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Multiple Simultaneous Intracerebral Hemorrhages
Clinical Features and Outcome
Jorge Mauriño, MD;
Gustavo Saposnik, MD;
Sandra Lepera, MD;
Raul C. Rey, MD;
Roberto E. Sica, MD
Arch Neurol. 2001;58:629-632.
ABSTRACT
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Background The simultaneous occurrence of intracerebral hemorrhages in different
arterial territories is an uncommon clinical event. Its predisposing factors
and pathophysiological mechanisms are not clearly defined.
Objective To analyze the frequency, risk factors, clinical features, neuroimaging
findings, and outcome of multiple simultaneous intracerebral hemorrhages (SIHs).
Patients and Methods We studied all patients with acute stroke admitted to our hospital from
July 18, 1997, through December 18, 1999. Multiple SIHs were defined as the
presence of 2 or more intracerebral hemorrhages affecting different arterial
territories with identical computed tomographic density profiles. Patients
with a history of traumatic brain injury were excluded from this study. Diagnostic
investigation included routine blood and urine tests, coagulation studies,
a chest radiograph, electrocardiogram, 2-dimensional transthoracic echocardiography,
and computed tomography of the head without contrast medium. Disability was
assessed using the National Institutes of Health Stroke Scale and Modified
Rankin Scale.
Results Among 142 patients with hemorrhagic stroke, we found 4 (2.8%) with SIHs.
All 4 patients had a history of uncontrolled arterial hypertension. We excluded
other potential causes of multiple SIHs by using appropriate diagnostic tests.
The most common clinical manifestations were headache and weakness. Localization
of hematomas was supratentorial, except for one patient who had both infratentorial
and supratentorial hemorrhages. The mean National Institutes of Health score
on admission was 15 and the Modified Rankin Scale score was higher than 4
at 3 months.
Conclusions In our study, all patients with multiple SIHs had arterial hypertension
and a poor outcome. Additional analytic studies, including new imaging techniques,
can help to elucidate the association between arterial hypertension and multiple
SIHs, risk factors, and underlying mechanisms of this clinical condition.
INTRODUCTION
THE SIMULTANEOUS occurrence of intracerebral hemorrhages (ICHs) in different
arterial territories is uncommon.1, 2, 3
The predisposing pathologic factors and underlying mechanisms involved in
this clinical condition have not been clearly defined.2, 3
Historically, multiple simultaneous intracerebral hemorrhages (SIHs) were
associated with hematologic disorders, vasculitis, anticoagulant therapy,
illicit drug use, cerebral amyloid angiopathy, or were due to multiple infarctions
with hemorrhagic transformation.4, 5
In 1981, Weisberg2 described multiple
SIHs in 12 patients without finding any identifiable causative factor. Later,
Seijo et al3 reported another 7 cases of multiple
SIHs. Three of the 7 cases were associated with hematologic disorders. To
our knowledge, these are the 2 largest series describing multiple SIHs. This
study analyzes the frequency, risk factors, clinical features, neuroimaging
findings, and outcome of multiple SIHs.
PATIENTS AND METHODS
We studied all consecutive patients who had an acute stroke and were
admitted to our hospital from July 18, 1997, through December 18, 1999. Patients
with traumatic brain injury were excluded from this study. Diagnostic investigation
included the following: routine blood and urine tests, coagulation studies,
a chest radiograph, electrocardiogram, 2-dimensional transthoracic echocardiography,
and computed tomography of the head without contrast medium. Magnetic resonance
imaging, transesophageal echocardiography, and magnetic resonance angiography
were performed when necessary. All patients were evaluated by at least 2 neurologists
(J.M. and G.S.), one of them specializing in cerebrovascular diseases. Patients'
data were recorded on a form that included the following: date and time of
admission, risk factors, symptoms at onset, neurologic examination findings,
National Institutes of Health Stroke Scale score, and brain templates based
on Damasio's article6 for lesion location.
Outcome at 3 months was determined by Modified Rankin Scale score (>4).
Risk factors were defined as follows: arterial hypertension, systolic
pressure greater than 160 mm Hg and/or diastolic pressure greater than 90
mm Hg for more than 2 examinations, use of antihypertensive drugs, previous
medical diagnosis of hypertension, or any combination of these; tobacco use,
daily use of more than 10 cigarettes during the previous 6 months; diabetes
mellitus, fasting glucose level higher than 6.7 mmol/L (>120 mg/dL) at the
time of admission; hypercholesterolemia, fasting cholesterol level higher
than 5.69 mmol/L (>220 mg/dL); and alcohol use, ingestion of more than 100
g/d of alcohol during the previous 2 months. Hemorrhagic stroke was defined
as a sudden development of neurologic deficit with ICH or subarachnoid hemorrhage
on cerebral computed tomography or magentic resonance imaging. Multiple SIHs
were defined as the presence of 2 or more ICHs affecting different arterial
territories with identical computed tomographic density profiles. All brain
images were evaluated by a radiologist, who was blinded to the neurologic
condition.
