What is Carcinomatous Meningitis (leptomeningeal meningitis, neoplastic meningitis)?
Carcinomatous meningitis (CM) refers to the spreading of cancer cells from their original location to different areas of the brain and spinal cord, such as the subarachnoid, pia mater, and cerebrospinal fluid (CSF). This condition is also called ‘leptomeningeal meningitis,’ ‘leptomeningeal carcinomatosis,’ ‘leptomeningeal metastasis,’ or ‘neoplastic meningitis.’ Interestingly, the term ‘carcinomatous meningitis’ was first used in 1912 by Beerman to describe a situation where cancer cells spread to the protective layers of the brain (meninges) without affecting the brain tissue itself.
CM can happen during the advanced stage of many types of cancer. This occurs when cancer cells travel through the cerebrospinal fluid (the fluid in the brain and spinal cord) and settle down in the meninges. The deposits of cancer are usually in multiple areas and can lead to a variety of symptoms. Doctors use tests on the cerebrospinal fluid in combination with advanced imaging techniques to diagnose CM. Treatment often involves radiation therapy and chemotherapy. However, it’s often difficult to diagnose CM early on, and the condition generally has a poor prognosis. With the development of newer diagnostic tools and innovative treatment strategies, there may be potential to improve outcomes and reduce the negative effects of this disease.
What Causes Carcinomatous Meningitis (leptomeningeal meningitis, neoplastic meningitis)?
Primary cancers, which are initial tumor growths, can spread to a part of the brain called the leptomeninges. This happens both in cases where the primary cancer is inside the skull (intracranial) or outside the skull (extracranial). The most frequent types of external skull cancers that spread in this way are breast cancer, lung cancer, and a skin cancer known as melanoma.
On the other hand, the most common types of cancers that start inside the skull and then spread to the leptomeninges include cerebellar medulloblastoma, a form of brain tumor that usually arises at the back part of the brain known as the cerebellum; malignant ependymomas, which are cancers originating from the ependymal cells lining the ventricles of the brain; neuromas, which are usually benign tumors that develop on the nerve tissue; and gliomas, tumors that grow in the gluey supportive cells, or glial cells, that surround nerve cells and help them function.
Risk Factors and Frequency for Carcinomatous Meningitis (leptomeningeal meningitis, neoplastic meningitis)
Leptomeningeal metastasis, or cancer spread to the membranes around the brain and spinal cord, occurs in 5% to 8% of cases of solid tumors and 5% to 15% of blood cancers. The most common type of blood cancer causing this condition is B-cell lymphoma. However, the incidence might be as high as 20% due to undiagnosed cases that are only identified during autopsies.
When it comes to solid organ tumors, lung cancer, melanoma, and breast cancer are the most common causes of what’s known as carcinomatous meningitis. This condition can also be caused by brain cancers like gliomas, ependymomas, and medulloblastomas. In about 60% of cases, carcinomatous meningitis is associated with cancer in the brain tissue. Interestingly, in 1 to 7% of all cases, the primary location of the cancer cannot be found, even after thorough examinations.
Signs and Symptoms of Carcinomatous Meningitis (leptomeningeal meningitis, neoplastic meningitis)
Carcinomatous meningitis is a complicated illness because it involves much of the nervous system. Symptoms can vary depending on how the disease is affecting the brain. The key mechanisms of the disease are:
- Increased pressure in the brain due to blockage of cerebrospinal fluid flow, leading to different types of hydrocephalus.
- Blood-brain barrier disruption causing brain swelling.
- Direct invasion of malignant cells into brain and spine nerves.
These malignant cells invade the brain’s tissue, using up important resources like oxygen and glucose. This can lead to lower metabolic function in the brain and cause symptoms similar to a stroke. The presence of these cells in both the membrane around the brain and in the brain tissue itself can cause different symptoms depending on where the cells are located.
