Aquaporin-4 seropositivity in a patient with coeliac disease but normal neurological examination and imaging

Abstract

A 32-year-old woman presented in 2002 with a headache associated with numbness of her right arm, right side of her face and left leg. Examination was normal. Investigations revealed prolonged visual evoked responses (VER) on the right and a low vitamin B12 level. Cerebrospinal fluid (CSF) analysis and magnetic resonance imaging (MRI) of her brain and spine were normal. She was given a diagnosis of multiple sclerosis (MS) and commenced on vitamin B12 replacement. Three years later, her case was reviewed by the neurology service. She had experienced ongoing sensory disturbances, urinary dysfunction and episodic visual disturbances, consisting of blurred vision, particularly in her right eye, which would last for hours. She also experienced episodes of loss of strength of her right arm and a sensation of dragging her legs. Relevant past medical history included coeliac disease. Examination was normal. Investigations showed prolonged VERs, initially only on the right then bilateral. Somatosensory evoked potentials showed defective conduction in both lower limbs. MRI brain and spine were repeated and were normal. Oligoclonal bands in the CSF were normal. Autoimmune screen was negative. B12 and folate levels, thyroid function tests and syphilis serology were all negative. Tests for aquaporin-4 antibodies were performed twice using a cell based assay with aquaporin-4 M23 isoform and were positive. The titre was three out of four. Given her worsening VERs, with both being greater than 150 ms, her ongoing symptoms and positive aquaporin-4 antibodies, she was commenced on azathioprine. We believe that this patient’s symptoms are due to neuromyelitis optica (NMO). Therapy was initiated due to her prolonged VERs and our concerns regarding future functional visual deterioration. The patient was counseled with regard to the side effects of azathioprine but was very keen herself to commence therapy. Subjectively she feels better on treatment but there has been no change electrophysiologically. We believe that this patient is part of the evolving spectrum of NMO due to her clinical history, prolonged VERs, co-existent autoimmune disease and strongly positive aquaporin-4 antibodies. NMO is an inflammatory, demyelinating syndrome of the central nervous system with predominance of optic nerve and spinal cord involvement [1]. Aquaporin-4 antibodies were first described in 2004 [2]. The sensitivity of the aquaporin-4 antibody cell based assay ranges from 85 to 91% and the specificity is 100% [3, 4]. This patient’s symptoms were mild and her neurological examination was normal. Her symptoms were suggestive of mild transient optic neuritis and myelitis. Although her imaging has been normal thus far, it is possible that her disease may represent a milder phenotype of NMO and any radiological abnormalities present at the time of symptoms could reverse quickly leaving no appreciable abnormalities. The neurophysiological testing and the aquaporin-4 antibodies aided greatly in reaching a diagnosis in this patient and facilitating therapeutic decisions. Given the sensitivity P. H. McNamara (&) 32 Albert College Avenue, Glasnevin, Dublin 9, Ireland e-mail: pmcnamara2004@hotmail.com