Management of Tumors of the Fourth Ventricle

Surgical Approach

The safest and the most direct approach to the fourth ventricle is the midline suboccipital approach. The operative corridor to the fourth ventricle using this approach is somewhat superiorly directed. Preoperatively, all imaging and labs should be reviewed carefully. Antibiotics should be given with incision. Preoperative treatment with steroids can decrease vasogenic edema, alleviate headache and neck pain, decrease the incidence and severity of aseptic meningitis and the posterior fossa syndrome, and decrease nausea and vomiting, allowing for better hydration and nutrition prior to surgery. It is helpful to have an automatic retractor system available.

Intraoperative monitoring, including brainstem auditory-evoked potentials, somatosensory-evoked potentials (SSEPs), and electromyography with facial nerve or nucleus, can be helpful for lesions in or in proximity to the brainstem or cranial nerves. Any alterations in vital signs while working near the floor of the fourth ventricle should be considered a serious warning sign to stop manipulation.

There are three possibilities for positioning: prone, lateral oblique, or sitting. The prone position is optimal for very young children, but there is some controversy over which is the best position for older children and adults. Each of the positions requires the head to be pinned using a Mayfield or Sugita head holder as long as the patient is older than 2 years of age. Very young children should be placed face down with the head on a padded horseshoe, ensuring there is no pressure on the eyes. All three positions require a certain amount of neck flexion, so caution should be used if there is known preexisting neck pathology, especially a craniocervical anomaly, spinal instability, significant cervical spondylosis, or herniation of the cerebellar tonsils on preoperative imaging.

The most commonly used position for the midline suboccipital approach (especially in very young patients) is the prone position, in which the patient is rolled after induction of anesthesia so that the face is toward the floor ( Fig. 22.3 ). There are many advantages to this position: the anatomy is clearly visualized, it is easy for two operators to work together, and the multiple complications of the sitting position do not occur. The most significant disadvantage of the prone position is venous congestion that can lead to more significant blood loss, pooling of blood in the operative field, and soft tissue swelling of the face. The neck is placed in the “military tuck position” with moderate flexion of the upper cervical spine (to open up the space between the foramen magnum and the arch of C1) and less flexion of the lower cervical spine (to bring the occiput parallel with the patient’s back).

The lateral oblique or lateral decubitus position is similar to the prone position, except that the patient is lying on his or her side. This allows superior visualization of pathology high in the fourth ventricle, in the lateral recesses, and in the cerebellopontine angle. The posterior fossa contents do not sink inward as they do in the prone position, and the operative distance is more comfortable for the surgeon. The principal disadvantage of the lateral oblique position is that the anatomy is not centered, so the surgeon must visualize all structures rotated. Also, it is constantly necessary to support the upper cerebellar hemisphere to maintain exposure, although the lower hemisphere naturally falls away.

The third option for positioning is the sitting position, in which the patient is positioned sitting upright so that the operative corridor is parallel to the floor ( Fig. 22.4 ). The sitting position offers a very clear operative field because blood and CSF drain out of the operative site. However, there are many risks to the sitting position. The most significant dangers are cardiovascular instability and hypotension, air embolism, and subdural hematoma. All patients should have an agitated saline echocardiogram to exclude right to left shunt through a patent foramen ovale that could complicate air embolism, and presence of such a shunt is an absolute contraindication for the sitting position. Precordial Doppler ultrasonic flow and end-tidal CO ₂ should be monitored throughout the case. The risk of subdural hematoma is greatly increased by presence of a shunt, and if possible, the shunt should be occluded prior to attempting an operation in the sitting position. Other risks of the sitting position include tension pneumocephalus, cervical myelopathy, thermal loss (especially in children), surgeon fatigue, and sudden loss of CSF from enlarged lateral and third ventricles after removal of a fourth ventricle mass lesion. When applying the head holder, the pin sites must be covered with Vaseline gauze to minimize entry of air, and the head taped to the head holder for extra support in case the pins become dislodged. The patient is elevated slowly into the sitting position so that the foramen magnum is at the surgeon’s eye level with both of the patient’s legs flexed at the knees to prevent postoperative sciatica. The instrument table is placed over the patient’s head. Infants too young for pins may be taped to a padded headrest to support the forehead and chin, but it is probably safer to use the prone position. Throughout the case, the patient should be carefully monitored for signs of hypotension or air embolism. If air embolism occurs, the wound should be packed with a saline-soaked sponge, and anesthesia should aspirate the atrial catheter to attempt to remove the embolus from the left atrium. If the embolus is severe, the patient should be placed in left decubitus position; otherwise, as soon as the patient is stable, the wound may be slowly exposed while covering the potential source of air with Gelfoam and Surgicel. If careful preparation is undertaken and complications dealt with promptly, the sitting position can be relatively safe. ^,

• 1.

