Special Article

Nontraumatic Brain Hemorrhage in Children:

Etiology and Presentation
Ahmed Al-Jarallah, MD; Muhammad T. Al-Rifai, MD; Anthony R. Riela, MD; E. Steve Roach, MD

ABSTRACT

The clinical and radiographic findings of 68 children and adolescents with nontraumatic intraparenchymal brain hemor-
rhage were analyzed retrospectively. There were 43 boys and 25 girls, and the average age was 7.1 years (range, 3 months
to 18 years). The most common presenting symptom was a combination of headache or vomiting (40 cases, or 58.8%).
Hemiparesis was the major presenting sign in 11 (16.2%) of the children, seizures occurred in 25 (36.8%) patients, and 6
(8.8%) children were irritable. Only 2 (2.9%) children were comatose at presentation. One or more risk factors for hemor-
rhage were found in 61 (89.7%) of 68 children. A third (23 cases, or 33.8%) had an arteriovenous malformation or fistula;
altogether 29 (42.6%) children had some type of congenital vascular anomaly. Hematologic or coagulation disorders were
present in 22 (32.4%) patients, and 9 (13.2%) patients had brain tumors. Hemorrhage could not be attributed to systemic
hypertension in any child. The likelihood of establishing the cause of bleeding was greater when evaluation included cere-
bral angiography (97.3% versus 80.4% without angiography). Half (34 cases, or 50.0%) of the patients regained normal
neurologic function. Six (8.8%) patients died, either directly or partly as a consequence of the hemorrhage. The remaining
patients had various neurologic sequelae, including 17 (25.0%) with hemiparesis, 5 (7.4%) with aphasia, 7 (10.3%) with
epileptic seizures, and 3 (4.4%) with hydrocephalus. More detailed follow-up studies are needed to obtain more informa-
tion about the frequency of cognitive sequelae. ( J Child Neurol 2000;15:284-289).

Population surveys indicate that cerebral hemorrhage is of children with intraparenchymal hemorrhage in the light
more common than ischemic infarction in children, even of modem diagnostic techniques.
when neonatal intraventricular hemorrhage and traumatic
lesions are excluded.’,’ Structural vascular lesions are the PATIENTS AND METHODS
greatest risk factor in children with spontaneous intra-
parenchymal hemorrhage, but numerous other conditions We reviewed the medical records and radiographs for all children
also promote brain hemorrhage in children.3,4 The cause of with nontraumatic intracranial hemorrhage seen at University of
an intracranial hemorrhage is more likely to be identified Texas Southwestern Medical Center and Children’s Medical Center
than the cause of a cerebral infarction; nevertheless, before hospital during the 8.5 years between January 1990 and July 1998.
the advent of newer neuroimaging techniques and coagu- Patients with traumatic hemorrhage and neonates were excluded.
lation assays, many brain hemorrhages in children remained Data were collected on patients with nontraumatic subdural and sub-
unexplained. The purpose of this paper is to analyze the clin- arachnoid hemorrhage without intraparenchymal hemorrhage.
ical features, risk factors, and outcomes of a large cohort However, only children with intraparenchymal brain hemorrhage
(with or without subdural or subarachnoid hemorrhage) are included
in this report.
Each patient’s medical record was reviewed to determine age,
Received July27, 1999. Accepted for publication August 9, 1999. clinical presentation, radiographic findings, outcome, and possible
From the Division of Child Neurology, University of Texas Southwestern risk factors for hemorrhage. Not every child was seen by the authors
Medical Center and Children’s Medical Center, Dallas, TX. and the varied.
diagnostic approach Radiographic studies were
Presented in part at the 27th meeting of the Child Neurology Society, reviewed whenever possible. A few of the initial radiographs done
Montreal, Canada, October 14-16, 1998.
in other institutions were unavailable for review, and for these
Address correspondence to Dr E. Steve Roach, Department of Neurology,
University of Texas Southwestern Medical School, 5323 Harry Hines Blvd, patients the radiology interpretation recorded in the medical records
Dallas, TX 75235. Tel: 214-456-8163; fax: 214-456-6108. was tabulated.

