To the editor: Systemic lupus erythematosus (SLE) can have multiple neuropsychiatric manifestations, which also are main reasons of disability and death. Neuromyelitis optica (Devic's syndrome/NMO) is one of the rarest and most serious neurological manifestations, with limited cases reported.1 Here, we report a patient who developed neuromyelitis optica with SLE.
In April 2009, this 19-year-old woman presented with Raynaud's phenomenon and left eye sore and gradually vision losing. Visual evoked potential and ophthalmoscopy evaluation revealed evidences of optic neuritis. The laboratory testing showed persisting thrombocytopenia, positive antinuclear antibody (ANA) in serum (1:640) and cerebrospinal fluid (CSF) (1:40), detectable SS-A and dsDNA antibodies, rheumatoid factor (87 IU/ml), thyroglobulin antibody (>500 IU/ml) and antithyroid peroxidase antibodies (>1300 IU/ml), as well as a slightly decreased level of serum complement factor C3 (0.31 g/L). So SLE was also diagnosed. After treating with intravenous (IV) methylprednisolone/immunoglobulin, her symptoms showed no obvious improvement, and started to appear right lower limb paresthesia and rapidly progressing paraparesis.
In June 2009, she developed bilateral visual acuity losing, ataxia in lower extremities and tetraparesis, encopresis and urinary retention. The lumbar puncture test revealed increased protein/glucose level and positive aquaporin-4 autoantibody. Cervico-dorsal magnetic resonance imaging (MRI) showed edema throughout the spinal cord with multiple longitudinal hyperintense signals at the lower cervical and thoracic cord and intramedullar high signal intensity lesions in axial T2-weighted images (Figure 1 A-C). The visually evoked response of right eye was delayed in the P100 and response of left eye was undetectable. Based on these clinical, radiological and laboratory findings and the previous history, the diagnosis of NMO was made.
The patient received a combination of IV methylprednisolone (120 mg/d for 5 days) and IV cyclophosphamide (CYC, 200 mg every other day for 1 month), followed by oral prednisone (first 60 mg/d, with gradually regular reduction) and mycophenolate mofetil (0.75g twice daily). After 70 days' treatment, her limb power improved significantly, and her visual acuity of right eye totally recovered, although the left eye just showed mild improvement. With the oral prednisone (10 mg/d) for subsequent 21 months, there was no deterioration of her neurological status or clinical relapses. In December 2011, the follow-up examination found that the eye blindness, weak paraparesis and neurological symptoms were all resolved. A repeat MRI showed marked reduction in hyperintense spinal cord signals without obvious cord atrophy (Figure 1 D-F) and her aquaporin-4 autoantibody also converted to negative.
SLE-associated NMO usually has a poor prognosis, potentially causing disability, so early diagnosis is important.2 The most widely accepted diagnostic criteria require the presence of optic neuritis, acute myelitis with at least 2 out of 3 supportive criteria: (1) a contiguous spinal cord MRI lesion spanning over 3 vertebral levels; (2) absence of brain MRI findings of multiple sclerosis; and (3) a positive NMO IgG antibody status.3 According to recent studies, NMO specific aquaporin 4 (AQP4) positivity can help confirm diagnosis of NMO spectrum disorders and distinguish lupus nerve system manifestations from multiple sclerosis.4
Only a few NMO/SLE overlapping cases has been reported without evidence-based treatment recommendations.2 The neurological recovery is likely based on aggressive treatment with high dose corticosteroids/ cyclophosphamide in the acute attack.3 Our patient was refractory to IV immunoglobulin/ methylprednisolone. After combination therapy followed by oral prednisone and mycophenolate mofetil, her clinical symptoms improved obviously. Maintenance treatment with oral prednisone (21 months) resolved her neurological disorders steadily, and achieved a remarkable decrease of MRI abnormalities. This case suggests that a combination immunosuppressive therapy may be an alternative option for the NMO patient who is resistant to the recommended single drug treatment.
1. Wingerchuk DM, Lennon VA, Lucchinetti CF, Pittock SJ, Weinshenker BG. The spectrum of neuromyelitis optica. Lancet Neurol 2007; 6: 805-815.
2. Polgar A, Rozsa C, Muller V, Matolcsi J, Poor G, Kiss EV. Devic's syndrome and SLE: challenges in diagnosis and therapeutic possibilities based on two overlapping cases. Autoimmun Rev 2011; 10: 171-174.
3. Sellner J, Boggild M, Clanet M, Hintzen RQ, Illes Z, Montalban X, et al. EFNS guidelines on diagnosis and management of neuromyelitis optica. Eur J Neurol 2010; 17: 1019-1032.
4. Jarius S, Wildemann B. AQP4 antibodies in neuromyelitis optica: diagnostic and pathogenetic relevance. Nat Rev Neurol 2010; 6: 383-392.