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Benign intracranial hypertension and disorders of CSF absorption
Benign Intracranial Hypertension and Disorders of CSF Absorption Pierre Janny, M.D., Jean Chazal, M.D., Gilles Colnet, M.D., Bernard Irthum, M.D., and Anne-Marie Georget, M.D.
Sixteen patients suffering from benign intracranial hypertension were studied by a continuous measurement of intraventricular pressure, a simultaneous recording of intraventricular and sagittal sinus pressures, and a measurement of the cerebrospinal fluid (CSF) resistance to drainage. Isotope cisternography was performed and the patency of the dural sinuses verified by direct sinography or phlebography or both. The same procedure was used to study 6 other patients suffering from disorders leading to the same type of intracranial hypertension. In 16, our results confirm a defect in CSF absorption mechanisms linked to an abolition of the pressure gradient between CSF and sagittal sinus in 6 patients, as well as an important increase in CSF resistance to drainage in 10 others. Despite this defect, the CSF circulation was normal in most patients (10 of 12) as demonstrated by isotope cisternography.
Benign intracranial hypertension has been variously attributed to increased cerebral blood volume [6, 18, 21], cerebral edema [24], or enlargement of the cerebrospinal fluid (CSF) compartment related to some disorder of CSF absorption mechanisms. The last hypothesis was initially proposed by Bercaw and Greer [3] on the basis of a delayed isotope transit study in 2 patients. This hypothesis was subsequently accepted by Johnston [13]; knowing of the work by Davson and associates [7] on CSF absorption mechanism, Johnston proposed that a reduction of the CSF absorption rate resulted either from an abolition of the pressure gradient between CSF and the superior sagittal sinus or from the elevation of resistance to drainage of CSF across the arachnoid villi. Johnston [13] experimentally confirmed his theory; Martins [17], in a study on the measurement and importance of CSF resistance to drainage, made an incidental reference to 4 cases of benign intracranial hypertension. Nevertheless, a large clinical study is still needed for verification. The goal of this paper is to provide such a study. Fromthe Departmentsof Neurosurgeryand Neuroradiology,Universityof Clermont-Fen'and,Clermont-Ferrand,France. Address reprint requests to Prof. P. Janny, CliniqueNeurochirtagicale, HOpitalFontmaure,63400 Chamalieres, France. Key words: benign intracranial hypertension;CSF absorption; sagittal sinus pressure; CSF flowresistance.
Clinical Observations and Method From 1973 to 1979, 16 patients considered to have benign intracranial hypertension were observed (Table 1). This group consisted of 8 men and 8 women ranging from 2 to 56 years of age (mean, 24.5 years). All presented a pure intracranial hypertension syndrome without any sign of focal disease. Bilateral papilledema was found in all patients. Possible etiologic factors, widely accepted by many authors, were clearly present in 8 patients: 3 with ear, nose, or throat infection, 4 with head injury, and 1 patient using oral contraceptives. Among the 8 remaining patients were 3 obese women (1 of whom was pregnant), 1 young girl beginning puberty, a 56-year-old man treated with perhexiline maleate (a drug that has been reported to cause papilledema), and 3 patients without any suggested etiology. Electroencephalograms, brain scintigraphy, and the composition of lumbar CSF were normal in all patients. Plain roentgenogram of the skull, angiography of the carotid or vertebral systems, and ventriculography with air or Pantopaque (or both) were carried out to eliminate a space-occupying lesion. The mean Evans [10] index was 0.29 - 0.04, characterizing lateral ventricles most often of normal size or sometimes slightly enlarged, but rarely diminished. As a means of comparison, we studied another group of 6 patients (Table 2) who presented the same pure intracranial hypertension syndrome with equally normal ventricular and subarachnoid systems; in these patients there existed an evident affection that precluded their acceptance among the group of patients with benign intracranial hypertension. These 6 patients, specified here as the "nonbenign intracranial hypertension group," included a patient with an arteriovenous malformation of the scalp draining profusely into the superior sagittal sinus, one with meningioma en plaque obstructing a single lateral sinus, and 4 patients who had chronic lymphocytic meningitis of various causes, 1 case of lupus erythematosus, 1 neoplasm, and 2 of unknown cause). The following determinations were made for these two groups of patients: (1) monitoring of intraventricular pressure; (2) measurement of the various parameters of CSF absorption; and (3) patency of the dural sinuses. Monitoring of intraventricular pressure was accomplished by placing an
168 0090-3019/81/030168-07501.25 © 1980 by Little, Brown and Company (Inc.)
Janny et al: CSF Absorption with Benign lntracranial Hypertension
169
Table 1. Clinical Data in 16 Patients Suffering from Benign Intracranial Hypertension CSF Patient
Age (yr)
Sex
History
Papilledema
Cells (per mm 3)
Protein (gm/liter)
Evans Indexa
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
2 5 55 42 27 14 51 56 26 35 19 19 8 12 5 2
M F M M F F M M F F F F M F M M
Head injury Otitis None Head injury Obesity Menarche Head injury Perhexiline maleate Obesity None Pregnancy, obesity Oral contraceptive Otitis None Head injury Otitis
+ + + + + + + + + + + + + + + +
5 1 3 2 1 •• 1 0 0 0 0 2 11 2 2 0
0.37 0.34 0.60 0•50 0.36 •.. 0.44 0.40 0.35 0.40 0.18 0.55 0.20 0.52 0.18 0.37
0.36 0.36 ... 0.30 0.25 0.30 0.27 0.30 ... 0.29 0.26 0.24 0.25 0.33 O.34 0.30
Protein (gm/liter)
Evans Index a
aEvans index is normally between 0.16 and 0.29.
Table 2. Clinical Data in 6 Patients Suffering from Nonbenign Forms of Intracranial Hypertension CSF Patient
Age (yr)
Sex
History
Papilledema
Cells (per mm3)
17
56
M
0.78
0.27
56
M
+ (optic atrophy) +
0
18
...
