Devastating aquaporin-4 and HTLV-1-associated necrotizing encephalopathy

Abstract

Anti-aquaporin 4 (AQP4) antibody is a marker of neuromyelitis optica (NMO) spectrum diseases, characteristically presenting with myelitis longitudinally extensive transverse myelitis or optic neuritis (ON). While cerebral lesions are recognized, extensive brain involvement and cognitive impairment is rare. We report a case of subacute encephalopathy associated with fulminant subcortical brain lesions. A 19-year-old Jamaican woman reported decreased sensation and power in the left leg, recovering over 2 weeks without medical investigation. Eight months later, she developed painless bilateral visual loss (no perception of light on right, counting fingers on left), treated with intravenous methylprednisolone and plasma exchange. Vision improved gradually to 1/60 (right) and 6/6 (left). Recurrent ON 10 months later reduced acuity to counting fingers bilaterally. With further methylprednisolone, and azathioprine commencement (100 mg/day, low dose because of lymphopenia), acuities improved over 2 months. However, another relapse reduced vision to hand movements bilaterally, necessitating further plasma exchange. Two months thereafter, she developed gait failure, worsening vision, confusion and aggression, severe executive dysfunction, impaired attention, memory and verbal fluency, and suffered a generalized tonic–clonic seizure. There was no perception of light bilaterally, spastic paraparesis and hemisensory loss. With no response to further methylprednisolone and plasma exchange, she was given rituximab (375 mg/kg weekly for 4 weeks). Despite this, 2 weeks later she developed flaccid paraplegia with an extensive cord lesion from cervical to L1 vertebral segments. She remains profoundly disabled; blind, paraplegic, and with impaired comprehension. AQP4-IgG antibody titers were extremely high (maximal level 1:45,000 dilution). Double-stranded DNA antibodies (244 IU/l) and pANCA staining (myeloperoxidase antibody negative) were found. Cerebrospinal fluid (CSF) showed \3 white cells/ll, with normal protein (0.17 g/l). Oligoclonal bands were present in CSF, but not in blood. Antibodies to human T cell lymphotrophic virus (HTLV-1) were present in blood. Viral load was three HTLV-1 DNA copies per 100 peripheral blood mononuclear cells (3 % PBMCs) in blood and 14 % in CSF. MRI revealed T2-hyperintense changes in optic pathways, and numerous periventricular, callosal and juxtacortical white-matter lesions. Over 10 months, scans deteriorated (Fig. 1a, b). A brain biopsy, to exclude other treatable diagnoses, showed features consistent with necrotizing active demyelination (Fig. 1c, e, f; Fig. S1), and absence of AQP4 (Fig. 1d; Figs. S2, S3). Our patient presented with recurrent bilateral ON leading to blindness, and an evolving encephalopathy with necrotizing cerebral white matter destruction. Several features may explain this severity. Electronic supplementary material The online version of this article (doi:10.1007/s00415-012-6651-y) contains supplementary material, which is available to authorized users.