Medulloblastoma
Disease Details
Family Health Simplified
- Description
- Medulloblastoma is a highly malignant primary brain tumor that originates in the cerebellum, predominantly affecting children.
- Type
- Medulloblastoma is a type of primary central nervous system tumor that originates in the cerebellum or posterior fossa of the brain. The type of genetic transmission associated with medulloblastoma is generally sporadic, meaning it usually occurs with no clear inheritance pattern. However, there are rare cases in which it is associated with hereditary syndromes such as Li-Fraumeni syndrome, Gorlin syndrome, or Turcot syndrome, which follow an autosomal dominant inheritance pattern.
- Signs And Symptoms
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Signs and symptoms are mainly due to secondary increased intracranial pressure due to blockage of the fourth ventricle and tumors are usually present for 1 to 5 months before diagnosis is made. The child typically becomes listless, with repeated episodes of vomiting, and a morning headache, which may lead to a misdiagnosis of gastrointestinal disease or migraine. Soon after, the child will develop a stumbling gait, truncal ataxia, frequent falls, diplopia, papilledema, and sixth cranial nerve palsy. Positional vertigo and nystagmus are also frequent, and facial sensory loss or motor weakness may be present. Decerebrate attacks appear late in the disease.
Extraneural metastasis to the rest of the body is rare, and when it occurs, it is in the setting of relapse, more commonly in the era prior to routine chemotherapy. - Prognosis
- Medulloblastoma prognosis can vary based on several factors, including the molecular subtype of the tumor, the age of the patient, the extent of tumor resection, and the presence of metastasis at diagnosis. Generally, the 5-year survival rate for standard-risk medulloblastoma in children is around 70-80%. High-risk cases, which may involve metastasis or other adverse factors, have a lower survival rate, approximately 60%. Aggressive treatment with surgery, radiation, and chemotherapy can improve outcomes, but long-term effects and complications from the treatment can impact quality of life. Individual prognosis should always be discussed with a healthcare provider who can consider all relevant factors.
- Onset
- Medulloblastoma is a type of brain tumor that primarily affects children, typically presenting with symptoms around the ages of 3 to 8, but it can also occur in older children and adults. The onset usually involves signs like headaches, nausea, vomiting, and balance or coordination issues due to increased intracranial pressure and cerebellar involvement.
- Prevalence
- Medulloblastoma is relatively rare, with an estimated incidence of about 1.5 cases per million people annually. It is the most common malignant brain tumor in children, representing approximately 20% of all pediatric brain tumors.
- Epidemiology
- Medulloblastomas affect just under two people per million per year, and affect children 10 times more than adults. Medulloblastoma is the second-most frequent brain tumor in children after pilocytic astrocytoma and the most common malignant brain tumor in children, comprising 14.5% of newly diagnosed brain tumors. In adults, medulloblastoma is rare, comprising fewer than 2% of CNS malignancies.The rate of new cases of childhood medulloblastoma is higher in males (62%) than females (38%), a feature that is not seen in adults. Medulloblastoma and other PNET`s are more prevalent in younger children than older children. About 40% of medulloblastoma patients are diagnosed before the age of five, 31% are between the ages of 5 and 9, 18.3% are between the ages of 10 and 14, and 12.7% are between the ages of 15 and 19.
- Intractability
- Medulloblastoma is a type of brain tumor that primarily affects children. While challenging to treat, it is not universally intractable. Treatment options such as surgery, radiation therapy, and chemotherapy can be effective, especially when diagnosed early. The prognosis varies depending on factors like the patient's age, the tumor's location, and molecular characteristics. Advances in medical research continue to improve outcomes for many patients.
- Disease Severity
- Medulloblastoma is a highly malignant and aggressive brain tumor primarily affecting children. It tends to disseminate through the cerebrospinal fluid and can metastasize to other parts of the central nervous system and beyond if not promptly treated. Early diagnosis and aggressive treatment are crucial for improving outcomes.
- Healthcare Professionals
- Disease Ontology ID - DOID:0050902
- Pathophysiology
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Medulloblastoma is a highly malignant primary brain tumor that originates in the cerebellum or posterior fossa. It is most common in children but can occur in adults. The pathophysiology involves genetic mutations and alterations that lead to uncontrolled cell proliferation. Medulloblastomas can be classified into different molecular subgroups, each with distinct genetic profiles and clinical outcomes. The four main subgroups are:
1. **WNT (Wingless)**: Characterized by mutations in the CTNNB1 gene, usually associated with a good prognosis.
