A letter in NEJM describes a potential new neurological disease, pegivirus-associated encephalomyelitis (PAEM), linked to the common virus Pegivirus hominis (HPgV-1). Four immunosuppressed patients presented with progressive optic neuropathy and myelopathy, including spastic paraparesis or tetraparesis and sensory disturbances.
Two patients died within two years of symptom onset, while the others remained severely disabled. MRI scans revealed a distinctive pattern of bilateral, symmetrical lesions in the anterior visual pathway and spinal cord's corticospinal tracts and posterior columns.
HPgV-1 was detected in the patients' cerebrospinal fluid, serum, and brain tissue, but not in controls, suggesting a causative role. Viral loads were highest in the optic nerve and spinal cord, and genomic sequencing revealed compartmentalization within the CNS, further supporting this link.
The authors propose that PAEM, characterized by these specific clinical, radiological, and virological findings, may be underdiagnosed and that characteristic MRI findings should prompt HPgV-1 testing.
The appendix includes in-depth methods, results, discussion, and individual patient case reports. It elaborates on the clinical presentation, MRI and CSF findings, HPgV-1 RNA detection and quantification, and full-genome sequencing analysis supporting viral compartmentalization within the CNS. Two of the 4 patients were renal transplant recipients.
One of them was a 57-year-old kidney transplant recipient due to pANCA-associated vasculitis, presented with progressive hypoesthesia and weakness in his legs, followed by vision loss, nausea, vomiting, and cognitive difficulties. He was on CNI, MMF and steroids and had received cyclophosphamide in the past. He developed bladder and bowel dysfunction and lost the ability to walk. MRI showed abnormalities in the optic nerves, chiasm, pyramids, and spinal cord. HPgV-1 RNA was detected in both serum and CSF. Despite immunosuppression reduction and treatment with ribavirin, his condition didn't improve, and he died 17 months after symptom onset. Autopsy revealed myelin loss, glial cell abnormalities, and T-cell and macrophage infiltration in affected brain regions. Viral loads were highest in the optic nerve and cervical spinal cord.
Another patient was a 62-year-old kidney transplant recipient due to polycystic kidney disease, experienced progressive paresthesia and leg weakness, leading to spastic tetraparesis. She was on mTORi, Steroids and belatacept. She later experienced vision loss. Spinal MRI revealed lesions in the cervical and upper thoracic spinal cord. HPgV-1 RNA was detected in both serum and CSF. Belatacept was discontinued, and she was maintained on methylprednisolone and later azathioprine. Her condition was complicated by aspiration pneumonia, infections, and renal graft failure requiring ICU care. While her neurological symptoms partially improved, allowing for ventilator weaning and improved arm strength, she remained paralyzed in her legs and required dialysis. Follow-up revealed no HPgV-1 RNA in serum but persistent presence in CSF.
This new virus will require us to be more vigilant in the transplant world and perhaps even in the world of immunosuppression.
