CSF hydrodynamic studies in man1 - Method of constant pressure CSF infusion - Journal of Neurology ...
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J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.2.105 on 1 February 1977. Downloaded from http://jnnp.bmj.com/ on May 12, 2021 by guest.
Journal ofNeurology, Neurosurgery, and Psychiatry, 1977, 40, 105-119
CSF hydrodynamic studies in man1
1. Method of constant pressure CSF infusion
J. EKSTEDT2
From the Department of Neurology, the University of Uppsala and the Department of Neurology,
the University of Umed, Sweden
SUMMARY The constant pressure method for the study of the hydrodynamics of CSF is presented.
By infusing artificial CSF at constant pressures and recording the resultant flow, it is possible to
obtain information about the hydrodynamic conductance of the CSF outflow pathways. By lowering
the infusion pressure below the pressure ofthe sagittal sinus all CSF produced can be collected and the
CSF formation rate may thus be calculated. There is a rectilinear relationship between CSF pressure
and the flow necessary to maintain the pressure. It is thus concluded that the arachnoidal villi, when
once opened, are not further distended by pressure. This method makes possible indirect calculation
of the pressure of the sagittal sinus and the pressure difference between the subarachnoid space
and the sagittal sinus.
Protected by copyright.
Since the introduction of lumbar puncture by soon reached a plateau which was higher as the
Quincke in 1878 measurement of the lumbar CSF flow rate was higher. The relationship between
pressure has become a routine procedure in clinical pressure and rate of infusion was, however, not
work. Numerous attempts have been made to linear. Rubin et al. (1966), Cutler et al. (1968), and
acquire more information about the hydrodynamics Lorenzo et al. (1970) were the first to use the method
of the CSF than only that related to pressure. of ventriculoventricular or ventriculolumbar per-
Ayala (1923, 1925) drew conclusions concerning the fusion in human studies. By adding various trace
pressure/volume relationship in the craniospinal substances to the perfusion solution, CSF formation
space by studying the pressure decrease after with- and elimination could be measured at different
drawal of a certain volume of CSF. Masserman pressure levels. The necessity for ventricular puncture
(1934) withdrew CSF and studied the time for restricts the use of the method to special human
return of the CSF pressure to its initial value. He cases and to animal experiments.
thereby estimated the rate of production of CSF. Katzman and Hussey (1970) developed a clinical
By reinjection of the CSF, information about test based on constant rate fluid infusion. Their
elimination was also obtained. Schaltenbrand and test started with removal of 10 ml of CSF. The
Wordehoff (1947) further elaborated this method pressure return to the initial value was studied by
to the status of a clinical diagnostic procedure. open manometry in order to determine the rate of
Sokolowski (1974) has also used a single bolus formation of CSF. Saline was then infused at a
injection of fluid for studying the CSF hydro- constant rate of 12.7 mm3/s (0.76 ml/min) during
dynamics. 40 to 60 minutes. Sometimes a higher infusion rate of
Constant flow rate, subarachnoid infusions were 32 mm3/s (1.9 ml/min) was also used. The plateau
first performed in human subjects by Foldes and values of the pressure at the different infusion rates
Arrowood (1948). They pointed out that, when were the parameters used to describe the CSF
increasing the flow rate, the CSF pressure rose but absorption. Clinical experience with the method was
described by Hussey and Schanzer (1970).
'Presented in part at the Second and Third International Symposia on Nelson and Goodman (1971) modified the con-
Intracranial Pressure, Lund, June 1974 and Groningen, June 1976. rate infusion method by using the rate of rise
Supported by grants from Swedish Medical Research Council stant
B 74-04X 4125 and B 77-04X-04125-04A. of CSF pressure as the measured parameter. They
2Address for correspondence and reprint requests: Dr Jan Ekstedt, also used artificial CSF instead of saline for infusion
Department of Neurology, University Hospital, S-901 85 UmeA,
Sweden. and electromanometric recording of the CSF
Accepted 12 October 1976 pressure. Martins (1973) used the constant rate
105;g~-. J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.2.105 on 1 February 1977. Downloaded from http://jnnp.bmj.com/ on May 12, 2021 by guest.
106 J. Ekstedt
infusion method but treated the results in another reported by Ekstedt (1973, 1975) and Ekstedt and
way by calculating the resistance to drainage of Friden (1976). In a modified version the method has
CSF. Trotter et al. (1974) also used a modified also been used by Portnoy and Croissant (1976).
Katzmann and Hussey method. They read the
CSF pressure after 20 minutes infusion at a rate of Methods
12.7 mm3/s (0.76 ml/min) and five minutes after a
change of the rate to 32 mm3/s (1.91 ml/min). Di INVESTIGATION CHAIR/BED
Rocco et al. (1976) have also used the constant rate The chair used was modified from an investigation
infusion test in human studies. A recent extensive chair common in Swedish hospitals. Originally, it
review of the physiology of the CSF, including was supplied with a back support made of springs
numerous references, is that of Welch (1975). and steel bands. This was replaced by a bottom of
In the present paper, another technique for the double canvas reinforced by straps on critical sites.
study of the hydrodynamics of the CSF is described, An opening of 150 x 150 cm was made centred about
the constant pressure infusion method. The infusion the fourth lumbar spinal process.
pressure is kept at a constant level and the resulting By means of a sterile tape sheet (Steridrape No.
