Reader response: Idiopathic intracranial hypertension: The veno glymphatic connections
RobertoDe Simone, Neurologist, Headache Centre, Reproductive Sciences and Odontostomatology, University of Naples Federico II (Naples, Italy)
AngeloRanieri, Neurologist, Division of Neurology and Stroke Unit, Hospital Antonio Cardarelli (Naples, Italy)
Published October 01, 2018
We read the interesting idiopathic intracranial hypertension (IIH) pathogenetic Medical Hypothesis by Lenck et al.1 We agree that the lymphatic interstitial/cerebrospinal fluid (ISF/CSF) outflow is increased by intracranial hypertension and may explain part of IIH symptoms. However, the asymptomatic primary impairment of ISF/CSF outflow proposed by the authors—mediated by a putative acquaporine 4 (AQP4) dysfunction at the vascular arachnoid granulations (VAG) interface with the dural sinuses and followed by the secondary sinus stenosis with symptomatic shift—is exceedingly weak and possibly misleading. In fact, the AQP4-glymphatic existence as a convective vs diffusive ISF/CSF outflow route has been very recently questioned.2 ISF/CSF containing intraventricular administered tracers do not drain through venous sinus, as proposed, but through nasal lymphatic.3 The VAG are very common in subjects without intracranial vascular pathology,4 while IIH is rare. The sinus wall should bear CSF pressure much higher than that possibly associated with an asymptomatic stage of lymphatic dysfunction.5 Finally, after sinus stenting, the intracranial pressure returns to fully physiologic values in responders.6 Therefore, the hypothesis of an asymptomatic primary CSF hypertension by glymphatic impairment leading to a secondary symptomatic sinus stenosis is highly unlikely.
Lenck S, Radovanovic I, Nicholson P, et al. Idiopathic intracranial hypertension: The veno glymphatic connections. Neurology 2018;91:515-522.
Abbott NJ, Pizzo ME, Preston JE, et al. The role of brain barriers in fluid movement in the CNS: is there a ‘glymphatic’ system? Acta Neuropathol 2018;135:387-407.
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.
Gailloud P, Muster M, Khaw N, et al. Anatomic relationship between arachnoid granulations in the transverse sinus and the termination of the vein of Labbe: an angiographic study. Neuroradiology 2001;43:139-143.
Martins AN, Kobrine AI, Larsen DF. Pressure in the sagittal sinus during intracranial hypertension in man. J Neurosurg 1974;40:603-608.
Patsalides A, Oliveira C, Wilcox J, et al. Venous sinus stenting lowers the intracranial pressure in patients with idiopathic intracranial hypertension. J NeuroInterv Surg Epub 2018 Jun 5.
We read the interesting idiopathic intracranial hypertension (IIH) pathogenetic Medical Hypothesis by Lenck et al.1 We agree that the lymphatic interstitial/cerebrospinal fluid (ISF/CSF) outflow is increased by intracranial hypertension and may explain part of IIH symptoms. However, the asymptomatic primary impairment of ISF/CSF outflow proposed by the authors—mediated by a putative acquaporine 4 (AQP4) dysfunction at the vascular arachnoid granulations (VAG) interface with the dural sinuses and followed by the secondary sinus stenosis with symptomatic shift—is exceedingly weak and possibly misleading. In fact, the AQP4-glymphatic existence as a convective vs diffusive ISF/CSF outflow route has been very recently questioned.2 ISF/CSF containing intraventricular administered tracers do not drain through venous sinus, as proposed, but through nasal lymphatic.3 The VAG are very common in subjects without intracranial vascular pathology,4 while IIH is rare. The sinus wall should bear CSF pressure much higher than that possibly associated with an asymptomatic stage of lymphatic dysfunction.5 Finally, after sinus stenting, the intracranial pressure returns to fully physiologic values in responders.6 Therefore, the hypothesis of an asymptomatic primary CSF hypertension by glymphatic impairment leading to a secondary symptomatic sinus stenosis is highly unlikely.
For disclosures, please contact the editorial office at journal@neurology.org.