Six pediatric patients with NMOSD who were referred to the First Medical Center of Chinese PLA General Hospital between June 2015 and June 2022 and underwent PE were enrolled. The most recent criteria were used for NMOSD diagnosis (1).

The patients’ serum and cerebrospinal fluid (CSF) were collected before PE treatment for analysis. CSF test included total CSF cell counts, white blood cell (WBC) count, total protein level, glucose level, IgG index (the normal IgG index reference was <0.65), and oligoclonal band (positive as 2 or more bands were present in the CSF but not in the corresponding serum). Serum test included antinuclear antibody (ANA) titers, autoantibodies against double stranded DNA, Sjögren syndrome A (SSA)/B (SSB), ribosomal p protein, Scl-70, Jo-1, thyroglobulin (TG), thyroid peroxidase (TPO), β2-glycoprotein I antigen, AQP4-IgG and MOG-IgG. As the main assessment component, the AQP4-IgG was test by the cell-based assays (CBA), as previously reported, using HEK-293 cells stably transfected with the M23 isoform of AQP4 (14). A twofold dilution (1:80, 1:160, 1:320, 1:640, 1:1280) was used to create endpoint titers. The MOG-IgG was detected by Euroimmun fixed CBA as reported (15).

Complete blood count, prothrombin time, fibrinogen levels, partial thromboplastin time, and comprehensive metabolic panel were evaluated before PE initiation. The transfusion department assessed the children’s vascular condition and lab results before deciding which vascular access to use and the total amount of plasma to be exchanged. The volume of plasma replacement and frequency and number of procedures were based on the American Society for Apheresis guidelines (11). Considering the body weight and physical condition, the total amount of plasma exchange is typically 40 mL/kg each cycle. COM.TEC Cell Separators (Fresenius Healthcare) were used for the PE procedure. PE was performed every alternate day for five cycles. We performed plasma exchange with 5% albumin (ALB). Plasma was removed during the PE process, and fresh frozen plasma (FFP) or/and frozen plasma (FP) along with 0.9% sodium chloride solution, albumin, acid-citrate-dextrose (ACD) anticoagulant, and calcium gluconate solution was infused as a substitution. The plasma exchange procedures of six patients are summarized in Table 1 .

By reviewing the medical charts, detailed clinical information was collected including age at onset, clinical manifestations, magnetic resonance imaging (MRI), physical examination, delay in PE initiation, acute phase and maintenance immunosuppressive therapy, time to first relapse after PE, and EDSS scores during nadir, and before and after PE procedures. Adverse events associated with the PE procedure were recorded such as hypotension, nausea, hypocalcemia, hypofibrinogenemia, thrombocytopenia, and acute non-occlusive thrombosis of the internal jugular vein.

A 8-year 3-month-old girl was admitted to the local hospital because of progressive vision loss in the left eye with visual field defects appearing one week before admission. Her right visual acuity was 1.2 and her left visual acuity was hand movements (HM) at 10 cm with no improvement after correction. Lab tests revealed the presence of AQP4-IgG, antinuclear antibodies (ANA), rheumatoid factor, and HLA-B27. MRI results showed a slight thickening of the left optic nerve with significant enhancement; thus, optic neuritis was considered. After receiving intravenous methylprednisolone (IVMP) and intravenous immunoglobulins (IVIG), the patient’s left visual field deficit improved but there was no improvement in vision. Then oral MP was given as maintenance therapy. The patient was then admitted to our hospital, and five cycles of PE procedures were performed. However, the child’s visual acuity did not improve at the time of discharge. Adverse events included rashes and acute non-occlusive thrombosis of the internal jugular vein. The patient received oral MP, mycophenolate mofetil (MMF), and aspirin treatment after being discharged from the hospital. After PE, the patient suffered 3 relapses within 47 months of follow-up. The duration between the acute attack and the PE procedure was 98 days while that between admission and the PE procedure was 91 days ( Table 2 ).

A 12-year 7-month-old girl was admitted to the local hospital due to a 2-day history of numbness and immobility of the extremities, accompanied by vomiting and urinary retention. MRI showed high T1- and T2-weighted signals in the bilateral centrum semiovale and periventricular white matter. After receiving IVMP, the patient’s symptoms progressively improved. Then oral MP was given as maintenance therapy. Six months later, the patient was admitted to the Pediatric Department again because of vision loss in the right eye and ocular pain. MRI revealed long T2- and T1-weighted signal enhancement in the retrobulbar and intraorbital of the right optic nerve. The patient recovered after receiving IVIP. Five months after the second attack, the patient was admitted to our hospital due to loss of vision in the left eye and ocular pain. Her right visual acuity was 0.15 with no improvement after correction, while the left eye exhibited loss of light perception. Lab tests revealed the presence of AQP4-IgG, ANA, anti-SSA antibodies, and anti-Ro-52 antibodies. Following high-dose IVMP, the patient’s vision did not improve, and plasma exchange was initiated. PE treatment was stopped after two cycles due to the development of severe thrombocytopenia. After the PE therapy, the patient regained light perception in the right eye, but the vision remained poor. Rituximab (RTX) was used to prevent relapse. During the 45 months of follow-up, no relapse was observed. The duration between the acute attack and PE initiation was 40 days, while the duration between admission and PE initiation was 15 days ( Table 2 ).

