Metastases to Meninges

When cancer spreads to the thin membranes surrounding the brain and spinal cord, it creates a rare but serious condition that affects thousands of people each year. Understanding this disease can help patients and families navigate diagnosis, treatment options, and what to expect.

leptomeningeal metastases, leptomeningeal disease, neoplastic meningitis, carcinomatous meningitis, leptomeningeal carcinomatosis, meningeal carcinomatosis

Table of contents

• What Is Metastases to Meninges
• The Affected Areas
• How Cancer Spreads to the Meninges
• How Common Is This Condition
• Signs and Symptoms
• How Doctors Make a Diagnosis
• Treatment Options
• What to Expect

What Is Metastases to Meninges

Metastases to meninges, also called leptomeningeal metastases, happens when cancer cells spread from their original location in the body to the thin tissue layers that cover the brain and spinal cord^[2]. These protective membranes are called leptomeninges, which are part of the brain’s outer covering system^[2].

This condition represents an advanced stage of cancer, when cells have broken away from where the cancer first started and traveled to a new area. Healthcare providers are seeing more cases of this disease as people with cancer are living longer thanks to better treatments^[3].

There is currently no cure for metastases to meninges. Instead, doctors focus on controlling the cancer’s growth, relieving symptoms, and helping maintain quality of life^[3].

The Affected Areas

• Brain
• Spinal cord
• Leptomeninges (pia mater and arachnoid membranes)
• Cerebrospinal fluid

The leptomeninges are delicate, thin membranes that cover and protect the brain and spinal cord^[6]. Around these membranes flows a clear liquid called cerebrospinal fluid, which surrounds the entire central nervous system and has direct contact with the leptomeninges^[3]. This fluid normally drains through a network of veins, but cancer cells can block this drainage and disrupt the fluid’s normal flow^[3].

The leptomeninges consist of two specific layers: the pia mater and the arachnoid. When cancer affects this area, it involves both these membrane layers as well as the cerebrospinal fluid that flows between them^[6].

How Cancer Spreads to the Meninges

Cancer cells reach the meninges by traveling through the bloodstream from a cancer somewhere else in the body. Sometimes they spread from a secondary cancer that has already developed in the brain^[2].

This process starts when cancer cells from the primary cancer invade nearby normal tissue. Then they move through the walls of nearby lymph vessels or blood vessels, traveling to the leptomeninges and cerebrospinal fluid where they can form new tumors^[6].

When cancer cells infiltrate the leptomeninges, they can disrupt the normal flow of cerebrospinal fluid and cause various problems throughout the nervous system^[6]. The cancer usually affects multiple areas rather than just one spot, which is why symptoms can vary widely from person to person^[4].

How Common Is This Condition

Between 5 and 10 out of every 100 people (5 to 10%) with solid tumors might develop metastases to meninges^[2]. Approximately 5% of all people who have cancer develop this condition^[3].

The most common cancers that lead to metastases to meninges are breast cancer, lung cancer, and melanoma skin cancer^[2]. More specifically, breast cancer accounts for 12 to 35% of cases, lung cancer for 10 to 26%, melanoma for 5 to 25%, and gastrointestinal cancer for 4 to 14%^[6].

For blood cancers, 5 to 15 out of every 100 people (5 to 15%) might develop this complication^[2]. Among blood cancers, B-cell lymphoma is the most common cause^[4]. About 5% to 10% of people with non-Hodgkin’s lymphoma develop metastases to meninges, while approximately 1% to 10% of people with acute lymphocytic leukemia are affected^[3].

It is estimated that 110,000 cases from solid tumors are diagnosed in the United States each year^[6]. The actual number may be higher because some cases go undiagnosed and are only found during autopsies^[4].

Signs and Symptoms

The symptoms result from cancer cells blocking the normal exits for cerebrospinal fluid, causing fluid buildup and increased pressure in the brain^[6]. This increased pressure can cause uncomfortable symptoms that may seem vague at first.

Cancer cells in the covering of the brain can cause a wide range of symptoms, including^[2]:

• Headaches, often worse in the morning^[6]
• Nausea and vomiting^[3]
• Changes to vision, such as double vision or loss of sight^[2]
• Confusion and changes in alertness, mood, or behavior^[3]
• Weakness^[2]
• Seizures (fits)^[2]
• Changes to how you walk^[3]
• Hearing changes or hearing loss^[2]
• Facial drooping^[2]
• Pain in the lower back, legs, or neck^[2]
• Numbness or weakness in one or both legs and buttocks^[2]
• Problems with passing urine or stool^[2]

The specific symptoms depend on where the cancer cells settle in the membranes around the brain and spinal cord. For example, if the cancer affects the front of the brain, it might cause sadness or memory problems. If it affects the back of the brain, it might cause balance or vision problems^[6].