CSF flow recorded. Constant pressure infusion has 1092, 3M Company, Minnesota, USA) fastened to
been used for investigating the hydrodynamics of the the skin, a sterile field for puncture was obtained.
animal eye (Becker and Constant, 1956; Armaly, After the lumbar puncture the chair was folded back
1959; Bara'ny, 1962, 1964) and of CSF in animal to a horizontal position. The chair is shown in
experiments (Davson et al., 1970), but not previously Fig. 1.
for human investigations. Constant pressure infusion
permits a detailed analysis of the CSF hydro- LUMBAR PUNCTURE
dynamics, mainly because much more experimental For pressure recording a 0.9 x 90 mm lumbar
needle was used (conductance 35 mm3 kPa-' * s-1).
Protected by copyright.
data of pressure/flow can be obtained during a given
time period than with the constant rate infusion For infusion a 1.2 x 100 mm needle was used (con-
method. The present study has been preliminarily ductance 85 mm3 * kPa-1 * s-1).
.. ...
......
...:...;
Fig. 1 Experimental chairlbed.
The lumbar needles are inserted
via the opening in the back
support with the patient in the
sitting position. The chair is then
folded back and the rest of the
investigation made with the
patient supine.J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.2.105 on 1 February 1977. Downloaded from http://jnnp.bmj.com/ on May 12, 2021 by guest.
CSF hydrodynamics: constant pressure CSF infusion 107
The needles were connected to the experimental K+ 4.0 mmol/l; Ca++ 1.4 mmol/l; Mg++ 0.4 mmol/l;
equipment with non-elastic PVC tubes filled with Cl 130.4 mmol/l; HCO3- 21.7 mmol/l; HPO4- 0.6
artificial CSF. The tubes and stopcocks were dis- mmol/l; pH = 7.40.
posable, replaced for each experiment. The differences in side-effects when using the
artificial CSF instead of saline were considerable.
PRESSURE RECORDING There was no reaction of the type described above.
Two pressure transducers (Hewlett-Packard 1280 C, In three cases (of 783) there was a meningitic reaction
Waltham, Mass., USA) were used. They were with fever for a few days. All patients recovered
connected to carrier frequency amplifiers (Hewlett- completely. In these three cases the rest of the
Packard 8805 B). All connections between tubes contents of the bottles were sent for bacteriological
were made by means of plastic three-position stop- examination; however, there was no bacterial
cocks (Viggo, Helsingborg, Sweden). Calibration growth. There might have been chemical or viral
was made by connecting the transducer with either of contamination.
two sterile water columns, one with its water level The artificial CSF was at room temperature in both
at the height of the zero reference level of the patient, bottle and tubes. However, about 50 mm of the
the other 306 mm above that level, thus corresponding needle was within the body and thus heated the
to a pressure of 3 kPa. The accuracy of pressure solution. In in vitro experiments when a 50 mm
measurement was better than 0.03 kPa. Careful segment of the needle was heated to 37.0°C it was
flushing of tubes, stopcocks, and transducers was found that when flow was below 25 mm3 S-1 the
performed before each experiment to avoid air artificial CSF had a temperature of more than 34°C
bubbles. The compliance of the pressure recording when leaving the tip of the needle. At 100 mm3 s-'
system, measured at the tip of the lumbar needle, the temperature was 29°C. It has not been considered
proved to be less than mm3/kPa. The pressure signals essential to preheat the artificial CSF.
Protected by copyright.
during recording were usually low pass filtered with a
time constant of 0.05-0.01 s. INFUSION APPARATUS
The experimental set-up is shown in Fig. 2. The bottle
CSF INFUSION with artificial CSF hung about 200 mm below the
During the first 50 experiments a 0.9 % saline solution reference level (the cranial mid-point). The infusion
was used. Nearly all patients experienced some kind pressure was created with a membrane air pump
of discomfort during the infusion. Sometimes there (aquarium pump Rena super 300, Annecy, France)
were very prominent signs of distress, which neces- which pumped air into the bottle. An adjustable air
sitated termination of the investigation. In a few leak maximised the air pressure. The voltage to the
cases the patient became very excited, requiring air pump was automatically adjusted by a servo
intravenous sedation. In most cases the side-effects device.
took the form of pain, paraesthesia or paralgesia The air entering the pump was filtered by a sterile
(especially in the legs and buttocks), urgency for filter (Aga Sterile Filter 323 900 002, Stockholm,
vomiting or defaecation, and symptoms from the Sweden). The air leaving the air leak was again led
autonomous nerve system, such as piloerection or into the pump, so that there was very little intake of
sweating. The side-effects with saline were similar new air into the pump. Furthermore, the output from
to those that have already been reported by Weed the pump was twice filtered by means of Munktel air
and Weyeforth (1919) and by Nelson and Goodman filters MS 20 (Stora Kopparberg, Grycksbo, Sweden).
(1971). It was obvious that an infusion solution that The air was then free of any particles and sterile.
could produce such dramatic symptoms should not
be considered suitable for these types of experiments, LIQUID FLOW RECORDING
and that it was potentially dangerous. The side- The infusion bottle was suspended by a thin nylon
effects also made it very difficult for the patient to wire in a strain gauge transducer. The tubes leading
keep a stable position for any length of time. There- air into the top of the bottle and taking fluid from
fore, a solution closely resembling the one devised by the bottom of it were pliable, exerted no elastic
Elliot and Jasper (1949) (the B solution) was made. forces on the bottle and acted on it only by their
The first 200 bottles contained glucose but in later weight.
bottles the glucose has been omitted without notable The bottle had a volume of 120 ml. Before and after
effect.
