REDUCED C.S.F. ABSORPTION SYNDROME

418 " lock on " the cortical rhythm and could thereby of the cortex to be " busy ". The lack of correlation between the traditional acupuncture sites and the anatomy of the peripheral nervous system would not invalidate this hypothesis. One could postulate that the acupuncture sites happen to be supplied by nerves which, by reason of appropriate lengths and pathways, have time constants of transmission which " tune " them to the

to

cause areas

stimulating frequency. This hypothesis is moreover not inconsistent with a participation of hypnotic effects. The mechanism of hypnosis has never been adequately explained. Perhaps it facilitates establishment of a " busy " cortex just as with voluntary inhibition or augmentation of rhythmic responses mentioned above. The " busy cortex" hypothesis could be studied by varying the frequency of acupuncture-needle vibration while assessing the pain threshold and correlating the findings with the electroencephalographic pattern. One could also predict from this hypothesis that an enhancement of the anaesthetic effect would be likely if larger areas of the cortex were recruited to the dominant rhythm by synchronous photic or auditory stimulation.

factor which increases either PS. S or RA.V., and it is suggested therefore that the general term " reduced C.S.F. absorption syndrome " should replace " benign intracranial hypertension" and similar terms. INTRODUCTION

SINCE the early descriptions of Gowers, Quincke, Nonne, and others over 75 years ago 1-3 there have been many clinical reports of the condition now commonly termed benign intracranial hypertension.’ Typically, in this condition, there is raised intracranial pressure with no apparent cause, no associated neurological abnormalities, and normal investigative findings-in particular, a normal ventricular system.’’ The cause of the intracranial hypertension remains unknown; indeed even which intracranial compartment (brain, blood, or c.s.F.) is involved is uncertain. In addition a wide variety of Eetiological agents have been linked to the condition,6,7 although without knowledge of the underlying pathophysiology it is impossible to say how these factors are related to The present the increase in intracranial pressure. the intracranial is advanced to hypothesis explain to a more hypertension, suggest appropriate term for this condition, and to show how it is related to known astiological agents.

REFERENCES 1. 2. 3. 4. 5.

Lancet, 1973, i, 1372. Melzack, R., Wall, P. D. Science, 1965, 150, 971. Jackson, J. Hughlings. Lancet, 1868, i, 618. Wilson, S. A. Kinnier. Neurology. London, 1940. Walter, V. J., Walter, W. Grey. J. Electroenceph. clin. Neurophysiol. 1949, 1, 1. 6. Kiloh, L. G., McComas, A. J., Osselton, J. W. Clinical Electroencephalography. London, 1972.

REDUCED C.S.F. ABSORPTION SYNDROME Reappraisal of Benign Intracranial Hypertension and Related Conditions IAN

JOHNSTON

Department of Neurosurgery, Hospital for Sick Children, Toronto

A reduced

cerebrospinal-fluid (C.S.F.) absorption syndrome has been defined by considering the factors controlling C.S.F. absorption; the pressure-gradient between the subarachnoid space and the superior sagittal sinus (PC..S.F.-PS.S.), and the resistance to flow across the absorptive channels (RA.V.). The hypothesis is advanced that this syndrome is the same as that previously described by various terms (benign intracranial hypertension, pseudotumour cerebri, otitic hydrocephalus, &c.), since the clinical evidence favours an increase in C.S.F. volume due to impaired absorption as the cause of the intracranial hypertension. In known such as occlusion addition, ætiological agents of the sagittal sinus or the major neck veins (increasing PS.S) or acute steroid withdrawal (increasing RA.V.) have been shown experimentally to cause a marked reduction in C.S.F. absorption. Clinically the syndrome may be produced by any Summary

HYPOTHESIS

It is suggested that the syndrome is due to a reduction in c.s.F. absorption causing an increase in c.s.F. volume. It is this increase in volume, which is accommodated in a distended subarachnoid space, that is responsible for the increase in intracranial pressure. The reduction in c.s.F. absorption is due to a change in the relation between the factors which control the passage of C.S.F. across the arachnoid villi. This relation may be formulated as follows:

where FC.8.F. represents flow of C.S.F. across the arachnoid villi (i.e., absorption), PC.S.F. the c.s.F. pressure within the subarachnoid space, Pgs. the sagittal-sinus pressure, and R.y. the resistance to flow across the arachnoid villi. Any factor which leads to a sufficient increase in sagittal-sinus pressure or in the resistance across the arachnoid villi may, therefore, cause the syndrome provided that c.s.F. production remains relatively constant. c.s.F. absorption under these circumstances will depend on the resultant increase in PC.S.F. compensating for the increase in either P88g or R.B..v. In addition, alternative pathways of c.s.F. absorption may be utilised. CLINICAL

