Presentation of Brainstem Gliomas in Children

Symptoms

The presenting symptoms associated with intrinsic brainstem tumors are somewhat variable because they depend on the tumor location, focality versus diffuse involvement, and age of the patient.

• Cranial neuropathies are common in most patients with tumors of the brainstem. Simultaneous involvement of multiple cranial nerves is more frequently encountered with diffuse lesions. Focal lesions, in contrast, are often associated with more limited cranial nerve involvement. Upper brainstem involvement is more often associated with oculomotor deficits, whereas lesions of the lower brainstem more frequently have lower cranial nerve involvement, resulting in changes in voice and dysphagia and/or aspiration pneumonias (8).
• Long tract signs are most often associated with diffusely involved tumors or focal tumors of the cervical medullary junction. Long tract signs are often conspicuously absent with dorsally exophytic tumors (26).
• Hydrocephalus with its associated signs and symptoms is often associated with dorsally exophytic tumors, which tend to grow dorsally into the fourth ventricle and result in obstruction of the normal CSF pathways. Focal midbrain tumors may also affect CSF flow dynamics through the aqueduct of Sylvius, causing an obstructive hydrocephalus.
• Failure to thrive is commonly encountered in infants with tumors of the cervicomedullary junction due to lower cranial nerve dysfunction and swallowing difficulties.
• Diffuse intrinsic pontine gliomas: Patients with a diffuse intrinsic pontine glioma usually have an acute onset and present with a short history of rapid deterioration of 1–2 months. Physical examination reveals classic brainstem signs: cranial nerve deficits, long tract signs, and ataxia, or combinations of the three. At least two of the triad must be present along with MRI evidence to establish this diagnosis.
• Cervicomedullary gliomas: Cervicomedullary tumors are often associated with an indolent course because most of these tumors are slow-growing, benign lesions. Two presenting syndromes, medullary or cervical cord, have been described based on the epicenter of the tumor (8).
• Midbrain gliomas: Gliomas in the midbrain are indolent with symptoms frequently attributable to an obstructive hydrocephalus. Symptoms seen with tumors arising in the tectum are those of increased ICP: headache, vomiting, diplopia, and papilledema. Long tract signs are commonly present when the tumor arises in the tegmentum. These include motor dysfunction, cranial nerve dysfunction, and ataxia (27).
• Dorsally exophytic brainstem gliomas: These tumors grow within the fourth ventricle and the symptoms associated with them are commonly due to obstructive hydrocephalus.

Patterns of evolution

Symptoms of brainstem tumors are a function of growth rate and location. Benign tumors typically grow slowly, respecting fiber tracts and pial borders.  In contrast, high-grade tumors grow rapidly, and their expansion does not respect the anatomic boundaries of the surrounding tissues (18,19). Thus, low-grade tumors typically cause symptoms secondary to compression, whereas high grade tumors have an infiltrative pattern that results in more rapid clinical deficits of the cranial nerves or motor pathways.

Time for evolution

The time frame for the evolution of symptoms related to tumors of the brainstem is attributable to the underlying pathology and location of the lesion in question.

• Focal tumors: Focal tumors are more often low-grade benign lesions with expectedly slow growth. Symptoms are often insidious in onset and may not be readily recognized. Comparison to photographs may be necessary to evaluate subtle changes associated with cranial nerve dysfunction in these slowly growing tumors. Behnke et al. reported on a series of 30 children with tumors of the pons and cervicomedullary junction. The authors noted that symptoms lasting for more than 6 months correlated with a benign pathology (28).
• Diffuse intrinsic pontine gliomas: By contrast, diffuse intrinsic pontine gliomas typically present with a short prodrome of symptoms (1–2 months or less) (9). Survival varies, with a median of 10–12 months (94).

