Stroke JULY-AUGUST
A Journal of Cerebral Circulation VOL 12
Progress in Cerebrovascular Disease
Treatment of Progressing Stroke
CLARK H. MILLIKAN, M.D.,
A PROGRESSING STROKE refers to that tem-
poral clinical category where progression or an in-
crease of severity of the neurological signs has oc-
curred within recent minutes.1 This diagnosis is made
from analysis of the patient's history and by repeated
examination. When a patient is admitted to the
hospital with a moderate neurological deficit in his
right arm, who on re-examination is worse, his stroke
is considered to be progressing. If the deficit is the
same, progress may be completed, and if the defect
has disappeared the diagnosis is usually a transient
ischemic attack (TIA). When an area of the brain
believed to be ischemic or infarcted is supplied by the
carotid arterial system, 18 to 24 hours without pro-
gression is needed to be sure that further progression
is unlikely. Then the patient's clinical temporal status
is no longer categorized as "progressing stroke."
When an area of the brain believed to be ischemic or
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infarcted is supplied by the vertebrobasilar system, a
longer period (up to 72 hours) should pass before the
patient is believed to have no further chance of
progressing and is diagnosed as having a "completed
stroke." Progression may be periodic and episodes of
progression may be separated by hours or minutes, es-
pecially when circulation to the brainstem is impaired.
Diagnosis
The physician confronted with a patient whose
paresis or speech impairment is worsening over
minutes or a few hours, needs to have a clear program
for action. The highest priority must be given to
precise diagnosis. If a diagnosis of progressing stroke
is made (stroke-in-evolution) immediate action to stop
progression is indicated, as once such progression is
apparent there is no evidence that cerebral infarction
is reversible. Preventive therapy, if available, is the
most important action.
In the diagnosis of progressing stroke it is desirable
to differentiate between impaired brain function due
to a decreased blood supply from the carotid artery
system and impaired function caused by decreased
blood supply in the vertebrobasilar arterial systems.
The clinical situation for progressing stroke due to ca-
rotid artery insufficiency generally includes some
evidence of monoparesis or hemiplegia with or
From the University of Utah Medical School, Salt Lalte City,
UT, 84132 and Cornell Medical School, New York, NY, 10021.
1981
NO. 4
AND FLETCHER H. MCDOWELL, M.D.
without a homonymous visualfielddefect and includes
often some degree of impairment of speech and
language and evidence of partial to full sensory
perception loss on the opposite side of the body. The
combination of symptoms and signs associated with
vertebrobasilar occlusive events is more complex. The
most common symptoms include impaired motor
functions such as weakness, clumsiness, or paralysis
involving any combination of the limbs with evident
signs of cortico-spinal tract dysfunction associated
with unilateral or sometimes bilateral cranial nerve
paralysis, most often oculomotor, or evidence of
trigeminal or facial nerve impaired function. A
"crossed" defect (motor or sensory on the one side of
the face and opposite side of the body) is considered
unequivocal evidence of impaired brainstem function
until proven otherwise. If motor or sensory abnor-
malities are bilateral and impaired with cranial nerve
function, this too indicates brainstem involvement.
Physical Examination
The physical examination of a patient suspected of
having an acute progressing stroke must proceed im-
mediately. It is important to emphasize the neuro-
vascular examination, which includes:
1. Inspection of peripheral vessels (i.e. tem-
poral, radial, pedal arteries)
2. Palpation of vessels
3. Auscultation over vessels at cranial and cer-
vical sites to detect bruit
4. Ophthalmoscopy
5. Ophthalmodynamometry
/. Inspection of Peripheral Vessels. A prominent, tor-
tuous temporal artery often indicates cranial arteritis,
which is a possible but an unusual cause of stroke.
Significant arterial change can be detected by inspect-
ing the superficial temporal arteries, coupled with
palpation.
2. Palpation. The superficial temporal artery, the
cerebral vessels in the neck, the radial and the pedal
arteries should always be palpated. When palpating
the cervical cerebral vessels, this should be performed
gently to discover changes of arterial pulsations.
Minor differences in the pulses from the 2 sides may
be difficult to interpret. It is possible but difficult to
distinguish a pulse coming from the first portion of the
internal carotid or from the external carotid artery.
Atherosclerotic lesions in cervical vessels may be ul-
397
 398 STROKE
cerated or covered by thrombi; both situations carry
the risk of dislodging emboli during manipulation of
the arteries.
3. Auscultation. Auscultation over cervical vessels
may detect evidence of altered patterns of blood flow.
A bell stethoscope is most useful. First the aortic valve
is auscultated and then the stethoscope is moved (1 cm
or less at a time) upwards. This is needed to deter-
mine if cardiac sounds are transmitted to the in-
nominate, subclavian, common carotid or internal ca-
rotid arteries. The patient should be sitting or lying
supine with face forward. This position is less likely to
create sounds which are difficult to interpret. When
respiratory sounds make auscultation difficult the
patient is told to "stop" breathing for a few seconds.
Bruits localized over extracranial cerebral vessels,
such as the common and internal carotid arteries, are
reliable indicators of sites of turbulent flow caused by
arterial obstruction.1"1
4. Ophthalmoscopy. This provides an opportunity to
inspect blood vessels that are a direct continuation of
the internal carotid arterial system. Sometimes little
use is made of this simple method of obtaining impor-
tant clinical data. The retina must be inspected care-
fully for arterial or venous occlusion, including em-
boli, such as cholesterol, platelet-fibrin, calcific (mixed
or foreign body), and changes such as hemorrhages,
cotton wool patches, venous stasis, microaneurysms,
vessel narrowing associated with arterial hyper-
tension, papilledema, and ischemic retinopathy.* The
importance of detecting a retinal embolus or emboli in
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the diagnosis of TIA or progressing stroke has been
demonstrated. The most common observed emboli are
made up of cholesterol crystals which appear as shiny
orange-yellow plaques, often localized at the bifurca-
tion of retinal arterioles.8'' The cholesterol plaque
may appear wider than the arteriole as one is looking
at the outer dimension of the column of red blood
cells, rather than the wall of the arteriole. Pressure on
the eye may change the position of the embolus and
the material may then appear to glint or change shade,
a characteristic sometimes referred to as a helio-
graphic reflection. These bright, orange-yellow
plaques do not seem to impede blood flow. Such em-
boli move distally and disappear. One or more cho-
lesterol retinal emboli usually signifies an ulcerated
atheromatous carotid (internal) lesion until proved
otherwise. An important embolus in retinal vessels
consists of blood platelets and fibrin, and is usually
grey-white in color. These may be long and move
through an arteriole but are commonly stationary.'• *
Eye pressure does not cause this type of embolus to
move and there is no heliographic reflection. These
emboli block flow and there may be retinal infarction.
