What is Medulloblastoma & How is it Treated?
A brain tumor starts developing when any healthy brain cells undergo cell division process without any control, thus forming a mass known as a tumor. Medulloblastoma comprises of three small words – Latin word 'medulla' represents inner substance, marrow or core; next is Greek word 'blastos' meaning germ or primitive, or not fully developed, and the last one is Greek word 'oma' meaning tumor. In short, Medulloblastoma is a type of central nervous system malignant tumor of undeveloped or primitive brain cells present inside the cerebellum. Although rare, Medulloblastoma is the most common pediatric non-invasive malignant, rapidly growing tumor representing about 20% of central nervous system cancer. Mostly, medulloblastoma is seen to occur in children around 15 years of age and rarely affect adults. Medulloblastoma is slightly more common in a male child than female. Usually, this tumor responds well to medical treatment.
What is Medulloblastoma?
Medulloblastoma is a most common central nervous system, high-grade, fast-growing embryonic cancerous brain tumor affecting mostly 10 to 20% of children between 3 and 5 years of age. Medulloblastomas usually develop in the posterior fossa, a part of the cerebellum on the floor of the skull in the brain and from there it may spread and metastasize to the various regions of the brain or the spinal cord through the CSF or cerebrospinal fluid. Medulloblastomas may often spread to different parts of the body, particularly in the bone marrow or bones.
Symptoms of Medulloblastoma
The signs and symptoms of medulloblastoma vary from one patient to another. The probable manifestation of the disease is mentioned in the following:
- Increased intracranial pressure due to blockage in the fourth ventricle and this generally starts as the first symptom after 1 to 5 months' of the disease progression.
- Child usually becomes listless or would lack energy.
- Abrupt onset of a morning headache.
- Truncal ataxia.
- Papilledema, i.e., blurry vision due to swelling of the optic disc of the eye.
- Frequent falls.
- Positional dizziness.
- Sixth cranial nerve palsy.
- Facial sensory loss may be present.
- Repeated episodes of morning nausea or vomiting that gets worse gradually.
- Visual problems such as diplopia or double vision.
- Weakness in motor skills, such as poor handwriting or clumsiness.
- Tiredness and drowsiness.
- Walking difficulty with a stumbling gait.
- Loss of balance and coordination.
- Tilting of the head at any one side.
- Decerebrate attacks appear late in the disease.
Epidemiology of Medulloblastoma
Medulloblastomas usually affect every 2 people per million per year and affects children 10 times more than adults i.e., it comprises for about 20% of all types of childhood brain tumors. The rate of medulloblastoma is higher in male (65%) than female (35%) child. Medulloblastoma is more prevalent in a younger child than the older one, i.e., 40% of children are diagnosed at 5 years of age, 31% between 5 and 9 years of age, 18% between 10 and 14 years of age, and 13% between 15 and 19 years of age.
Prognosis of Medulloblastoma
Prognosis of medulloblastoma usually depends on the age of the patient when the diagnosis is done, the extent and sizes of the tumor, level of metastasis, and finally, the amount of tumor mass removed safely. All these factors also determine the survival rate. Generally, a child below 3 years of age has very low survival rate mainly because of the more aggressiveness of the disease. Otherwise, if the tumor has spread to spinal cord then survival rate is around 60% and if has not spread, then survival rate is about 80%.
Causes of Medulloblastoma
The actual cause of medulloblastoma is completely unknown. However, researches are still going on in understanding the exact pathophysiology behind the cause of this tumor. Chromosome or gene alteration is supposed to play a vital role in the development of this tumor. Medulloblastoma has not seen to be inherited generations after generations and no family history is responsible for the cause of this disease. However, medulloblastoma is often associated with rare genetic ailments or any specific chromosomal abnormalities at some phase of development of a child.
Pathophysiology of Medulloblastoma
Medulloblastomas usually develop near the 4th ventricle, between the cerebellum and the brainstem. It is believed that medulloblastomas arises from embryonic or immature brain cells at the early phase of development, depending upon the different subgroup of medulloblastoma. Recent genomic studies have found out that this type of tumor actually has four distinct clinical as well as molecular variants; such as Sonic Hedgehog or SHH, Group 4, WNT/β-catenin, and Group 3. Repeated mutations are also seen in individuals with medulloblastoma in genes like PTCH1, CTNNB1, SMARCA4, MLL2, CTDNEP1, DDX3X, TBR1, and KDM6A. Additional signaling pathways that are disrupted in medulloblastoma include Notch, MYC, TGF-β, and BMP.
Other studies have revealed that over expression of different oncogenes like MYCC and ERBB2 are related to the worse outcome of this disease. The huge amplification of oncogene OTX2 is also thought to be linked with medulloblastoma. Gene MYCC can also produce a more violent effect on some of the anaplastic variation of medulloblastoma.