Evaluation at Presentation

• See EVALUATION

Intervention

Initial evaluation should include the following:

• Detailed history and physical: For lesions with an indolent course, careful inquiry is often necessary due to the subtle onset of signs and symptoms. Photographs may be necessary for comparison to determine slow progression of cranial neuropathies.
• MRI: MRI of the brain and upper cervical spine with and without gadolinium is important both in the initial diagnosis of a suspected lesion and in the planning of subsequent management.

Preparation for definitive intervention, nonemergent

Nonemergent patients are children who present with a slowly progressive prodrome of symptoms and appear clinically stable. They can be assessed in a systematic manner and are then prepared for treatment as appropriate.

• Steroids: Steroids can be used to temporize the patient’s condition, particularly in cases of marked edema of the tumor or of the surrounding parenchyma.
• Imaging: MRI of the brain and upper cervical spine with and without gadolinium is required.
• Consultations: Evaluation by a pediatric oncologist should be obtained. Additional evaluations to be considered include otolaryngology for concerns about vocal cord function and ability to protect the airway and pulmonology for concerns about respiratory status.
• Surgery: The need for surgical intervention depends on the location and nature of the mass demonstrated on imaging. Typically, focal tumors of the pons, medulla, and cervicomedullary junction are amenable to surgical intervention. For patients with diffuse pontine lesions, surgery typically has no role, and no evidence exists to suggest that intervention modifies prognosis (29).

Preparation for definitive intervention, emergent

Emergent patients are children with surgically amenable lesions who present with rapid clinical deterioration due to direct brainstem compression or diminished level of consciousness from obstructive hydrocephalus. Prompt interventions aimed at stabilizing these patients should be initiated with the goal of preparing them for definitive surgical treatment in a controlled environment.

• Steroids: High dose IV steroids should be administered to temporize the effects of tumor swelling and surrounding brain edema.
• Imaging: MRI with and without gadolinium should be obtained as soon as possible. Arrangements for obtaining the study under general anesthesia may have to be made if the child cannot safely protect his/her airway or is unable to remain still. If obstructive hydrocephalus is suspected as the underlying cause of the child’s deteriorating condition, a CT should be obtained quickly to evaluate the ventricles and basal cisterns.
• CSF diversion for obstructive hydrocephalus:  Definitive treatment options include ETV and ventricular shunting.  For patients with rapid deterioration and altered mental status, an EVD can be placed emergently to alleviate intracranial hypertension and monitor ICP.

Admission Orders

• HOB, positioning and activity: The level of patient activity allowed is dependent on clinical status. If the patient has an altered level of consciousness, he or she is placed at bed rest with the HOB at ~30–45 degrees. The patient should be periodically repositioned to avoid dependent tissue breakdown.
• Vital signs: Vital signs should be monitored every 1–2 hours. In the unstable child, continuous monitoring of vital signs is strongly recommended, with neurological examinations performed every 1–2 hours depending on the capabilities of the admitting unit and the severity of the child’s clinical presentation.
• Blood pressure parameters: BP parameters in children are age dependent. In general, the child with a brainstem tumor should be kept normotensive to promote adequate cerebral perfusion.

• Intravenous fluids: Isotonic fluid is the mainstay in the neurosurgical patient; normal saline (0.9% NaCl) is the preferred fluid. Hypotonic and dextrose-containing solutions should be avoided as they can propagate swelling in the setting of pre-existing cytotoxic edema and blood-brain barrier disruption secondary to a neoplastic process. In the child, IV fluid rates are dependent on body weight (in kg); fluid requirements and rate can be approximated by the Holliday-Segar or 4,2,1 method (103).

• CSF drainage parameters: The goal is to drain to a high normal pressure. The collection chamber of the EVD should be placed at a level equal to the upper limit of a normal ICP specific for the patient’s age to reduce the possibility of upward herniation due to a pressure differential from CSF outflow obstruction by the presence of a brainstem lesion. The normal ICP range for various age groups is shown below.

Normal ICP range in mmHg as a function of age