Correspondence:
Dr.Olivier Balédent, Jules Verne University of Picardie, Amiens, France
January 2004
Questions (Olivier Balédent) and answers (Darko Lavrencic):
Question: I do not know what do you mean by a passive depression?
Answer: Marvin Bergsneider says: "There has been a long-standing debate as to whether the CSF production rate is constant irrespective of intracranial pressure...” [1]. The hypothesis presents CSF formation as dependent on CSF pressure. The CSF pressure directly, without any active regulatory mechanism, therefore, passively, influences the CSF formation, i.e., the higher the CSF pressure the lower the CSF formation.
Question: I do not understand why the pressure of compartment IV is specific (what do you mean by “specific”).
Answer: From a hydrostatic point of view the pressure is transmitted among intracraniovertebral volumes through direct contact, e.g., brain parenchyma and cerebrospinal fluid are separated by pia mater that does not represent a barrier from a hydrostatic point of view. In contrast, the CSF space and volume IV (spinal extradural space and cranial venous sinuses) are separated by dura mater, which is nearly rigid in cranial part (at points compressible, especially transverse-sigmoid sinus joint: see (a)discussion, (b)discussion) and to certain degree elastic in the spinal part, and thus influence the pressure transmission between the two spaces so that dura mater is able to maintain a certain pressure difference between compartment III (CSF space) and compartment IV. That is why this latter mechanism is called specific.
Question: Why do you affirm that the disturbance in compartments always occurs primarily?
Answer: The hypothesis is not dealing with conditions in which just hydrostatic pressure changes are involved, e.g., body posture, scuba diving etc. From a hydrodynamic point of view we must first have a volume change, which would secondarily have a pressure change, when a body remains in the same posture and in a stable environment.
Question: Can you explain how you obtained all your figures, are they taken from literature or are they your own work?
Answer: All figures are my own personal illustration of the presented hypothesis and have never been published anywhere in other literature.
Question: What do you mean by “quality” of arachnoidal villi?
Answer: Arachnoidal villi are the sites of removal. They could be morphologically and functionally altered e.g., inflammation of them could cause decreased CSF removal while their degeneration could cause increased CSF removal.
Question: It is difficult for me to accept the figure which represents the volume III (CSF space), according to Monro-Kellie doctrine and Marmarou pressure-volume variation law, I do not understand why CSF volume decreases, after point A, while at the same time the pressure increases?
Answer: The Monro-Kellie doctrine and the Marmarou pressure-volume variation law say that if you add some new volume into the cranial vault the intracranial pressure would increase e.g., if patient experiences epidural hematoma of five ml, this will increase intracranial pressure by translocation of nearly five ml CSF from cranial to spinal part of CSF space, which is enabled by elastic dural sac. At this point you must turn to Fig.5 presenting volume III (CSF space) as a secondary result of the intracranial pressure change. If the intracranial pressure occurs between point A and point B-high, then the CSF formation at this higher pressure is lower then CSF removal, therefore this dynamic process would cause that the volume III (CSF space) starts to decrease. The decrease of volume III would cause the decrease of CSF pressure until equilibrium between CSF formation and CSF removal re-established. The final result of this dynamic process is that the optimal CSF pressure is re-established where there exists a five ml epidural hematoma and a volume III (CSF space), which is decreased for five ml. Experimentally, the new volume could be added directly (e.g., five ml of artificial CSF) into the CSF space (this could never happen naturally, without invasive medical procedure). The starting CSF volume in this case would be increased for five ml and the above-mentioned dynamic process would decrease it for five ml.
Question: If your figure concerning CSF flow represents the difference between CSF formation and CSF removal flow, the curve will be different (see attached file).
Answer: The CSF flow (per hour) is defined in the hypothesis by the amount of CSF volume transported from sites of CSF formation to sites of CSF removal. This means that e.g., if there is zero CSF removal at very high pressure, there would also be zero CSF flow and the temporary CSF formation could still be present. This temporary CSF formation contributes solely to the increase of CSF volume, but it is not in any case representative of CSF flow, because there is zero CSF volume transport from the sites of CSF formation to the sites of CSF removal. In the opposite situation, e.g., if there is zero CSF formation at very low CSF pressure, then again, there would also be zero CSF flow while the temporary CSF removal could still be present. This temporary CSF removal contributes solely to the decrease of CSF volume, but it is not in any case representative of CSF flow, because there is zero CSF volume transport from the sites of CSF formation to the sites of CSF removal. Thank you for your graph, which accurately represents the dynamic net CSF volume change from another perspective and as new illustration provides better understanding of the hypothesis. Relation between CSF formation and CSF removal depicts positive values as CSF accumulation in CSF space and negative values as CSF depletion in CSF space.