2. **SHH (Sonic Hedgehog)**: Features mutations in the PTCH1, SUFU, or SMO genes and is often seen in infants and adults.
3. **Group 3**: Often associated with MYC amplification and has a poor prognosis.
4. **Group 4**: Frequently shows isochromosome 17q and has intermediate prognosis.
The tumor cells in medulloblastoma arise from progenitor cells in the cerebellar vermis or roof of the fourth ventricle and can spread through the cerebrospinal fluid to other parts of the central nervous system.
Treatment typically involves a combination of surgery, radiation, and chemotherapy. Recent advances focus on targeted therapies based on the molecular characteristics of the tumor. - Carrier Status
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Medulloblastoma is a type of brain tumor that primarily affects children. It arises in the cerebellum, which controls balance and motor functions. While most cases of medulloblastoma are not inherited and occur sporadically, there are some genetic syndromes associated with an increased risk of developing this tumor. These include:
1. **Gorlin Syndrome (Nevoid Basal Cell Carcinoma Syndrome)**: Caused by mutations in the PTCH1 gene.
2. **Turcot Syndrome**: Associated with mutations in the APC or MMR genes.
3. **Li-Fraumeni Syndrome**: Involves mutations in the TP53 gene.
Carrier status for these syndromes can be inherited in an autosomal dominant pattern, meaning a person only needs one copy of the mutated gene from one parent to be at increased risk. Genetic counseling and testing are recommended for families with a history of these syndromes. - Mechanism
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Medulloblastoma is a type of malignant brain tumor predominantly occurring in children. Its pathogenesis involves several mechanisms and molecular pathways:
1. **Hedgehog (HH) Signaling Pathway**: Mutations and aberrations in this pathway, such as in the PTCH1 gene, are commonly involved. Dysregulation leads to uncontrolled cell proliferation.
2. **Wnt Signaling Pathway**: Mutations in genes such as CTNNB1, which codes for β-catenin, lead to activation of this pathway and contribute to tumorigenesis.
3. **MYC Oncogene Activation**: Amplification of the MYC gene, particularly in Group 3 medulloblastomas, is associated with a worse prognosis and aggressive tumor growth.
4. **p53 Pathway**: Mutations in TP53, a tumor suppressor gene, are found in certain subsets (i.e., SHH-activated, TP53-mutant medulloblastomas) and are associated with genetic instability and poor outcomes.
5. **DNA Repair Mechanisms**: Defects in DNA repair genes and pathways, commonly found in various cancers, also play a role in the development of medulloblastoma by increasing genetic mutations.
The interplay of these molecular mechanisms results in the uncontrolled growth and survival of medulloblastoma cells, making it a complex and heterogeneous disease. - Treatment
- Treatment begins with maximal surgical removal of the tumor. The addition of radiation to the entire neuraxis and chemotherapy may increase the disease-free survival. This combination may permit a 5-year survival in more than 80% of cases. Some evidence indicates that proton beam irradiation reduces the impact of radiation on the cochlear and cardiovascular areas and reduces the cognitive late effects of cranial irradiation.The presence of desmoplastic features such as connective tissue formation offers a better prognosis. Prognosis is worse if the child is less than 3 years old, degree of resection is inadequate, or if any CSF, spinal, supratentorial, or systemic spread occurs. Dementia after radiotherapy and chemotherapy is a common outcome appearing two to four years following treatment. Side effects from radiation treatment can include cognitive impairment, psychiatric illness, bone growth retardation, hearing loss, and endocrine disruption. Increased intracranial pressure may be controlled with corticosteroids or a ventriculoperitoneal shunt. An approach to monitor tumor development and treatment response by liquid biopsy is promising, but remains challenging.
- Compassionate Use Treatment
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For medulloblastoma, compassionate use treatments, off-label, and experimental treatments include the following options:
1. **Compassionate Use Treatments**: These may involve access to investigational drugs outside clinical trials for patients with no other treatment options. Specific drugs granted under compassionate use are determined case-by-case by regulatory bodies.
2. **Off-Label Treatments**: Some off-label drugs used for medulloblastoma include:
- **Bevacizumab (Avastin)**: Typically used for treating certain cancers, but can be applied off-label to medulloblastoma to inhibit tumor blood vessel growth.
- **Temozolomide (Temodar)**: Although primarily used for glioblastoma, it may be prescribed off-label for recurrent medulloblastoma.
