Leptomeningeal Disease


Leptomeningeal disease (LM) is a form of cancer affecting the brain and spinal cord  with around 110,000 diagnoses in the U.S alone each year.[2] It is a late-stage complication of cancer, and so often has a poor disease outlook and is difficult to treat.[2] The name ‘leptomeningeal’ comes from the word Leptomeninges, which are the innermost tissue layers covering the brain and spinal cord.[10]

This article will answer the following questions:

  • What is Leptomeningeal disease?
  • What causes Leptomeningeal disease?
  • What are the symptoms of LM?
  • What are the different diagnosis methods of LM?
  • What treatment strategies are there?
  • Can LM be cured?

What is Leptomeningeal disease?

Leptomeningeal disease (LM), sometimes known as leptomeningeal metastases or leptomeningeal carcinomatosis, is an uncommon form of cancer. In this disease, the cancer cells spread to the leptomeninges tissue. 

This tissue is present on the outside of the brain and spinal cord. The cancer cells from a primary tumor can migrate into the cerebrospinal fluid that surrounds the brain and spinal cord. 

The function of the cerebrospinal fluid is to circulate nutrients and chemicals to the central nervous system (CNS). Due to this, the cancer can spread quickly throughout the CNS.  [3]

Between 5-10% of cancer patients develop Leptomeningeal disease and is most common for patients with lung cancer, breast cancer or melanoma.[3] Breast cancer is the most common cause of LM, followed by lung cancer, predominantly small cell lung cancer.[10]

Signs and Symptoms

As the disease causes cancer cells in the outer tissue of the brain, symptoms of LM revolve around ‘an altered mental state’, meaning pressure headaches and general confusion. While some patients are asymptomatic[8], other commonly experienced symptoms include:

  • Headache [6]
  • Back pain
  • Visual disturbances (such as double vision) [6]
  • Hearing loss
  • Radicular pain (pain from back to leg)
  • Onset of psychiatric disorders or seizures [2]

It is thought that the symptoms are related to the disruption of the blood-brain barrier, metabolic strain, and direct compressions of the affected tissue. [2]

Disease Progression

Before Leptomeningeal disease develops, a pre existing tumor must be present in the body. These are most commonly found in the breast, lung or skin. LM can then develop in two main ways:

  • From the production of a secondary cancer, called metastases. Cells break off from the primary cancer tumor and travel to a new site in the brain or spinal cord to form a secondary cancer. This can then reach the meninges and cause leptomeningeal disease
  • Cancer cells can travel through the bloodstream from a cancer somewhere in the body and reach the meninges and cause cancer.

Leptomeningeal disease is a progressive disease, which develops most commonly  1-2 years from the diagnosis of metastatic disease for solid tumors [8] however in 5-10% of patients with metastatic cancer, LM can present itself initially. 

As the disease progresses, the observed non-specific neurological symptoms will worsen. Growth of the cancerous cells can cause inflammation, and eventually impair flow of cerebrospinal fluid in over 50% of patients [2] and can cause further symptoms:

  • Nausea
  • Vomiting
  • Positional headaches


Diagnosis is very difficult in leptomeningeal disease, but it can show up on an MRI scan but this does not always work. Gadolinium enhanced MRI is the most sensitive MRI scan at detecting LMD currently. [8]

Other ways of diagnosing the disease is by a lumbar puncture, where fluid called cerebrospinal fluid is removed from the spine using a lumbar puncture needle to check for cancerous cells. A process called cytology, which is the study of cells, can identify the cancer and definitively confirm the disease. [2]

Small cell lung cancer patients also have a higher risk for developing brain metastases, and leptomeningeal diseases. So it is important to screen the patient, including a full neurological exam, MRI and a brain and lumbar puncture (called a spinal tap) .

This allows for earlier diagnosis by taking into account the increased risk factors of more effective treatment.

Being diagnosed with, or worrying about somebody else having LM can inevitably cause anxiety. If you feel you need somebody to talk to, reach out to your healthcare provider for advice and support. They can often provide you with information on cancer support groups in your local area. Remember that you don’t need to face this alone.


Currently, there is no cure for the disease and without treatment, patient life expectancy can be as little as 4-8 weeks after diagnosis. [8] The main goal for treatment is to prolong survival and to stabilize neurological symptoms where possible. As the blood brain barrier restricts entry of anticancer medications, treatment can be difficult.

