Disease Overview
Medulloblastoma is the most common neuroectodermal tumor, which can be divided into two categories according to the tissue in which it occurs: one type of tumor originates from the remnants of the cells of the outer granular layer during brain development, which is mostly seen in adults and occurs in the cerebral hemisphere;
The other type of tumor is the abnormal cells in the germinal zone of the posterior cerebellar medulla, which are mostly found in children. The tumor has a tendency to metastasize along the cerebrospinal fluid and can spread to the lateral ventricles and the three ventricles, or down the subarachnoid space, invading the spinal cord and causing neurogenic symptoms or paraplegia.
Clinical presentation
The course of medulloblastoma is short, with nearly half of the patients having a course of less than 1 month and a few having a course of several years. The first symptoms are headache (68.75%), vomiting (53.75%) and unsteadiness in walking (36.25%). Later, diplopia, ataxia, and vision loss may occur.
1.Expression of increased intracranial pressure
Due to the growing tumor in the cerebellar earthworm, the fourth ventricle and/or the middle cerebral aqueduct are compressed, resulting in obstructive hydrocephalus and increased intracranial pressure. The clinical manifestations are headache, vomiting and fundus optic disc edema. Vomiting is the most common and can be the only clinical manifestation in the early stage. In addition to the increased intracranial pressure, direct stimulation of the vagus nucleus at the base of the fourth ventricle by the tumor is also an important cause of vomiting.
Vomiting is usually seen in the morning and is often accompanied by hyperventilation. This may be because the increased intracranial pressure in children can be partially compensated by the separation of cranial sutures, while in adults, optic disc edema is almost always present.
2. Cerebellar damage
The main manifestation is trunk ataxia. Patients with different degrees of severity may show staggering gait, widening distance between walking feet, or even unstable standing and sitting. The tumor invades the upper cerebellum and the patient falls forward, while the tumor in the lower cerebellum tilts backward. As tumors invading the lower cerebellum are more common, the posterior tilt is also more frequent.
The development of tumor on one side may cause different degrees of cerebellar hemispheric symptoms, mainly manifesting as ataxic movement disorder of the affected limb. Those with primary cerebellar hemispheres may show cerebellar language, and more than half of the patients show ataxia of eye muscles, mostly horizontal nystagmus.
3.Other manifestations
Diplopia: Bilateral incomplete paralysis of the adductor nerve due to increased intracranial pressure, manifesting as internal strabismus of both eyes and limited abduction movements. The presence of unilateral adductor nerve palsy with ipsilateral peripheral facial palsy often indicates that the tumor has invaded the facial nerve thalamus at the base of the fourth ventricle.
Facial palsy: The tumor directly invades the facial nerve thalamus at the base of the fourth ventricle, which is less common.
Forced cephalic position: When the tumor or the lower herniated cerebellar tonsils penetrate deep into the spinal canal, they irritate and compress the cervical nerve roots, causing the patient’s protective position response.
Skull enlargement and McCewen’s sign: Mostly seen in younger children, due to increased intracranial pressure and separation of cranial sutures.
Cone bundle sign: It is caused by the increase of tumor volume and forward pressure pushing the brainstem, and pathological reflexes are more common in both lower limbs.
Choking: It occurs when the tumor compresses the brainstem and/or the Ⅸth and Xth pairs of cerebral nerves, and the gag reflex is weakened or disappeared in clinical examination.
Cerebellar crisis: Due to the obstruction of cerebrospinal fluid circulation, the aggravation of subungual herniation of cerebellum or direct compression of brainstem by tumor, resulting in loss of consciousness, slowed breathing and elevated blood pressure, accompanied by positive bilateral pathological reflexes, and even decortical ankylosis. Death may occur within a short period of time due to rapid respiratory arrest.
Subarachnoid hemorrhage: Tumor hemorrhage from medulloblastoma is one of the main sources of hemorrhage in children with nontraumatic posterior cranial recess subarachnoid hemorrhage.
4.Metastasis symptoms of brain tumor
Tumor metastasis is the main feature of medulloblastoma. After the tumor cells are shed, disseminated implantation may occur along the subarachnoid space through cerebrospinal fluid circulation. The spinal cord, especially the cauda equina, is a common site of involvement, and the anterior cranial recess is also a common site of metastasis, while a few metastases to various parts of the brain. Metastases can occur both preoperatively and postoperatively, but the latter is significantly more common. The common sites of distant metastases are lung and bone, and localized metastatic lesions in wounds have also been reported.
