Leptomeningeal cancer (also called leptomeningeal carcinomatosis, leptomeningeal disease (LMD), leptomeningeal metastasis, neoplastic meningitis, meningeal metastasis and meningeal carcinomatosis) is a rare complication of cancer in which the disease spreads from the original tumor site to the meninges surrounding the brain and spinal cord. This leads to an inflammatory response, hence the alternative names neoplastic meningitis (NM), malignant meningitis, or carcinomatous meningitis.

It occurs with cancers that are most likely to spread to the central nervous system. The most common cancers to include the leptomeninges are breast cancer, lung cancer, and melanomas because they can metastasize to the subarachnoid space in the brain which offers a hospitable environment for the growth of metastatic tumor cells. Individuals whose cancer has spread to an area of the brain known as the posterior fossa have a greater risk of developing a leptomeningeal cancer. The condition can also arise from primary brain tumor like medulloblastoma.

Causes

Leptomeningeal carcinomatosis occurs when the cancer cells invade the cerebrospinal fluid and spread throughout the central nervous system. The metastatic tumor cells grow either attached to the pia mater covering the brain and spinal cord or floating unattached to the subarachnoid space. Tumors of diverse origins and hematologic cancers may spread to this space. Some patients can develop a leptomeningeal tumor while receiving chemotherapy for their primary tumor.

Signs and symptoms

Most common symptoms of leptomeningeal cancer is pain and seizures. The other symptoms may include headaches (usually associated with nausea, vomiting, light-headedness), gait difficulties from weakness or ataxia, memory problems, incontinence, sensory abnormalities. In some cases, symptoms may include double vision, numb chin, back pain, leg weakness, sphincter-related problems, hydrocephalus, loss of urine control, and difficulty walking.

Diagnosis

Screening involves an MRI scan to identify and diagnose tumors in the subarachnoid region of the brain. MRI can make a diagnosis even without an analysis of the cerebrospinal fluid but it can sometimes be difficult to detect because MRI scans cannot always pick up the problem.

Diagnosis is most commonly made by lumbar puncture to detect malignant cells in the CSF, although the tests may be negative in roughly 10% of patients. Diagnosis often requires a high index of suspicion and is confirmed by neuroimaging and cerebrospinal fluid analysis.

CSF examination is the most useful diagnostic tool for NM. Patients with suspected NM should undergo one or two lumbar punctures, cranial magnetic resonance imaging (MRI), spinal MRI, and a radioisotope CSF flow study to rule out sites of CSF block. If the cytology remains negative and radiological studies are not definitive, consideration may be given to ventricular or lateral cervical spine CSF analysis based on the suspected site of predominant disease. Consideration of signs, symptoms, and neuroimaging can help with the placement to where CSF is drawn. Median time of diagnosis from initial primary cancer diagnosis is between 76 days and 17 months.

Treatment

There is currently no cure for leptomeningeal disease as the tumor is hard to eradicate. Current treatments for leptomeningeal tumors are palliative. The goals for treatment include prolonging survival and stabilizing neurological symptoms.

• Radiotherapy

Radiotherapy is used mostly for focal type of NM due to the nature of damage and success rate associated with the treatment. Radiotherapy targets the tumor and destroys the collective tissues of cancerous cells.

• Chemotherapy

Chemotherapy is injected directly into the cerebrospinal fluid, either by lumbar puncture (“spinal tap”) or through a surgically implanted device called an Ommaya reservoir. Intrathecal Therapy is preferred since intravenous chemotherapy does not penetrate the BBB. The most common chemicals used are liposomal cytarabine (DepoCyte) and intrathecal methotrexate (MTX).

The downside of a spinal tap diagnosis is that while it is highly accurate and reliable, it can also report false-negative results. Chemotherapy is delivered intrathecally as it is hard for drugs to make it into the central nervous system. Intrathecal chemotherapy can only penetrate a few millimeters. If the tumor is any thicker, radiation is given to shrink it down.

The treatment is done to reduce pressure on the brain caused by any cerebrospinal fluid buildup and to reduce the number of cancer cells causing the pressure.

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