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(Stroke. 1995;26:1020-1023.)
© 1995 American Heart Association, Inc.
Articles |
Acute Leukocyte and Temperature Response in Hypertensive Intracerebral Hemorrhage
From the Departments of Neurology (S.S., R.E.K., B.K.D., Y.R.-I., W.D.D.) and Medical Oncology, Division of Biostatistics (R.C.D.), University of Miami School of Medicine (Fla).
Correspondence to Roger E. Kelley, MD, Department of Neurology, Louisiana State University Medical Center, 1501 Kings Hwy, PO Box 33932, Shreveport, LA 71130-3932.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Background and Purpose We undertook this study to investigate the relationship between outcome, hematoma volume, and admission peripheral white blood cell count and body temperature in acute hypertensive intracerebral hemorrhage.
Methods Eighty-two consecutive patients who presented with hypertensive intracerebral hemorrhage within 72 hours of onset were retrospectively assessed. The peripheral white blood cell count, polymorphonuclear leukocytes, and the body temperature on admission were measured. The outcome at 30 days after ictus was determined with a modified Glasgow Outcome Scale. Correlation analysis was performed between these measurements and hematoma volume, which was calculated by brain computed tomography. We also looked at the presence or absence of intraventricular extension.
Results The mean hematoma volume was significantly greater in those patients who died compared with those with a good, moderate, and severe outcome (79.6 cm3 versus 10.7, 18.3, and 19.9 cm3, respectively; P<.0005). The mean peripheral white blood cell count was higher in those who died than in the other three groups (12.580±0.521 versus 8.160±0.543, 8.565±0.543, and 7.427±0.786x109/L, respectively; P<.0005). The mean body temperature of those who died tended to be higher than those in the good-outcome group (99.12±0.21 versus 98.18±0.21°F, P<.05). A positive linear correlation was observed between hematoma volume and white blood cell count (r=.506, df=77, P<.001), as well as the polymorphonuclear leukocyte count (r=.561, df=76, P<.001). A trend was also observed for admission temperature (r=.265, df=74, P<.05). The leukocyte response was enhanced by the presence of intraventricular extension.
Conclusions There is a relationship between the size of the hematoma and the degree of leukocytosis in hypertensive intracerebral hemorrhage. This relationship appears to most likely represent a stress-induced reaction of the white blood cell count.
Key Words: intracerebral hemorrhage • leukocytes • prognosis • temperature
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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A relationship between an increased peripheral white blood cell (WBC) count and a poorer prognosis in patients with acute myocardial infarction1 and subarachnoid hemorrhage2 3 has been reported. After acute cerebral infarction, there is typically an elevation of the WBC count,4 specifically in the polymorphonuclear leukocyte (PMNL) fraction.5 This peripheral PMNL response correlates with the extent of cerebral infarction.5 A possible relationship between the volume of hypertensive intracerebral hemorrhage (ICH) and leukocyte response has not been assessed to the best of our knowledge.
Also of pertinence, experimental ischemic stroke models have demonstrated that small variations in body and brain temperature can have an impact on prognosis.6 7 8 9 Clinically, in severe brain stem hemorrhage, hyperthermia frequently is associated with a poorer prognosis.10 In patients with severe head injury, the intracranial temperature was observed to be higher than the body temperature,11 and it is possible that body or brain temperature could be indicative of the prognosis in ICH patients.
In this study, we investigated the relationships between leukocyte response, body temperature, volume of ICH, and outcome at 30 days after ictus.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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We assessed 384 consecutive patients with ICH who were admitted to our medical center between January 1, 1989, through December 31, 1993. A CT brain scan was obtained for all patients to document ICH. The diagnosis of hypertensive ICH was based on history of hypertension, medications on admission, hypertensive retinopathy, and/or evidence of left ventricular hypertrophy determined by electrocardiogram or echocardiogram. We excluded patients with a postictal period of greater than 72 hours and those with a hemorrhage secondary to a bleeding diathesis, brain tumor, or vascular anomaly, as well as patients with infratentorial hemorrhage. We also excluded patients with lobar hemorrhage, since only approximately 50% of such patients have hypertension as the primary mechanism.12 13 In addition, we eliminated patients with infection, inflammatory disease, and acute ischemic heart disease and patients on immunosuppressive therapy.
This resulted in a total study population of 82 subjects. All patients who survived were followed up for at least 30 days. The inclusion of only those subjects with a "pure" hypertension-mediated ICH allowed us to minimize the possibility of a superimposed process (eg, illicit drug use or mycotic aneurysm) that might influence the potential leukocyte or temperature response.
A CT brain scan was obtained on admission, and the volume of the high-attenuation zone was calculated as the hematoma volume. The hematoma volume was calculated with the following formula14 15 : hematoma volume=(axbxc)/2, where a is the maximal length, b is the maximal width, and c is the number of 10-mm slices. This method correlates well with a more sophisticated planimetric measurement of volume.16 17 The presence or absence of ventricular extension of the hemorrhage was also assessed.
Prognosis was determined by a modification of the Glasgow Outcome Scale.18 This scale consists of five categories: 1, death; 2, persistent vegetative state; 3, severe disability; 4, moderate disability; and 5, good recovery. For simplification and to enhance statistical power, it was modified into four categories: 1, death; 2, severe disability; 3, moderate disability; and 4, minor disability.