Ancillary tests
Laboratory tests: Because most patients with medulloblastoma have increased intracranial pressure, preoperative lumbar puncture is advisable with caution, and cerebrospinal fluid can be searched for exfoliated cells in addition to routine laboratory tests. The lumbar puncture usually indicates increased intracranial pressure, while only 1/5 of the patients have increased cerebrospinal fluid protein and leukocytes. postoperative lumbar puncture for tumor cell examination is of great significance and suggests the need for postoperative whole brain and spinal cord radiotherapy.
Other auxiliary examinations.
1.Cephalometric X-ray examination
Intracranial hypertension signs such as widening of cranial suture can be seen on cranial X-ray.
2.CT examination
Typical medulloblastoma is usually larger than 3.5cm in diameter and located in the cerebellar earthworms in the midline of the posterior cranial recess. The tumor involving the upper earthworm extends above the cerebellar curtain notch. 87% of the tumors appear as uniform high-density shadow on cranial CT and 10% as isointense lesions.
The foci are well-defined, mostly located in the cerebellar earthworm, and in the cerebellar hemisphere in adult patients. Enhanced examination shows uniform enhancement. Sometimes a thin band of hypointense edema surrounds the lesion. The fourth ventricle is often pushed forward and may be associated with signs of obstructive hydrocephalus. When subventricular ventricular metastases are present, complete or incomplete slightly dense images may appear in a band around the ventricles, which may be significantly enhanced. The main differentiation with ventricular meningioma is that calcification and cystic changes of medulloblastoma are rare, and the density of the lesion is more uniform.
3.MRI examination
Since the signal intensity of the parenchymal part of medulloblastoma is not very prominent, the location of the tumor and the resulting indirect signs are more important to understand the relationship with the brainstem, so the median sagittal scan image is especially critical, and the coronal scan can be used as a three-dimensional image reference. A very thin, low-signal zone separating the tumor from the base of the fourth ventricle is seen on 74% of MRI sagittal images.
Unlike ventricular meningioma, medulloblastoma rarely extends into the lateral saphenous fossa of the fourth ventricle and the pontocerebellar horn. In a few patients, MRI reveals metastases along the subarachnoid space, showing blurred borders of the cerebellar lobes, which are more valuable on MRI sagittal or coronal scans, while the implantation lesions can be significantly enhanced by Gd-DTPA. 97.5% have moderate to severe hydrocephalus.
In medulloblastoma, the parenchymal portion of the tumor shows significant abnormal enhancement on Gd-DTPA enhancement scan, while the cystic or necrotic area does not show enhancement on non-delayed scan. Medulloblastoma rarely has cystic changes, and tumors located in the superior earthworm may extend into the pineal region through the foramen ovale. Tumors located in the superior cerebellar earthworm often compress, anteriorly shift, or narrow the midbrain aqueduct.
In tumors located at the top of the fourth ventricle, the tetrasomal plate and anterior medullary sail change from their normal upright position to a nearly horizontal position, and the aqueducts dilate and move upward. Medulloblastoma may show a crescent-shaped cerebrospinal fluid residual shadow anterior and/or superior to the tumor on T1 images, which is the remaining portion of the fourth ventricle that is not completely occupied by the tumor.
Differential diagnosis
Diagnosis: In children, especially boys aged 4 to 10 years, with unexplained headache, vomiting and unsteady walking, the possibility of medulloblastoma should be considered first. If fundus optic disc edema, truncal ataxia, nystagmus or forced head position are found, the disease should be highly suspected and further neuroimaging is required.
Medulloblastoma is mainly differentiated from the following diseases.
1. Ventricular ventricular meningioma originates from the fourth ventricular ventricle and causes vomiting in early stage due to irritation of the fourth ventricle. The course of the disease is longer than that of medulloblastoma, and the substantial damage to the cerebellum is not as serious as that of medulloblastoma, and some cases even have no obvious cerebellar signs.
2. Cerebellar astrocytomas are mostly found in the cerebellar hemispheres and can have a long course, mainly manifesting as increased intracranial pressure and ataxic movement disorders of the limbs. Cranial X-ray calcification is more common, and in younger children, there may be bulging of occipital scales and bone thinning on the side of the tumor; the tumor is mostly cystic, with tumor nodules on the wall and the fourth ventricle shifted to the lateral side.
The age of the tumor is usually below 50 years old and about 1/3 of the children under 10 years old. CT shows a high-density mass with irregular margins, mostly calcifications, and significant enhancement.
Treatment options
Treatment of medulloblastoma is mainly surgical resection and postoperative radiation therapy, which can be supplemented with chemotherapy in some cases. Because the tumor is highly malignant and the boundaries of the tumor are not very clear, it is prone to recurrence after surgery. Most neurosurgeons advocate surgery to remove as many tumors as possible at least to restore the cerebrospinal fluid circulation obstruction, and then give radiotherapy after surgery.