The most common symptom reported by patients is a headache, affecting 39% of patients. The type of headache can be different depending on the cause. A feeling of confusion is the second most common symptom, and this is caused by active malignant cells impacting the cortex of the brain. Other symptoms can include seizures with unusual experiences like déjà vu, euphoria, hallucinations, and amnesia.
Other symptoms relate to the involvement of the back part of the brain including nausea, vomiting, dizziness, coordination problems, and vision changes. These are seen in 65% of patients. There can also be issues with cranial nerves leading to double vision, loss of vision, facial weakness, hearing loss, balance problems, difficulty swallowing, problems with speech, and a hoarse voice.
Malignant cells can also involve the spinal cord leading to symptoms like tingling, pain, and limb weakness in different areas depending on the affected nerve roots. This can also affect bowel and bladder function. Some specific conditions involving parts of the spinal cord can be the only symptom in some patients. Symptoms like leg weakness and back pain or paralysis can be the first things patients with spinal involvement notice.
2% of patients might not show any symptoms at all.
Testing for Carcinomatous Meningitis (leptomeningeal meningitis, neoplastic meningitis)
If you’re being checked for carcinomatous meningitis, a condition where cancer cells spread to the membranes surrounding your brain and spinal cord, the first steps are taking a detailed medical history and doing a physical exam. The physical exam will include a detailed check of your nervous system which can indicate whether the issue is located in a specific area or is affecting multiple areas. After this initial assessment, your doctor may order a cerebrospinal fluid (CSF) evaluation and imaging studies to further confirm the diagnosis.
Analysing cerebrospinal fluid involves looking at a number of things:
Neuroimaging, including gadolinium-enhanced MRI scans, can help doctors diagnose carcinomatous meningitis. These scans can reveal changes in the brain’s structure that indicate the presence of the disease.
Tumor markers, or proteins produced by cancerous cells, can also assist in diagnosis. Specific markers may even help determine the prognosis of the disease. Some specific tests that can be run on cerebrospinal fluid samples to help with diagnosis include: immunohistochemical staining, flow cytometry, FISH (fluorescent in situ hybridization), and PCR (polymerase chain reaction). These can help doctors to identify the type of tumor and sometimes even predict how the disease will progress.
It’s also essential to perform CSF flow studies to ensure the appropriate flow of cerebrospinal fluid. In some cases, cancer cells can block the flow of CSF, jeopardizing the effectiveness of chemotherapy treatment and increasing the risk of side effects.
In conclusion, diagnosing carcinomatous meningitis requires careful evaluation of symptoms, testing of the cerebrospinal fluid, and advanced imaging techniques. Accurate diagnosis is crucial to start the appropriate treatment and improve patient outcomes.
Treatment Options for Carcinomatous Meningitis (leptomeningeal meningitis, neoplastic meningitis)
Managing carcinomatous meningitis, a type of cancer that affects the protective layers around the brain and spinal cord, can be complex. The aim is to improve quality of life, prolong survival, and manage the progression of neurological deterioration with as little harm from treatments as possible. Treatment strategies will vary based on a patient’s overall health situation, the aggressiveness of the tumor, how much the disease has spread, and their neurological status.
Healthcare providers use the Karnofsky performance score (KPS) and Eastern Cooperative Oncology Group (ECOG) scoring systems to rate how well a patient with cancer is functioning. Likely treatment options will depend on these scores. For patients with a low functional status, doctors often recommend pallative care, which aims to provide comfort and improve quality of life, because the negative impacts of treatment could outweigh potential benefits. Assessing how patients are responding to treatments and monitoring for any negative side effects are crucial at every stage of treatment.