The most effective and common treatment methods currently are Radiotherapy and Chemotherapy. The European Association of Neuro-Oncology and European Society of Medical Oncology recommends that patient treatment should be individualized based on variables such as the type of primary cancer and the health status of the patient. [8]

Treatment for LM  is often challenging because many chemotherapy treatments cannot reach sufficient concentrations in the cerebrospinal fluid to kill the cancer cells. As this is a rare disease it is difficult to gather patients for clinical trials; as a result, advances in treatment are slow. [10]

Often, a combination of therapies is most successful in improving the prognosis of the disease and increasing life expectancy.

There are treatments for some of the symptoms of LM; for example, anticonvulsants may be provided to treat the patients’ seizures. However, there are reports on serious side effects created by  metastatic cancer and anticonvulsants. [6] 


Radiotherapy, sometimes known as radiation oncology, uses X-rays to treat cancerous cells and is used in two-thirds of cancer treatments in higher income developed countries. [7] Specifically, for patients with LM, radiotherapy of the whole brain, or specific targeted areas of the brain is used in treatment. 

Whole-brain radiotherapy is a standard treatment for patients with brain metastases, with the ability to delay neurological disease progression and restore some lost functions. It can also stabilize symptoms or alleviate cerebrospinal fluid obstruction. [8]

However, radiotherapy can cause its own acute symptoms. These are:

  • Nausea and vomiting
  • Headache
  • Ear blockage
  • Hair loss

For longer-term patients who will receive the therapy for a long time, symptoms and side effects can be worse:

  • Progressive dementia
  • Ataxia (disorders affecting balance, speech and coordination)

For many patients, these symptoms can be dealt with if it means extending their life.


Chemotherapy is a type of anti cancer drug; it is a form of systemic treatment, meaning it works throughout the whole body. The most common chemotherapy drugs are:

  • Cytarabine
  • Methotrexate
  • Thiotepa

Because of the blood-brain barrier, chemotherapy cannot be delivered orally as it will not reach the brain to treat brain metastases in leptomeningeal disease. [6]

Chemotherapy can be delivered directly into the cerebrospinal fluid using a ventricular access device. This is called an Ommaya reservoir

Using this device enables repeated access to the spinal fluid without a ‘spinal tap to test for cancer cells and delivery chemotherapies]. Using a ventricular access device is often seen as the superior treatment by neuro oncologists due to its more accurate drug delivery, and less associated pain. 

Other ways of entry include intravenous injection or injection using a lumbar puncture ​​(however, neuro-oncologists no longer favor these methods).

Targeted Therapy

This is a cancer treatment using drugs to target specific genes and molecular targets involved with the growth, proliferation and survival of cancerous cells that cause leptomeningeal disease. They are cytostatic, which means they block tumor cell proliferation. 

Targeted therapies are special because they can personalise anticancer medication to use a person's genes and proteins.

This type of treatment is vastly different from chemotherapy, which works on all rapidly dividing cells, whether they are cancerous or normal, and destroys them. Targeted therapy acts only on specific molecular targets on cells present on the surface of cancer cells meaning they are a form of precision medicine

Just a few types of targeted therapies include:

  • Hormone therapies
  • Signal transduction inhibitors
  • Immunotherapies
  • Toxin delivery molecules 

However, there are some issues with targeted therapy, such as the cancer cells can become resistant to the targeted therapy through mutation.


Another form of targeted therapy is Immunotherapy, which involves using drugs to help the immune system fight off cancer cells.

Many immunotherapies involve monoclonal antibodies, which can recognise molecules on the surface of the cancer cells and destroy them without damaging other cells in the body. 

This destruction process occurs by the monoclonal antibody binding to the cancer cell and ‘marking’ it, for destruction, by the immune system. 

The most common immunotherapy treatment uses Immune Checkpoint Inhibitors to increase the ability of the immune response to fight off cancer cells. During therapeutic treatment, concentration of specific cancer killing immune cells are increased. [11]

Further research into newer treatments for LM involves using different combinations of drugs already used in treatment or replacing existing drugs with newer cancer drugs that are more targeted. 

Examples of novel agents that are in development include:

  • Nivolumab
  • Ipilimumab
  • Pembrolizumab [10]

Can Leptomeningeal disease be cured?

