A case of natalizumab-associated progressive multifocal leukoencephalopathy followed by immune reconstitution inflammatory syndrome with difficulty in the timing of immunotherapy

Abstract

Background

Details regarding the clinical course of natalizumab-associated progressive multifocal leukoencephalopathy (NAT-PML) have not been reported in Japanese patients. We experienced a Japanese NAT-PML case and report it for the purpose of clarifying the challenge it posed in medical treatment.

Case Presentation

Herein, we describe a 58-y-old multiple sclerosis patient who had NAT-PML with immune reconstitution inflammatory syndrome (IRIS). Before NAT-PML developed, the patient's Expanded Disability Status Scale (EDSS) score was 5.5. She received natalizumab (300 mg) every 3–7 w, and her EDSS score had not changed for 9.1 y. The John Cunningham virus (JCV) index was 0.43 before NAT-PML developed. She developed a gait disturbance when NAT-PML emerged. Natalizumab was administered a total of 108 times. The patient was diagnosed with probable NAT-PML on the basis of punctate lesions on T2-weighted imaging and a JCV-PCR result of 29 copies/ml from cerebrospinal fluid (CSF) testing. Intravenous methylprednisolone (IVMP) was initiated when the contrast-enhanced lesion was first detected, but the NAT-PML lesion was rather enlarged despite the temporary disappearance of the contrast-enhanced lesion. An obvious increase in the IgG index and a slight increase in the CSF cell count were recognized at the time the immunological response was activated. Three cycles of a 3-d course of IVMP were administered every 2 w for IRIS, and the patient's worst EDSS score was 9.5.

Conclusion

Treatment sequencing should be executed before the onset of NAT-PML. Changes in CSF cell count and IgG index may be useful for treatment decision; further research is needed.