The solution was prepared in two bottles (90 ml 'Solhtion I (90 ml): NaCI: 7.98 g; KCI: 0.33 g; CaCI, * 2 H,O: 0.22 g;
and 10 ml) which were mixed immediately before the MgCl 6 H.O: 0.08 g; HCI I mol/l to pH 2.8; pyrogen free distilled
-
experiment.3 The solution was made by the hospital NaHCO,:water to 1.0 1. Autoclaved at 1 20°C for 20 minutes. Solution 11 (10 ml):
18.2 g; Na2HPO4 * 2 H2O: 0.98 g; pyrogen free distilled
pharmacist and contained Na+ 145.7 mmol/l; water to 1.0 1. Autoclaved at 11I0°C for 35 minutes.J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.2.105 on 1 February 1977. Downloaded from http://jnnp.bmj.com/ on May 12, 2021 by guest.
108 J. Ekstedt
Fig. 2 Experimental set-up. The patient is lying supine with two lumbar needles(A
andB) in the subarachnoid space. A is connectedto transducer C with a tubefilled with
artificial CSF. Similarly the needle B is connected to transducer D. By means of
stopcock E, connection can be made to bottle F, containing artificial CSF. The bottle
can bepressurised by airfrom the airpump G. Air is leaking through the adjustable
Protected by copyright.
valve Hin order to maximise thepressure and topermit a smoother regulation. The
power to the airpump is delivered by the cerebrospinalpressure regulator I, governed by
either C or D. Flow is calculatedby weighing the bottle in the strain gauge balanceJ, in
which the bottle is hung up with a 0.30 mmfishing line K. A multi-pen recorderL
records the resultgraphically. The sagittal midpoint ofthe cranium is chosen as the
reference level (M).
each experiment the balance was calibrated by chosen point of reference then proved to correspond
applying a 5 g weight to the bottle. reasonably well with the centre of the right atrium.
On the ink recorder (Rika Denki KA 4 Tokyo, If another point of reference is chosen, the pressure
Japan) 1 g represented a deflection of 25 mm on the will change with the weight of the water column that
250 mm wide paper. The accuracy of measured separates the reference points.
weight was better than 0.03 g.
UNITS OF MEASUREMENTS
REFERENCE LEVEL FOR PRESSURE SI units have been used throughout. Pressure: I
In 10 patients the intraspinal pressure was first kilopascal (1 kPa)= 7.5 mmHg= 102 mmH2O.
recorded in the lateral recumbent position with the The hydrodynamic conductance of the CSF outflow
reference line along the spine. The patient was then pathways has the dimension mm3 kPa-1 s-1.
turned to the supine position and the pressure again 1 mm3 kPa-1 s-1 = 6 10-3 ml (cmH2O)'1 * min'-=
measured in relation to the external auditory 8 . 10-3 ml. (mmHg)-l min-'.
meatus. The procedure was repeated a few times.
It was then found that a reference level at the cranial EXPERIMENTAL PROCEDURES
midpoint between inion and glabella best corres- With the patient in the sitting position the needles
ponded to the reference level of the spine in the were inserted in the L3-L4 or L4-L5 intervertebral
lateral recumbent position. This point was therefore space after local anaesthesia of the skin and the
chosen as reference point for all measurements. intraspinal ligament with 1 % lidocaine (Xylocaine,
On the exterior, it corresponds to a level through the Astra S6dertalje, Sweden). Care was taken to insert
mandibular joint and to the anterior part of the the needles with minimal trauma. Multiple punctures
osseous channel of the external auditory meatus. of the dura mater were avoided. Two millilitres of
It also corresponds to the level of the foramina of CSF were withdrawn with a syringe for protein
Monro chosen by Janny (1974) as his reference point. determination and cell count and immediately
In seven patients radiographs were taken of the skull replaced by the same amount of artificial CSF.
and thorax with the patient in a supine position. The This also served as a check of correct needle position~/ J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.2.105 on 1 February 1977. Downloaded from http://jnnp.bmj.com/ on May 12, 2021 by guest.
CSF hydrodynamics: constantpressure CSFinfusion 109
in the subarachnoid space. The amount lost during good drainage, the content (120 ml) of the bottle with
the needle insertion was also replaced. The patient artificial CSF was not sufficient to attain this level.
was then folded back to the supine position and the Eight to 15 corresponding values of pressure flow
pressure transducers were adjusted to the reference were obtained in each case. A part of a recording is
level. The different steps of the procedures are shown shown in Fig. 4.
in Fig. 3. The next step was the 'post-infusion'. The con-
The resting pressure was recorded continuously. nection to the bottle was shut off and the pressure
Usually 60 minutes of recording was aimed at, but was allowed to return spontaneously by elimination
sometimes a shorter time could be allowed if the of CSF through the physiological pathways. This was
curve was steady. The resting pressure was not continued until a steady plateau value was recorded,
measured until there had been a period of at least which, in most cases, closely corresponded to the
15 minutes without any upward or downward trend. initial resting value. If this level was different from
In order to detect whether there was any leakage the initial resting value, there was a strong suspicion
around the lumbar needles 20 experiments were that the resting pressure had been wrongly recorded
performed in the following way: the resting pressure and the investigation was therefore often repeated
was recorded during 30 minutes and, if constant some days later. In some 20 experiments the infusion
during the last 15 minutes, the chair/bed was folded was also continued after the maximum pressure was
to the sitting position and kept so for 15 minutes. reached. Infusion pressure was lowered in steps of
Thereafter, the chair was again folded back to the 1 kPa. This was done in order to detect any hysteresis
supine position and recording of the resting pressure in the pressure/flow relationship.
