Abstract
Purpose::
Idiopathic intracranial hypertension (IIH) is a blinding condition of young obese women with a quarter of patients suffering permanent and severe visual loss due to raised intracranial pressure. The pathophysiology of IIH is not known, but its association with obesity is well recognised. Recent studies have shown that obesity is associated with a low grade inflammatory response with increased recruitment of macrophages in adipose tissue. In this study we characterise inflammatory and adiposity-related cytokine profiles in IIH and compare to other neuro-ophthalmic disorders.
Methods::
Paired serum and cerebrospinal fluid (CSF) specimens were collected from 85 patients (female, 63; median age 40 (range 16-82) years) undergoing diagnostic lumbar puncture, and stored at -80oC. Patients groups consisted of IIH, control subjects (normal investigations) or disease controls (other neurological or ophthalmological disease). Samples were analysed after a maximum of one freeze-thaw cycle for IL-1ß, IL-6, IL-8, TNFα, MCP-1(CCL2), HGF, NGF, insulin, leptin, resisitin, adiponectin and PAI-1 using multiplex bead immunoassays. Intracranial pressure, anthropometric (body mass index, waist-hip ratio) and other clinical data were collected from each participant.
Results::
Cytokines were detected in both CSF and serum of subjects with IIH (22), demyelinating disease (16), cerebrovascular disease (12), inflammatory (6) and non-inflammatory (13) central nervous system disease, and those with normal investigations (15). IIH, compared with all controls, was characterised by significantly higher levels of leptin (p<0.001) and low levels of adiponectin (p<0.001) in both serum and CSF, even after adjustment for measures of obesity. Serum IL-1ß and IL-6 together with CSF IL-6, TNFα, insulin and NGF were below the limits of detection in most subjects. IL-8 levels were higher in patients with demyelinating (p<0.05) and cerebrovascular disease (p<0.05). MCP-1 levels were lowest amongst patients with IIH (p<0.05) and subjects with normal investigations (p<0.05). HGF, PAI-1 and resistin did not differ significantly between groups.
Conclusions::
We have identified distinct patterns of cytokines in IIH. Whilst not showing a classically pro-inflammatory cytokine profile, IIH appears to be associated with a novel abnormality of the adipokine profile.
Keywords: cytokines/chemokines • immunomodulation/immunoregulation • visual impairment: neuro-ophthalmological disease