A 68-year-old male Chinese patient presented with headache and fever of up to 39 °C, accompanied by chills, paroxysmal cough and sputum, and systemic myalgia at the end of September 2021. The patient was treated with antiviral and antibacterial therapy that included moxifloxacin combined with piperacillin, tazobactam, and oseltamivir, and his body temperature declined and headache disappeared. The lumbar puncture (LP) revealed a opening pressure of 150 mmH2O, white blood count (WBC) of 149 × 106/L (96.6% lymphocytes), decreased glucose level of 1.99 mmol/L, and significantly increased protein level of 2356.3 mg/dL. Initial brain magnetic resonance imaging (MRI) and electroencephalography were unremarkable. However, 1 week later, the patient gradually developed disturbance of consciousness with dysuria, and then was transferred to our hospital. The patient had the medical history of hypertension, and he worked as a farmer with frequent contact with pigs and sheep. Neurological examination revealed a lethargic state, stiff neck, weakened tendon reflex, positive Kernig’s sign, and positive bilateral pathological signs.
Differential diagnoses included inflection etiology (e.g., neurobrucellosis and tuberculous meningoencephalitis) and autoimmune etiology. As atypical bacterial meningitis or viral meningitis could not be ruled out, the patient received treatment with ceftriaxone sodium, rifampicin, doxycycline, and ganciclovir infusion. On admission, his serum inflammatory indicators were normal. Tests for antinuclear antibody, anti-neutrophil cytoplasmic antibody subtype, lupus anticoagulant, rheumatoid factor, autoantibody screen, anti-Hantavirus antibody (IgG, IgM), and Brucella antibody (IgG) were negative. Serum Epstein-Barr virus (EBV) DNA test indicated prior infection.
After 3 days of treatment, the patient’s consciousness gradually became clear and his neck stiffness improved, but he exhibited tremor in both upper limbs and weakened strength in both lower limbs, mainly in the right lower limb, which was accompanied by paresthesia. Enhanced brian MRI showed uneven enhancement and T2 hyperintense lesions of medulla oblongata (Fig. 1 a, b); Cervical spine MRI showed T2 hyperintense lesions in medulla oblongata and upper margin of the T2 vertebral body (Fig. 1 c). A contrast-enhanced thoracic spine MRI showed uneven enhancement and T2 hyperintense lesions of T1 to T6 vertebral segments (Fig. 1 d, e, f), reminiscent of autoimmune and demyelinating diseases. Electromyography was normal. LP showed a pressure of 80 mmH20, WBC count of 76 × 106/L (97.4% lymphocytes), normal glucose level (2.73 mmol/L), and protein level of 2356.3 mg/dL. Next-generation sequencing (NGS) of CSF showed 15 reads of EBV; Xpert, T-SPOT, and brucellosis antibody in the CSF and serum were negative. Autoimmune antibodies in the CSF and serum, including anti-N-methyl-D-aspartate receptor antibodies, anti-aquaporin 4, anti-myelin oligodendrocyte glycoprotein, and anti-contactin-associated protein-like 2 antibodies, anti-leucine-rich glioma-inactivated 1, anti-gamma-aminobutyric acid type receptor antibodies, anti-α amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid 1/2 receptor antibodies were negative. However, GFAP-IgG in CSF was positive in both cell- and tissue-based assays (Fig. 2). The patient was diagnosed with A-GFAP-A, and then he was administered intravenous immunoglobulin (IVIg) and methylprednisolone.
The patient’s lower limb weakness and fever gradually improved, but developed dizziness, fatigue, and sweating after prolonged sitting (approximately 30 min). Ambulatory blood pressure monitoring showed a drop in systolic blood pressure of approximately 30 mmHg after 30 minutes of sitting, suggesting postural hypotension. The mean circadian rhythm variability in systolic blood pressure was non-dipper. 24-hour ambulatory electrocardiogram (Holter) showed a standard deviation of normal-to-normal interval (SDNN) of 84 ms, standard deviation of the average of normal-to-normal interval (SDANN) of 52 ms, and percentage of R-R interval difference > 50 ms (pNN50) of 4.4% (Fig. 3). Additionally, DRs suggested a medium risk of SCD (DR4 = 0.0649%, DR2 = 5.6803%, DR8 = 0.0024%). Electrocardiogram and echocardiography was normal. No abnormalities were observed on the thoracolumbar MRI.
After treatment with a standard IVIg regimen (0.4 g/kg body weight/day) for 5 days and pulses of 500 mg/d methylprednisolone for 3 days, 250 mg/d methylprednisolone for 3 days, 125 mg/d methylprednisolone for 3 days, and 60 mg/d prednisone with a dose reduction of 5 mg every 2 weeks, the patient’s fever disappeared and lower limb weakness improved. 3 months later, his orthostatic hypotension disappeared, SDNN, SDANN and pNN50 increased to normal levels (Fig. 3), blood pressure variability (BPV) became normal. Patient condition gradually improved and he could mobilise independently.