continued for a further 30 minutes. During sitting, In 10 experiments the pressure was, for a period of
the hydrostatic pressure on the needle insertion one hour, switched between two high values every
area was increased by the weight of the column of the five to 10 minutes, to detect possible changes in flow
Protected by copyright.
spinal liquid and the flow through a leak should with time.
have increased. The resting pressure when the The next step in the investigation was then to
patient was then folded back to the supine position perform the drainage. The pressure in the infusion
should have been lower if there was a CSF leak bottle circuit was lowered to 0.25 kPa. This caused an
around the needles. outflow of CSF from the subarachnoid space into
The infusion was then started. The first infusion the bottle. Initially, the rate of outflow was high,
pressure was chosen to be about 0.5 kPa above but within 10 to 15 minutes the rate levelled off
the resting pressure. The pressure was kept at when the intraspinal pressure approached the
this level until the rate offlow had levelled off after the pressure in the infusion circuit. The drainage period
initial high rate and the CSF pressure was constant. was planned to last one hour but sometimes had to be
Then the pressure level was increased by a further shortened because the investigation had persisted
0.5 kPa and the same procedure was repeated. for more than three hours and the patient might be
The pressure was kept at a certain level for at least hungry and unwilling to cooperate. In some cases the
five minutes. In most cases a final pressure of 6 kPa drainage was postponed to a separate investigation a
was aimed at, but sometimes, when there was a very few days or some weeks later. This part of the
Fig. 3 Schematic layout ofthe
T Weight of infusion bottle investigation. During30-60
minutes the restingpressure is
7.5 kPa recorded. The CSFpressure is then
increased in steps of0.5 kPa up to a
maximum of7.5 kPa. The resulting
decrease in the bottle weight is
shown in the upper trace. After
kP
obtaining the highestpressure the
CSFpessure .5 bottle is shut offand thepressure
0.25 k P a returnfollowed during the
_ postinfusionperiod. During the
'Resting pressure > Influsion 4Post- ; 'CSFC
drainage period ofCSFdrainage the CSF
pressure is loweredbelow that ofthe
10 pressure infusion venouspressure in the sagittal sinus.
levels
m
ini~om When the pressure has stabilised the
0 60 miR 120 ml 1501 outflow is equal to the CSF
L---b T;ime
production rate.J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.2.105 on 1 February 1977. Downloaded from http://jnnp.bmj.com/ on May 12, 2021 by guest.
110 J. Ekstedt
kPa
9 1 483 1974 - 10-23 1
Male 6 8 years
8-
I
7-
K~~~~ /~~~~
6- / .
5-~ Artificial CSF
bottle weight
I X,
/~~~~~
/~~~~~
4-t
Infusion pressure _. A1 _
CSF pressure / Low pass filteroff
I _
0
_ I * I *
0 1 2 3 4 5 6 7 8 9 10 I, 12 13 14
Time (min)
Fig. 4 Part ofan actual recording during infusion. At A the infusion pressure is changedby 0.5 kPa,
which causes an increase offlow measurablefrom the bottle weight curve. A differentplateau valuefor
the infusion pressure and CSFpressure is caused by the resistance in the lumbar needle through which
Protected by copyright.
infusion is made. This is the reason why a separate needlefor CSFpressure recording is convenient.
investigation was done in order to determine the rate minute. When selecting a part of the recording for
of formation of the CSF. A part of a recording is measurement, the mean pressure had to be constant
shown in Fig. 5. during several minutes. During this time the slope of
If the intracranial resting pressure was considerably the weight curve had to be as constant as possible and
increased from the beginning of the experiment or if approximated by a straight line. At the time of
the investigation had given a suspicion of an intra- experiment a check was always made that there was a
cranial, space-occupying lesion, then no drainage well measurable part of the curve before proceeding
was performed because of the risk of tentorial to a new pressure level.
herniation. All calculations were made on a small calculator,
In order to minimise post-lumbar puncture head- Compucorp 445-444 (Computer Design Corporation,
ache, the drained CSF was in most investigations Los Angeles, Calif., USA). The output from the
reinfused until a pressure was attained which ex- calculator is shown in Fig. 6.
ceeded the resting pressure by 0.5 kPa. Reinfusion Three different methods were employed for the
was not made in those cases where the clinical result calculation of the curves. In method 1 the value of the
of a pressure lowering was to be investigated. resting pressure is given a very strong weighting. It is
Once every 10 minutes, or at the end of each pres- thus considered that the curve should pass through
sure level, during the infusion period, the blood the point of the resting pressure and the regression
pressure and pulse rate were measured with a line was calculated according to Snedecor and
semiautomatic sphygmanometer cuff recorder Cochran (197 1, p. 166).
