Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on sleep in brain health

LIVE: Thursday 2nd May 2024, 18:00-19:30 (CEST)

Quality sleep is essential for health. But what happens to our brains when sleep patterns are disturbed? Join our experts to explore the interplay between sleep disruption and neurological diseases, and the questions that you need to be asking your patients to help you prevent the harmful effects of sleep deprivation.
ADVANCED SEARCH
Log in
Top
Neuroradiology
Published in: Neuroradiology 2/2015

01-02-2015 | Continuing Education

Pathways of cerebrospinal fluid outflow: a deeper understanding of resorption

Authors: Long Chen, Gavin Elias, Marina P. Yostos, Bojan Stimec, Jean Fasel, Kieran Murphy

Published in: Neuroradiology | Issue 2/2015

Login to get access

Abstract

Introduction

Cerebrospinal fluid (CSF) absorption has long been held to predominantly entail drainage into the venous outflow system via the intracranial arachnoid granulations. Newer data suggest pathways involving spinal arachnoid granulations and lymphatic channels may also make substantial contributions to CSF outflow.

Methods

The putative major CSF outflow pathways and their proportionate contribution to CSF absorption were reviewed in this article.

Results

CSF is absorbed and drained in bulk not just through cerebral arachnoid granulations (CAG) but also through spinal arachnoid granulations (SAG) and a lymphatic pathway involving egress through cranial and spinal nerve sheaths. The proportions of CSF that efflux through each of these major pathways have yet to be determined with any certainty in humans, though existing evidence (the majority of which is derived from animal studies) suggests that lymphatic pathways may account for up to 50 % of CSF outflow—presumably leaving the CAG and SAG to process the balance.