The source for retinal emboli is usually an atheroma-
tous plaque at the origin of the internal carotid artery.
Another type of retinal embolus may consist of
calcium particles which are white in color and
stationary. Calcium emboli are believed to come from
heart valve lesions. Other observed retinal emboli con-
sist of septic material such as talc and cornstarch.
5. Ophthalmodynamometry. This measures arterial
VOL 12, No 4, JULY-AUGUST 1981
pressures both systolic and diastolic in the main ret-
inal branches of the ophthalmic artery.10- " When the
retinal artery pressures are different in the 2 eyes it
becomes clinically significant. A difference in pres-
sure between the eyes of 15 to 20 percent is a reliable
sign of stenosis or occlusion of the internal carotid
artery on the side of the lower pressure. Retinal
arterial pressures can be equal and normal with uni-
lateral carotid stenosis or occlusion because collateral
blood supply develops. Following internal carotid
artery occlusion, the ipsilateral retinal arterial pres-
sure is reduced and the return of retinal artery pres-
sure depends on how rapidly collateral circulation
develops. If retinal pressure decreases significantly
while brachial arterial pressure remains normal as a
patient stands up (ocular orthostatism), this is impor-
tant evidence of carotid occlusive disease.
Laboratory Examination
The need for laboratory tests is determined by the
initial history and physical examination. Recent pre-
cordial pain and cardiac dysrhythmia should prompt
an electrocardiogram as the first test performed.
Computer assisted tomography (CAT scan) has
radically altered the program of differential diagnosis
of stroke.11 A CAT scan should be done in the first
hours following the admission of the patient with
progressing stroke. The scan may be normal unless the
infarction is hemorrhagic — an important clinical dis-
tinction. This diagnostic method has become so useful
that it is common practice to perform a scan before
the patient is admitted to a hospital bed.
Urine is collected for urinalysis and blood tests
started. Basic laboratory tests, including red blood
count, white blood count, differential blood count,
blood hemoglobin, hematocrit, platelet count,
sedimentation rate, fasting blood sugar, creatinine or
urea, prothrombin time, cholesterol, triglycerides, uric
acid and a test for syphilis should be promptly per-
formed. The patient should be screened for renal
dysfunction and a prothrombin time determined for
baseline values. This laboratory screen will make it
possible to diagnose such disorders as polycythemia
which are known to carry the risk of a high incidence
of focal cerebral vascular disease. Recently, questions
have been raised about the role of even moderate ele-
vations of hemoglobin and hematocrit as risk factors
for stroke.
If cranial arteritis is present the sedimentation rate
is almost always elevated. A diagnosis of cranial
arteritis must be made quickly as there is a risk of
permanent impairment of vision if treatment is
delayed.
Where CAT scanning is available, examination of
the cerebrospinal fluid is carried out only if menin-
gitis or abscess arc suspected or where the scan shows
small amounts of bleeding.
In the usual patient with progressing stroke, the
electroencephalogram does not add significant infor-
mation and is not necessary in the work-up of the pa-
tient.
 TREATMENT OF PROGRESSING STROKE/Millikan and McDowell
Non-invasive studies using Doppler flowmeters and
ultra sound, however, may indicate extracranial ca-
rotid stenosis or occlusion but they rarely give signifi-
cant information concerning the nature of the brain le-
sion and they are not accurate enough to replace
arteriography.18' "
In hospitals where CAT scanning is available, the
static brain scan in the differential diagnosis of
progressing stroke is not useful.
Cerebral Angiography
In hospitals where angiography has a low complica-
tion rate (complications less than lA of 1%), the indica-
tions for its use in progressing stroke are:16""
1. If there is a question about the differential
diagnosis of the brain pathology not settled
by the CAT scan.
2. In early progressing stroke (or very frequent
TIAs) in the carotid system, where there is a
history of amaurosis fugax, an appropriate
bruit, retinal cmboli, etc. suggesting the
development of increasing carotid stenosis or
an ulcerated atherosclerotic plaque.
3. When there is difficulty in making a clear
clinical distinction between the carotid and
vertebrobasilar system circulatory failure
causing the progressing stroke.
4. When the clinical diagnosis of progressing
stroke is not accurate and the patient is
believed to have had a lengthy carotid TIA,
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then angiography needs to be done to identify
the site of the lesion.
Angiography should not be performed if the patient
has:
1. decreased level of consciousness.
2. a severe, focal neurological deficit.
3. clearly an evident cardiac source for emboli.
4. acutely defective heart function.
5. CAT scan evidence of brain edema, shift or
intracranial or intracerebral bleeding.
Prognosis
Little has been written about prognosis for patients
with progressing stroke. Mortality statistics for
patients with progressing stroke vary, depending on
the type of hospital where treatment is given, the pop-
ulation being hospitalized and availability of intensive
care units. The natural history of acute progressing
stroke is quite variable which makes it desirable to
compare treated and untreated patients. In 195518 204
consecutive patients with acute onset of progressing
stroke believed to be due to disease in the carotid arte-
rial system were reported. Within 2 weeks after onset,
12% of the patients were normal, 5% had some degree
of monoparesis, 60% had some degree of hemiparesis
and 14% died.
In the literature, usually little or no distinction is
made between patients who have progressing stroke in
the parts of the brain supplied by the vertebrobasilar
artery and in parts of the brain supplied by the ca-
rotid artery. Treatment with anticoagulant indicated"
399
that 8.5% of patients with acute progressing stroke in
the brainstem died, but among untreated patients
58.9% died.
In studies where treatments are compared, it is
necessary to include only those with onset of symp-
toms in the preceding hours. Patients included in a
study with an onset of a focal neurologic focal deficit
beginning 48 or 72 hours prior, will contain many in
whom the process has reached its maximum degree
and who could not be considered as having progress-
ing stroke. From that point the natural history is one
of improvement. Including such patients in a study of
treatment biases the results in favor of the treatment.
Jones and Millikan*0 reviewed the records of 179 con-
secutive patients with acute cerebral infarction due to
carotid artery system disease in order to analyze the
clinical events during the first week. Patients admitted
to the hospital within 26 hours of the onset of the first
symptom were included. At the end of the first week,
39% were stable (unchanged) and 35% had gradually
improved. In 19%, a progressing neurological deficit
occurred which stopped within 48 hours of the onset.