How Doctors Make a Diagnosis

Diagnosing metastases to meninges can be challenging, and the disease is sometimes missed or diagnosed late^[6]. This is mainly because the symptoms can be similar to other conditions, making accurate diagnosis difficult. Since this is a disease that spreads from another cancer, it often occurs in patients who are already battling cancer, which can further complicate the diagnosis^[6].

Doctors may suspect metastases to meninges if symptoms develop in someone with other cancers such as breast or lung cancer^[6]. The diagnosis relies on two main approaches^[2]:

An MRI scan (magnetic resonance imaging) can often show the cancer in the meninges. This imaging test uses magnets and radio waves to create detailed pictures of the brain and spinal cord^[2].

A lumbar puncture, also called a spinal tap, is considered the best test for diagnosing metastases to meninges. During this procedure, a needle is inserted through the skin in the lower back into the space around the spinal cord to collect a sample of cerebrospinal fluid^[2][6]. Doctors then examine the fluid to look for cancer cells^[2].

Treatment Options

The goal of treatment is to improve survival and maintain quality of life by controlling the growth of the cancer and relieving symptoms^[8]. Treatment decisions are made on a case-by-case basis, considering factors such as the type of original cancer, the person’s overall health, and how far the disease has spread^[12].

Some people may not be able to have treatment for their cancer because they are too unwell. In these cases, they will receive medicine to control any pain or other side effects^[2].

Chemotherapy

Chemotherapy uses anti-cancer drugs to kill cancer cells throughout the body. For metastases to meninges, chemotherapy can be given in different ways^[10]:

• Injected into a vein (intravenous)
• Injected directly into the spinal fluid through a lumbar puncture
• Injected through a special device called an Ommaya reservoir, which allows chemotherapy to go straight into the fluid-filled spaces of the brain^[10]

The most commonly used chemotherapy drugs include methotrexate, cytarabine, and thiotepa. The specific drug depends on the type of original cancer^[10].

Recently, improvement in disease control has been observed in a study for patients with breast cancer when intrathecal liposomal cytarabine was added to regular treatment^[8].

Targeted Cancer Drugs

Targeted cancer drugs work by targeting specific differences in cancer cells that help them survive and grow. Some targeted drugs being used to treat metastases to meninges include^[10]:

• Trastuzumab emtansine for HER2-positive breast cancer
• Erlotinib or gefitinib for a type of lung cancer called adenocarcinoma
• Ceritinib for non-small cell lung cancer

The safety and effectiveness of giving some of these drugs, such as trastuzumab, directly into the spinal fluid are still being studied^[8].

Radiotherapy

Radiotherapy uses radiation, usually x-rays, to treat cancer cells. Radiotherapy to the brain can help reduce symptoms^[10]. This treatment is commonly used for areas with visible disease, such as nodules on the meninges, or for parts of the central nervous system causing symptoms, like the base of the skull affecting cranial nerves^[8].

Some people receive radiotherapy to the whole brain, while others might have targeted radiotherapy to one specific area^[10]. Radiotherapy typically consists of multiple doses given over several days or weeks^[12].

What to Expect

Metastases to meninges is a serious and life-threatening condition^[6]. Without treatment, most people survive only 4 to 6 weeks after diagnosis^[4]. With treatment, survival is typically limited to 3 to 9 months, depending on the type of primary cancer and the treatment given^[6].

Treatment aims to control the growth of the cancer and relieve symptoms. For certain cancers, treatment might be able to control the cancer cells in the meninges for some months. With newer targeted cancer drugs, this might possibly extend to more than a year for specific cancer types^[2].

Individual outlook depends on many factors, including whether the cancer has spread to more than one part of the body, how quickly it is growing, and how it responds to treatment^[2]. It is difficult for doctors to predict someone’s outlook with certainty, and this uncertainty can be hard to deal with^[2].

Maintaining quality of life is a major consideration for patients with this disease. Healthcare providers work to balance treatment benefits with potential side effects to help patients feel as well as possible^[12].