Supratentorial and Infratentorial Cavernous Malformations

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CHAPTER 394 Supratentorial and Infratentorial Cavernous Malformations

Gregory P. Lekovic, Randall W. Porter, Robert F. Spetzler

Cavernous malformations (CMs) account for 5% to 13% of vascular lesions of the central nervous system. Historically, these lesions have been considered quite rare.¹^–³ With the advent of magnetic resonance imaging (MRI), however, the diagnosis of cerebral CMs has increased. They are now understood to be more common than was appreciated before MRI was available, with an incidence of 0.4% to 0.5% in the general population.⁴^–⁷

Unfortunately, the nomenclature regarding CMs is cluttered. Before MRI, these lesions were grouped with other angiographically cryptic hemorrhagic lesions. Hence, they are variously referred to (especially in the older literature) as cavernous angiomas, cavernous hemangiomas, cryptic vascular formations, or angiographically occult vascular malformations. We prefer the term cavernous malformation. Furthermore, CMs occurring in extra-axial cranial locations, including the dural sinuses, temporal bone, and orbit, are also often referred to with different terminology (e.g., cavernous hemangiomas of the cavernous sinus). Pathologically, however, these extra-axial CMs are identical to cerebral CMs. They differ from intra-axial CMs only in that they enhance with gadolinium.

This chapter reviews the contemporary surgical management of deep-seated CMs, including CMs of the brainstem, posterior fossa, cranial nerves, and deep supratentorial structures (i.e., basal ganglia and thalamus). Superficial supratentorial CMs manifested as epilepsy are more appropriately discussed with the treatment of lesional epilepsies and are only briefly considered here.

Epidemiology and Clinical Manifestations

As mentioned, CMs account for 5% to 13% of vascular lesions of the central nervous system, with an incidence of 0.4% to 0.5% in the general population.⁴^–⁷ Most cerebral CMs are supratentorial, and 9% to 35% are found in the brainstem.¹^–³ Although these lesions are histologically identical, their behavior and management depend on the location of the lesion.

Regardless of location, the defining pathophysiology of CMs is repeated hemorrhage. CMs are formed by endothelin-lined sinusoidal vascular spaces. There is a lack of intervening brain parenchyma inside the collagenous matrix of the lesion. On electron microscopy, the endothelin-lined CMs contain cells that lack tight junctions.⁸ It has been hypothesized that these “leaky” cell junctions are responsible for the extravasation of blood products seen as extralesional hemosiderin staining on histologic preparations of CMs.

The signs and symptoms of patients with cerebral CMs are highly variable. Many of these lesions are now discovered incidentally (see the section “Imaging”). For superficial supratentorial lesions, a seizure manifestation is typical. For deep-seated supratentorial and infratentorial lesions, symptoms are more dependent on location. In all cases, regardless of whether the onset of symptoms is insidious or apoplectic, the presence of symptoms can be traced back to hemorrhage from the CM. These hemorrhages may be large bleeding episodes that are manifested as apoplectic events, repeated “microhemorrhages” that cause hemosiderin to accumulate in the surrounding brain and subsequently give rise to seizures, or progression of the CM from repeated intralesional hemorrhage and mass effect. With each hemorrhage, symptoms tend to worsen and then improve, but less so after each ictus. In effect, a stepwise progression of “two steps forward, three steps back” is observed. After one hemorrhage, the likelihood of a subsequent hemorrhage is substantially higher than with a silent lesion.

The typical symptoms of brainstem CMs include the acute onset of multiple cranial neuropathies associated with hemisensory loss or hemiparesis and either headache, nausea, or vertigo. Slowly expanding lesions (i.e., CMs growing from repeated intralesional hemorrhage) may cause the neurological deficits to worsen insidiously. Clinically, multiple sclerosis is often misdiagnosed in many of these patients, especially those harboring brainstem CMs. Patients may also be misdiagnosed as having stroke, tumor, or infection.