  After positioning, a linear midline incision is outlined 1 to 2 cm above the external occipital protuberance down to the level of C4 ( Fig. 22.5 ). If there is concern that it will be necessary to rapidly decompress the lateral ventricles intraoperatively or postoperatively, a burr hole may be drilled in the right posterior parietal region. A hockey-stick incision may be more appropriate for a more laterally situated tumor. The skin is undermined superficial to the fascia on both sides of the superior half of incision in preparation to create a fascial flap for closure ( Fig. 22.6 ). The fascia can be incised using a Y-shaped incision, keeping the lateral ends of the Y below the ligamentous insertion ( Fig. 22.7 ). While a linear midline fascial incision without the upper limbs of the Y allows use of the avascular plane between the splenius capitis and semispinalis capitis muscles, it is often difficult to reapproximate such an incision tightly at the superior nuchal line. Periosteal elevators are used to strip the muscle from the bone, the junction between the pericranium and dura at the foramen magnum is sharply dissected, and then, the posterior fossa dura separated from the inner table of the occipital bone using a curette.

  
  
  

• 2.

  The suboccipital craniotomy is begun with burr holes on either side of midline just below the transverse sinuses, about 3 cm from midline ( Fig. 22.8 ). A third burr hole can be placed below the torcula in older patients. In children, the dura is not firmly adherent to the skull, so it is safe to drill close to or even on top of the sinuses, but more caution must be used with adults. The superior and lateral limits of the craniotomy are the transverse and sigmoid sinuses ( Fig. 22.9 ). Inferiorly, the craniotomy should always include the posterior edge of the foramen magnum to prevent laceration of the brain against the closed bony rim when cerebellar elements are retracted downward and minimize damage from herniation if hematoma or swelling should occur postoperatively. Because of the irregular contour of the inner bone surface in adult patients, it is sometimes necessary to perform a craniectomy rather than a craniotomy, removing the bone in a piecemeal fashion. A C1 laminectomy is helpful for lesions that herniate beneath the foramen magnum. To remove the lamina, small angled curettes can be used to strip the deep surface of the bone, and then the bone itself removed with an angled Kerrison punch or Leksell rongeur ( Fig. 22.10 ). Because extending a laminectomy below C2 in young children increases the risk of swan neck deformity, it is prudent to remove the smallest amount of bone possible. For most tumors, it is usually only necessary to remove as far as one level above the most caudal aspect of the tumor.

  
  
  

• 3.

  Once the dura is exposed ( Fig. 22.11 ), intracranial pressure can be reduced if necessary with external ventricular drainage, hyperventilation, or hyperosmolar therapy. A Y-shaped incision allows wide visualization and can be extended if necessary ( Fig. 22.12 ). One superior limb should be incised first just inferior to the transverse sinus and travel obliquely to the midline, stopping short of the occipital sinus. The other superior limb is incised next, and then, they are connected over the midline. If there is significant bleeding from the midline occipital sinus, it should be controlled with obliquely placed hemostatic clips or suture ligatures ( Fig. 22.13 ). Either way, both the superficial and deep layers of the dura must be incised, or the sinus will be tented open. The vertical limb of the Y is opened last using scissors so that the dura can be tented if bleeding is seen. The vertical incision extends to the foramen magnum so that it will extend below the falx cerebelli, which is occasionally present in childhood. If bleeding is very troublesome, the dura can be opened paramidline. The dura is then covered with a moist collagen sponge or wet Gelfoam sandwich to prevent desiccation and anchored to the fascia with 4-0 Nurolon Suture. This allows wide exposure of the cerebellar vermis and hemispheres ( Figs. 22.14 and 22.15 ). The arachnoid is opened next over the cisterna magna to allow drainage of CSF ( Fig. 22.16 ). If the tumor is in the cerebellar hemisphere, another dural incision can be extended laterally to more fully expose the involved cerebellum.

  
  
  
  
  
  

• 4.