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Table 1. Initial Presentation of Intraparenchymal Brain Hemorrhage with irritability (Table 1). Focal (6 patients) and generalized
(19 patients) seizures were also common (36.8% combined),
but both coma (2 of 68, or 2.9%) and hemiparesis (11 of 68,
or 16.2%) occurred less often than expected. An acute hem-

orrhage was found unexpectedly in one child who was eval-

uated because of an enlarging head circumference.
The authors were not involved in all of the patients’ care,
and the extent of the diagnostic evaluation and the avail-
ability of follow-up information varied substantially. A major
risk factor for hemorrhage was found in 61 of 68 (89.7%) chil-
dren (Table 2). One-third (23, or 33.8%) had an arteriovenous
malformation or fistula. Altogether, 29 (42.6%) children had
some type of vascular anomaly, including arterial aneurysm,
cavernous malformation, arteriovenous malformation, or
Subtotals in italics. arteriovenous fistula. Almost all of these lesions were con-
*Some patients are listed more than once.
genital anomalies (Figure 1), although one child had a
mycotic arterial aneurysm.
Thrombocytopenia was the most common (8 of 68, or
RESULTS 11.8%) hematologic risk factor for brain hemorrhage. Five
patients developed thrombocytopenia from cancer
Sixty-eight patients with nontraumatic intraparenchymal chemotherapy, two from isoimmune thrombocytopenia,
brain hemorrhage were identified. Sixty of these 68 children and one patient had thrombocytopenia-absent radius (TAR)
had only intraparenchymal brain hemorrhage, 6 had brain syndrome. Three patients with sickle cell disease (ages 6,
and subdural hemorrhage, and 2 had both intraparenchymal 4, and 2.5 years) developed an intraparenchymal hemor-
and subarachnoid hemorrhage. There were 43 boys and 25 rhage. At least one of these three children had a well-doc-
girls, and the average age was 7.1 years (range, 3 months to umented hemorrhagic infarction. Two additional patients
18 years). with sickle cell disease with only subarachnoid hemorrhage
Not surprisingly, over half of the children presented with were excluded.
symptoms suggestive of increased intracranial pressure. Ten (14.7%) patients with various congenital or acquired
Forty (58.8%) children presented with the dominant symp- coagulation defects were encountered. Factor VIII defi-
toms of headache and/or vomiting, and 6 (8.8%) presented ciency (three patients) and coagulopathy secondary to
hepatic failure (two patients) were the most common coag-
ulopathies in this series. One patient had factor XIII defi-
Table 2. Risk Factors for Intraparenchymal Hemorrhage* ciency, and a 3-month-old boy suffered a subdural and
intraparenchymal hemorrhage due to vitamin K deficiency
following his birth without vitamin K supplementation. One
child’s hemorrhage was attributed to warfarin. One child had
protein C deficiency and one protein S deficiency; these defi-
ciencies usually promote thrombosis with infarction and not
hemorrhage, so both of these children likely suffered a
hemorrhagic infarction.
Nine (13.2%) patients bled into the region of a brain
tumor (Figure 2). Although tumor was usually suspected after
imaging studies were completed, these patients were nonethe-
less included since initial presentation was sufficiently acute
to suggest a clinical diagnosis of brain hemorrhage and ini-
tial neuroimaging studies indicated hemorrhage into the
tumor or adjacent brain parenchyma. Various histologic
types of malignant brain tumor were found.
A few children had modestly elevated systemic blood
pressure at presentation, but none had long-standing arte-
rial hypertension or markedly elevated blood pressure read-
ings. It was concluded that systemic hypertension did not
cause the hemorrhage in these children.

Thirty-six (52.9%) patients underwent standard cerebral

Subtotals in italics.
*Some patients had more than one risk factor. angiography. The likelihood of establishing the cause of bleed-
’One patient had a mycotic aneurysm, the others had saccular aneurysms. ing was greater when evaluation included standard cerebral

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Figure 1. A, Magnetic resonance scan reveals the flow void of an arte-

riovenous malformation in the left parietal region (arrowhead); B, Com-
puted cranial tomography of the same patient after clinical deterioration
shows an intraparenchymal hemorrhage in the same area; C, Angio-
graphy confirmed the arteriovenous malformation (arrow).

