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Definition and History
The cavernous malformation (CM),
also known as the cavernous angioma or cavernoma, is a vascular anomaly
characterized by the presence of sinusoid-like capillary vessels. These
capillaries are adjacent to one another, with little or no intervening brain
parenchyma; the feeding arteries and draining veins are most often normal in
size. The blood flow in the cavernous angioma is slow; therefore, standard
angiography techniques usually fail to visualize this type of lesion. Stagnation
of blood is also characteristic and is frequently the cause of thrombosis and
calcification.
CMs can occur anywhere in the
central nervous system. Their distribution seems to reflect the relative volume
of the different structures. Multiple lesions are common: in one large series of
8131 magnetic resonance (MR) scans, the incidence of CMs was 0.4 percent; the
incidence of multiple lesions in this group was 18.7 percent. In patients with
multiple cerebral CMs, similar lesions can be found in other organ systems.
Cerebral CMs are generally sporadic; at least 6 percent of cases are familial.
however.
On microscopic examination, the
cerebral CM is a well-lobulated, circumscribed lesion; since it is either dark
red or purple in color, often it is described as mulberry-like. An average
diameter of 4.9 mm was reported in one large prospective autopsy series;
clinical descriptions usually give a greater diameter. The mean lesion size in a
surgical series conducted by Giombini and Morello was 3.5 cm; Yasargil reported
a mean lesion size of 2.2 cm in one surgical series. There is a significant
correlation between size and symptomatology.
CMs vary in consistency from
soft to hard, depending on the relative proportions of blood-filled spaces,
calcification, ossification, and areas of thrombosis. The surrounding brain
parenchyma is typically gliotic and stained yellow by hemosiderin. This staining
is the result of either frank hemorrhage or slow diffusion of pigment into the
surrounding tissue following lysis of red blood cells. The presence of highly
epileptogenic iron salts in the susceptible brain structures explains the high
incidence of seizures in patients with CMs.
Microscopically, the CM is
characterized by enlarged capillaries, which are composed of a thin collagenous
wall covered by a single layer of endothelium without smooth muscle fibers or
elastic fibers. Typically, CMs do not have intermingled brain parenchyma: at the
periphery. however, the dilated capillaries of many CMs may be separated by
normal brain. Hemosiderin-laden macrophages are invariably found secondary to
previous hemorrhage or red blood cell lysis. Varying degrees of thrombosis,
fibrous scarring, calcification and ossification are often present.
Clinical Features
A comprehensive review of the
literature shows that patients with symptomatic CMs have presented with seizures
(39 percent), hemorrhage (32 percent), or a mass effect (29 percent). A study of
the members of six families with CMs, however, confirms that these malformations
are asymptomatic in a significant percentage of cases (11 percent). In one
study, seizures were the most common symptom (55 percent), followed by
progressive neurological deficit (15%), headache (15 percent), and hemorrhage (4
percent). Another compilation of 664 patients assembled from the literature
corroborates seizures as the predominant symptom (31 percent), followed by
progressive neurological deficits (25 percent), hemorrhage (13 percent), and
headache (6 percent); asymptomatic cases were more common than previously
reported (21 percent).
Two CM variants have been
described: a cystic form and the so-called hemangioma calcificans. The cystic
form tends to cause recurrent bleeding and is common in the posterior fossa,
with a noticeable degree of surrounding edema. In the absence of clear
histologic confirmation, the hemangioma calcificans is presumed to be a
calcified CM. Commonly located in the temporal lobe, it causes seizures and
usually, because of its densely calcified structure, does not bleed.
Imaging
The use of magnetic resonance
imaging (MRI) means that CMs are now usually diagnosed at an earlier and much
smaller stage than before, and rarely is calcification seen. Two old surgical
studies reported the presence of calcification on conventional skull radiographs
in 8 to 10 percent of the patients. Similarly, earlier reports described
angiographic abnormalities in 60 to 70 percent of cases; this result also
reflects a time before the advent of MRl, when patients typically had larger,
symptomatic lesions. A capillary blush and early filling of the veins without
enlargement of the arteries is very rarely seen. Opacification of the cavernous
spaces has been noted occasionally when using prolonged arterial injection.