Imaging

The imaging appearance of CMs is pathognomonic. Hemorrhage in the hyperacute period is isointense with brain tissue on T1-weighted MRI with a short TR (repetition time) and hypointense on T2-weighted MRI. Subacute hematomas (3 weeks to several months old) have a classic “salt and pepper” appearance. They are characterized by a hyperintense center (methemoglobin) on both T1- and T2-weighted images (Fig. 394-1) and by a hypointense surrounding rim of hemosiderin, especially on the latter. Gradient-echo images in particular can be used to screen for small occult lesions.

FIGURE 394-1 A, Sagittal T1-weighted magnetic resonance imaging (MRI) revealing a massive hemorrhage within the substance of the pons with a homogeneous hyperintense signal compatible with subacute blood products. B, Axial T1-weighted MRI in a 16-year-old girl with heterogeneous blood products from hemorrhages of different age within the cavernous malformation of the medulla. C, T2-weighted MRI revealing various intensities of blood products with layers of fluid within the center of the medulla, consistent with new and old hemorrhage. D, Gradient-echo sequencing revealing multiple cavernous malformations with hypointense rims of surrounding hemosiderin.

Natural History

Risk for Hemorrhage

The risk for hemorrhage from an incidentally discovered CM is controversial. Naturally, this risk is a function of how hemorrhage is defined and whether these lesions are assumed to be present at birth. We define a hemorrhagic event as a clinical history of an apoplectic episode or evidence of subacute or acute blood products on computed tomography or MRI. The characteristic hypointense ring seen on T2-weighted MRI, however, is due to hemosiderin and, in our opinion, does not define an acute hemorrhagic episode.

Kondziolka and coauthors reported prospective hemorrhage and rehemorrhage rates of 2.4% to 5% per year, respectively.⁹ In contrast, in our institutional retrospective review, hemorrhage and rehemorrhage rates were 5% and 30%, respectively.¹⁰ Regardless, the timing of a subsequent hemorrhage is impossible to predict, with the interval between hemorrhages ranging from hours to years.

Several factors have been proposed to predispose a CM to rupture, including its location,^7,¹¹ a history of previous rupture, its size,^12,¹³ and the presence of an associated developmental venous anomaly.¹⁴ The factor most consistently associated with increased risk for rupture across series is location. The hemorrhage rate of infratentorial lesions may be 30 times that of lesions in the supratentorial compartment. Both retrospective and prospective studies undertaken to define risk factors for hemorrhage from CMs have consistently identified the location of a lesion as having a significant impact on the rate of rupture. Brainstem CMs consistently have a higher rate of symptomatic hemorrhage than those at other locations. Hemorrhage rates as high as 60% have been reported for brainstem CMs.¹⁵

The mechanism for such a disparity in rupture rates, however, remains obscure. Most authors attribute this difference, at least partially, to the sensitivity of the brainstem to hemorrhage. In the literature, a history of previous rupture is strongly associated with as much as a sevenfold increase in the risk for prospective rupture.^9,¹⁶

Some authors have attempted to link the presence or absence of an associated venous malformation with a higher rate of rupture.¹⁴ In our experience, though, CMs have universally been associated with venous anomalies, whether supratentorial, infratentorial, or even extra-axial (e.g., for CMs of the cranial nerves). Venous malformations are completely benign, but abnormal constellations of veins that drain normal brain tissue. They are the most frequent form of vascular malformation and are a common incidental finding on MRI.