Risk Factors of Medulloblastoma
The probable risk factors associated with this health condition include the following:
- Genetic Factors posing a Risk for Medulloblastoma: Children with NBCCS or nevoid basal cell carcinoma syndrome, also called as Gorlin syndrome and i-Fraumeni syndrome have a higher chance to get affected by Medulloblastoma.
- Sex: Medulloblastoma more commonly affects boys than girls.
- Age: Mostly, medulloblastoma is diagnosed before the age of 16 years, and thus usually between 3 and 9 years of age.
Complications of Medulloblastoma
The probable complications of Medulloblastoma include the following:
- Brain Herniation: This involves the occurrence of damage in the lower part of the brain mainly because of increased intracranial pressure.
- Loss of cognitive skills or Aphasia.
- Permanent neurological dysfunction.
- Loss of the ability to perform daily activities.
The most serious one is spreading of tumor growth from the original location to various parts of the brain and the spinal cord via cerebrospinal fluid. Once the tumor reaches the spinal cord, the complications that arise like:
- Poor controlling of bowel and bladder functions.
- Trouble in proper walking.
- Mild to severe back pain.
Diagnosis of Medulloblastoma
Doctors first do the physical diagnosis after hearing the symptoms of the ailments. Then, for a correct diagnosis of medulloblastoma, one may need the following tests to be done as early as possible:
- Biopsy: A biopsy is the only way to diagnose medulloblastoma properly together with the exact analysis by a pathologist.
- Magnetic Resonance Imaging (MRI): MRI scan of the brain in a magnetic field with gadolinium contrast-enhancement, the gold standard, is done to produce detailed images of the brain and measure the actual size of the tumor for detecting medulloblastoma.
- CT Scan to diagnose Medulloblastoma: Computerized Tomography or CT scan uses x-rays to generate a 3D picture of a tumor inside of the brain.
- Lumbar Puncture or Spinal Tap: In this test, a sample of cerebral spinal fluid or CSF is taken out to examine the level of tumor markers, blood, or growth of cancer cells.
- PET Scan: Positive emission tomography or PET scan is also done to diagnose the malignant tumor growth inside the brain of a child.
- Tumor Appearance: Histologically, if detected, then the tumor is pink-gray in color, solid and is well confined by numerous cells with a very little amount of cytoplasm, and usually, has the tendency to transform into rosettes or clusters.
Treatment for Medulloblastoma
The probable treatments for medulloblastoma include the following:
- Surgery for Medulloblastoma: This is typically the first step of therapy to treat medulloblastoma. Surgery usually involves partial or complete removal of the tumor growth without harming the surrounding brain tissue during an operation.
- Chemotherapy to Treat Medulloblastoma: Chemotherapy is often used as a treatment for medulloblastoma. The different chemotherapeutic course of therapy for medulloblastoma mostly involves a grouping of cyclophosphamide, carboplatin, cisplatin, CCNU, vincristine or lomustine. Usually, for patients below 3 to 4 years of age, chemotherapy can be possibly delayed. Chemotherapy is injected into the blood stream or administered orally. Chemotherapy normally enhances the rate of disease-free survival among patients. Normally, increased intracranial pressure can be regulated by using a ventriculoperitoneal shunt or corticosteroids.
- Radiation Therapy to Treat Medulloblastoma: This therapy uses high-energy X-rays or any other forms of radiation to kill or stop the growth of tumor cells in the central nervous system. Craniospinal radiation therapy is recommended to prevent the relapse or recurrence of the tumor mass.
- Intensity Modulated Radiation Therapy or IMRT: This is a more advanced type of radiation that usually shapes the decreased rate of radiation beams to focus directly on the structures like posterior fossa.
- Proton Therapy to Treat Medulloblastoma: Proton therapy works completely in a different manner and its peak dose either kills or stops the growth of tumor cells.
- Stereotactic Radiosurgery for Treating Medulloblastoma: This is not an actual form of surgery, which is delivered from different angles possible in the form of a pin down method with prescribed amount of radiation.
- Whole-Brain Radiation Therapy: This therapy is applied if a patient has more than one medulloblastoma.
- Focused Radiation Therapy: This therapy is aimed precisely at the tumor mass or the surrounding affected area.
Prevention of Medulloblastoma
As such, there are no preventive measures to get rid of medulloblastoma. However, it is recommended to do a regular screening of a child from the time of birth to adulthood, so that if he suffers from medulloblastoma then it can be restricted to the first stage of metastasis.
Recovery for medulloblastoma can sometimes show within a month or two just after the treatment is completed. It is essential to talk to an oncologist regarding cancer-focused follow-up care or development of any survivorship care plan. With the advancement of science and technology in the recent years, the understanding of medulloblastoma has increased significantly at the molecular level through better genetic analysis. There are a number of ongoing researches in the field which might give much better view of the causative factors.