Please note the relevant information for patients suffering from brainstem tumors is presented in another chapter. Please click here for patient-related content.

Brainstem gliomas include a collection of clinically and surgically heterogeneous tumors and are most commonly found in children. Approximately 10% to 20% of pediatric brain tumors fall into this category, presenting in patients with a mean age of 5 to 10 years old. Intrinsic tumors of the brainstem and cervicomedullary junction were largely considered inoperable before the modern neurosurgical era because of their poor postoperative prognosis and high surgical morbidity.

With the advent of magnetic resonance imaging (MRI), however, it became possible to delineate two key imaging features that are vital for surgical decision-making process in these tumors: precise anatomic location and a focal versus diffuse morphology. As a result, distinct subgroups have emerged based on these imaging features rather than tumor histology, guiding operative paradigms. These basic brainstem glioma subgroups are:

1. diffuse,
2. focal,
3. tectal,
4. dorsally exophytic, and
5. cervicomedullary.

In fact, the diagnosis can frequently be made via preoperative imaging, which can guide the decision to pursue surgery.

Also known as diffuse pontine glioma (DPG), this tumor, regardless of its histopathology, follows a malignant course. More than two-thirds of brainstem gliomas are DPGs, and their diagnosis can usually be made radiographically through MRI. They have a diffusely expanded pons as their epicenter, extend into the medullary and/or midbrain, and lack a focal or exophytic component.

Engulfment of the basilar artery is commonly seen with DPGs. Patients with these tumors usually present with rapidly progressive cranial neuropathies, usually bilateral, followed by corticospinal tract dysfunction and hydrocephalus. Biopsy is generally not recommended because there is a high risk that a biopsy procedure would cause additional neurologic deficits. Also, a biopsy would have no effect on the patient’s treatment that consists of palliative chemotherapy and radiation only; prognosis unfortunately is dismal.

Tumors in this category may present either as a solid mass or as a cystic tumor similar to a pediatric cerebellar astrocytoma. Symptoms are usually indolent and localized to structures in the immediate vicinity of the tumor. If imaging indicates a focal lesion, but the clinical course is consistent with that of a diffuse pontine glioma, a more malignant tumor is present. For this reason, a careful clinical history is imperative.

Although most commonly located in the medulla, where presentation is that of lower cranial neuropathies (aspiration, dysphagia, apnea, tongue weakness/atrophy), these tumors may also occur in the pons (causing facial nerve or hearing as well as corticospinal tract dysfunction) or midbrain (causing oculomotor dysfunction or hydrocephalus).

Most such tumors are not operative candidates unless the tumor is cystic and the nodule is in the proximity of a safe pial surface.

These focal tumors of the quadrigeminal plate are usually clinically benign. They present with hydrocephalus. Parinaud’s syndrome is uncommon, unlike other pineal region masses.

As with other focal gliomas, a more aggressive clinical course should raise the physician’s concern for a malignant tumor, despite inconsistent imaging findings. Unlike other focal tumors, treatment of the hydrocephalus, ideally via third ventriculostomy, is often adequate, with no need for biopsy or resection unless radiographic progression occurs.

Also focal, exophytic gliomas arise from the floor of the fourth ventricle/medulla and expand posteriorly. Usually histologically low-grade, their initial presentation is that of progressive hydrocephalus from the mass obstructing the ventricle. Usually only a small portion of the tumor is within the brainstem itself. Subtotal resection of the exophytic component is reasonable for symptomatic tumors.

These tumors, although usually low-grade, clinically fall into two groups. Cervical tumors present with slowly progressive myelopathy and cervical pain, whereas medullary tumors present with dysphagia, respiratory dysfunction, lower cranial neuropathies, and possibly hydrocephalus from mass effect on the lower fourth ventricle.

A complete thorough history and neurologic examination, with special emphasis on the timeline of symptom development and cranial nerves’ function, is critical, in addition to imaging.