EVIDENCE

The most direct clinical evidence in favour of this concept is the demonstration of delayed c.s.F. flow and reduced absorption on isotope studies of patients with benign intracranial hypertension.8,9 In particular, two patients in the latter study showed a normal clearance of c.s.F. from the ventricles but had a marked delay in flow through the subarachnoid space. Evidence of an increase in c.s.F. volume includes the common finding of distended subarachnoid spaces," low c.s.F.

419

protein levels," increases in the Ayala index,12 and the relatively large volumes of c.s.F. which may be drained at lumbar puncture,13,14 Continuous intracranial-pressure monitoring has provided additional support.9 First, there is the nature of the intracranialpressure changes with the typical finding of relatively low levels of pressure building up slowly and intermittently to high levels before falling rapidly, suggesting sudden venting of c.s.F. as the increased c.s.F. pressure overcomes either a raised sagittal-sinus or an increase in resistance across the arachnoid villi. Secondly, simultaneous measurements of ventricular and lumbar c.s.F. pressures have shown an exact correspondence at all times, confirmation of freely patent c.s.F.-containing spaces. Finally, indirect calculations of rates of c.s.F. formation have shown values within the normal ranged

pressure

Evidence against the proposed hypothesis would include that of an increase in volume of one of the other intracranial compartments (brain or blood) as well as evidence against there being any increase in c.s.F. volume or reduction of absorption. Thus, it has been suggested that diffuse cerebral oedema is the cause of the increase in intracranial pressure in benign intracranial hypertension, although the only objective finding to support this is the histological demonstration of extracellular and intracellular cedema in a small number of cortical-biopsy specimens taken from patients with this condition 15 The necessarily small size of die specimens, the use of light microscopy alone, and, in some cases, doubt about the diagnosis all detract from the significance of these observations. In addition, it is difficult to reconcile the marked well-being of patients with benign intracranial hypertension (who, apart from papilloedema, have no neurological abnormalities whatsoever) with the presence of diffuse cerebral oedema. The idea of an increase in cerebral blood-volume, originally put forward by Dandy,16 is supported only by the finding of a marginal increase in cerebral blood-flow (not volume) in 3 patients with benign intracranial hypertension.4 The postulated increase in cerebral blood-volume has been attributed by some workers to changes in the reactivity of the cerebral resistance vessels, and by others to changes in volume of the cerebral capacitance vessels secondary to venousIn the light of the observed outflow obstruction. intracranial-pressure changes it is hard to conceive of a mechanism responsible for the former, while the latter could only apply to those cases with a demonstrable venous occlusion."," There is, in short, little evidence to incriminate an increase in either brain bulk or cerebral blood-volume as the cause of the raised intracranial pressure in this condition. There is also little direct evidence against there being a reduction in c.s.F. absorption; the only reported study is that of Frigeni et al.,19 who found normal isotope cisternograms in 2 patients said to have benign intracranial hypertension (no clinical details were given). The main theoretical objection to there being an increase in c.s.F. volume is the absence of ventricular dilatation. Such dilatation depends, in general terms, on three factors: the magnitude of the increase in c.s.F. volume, the site

to c.s.F. flow, and the ability of the to adjust for the increased mechanisms compensatory With a volume. c.s.F. completely patent c.s.F.addition to c.s.F. volume will containing system any in be accommodated the most capacious and initially of distensible the physically part system-the subarachnoid space (vide infra). Reduction in brainbulk and cerebral blood-volume may also help to compensate for the increase in c.s.F. volume and, therefore, in c.s.F. pressure. Only if the additional c.s.F. volume exceeds the capacity of these systems

of obstruction

will ventricular enlargement occur. With a nonpatent c.s.F.-containing system a different situation exists, since the relative contribution which different areas of the c.s.F.-containing space may make to the accommodation of the increased c.s.F. volume depends on the site of obstruction to c.s.F. flow relative to the site of c.s.F. production. In addition, obstruction to the c.s.F. circulation may result in the failure of immediate transmission of pressure changes throughout the cranial and spinal subarachnoid spaces, thus setting up pressure-gradients between the ventricles and subarachnoid space which may contribute to the development of ventricular dilatation. EXPERIMENTAL

