Introduction
Intracranial aneurysms (ICA) are rare in the pediatric
population (age< 18 years). German pathologist
Eppinger first reported a case of childhood aneurysm
in a 15-year-old boy who collapsed during strenuous
gymnastics. His postmortem examination revealed
a ruptured saccular aneurysm of the right anterior
cerebral artery1.After several years Edward Bull
described the first ante mortem casein a 17-year-old
girl who presented with severe headache and her
diagnosis of a ruptured posterior communicating artery
aneurysm was subsequently confirmed on autopsy2.In
the current era, modern neuro - imaging techniques and
availability of angiography has greatly enhanced the
ability of physicians to diagnose cerebral aneurysms.
However, even today timely diagnosis of a pediatric
aneurysm and aneurysmal subarachnoidhemorrhage
continues to be challenging.
Incidence
Intracranial aneurysms are extremely uncommon in
the pediatric population with a reported prevalence
ranging from 0.5% to 4.6%. There is an overall male
predominance (male: female ratio 1.75:1)3.
Location of Intracranial Aneurysms
More than 80% of the pediatric ICA are located in
the anterior circulation while about 15% are located
in the posterior circulation. The most common site
in the anterior circulation is the internal carotid
artery bifurcation (26%), followed by the anterior
communicating artery complex (19%) and middle
cerebral artery bifurcation (17%)3. Multiple
aneurysms in children are uncommon and seen in
less than 5% of all pediatric cases.
Etiology/Pathophysiology
The ICA can be congenital or acquired. The congenital (also known as berry or saccular) aneurysms are found
in about 30% of cases4. The exact pathophysiology
of congenital ICA is debatable. It is likely due to a
combination of congenital and degenerative factors.
The pathological specimens show an absence of
internal elastic lamina and tunica media at the site
of aneurysm formation. The consensus view is that
the transition zone from normal vessel into the
aneurysmal sac is characterized by a congenital
defect of the internal elastic lamina and tunica media.
This site undergoes additional degenerative changes
throughout life and turbulent blood flow can cause
a saccular out pouching at the area of defect. This
combined effect of underlying congenital defect in
the vessel wall along with additional degenerative
factors is responsible for the rarity of aneurysms in
children and their increasing incidence in adulthood3.
Acquired causes of ICA in children include trauma,
infection and dissection. According to Krings et al.
dissecting aneurysms are the most often encountered
pediatric aneurysm and may account for up to 50%
of all aneurysms in this age group4. Traumatic
aneurysms account for 14 to 39% of all pediatric
aneurysms in different case series, and may occur
after both penetrating and nonpenetrating trauma.
Infectious aneurysms account for up to 2 to 10% of all
pediatric aneurysms. They are most often of bacterial
origin and are rarely caused by fungal infections. The
most common organism is staphylococcal aureus,
followed by streptococcus viridians and other gramnegative
organisms.
Other conditions associated with increased risk of ICA
are polycystic kidney disease, coarctation of aorta,
sickle cell anemia, Ehlers-Danlos syndrome type 4,
collagenopathy, and pseudoxanthoma elasticum.
Clinical Presentation
The most common presentation of ICA in children
is an acute aneurysmal rupture with subarachnoid hemorrhage (SAH). The signs and symptoms of SAH
in neonates or infants are nonspecific and include
irritability, drowsiness, poor oral intake, or vomiting.
Symptoms in older children are similar to those in
adults, such as acute headache, nausea, vomiting,
photophobia, neck stiffness, loss of consciousness
and neurological deficits. Seizures are common in
both infants and older children.
An unruptured aneurysm may be asymptomatic and
present as an incidental finding on neuroimaging
or may cause symptoms due to mass effect such as
partial complex seizures, cranial nerve palsies, or
focal neurological deficit. These symptoms are more
frequently seen in children than in adults.
Aneurysms presenting with SAH tend to re-bleed.
If left untreated, 2 to 4 percent bleed again within
the first 24 hours after the initial episode, and
approximately 15 to 20 percent bleed a second time
within the first two weeks5. The risk of rupture of an
ICA that is found incidentally is much less certain.
Diagnosis
The timely diagnosis of an ICA and SAH depends on
high index of suspicion. If SAH is suspected, urgent
computed tomography (CT) scan of the head without
the administration of contrast material should
be performed to confirm the clinical impression.
Patients with a negative CT but a high index of
suspicion should be considered for lumbar puncture.
In those with SAH, the red blood cell (RBC) count
is usually >100,000 cells/mm3 in the third tube
of the cerebrospinal fluid (CSF) collection, and
xanthochromia is present. The more sensitive and
specific test to diagnose SAH is the measurement of
excess bilirubin content in the CSF sample.
The next step after making a definitive diagnosis
of a SAH should be to determine the etiology and
to see whether an aneurysm is the cause of SAH in
this patient. To do so, there are different imaging
modalities currently used in clinical practice. The
three imaging techniques to rule out an intracranial
aneurysm and to delineate its size and morphological
features are CT angiography (CTA), magnetic
resonance angiography (MRA), and conventional
catheter angiography.
