Effect of Etiology and Topography of Lesion on Body

Temperature at Stroke Onset

Emre Kumral,

MD,

Sultan Tarlaci,

MD,

and Ahmet Acarer,

MD

Background and purpose: Hyperthermia is a well-known factor for neurologic deterioration, morbidity, and mortality in the early phase of stroke. However, the
timing, localization of lesion, origin of stroke, which may influence body temperature, have not been clearly established. Methods: The purpose of this study was to
determine the relationship between body temperature and origin, lesion topography, and prognosis at 3 months after onset of stroke. Axillary temperature was
taken every hour for 72 hours in 473 patients with supra- or infratentorial cerebral
vascular lesion. The time at which hyperthermia (38C) appeared was evaluated
by logistic regression analyses regarding to stroke origin and lesion localization.
The correlation between body temperature and stroke outcome was quantified by
Barthel index and American Heart Association Stroke Outcome Classification by
recording in each 12- hour interval from stroke onset during 72 hours and after 3
months. Results: The body temperature was higher in patients with large-artery
atherosclerosis (odds ratio [OR], 3.98; 95% confidence interval [CI] 2.16-8.97; P
.001) and hemorrhagic stroke (OR 2.05, 95% CI 1.07-8.68, P .001) than those
with small-artery disease. In patients with posterior circulation infarct, the body
temperature was higher than those with anterior circulation infarct (OR 3.71, 95%
CI 2.07-6.67, P .001), whereas there was no difference between patients with
infratentorial hemorrhage and those with supratentorial hemorrhage (OR 1.04,
95% CI 0.75-1.43, P .80). High body temperature at 24 hours of stroke onset
(OR 2.17, 95% CI 2.09-7.57, P .001) and 48 hours (OR 1.27, 95% CI
1.06-4.84, P .02) was correlated with poor outcome and mortality. Conclusion: An
association between hyperthermia within 72 hours of ictus and stroke subtypes was
observed among patients with ischemic and hemorrhagic stroke. Hyperthermic
patients with total anterior circulation infarct, posterior circulation infarct, and
supratentorial hemorrhage were associated with a marked increase of 3-months
mortality. Large-artery atherosclerosis, cardioembolism, and supra-infratentorial
hemorrhage associated with hyperthermia may increase the severity of neurologic
deficits.
Copyright 2001 by National Stroke Association

Recent studies have clarified that changes in body

temperature can influence long-term prognosis of patients with acute stroke.1-10 Early laboratory findings in
From the Department of Neurology, Ege University, Izmir,
Turkey.
Received January 26, 2001; accepted May 22, 2001.
Address reprint requests to Prof. Emre Kumral, MD, Stroke Unit,
Department of Neurology, Ege University Faculty of Medicine,
Bornova, 35100, Izmir, Turkey.
Copyright 2001 by National Stroke Association
1052-3057/01/1004-0004$35.00/0
doi:10.1053/jscd.2001.26867

150

animal models showed that small elevations of body

temperature after induced cerebral infarction may cause
increase in cerebral infarct volume.11-13 Similarly, in humans, 0.5 to 1.4C temperature increases were associated
with a worse outcome in humans after acute stroke.14 A
recent meta-analysis of 9 studies evaluating the effects of
post-stroke hyperthermia on stroke outcome suggested
that pyrexia after stroke onset is associated with a
marked increase in morbidity and mortality.15 Regarding
these results, hypothermia was entered in open-heart
surgery and neurosurgery to combat the detrimental
effects of cerebral hypoxic or ischemic events.16,17

Journal of Stroke and Cerebrovascular Diseases, Vol. 10, No. 4 (July-August), 2001: pp 150-156

EFFECT OF ORIGIN AND TOPOGRAPHY

We sought the relationship between body temperature

at acute stroke and stroke subtypes, including topography of lesion. The effect of body temperature on stroke
outcome regarding the cause and localization of lesion
was also studied.

