Methotrexate is a medication known as an antimetabolite that works by interfering with the processes of DNA synthesis and cellular replication, which is why it is used in the treatment of certain cancers. While methotrexate can be given orally or through a vein, this article focuses on a specific method called intrathecal administration.
Intrathecal administration means the drug is delivered directly into the cerebrospinal fluid (CSF). This fluid surrounds the brain and spinal cord, acting as a protective cushion. The procedure involves an injection into the spinal canal, allowing the medication to reach the central nervous system directly.
Why Intrathecal Methotrexate is Used
The primary reason for using intrathecal methotrexate is to treat or prevent cancer from spreading to the central nervous system (CNS). Certain cancers, particularly leukemia like acute lymphoblastic leukemia (ALL) and some lymphomas, have a tendency to infiltrate the CSF. Standard chemotherapy given through a vein or by mouth often struggles to reach these areas in effective concentrations.
This difficulty is due to the blood-brain barrier, a network of tightly packed cells that lines the blood vessels in the brain. This barrier selectively controls which substances can pass from the bloodstream into brain tissue. While protective, this barrier also blocks many chemotherapy drugs from reaching cancer cells that may be hiding within the CNS.
By administering methotrexate directly into the CSF, clinicians bypass the blood-brain barrier. This ensures a high concentration of the drug reaches the CNS to be effective against cancer cells. This approach is used to treat active cancer found in the CSF and as a preventative measure in patients with cancers that have a high risk of spreading to the CNS.
How Intrathecal Methotrexate is Given
Intrathecal methotrexate is administered through a lumbar puncture, also known as a spinal tap. The procedure is performed by a trained medical professional, such as an oncologist, neurologist, or anesthesiologist, in a hospital or specialized clinic.
To begin, the patient is positioned to help spread the bones of the lower spine apart, making access to the spinal canal easier. Common positions include lying on one’s side with knees drawn toward the chest or sitting and leaning forward over a table.
The clinician cleans the skin on the lower back with an antiseptic and injects a local anesthetic to numb the area. Once numb, a thin, hollow needle is carefully inserted between two vertebrae into the spinal canal, which contains the cerebrospinal fluid. The clinician may first withdraw a small sample of CSF for testing before slowly injecting the preservative-free methotrexate. The entire process usually takes about 30 minutes.
Possible Side Effects
Common and milder reactions often relate to the lumbar puncture itself and can include headache, back pain at the injection site, nausea, and vomiting. Some individuals might also develop a fever or feel tired for a few hours after the procedure. These symptoms are generally temporary and can often be managed with rest and medication.
Less frequently, more significant neurological side effects can occur. A known complication is chemical arachnoiditis, which is an inflammation of the membranes surrounding the brain and spinal cord. This condition can cause a severe headache, stiff neck, and vomiting. In rare instances, intrathecal methotrexate can lead to more serious neurotoxicity, with symptoms like confusion, seizures, or weakness in the limbs.
Medical teams monitor patients for these reactions. It is important to report any unusual or severe symptoms to a healthcare provider, as prompt reporting allows for timely management of complications.
What Patients Should Know
Patients should have a thorough discussion with their medical team before the procedure. They should inform their doctor about all current medications, including over-the-counter drugs and supplements, as some can interact with methotrexate. The healthcare provider will also give specific instructions on eating or drinking before the procedure.
During the lumbar puncture, patients can expect to feel some pressure as the needle is inserted, but the local anesthetic prevents pain. After the procedure, patients are instructed to lie flat for a period, often at least an hour, to help prevent developing a headache. Drinking extra fluids is also frequently recommended to help the body replenish the cerebrospinal fluid that was removed.
Patients should contact their doctor if they experience symptoms that include:
- A severe headache that does not improve with simple pain relievers
- Persistent nausea or vomiting
- A fever
- Any new neurological symptoms like confusion, extreme drowsiness, or weakness