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Diagnosis of LM

There are 3 key elements to diagnose LM and to assess disease progression: A neurologic exam, imaging with an MRI, and testing the cerebrospinal fluid through a lumbar puncture

Neurologic Exam

People with LM have several different symptoms and signs. Testing for these signs and symptoms help with diagnosis.

First, your doctor – a neurologist or neuro-oncologist – will look at your level of consciousness, seeing if you appear drowsy and only respond if spoken to, or if you are so sleepy that you need to be shaken awake or cannot be woken. Only people who are awake and alert can receive a neurologic exam that will be helpful for diagnosis.

As cancer cells spread and affect various nerves in your brain and spine, various symptoms can result from LM. Your doctor will ask you about various symptoms, such as nausea, headache, neck or back pain and mental status. They will test you for signs of nerve damage by looking at the following:

  • Cognition: Your neurologist will want to see if you understand simple tasks, can have conversations, and are clear in mind and not confused.
  • Vision: Leptomeningeal spread can affect your vision by damaging cranial nerves or increased intracranial pressure. You may experience blurred vision, double vision or decreasing vision. They will shine a small light in your eyes to see how your pupils respond to light.
  • Eye movement: Your neurologist will ask you to follow their penlight or a finger to check if your eyes can follow movement left and right or up and down. Tumor cells can cause difficulty with eye movement if they affect certain cranial nerves.
  • Facial strength: As LM spreads, it can compress nerves and cause facial weakness or paralysis. You may have numbness in your face, a drooping in your face or smile, slurred speech or an inability to lift your eyebrows. Your doctor may ask you to smile, raise your eyebrows or do other facial movements.
  • Limb strength and sensation: Your doctor will test the strength of your arms and legs, your hand strength and your reflexes. They will ask you to use your strength to push against their arm or body or squeeze their finger or hand. They also will check to see if you can feel sensation in various parts of your body.
  • Fine motor skills: Your doctor may have you touch each of your fingers to your thumb in a fast motion to demonstrate your ability to move your fingers in a coordinated way.
  • Walking and balance: Balance and gait will often change as disease spreads. Your doctor may ask you to walk across the room or down the hall and stand on one foot with or without your eyes closed.

Doctors will also ask about your use of any medications to ease these symptoms, such as steroids, anti-nausea medications and pain medications. This will influence the neurological exam results.

Up to 5% of patients with leptomeningeal cancer have a normal neurological exam.

 

Magnetic Resonance Imaging (MRI)

An MRI scan takes images of internal organs and body tissues from many angles. An MRI does not use radiation.

  • Note: Brain and spine MRIs are preferred over CT scans, as they have better resolution and you can see enhancement easier

To look for leptomeningeal cancer, an MRI scan of the brain and spine will be done with and without contrast. An MRI with contrast uses a special dye called gadolinium that makes the cancer more visible on images. Contrast is needed to detect:

  • Leptomeningeal enhancement: when tissues or abnormalities light up on a scan
  • Hydrocephalus: build-up of fluid in the ventricles of the brain
  • Nodules in the lining of the brain and spine

Leptomeningeal cancer can take on many shapes depending on where it settles over the cranial and spinal nerves, the folds of the brain and the spinal cord. It may appear as a thin line or “glaze,” like a coating of sugar in the folds of the brain, or in the spaces of the brain as small nodules or spots. Sometimes leptomeningeal cancer cannot be seen on an MRI.

If possible:

  • Ask your facility if they use a5 or 3 Tesla MRI scanner. These are preferred for seeing leptomeningeal enhancement.
  • Get the MRI done at the same place each time with the same MRI scanner at diagnosis and for monitoring your disease. There are differences between MRIs in different facilities.
  • Go to a center with LM experts where they see a lot of patients with LM. This will ensure that the neuroradiologist (the person who is reading the scan) knows what to look for and how to read the MRI scan.

Even if you follow all these steps, it still can be hard to detect small deposits of cancer cells. There is also variability between scans due to several issues, including small differences in your positioning on the MRI scanning bed. And although leptomeningeal enhancement is commonly due to metastatic disease, there are situations where the enhancement is not from LM but other diseases that can look similar on a scan. Doing a lumbar puncture can help with providing a more definitive diagnosis

Getting an MRI:

  • You will change into a hospital gown or pants. You’ll need to remove any metal items, hearing aids or jewelry.
  • If you are getting contrast, you will be given an intravenous (IV) injection in your arm.
  • The MRI machine is open at both ends and well lit. There is a way to communicate throughout the exam with a technologist if you have questions.
  • You will need to lie still during an MRI. You may be asked to hold your breath at certain times.
  • The machine can be loud as it is scanning your body. You can use earplugs or headphones provided by the technologist to help decrease the noise
  • Depending on what type of scan you are having, the MRI process can take up to several hours.

 

Lumbar puncture for Cerebrospinal Testing

If a doctor suspects leptomeningeal cancer, either because of symptoms or enhancement on an MRI, they will want to perform a lumbar puncture to test your cerebrospinal fluid (CSF). CSF is a clear liquid that cushions and protects your brain and spinal cord. It is made up of 99% water and contains other substances such as glucose, proteins, electrolytes, vitamins, and white blood cells. It can also have pieces of DNA circulating through the CSF.