Surgical resection is the main method to treat this disease. When removing the tumor, the tumor should be separated along the arachnoid interface of the tumor surface as much as possible, and the operation should be performed gently. When separating the lower pole of the tumor, it is often found that the bilateral posterior inferior cerebellar arteries are located posteriorly and laterally to the tumor. Because they often have branches supplying the brainstem, they should be strictly protected to avoid damage during surgery. Before dealing with the tumor supplying arteries, it should be excluded that the treated vessels are not the returning arteries of the posterior inferior cerebellar artery or superior cerebellar artery into the brainstem to avoid ischemia and functional failure of the brainstem after accidental injury.
When dealing with the superior pole of the tumor, it is crucial to open the outlet of the middle cerebral aqueduct, but generally this step should be done after the tumor has been removed from other parts, so as to avoid the backflow of blood from the operation field blocking the aqueduct and the third ventricle. If the tumor is severely adhered to the brainstem, forced separation should be avoided to avoid damaging the brainstem and causing adverse consequences. If the tumor is largely resected and the conduit cannot be opened, extraventricular drainage should be left intraoperatively and ventriculoperitoneal shunt or intraoperative shunt should be done later to relieve supratentorial hydrocephalus.
In the selection of postoperative treatment plan, the current conventional practice is to divide the children into two groups, high-risk and low-risk, according to the patient’s age, the degree of surgical resection and the presence of metastasis, and to take corresponding measures for the different groups. For the low-risk group (age >3 years, total tumor resection, and no metastasis, the main postoperative treatment aims to prevent tumor recurrence and subarachnoid spreading metastasis.
For high-risk children (age <3 years, residual tumor >1.5 cm or with metastatic dissemination), postoperative local radiotherapy for residual tumor and metastases and prophylactic whole brain spinal cord radiotherapy (CSI) are essential. However, most children <3 years old are susceptible to neurological and endocrine system damage, so studies on how to use early high-dose chemotherapy to delay the start of regular radiotherapy without compromising the overall treatment outcome are now the focus of research, but it is also believed that recurrence and metastases already occur in 74% of children during the course of chemotherapy, and subsequent csi does not provide complete remedy for the deterioration, and the hematological picture caused by chemotherapy suppression, which also allows for later radiotherapy, suggests early initiation of formal chemotherapy.
Because of the rapid growth of medulloblastoma, the high cytokinesis index, and the location close to the ventricles and subarachnoid space, many conditions exist that favor radiotherapy for incipient medulloblastoma that is sensitive to radiotherapy. To address the metastasis-prone nature of medulloblastoma, radiotherapy should include the entire central nervous system (whole brain, posterior cranial fossa and spinal cord).
The dose of radiotherapy should be adequate according to the patient’s age, with the dose of whole brain radiation at 35-40 Gy above 4 years of age, and the dose of posterior cranium at 50-55 Gy. The dose should be reduced appropriately between 2 and 4 years of age, and no radiotherapy should be given for the time being within 2 years of age. Radiotherapy should generally be administered within 4 weeks after surgery. It has been proposed that there is no difference in survival rate between whole brain whole spinal cord low dose irradiation and high dose irradiation, and the key to radiotherapy for medulloblastoma is posterior cranial fossa high dose irradiation. Therefore, the current recommendations are 30-35 Gy for the whole brain, 50 Gy for the posterior cranial fossa, and 30 Gy for the spinal cord. attention should also be paid to the occurrence of long-term complications (e.g., developmental delay due to endocrine hypofunction in children) during radiotherapy.
In medulloblastoma, chemotherapy is effective but not long-lasting, especially single-drug chemotherapy, which is usually not effective, so the combination of drugs is mostly used now. benzhydrazine), hydroxyurea, cisplatin, cytarabine, arabinoside, and cyclophosphamide have been shown to be effective in young patients with medulloblastoma who are unable to undergo radiotherapy or whose dose of radiotherapy is limited.
Some authors have also suggested the prognostic importance of complete tertiary chemotherapy after surgery, i.e. VM26, methotrexate and procarbazine within 1 week after surgery, vincristine 3-4 weeks later, and lomustine and vincristine once more 8 weeks after surgery.
Complications
If surgical treatment is performed, the following complications may occur.
1. Hemorrhage Four ventricles and cerebellar earth tumor bleeding after surgery may easily cause acute obstructive hydrocephalus or direct compression of the medulla oblongata respiratory center resulting in respiratory arrest. If there is lateral ventricular external drainage before surgery, it can help to identify whether there is postoperative hemorrhage. A small amount of bleeding can be relieved by extraventricular drainage; if the bleeding is large, a second operation is necessary to stop it.
