Medulloblastoma · What Is It, Signs and Symptoms, Treatment, and More

The exact cause of medulloblastoma is not well understood, but it is likely to result from a combination of genetic and environmental factors. Some genetic syndromes, such as Li-Fraumeni and nevoid basal cell carcinoma syndrome (i.e., Gorlin syndrome), have been associated with an increased risk of developing medulloblastoma. Nonetheless, the majority of cases occur sporadically without a clear genetic predisposition. 

Research suggests that mutations in genes that regulate cell growth and death may play a role in the development of medulloblastoma. For example, mutations in the Sonic Hedgehog (SHH) pathway and WNT pathway (i.e., a network of proteins regulating cell growth and tissue regeneration) have been identified in individuals with medulloblastoma and currently serve as prognostic markers for the disease. For example, medulloblastomas with WNT mutations generally have a more favorable prognosis compared to other subgroups. Additionally, exposure to ionizing radiation, particularly during childhood, is considered a risk factor for the development of medulloblastoma.  

The most common symptoms of medulloblastoma include headaches, nausea, vomiting, and seizures, which are a result of the compression and destruction of healthy brain tissue. At first, some of these symptoms may go unnoticed, but they often progress rapidly over the course of weeks to a few months. As the tumor grows in size, it can compress nearby structures, blocking the flow of cerebrospinal fluid and causing an increase in intracranial pressure.   

Additional symptoms are often related to the location of medulloblastoma at the base of the brain. Most medulloblastomas form in or around the cerebellum, which is the part of the brain responsible for coordination and balance. Compression of the cerebellum can result in walking difficulties; clumsiness; and intention tremor, which is an involuntary shaking of the hands or arms seen when performing a purposeful activity, such as reaching for a cup of coffee.  

Some individuals may also experience blurred or double vision, and in some cases, difficulty controlling eye movements. These symptoms can be caused by cerebellar dysfunction as well as compression of the brainstem or cranial nerves from increased intracranial pressure. Although rare, in cases where the tumor has spread down through the spinal canal, symptoms may also include back pain as well as bladder and bowel dysfunction.  

Diagnosis of medulloblastoma begins with a thorough medical history and physical examination. Some indirect features of medulloblastoma that can be seen on physical examination include signs of increased intracranial pressure, such as optic pallor or papilledema on a fundoscopic examination, and increased head circumference or macrocephaly. Imaging tests, such as an MRI of the brain can help establish a diagnosis; however, a definitive diagnosis is made based on the histologic and molecular characteristics of a tissue biopsy obtained during the tumor removal.  

Additionally, a spinal MRI may be performed to determine the involvement of the meninges and spinal cord. If possible, a lumbar puncture (i.e., spinal tap) may be performed to assess the presence of cancer cells in cerebrospinal fluid. Medulloblastoma rarely metastasizes outside of the central nervous system, which is why additional tests (e.g., CT scan of the chest or abdomen, PET scan) are generally not necessary for staging the disease.  

Treatment of medulloblastoma typically involves a combination of surgery, radiation therapy, and chemotherapy. The specific treatment plan may vary depending on factors such as the age of the individual, the size and location of the tumor, and the presence of leptomeningeal dissemination. A multidisciplinary team of healthcare professionals, including neurosurgeons, oncologists, and radiation therapists typically work together to decide on the best treatment plan. 

The main goal of surgery is to remove as much of the tumor as possible without damaging any important brain structures. Surgery is typically followed by radiation therapy, which is aimed at killing any cancer cells that may remain in the tumor bed as well as preventing the risk of recurrence. Radiation therapy may be administered to the entire brain and spinal cord, especially in cases where the tumor has spread to the spinal cord. Radiation therapy may have long-term side effects in young children (e.g., neurodevelopmental delays, decreased skeletal growth, endocrine anomalies), which is why the area of radiation and dosage may be adjusted to minimize these effects. Finally, chemotherapy is often administered after surgery and radiation therapy to treat individuals with moderate or high-risk diseases. In cases where surgery has resulted in neurological sequelae, individuals may benefit from speech, occupational, and physical therapy, depending on the specific symptoms. 

Long-term survival is achieved in around 75% of individuals with medulloblastoma; however, the prognosis varies highly depending on the individual and specific characteristics of the tumor. Ongoing research aims to identify molecular and genetic characteristics of medulloblastomas that allow the development of targeted therapies that may improve survival rates over time.