Computed Tomography
CT-scan can detect cavernous
malformations and the distortions produced by a mass effect. On unenhanced CT
scans, cavernous malformations appear as focal areas of increased attenuation:
only a few lesions appear hypodense. An increase in density is characteristic of
recent hemorrhage as well as of calcification, and increased attenuation can be
observed on scans following an acute hemorrhage, which is frequently accompanied
by a mass effect. Areas of punctate calcification are visualized in 14 percent
of cases.
The intravenous (IV)
administration of a contrast agent permits a faint enhancement. The CT can
outline abnormalities encroaching on the brain stem: however, an acute brain
stem hemorrhage that produces subarachnoid or fourth ventricular hemorrhage is
more likely to be due to a cryptic arteriovenous malformation (AVM) than to a
CM.
Magnetic Resonance Imaging
MRI yields extraordinary
resolution and is particularly helpful in identifying CMs. On both T1- and
T2-weighted images, the CM is represented as a well-defined, usually rounded
lesion. The lesion is characterized by a rim of decreased signal intensity at
the periphery and a heterogeneous central signal. The hypodensity of the rim is
produced by the presence of hemosiderin: the appearance of the central core is
generated by blood and blood byproducts in various stages of evolution, Areas of
increased signal outside the hemosiderin rim on T2-weighted images may represent
edema. Smaller CMs may appear only as petechial areas of decreased signal
intensity ("black dots" ). Although enlarged vessels are not characteristic of
CMs, a coexisting venous angioma has been identified now and then.
It is important to recognize
that these appearances are not limited to CMs and that a differential diagnosis
is important to rule out the presence of a cryptic AVM or hemorrhagic neoplasm.
Hemorrhagic neoplasms, even when small, are accompanied by edema, which is
usually absent from small CMs. Magnetic resonance angiography (MRA) permits
visualization of the CM by the time-of-flight technique but not by the phase
contrast technique.
Positron Emission Tomography
Positron emission tomography
(PET) uses the uptake of radioisotopes to scan the brain. Both CT and MRI
provide far more structural detail, but PET scanning can differentiate a CM from
a tumor, since radioisotope uptake is markedly elevated in tumors but not in
CMs. One small series reported normal or decreased radioisotope uptake in CMs.
Management
A prerequisite for the
management of CMs is a knowledge of their natural history. Several prospective
MRI series of patients harboring characteristic lesions have yielded a clearer
understanding of the true risk of overt hemorrhage from a CM. One report
estimates that the annual bleeding risk is 0.7 percent per patient. Based on the
assumption of uniform risk from birth to the age at which a hemorrhage is
diagnosed, the risk is calculated to be 0.25 percent per lesion per year.
Although this information is useful, it is not necessarily accurate: The risk of
hemorrhage may not be uniform and may depend on other factors, such as gender,
age and previous hemorrhage. It also is important to compare the lower risk of
bleeding from a CM to the higher risk of bleeding from an AVM, which is
calculated to be approximately 4.0 percent per year. Furthermore, the
consequences of a hemorrhage from a CM are rarely catastrophic, in contrast to
the case with an AVM or aneurysm.
The course of a non hemorrhagic
lesion seems to correlate with the initial clinical presentation. In the absence
of gross hemorrhage, one study reported a poor to fair outcome for 16 percent of
patients. Patients who present with seizures are very likely to become
symptomatic again, and, frequently, seizure control becomes more difficult with
time. The location of the lesion also may be significant: CMs in the
infratentorial compartment may be associated with a more aggressive natural
history.
Most lesions discovered
incidentally require no therapy. Occasionally, these lesions cannot be
differentiated from tumors, and a biopsy is indicated. Surgical intervention can
be attempted when a CM is identified as a seizure focus in patients with
refractory seizures. Several authors consider that, surgery is not indicated as
a measure to decrease the risk of bleeding in a patient who has never bled.
In children, surgical
intervention is indicated to treat symptoms related to mass effect, hemorrhage,
or seizures. Surgery is favored more for children than for adults because of the
higher risk of hemorrhage and greater epileptic potential in children.
The effect of pregnancy on CMs
remains speculative. Although a statistically significant association between
hemorrhage and pregnancy has yet to be established, pregnant women accounted for
86 percent of the hemorrhages (one-third in the first trimester) in one series.
There also are anecdotal cases of CMs expanding and becoming symptomatic during
early pregnancy. It seems that an increased risk of lesion expansion and
hemorrhage exists during pregnancy.
If the mother is stable,
conservative management may be appropriate, and vaginal delivery is not
contraindicated. Surgical resection before conception is preferred, provided the
CM is located in a favorable location. Possible risks and management options
should be discussed with women who plan to become pregnant, and surgical
recommendations can be made at that time.
