Leptomeningeal Disease

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Leptomeningeal metastases are a relatively uncommon but serious complication of cancers such as breast cancer, lung cancer, and melanoma. Most often seen in advanced cancers, the incidence of leptomeningeal disease is increasing as people are living longer with advanced cancer.

Most often, people have multiple neurological symptoms such as visual changes, speech problems, weakness or numbness of one side of the body, loss of balance, confusion, seizures, and more. Diagnosis is usually made with a combination of an MRI and spinal tap. Treatments may include radiation and/or chemotherapy given directly into the spinal fluid (intrathecal chemotherapy), along with systemic treatments for the particular cancer being treated.

leptomeningeal disease diagnosis
Verywell / Emily Roberts 

Leptomeningeal disease may also be referred to as carcinomatous meningitis or neoplastic meningitis.


Unlike the spread of cancer to the brain itself (brain metastases), leptomeningeal metastases involve the spread of cancer cells to the cerebrospinal fluid that bathes the brain and spinal cord. It arises due to the seeding of cancer cells into the leptomeninges, the two innermost layers of the meninges that cover and protect the brain. Cancer cells may float freely between these membranes (the subarachnoid space) in the cerebrospinal fluid (and hence, travel throughout the brain and spinal cord), or be attached to the pia mater. Since the cerebrospinal fluid is rich in nutrients and oxygen, cancer cells don't need to form large tumors, unlike in other regions of the body.

Cancers That May Have Leptomeningeal Metastases

The most common cancers to spread to the leptomeninges are breast cancer, lung cancer (both non-small cell and small cell), and melanoma. Other cancers where these metastases are sometimes found include digestive tract cancers, renal cell cancer (kidney cancer), thyroid cancer, and some leukemias and lymphomas.


The incidence of leptomeningeal metastases is increasing, especially among people who have advanced (stage 4) cancers that can be controlled for a significant period of time with targeted therapies (especially people who have lung adenocarcinoma with an EGFR mutation).


The symptoms of leptomeningeal carcinomatosis can vary significantly, and often include several different neurological problems at the same time. Doctors use the term "multifocal deficits" to describe the variety of symptoms that may occur. For example, a person may have symptoms (described below) of encephalopathy as well as a radiculopathy.

Signs and symptoms of these metastases may include:


Radiculopathies are conditions that affect the spinal nerve roots, nerve fibers that exit the spinal cord on their way to different parts of the body and can affect any region from the neck down to the lower spine.

Injury (such as compression) of the spinal nerve root often causes symptoms that are felt in another region. For example, nerve root compression in the neck (cervical radiculopathy) may cause pain, numbness, tingling, and/or weakness in the arms, as well as neck pain. With spinal nerve root compression in the lower back (sciatica), pain, numbness, and weakness may be felt in one or both legs (often with an electrical sensation going down the leg) in addition to back pain.

Cranial Nerve Palsies

Involvement of the cranial nerves can cause symptoms that vary depending on the particular cranial nerve or nerves affected. Perhaps the best known cranial nerve palsy is Bell's palsy, a condition that causes drooping on one side of the face.

Symptoms that may occur based on the nerve affected include:

  • Olfactory nerve: Changes in smell and taste
  • Optic nerve: Changes in vision or blindness
  • Oculomotor nerve: A pupil that doesn't constrict when a bright light is shown
  • Trochlear nerve: Double vision
  • Trigeminal nerve: Facial pain
  • Abducens: Double vision (sixth nerve palsy)
  • Facial nerve: Facial muscle weakness
  • Glossopharyngeal: Hearing loss and vertigo
  • Vagus: Difficulty swallowing and/or speaking
  • Spinal accessory: Shoulder weakness
  • Hypoglossal: Difficulty speaking (due to problems moving the tongue)


Encephalopathy is a general term meaning inflammation of the brain and can have many causes. The cardinal symptom is an altered mental state. This may include confusion, personality changes, decreased memory, poor concentration, lethargy, and when severe, loss of consciousness.

Symptoms of Increased Intracranial Pressure

With leptomeningeal metastases, blockages in the flow of cerebrospinal fluid in the brain due to clumps of cells can lead to elevated intracranial pressure. Symptoms can include headaches, vomiting (often without nausea), behavior changes, lethargy, and loss of consciousness. Other neurological symptoms may occur as well depending on the location of the blockage.

Stroke Symptoms

Cancer cells in the cerebrospinal fluid may also cause an obstruction in the blood vessels of the brain leading to a stroke (often by compressing the blood vessels). Symptoms will depend on the particular part of the brain that is affected and may include visual changes, changes in speech, loss of balance or coordination, or weakness on one side of the body.

Brain Tumor Symptoms

Since roughly 50 to 80 percent of people (depending on the study) of people who have carcinomatous meningitis also have brain metastases (metastases within the brain in contrast to metastases within the spinal fluid), it's not uncommon for people to have neurological symptoms related to brain tumors as well.

In some locations in the brain, brain metastases will have no symptoms. When symptoms occur, they will depend on the location of the metastases and may include headaches, new onset seizures, visual changes, problems with speech, numbness or weakness of one side of the body, and more.

Brain metastases due to breast cancer are more common in younger women and in those who have HER2 positive tumors. Brain metastases due to lung cancer are also common, occurring in roughly 40 percent of people with stage 4 disease.


Diagnosing leptomeningeal disease can be challenging, both due to the overlap of the symptoms with those of brain metastases and because of the testing process. A high index of suspicion is needed so that the appropriate testing is done to make a timely diagnosis of this complication.


Magnetic resonance imaging (MRI) of the brain and spine, both with and without contrast, is the gold standard in diagnosing leptomeningeal disease. Sometimes the disease is only seen in the spine and not the brain, and therefore a scan of the full spine along with the brain is recommended. On an MRI, radiologists can see the inflamed meninges, as well as any co-existing brain metastases.

