Absence of aquaporin-4 antibodies in patients with idiopathic intracranial hypertension

Abstract

The pathophysiology of abnormal cerebrospinal fluid (CSF) dynamics in idiopathic intracranial hypertension (IIH) is not clear [1]. In healthy individuals, CSF is mostly formed in the choroid plexus with small contributions from extrachoroidal tissues, including ependymal surfaces of the brain and the capillary–astrocyte complex in the blood-brain barrier. It is reabsorbed into the dural venous sinuses through the arachnoid villi, although other sites are increasingly being recognised [10]. Several theories have been suggested to explain the aetiology of raised CSF pressure in IIH, including increased CSF production, impaired CSF absorption, obstruction of dural venous sinuses and increased brain volume due to cerebral oedema [6]. More recently, the potential role of proinflammatory CSF profiles have been suggested in some studies [2, 5]. Aquaporins are a recently discovered family of transmembrane water channels which play an important role in water homeostasis in the central nervous system (CNS) and are thought to be involved in the pathophysiologic mechanisms of cerebral oedema [3]. Aquaporin (AQP)-1 is natively expressed in the choroid plexus and contributes to water transport across the choroidal epithelium during CSF secretion. AQP-4 is more widely distributed within the CNS, including the choroid plexus [13] and ependymal cells of the ventricles [9]. Bloch et al. [4] suggested that AQP-4 could facilitate CSF absorption in hydrocephalus. Recently, antibodies to AQP-4 have been suggested to play a role in the pathogenesis of neuromyelitis optica (NMO) [11]. We hypothesised that a dysfunction of AQP-4 expression could affect CSF secretion or absorption and potentially contribute to the pathogenesis of IIH. In this study, we utilised a recently described anti-AQP-4 antibody assay [14] to look for AQP-4 antibodies in the serum and CSF of patients with IIH. We were not able to investigate the role of anti-AQP-1 antibodies because such an assay is currently not available. Paired CSF and serum samples from 10 female symptomatic IIH patients [mean age 31.8 ± 7.8 years; mean body mass index (BMI) 33.4 ± 6.9 kg/m] who were diagnosed according to the updated modified Dandy criteria [8] and 10 female control subjects (mean age: 35.8 ± 12.1 years; mean BMI: 31.7 ± 8.8 kg/m) were examined for anti-AQP-4 antibodies. Control subjects were patients who presented with headache and had lumbar puncture to exclude subarachnoid haemorrhage or raised intracranial pressure, and who were subsequently diagnosed with migraine or tension-type headache. The study was approved by South Yorkshire research ethics committee and all participants provided written informed consent. S. Dhungana A. Ismail B. Sharrack Department of Neurology, Sheffield Teaching Hospitals NHS Trust, University of Sheffield, Sheffield, UK