A 10-year 9-month-old girl was admitted to the local hospital because of vision loss in the right eye, ocular pain, and headache. The right eye exhibited loss of light perception and the left visual acuity was 1.5. After receiving IVMP, ocular pain and headache improved and the light perception of the right eye recovered, however, vision remained poor. Then oral MP was given as maintenance therapy. After 27 months, the patient was admitted to the local hospital again because of vision loss in the left eye and ocular pain. Her right visual acuity was 0.02 and her left visual acuity was 0.06 with no improvements after correction. Following high-dose IVMP, the patient’s vision did not improve and she was admitted to our hospital. Lab tests were positive for AQP4-IgG. MRI revealed abnormal and slightly enhanced signals from the bilateral optic nerve. The patient received five cycles of PE without any significant adverse events, except for rashes that were visible on day 1. Following PE, the left visual acuity increased to 0.6 (spectacle-corrected visual acuity was 1.0) at the time of discharge. RTX was used to prevent relapse. During the 81 months of follow-up, no recurrence was observed. The duration between the acute attack and PE initiation was 10 days while that between admission and PE initiation was 3 days ( Table 2 ).

A 13-year 2-month-old girl was admitted to the local hospital because of vision loss and ocular pain in the left eye. Her right visual acuity was 0.1 (spectacle-corrected visual acuity was 1.0) and her left visual acuity was counting fingers (CF) at 20 cm with no improvement after correction. After receiving IVMP, ocular pain progressively improved, and the spectacle-corrected visual acuity of the left eye improved to 0.3. Then oral MP was given as maintenance therapy. Two weeks later, the patient was admitted to the local hospital again due to a decrease in visual acuity (0.02) in the left eye. Lab tests were positive for AQP4-IgG. MRI revealed long T2-weighted signals with enhancement in the left intraorbital optic nerve. Following high-dose IVMP, the patient’s vision did not improve. The patient was then admitted to our hospital, and five cycles of PE procedures were performed without any adverse events. Following PE, the child’s visual acuity did not improve at the time of discharge. RTX was used to prevent relapse. During the 34 months of follow-up, no recurrence was observed. The duration between the acute attack and PE initiation was 28 days while that between admission and PE initiation was 8 days ( Table 2 ).

A 10-year-old girl was admitted to the local hospital because of vision loss and loss of light perception in bilateral eyes. After receiving IVMP, the left visual acuity recovered while the right visual acuity showed no improvement. Then oral MP was given as maintenance therapy. After 24 months, the patient was readmitted to the local hospital because of numbness in the right upper extremity with limb weakness. MRI revealed abnormal signals from L2-L3. Following high-dose IVMP, the patient’s symptoms progressively remitted. Ten months after the second attack, the patient was again admitted to the local hospital because of vision loss in the left eye with visual field defects. Following high-dose IVMP, the patient’s vision did not improve this time, and she was admitted to our hospital. Lab tests were positive for AQP4-IgG. Five cycles of PE procedures were performed without any adverse events. The child’s visual acuity showed no improvement at the time of discharge. Azathioprine (AZA) was used to prevent relapse. During the 33 months of follow-up, no recurrence occurred. The duration between the acute attack and PE initiation was 30 days while that between admission and PE initiation was 11 days ( Table 2 ).

A 12-year 2-month-old girl was admitted to the local hospital because of vision loss and ocular pain in the right eye. Her right eye exhibited loss of light perception and her left visual acuity was 1.0. The patient was then admitted to our hospital. After receiving IVMP, ocular pain progressively remitted, and light perception of the right eye improved, but the vision remained poor. Then oral MP was given as maintenance therapy. Lab tests revealed AQP4-IgG and ANA positivity. MRI revealed long T2- and T1-weighted enhancements in the retrobulbar of the right optic nerve. After receiving IVMP, ocular pain improved progressively, and light perception of the right eye recovered, however, vision remained poor. Five months later, the patient was readmitted to our hospital because of vision loss and ocular pain in the left eye. Her right visual acuity was 0.05 with no light perception in the right eye. MRI revealed abnormal signal enhancement of the left optic nerve. Following high-dose IVMP, ocular pain showed progressive remission, and light perception of the left eye recovered, but the vision remained poor. Five cycles of PE procedures were performed without adverse events; however, the child’s visual acuity did not improve. RTX was used to prevent relapse. After PE, the patient suffered a relapse within 40 months of follow-up. The duration between the acute attack and PE was 17 days while that between admission and PE was 8 days ( Table 2 ).

All six patients received IVMP at an initial dose of 10–20 mg/day after the acute attack. PE was performed when the patient’s symptoms did not considerably improve after administering high doses of steroids. The median duration between the acute event onset and PE initiation was 29 days (range 10–98). Five patients (P1, P3-P6) received five rounds of PE while one patient (P2) underwent two rounds of PE before stopping the procedure due to severe thrombocytopenia ( Table 2 ).

Regarding the efficiency of PE, only one patient (P3) exhibited clinical improvement after PE. Her left visual acuity increased from 0.06 to 0.6 (spectacle-corrected visual acuity was 1.0) and her EDSS score decreased from 4 to 3 points after PE. No improvement was observed in the other five patients after PE ( Figure 1 ). Following plasma exchange, patients were administered RTX (P2, P3, P4, and P6), MMF (P1), and AZA (P5) to prevent relapse. At the last follow-up [3.71 (2.00–5.73) months] four patients (P2-P5) experienced no relapse following PE and immunosuppressive therapy, P1 suffered three relapses within 47 months of follow-up, and P6 suffered 1 relapse within 40 months of follow-up ( Table 2 ).

Adverse events included rashes (P1, P3), acute non-occlusive thrombosis of the internal jugular vein (P1), and thrombocytopenia (P2) ( Table 3 ).