Materials and Methods

The study subgroup was recruited from 1097 stroke
patients (913 with ischemic stroke, 184 with intracerebral
hemorrhage) admitted consecutively between April 1997
and November 1998. We analyzed only 473 stroke patients without a source of infection and who were eligible
for the study design. The inclusion criteria were the
following: (1) admission less than 4 hours from onset of
symptoms; (2) presence of parenchymal hemorrhage on
the cranial computed tomography (CT) scan; (3) presence
of neurologic deficit at admission with or without sign of
hypodensity or obscuration of brain tissue on the CT
scan; (4) lack of pulmonary and urinary infections at the
time of hospital admission, deep venous thrombosis, and
cancer; and (5) lack of treatment with sympathomimetics,
antidepressants, antiepileptics, and antibiotics. Patients
without detailed medical records or without CT scan or
magnetic resonance imaging (MRI) and with primary
subarachnoid hemorrhage or subdural hemorrhage were
excluded.
On admission, axillary temperature was recorded every hour after admission during the first 3 days. For the
aim of this study, only the time at which hyperthermia
appeared was recorded each hour from admission. Hyperthermia was defined as an axillary temperature above
38C. Blood analyses, chest radiograph, hemocultures,
and urine cultures were performed to exclude a potential
infection. Hyperthermia was considered to be of infectious origin if the patients had positive test results after
stroke onset, and the patients were not included in the
study. We treated patients who had body temperature
38C with antipyretics or with external cooling during the
hospitalization.
We performed 2 to 5 CT examinations in different
stroke patients depending on their neurologic status.
Noninvasive investigations that were performed in all
cases included transcranial Doppler sonography; duplex
sonography; and cardiac investigations consisting of a
clinical examination, 12-lead electrocardiogram, as well
as transthoracic/transesophageal echocardiography. The
following vascular risk factors were recorded: age, sex,
hypertension (on 2 or more blood pressure recordings
higher than 160/90 mm Hg), diabetes mellitus (fasting
serum glucose level higher than 6.5 mM/L), hypercholesterolemia (fasting blood cholesterol higher than 6.5
mM/L), cigarette smoking, ischemic heart disease, atrial
fibrillation, and cardiac valve prosthesis.

151

Topography of ischemic stroke was classified into 4

main groups based on the definitions of the Trial of ORG
10172 in Acute Stroke Therapy (TOAST) criteria.18 They
were as follows: (1) total anterior circulation infarct was
presumed in patients with hemiplegia, hemianopia, and
disturbance of higher cerebral function; (2) partial anterior circulation infarct was presumed in those with sensory motor deficit plus hemianopia or higher cerebral
dysfunction; (3) posterior circulation infarct was presumed in patients with ipsilateral cranial nerve palsy
with contralateral motor/sensory deficits or disorder of
conjugate gaze palsy or cerebellar dysfunction or isolated
hemianopia; and (4) lacunar infarct (or small-artery disease) was considered in patients having pure motor
stroke, pure sensory stroke, homolateral ataxia and crural
paresis, and dysarthia clumsy-hand syndrome. The cause
of stroke was divided into ischemic and hemorrhagic
stroke (or primary intracerebral hemorrhage). The origin
of ischemic stroke was classified as follows: (1) largeartery atherosclerosis (LAA) was presumed in patients
who had a stenosis of at least 30% of the lumen diameter
in the appropiate large artery as shown on Duplex, transcranial Doppler, or magnetic resonance angiography in
the absence of other origins; (2) small-artery disease
(SAD) was presumed in patients with longstanding hypertension or diabetes mellitus, and an infarction with a
diameter of 15 mm limited to the territory of deep
perforators on CT scan or MRI in the absence of other
etiologies; (3) cardiac embolic sources including nonvalvular atrial fibrillation, left ventricular dyskinetic segment, intracardiac thrombus or tumor, mitral stenosis,
and other less common sources; (4) mixed origin was
assumed in cases of coexistence of large-artery disease
and cardiac embolic sources; and (5) undetermined and
other causes, which were not compatible with largeartery atheroma or cardiac embolic sources or remained
undetermined. The origin of hemorrhagic stroke was
considered as hypertension, vascular malformations, anticoagulation, amiloid angiopathy, and others. Intracerebral hemorrhage topography was subdivided into 2 main
subgroups: (1) supratentorial hemorrhage (including lobar, putaminal, thalamic, and caudate) and (2) infratentorial hemorrhage (including cerebellar, pontine, mesencephalic). American Heart Association Stroke Outcome
Classification was used to assess the severity of impairment and functional outcome.19 The severity of impairment(s) was defined as the following: (1) level A, no/
minimal neurologic deficit caused by stroke in any
domain (neurologic domains are motor, sensory, vision,
affect, cognition, and language functions); (2) level B,
mild/moderate deficit caused by stroke in more than 1
domain; and (3) level C, severe deficit caused by stroke in
more than 1 domain. The functional outcome of patients
during follow-up was categorized as the following: (1)