...
0.19
19
37
M
+
36
0.72
0.30
20
12
M
+
16
0.44
0.28
21
21
F
+
28
2.24
0.30
22
52
F
Arteriovenous malformation Meningioma en plaque Chronic meningitis Chronic meningitis Chronic meningitis Chronic meningitis (lupus)
+
67
1.84
0.38
"Evans index is normally between O. 16 and 0.29.
indwelling catheter inside the frontal h o m of a lateral ventricle for a period of at least 24 hours (mean, 2.5 days) while using a p o i n t - b y - p o i n t Philips slow recorder* (2 cm per hour) to produce the tracings. Measurement of the various parameters of C S F absorption was accomplished under general anesthesia and included a simultaneous re-
cording of the intraventricular and superior sagittal sinus pressures and a measurement of C S F resistance to flow. T h e superior sagittal sinus pressure was measured through a 16-gauge, 6.25 c m (2½ inch) Teflon catheter* introduced into the sinus by passing it through a burr hole situated at the m i d p o i n t of the coronal region of the skull. Continuous
*Pointax recorder; Philips, Division Sciences et Industrie, 105 rue de Paris, 93002 Bobigny, France.
*Longdwellcatheter needle with obmrator; Becton Dickinson Company, Rutherford, NJ 07070•
170
Surgical Neurology Vol 15 No 3 March 1981
nonheparinized perfusion was used to prevent clotting inside the catheter. The sinus pressure was then recorded on an optic ultraviolet recorder,* together with the CSF pressure from the previously catheterized ventricle, allowing one to determine at each time the pressure gradient between them. This pressure gradient was studied at rest, during compression of the jugular veins, and during the intraventricular perfusion, but only the resting pressure gradient was taken into consideration in the present paper. The duration of the recording was about 2 hours, except in 1 patient (Patient 21), in whom it was possible to maintain the catheter inside the sinus for 24 hours while recording the pressure gradient on the patient while awake. The CSF resistance to flow was measured using Katzman and Hussey's [15] constant infusion manometric test; the perfusion was administered by the intraventricular catheter at the rate of 0.5 ml/min. Calculation of CSF resistance to drainage previously gave us a normal value of 10 - 5 mm Hg/ml/min [12]. The patency of the dural sinuses was verified by direct sinography, performed after pressure measurements with the aid of the intrasinus catheter. In 7 patients who had undergone both angiography and direct sinography studies, we compared the venous filling aspect of their angiograms with films of their sinograms. Twelve patients underwent isotope cisternography with technetium 99m or indium 111 diethylenetriamine penta*Ultraviolet optic recorder OM 4501; Schlumberger, 1 rue de Nieuport, 78140 Velizy-ViUacoublay,France.
acetic acid; the isotope transit was interpreted according to criteria proposed by Di Chiro [8]. Results Tables 3 and 4 show the collected numerical data, together with the results from sinography and cisternography.
Intraventricular Pressure A mean intraventricular pressure greater than 15 mm Hg was found in 14 of 16 patients in the group with benign intracranial hypertension and all 6 patients of the group with nonbenign intracranial hypertension; the pressure even exceeded 30 mm Hg in 6 patients. Varying pressure waves were seen in almost all of the tracings, but typical plateau waves were encountered in only 6 patients. The two tracings with intraventricular pressure less than 15 mm Hg presented pressure waves characteristic of increased cerebral compliance and thus were interpreted as indicative of effective intracranial hypertension.
Patency of Dural Sinuses Five patients in the group with benign intracranial hypertension (Patients 12, 13, 14, 15, 16) and 1 patient of the group with nonbenign intracranial hypertension group (Patient 18) had obstructed dural sinuses; complete obstruction was found in 2 patients and partial obstruction in 4 patients. Obstruction of the superior sagittal sinus was found in 1 patient (Fig. 1), and of a lateral sinus in 5 patients. In these last patients, the obstructed sinus was either single or functionally predominant. In the remaining 16
Table 3. Numerical and Experimental Data in 16 Patients Suffering from Benign Intracranial Hypertension Patient No.
Mean ICP (mm Hg)
CSF-SSS Gradient (mm Hg)
Flow Resistance (mm Hg/ml/min)
Sinuses
Isotope Cistemography
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
20 38 23 38 13 18 3O 35 32 15 20 28 19 2O 23 13
+13 + 3 ... +15 + 6 + 8 ... +25 + 3 ... + 5 - 2 - 18 0 0 0
72 8 30 60 16 20 100 70 13 21 40 12 20 8 12 23
Patent Patent Patent Patent Patent Patent Patent Patent Patent Patent Patent Obstructed Obstructed Obstructed Obstructed Obstructed
... ... Delayed Delayed ... ... Normal ... Normal ... ... ... Normal Normal Normal Normal
ICP = intracranial pre~ure; SSS = supermrsagittalsinus.
Janny et ah CSF Absorption with Benign Intracranial Hypertension
171
Table 4. Numerical and Experimental Data in 6 Patients Suffering from Nonbenign Forms of Intracranial Hypertension Patient No.
ICP (mm Hg)
CSF-SSS Gradient (mm Hg)
Flow Resistance (ram Hg/ml/min)
Sinuses
Isotope Cisternography
17 18 19 20 21 22
35 21 23 20 20 10
-40 + 1 + 5 + 9 + 4 + 18
26 12 40 60 56 92
Patent (AVM) Obstructed Patent Patent Patent Patent
Normal ... Normal Normal Normal
Abbreviations the same as in Table 3; AVM = arteriovenous malformation.