RESULTS
Among 507 patients who had a stroke and who were admitted during the
study period, 187 (37%) had a hemorrhagic stroke. Forty-five patients (24%)
had subarachnoid hemorrhage and 142 (76%) had ICHs. Among those patients with
ICHs, we found 4 (2.8%) with SIHs (mean age, 55 years; age range, 40-63 years).
All patients with multiple SIHs had a history of arterial hypertension. We
excluded other causes of multiple SIHs by appropriate diagnostic testing.
Risk factors of patients with a single ICH and multiple SIHs are summarized
in Table 1. The most frequent
symptoms at presentation were headache and weakness. The mean National Institutes
of Health score on admission in patients with ICHs and multiple SIHs was 12
and 15, respectively. In multiple SIHs, all hematomas were supratentorial,
except for 1 patient (patient 2) who had a right thalamic and a left cerebellar
hemorrhage (Figure 1). The Modified
Rankin Scale score was higher than 4 at 3 months. Clinical features of patients
with multiple SIHs are given in Table 2.
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Table 1. Frequency of Risk Factors*
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A, Patient 2. Brain computed tomographic scan with no contrast medium
shows a right thalamic and a left cerebellar hemorrhage. B, Patient 1. Brain
computed tomographic scan with no contrast medium shows hemorrhage on the
left side of the thalamus and the right side of the putamen.
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Table 2. Characteristics of Patients With Simultaneous Intracerebral
Hemorrhages*
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COMMENT
Multiple SIHs have been observed in only 2% to 3% of hemorrhagic strokes.1, 2, 3 There is no agreement
between different authors about the predisposing factors and underlying mechanisms
involved. McCormick and Rosenfield4 described
16 patients with multiple ICHs. Nine had leukemia, 3 had other bleeding disorders,
2 had neoplasms, and 2 had vasculitis. Among 600 patients with hemorrhagic
stroke, Weisberg2 found 12 (2%) with multiple
SIHs. Hemorrhages affected the following areas: the lobe (8 patients), the
lobe and putamen (2 patients), thalamus and cerebellum (1 patient), and cerebellum
only (1 patient). Only 2 patients had a history of arterial hypertension.
No identifiable precipitating factors were found in the other patients. Seijo
et al3 found 7 patients (2.3%) with multiple
SIHs among 297 individuals with ICHs. The location of the bleedings was supratentorial
in all cases. Three patients had hematologic disorders and the other 3 had
hypertension. Cerebral amyloid angiopathy has also been associated with multiple
ICH although it generally occurs in nonhypertensive individuals older than
65 years, sparing the basal ganglia and cerebellum.5
As defined in the literature, arterial hypertension is the major cause of
single intracerebral hematoma. Infrequently, it has been associated with multiple
SIHs.2, 3, 7 In agreement
with previous reports from Japan8, 9, 10
and with other anecdotal cases,11, 12
all of our patients had a history of uncontrolled arterial hypertension. Only
1 patient with multiple SIHs was being treated with 10 mg/d of oral enalapril
prior to admission to our hospital. The remaining 3 patients discontinued
antihypertensive treatment in the 3-month period before the hemorrhages occurred.
On admission, sodium nitroprusside infusion was used to titrate blood pressure
in 2 patients.
In addition, the topographic pattern of the bleeding was similar to
the usual location of single hypertensive hematomas. We have not found any
other potential cause of ICH such as, hematologic disorders, multiple infarctions
with hemorrhagic transformation, vasculitis, or anticoagulant use. Although
amyloid angiopathy may also be a differential diagnosis, the localization
of the hematomas makes this consideration unlikely. Thus, multiple SIHs in
our patients may probably be related to arterial hypertension. The pathophysiological
mechanisms of multiple SIHs still remain uncertain. Anatomopathologic studies
showed degenerative changes due to hypertension (eg, lipohyalinosis and Charcot-Bouchard
aneurysms) in penetrating arteries. These vulnerable wall segments may be
directly related to the occurrence of multiple hemorrhages in more than 1
arterial region.7 Komiyama et al13
found simultaneous bleeding from multiple lenticulostriate arteries in a man
with hypertension and ICHs by conventional cerebral angiography. Broderick
et al14 found that some patients with ICHs
had an increase in hemorrhage volume. Most of them were persistently hypertensive
during the early course of the bleeding. Broderick et al suggested that reactive
hypertension might be the cause of continued bleeding. Recently, new techniques
with gradient-echo magnetic resonance imaging have shown multiple asymptomatic
microhemorrhages in patients with chronic hypertension and ischemic stroke
that were not seen on computed tomographic scan.15, 16
Kwa et al17 found that 26% of the patients
who had ischemic stroke also had evidence of hemosiderin deposits coexisting
with white matter lesions on brain magnetic resonance imaging.
We hypothesize that sustained hypertension during a cerebral hemorrhage
could trigger another bleeding owing to acute vascular changes in the penetrating
arteries, affecting previously injured intima and media layers. The confirmation
of such consideration may influence the acute management of arterial blood
pressure after hemorrhagic stroke.
