Etanercept is a tumor necrosis factor (TNF) inhibitor, a special anti-inflammatory drug that is approved for certain medical conditions that cause excessive inflammation, including rheumatoid arthritis, other forms of arthritis in adults of any age, and psoriasis. It has been used in the U.S. for more than 25 years for the above conditions. In 2010 the first patients with chronic stroke were treated with etanercept off-label. Since then more than 5,000 patients, from more than 100 countries, have traveled to the Institute of Neurological Recovery, where etanercept for stroke was invented, for treatment of their intractable chronic stroke symptoms. The Institute uses etanercept delivered in a novel way (perispinal administration) that basic science research has shown enables etanercept to bypass the blood-brain-barrier. This enables perispinal etanercept to gently reach the brain and produce rapid neurological improvement, starting within minutes. Perispinal etanercept for treatment of stroke is not experimental. Two randomized, placebo-controlled clinical trials of perispinal etanercept have been completed, each having favorable safety outcome. The most recent independent, multi-center randomized clinical trial results (2025) had an unequivocal conclusion regarding safety: “Perispinal etanercept was safe,” although this was a small trial (n=126), so the trial’s conclusion has significant limitations.
🧠 Why It’s Being Used for Chronic Stroke
- Post-stroke inflammation: Strokes result in brain neuroinflammation that scientific evidence suggests contributes to the severity of ongoing stroke symptoms.
- TNF’s role: Excess TNF, released by activated microglia in the brain, is a key driver of brain inflammation. By blocking it, etanercept may help reduce neuroinflammation and improve neurological function.
- Delivery method: For chronic stroke symptoms, since 2010 it’s been given as perispinal etanercept — injected with a small needle overlying (but not into) the spine, followed by the patient being tilted on an examination table to help the drug reach the brain. No anesthesia is needed.
📊 Evidence So Far
- 2011-present: Published and peer-reviewed medical case reports; case series; on-site, real-time videos; videos taken by family members; and detailed, independent video interviews: Thousands of these patient-centered accounts describe benefits beginning within minutes of treatment, providing real world (but uncontrolled) supporting evidence of unprecedented effectiveness. Individual results vary, not all patients respond. Additional doses may be necessary to maintain the clinical improvement. Treatment is innovative (“off-label”). Terms of Use.
- 2012: Large observational study (n=629, 617 stroke, 12 TBI): Many patients — even years after stroke — reported rapid improvements in pain, mobility, speech, and cognition, that had not been thought possible. These improvements following perispinal etanercept treatment have been observed, in person, by many independent observors.
- 2020: Successful placebo-controlled, double-blind, randomized university clinical trial (RCT) in Australia: Showed statistically significant, unprecedented benefit for previously debilitating and intractable central post-stroke pain syndrome and shoulder mobility — pain scores dropped by 19.5–24 points, ~30% had near-complete pain relief, and shoulder rotation in active forward flexion improved by 55°.
- 2025: RCT (PESTO Trial in Australia): Results: To test efficacy it used a trial design that has been criticized and failed to generate an efficacy signal. Check back for a detailed analysis of the PESTO trial’s results.
💡 Key Takeaways
- Potential: 15 years of positive clinical experience confirmed by family members, independent physicians, neuroscientists and therapists; multiple peer-reviewed, published scientific reports; hundreds of patient reports; and placebo-controlled, randomized clinical trial evidence document the potential for rapid improvement that can be life-changing.
- Perispinal etanercept is not experimental. it has been routinely used daily for more than a decade at the Institute of Neurological Recovery, where it was invented.
Further information is available by calling the Institute of Neurological Recovery, M-F, 9 AM – 5 PM, (561) 353-9707, at www.strokebreakthrough.com, and in peer-reviewed scientific publications, available here.