60 n~m Hg Jugular / Compression 4 0
30_ mm Hg 20 ~ ~N.f'vwr ~
4 / ~
cle
Sinus ~ N./-N/"N)N.Ventricle
Gradient: - 2 mm Hg Flow Resistance: 12 mm Hg/ml/min
10S Gradient: + 18 mm Hg Flow Resistance: 92 mm Hg/ml/min
Fig. 1. Patient 12. Sagittal sinus thrombosis in a 19-year.old woman who had been using oral contraceptives. The pressure gradient is reversed, but the flow resistance is normal.
Fig. 2. Patient 22. Patent sinuses in a case of lymphocytic meningitis (lupus erythematosus). The pressure gradient is slightly increased, whereas the flow resistance is considerably increased.
patients, the cerebral venous channels were patent. However, in Patient 17 an early opacification of the dural sinuses was present due to the drainage of an important cirsoid aneurysm of the occipital scalp.
cirsoid aneurysm, these values were respectively - 4 0 mm Hg and 26 mm Hg/ml/min. In the 15 patients with patent sinuses, the mean CSF resistance to flow was 46.6 mm Hg/ml/min; in the 12 of these patients who also underwent pressure gradient measurements, a mean value of + 9 . 5 mm Hg was found. Figure 2 shows an example of a patient with patent sinuses with such an increase of CSF resistance to flow.
CSF Absorption In the 6 patients with an obstructed sinus, the mean pressure gradient between the ventricle and the superior sagittal sinus was - 3 . 1 6 mm Hg and the mean CSF resistance to flow was 14.5 mm Hg/ml/min. A n example of such a reversed gradient is given in Fig. 1. In the patient with the
Cisternography Isotope cisternography was normal in 10 out of the 12 cases studied, the transit being slightly delayed without
172 SurgicalNeurology Vol 15 No 3 March 1981
ventricular reflux in 2 patients with patent sinuses belonging to the group with benign intracmnial hypertension.
tion are often present in benign as well as some forms of nonbenign intracranial hypertension; this suggests that the mechanism of intracranial hypertension could be the same in both cases. Measurement of the pressure gradient between CSF and the sagittal sinus and of CSF resistance to flow in relation to the degree of patency of the dural sinuses has brought to light the important finding that in the 7 patients with sinus obstruction (whether by venous thrombosis, by tumor, or by venous drainage of an angioma), the pressure gradient was reversed or nullified, whereas CSF resistance to drainage was normal or slightly elevated. These findings can be explained by the relation that constantly exists between the cortical venous pressure (PVco), the CSF pressure (Pcsf), and the superior sagittal sinus pressure (Psss). In normal individuals this relationship is PVco > Pcsf > Psss [2]. In patients with sinus obstruction, blood flow in the sinus as well as in the afferent cortical veins is blocked to the extent
l~iscusslon It is generally accepted that the pressure gradient between CSF and the superior sagittal sinus varies between + 2 and +6 mm Hg in anesthetized humans lying in the supine position [2]. Under the same conditions, the CSF resistance to drainage (as measured by intrathecal perfusion methods) ranges from 5 to 15 mm Hg/ml/min [9, 12]. Compared to these figures, our findings show that the pressure gradient or CSF resistance to flow (or both) was altered in the majority of our patients. Of the 19 patients who underwent measurements of both factors, only 2 (Patients 2, 19) had normal values. Pressure measurements are certainly subject to artifacts and errors. Anesthesia can alter CSF pressure as well as the venous pressures; occult leakages can falsify the result of intrathecal perfusion tests [19]. Moreover, the normal fluctuations of the pressure gradient between CSF and sinus blood, as well as fluctuations of CSF resistance to drain- Fig. 3. Patient 22. (A) Pacchionian bodies showing axes of thick, age, are not yet perfectly understood. Nevertheless, many poorly vascularized connective tissue surrounded with a meningothelial layer which is sometimes very thick. (H&E; x27.) (B) Whorls of values obtained by us differ substantially from those meningothelial cells in the pacchionian bodies. Note the lymphocytes generally accepted as normal. This finding probably con- scattered in the tissue. (H&E; x 180.) These alterations seem able to firms the hypothesis that some disorders of CSF absorp- increase the flow resistance across the villi. A
Janny et al: CSF Absorption with Benign Intracranial Hypertension
that PVco equals Psss; this changes the above relationship to PVco = Psss >/ Pcsf (since PVco must remain greater than Pcsf [2]). Thus, when this sinus obstruction exists, CSF can no longer drain through the villi which depend on the obstructed sinus; it must now be diverted towards other outlet c h a n n e l s - - e i t h e r the villi distal to the obstruction or those villi that were described in the spinal roots [27, 28]. These new channels may have a CSF resistance to drainage somewhat higher than the usual ones, thus accounting for the slight rise that we found in this parameter. This hypothesis is well supported by those authors who have demonstrated that there are potentially two systems of CSF absorption; one is rapid, with a high functioning pressure, and one is slow, with a low functioning pressure, and the latter system would be the only one functioning in patients with sinus obstruction [16, 19, 25]. In the 15 patients with patent cerebral venous channels, CSF resistance to drainage was on the average three times the normal value while the pressure gradient was normal or slightly increased. Since the CSF channels (ventricles and subarachnoid spaces) were found to be patent in all 15 patients in whom ventriculography was used, this substantial increase in CSF resistance to drainage suggests a specific alteration in the villi themselves. Unfortunately we were able to obtain histopathological correlation in only 1 case (Patient 22), a patient suffering from chronic lymphocytic meningitis (lupus). A brain biopsy was performed during which it was possible to obtain a fragment of an arachnoid villus as well. T h e modifications of this villus (Fig. 3) were found to be consistent with an increase in CSF resistance to drainage across it. No correlation has been obtained in the other 14 patients, although 3 with a recent history of head injury could possibly have suffered subarachnoid hemorrhage with blood subsequently clogging the villi as was experimentally shown by Alksne and Lovings [1]. Our findings on isotope cisternography contradict those of Johnston and Patterson [14] and Bercaw and Greer [3]. These authors found in their patients a marked delay in isotope CSF transit. Johnston [13], working on dogs, found a substantial reduction in CSF absorption in all animals treated either by the rapid termination of high doses of steroids or by the ligature of the major veins in the neck. Thus, for these authors, a delayed CSF transit is indicative of reduced CSF absorption. In our study, 10 out of 12 patients had normal isotope cisternograms, as was also the case in several patients reported by Frigeni and co-workers [11], Martins [17], and Boddie and colleagues [4]. It is our opinion that in benign intracranial hypertension, cisternography is sometimes delayed but most often is normal, indicating that CSF flow is generally preserved. T h e reason for CSF flow conservation is probably the intracranial pressure itself, which rises until it forces the regular CSF flow either to be absorbed into channels other than the
173
obstructed sinuses, or to overcome the high resistance offered by the altered arachnoid villi. In accordance with this statement is the widely accepted opinion that the CSF secretion rate is largely independent of intracranial pressure [5, 20, 22]. Moreover, Johnston [13] in his experimental work computed the CSF formation rate by indirect calculation and found values close to normal. O n the other hand, Sahar [23] showed that a rise in intracranial pressure could reduce the rate of CSF formation, thereby accounting for the cases in which there exists a delayed cisternography.