(Metronik A 900 Koln, W-Germany). L[(pcl-pclr) * q]
CALCULATIONS
Gop = ,2pel-pcir) 2q Formula 1
All experimental data were measured from the (Gop = the hydrodynamic conductance of CSF
multichannel ink recorder. The CSF pressure was outflow pathways, pet = the actual CSF pressure,
subject to variations with time. The arterial pulse P clr = the resting CSF pressure, q = the actual flow of
synchronous and respiration synchronous varia- artificial CSF).
tions were low pass filtered with a time constant of When there is an experimental error both in the X
0.05 s. There were still slower variations of the and Y measurement values the following formula
pressure, with a frequency of one or more waves per 'The programme was written by Ulf Ekstedt.J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.2.105 on 1 February 1977. Downloaded from http://jnnp.bmj.com/ on May 12, 2021 by guest.
CSF hydrodynamics: constant pressure CSF infusion III
kPa
7- 483 1974-10-23
r Male 68years
6-
5- CSF bottle weightT 11-\ CSF
/ 1cm3- CSF outflow rate outf low
rate
4-
[10
3-
---
20
2-
I- Drainage
CSF pressure pressure
I
0 42 45 48
-. -
.-
51 5 min
727 3.0
30 3~~~33 36 42 45 48 51 54min
Fig. 5 Part ofan actualrecording during drainage. The drainage pressure isO.25 kPa. The CSF
pressure has stabilisedat a slightly higher value because ofthe pressure drop causedby the CSF
flow in the needle resistance. The CSFformation rate is calculatedfrom the increase ofthe
Protected by copyright.
bottle weight. For monitoringpurposes during the investigation the instantaneousformation rate
is calculatedand displayed on the recording.
may be theoretically more suitable. It has been cal- been performed strictly according to the procedures
culated for the last 300 investigations but proved to described here. All investigations were made for
give values for Gop that differed very little from those diagnostic purposes because of a suspicion of altered
obtained by formula 1. CSF hydrodynamics and none on volunteers. The
[(pci pcer) * q2]
- project was approved by the ethics committee of
Gop = E[(pel pclr)2 . q] Formula 2 Uppsala University. The findings in pathological
cases will be reported separately. In the material 58
If using the constant rate infusion method the follow- patients (aged 17-83 years) have been selected as
ing formula will probably be more accurate. probably not having any intracranial or circulatory
'Eq2 disease, judged by medical history, clinical neuro-
p = *Eq Formula 3 logical investigation, and further medical develop-
,E[(P,cl
pelr) qj
-
ment. These patients constitute the normal material.
In method 2 the point for the resting pressure is The CSF hydrodynamic parameters in these patients
omitted entirely from the calculation. All the other will be reported separately by Ekstedt. In the present
experimental points were used for a conventional paper this group of patients is also used as a reference
regression analysis by the method of least squares. A group for normality. Of course, this post-
value of the resting pressure was then calculated from experimental method of deciding which patient shall
this regression line and the calculated value was com- be considered as normal or not is open to criticism.
pared with the actually recorded value. However, in the absence of an investigation on healthy
In method 3 each experimental point is taken in volunteers, which is, for obvious reasons, difficult to
relation to the resting pressure. The slope of the line do, the present 58 patients must serve as a provisional
joining the experimental point and the resting pres- normal sample.
sure point was calculated. The mean value of all these
values was then calculated. Results
SUBJECTS In the present paper the results will be presented from
To date 783 investigations have been performed in the qualitative point of view only. The general
705 patients aged between 3 days and 92 years during character of the resting CSF pressure recording was
a period of six years. About 500 investigations have the same for the supine position as for the lateralJ Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.2.105 on 1 February 1977. Downloaded from http://jnnp.bmj.com/ on May 12, 2021 by guest.
112 J. Ekstedt
3 13
all other cases the post-sitting value within a few
147I -, -31 minutes approached the pre-sitting by ±0.1 kPa
3o
i 7 4 -7
e (Fig. 7). Hydrostatically increasing the pressure on a
0O dural rift should induce a leakage. It can then be
0.
assumed that a leakage around the needle, as des-
0* 5
I 660
7*
1 C* 5
c; cribed by Lundberg and West (1965), did not occur
1 6C 2 *
2.J0 16.0U 17.1 frequently in the present experiments.
2.* ,O
23.4
23 *7
26*0
1 5*
13.3
c
oc
During the infusion period the patient usually ex-
3.30 34.0 1.4* 5 perienced only slight unpleasantness. Sometimes he
3.70
2 0
35.0
4 75
12.7
1 4. t
44
47
became sleepy and fell asleep at pressure levels above
4.50 4;15 14.0*
o 6 373 5 kPa and then woke up again when the pressure
5.00
5*50
5* C 14.*3
v45 0
04
14S* o
250526-753 0
1 374-01-31
decreased. Pulse and blood pressure were usually
6 - JO
6.30
?3e z l 4- 5
14.0,, 1474-05-120
unaffected.
3 c.
All spontaneous variations in the CSF pressure
0 16.3345 /
O: 2
were exaggerated at increasing mean pressure. In
; 4 43 P S
0.~~~~~~~
spite of this it was nearly always possible to obtain
3 *7 4 v
104643
p well measurable sections of the pressure and weight
4 5
5 ;o curves even at the highest pressure levels.
B2 .
