Video Case Report: Action Myoclonus After CAR-T Cell Therapy

Clinical Presentation

Mr. H, age 50, had a rapid-onset movement disorder, for which the neurologists at our institution were consulted. Mr. H was hospitalized because of relapsed diffuse large B-cell lymphoma. He had been treated with chimeric antigen receptor (CAR)-T cell therapy. Mr. H experienced bilateral hand movements that evolved over the course of an evening and were described as “tremor” (Video) 10 days after infusion of therapeutic T cells.

As can be seen in the video, Mr. H had no excessive movement at rest; however, during movement and postural examination, a high-frequency jerky myoclonus appeared. The distribution was predominantly distal, in his outstretched fingers. Both positive and negative myoclonus occurred and the movements were not stimulus sensitive. His speech and gait were unaffected. The action myoclonus complicated activities of daily living, such as drinking from a glass, as Mr. H demonstrates at the end of the video.

Diagnosis and Diagnostic Testing

The distribution, high frequency, and increase in symptoms with activity all suggest cortical myoclonus.^1-3 Laboratory evaluations were unremarkable and included normal electrolyte levels, renal and liver function, and no signs of infection. Because Mr. H was seen during the first wave of the coronavirus 2019 (COVID-19) pandemic in 2020, we were unable to perform clinical neurophysiologic testing, and we did not obtain MRI. We relied on the typical presentation of cortical myoclonus for a clinical diagnosis, which (as described below) responded to treatment with a typical course for cortical myoclonus.

Treatment and Follow-up

Mr. H was treated with a single dose of dexamethasone (10 mg) and began treatment with levetiracetam (750 mg twice daily), after which his symptoms resolved gradually over the course of a week. He continued with levetiracetam treatment and at 5 months follow-up, he reported a slight action myoclonus appears at the end of his day but is not bothersome to him.

Discussion

Background

CAR-T–cell therapy is an emerging tool in the treatment of relapsed and refractory malignancies. It is, however, associated with neurologic complications, including movement disorders.^1,2 In the literature, these movement disorders are most commonly classified as tremor.² The most comprehensive study of 100 people treated with CAR-T therapy reported a movement disorder in 39 individuals and 28% (11/39) of those individuals had some form of myoclonus.¹

Distinguishing between myoclonus and tremor is important because the symptomatic treatment is different for these 2 classes of movement disorders. It is also important to note that movement disorders are often the first sign of neurotoxicity to develop, preceding other complications such as headache, encephalopathy, and autonomic instability.¹

This case illustrates that action myoclonus can be a presenting symptom of immune effector cell-associated neurotoxicity syndrome (ICANS) after CAR T-cell therapy. As CAR-T cell therapy is implemented in more patients, clinicians will see myoclonus as a complication more often.

Treatment

ICANS can be treated with corticosteroids and seizure prophylaxis with levetiracetam.⁴ In the case of Mr. H, presented here, levetiracetam had the added benefit of being a first-line choice for the symptomatic treatment of cortical myoclonus.⁵

Summary

Here we report and show a case of rapid-onset action myoclonus after CAR-T cell therapy. As this therapeutic tool for relapsed and refractory malignancies is used more often, neurologists need to recognize myoclonus as one of its complications.