Conclusion We conclude that in many cases of benign intracranial hypertension a real disorder of the mechanism of CSF absorption does exist, as was claimed by Johnston; however it appears to coexist in most cases with a normal CSF flow. This disorder of CSF absorption can exist in many forms of nonbenign intracranial hypertension as well, and thus does not appear to be specific for benign intracranial hypertension.
We would like to acknowledge the valuable help of Dr Nicole Heldt (Institut d'Anatomie Pathologique de Strasbourg), who examined the arachnoid villus specimen, and Dr Annie Veyre (Service de M6decine Nucl6aire, Clermont-Ferrand), who reviewed the isotope cisternograms.
References 1. Alksne JF, Lovings ET: The role of the arachnoid villus in the removal of red blood cells from the subarachnoid space. An electron microscope study in the dog. J Neurosurg 36:192-200, 1972 2. Benabid AL, de Rougemont J, Barge M: Pression veineuse c6r6brale, pression sinusale et pression intracranienne. Neurochirurgie 20:623632, 1974 3. Bercaw BL, Greer M: Transport of intrathecal 131IRISA in benign intmcranial hypertension. Neurology 20:787- 790, 1970 4. Boddie HG, Banna M, Bradley WG: "Benign" intra¢ranial hypertension. A survey of the clinical and radiological features and long-term prognosis. Brain 97:313-326, 1974 5. Cutler RW, Page L, Galicich J, Watter GW: Formation and resorption of cerebrospinal fluid in man. Brain 91:707, 1968 6. Dandy W: Intracranial pressure without brain tumor. Diagnosis and treatment. Ann Surg 106:492-513, 1937 7. Davson H, Hollingworth G, Segal MB: The mechanism of drainage of the cerebrospinal fluid. Brain 93:665-678, 1970 8. Di Chiro G: Radioisotope cistemography, ventriculography and myelography, in Gibson AJ, Smoak WM (eds): Central Nervous System Investigations with Radionuclides. Springfield, IL: Thomas, 1971, pp 310-321 9. Eckstedt J: C.S.F. hydrodynamics in man. 2. Normal hydrodynamics variables related to C.S.F. pressure and flow. J Neurol Neurosurg Psychiatry 41:345-353, 1978 10. Evans WA: An encephalographic ratio for estimating the size of the cerebral ventricles. Am J Dis Child 64:820-830, 1942 11. Frigeni G, Giani SM, Paoletti P, Villani R: Isotope cistemography. Considerations on abnormal pictures. Acta Neurochir (Wien) 25:145-163, 1971 12. Janny P, Flori B, Georget AM, Veyre A: La r6sistance ~ l'6coulement du L.C.R. dans l'hydroc6phalie ~ pression normale. Rev Neurol (Paris) 131:211-217, 1975
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13. Johnston I: Reduced C.S.F. absorption syndrome. Reappraisal of benigh intracranial hypertension and related conditions. Lancet 2:418-420, 1973 14. Johnston 1, Patterson A: Benign intracranial hypertension: II. C.S.F. pressure and circulation. Brain 97:301-312, 1974 15. Katanan R, HusseyF: A simple constant infusion manometric test for measurement of C.S.F. absorption: I. Rationale and method. Neurology 20:534-544, 1970 16. Lorenzo AV, Page LK, Watters GV: Relationships between C.S.F. formation, absorption and pressure in human hydrocephalus. Brain 93:679-692, 1970 17. Martins AN: Resistance to drainage of cerebrospinal fluid: clinical measurement and significance. J Neuroi Neurosurg Psychiatry 36:313-318, 1973 18. Mathew NT, Meyer JS, Ott EO: Increased cerebral blood volume in benign intracranial hypertension. Neurology 25:646-649, 1975 19. Nelson JR, Goodman SJ: An evaluation of the cerebrospinal fluid infusion test for hydrocephalus. Neurology 91:1037-1053, 1971 20. PappenhaimerJR, HeiseySR, Jordan EF, DownerJC: Perfusionof the cerebral ventricular system in the unanesthetized goat. Am J Physiol 203:763-774, 1962 21. Raichle ME, Gado MH, Eichling JO, Phelps, MS, Grubb RL Jr,
22. 23. 24. 25. 26.
27. 28.