E. KUMRAL ET AL.

152

independent, patient is able to live alone, maintain a

household, and access the community for leisure or productive activities (requires minimal assistance); (2) partially dependent, patient is able to live alone with substantial daily help from family or community; (3)
completely dependent, patient is unable to live alone
safely and requires full-time care. Disability score after
the stroke was quantified using Barthel index.20 The
severity of functional impairment, functional outcome,
and disability score of patients were assessed at 24 hours,
48 hours, and 72 hours on the 7th day and after 3 months
of stroke onset.
Statistical Methods
Continuous variables are expressed as mean standard deviation or as median. Proportions were compared
with chi square test in a univariate analysis for screening
of variables. The time at which hyperthermia was recorded during the first 72 hours for stroke prognosis was
assessed by stepwise logistic regression analysis. Correlations between the highest body temperature (38C)
recorded at every hour period and stroke subtypes, topography, and stroke outcome measure at 3 months were
performed with Cox proportional hazards regression
models. Cutoff points for BI was 1 (poor outcome, 0-50);
2 (moderate outcome, 51-75); and 3 (good outcome,
76-100). Functional outcome evaluation was assessed as
independent, partially dependent, completely dependent
and death, and severity of impairment was considered as
level a, b, and c, with consideration of the mean values in
hyperthermic and normothermic patients. Origins of
hemorrhagic stroke were considered in 1 group because
hypertension was the main origin of hemorrhagic stroke.
Kaplan-Meier survival curves were obtained to describe
3-month mortality. All analyses were performed with the
SPSS data analysis system (SPSSInc, Chicago, IL).

Results
There were 250 men (mean age, 61.7 11 years; range,
48-83), and 223 women (mean age, 65.4 10 years; range,
44-80 years). Three hundred-six patients had infarct in
the anterior circulation, and 81 had infarct in the posterior circulation, whereas 68 patients had supratentorial
hemorrhage, and 18 had infratentorial hemorrhage. The
origin of ischemic stroke was LAA in 199 patients, CE in
73, SAD in 60, coexistence of LAA and cardioembolic in
31, and undetermined in 24 patients. The origin of hemorrhagic stroke was hypertension in 65 patients (76%).
Table 1 shows the demographic data risk factors, and
stroke subtypes. Among 473 patients, 53 patients (11%)
had hyperthermia (38.2 1.4C) at hospital admission,
and 82 patients (17%) showed hyperthermia (38.3
1.2C) during the first 3 days of stroke onset. Sixteen

Table 1. Baseline characteristics of the 473 patients

with acute stroke

Variables

Ischemic
stroke
(n 387)

Age (y) (SD)

63.5 11
Gender (M/F)
197/190
Hypertension
151 (39)
Current smoking
140 (36)
Diabetes mellitus
70 (18)
Hypercholesterolemia
134 (35)
History of stroke
19 (5)
History of MI
81 (21)
Atrial fibrillation
77 (20)
Hematocrit (50)
31 (8)
History of migraine
21 (5)
Carotid stenosis (70%)
25 (7)
(30%-69%)
149 (39)
Vertebral/basilar artery stenosis
(30%)
25 (6)
Hyperuricemia
34 (9)
Hyperthermia (38C)
At admission
35 (9)
4 hours
42 (11)
12 hours
56 (14)
24 hours
61 (16)
48 hours
43 (11)
72 hours
58 (15)
Cause of ischemic stroke
LAA
199 (51)
CE
73 (19)
SAD
60 (16)
Mixed etiology (LAA CE)
31 (8)
Undetermined
24 (6)
Cause of hemorrhagic stroke
Hypertension

Vascular malformations

Anticoagulation

Undetermined

Functional outcome
Independent
171 (44)
Partially dependent
117 (30)
Dependent
19 (5)
Death
80 (21)

Hemorrhagic
stroke
(n 86)
59.5 10
53/33
65 (76)
61 (71)
18 (21)
28 (33)
2 (2)
13 (15)
9 (11)
3 (4)
5 (6)
0
5 (6)
2 (2)
8 (9)
18 (21)
28 (33)
23 (27)
21 (24)
11 (13)
16 (19)

65 (76)
2 (2)
3 (4)
16 (19)
28 (33)
17 (20)
3 (4)
38 (44)

NOTE. Values in parentheses are percentage.

