In 2001, a 44-year-old woman began having focal aware seizures characterized by episodic expressive aphasia. MRI at that time did not reveal abnormalities and her seizures were well controlled with AED polytherapy. Repeat MRI 1 year later revealed a small left frontal lobe T2 hyperintensity without enhancement. Her seizures remained well controlled over the next 10 years on a combination of oxcarbazepine, topiramate, and levetiracetam, and she continued working. Approximately 11 years after first lifetime seizure, she experienced an episode of complete expressive aphasia lasting hours and presented to our institution. She was diagnosed with focal status epilepticus, characterized clinically by expressive aphasia. EEG findings were significant for electroclinical seizures with left frontal onset as well as continuous spike/wave activity in the left frontal region (Figure ). MRI at that time showed swelling of the left cortical frontal lobe and operculum gray matter as well as mild left frontal atrophy (Figure ). Initial serum and CSF studies, including cell counts were normal. Further testing was notable for the following negative studies: paraneoplastic and autoimmune encephalitis antibody (NMDA-R, ANNA-1, ANNA-2, ANNA-3, AGNA-1, PCA-1, PCA-2, PCA-Tr, Amphiphysin, CRMP-5, VGKC, GAD), 14-3-3, serum lyme, NYS viral encephalitis panel, ANA, ACE. The patient was acutely treated with phenobarbital, which abolished the status epilepticus. IVIG was also initiated over this hospitalization for the possibility of an autoimmune etiology without specific consideration of RE. She was discharged from the hospital on four AEDs—oxcarbazepine, topiramate, levetiracetam, and phenobarbital. Subsequent clinical improvement over the next several months, initially thought to be related to phenobarbital, waned, leading to the conclusion that IVIG had been the ameliorative therapy. The patient began monthly IVIG infusions to supplement AED pharmacotherapy and experienced improvement in expressive aphasia and a decline in seizure frequency.\nApproximately 6 months later, the semiology of the patient’s seizure again evolved to include right rhythmic facial twitching in addition to expressive aphasia. Less than 1 year from prior episode of status epilepticus, she was re-admitted to the EMU. There was no evidence of electrographic seizures, but the presence of left frontal spike/wave complexes persisted as did episodes of right facial twitching and mutism. Ictal SPECT imaging revealed a focus of increased uptake in the left anterior frontal lobe, relative to the right frontal lobe, correlating with MRI abnormality. Over the following months, patient’s aphasia became nearly constant and semiology again began to involve the right arm. Repeat MR imaging now very clearly showed focal atrophy in the left frontal lobe, particularly involving the frontal pole, as well as the left temporal lobe (Figure ). This finding coupled with the progressive nature of the patient’s focal epilepsy solidified the diagnosis of RE. Monthly IVIG treatments were continued, topiramate does was augmented, and PRN lorazepam was added to the patient’s AED regimen. Unfortunately, the patient continued to have brief focal seizures several times per week and her mild expressive aphasia was static. In September 2016, approximately 3 years after her presentation to our institution and 15 years from first seizure, she began treatment with Rituximab. While her overall seizure frequency appears to have improved, she continues to have weekly focal seizures, a static mild expressive aphasia and remains on four AEDs.
In July 2010, a 53-year-old woman with no significant neurologic history experienced a single convulsion. Four months later, she experienced two similar convulsions, quickly progressing to status epilepticus. She was treated at an outside institution and recovered full function and returned to work. Initial MR imaging at that time was reported as normal. However, despite AED treatment, she continued to have focal seizures, characterized by clonic jerks of the right face. Over the next year, her seizures progressed in both frequency as well as semiology, involving the right arm as well as language. Admission to an outside epilepsy monitoring unit (EMU) revealed both electroclinical (semiology of right face/arm movements) and purely electrographic seizures arising from the left frontal region in the context of minimal responsiveness, consistent with focal status epilepticus. She was again treated for status epilepticus and discharged on AED polytherapy: phenytoin, valproic acid, levetiracetam, and oxcarbazepine.\nAs her epilepsy became more refractory, a very extensive etiologic work-up was performed at an outside institution, approximately 2 years from epilepsy onset. MRI demonstrated a left parietal FLAIR hyperintensity with mild associated volume loss (Figure ). CT imaging of the chest, abdomen, and pelvis did not reveal malignancy. Extensive serum and CSF studies, notably paraneoplastic and autoimmune encephalitis antibody testing (including AMPA-R, GABA B-R, ANNA-1, ANNA-2, ANNA-3, AGNA-1, PCA-1, PCA-2, PCA-Tr, amphiphysin, CRMP-5, VGKC, NMDA-R) as well as genetic testing for CADASIL and MELAS were also negative.\nIn addition to a known left frontoparietal epileptic focus, the patient then developed a second focus in the ipsilateral occipital quadrant, first observed in May 2013 (Figure ). Brain PET imaging performed showed overall left hemisphere hypometabolism, with areas of increased metabolism in the left frontal, parietal, and occipital regions, thought to represent ictal changes. Treatment broadened to include rescue doses of benzodiazepines and implantation of a vagal nerve stimulator, approximately 3 years from epilepsy onset. After whole body FDG PET imaging did not reveal occult malignancy, an autoimmune etiology of her epilepsy was presumed and immune therapy was initiated. Single trials of high dose intravenous methylprednisolone (1000 mg × 5 days, March 2014), plasma exchange treatments (5 treatments over 10-day period, May 2015), as well as an induction dose of Rituximab (1000 mg, May 2015) had no clinical effect. During these immunotherapy trials, the patient also underwent brain biopsy targeting the left frontal lobe. The biopsy showed only mild gliosis and rare T lymphocytes, without evidence of vasculitis, microglial nodules, or viral cytopathic changes. Concurrent AED therapy included trials of vigabatrin, zonisamide, and clobazam, with only the last having a meaningful impact on seizure frequency, albeit at a high dose (40 mg daily).\nAt this point, approximately 4 years from first clinical manifestation, the patient presented to our institution. At the time, the patient was having roughly 20 clinical seizures per day and her AED regimen was as follows: lacosamide, levetiracetam, carbamazepine, zonisamide, clonazepam, and clobazam. Her clinical exam was notable for a moderate mixed aphasia and a mild right hemiparesis. She was admitted to the EMU and found to be in epilepsia partialis continua with near continuous right face and arm twitching. After loading doses of levetiracetam and fosphenytoin, the patient began having distinct episodes of right arm and face movements coupled with mutism. The electrical correlate on EEG monitoring was frequent, brief (average duration of 30 s) left frontal seizures (Figure ). AEDS were further adjusted, with the addition of perampanel and prn dosing of lorazepam having the greatest effect on seizure frequency reduction. Based on progressive hemiatrophy on imaging (Figure ), medically refractory epilepsy, static neurologic deficits (right hemiparesis and mixed aphasia), and the extensive serum and CSF sampling, the diagnoses of RE, while conjectured in the past, was finally established. The patient was treated with regular dosing of IVIG. A dose interval of 3 weeks was determined based on the patient family’s impression of when seizure frequency began to increase after the last dose of IVIG. Despite regular IVIG dosing for approximately 6 months as well as concomitant AED therapy, the patient’s epilepsy remained refractory. Currently, the patient is under the care of another institution and IVIG therapy has been discontinued at the behest of the family and her AED regimen was adjusted to include felbamate, lacosamide, levetiracetam, phenobarbital, and lorazepam. Presently, she has a dense right hemiparesis and severe global aphasia.