During a lumbar puncture, also known as an LP or a spinal tap, a small amount of cerebrospinal fluid (CSF) is removed from below your spinal cord. Your body will make more CSF to replace the CSF that was removed. Some patients find that symptoms, such as headaches, vomiting, dizziness, and visual changes, improve after the lumbar puncture. It is important that you let your doctor know if you feel better or worse after the procedure.

Getting a lumbar puncture:

A lumbar puncture can be done at an outpatient center, a medical office or the hospital.

  • You will lay on your side or sit and lean forward. In either position, you will be instructed to stay as still as possible.
  • You will receive a local injection of a numbing medication (anesthetic) in your lower back. This anesthetic is the same that your dentist uses when you get certain dental procedures.
  • A needle is inserted into the back between the bones of the spine, below the level of the spinal cord. This procedure is like an epidural women get when they are having a baby. The needle just goes in a little bit further.
  • A sample of cerebrospinal fluid is removed from this space
  • The procedure takes about 15 to 30 minutes.
  • The sample is then sent to a pathology lab to look for cancer cells under a microscope. This method of examining the CSF is called cytology.
  • It can take a few hours or several days to get results.

After the lumbar puncture, you will be given instructions to drink plenty of water and get a lot of rest. You also should not drive or do strenuous activities or exercises for 24 to 48 hours.

Some people may get a spinal headache after the lumbar puncture. A spinal headache is pain in your head when you sit or stand. Ask your doctor about taking over-the-counter pain medicine. Staying hydrated and drinking caffeinated beverages can help.

CSF Cytology

Cytology is the analysis of cells under a microscope to look for cancer cells in the cerebrospinal fluid. Although it is the most used test to diagnose leptomeningeal spread, cytology is not always reliable.

What the results mean:

  • If the results come back positive for malignant cancer cells, this confirms that you have leptomeningeal metastases.
  • If the results come back negative for malignant cancer cells, this can mean one of two things:
    • You do not have leptomeningeal metastases
    • You have a false negative result. This means that you have leptomeningeal metastases, but your test was negative.

Why would I have a false negative test?

When it comes to CSF cytology, false negative results are very common. In fact, this happens in up to 50% of cases or 1 in 2 cases.

You are more likely to have a false negative if your disease is limited to a specific, localized area rather than being spread throughout the leptomeninges. You can think of CSF as a river. If you sample a river in one spot, you may pull out a few small fish. But if you sample in another spot, you may catch none. In the CSF, if you sample in one spot, you may pick up cancer cells. And if you sample in another spot, there may be no cancer cells. The more fish throughout the river, the more likely you’ll catch fish. The more widespread the cancer cells are, the more likely your lumbar puncture will test positive.

Other reasons for false negative results include taking too little CSF during the procedure or a delay in processing the sample.

If your test comes back negative but there are reasons to believe you have leptomeningeal metastases, your doctor will want to do a second and possibly even a third lumbar puncture. The more tests you do, the better chance you will find cancer cells if they exist.

Additional Results in CSF

Along with looking for a cancer cells in the CSF, the lab will also analyze the fluid for other components:

  • White blood cells: increased in up to 75% of patients with LM
  • Glucose: decreased in up to 40% of patients with LM
  • Protein: increased in up to 90% of patients with LM

The opening pressure will also be measured, as this is often elevated in patients with LM. This means that there is an imbalance between your brain tissue, your CSF and your blood. If you have increased brain volume, increased CSF volume or increased blood volume, the overall pressure in the top part of your skull will be increased. This can be caused by leptomeningeal cancer.

CSF Liquid Biopsy

A liquid biopsy is another way of analyzing the cerebrospinal fluid. Liquid biopsies test for the presence of material from tumor cells. The following may be detected by liquid biopsy:

  • Circulating tumor cells (CTCs): CTCs are cancer cells that have shed from a tumor and can be found circulating in blood or cerebrospinal fluid. The presence of CTCs in blood or CSF is a marker that cancer has metastasized (spread).

 

  • Cell-free DNA (cfDNA): When cells break down and die as part of the body’s normal maintenance, various parts of the cell, including DNA, are released into your blood and CSF. These pieces of DNA moving around in the blood or CSF are known as cell-free DNA or cfDNA. cfDNA can come from normal cells or tumor cells. The analysis of cfDNA could help with early diagnosis of leptomeningeal metastases and monitoring a person’s response to treatment. It could also provide genetic information of an individual.

  • Circulating tumor DNA (ctDNA): ctDNA is a tiny part of the cfDNA and can only come from tumor cells. These small DNA fragments are shed by the tumor into the bloodstream. ctDNA can provide information about the extent of metastases and any genetic mutations, which can help with making treatment decisions.

  • Circulating tumor RNA (ctRNA): ctRNA is another part of the cell released into blood and CSF that provides information about genetic mutations. Adding ctRNA to ctDNA liquid biopsy gives your care team more information that could be used for diagnosis and management decisions.


Current tests that are being used to detect CTCs, cfDNA, ctDNA and/or ctRNA include:

  • CNSide test
  • Belay Summit test
  • Menarini CellSearch© CTC Test

 

These tests may or may not be covered by your insurance plans. Each test also may have out-of-pocket costs depending on your plan benefits. However, it is best to check with your doctor and your health insurance plan to see what your costs will be. The companies may have patient access programs to help patients cover the costs of the test.