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, leptomeningeal disease is increasing in incidence as people are living longer with advanced cancer.

Leptomeningeal disease may also be referred to as carcinomatous meningitis or neoplastic meningitis. Most often with this complication, people have multiple neurological symptoms including visual changes, speech problems, weakness or numbness of one side of the body, loss of balance, confusion, or seizures. Diagnosis is usually made with a combination of an MRI and spinal tap. Treatments may include radiation and/or chemotherapy directly into the spinal fluid (intrathecal chemotherapy), along with systemic treatments for the particular cancer being treated.

leptomeningeal disease diagnosis
Verywell / Emily Roberts 


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. Because cerebrospinal fluid is rich in nutrients and oxygen, cancer cells don't need to form large tumors to be viable, as they do in other regions of the body.

Cancers That May Lead to 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 sometimes develop include digestive tract, renal cell (kidney), and thyroid, 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 (and particularly among people who have lung adenocarcinoma with an EGFR mutation).


The symptoms of leptomeningeal carcinomatosis can vary significantly, and often include numerous neurological problems. 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 affect the spinal nerve roots—nerve fibers that connect to different parts of the body via the spinal cord—and can occur anywhere from the neck (cervical) to the lower spine (lumbar).

Injury (such as compression) of the spinal nerve root will often create symptoms in another region. For example, nerve root compression in the neck may cause pain, numbness, tingling, and/or weakness in the arms, in addition to neck pain. With spinal nerve root compression in the lumbar area (also known as sciatica), a person may not only feel back pain, but also numbness and weakness in one or both legs, often with an electrical sensation traveling down the leg.

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: Pupil doesn't constrict in bright light, difficulty moving upper eyelid
  • Trochlear nerve: Double vision
  • Trigeminal nerve: Facial pain
  • Abducens: Double vision (sixth nerve palsy)
  • Facial nerve: Facial muscle weakness
  • Vestibulocochlear: Hearing loss and vertigo
  • Glossopharyngeal: Hearing loss and vertigo
  • Vagus: Difficulty swallowing and/or speaking
  • Spinal accessory: Shoulder weakness
  • Hypoglossal: Difficulty speaking because of trouble moving the tongue


Encephalopathy is a general term meaning inflammation of the brain, and it has 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 can lead to elevated intracranial pressure. Symptoms can include headaches, vomiting (often without nausea), behavioral 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 obstruction or compression of the blood vessels of the brain, leading to a stroke. Symptoms will depend on the particular part of the brain affected and may include visual changes, speech changes, loss of balance or coordination, or one-sided weakness.

Brain Tumor Symptoms

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

Brain metastases in some locations in the brain will have no symptoms. When symptoms occur, they will depend on the location of metastases and may include headaches, new-onset seizures, visual changes, speech difficulty, or one-sided numbness or weakness, among others.

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


Diagnosing leptomeningeal disease can be challenging, not only because of the overlap of symptoms with those of brain metastases, but because of the testing process. A high index of suspicion is necessary to ensure that the appropriate tests are run for a timely diagnosis.


Magnetic resonance imaging (MRI) of the brain and spine, with and without contrast, is the gold standard in diagnosing leptomeningeal disease. Sometimes the disease occurs only in the spine and not the brain, and therefore a scan of the full spine and brain is recommended. On an MRI, radiologists can see inflamed meninges and 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 ensure that a spinal tap will be safe. Positive findings on a spinal tap include:

  • Cancer cells, which are not always detected, 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 very soon improve the accuracy of diagnosis.

CSF Flow Study

If intraventricular chemotherapy (see below) is considered, a cerebrospinal fluid (CSF) flow study may be performed. This study can determine whether blockages have occurred 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

A number of conditions can mimic leptomeningeal metastases and cause similar signs and symptoms. Some of these include:

  • Brain metastases: The symptoms of leptomeningeal disease and brain metastases can be very similar, and the two are often diagnosed together.
  • Bacterial meningitis: This includes meningococcal or tuberculous meningitis.
  • Viral meningitis: These conditions include cytomegalovirus, herpes simplex, Epstein-Barr, and varicella zoster meningitis.
  • Fungal meningitis: Included are histoplasmosis, cocciodiomycosis, and cryptococcosis.
  • Toxic/metabolic encephalopathy: Drug-induced encephalopathy (often due to anti-cancer drugs, antibiotics, or pain medications) can create similar symptoms to leptomeningeal metastases.
  • Epidural or extramedullary spinal metastases
  • Paraneoplastic syndromes
  • Sarcoidosis


The treatment of leptomeningeal metastases depends on many factors, including severity of symptoms, type of primary cancer, the person's general health, 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 advanced stages of cancer and after a person has been ill for a significant period. For this reason, people with the disease may be less able to tolerate treatments such as chemotherapy.

As with brain metastases, the blood-brain barrier poses problems in treatment. This tight network of capillaries is designed to prevent toxins from getting into the brain, but for the same reason it limits chemotherapy drug access in the brain and spinal cord. Some targeted therapies and immunotherapy drugs, however, can penetrate this barrier.

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

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

Radiation Therapy

Radiation therapy (or proton beam therapy) is the most rapidly effective of treatments for leptomeningeal disease. Most often, fractionated external beam radiation is directed toward areas where clusters of cancer cells are causing symptoms.

Intraventricular Chemotherapy

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

Intrathecal chemotherapy was once administered via a spinal tap needle. Today, surgeons usually place an Ommaya reservoir (an intraventricular catheter system) under the scalp, with the catheter traveling into the cerebrospinal fluid. This reservoir is left in place for the duration of chemotherapy treatment.

Systemic Treatments

It's important to control cancer in other regions of the body as well, so specialists often use additional treatments along with intrathecal chemotherapy and/or radiation.

Some systemic treatments penetrate the blood-brain barrier and can be helpful with leptomeningeal metastases. With lung cancer, some EGFR inhibitors and ALK inhibitors will breach the blood-brain barrier and may aid in treating these metastases.

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

With melanomas, BRAF inhibitors such as vemurafenib (Zelboraf), dabrafenib (Tafinlar), and encorafenib (Braftovi) 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 immunotherapeutic checkpoint inhibitors nivolumab (Opdivo) and ipilimumab (Yervoy) showed increased survival rates when used together to treat people with melanoma and leptomeningeal metastases.

Intrathecal Targeted Treatments

With HER2-positive breast cancer, the HER2-targeted therapy trastuzumab (Herceptin) can also be administered intrathecally (a route of administration for drugs via an injection into the spinal canal, or into the subarachnoid space so that it reaches the cerebrospinal fluid.)

Palliative Care

In some cases, such as when a tumor is very advanced, these types of treatments are not considered useful. In these instances, palliative care can still help tremendously with managing symptoms.

Many cancer centers now have palliative care teams that work with people to make sure they have the best possible quality of life while living with cancer. People don't have to have terminal cancer to receive a palliative care consult: This type of care can 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 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 grow now that newer treatments that can penetrate the blood-brain barrier are available.

A Word From Verywell

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

11 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
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Additional Reading

By Lynne Eldridge, MD
 Lynne Eldrige, MD, is a lung cancer physician, patient advocate, and award-winning author of "Avoiding Cancer One Day at a Time."