A remitting-relapsing course during the first 36 hours
was observed in 6 patients (3%) and 8 patients (4%)
became worse after 48 hours after being stable or im-
proving. For the entire group, the mortality was 11%.
A "high risk of death" group was identified in which
the mortality was 41% for patients with any evidence
of a decreased level of consciousness and hemiplegia
on admission. Among the 67 patients with hemiplegia
or a similar neurological deficit, who had normal con-
sciousness when admitted, only one died giving a mor-
tality of less than 2%. These percentages are useful in
comparing a possible new therapy to earlier treat-
ments. In medical centers, if there is a large popula-
tion of patients with acute cerebral infarction, it is
desirable to determine similar percentages, as such
data can be used to compare new treatments in that
particular hospital.
Treatment
When confronted with a patient with progressing
stroke what treatment can be offered? Treatment is
divided into general and specific therapy.
General Therapy
General therapeutic measures available for the
patient with a progressing stroke are similar to those
given to other ill patients. The nature of the treatment
is governed by whether there are alterations in the
level of consciousness. Patients with progressing
stroke usually have no depression of consciousness but
some with progressing stroke in the vertebrobasilar
system can become comatose and will require special
measures including careful attention to the airway and
removal of excessive secretions. Patients with brain-
stem infarction may have respiratory insufficiency and
may need assisted ventilation. The need for assistance
is determined by the ventilatory rate and depth and
arterial oxygenization.
The patient should be examined to determine ab-
 400 STROKE
normalities in heart size and rhythm and signs of con-
gestive heart failure. When present, these conditions
must be treated rapidly during the evaluation of the
patient's neurologic defect with suitable anti-arrhyth-
mic drugs and diuretics.
Measurement of blood pressure on several oc-
casions is essential to determine if progressing stroke
is due to hypertensive encephalopathy. Patients with
progressive stroke may be known to be hypertensive
before the onset and at times hypertension becomes
evident during the acute episode. If the blood pres-
sure is not excessively elevated, it is usually not
necessary to lower it but if the decision is made to
reduce blood pressure, it must be done slowly.
Precipitious lowering of blood pressure can increase
cerebral ischemia by reducing cerebral blood flow in
parts of the brain with deficient vascular auto-
regulation.
Patients who become comatose need careful atten-
tion to pressure areas on the skin. This problem
should not be overlooked as bedfast patients easily
develop ischemic ulceration of the skin which is
difficult to heal.
A patient with a brainstem stroke may develop
urinary retention or incontinence. Preferable treat-
ment is intermittent catheterization with sterile tech-
niques carried out through the acute phase rather than
to use an indwelling catheter with its attendant risk of
infection.
Patients with progressive stroke may vomit and
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they must be protected from aspiration, if the level of
consciousness is depressed. Acute stroke may lead to
gastro-intestinal ulceration and bleeding. If this oc-
curs, suitable anti-acid medications should be used.
Bowel action is often impaired and patients easily
become impacted which requires prompt attention, es-
pecially if the patient becomes obtunded.
When brainstem infarction results in paralysis of
eye closure, attention must be paid to protect the cor-
neal surface and keep it from drying or ulcerating.
Usually taping the eyes shut is the only treatment
needed.
Nutrition and adequate fluid and caloric intake re-
quire approximately 2,000 cc's of fluid per day and a
1,000 calorie intake per day. This should be given in
small feedings but it may be necessary to give food
and fluids intravenously.
If patients become febrile during an acute pro-
gressive stroke, it is important not to overlook an in-
fection. The physician should never miss the possi-
bility that the patient has an undiagnosed infectious
disease. Elevations in body temperatures should not
be dismissed as being solely due to neurologic deficits.
When seizures occur during a progressing stroke, anti-
convulsive medication should be used.
Patients who have pain as they develop an acute
stroke can be managed by careful positioning and fre-
quent changes of position. Small amounts of aspirin
can be given or a small amount of codeine usually
relieves the patient of discomfort.
VOL 12, No 4, JULY-AUGUST 1981
Specific Therapeutic Measures
The aim of therapy in progressing stroke is to stop
progression. This is attempted by maintaining sub-
strates for tissue metabolism through maintenance of
blood delivered and removed from brain tissue. To at-
tain this goal treatment may be directed at a number
of factors which include:
1. Interference with the capacity of the heart to
provide normal cerebral blood flow.
2. Conditions which alter blood and reduce
neurometabolic substrate; conditions which
cause thrombus formation and alterations in
blood constituents — anemia, polycythemia,
hyperlipidemia and hyponatremia.
3. Arterial lesions which cause occlusion or
thrombus formation (these include athero-
sclerosis, arteritis, etc.).
4. Protection of neuronal metabolism by
methods such as hypothermia, steroids, etc.
1. Cardiac Disorders
Cardiac disorders may interfere with cerebral per-
fusion by cardiac failure, cardiac dysrhythmia, em-
bolus formation and excessive elevations of blood
pressure. Cardiac arrhythmia occurring in a patient
with progressing stroke may be associated with a re-
cent myocardial infarction, an independent entity, or
be associated with valvular disease. The physician
must determine whether an arrhythmia has patho-
genetic significance in the development of progressing
stroke, particularly in producing a cerebral embolus.
If there is a causal relationship, the change in cardiac
rhythm should be corrected.
Cardiac emboli may be a more frequent cause of
progressing stroke than suspected. Carter11 has
reported that usually cerebral emboli are caused by
mitral stenosis, myocardial infarction or atrial fibrilla-
tion or a combination of these. Cerebral embolism oc-
curs most commonly within the first 6 weeks after a
myocardial infarction. Anticoagulant therapy has
been recommended to prevent emboli in these
situations but it also acts to improve the cerebral le-
sion itself. Such treatment is reported to decrease
overall mortality (Carter," Wells,11 McDevitt24). All
reports conclude that the reason for using anticoag-
ulant therapy is to prevent further emboli from form-
ing and going to the brain. Whether anticoagulant
therapy should be started immediately for patients
with progressing stroke caused by an embolus from
the heart is a difficult clinical question which arises be-
cause of the possibility of increased risk of bleeding
into the infarcted tissue, with bleeding made more
likely by anticoagulant treatment. Experimental
studies"1 *• in dogs have shown that cerebral infarc-
tion is more hemorrhagic when anticoagulants were
given after embolization as contrasted to a control
group. Recurrent embolization can happen within a
few hours after the first clinically evident embolus, so
there is reason to begin anticoagulant therapy as early
 TREATMENT OF PROGRESSING STROKE/Millikan and McDowell
as possible when there is evidence that progressing
stroke is not accompanied by gross intracerebral
bleeding. This question can be settled by using the
CAT (head) scan and by examination of the spinal
fluid for blood.