3.51327 j~ In Fig. 8a is shown a pressure flow diagram from
, 1 4 *1 4 4, a
1614 - an investigation which was, from the technical point
, 7a3
7
4 733
a .7
' of view, very successful. There is no doubt that the
P 4.U4Jl4 F
s 06 7 r SI*2 3 4 5 6 *7 relation between pressure and flow is linear. The
.4,22 i' L~ conductance, calculated by the three methods des-
Protected by copyright.
3.L740 ;, cribed in the Method section, were all numerically
4 3.5 1 34 'I close to each other. It has been postulated that if the
50vj. 12'3
3 662 1 7
three methods give values that differ by less than 15 %,
_
I j;0 30 the pressure/flow relation can be considered
B3 .............
054493 In. rectilinear.
14.6411 F3
4 14.*23 744* @7
In the majority of the several hundred recordings
o 6 00.343
1 51 v
i! 6 * )6 3 3 there seems to be a rectilinear relation between
C 33 t, 01
3.-3334 4 Y 0.4463 p pressure and flow. This holds true for patients con-
Z) .4 7* 3
* 4756
i5
;
1t, sidered to be normal from the point of view of CSF
Fig. 6 Outputfrom the calculator. First the original data hydrodynamics (Fig. 9) as well as for patients with
are listed (A).Then the regression line ofthe experimental abnormal CSF hydrodynamics (Fig. 10). In a few
points is calculated by three different methods (BJ, B2, B3, cases, however, an obviously nonlinear relationship
see text). The experimentalpoints are then automatically between pressure and flow was obtained which
plotted with pressure in kPa as the abscissa andflow rate could not be explained by technical errors (Fig. I 1).
in mm3s-1 as the ordinate (C). In many early experiments there was a tendency for
lower pressure values to give unexpectedly high flow
recumbent. It was found to be very important not to values, and this was dependent upon the fact that
turn the head, as this invariably increased the pressure. there was not enough time left for the flow curve to
In three investigations, where the intraventricular level off. When this fact was noticed, this source of
pressure was recorded during the whole experimental error was eliminated.
procedure, the arterial pulse synchronous variations In 20 experiments the infusion pressure was in-
were about 10% higher intraventricularly, but in all creased in steps of 0.5 kPa up to a pressure of 6.5 kPa
other respects the pressure was always equal. This and thereafter again decreased in steps of 1.0 kPa.
held true both for the spontaneous variations in The flow values obtained with increasing pressure
pressure and the variations induced during the in- did not differ significantly from those obtained with
fusion. There is thus no reason to believe that a CSF decreasing pressure.
hydrodynamic investigation should give different In five experiments the pressure was alternatively
results when performed via the ventricles than when held at 4.5 or 5.5 kPa in periods of five minutes for 60
performed by the lumbar route. to 90 minutes in order to detect possible changes in
In 20 experiments, when raising the patient to a the outflow pathways with time-for example, a
sitting position for 15 minutes and thereafter re- distention of the arachnoid villi. There was no
suming the supine position, there was only one case systematic change in the outflow conductance de-
which showed decrease of the pressure by 0.4 kPa. In tectable in these experiments (Fig. 12).J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.2.105 on 1 February 1977. Downloaded from http://jnnp.bmj.com/ on May 12, 2021 by guest.
CSF hydrodynamics: constant pressure CSF infusion 113
kPa
81 737 1976-04-08
7.- Male 571ears
LA.,"L.LJA JJICIA
Ir 'r ir,rrjwqm,-.
-TV,-rw
-r
6
5-
4.-
Infusion pressure
1, iA.1
3 . a1- AL-M II A
hi.L^A ..~ 1 .iA
2.pre
M. AL AM MM
e v WI kfAillolildoA
.
-w , "
1
2 CSF pressure
--,rI--, ,^J9-4 zJ%_}J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.2.105 on 1 February 1977. Downloaded from http://jnnp.bmj.com/ on May 12, 2021 by guest.
114 J. Ek-stedt
CSF FLOW CSF FLOW
mm3.*l mm3 s$
90 90
80 234 SM 1973-05-11 801 506 1975-11-18
01 04 d" 72 years 9 65 years
70 PCIr 1.3 kPa 70k
qf 4.2 mm3s' PCIr 1.4 kPa
60 Gop12.2 mm3kPi!s' 5 .3 mm3s /
60
,s 1.o kPa dO 20.3 mm3 kpi'
50 Pdop 0.3 kPa 50' Pss 1.i kPa
Pdop 0.3 kPa
40 40'
30 0>/
0~~~ 30
20 20
10 10
PRESSURE PRESSURE
Az"" 2 3 4 5 6 7 kPa 0 3&1 2 3 4 5 6 7 kPa
io 30 io eo mmHg sb io so mmHg
Protected by copyright.