Conclusion

Knowledge of the CSF pathways holds implications for our ability to understand, prognose, and even treat diseases related to CSF circulation and so is a matter of considerable relevance to neuroradiology and neurology.
Literature
1.
Kapoor KG, Katz SE, Grzybowski DM, Lubow M (2008) Cerebrospinal fluid outflow: an evolving perspective. Brain Res Bull 77:327–334CrossRefPubMed
2.
Oreskovic D, Klarica M (2010) The formation of cerebrospinal fluid: nearly a hundred years of interpretations and misinterpretations. Brain Res Rev 64:241–262CrossRefPubMed
3.
Brunori A, Vagnozzi R, Giuffre R (1993) Antonio Pacchioni (1665–1726): early studies of the dura mater. J Neurosurg 78:515–518CrossRefPubMed
4.
Galarza M (2002) Evidence of the subcommissural organ in humans and its association with hydrocephalus. Neurosurg Rev 25:205–215CrossRefPubMed
5.
6.
Gomez DG, DiBenedetto AT, Pavese AM, Firpo A, Hershan DB, Potts DG (1982) Development of arachnoid villi and granulations in man. Acta Anat (Basel) 111:247–258
7.
8.
Johnston M, Papaiconomou C (2002) Cerebrospinal fluid transport: a lymphatic perspective. News Physiol Sci 17:227–230PubMed
9.
Weed LH (1914) Studies on cerebro-spinal fluid. No. II: the theories of drainage of cerebro-spinal fluid with an analysis of the methods of investigation. J Med Res 31:21–49PubMedCentralPubMed
10.
D’Avella D, Cicciarello R, Albiero F, Andrioli G (1983) Scanning electron microscope study of human arachnoid villi. J Neurosurg 59:620–626CrossRefPubMed
11.
Yamashima T (1986) Ultrastructural study of the final cerebrospinal fluid pathway in human arachnoid villi. Brain Res 384:68–76CrossRefPubMed
12.
Kida S, Yamashima T, Kubota T, Ito H, Yamamoto S (1988) A light and electron microscopic and immunohistochemical study of human arachnoid villi. J Neurosurg 69:429–435CrossRefPubMed
13.
Ohta K, Inokuchi T, Hayashida Y, Mizukami T, Yoshida T, Kawahara T (2002) Regional diminution of von Willebrand factor expression on the endothelial covering arachnoid granulations of human, monkey and dog brain. Kurume Med J 49:177–183CrossRefPubMed
14.
Welch K, Pollay M (1961) Perfusion of particles through arachnoid villi of the monkey. Am J Physiol 201:651–654PubMed
15.
16.
Tripathi RC (1977) The functional morphology of the outflow systems of ocular and cerebrospinal fluids. Exp Eye Res 25(Suppl):65–116CrossRefPubMed
17.
Grzybowski DM, Holman DW, Katz SE, Lubow M (2006) In vitro model of cerebrospinal fluid outflow through human arachnoid granulations. Invest Ophthalmol Vis Sci 47:3664–3672CrossRefPubMed
18.
Glimcher SA, Holman DW, Lubow M, Grzybowski DM (2008) Ex vivo model of cerebrospinal fluid outflow across human arachnoid granulations. Invest Ophthalmol Vis Sci 49:4721–4728CrossRefPubMed
19.
Brierley JB, Field EJ (1948) The connexions of the spinal sub-arachnoid space with the lymphatic system. J Anat 82:153–166PubMedCentral
20.
Welch K, Pollay M (1963) The spinal arachnoid villi of the monkeys Cercopithecus aethiops sabaeus and Macaca irus. Anat Rec 145:43–48CrossRefPubMed
21.
Shantha TR, Evans JA (1972) The relationship of epidural anesthesia to neural membranes and arachnoid villi. Anesthesiology 37:543–557CrossRefPubMed
22.
Kido DK, Gomez DG, Pavese AM Jr, Potts DG (1976) Human spinal arachnoid villi and granulations. Neuroradiology 11:221–228CrossRefPubMed
23.
Miura M, Kato S, von Ludinghausen M (1998) Lymphatic drainage of the cerebrospinal fluid from monkey spinal meninges with special reference to the distribution of the epidural lymphatics. Arch Histol Cytol 61:277–286CrossRefPubMed
24.
Tubbs RS, Hansasuta A, Stetler W, Kelly DR, Blevins D, Humphrey R, Chua GD, Shoja MM, Loukas M, Oakes WJ (2007) Human spinal arachnoid villi revisited: immunohistological study and review of the literature. J Neurosurg Spine 7:328–331CrossRefPubMed
25.
Seyfert S, Koch HC, Kunzmann V (2003) Conditions of iodine contrast transfer from lumbosacral CSF to blood. J Neurol Sci 206:85–90CrossRefPubMed
26.
Biceroglu H, Albayram S, Ogullar S, Hasiloglu ZI, Selcuk H, Yuksel O, Karaaslan B, Yildiz C, Kiris A (2012) Direct venous spinal reabsorption of cerebrospinal fluid: a new concept with serial magnetic resonance cisternography in rabbits. J Neurosurg Spine 16:394–401CrossRefPubMed
27.
Bozanovic-Sosic R, Mollanji R, Johnston MG (2001) Spinal and cranial contributions to total cerebrospinal fluid transport. Am J Physiol Regul Integr Comp Physiol 281:R909–916PubMed
28.
Kelkenberg U, von Rautenfeld DB, Brinker T, Hans VH (2001) Chicken arachnoid granulations: a new model for cerebrospinal fluid absorption in man. Neuroreport 12:553–557CrossRefPubMed