Surgical Intervention
A thorough medical history,
family history- and physical examination, and detailed neuroimaging studies are
crucial to the preoperative evaluation. MRI is particularly helpful in
identifying the exact preoperative location of the lesion and multiple lesions,
which often are not detected by CT. For patients with a seizure disorder,
electroencephalography (EEG) can confirm whether the epileptic focus is
anatomically related to the CM and can localize the seizure focus when multiple
CMs are present.
Standard microsurgical
techniques are employed for the resection of CMs. The surgical microscope and
microsurgical instrumentation have revolutionized the surgical treatment of CMs,
particularly the treatment of lesions located in the brain stem or deep in the
cerebral hemispheres. Some authorities have recommended the use of the CO2
laser, but it does not seem necessary for extirpation of these lesions. One
useful addition to the surgical armamentarium is a stereotactic system, which
can be used to precisely localize deep-seated lesions intraoperatively.
Usually, significant
intraoperative bleeding does not accompany the resection of a CM. One area of
notable exception is the extracerebral middle fossa CM. Significant bleeding in
this area is probably due to intralesional pressures that are at once decidedly
lower (38.2 ±0.5 mmHg) than mean arterial
blood pressures (99.6 ±15.1 mmHg) and higher
than central venous pressures (5.0±1.0
mmHg).
In Giombini's first large,
personal series accompanied by a review of the literature, 33 patients were
known to have undergone radical resection of the lesion. All but three (10
percent) had improved or else continued with stable deficits after a follow-up
averaging several years. The two factors given as relating to surgical success
were (1) the presence of a dissection plane and (2) a relatively scarce supply
of blood to the CM.
Another publication reported 17
cases with an excellent outcome and 2 cases with a good outcome among 19
patients who had hemispheric lesions: on the other hand. the outcome in patients
with lesions in the thalamus, pineal region or spinal cord was consistently
poor. The higher surgical morbidity associated with deep-seated CMs has several
distinct causes: damage to the internal capsule. injury to the lenticulostriate
arteries, damage to the venous drainage, air embolism and recurrent hemorrhage
from a residual angioma:
A fairly high incidence of
surgical complications has chilled some of the initial enthusiasm. The report on
the largest series of brain stem CMs stresses the importance of combining
clinical examination findings and MRI data to determine a safe surgical corridor
for approaching the lesion. The authors recommend surgical resection for
symptomatic brain stem CMs because the brain stem's ability to withstand
expansion is poor.
Deep CMs located in critical
areas have been treated with radiosurgery. The results have not been favorable:
the incidence of complications, presumably due to delayed radiation injury, is
much higher than in a similar series of AVM patients. It is discouraged to
perform radiosurgical treatment for CMs, as its efficacy is very difficult to
evaluate. To start with, angiographic findings appear normal, even before
radiosurgery and any spontaneous reduction in the size of the CM following a
hemorrhage would further complicate evaluation.
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Middle Cranial Fossa Cavernous
Malformations
Middle cranial fossa CMs are
extraparenchymal and usually extradural. Histologically. these lesions are
composed of dilated cavernous channels lacking mural smooth muscle. They
routinely surround the structures in the cavernous sinus. including the internal
carotid artery and cranial nerves III through VI. These lesions are rare and
primarily affect women.
The clinical presentation
includes headaches and, more commonly. acute or subacute visual symptoms. Ocular
findings include proptosis, visual loss, field cuts and diplopia. Facial
numbness and pituitary dysfunction are less common. Lesion growth often erodes
the bone in the area of the cavernous sinus. Angiography outlines a vascular
mass without an arteriovenous shunt. These lesions are a formidable surgical
problem, as they tend to cause intraoperative, life-threatening hemorrhages.
After biopsy, terminating attempts to further resect the lesion will drastically
reduce mortality and morbidity, as will giving a course of radiotherapy prior to
definitive surgical treatment.
Retinal Cavernous Angioma
Retinal cavernous angiomas have
been linked to one of four neurooculocutaneous syndromes (ophthalmic
phakomatoses), characterized by disseminated hamartomas of the eye, skin and
brain. On direct visualization of the retina, these lesions resemble clusters of
grapes protruding from the inner retinal surface into the vitreous. The
capillaries appear thin-walled and are similar to those of cerebral CMs. The
arteries and veins surrounding the lesion are normal in appearance.