  Techniques for intradural exposure and resection of the tumor will vary depending on the location and size of the tumor. Gentle separation of the cerebellar tonsils will expose the cerebellomedullary fissure through the opened vallecula giving an unimpeded view of the inferior roof of the fourth ventricle ( Fig. 22.17 ). Narrow malleable automatic retractors can be used to maintain separation of the tonsils; the retractor system should be kept close to the patient so as to not interfere with the subsequent operation. The operating microscope is brought into the field, and the anatomy is identified. In particular, the location of the caudal loops of PICA should be carefully noted because they are often tethered to the tonsils and the walls of the cerebellomedullary fissure by small perforating branches. The foramen of Magendie and the small tuft of choroid plexus protruding from it will be clearly seen, as well as any tumor that protrudes from the foramen. The thin layers forming the lower part of the roof can be opened to expose the cavity of the fourth ventricle. Often, this will provide sufficient exposure, but if not, it is sometimes helpful to retract the inferior vermis rostrally or incise the caudal vermis, avoiding the gutter between the vermis and the hemisphere to prevent injury to the inferior vermian veins there ( Fig. 22.18 ). Lateral lesions may require removal of one tonsil, and part of the cerebellar hemisphere can be resected without significant morbidity as long as the dentate nuclei are not violated. If the tumor is not adherent to the floor of the fourth ventricle, cottonoid patties should be placed beneath the tumor to protect the delicate brainstem structures just beneath the floor. These cottonoids should be placed under direct vision and never used as a tool to dissect the tumor from the floor of the fourth ventricle. After the tumor has been removed, the glistening white floor of the fourth ventricle should be clearly visible. The retractors are then removed and the cerebellar hemispheres allowed to fall back into place. If there is extension of the tumor through one of the foramina of Luschka into the cerebellopontine cistern, the ipsilateral tonsil and cerebellar hemisphere can be retracted medially to expose it. Sometimes, it is necessary to do a secondary retromastoid approach to completely resect the tumor.

  
  

• 5.

  The dura is closed primarily ( Fig. 22.19 ) or with a watertight pericranial or fascial graft ( Fig. 22.20 ). The use of autogenous material is less likely to produce postoperative aseptic meningitis. A Valsalva maneuver will identify potentially dangerous venous bleeding. If the dura is not watertight, there is increased risk of pseudomeningocele due to a ball-valve effect or hydrocephalus from arachnoid adhesions produced by blood from the muscles. If a craniotomy was performed, the bone flap can be secured with wires, plates and screws, or sutures. Alternatively, the defect can be covered with a titanium screen held in place by gently compressing the screen and allowing it to insert itself between the dura and inner margins of the bony defect. The fascia is closed with interrupted absorbable sutures to approximate the muscle and fascia ( Fig. 22.21 ). If the fascia is dried and difficult to approximate, the skeletal fixation apparatus can be loosened and the neck extended to facilitate closure. An adequate amount of tissue must be left at the superior fascial flap to prevent buttonholes at superior nuchal line. The scalp is then closed in layers, and the wound is then closed with sutures or staples ( Fig. 22.22 ).

  
  
  
  

Complications

Hydrocephalus is common with fourth ventricular tumors and is one of the most significant causes of morbidity and mortality associated with these tumors. ^, In the past, many patients with tumors and hydrocephalus underwent temporizing preoperative shunting to treat hydrocephalus and prevent pseudomeningocele, CSF leak, and meningitis from fistula. However, more recently, it has been observed that shunting is associated with many complications, and the increased incidence of subdural hematoma, infection, and brainstem compression from upward herniation may outweigh its benefits. Today, only about 10% to 20% of patients with cerebellar and posterior fossa tumors require permanent shunting, ^{, ,} and most of these are slow-growing tumors such as astrocytomas, because more acute tumors distend the ventricles for a short period of time and do not allow outlet adhesions to form. Risk factors for shunt dependence include younger age, larger preoperative ventricle size, and more extensive tumors. Although external ventricular drainage reduces the need for permanent shunts, the infection rate may be as high as 10%, so it should be used judiciously. If a shunt is required for a malignant tumor, there may be an increased risk of extraneural metastasis through the shunt tubing (especially to the peritoneum), although some studies have suggested that such metastases may occur as often in patients without shunts.

Pneumocephalus in the ventricles and subdural space is common after fourth ventricular surgery, especially when patients are operated in the sitting position, and often results from overzealous drainage of CSF through an external ventricular drain intraoperatively. Because nitrous oxide can diffuse into air-filled spaces, it is possible that nitrous oxide contributes to tension pneumocephalus, although this is controversial. If tension pneumocephalus is recognized intraoperatively, the patient should be placed in Trendelenburg position and the operative bed irrigated to replace air with the irrigating fluid. Symptomatic postoperative tension pneumocephalus can be treated with a small frontal burr hole to relieve the pressure caused by the trapped air. Intraventricular air may cause ventriculoperitoneal shunt malfunction due to airlock.