Question: If it is possible for you I would like to study your original paper, what was the revue?
Answer: Original paper was edited and published by myself [2]. It is accessible in the Slovene National and University Library as a book (thesis) published by author with the Catalogue Number II 229751. The printed version on my website includes photocopies of all figures from original paper, the original text being retyped for minor style/language improvements and spelling/grammar corrections, while the subject and presentation of the hypothesis remained unchanged.
1) Bergsneider M. Evolving concepts of cerebrospinal fluid physiology. Neurosurg Clin N Am 2001;12(4):631-8.
2) Lavrencic D. The Intracraniovertebral Volumes, the Cerebrospinal Fluid Flow and the Cerebrospinal Fluid Pressure, Their Homeostasis and Its Physical Regulation. Ljubljana: Darko Lavrencic; 1970.
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Prof. Maria I. Argyropoulou, University of Ioannina, Greece
November 2003
Dear Professor Maria I. Argyropoulou,
In your article [1] you are reporting the measurements of the systolic and the diastolic cerebrospinal fluid (CSF) flow volume at the level of the aqueduct of Sylvius during spontaneous intracranial hypotension (SIH) and after recovery of the patient:
|
During SIH: |
after recovery: |
| Systole: |
0,013 ml/cardiac cycle |
0,039 ml/cardiac cycle |
| Diastole: |
0,011 ml/cardiac cycle |
0,016 ml/cardiac cycle |
I have calculated from your measurements the net caudal CSF flow by subtracting the diastolic flow from the systolic flow per cardiac cycle:
|
During SIH: |
after recovery: |
| Net caudal flow: |
0,002 ml/cardiac cycle |
0,023 ml/cardiac cycle |
In my opinion, the results of the net caudal flow are very important because a 11,5-fold rate difference (0,021 ml/cardiac cycle) occurs between them. Your measurements clearly show that during SIH the CSF flow was very low due to decreased CSF formation that has caused secondary CSF hypovolemia. I would suggest to consider in your case the decreased CSF formation to be, most probably, the primal cause of SIH.
Darko Lavrencic
1) Metafratzi Z, Argyropoulou MI, Mokou-Kanta C, Konitsiotis S, Zikou A, Efremidis SC. Spontaneous intracranial hypotension: morphological findings and CSF flow dynamics studied by MRI. Eur Radiol 2003 Nov
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Prof. Jeffrey S. Kroin, Rush-Presbyterian-Luke's Medical Center, Chicago
January 2003
Dear Professor Jeffrey S.Kroin and Colleagues,
I have read your article [1] with great attention. Your valuable experimental evidence on a rat model is supporting my hypothesis presented on web page http://www.med-lavrencic.si/raziskava.htm and my opinions expressed on web page http://www.med-lavrencic.si/correspondence.htm.
I believe that the intracraniovertebral volumes' homeostatic equilibrium i.e. volumes' balance is relatively stable regardless to different body postures i.e. standing up, lying or hanging with head upside down. The relative hydrostatic pressure difference among CSF pressures and opposite hydrostatic pressures at CSF drainage paths remains relatively constant during different body postures while passively floating CSF formation/removal homeostatic equilibrium along the CSF formation curve supports this stable volumes' balance at the expense of CSF flow: when standing up it is increased and when hanging down it is decreased.
What is your opinion about this?
Darko Lavrencic
1) Kroin JS, Nagalla SK, Buvanendran A, McCarthy RJ, Tuman KJ, Ivankovich AD. The mechanisms of intracranial pressure modulation by epidural blood and other injectates in a postdural puncture rat model.Anesth Analg. 2002 Aug;95(2):423-9
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Prof. Miles G. Johnston, University of Toronto
November 2002
Dear Professor Miles G.Johnston,
I have read the abstract of your article: "Johnston M,Papaiconomou C. Cerebrospinal fluid transport: a lymphatic perspective. News Physiol Sci. 2002 Dec;17:227-30" with great interest. I believe that the classical hypothesis based on CSF drainage exclusively into the cranial venous sinuses (prevailing for three decades) seriously underestimated or even neglected prior evidences of other CSF drainage paths. Robert Elman reported in 1923: "A foreign, non-toxic, isotonic solution, introduced into the sub-arachnoidal space by the replacement of an equal quantity of cerebrospinal fluid, escaped from the cord through arachnoidal, mesothelial cell-nests and made its way into veins outside the cord and possibly also into lymphatic channels in this region" [1]. After the acceptance of the classical hypothesis any new evidences of other CSF drainage paths was completely ignored in textbooks. I believe that other CSF drainage paths allow regular CSF removal at CSF pressures lower than 68 mm H20 (venous hydrostatic pressure in superior sagittal sinus).
