneuver is tested by observing eye movements in response to lateral

rotation of head (neck injury is a contraindication); full movement of eyes occurs

in bihemispheric dysfunction. In comatose pts with intact brainstem function,

raising head to 60_ above the horizontal and irrigating external auditory

canal withcool water causes tonic deviation of gaze to side of irrigated ear. In

conscious pts, it causes nystagmus, vertigo, and emesis.

Respirations Respiratory pattern may suggest site of neurologic damage.

Cheyne-Stokes (periodic) breathing occurs in bihemispheric dysfunction and is

common in metabolic encephalopathies. Respiratory patterns composed of

gasps or other irregular breathing patterns are indicative of lower brainstem

damage; suchpts usually require intubation and ventilatory assistance.

Other Comatose pt’s best motor and sensory function should be assessed

by testing reflex responses to noxious stimuli; carefully note any asymmetric

responses, whichsuggest a focal lesion. If possible, pts withdisordered consciousness should have gait examined. Ataxia may be the prominent neurologic

finding in a stuporous pt witha cerebellar mass.

Radiologic Examination

Lesions causing raised ICP commonly cause impaired consciousness. CT or

MRI scan of the brain is often abnormal in coma but may not be diagnostic;

appropriate therapy should not be postponed while awaiting a CT or MRI scan.

Pts withdisordered consciousness due to high ICP can deteriorate rapidly; emergent CT study is necessary to confirm presence of mass effect and to guide

surgical decompression. CT scan is normal in some pts with subarachnoid hemorrhage; the diagnosis then rests on clinical history combined with RBCs in

spinal fluid. MR angiography or cerebral angiography may be necessary to

establishbasilar artery stroke as cause of coma in pts with brainstem signs.

The EEG is useful in metabolic or drug-induced states but is rarely diagnostic;

exceptions are coma due to seizures, herpesvirus encephalitis, or prion disease.

Brain Death

This results from total cessation of cerebral function and blood flow at a time

when cardiopulmonary function continues but is dependent on ventilatory assistance.

The pt is unresponsive to all forms of stimulation, brainstem reflexes are absent, and there is complete apnea. Demonstration of apnea requires that

the PCO be highenoughto stimulate respiration, while PO and bp are main- 2 2

tained. EEG is isoelectric at high gain. The absence of deep tendon reflexes is

not required because the spinal cord may remain functional. Special care must

be taken to exclude drug toxicity and hypothermia prior to making a diagnosis

of brain death. Diagnosis should be made only if the state persists for some

agreed-upon period, usually 6–24 h.

18

Stroke

Sudden onset of a neurologic deficit from a vascular mechanism: 85% are ischemic; 15% are primary hemorrhages [subarachnoid (Chap. 19) and intraparenchymal].

An ischemic deficit that resolves rapidly is termed a transient ischemic

attack (TIA); 24 his a useful boundary between TIA and stroke,

although most TIAs last between 5 and 15 min. Stroke is the leading cause of

neurologic disability in adults; 200,000 deaths annually in the United States.

Muchcan be done to limit morbidity and mortality through prevention and acute

intervention.

Ischemic stroke is most often due to embolic occlusion of large cerebral

vessels; source of emboli may be heart, aortic arch, or a more proximal arterial

lesion. Primary involvement of intracerebral vessels withath erosclerosis is less

common than in coronary vessels. Small, deep ischemic lesions are most often

related to intrinsic small-vessel disease (lacunar strokes). Low-flow strokes are

seen withsevere proximal stenosis and inadequate collaterals challenged by

systemic hypotensive episodes. Hemorrhage most frequently results from rupture

of aneurysms or small vessels within brain tissue.

Clinical Presentation

Ischemic Stroke Abrupt and dramatic onset of focal neurologic symptoms

is typical of ischemic stroke; with hemmorhage, deficits typically evolve more

slowly and drowsiness is common. Pts may not seek assistance on their own

because they are rarely in pain and may lose appreciation that something is

wrong (anosagnosia). Symptoms reflect the vascular territory involved (Table

18-1). Transient monocular blindness (amaurosis fugax) is a particular form of

TIA due to retinal ischemia; pts describe a shade descending over the visual

field. Rapid resolution of symptoms excludes hemorrhage as cause. Variability

in stroke recovery is influenced by collateral vessels, blood pressure, and specific

site and mechanism of vessel occlusion.

Lacunar Syndromes Most common are (1) pure motor hemiparesis of

face, arm, and leg (internal capsule or pons); (2) pure sensory stroke (ventrolateral thalamus); (3) ataxic hemiparesis (pons); (4) dysarthria–clumsy hand

(pons or genu of internal capsule); and (5) pure motor hemiparesis with motor

(Broca’s) aphasia (internal capsule and adjacent corona radiata).

