A 16-year-old girl presented with a 2-year history of remitted focal seizures and memory deficits. She was diagnosed with thyroiditis at 11 years old, and her father had hyperthyroidism. Initial brain MRI revealed bilateral hippocampal hyperintensity in T2-weighted sequences and FLAIR sequences (Figures 1C,D). CSF analysis demonstrated pleocytosis (310 white blood cells per cubic millimeter), but the cytopathology was unremarkable. EEG revealed a slowed theta rhythm with bilateral temporal spike-wave discharges. The thyroid peroxidase (TPO) antibody titer was increased to 149.10 IU/ml (normal 0-60 IU/ml). Five months after onset, screening for autoimmune encephalitis-associated antibodies showed that the patient's serum and CSF were both positive for GAD65-Abs at a titer of 1:10 (TBA, by EUROIMMUN), OCB was positive, and the Ig index was increased to 1.34 (normal: 0.3-0.7). The patient's symptoms and memory were transiently improved after IVIG (2 g/kg) and methylprednisolone (20 mg/kg.d x 3 d) were given. Fifteen months after onset, she developed autonomic imbalance, including dysrhythmia, hypothermia/hyperthermia, and hyperhidrosis. Repeat brain MRI showed abnormalities in the bilateral frontal lobe, left parietal lobe, right temporal lobe, and insular cortex as well as the subcortical white matter and bilateral hippocampus (Figures 1E,F). Both serum and CSF were still positive for GAD65-Abs, with titers of 1:10 and 1:32, respectively. However, the symptoms of refractory focal motor seizures and dysautonomia did not respond to treatment with antiepileptic drugs, methylprednisolone, immunoglobulins, and one cycle of rituximab (375 mg/m2 x 4 times). Twenty-five months after onset, the patient developed persistent depression and was given sertraline. For economic reasons, she was irregularly receiving IVIG and steroid immunotherapy at the local hospital. At the last follow-up, 5 years after onset, she had persistent memory impairment and refractory focal seizures. Repeat brain MRI showed parenchymal atrophy (Figures 1G,H).
A girl aged 4 years and 9 months presented with a 1-day history of fever, vomiting, headache, and diplopia followed by coma. Her personal history and family history were unremarkable. Neurologic examination showed coma (Glasgow Coma Scale score 8), hyperactive deep tendon reflexes, and a positive Babinski sign. Brain MRI showed multiple diffuse abnormalities in the brainstem, thalamus, basal ganglia, and bilateral cerebral and cerebellar hemispheres on T2-weighted FLAIR imaging without enhancement (Figures 1I-L). A 2-h VEEG recording showed a slowed theta rhythm. CSF analysis revealed 11 white blood cells per cubic millimeter, along with normal glucose and protein. CSF cytopathology was unremarkable. Both serum and CSF were positive for GAD65-Abs, with titers of 1:100 and 1:320, respectively (Figure 2). OCB was positive. Screenings for paraneoplastic antibodies, anti-myelin oligodendrocyte glycoprotein (MOG) antibodies, and tumors were all negative. The patient was treated with methylprednisolone (20 mg/kg.d x 3 d) and IVIG (2 g/kg) and made a full recovery. After 2 weeks, she had no remaining symptoms and was discharged. A follow-up MRI after 1 month showed that the scope of the lesions was narrowed, the signal intensity was decreased, and the CSF GAD65-Ab titer was reduced to 1:32. At the last follow-up, 13 months after diagnosis, the patient had no symptoms, and MRI was normal.