Natural History and Epidemiology

Brainstem gliomas account for less than 2% of all gliomas in adults, whereas pediatric brainstem gliomas constitute 20% of pediatric brain tumors. ^{3 , 18} The median survival time of adult patients with brainstem gliomas is estimated to range between 30 and 40 months, which is apparently longer than the median survival of 10 months in pediatric brainstem glioma patients. ²⁰

Because adult brainstem gliomas comprise a heterogeneous group of various tumor entities, the prognosis of each individual adult patient harboring a brainstem glioma is difficult to predict. In the most recent literature, four types of brainstem gliomas with different epidemiology were distinguished. ^{3 , 21} (1) Diffuse intrinsic low-grade gliomas seen in young adults 20 to 50 years of age are the most common brainstem lesions (45%–50%). (2) Enhancing malignant gliomas that occur in patients older than 40 years of age account for 30% of all adult brainstem tumors. (3) Focal tectal brainstem gliomas, which are well-circumscribed but rare tumors, constitute only 8% of brain-stem gliomas in adults. (4) Exophytic brainstem gliomas are rare among adults, in contrast to their prevalence among children.

Table 13.1 compares several characteristic features of brainstem gliomas in adult and pediatric patients.

Clinical Presentation

The most frequent symptoms encountered in patients with a brainstem tumor are headache, gait disturbance, and diplopia. Some authors divide the clinical presentations of patients into four categories: symptoms and signs of raised intracranial pressure, cranial nerve dysfunction, cerebellar dysfunction, and long tract signs. Mood and behavioral changes also occur frequently. Usually, symptoms of cranial nerve dysfunction correlate well with tumor location in the brainstem—eye movement disorders with lesions of the midbrain; sixth nerve palsy, facial weakness, and facial sensory deficits with pontine lesions; and dysphagia and dysarthria in medullary tumors. In patients with bulbar impairment, sometimes a tracheostomy and nasogastric tube feeding or percutaneous endoscopic gastrostomy may become necessary. Symptoms can fluctuate, and often patients may deteriorate clinically before radiologic changes are clearly visible because any space-occupying neoplasm within the brainstem can cause some dysfunction because of the high density of critical structures in a very limited space. ^{1 , 12}

Diffuse and Focal Tumors

The most common and typical diffuse brainstem tumor is the DIPG, which is encountered mostly in the pediatric population. ⁷ These DIPGs have characteristic features on magnetic resonance imaging (MRI)—they are hypointense on T1-weighted and hyperintense on T2-weighted images, usually with little or no contrast enhancement. These tumors usually have no clear-cut margin. Generally, the tumors involve the entire pons, which will show signs of swelling, sometimes with exophytic portions. In the 2016 World Health Organization (WHO) classification of brain tumors, DIPGs now constitute a separate entity. ²² Only rarely are they encountered in adult patients. These tumors carry a poor prognosis, with patients having a survival time similar to the clinical course of patients with glioblastomas.

Focal gliomas are demarcated lesions. They can be solid or cystic, and in the vast majority of cases there is a clear-cut interface between the tumor and brainstem parenchyma. Most focal gliomas show contrast enhancement, and the majority correspond to low-grade tumors. They tend to originate more frequently within the midbrain and medulla oblongata, and they represent only approximately 9% of tumors arising within the pons. ²³

Neuroradiologic Evaluation

Computed tomography played a role in evaluating patients with brainstem tumors until the 1980s, ¹³ when it was rapidly replaced by MRI, which became the main diagnostic tool. MRI gives a first and very clear impression about the site, extent, and direction of tumor growth, as well as other morphological features, such as whether the lesion is focal, diffuse, solid, or cystic. Thus, MRI allowed clinicians to establish a more precise characterization of brainstem gliomas and to identify tumor location and the biological behavior of brainstem tumors. ²

