Surgical Management of Brain Stem Tumors in Adults

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Chapter 13 Surgical Management of Brain Stem Tumors in Adults

Brain stem tumors account for 1.5% to 2.5% of all intracranial tumors in adults while comprising 10% to 20% of all pediatric tumors.14 These tumors are less common in adults and, therefore, more clinical studies have been conducted in children with brain stem tumors, specifically brain stem gliomas, since they are more common in this patient population.310 Adults with brain stem gliomas have a median survival of 5 to 7 years which is longer than that of children.25 Historically, brain stem tumors were treated as a homogenous group of lesions with radiotherapy, which usually proceeded without histopathologic confirmation. Surgery for these tumors was rare and typically limited to biopsy, extirpation of cystic lesions, and the placement of shunts for obstructive hydrocephalus. However, Pool documented one of the first surgical resections of a brain stem tumor located in the area of the cerebral aqueduct in 1968.11 This reported case led to the advent of further investigation and development of surgical techniques to treat lesions located in the brain stem.

Although brain stem tumors were thought to be homogeneous, the advent of computed tomography (CT) and magnetic resonance imaging (MRI) changed this belief, and imaging of the brain provided evidence that these lesions comprised a heterogeneous group. Detailed imaging allowed distinction among different tumor types according to location and growth pattern. This tumor heterogeneity would be confirmed by histopathologic examination as surgery was increasingly used as neurosurgical operative techniques, including stereotactic biopsies, and perioperative care significantly evolved.

Imaging and Classification

Prior to the advent of MRI, CT was utilized to assess the pathology of brain stem lesions and biopsy was often needed to guide management. MRI has become the primary diagnostic modality for patients with brain stem tumors because it has advanced the diagnosis and categorization of these lesions by providing superior anatomic detail of the brain stem and posterior fossa.1216 T1- and T2-weighted MR imaging have provided the ability to differentiate the tissue characteristics of tumors in many cases. In adults, the differential diagnosis for brain stem lesions may be broad and may include such pathologic entities like metastatic tumors, demyelinating processes, infectious processes, granulomas, cavernous malformations, hemangioblastomas, or hematomas that should be differentiated from gliomas.

Based upon MRI and CT data, classification schemes have been developed for grouping brain stem tumors according to growth patterns and the feasibility of surgical resection (Table 13-1).13,14,1721 The earliest classification schemes were based on CT images and surgical observation.17,19,21 Later schemes relied on MR imaging, in which better neuroanatomic details were made available.13,14,18 The most recently developed classification system relied on both CT and MRI.20 All of these schemes classify the tumor into either a focal or diffuse growth pattern, while the more complex classifications further subdivide the tumors into location within the brain stem, presence or absence of an exophytic component, and the presence of hydrocephalus or hemorrhage. The more complex schemes were developed in an attempt to predict tumor behavior and guide operative versus nonoperative management. In general, tumors with a focal growth pattern have been considered amenable to surgical extirpation in contrast to those with a diffuse growth pattern.

Table 13-1 Classification Schemes for Brain Stem Tumors

Author Method Used to Create System Classification System
Epstein21 CT Intrinsic
    Diffuse
    Focal
    Cervicomedullary
    Exophytic
    Anterolateral into cerebellopontine angle
    Posterolateral and into brachium pontis
    Disseminated
    Positive cytology
    Positive myelography
Epstein and McCleary19 CT, MRI, and surgical observation Diffuse
    Focal
    Cervicomedullary
Stroink et al.17 CT Group I—dorsal exophytic glioma
    Group IIa—intrinsic brainstem tumors
    Hypodense, no enhancement
    Group IIb—intrinsic brainstem tumors
    Hyperdense, contrast enhancing exophytic
    Group III—focal cystic tumor with contrast enhancement
    Group IV—focal intrinsic isodense contrast enhancement
Barkovich et al.14 MRI Location (midbrain, pons, medulla)
    Focality (diffuse or focal)
    Direction and extent of tumor growth
    Degree of brainstem enlargement
    Exophytic growth
    Hemorrhage or necrosis
    Evidence of hydrocephalus
Albright18 MRI Focal (midbrain, pons, medulla)
    Diffuse
Fischbein et al.13 MRI MidbrainDiffuse
    Focal
    Tectal
    Pons
    Diffuse
    Focal
    Medulla
    Diffuse
    Focal
    Dorsal exophytic
Choux et al.20 CT and MRI Type I—diffuse
    Type II—intrinsic, focal
    Type III—exophytic, focal
    Type IV—cervicomedullary

Focal Tumors

Focal tumors are intrinsic to the brain stem and may be cystic or solid (Fig. 13-1). They are typically not associated with edema and contrast enhancement may be variable. A majority of these tumors are low-grade gliomas, but some malignant tumors, such as a World Health Organization (WHO) grade-IV astrocytoma, may imitate a focal one, known as a pseudofocal tumor. In pseudofocal tumors, MRI and CT imaging demonstrate focal enhancement after the administration of contrast with normal signal characteristics from the peritumoral area that imitates the focal lesion.