What is your opinion about this?
Darko Lavrencic
1) Elman R.Spinal arachnoid granulations with especial reference to cerebrospinal fluid. Johns Hopkins Hosp. Bull. Mar 1923;385 :99-104
Dear Darko Lavrencic,
In terms of CSF absorption, we now believe that the current concepts are incorrect. We believe that the majority of CSF absorption takes place into lymphatic vessels external to the brain and spinal cord. There is considerable experimental evidence that CSF is absorbed from the spinal subarachnoid compartment. The problem with the spinal arachnoid projections is that many of these are not associated with veins. Therefore, their role is unclear. In any event, it looks like the majority of CSF transport occurs into lymphatics at low to moderate CSF pressures. Only at very high pressures, can any case be made for CSF transport into the cranial venous sinuses.
Miles Johnston, Ph.D.
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Cochrane Library review item entitled "Shunting for Normal Pressure Hydrocephalus (NPH)" ( review abstract )
September 2002
D. Lavrencic's comments entitled "A severe complication of shunt"
(see attached file).
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Devin K. Binder, M.D., Ph.D., University of San Francisco
September 2002
Dear Dr.Devin K.Binder and Colleagues,
It was very interesting to read your article "Intrathecal saline infusion in the treatment of obtundation associated with spontaneous intracranial hypotension: technical case report. Neurosurgery. 2002 Sep;51(3):830-7.", specifically where you conclude that for life threatening low ICP syndrome the therapy of choice is intrathecal infusion as it is proposed in literature [1,2,3]. You find epidural blood patching not effective in such case as it was already previously reported [2]. Did you consider applying artificial CSF infusion instead of saline one? What was the CSF pressure at the time you have applied epidural blood patching after the recovery of the patient?
Darko Lavrencic
1) Zlotnik EI, Stolkarts IZ.[Cerebrospinal fluid hypotension after brain surgery]Zh Vopr Neirokhir Im N N Burdenko. 1984 Mar-Apr;(2):48-53.
2) Pleasure SJ, Abosch A, Friedman J, Ko NU, Barbaro N, Dillon W, Fishman RA, Poncelet AN. Spontaneous intracranial hypotension resulting in stupor caused by diencephalic compression.Neurology. 1998 Jun;50(6):1854-7.
3) D.Lavrencic's comments (review comments ) and response from the lead author of Cochrane Library review item entitled "Epidural blood patching for preventing and treating post-dural puncture headache" ( review abstract ).
July - August 2002.
Dear Darko Lavrencic,
I am of the opinion that this condition is more common than most people think, I have seen at least two people since this report that meet the diagnosis. You make an interesting point about artificial CSF solution (ACSF) rather than saline infusion. As you probably know, normal saline solution is slightly acidic (pH about 5) and may be painful to an awake patient. To answer your second question, the ICP remained normal after epidural blood patch (10-18 cm H2O).
Devin K. Binder, M.D., Ph.D.
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Cochrane Library review item entitled "Epidural blood patching for preventing and treating post-dural puncture headache" ( review abstract )
July, August 2002
D. Lavrencic's comments and response from the lead author of Cochrane Library review (review comments )
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Dr.Wouter I. Schievink, University of California, Irvine
April 2002
Dear Dr. Wouter I.Schievink,
It was very interesting to read your article: "Spontaneous Spinal Cerebrospinal Fluid Leaks: A Review. Neurosurg Focus 9(1), 2000" and specifically where you say: "Not infrequently, a "dry tap" is initially encountered, and CSF can only be obtained with a Valsalva maneuver, placing the patient in an upright position, or with aspiration by using a syringe. A sucking noise has also been described as the stylet is withdrawn and air enters the subarachnoid space, indicating sub atmospheric pressure".
I wonder how CSF leakage could cause negative pressure in entire CSF space and how it could take place from lower to higher hydrostatic pressure. This is not compatible with basic physical hydrodynamic law that liquid is moving only from higher to lower pressure. As you mention there can be a sucking noise as the stylet is withdrawn, indicating that an anti-leaking i.e. reverse leaking is taking place.