Guidelines for managing carcinomatous meningitis have been established by various professional groups. Treatment typically involves three primary strategies:
1. Radiation therapy
2. Intrathecal chemotherapy (directly into the spinal fluid)
3. Systemic chemotherapy (throughout the body)
Radiation therapy can be either focused to specific affected areas or distributed generally, depending on the location and extent of the disease. This treatment works by irradiating (killing) tumor cells to control disease symptoms. How they are used depends on areas where the disease is most active or causing the most problems. For example, cranial irradiation (radiation to the head) is helpful for neurological symptoms and conditions like obstructive hydrocephalus (a buildup of fluid in the brain). Focal spinal irradiation (radiation to specific parts of the spine) can be beneficial for lower limb weakness and issues with the bladder or bowel. While such treatments might not always improve neurological deficits, they can decrease pain. Whole-brain radiation therapy (WBRT), which irradiates the whole brain, can be beneficial in certain settings.
Chemotherapy, a treatment regimen involving drugs to kill cancer cells, can be administered in two ways: intrathecally and systemically. Intrathecal chemotherapy is injecting the drug directly into the spinal fluid. This is often done by either injecting the drug into the lower part of the spinal column (using a technique known as lumbar puncture or LP) or using a special device called an Ommaya catheter, which creates a direct pathway to the fluid around the brain.
Systemic chemotherapy treats the entire body and is especially beneficial for managing both leptomeningeal disease (cancer within the membranes covering the brain and spinal cord) and any cancer present elsewhere in the body. Certain criterias like the ability of the drug to cross the blood-brain barrier (a natural protective mechanism of the brain), safety at high doses and solubility of drug is considered.
A combination of both chemotherapy and radiation therapy is typically the best approach for patients in relatively good health.
Along with these traditional treatment approaches, targeted therapy, which attacks specific cancer cells without harming normal cells, can also be used depending on the type of primary cancer. For instance, EGFR inhibitors are used in certain types of lung cancer, while BRAF inhibitors may be beneficial in melanoma treatment.
In conclusion, the treatment of carcinomatous meningitis is personalized depending upon a patient’s specific situation and may involve a combination of strategies for the best outcome.
What else can Carcinomatous Meningitis (leptomeningeal meningitis, neoplastic meningitis) be?
There are many health conditions that can show the same symptoms as carcinomatous meningitis (CM). These conditions should be considered when a patient shows similar signs and symptoms:
- Primary brain lesions or metastasis within the brain itself could have the same symptoms. It’s important to rule out any issues with the skull bones or dura mater, a protective membrane in the brain. Leptomeningeal metastasis, which is cancer spread to the membranes covering the brain and spinal cord, can also occur on its own or alongside these issues.
- Chronic or recurring meningitis caused by various bacterial, fungal, viral, or protozoal organisms can also resemble CM. Autoimmune causes and factors triggered by certain drugs should be considered as well.
- Paraneoplastic syndromes, which are a group of rare disorders triggered by an abnormal immune response to a cancerous tumor, can also mimic CM. These include Lambert Eaton syndrome, Myasthenic crises, cerebellar degeneration, encephalomyelitis, different types of nerve diseases, and limbic encephalitis. These conditions are associated with advanced diseases.
What to expect with Carcinomatous Meningitis (leptomeningeal meningitis, neoplastic meningitis)
Carcinomatous meningitis is a late-stage disease that generally has a poor outlook. On average, even with treatment, people only live for around 2 to 4 months after diagnosis. However, early detection, normal protein levels in the cerebrospinal fluid (also known as CSF which is the fluid around the brain and spinal cord), and less spread of the disease can contribute to a better outcome.
Patients with a Karnofsky Performance Status (KPS is a scale used by doctors to measure a patient’s ability to perform ordinary tasks) score above 60, little disease spread throughout the body, minimal neurological problems, and options for effective systemic therapy (treatment involving the whole body, such as chemotherapy) are thought to have favorable disease conditions. For this group, systemic treatment combined with intrathecal treatment (drug delivery into the CSF) or radiotherapy can be beneficial.
People who are high-risk may find palliative care (providing relief from symptoms, instead of curing the disease) is the best choice. It’s important to note that carcinomatous meningitis due to lymphomas or leukemias (types of cancers) tends to have a better outcome compared to that caused by solid tumors.