DISCUSSION

Clinical Presentation
Thirty-one children presented with headache and 14 with
vomiting (Table 1). A combined 40 (58.8%) of 68 children pre-
sented with the dominant symptoms of headache or vom-
iting, similar to the frequency of headache and vomiting seen
in adult patients with intraparenchymal hemorrhage.5 It
was surprising, however, that only two (2.9%) children pre-

sented with coma.

Epileptic seizures occurred acutely in 25 (36.8%) of 68
children. Six of these patients had recognizable focal
angiography. A probable cause for the hemorrhage was iden- seizures, and 19 had generalized seizures. Others have also
tified in 35 (97.2%) of 36 patients who had angiography ver- reported a similar seizure frequency in children with brain
sus 26 (81.3%) of 32 in the group without angiography. The hemorrhage. Yang and colleagues, for example, mention 3
timing of angiography after hemorrhage varied, but no major children with acute seizures among 12 children with brain
complications resulted from the angiography. hemorrhage, similar to the seizure frequency in the current
The degree of recovery varied with the size and intracra- series, but substantially less than the 49.3% these authors
nial location of the hemorrhage. Half (34, or 50.0%) of the recorded in children with cerebral infarction.66
patients regained normal neurologic function. Six (8.8%)
patients died directly or partly as a consequence of the Risk Factors
hemorrhage. The remaining patients had various neurologic A likely cause of hemorrhage was identified more often in
sequelae including hemiparesis (17 of 68, or 25.0%), apha- the patients in the series presented here than in previ-
sia (5, or 7.4%), epileptic seizures (7, or 10.3%), and hydro- ously published series, perhaps reflecting the availability
cephalus (3, or 4.4%). Various cognitive defects were of noninvasive diagnostic tests and perhaps the aggressive
documented in nine (13.2%) children. Unfortunately, formal diagnostic approach taken for children with unexplained
follow-up assessment was not done for many of the children, hemorrhage. While only 36 of 68 children with intra-
limiting the ability to precisely document clinical outcome. parenchymal or subarachnoid hemorrhage underwent

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Figure 2. A, Computed cranial tomography of a boy with an anaplas-

tic oligodendroglioma reveals a hematoma with a blood-fluid level in
the left frontal lobe (arrows), an atypical appearance for an isolated
intracerebral hemorrhage; B, Coronal view of his magnetic resonance
scan revealed a large tumor (arrowheads) with a marked left to right
shift; C,The tumor is surrounded by a ring of gadolinium contrast
enhancement.

A common approach is to curtail diagnostic evalua-

tion once a probable cause has been established unless
there is reason to suspect more than one risk factor. For
example, a cerebral angiogram is probably unnecessary for
a child known to have a coagulopathy, and children with a

known arteriovenous malformation also are not routinely

tested for coagulopathy. However, children with unex-
plained hemorrhage should have a complete evaluation,
including standard four-vessel cerebral angiography, in
order to identify potentially treatable risk factors before
another hemorrhage occurs. A normal angiogram done
immediately after a hemorrhage sometimes fails to reveal
the source of bleeding, probably because local tamponade
from the hemorrhage occludes the abnormal vessels, and
standard cerebral angiography, the success rate of explain- the optimal timing for angiography after a hemorrhage is not
ing the hemorrhage was slightly higher in these children always clear.
(35 of 36, or 97.2%) than in children who did not have an Various vascular anomalies contributed to hemorrhage
angiogram (26 of 32, or 81.3%). In some instances, the in 26 (41.2%) of 68 children. Arteriovenous malformation and
angiogram was done to confirm and further define a vas- arteriovenous fistula accounted for almost a third (22 of 68,
cular malformation that was clearly evident with non- or 32.4%) of the hemorrhages. Arterial aneurysm was doc-

invasive tests (Figure 1), possibly inflating the diagnostic umented in only four (5.9%) children, three of whom had a
value of standard angiography. congenital saccular aneurysm and one a mycotic aneurysm.