Table 18-1

Anatomic Localization in Stroke

Signs and Symptoms

CEREBRAL HEMISPHERE, LATERAL ASPECT (MIDDLE CEREBRAL A.)

Hemiparesis

Hemisensory deficit

Motor aphasia (Broca’s)—hesitant speech with word-finding difficulty and

preserved comprehension

Central aphasia (Wernicke’s)—anomia, poor comprehension, jargon speech

Unilateral neglect, apraxias

Homonymous hemianopia or quadrantanopia

Gaze preference witheyes deviated to side of lesion

CEREBRAL HEMISPHERE, MEDIAL ASPECT (ANTERIOR CEREBRAL A.)

Paralysis of foot and leg withor without paresis of arm

Cortical sensory loss over leg

Grasp and sucking reflexes

Urinary incontinence

Gait apraxia

CEREBRAL HEMISPHERE, POSTERIOR ASPECT (POSTERIOR CEREBRAL A.)

Homonymous hemianopia

Cortical blindness

Memory deficit

Dense sensory loss, spontaneous pain, dysesthesias, choreoathetosis

BRAINSTEM, MIDBRAIN (POSTERIOR CEREBRAL A.)

Third nerve palsy and contralateral hemiplegia

Paralysis/paresis of vertical eye movement

Convergence nystagmus, disorientation

BRAINSTEM, PONTOMEDULLARY JUNCTION (BASILAR A.)

Facial paralysis

Paresis of abduction of eye

Paresis of conjugate gaze

Hemifacial sensory deficit

Horner’s syndrome

Diminished pain and thermal sense over half body (with or without face)

Ataxia

BRAINSTEM, LATERAL MEDULLA (VERTEBRAL A.)

Vertigo, nystagmus

Horner’s syndrome (miosis, ptosis, decreased sweating)

Ataxia, falling toward side of lesion

Impaired pain and thermal sense over half body with or without face

Intracranial Hemorrhage Vomiting occurs in most cases, and headache

in about one-half. Signs and symptoms not usually confined to a single vascular

territory. Hypertensive hemorrhage typically occurs in (1) the putamen, adjacent

internal capsule, and central white matter; (2) thalamus; (3) pons; and (4) cerebellum. A neurologic deficit that evolves relentlessly over 5–30 min strongly

suggests intracerebral bleeding. Ocular signs are important in localization: (1)

putaminal—eyes deviated to side opposite paralysis (toward lesion); (2) thalamic— eyes deviated downward, sometimes withunreactive pupils; (3) pontine— reflex lateral eye movements impaired and small (1–2 mm), reactive

pupils; (4) cerebellar—eyes initially deviated to side opposite lesion.

TREATMENT

Principles of management are outlined in Table 18-2. Stroke needs to be

distinguished from potential mimics, including seizure, tumor, migraine, and

metabolic derangements. After initial stabilization, an emergency noncontrast

head CT scan is necessary to differentiate ischemic from hemorrhagic stroke.

With large ischemic strokes, CT abnormalities usually evident within the first

few hours, but small infarcts can be difficult to visualize by CT.

Acute Ischemic Stroke

Treatments designed to reverse or lessen tissue infarction include: (1) medical

support, (2) thrombolysis, (3) antiplatelet agents, (4) anticoagulation, and (5)

neuroprotection.

Medical Support Immediate goal is to optimize perfusion in ischemic

penumbra surrounding the infarct. Blood pressure should never be lowered

precipitously (exacerbates the underlying ischemia), and only in the most

extreme situations should gradual lowering be undertaken (e.g., malignant

hypertension or, if thrombolysis planned, bp_185/110 mmHg). Intravascular

volume should be maintained with isotonic fluids as volume restriction is

rarely helpful. Osmotic therapy with mannitol may be necessary to control

edema in large infarcts, but isotonic volume must be replaced to avoid hypovolemia.

In cerebellar infarction (or hemorrhage), rapid deterioration can

occur from brainstem compression and hydrocephalus, requiring neurosurgical

intervention.

Thrombolysis Ischemic deficits of _3 h duration, with no hemorrhage

by CT criteria, may benefit from thrombolytic therapy with IV recombinant

tissue plasminogen activator (Table 18-3). Only a small percentage of stroke

pts are seen early enoughto receive treatment withth is agent.

Antiplatelet Agents Aspirin (up to 325 mg/d) is safe and has a small

but definite benefit in acute stroke.

