Differences of contrast loaded CSF concentrations are indicators for compartmentalization. According to the second law of thermodynamics, the injected contrast agent is expected to diffuse homogenously throughout all CSF spaces (ventricles, subarachnoid spaces, cisterns), given that these spaces communicate freely. In a series of 18 NTG patients, large concentration gradients of contrast loaded CSF were measured between the basal cisterns and the SAS of the optic nerve (paper in review). Similar results have been recently reported in patients with longstanding papilledema, in whom conventional medical treatment was ineffective and who underwent optic nerve sheath decompression.8
Compartmentalization of CSF spaces can lead to dissociation/discontinuation of CSF flow and content and also to pressure gradients between the different CSF spaces. Evidence for such a dissociation of pressure between the lumbar CSF space and the SAS of the optic nerve is based on the relationship between intracranial pressure and the diameter of the optic nerve sheath. Previous studies have shown a relationship between the intracranial pressure and the optic nerve sheath diameter in patients with brain tumors and increased intracranial pressure due to high altitude.9–11
Enlargement of the SAS of the optic nerve in patients with NTG have also been measured.12 In all these patients, however, the intracranial pressure determined with lumbar puncture was in the normal range and the reason for the distension of optic nerve sheath is unclear. The question therefore is whether NTG patients might have a local elevated pressure confined to the SAS of the affected and compartmentalized optic nerves. This idea seems to conflict with previous data that reported lower intracranial pressure (measured with lumbar puncture) in patients with NTG.13,14 In these series of patients the diameter of the optic nerve sheath was not measured. The reason for this contradiction may be do to the current, but incomplete, understanding of the patency of the CSF pathways and the limitation of the value of lumbar spinal tap.
It is still generally assumed that lumbar pressure represents the intracranial pressure and the pressure in the SAS of the optic nerve as well, i.e. measuring at one point in the CSF system allows for extrapolation to other points. Given the high complexity of the SAS anatomy in the CSF pathways15 as well as the long distance from the lumber spine to the SAS of the optic nerve, it is indeed questionable whether this assumption is true, especially in patients with diseases of the optic nerve sheath, such as compartmentalization. In a small study performed on patients with normal-pressure hydrocephalus, a high correlation of lumbar pressure and parenchymal pressure of the brain was demonstrated.16 The authors concluded that lumbar puncture is an accurate technique to determine the intracranial pressure in patients with communicating CSF systems.16 This assumption, however, might not be true in patients with NTG that demonstrate impaired CSF flow on CT cisternography.
Compartmentalization inhibits free CSF communication due to altered anatomic structures in the SAS of the optic nerve, mainly thickening of the menigothelial cell layer, as shown in patients with glaucoma.17 The mechanism leading to compartmentalization is currently under investigation. Several pathways may be included in this process, such as failure of CSF drainage due to insufficient lymphatic drainage, impaired phagocytosis of menigothelial cells, or thickening of the menigothelial cell layer following low grade inflammatory processes.3,4
1. Killer HE, Laeng RH, Groscurth P.Lymphatic capillaries in the meninges of the human optic nerve.J Neuro-Ophthalmol.1999;19:222–228.
2. Killer HE, Jaggi G, Miller NR, et al..Does immunohistochemistry allow easy detection of lymphatics in the optic nerve sheath?J Histochem Cytochem.2008;56:1087–1092.
3. Xin X, Fan B, Flammer J, et al..Meningothelial cells react to elevated pressure and oxidative stress.PLoS One.2011;6:20142.
4. Jaggi GP, Harlev M, Ziegler U, et al..Cerebrospinal fluid segregation optic neuropathy: an experimental model and a hypothesis.Br J Ophthalmol.2010;94:1088–1093.
5. Xin X, Huber A, Meyer P, et al..Betatrace protein – L-PGDS – inhibits astrocyte proliferation and astrocyte mitochondrial ATP production in vitro.J Mol Neurosci.2009;39:366–3671.
6. Killer HE, Jaggi GP, Flammer J, et al..The optic nerve: a new window into cerebrospinal fluid composition.Brain.2006;129:1027–1030.
7. Killer HE, Jaggi GP, Flammer J, et al..Cerebrospinal fluid dynamics between the intracranial –and the subarachnoid space of the optic nerve. Is it always bidirectional?Brain.2007;130:514–520.
8. Killer HE, Jaggi GP, Miller NR, et al..Cerebrospinal fluid dynamics between the basal cisterns and the subarachnoid space of the optic nerve in patients with papilloedema.Br J Ophthalmol.2011;95:822–827.
9. Watanabe A, Kinouchi H, Horikoshi T, et al..Effect of intracranial pressure on the diameter of the optic nerve sheath.J Neurosurg.2008;109:255–258.
10. Kimberly HH, Noble VE.Using MRI of the optic nerve sheath to detect elevated intracranial pressure.Crit Care.2008;12:181.
11. Sutherland AI, Morris DS, Owen CG, et al..Optic nerve sheath diameter, intracranial pressure and acute mountain sickness on Mount Everest: a longitudinal cohort study.Br J Sports Med.2008;42:183–188.
12. Jaggi GP, Miller NR, Flammer J, et al..Optic nerve sheath diameter in normal-tension glaucoma patients.Br J Ophthalmol.2012;96:53–56.
13. Berdahl JP, Fautsch MP, Stinnett SS, et al..Intracranial pressure in primary open angle glaucoma, normal tension glaucoma, and ocular hypertension: a case-control study.Invest Ophthalmol Vis Sci.2008;49:5412–5418.
14. Ren R, Zhang X, Wang N, et al..Cerebrospinal fluid pressure in ocular hypertension.Acta Ophthalmol.2011;89:142–148.
15. Killer HE, Laeng HR, Flammer J, et al..The arachnoid trabeculae and septae in the subarachnoid space of the human optic nerve: anatomy and clinical considerations.Br J Ophthalmol.2003;87:777–781.
16. Lenfeldt N, Koskinen LO, Bergenheim AT, et al..CSF pressure assessed by lumbar puncture agrees with intracranial pressure.Neurology.2007;68:155–158.
17. Pache M, Meyer P.Morphological changes of the retrobulbar optic nerve and its meningeal sheaths in glaucoma.Ophthalmologica.2006;220:393–396.