Relapsing meningitis and limbic encephalitis in anti-AQP4-Ab-associated neuromyelitis optica spectrum disorder

Abstract

Objectives: neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease mainly affecting optic nerves and the spinal cord. Due to the potentially irreversible tissue damage, prevention of relapses is of utmost importance.

Methods: We describe the atypical clinical course and pathology results of a patient with anti-aquaporin-4 antibody (anti-AQP4-Ab)-associated NMOSD who developed aseptic meningitis followed by limbic-encephalitis-like presentation with extensive brain lesions upon treatment with rituximab and tocilizumab.

Results: The patient developed subacute cognitive decline with magnetic resonance imaging (MRI) evidence of extensive brain white matter lesions. In the hypothesis of an opportunistic brain infection, she underwent brain biopsy of the temporal pole. Pathology results revealed typical NMOSD findings with complement activation, supporting the hypothesis of an atypical presentation of anti-AQP-Ab-associated NMOSD. Accordingly, treatment with the complement-targeting drug eculizumab was started, leading to a dramatic clinical and MRI improvement.

Discussion: aseptic meningitis and limbic encephalitis could represent a rare phenotype of anti-AQP4-Ab-associated NMOSD.

Keywords: NMOSD; eculizumab; limbic encephalitis; meningitis.

Figure 1.

Fluid attenuated inversion recovery (FlAIR) sequences on the axial plane showing white matter hyperintensities involving the temporal lobe bilaterally (a), the insula (b), and frontal white matter (c).

Figure 2.

Neuropathological assessment of the expression of the complement activation marker C9Neo of brain biopsy: C9Neo immunostaining was prevalently detected on perivascular lympho-monocytic infiltrates (red arrows in a, b), but also on parenchymal cells morphologically resembling astrocytes (blue arrows in c, d), as confirmed by double immunofluorescence immunostaining with C9Neo and GFAP antibodies (inset in Figure 2(c)). Original magnifications: 200× (a, b), 400× (c, d, inset in c).

Figure 3.

Fluid attenuated inversion recovery (FlAIR) sequences on the axial plane showing, after eculizumab initiation, a reduction of white matter hyperintensities involving the temporal lobe bilaterally (A), the insula (B), and frontal white matter (C).