ABSTRACT
Chimeric antigen receptor-modified T cells (CAR-T) have emerged as a promising immunotherapeutic approach in relapsed/refractory haematolgical malignancies. Broader application is limited by unique toxicities, notably, neurotoxicity (NTX). Language dysfunction is among the most frequent symptoms of NTX, the underlying mechanisms of which remain to be elucidated. Electroencephalogram (EEG) is an important tool to monitor for NTX and may provide insights into language dysfunction. AIM: We aimed to characterise language dysfunction and define electroencephalographic signatures after CAR-T cell therapy. METHODS: We reviewed the clinical presentation and EEG findings of 20 adult patients presenting with language dysfunction after CAR-T cell infusion. The cohort included a subset of patients treated with investigational CD19-directed CAR-T cells for non-Hodgkin's lymphoma (n=17), acute lymphoblastic leukaemia (n=1), follicular lymphoma (n=1) and chronic lymphocytic leukaemia (n=1). RESULTS: Language dysfunction presented within 14 days of CAR-T cell infusion in 16 (84%) patients. Ten (50%) patients had mild word-finding difficulties and 10 (50%) had marked dysphasia with profound word-finding difficulties; the latter were all associated with generalised rhythmic delta activity or generalised periodic discharges on EEG. CONCLUSIONS: Language dysfunction after CAR-T cell therapy is associated with generalised EEG abnormalities.
ABSTRACT
PURPOSE: Predicting seizure control after epilepsy surgery is difficult. The objectives of this work are: (a) to estimate the value of surgical procedure, presence of neuroimaging abnormalities, need for intracranial recordings, resection lobe, pathology, durations of epilepsy and follow-up period to predict postsurgical seizure control after epilepsy surgery and (b) to provide empirical estimates of successful outcome after different combinations of the above factors in order to aid clinicians in advising patients presurgically about the likelihood of success under their patients' individual circumstances. METHODS: We report postsurgical seizure control from all 243 patients who underwent resective surgery for epilepsy at King's College Hospital between 1999 and 2011. Among the 243 patients, 233 had lobar or sub-lobar resections, 8 had multilobar resections and 2 had excision of a hypothalamic hamartoma. We examined the relation between postsurgical seizure control and type of surgical procedure, presence of neuroimaging abnormalities, pathology, resection lobe and the need of intra-cranial electrodes to identify seizure onset. RESULTS: Among the 243 patients, 126 (52%) enjoyed outcome grade I, 40 (16%) had grade II, 51 (21%) had grade III and 26 (11%) had grade IV (mean follow-up 41.1 months). Normal neuroimaging or need for intracranial recordings was not associated with poorer outcome. Patients undergoing temporal resections showed better outcome than those with frontal resections, due to the poor outcome seen in frontal patients with normal neuroimaging. Among temporal resections, there was no difference in outcome between patients with and without neuroimaging abnormalities. Among patients with lesions on imaging, temporal and frontal resections showed similar outcomes. Likelihood of favourable outcome under the patient's individual circumstances was estimated by the tables provided. There was an 8-9% decrease in the percentage of grade I between follow-up at 12 and >36 months. CONCLUSION: Overall, nearly 70% of patients undergoing resective surgery enjoy favourable post-surgical seizure control. Normal neuroimaging should not discourage surgery in temporal patients but is a negative prognostic sign in normal MRI frontal patients. There were no statistical differences in outcome between patients with neuroimaging lesions in frontal or temporal lobes.