Diffuse gliomas and tectal gliomas are best visualized on T2 and fluid attenuated inversion recovery (FLAIR) sequences because they typically lack enhancement; the extent of the tumor is best represented by the area of T2 hyperintensity. Focal brainstem gliomas often vividly enhance within a well-circumscribed lesion, and exophytic and cervicomedullary lesions enhance variably.

Other studies of possible value include MR spectroscopy and tractography. Spectroscopy may be of value in differentiating low-grade versus high-grade tumors, or neoplastic versus rare inflammatory mimics that can present in this region. This technology can potentially obviate the need for a high-risk biopsy. Tractography is potentially valuable during surgical planning to visualize corticospinal and other white matter tracts relative to the approach corridor, although this technology is in evolution and can be unreliable for the brainstem.

The majority of brainstem gliomas are gangliogliomas and astrocytomas of variable grades. Other possibilities include hemangioblastoma, primitive neuroectodermal tumor, pediatric atypical teratoid/rhabdoid tumor, lymphoma, cavernous malformation, abscess, and possibly demyelination.

As stated above, brainstem gliomas fall into two main categories: focal and diffuse. Diffuse gliomas are generally nonoperative lesions. However, in rare cases when the radiographic diagnosis is in question, a biopsy may be indicated.

Tectal gliomas are benign and typically do not require resection. Hydrocephalus may be treated before or at the time of resection for surgical lesions; temporary cerebrospinal fluid (CSF) diversion (third ventriculostomy,) just before surgery, aids both with improving the symptoms and provides protection against CSF leakage through the surgical closure site postoperatively. After resection of an obstructive tumor mass, the patient may not need permanent CSF diversion.

Growing focal, exophytic, and cervicomedullary gliomas with reasonably well-defined borders on imaging may undergo subtotal resection for their symptomatic extra-axial component. Removal of gliomas located within the brainstem is risky and not advised. Very focal benign gliomas, such as pilocytic astrocytomas, are an exception; the offer of surgery should be judiciously considered.

Baseline appraisal of lower cranial nerve function via otolaryngologic evaluation is a key component of preoperative assessment. In the presence of significant bulbar dysfunction, perioperative tracheostomy and/or gastrostomy procedures should be strongly considered.

Endonasal intubation is an option if longer postoperative ventilation is expected. Significant hydrocephalus should be addressed through a third ventriculostomy. Arterial line placement for closer blood pressure monitoring is recommended, both because of the smaller circulating volume in pediatric patients and the risk of autonomic instability with surgery near the medulla.

Neurophysiologic monitoring is used based on the location of the tumor. Electomyographic (EMG) monitoring of cranial nerves (CNs) VII, IX/X, and XII is indicated. Concomitant low-amplitude monopolar stimulation maps the floor of the ventricle prior to myelotomy along the floor of the fourth ventricle, the pons, and upper medulla in select cases. The facial colliculus, as well as the vagal and hypoglossal trigones, should be avoided.

For subpial lesions, the safest corridor to expose the tumor is most often, but not always, where the tumor has reached closest to the surface. If ascending and descending tracts are involved, somatosensory (SSEP) and motor evoked potential (MEP) monitoring are used, especially for cervicomedullary tumors. In addition to traditional peripheral electrode placement, epidural electrodes, implanted just caudal to the operative bed, allow faster updates in MEP signaling.

MEP decrement is the most reliable marker if these potentials decline. In the case of a decline in the signals, resection should cease, the cavity irrigated, and any retraction on the brainstem/spinal cord relieved. If the potentials return to baseline, surgery may continue; if not, further intervention risks permanent neurologic deficit and must be weighed accordingly.

There are numerous approaches adopted for reaching brainstem lesions. The telovelar approach is suitable for dorsally exophytic tumors. The retromastoid craniotomy is effective for anterior and lateral focal pontomedullary tumors. The paramedian supracerebellar route is ideal for dorsal mesencephalic masses.

Solid focal tumors of the brainstem carry the highest surgical risk among the intrinsic brainstem lesions. The approach and trajectory is entirely guided by where the tumor abuts the pial surface.