HoffmanEJ, Ter-PogossianMM: Cerebral hemodynamicsand metabolism in pseudotumor cembri, in Lundberg N, Ponten U, Brock M (eds): Intmcranial Pressure, vol 2. Berlin, Heidelberg, New York: Springer, 1975, pp 198-200 Rubin RC, Henderson ES, Ommaya AK, Walker MD, Rail DP: The production of cerebrospinal fluid in man and its modifications by acetazolamide. J Neumsurg 25:430-436, 1966 Sahar A: The effect of pressure on the production of cerebrospinal fluid by the choroid plexus. J Neurol Sci 16:49-58, 1972 Sahs AL, Joynt RL: Brain swelling of unknown cause. Neurology 6:791-803, 1956 SokolowskiSJ: Bolus injection test for measurement of cerebrospinal fluid absorption. J Neurol Sci 28:491-504, 1976 Van Effenterte R, PoissonM, Van Effenterre G, Schaison M, Sichez JP, Haut J: Neuropathie optique oedemateuse au maldate de perhexiline associd ~ une polyneuropathie pdriphdrique. Arch Ophtalmol (Paris) 37:709-714, 1977 Welch K, Pollay M: The spinal arachnoid villi of the monkeysCer. cop/thecus aeth/ops sabaeus and Macaca ires. Anat Rec 145:43-46, 1963 Wislocki GB: The cytology of the cerebrospinal fluid pathway, in Cowdry EV (ed): Special Cytology. New York: Hoeber, 1932, vol 3
Announcement: Daniel Ruge Appointed Physician to President It has recently been announced that Dr. Daniel Ruge has been appointed as Physician to President Ronald Reagan. Dr. Ruge is a neurological surgeon who was formerly Prolessor of Surgery (Neurosurgery) at Northwestern University Medical School in Chicago. Recently he has served as Director of the Spinal Cord Injury Service of the Veterans Administration in Washington, D.C. All neurological surgeons will be proud that Dr. Ruge has received this appointment. They will wish him well and will be willing to render any service with which they can be helpful to him in this responsible position. Paul C. Bucy, M.D., Editor
Sixteen patients suffering from benign intracranial hypertension were studied by a continuous measurement of intraventricular pressure, a simultaneous recording of intraventricular and sagittal sinus pressures, and a measurement of the cerebrospinal fluid (CSF) resistance to drainage. Isotope cisternography was performed and the patency of the dural sinuses verified by direct sinography or phlebography or both. The same procedure was used to study 6 other patients suffering from disorders leading to the same type of intracranial hypertension. In 16, our results confirm a defect in CSF absorption mechanisms linked to an abolition of the pressure gradient between CSF and sagittal sinus in 6 patients, as well as an important increase in CSF resistance to drainage in 10 others. Despite this defect, the CSF circulation was normal in most patients (10 of 12) as demonstrated by isotope cisternography.
Benign intracranial hypertension has been variously attributed to increased cerebral blood volume [6, 18, 21], cerebral edema [24], or enlargement of the cerebrospinal fluid (CSF) compartment related to some disorder of CSF absorption mechanisms. The last hypothesis was initially proposed by Bercaw and Greer [3] on the basis of a delayed isotope transit study in 2 patients. This hypothesis was subsequently accepted by Johnston [13]; knowing of the work by Davson and associates [7] on CSF absorption mechanism, Johnston proposed that a reduction of the CSF absorption rate resulted either from an abolition of the pressure gradient between CSF and the superior sagittal sinus or from the elevation of resistance to drainage of CSF across the arachnoid villi. Johnston [13] experimentally confirmed his theory; Martins [17], in a study on the measurement and importance of CSF resistance to drainage, made an incidental reference to 4 cases of benign intracranial hypertension. Nevertheless, a large clinical study is still needed for verification. The goal of this paper is to provide such a study. Fromthe Departmentsof Neurosurgeryand Neuroradiology,Universityof Clermont-Fen'and,Clermont-Ferrand,France. Address reprint requests to Prof. P. Janny, CliniqueNeurochirtagicale, HOpitalFontmaure,63400 Chamalieres, France. Key words: benign intracranial hypertension;CSF absorption; sagittal sinus pressure; CSF flowresistance.
Clinical Observations and Method From 1973 to 1979, 16 patients considered to have benign intracranial hypertension were observed (Table 1). This group consisted of 8 men and 8 women ranging from 2 to 56 years of age (mean, 24.5 years). All presented a pure intracranial hypertension syndrome without any sign of focal disease. Bilateral papilledema was found in all patients. Possible etiologic factors, widely accepted by many authors, were clearly present in 8 patients: 3 with ear, nose, or throat infection, 4 with head injury, and 1 patient using oral contraceptives. Among the 8 remaining patients were 3 obese women (1 of whom was pregnant), 1 young girl beginning puberty, a 56-year-old man treated with perhexiline maleate (a drug that has been reported to cause papilledema), and 3 patients without any suggested etiology. Electroencephalograms, brain scintigraphy, and the composition of lumbar CSF were normal in all patients. Plain roentgenogram of the skull, angiography of the carotid or vertebral systems, and ventriculography with air or Pantopaque (or both) were carried out to eliminate a space-occupying lesion. The mean Evans [10] index was 0.29 - 0.04, characterizing lateral ventricles most often of normal size or sometimes slightly enlarged, but rarely diminished. As a means of comparison, we studied another group of 6 patients (Table 2) who presented the same pure intracranial hypertension syndrome with equally normal ventricular and subarachnoid systems; in these patients there existed an evident affection that precluded their acceptance among the group of patients with benign intracranial hypertension. These 6 patients, specified here as the "nonbenign intracranial hypertension group," included a patient with an arteriovenous malformation of the scalp draining profusely into the superior sagittal sinus, one with meningioma en plaque obstructing a single lateral sinus, and 4 patients who had chronic lymphocytic meningitis of various causes, 1 case of lupus erythematosus, 1 neoplasm, and 2 of unknown cause). The following determinations were made for these two groups of patients: (1) monitoring of intraventricular pressure; (2) measurement of the various parameters of CSF absorption; and (3) patency of the dural sinuses. Monitoring of intraventricular pressure was accomplished by placing an
168 0090-3019/81/030168-07501.25 © 1980 by Little, Brown and Company (Inc.)