Furthermore, the majority of cervicomedullary gliomas are low-grade, noninfiltrative tumors, and their growth is usually confined rostrally by the white matter of the corticospinal tract and medial lemniscus.22

Additional Imaging Modalities

Imaging of the central nervous system has evolved with the continual development of more sophisticated techniques. Positron emission tomography (PET) has been used in an attempt to differentiate low-grade from high-grade brain stem gliomas, particularly in the pediatric population.2326 Although the MR imaging characteristics of gliomas may be highly diagnostic in the pediatric population allowing for the potential use of PET imaging to attempt to determine the degree of malignancy, the heterogeneity of lesions in the adult population may not allow for the procurement of useful data until studies are conducted correlating preoperative PET imaging with histologic diagnosis. One study utilized PET imaging in two adults with dorsal midbrain lesions and obstructive hydrocephalus.27 The lesions were hyperintense on T2-weighted images and partial contrast enhancement was observed in one patient. The patients underwent preoperative PET studies followed by an endoscopic third ventriculostomy combined with endoscopic biopsy sampling of the lesions. Glial proliferation, which contained the partial enhancement with contrast, and a possible low-grade glioma were diagnosed in the two patients, respectively. Results of the PET imaging in both patients suggested that the lesions had nontumorous characteristics and portended a good prognosis. With larger-scale studies, PET imaging may someday prove to be more informative and predictive of the biological behavior of dorsal midbrain lesions than a biopsy.

Magnetic resonance spectroscopy (MRS) is a noninvasive imaging modality used for tissue characterization and complements data obtained from MRI. The concentrations of creatine, phosphocreatine, choline, N-acetylaspartate, lactate, and lipids are analyzed in an effort to differentiate various pathologic processes. It has been used to distinguish between normal and abnormal tissues and grading of brain tumors. Inflammation, infectious processes, and tumors may potentially be distinguished with MRS.28 Studies have been conducted with MRS to investigate brain stem lesions with histologic correlation in some cases.2831 MRS can provide additional information on brain stem lesions, but further studies are needed with histologic confirmation given the broad differential diagnosis of brain stem lesions in adults.

Diffusion tensor imaging (DTI) is an imaging modality that demonstrates white matter tracts. The relationship of sensory and motor tracts to brain stem tumors has been investigated in pediatric patients.32,33 With further studies and evolution of this technique for use in the brain stem, DTI may play a role in assisting the treatment planning for brain stem lesions in adults.

Stereotactic Biopsy

Since the late 1970s, stereotactic biopsies of brain stem lesions have been performed and account for 5% to 12% of all brain biopsies.3456 This procedure was not used widely in the pediatric population because it was reported that characteristic MRI features were sufficient to diagnose diffuse brain stem gliomas without the need for a biopsy.14,5759 Biopsies of brain stem lesions are not as common as other brain biopsies because of the risk involved in obtaining tissue. However, studies have shown that stereotactic brain stem biopsies can be routinely performed in a safe and effective manner.34,40,4246,5156 In some published series, the reported rate of complications has ranged between 2.5% and 7.7%.54,56,60

In adults with contrast-enhancing brain stem lesions, other pathologic processes must be considered in the differential diagnosis because studies have demonstrated preoperative radiographic diagnoses to be incorrect in 10% to 25% of cases in patients over 20 years of age presenting with a contrast-enhancing lesion in the brain stem.60,61 In addition to malignant glioma, the differential diagnosis may include infectious processes, such as abscess, tuberculomas, and toxoplasmosis, demyelinating disease, sarcoidosis, progressive multifocal leukoencephalopathy, metastasis, lymphoma, and vascular processes, such as vasculitis and infarction (Figs. 13-5, 13-6, and 13-7).2 This heterogeneity of brain stem lesions in adults makes it difficult to make a diagnosis on the basis of imaging alone. Therefore, image-guided stereotactic biopsies are indicated in many adult brain stem lesions that enhance with contrast and generally in cases in which the diagnosis of the lesion is in doubt to determine the histology of the abnormal process.

