Authors :
Presenting Author: Andrea Stabile, MD – Foundation IRCCS C. Besta Neurological Institute, Milan, Italy
Francesco Deleo, MD – Epilepsy Unit – Foundation IRCCS C. Besta Neurological Institute, Milan, Italy; Joana Fonte, MD – Neurology Department – Centro Hospitalar Universitário de Santo António, Porto, Portugal; Chiara Pastori, MD – Epilepsy Unit – Foundation IRCCS C. Besta Neurological Institute, Milan, Italy; Roberta Di Giacomo, MD – Epilepsy Unit – Foundation IRCCS C. Besta Neurological Institute, Milan, Italy; Giuseppe Didato, MD – Epilepsy Unit – Foundation IRCCS C. Besta Neurological Institute, Milan, Italy; Francesca Andreetta, PhD – Neurology IV-Neuroimmunology and Neuromuscolar Diseases Unit – Foundation IRCCS C. Besta Neurological Institute, Milan, Italy; Fabio Martino Doniselli, MD, PhD – Department of Neuroradiology – Foundation IRCCS C. Besta Neurological Institute, Milan, Italy; Marco de Curtis, MD – Epilepsy Unit – Foundation IRCCS C. Besta Neurological Institute, Milan, Italy
Rationale:
Autoimmune-associated epilepsy (AAE) defines a chronic predisposition to seizures due to ongoing brain autoimmunity, structural abnormalities or both. In some patients with a suspected AAE autoantibodies are not found. Anti-seizure medications (ASMs) and immunotherapy (IT) are thought to exert little benefit in this context.
1,2 Our study examines seizure outcome in a cohort of patients with seronegative suspected AAE treated with ASMs and IT.
Methods:
We retrospectively reviewed medical records of patients with epilepsy of suspected immune etiology (defined by the Antibody Prevalence in Epilepsy and Encephalopathy score
3,4 and exclusion of alternative etiology
2) and negative antibody testing followed at Besta Institute Epilepsy Unit between 2009 and 2023. Inclusion criteria are: (1) at least 12-month follow-up after IT; (2) at least 1 long-term VEEG monitoring. Outcomes are: (1) seizure frequency at last follow-up; (2) unreported seizures during VEEG.
Results:
Nine patients (F:M = 5:4) met the inclusion criteria. First evaluation ranged between < 1 year and 2 years from seizures onset. Antibody testing was negative in 9/9 serum and 8/9 CSF samples. Tumor screening found no malignancy in the cohort. Patients had multiple seizure types: aware focal motor seizures (2/9), focal seizures with impaired awareness (8/9) with/without automatisms. In three patients cognitive, sensory and autonomic phenomena also occurred. Four patients had focal to bilateral tonic clonic seizures. At onset, seizure frequency varied between sporadic and daily. Most patients (4/9) had more than weekly seizures. All underwent VEEG monitoring lasting from two to nine days. Seizures were recorded in seven patients: only one notified them; in sixseizures were unreported. Most brain MRI showed T2/FLAIR hyperintensities restricted to the medial temporal lobe, either unilaterally (4/9) or bilaterally (3/9). Two patients had bilateral temporal and extratemporal T2/FLAIR hyperintensities. Seizures were refractory to at least 2 ASMs in 5/9 patients. All patients received IV methylprednisolone followed by PO prednisone in 8/9 cases. IV immunoglobulins (2/9), plasma exchange (1/9) and cyclophosphamide (1/9) were also used. Time to last follow-up varied between one year and 14 years. At last follow-up, only one patient reported overt seizures. Among patients not referring epileptic episodes, VEEG revealed unreported seizures in one and confirmed seizure freedom in seven. Brain MRI remained unchanged in eight cases. Contralateral temporal lobe involvement was seen in one case. Seven patients continued IT: 5 patients were on prednisone, in 1 associated with mycophenolate; two patients on azathioprine and mycophenolate alone. Two patients continued with ASMs alone.
Conclusions:
In our nine patient case series the combination of ASMs and IT resulted in seizure freedom in > 70% cases. Given the presence of unreported seizures, long-term VEEG monitoring has proved critical to confirm the true seizure frequency.
References:
1. Steriade C. et al.Epilepsia.2020;61:1341-1351
2. Dubey D. et al.Epilepsia.2019;60:367-369
Funding: None.