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.
An 8 year-old girl presented with history of repeated episodes of clonic seizures involving right upper and lower limbs and each episode lasting for 2–5 minutes with prolonged postictal state. The episodes didn't involve a sudden loss of consciousness but she had a bladder incontinence. The first episode started at the age of 7 years with rapid increase in seizure activity followed by decrease in frequency 10–15 episodes in the day with slurring of speech, cognitive delay and abnormal gait. She was born as a second twin and cried immediately after birth with normal APGAR score. No history of neonatal seizures. She had no history of blood transfusions, neurosurgery, traumatic head injury, proven allergies and family history of epilepsy. An initial routine electroencephalogram (EEG) was normal. Magnetic resonance imaging (MRI) was normal. The patient put on Oxcarbazepine and then, Valproate Sodium and Clonazepam were added gradually.\nOne month ago, she suffered from paraesthesia and twitching of right arm.\nShe admitted to our neurology department when the patient experienced an exacerbation of focal status epilepticus and generalized seizures.\nHer seizures could not be controlled with antiepileptic drugs alone.\nNeurologic exam at admission showed constant twitching of the right hand and intermittent stiffening of the right leg and pelvic. She had a right hemiparesis and muscle power Medical Research Council (MRC) grade 3 on the right upper and lower limb, but a full 5 on the left upper and lower limbs.\nShe also had exaggerated tendon reflexes on the right side. She showed severe global developmental delay.\nThere were no signs of meningeal irritation, and cranial nerves were intact. Cerebrospinal fluid analysis was normal, (PCR) for Herpes Simplex Virus, EBV, measles, Rubella and CMV appeared to be negative.\nEEG showed slow activity with focal left frontal biphasic spikes paroxysmal discharges ().\nMRI brain T1 revealed left hemispheric atrophy and in the left insular cortex ().\nMRI T2 axial revealed atrophy in left Caudate and putamen nuclei ().\nA diagnosis of RE was suspected.\nShe was given Immunotherapy with IVIG for one dose followed by IV. methyl prednisolone 30mg/kg for 5 days. Followed by oral prednisolone for 28 days. She slightly improved.\nThe parents however noticed an increase in the frequency of her seizure to three times a day every day. She is currently on outpatient review, and a more aggressive treatment (including surgical intervention) is being considered.