Abbreviations: CE, cardioembolic; MI, myocardial infarction.

percent (61/387) of patients with ischemic stroke and

24% (21/86) of those with hemorrhagic stroke presented
with hyperthermia.
The body temperature was higher in patients with
LAA (OR 3.98, 95% CI 2.16-8.97, P .001), and
hemorrhagic stroke (OR 2.05, 95% CI 1.07-8.68, P
.001) than those with SAD (OR 0.5, 95% CI
0.001-0.63, P .5) and cardioembolic stroke (OR 1.27,

EFFECT OF ORIGIN AND TOPOGRAPHY

153

Figure 1. Kaplan-Meier survival curve showing the cumulative survival

rate of patients with high body temperature ( 38C) and normal temperature. Patients with hyperthermia had worse survival rates than those
without after 3 months of stroke onset (P .001). (- - -, hyperthermia; ,
normothermia.)

95% CI 0.93-1.18, P .40 ). In patients with posterior

circulation infarct, the body temperature was higher than
those with anterior circulation infarct (OR 3.71, 95%
CI 2.07-6.67, P .001), whereas there was no difference
between patients with infratentorial hemorrhage and
those with supratentorial hemorrhage (OR 1.04, 95%
CI 0.75-1.43, P .08).
Three months after stroke, in logistic regression analysis, high body temperature at 24 hours (OR 2.17, 95%
CI 2.09-7.57, P .001) and 48 hours (OR 1.27, 95%
CI 1.06-4.84; P 0.02) was correlated with poor outcome and mortality (Fig 1). Mortality ratio was 63.4%
(52/82) in patients with hyperthermia; it was 16.8% (66/
391) in those with hypothermia (OR 2.27, 95% CI
1.70-3.03, P .001) (Table 2). BI scores at discharge were
significantly lower in hyperthermic patients (mean,
49.4 17.8) than normothermic patients (mean, 64.2
19.4) (P .001). The correlation coefficients between the
mean body temperature recordings within 72 hours and
BI scores decreased significantly after 3 months of stroke
onset (P .0001, r 0.26).

Table 2. Univariate Cox regression analysis of functional outcome regarding origins of stroke and topography of lesions in
patients with hyperthermia vs normothermia
Risk ratio (95% CI)

Origins of stroke
LAA (n 199)
SAD (n 60)
CE (n 73)
Mixed Origin (LAA & CE)
(n 31)
Other and undetermined
(n 24)
Intracerebral hemorrhage
(n 86)
Topography of Lesions
Total anterior circulation
infarct (n 220)
Partial anterior circulation
infarct (n 51)
Posterior circulation infarct
(n 56)
Supratentorial hemorrhage
(n 68)
Infratentorial hemorrhage
(n 18)

Independent
(n 199)

Partially dependent
(n 134)

Completely dependent
(n 22)

Death
(n 118)

1.62 (0.98-4.26)
0.002 (0.001-0.54)
0.64 (0.35-1.16)

0.33 (0.18-6.82)
0.66 (0.54-4.71)
1.34 (0.07-2.41)

1.66* (1.01-10.12)

1.99 (0.61-6.40)

0.38 (0.37-2.12)

0.61 (0.23-1.64)

0.12 (0.10-4.92)

0.66 (0.40-0.98)

0.32 (0.11-9.44)

1.11 (0.18-2.88)

1.83 (0.44-7.41)

2.81* (0.78-10.16)

1.25 (0.34-4.55)

0.37 (0.20-0.60)

0.25 (0.13-0.51)

0.57 (0.18-1.8)

0.54* (0.29-0.96)

0.22 (0.19-1.46)

0.52 (0.21-1.30)

0.61 (0.04-0.23)

0.54 (0.20-1.47)

0.72 (0.24-2.11)

1.67 (0.14-20.05)

2.97 (0.99-8.86)

0.57 (0.28-1.12)

2.59 (1.50-4.47)

2.20 (1.12-4.32)

1.94 (0.73-5.12)

0.64 (.23-1.81)

Abbreviation: CE, cardioembolism.

