EEG findings in CAR T-cell-associated neurotoxicity: Clinical and radiological correlations

Abstract

Background While EEG is frequently reported as abnormal after CAR T cell therapy, its clinical significance remains unclear. We aim to systematically describe EEG features in a large single-center cohort and correlate them with clinical and radiological findings. Methods We retrospectively identified patients undergoing CAR T cell therapy who had continuous EEG. Neurotoxicity grades, detailed neurological symptoms, and brain MRI or FDG-PET were obtained. Correlation between clinical and radiological findings and EEG features was assessed. Results In 81 patients with median neurotoxicity grade 3 (IQR 2-3), diffuse EEG background slowing was the most common finding and correlated with neurotoxicity severity (p <0.001). A total of 42 patients had rhythmic or periodic patterns, 16 of them within the ictal-interictal-continuum (IIC), 5 with clinical seizures, and 3 with only electrographic seizures. Focal EEG abnormalities, consisting of lateralized periodic discharges (LPD, n=1), lateralized rhythmic delta activity (LRDA, n=6), or focal slowing (n=19), were found in 22 patients. All patients with LRDA, LPD, and 10/19 patients with focal slowing had focal clinical symptoms concordant with these EEG abnormalities. In addition, these focal EEG changes often correlated with PET hypometabolism or MRI hypoperfusion, in absence of a structural lesion. Conclusion In adult patients experiencing neurotoxicity after CAR T cell infusion, EEG degree of background disorganization correlated with neurotoxicity severity. IIC patterns and focal EEG abnormalities are frequent and often correlate with focal clinical symptoms and with PET-hypometabolism/MRI-hypoperfusion, without structural lesion. The etiology of these findings remains to be elucidated.

EEG-based grading of immune effector cell-associated neurotoxicity syndrome

“…Although prior investigations have described qualitative EEG findings in moderate to severe ICANS 33 , 34 , our study is the first to incorporate these features into a model of ICANS severity, whose coefficients reveal the importance of each EEG finding in predicting ICANS. The lower EEG frequencies (i.e.…”

“…Other features, such as LPDs and LRDA, were not retained in our model due to LASSO regularization rather than collinearity with other features, even though these findings have also been observed in other studies of ICANS. This may reflect underpowering of our dataset for these features, or may indicate that such features are only relevant in certain subtypes of ICANS, particularly since LPDs and LRDA have been associated with focal neurological findings 33 .…”

“…This scale shows promise as an objective diagnostic biomarker of ICANS and is readily amenable to implementation, given its qualitative features are easily identified through visual inspection. Although prior investigations have described qualitative EEG findings in moderate to severe ICANS 33,34 , our study is the first to incorporate these features into a model of ICANS severity, whose coefficients reveal the importance of each EEG finding in predicting ICANS. The lower EEG frequencies (i.e.…”

Continuous EEG monitoring detects nonconvulsive seizure and Ictal-Interictal Continuum abnormalities in moderate to severe ICANS following systemic CAR-T therapy

“…This is consistent with recent cohorts assessing periodic discharges on EEG. 10,14,15 Both triphasic and epileptiform GPDs were found across a range of clinical severity (Grade 2-3), however the majority of epileptiform GPDs (86%) were found in patients with severe neurotoxicity (Grade 3). The significance of this is unclear, as it may reflect a more severe generalized cortical dysfunction, and/or represent a concomitant epileptogenic process.…”

“…Rates of seizure in ICANS range from 3.7%-7.4%. [13][14][15] Data on ictal-interictal electroencephalography (EEG) findings in a series of 36 patients shows high frequency of rhythmic activity (53%) and epileptiform discharges (19%). 14 EEG as a diagnostic tool, biomarker of clinical severity, or as a prognostic tool of clinical outcome is of significant interest.…”