A 7-year-old girl was admitted to our hospital with frequent focal seizures for fifteen days. The seizures manifested as bilateral eye deviation to the right; rhythmic clonic movements of the right facial muscles; upturned corners of the right mouth; and clawing of the right hand with right upper limb tonic movements, with or without right lower limb tonic movements lasting approximately 3-20 s, 1-2 times per day initially. The frequency gradually increased to approximately 20 times per day. The patient was normal during the interictal period. Other neurologic symptoms, such as behavioral changes, hallucinations, confusion, memory impairment, and cognitive impairment, were not observed. No treatment was administered during the first 15 days. She visited our hospital because the seizures were worsening. Physical and neurological examination results were normal upon admission. Memory, numeracy, and spatial cognition were normal. The patient was healthy with normal developmental milestones. The patient had no family history of seizures or autoimmune disorders. She participated in school activities that were appropriate for her age. She was in 1st grade at primary school and had excellent academic performance.
On laboratory examination, complete blood count, renal and liver function tests, and thyroid function tests were normal. No hyponatremia was observed. The metabolic examination results, including serum ammonia, lactate, homocysteine, and blood urine amino acid organic acid profiles, were normal. Cranial magnetic resonance imaging (MRI) was normal. Electroencephalography (EEG) revealed slow background activity (Figure 1A) and epileptiform activity in the left frontocentral region (Figure 1B). The ictal video-EEG (VEEG) captured focal epileptic seizures originating from the left frontal and central regions (Figures 1C-F). Tumor screening for blood tumor markers (HCG, AFP, CEA, and NSE), lung computed tomography, and abdominal B-scan ultrasonography were negative. Cerebrospinal fluid (CSF) cytology results were normal and negative for oligoclonal bands. CSF glucose, chloride, protein, and lactic acid levels were within normal ranges. Serological and CSF assays for infectious agents, including viral etiologies, tuberculosis, Mycoplasma pneumoniae, and Chlamydia pneumoniae, yielded negative results. A cell-based indirect immunofluorescence antibody assay was used to detect the related antibodies (Abs). Anti-LGI1 Abs was detected at a titer of 1:30 (Figure 1G) in the serum and was negative in the CSF. Abs against NMDAR, GABABR, AMPAR, Caspr2, Amphiphysin, CV2, PNMA2 (Ma2), Hu, Ri, Yo, and anti-thyroid Abs were negative in the CSF and serum.
Oxcarbazepine (OXC) was administered to control frequent seizures after admission (17th day after onset), with poor response. The etiology of the patient's epilepsy is important for treatment. The six etiologies of epilepsy include structural, genetic, infectious, metabolic, and immune disorders, and also an unknown group. Structural etiology was excluded by the normal brain MRI. The patient was previously healthy, with normal developmental milestones, and all metabolic examinations were normal, hence metabolic etiology was excluded. She had acute onset with no family history of seizures, which did not support genetic epilepsy. Infectious etiology was excluded for the absence of infection symptoms, normal CSF test results, and infectious agents. Since she had an acute onset condition with positive anti-LGI1 antibody in serum and slow background activity in EEG, autoimmune epilepsy should be considered. Hence, we tried immunotherapy. Immunotherapy was initiated on the 21st day after onset. Intravenous immunoglobulin (0.4 g/d/kg body weight, 5 days) was administered, and the number of seizures significantly decreased. On the 25th day after onset, high-dose intravenous methylprednisolone (20 mg/kg) was administered once a day for 3 days, followed by oral prednisolone treatment for 6 months. The seizure frequency gradually decreased 2 days after intravenous methylprednisolone, and the seizures disappeared. One month later, serum anti-LGI1 Abs were negative (Figure 1H). The slow waves of the VEEG improved. The patient was seizure-free at the last follow-up (2 years). She was as healthy as before, without neurological dysfunction. She returned to school soon after she was discharged from the hospital, and everyone around her thought her performance was the same as that before she was ill.