Chronic rheumatic heart disease is a frequent
source of cerebral embolism when there is atrial
fibrillation. The incidence of embolism is reported to
be 1.5% per patient year for a group of 754 patients
with chronic rheumatic heart disease." When atrial
fibrillation was present, it was 7 times higher than
when there was normal sinus rhythm, but "anticoag-
ulant treatment reduced the incidence of embolic
recurrences . . . " Freeman and Wexler*8 reported the
effect of treatment with anticoagulants on morbidity
and mortality associated with chronic atrial fibrilla-
tion and organic heart disease. Among 300
hospitalized patients with decompensated hearts and
atrial fibrillation for more than 18 days, 100 patients
served as a control group, 100 patients received
quinidine sulfate and bishydroxycoumarin (Di-
coumarol) and 100 received only anticoagulant. Death
and non-fatal emboli were decreased most in the
patients who were given anticoagulant alone. The
report concludes that, "anticoagulant and conversion
to normal sinus rhythm would seem to offer the best
prognosis for patients with organic heart disease and
chronic atrial fibrillation."48
If an embolus comes from prosthetic heart valves,
the usual means of prevention of recurrence has been
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oral anticoagulant medication. Sullivan et al.M have
reported one patient of 42 (553 months follow up) with
2 emboli who received dipyridamole and anti-
coagulant, and 9/50 patients (695 months follow up)
with 17 emboli who received anticoagulant and a
placebo. Duvoisin reports the risk of thrombo-
embolism from prosthetic heart valves declines over
time, particularly by the third postoperative year." A
physician with a patient having a progressing stroke
from this cause should consider giving anticoagulants
to prevent additional emboli.
Patients with rheumatic heart disease with mitral
stenosis (with or without atrial fibrillation) have em-
boli to various organs, often the brain. Giving oral
anticoagulant to such patients has been found to be
the preventive treatment of choice through the work of
Owren,'1 Szekely" McDevitt," Fleming and Bailey,81
Adams et al.M and Wright and McDevitt." Treatment
is started after the first embolus, whatever the site. A
physician must make a decision on the time to begin
anticoagulant therapy since the need is to prevent
further emboli. Carter" reported that the recurrence
rate for this type of embolism is about 50% during the
first year but that the incidence can be reduced in the
first 6 months by giving anticoagulants. When
rheumatic atrial fibrillation is the cause of cerebral
emboli, anticoagulant treatment must be continued in-
definitely unless sinus rhythm returns. Generally, an-
ticoagulant therapy is begun immediately by giving in-
travenous heparin if the neurological defect is
401
associated with normal consciousness and mild hemi-
paresis. When a neurological deficit is marked, it is
better to wait 3 to 5 days before beginning treatment
as in this instance an embolic infarction can be hemor-
rhagic and could be made worse by immediate an-
ticoagulation.
Progressing stroke can be caused by emboli follow-
ing bacterial endocarditis. In this situation the role of
anticoagulation is unclear. Loewe" found that ad-
ministration of penicillin and heparin was successful in
the treatment of bacterial endocarditis, but Dawson
and Hunter** found no difference between patients
receiving penicillin alone and those given penicillin
and heparin. Thill and Meyer*7 reported an increased
incidence of fatal cerebral hemorrhage when penicillin
and anticoagulants together were used as treatment
for subacutc bacterial endocarditis. Lerne and Wein-
stein" believed that antibiotics and anticoagulants
should be used for the same reasons that they are con-
sidered for persons not having endocarditis. In 1974 a
patient with bacterial endocarditis with emboli, who
died from cerebral damage after treatment with hep-
arin, was reported by Kanis." It is generally con-
sidered to be unwise to give anticoagulants to such
patients.
When cardiac output is impaired from primary car-
diac failure or from hypertension, the cardiac output
should be returned to normal, if possible, by suitable
treatment.
Hypertensive encephalopathy is, in fact, a form of
progressive stroke. The diagnosis of "hypertensive
encephalopathy," is specifically reserved for patients
with a stereotyped sequence of clinical events of
serious, important, and dramatic development. It oc-
curs in patients with moderate or severe hypertension
and is associated with an increase in severity of the
high blood pressure in a few hours time. The usual
symptoms include intense headache, often associated
with nausea and/or vomiting, and alterations in con-
sciousness with semi-stupor or stupor progressing to
coma and convulsions. Hypertensive retinopathy is
generally found, as is some degree of renal impair-
ment. The cerebrospinal fluid pressure is increased but
examination of the fluid is commonly normal. To
these basic features of hypertensive encephalopathy
are usually added focal neurological signs, which on
repeated examination may increase, thus constituting
a progressing stroke. The addition of these focal
neurological signs must be found with the syndrome
described. Immediate control of the hypertension is
needed and constitutes a medical emergency. The
arterial pressure should be lowered before decreased
consciousness begins because hypertensive en-
cephalopathy treated can reverse all symptoms. The
patient who becomes stuporous or comatose may re-
spond slowly or not at all to a reduction of blood
pressure. Sodium nitroprusside, prepared for intra-
venous use, is the most suitable treatment and is now
widely available. This medication can produce a satis-
factory lowering of blood pressure, but using it re-
 402 STROKE VOL. 12, No 4, JULY-AUGUST 1981

quires constant monitoring of the patient by ex-
perienced personnel. Blood pressure should be reduced
promptly, but it should not be precipitously reduced as
brain ischemia and/or myocardial ischemia can
result, especially if the diagnosis is not correct. Con-
tinued careful attention to blood pressure control is
mandatory, usually for the remainder of the patient's
life.40 For the patient with the usual progressing cere-
bral infarction, hypertension should be treated
cautiously and the blood pressure should not be
reduced as quickly as for hypertensive encephalop-
athy.
Blood Constituents
Treatment of progressing stroke may involve
changing the characteristics of the blood constituents
by the use of anticoagulant, platelet antiagglutinating
agents, agents such as low molecular weight dextran,
and fibrinolytic drugs. In addition, care should be
given for a variety of phenomena, including poly-
cythemia, anemia, hypoglycemia, etc.