Stereotactic biopsies of the brain stem are performed with image guidance utilizing either CT or MRI. Approaches used include the transfrontal, transtentorial, and transcerebellar routes depending on the location of the lesion within the brain stem. The transtentorial approach, which is really not used, places vital vasculature and cranial nerves at risk and may cause pain with tentorial puncture.62,63 In addition, this route crosses the pia two additional times above and below the tentorium. The ipsilateral transfrontal route frequently requires traversing the lateral ventricle and is limited to midline regions of the pons and medulla by the tentorial incisura.41,51,64,65 Moreover, the suboccipital transcerebellar approach has been used for lesions in the lower midbrain, pons, middle cerebellar peduncle, and rostral medulla.34,46,47,54,66,67 Due to patient positioning, intubation and general anesthesia is generally required although the use of local anesthesia has been reported.54,67 With this approach, a potential drawback is the discomfort associated with muscle dissection prior to placement of the twist-drill hole.

An alternative contralateral, transfrontal, extraventricular approach using a Leksell stereotactic frame system has been described for reaching lesions in the lateral pons and middle cerebellar peduncle (Fig. 13-8).53 The needle’s trajectory crosses only one pial surface and avoids the ventricle and tentorium. In a reported series of six patients, diagnostic samples were obtained in all patients and there was no surgical morbidity.53

Indications for Surgery

In general, patients with a clinical presentation and imaging consistent with a diffuse glioma will not benefit from surgical intervention, although experimental studies are being conducted for the local intracranial delivery of therapeutic agents to these lesions.1,6872 Focal brain stem tumors are considered amenable to surgical resection, which is often the primary treatment of choice. Dorsal midbrain tumors, such as tectal gliomas known to be indolent and stable clinically and radiographically for many years, may be initially managed in a nonoperative manner with serial imaging, and surgery is performed in cases of tumor progression on MRI.73 Obstructive hydrocephalus, if present, may be treated with an endoscopic third ventriculostomy and the tumor can be followed with serial MR imaging.

For those undergoing brain stem surgery, patients should be informed that there may be a transient or permanent worsening of their neurologic condition.

Intraoperative Neurophysiologic Monitoring and Mapping

The complex neuroanatomic organization of the brain stem presents a formidable challenge to neurosurgeons when operating on lesions in this complex, small structure. Within the brain stem, cranial nerve nuclei and ascending and descending pathways are contained here. Tumors can distort the normal anatomy of the brain stem, such as anatomic landmarks on the floor of the fourth ventricle like the facial colliculus and striae medullares, and make surgery even more challenging. The introduction of intraoperative neurophysiologic monitoring and mapping has allowed for safer surgery and assisted in formulating the operative plan while minimizing risk to critical brain stem structures.

Brain stem auditory, somatosensory, and motor-evoked potentials are utilized to monitor their corresponding pathways during surgery. This form of monitoring does not help to prevent the injury of vital brain stem structures because functional mapping is not taking place to identify danger zones during surgery.

Functional mapping of the fourth ventricular floor has allowed the identification of brain stem cranial nerve motor nuclei and their relationship to the tumor.7476 The responses from muscles innervated by cranial nerves VII, IX, X, and XII can be recorded during surgery as the neurosurgeon stimulates the floor of the fourth ventricle with a hand-held monopolar probe. To prevent the occurrence of damage to the floor of the fourth ventricle during stimulation, the tip of the probe is round and approximately 0.75 mm in size. Muscle action potentials, through the utilization of EMG, can be recorded from the orbicularis oculi and oris muscles (CN VII), posterior pharyngeal wall (CN IX, X), and tongue muscles (CN XII). Confirmation should be obtained that the muscle relaxant does not interfere with EMG recordings. Moreover, the extent of brain stem compression, pathology, and distance to the cranial nerve motor nuclei play important roles in determining the threshold intensity, which can be as low as 0.2 mA for a hematoma, while brain stem tumors usually require higher threshold intensities up to 2.0 mA. After a muscle response is recorded, utilization of the threshold intensity allows for localization of the nuclei by moving the stimulation probe every 1 mm. This information allows for a safe site for an incision and attempts to minimize injury during tumor removal.7476 If muscle responses are not detected, technical problems with the stimulator and/or recording system may be present, or the cranial nerve motor nuclei may be located ventral to the pathology. If the nuclei are located ventral to the brain stem pathology, then repeated stimulation would be required through the lesion for detection of the nuclei.

Moreover, the corticospinal tracts can be mapped at the level of the cerebral peduncles.77 A Kartush handheld stimulator (Medtronic Xomed, Inc.) is used to focally stimulate the midbrain with EMG monitoring of specific muscles. This intraoperative modality allows the surgeon to determine the location of the aforementioned pathways in relation to the tumor and safely make an incision in the midbrain. Localization of the corticospinal tracts assists the surgeon in an endeavor to protect them during the dissection around and mobilization of the lesion.