3. **Experimental Treatments**: These are primarily studied in clinical trials and include:
- **Molecularly Targeted Therapies**: Drugs such as vismodegib (targeting the Hedgehog pathway) and sonidegib are being studied for specific medulloblastoma subtypes.
- **Immunotherapy**: Approaches such as immune checkpoint inhibitors (e.g., pembrolizumab) are being explored.
- **CAR-T Cell Therapy**: A cutting-edge treatment where a patient's T cells are modified to target cancer cells.
- **Gene Therapy**: Investigates altering genes within the cancer cells to slow down or stop their growth.
Patients interested in these approaches should consult their healthcare providers to understand eligibility, potential benefits, and risks. - Lifestyle Recommendations
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Medulloblastoma is a type of brain tumor that primarily affects children. While lifestyle recommendations cannot prevent or cure medulloblastoma, they can support overall well-being and recovery during and after treatment. Key lifestyle recommendations include:
1. **Healthy Diet:** A balanced diet rich in fruits, vegetables, lean proteins, and whole grains supports general health and helps the body recover from treatment.
2. **Regular Exercise:** As tolerated and approved by healthcare providers, regular physical activity can improve physical function, reduce fatigue, and enhance emotional well-being.
3. **Adequate Sleep:** Ensuring plenty of restful sleep is crucial for recovery and overall health.
4. **Hydration:** Maintain proper hydration to aid in overall bodily functions and support recovery.
5. **Psychosocial Support:** Mental and emotional support for the patient and family can help manage the stress and emotional burden of the disease and its treatment.
6. **Follow-Up Care:** Regular follow-up appointments with healthcare providers to monitor for recurrence and manage any long-term side effects of treatment.
Consult with healthcare professionals for personalized guidance tailored to individual needs and treatment plans. - Medication
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Medulloblastoma is a type of brain cancer that primarily affects children. Treatment generally involves a combination of surgery, radiation therapy, and chemotherapy. Medication specifically used in the chemotherapy component of treatment may include:
1. **Carboplatin**
2. **Cisplatin**
3. **Vincristine**
4. **Cyclophosphamide**
5. **Etoposide**
These medications aim to target and kill cancer cells to improve patient outcomes. Treatment regimens can vary based on the individual case and medical guidelines. - Repurposable Drugs
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Medulloblastoma is a type of brain tumor primarily affecting children. Several drugs currently approved for other indications are being explored for potential use in medulloblastoma treatment. These repurposable drugs may include:
1. **Arsenic trioxide**: Originally used for acute promyelocytic leukemia, it's being studied for its potential efficacy in treating medulloblastoma.
2. **Celecoxib**: A COX-2 inhibitor used for pain and inflammation that is under investigation for its anticancer properties.
3. **Itraconazole**: An antifungal medication that has shown promise in inhibiting the Hedgehog signaling pathway, which is active in some medulloblastomas.
4. **Thalidomide and its derivatives (lenalidomide)**: Primarily used for multiple myeloma, these drugs have anti-angiogenic and immunomodulatory effects that might benefit medulloblastoma patients.
5. **Metformin**: Commonly used for Type 2 diabetes, it has shown potential anticancer effects by inhibiting certain cellular pathways.
Ongoing clinical trials and research are essential to determine the safety and efficacy of these repurposable drugs for treating medulloblastoma. - Metabolites
- Medulloblastoma is a type of brain tumor that commonly affects children. Commonly altered metabolites in medulloblastoma include those involved in glycolysis, the TCA cycle, and lipid metabolism. Elevated lactate levels are frequently observed, indicating a reliance on anaerobic glycolysis. Additionally, alterations in metabolites such as glutamine, glutamate, and various lipid metabolites may also be seen. These metabolic alterations can provide insights into tumor biology and potential therapeutic targets.
- Nutraceuticals
- For medulloblastoma, a type of brain tumor, nutraceuticals are still an emerging area of research. There isn't currently sufficient evidence to support the use of specific nutraceuticals for treating or managing medulloblastoma. The primary treatments remain surgery, radiation, and chemotherapy. Always consult healthcare professionals for personalized medical advice.
- Peptides
- Medulloblastoma is a type of brain tumor primarily affecting children. Peptides, such as those used in targeted therapies, can serve as molecular agents to inhibit tumor growth or enhance the immune response against cancer cells. Nanotechnology, including the use of nanoparticles, is being investigated to improve drug delivery directly to the tumor site, thereby enhancing treatment efficacy and minimizing side effects. Both approaches are part of ongoing research aiming to develop more effective treatments for medulloblastoma.