According to the probable mechanism presented on my website www.med-lavrencic.si the regular CSF removal is taking place during negative CSF pressure. Oncotic pressure difference between CSF and venous blood in spinal extradural veins plexuses could be the only possible force that could create a negative pressure in entire CSF space.
Darko Lavrencic
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Dr. Noam Alperin, University of Illinois at Chicago
March 2002
Dear Dr. Noam Alperin,
I have read some of your articles about MRI in connection with CSF hydrodynamics. I would like to inform you of a CSF hydrodynamic mechanism I suggest on my website www.med-lavrencic.si. Have you measured CSF flow with MRI technique on patients with intracranial hypotension hypovolemic syndrome or obstructive hydrocephalus?
Darko Lavrencic
Darko Lavrencic,
Please email me a brief summary of the mechanism you are referring to.
Dr. Alperin
Dr. Alperin,
Fig.5 shows basic relations between intracranial pressure (as independent variable) and CSF formation, CSF removal, volume of CSF space and CSF flow (as dependent variables). From B-low to B-high is physiological phase of homeostasis that maintains homeostatic equilibrium (optimal ICP, formation, removal, CSF volume and flow). In pathophysiological phase beyond B-high the relation between formation and removal is reverse (formation higher than removal) so the final result is self-sustaining state of maximal ICP, maximal volume of CSF space and zero flow (various clinical pictures with high ICP around 30 mmHg). In pathophysiological phase below B-low the removal is higher than formation so the final result is minimal CSF pressure with minimal CSF space volume and zero flow (clinical picture: intracranial hypotension hypovolemic syndrome). Masserman based techniques and perfusion based techniques are inappropriate as far as measuring formation, removal, volumes and flow in pathophysiological phases are concerned. I see MRI based techniques as the only optional technique to analyse what is really happening in pathophysiological phases where we haven't got answers to the opened questions yet.
Darko Lavrencic
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Prof. Gerald D. Silverberg, University Medical Center Stanford
February, March 2002
Dear Professor Gerald D. Silverberg,
It was very interesting to read your article: "The cerebrospinal fluid production rate is reduced in dementia of the Alzheimer's type. Neurology 2001 Nov 27;57(10):1763-". Your results indicate that CSF production is markedly reduced in patients with AD. Please see on my website www.med-lavrencic.si a possible homeostatic mechanism. What was the difference between CSF pressure of both groups ?
Darko Lavrencic
Dear Darko Lavrencic,
There was no difference in opening pressure or measured compliance between the two groups. The data was sent in response to a criticism of the article by Dr. Fishman and should be appearing shortly in Neurology.
GD Silverberg
Dear Professor Gerald Silverberg,
Regarding your response "On-line Post-Publication Peer Review. Neurology. February 18, 2002", I specifically agree with your statements: "Unfortunately, there is no good way to control for CSF absorption variations with any measurement technique", "We also agree with Dr.Fishman that a less invasive and less error-prone measurement method for CSF production rates would be important (Dr.Fishman: "sorely needed"). To that end we are working on an MRI approach".
Darko Lavrencic
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Prof. David N. Levine, New York University School of Medicine
December 2001
Dear Professor David N. Levine,
It was very interesting to read your article "The pathophysiology of lumbar puncture headache. J Neurol Sci 2001 Nov 15;192(1-2):1-8". There are many questions opened. I am sending to you a hypothesis of probable mechanism, which could explain some questions. According to the hypothesis there is no "CSF leaking" but regular CSF removal during intracranial hypotension (hypovolemic) syndrome (pathophysiological phase of intracranial spinal volumes homeostasis). Elasticity of dural sac plays key role. Epidural injections of blood or saline give immediate relief by elevating ICP from pathophysiological to physiological phase of homeostasis, which restore CSF space.
Darko Lavrencic
Dear Darko Lavrencic.
The ideas are very interesting, although they are somewhat unorthodox. The usual view is that the rate of CSF formation is constant, except possibly for a mild decrease at high CSF pressure; and the rate of CSF removal is linearly related to the difference between CSF pressure and dural venous sinus pressure. Your hypothesis certainly allows for greater complexities, including the prediction of self-sustaining states of low CSF volume at very low pressure and high CSF volume at very high pressure. I wonder what evidence exists for such states.