29.
Koh L, Zakharov A, Johnston M (2005) Integration of the subarachnoid space and lymphatics: is it time to embrace a new concept of cerebrospinal fluid absorption? Cerebrospinal Fluid Res 2:6CrossRefPubMedCentralPubMed
30.
Svane-Knudsen V (1958) Resorption of the cerebro-spinal fluid in guinea-pig; an experimental study. Acta Otolaryngol 49:240–251CrossRefPubMed
31.
Czerniawska A (1970) Experimental investigations on the penetration of 198Au from nasal mucous membrane into cerebrospinal fluid. Acta Otolaryngol 70:58–61CrossRefPubMed
32.
Arnold W, Nitze HR, Ritter R, von Ilberg C, Ganzer U (1972) Qualitative study of the connections of the subarachnoid space with the lymphatic system of the head and neck. Acta Otolaryngol 74:411–424CrossRefPubMed
33.
Pile-Spellman JM, McKusick KA, Strauss HW, Cooney J, Taveras JM (1984) Experimental in vivo imaging of the cranial perineural lymphatic pathway. AJNR Am J Neuroradiol 5:539–545PubMed
34.
Kida S, Pantazis A, Weller RO (1993) CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Neuropathol Appl Neurobiol 19:480–488CrossRefPubMed
35.
Boulton M, Young A, Hay J, Armstrong D, Flessner M, Schwartz M, Johnston M (1996) Drainage of CSF through lymphatic pathways and arachnoid villi in sheep: measurement of 125I-albumin clearance. Neuropathol Appl Neurobiol 22:325–333CrossRefPubMed
36.
Mollanji R, Papaiconomou C, Boulton M, Midha R, Johnston M (2001) Comparison of cerebrospinal fluid transport in fetal and adult sheep. Am J Physiol Regul Integr Comp Physiol 281:R1215–1223PubMed
37.
Mollanji R, Bozanovic-Sosic R, Silver I, Li B, Kim C, Midha R, Johnston M (2001) Intracranial pressure accommodation is impaired by blocking pathways leading to extracranial lymphatics. Am J Physiol Regul Integr Comp Physiol 280:R1573–1581PubMed
38.
Mollanji R, Bozanovic-Sosic R, Zakharov A, Makarian L, Johnston MG (2002) Blocking cerebrospinal fluid absorption through the cribriform plate increases resting intracranial pressure. Am J Physiol Regul Integr Comp Physiol 282:R1593–1599PubMed
39.
Silver I, Kim C, Mollanji R, Johnston M (2002) Cerebrospinal fluid outflow resistance in sheep: impact of blocking cerebrospinal fluid transport through the cribriform plate. Neuropathol Appl Neurobiol 28:67–74CrossRefPubMed
40.
Zakharov A, Papaiconomou C, Djenic J, Midha R, Johnston M (2003) Lymphatic cerebrospinal fluid absorption pathways in neonatal sheep revealed by subarachnoid injection of Microfil. Neuropathol Appl Neurobiol 29:563–573CrossRefPubMed
41.
Johnston M, Zakharov A, Papaiconomou C, Salmasi G, Armstrong D (2004) Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species. Cerebrospinal Fluid Res 1:2CrossRefPubMedCentralPubMed
42.
Mathieu E, Gupta N, Macdonald RL, Ai J, Yucel YH (2013) In vivo imaging of lymphatic drainage of cerebrospinal fluid in mouse. Fluids Barriers CNS 10:35CrossRefPubMedCentralPubMed
43.
Lowhagen P, Johansson BB, Nordborg C (1994) The nasal route of cerebrospinal fluid drainage in man. A light-microscope study. Neuropathol Appl Neurobiol 20:543–550CrossRefPubMed
44.
Jackson RT, Tigges J, Arnold W (1979) Subarachnoid space of the CNS, nasal mucosa, and lymphatic system. Arch Otolaryngol 105:180–184CrossRefPubMed
45.
Voelz K, Kondziella D, von Rautenfeld DB, Brinker T, Ludemann W (2007) A ferritin tracer study of compensatory spinal CSF outflow pathways in kaolin-induced hydrocephalus. Acta Neuropathol 113:569–575CrossRefPubMed
46.
Faulhauer K, Donauer E (1985) Experimental hydrocephalus and hydrosyringomyelia in the cat. Radiological findings Acta Neurochir (Wien) 74:72–80CrossRef
47.
Luedemann W, Kondziella D, Tienken K, Klinge P, Brinker T, Berens von Rautenfeld D (2002) Spinal cerebrospinal fluid pathways and their significance for the compensation of kaolin-hydrocephalus. Acta Neurochir Suppl 81:271–273PubMed
48.
Brinker T, Ludemann W, von Rautenfeld DB, Brassel F, Becker H, Samii M (1997) Breakdown of the meningeal barrier surrounding the intraorbital optic nerve after experimental subarachnoid hemorrhage. Am J Ophthalmol 124:373–380CrossRefPubMed
49.
Iliff JJ, Lee H, Yu M, Feng T, Logan J, Nedergaard M, Benveniste H (2013) Brain-wide pathway for waste clearance captured by contrast-enhanced MRI. J Clin Invest 123:1299–1309CrossRefPubMedCentralPubMed
50.
51.
Boulton M, Flessner M, Armstrong D, Hay J, Johnston M (1998) Determination of volumetric cerebrospinal fluid absorption into extracranial lymphatics in sheep. Am J Physiol 274:R88–96PubMed