Anticoagulant Medication
For the patient with an acute progressing stroke
who is to be treated with anticoagulants there is often
uncertainty about whether intraccrebral bleeding is
present. The question can be answered with satis-
factory accuracy, as the CT head scan is nearly 100%
accurate in determining an intracranial hemorrhage
and it should be used in the initial evaluation. When
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arin is initiated, it is usual to continue therapy with an
oral anticoagulant. Treatment with anticoagulant is
continued during the period of hospitalization and
sometimes for 1-2 months after.
Table I summarizes the studies reported in the liter-
ature of the use of anticoagulants in progressing
stroke. These studies are relatively comparable. In
each study an evaluation was made of the patient as to
whether progression of the neurological deficit had oc-
curred in the preceding few minutes. Frequent re-
evaluations were made and later comparison between
the maximal neurologic deficit which developed and
the neurologic deficit evident at the start of the study
was made. The number of patients having progres-
sion of their neurological deficit in both groups, con-
trol and treated, for each study reported is shown. In
every report, the patients treated with anticoagulant
fared better than those who did not receive the anti-
coagulant. In one report 20% of those treated with
anticoagulant progressed after entry into the study
and 52% of those who did not receive anticoagulant
progressed. The report of the National" study is
difficult to interpret but it is included since patients
were randomized for treatment of control. In
Fisher's" personal study, the number of patients is
small for statistically significant results, but the trend
is definite, as 21% of the treated patients progressed,
and 64% of those not receiving anticoagulant
progressed.
The report of the cooperative group also supports

this trend, as twice as many non-treated patients

there is no evidence of bleeding, heparin is started in-
travenously because of the acute, usually emergency
nature of a progressing stroke. High blood pressure
must be appropriately and carefully controlled. When
the patient is hemiplegic and/or has a depressed level
of consciousness, it can be assumed that maximum
ischemia is probably present and progression of focal
ischemia is unlikely. In this situation, it is not ad-
visable to start heparin. Where treatment with hep-
progressed as compared to patients receiving anti-
coagulant. In reports it is often difficult to find a de-
tailed description of anticoagulant treatment. The re-
cent report from Massachusetts General Hospital
concerning symptomatic middle cerebral artery
stenosis in 16 patients41 indicates that medical
therapy, including anticoagulant, should be initiated
early, before the occurrence of complete occlusion but
the duration of therapy is unclear. The chance of in-

TABLE 1 Treatment of Progressing Stroke With Anticoagulants

FUher 44 Fisher" C«rter° Cooperative0 Millikan"
1958 1961 1961 Study of 1962 1965

Patients
Treated 14 51 38 61 181
Control 14 49 38 67 60
Follow up
Treated — 5.7/mo. 6 mo. 12 mo. 12 mo.
Control 7.4/mo. 6 mo. 15 mo. 12 mo.
Lethal cerebral infarcts
Treated 0 4 3(7%) 5(8%) 12 (7%)
Control 0 7 7 (17%) 10 (15%) 25(40%)
Progressive infarcts
Treated 3 7 (14%) 9(24%) 8 (13%) 25 (14%)
Control 9 14 (29%) 12 (33%) 21 (31%) 8(13%)
Cerebral hemorrhage
Treated 0 1 0 1(2%) 0
Control 0 0 0 0 0
Percent progressive
Treated 21 7 (14%) 32 23 20
Control 64 20 (40%) 50 46 52
 TREATMENT OF PROGRESSING STROKE/A//7//A;a/j and McDowell
tracerebral hemorrhage associated with anticoagu-
lant treatment increases greatly after one year of
treatment47 and it is reported as being small during
acute treatment. In a report of 9 patients who
developed intracerebral hemorrhage while taking anti-
coagulant, 8 had been on treatment for more than one
year.
If hypertension is present, it must be controlled at
the time anticoagulants are considered during treat-
ment and should continue to be controlled. The report
of Marshall and Shaw4* on a controlled trial of anti-
coagulant therapy in 51 patients with acute non-
embolic, non-hemorrhagic cerebral vascular accident
concluded that anticoagulants were not of value. All
of the patients included in this trial had severe and per-
sistent damage to brain function during the 72 hours
before admission, and the extent of the neurologic
damage was not reported. It is likely that many of
those included had completed stroke which does not
respond to treatment with anticoagulants when begun
72 hours after onset of symptoms. It is possible that
many patients with severe neurological damage had
cerebral edema and there is no effective means to
reverse this catastrophic situation.
In the carefully performed investigations of acute
progressing stroke treated with anticoagulant, each
study points to fewer patients progressing when receiv-
ing anticoagulant, compared to those not getting such
therapy.
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Platelet Antiaggregating Agents
Unfortunately there are no current reports of the
effectiveness or lack of it, in the use of platelet anti-
aggregating agents for progressing stroke.
Dextran Therapy
In a study by Gilroy,49 100 patients with acute cere-
bral infarction or progressing stroke due to thrombo-
embolism were assigned in a random manner to
receive continuous intravenous treatment with dex-
tran-40 for 3 days, or (the second group) an equal
volume of fluid without the dextran-40. Each patient is
reported to have had the onset of moderate to severe
neurological deficit without improvement 24 to 72
hours before being accepted into the study. This report
did not separate out progressing stroke. The patients
were not divided into those who had their stroke 70
hours before treatment or 6 hours before. Successive
evaluation of the neurologic status of each patient in-
dicated that the group treated with dextran-40 had a
lower mortality and better "quality of survival" than
the untreated patients. Anaphylactic reaction to an in-
travenous infusion of dextran-40 has been reported.80
Spudis et al.*1 randomly treated 50 patients with
dextran-40 who had onset of moderate to severe unim-
proving weakness or paralysis of less than 24 hours
duration. They reported that "a greater percentage of
dextran-treated patients improved with respect to con-
sciousness and strength in upper and lower extrem-
ities but showed less restoration of language than the
403
untreated patients." However, the differences in the 2
groups were not significant.
Kastc et al.*1 performed a double blind trial by
selecting 2 groups of patients with acute stroke. In
each patient treatment started 24-29 hours after the
onset of symptoms. The group that received intra-
muscular dcxamethasone combined with intravenous
low-molecular weight dextran showed no difference in
mortality or neurologic status compared to the other
group that received placebo." Random selection by
Matthews*8 of 2 groups of patients, 52 treated with
dextran-40 and 48 in a control group, who were
thought to have had a cerebral infarction during the
previous 48 hours, indicated that, "in the treatment
group mortality in the acute stage in patients with
severe strokes was significantly reduced but survivors
were severely disabled and 6 months later no signifi-
cant benefits could be detected. In less severe strokes
no effect of treatment was found."" The results of
these many reports indicate that no wide-spread
enthusiasm for this treatment has developed and, most
important, it should never be the exclusive treatment
for progressing stroke.
