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 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.