52.
Boulton M, Armstrong D, Flessner M, Hay J, Szalai JP, Johnston M (1998) Raised intracranial pressure increases CSF drainage through arachnoid villi and extracranial lymphatics. Am J Physiol 275:R889–896PubMed
53.
Boulton M, Flessner M, Armstrong D, Mohamed R, Hay J, Johnston M (1999) Contribution of extracranial lymphatics and arachnoid villi to the clearance of a CSF tracer in the rat. Am J Physiol 276:R818–823PubMed
54.
Johanson CE, Duncan JA 3rd, Klinge PM, Brinker T, Stopa EG, Silverberg GD (2008) Multiplicity of cerebrospinal fluid functions: new challenges in health and disease. Cerebrospinal Fluid Res 5:10CrossRefPubMedCentralPubMed
55.
Koh L, Zakharov A, Nagra G, Armstrong D, Friendship R, Johnston M (2006) Development of cerebrospinal fluid absorption sites in the pig and rat: connections between the subarachnoid space and lymphatic vessels in the olfactory turbinates. Anat Embryol (Berl) 211:335–344CrossRef
56.
Papaiconomou C, Bozanovic-Sosic R, Zakharov A, Johnston M (2002) Does neonatal cerebrospinal fluid absorption occur via arachnoid projections or extracranial lymphatics? Am J Physiol Regul Integr Comp Physiol 283:R869–876PubMed
57.
Jones HC (1985) Cerebrospinal fluid pressure and resistance to absorption during development in normal and hydrocephalic mutant mice. Exp Neurol 90:162–172CrossRefPubMed
58.
Nagra G, Johnston MG (2007) Impact of ageing on lymphatic cerebrospinal fluid absorption in the rat. Neuropathol Appl Neurobiol 33:684–691CrossRefPubMed
59.
Marmarou A, Shulman K, LaMorgese J (1975) Compartmental analysis of compliance and outflow resistance of the cerebrospinal fluid system. J Neurosurg 43:523–534CrossRefPubMed
60.
Edsbagge M, Tisell M, Jacobsson L, Wikkelso C (2004) Spinal CSF absorption in healthy individuals. Am J Physiol Regul Integr Comp Physiol 287:R1450–1455CrossRefPubMed
61.
Sakka L, Coll G, Chazal J (2011) Anatomy and physiology of cerebrospinal fluid. Eur Ann Otorhinolaryngol, Head Neck Dis 128:309–316CrossRef
62.
Rexed B (1947) Arachnoidal proliferations with cyst formation in human spinal nerve roots at their entry into the intervertebral foramina; preliminary report. J Neurosurg 4:414–421CrossRefPubMed
63.
Naruse I, Ueta E (2002) Hydrocephalus manifestation in the genetic polydactyly/arhinencephaly mouse (Pdn/Pdn). Congenit Anom (Kyoto) 42:27–31CrossRef
64.
Linninger AA, Sweetman B, Penn R (2009) Normal and hydrocephalic brain dynamics: the role of reduced cerebrospinal fluid reabsorption in ventricular enlargement. Ann Biomed Eng 37:1434–1447CrossRefPubMed
65.
Calcagni ML, Lavalle M, Mangiola A, Indovina L, Leccisotti L, De Bonis P, Marra C, Pelliccioni A, Anile C, Giordano A (2012) Early evaluation of cerebral metabolic rate of glucose (CMRglu) with 18F-FDG PET/CT and clinical assessment in idiopathic normal pressure hydrocephalus (INPH) patients before and after ventricular shunt placement: preliminary experience. Eur J Nucl Med Mol Imaging 39:236–241CrossRefPubMed
66.
Reiss-Zimmermann M, Scheel M, Dengl M, Preuss M, Fritzsch D, Hoffmann KT (2013) The influence of lumbar spinal drainage on diffusion parameters in patients with suspected normal pressure hydrocephalus using 3T MRI. Acta Radiol 55:622–630CrossRefPubMed
Metadata
Title
Pathways of cerebrospinal fluid outflow: a deeper understanding of resorption
Authors
Long Chen
Gavin Elias
Marina P. Yostos
Bojan Stimec
Jean Fasel
Kieran Murphy
Publication date
01-02-2015
Publisher
Springer Berlin Heidelberg
Published in
Neuroradiology / Issue 2/2015
Print ISSN: 0028-3940
Electronic ISSN: 1432-1920
DOI
https://doi.org/10.1007/s00234-014-1461-9

Other articles of this Issue 2/2015

Neuroradiology 2/2015 Go to the issue

Diagnostic Neuroradiology

Infarct volume predicts critical care needs in stroke patients treated with intravenous thrombolysis

Interventional Neuroradiology

Microembolic signal monitoring and the prediction of thromboembolic events following coil embolization of unruptured intracranial aneurysms: diffusion-weighted imaging correlation

Diagnostic Neuroradiology

Whole-brain 320-detector row dynamic volume CT perfusion detected crossed cerebellar diaschisis after spontaneous intracerebral hemorrhage

Diagnostic Neuroradiology

Potential of 80-kV high-resolution cone-beam CT imaging combined with an optimized protocol for neurological surgery

Interventional Neuroradiology

Cranial Doppler ultrasound in Vein of Galen malformation

Interventional Neuroradiology

Ultra-early versus delayed coil treatment for ruptured poor-grade aneurysm