There are many different variables that control the prognosis (outlook) of leptomeningeal disease. Unfortunately, there is no cure for LM; instead, the disease can be controlled and managed through treatment. [2] 

Currently, there is no gold standard treatment available for entering the cerebrospinal fluid and treating the disease successfully. In the meantime, advances in treatments using chemotherapy and radiotherapy must be carried out, although the limitation of low patient numbers makes clinical trials difficult

Treatment may be able to control the growth of cancer cells in the meninges for anywhere between a few months to a year,  depending on factors such as the cancer spreading to other parts of the body. [1]


Leptomeningeal disease can be a very challenging disease in regards to symptoms, diagnosis and treatment. For best chances of successful treatment, an early diagnosis is useful and patients with pre-exposing risk factors should be screened for the disease for earlier treatment to increase life expectancy.

There are many treatment options that can be tailored to each patient to fit in with their condition and personal preferences. Despite the volume of treatment options, there is currently no cure and treatment can only control symptoms. 

Disease outlook from Leptomeningeal disease is still poor, but can be significantly increased when treatment is used early. 

If you are worried about yourself or a loved one suffering from leptomeningeal disease, or any cancer, please contact your GP or healthcare practitioner immediately. Alternatively, get in contact with a Cancer Research UK helpline or Macmillan support.

Frequently asked questions:

Can leptomeningeal disease be cured?

Unfortunately, leptomeningeal disease currently cannot be cured. However, there are treatments available to control your symptoms and increase your life expectancy

Is leptomeningeal disease fatal?

As leptomeningeal disease cannot be cured, the outlook is very poor, with patients surviving anywhere between 2 weeks to a year depending on the speed of diagnosis and treatment.

Is leptomeningeal disease a terminal illness?

Leptomeningeal disease is a terminal, late stage complication of cancer, and there is currently no cure for this cancer meaning it is a life-limiting disease.

How long can you live with leptomeningeal disease?

On average, after diagnosis, patients usually live for approximately 1-4 months during treatment. Without treatment, a patient will only live for 2-4 weeks. Life expectancy is highly dependent on factors such as the speed of diagnosis, the location and growth rate of the cancer and the type of treatment you receive. Patients have been able to live for up to 1 year.


  1. Cancer Research UK. What are leptomeningeal metastases? [online]; 2019 [accessed 14 Mar 2022]. Available from: https://www.cancerresearchuk.org/about-cancer/secondary-cancer/leptomeningeal-metastases/what-are 
  2. Nayar G, Ejikeme T, Chongsathidkiet P, Elsamadicy AA, Blackwell KL, Clarke JM, Lad SP, Fecci PE. Leptomeningeal disease: current diagnostic and therapeutic strategies. Oncotarget; 2017;(42): 73312-73328. 
  3. MD Anderson Cancer Center. New hope for leptomeningeal disease care [online]; 2017 [accessed 14 Mar 2022]. Available from: https://www.mdanderson.org/cancerwise/new-hope-for-leptomeningeal-disease-care.h00-159144456.html 
  4. Cancer Research UK. Treatment for leptomeningeal metastases [online]; 2019 [accessed 14 Mar 2022]. Available from: https://www.cancerresearchuk.org/about-cancer/secondary-cancer/leptomeningeal-metastases/treatment 
  5. Mount Sinai. Leptomeningeal Disease [online]; undated [accessed 15 Mar 2022]. Available from: https://www.mountsinai.org/care/neurosurgery/services/brain-tumors/leptomeningeal-disease 
  6. Chang EL, Lo S. Diagnosis and Management of Central Nervous System from Metastases from Breast Cancer. The Oncologist; 2003;8(5): 398-410.
  7. Chen HHW, Kuo MT. Improving radiotherapy in cancer treatment: Promises and challenges. Oncotarget; 2017;8(37): 62742-62758.
  8. Nguygen TK, Nugygen EK, Soliman H. An overview of leptomeningeal disease. Annals of Palliative Medicine; 2021;10(1).
  9. National Cancer Institute. Targeted Cancer Therapies [online]; 2022 [accessed 15 Mar 2022]. Available from: https://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet
  10. Batool A, Kasi, A. Leptomeningeal Carcinomatosis. StatPearls [Internet]; 2021 Mar 25.
  11. The ASCO post. Two Studies Examine the Efficacy of Immunotherapy for Leptomeningeal Carcinomatosis [online]; 2021 [accessed 16 Mar 2022]. Available from: https://ascopost.com/news/october-2021/two-studies-examine-the-efficacy-of-immunotherapy-for-leptomeningeal-carcinomatosis/
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Laura Preece

BSc Pharmaceutical Sciences and MRes Pharmacy and Pharmaceutical Sciences
I am a researcher and medical writer with a passion for pharmaceutics, disease and biological sciences. I am currently researching cellular and molecular biology, investigating the use of vitamin C as an adjunctive therapy for diabetes mellitus.

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