Surgery for Pediatric Brain Tumors

Nalin Gupta, Chief of Pediatric Neurosurgery at UCSFFor the majority of brain tumors in children, the ability to remove all the visible tumor is the most important factor predicting long-term outcome. For this reason, most neurosurgeons will be as aggressive as possible during the initial procedure in order to achieve “gross total resection” (GTR). GTR is not the primary goal for tumors that respond very well to chemotherapy (such as germinoma), or where very important parts of the brain are involved (such as brainstem and thalamic glioma). In the past ten years, several technological advances have allowed surgeons to build maps of the brain in their patients, which allows important areas of the brain to be identified before the actual operation. UCSF’s Pediatric Brain Tumor Center is equipped with the most up-to-date imaging and surgical navigation systems available:


Ultrasound

Intraoperative ultrasound is a safe method used to determine depth, the consistency of the tissues (solid, fluid-filled, complex, etc.), and the relationship to adjacent structures. Ultrasound provides real-time updates during surgery.


Neuronavigation

Neuronavigation refers to several tools that are combined to allow the surgeon to have a better sense of where tumor are located within the brain. Several manufacturers supply systems that use a preoperative MRI scan as the basis for an intraoperative three-dimensional guidance system. Standard MRI may be complemented by more specialized MR techniques such as MR spectroscopy, diffusion tensor imaging, and functional MRI. These special MR sequences can be merged with conventional anatomic images and then used in the operating room during surgery.

BrainLab Neuronavigation for Pediatric Brain Tumors
Above: Intraoperative neuronavigation image demonstrating the biopsy procedure for a brainstem glioma. Preoperatively, diffusion tensor imaging allows identification of the corticospinal tracts (oragne outlines), which can then be avoided to reduce the likelihood of a motor deficit.

Neuronavigation has impacted brain tumor surgery in three major ways. First, surgery can be simulated and planned preoperatively, allowing maximum accuracy of incisions and routes. As a result, mistakes in trajectory and depth during tumor resection are prevented. Second, the shortest and safest route can be selected that avoids important neural and vascular structures. This reduces the risk of postoperative neurologic deficits and improves assessment of risk preoperatively. Third, the use of neuronavigation improves the ability to remove the tumor by providing “feedback” to augment the surgeon's perception of the anatomy.


Functional Imaging

Perfusion imaging for pediatric glioma - UCSFSeveral technologies are used to create functional maps of the brain: functional MRI (fMRI), diffusion-weighted imaging , positron emission tomography (PET), and magnetoencephalography (MEG). Differences that occur in blood flow between active and inactive cortical areas are exploited by fMRI. These differences are magnified by instructing the patient to perform repetitive tasks — which may be as simple as repeatedly moving the fingers. Local increases in blood flow are then detected by specific MRI sequences. Diffusion tensor imaging exploits the differences in the diffusion of water molecules depending upon the local environment of those molecules. This information can then be extracted to create maps demonstrating the location and direction of white matter pathways.

PET relies upon metabolic differences within active cortex to isolate functional areas. MEG relies on the ability to detect magnetic fields created by areas of seizure activity. This information is especially valuable when correlated with tumor localization. UCSF is one of few institutions on the West Coast with MEG capabilities.


Cortical Mapping

Brain mapping techniques are essential to identifying and avoiding injury to vital sites of language, motor, and sensory function. Many of these techniques were pioneered at UCSF. The major limitations of cortical mapping in children are the relative immaturity of the central nervous system in very young children and the inability of children to cooperate during repetitive language tasks during speech mapping.

Motor Mapping
Motor mapping is the most robust technique that can be done in the operating room. Patients remain under general anesthesia and direct stimulation permits accurate mapping of the primary motor cortex. Areas of cortex responsible for specific muscle groups (e.g., face, arm, hand, leg) can be reliably identified.

Language mapping
Language mapping is dependent upon patient cooperation and, therefore, is the most difficult technique to accomplish in young children. During awake craniotomy, a handheld stimulator is used to directly inactivate the cortex while the patient names objects shown to them. In general, awake craniotomy is performed on patients older than 12 to 14 years of age. In children unable to cooperate with an awake craniotomy, and for whom functional localization is crucial to the success of the procedure, placement of subdural grids will permit bedside cortical mapping. This requires two procedures for the patient, a substantial degree of patient cooperation, and close communication between child neurologists, psychologists, and nursing staff. The contacts on the grid are stimulated while the patient is led through specific language tasks such as naming, counting, and repeating. As with awake craniotomy, speech arrest during stimulation is the clue for identifying active cortex. The procedure often requires sessions over 2 or 3 days.