Fluorescein angiography is
helpful, demonstrating a significant delay in the perfusion of dye through the
lesion. This is why some workers recommend angiography with a very late venous
phase to cavernous heamangiomas.
Calvarial hemangiomas occur more
often in females than males and present as a painless, bony swelling usually in
the parietal or frontal region. The scalp moves freely over the mass and
roentgenograms depict a well-defined lucent area with a trabeculated appearance.
During angiography, the contrast agent pools within the lesion in the venous
phase. Histologically, cavernous capillaries are separated by bony spicules.
Capillary Telangectasias
The capillary telangiectasia
(also called a capillary malformation) is a lesion characterized by the presence
of capillary vessels with saccular and fusiform dilation interspersed among
normal brain parenchyma. Capillary telangiectasias are punctate lesions composed
of small dilated capillaries that are devoid of muscle and elastic fibers. On
gross inspection, a capillary telangiectasia resembles a cluster of petechial
hemorrhages. No abnormal arteries are present in the periphery of the lesion,
but it may drain into an enlarged central vein. The feature that most
distinguishes these lesions from CMs is the presence of normal brain parenchyma
between the dilated vessels, Typically, the parenchyma does not show evidence of
gliosis or hemorrhage. Most of these malformations are clinically silent and are
discovered at autopsy. They occur in the same locations as CMs and like them,
are frequently multiple, Observations of lesions transitional between capillary
telangiectasia and cavernous malformation have been documented for years, which
leads to the supposition that one lesion is the precursor of the other.
Radiologic studies were not able to detect capillary telangiectasias in the
past: however, MRI can detect them as punctate areas of decreased signal
intensity on T2-weighted images. The hypodensity is due to the presence of small
amounts of hemosiderin and most likely, previous subclinical hemorrhages or
diapedesis of red blood cells through the walls of the lesion. A true massive
hemorrhage is exceedingly rare and only anecdotal cases have been reported. The
importance of this lesion is that it represents a possible link between
different types of vascular malformations.
Venous Angiomas
The venous angioma (venous
malformation, medullary venous malformation) is characterized by an
abnormal-looking but physiologically competent venous drainage. Venous angiomas
are usually located in the deep white matter, drain an array of fine medullary
veins that converge on them and drain in turn into either the superficial or
deep venous system: most are located in the cerebral hemispheres or cerebellum.
Macroscopically, a tuft of fine
veins converge into an enlarged central venous trunk that appears much larger
than the veins joining it. Microscopically, the vein appears normal in
structure, except for occasional evidence of hyalinization and thickening. No
abnormal arteries are associated with the venous malformation and evidence of
thrombosis, hemorrhage or calcification is rare. The intervening parenchyma
appears normal.
The classic angiographic term
for this lesion is caput medusae, coined because the numerous small veins appear
in a radial arrangement around the enlarged central trunk: the arterial and
capillary phases appear angiographically normal. By CT and MRI. the venous
angioma typically appears as a linear or curvilinear structure with a nidus at
the vessel origin resembling the spokes of a wheel. Clinically, venous angiomas
are usually asymptomatic and their discovery is incidental: however, venous
malformations located in the posterior fossa tend to be more symptomatic.
Some authorities recommend more
aggressive management of posterior fossa venous angiomas when they are
associated with a hemorrhage. This approach, however, carries a significant risk
because the elimination of an abnormal-looking but functional draining vein,
whether by surgical, endovascular, or radiosurgical techniques, can precipitate
a venous infarction. The natural history of this malformation seems to be quite
benign, according to some initial follow-up studies. A most interesting and
clinically relevant characteristic of this lesion is its relatively common
association with a cavernous malformation. This phenomenon is too common to be
only coincidental. It raises several interesting questions regarding the
possible genesis of cavernous malformations and the causative effect a venous
angioma may have on the dilatation of the capillaries with which it is
connected. Another important corollary to this previously underestimated
association is that, if hemorrhage occurs, it most likely arises from the
cavernous malformation rather than the venous angioma. Prior to the use of CT
and MRI, a hematoma in the vicinity of a venous malformation was thought to be
due to the venous malformation: any coexisting cavernous malformation could not
be detected on the angiogram. Nowadays, it is standard to look for a cavernous
angioma in the vicinity of a venous angioma. If a hemorrhage occurs, the clot
and cavernous angioma are removed, while the venous malformation is best left
alone.
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