Although an area of pial discoloration and displacement of the midline raphe generally mark this trajectory, intraoperative navigation is critical to confirm the underlying lesion. If there is any confusion about the entry point, intraoperative ultrasound provides live feedback/visualization of the tumor-brain interface.

A general consideration is to abstain from the dorsal midline to avoid injury to the major cranial nerves’ nuclei. To assist with this goal, stimulation of the fourth ventricle floor ensures that the chosen operative trajectory does not traverse any of the major motor nuclei. The combination of electrophysiologic mapping of the ventricle floor, visual microscopic inspection, and neuronavigation ensures the safest entry point.

A small myelotomy is made and gentle blunt dissection around and parallel to the white matter fibers continues until the discolored tumor is identified. Central debulking is pursued using a combination of gentle suction and ultrasonic aspiration. A small myelotomy is used as a keyhole to work within the tumor piecemeal, rather than making a larger incision to expose the entire tumor capsule at one time. Dynamic retraction using the suction device is a key maneuver for the success of maximal resection through minimal corridors.

Ultrasonic aspiration allows gentle removal of the firm tumor in layers without undue pulling and traction on the vital tracts. The extent of resection is guided by multiple modalities: visual inspection (resection is halted if the dissection planes are approaching and not clearly reaching peritumoral normal tissue), neuronavigation, and physiologic changes (either hemodynamics or neuromonitoring).

Cystic focal tumors of the brainstem are handled similarly. The entrance into the cyst is decided through inspection, neuronavigation, and neuromonitoring. The cyst wall is not lined with neoplastic tissue; the goal is resection of the enhancing nodule, similar to surgery for cerebellar pilocytic astrocytomas. Once the cyst is penetrated and drained, even a slight shift in the location of the brainstem will disrupt neuronavigation accuracy. Therefore, it is important to establish the tumor’s pathoanatomy ahead of time before cyst drainage.

A smaller subset of brainstem tumors may abut the surface or even become exophytic laterally. In these cases, a lateral approach may be used, either a retrosigmoid approach through the cerebellopontine angle for lateral pontomedullary tumors, or a subtemporal transtentorial approach for lateral mesencephalic or peduncular tumors.

For focal lateral pontomedullary tumors, the surrounding cranial nerves are at risk of significant injury, so a more conservative resection is advised. Posterior mesencephalic tumors can be more radically excised, while the surgeon takes care to create a pial incision in a rostral-caudal direction parallel to the pathway of the ascending/descending white matter tracts.

After the telovelar approach is completed, the tumor filling the fourth ventricle is delineated. These lesions arise subependymally and expand into the ventricle; as such, they do not respect the floor of the ventricle and cannot be totally excised. The operator’s first step is to identify the plane of the ventricular floor. This is readily done inferior to the tumor, whereas the rostral extent is often not readily accessible.

The tumor is internally debulked, while the dissection plane stays dorsal to the plane of the ventricular floor. Next, the rostral extent of the tumor is gently rolled caudally until the aqueduct and rostral ventricular floor are visualized. The floor is covered with a cottonoid patty and meticulously protected from any inadvertent suction injury.

With the plane of the ventricular floor defined, I debulk the mass and shave off the tumor using an ultrasonic aspirator to the level of the ventricle, but not into the brainstem parenchyma. When flush with the ventricular floor, the residual tumor is left in situ. Pursuing the residual tumor into the brainstem portends a high rate of injury to normal brainstem structures, especially CNs VI and VII. The facial colliculus will be distorted and/or infiltrated, lying in close proximity to the intrinsic component of the tumor.

Because these tumors are usually histologically benign, similar to cerebellar pilocytic astrocytomas, the residual mass may be observed expectantly over time and will most likely remain stable indefinitely or even involute. In rare cases, regrowth of an exophytic component may be reresected if needed.

In the presence of a laterally exophytic tumor, resection may be performed via the cerebellopontine angle. However, since the tumor most commonly originates from the ventricular floor, conversion to a midline approach may allow a greater extent of resection.

