On 2016 Jan 29, Darko Lavrencic commented:

I have a comment in regard to the following statement in the article: “However, the novel concepts are also challenged mainly by the lack of validated supporting data. For example, Klarica et al. failed to reproduce the historical experiments of Dandy, since no circulation of CSF was found along a plastic cannula introduced into the aqueduct of cats.«

In the article by Dandy and Blackfan, which you cite, it is said »a piece of cotton in a small gelatin capsule … into the aqueduct of Sylvius, where it is deposited. « In the article by Oreskovic, Klarica and Vukic ( here I would like to point out the correct order of authors as opposed to “Klarica, Oreskovic and Vukic” used in the article), which you cite, it is said “A plastic cannula was introduced into the aqueduct of Sylvius through the vermis cerebelli and the outflow of CSF from the cannula was used as the CSF formation and circulation index” (also described in other similar articles by the above authors).

Dandy and Blackfan blocked CSF flow in the aqueduct of Sylvius, while Oreskovic, Klarica and Vukic allowed CSF flow in the aqueduct of Sylvius through cannula. Can we assume that both experimental methods are the same? If the release of freshly actively formatted CSF happens during diastole when brain and choroid plexus shrink and create relative negative pressure in brain ventricles, this could explain hydrocephalus in Dandy and Blackfan experiment. For the comment on Oreskovic, Klarica and Vukic experiment, please see my on-line comment (Lavrencic 2013).

References: Lavrencic, D. D. (2013). “During which phase of cardiac cycle is freshly actively formatted (FAF) cerebrospinal fluid (CSF) released into the brain ventricles: systole or diastole?”. Retrieved 30 April 2013, from http://www.med-lavrencic.si/download/Lavrencic_CSF_release_cardiac_cycle.pdf

On 2014 Sep 18, Thomas Brinker commented:

We greatly appreciate your comments. However, the primary message of our review is that both experimental and clinical in-vivo observations must correspond to morphological and physiological findings. Regarding the perivascular space (PVS) it is unfortunate that, in humans, it is primarily still considered to be an optional rather than physiologically significant space. This view, based on morphological examination of human brain tissue, seems to contradict our mutual observations as well as those of others, i.e. the recent findings of the group of Needergard. We have discussed this point in our review and believe that substantial research efforts are warranted to clarify whether the PVS in humans is functionally significant.

On 2014 Sep 15, Andrew Tarnaris commented:

Corresponding author: Andrew Tarnaris University Hospitals Birmingham Foundation NHS Trust Department of Neurosurgery Queen Elizabeth Medical Centre, Birmingham B15 2TH, United Kingdom.

Email: andrewtarnaris@gmail.com

I have read with interest the review article by Brinker et al. titled "A new look at cerebrospinal fluid circulation" published in Fluids Barriers CNS, 2014 May. The authors discuss key developments regarding cerebral cerebrospinal fluid (CSF) circulation including of production and absorption touching particularly among others the Virchow-Robin space (VRS) circulation.

The significance of VRS in hydrocephalus in general has not been thus far well investigated [1]. Our group first attempted to examine the significance of VRS circulation in idiopathic normal pressure hydrocephalus (iNPH), and in particular investigate whether they could represent a surrogate imaging marker for coexisitng microvascular disease which is known to co-exist in a subset of patients with iNPH [2]. In that preliminary study we concluded that there may be a higher incidence of VRS in patients with iNPH, when compared with normal patients of similar age, however we could not prove with that initial study that there was any correlation with microvascular co-morbidities. We suggested that our data should be followed in a larger set of patients.

We thus followed with a second study that was first presented in Hydrocephalus 2012 in Kyoto Japan entitled “In vivo study of the relationship of CSF dynamics and Virchow-Robin spaces in idiopathic normal pressure hydrocephalus “ (1OS-A2-05). We presented data from 17 patients with a diagnosis of iNPH and correlated the frequency of VRS with physiological data from lumbar infusion studies. Lumbar infusion studies can give unique information about the state of CSF dynamics in an individual. In summary we noted a lower compensatory reserve being associated with more intense perivascular CSF absorption, that resulting in a decrease in global outflow resistance. In that larger study (data submitted elsewhere) we confirmed that the incidence of VRS does not differ in normal population with the same risk factors for microvascular disease and proposed that VRS in iNPH may have a different pathophysiological origin representing impaired CSF circulation [3].

We are glad that the concept of our previous work is now acknowledged in this excellent review and hope that other groups will investigate the role of VRS in iNPH or hydrocephalus in general with modern imaging or by employing other experimental models.

References

[1] Gideon P, Thomsen C, Gjerris F, Sørensen PS, Henriksen O. Increased self-diffusion of brain water in hydrocephalus measured by MR imaging. Acta Radiologica. 1994;35(6):514-9.

[2] Tarnaris A, Tamangani J, Fayeye O, Kombogiorgas D, Murphy H, Gan YC, et al. Virchow-Robin Spaces in Idiopathic Normal Pressure Hydrocephalus: A Surrogate Imaging Marker for Coexisting Microvascular Disease? Hydrocephalus.33-7.

