A 22-year-old man was referred to the nearby hospital due to headache, dizziness, and disorientation. At the hospital, he had generalized seizures. His past medical history was significant for recurrent oral ulcer and nodular erythema since childhood. He also had a family history of epilepsy. The patient grew up in an orphanage, which made it difficult to collect further detailed information about his family and his childhood, including the presence of perinatal abnormality and febrile convulsion. The medical record after his initial assessment reported that magnetic resonance imaging (MRI) revealed cerebellar hyperintensity lesion in T2-weighted image (T2WI). CSF had elevation of cells (35 cells/muL; reference, 0-5) and total protein (69 mg/dL; reference, 8-43), normal glucose level (60 mg/dL; reference, 50-75), and was negative for herpes simplex virus-deoxyribonucleic acid (DNA), tuberculosis-DNA, myelin basic protein, oligoclonal band, and cell culture. A diagnosis of NBD was considered owing to the past medical history. He received steroid pulse therapy, after which his symptoms improved.
Discontinuation of oral prednisone (30 mg/day) a year after discharge resulted in recurrence of headache and diplopia, and he was referred and admitted to our hospital. Examination revealed erythema on the left side of the neck and back scalp skin, and small papules in the genital region. MRI demonstrated high intensities in T2WI in the brain stem, cerebellum, right mesial temporal lobe, and bilateral basal ganglia (Fig. 1). This MRI also revealed atrophy of the left hippocampus. The erythema papules and elevated interleukin (IL)-6 (106 pg/mL; reference <4.0) in CSF were suggestive of BD, but a positive result for serum human leukocyte antigen (HLA)-B54 was characteristic of Sweet syndrome, which is a rare inflammatory skin condition characterized by sudden onset of fever and painful rash. Skin biopsy showed infiltration of inflammatory cells accompanied by vasculitis, which is typical of NBD. His condition was diagnosed as NBD from these results despite his symptoms not fulfilling the diagnostic criteria. Steroid therapy improved neurological symptoms and inflammatory markers in blood and CSF. MRI lesions in brain stem, cerebellum, and basal ganglia also resolved. He continued oral prednisolone (30 mg/day) and oral azathioprine (100 mg/day) as an out-patient.
Three years after first admission to our hospital, the patient presented with features suggestive of focal aware seizure (FAS) (the feeling of being driven to a corner), focal impaired awareness seizure (FIAS) (loss of consciousness and automatism), and focal to bilateral tonic clonic seizure (FBTCS) following FIAS. Electroencephalography (EEG) showed interictal discharge in the left temporal lobe, and MRI showed left hippocampal atrophy (Fig. 2a), which was similar to the previous imaging result (Fig. 1). A diagnosis of left MTLE was made, rather than an exacerbation of NBD, and sodium valproate (400 mg/day) was initiated. IL-6 in CSF was 20.9 pg/mL, which indicated that the NBD could be chronic.
After years of follow-up, three antiepileptics:sodium valproate (1000 mg/day), levetiracetam (2000 mg/day), and gabapentin (2400 mg/day):failed to inhibit the seizures, and the patient continued experiencing FAS, including Deja vu twice weekly, FIAS three times a month, and FBTCS yearly. The severity of NBD did not correlate with frequency of seizures. He had to temporarily retire from work because of the frequent seizures and was referred to the epilepsy center to be evaluated for epilepsy surgery, 12 years after NBD onset. Before and during evaluation, three more antiepileptic drugs (carbamazepine [500 mg/day], lacosamide [300 mg/day], and perampanel [10 mg/day]) were tried for 1 year, but they failed to control the seizures. Interictal EEG showed multiple sharp waves in the left sphenoidal electrode and sometimes in the left anterior temporal lesion (F3) in long-term video-EEG study. There was no interictal epileptic discharge in the contralateral hemisphere. During a 5-day monitoring period under the off-drug condition, we could catch five ictal events. In the ictal state, the patient slightly turned his head to the left and stopped moving for some time while staring blankly to the left, followed by oroalimentary and gesture automatism. In one of these ictal events, the patient presented with automatism followed by rotation of the head to the right and tonic symptoms of the right upper and lower limbs, and progressed to FBTCS. All ictal EEGs showed a similar pattern of lateralized rhythmic sharp waves, which appeared in the left sphenoidal electrode followed by background activity change. This activity evolved and spread to the temporal tip and the contralateral medial temporal lobe (Fig. 3). MRI in T2WI demonstrated shrinking and hyperintensity in the left hippocampus, and no findings were suggestive of NBD (Fig. 2b). 18F-fluorodeoxyglucose-position emission tomography (FDG-PET) showed low metabolism in the left medial and anterior temporal lobe (Fig. 2c). In the other area, FDG-PET did not reveal hypometabolism, which would have indicated hypofunction after NBD history. 123Iomazenil single photon emission computed tomography also showed similar results. Magnetoencephalography showed the scattering of equivalent dipole along the left Sylvian fissure. The Wechsler Adult Intelligence Scale-III (WAIS-III) found that the verbal intellectual quotient (VIQ) of the patient was 58; performance IQ (PIQ) was 68, and full-scale IQ (FIQ) was 59. The Wechsler memory scale-revised (WMS-R) indicated that his verbal memory was 66; visual memory was 108; attention/concentration was 90, and delayed recall was 77. The Wisconsin Card Sorting Test (WCST), used to evaluate frontal lobe function, showed that categories achieved (CA) was 3; perseverative errors of Nelson (PEN) was 9, and difficulty of maintaining set (DMS) was 1. The patient's overall score was 45.4 in the quality of life in epilepsy inventory (QOLIE) -31-P. The patient was right-handed, and Wada test and functional MRI showed left-sided speech dominance. We diagnosed his seizure as left MTLE due to HS. While NBD was well controlled on low-dose steroid, the impact of the seizures on his social life was immense.
He had left ATL 13 years after NBD onset. Histopathological examination revealed left HS and the temporal cortex did not have findings related to NBD or any chronic inflammatory diseases (Fig. 4). Two to three months after surgery, the patient felt causeless frustration, and was temporarily managed with anxiolytics; his symptoms improved in a few months. Intelligence quotient improved, but his memory worsened after surgery. In neuropsychological tests 2 years after surgery, memory function in WMS-R has deteriorated considerably, such that verbal memory was 51; visual memory was 60; attention/concentration was 84, and delayed recall was 50. On the other hand, WAIS-III and WCST had risen considerably; 61, 90, and 78 in VIQ, PIQ, and FIQ, respectively; and 3, 9, and 0 in CA, PEN, and DMS, respectively. As for QOL in QOLIE-31-P, although cognitive function declined by 1.6 points, social function and total QOL increased by 12 points and 3.5 points, respectively, and the overall score increased to 62. He had no major problems in his daily life, has been seizure-free for more than 2 years after surgery while being on two antiepileptic drugs (carbamazepine [500 mg/day] and lacosamide [300 mg/day]) and has been able to return to work with NBD well controlled.