Authors :
Presenting Author: Stephen Klaus, MB, BCh, BAO, M.Sc, MRCPI – Trinity College Dublin
Raluca Stanila, MD – St. James's Hospital; Hugh Kearney, MB BCh NUI – St. James's Hospital; Elisabeth Doran, MD – St. James's Hospital
Rationale:
Chimeric antigen receptor (CAR) T-cell therapy is a novel treatment for refractory and previously incurable hematological malignancies. The frequent complication of this treatment: immune effector cell-associated neurotoxicity syndrome (ICANS) resulting from the activation and infiltration of T cells into the CNS has led to the involvement of hospital-based epilepsy departments in the surveillance and management of these patients. Our case identifies a novel finding with ICANS related encephalopathy and post-ictal MRI signal abnormality appearing simultaneously with overlapping features.
Methods:
A 59-year-old woman with refractory diffuse large B-cell lymphoma (DLBCL) developed an acute encephalopathy five days post Yescarta (Axicabtagene ciloleucel) infusion. Initially presenting with a mild encephalopathic state lasting 24 hours, she deteriorated rapidly necessitating intubation and ICU admission. She was subsequently diagnosed with ICANS grade 4 and commenced on standard treatment including dexamethasone, Tocilizumab (humanized monoclonal Ab against IL-6), Anakinra (IL-1 receptor antagonist) and prophylactic Levetiracetam (500mg BD IV). Multiple clinical seizures were observed with focal motor onset involving both upper limbs.
Results:
Scalp EEG showed a marked deterioration from baseline with a diffuse mixture of slow rhythms including 4-6Hz and 2-3Hz flurries bilaterally maximally of the frontal leads. An electrographic seizure was captured with rhythmic theta evolving into bi-frontal sharp discharges and 2Hz slow wave activity. Seizures were successfully treated with benzodiazepines, Levetiracetam and Lacosamide however for several days she exhibited profound weakness of the left upper limb consistent with Todd’s paresis. MRI brain revealed bilateral T2 FLAIR hyperintensities and diffusion restriction involving the medial temporal lobes and the right hippocampus. Findings were identified as ICANS related encephalopathy and concurrent post-ictal signal change reflecting underlying cytotoxic edema. Following treatment, the patient improved dramatically and within days returned to baseline cognition with cessation of clinical seizures.
Conclusions:
ICANS, a new clinical entity secondary to CAR T-cell therapy, is being increasingly recognized with expanding use. Our patient’s MRI findings revealed dual etiologies with overlapping features and near resolution when repeated after one week. EEG is a vital tool used for both baseline investigation and routinely at seven and fourteen days post CAR T-cell treatment. Onset of profound encephalopathy and new onset seizures are frequent complications. This case highlights the emerging role of epilepsy services, the importance of aggressive seizure management in patients with ICANS, and the MRI findings associated with this condition.
Funding: Not applicable