*P .05.
P .001.
Not calculable because of lack of convergence in Cox regression.

E. KUMRAL ET AL.

154

Table 3. Univariate Cox regression analysis of severity of impairment(s) regarding origins of stroke and topography of lesions
in patients with hyperthermia versus normothermia
Risk ratio (95% CI)
Level A
(n 83)

Level B
(n 282)

Level C
(n 108)

LAA (n 199)
SAD (n 60)
CE (n 73)
Intracerebral hemorrhage (n 86)
Topography of Lesions

1.33 (0.9-2.3)
(0.001-0.54)
0.2 (0.22-2.92)
2.7 (0.89-5.56)

2.4 (1.1-3.8)
(0.54-4.71)
0.14 (0.09-0.28)
2.8* (0.89-3.9)

1.7 (1.3-2.1)

1.9* (1.5-2.8)

Total anterior circulation infarct (n 220)

Partial anterior circulation infarct (n 51)
Posterior circulation infarct (n 56)
Supratentorial hemorrhage (n 68)
Infratentorial hemorrhage (n 18)

0.9 (0.5-1.8)

0.8 (0.4-1.4)
0.6 (0.3-1.4)
0.26 (0.35-2.8)

1.7 (1.1-2.6)

1.8 (1.2-2.6)
0.7 (0.4-1.2)
0.4 (0.1-1.6)

2.3 (1.4-3.9)

3.0 (1.8-4.9)
1.9* (1.1-3.2)
4.5 (1.7-11.8)

Origins of stroke

Abbreviation: CE, cardioembolism.

*P .05.
P .001.
Not calculable because of lack of convergence in Cox regression.

At 3 months after stroke, 83 patients (18%) had no/

minimal deficit in any neurologic domain (level A), 35 of
247 (14%) patients with hyperthermia had mild deficit in
more than 1 neurologic domain (level B), and 47 of 61
(77%) hyperthermic patients had severe deficit in more
than 1 neurologic domain (level C). In logistic regression
analysis, hyperthermic patients with LAA and cardioembolism had significant severe neurologic deficit in more
than 1 neurologic domain compared with hypothermic
patients (P .0001) (Table 3). Regarding lesion site in
patients with total anterior circulation infarct (TACI),
posterior circulation infarct (PCI), supra- and infratentorial hemorrhage, hyperthermia was associated with severe neurologic deficit compared with hypothermia at 3
months after onset of stroke (P .001, P .0001, P .02,
P .001, respectively).

Discussion
Our findings suggest that body temperature in 3 days
of acute stroke affect the prognosis and mortality depending on origin and localization of lesion. A similar
trend for in-hospital poor prognosis was found in a
recent meta-analysis that included patients with ischemic
and hemorrhagic stroke.15 The cause of hyperthermia
after stroke and the effect of stroke subtypes with pyrexia
on the prognosis are not always evident. Among stroke
subtypes, patients with intraventricular or subarachnoid
hemorrhages and brain stem infarct seem to have greater
central or neurogenic fever.4,8 Patients with subarachnoid
hemorrhage were not included in the design of our study.