Janny et al: CSF Absorption with Benign lntracranial Hypertension
169
Table 1. Clinical Data in 16 Patients Suffering from Benign Intracranial Hypertension CSF Patient
Age (yr)
Sex
History
Papilledema
Cells (per mm 3)
Protein (gm/liter)
Evans Indexa
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
2 5 55 42 27 14 51 56 26 35 19 19 8 12 5 2
M F M M F F M M F F F F M F M M
Head injury Otitis None Head injury Obesity Menarche Head injury Perhexiline maleate Obesity None Pregnancy, obesity Oral contraceptive Otitis None Head injury Otitis
+ + + + + + + + + + + + + + + +
5 1 3 2 1 •• 1 0 0 0 0 2 11 2 2 0
0.37 0.34 0.60 0•50 0.36 •.. 0.44 0.40 0.35 0.40 0.18 0.55 0.20 0.52 0.18 0.37
0.36 0.36 ... 0.30 0.25 0.30 0.27 0.30 ... 0.29 0.26 0.24 0.25 0.33 O.34 0.30
Protein (gm/liter)
Evans Index a
aEvans index is normally between 0.16 and 0.29.
Table 2. Clinical Data in 6 Patients Suffering from Nonbenign Forms of Intracranial Hypertension CSF Patient
Age (yr)
Sex
History
Papilledema
Cells (per mm3)
17
56
M
0.78
0.27
56
M
+ (optic atrophy) +
0
18
...
...
0.19
19
37
M
+
36
0.72
0.30
20
12
M
+
16
0.44
0.28
21
21
F
+
28
2.24
0.30
22
52
F
Arteriovenous malformation Meningioma en plaque Chronic meningitis Chronic meningitis Chronic meningitis Chronic meningitis (lupus)
+
67
1.84
0.38
"Evans index is normally between O. 16 and 0.29.
indwelling catheter inside the frontal h o m of a lateral ventricle for a period of at least 24 hours (mean, 2.5 days) while using a p o i n t - b y - p o i n t Philips slow recorder* (2 cm per hour) to produce the tracings. Measurement of the various parameters of C S F absorption was accomplished under general anesthesia and included a simultaneous re-
cording of the intraventricular and superior sagittal sinus pressures and a measurement of C S F resistance to flow. T h e superior sagittal sinus pressure was measured through a 16-gauge, 6.25 c m (2½ inch) Teflon catheter* introduced into the sinus by passing it through a burr hole situated at the m i d p o i n t of the coronal region of the skull. Continuous
*Pointax recorder; Philips, Division Sciences et Industrie, 105 rue de Paris, 93002 Bobigny, France.
*Longdwellcatheter needle with obmrator; Becton Dickinson Company, Rutherford, NJ 07070•
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nonheparinized perfusion was used to prevent clotting inside the catheter. The sinus pressure was then recorded on an optic ultraviolet recorder,* together with the CSF pressure from the previously catheterized ventricle, allowing one to determine at each time the pressure gradient between them. This pressure gradient was studied at rest, during compression of the jugular veins, and during the intraventricular perfusion, but only the resting pressure gradient was taken into consideration in the present paper. The duration of the recording was about 2 hours, except in 1 patient (Patient 21), in whom it was possible to maintain the catheter inside the sinus for 24 hours while recording the pressure gradient on the patient while awake. The CSF resistance to flow was measured using Katzman and Hussey's [15] constant infusion manometric test; the perfusion was administered by the intraventricular catheter at the rate of 0.5 ml/min. Calculation of CSF resistance to drainage previously gave us a normal value of 10 - 5 mm Hg/ml/min [12]. The patency of the dural sinuses was verified by direct sinography, performed after pressure measurements with the aid of the intrasinus catheter. In 7 patients who had undergone both angiography and direct sinography studies, we compared the venous filling aspect of their angiograms with films of their sinograms. Twelve patients underwent isotope cisternography with technetium 99m or indium 111 diethylenetriamine penta*Ultraviolet optic recorder OM 4501; Schlumberger, 1 rue de Nieuport, 78140 Velizy-ViUacoublay,France.
acetic acid; the isotope transit was interpreted according to criteria proposed by Di Chiro [8]. Results Tables 3 and 4 show the collected numerical data, together with the results from sinography and cisternography.
Intraventricular Pressure A mean intraventricular pressure greater than 15 mm Hg was found in 14 of 16 patients in the group with benign intracranial hypertension and all 6 patients of the group with nonbenign intracranial hypertension; the pressure even exceeded 30 mm Hg in 6 patients. Varying pressure waves were seen in almost all of the tracings, but typical plateau waves were encountered in only 6 patients. The two tracings with intraventricular pressure less than 15 mm Hg presented pressure waves characteristic of increased cerebral compliance and thus were interpreted as indicative of effective intracranial hypertension.
Patency of Dural Sinuses Five patients in the group with benign intracranial hypertension (Patients 12, 13, 14, 15, 16) and 1 patient of the group with nonbenign intracranial hypertension group (Patient 18) had obstructed dural sinuses; complete obstruction was found in 2 patients and partial obstruction in 4 patients. Obstruction of the superior sagittal sinus was found in 1 patient (Fig. 1), and of a lateral sinus in 5 patients. In these last patients, the obstructed sinus was either single or functionally predominant. In the remaining 16
Table 3. Numerical and Experimental Data in 16 Patients Suffering from Benign Intracranial Hypertension Patient No.
Mean ICP (mm Hg)
CSF-SSS Gradient (mm Hg)
Flow Resistance (mm Hg/ml/min)
Sinuses
Isotope Cistemography
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
20 38 23 38 13 18 3O 35 32 15 20 28 19 2O 23 13
+13 + 3 ... +15 + 6 + 8 ... +25 + 3 ... + 5 - 2 - 18 0 0 0
72 8 30 60 16 20 100 70 13 21 40 12 20 8 12 23
Patent Patent Patent Patent Patent Patent Patent Patent Patent Patent Patent Obstructed Obstructed Obstructed Obstructed Obstructed
... ... Delayed Delayed ... ... Normal ... Normal ... ... ... Normal Normal Normal Normal
ICP = intracranial pre~ure; SSS = supermrsagittalsinus.
