Abstracts

Rationale: Chimeric antigen receptor T-cell therapy is a cell-based gene therapy which reengineers autologous T-cells to attack neoplastic cells (Saw et al., 2022). Super-refractory status epilepticus (SE) can present rarely as a side effect as part of immune effector cell-associated neurotoxicity syndrome (ICANS). Prognosis depends on treatment response to steroids, antiseizure medications (ASM), sedating agents, and anakinra (Rees, 2022).


Methods: A 56-year-old right-handed woman with follicular lymphoma developed CRS after CAR-T cell therapy with Yescarta. Infectious work-up was negative. Tocilizumab and dexamethasone were started. On day 5 after Yescarta, she had a bilateral tonic-clonic seizure. After midazolam (MDZ) bolus, levetiracetam (LEV) full load, IV methylprednisolone (IVMP), and anakinra, continuous EEG (cEEG) showed interictal activity in the right temporal region. Lacosamide (LCM), and valproic acid (VPA) loads, and increase of LEV did not abolish cortical hyperexcitability. CT and MRI were unremarkable. Diffuse electrographic seizures were seen over the next two days, refractory to burst suppression on propofol. Anakinra increase and MDZ drip finally halted seizures. CSF studies showed only protein at 300. Seizures resumed after steroid and sedation wean attempt and sedation was restarted. VPA and LCM were increased, and topiramate and diazepam were added for 48 h in the setting of interictal activity and signs of intracranial hypertension. IT methotrexate and hydrocortisone were initiated. Over the next 8 days Anakinra and sedation, and later steroids and VPA were tapered down and discontinued while EEG continued to improve. Mild residual aphasia progressively improved. LEV and LCM were discontinued without complications, and at three months follow up no seizures were reported, and EEG, clinical examination were normal.


Results: ICANS can present on days 3-10 post-infusion with encephalopathy, aphasia and in 6-10% with seizures, but rarely with status epilepticus (SE) (Amidi et al., 2022). All three manifestations were seen in our patient. Recommended work-up to rule out infection and structural correlates includes clinical exam, EEG, MRI, and CSF studies.

In this case, EEG showed initial right temporal focal cortical irritability and later subsequent generalized electrographic seizures. Transient expressive aphasia post-extubation reflected global dysfunction of thalamocortical networks. MRI did not show focal structural anomalies despite focal findings. Aggressive management of super-refractory SE with four ASM, sedating agents, and anakinra successfully resolved SE with complete neurologic recovery, and discontinuation of ASM.

Successful management of SE is seen in 16% of patients in the literature (Mauget et al., 2024). Complete resolution of symptoms suggests reversible focal cortical and subcortical changes related to neuro-inflammation, while irreversible damage is associated with uncontrolled cerebral edema, hemorrhage, and ischemia along with structural changes in MRI.


Conclusions: Resolution of focal deficits, and seizures, as well as ASM cessation is possible in ICANS related SE when neuro-inflammation is stopped before structural damage is established.


Funding: None.