Anticoagulation Role uncertain; clinical trials show no clear benefit of

low molecular-weight heparin or SC heparin over aspirin. Heparin is often

used for crescendo TIAs (TIAs that increase in frequency) and for progressive

stroke worsening over hours or days (20% of pts), despite absence of data.

Neuroprotection Hypothermia is effective in coma following cardiac

arrest but has not been adequately studied in pts with stroke.

Acute Intracerebral Hemorrhage

Noncontrast head CT will confirm diagnosis. Rapidly identify and correct any

coagulopathy. Nearly 50% of pts die; prognosis is determined by volume and

location of hematoma. Neurosurgical consultation should be sought for possible

urgent evacuation of cerebellar hematoma; in other locations, evacuation

is usually not helpful. Treatment for edema and mass effect with osmotic

agents and induced hyperventilation may be necessary; glucocorticoids not

helpful.

Determining the Cause of Stroke

Although initial management of acute ischemic stroke or TIA does not depend

on the etiology, establishing a cause is essential to reduce risk of recurrence

(Table 18-4). Nearly 30% of strokes remain unexplained despite extensive evaluation, however. Clinical examination should be focused on the peripheral and

cervical vascular system. Routine studies include CXR and ECG, CBC/platelets,

electrolytes, glucose, ESR, lipid profile, PT, PTT, and serologic tests for syphilis.

If a hypercoagulable state is suspected, further studies of coagulation are

indicated. Imaging evaluation may include brain MRI (compared withCT, increased sensitivity for small infarcts of cortex and brainstem); MR angiography

(evaluate patency of intracranial vessels and extracranial carotid and vertebral

vessels); noninvasive carotid tests (“duplex” studies, combine ultrasound imaging

of the vessel with Doppler evaluation of blood flow characteristics); or

cerebral angiography (“gold standard” for evaluation of intracranial and extracranial vascular disease). For suspected cardiogenic source, cardiac ultrasound with attention to right-to-left shunts, and 24-h Holter monitoring indicated.

Primary and Secondary Prevention of Stroke

Risk Factors Atherosclerosis is a systemic disease affecting arteries

throughout the body. Multiple factors including hypertension, diabetes, hyperlipidemia, and family history influence stroke and TIA risk (Table 18-5). Cardioembolic risk factors include atrial fibrillation, MI, valvular heart disease, and cardiomyopathy. Hypertension and diabetes are also specific risk factors for

lacunar stroke and intraparenchymal hemorrhage. Smoking is a potent risk factor

for all vascular mechanisms of stroke. Identification of modifiable risk factors

and prophylactic interventions to lower risk is probably the best approach

to stroke overall.

Antiplatelet Agents Platelet antiaggregation agents can prevent atherothrombotic

events, including TIA and stroke, by inhibiting the formation of

intraarterial platelet aggregates. Aspirin (50–325 mg/d) inhibits thromboxane

A2, a platelet aggregating and vasoconstricting prostaglandin. Aspirin, clopidogril

(blocks the platelet ADP receptor), and the combination of aspirin plus

extended-release dipyrimadole (inhibits platelet uptake of adenosine) are the antiplatelet agents most commonly used. In general, antiplatelet agents reduce

new stroke events by 25–30%. Every patient who has experienced an atherothrombotic stroke or TIA and has no contraindication should take an antiplatelet agent regularly because the average annual risk of another stroke is 8–10%.

Embolic Stroke In pts with atrial fibrillation, the choice between warfarin

or aspirin prophylaxis is determined by age and risk factors (Table 18-6). Anticoagulation reduces the risk of embolism in acute MI; most clinicians recommend a 3-month course of therapy when there is anterior Q-wave infarction

or other complications; warfarin is recommended long term if atrial fibrillation

persists. For prosthetic heart valve pts, a combination of aspirin and warfarin

(INR, 3–4) is recommended. If an embolic source cannot be eliminated, anticoagulation is usually continued indefinitely. For patients who “fail” one form

of therapy, many neurologists recommend combining antiplatelet agents with

anticoagulation.

Anticoagulation Therapy for Noncardiogenic Stroke In contrast to cardiogenic

stroke, there are few data to support long-term warfarin for preventing

atherothrombotic stroke. Secondary prophylaxis for ischemic stroke of unknown

origin is controversial; some physicians prescribe anticoagulation for 3–6

months, followed by antiplatelet treatment.

Surgical Therapy Carotid endarterectomy benefits many pts with symptomatic

severe (_70%) carotid stenosis; the relative risk reduction is _65%.

However, if the perioperative stroke rate is _6% for any surgeon, the benefit

is lost. Surgical results in pts with asymptomatic carotid stenosis are less robust,

and medical therapy for reduction of atherosclerosis risk factors plus aspirin is

generally recommended in this group.