Janny et ah CSF Absorption with Benign Intracranial Hypertension
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Table 4. Numerical and Experimental Data in 6 Patients Suffering from Nonbenign Forms of Intracranial Hypertension Patient No.
ICP (mm Hg)
CSF-SSS Gradient (mm Hg)
Flow Resistance (ram Hg/ml/min)
Sinuses
Isotope Cisternography
17 18 19 20 21 22
35 21 23 20 20 10
-40 + 1 + 5 + 9 + 4 + 18
26 12 40 60 56 92
Patent (AVM) Obstructed Patent Patent Patent Patent
Normal ... Normal Normal Normal
Abbreviations the same as in Table 3; AVM = arteriovenous malformation.
60 n~m Hg Jugular / Compression 4 0
30_ mm Hg 20 ~ ~N.f'vwr ~
4 / ~
cle
Sinus ~ N./-N/"N)N.Ventricle
Gradient: - 2 mm Hg Flow Resistance: 12 mm Hg/ml/min
10S Gradient: + 18 mm Hg Flow Resistance: 92 mm Hg/ml/min
Fig. 1. Patient 12. Sagittal sinus thrombosis in a 19-year.old woman who had been using oral contraceptives. The pressure gradient is reversed, but the flow resistance is normal.
Fig. 2. Patient 22. Patent sinuses in a case of lymphocytic meningitis (lupus erythematosus). The pressure gradient is slightly increased, whereas the flow resistance is considerably increased.
patients, the cerebral venous channels were patent. However, in Patient 17 an early opacification of the dural sinuses was present due to the drainage of an important cirsoid aneurysm of the occipital scalp.
cirsoid aneurysm, these values were respectively - 4 0 mm Hg and 26 mm Hg/ml/min. In the 15 patients with patent sinuses, the mean CSF resistance to flow was 46.6 mm Hg/ml/min; in the 12 of these patients who also underwent pressure gradient measurements, a mean value of + 9 . 5 mm Hg was found. Figure 2 shows an example of a patient with patent sinuses with such an increase of CSF resistance to flow.
CSF Absorption In the 6 patients with an obstructed sinus, the mean pressure gradient between the ventricle and the superior sagittal sinus was - 3 . 1 6 mm Hg and the mean CSF resistance to flow was 14.5 mm Hg/ml/min. A n example of such a reversed gradient is given in Fig. 1. In the patient with the
Cisternography Isotope cisternography was normal in 10 out of the 12 cases studied, the transit being slightly delayed without
172 SurgicalNeurology Vol 15 No 3 March 1981
ventricular reflux in 2 patients with patent sinuses belonging to the group with benign intracmnial hypertension.
tion are often present in benign as well as some forms of nonbenign intracranial hypertension; this suggests that the mechanism of intracranial hypertension could be the same in both cases. Measurement of the pressure gradient between CSF and the sagittal sinus and of CSF resistance to flow in relation to the degree of patency of the dural sinuses has brought to light the important finding that in the 7 patients with sinus obstruction (whether by venous thrombosis, by tumor, or by venous drainage of an angioma), the pressure gradient was reversed or nullified, whereas CSF resistance to drainage was normal or slightly elevated. These findings can be explained by the relation that constantly exists between the cortical venous pressure (PVco), the CSF pressure (Pcsf), and the superior sagittal sinus pressure (Psss). In normal individuals this relationship is PVco > Pcsf > Psss [2]. In patients with sinus obstruction, blood flow in the sinus as well as in the afferent cortical veins is blocked to the extent
l~iscusslon It is generally accepted that the pressure gradient between CSF and the superior sagittal sinus varies between + 2 and +6 mm Hg in anesthetized humans lying in the supine position [2]. Under the same conditions, the CSF resistance to drainage (as measured by intrathecal perfusion methods) ranges from 5 to 15 mm Hg/ml/min [9, 12]. Compared to these figures, our findings show that the pressure gradient or CSF resistance to flow (or both) was altered in the majority of our patients. Of the 19 patients who underwent measurements of both factors, only 2 (Patients 2, 19) had normal values. Pressure measurements are certainly subject to artifacts and errors. Anesthesia can alter CSF pressure as well as the venous pressures; occult leakages can falsify the result of intrathecal perfusion tests [19]. Moreover, the normal fluctuations of the pressure gradient between CSF and sinus blood, as well as fluctuations of CSF resistance to drain- Fig. 3. Patient 22. (A) Pacchionian bodies showing axes of thick, age, are not yet perfectly understood. Nevertheless, many poorly vascularized connective tissue surrounded with a meningothelial layer which is sometimes very thick. (H&E; x27.) (B) Whorls of values obtained by us differ substantially from those meningothelial cells in the pacchionian bodies. Note the lymphocytes generally accepted as normal. This finding probably con- scattered in the tissue. (H&E; x 180.) These alterations seem able to firms the hypothesis that some disorders of CSF absorp- increase the flow resistance across the villi. A
Janny et al: CSF Absorption with Benign Intracranial Hypertension
that PVco equals Psss; this changes the above relationship to PVco = Psss >/ Pcsf (since PVco must remain greater than Pcsf [2]). Thus, when this sinus obstruction exists, CSF can no longer drain through the villi which depend on the obstructed sinus; it must now be diverted towards other outlet c h a n n e l s - - e i t h e r the villi distal to the obstruction or those villi that were described in the spinal roots [27, 28]. These new channels may have a CSF resistance to drainage somewhat higher than the usual ones, thus accounting for the slight rise that we found in this parameter. This hypothesis is well supported by those authors who have demonstrated that there are potentially two systems of CSF absorption; one is rapid, with a high functioning pressure, and one is slow, with a low functioning pressure, and the latter system would be the only one functioning in patients with sinus obstruction [16, 19, 