David Levine
Dear Professor Levine,
I am very aware of my unorthodox view on the issue, which has been even more unusual at the time of publishing it. Contemporary view on relation between CSF formation and CSF removal mainly deals with the physiological phase of homeostasis in cranial part. During intracranial hypovolemic hypotension syndrome (which is a self-sustaining state without therapy or until other bio mechanisms start to take place and influence on relation between CSF formation and CSF removal) spinal processes play key role as shown by radioisotope cisternography. It clearly shows that there is no CSF flow (no formation and no removal) in cranial part; removal or 'leaking' takes place in spinal part. Spinal part contributes one fourth of total CSF transport in sheep (Bozanovic-Sosic R, Mollanji R., Johnston MG. Spinal and cranial contributions to total cerebrospinal fluid transport. Am J Physiol Regul Integr Comp Physiol 2001 Sep;281(3):R909-16). Can we rely only on the removal depending on the difference between CSF pressure and dural venous sinus pressure?
How a very high self-sustaining ICP is behaving has been documented by Mary E. Kerr et al. (Mary E. Kerr et al. Dose response to cerebrospinal fluid drainage on cerebral perfusion in traumatic brain-injured adults. Neurosurg Focus 11(4):Article 1,2001). If there were complete ventricular block of CSF flow, which prevents any CSF removal from ventricles while there is still persisting some CSF formation (contribution to CSF volume), the skull would explode. The stop of CSF formation must occur at certain high ICP.
Your hypothesis on mechanism about processes, which cause headache during intracranial spinal hypotension hypovolemic syndrome, is perfectly compatible with overall intracraniovertebral volumes homeostasis in pathophysiological phase. When I mentioned, in discussion with my colleague 30 years ago, that looking at the spinal processes during intracranial hypotension syndrome we can have something like "lumbar headache" he warned me that nobody would take me seriously. Therefore I was very pleased by your hypothesis.
Darko Lavrencic
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Prof. Mary E. Kerr, University of Pittsburgh
November 2001, January 2002
Dear Professor Mary E. Kerr,
It was very interesting to read your article: "Dose response to cerebrospinal fluid drainage on cerebral perfusion in traumatic brain-injured adults. Neurosurg Focus 11(4): Article 1, 2001". I believe that you can achieve permanent relief instead of a temporary one. Increasing the amount of drainage in pathophysiological zone will cause the enter into physiological zone by crossing turning point B-high. Physiological homeostatic mechanism will rebuild optimal volumes, pressure and flow. For the mechanism see attached files.
Darko Lavrencic
Dear Darko Lavrencic,
What we also did, but was not reported in this manuscript, was a fourth trial after the first three randomly ordered drainages and that was to drain until no further CSF was removed. Again the result was temporary. I believe that there are subsets of patients that CSF drainage is effective and there are periods after injury when CSF drainage is more effective than others but more research needs done in this population to sort it out. What we don't know at all is whether CSF drainage has any negative effects on outcome.
Mary Kerr
Dear Professor Mary Kerr,
If the result of the fourth trial restores starting high ICP it could be caused by de-compensated condition (Fig. 6) with decreased removal curve. Do you have any data of CSF transport during the trial?
Darko Lavrencic
Darko Lavrencic
There was an extremely similar response in the ICP during each successive trial. The fourth trial we removed CSF “until it stopped draining” but again we saw the ICP return to baseline levels in most patients within 10-15 minutes. This was very surprising to us.
Unfortunately we did not collect data regarding CSF transport.
Mary Kerr
Professor Mary Kerr,
Your findings clearly show how self-sustained high ICP is restoring its starting high ICP after CSF drainage. Such results are expected according to pathophysiological high ICP phase of intracraniovertebral volumes homeostasis, which I have presented to you. Therefore I am very pleased by your valuable contribution to CSF pathophysiology.
Darko Lavrencic
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Ruth Porter, M.R.C.P., Deputy Director, The CIBA Foundation, London
February 1971
Dear Darko Lavrencic,
I have asked two very knowledgeable workers in this field about your paper on intracraniovertebral volumes and I am sorry to say that I cannot be very much help over it. It is obviously a very thoughtful commentary and your hypothesis needs to be proved or disproved, but I think you will have to go on with this work in your own country. As far as publication is concerned, I would suggest that you would have to do a bit more experimental work before submitting the paper to a journal. I do hope this letter won’t be too much of a disappointment to you because it really is an excellent study and an interesting idea.
Ruth Porter, M.R.C.P.
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Prof. David Woollam, Emmanuel College Cambridge, UK
November 1969 (pdf)
Dear Darko Lavrencic,
I am very interested in your hypothesis. As I work through it I am taking the liberty of editing the English in case you wish to publish it in the B.M.J. which as you may know has a special series weekly of ideas, hypotheses etc. If you are in this country do come and see me.
David Woollam
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