StephanieLenck, Interventional Neuroradiologist, Department of Neuroradiolgy, Groupe Hospitalier Pitié-Salpêtrière, Université Paris Sorbonne (Paris, France)
PatrickNicholson, Interventional Neuroradiologist, Department of Medical Imaging, Toronto Western Hospital, University of Toronto (Toronto, Canada)
Published October 14, 2018
We thank Drs. De Simone and Ranieri for their comments and interest in our paper.1
Our hypothesis doesn't support a dysfunction of aquaporin 4 (AQP-4) in idiopathic intracranial hypertension (IIH); rather, an unknown type of AQP (e.g., aquaglyceroporin) may be involved at the venodural junction and may trigger the hydrodynamic cascade of IIH. We agree that a direct discharge of glymphatic fluid into the venous blood has not been documented in studies of CSF hydrodynamics;2 however, the techniques used to demonstrate the existence of the glymphatic and lymphatic systems of the brain were not able to detect any venous CSF outflow, leading some to question even the existence of a venous CSF outflow pathway in the brain.3 Based on our clinical experience (i.e., cerebral venous thrombosis) and on previous experimental studies, we feel that a direct discharge of glymphatic fluid into venous blood seems highly likely.4
It may seem hazardous to extrapolate the physiology of CSF excretion from animals to humans, since the venous physiology and anatomy of quadrupedal animals are very different from those of bipedal humans.5 We agree that the discovery of an arachnoid granulation (AG) may be incidental and that the prevalence of AG in the lumen of the sinuses increase with age; however, pathologic and radiologic studies have described a specific type of AG, mostly observed in the transverse sinus and particularly at the junction between the vein of Labbé and the transverse sinus (e.g., lateral sinus stenoses in IIH). These granulations are centered on a vein and associated with the point of entry of a cortical vein into the dural sinus. We named them "vascular AGs" to differentiate from avascular granulations which allow the pressure-dependant transport of CSF from the subarachnoid space to the venous blood of the dural sinuses. These vascular AGs may allow a connection between the perivascular spaces of large cortical veins to the venous blood of the dural sinuses and may be involved in the discharge of interstitial fluid (CSF) from the glymphatic system to the venous blood of the dural vessels.6
Several arguments support the hypothesis that extrinsic stenoses are caused by the compression of the lateral sinus by the congested brain and CSF (and not by the increased intracranial pressure [ICP]), including the radiologic aspect of such stenoses on MRI, the propensity of such stenoses to reoccur outside the stented portion of the sinus, the fact that the radial force of the stent is usually enough to reopen the sinus with no need for balloon angioplasty, and their disappearance after CSF removal.7,8 We agree that the venous sinus stenosis is the main precipitating factor in IIH symptoms since it makes the venous outflow pathway ineffective for the glymphatic reabsorption and the direct reabsorption, which aims to balance the ICP. Stent placement allows reestablishment of the direct reabsorption of the CSF from the subarachnoid space to the venous blood of the dural sinuses, thus regulating the ICP and resolving IIH symptoms.
Lenck S, Radovanovic I, Nicholson P, et al. Idiopathic intracranial hypertension: The veno glymphatic connections. Neurology 2018;91:515–522.
Iliff JJ, Wang M, Liao Y, et al. A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β. Sci Transl Med 2012;4:147ra111.
Murtha LA, Yang Q, Parsons MW, et al. Cerebrospinal fluid is drained primarily via the spinal canal and olfactory route in young and aged spontaneously hypertensive rats. Fluids Barriers CNS 2014;11:12.
Boulton M, Young A, Hay J, et al. Drainage of CSF through lymphatic pathways and arachnoid villi in sheep: measurement of 125I-albumin clearance. Neuropathol Appl Neurobiol 1996;22:325–333.
Aurboonyawat T, Suthipongchai S, Pereira V, Ozanne A, Lasjaunias P. Patterns of cranial venous system from the comparative anatomy in vertebrates. Part I, introduction and the dorsal venous system. Interv Neuroradiol 2007;13:335–344.
Trimble CR, Harnsberger HR, Castillo M, Brant-Zawadzki M, Osborn AG. "Giant" arachnoid granulations just like CSF?: NOT!! AJNR Am J Neuroradiol 2010;31:1724–1728.
Baryshnik DB, Farb RI. Changes in the appearance of venous sinuses after treatment of disordered intracranial pressure. Neurology 2004;62:1445–1446.
Lenck S, Vallée F, Labeyrie MA, et al. Stenting of the Lateral Sinus in Idiopathic Intracranial Hypertension According to the Type of Stenosis. Neurosurgery 2017;80:393–400.
We thank Drs. De Simone and Ranieri for their comments and interest in our paper.1
Our hypothesis doesn't support a dysfunction of aquaporin 4 (AQP-4) in idiopathic intracranial hypertension (IIH); rather, an unknown type of AQP (e.g., aquaglyceroporin) may be involved at the venodural junction and may trigger the hydrodynamic cascade of IIH. We agree that a direct discharge of glymphatic fluid into the venous blood has not been documented in studies of CSF hydrodynamics;2 however, the techniques used to demonstrate the existence of the glymphatic and lymphatic systems of the brain were not able to detect any venous CSF outflow, leading some to question even the existence of a venous CSF outflow pathway in the brain.3 Based on our clinical experience (i.e., cerebral venous thrombosis) and on previous experimental studies, we feel that a direct discharge of glymphatic fluid into venous blood seems highly likely.4
It may seem hazardous to extrapolate the physiology of CSF excretion from animals to humans, since the venous physiology and anatomy of quadrupedal animals are very different from those of bipedal humans.5 We agree that the discovery of an arachnoid granulation (AG) may be incidental and that the prevalence of AG in the lumen of the sinuses increase with age; however, pathologic and radiologic studies have described a specific type of AG, mostly observed in the transverse sinus and particularly at the junction between the vein of Labbé and the transverse sinus (e.g., lateral sinus stenoses in IIH). These granulations are centered on a vein and associated with the point of entry of a cortical vein into the dural sinus. We named them "vascular AGs" to differentiate from avascular granulations which allow the pressure-dependant transport of CSF from the subarachnoid space to the venous blood of the dural sinuses. These vascular AGs may allow a connection between the perivascular spaces of large cortical veins to the venous blood of the dural sinuses and may be involved in the discharge of interstitial fluid (CSF) from the glymphatic system to the venous blood of the dural vessels.6
Several arguments support the hypothesis that extrinsic stenoses are caused by the compression of the lateral sinus by the congested brain and CSF (and not by the increased intracranial pressure [ICP]), including the radiologic aspect of such stenoses on MRI, the propensity of such stenoses to reoccur outside the stented portion of the sinus, the fact that the radial force of the stent is usually enough to reopen the sinus with no need for balloon angioplasty, and their disappearance after CSF removal.7,8 We agree that the venous sinus stenosis is the main precipitating factor in IIH symptoms since it makes the venous outflow pathway ineffective for the glymphatic reabsorption and the direct reabsorption, which aims to balance the ICP. Stent placement allows reestablishment of the direct reabsorption of the CSF from the subarachnoid space to the venous blood of the dural sinuses, thus regulating the ICP and resolving IIH symptoms.
For disclosures, please contact the editorial office at journal@neurology.org.