Postoperative pseudomeningoceles affect 10% to 15% of all children with posterior fossa tumors. Normally, these are small collections of fluid that respond well to serial lumbar punctures. Occasionally, they can put the closure under tension and eventually produce a leak, which carries a risk of meningitis. Pseudomeningocele may be a manifestation of hydrocephalus and in some cases may require a CSF diversion shunt to control.

Aseptic meningitis is a rare occurrence after posterior fossa surgery that can be associated with epidermoid or dermoid resection, during which intraoperative cholesterol cyst fluid is encountered, although it can also occur after resection of astrocytoma or medulloblastoma. Patients usually present about 1 week after surgery with fever, headache, irritability, and CSF pleocytosis. It can be difficult in some cases to differentiate aseptic meningitis from true bacterial meningitis, which should always be carefully excluded before treating for aseptic meningitis. The condition resolves with steroid or anti-inflammatory treatment and serial lumbar punctures to remove CSF.

Transient or permanent cranial nerve palsies sometimes occur after surgery of the fourth ventricle, the most common deficits being cranial VI and VII palsies caused by disruption of the fourth ventricular floor along the facial colliculus where the intrapontine course of the facial nerve loops around the abducens nucleus.

The “posterior fossa syndrome,” also called posterior fossa mutism or pseudobulbar palsy, is characterized by the delayed onset of mutism, emotional lability, and supranuclear lesions that occurs within a few days after midline posterior fossa operations. The syndrome has been seen in as many as 15% of intraventricular approaches to lesions near the brainstem, with patients presenting with global confusion, disorientation, combativeness, paranoia, or visual hallucinations. They are generally alert and will follow simple commands but will sometimes refuse to speak or present with scanning speech. Because of the delay in onset, it has been suggested that edema from operative manipulation may play a role, for example, through transmission of retractor pressure from the medial cerebellum through fiber pathways along the middle and superior cerebellar peduncles into the upper pons and midbrain. There are no consistent neuropathologic findings, and most patients have some improvement over several weeks to months.

Because the superior and inferior cerebellar peduncles make up the lateral walls of the superior roof of the fourth ventricle, they are susceptible to damage during intraventricular procedures. The superior cerebellar peduncle contains pathways connecting the dentate nucleus to the red nucleus and thalamus, so damage to the superior cerebellar peduncle produces a similar clinical syndrome to damage of the dentate nucleus with ipsilateral ataxia and intention tremor. Injury to the inferior cerebellar peduncle produces a syndrome similar to ablation of the flocculonodular lobe with equilibrium disturbances, truncal ataxia, staggering gait, and oscillation of head and trunk on assuming erect position without ataxia of voluntary movement of the extremities. Injury to the middle cerebellar peduncle (which causes ataxia and dysmetria) is rare during intraventricular procedures but can occur during an approach to the cerebellopontine cistern.

Acute urinary retention is an uncommon complication of dissection of the fourth ventricular floor near the striae medullaris, presumably due to injury to the pontine micturition center in the pontine tegmentum, the structure that integrates the cortex with sacral and pelvic sensory pathways that apprise bladder filling status.

Injury to major vessels is rare with fourth ventricular surgery. The most likely artery to be injured is PICA. Most patients with PICA injury present with postoperative flocculonodular dysfunction with nausea, vomiting, nystagmus, vertigo, and inability to stand or walk without appendicular dysmetria. Venous injury is extremely rare even if veins are sacrificed due to diffuse anastomosis in this region. Veins near the tonsils, vermis, and inferior roof can be safely sacrificed. Medial retraction of the cerebellar hemisphere to expose the lateral recess and cerebellopontine cistern can stretch bridging veins to the sigmoid sinus, but it is seldom necessary to sacrifice these. Most venous infarctions of the posterior fossa have followed sacrifice of the petrosal veins or veins of the cerebellomesencephalic fissure (including the precentral cerebellar vein).