[3] W.A. Mohamed, A. Tarnaris, H. Murphy, M. Csoznyka, Flint G. In vivo study of the relationship of CSF dynamics and Virchow – Robin spaces in idiopathic normal pressure hydrocephalus. Society of British Neurological Surgeons; 2012 October 2012; Leeds: British Journal of Neurosurgery; 2012. p. 596-629.

On 2014 Sep 15, Andrew Tarnaris commented:

Corresponding author: Andrew Tarnaris University Hospitals Birmingham Foundation NHS Trust Department of Neurosurgery Queen Elizabeth Medical Centre, Birmingham B15 2TH, United Kingdom.

Email: andrewtarnaris@gmail.com

I have read with interest the review article by Brinker et al. titled "A new look at cerebrospinal fluid circulation" published in Fluids Barriers CNS, 2014 May. The authors discuss key developments regarding cerebral cerebrospinal fluid (CSF) circulation including of production and absorption touching particularly among others the Virchow-Robin space (VRS) circulation.

The significance of VRS in hydrocephalus in general has not been thus far well investigated [1]. Our group first attempted to examine the significance of VRS circulation in idiopathic normal pressure hydrocephalus (iNPH), and in particular investigate whether they could represent a surrogate imaging marker for coexisitng microvascular disease which is known to co-exist in a subset of patients with iNPH [2]. In that preliminary study we concluded that there may be a higher incidence of VRS in patients with iNPH, when compared with normal patients of similar age, however we could not prove with that initial study that there was any correlation with microvascular co-morbidities. We suggested that our data should be followed in a larger set of patients.

We thus followed with a second study that was first presented in Hydrocephalus 2012 in Kyoto Japan entitled “In vivo study of the relationship of CSF dynamics and Virchow-Robin spaces in idiopathic normal pressure hydrocephalus “ (1OS-A2-05). We presented data from 17 patients with a diagnosis of iNPH and correlated the frequency of VRS with physiological data from lumbar infusion studies. Lumbar infusion studies can give unique information about the state of CSF dynamics in an individual. In summary we noted a lower compensatory reserve being associated with more intense perivascular CSF absorption, that resulting in a decrease in global outflow resistance. In that larger study (data submitted elsewhere) we confirmed that the incidence of VRS does not differ in normal population with the same risk factors for microvascular disease and proposed that VRS in iNPH may have a different pathophysiological origin representing impaired CSF circulation [3].

We are glad that the concept of our previous work is now acknowledged in this excellent review and hope that other groups will investigate the role of VRS in iNPH or hydrocephalus in general with modern imaging or by employing other experimental models.

References

[1] Gideon P, Thomsen C, Gjerris F, Sørensen PS, Henriksen O. Increased self-diffusion of brain water in hydrocephalus measured by MR imaging. Acta Radiologica. 1994;35(6):514-9.

[2] Tarnaris A, Tamangani J, Fayeye O, Kombogiorgas D, Murphy H, Gan YC, et al. Virchow-Robin Spaces in Idiopathic Normal Pressure Hydrocephalus: A Surrogate Imaging Marker for Coexisting Microvascular Disease? Hydrocephalus.33-7.

[3] W.A. Mohamed, A. Tarnaris, H. Murphy, M. Csoznyka, Flint G. In vivo study of the relationship of CSF dynamics and Virchow – Robin spaces in idiopathic normal pressure hydrocephalus. Society of British Neurological Surgeons; 2012 October 2012; Leeds: British Journal of Neurosurgery; 2012. p. 596-629.

On 2016 Jan 29, Darko Lavrencic commented:

I have a comment in regard to the following statement in the article: “However, the novel concepts are also challenged mainly by the lack of validated supporting data. For example, Klarica et al. failed to reproduce the historical experiments of Dandy, since no circulation of CSF was found along a plastic cannula introduced into the aqueduct of cats.«

In the article by Dandy and Blackfan, which you cite, it is said »a piece of cotton in a small gelatin capsule … into the aqueduct of Sylvius, where it is deposited. « In the article by Oreskovic, Klarica and Vukic ( here I would like to point out the correct order of authors as opposed to “Klarica, Oreskovic and Vukic” used in the article), which you cite, it is said “A plastic cannula was introduced into the aqueduct of Sylvius through the vermis cerebelli and the outflow of CSF from the cannula was used as the CSF formation and circulation index” (also described in other similar articles by the above authors).

Dandy and Blackfan blocked CSF flow in the aqueduct of Sylvius, while Oreskovic, Klarica and Vukic allowed CSF flow in the aqueduct of Sylvius through cannula. Can we assume that both experimental methods are the same? If the release of freshly actively formatted CSF happens during diastole when brain and choroid plexus shrink and create relative negative pressure in brain ventricles, this could explain hydrocephalus in Dandy and Blackfan experiment. For the comment on Oreskovic, Klarica and Vukic experiment, please see my on-line comment (Lavrencic 2013).

References: Lavrencic, D. D. (2013). “During which phase of cardiac cycle is freshly actively formatted (FAF) cerebrospinal fluid (CSF) released into the brain ventricles: systole or diastole?”. Retrieved 30 April 2013, from http://www.med-lavrencic.si/download/Lavrencic_CSF_release_cardiac_cycle.pdf