Serum Concentrations of Retinol-binding Protein and Retinol in Patients with and without IIH

Abstract & Commentary

By Erik J. Kobylarz, MD, PhD, Assistant Professor of Neurology and Neuroscience, Weill Cornell Medical College, Cornell University. Dr. Kobylarz reports no financial relationship relevant to this field of study.

Synopsis: Increased levels of retinol in CSF in patients with IIH suggests that vitamin A may be involved in the pathogenesis of IIH.

Source: Warner JE, Larson AJ, Bhosale P, et al. Retinol-binding protein and retinol analysis in cerebrospinal fluid and serum of patients with and without idiopathic intracranial hypertension. J Neuroophthalmol 2007;27:258-262.

Idiopathic Intracranial Hypertension (IIH), or Pseudotumor Cerebri, is a neurologic condition with increased intracranial pressure (ICP) in the setting of normal cerebrospinal fluid (CSF) composition. This condition causes headache and papilledema, often resulting in progressive vision loss. In an effort to further understand the potential role of vitamin A-related compounds in the pathogenesis of IIH, Warner and colleagues compared CSF and serum concentrations of retinol and retinol-binding protein (RBP) in patients with and without IIH.

CSF and serum samples were collected from 87 patients, 28 of whom had been diagnosed with IIH. Of the remaining patients, 42 had non-IIH neurologic conditions and 17 had no known neurologic conditions but were undergoing preoperative lumbar punctures for anesthesia. RBP levels were determined using radial immunodiffusion (RID), and retinol levels were measured by means of high-performance liquid chromatography (HPLC).

In this study, higher serum retinol levels and lower CSF RBP levels occurred in the IIH patients, compared with those in controls. In addition, there was a more significant elevation in the CSF retinol/RBP ratios compared with those in serum in patients with IIH.


A number of studies have implicated vitamin A compounds in the pathogenesis of idiopathic intracranial hypertension.1-4 However, this is the first study comparing serum and CSF concentrations of both retinol and RBP in patients with and without IIH.

In this article, Wagner and coworkers report significantly increased unbound CSF and serum retinol levels, elevated retinol to RBP ratios more significantly in CSF, and significantly decreased CSF RBP levels in patients with IIH. When controlling for increased body mass index (BMI), the IIH patients had significantly increased serum RBP and free retinol, as well as decreased CSF RBP levels and elevated CSF retinol/RBP ratios compared with the controls. These results provide further evidence for the involvement of vitamin A in this disease process.

Additional studies with a larger number of subjects are needed to elucidate the pathophysiology of IIH (i.e., the specific role of vitamin A, such as its potential toxicity to arachnoid villi, resulting in decreased CSF reabsorption). These studies should take into account the concurrent effects of BMI, estrogen levels, and age. In addition, due to the multivariate statistical relationships demonstrated by this group, further investigation of the correlations between vitamin A and retinol and RBP levels in CSF and serum is warranted.


1. Jacobson DM, Berg R, Wall M, et al. Neurology 1999;53:1114-1118.

2. Selhorst JB, Kulkantrakorn K, Corbett JJ, et al. J Neuroophthalmol 2000;20:250-252.

3. Tabassi A, Salmasi AH, Jalali M. Neurology 2005;64:1893-1896.

4. Warner JE, Bernstein PS, Yemelyanov A, et al. Ann Neurol 2002;52:647-650.