Lumbar Puncture (Spinal Tap)

If leptomeningeal metastases are suspected, a lumbar puncture (spinal tap) is often recommended as the next step. Before this test, doctors carefully review the MRI to make sure that a spinal tap will be safe. Positive findings on a spinal tap include:

  • Cancer cells, which are not always seen, and a tap may need to be repeated
  • An increased number of white blood cells (WBCs)
  • An increased protein content
  • A decreased glucose level

Advances in liquid biopsy testing of CSF looking for tumor cell-free DNA may improve the accuracy of diagnosis in the near future.

CSF Flow Study

If intraventricular chemotherapy (discussed below) is being considered, a cerebrospinal fluid (CSF) flow study may be done. This study can determine if there are any regions of blockage in the flow of CSF due to the tumor. If chemotherapy is given into an area that is blocked, it will not be effective and can be toxic.

Differential Diagnosis

There are a number of conditions that can mimic leptomeningeal metastases and cause similar signs and symptoms. Some of these include:

  • Brain metastases: As noted, there is a lot of overlap between the symptoms of leptomeningeal disease and brain metastases, and the two are often found together
  • Bacterial meningitis: Such as meningococcal or tuberculous meningitis
  • Viral meningitis: Such as cytomegalovirus, herpes simplex, Epstein-Barr, and varicella zoster meningitis
  • Fungal meningitis: Such as with histoplasmosis, cocciodiomycosis, and cryptococcosis
  • Toxic/metabolic encephalopathy: Such as drug-induced encephalopathy (often due to anti-cancer drugs, antibiotics, or pain medications)
  • Epidural or extramedullary spinal metastases
  • Paraneoplastic syndromes
  • Sarcoidosis


The treatment of leptomeningeal metastases depends on many factors, including the severity of symptoms, the type of cancer, the general health of a person, the presence of other metastases, and more.

It's important to note that, while treatment may inhibit the progression of neurological symptoms, those that are present at the time of diagnosis often persist.

Leptomeningeal metastases are challenging to treat for several reasons. One is that they often occur in the advanced stages of cancer and after a person has been ill for a significant period of time. For this reason, people may be less able to tolerate treatments such as chemotherapy.

As with brain metastases, the blood-brain barrier poses problems. This tight network of capillaries is designed to prevent toxins from getting into the brain but also limits the ability of chemotherapy drugs to enter the brain and spinal cord. Some targeted therapies and immunotherapy drugs, in contrast, are able to penetrate this barrier.

Finally, the symptoms related to leptomeningeal disease may progress rapidly, and many cancer treatments work relatively slowly compared to the progression.

In addition to the steroid medications often used to control swelling in the brain, treatment options may include:

Radiation Therapy

Radiation therapy (or proton beam therapy) may be used and works the most rapidly of treatments. Most often fractionated external beam radiation is directed towards areas where clusters of cancer cells are causing symptoms.

Intraventricular Chemotherapy

Since chemotherapy drugs given intravenously don't usually cross the blood-brain barrier, chemotherapy is frequently injected directly into the cerebrospinal fluid. This is referred to as intraventricular, CSF, or intrathecal chemotherapy.

In the past, intrathecal chemotherapy was usually given via a spinal tap needle. Now, surgeons usually place an Ommaya reservoir under the scalp, with a catheter that travels into the cerebrospinal fluid. This reservoir is then left in place for the duration of chemotherapy treatments.

Systemic Treatments

Other treatments often may be used along with intrathecal chemotherapy and/or radiation, since it's important to control the cancer in other regions of the body as well.

Some systemic treatments may also penetrate the blood-brain barrier and can be helpful with leptomeningeal metastases. With lung cancer, some EGFR inhibitors and ALK inhibitors are able to penetrate into the brain and may play a role in treating these metastases.

One EGFR inhibitor in particular, Tagrisso (osmertinib), has a high penetrance into the cerebrospinal fluid and is now recommended first line for people with EGFR mutations who have brain or leptomeningeal metastases.

With breast cancer that is HER2 positive, the HER2 targeted therapy Herceptin (trastuzumab) appears to similarly enter the CSF. With melanomas, BRAF inhibitors may be helpful. For a variety of cancers, immunotherapy drugs have also shown promise in treating tumors that have spread to the brain or leptomeninges. The checkpoint inhibitors Opdivo (nivolumab) or Yervoy (ipilimumab), a type of immunotherapy, increased survival from 3 weeks to 17 weeks in one study looking at people with melanoma and leptomeningeal metastases.

Palliative Care

In some cases, such as when a tumor is very advanced, specific treatments are not used. In this case, however, palliative care can still help tremendously with managing the symptoms of the cancer.

Many cancer centers now have palliative care teams that work with people to make sure they have the best quality of life possible while living with cancer. People don't have to have terminal cancer to receive a palliative care consult, and this care can still be beneficial even with early-stage and highly curable cancers.


In general, the prognosis of leptomeningeal metastases is poor, with life expectancy often measured in months or even weeks. That said, some people who are otherwise in reasonable health and can tolerate treatments do very well. This number of longer-term survivors living with leptomeningeal disease is expected to increase now that newer treatments that can enter the brain and spinal cord are available.

A Word From Verywell

A diagnosis of leptomeningeal metastases can be heart-wrenching, and more people are having to cope with this complication as survival rates from cancer improve. Fortunately, recent advances in cancer treatment promise more options when it comes to treatment. If you have been diagnosed with this complication, it's important to understand that much of what you may hear and read pertains to the prognosis of this complication before these advances, and it's important to talk to your oncologist about your individual situation today.

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Article Sources

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