Medulloblastoma

Medulloblastoma is the most common malignant primary brain tumor in children, accounting for 20% to 25% of all childhood primary brain tumors and 40% of all childhood posterior fossa tumors. ^, Peak incidence is 3 to 5 years of age; half of all patients with medulloblastoma are younger than 10 years of age at diagnosis, and three quarters are younger than 15 years of age. Medulloblastoma is uncommon in infancy, and less than 5% of patients present younger than 1 year of age. There is a second peak between 20 and 40 years so that medulloblastoma accounts for 5% of all adult posterior fossa tumors and 1% of all adult brain tumors. Adult medulloblastomas are more likely to be hemispheric than midline, likely due to the lateral migration of cells of the granular layer of cerebellum from the inferior medullary velum. Adult medulloblastomas are also more likely to be cystic or necrotic and have poorly defined margins and less contrast enhancement. They may even involve the cerebellar surface and resemble meningiomas. There is a slight male preponderance in most clinical series, and for reasons that are unclear, medulloblastomas have a significantly higher incidence in North America than elsewhere in the world. Medulloblastomas frequently metastasize in the subarachnoid space, and some dissemination is evident in 20% to 30% of all patients and 50% of young patients at diagnosis. ^, Familial medulloblastoma has also been reported.

Medulloblastomas grow quickly, so symptom onset is usually fairly acute; most patients are symptomatic less than 2 months before the tumor is diagnosed, and very few report symptoms for longer than 6 months. Most patients initially experience symptoms of increased intracranial pressure from CSF obstruction, such as morning headaches, vomiting, and eventually, gait problems. Gait difficulties include wide-based gait and inability to tandem walk; these findings are often subtle and not appreciated by the child or the parents but frequently alert the physician to the presence of a neurologic lesion. Clinical signs include ataxia for midline tumors or dysmetria/dysdiadochokinesia for lateral tumors. Most patients have papilledema by the time they present for evaluation. Less common signs include diplopia from abducens palsy, facial paresis or lower cranial nerve palsy from tumor invasion, or head tilt from tumor extension into the upper spinal canal or impaction of the cerebellar tonsils at the foramen magnum against the first two cervical nerve roots. Because medulloblastomas can metastasize along the subarachnoid space, some patients present with cranial or spinal nerve root symptoms from distant metastases or even seizures from cortical metastases. Patients who present with signs of metastatic disease have a limited life expectancy.

Medulloblastomas usually appear as midline solid tumors on neuroimaging, although cystic change is sometimes observed. Eighty-five percent are midline vermian lesions, usually arising from the vermis or inferior medullary velum and growing into the fourth ventricle, sometimes appearing to be entirely intraventricular. Computed tomography (CT) demonstrates a homogeneous, hyperdense lesion that enhances intensely and diffusely after contrast administration. Calcification will be apparent in 10% of medulloblastomas, but presence of calcium or cystic change is more typical of ependymomas. On magnetic resonance imaging (MRI), the lesion is hypointense to isointense to the brain on T1 and hyperintense or hypointense on T2 with heterogeneous signal due to microcysts, necrotic cavities, tumor vessels, or calcification ( Fig. 22.23 ). The tumor displays irregular enhancement with MRI contrast material, ^, and enhanced MRI will disclose small cortical or basal metastases in 5% to 10% of cases. Sagittal MRI can differentiate true intraventricular tumors from extraventricular vermian lesions: intraventricular tumors will widen the aqueduct and displace the quadrigeminal plate posterosuperiorly, while dorsal lesions will kink the quadrigeminal plate giving it a C-shaped appearance. Tumors extending out of the foramen of Luschka are far more typical of ependymomas. In young children, medulloblastomas are often indistinguishable from ependymomas from radiographic appearance alone. All patients should get a contrasted MRI of the entire craniospinal axis.

Medulloblastomas can be divided into two broad histologic patterns: classical and desmoplastic. Classical medulloblastomas, which make up three quarters of the total, are seen to have dense, diffusely monotonous sheets of cells with intensely basophilic nuclei and scant cytoplasm (“small round blue cells”). Desmoplastic medulloblastomas have a higher proportion of fibrous stroma associated with the perivascular collagen skeleton of tumor. Sometimes, there are uniform compact lines of cells around islands of relative hypocellularity; when this is seen, the compact rims stain heavily with reticulin and the hypocellular areas stain for glial fibrillary acidic protein (GFAP). Occasionally, individual cells resembling oligodendrocytes are seen, having perinuclear halos and staining with tubulin and synaptophysin. The desmoplastic variant is more common in older patients. In young patients, location is not associated with histology, but older patients are more likely to have desmoplastic histology in more lateral tumors. In both histologic patterns, there are occasionally neuroblastic areas with histology similar to neuroblastomas with Homer–Wright rosettes (rings of nuclei surrounding a central zone of fibrillary processes) and perivascular pseudorosettes that resemble those in ependymomas except that they do not stain for GFAP.