Typically, diffuse low-grade gliomas appear on MRI as infiltrative and poorly demarcated tumors in the medulla (60%) and in the pons (30%). Images are isointense or hypointense on T1-weighted MRI and hyperintense on T2-weighted or fluid-attenuated inversion recovery (FLAIR) images. They usually lack contrast enhancement. Sometimes infiltration along the middle cerebellar peduncle into the cerebellum or directly into the midbrain can be observed. Malignant brainstem gliomas in adults appear as contrast-enhancing tumors accompanied by perifocal edema. The ring-like enhancement on MRI suggests intralesional necrosis. Often differential diagnosis is necessary because other pathologic entities resemble this type of brain-stem glioma with similar contrast enhancement (lymphoma, inflammatory disease, abscess, metastasis, demyelinating disease, ependymoma, hemangioblastoma, and infarction). Focal tectal brainstem gliomas are well-defined lesions in the tectal plate or in the periaqueductal region. These tumors appear as isointense or hypointense on T1-weighted images and as hyper-intense on T2-weighted images. Contrast enhancement is usually not present. Typically, they remain morphologically stable for many years. An exophytic brainstem glioma often appears as a mass originating from the floor of the fourth ventricle. Such lesions can be misdiagnosed as ependymoma or choroid plexus papilloma in cases of contrast enhancement.

Magnetic resonance spectroscopy can be useful for differential diagnosis, similar to its use in patients with supratentorial lesions. Salmaggi et al ¹⁸ first reported the elevation of the choline/N-acetyl-aspartate ratio in adult brainstem gliomas. However, the application of magnetic resonance spectroscopy in the brainstem is limited so far by the relatively small size of the brainstem and by the close vicinity of adjacent skull base structures, such as bone and fat tissue. Single-voxel magnetic resonance spectroscopy is currently used to evaluate pontine lesions with a diameter of more than 2 cm. ^{3 , 21}

Fluorodeoxyglucose and fluoroethyl-L-tyrosine positron emission tomography (FDG-PET and FET-PET, respectively) can be effective in detecting the aggressive part of a brainstem glioma. It is known that neoplastic lesions show significantly higher ¹⁸F-FET uptake than nonneoplastic lesions. In all gliomas, ¹⁸F-FET uptake is observed in about 80% of grade I gliomas, 92% of both grade II and grade III gliomas, and 100% of grade IV gliomas. ^{21 , 24} Therefore, FET-PET can be used to distinguish a low-grade glioma from a high-grade brainstem lesion or to define the biopsy target and the extent of surgical resection.

Tumor Classification

Since the 1980s, various brainstem tumor classifications based on tumor location, growth pattern, and histopathologic criteria have been introduced. Epstein and McCleary ⁵ and Epstein and Wisoff ^{6 , 7} were the first to classify brainstem tumors according to their appearance on computed tomography; other authors followed with slightly modified classifications. The authors’ main purpose was to identify those patients who might benefit from tumor resection surgery. In 1985, Epstein et al ²⁵ distinguished three tumor types according to their growth pattern: exophytic (subdivided into diffuse, focal, and cervicomedullary types), intrinsic (subdivided into cerebellopontine angle, brachium pontis, and fourth ventricle types), and disseminated. In the 1990s, a new classification system based on MRI described the management of brainstem gliomas. ² This improved imaging technique enabled identification of tumor location and better understanding of their biological behavior. ² MRI-dependent classification was also proposed for brainstem gliomas in adults, distinguishing diffuse intrinsic low-grade tumors, enhancing malignant gliomas, focal tectal gliomas, and exophytic gliomas. ^{3 , 21} Because biopsy or open surgery was often considered inappropriate in adult patients with diffusely infiltrating gliomas, this type of MRI-based classification remained important in the management of brainstem gliomas in adults.

History of Management

Since the early years of neurosurgery, a brainstem neoplasm was regarded as an inoperable tumor. Accordingly, even if neurosurgical interventions in brainstem tumors were considered, they were not primarily directed at tumor removal but occasionally were directed at reducing the increased intracranial pressure or at obtaining tumor tissue for histopathologic diagnosis and rarely were directed at tumor debulking to improve the clinical situation. Walker et al ¹² mentioned that surgery of brainstem tumors in children should not be termed “impossible” but rather “unhelpful.” Management of brainstem tumors mainly consisted of combined radiochemotherapy. ¹ Surgical treatment of adult brainstem gliomas has been mentioned in the literature only since 1968, ²⁸ but there is no consensus among specialists regarding the optimal treatment.