A peripheral WBC with differential was obtained for all subjects within 72 hours of ictus. Possible relationships between hematoma volume and the peripheral WBC count, PMNL count, and body temperature on admission were assessed by Pearson's correlation coefficient analysis.19 The difference in hematoma volume, peripheral WBC count, and body temperature on admission among the four prognostic groups was examined by one-way ANOVA, followed by Tukey's intergroup comparison test.20 Student's t test was used for between-group analysis of the presence or absence of ventricular rupture. Because of multiple comparisons, the Bonferroni correction21 resulted in a significance level of P<.01.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The 82 patients were classified into one of four groups according to the above-cited outcome scale. Table 1
presents
age, sex, hematoma volume, admission body temperature, frequency of
ventricular rupture, and peripheral WBC counts in each group. There was
no significant difference in age or sex among the groups. When the
group of those who died was compared with the groups with minor,
moderate, and severe disability, the hematoma volume was significantly
greater in those who died, with a mean±SEM of 79.6±6.3
cm3 versus 10.7±6.7, 18.3±6.7, and 19.9±10.5
cm3, respectively; P<.0005 (Fig 1A).
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The patients who died had a significantly higher peripheral WBC count
on average than the other three groups (12.580±0.521 versus
8.160±0.543, 8.565±0.543, and 7.427±0.786x109/L,
respectively; P<.0005) (Fig 1B
). This was also observed for
the peripheral PMNL count, where those patients who died had a count of
10.372±0.519 versus 5.418±0.541, 5.947±0.541, and
5.383±0.782x109/L, respectively;
P<.0005 (Fig 1C). To assess a possible relationship between
the magnitude of the WBC count and hemorrhage onset, we looked at the
mean±SEM WBC and PMNL count values as a function of four time
intervals from ictus (Table 2). There was no significant
difference in the WBC count between the four time intervals by ANOVA
(P=.145), nor was there a difference in the PMNL count
(P=.378).
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To assess a possible relationship between WBC count and outcome, as a
function of hematoma volume, we looked at patients with an ICH volume
of 
29 cm3 compared with 
30 cm3 (Table 3). This volume delineation was based on a previously
described criterion of Broderick et al.16 The comparison
by ANOVA was not statistically significant for either the WBC count
(P=.39) or the PMNL count (P=.09), although the
WBC and PMNL counts were higher on average in the 22 patients with
larger hematomas who died. The body temperature on admission tended to
be higher in patients who died compared with those in the
minor-disability group (99.12±0.21°F versus 98.18±0.21°F,
P<.05) (Fig 1D).
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We found a statistically significant positive linear relationship
between hematoma volume and peripheral WBC count (r=.506,
df=77, P<.001; Fig 2A) as well as
for the PMNL count (r=.561, df=76,
P<.001; Fig 2B). We also observed a trend toward a positive
linear relationship between hematoma volume and admission body
temperature (r=.265, df=74, P<.05;
Fig 2C). However, the correlation analyses of each of the four
subgroups, as a function of clinical outcome, did not show a
significant linear relationship.
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The presence or absence of intraventricular extension was
analyzed with reference to hematoma volume, peripheral WBC count,
peripheral PMNL count, and admission body temperature. A relationship
was observed between the presence of intraventricular blood and
hematoma volume: 54.87±7.7 cm3 with ventricular rupture
versus 14.1±2.5 cm3 without (mean±SEM),
P<.0005 (Fig 3A). A relationship was also
observed between the peripheral WBC count of
10.721±0.554x109/L with ventricular rupture versus
8.211±0.455x109/L without, P<.002 (Fig 3B). This latter finding was reflective of the peripheral PMNL count
(8.473±0.583x109/L versus
5.507±0.341x109/L, P<.0005; Fig 3C).
The relationship with admission body temperature was of borderline
significance (98.82±0.22°F versus 98.25±0.12°F,
P<.05; Fig 3D).
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Hematoma volume has been reported to be the strongest predictor of 30-day outcome for all locations of spontaneous ICH.16 Our data are in agreement with this finding. We observed that the severity of the hemorrhagic insult was reflected in the peripheral WBC count, especially the PMNL count, and there was a tendency for the admission body temperature to be higher in those subjects with larger hematomas and a resultant poorer prognosis.
Jenkins et al22 found that leukocytic infiltration within intracerebral hematoma from adjacent vessels peaked at 24 to 48 hours in an experimental model. Therefore, if a marked leukocytic response is observed in a patient with acute ICH, one would expect that the mechanism would more likely reflect a stress-induced response rather than a local inflammatory response in brain. Such a stress-induced mechanism of leukocytosis remains speculative, however.
In subarachnoid hemorrhage, Neil-Dwyer and Cruickshank2 reported a significant elevation of the WBC count in association with deteriorating level of consciousness, cerebral vasospasm, and death. Parkinson and Stephensen3 noted that as the initial WBC count exceeds 20 000 in subarachnoid hemorrhage a poorer clinical outcome is observed. The mechanism of the increased WBC count was attributed to enhanced catecholamine release and corticosteroid production.2 Our study demonstrates that ventricular extension of the hematoma promotes a greater rise in the WBC count and reflects a larger hematoma volume than in the nonruptured group. This may be explained by augmented catecholamine release and corticosteroid production due to extension of the blood into the subarachnoid space, but the inflammatory response of ventricular extension, ie, ventriculitis, might also be a contributing factor.
We observed a relationship between admission body temperature and hematoma volume. Patients had a worse prognosis, in general, when there was intraventricular extension of the hematoma, and this was associated with a trend toward higher body temperature. The mechanism of rising body temperature is possibly related to stimulation of the thermoregulatory center of the hypothalamus by the hematoma itself or by blood in the third ventricle after the rupture of the hematoma.23
In summary, our study is in agreement with prior reports that demonstrated that the peripheral WBC count, specifically the PMNL count, reflects the degree of brain insult. Because we excluded patients with evidence of infection or other systemic processes, this peripheral leukocytosis appears most likely to be a stress-induced response.
Received October 11, 1994; revision received March 9, 1995; accepted March 9, 1995.
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