CSF opening pressure: Reference interval and the effect of body mass index

Our major criticism is the exclusion criteria utilized in the study by Whiteley et al. The syndrome of increased ICP is not always associated with either persistent daily headache or papilledema, and no direct correlation exists between the degree of CSF pressure elevation and the presence of headache. Moreover, the headache profile of idiopathic intracranial hypertension (IIH) may be indistinguishable from that of migraine. [3,4]

In the study by Whiteley et al, only patients with papilledema, persistent daily headaches, tinnitus, or mass lesions on brain imaging were excluded while the authors included 9% of subjects with headache. This contrasts with reports that IIH may occur without papilledema, and it may be associated with both recurrent headache mimicking migraine and visual symtoms such as diplopia or transient visual obscuration. In addition, it is not clear how the authors excluded papilledema. Simple ophthalmoscopy with an ophthalmoscopy may not be sensitive enough to diagnose papilledema.

Furthermore, the authors did not characterize potential confounders such as factors that can increase ICP. It is well known that sinovenous stenosis, as revealed by MR venography, is strongly associated with increased ICP. [4,5] Sinovenous stenosis, however, was not investigated in the study by Whiteley et al. Another question is the presence in their series of 33% of patients with neuroinflammatory disorders often associated with CSF abnormalities, such as elevated levels of protein which can increase CSF pressure. Finally, the use of drugs potentially increasing CSF pressure should be carefully considered in investigating the reference interval for CSF pressure.

Taken together, these observations suggest that the reference interval for CSF pressure found by Whiteley et al must be accepted with caution. We are concerned that a misinterpretation of the data could transform clinical practice in neurologic centers. This will stall a line of research on IIH with or without papilledema that may yet revolutionize our understanding of increased ICP disorders.

References

1. Whitheley W, Al-Shahi R, Warlow CP, et al. CSF opening pressure: Reference interval and the effect of body mass index. Neurology 2006; 67;1690-1691.

2. Bono F, Lupo MR, Lucisano A, et al. Obesity does not induce abnormal CSF pressure in subjects with normal MR venography. Neurology 2002;59:1641 -1643.

3. Mathew NT, Ravishankar K, Sanin LC. Coexistence of migraine and idiopathic intracranial hypertension without papilledema. Neurology 1996;46:1226-1230.

4. Bono F, Messina D, Giliberto C, et al. Bilateral transverse sinus stenosis predicts IIH without papilledema in patients with migraine. Neurology 2006;67:419-423.

5. Bono F, Lupo MR, Lavano A, et al. Cerebral MR venography of transverse sinuses in subjects with normal CSF pressure. Neurology 2003;61:1267-1270.

Disclosure: The authors report no conflicts of interest.

The purpose of our study was to provide a robust reference interval for CSF opening pressure for clinical neurologists. Our exclusion criteria – patients with papilloedema, persistent daily headache, tinnitus, mass lesions on brain imaging and headache characteristic of spontaneous intracranial hypotension - left us with patients where most practicing neurologists would not consider treatment which aimed to reduce CSF pressure.

In this study, the reference interval of patients with neuroinflammatory disorders was not significantly different from the overall estimate. Papilloedema was diagnosed by ophthalmoscopy by an experienced clinician with slit lamp examination in cases of doubt.

Patients with the syndrome of idiopathic intracranial hypertension without papilloedema (IIHWOP) are unlikely to have been included in this study. The interval for patients with any complaint of headache was not significantly different from the overall result and showed no evidence of a skewed distribution. The definition of the syndrome of IIHWOP is problematic because the diagnosis relies on the measurement of CSF pressure; it cannot be reliably diagnosed clinically.

As few patients with CSF pressures over 20cm CSF in our study had headache, we maintain that with current knowledge, the diagnosis of IIHWOP should be made with extreme caution, if at all, where CSF opening pressure is less than 25cm CSF and in some patients CSF pressures of up to 28cm CSF may be normal.

Disclosure: The authors report no conflicts of interest.