The patient is a 13-year-old male who initially presented at the age of 4 years with seizures, marked by staring, twitching of the left eyelid and projectile vomiting. He experienced anywhere between 10–60 seizures a day. Starting at the age of 7 years, after multiple failed attempts to control the seizures using various pharmacologic regimens, the patient underwent the first of 7 surgical resections. The first two surgeries were performed outside the United States and consisted of resections of the left hippocampus and neocortex and the left anterior temporal lobe and hippocampus. Nonspecific diagnoses of gliosis were reportedly made in examining the resected tissue from the first two surgeries. A third surgical resection for continued seizures at the age of 10 years included resections of the left frontal lobe and portion of the left temporal lobe; the pathologic diagnosis was focal cortical dysplasia, Palmini type IA []. The patient was seizure-free for 14 months postoperatively but eventually developed seizure recurrence. Three subsequent surgeries within a 3-week period ensued and included resections of the left temporal lobe, orbitofrontal region, and insula. The pathology in all three cases was interpreted as representing Palmini type IA focal cortical dysplasia. Seizures recurred within 2 weeks of the sixth surgery and persisted for the next 5 months. A seventh surgery included a left frontoparietal resection.\nHistopathologic examination of tissue from the final surgical resection showed focal evidence of contusional damage, related to previous surgery. Areas of cortical architectural disorganization marked by an abnormal layering pattern with focal absence of cortical layer two and occasional enlarged and dysmorphic neurons characterized by an atypical distribution of Nissl substance in the cytoplasm were observed (). The findings were interpreted as being consistent with a Palmini type IIA pattern of focal cortical dysplasia. Balloon cells were not identified. Additionally, multiple foci of perivascular meningeal and parenchymal chronic inflammation consisting of benign appearing lymphocytes were observed (). Most of the lymphocytes stained with T-cell antibody to CD3 (prediluted, Ventana, Tucson, AZ, USA) (); only rare CD20 (1 : 25 dilution, Dako, Carpenteria, CA, USA) positive staining B lymphocytes were present. Infiltration of the parenchyma by scattered lymphocytes was highlighted on the CD3 immunostain. Distributed primarily within the cortex were small collections of microglial nodules, highlighted with an CD68 immunostain (1 : 60 dilution, Dako, Carpenteria, CA, USA) (). Viral inclusions were not identified. Neutrophils, eosinophils and granulomatous inflammation were not observed. Focally, prominent cortical atrophy with gliosis was observed (). The histopathologic findings were interpreted as representing Rasmussen's encephalitis associated with focal cortical dysplasia (Palmini et al. type IIA pattern or ILAE focal cortical dysplasia type IIId) [].
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.