Co-Existing PML-IRIS and Myelitis In Neuromyelitis Optica Spectrum Disorder

Background: Progressive multifocal leukoencephalopathy (PML) is associated with natalizumab treatment of multiple sclerosis (MS), but not with neuromyelitis optica (NMO) or NMO spectrum disorders (NMOSD’s).  Patients with NMO/NMOSD’s may be predisposed to PML by coexisting systemic autoimmune disorders or immunosuppressant use.

Objectives: To describe a case of NMOSD who simultaneously developed PML-IRIS and longitudinally-extensive-transverse-myelitis (LETM).

Methods: Case report at academic medical center

Results: A 72-year-old woman with a history of an NMOSD developed progressively worsening gait unsteadiness and falls over many months. Neurological examination revealed new nystagmus, left-sided dysmetria, gait ataxia and preexisting mild right spastic-hemiparesis. Her neurological history included recurrent attacks of longitudinally-extensive-transverse-myelitis over 8 years and she was seropositive for NMO-IgG. She received maintenance azathioprine 100 mg per day for 6 years and was attack-free for the preceding 4 years. Systemic lupus erythematosus was diagnosed 21 years previously and was manifest by photosensitivity, butterfly rash and strongly positive antinuclear antibody (>12 units; NR, <1), although she had never been treated with immunosuppression for these symptoms. Magnetic resonance imaging (MRI) revealed suggestive cerebellar white matter lesions of PML. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) detected JC virus, confirming PML. Azathioprine was discontinued and she received a 5-day course of cytosine arabinoside (ARA-C). She stabilized until 9-10 months later when she developed dysarthria followed by subacute right leg weakness. Examination revealed worsened cerebellar dysarthria and right lower extremity weakness. Repeat MRI revealed enhancement of previously nonenhancing cerebellar lesions and a longitudinally-extensive gadolinium enhancing thoracic cord lesion. NMO-IgG titer remained high (>160 U/mL; normal range, <1.6). Simultaneous acute NMOSD relapse and immune-reconstitution-inflammatory syndrome (IRIS) were diagnosed. Treatment with 5 days of high-dose intravenous methylprednisolone was followed by improved strength and speech. Maintenance intermittent plasma exchange was initiated.

Conclusions: To our knowledge, this is the first case of PML in a patient with NMO/NMOSD. PML should be considered in NMO patients with progressive symptoms or suspicious white matter lesions. Our case highlights the dilemma of managing simultaneous PML-IRIS and NMO disease activity.