Surgical Approaches

The location and size of the tumor within the brain stem dictates the surgeon’s operative approach for resection. The complex neuroanatomic structure of the brain stem and surrounding vasculature must be taken into consideration when formulating the surgical strategy. MRI is utilized to localize the tumor and plan the most optimal route to the tumor that will minimize the risk of injury to neurovascular structures.

For tumors in the dorsal pons, fourth ventricular floor, dorsal medulla, and posterior cervicomedullary junction, we prefer the suboccipital approach with the patient placed in the prone position. Tumors in the midline tectal region can be reached by the supracerebellar-infratentorial approach, and we also perform this procedure with the patient in the prone position. Lesions in the posterolateral pons, lateral middle cerebellar peduncle, superior lateral medulla, and cerebellopontine angle can be accessed through a retrosigmoid approach, and the far-lateral approach, which provides an anterolateral trajectory to the brain stem, is utilized for lesions in the inferolateral pons and anterolateral medulla. We use the park-bench position for both the retrosigmoid and far-lateral approaches.

The subtemporal approach provides access to lesions of the lateral midbrain. An orbitozygomatic approach provides additional access to the rostral pons, interpeduncular region, and pontomesencephalic junction in addition to the lateral midbrain.7880 These approaches may be combined with an anterior petrosectomy for lesions located more inferior in the ventral pons.

Surgical Techniques

The complex neuroanatomic structure of the brain stem requires very careful microsurgical technique when resecting tumors. The small dimensions of the brain stem demand precise movements and good intraoperative judgment at all times. An optimally functioning surgical microscope is vital to operations in and around the brain stem.

Intrinsic tumors necessitate an incision in the surface of the brain stem and require a thorough understanding of the anatomy. Although many tumors can be accessed where it is closest to the surface, it must bear in mind that this may not be the optimal route in some cases. The incision is usually small and less than 1 cm, which typically provides enough space for the resection of large tumors. Tumors in the vicinity of the corticospinal tracts in the cerebral peduncles can be mapped for a safe entry point. For tumors approached through the fourth ventricular floor, mapping of the floor is extremely important for placement of the incision to avoid cranial nerve nuclei, such as VII, IX, X, and XII. In addition, there are areas of the brain stem that can be entered relatively safely. Dorsal pontine tumors approached through the fourth ventricular floor can be entered through the median sulcus above the facial colliculus, suprafacial, infrafacial, and area acoustica. Tectal mesencephalic tumors can be accessed through the supracollicular, infracollicular, and lateral mesencephalic sulcus, while longitudinal myelotomies can be performed in the posterior median fissure below the obex, posterior intermediate sulcus, and posterior lateral sulcus for medullary and cervicomedullary tumors.81

Once the tumor has been reached, its consistency is evaluated and will determine the method of extirpation according to the surgeon’s preference. A tumor specimen should be submitted as soon as possible for determination of the histology. The histology will determine if a gross-total resection is feasible, which is more likely in the case of benign tumors. Depending on the surgeon’s preference, microretractors may be used. Tumors should be removed in a piecemeal fashion and not en bloc. If a cyst is associated with the tumor, removal of the cystic fluid aids in tumor debulking by providing additional space for manipulation. Ultrasonic aspiration set at a low intensity and suction rate and/or microscissors are more effective for solid tumors. Microbipolar coagulation and simultaneous aspiration of coagulated tissue may be used for soft tumors. The surgical resection must be confined to the inside of the tumor to avoid injury to normal surrounding structures. After a majority of the tumor is debulked, a normal boundary between the tumor and normal brain is sought. When delineation between tumor and normal brain is identified, gross-total resection is feasible in most cases. Tumor resection should be stopped when an interface between the two cannot be visualized because the decision to continue with debulking the lesion may increase the chances of postoperative neurologic morbidity. In addition, some tumors may be highly vascular and the vessels must be coagulated during tumor debulking, which may cause ischemic damage to surrounding normal brain.

For focal tumors with an exophytic component, this protruding aspect of the tumor provides an avenue for surgical access to the tumor. Moreover, tumors that penetrate the subarachnoid space may contact or encase vital arteries, and those that penetrate the ventral brain stem may contact the vertebral or basilar arteries and their branches; therefore, these tumors must be approached with extreme caution. Tumors arising from the subependymal aspect of the pons or medulla with no or minimal brain stem invasion and protruding into the fourth ventricle comprise a subgroup of dorsally exophytic tumors that are benign and can be resected with success.22,82,83

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