To resect a medulloblastoma, the posterior fossa is exposed as described previously. Because most medulloblastomas arise from the vermis or inferior medullary velum, the tumor will often be immediately visible either protruding through the foramen of Magendie or immediately deep to the vermis. If the tumor protrudes through the foramen, it often will fill the cisterna magna and even extend into the upper cervical canal. If the tumor is deep to the vermis, the tonsils will usually be displaced backward, and it may be necessary to retract the cerebellar tonsils or biventricular lobules using self-retraining retractors to visualize the inferior vermis. By exposing the cerebellomedullary fissure on each side, it is sometimes possible to resect the tumor without dividing the cerebellar vermis, although sometimes midline incision of the vermis is necessary to obtain adequate exposure. Gentle retraction of the cerebellar hemispheres will expose the intraventricular tumor, which generally appears purple-gray, friable, and quite vascular.

Even with a vermian incision, it is seldom possible to expose the entire tumor. Therefore, the next step is to debulk the central portion of the tumor using blunt or sharp dissectors with microscissors and microsuction aspiration. Desmoplastic tumors cannot be aspirated with microsuction, so ultrasonic aspiration can be used for these tumors, but this must be used with caution around the brainstem because of increased destruction of tissue. Bleeding is controlled with bipolar cautery. To expedite removal of the tumor and minimize blood loss, the tumor can be divided into four quadrants; as soon as bleeding becomes troublesome from one quadrant, a micropatty is placed there, and attention turned to a different quadrant, and so on. By the time the dissection returns to the first quadrant, the bleeding will have slowed enough to allow continued resection. Cottonoid patties should be placed along the fourth ventricular floor as early as possible to protect the brainstem, and it is important to constantly ensure that the trajectory is correct to prevent diving into the brainstem at an angle. The tumor is rarely adherent or invasive into the brainstem, but when it is, gross total resection should not be attempted due to the risk of permanent cranial nerve defects. The next step is to resect the lateral and anterior portions of the tumor. Because there are minimal postoperative neurologic deficits that result from removing a thin rim of cerebellum, the dissection should be carried out on the brain side of the brain–tumor interface so that all of the tumor is resected and hemostasis is easier to obtain. At the end of the dissection, there will be a bed of clean white brain. The lateral dissection is extended onto the ependymal surface, where the tumor attaches to the cerebellum, and this margin is defined upward and forward until the dilated caudal aqueduct is reached, producing a conical dissection field. Finally, the anterosuperior tumor pole is removed, leaving the tip of the tumor covering the opening of the caudal aqueduct until the end of the operation so that no blood from the dissection will enter the lateral or third ventricles.

Because medulloblastoma often spreads through the subarachnoid space and the tumors are highly radiosensitive, radiotherapy to the entire neuraxis is considered standard even when there are no obvious lesions on postoperative imaging. The best survival rates are obtained with 3600 to 4000 cGy to whole craniospinal axis supplemented to 5400 to 5600 cGy to the primary site and 1800 to 3000 cGy extra to any area of lump disease. Young children have a high incidence of postradiation neurocognitive deficits, so radiation should be delayed or eliminated in the very young; various studies have suggested lower dosage or chemotherapy until the brain is mature enough to handle radiation. Trials using various chemotherapy regimens have demonstrated improved survival, especially for locally extensive or widely disseminated tumors. ^{, ,}

Prognosis for patients with medulloblastoma is related to size, invasiveness, and dissemination of tumor at diagnosis; age of the patient; and postoperative residual tumor. Large tumors have been shown to have a lower 5-year disease-free survival. Brainstem invasion also carries a poorer prognosis and is problematic for preoperative staging because it cannot be predicted based on MRI. ^, Presence of dissemination through the neuraxis is the single most significant predictor of outcome for all histologic types of medulloblastoma. Even microscopic dissemination (determined by lumbar puncture performed at least 10 days postoperatively) carries a significantly lower 5-year survival. Extraneural metastases to bone and even lymph nodes have been reported, but the incidence is too low to warrant screening all patients with medulloblastoma. Young patients are much more likely to have dissemination, but patients younger than 4 years of age have a worse prognosis out of proportion to the increased dissemination rates. Finally, completeness of resection is thought to impact subsequent behavior of the tumor, ^, and presence of more than a cubic millimeter of residual tumor has been associated with worse survival. Histology has not been shown to impact prognosis except for rare tumor subtypes at the extreme ends of the histologic spectrum; specifically, medulloblastomas with extensive nodularity and large cell/anaplastic medulloblastomas are associated with better and worse clinical outcomes, respectively. However, histologic features have not been shown to correlate with clinical outcome for the vast majority of medulloblastomas that lie between these extremes.