The sensitivity and specificity of CTAto diagnose ICA varies from 0.77 to 0.97 and 0.87 to 1.00 respectively6.
However, the sensitivity for aneurysms less than 3
mm is low and is estimated to be 0.40 to 0.91. Its
drawback is thatit involves the use of intravenous
contrast medium and thus it is contraindicated in
patients with renal failure or in those who are allergic
to iodinated contrast dye. (Fig 1-shows left terminal
internal carotid artery aneurysm)
Magnetic resonance angiography (MRA) produces
images of the intracranial vasculature by detecting a
specific range of blood flow velocities allowing the
isolation of intracranial arteries. It is highly sensitive
(0.69 to 0.99) and specific (1.00) in detecting
aneurysms >3 mm in diameter6. Its advantage is that it
does not require intravenous contrast agent, however,
it takes considerably longer time than CTA and thus
is more difficult to use in critically ill patients.
Conventional cerebral angiography is the “gold
standard” for imaging of ICA. It provides exceptional
resolution, can detect small aneurysms and
demonstrate dynamic flow of cerebral vasculature
and of the aneurysm itself. It is a safe diagnostic
modality in infants and children with low risks
particularly in the hands of an experienced operator.
SAH Grading scales
Numerous SAH grading scales have been proposed
in the past, with the aim to stratify the patients into
various risk categories based on their presenting
signs and symptoms. The most commonly used are
Hunt and Hess scale and Fisher scale. Hunt and Hess
scale (Table 1) is used to describe the neurological condition on admission and is considered a good
predictor of ultimate outcome7. The Fisher grade
(Table 2) uses a four-point scale to describe the
amount of blood on non-contrast-enhanced CT of
the head and has been shown to correlate with the
development of vasospasm8.
Management
A multidisciplinary team including neurosurgeon,
interventional neuroradiologist, neurologist and
pediatric intensivist best managepediatric ICA.
Theinitial treatment of a child with ruptured ICA
focuses on maintenance of adequate ventilation,
hemodynamic stabilization, maintenance of cerebral
perfusion, preventing intracranial hypertension and
minimizing the risk of re-bleeding. The unconscious
patients or those with a falling Glasgow Coma Scale
(GCS) should be intubated and ventilated. Prior to
securing the aneurysm, blood pressure should be
adequately maintained, as hypertension increases
the risk of re-bleeding while excessive fall in blood
pressure increases risk of cerebral ischemia. Some of
the patients may develop hydrocephalus as a result of aneurysmal SAH and may need external ventricular
drain placed for initial stabilization before aneurysm
obliteration. The ruptured ICA should be secured
as soon as possible after initial stabilization as the
greatest risk of re-bleeding occurs within the first 24
hours.
Securing the aneurysm:
There are three options for treating ICA: observation,
clipping and endovascular coiling. The management
of unruptured aneurysms that are discovered
incidentally depends on the patient’s clinical
condition, and size and locationof the aneurysm.
Depending upon their size and location, they can
be either observed with routine periodic follow-up
imaging or treated electively. All ruptured aneurysms
should be secured as early as possible by either
clipping or coiling.
Clipping of aneurysms requires craniotomy and
placement of MRI compatible permanent clips
across the neck of the aneurysm, excluding it from
the circulation (Fig 2 A). During the last decade
endovascular procedures have been increasingly
used to treat ICA. An interventional neuroradiologist
usually performs endovascular coiling. With the
use of angiographic techniques, a microcatheter is
advanced into the aneurysm, and detachable coils of
various sizes are deployed to decrease the amount
of blood or to stop blood from filling the aneurysm
(Fig 2 B).
Clipping or Coiling
Both the techniques have their own advantages
and disadvantages. Though successful clipping
is generally associated with definitive protection
against re-rupture, it has risks associated with
craniotomy. Endovascular coiling does not need
craniotomy but aneurysms treated with coiling may
reoccur and there is a risk of rupture of the aneurysm
during catheter advancement into the aneurysm or
during coil placement.
The International Subarachnoid Aneurysm Trial
(ISAT) was a large, multicenter prospective study
in adults comparing endovascular and surgical
techniques for aneurysms presenting with SAH.
Though the trial was criticized for many reasons,
it showed an improvement in early survival in
selected patients receiving endovascular therapy9.
There are very few pediatric studies comparing
both modalities of treatment. In the study by Agid
et al, 77% of the patients in the endovascular group
had good recovery as compared to 45% of the
patients in surgical group10. In their study Sanai et
al, had shown that patients treated with clipping had
more complete obliteration of their aneurysm and
significantly lower recurrence risk as compared to
patients in coiling group11. Stiefel et al, found no
difference in outcome of patients treated with either
clipping or coiling12.