We understand that our study has several limitations. First, this is
a case-series design. These types of studies are useful for hypothesis formulation,
but not for testing the presence of a valid statistical association. Another
limitation constitutes the lack of a control group. Thus, risk factors or
predisposing conditions, even suggestive, may simply be coincidental. Second,
the frequency of multiple SIHs in this study could be biased because of the
high incidence of ICHs in our population. However, our hospital is not a referral
center. We presume that several factors could be involved, such as a poor
control of blood pressure, high consumption of alcohol, or ethnicity.
In conclusion, simultaneous intracerebral bleeding may be more common
than reported. Further analytic studies, including new imaging techniques,
are necessary to determine the association between arterial hypertension and
multiple SIHs, the predisposing factors, and underlying pathophysiological
mechanisms.
AUTHOR INFORMATION
Accepted for publication July 20, 2000.
We thank Jose A. Bueri, MD, for his helpful comments and assistance.
From the Department of Neurology, Stroke Service, Hospital J. M. Ramos
Mejía, Universidad de Buenos Aires, Buenos Aires, Argentina.
Corresponding author: Jorge Mauriño, MD, Department of Neurology,
Hospital J. M. Ramos Mejía, Soler 4019, Sexto Piso, Buenos Aires 1425,
Argentina (e-mail: jorgemaurino{at}hotmail.com).
REFERENCES
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1. Freytag E. Fatal hypertensive intracerebral haematomas: a survey of the pathological
anatomy in 393 cases. J Neurol Neurosurg Psychiatry. 1968;31:616-620.
ISI
| PUBMED
2. Weisberg L. Multiple spontaneous intracerebral hematomas: clinical and computed
tomographic correlations. Neurology. 1981;31:897-900.
FREE FULL TEXT
3. Seijo M, Ucles A, Gil-Nagel A, Balseiro J, Calandre L. Hematomas cerebrales múltiples: revisión de siete casos. Rev Neurol. 1996;24:549-553.
PUBMED
4. McCormick WF, Rosenfield DB. Massive brain hemorrhage: a review of 144 cases and an examination
of their causes. Stroke. 1973;4:946-954.
ABSTRACT
5. Gilles C, Brucher JM, Khoubesserian P, Vanderhaeghen JJ. Cerebral amyloid angiopathy as cause of multiple intracerebral hemorrhages. Neurology. 1984;34:730-735.
FREE FULL TEXT
6. Damasio H. A computed tomographic guide to the identification of cerebral vascular
territories. Arch Neurol. 1983;40:138-142.
ABSTRACT
7. Hickey WF, King RB, Wang AM, Samuels MA. Multiple simultaneous intracerebral hematomas: clinical, radiologic,
and pathologic findings in two patients. Arch Neurol. 1983;40:519-522.
ABSTRACT
8. Tanikake T, Kawaguchi S, Tada T, Kyoi K, Utsumi S, Nakasone K. Simultaneous, bilateral hypertensive intracranial hematomas [in Japanese]. No Shinkei Geka. 1983;11:1085-1090.
PUBMED
9. Tanno H, Ono J, Suda S, et al. Simultaneous, multiple hypertensive intracerebral hematomas: report
of 5 cases and review of the literature [in Japanese]. No Shinkei Geka. 1989;17:223-228.
PUBMED
10. Uno M, Hondo H, Matsumoto K. Simultaneous supra- and infratentorial hypertensive intracerebral hemorrhage
[in Japanese]. No Shinkei Geka. 1991;19:933-938.
PUBMED
11. Verstichel P, Riss J, Raybaud C, Brosset C, Dano P. Hémiparésie ataxique et hématomes simultanés
sus et sous-tentoriels. Rev Neurol (Paris). 1991;147:671-673.
PUBMED
12. Guerrero A, Benito-Leon J, Tembl J, Ramos A. Simultaneous supra- and infra-tentorial brain hemorrhage probably caused
by hypertension [letter in Spanish]. Neurologia. 1997;12:320-322.
PUBMED
13. Komiyama M, Yasui T, Tamura K, Nagata Y, Fu Y, Yagura H. Simultaneous bleeding from multiple lenticulostriate arteries in hypertensive
intracerebral haemorrhage. Neuroradiology. 1995;37:129-130.
ISI
| PUBMED
14. Broderick JP, Brott TG, Tomsick T, Barsan W, Spilker J. Ultra-early evaluation of intracerebral hemorrhage. J Neurosurg. 1990;72:195-199.
ISI
| PUBMED
15. Offenbacher H, Fazekas F, Schmidt R, Koch M, Fazekas G, Kapeller P. MR of cerebral abnormalities concomitant with primary intracerebral
hematomas. AJNR Am J Neuroradiol. 1996;17:573-578.
ABSTRACT
16. Chan S, Kartha K, Yoon SS, Desmond DW, Hilal SK. Multifocal hypointense cerebral lesions on gradient-echo MR are associated
with chronic hypertension. AJNR Am J Neuroradiol. 1996;17:1821-1827.
ABSTRACT
17. Kwa VI, Franke CL, Verbeeten B Jr, Stam J for the Amsterdam Vascular Medicine Group. Silent intracerebral microhemorrhages in patients with ischemic stroke. Ann Neurol. 1998;44:372-377.
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