Overall, with surgery and radiation, 5-year disease-free survival rates approach 80%. Medulloblastomas have classically been said to follow Collins law, which says that a cure has been obtained if there is no tumor recurrence over period equal to the age at diagnosis plus 9 months. However, one-third of survivors at 5 years have recurrence, and one-third of the recurrences are outside of the period predicted by Collins law. Most recurrence occurs in the cerebellum or along CSF pathways. Surveillance imaging has been shown to improve survival. ^,

Atypical Teratoid/Rhabdoid Tumor

Atypical teratoid/rhabdoid tumors share many clinical and pathologic features with medulloblastomas but appear to be a unique entity with a more aggressive course and worse prognosis. They may occur anywhere in the neuraxis but are most commonly found in the cerebellum, and clinical presentation is similar to that of medulloblastomas. Most patients are younger than 2 years of age at diagnosis. One-third of patients have subarachnoid dissemination upon presentation. Histologically, they are composed at least partly of rhabdoid cells but also have areas typical for medulloblastoma and malignant mesenchymal or epithelial tissue. They stain for epithelial membrane antigen, vimentin, and smooth muscle actin. They are associated with abnormalities of chromosome 22, whereas medulloblastomas typically have an i(17q) abnormality. Prognosis is dismal, and most patients die within 1 year of diagnosis regardless of treatment.

Astrocytoma

In the pediatric population, astrocytomas account for about one-fourth of all brain tumors and one-third of posterior fossa tumors. These tumors occur most often during the first 20 years of life, with peak incidence from 5 to 8 years of age, and very few patients are younger than 1 year or older than 40 years of age. Males and females are affected equally. ^, Unlike astrocytomas of the cerebrum, they are chronic and slowly progressive tumors that usually present subacutely and can be resected with minimal morbidity and a high cure rate.

Because they are slow-growing tumors, onset of symptoms is usually far more insidious than medulloblastomas and ependymomas. In 1931, Cushing remarked with amazement that “tumors of such high magnitude in such a critical situation and so certain to produce early hydrocephalus can be tolerated for so many years with no comparatively insignificant symptoms.” Most patients have had symptoms for many months by the time the tumor is diagnosed, including headache, vomiting, abducens palsy, and papilledema. Other common symptoms include altered gait, clumsiness, and head tilt. Common signs include papilledema, ataxia that is often unilateral, appendicular dysmetria, nystagmus, and macrocephaly that occasionally dates back several years even to infancy. Severe neck pain, opisthotonus, bradycardia, hypertension, and altered neurologic function are less common but require immediate attention, and rarely patients will present with signs of acute hydrocephalus such as stupor or coma, projectile vomiting, and oculomotor and facial palsies. Blindness was once a very common presenting symptom (present on presentation in 23 of the 76 patients reviewed by Cushing) but is rarely seen today.

On imaging, astrocytomas are solid, cystic, or mixed lesions that arise from the medial hemisphere or vermis ^, ; one-third are entirely in one cerebellar hemisphere ( Fig. 22.24 ). When in the midline, they can be difficult to differentiate from medulloblastomas and ependymomas. MRI will usually disclose a round to oval mass with well-defined margins and of mixed intensity, hypointense to surrounding brain on T1 and hyperintense on T2. On CT, the tumor is hypodense or isodense to surrounding brain. Unlike low-grade supratentorial astrocytomas, the tumor enhances brightly with CT and MRI contrast material. If the tumor is cystic, there may be an enhancing mural nodule and the cyst fluid will be slightly denser than CSF on T2-weighted images. The cyst wall is sometimes denser than surrounding brain but does not contain tumor unless it enhances ( Figs. 22.25, 22.26, and 22.27 ). Calcification and peritumoral edema are infrequently observed.