On the basis of literature, it remains controversial
whether a given ICA should be treated surgically or
managed endovascularly. However, recent American
Heart Association (AHA) guidelines for the management of SAH in adults have recommended
that in patients with ruptured aneurysms who are
technically amenable to endovascular coiling and
surgical clipping, the former should be considered13.
However, there are no pediatric guidelines and the
decision to do surgical clipping or endovascular
coiling should be taken after discussion with
multidisciplinary team.
Medical management of aneurysmal subarachnoid
hemorrhage
The medical management of pediatric patients
with aneurysmal SAH is as important as the
surgical or endovascular intervention in ensuring
a favorable outcome. Following securing of the
aneurysm, management of SAH involves close
neuromonitoring, prevention or treatment of
vasospasm and other complications. Most of these
patients need admission to the intensive care unit.
Vasospasm and Delayed Cerebral Ischemia
Vasospasm causing delayed cerebral ischemia (DCI)
is defined as any neurological deterioration, including
focal neurological deficits and altered consciousness,
of which no other cause can be identified by
radiographic, laboratory or electrophysiological
investigations. It is very common in adult population
with an incidence of about 30% but incidence of
both radiographic and symptomatic vasospasm in
pediatric population is much less. It usually happens
between days four and ten after initial hemorrhage
and persists for several days.
Diagnosis and monitoring for Vasospasm
All patients with aneurysmal SAH should be closely
monitored clinically. Reduction in the level of
consciousness with or without focal neurological
deficit should raise suspicion of vasospasm. Digital
subtraction angiography remains the diagnostic gold
standard however CTA and MRA can be helpful
at initial suspension (Fig 3). Transcranial Doppler
Ultrasonography measures blood flow in basal
cerebral arteries and is a useful noninvasive method
to detect vasospasm.
Treatment of Vasospasm
Several pharmaceutical agents like magnesium,
anti-fibrinolytics, anti-platelets, and statins have
been tried for the prevention and treatment of
vasospasm but none has any proven benefits except
Nimodipine. Nimodipine is the only agent that has
been shown to reduce the incidence of vasospasm
and DCI and improve neurological outcome14. The
AHAguidelines recommend that oral nimodipine
should be administered to all the patients with
aneurysmal SAH immediately after diagnosis. The
recommended dose in adults is 60 mg every four
hours and is usually continued for 21 days. Although
intravenous nimodipine is sometimes used, this route
of administration remains unproven.
Another therapy that has been widely used to prevent
and treat vasospasm is Triple H (hypertension,
hypervolemia and hemodilution) therapy. However,
this combination therapy has never been clinically
proved to be useful and hypervolemia can be
potentially harmful to critically ill patients. As
per the recent guidelines, euvolemia rather than
hypervolemia is recommended for both prophylaxis
and treatment of vasospasm, and that hemodilution
is not recommended13. Hypertensive therapy
(induction of hypertension with vasopressors) is
only recommended in patients with symptomatic
vasospasm. Patients with symptomatic cerebral
vasospasm, particularly those who have no response
to medical treatment should undergo cerebral
angioplasty of the narrowed vessels and/or selective
intra-arterial vasodilator therapy13.
Management of other complications
Seizures
Seizures occur commonly in patients after aneurysmal SAH. The routine long term use of anticonvulsants
is not recommended but the use of prophylactic
anticonvulsants may be considered in the immediate
post hemorrhagic period13. Levetirecetam is
preferred and phenytoin should be avoided because
of associated cognitive effects and poor outcome15.
Fever
Fever occurs in up to two-third of patients with
aneurysmal SAH. Although the cause of fever can be
related to the hypothalamic effects of subarachnoid
blood, an infective cause should always be ruled out.
Fever should be aggressively controlled with a target
to achieve normothermia by the use of standard or
advanced temperature modulating systems.
Dysnatraemia
Both hypernatremia and hyponatremia can occur
in patients after aneurysmal SAH. Hyponatremia
can develop from different mechanisms after SAH.
It can be related to the syndrome of inappropriate
antidiuretic hormone secretion (SIADH), cerebral
salt wasting syndrome or iatrogenic hemodilution. It
is important to monitor and diagnose hyponatremia
as treatment varies with etiology.
Anemia
Anemia is common after aneurysmal SAH and
may compromise brain oxygen delivery. Current
guidelines recommend that the use of packed red cell
transfusion to maintain hemoglobin concentration
between 8-10 g/dl is reasonable in patients with
SAH16.
Cardiac dysfunction
Left ventricular dysfunction requiring inotropic
support can occur in patients after SAH. It results
from excessive catecholamine release in response to
intracranial hemorrhage. In most cases it is temporary
and resolves spontaneously after a variable period.
Outcome
Outcomes after aneurysm surgery and aneurysmal
SAH are much better andfavorable in children as compared to adults. In general, children have a
lower incidence of vasospasm, which accounts for
most of the morbidity and mortality associated with
aneurysmal rupture. Overall, in different case series
90-95% of pediatric patients has good outcome with
Glasgow coma outcome scale of 4 or 5.
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