It is important to emphasize that venous malformations, per se, do not rupture; however, they are frequently associated with CMs that do.¹⁷ Thus, given the association between CMs and venous anomalies, it is currently thought that any hemorrhage in the vicinity of a venous anomaly is the result of rupture of an associated CM, regardless of whether it is visualized on imaging studies (some CMs may be small enough to be missed on routine imaging studies). Unfortunately, a complete consensus on this point is lacking. Because of the association between CMs and venous anomalies, the older literature is replete with suggestions that venous anomalies may occasionally hemorrhage.¹⁸

Treatment Options

Observation

Conservative management consisting of observation and repeated neuroimaging is appropriate for patients whose symptoms resolve completely after an acute hemorrhagic event or for patients with incidentally discovered lesions. Patients often express concern regarding activities or medications that may exacerbate the hemorrhagic tendency of CMs. Patients harboring incidental CMs should be advised that the risk for hemorrhage from an incidental lesion is extremely low (some studies suggest less than 1%) and that the chance of a seizure disorder developing (with supratentorial lesions) may be 2% to 3% per year. Furthermore, besides pregnancy, no other factors are known to be likely to increase the risk for hemorrhage. Patients should not restrict their activities or exercise based on a theoretically increased risk. To date, no evidence suggests that there is a protective effect from avoiding even strenuous exercise. Anticoagulation is not contraindicated in these patients, although the risk of having a slightly more symptomatic hemorrhage may arguably be increased relative to normal.

Patients should also be reassured that for supratentorial lesions in ineloquent locations, hemorrhage from CMs is exceedingly unlikely to be catastrophic and rarely, if ever, causes death. A benign manifestation consisting of headache is much more likely. This statement is not necessarily true, however, for deep-seated lesions, including infratentorial CMs or those located supratentorially in eloquent cortex (e.g., motor strip).

Radiation Therapy

Radiation therapy, including stereotactic irradiation, has not been shown to confer a protective benefit from hemorrhage in the treatment of CMs, partially because the natural history of CMs has remained difficult to define and because CMs treated with radiosurgery do not disappear on subsequent imaging studies. Furthermore, the hemorrhage rate never approaches zero. In fact, radiation has been implicated in the pathogenesis of these lesions. Moreover, for CMs in eloquent regions such as the brainstem and basal ganglia, new neurological deficits related to a treatment effect have been reported in 17% to 59% of patients.^19,²⁰ At present, therefore, most authors do not recommend radiation therapy for the treatment of deep-seated CMs.

Surgical Indications

The indications for surgery depend on the lesion’s location and symptoms. For lesions causing medically refractory epilepsy, surgery may be indicated to reduce or eliminate the seizures when a seizure focus can be reliably determined. Although most supratentorial CMs that do not cause seizures can be observed safely, there are several important exceptions. CMs located anywhere in the ventricular system should be considered for resection. A ventricle would not be expected to provide sufficient tissue pressure to tamponade bleeding from a ruptured CM. Hence, patients would be at risk for a devastating intraventricular hemorrhage. Furthermore, the behavior and surgical management of deep-seated supratentorial CMs, such as CMs of the thalamus or basal ganglia, are more akin to those of brainstem CMs than to other supratentorial lesions. They are consequently managed with the same considerations in mind.

For these deep-seated lesions, including brainstem CMs, surgical resection is appropriate if the CM reaches a pial surface, hemorrhages repeatedly in association with progressive neurological deficits, is manifested as acute hemorrhage outside the lesion capsule, or causes a significant mass effect from large intralesional hemorrhages. We recommend avoiding a myelotomy through even the thinnest amount of tissue in the floor of the fourth ventricle. Typically, we resect only clearly exophytic lesions in this location. The thickness of the rim is best ascertained on T1-weighted MRI. Lesions that clearly reach a pial surface on T1-weighted imaging can be considered for resection.

Surgery is indicated for posterior fossa locations outside the brainstem (i.e., cerebellar hemispheric CMs) in the event of acute hemorrhage producing a mass effect, for CMs that have ruptured multiple times, and for lesions exerting a significant mass effect from intralesional hemorrhage or expansion of the lesion. It is unnecessary for cerebellar CMs to approach a pial surface for it to be resected without causing morbidity. Similarly, lesions arising from the middle cerebellar peduncle that are exophytic into the fourth ventricle may be resected safely (we prefer the telovelar approach for these lesions, see later).

