A 62-year-old woman was admitted to the neurology department of Tianjin Huanhu Hospital. The patient complained of paroxysmal falls accompanied by impaired consciousness for the last nine days and paroxysmal limb twitch accompanied by gibberish speech for four days. Initially, the patient experienced tonic-clonic seizures, accompanied by impaired consciousness. Later, the patient experienced tonic seizures with head turning to the right and retained consciousness similar to faciobrachial dystonic seizures (FBDS) (Supplementary Materials S1). These incidences occurred more than ten times in a day. The patient was first seen in another hospital, and a brain MRI was done. The MRI showed no abnormalities. The patient was started on sodium valproate, diazepam, and levetiracetam (drug doses unknown). Due to no clinical improvement, the patient was referred for further management. The patient had no previous history of hypertension, coronary heart disease, diabetes, cerebrovascular disease, mental illness, hepatitis, tuberculosis, and no family history of any hereditary disease.
On admission, the patient had a body temperature of 36.3 C, a heart rate of 91 beats/min, a respiratory rate of 20 breaths/min, and a blood pressure of 162/85 mmHg. The neurological assessment revealed that the patient had cognitive dysfunction (poor memory and poor calculation ability). However, other categories of the neurological examination, including cranial nerves, motor system, reflexes, sensation, coordination, movement, gait, and signs of meningeal irritation, were normal.
The serum testing of routine blood tests, coagulation profile, liver function and kidney function tests, blood sugars, lipid profile, and serological testing for hepatitis B, syphilis, and HIV were negative. In addition, the results of anti-nuclear antibodies, antineutrophil cytoplasmic antibodies, rheumatoid factors, thyroid-stimulating hormone receptor antibodies, anti-thyroglobulin antibodies, and serum tumor markers, including carcinoembryonic antigen, squamous cell carcinoma antigen, cytokeratin-19 fragment, carbohydrate antigen 199, carbohydrate antigen 125, and neuron-specific enolase were normal. The patient had abnormal serum chloride levels of 95mmol/L. Further, the serum AE-related antibodies determined with both tissue-based and cell-based indirect immunofluorescence (IIF) assay in V-Medical Laboratory (Guangzhou, China), including anti-N-methyl-D-aspartate receptor (NMDAR), anti-leucine-rich glioma-inactivated 1 (LGI1), anti-contactin-associated protein-like 2 (CASPR2), anti-gamma-aminobutyric-acid B receptor (GABABR), anti-dipeptidyl-peptidase-like protein-6 (DPPX), and anti-glutamic acid decarboxylase 65 (GAD65) and paraneoplastic neurological syndrome (PNS)-related antibodies including anti-Hu, anti-Ri, anti-Yo, anti-Ma2, anti-CV2, and anti-amphiphysin, was remarkable only for positive anti-LGI1 antibody with a titer of 1:16 (normal <1:10). The CSF showed slight leukocytosis of 10 x 106 / L with lymphocytic predominance. However, the pressure, color, turbidity, glucose levels, chloride levels, Gram staining, acid-fast staining, ink staining, metagenomic next-generation sequencing (mNGS), AE-related antibodies which were also determined with both tissue-based and cell-based IIF assay in V-Medical Laboratory (Guangzhou, China), and PNS-related antibodies of the CSF were normal. The patient had a positive RPR with a serum titer of 1:16 and a positive TPPA. Subsequently, TPPA and RPR in CSF were tested, and both results were positive.
The electroencephalography (EEG)showed irregular slow waves with medium to high amplitudes in the right temporal lobe, which spread to the other lobes and showed sharp waves (Figure 1). The brain MRI showed increased signals on T2-weighted and FLAIR imaging in the medial temporal lobe (Figure 2A). The gadolinium-enhanced MRI of the brain showed mild to moderate cord enhancement in the right temporal lobe (Figure 2B). Syphilis can cause multiple system damage. Therefore, magnetic resonance angiography (MRA) was carried out to investigate vascular stenosis or vasculitis-like changes. However, the results revealed no abnormalities (Figure 2C). Moreover, CT of the chest, echocardiography, abdominal ultrasound, urinary tract ultrasound, electromyography, and nerve conduction velocities of the limbs were normal.
Therefore, uncertainty arose as to whether the patient had both anti-LGI1 encephalitis and NS or whether the LGI1 antibody and LE manifestations were due to the NS. The patient received intravenous penicillin sodium 3.5 million units every 4 h for 14 days to treat the NS. Furthermore, the patient was initiated on intravenous sodium valproate 400 mg two times daily and oral levetiracetam 500 mg two times daily. The drugs were then changed to oral sodium valproate 500 mg two times daily and oral levetiracetam 750 mg two times daily. Improvement was noted with no convulsions and normal cognitive function. Two months later, the serum TPPA was still positive. In addition, the serum RPR was still positive with a titer of 1:8, while the serum LGI1 antibody was positive with a titer of 1:10. Furthermore, a revaluation of the CSF showed that the CSF TPPA and RPR were positive. However, the other CSF tests remained negative. In addition, a repeat of the EEG showed no epileptiform wave emission (Figure 3). Moreover, a repeat of the brain MRI showed no abnormality (Figure 2D). A second course of intravenous penicillin G sodium 3.2 million units every 4 h for 14 days was started. After another four months, the serum TPPA was still positive, the serum RPR test was positive with a titer of 1:8, while the serum LGI1 antibody was negative. Changes in TPPA, RPR, and LGI1 antibodies during the syphilitic treatment are shown in Figure 4. A repeat of the EEG and brain MRI showed normal findings. The third course of intravenous penicillin G sodium 3.2 million units every four hours, was given for 14 days. In addition, oral doses of sodium valproate 500 mg two times daily and levetiracetam 750 mg two times daily were continued. The patient was then followed up for additional three months. The patient reported no further convulsive episodes. In addition, the memory and calculation ability were noted to be normal.