Fibrinolytic Agents
The possibility that a thrombolytic drug could lyse a
clot which obstructed arterial flow has always been an
attractive one. This form of treatment should be possi-
ble for progressing stroke. Meyer et al.M reported a
study of the effect of an intravenous infusion of strep-
tokinase, treating 73 patients. The study was ter-
minated because the therapy was found to be
detrimental to patients with progressing stroke.
Fletcher et al." studied 31 patients with acute cere-
bral infarction and treated them with urokinase, each
for about 10 hours. He found a prompt sustained in-
crease of plasma thrombolytic activity but hemor-
rhagic complications occurred in several patients. He
did not indicate a favorable therapeutic effect. Han-
naway et al.** reported in detail the clinical and patho-
logical studies of 4 patients in Fletcher's series who
developed cerebral hemorrhage during or within 24
hours of urokinase treatment. The ability to make a
more accurate diagnosis of acute cerebral arterial
obstruction due to thrombus and improved tech-
nology to administer and measure thrombolytic
agents, might make this form of treatment feasible in
the future.
Alterations In Circulating Blood Constituents
Polycythemia
There are no comparative studies to guide treat-
ment of polycythemia, anemia and hypoglycemia in
patients with an acute progressing stroke. Kannel et
al." have reported, "men with hemoglobin values of
15 gm or greater and women with 14 gm or more had
twice as many cerebral infarctions as did their cohorts
with lower values." Tohgi" reported on the
relationship between the incidence of cerebral infarc-
tion and the level of the hematocrit in 432 consecutive
 404 STROKE
patients who came to autopsy. These patients had an
average age of 77.1 years. If the hematocrit was above
46%, the incidence of cerebral infarction was higher.
He also noted an increase in the frequency of stroke in
patients with severe atherosclerosis when compared
with those with small amounts of atherosclerosis.
Thrombotic cerebral events have been reported to oc-
cur in 7 to 15 or more percent of patients with poly-
cythemia vera; polycythemia must be actively treated
if it is detected in a patient with progressive stroke.
The availability of CAT head scanning has assisted in
differentiating a focal ischemic lesion from one which
is markedly hemorrhagic" or from a frank intra-
cerebral hemorrhage — which can also occur with
polycythemia vera.
Hyperlipidemia
In the usual patient with acute progressing stroke,
hyperlipidemia has not received any special therapeu-
tic attention during the acute hospital admission.
Hyponatremia Treatment
At times with progressing stroke, the syndrome of
inappropriate antidiuretic hormone secretion may oc-
cur with fluid retention and hyponatremia. The symp-
toms are irritability, confusion, unexplained muscular
weakness and decrease in tendon reflexes. If hypo-
natremia is found with hypernatruria and increased
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urine osmolality inappropriately high for the serum
osmolarity, the patient's fluid intake should be
restricted to about 1,000 cc a day until the abnormali-
ties have disappeared.
Arterial Lesions
Vasospasm
Vasospasm has been considered as a possible cause
of progressing stroke and vasodilating drugs have
been used with uneven reports of effectiveness.
Mackey and Scott90 reported on the treatment of
"apoplexy" by procaine infiltration of the stellate
ganglion and found a marked benefit. Denny-Brown81
could not confirm these observations when he
similarily treated 8 patients. Millikan et al." studied
the effect in 27 patients who had stellate ganglion
block and compared them to 60 patients who did not
have the treatment and no benefit was found.
The inhalation of 5% CO, will cause 50% to 75%
increase in cerebral blood flow.4* Utilizing this great
increase in cerebral blood flow following CO, inhala-
tion, Millikan18 studied its effect on acute focal cere-
bral infarction in 50 patients and compared them to
225 untreated patients. No statistically significant
difference in the results in the 2 groups was found.
Meyer et al.M reported that "intermittent inhalation
of 5% CO, may be beneficial in patients with TIAs and
in mild and moderate cerebral infarctions, as
evidenced by the clinical state of the patient and diag-
nostic and laboratory findings (lumbar puncture,
VOL 12, No 4, JULY-AUGUST 1981
arteriography, isotope brain scan). Inhalation of 5
percent CO, can cause a rise in cardiac work and car-
diac output and is contraindicated in patients with
coronary artery disease, congestive heart failure and
systemic and pulmonary arterial hypertension."
Despite these reported effects this treatment of
progressing infarction is not generally regarded as
useful.
Other agents which are believed to cause cerebral
vasodilation include papaverine, isoxsuprine, and
acetazolamide. Gilroy and Meyer" treated 70 patients
with progressing stroke; 34 of them received intra-
venous papaverine and 36 made up a control group.
Statistical analysis of the results showed that improve-
ment in the treated group was significantly greater
than in controls. Gilroy and Meyer also studied 33 pa-
tients, of whom 17 received intravenous acetazola-
mide and 16 did not receive it. For this treatment there
was no difference in outcome between the 2 groups.
There has been no further indication of usefulness for
this mode of therapy.
Meyer et al.84 reported clinical improvement and in-
creased cerebral blood flow in patients given dimethyl
trimethoxybenzoloxy propylethylendiamine (hexo-
bendine) by either the intravenous, intramuscular or
oral routes. This form of treatment is not currently
used in the United States.
Vasoconstrictors
Hypocarbia has been evaluated as therapy for acute
cerebral infarction by Paulson88 who measured cere-
bral circulation in patients with acute cerebral infarc-
tion and found that focal vasoparalysis often occurred
during the acute phase. He also found that often there
was a focal loss of autoregulation and elsewhere a nor-
mal response to changes of arterial Pco a and to the
application of vasoconstricting or vasodilating drugs.
Paulson67 also found paradoxic responses; focal flow
decreases in response to hypercarbia which normally
causes aflowincrease. At times there was a focal flow
increase following stimuli which cause a flow de-
crease. These various reactions led him to treat a
group of 50 patients with severe acute cerebral infarc-
tion by using artificial ventilation to produce hypo-
carbia.87 This was started within the first 24 hours
after the stroke began and continued for 72 hours. To
serve as a control group, 21 patients with severe cere-
bral infarction not treated by hypocarbia were
observed. No significant benefit was found when the
clinical course of the 2 groups was analyzed later but
he found that during the first few weeks the clinical
response of the non-ventilated group was statistically
better than that of the ventilated group. This method
of treatment has not been studied further and is not
used.
