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 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.