A 43-year-old woman was transferred to the neurological intensive care unit on September 15, 2020, for fever and disturbance of consciousness for 6 days. Body temperature during the fever was 38.5-39.0 C. The patient had intermittent generalized tonic-clonic seizures, which lasted for 1-2 min and then resolved. The patient was previously healthy, had no history of autoimmune diseases or immunosuppressive drugs, no drug abuse, or psychiatric disorders. On the first day of onset, the patient was unresponsive, and on day 2, the patient fell into a light coma and developed a stiff neck. Blood anti-thyroglobulin antibody level was 751.4 IU/mL ( Figure 1A ), hemoglobin level was 70 g/L, and cerebrospinal fluid (CSF) white blood cell count was 120x 106/L (see  Supplementary Table 1 ). Head magnetic resonance imaging (MRI) indicated symmetrical lesions in the bilateral thalamus, caudate nucleus, lentiform nucleus, and bilateral hippocampus. On day 5, tracheal intubation was performed, CSF white blood cell count was 58 x 106/L (mononuclear cell ratio: 96.6%), and protein level was 1022.4 mg/L. The patient received ganciclovir (0.25 g q. 12 h ivgtt, 2 days), vidarabine (0.4 g q.d. ivgtt, 3 days), and supportive symptomatic treatment at two hospitals and the emergency department of our hospital.
At the time of transfer, her Glasgow Coma Scale (GCS) was E1TM1, and neck stiffness was present. Brain stem reflexes were present, tendon reflexes of both lower limbs were positive, and no pathological signs were elicited. Blood lymphocyte count and the number of each subgroup decreased (see  Supplementary Table 1 ). T2WI head MRI indicated hyperintense signals in the thalamus and caudate nucleus, and new-onset lesions in the bilateral cerebral peduncles (substantia nigra) ( Figures 2A   , B ). Ultrasonography showed diffuse echo changes of the thyroid. JEV-immunoglobulin M (IgM) antibody was positive in the serum and CSF. We tested the patient's blood and CSF for other viruses, bacteria, fungi, mycobacterium tuberculosis, markers of the tumor and paraneoplastic, antibodies to autoimmune encephalitis, and infectious disease tests (including antibodies to HIV and treponema pallidum, etc.), all of which were negative. The patient was diagnosed with JE, HT, and iron deficiency anemia. Intravenous infusion of penciclovir 5mg/kg and glucocorticoid 80 mg every 12 h, intravenous immunoglobulin (IVIG) provided at 0.4g/kg/d for 5 days, and palliative treatment were administered ( Figure 3 ). On day 7, the patient was treated with mechanical ventilation. Interleukin (IL)-8 and interferon gamma (IFN-gamma) in the CSF were significantly elevated ( Figure 1B ). Free triiodothyronine, free thyroxine, and thyroid stimulating hormone in the blood were 2.79 pmol/L, 7.84 pmol/L, and 0.08microlU/mL. On day 12, fever and epilepsy disappeared, consciousness gradually recovered, muscle tone in the extremities increased (the upper extremities exhibited cogwheel rigidity), and the muscle strength of the extremities was grade 0. Over the next few days, the patient was weaned from ventilation for short periods of time. On day 17, the right forehead creases became shallower, the right eye was incompletely closed, the extremities exhibited low muscle tone, and the patient required continuous ventilation. Electromyography (EMG) indicated primarily demyelinating lesions in the peripheral nerves of the extremities (see  Supplementary Table 2 ). On day 19, the patient suddenly became unconscious, and head computed tomography (CT) indicated hemorrhage in the right thalamus ( Figure 2C ). On day 24, the patient regained consciousness, but the cranial nerve and extremity symptoms did not improve. On day 27, IVIG 0.4g/kg/d was resumed for five consecutive days. On day 31, GCS was E3TM1, the patient was breathing spontaneously without ventilation, cytokines decreased during the treatment ( Figure 1B ). However, EMG showed the amplitude of compound muscle action potential was low, indicating axonal injury in partial peripheral nerve. She exhibited an involuntary smacking motion and limb muscle strength was grade 0. Symptoms did not improve over the next week. On day 36, GCS was E3TM1, and the Hughes score was 4. Considering the EMG and clinical symptoms of the patient, we believed that the disease was progressing and treatment strategies need to be changed ( Figure 3 ).
The patient was started on PAIA treatment (adsorption column model: KCIA08; KONPIA ; Koncen Bioscience, Guangzhou, China). The plasma regenerated in each treatment was approximately 1.5-2 times the circulating plasma volume. Blood IgG level was monitored after PAIA treatment, and when it was lower than 4 g/L, IVIG 5 g was supplemented to maintain some level of resistance in the body. The treatment was continued for 5 days.
On day 41, GCS was E4TM3, and the best limb muscle strength was grade 2. Blood IgG and IgM were significantly lower than that before treatment, and thyroid antibodies were normal. There was an obvious urinary tract infection, and PAIA was suspended. After improvement, PAIA was resumed on day 51 and the treatment was continued for 3 days. Blood IgG and IgM levels are shown in  Figure 1C . On day 55, GCS was E4V2M4, the muscle strength of the distal left upper limb and both lower limbs was grade 3, the muscle strength of the distal right upper limb was grade 2, and the muscle strength of both proximal upper limbs was grade 1. On day 56, EMG showed partial nerve conduction velocities and amplitudes improved, but abnormal spontaneous electric potentials were present. The patient was discharged after undergoing physical therapy and gait rehabilitation training for 1.5 months. At the time of discharge, she was able to walk with support from her family, and exhibited flat affect, slow speech, increased muscle tone, and a Hughes score of 3.
At the 4-months follow-up after PAIA treatment (month 6 of the disease course), the patient's Hughes score was 2, and she exhibited a smiling facial expression, slow speech, alleviated high muscle tone, and a Montreal Cognitive Assessment score of 20. MRI indicated extensive brain atrophy, but the lesion area was smaller than before ( Figures 2D   -F, 4 ). On a telephonic follow-up 6 months after the treatment, the patient's Hughes score was 1 (month 8 of the disease course), the muscle strength of the left upper limb was grade 4+, and the muscle strength of the remaining regions was grade 5. At the 12-months follow-up after treatment (month 14 of the disease course), the patient's Hughes score was 1, lower limbs muscle tone was slightly higher, EMG indicated greater improvement in peripheral nerve injury (see  Supplementary Table 2 ), the Montreal Cognitive Assessment score was 21, thyroid function and thyroid antibodies were normal (see  Supplementary Table 1 ). The patient exhibited natural facial expression and could speak normally. However, MRI still indicated brain atrophy ( Figure 2G ) and DTI showed that the patient's corpus callosum tract was partially broken ( Figure 2H ).