Written by a parent, not a doctor. Nothing here is medical advice.

Childhood Cancer Lantern
Search Saved
Medicine

Methotrexate — intrathecal (spinal)

Updated September 2026.

Also known as: IT MTX, ITT, triple intrathecal

Methotrexate put into the spinal fluid during a lumbar puncture, because most chemo cannot reach there.

Intrathecal methotrexate is methotrexate put directly into the spinal fluid during a lumbar puncture, usually with the child asleep. The fluid around the brain and spinal cord sits behind a barrier that most drugs in the blood cannot cross well, so leukemia cells can hide there. Putting the drug straight into that fluid reaches them.

The drug itself works the same way everywhere: it is shaped like folate, the vitamin a cell needs to make fresh DNA building blocks, and it jams the enzyme that keeps folate usable, so dividing cells run out of parts and stop. “Triple intrathecal” means methotrexate given together with cytarabine and hydrocortisone in the same lumbar puncture.

I made an everyday analogy and a more scientific visualization of intrathecal methotrexate.

Everyday analogy

Methotrexate is like a pencil jammed in a shared sharpener.

Methotrexate is like a pencil jammed in a shared sharpener. Two seated, yellow-skinned workers copy house drawings at a shared workbench. They read their original sheets, make copies and sharpen their ordinary pencils in turn; three successful sharpening visits establish the routine. The worker on the right puts an ordinary pencil into a pot, lifts the teal pencil and tries the same sharpener. Its tip stays lodged in the feed opening. The worker returns the remaining teal pencil to the pot and takes back the ordinary pencil. Both workers keep copying until their points wear down. Each tries the blocked sharpener separately, then returns to the paper without a renewed point. The final faint marks leave both copies unfinished. A close-up makes the blunt point visible. Teal identifies methotrexate. Copying represents copying DNA; the sharpener represents an enzyme that keeps folate usable, and sharp pencils represent usable folate needed to help make DNA building blocks. The jam is a simplified picture of inhibition, not a permanently broken enzyme. The shared sharpener Read the original. Make a copy. Keep the pencil sharp. COPYING ROOM ORIGINAL COPY COPY ORIGINAL JAMMED Teal pencil = methotrexate Worn-down point No clear line to copy with UNFINISHED UNFINISHED The workers read, copy and sharpen their pencils again and again. A teal pencil jams the sharpener, like methotrexate blocking a needed step. Their points wear down. Sharpening fails, and the copies are left unfinished.

1 / 3 Copy and sharpen

The workers read, copy and sharpen their pencils again and again.

  • The teal pencil blocking the sharpener represents methotrexate. The jam shows a blocked process, not a permanently broken enzyme.

  • Copying a sheet represents copying DNA, the instructions a cell copies before it divides.

  • The sharpener represents an enzyme that keeps folate usable. Sharp pencils represent usable folate, which helps cells make DNA building blocks.

  • Without that help, DNA copying can slow or stop. This is a simplified picture of one action of methotrexate.

Press play below for a more accurate visualization.

Interactive visual

How intrathecal methotrexate reaches leukemia cells hiding around the brain and spine

Poster for How intrathecal methotrexate reaches leukemia cells hiding around the brain and spine
Read transcript

## 1. A protected fluid space (0–10 s) A clear fluid bathes the brain and spinal cord. Barriers keep most medicines carried in the blood out of it. Leukemia cells can hide in this fluid space, so methotrexate is put directly into it, even when tests find no cells there. ## 2. Straight into the fluid (10–20 s) A needle enters fluid between lower-back bones, below the cord’s end, so it avoids the spinal cord. Nerve roots float in this space. Methotrexate, a yellow liquid, is injected. It spreads up through the fluid around the cord and over the surface of the brain. ## 3. Where cells can hide (20–26 s) At the brain’s surface, methotrexate bathes the thin membranes where leukemia cells hide. It enters the cell through a folate doorway. ## 4. Blocking the folate enzyme (26–39 s) Inside, an enzyme turns folate, a vitamin, into an active form the cell needs to make DNA building blocks. Methotrexate looks like folate and fits the same pocket, but it stays stuck. The enzyme is jammed, and building blocks stop. ## 5. The cell cannot keep copying (39–49 s) DNA copying needs a steady supply of building blocks. When they run out, the copying machine stalls on the DNA. A stalled cell switches on its self-destruct program: its mitochondria leak, and dormant caspases wake and take it apart. ## 6. Sealed packets, then cleanup (49–57 s) The cell shrinks into many small sealed packets on the brain’s surface. The body’s cleanup cells swallow them. This visual shows methotrexate alone. Some protocols use triple intrathecal treatment with methotrexate, cytarabine and hydrocortisone. The animation compresses treatment and cell responses in time.

Side effects

The full list, kept up to date:

Where I read this