Another possible cause of pyrexia at stroke onset could

be a superimposed infection,4,9,21 but in our study, we
excluded any cause of sepsis by clinical and laboratory
examinations. Moreover, coexistent infection within the
first 3 days of stroke was not independently associated
with poor prognosis,9 and results from a previous study
generally support that fever may be directly related to the
size of the cerebral lesior.1
A previous study on human stroke showed that hyperthermia within 72 hours of stroke significantly may increase mortality and hyperthermia within the first 24
hours after stroke, which may cause significantly greater
morbidity.9 In our analysis, we used 72 hours fever data
affecting the prognosis of patients regarding the origin
and topography of lesions. We found that in patients
with large supratentorial hemorrhage, TACI and PCI,
coexistent pyrexia had a significant effect on mortality.
Moreover, hyperthermic patients with LAA and supratentorial hemorrhage had significantly greater morbidity
compared with those with normothermia. Recent studies
on hyperthermia-related brain damage in acute stroke
showed that there was a strong relationship between
intensity of hyperthermia within the first 24 hours and
larger infarct volume, higher neurologic deficit, and
dependency at 3 months.4,7 In contrast, hypothermia
( 36.5C) in ischemic stroke patients was associated
with a significant reduction of in-hospital mortality and
morbidity.10,22
The probable mechanism for the higher mortality and
morbidity after hyperthermia in ischemic stroke seems to
be related to the size of the area with functionally im-

EFFECT OF ORIGIN AND TOPOGRAPHY

paired but potentially viable tissue surrounding the irreversibly damaged tissue, called the ischemic penumbra.
Hyperthermia causes the transformation of ischemic penumbra into infarction and accelerates the development of
ischemic necrosis either by breaking the blood-brain barrier and changing cerebral blood flow at the vascular
level23 or by specific alterations in neurotransmitter
release,24 excitation of apoptosis, and increasing the inflammatory response at the molecular level.25,26 In hemorrhagic stroke, MRI evidence points to another pathophysiologic process rather than penumbral region,27 a
hypointense peripheral rim around the hematoma in the
acute phase that represents either early phagocytic activity or a boundary region between blood and brain.28 The
size of this critical zone in the large supratentorial hemorrhage could be a contributing factor, causing higher
incidence of mortality and morbidity in patients with
hyperthermia.
The level of fever is also an important predictor of
outcome in patients with stroke,3,7,10 but what the critical
threshold of detrimental fever is is still debatable. Experimental studies provide evidence that ischemic neuronal
injury may be increased significantly with even mild
hyperthermia of up to 2C above normal body temperature.3 We defined hyperthermia as body temperature
above 38C as in most of the previous studies.3,7,21 According to this criteria, we found that among the origins,
LAA, cardioembolism, and intracerebral hemorrhage
may cause severe neurologic deficits in more than 1
neurologic domain in the presence of hyperthermia compared with normothermia. In our study, topographic
analysis showed that patients with TACI, PCI, and supraand infratentorial hemorrhage with hyperthermia at
stroke onset seems to have detrimental effect in more
than 1 neurologic functional domain after 3 months of
stroke.
In conclusion, our data suggest that hyperthermia with
total anterior circulation infarct, posterior circulation infarct, and supratentorial hemorrhage is associated with a
marked increase of 3-month mortality. Large artery disease, cardioembolism, and supra- and infratentorial hemorrhage associated with hyperthermia may increase the
severity of neurologic deficits. Particularly in the acute
phase of stroke, therapeutic interventions against hyperthemia must remain one of the goals in the clinical setting
to prevent stroke progression.

References
1. Przelomski MM, Roth RM, Gleckman RA, et al. Fever in
the wake of a stroke. Neurology 1986;36:427-429.

