Natriuretic pro-peptides in idiopathic intracranial hypertension

Abstract

Idiopathic intracranial hypertension is a disorder of unknown pathogenesis. Natriuretic peptides may be involved in intracranial pressure regulation, but cerebrospinal fluid (CNS) and plasma concentrations in this disorder are unknown. We evaluated venous and intrathecal concentrations of ANP, BNP and CNP precursor peptides in 40 patients with idiopathic intracranial hypertension and in 20 controls. Natriuretic pro-peptides were quantitated using processing-independent assays. In CSF, no differences in peptide concentrations between patients and controls were found (proANP: 239 ± 23 vs 231 ± 22 pmol/L, proBNP: < 2 pmol/L in all, proCNP: 1079 ± 318 vs 1138 ± 323 pmol/L). In plasma, proCNP was lower in IIH compared with controls (35.3 ± 4.8 pmol/L vs 43.8 ± 5.9 pmol/L, p < 0.0001). Moreover, plasma proBNP was significantly lower in patients compared with controls (47.1 ± 21.4 pmol/L vs 59.2 ± 22.0 pmol/L, p = 0.045). There were no associations between peptide concentrations and ICP and BMI, respectively. Plasma proANP and proCNP increased during 3 months follow-up (p = 0.01 and p = 0.006), n = 12. We suggest that decreased plasma proCNP concentration in idiopathic intracranial hypertension may reflect endothelial dysregulation of vascular tone and may be a marker in this disease. Further studies of proCNP and endothelial function are needed to establish such role.

Introduction

Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure (ICP) in the absence of an identifiable neurological pathology and associated to increased risk of permanent visual defects [1], [2]. IIH is linked to obesity and may be more rapidly reversed if weight-loss is achieved [3], [4]. A disturbed ICP autoregulation in IIH is likely, but pathophysiological mechanisms of IIH are still unknown.

The natriuretic peptide system comprises a family of structurally related peptides with antagonizing properties against the renin–angiotensin–aldosterone system. The atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) are released primarily from cardiomyocytes in response to increased wall-tension and promote natriuresis and diuresis [5]. In contrast, C-type natriuretic peptide (CNP) is released from various tissues, including endothelial cells, and acts as a paracrine relaxant of vascular tone [6]. The plasma concentrations of ANP and BNP are inversely associated with body mass index (BMI) and may increase during weight-loss [7], [8], [9].

The natriuretic peptides (NPs) are also expressed in the central nervous system (CNS) [11]. Increased concentrations of NPs in CSF have been shown in intracranial hypertension, i.e. subarachnoidal haemorrhage [12], [13], [14], [15]. Moreover, intraventricular administration of ANP reduces elevated intracranial pressure (ICP) and CSF production in rodent models [16], [17]. Since two of three NP receptors, NPR-A and NPR-C, have been located to the choroidal plexus where two-thirds of the total cerebrospinal fluid (CSF) production is generated, it has been suggested that NPs may be involved in liquor dynamic regulation [17], [18].

Considering the association between peripheral NP production and obesity, and the proposed ICP regulatory actions of NPs, it is tempting to hypothesize that there is a link between IIH and NP concentrations. However, this has not been evaluated before. If the NP system is involved in IIH, it may serve as a target for future diagnostic and therapeutic strategies. The aim of this pilot study was, therefore, to quantify the systemic and intrathecal concentrations of the natriuretic precursor-derived peptides proANP, proBNP and proCNP in IIH in relation to CSF pressure.