Grossly, astrocytomas are firm with discrete borders. About half will have some degree of cystic degeneration (compared with 80% of supratentorial astrocytomas). There is usually one cyst with a prominent mural nodule, although honeycombing of small cysts is also seen. The cyst wall is most commonly smooth and glistening, although sometimes there will be a coating of tumor or raised tumor nodules on the inner surface of the cyst (seen more often when there is enhancement of the cyst wall on neuroimaging). Histologically, areas of loose glial tissue resembling cerebral protoplasmic astrocytes with round or oval nuclei are intermixed with compact areas of fusiform, fibrillated cells that often have elongated eosinophilic bodies called Rosenthal fibers. When the cells conform to white matter tracts, they have an elongated hair-like structure and are described as “pilocytic” (hair cell). The cells stain weakly for GFAP and have bundles of intermediate filaments in perikaryon and cell processes.

Some posterior fossa astrocytomas have histology and clinical behavior that deviate from the typical pilocytic astrocytoma described previously. These tumors resemble low-grade astrocytomas of the cerebral hemispheres. They have diffusely homogeneous histology, lack microcysts and Rosenthal fibers, and are characterized by pseudorosettes, high cell density, necrosis, mitoses, and calcification. Incidence of these tumors is much lower than pilocytic astrocytomas, and they are more common in older patients, especially those who have previously received radiation. ^, They have a much higher rate of malignant degeneration, and high-grade anaplastic astrocytomas and even glioblastomas have been reported in the posterior fossa. Even when histologically low grade, they may infiltrate into cerebellar nuclei or peduncles and often lack clear tumor margins, making gross tumor resection difficult. Survival rates with these tumors are lower than the typical astrocytomas, and there are reports of diffuse leptomeningeal spread and even spread to the muscles of the neck requiring several local surgical procedures to control.

The principles of resection for pilocytic astrocytomas are similar to those discussed for medulloblastomas. If there is a cystic component to the tumor, the cyst is entered and cyst fluid quickly suctioned, supporting the hemisphere with self-retaining retractors to prevent collapse away from the tentorium with rupture of bridging veins. The mural nodule should be identified and removed using the ultrasonic aspirator. If the tumor is mixed or enhancement of the cyst wall is seen, the entire cyst wall should be removed and normal cerebellar tissue exposed; otherwise, simple removal of the mural nodule is curative. To prevent contamination of the CSF with blood and cyst fluid (which can produce chemical meningitis that increases the likelihood of postoperative communicating hydrocephalus), the cisterna magna and fourth ventricle should not be opened unless it is necessary to do so to achieve gross total resection. All walls of the tumor bed are then carefully inspected to ensure there is no residual tumor. Finally, before closing, it is important to ensure that bridging tentorial veins are not stretched. These veins can be safely sacrificed, but tearing one later can lead to a life-threatening hematoma. All patients should get a postoperative contrast-enhanced scan within the first 24 hours to evaluate the extent of resection, provide a baseline if hydrocephalus should develop, and evaluate for cerebellar/brainstem retraction edema or clinically silent hematomas. If more than 1 cm³ has been left behind, early re-exploration to remove the residual tumor is indicated.

True pilocytic astrocytomas are almost always resectable by modern techniques and have excellent prognosis with no adjuvant therapy if gross total resection is possible. ^, If there is a small amount of residual tumor, serial imaging can be used to follow its growth. Although there are several well-documented cases of low-grade astrocytoma undergoing malignant degeneration several years after surgical resection, this is probably quite rare and each of the documented cases having received radiation therapy. Radiation therapy has not been shown to be successful in the management of these tumors and is associated with significant side effects, although focused radiation may be helpful for surgically inaccessible or rapidly growing lesions. Combined chemotherapy and radiotherapy for high-grade cortical astrocytomas have been shown to decrease rates of metastasis for children with high-grade astrocytomas. As with pilocytic astrocytomas, patients with more complete resection of infiltrative tumors fare better.

Recurrence of posterior fossa astrocytomas is related to the extent of resection, location, invasiveness, and histology of the original tumor. ^{, ,} Age of the patient does not appear to have any effect on outcome. Recurrence is most common at the primary site, and if any tumor is left behind, symptoms almost invariably recur. Cystic tumors can usually be totally extirpated, but solid tumors tend to regrow after prolonged remission even if grossly resected. Solid midline tumors are most likely to recur because they more often extend toward the cerebellar peduncles, aqueduct, or brainstem, which may prevent total excision. Invasion of the subarachnoid space often occurs, but this does not indicate a poor prognosis as with most other tumors. Astrocytomas do not follow Collins law for tumor recurrence and can have recurrences long after complete resection. Overall 10-year survival for astrocytomas is close to 100% with complete resection, and 20-year survival is above 70%. ^,