Neuromyelitis Optica Presenting as Multiple Sclerosis Worsening on Natalizumab

Background: NMO is a disabling CNS demyelinating disease.   Treatment is usually immunosuppression or B-cell targeted therapy.  There are conflicting reports about the benefit of natalizumab in patients with NMO. 

Objectives: To describe a case of NMO presenting as MS, worsening on natalizumab

Methods: Case report of a patient presenting as MS with negative serum NMO Ab who significantly worsened on natalizumab. 

Results:

A 51 year-old Hispanic woman developed bilateral, sequential optic neuritis with incomplete recovery, followed quickly by partial myelitis.   MRIs showed multiple enhancing brain lesions and 5-6 small, non-enhancing spinal lesions.  Serum NMO-IgG was negative.  She did poorly on Copaxone and Betaseron with relapses with new brain and spinal cord lesions.    She was then started on natalizumab with a negative serum JCV Ab.  She did well for six months, then developed confusion (asking repetitive questions), aphasia, right sided weakness, numbness and apraxia. 

Her MRI revealed large, bilateral, T2 hyperintense, subcortical white matter lesions with patchy enhancement. Due to concerns about PML, she was started on PLEX. She had a LP with JCV PCR sent, which came back negative, twice. Initial CSF - WBC 19 with 44N, 28L, gluc 33, prot 153. Repeat CSF - WBC 27, prot 53, gluc 56. Viral studies, gram and stain and culture all negative.

She continued to decline with worsening right sided weakness. MRI of her spine was done which revealed subtle enhancement at T3-5. With this new finding, her current symptoms were felt to be due to a relapse; therefore, she was started on IVMP. She had minimal improvement and was transferred to rehab.

By follow-up on 5/22/12 in our clinic, she had significant improvement.  After discussion with the patient and her family, it was decided to start her on Cytoxan.  She received her first dose of Cytoxan on 6/4/12 and her second dose on 6/27/12.  Repeat MRI C- and T-spine (done at outside facility) revealed a longitudinally extensive (C1-C7) lesion.  Due to this she re-tested for NMO-Ig G - this came back positive at >160.

She was admitted to the hospital on 7/19/12 with confusion and dizziness.  She was found to have a multi-drug resistant UTI and was treated with IV antibiotics. During this admission, she developed acute left optic neuritis and was treated with IVMP x 5 days followed by PLEX x 6.  After PLEX, she received her first dose of Rituximab.

Conclusions: While natalizumab has been shown to inhibit migration of T and B cells across the blood-brain barrier, it may be that the increased peripheral B-cells, particularly the CD19+ cells, may increase disease activity in patients with NMO.  In addition, this case highlights how closely NMO can mimic MS and the importance of re-testing patients for NMO Ab, if clinical suspicion is high.