155
2. Ginsberg MD, Strenau LL, Globus MY, et al. Therapeutic
modulation of brain temperature: Relevance to ischaemic brain injury. Cerebrovasc Brain Metab Rev 1992;
4:189-225.
3. Azzimondi G, Bassein L, Nonino F, et al. Fever in acute
stroke worsens prognosis. A prospective study. Stroke
1995;26:2040-2043.
4. Reith J, Jorgensen HS, Pedersen PM, et al. Body temperature in acute stroke: Relation to stroke severity, infarct
size, mortality, and outcome. Lancet 1996;347:422-425.
5. Davalos A, Castillo J, Pumar JM, et al. Body temperature
and fibrinogen are related to early neurological deterioration in acute ischemic stroke. Cerebrovasc Dis 1997;7:
64-69.
6. MacWalter R, McMahon A, Fraser H, et al. Does body
temperature on admission predict long-term outcome
after an acute stroke? Cerebrovasc Dis 1998;8:11 (suppl,
abstr).
7. Castillo J, Davalos A, Marrugat J, et al. Timing for
fever-related brain damage in acute ischemic stroke.
Stroke 1998;29:2455-2460.
8. Albrecht RF, Wass CT, Lanier WLL. Occurrence of potentially detrimental temperature alterations in hospitalized patients at risk for brain injury. Mayo Clin Proc
1998;73:629-635.
9. Ginsberg M, Busto R. Combating hyperthermia in acute
stroke: A significant clinical concern. Stroke 1998;29:529534.
10. Wang Y, Lim LLY, Levi C, et al. Influence of admission
body temperature on stroke mortality. Stroke 2000;31:
404-409.
11. Busto R, Dietrich WD, Globus MY, et al. Small differences in intraischemic brain temperature critically determine the extent of ischemic injury. J Cereb Blood Flow
Metab 1987;7:729-738.
12. Wass CT, Lanier WL, Hofer RE, et al. Temperature
changes of 1C alter functional neurologic outcome and
histopathology in a canine model of complete cerebral
ischemia. Anesthesiology 1995;83:325-335.
13. Kim Y, Busto R, Dietrich WD, et al. Delayed postischemic hyperthermia in awake rats worsens the histopathological outcome of transient focal cerebral ischemia. Stroke 1996;27:2274-2281.
14. Kakuda W, Naritomi H, Shimizu T, et al. Body temperature increases following embolic stroke correlating with
the size of infarction. J Cereb Blood Flow Metab 1997;
17:43 (suppl, abstr).
15. Hajat C, Hajat S, Sharma P. Effects of poststroke pyrexia
on stroke outcome. Stroke 2000;31:410-414.
16. Svensson LG, Crawford ES, Hess KR, et al. Deep hypothermia with circulatory arrest. Determinants of stroke
and early mortality in 656 patients. J Thorac Cardiovasc
Surg 1993;106:19-31.
17. Crowder CM, Tempelhoff R, Theard MA, et al. Jugular
bulb temperature: comparison with brain surface and
core temperature in neurosurgical patients during mild
hypothermia. J Neurosurg 1996;85:98-103.
18. Bamford J, Sandercock P, Dennis M, et al. Classification
and natural history of clinically identifiable subtypes of
cerebral infarction. Lancet 1991;337:1521-1526.
19. American Heart Association Stroke Outcome Classification. Stroke 1998;29:1275-1280.
20. Wade DT, Mewer RL. Functional abilities after stroke:

E. KUMRAL ET AL.

156

21.

22.

23.

24.

Measurement, natural history and prognosis. J Neurol

Neurosurg Psych 1987;50:177-182.
Terent A, Andersson B. Prognosis for patients with cerebrovascular stroke and transient ischaemic attacks.
Ups J Med Sci 981;86:63-74.
Wass CT, Lanier WL. Hypothermia-associated protection from ischemic brain injury: implications for patient
management. Int Anesthesiol Clin 1996;34:95-111.
Dietrich WD, Halley M, Valdes I, et al. Interrelationships
between increased vascular permeability and acute neuronal damage following temperature-controlled brain
ischaemia in rats. Acta neuropathol (Berl) 1991;81:615625.
Ginsberg MD, Busto R, Martinez E. The effects of cerebral ischaemia on energy metabolism. In: Schousboe A,
Diemer NH, Kofod H, eds. Drug Research related to

25.

26.

27.

28.

neuroactive Amino Acids: Alfred Benzon Symposium

32. Copenhagen, Denmark: Munksgaard; 1992:207-224.
Maier CM, Ahem KVB, Cheng ML, et al. Optimal depth
and duration of mild hypothermia in a focal model of
transient cerebral ischemia. Effects on neurologic outcome, infarct size, apoptosis, and inflammation. Stroke
1998;29:2171-2180.
Boisvert D. In vivo assessment of hydroxyl radical free
radical production in the brain. J Cereb Blood Flow
Metab 1991;11:S637 (abstr).
Hirano T, Read S, Abbott D, et al. No evidence of
ischaemic penumbra after cerebral hemorrhge. Cerebrovasc Dis 1998;8:53 (suppl, abstr).
Patel MR, Edelman RR, Warach S. Detection of hyperacute primary intraparenchymal hemorrhage by magnetic resonance imaging. Stroke 1996;27:2321-2324.