1o 10 20
(a) (b)
CSF FLOW
mm3 s7i
CSF FLOW 90
mm3 sci
90 80'
I~~~~
80 70'
70
60
0
60
50
50 51 1 H 1972-11-17
2877 AE 1973-10-04 40 dc 58 years
40 154(
0416 ci 58 years Pcl,,r 0.8 kPa
~~~~Pcl,'1
1.2 kPa 30 qf 5.8 mm3- s-'
30
/
3 -1
~~~qf5.313.8 mmmm3-s kPi"-i
'~I: ! God,pl8.3 mm3. kPas-'
~'pIO.s kPa 20 Pss; 0.4 kPa
/ ~~~PdcbopO.4 kPa
10' /0 pdop,0.4 kPa 10'
0o PRESSURE
_
PRESSURE
O > 2 3 7 kPa 0 1 2 4 5 6 7 kPa
10 2b 30 40 SO mm Hg io 30 40 5o mm Hg
(c) (d)
Fig. 9 Pressure/flowdiagramsfrompatients, normalasregard CSFhydrodynamics. CSFpressure onabcissa. CSF
inflow through the needle on ordinate. The numbers denote: investigation number, date ofinvestigation, sex, and age of
patient, pclr: resting CSFlumbarpressure, qf: CSFformation rate, Gop: conductance ofCSFoutflowpathways, p88:
sagittalsinuspressure,ppdop:pressure difference across CSFoutflow pathways. In this andallothergraphs the line is the
regression line ofpressure onflow calculated according to method l (see text,formula 1). There is a rectilinear relation
between pressure andflow. The horizontal line under the abscissa denotes the CSFformation rate. It represents the ordinate
valuefor zero outflow ofCSFthrough the arachnoid villi. The regression line is linearly extrapolated to the zero outflow line.
The intersectionpoint represents the CSFpressure that should have existedifthere were no internalproduction of CSF-
that is, the sagittal sinuspressure (seeformula 4).J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.2.105 on 1 February 1977. Downloaded from http://jnnp.bmj.com/ on May 12, 2021 by guest.
CSF hydrodynamics: constant pressure CSF infusion 115
CSF FLOW CSF FLOW
mm3 s-1 ..3 *1 .
90
80 498 1974-11-07
6 59 years
70 70
Pclr 2.2 kPa
60 201 1973-03-06 60 q, 6.5 mm3g'
cf 65 years aop 4.7 mm3kPci sl
50 Pclr 2.2 klPa3 - 50 P& 0.8 kPa
qf 4.2 mi Pdop 1.4 kPa
40 Go 5.2 mAm3- kPi-s' 40
PSS 1. 3 kIPa
30 0op.9 klIPa 30
0
20 Pdo 20
10 10
PRESSURE PRESSURE
O 1 -,1 4 5 6 7 kPa W4 5 8 7 kPa
mm Hg
10 20 3b 40 5o mmHg 3b 'o 5o
Protected by copyright.
(a) (b)
CSF FLOW CSF FLOW
mm3. fl mm3 s-1
90
80 523 1974-12-05
9 55years
341 1973-12-06 70 19 04 13 - 892
cd 28 years e?lr 3.7 kPa
/ Pclr 2.6 kPa 60 6.0 mm sl
qf
qf 5.8 mm3 s-' 15.7mm3 kPaT!s'
0 Gop49.1 mm3 kPis 50, Pss 3.3.kPa
PS 2.4 kPa Pdop 0.4 kPa
PdopO.2 kPa
0
20
0
10 /0
PRESSURE
0 1 2 3j/-4 5 6 7 kPa
io 4o0 So mm Hg oL -- 30 40 5o mm Hg
(c) (d)
Fig. 10 Pressure/flow diagramsforpatients with increased CSFpressure due to decreased conductance (a, b) or increased
sagittal sinuspressure (c, d). Symbols as in Fig. 7. There is a rectilinear relation between pressure andflow.J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.2.105 on 1 February 1977. Downloaded from http://jnnp.bmj.com/ on May 12, 2021 by guest.
116 J. Ekstedt
CSF FLOW CSF FLOW
mm3. i-I mm3. s7
90 90
80 80
..
70 70
365 9
60 60
50
7
50 0::
40 40
, ..
30 30 382 9
.. 0
20 20
..
10 10 ...:
P RESSURE * ~~~~~PRESSURE
0 i 2 3 4 5 6 i kPa 0 1 2..
'.
43 5 6 7 kPa
10 2o' 3s 40 50 mm Hg io io 370 io 50 mm Hg
Protected by copyright.
(a) (b)
CSF FLOW CSF FLOW
mm3.*l mm3. s1
90 90
80 80
I~~~~ 188 9
70 70 47 11 19
60 60
50 50
379
40 40
30 30 :::
20 20 _. ....
10 SP
10-
L P RESSURE PRESSURE
0 2 3 4 5 6 7 kPa O .. 2 3 4 5 6 7 k Pa
10 so
30 so mm Hg
50 io io 30 io 50 mmNH
(c) (d)
Fig. 11 Pressure/flow diagrams that were exceptions to the usual rule ofrectilinear relationship betweenpressure andflow.
The recordings (a) and(b)frompatients with sinus thrombosis. Patient (c) had sequelae after a traumatic intracranial
haemorrhage with secondary porencephaly. Patient (d) /ad had apneumoencephalogram three days earlier. A t a later
investigation her pressure/flow curve was again straight.J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.2.105 on 1 February 1977. Downloaded from http://jnnp.bmj.com/ on May 12, 2021 by guest.
CSF hydrodynamics: constant pressure CSF infusion 117
301 Conductance (Gp P -p 738 1976-04-12 Discussion
mm! kPas c,,/drPI/ d 52 years
'hr 1.5 kPa Welch and Friedman (1960) made in vitro perfusions
q, 8.6 M s-' of small discs of the sagittal sinus in young monkeys.