25]. In the 15 patients with patent cerebral venous channels, CSF resistance to drainage was on the average three times the normal value while the pressure gradient was normal or slightly increased. Since the CSF channels (ventricles and subarachnoid spaces) were found to be patent in all 15 patients in whom ventriculography was used, this substantial increase in CSF resistance to drainage suggests a specific alteration in the villi themselves. Unfortunately we were able to obtain histopathological correlation in only 1 case (Patient 22), a patient suffering from chronic lymphocytic meningitis (lupus). A brain biopsy was performed during which it was possible to obtain a fragment of an arachnoid villus as well. T h e modifications of this villus (Fig. 3) were found to be consistent with an increase in CSF resistance to drainage across it. No correlation has been obtained in the other 14 patients, although 3 with a recent history of head injury could possibly have suffered subarachnoid hemorrhage with blood subsequently clogging the villi as was experimentally shown by Alksne and Lovings [1]. Our findings on isotope cisternography contradict those of Johnston and Patterson [14] and Bercaw and Greer [3]. These authors found in their patients a marked delay in isotope CSF transit. Johnston [13], working on dogs, found a substantial reduction in CSF absorption in all animals treated either by the rapid termination of high doses of steroids or by the ligature of the major veins in the neck. Thus, for these authors, a delayed CSF transit is indicative of reduced CSF absorption. In our study, 10 out of 12 patients had normal isotope cisternograms, as was also the case in several patients reported by Frigeni and co-workers [11], Martins [17], and Boddie and colleagues [4]. It is our opinion that in benign intracranial hypertension, cisternography is sometimes delayed but most often is normal, indicating that CSF flow is generally preserved. T h e reason for CSF flow conservation is probably the intracranial pressure itself, which rises until it forces the regular CSF flow either to be absorbed into channels other than the
173
obstructed sinuses, or to overcome the high resistance offered by the altered arachnoid villi. In accordance with this statement is the widely accepted opinion that the CSF secretion rate is largely independent of intracranial pressure [5, 20, 22]. Moreover, Johnston [13] in his experimental work computed the CSF formation rate by indirect calculation and found values close to normal. O n the other hand, Sahar [23] showed that a rise in intracranial pressure could reduce the rate of CSF formation, thereby accounting for the cases in which there exists a delayed cisternography.
Conclusion We conclude that in many cases of benign intracranial hypertension a real disorder of the mechanism of CSF absorption does exist, as was claimed by Johnston; however it appears to coexist in most cases with a normal CSF flow. This disorder of CSF absorption can exist in many forms of nonbenign intracranial hypertension as well, and thus does not appear to be specific for benign intracranial hypertension.
We would like to acknowledge the valuable help of Dr Nicole Heldt (Institut d'Anatomie Pathologique de Strasbourg), who examined the arachnoid villus specimen, and Dr Annie Veyre (Service de M6decine Nucl6aire, Clermont-Ferrand), who reviewed the isotope cisternograms.
References 1. Alksne JF, Lovings ET: The role of the arachnoid villus in the removal of red blood cells from the subarachnoid space. An electron microscope study in the dog. J Neurosurg 36:192-200, 1972 2. Benabid AL, de Rougemont J, Barge M: Pression veineuse c6r6brale, pression sinusale et pression intracranienne. Neurochirurgie 20:623632, 1974 3. Bercaw BL, Greer M: Transport of intrathecal 131IRISA in benign intmcranial hypertension. Neurology 20:787- 790, 1970 4. Boddie HG, Banna M, Bradley WG: "Benign" intra¢ranial hypertension. A survey of the clinical and radiological features and long-term prognosis. Brain 97:313-326, 1974 5. Cutler RW, Page L, Galicich J, Watter GW: Formation and resorption of cerebrospinal fluid in man. Brain 91:707, 1968 6. Dandy W: Intracranial pressure without brain tumor. Diagnosis and treatment. Ann Surg 106:492-513, 1937 7. Davson H, Hollingworth G, Segal MB: The mechanism of drainage of the cerebrospinal fluid. Brain 93:665-678, 1970 8. Di Chiro G: Radioisotope cistemography, ventriculography and myelography, in Gibson AJ, Smoak WM (eds): Central Nervous System Investigations with Radionuclides. Springfield, IL: Thomas, 1971, pp 310-321 9. Eckstedt J: C.S.F. hydrodynamics in man. 2. Normal hydrodynamics variables related to C.S.F. pressure and flow. J Neurol Neurosurg Psychiatry 41:345-353, 1978 10. Evans WA: An encephalographic ratio for estimating the size of the cerebral ventricles. Am J Dis Child 64:820-830, 1942 11. Frigeni G, Giani SM, Paoletti P, Villani R: Isotope cistemography. Considerations on abnormal pictures. Acta Neurochir (Wien) 25:145-163, 1971 12. Janny P, Flori B, Georget AM, Veyre A: La r6sistance ~ l'6coulement du L.C.R. dans l'hydroc6phalie ~ pression normale. Rev Neurol (Paris) 131:211-217, 1975
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Announcement: Daniel Ruge Appointed Physician to President It has recently been announced that Dr. Daniel Ruge has been appointed as Physician to President Ronald Reagan. Dr. Ruge is a neurological surgeon who was formerly Prolessor of Surgery (Neurosurgery) at Northwestern University Medical School in Chicago. Recently he has served as Director of the Spinal Cord Injury Service of the Veterans Administration in Washington, D.C. All neurological surgeons will be proud that Dr. Ruge has received this appointment. They will wish him well and will be willing to render any service with which they can be helpful to him in this responsible position. Paul C. Bucy, M.D., Editor