A Rare Antibody Made This Axonal Neuropathy Nearly Untreatable — Until the Right Diagnosis Was Made

Guillain-Barré syndrome (GBS) is an acute autoimmune condition in which the immune system attacks the peripheral nerves, causing weakness, numbness, and in serious cases, paralysis. Most people with GBS recover with standard treatments like intravenous immunoglobulin (IVIG) or plasma exchange. But within the GBS family of disorders, there are rarer, more severe subtypes — including acute motor axonal neuropathy (AMAN) and acute motor and sensory axonal neuropathy (AMSAN) — that attack the nerve axons directly rather than the protective myelin sheath. These axonal variants tend to come with a worse prognosis and less reliable responses to standard therapy. A case report published in November 2025 in the journal Cureus illustrates what can happen when one of these conditions also comes paired with a rare antibody that actively resists treatment.

The patient was a 69-year-old man who developed progressive numbness ascending from both legs to his mid-trunk, bowel and bladder problems, and two unexplained falls. His symptoms began shortly after a course of antibiotics for a gut infection, a known trigger for GBS-type conditions. Initial nerve studies pointed to a sensory-ataxic presentation and he was treated with IVIG over five days. He was briefly stable, but within eight days was readmitted with dramatically worsening weakness, including significant loss of arm and hand strength, and eventually required ventilator support due to respiratory failure.

Detailed nerve conduction studies confirmed AMSAN: his motor responses were severely diminished and sensory responses were completely absent, while conduction velocities remained relatively preserved. This pattern shows that the axons themselves are being destroyed rather than the myelin insulation around them. Despite two rounds of IVIG and five sessions of plasmapheresis, he continued to deteriorate. The clinical team ultimately tested for neurofascin antibodies, and found anti-NF155 IgG4, a marker for axonal nodopathy, a condition in which antibodies attack the nodes of Ranvier — the critical gaps along nerve fibers where electrical signals jump to speed transmission.

Anti-NF155 nodopathy is known to be uniquely resistant to IVIG and corticosteroids, the drugs most commonly used for GBS and its variants. B-cell depleting agents like rituximab are considered the appropriate treatment for this antibody subtype, since they target the immune cells producing the harmful antibodies. Once rituximab was initiated, the patient began to show clinical improvement. The authors argue that testing for neurofascin IgG4 should happen early in any GBS or axonal neuropathy patient who is not responding to first-line therapy, rather than as a last resort after weeks of ineffective treatment.

For patients and caregivers navigating GBS or related conditions, this case carries an important message: not all axonal neuropathies are the same, and a treatment plan that works for one patient may not work for another. If standard therapies aren't producing improvement, it is worth asking about advanced antibody testing. Identifying the specific immunological mechanism behind the disease can unlock treatment strategies that would otherwise never be tried. In this case, a single lab result changed the entire course of care.