Inflammatory Lesions
If cerebral infarction follows an arterial obstruc-
tion caused by any form of arteritis or meningitis, pri-
 TREATMENT OF PROGRESSING STROKE/Millikan and McDowell
mary attention must be paid to treatment of the dis-
ease causing the inflammation of the arterial wall.
Patients with panarteritis (polyarteritis nodosa), lupus
erythematosis, cranial arteritis, etc. should receive
steroid therapy and patients with meningitis (bac-
terial, etc.) suitable antibiotic treatment, depending
upon the organism producing the inflammation.
Surgical Therapy
Blaisdell" found that patients with progressing
stroke should not have cerebral angiograms because
of the high risk of surgery and the possibility of an un-
favorable surgical result. The Joint Study of Extra-
cranial Arterial Occlusion8* found a mortality of 42%
in 50 patients operated upon within 2 weeks following
an acute stroke. The mortality was only 20% for
patients in the same category not having surgery.
Bruetman et al.70 and Wiley et al." reported intra-
cerebral hemorrhage as a complication of carotid sur-
gery and believe that the opening of carotid occlusion
and re-establishing a normal head of perfusion pres-
sure into an area of acute softening produced the in-
tracerebral bleeding. Millikan" reported a patient for
whom emergency anticoagulant treatment and sur-
gery appeared to be beneficial. The indications for sur-
gical therapy for progressing stroke are as follows:
A. Clinical Events. 1) A cluster of frequent, severe ca-
rotid arterial system TIAs (a persisting mild neuro-
logical deficit may eventually become a mild pro-
gressing stroke); 2) a recent small cerebral infarction
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in brain supplied by the carotid arterial system
followed by a cluster of TIAs; 3) onset of a focal
neurological deficit during or soon after arteriog-
raphy or sometimes immediately after carotid throm-
boendarterectomy.
B. Physical Signs. (These added to the clinical events,
suggest the basic pathologic process is current and ac-
tive) and include: 1) retinal emboli, 2) long systolic or
systolic-diastolic bruit of grade 2 or 3 or more heard
over the carotid bifurcation, 3) ipsilateral decrease in
the retinal artery pressure.
Fisher" reported: "we have continued to operate on
patients with the progressive stroke, with extremely
good results. We operate on these patients on an
emergency basis if emergency arteriography has
shown that their problem is in the carotid territory.
The results are extremely good, just as good as for pa-
tients with ischemic attacks. I would like to emphasize
that surgery for acute stroke must be reconsidered."
Goldstone and Moore" described the results in 26
patients, 8 of whom had a cluster of transient ischemic
attacks from the carotid arterial system and 18 of
whom had a stroke in evolution. They found that
"each of the 26 patients made a dramatic, complete,
and so far permanent neurological recovery following
operation. There was no morbidity from either the
angiographic or surgical procedures." They did not in-
clude patients for angiography and operation who had
acutely developed severe focal neurological deficits
(hemiplegia, etc.) or patients with a depressed level of
405
consciousness. Siekert and Millikan" reported that a
changing carotid bruit can indicate a change in the
morphology of the carotid lesion and this should be
added to the list of physical signs.
The risk factors for carotid surgery reported by
Sundt et al." should be carefully reviewed when
evaluating indications for thromboendarterectomy in
patients with progressing cerebral infarction. Careful
evaluation and selection of patients with a progress-
ing stroke will undoubtedly reveal some for whom
emergency surgery is indicated. Consideration for sur-
gery must be prompt and should not delay anti-
coagulant treatment.
Treatment To Protect Brain Parenchyma
The cerebral edema which can follow cerebral
infarction is the most serious threat to life. It begins
soon after an ischemic event, but usually it is impossi-
ble to predict who will have this complication and
should have treatment. Edema causing lethal cerebral
infarction begins in the first few hours after the start of
a progressing stroke. Bounds"' •• reported a study of
the records of all patients who came to autopsy at
Mayo Clinic from January 1966 through September
1975. He found 100 patients with acute cerebral in-
farction in the brain in the distribution of the internal
carotid artery. Sixty percent of the deaths occurred
during the first week with brain herniation, cardiac ab-
normalities and pulmonary embolus the usual causes.
Brain herniation was always secondary to brain edema
following cerebral infarction. The sequence of edema
formation should be understood when reviewing the
literature reporting clinical trials of antiedema agents.
Glycerol Therapy for Edema. A paper by Ott et al.90
reported a study of 24 patients evaluated before and
after glycerol treatment. In 16 patients the treatment
was started 10 or more days after the onset of the
stroke and the remaining patients received their treat-
ment on the 8th or 9th day after the stroke. The report
indicated that all patients were well through the period
when edema began and when glycerol was given.
Glycerol Therapy For Edema
Meyer et al.91 investigated treatment of cerebral
edema after acute cerebral infarction giving glycerol
intravenously in doses of 1.2 gm per kg of body weight
every 24 hours, and in some instances orally in doses
of 1.5 gm per kg of body weight. Therapy was ini-
tiated within 72 hours of the onset of infarction. They
found that glycerol "given within 5 days of onset of
severe, progressive or sustained neurological deficit
has been of benefit in patients with acute cerebral in-
farction." Matthew et al.w conducted a double blind
evaluation of glycerol therapy given intravenously
with 54 patients who had an acute onset of cerebral in-
farction and 8 patients with hypertensive intracere-
bral hemorrhage. Patients were admitted to the study
up to 4 days after the onset. They reported that
"patients with cerebral infarction treated with glycerol
 406 STROKE VOL 12, No 4, JULY-AUGUST 1981

showed significant improvement in neurological status
compared with the patients treated with placebo."
They did not find any benefit with glycerol therapy for
the patients with spontaneous intracerebral
hemorrhage. Gilsanz*3 compared 6 days of treatment
with 10% glycerol in 30 patients who had acute cere-
bral infarction to dexamethasone treatment in 31
similar patients. All patients entered the study only if
onset of their stroke was within 36 hours of beginning
treatment. One patient treated with glycerol had
hemoglobinuria and acute renal failure and died. Six
patients given dexamethasone died. Gilsanz found that
improvement was significantly greater in the group
treated with glycerol at 8 and 15 days. Fritz et al.M
studied 106 patients with acute stroke. Fifty received
intravenous glycerol and 56 did not receive this treat-
ment. Using a scoring system devised for grading the
neurological deficits, they found that those patients
with the "highest and lowest scores did not improve
from glycerol infusion." Patients with intermediate
scores were found to improve significantly when com-
pared to patients not receiving glycerol. In all patients,
treatment with glycerol was started within 24 hours
after the onset of stroke. Larsson et al.M conducted a
double blind trial of 27 patients with acute stroke.
