Objective: To describe the neurophysiologic characteristics of chimeric antigen receptor (CAR)-T cell therapy-associated tremor.

Background: Enhanced physiological tremor is the most common type of drug-induced tremor. Normal physiological tremor is composed of a mechanical component and, in some persons, an additional central component. Enhancement of the mechanical component by involvement of the peripheral reflex loop is the main mechanism in majority of cases of drug-induced tremor. CAR-T cell-associated tremor is a common early clinical manifestation of neurotoxicity. However, neurophysiological analysis of such tremor has been lacking.

Method: Neurophysiological study was performed using uniaxial accelerometry and bipolar surface EMG. Accelerometers were attached to the dorsal aspect of both hands. Surface EMG was recorded from flexor carpi radialis and extensor carpi radialis muscles. Recordings were performed during rest, posture (with and without weight loading) and action.

Results: A 59-year-old man with relapsed diffuse large B cell lymphoma developed bilateral hand tremor one week after bicistronic anti-CD19/CD20 CAR-T cell infusion. He also noted additional symptoms coinciding with the tremor, including generalized fasciculations, perioral tingling, back pain, and intermittent tinnitus. His physical exam showed fine bilateral hand postural and kinetic tremor. Diagnostic work up including brain and spine MRI was unremarkable. Neurophysiological study demonstrated a postural tremor with peak frequency of 8 Hz with EMG correlation in both hands. The tremor frequency did not change with weight loading, indicating a central origin of the tremor. The patient endorsed some benefit after dexamethasone treatment.

Conclusion: Enhancement of physiological tremor can be identified by reduction in frequency with weight loading when caused by recruitment of the peripheral reflex loop. Constancy of the frequency with weight loading implies that this patient’s tremor must have a central origin. Therefore, this case demonstrates that CAR-T cell therapy can produce tremor by such a mechanism and that drug-induced tremor is not always due to enhancement of the mechanical component. The generator of the patient’s tremor is not known, but the centrally generated component of physiological tremor is at a frequency of 8-12 Hz.  Hence, it can be speculated that what is seen in this patient is augmentation of this component.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/central-tremor-after-car-t-cell-therapy-a-case-with-neurophysiologic-characterization/