Tumors in this group behave like intrinsic spinal cord tumors rather than brainstem tumors. The initial intradural step involves identifying the true midline of the upper cervical spinal cord. The cord may be distorted or rotated because of the mass effect of the tumor, so the sensory root entry zones must be identified bilaterally in the dorsolateral sulcus to establish the true midline.

If tumor cysts are present, the myelotomy should begin over these cysts to decompress the spinal cord. The myelotomy should then be connected to the midline if necessary. In a noncystic tumor that reaches the pial surface, the myelotomy should begin over the middle of the lesion.

The surgeon should begin internal debulking using the suction device or preferably an ultrasonic aspirator. The latter will not place undue traction on the surrounding vital tissues and allows shaving off the tumor precisely to the level of the peritumoral borders. However, the ultrasonic aspirator does not provide the surgeon with the necessary proprioception or feel of the tumor versus the peritumoral tissues. I generally start enucleation caudally and then work rostrally.

If relatively clear planes between the normal and abnormal tissues are present, these planes can guide resection maneuvers. Most brainstem tumors do not own clear borders, and high-magnification microscopic visualization of the color and texture of the tumor can play an important role in guiding the extent of resection. A clear understanding of the tumor three-dimensional anatomy is also valuable during this undertaking.

Neurophysiologic monitoring, including motor evoked potentials (MEPs), does not guide resection, but alerts the surgeon regarding potentially harmful retraction maneuvers. If removal of a portion of the tumor leads to irreversible MEP changes despite relief of dynamic retraction on the tissues, the likelihood of permanent neurologic deficit is significant. Should motor responses decline, both retraction and resection should cease until the potentials return. In the absence of their return, the decision to proceed should be individualized.

The rostral extent of the tumor is usually exophytic, placing mass effect on the medulla oblongata rather than infiltrating it. Care should be taken to avoid injury to the posterior inferior cerebellar arteries underneath the tonsils. The exophytic component may be freely resected, but the surgeon must be cautious near the obex.

The closure for the craniotomy is described in the Cranial Approaches volume.

All patients are observed in a neurocritical care unit postoperatively. Steroids are continued for 2 weeks, and hypertension is aggressively avoided for the first 24 hours. Prophylactic anticonvulsant medications are not used.

Surgery near the medulla and upper cervical spinal cord can lead to postoperative respiratory compromise, either due to lower cranial nerve dysfunction or medullary respiratory center manipulation. I generally keep these patients intubated overnight after surgery until they are evaluated thoroughly for extubation the next day.

If lower cranial nerve dysfunction was present before surgery or an intraoperative injury is suspected, tracheostomy and/or feeding tube placement is performed early. For patients with more rostral tumors, dysfunction of conjugate gaze and eye movements or facial weakness may be evident. These complications require supportive care.

• Intrinsic and well-defined low-grade gliomas of the brainstem are generally not surgically curable without neurologic compromise. The goals of surgery should be clear at the onset, as guided by the patient’s imaging and neurologic status. These goals will likely include tissue for diagnosis, treatment of CSF flow obstruction, and tumor cytoreduction. Residual tumors will frequently stabilize over time.
• Surgical resection of brainstem neoplasms that are on a malignant course, as shown by either MRI findings suggestive of a diffuse pontine glioma or clinical behavior, does not benefit patient’s quality of life or survival. Indolent tumors such as cystic pilocytic astrocytomas with a focal appearance on MRI that cause only mild neurologic dysfunction generally benefit the most from surgical intervention.
• Tumors of the medulla oblongata should be carefully evaluated. If the mass is truly intrinsic to the medulla, surgical excision carries a high risk of medullary and lower cranial nerve dysfunction. However, high cervical tumors tend to displace the medulla rostrally rather than invading it, and thus are candidates for subtotal resection in patients with low-grade disease.

Contributor: Charles Kulwin, MD

DOI: https://doi.org/10.18791/nsatlas.v4.ch03.1