2. Respiratory arrest can be caused by pulling or directly injuring the medulla oblongata respiratory center during surgery, or by bleeding or edema compressing the medulla oblongata after surgery. Injury to the anterior inferior or posterior inferior cerebellar artery trunk, resulting in retrograde embolism leading to brainstem infarction, can also cause respiratory arrest.
3, intracranial pneumoperitoneum is related to excessive cerebrospinal fluid loss and intraoperative overhead position. In severe cases, tension pneumothorax can be formed. The gas may be located in the subdural, longitudinal fissure, fundic pool or lateral ventricle. In mild cases, the gas can be absorbed by itself, but in severe cases, puncture and deflation are needed.
4. Hydrocephalus is mostly caused by incomplete resection of tumor, postoperative adhesions of conduit, adhesions and fluid in surgical area, postoperative infection and edema of brain tissue. Measures can be taken to relieve the obstruction or to perform lateral ventricle-abdominal shunt for the cause of hydrocephalus.
Prognosis and prevention
Prognosis: The prognosis of medulloblastoma is poor, but in the past decade or so, the treatment outcome of medulloblastoma patients has improved significantly. In some reports, the 5-year survival rate has even reached 80 to 100 percent. The dramatic improvement in treatment outcomes has been attributed to three factors: microsurgical techniques that have led to a further increase in the extent of tumor resection; formal radiation therapy (local + whole brain + spinal cord); and a renewed understanding of the role of chemotherapy.
Adequate postoperative whole brain and spinal cord radiotherapy + multiple combination chemotherapy is now considered necessary to prolong survival and reduce recurrence and metastasis. The patient’s age of onset, clinical stage of the tumor and therapeutic measures are related to the patient’s prognosis. The younger the age, the worse the prognosis. The 5-year survival rate of pediatric patients is significantly lower than that of adult patients, 34% and 79% respectively, while the 10-year survival rate is more similar, 25%-28%, with no significant difference. The degree of surgical resection of the tumor directly affects the patient’s prognosis.
There was no significant difference between total and subtotal resection of the tumor on the 5-year survival rate, which ranged from 82% to 100%, while major resection significantly reduced the survival rate, which was only 42%. Medulloblastoma is more sensitive to radiotherapy, especially for patients with subtotal resection of tumor, the residual tumor can be found to disappear after one course of MRI or CT. Some studies have shown that the 5-year survival rates of patients treated with whole brain spinal cord radiotherapy and whole brain radiotherapy are 64.29% and 46.61%, and the 10-year survival rates are 41.84% and 27.01%.
The spinal cord radiotherapy is meaningful to improve the near-term survival rate, but spinal cord radiotherapy can cause radiation damage to the spinal cord and new neurological symptoms. children under 2 to 3 years of age should be treated with chemotherapy first after surgery and then whole brain spinal cord radiotherapy after 4 years of age. Recurrence and metastasis are important factors affecting the prognosis. Generally, medulloblastoma without recurrence within 10 years should be classified as “cured”, but there are cases of ectopic recurrence (metastasis) nearly 30 years after surgery. Local recurrence often occurs 2 to 4 years after treatment.
Surgery and radiotherapy for recurrent medulloblastoma are not as effective as for the first tumor. Recurrence usually does not exceed 2 years, except for individual patients who can survive for more than 5 years. CT or MRI should be reviewed once a year for the first 5 years after surgery plus radiotherapy, so that cases of recurrence or metastasis can be detected early. Clinical factors of poor prognosis in patients with medulloblastoma are: children under three years of age, those who present with symptoms of dissemination along the cerebrospinal fluid, and those with partially resected tumors.
Prevention: nothing specific.
Epidemiology
Medulloblastoma accounts for approximately 1.5% of intracranial tumors and 3.7% of intracranial neuroepithelial tumors, and is more common in children, accounting for 20% to 35% of intracranial tumors in children. Children account for about 80% of medulloblastoma patients, and the peak age of onset is before the age of 10 years, and about 68.8% of patients before the age of 8 years, with children aged 6 to 15 years accounting for 56% of all patients.
The mean age of onset among children under 15 years of age was 7.3 to 9.1 years. Among adult patients (>15 years old), 26-30 years old are more common, accounting for 43% of adult patients. It is more common in males, with a male-to-female ratio between 1.5:1 and 2:1. The incidence of astrocytoma accounts for 25% of intracranial tumors in children. 75% of the patients are under 15 years of age, occasionally seen in adults, and there are more males than females (2-3:1).