To facilitate the removal of acute hemorrhage, we typically wait 3 to 5 days for the hematoma to liquefy. If the patient is deteriorating rapidly, however, the brainstem may need to be decompressed in an emergency fashion. Acute hematomas tend to be tenacious and to require more manipulation of the surrounding parenchyma than do more subacute, yet liquefied, clots.

Contraindications

Patients should not be considered for surgical therapy if they have severe concomitant medical problems or if they have had a single hemorrhagic episode from a brainstem CM in an unfavorable location (e.g., far from a pial surface). In our experience, these patients can be managed conservatively until they suffer at least one more hemorrhage, especially if even the thinnest rim of tissue in the floor of the fourth ventricle must be traversed. If fixed deficits develop after another hemorrhage, surgery may be offered as a treatment option even for intrinsic brainstem lesions.

For patients with multiple CMs who become symptomatic with seizures, surgery should not be considered unless an individual seizure focus can be identified. Furthermore, although rare, the presence of multiple brainstem CMs is a relative contraindication to surgical intervention unless the patient’s initial signs and symptoms can be confidently attributed to a single lesion.

Finally, for posterior fossa lesions in general and for brainstem lesions in particular, surgeons should not hesitate to abort surgery if unexpected bleeding is encountered, significant changes in neuromonitoring develop, or unexpected intraoperative events occur. Even under ideal operative conditions during the treatment of these lesions, the potential for significant morbidity is high. Therefore, surgeons should have a low threshold for aborting procedures and returning at another operative sitting if necessary.

Operative Procedure

Goals of Surgery and Patient Counseling

For posterior fossa and other deep-seated lesions, the goals of surgery are to extirpate the CM completely while minimizing the amount of normal eloquent (i.e., brainstem or thalamus) tissue traversed. The associated venous anomaly or malformation should be preserved. If a large venous malformation is occluded, venous infarction may result. Superficial supratentorial CMs can usually be resected completely with minimal morbidity and excellent outcomes. Nevertheless, in these cases, too, every attempt should be made to preserve the associated abnormal venous drainage. Under image guidance, a tailored craniotomy is generally sufficient to expose these lesions. No attempt to resect the surrounding hemosiderin-laden brain is undertaken, regardless of whether the CM is in the supratentorial or infratentorial compartment.

Once the decision to operate has been made, appropriate preoperative counseling is critical, especially for patients with deep-seated lesions. Patients should be educated that their deficits are likely to worsen after surgery but will typically improve with time. Patients should be told that the surgical experience is similar to having another hemorrhage. They should be warned, if appropriate, that a tracheostomy or feeding tube may be necessary on a short-term basis and that a moderate course of rehabilitation will probably be necessary. Such information eases patients’ anxiety and provides them realistic expectations about the process.

To determine the best surgical approach, we use the “two-point method” (Fig. 394-2).²¹ One point is placed in the center of the lesion and a second is placed where the lesion most closely reaches a pial surface. The two points are connected, and the resultant straight line through the least eloquent tissue dictates the most appropriate surgical approach. Preoperative permanent neurological deficits, such as seventh or eighth cranial nerve palsies, can also influence the choice of approach. Such deficits, for example, may make a translabyrinthine or transcochlear approach more attractive.

FIGURE 394-2 Artist’s rendition of the “two-point” method applied to medullary cavernous malformations in similar locations. A first point is placed in the center of the lesion and a second at the point where the lesion comes closest to the surface. A line connecting the two points determines the optimal approach. The two lesions require different surgical approaches, the suboccipital (left) and the far lateral (right), because the points where they reach the surface are different.

(Used with permission from Barrow Neurological Institute.)

We avoid transcortical approaches whenever possible. Importantly, when using the two-point method to access deep-seated supratentorial lesions (e.g., thalamic CMs), an ependymal surface can be substituted for a pial surface. Hence, the two-point method might be used to select a posterior interhemispheric transcallosal approach for such a lesion.