Mapping of Seizure Foci

If seizures are particularly intractable or appear to be the major symptom associated with a brain tumor, the actual seizure focus may need to be identified. This can done non-invasively or with the implantation of electrode grids placed directly on the brain. The recording may either be done for short time periods during the surgery (5 to 20 min), or for longer periods of time in specialized monitoring units.


Special Issues With Posterior Fossa Tumors

Almost half of all brain tumors are located in the posterior fossa. This is the lower part of the head and normally contains the brainstem and the cerebellum. The three main tumor types that occur in this location are astrocytoma, medulloblastoma, and ependymoma. Cerebellar astrocytomas are usually one one side, have a cyst, and often cause hydrocephalus. Medulloblastomas are usually in the middle. Ependymomas can extend into the fourth ventricle and also may involve the cranial nerves. Both ependymoma and medulloblastoma can invade the brainstem.

In the past, most surgeons would remove the overlying bone without replacement (craniectomy), but currently, most surgeons attempt to replace the bone flap at the conclusion of the procedure (craniotomy). There is some evidence that this reduces the risk of cerebrospinal fluid (CSF) leakage and pseudomeningocele formation. The character of the interface between tumor and brain can vary across tumor types. In general, the interface is better defined with ependymomas as compared to medulloblastomas. Cerebellar astrocytomas have a clear margin between the tumor and the adjacent brain. The large size of most pediatric tumors and the need to avoid unnecessary brain retraction results in many tumors being resected piecemeal using either standard tools (cautery and suction) or ultrasonic aspirators that use a rapidly vibrating metal tip to disintegrate tissues. Finally, additional safety can be obtained by monitoring various cranial nerves. These nerves are sensitive to manipulation and can be difficult to identify when tumors surround them.

Surgical Complications

Surgical resection of brain tumors may lead to both non-neurologic and neurologic complications. Fortunately, the majority of these adverse effects are either temporary or treatable. Symptoms include weakness and loss of sensation, mutism, and problems with cranial nerve function. Unsteadiness is due to swelling and injury to the cerebellum.

Mutism
Mutism (inability to speak) is a well-recognized complication following removal of large tumors in middle of the cerebellum. The majority of patients will awake from surgery with intact speech function, but then develop mutism within 24 to 94 hours. Recovery from complete mutism begins with very slow or clumsy speech, usually with isolated words and phrases, progressively improving to full sentences. Most patients recover fluent speech within 4 months of surgery with an average duration of mutism lasting 6 weeks. Up to 20% of patients may have permanent dysarthria following recovery from mutism.

Cognitive Consequences
Alterations in higher cognitive function and affect can also occur. Irritability, impulsiveness, and disinhibition are the most common changes in affect. These neuropsychologic consequences are often temporary, but longer term studies indicate that neurologic and neuropsychologic changes persist more frequently with injury to the deep areas of the cerebellum. School performance and IQ are also affected by cerebellar surgery, but studies are confounded by the inability to separate the emotional and psychologic effects of childhood illness and stress from the surgical procedure. Overall, the rate of IQ decline is determined by multiple factors such as age at time of treatment, presence or absence of hydrocephalus, use of radiotherapy, and the volume of brain that received radiation.

Hydrocephalus
With a posterior fossa tumor, hydrocephalus is caused by obstruction of the CSF pathways. Children can have hydrocephalus at the time they start showing symptoms, or it can develop in the postoperative period, usually because of cerebellar swelling or a hematoma accumulating in the resection cavity. Acute symptomatic hydrocephalus, either pre- or postoperative, should be treated by immediate placement of an external ventricular drain. In most patients, complete removal of the mass lesion will result in resolution of the hydrocephalus.

The rate of CSF shunting following posterior fossa surgery ranges from 10 to 26% of patients. Endoscopic third ventriculostomy (ETV), or an opening of the floor of the third ventricle to bypass the posterior fossa obstruction, is another alternative to placement of a permanent shunt.