20- a 12.2 mWkPi's'
They found that the flow through the arachnoid villi
Pss 0.7 kPa
Pdop 0.7 kPa started at a critical opening pressure. The general
shape of the pressure/flow curve was that of an up-
10 ward bend very similar to the curves from the present
investigation shown in Fig. 1 1. The authors concluded
that the drainage of CSF was through open channels
from the subarachnoid space into the dural sinuses.
10 20 30 40 50 60 70 80 90 100 lO 120 min
Colloid osmotic pressure had no influence on the
flow. The upward bend of the pressure/flow curve
Fig. 12 Extended CSF infusion. Every five minutes the was interpreted as caused by an elasticity of the
CSF pressure changed between 4.5 kPa and 5.5 kPa. Time arachnoid villi. Further, in the rabbit experiments of
on abscissa. On the ordinate the conductance was calculated
according to the formula in the Figure. There was no Davson et al. (1970), made with a constant pressure
systematic change in the conductance during the 115 technique, there seems to be an upward bend of the
minute period. In the post-infusion period the pressure pressure/flow curve. However, the deviation from the
returned to the pre-infusion value. straight line is so slight that it may lie within the
experimental error.
In the usual type of experiment the pressure was In the present investigation a rectilinear relation-
allowed to return spontaneously in the post-infusion ship was found. This held also for the youngest
period. The plateau value then obtained was usually patients, the very youngest being 3 days old, and can
Protected by copyright.
very close to or identical with the resting pressure therefore not be explained as a decreased elasticity of
obtained before the infusion. This held true also in the the arachnoid villi due to age. Portnoy and Croissant
experiments where the pressure had been kept at a (1976) have also confirmed a rectilinear relation
high level for an extended time. During the drainage between pressure and flow in human experiments
period there were usually no subjective sensations with a slightly different technique.
felt. Only a few patients developed headache during The finding of equal flow values at a certain pres-
the procedure. On rising after the investigation, how- sure level when going from lower to higher pressures
ever, most patients who were left with a subnormal as when going from higher to lower pressures makes
CSF pressure felt a throbbing headache of the type it reasonable to assume that the arachnoid villi do
that is usual after lumbar puncture. not get further distended at increasing pressure, at
In Fig. 13 is shown the result of a several-hour long least not at pressures below 6 kPa.
drainage where the CSF formation rate was deter- Martins et al. (1974) made direct measurements of
mined for each 15 minute period. The variation in the sagittal sinus pressure in man via median burr
rate between the different periods is only slight. holes while they increased the CSF pressure by means
of intraventricular infusion. In most of their experi-
CSF Formation rate (qf) 700 1976-01-26
ments the sagittal sinus pressure was unaffected
7-
mm3s-I 9 54 years
when increasing CSF pressure by up to 6 kPa.
6 Altered sagittal sinus pressure can thus not explain
the rectilinearity of the ratio.
5 There still remains the possibility of a distension of
the villi and thus increased conductance at increasing
4,
pressure if that is compensated by a compression of
3 the lateral lacunae of the sinus and thus causes a de-
crease of the number of villi that could pass CSF to
2- the sinus. This viewpoint is purely hypothetical and
has no support in the literature. It is highly unlikely
that two mechanisms should balance each other so
well as to nearly always give a rectilinear relationship
30 60 90 120 150 180 210 240 270 min between pressure and flow.
Fig. 13 Extended CSFdrainage. When the rate ofoutflow The regression-line of flow on pressure is the hydro-
through the needle had stabilised the CSFformation rate dynamic conductance of the CSF outflow pathways.
was calculatedjor each l5 minute period and the The conductance of the intracranial pathways,
calculatedformation rateplotted. qf ± SD 4.0 ± 0.2. =
especially in the aqueduct and in the basal cisternsJ Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.40.2.105 on 1 February 1977. Downloaded from http://jnnp.bmj.com/ on May 12, 2021 by guest.
118 J. Ekstedt
and the subarachnoid space over the hemispheres, is in either direction, another value for the sagittal
probably very high in relation to the conductance in sinus pressure should be obtained. Whether or not the
the arachnoid villi. The conductance of the outflow assumption of a rectilinear extrapolation is true can
pathways may thus certainly be considered as the only be proved when the sagittal sinus pressure is
conductance of the arachnoid villi only. However, in measured directly during a CSF hydrodynamic
pathological cases there may be blocking of CSF experiment. Discussion of the different CSF hydro-
circulation in the subarachnoidal space-for example, dynamic parameters will be postponed to a later paper.
because of adhesions.
Leakage around the needles is probably only References
exceptionally an outflow pathway for the CSF in the
experimental situation (Fig. 7).
The flow through the arachnoid villi will, ac- Armaly, M. F. (1959). Studies on intraocular effects of the
cording to Davson et al. (1970), be determined by the orbital parasympathetic pathways. Archives ofOphthal-
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Ayala, G. (1923). Uber den diagnosticher Wert des
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pC = Pss + Gop q Formula 4 Liquor cerebrospinalis und der Rachidealquotient.
MonatschriftfurPsychiatrie und Neurologie, 58,65-101.
where Brirny, E. H. (1962). The mode of action of pilocarpine
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pss = the sagittal sinus pressure, pithecus ethiops). Investigative Ophthalmology, 1,
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mally the formation rate of CSF (qf), BarAny, E. H. (1964). Simultaneous measurement of
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There may also be an opening pressure of the vestigative Ophthalmology, 3,136-143.
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