Preoperative Imaging

As mentioned, the MRI appearance of CMs is pathognomonic and hence sufficient for surgical planning. Angiography is not indicated. Preoperative gadolinium-enhanced, contiguous, nonoverlapping, 1-mm axial-slice, single-echo MRI is routinely obtained for frameless stereotactic guidance. We use Stealth (Medtronic, Minneapolis, MN) for intraoperative image guidance integrated into the operative microscope such that the surgeon’s focal point with respect to the lesion’s location and operative trajectory is displayed.

Intraoperative Monitoring

Intraoperative monitoring is a valuable adjunct to help minimize complications during craniotomy. At our institution, monitoring of somatosensory evoked potentials (SSEPs) and compressed spectral analysis or electroencephalography is routinely performed. For brainstem lesions, motor evoked potentials and brainstem auditory evoked potentials (BAERs) are also monitored. These monitoring techniques should be applied before and after the patient is positioned because excessive flexion or rotation of the neck can cause disastrous outcomes such as vascular compression, brachial plexopathy, spinal cord injury in the presence of spondylosis, or excessive venous pressure.

Although these techniques provide continual feedback, postoperative neurological deficits are not always preceded by a change in the recorded waveforms. Both false negatives and false positives can occur. Consequently, the pathway being monitored must be relevant to the operation. Baseline recordings are useful so that changes can be evaluated as relative rather than as absolute. Surgeons can then make adjustments accordingly. BAERs are central signals in that they relate to the cochlear nucleus and can be monitored during surgery on an intrinsic pontine lesion. Intraoperative changes in wave latencies suggest an interruption in the auditory pathways. However, damage to motor or other cranial nerve nuclei can go undetected. When the floor of the fourth ventricle is involved, the facial colliculus can be stimulated to localize it accurately and to minimize the chance of compromising the function of the seventh or eighth cranial nerves. Disciplined and meticulous surgical technique is the best means for avoiding postoperative deficits. We have found no benefit in performing more extensive or invasive physiologic techniques such as motor mapping.

Surgical Technique

In general and regardless of location, CMs are accessed through minimal cortical openings. The CM is removed sharply and in piecemeal fashion. If intrinsic lesions fail to reach a pial surface of the brainstem, normal brainstem tissue will be violated during surgery. In this case, an opening is made by using hemosiderin staining or a bulge in the brainstem as a guide. Alternatively, the two-point method may be applied in conjunction with frameless stereotactic guidance. Entry into the brainstem is well tolerated, even in the case of deep-seated intrinsic lesions, if the cortical opening is small and the fibers of the brainstem are gently stretched to allow resection of the lesion. In contrast, exophytic lesions are readily apparent, assuming that the correct surgical approach was chosen. Lesions usually have a characteristic “mulberry” appearance with a thin layer of arachnoid (Fig. 394-3).

FIGURE 394-3 An exophytic cavernoma of the medulla with the classic “mulberry” appearance and a concomitant associated venous malformation to the right of the lesion.

(From Spetzler RF, Koos WT. Color Atlas of Microneurosurgery. Vol. 3. Intra- and Extracranial Revascularization and Intraspinal Pathology, 2nd ed. New York: Thieme; 2000:370.)

The CM can be entered with bipolar cauterization. Acute, subacute, and chronic blood products can be suctioned. The capillary network or hemangiomatous portion can then be gently dissected with microdissectors while the surrounding parenchyma is preserved. Microscissors may be necessary to detach the lesion from surrounding tissue. During dissection the surgeon should be mindful of the ubiquitous venous anomaly. If a large, associated venous malformation is entered and coagulated, venous infarction and a devastating outcome can result. Smaller venous tributaries, however, can generally be coagulated and transected with impunity. If a surgeon is unsure of their significance, associated veins within the resection cavity should be preserved.