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 March 2007, a 47-year-old woman with a history of bilateral optic neuritis at age 35 experienced her first seizure. One month later, she experienced a second seizure and was started on lamotrigine. She presented to our institution as an elective admission to the EMU 6 months after seizure onset. Many right temporal seizures (clinical semiology of paresthesias over left face and arm) were observed and the interictal EEG was notable for right periodic lateralized discharges (PLDs; Figure ). MRI showed abnormal T2 signal in the right frontal cortex, right thalamus as well as a small area of contrast enhancement in the right temporal uncus. MR SPECT showed normal choline:creatinine ratio. Serum studies were notable for the following normal/negative studies: ANA, ACE, anti-TPO, Lyme, paraneoplastic antibody (ANNA-1, ANNA-2, ANNA-3, AGNA-1, PCA-1, PCA-2, PCA-Tr, CRMP-5, VGKC). CSF evaluation was significant for a mild lymphocytic pleocytosis, negative HSV and CMV PCR, and cytology negative for malignant cells. Ultimately, after trials of several AEDs including lamotrigine, levetiracetam, and carbamazepine, oxcarbazepine and phenytoin were utilized for seizure control.\nOver the next 3 years, the patient had several admissions to our institution for breakthrough seizures. Her seizure semiologies over this time frame were isolated left face and arm paresthesias, focal motor seizures involving left face and arm as well as secondarily generalized tonic/clonic seizures. A static mild left hemiparesis, most affecting the left hand, was also noted during this time. Further diagnostic work-up over one of these later admissions was notable for normal CSF cell counts, a CT scan of the chest, abdomen, and pelvis negative for malignancy, and repeat negative paraneoplastic panel evaluation. At this point, the patient was lost to follow-up.\nShe re-presented to our institution 5 years later after she experienced a generalized convulsion. Collateral history indicated that she had become unable to live at home unassisted and often had confusional and agitated episodes. Since last seen at our institution, her AED regimen had been changed to levetiracetam and valproic acid. In addition, a third lumbar puncture was performed and notably NMDA-R antibody testing was negative. The patient was found to be in non-convulsive status epilepticus and treated with benzodiazepines and augmented doses of her AEDs. CT imaging done on this admission revealed marked right hemisphere atrophy. Continuous EEG monitoring showed both right frontal and temporal spikes and left temporal slowing. Clinical exam was significant for perseverative speech, inability to follow complex commands and a moderate left hemiparesis. Given the patient’s marked hemiatrophy, refractory epilepsy, and static neurologic deficits, she was diagnosed with RE and monthly IVIG was initiated.\nMR imaging performed showed marked right hemisphere volume loss, affecting both gray and white mater (Figure ). Despite the marked asymmetry on imaging findings, EEG monitoring during this advanced stage of disease revealed bihemispheric electrographic pathology; in addition to PLDs in the right posterior quadrant, PLDs and spikes were observed over the left temporal region as well as bilateral independent frontal spikes (Figure ). By family and caregiver report, patient’s overall seizure frequency decreased over the 5-month period she was treated with immunotherapy. As there was no significant change in the patient’s overall neurologic functional status, decision was made by family to discontinue IVIG infusions and pursue hospice.\nWritten informed consent was obtained from patients or next of kin for publication of these three case reports.