Glycerol was given intravenously in 12 and 15 received
placebo. All patients had developed sudden focal
neurological deficits within 6 hours before randomiza-
tion. They found that "there was no difference in mor-
tality or improvement of neurological score between
the 2 groups."
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evaluated, the importance of the temporal profile must
be considered as we suspect that glycerol, given a week
after the onset of cerebral infarction, will not have a
significant effect on edema. Few complications of this
treatment have been reported, which should encourage
further investigation. It may have a definite role in
treating patients with progressing stroke who rapidly
develop marked neurologic deficits and then, within 36
hours or less, have a marked reduction in their level of
consciousness. Table 2 compares the reported results
of treatment of edema with various hyperosmolar
agents.
Steroid Therapy
Since the study of Russek et al.™ there have been
few positive reports and enthusiasm for steroid ther-
apy in patients with acute stroke to protect them from
cerebral edema associated with cerebral infarction.
Table 3 shows the results of 11 reports in the litera-
ture. Mulley and Wilcox" evaluated 118 patients with
acute stroke allocated for treatment with either dexa-
methasone or placebo and found that one year later
there was no significant difference in the outcome of
the 2 groups, i.e., the number of survivors or the
quality of life. They concluded that there was no in-
dication for treatment with steroids for patients with
cerebral infarction.
Ottonello and Primavera*7 studied postmortem ex-
aminations of 73 patients dying with acute stroke and

found that the frequency of gastric erosion, gastric ul-

Infused glycerol must be administered with cau-
tion, especially to patients with diabetes or patients
with marked dehydration because the serum glucose
can be elevated to dangerously high levels and non-
ketogenic hyperosmolar hyperglycemia can be
produced.9*
The results of the various studies of glycerol therapy
are, unfortunately, inconsistent. When the reports are
cer, duodenal ulcer and multiple erosions in the
steroid treated group was significantly higher than in
those who did not receive corticosteroids.
In our experience there has been no startling or
dramatic improvement in patients who have been
given steroid. Jones and Millikan" found a mortality
rate of 41% for patients with acute cerebral infarction
with hemiplegia and a decrease in the level of con-

TABLE 2 Treatment for Acute Cerebral Infarction With Hyperosmolar Agents

Onietto
Treatment Companion
Interval No. of Un- No. of Un-
Study Drug (day») Patient! Better changed WOTM Dead Patient* Improved changed Worse Dead
91
Meyer et al.
1971 Glycerol 3 36 30 2 4
Mathew et al.w Glycerol 4 29 22 4 1 2 25* 14 6 3 2
Candelise"
et al. 1975 Mannitol + 1 75 — 40 — 35 64* — 42 — 22
Dexa-
methaaone
Fritz et al.94
1975 Glycerol 1 50 _ _ _ 14 56 _ _ _ 23
Gilsanz et al.93 Glycerol or 1.5 30 20 8 1 1 31 12 12 1 6
1975 Dexa-
methasone
Larsson et al.96
1976 Glycerol 1 12 3 2 3 4 15* 4 3 3 5
Santambrogio
et al.M 1978 Mannitol 1 28 12 — 16 32* 14 — 18 18
•Placebo
 TREATMENT OF PROGRESSING STROKE/A//7/(Awi and McDowell
TABLE 3 Treatment of Progressing Stroke and Acute Cerebral Infarction With Steroids
Omet to
Treatment
Author Patient! (houra)
Dyken & White78 1956 36 24
Rubenstein79 1965 19 24
Patten et al.80 1972 31 24
Candelise & Spinnler831972 49 24
Bauer & Tellez81 54 48
Candelise et al.841975 152 24
Norris 8 2 1976 53 24
Santambrogio et al.851978 66 24
sciousness at the time of admission to hospital.
Steroid therapy should be started in such patients
when they first come to the attention of the stroke
service. In this situation, a beneficial effect would be to
lower this mortality rate. In all the reports in table 3
there is no clear or satisfying evidence that steroid
treatment prevents or improves cerebral edema
associated after cerebral infarction.
Treatment with Hypothermia, Anesthesia (Sedation),
Hyperbaric Oxygenation, Normobaric Oxygenation and An-
ticonvulsants
Although hypothermia, anesthesia, hyperbaric
oxygenation and normobaric oxygenation should
theoretically change metabolism or provide a favor-
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able metabolic substrate for focal areas of brain
ischemia, none of these treatments has been reported
as useful for progressing stroke.
Hypothermia is cumbersome, requiring a large per-
sonnel effort, has many serious complications, and has
produced little benefit.
The suggestion has been repeatedly made that the
brain is not as vulnerable to hypoxia as clinicians have
traditionally believed." Yatsu et al.** report that
"results of our investigation support a growing body
of evidence showing the energy state (of brain) to be
relatively stable to ischemia." No practical way has
been found to acutely protect the brain from anoxia
despite these hopeful reports. Anesthetic agents
(forms of sedation including barbiturates) have been
found to change the metabolic requirement of brain,
but their practical application has not been studied in
stroke in the human except indirectly. In Paul-
son's98'8r studies the patients who were hyper-
ventilated were also under heavy sedation (essentially
anesthetized) for the many hours of hypocarbia, and
no benefit resulted.
Ingvar and Lassen*9 studied the use of hyperbaric
oxygen as treatment of focal cerebral ischemia in 4
patients. They were exposed to pure oxygen at a pres-
sure of 2.0 to 2.5 atmospheres for periods of 1.5 to 2.5
hours. Three of the patients appeared to be benefited
and in 2 this was objectively demonstrated in the EEC
Heyman et al.100 studied the therapeutic usefulness of
hyperbaric oxygenation in 22 patients with recent
focal cerebrovascular damage. He found that 4
407
Placebo Treated
Improved Died Improved Died
— 10/19 — 13/17
— 4/6 — 4/13
41% 0 64% 0
— 10/25 — 13/24
16/22 9/26 13/28 5/28
42/64 22/64 55/88 33/88
5/27 7/26
14/32 18/32 15/34 19/34
patients had remarkable improvement and in 2 the im-
provement persisted, but in 2 others the neurological
deficit recurred. Repeated exposure to high pressures
of oxygen produced only temporary improvement.
The problems of the mechanics of hyperbaric oxy-
genation, as well as possible complications, taken with
the lack of enthusiasm for the treatment, even by
those reporting some benefit from it, has resulted in a
situation where hyperbaric oxygenation is not used in
treatment.
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