According to Reyes-Botero et al, ³ each type of adult glioma requires a different treatment principle. In adults with diffuse intrinsic low-grade gliomas, total resection is regarded as technically impossible. MRI-guided stereotactic biopsy is recommended to obtain a histologic diagnosis. Radiotherapy is the standard treatment for this subgroup of adult brainstem gliomas, similar to treatment applied for pediatric DIPGs. The conventional radiotherapy is performed with a median dose of 50 to 55 Gy. Chemotherapy has not proven to be effective for this type of adult glioma. The median survival of adults with diffuse intrinsic low-grade gliomas is 4.9 to 7.3 years. ³

In enhancing malignant adult brainstem gliomas, only a limited biopsy or shunt replacement is considered. Radiotherapy does not have a significant effect on this subgroup. Chemotherapy combined with radiotherapy can be an option. Theeler et al ¹⁹ demonstrated that the standard Stupp regimen for brain-stem glioblastomas was effective in comparison with no treatment, but there is no prospective study that strongly supports the efficacy of chemotherapy in this subgroup of adult brain-stem glioma. Focal tectal brainstem glioma forms a different group of brainstem tumors with good prognosis; median survival among patients who receive this diagnosis is more than 10 years. Usually, observation is deemed appropriate, sometimes with shunt placement. Exophytic brainstem glioma is regarded as an extremely rare subgroup in adults; in only a few cases have lesions been found to extend into the fourth ventricle, which then allowed the lesions to become amenable to surgical resection. These treatment recommendations are based only on radiologic images. Because of the small number of patients with adult brainstem gliomas reported in the literature and the lack of histologic verification, the value of such treatment strategies has yet to be elucidated.

Patient Selection

Deciding whether surgery is indicated in a specific case is one of the most difficult aspects in brainstem glioma management. Because no widely accepted criteria are available, patient selection was highly individualized and based on the senior author’s experience and subjective estimation of each individual case. He took great care to identify those individuals for whom a real benefit from surgery could be expected and, conversely, to exclude from microsurgical management those for whom surgery was predicted to be unhelpful. Patients in this series were selected as surgical candidates in the majority of cases when the tumor appeared as a focal lesion, when it was estimated that at least a significant amount of tumor mass could be removed without adding substantial morbidity by surgical manipulation within the brainstem, and when concomitant long-term survival or even cure was deemed possible. In very few cases was it considered favorable to undertake only an open tumor biopsy to clarify the histopathologic diagnosis (in recent years, based on molecular criteria), to perform an endoscopic third ventriculostomy in case of obstructive hydrocephalus, or to release local pressure by evacuating an associated compressive tumor cyst.

Goals of Surgery

The main goal of surgery was to remove as much of the tumor mass as possible without additional damage to the brainstem parenchyma, with the hope of offering the patient much more than just good palliative care. In low-grade tumors, particularly pilocytic astrocytomas, rosette-forming glioneuronal tumors, and papillary glioneuronal tumors, even total tumor removal was possible in many patients, provided the tumor had not yet extensively invaded the brainstem. In the majority of such cases, we encountered a well-defined tumor-brainstem interface that enabled precise dissection. In other tumor types, for instance in diffuse or in high-grade gliomas, total tumor removal was not even attempted because of the lack of a clear-cut tumor border. In these latter cases, a significant tumor debulking was considered favorable for the patient in addition to obtaining a precise histopathologic diagnosis.

Timing of Surgery

Once a brainstem glioma was diagnosed and the patient was determined to be a good surgical candidate, tumor resection was undertaken at the earliest convenience to avoid further tumor growth. In a few patients with concomitant occlusive hydrocephalus, however, it seemed useful to apply cerebrospinal fluid (CSF) diversion (endoscopic third ventriculostomy or placement of a ventriculoperitoneal shunt) before tumor resection to facilitate the main surgical procedure that followed 1 to 2 weeks later. A similar tactic has been employed by others. ³⁸

Preoperative Planning

After careful assessment of the surgical resectability of a brain-stem tumor, the entire surgical procedure was meticulously planned. High-quality neuroradiologic imaging provided the basic morphological features of the lesion to be treated. Once these details were available, it was important to plan the surgical intervention in the reverse order of how the procedure would later be performed; first, the optimal entry zone into the brainstem was assessed, particularly in patients with nonexophytic lesions that would not be readily visible on the surface of the brainstem. This was followed by the second step, namely choosing an adequate exposure of the brainstem via the most suitable surgical approach. In patients with exophytic lesions, the decision for the optimal surgical approach was easier, as the lesion and the direction of its expansion dictated the choice of the best access route. Once the decision for the surgical approach was taken, patient positioning and skin incision were easily planned in a third step.

Care was taken to ensure that patients and families provided informed consent and fully understood the aim of surgery and the possibilities of tumor resection in each specific case, the amount of tumor that might safely be removed, and the risks of the scheduled surgical intervention. Additionally, the expected immediate surgical outcome and the necessity of postoperative adjuvant therapies were explained in detail.

