The case centers on a patient who, after receiving CAR T cell therapy, developed signs of profound neurological injury. Brain magnetic resonance imaging revealed abnormalities characteristic of immune effector cell-associated neurotoxicity syndrome, universally abbreviated as ICANS: fluid-attenuated inversion recovery sequences showed periventricular white matter hyperintensities involving the atrium and temporal horn of the lateral ventricles, while diffusion-weighted imaging demonstrated areas of cytotoxic edema within the hippocampi on both sides. But what made the case exceptional was the spinal imaging. T2-weighted magnetic resonance images of the spine disclosed a longitudinally extensive spinal cord lesion, with abnormal signal intensity extending over more than three vertebral body segments. Critically, the lesion showed no enhancement after gadolinium administration on post-contrast T1-weighted images.

That combination of findings, a long spinal cord lesion that refuses to light up with contrast, is diagnostically treacherous. In clinical practice, a longitudinally extensive T2 hyperintense lesion in the spinal cord is nonspecific and can be produced by infectious, autoimmune, or vascular processes. Acute autoimmune inflammation of the spinal cord, or ischemia-related breakdown of the blood-spinal cord barrier, typically produces contrast enhancement, because the damaged barrier allows the gadolinium to leak into the cord tissue. A non-enhancing lesion therefore sits uneasily with the classic picture of acute inflammatory myelitis. The Paris team reasoned that, given the concurrent brain lesions suggestive of ICANS and the exclusion of infectious causes, the most likely diagnosis was spinal cord involvement as a component of ICANS itself, a manifestation so rare that only a handful of cases have been described in the literature, and those published reports describe similar non-enhancing imaging features.

The first and most urgent diagnostic step the authors emphasize is the systematic exclusion of infectious myelitis. This is not a bureaucratic precaution. Patients who have undergone CAR T cell therapy are profoundly immunocompromised, both from the lymphodepleting chemotherapy that precedes the infusion and from the therapy’s effects on normal B cells and other immune populations. In such patients, opportunistic infections of the central nervous system are a constant threat. The authors single out viral etiologies that must always be considered: cytomegalovirus, herpes simplex virus, varicella-zoster virus, enteroviruses, and human herpesvirus-6, each of which can produce devastating spinal cord disease in the immunosuppressed host. In their patient, cerebrospinal fluid cultures and multiplex polymerase chain reaction testing were negative, making an infectious etiology unlikely and clearing the way for the diagnosis of ICANS-associated myelopathy.

Understanding why this matters requires appreciating what ICANS is and how it usually behaves. Immune effector cell-associated neurotoxicity syndrome is the most feared non-hematological toxicity of CAR T cell therapy, typically emerging days after infusion as the engineered cells expand and release inflammatory cytokines. It usually announces itself with aphasia, confusion, tremor, and, in severe cases, seizures, cerebral edema, and coma. Aseptic meningitis is a common feature, and brain imaging may show transient abnormalities. The syndrome is graded from I to IV, with grade IV representing life-threatening neurotoxicity. Standard management escalates from corticosteroids to the interleukin-1 receptor antagonist anakinra for severe disease. But the spinal cord has been largely absent from this picture, which is precisely why the Paris case is so valuable to the field.

The timing of spinal cord involvement poses its own diagnostic puzzle, and the authors are candid about this uncertainty. In patients with severe ICANS, concomitant severe encephalopathy frequently precludes a complete neurological examination. A patient who is obtunded or comatose cannot report numbness, weakness, or a sensory level, and the examiner cannot reliably test for the signs that would localize a spinal cord lesion. As a result, it is often impossible to determine when spinal cord symptoms first occur, or whether they emerged before, alongside, or after the encephalopathy. In the reported patient, cerebral and spinal cord involvement probably developed simultaneously, a synchrony that itself supports the idea that both represent facets of a single systemic neurotoxic process rather than two independent complications.

Therapeutically, the patient received the recommended treatment for grade IV ICANS: high-dose corticosteroids combined with anakinra, the interleukin-1 receptor antagonist that has become the mainstay of salvage therapy for steroid-refractory neurotoxicity. Beyond this standard regimen, however, the evidence base evaporates. The authors state plainly that there is no clear evidence supporting a specific therapeutic strategy for ICANS-associated myelopathy. Interventions that neurologists might reach for in other forms of acute myelitis, such as intravenous immunoglobulins or plasmapheresis, have no established role here, because the underlying biology of the spinal cord lesion remains obscure. Larger case series, the authors argue, are needed to define the optimal treatment and the prognosis of this rare manifestation.

The imaging findings deserve close attention from clinicians who will face similar dilemmas. The pattern reported here, a long T2-hyperintense cord lesion without contrast enhancement, occurring in a patient with hippocampal cytotoxic edema and periventricular white matter changes, effectively constitutes a signature that others can look for. The hippocampal involvement is particularly suggestive, because bilateral cytotoxic edema in the hippocampi has been described in severe CAR T cell neurotoxicity and reflects the vulnerability of this region to the inflammatory and possibly vascular disturbances that ICANS produces. When such brain findings are accompanied by a non-enhancing longitudinal cord lesion in a recently infused patient, ICANS-associated myelopathy moves to the top of the differential diagnosis, provided infection has been rigorously excluded.

The broader significance of the case lies in the growing recognition that CAR T cell neurotoxicity is not confined to the brain. As the therapy expands from refractory lymphomas and multiple myeloma into earlier lines of treatment and into autoimmune diseases, the population of exposed patients is growing rapidly, and rare complications become clinically meaningful at scale. Reports such as this one, published as part of the journal’s imaging series with practical tips for intensivists, serve as sentinels. They alert critical care physicians, neurologists, and hematologists that when a CAR T cell recipient deteriorates neurologically, the evaluation must extend beyond the cranial vault. Spinal imaging, cerebrospinal fluid analysis with multiplex pathogen testing, and careful correlation of brain and cord findings should be part of the diagnostic armamentarium.

For now, the message from the Paris team is one of disciplined caution. Infectious myelitis must be systematically ruled out before attributing a cord lesion to ICANS, because the treatments differ fundamentally and the stakes are enormous. The non-enhancing character of the lesion, while atypical for classic autoimmune myelitis, appears consistent across the few published cases of ICANS-associated myelopathy and may reflect a distinct pathophysiology, perhaps one that does not disrupt the blood-spinal cord barrier in the way conventional inflammation does. Until larger series clarify the mechanism, the optimal treatment, and the long-term prognosis of this unusual complication, the case stands as both a warning and a guide: the engineered immune cells that save lives can, in rare instances, reach beyond the brain, and clinicians must be ready to recognize when they do.

Subject of Research: Acute myelopathy as a rare manifestation of CAR T cell therapy-associated neurotoxicity

Article Title: Acute myelopathy following chimeric antigen receptor (CAR) T cell therapy: an unusual diagnostic challenge

Article References: Bois, A., Provost, C., Decroocq, J., & Benghanem, S. (2026). Acute myelopathy following chimeric antigen receptor (CAR) T cell therapy: an unusual diagnostic challenge. Intensive Care Medicine. https://doi.org/10.1007/s00134-026-08617-w

Image Credits: AI Generated

DOI: 10.1007/s00134-026-08617-w

Keywords: CAR T cell therapy, ICANS, neurotoxicity, myelopathy, spinal cord, immune effector cell, MRI, encephalopathy, anakinra, corticosteroids, immunocompromised, intensive care