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Figure 3. Intraparenchymal and intraventricular hemorrhage in a 6-month-old girl receiving daily ACTH injections for infantile spasms. A, Com-
puted tomography showed acute hemorrhage in the brain stem and enlarged temporal horns; B, Note the blood-cerebrospinal fluid level in
both occipital horns. An autopsy confirmed the hemorrhage and demonstrated cortical dysplasia, which probably caused the infantile spasms,
but no abnormal intracranial vessels.

Familial cavernous malformations are thought to occur occurred in other patients as well. Spontaneous dissec-
more Hispanic populations,7
often in but despite the large tion with hemorrhagic infarction occurred in two (2.9%) chil-
Hispanic population seen in our medical center, we found dren, and these may have caused hemorrhage via the same
only two patients, neither Hispanic, with hemorrhage attrib- mechanism. The occurrence of hemorrhagic infarction
uted to a cavernousmalformation. broadens the differential diagnosis of brain hemorrhage to
Although systemic arterial hypertension is a common include all of the risk factors for ischemic infarction. 10
cause of brain hemorrhage in adults and is occasionally Nine (13.2%) patients presented with signs of intra-
found in children with brain hemorrhage, hemorrhage parenchymal bleeding, but were eventually found to har-
could not be attributed to systemic arterial hypertension bor brain tumors (Figure 2). The clinical findings of these
in any of the children in this series. Similarly, an autopsy nine children were similar to those of the other children,
series found only 1 patient with systemic hypertension except for a few-days history of headache or seizures before
among 26 patients less than 20 years old with brain hem- deterioration in a few of the children with a tumor. Six of
orrhage.8 One of the children in the current series, who was the nine children presented with headache, one with epilep-
receiving adrenocorticotropic hormone (ACTH) injections tic seizures, one with epileptic seizures plus hemiparesis,
for infantile spasms, died from an extensive intra- and one with irritability. Similarly, 3 (11.5%) of 26 patients
parenchymal and intraventricular brain hemorrhage (Fig- less than 20 years old in McCormick’s hemorrhage series
ure 3). Systemic hypertension due to ACTH has been were found to have malignant brain tumors.8 Laurent and

suggested to explain the brain hemorrhage in one previous colleagues noted hemorrhage in about 10% of their series
patient;9 while it is possible that our child had unrecognized of 113 children with brain tumors,11 and Park and col-
systemic hypertension from ACTH, the blood pressure was leagues found 8 patients with hemorrhage among 144 chil-
not elevated, either at presentation for the hemorrhage or dren with medulloblastoma. 12
previously. Unlike the case with adult patients, systemic Both hereditary and acquired coagulation disorders
hypertension is not a common cause of intraparenchymal promote brain hemorrhage, although fortunately these con-
hemorrhage in children. ditions are relatively uncommon. The most common coag-
Hemorrhagic transformation of an arterial or venous ulopathy in this series was factor VIII deficiency, which
infarction occurred in six (8.8%) children, and may have accounted for 3 of the 10 patients in this category. However,

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Table 3. Outcome Following Intraparenchymal Hemorrhage develop epileptic seizures or other sequelae that are not yet
present.

CONCLUSIONS

There multiple risk factors for intraparenchymal brain

are

hemorrhage in children, but a likely cause for the bleeding

can usually be found if the children are fully evaluated.
Arteriovenous malformations and other vascular anomalies
*Some patients are listed in more than one category. cause over 40% of nontraumatic brain hemorrhages in chil-
dren. Children with unexplained brain hemorrhage should
intracranial bleeding has been documented in children with therefore undergo standard cerebral angiography. Brain
most other hereditary coagulation disorders, as well as tumors are relatively common in children initially suspected
to have only intraparenchymal hemorrhage.
acquired conditions such as warfarin therapy, hepatic failure
due to reduced production of clotting factors, and vitamin
K deficiency (Table 2). References
1. Schoenberg BS, Mellinger JF, Schoenberg DG: Cerebrovascular
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