Anesthesia, Intraoperative Guidance, and Monitoring

Details of the planned surgical procedure were always discussed with the anesthetist before surgery. It was important to avoid excessive venous congestion during the procedure by proper patient positioning, and adequate anesthesia facilitated achieving this goal. During surgical exposure and manipulation around the tentorium or within the brainstem, patients occasionally developed a vagal reaction with sudden bradycardia or a sudden rise in blood pressure. Therefore, the anesthetist was prepared for such events, and, if necessary, took appropriate action.

Intraoperative guidance using a neuronavigation system was applied in some cases; however, its benefit was limited in brainstem gliomas, and the navigation system was not always sufficiently reliable. We considered it more advantageous to identify well-known anatomical landmarks during surgery. The topographic anatomy of the brainstem with the exit points of cranial nerve rootlets offered valuable information for precise intraoperative orientation.

In contrast, electrophysiological monitoring during brain-stem glioma surgery is a most powerful tool that we consider mandatory for such procedures. In all instances, we routinely monitored motor, somatosensory, and auditory evoked potentials throughout the entire surgical intervention. ³⁹ Depending on which region of the brainstem was exposed, mapping of the rhomboid fossa ⁴⁰ and cranial nerve electromyography were applied as well. In three patients, intraoperative MRI was used and found to be most helpful in identifying residual tumor portions that were not easily recognized during surgery.

Selection of Surgical Approaches and Patient Positioning

The surgical approaches used in the present patient series are listed in Table 13.4 . We selected the most suitable surgical approach in each individual case according to the following criteria: the approach should allow for an optimal viewing trajectory toward the brainstem tumor, in the same direction as the tumor’s longitudinal axis, if applicable; venous congestion during surgery should be avoided; and the approach should allow for sufficient craniocaudal exposure without excessive compression or retraction of surrounding structures, such as the temporal lobe or cerebellum. The semisitting position has many advantages and is used by other authors as well. ²⁰ When performing surgery on younger patients, we preferred having the patient in the semisitting position whenever it was deemed useful; however, in patients older than 60 years, especially when the patient had associated hydrocephalus, the semisitting position could lead to excessive loss of CSF during surgery and was therefore used with great caution or, more often, the patient was placed in the prone position.

Tumor exposure for tectal gliomas was undertaken mainly with patients in the semisitting position via the supracerebellar infratentorial route. Focal tectal gliomas were approached via a lateral suboccipital infratentorial trajectory. Tumors involving the midbrain tegmentum have been approached through a subtemporal route. A lateral suboccipital craniotomy with cerebellopontine angle (CPA) exposure was applied for most pontine gliomas. To access the fourth ventricle, we used the midline suboccipital craniotomy and the telovelar approach. For cervicomedullary tumors without an exophytic part or pial presentation, a cervical laminotomy and midline myelotomy were undertaken.

Surgical Approaches to the Midbrain

Midbrain gliomas were exposed anteriorly, laterally, and posteriorly. An anterior lesion of the peduncle and tegmentum that extended into the anterior part of the thalamus and third ventricle was exposed via the anterior frontobasal interhemispheric approach ( Fig. 13.2 ). We have also performed this procedure in treating other lesion types with or without dividing the anterior communicating artery. ⁴¹ Intrinsic lesions of the peduncle or midbrain tegmentum were exposed either laterally via the sub-temporal transtentorial approach or dorsolaterally via the lateral supracerebellar infratentorial or transtentorial route. Before sub-temporal exposure of a midbrain tumor, we usually placed an external lumbar CSF drain that facilitated temporal lobe retraction until the ambient cistern was opened. Also, we took great care to preserve bridging veins of the temporal lobe, such as the vein of Labbé and its tributaries ( Fig. 13.3 ).

Lesions of the midbrain tectum were approached via the supracerebellar paraculminal infratentorial exposure, similar to the exposure of pineal region pathology ( Fig. 13.4 ). This surgical exposure required a number of precautions to avoid postoperative acute cerebellar swelling. ⁴²

Related posts:

15 Tumors of the Thalamus 14 Pediatric Brainstem Tumors 19 Pineal Region Tumors 21 Radiotherapy for Pineal, Thalamic, and Brainstem Tumors 20 Stereotactic Radiosurgery for Tumors of the Brainstem, Thalamus, and Pineal Region 22 Neuro-oncologic Considerations for Pineal, Thalamic, and Brainstem Tumors

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