A series of

experiments

EVIDENCE

was

proposed hypothesis 2° Firstly, to

increase the resistance

designed

the made

to test

attempt flow across the c.s.F.one of the agents known an

was

to

absorption pathways using to cause the benign intracranial hypertension

syn-

drome-steroid withdrawal.11,22 A group of 6 dogs was given a one-month course of high-dosage steroid therapy (cortisone acetate), which was terminated abruptly. One week later c.s.F. absorption was estimated, using an isotope recovery method, and the resistance to c.s.F. flow determined, using the method described by Davson and his colleagues.23 After steroid withdrawal there was both a significant reduction in c.s.F. absorption (table i) and a measurable increase in the resistance to C.s.F. flow (table II). TABLE I-C.S.F. ABSORPTION AFTER STEROID WITHDRAWAL, SAGITTALSINUS OCCLUSION, AND EXTERNAL JUGULAR VEIN LIGATION IN DOGS

Values

as

over

% recovery, from blood and urine, of indium-ll1-D.T.P.A. 4 hours after injection into the cisterna magna.

TABLE II-RESISTANCE TO C.S.F. ABSORPTION (mm. Hg per ml. per min.) AFTER STEROID WITHDRAWAL, SAGITTAL-SINUS OCCLUSION, AND EXTERNAL JUGULAR VEIN LIGATION IN DOGS

420

The

pressure-gradient between the subarachnoid space and the superior sagittal sinus did not, however, differ from control values. Thus, the decrease

in

c.s.F.

absorption could be attributed primarily

to

the increase in resistance to c.s.F. flow across the absorptive channels after acute steroid withdrawal. Secondly, an attempt was made to alter the pressure-gradient between the subarachnoid space and the superior sagittal sinus either by occluding the sinus at the torcula (5 dogs) or by ligating the external jugular veins (4 dogs). In both groups there was a significant reduction in c.s.F. absorption (table l) associated with a reduction, or reversal, of the Pc.s.F.-Ps.s. gradient. There was, however, no change in the resistance to c.s.F. flow in either group (table 11). Most animals with venous occlusion had some degree of intracranial hypertension together with an increase in sagittal-sinus pressure, but none showed any ventricular dilatation nor any increase in brain-weight. Thus, the decrease in c.s.F. absorption and the increase in intracranial pressure in these animals could be attributed primarily to a change in the gradient between subarachnoid space and superior sagittal sinus. Studies were also made of the distribution of fluid added to a freely patent c.s.F.-containing system, both in normal animals and in those with either or extracranial venous intracranial occlusion. with added Ringer’s-lactate solution, crystal-violet, was infused under pressure into the cisterna magna for up to 60 minutes. The fluid either was absorbed through the usual channels or alternate pathways,24 or was accommodated within the subarachnoid No fluid entered the lateral ventricles. space. ETIOLOGY

According to the hypothesis a reduced C.S.F. absorption syndrome may be caused by any factor which acts on the relationship defined earlier to reduce Fc.s.F. A large number of aetiological agents have, in fact, been identified,6 and these may be divided into those which increase Pgg and those which increase RA.v. Increase in Ps.s.-This may follow obstruction to the cranial venous outflow, either extracranially due to involvement of the major veins in the neck,25.26 or intracranially due to direct involvement of the venous sinuses. Most commonly such sinus involvement follows middle-ear disease where clinical measurements have shown an increase in sagittal-sinus pressure,27 but it may also occur after minor head injury 2g29 and possibly after acute infections.9 That both extracranial and intracranial venous obstruction may cause a marked reduction in c.s.F. absorption with an increase in intracranial pressure, but without ventricular dilatation or any increase in brain-weight to suggest diffuse cerebral oedema, was confirmed experimentally in the studies described earlier. Whether there is also, under these circumstances, an increase in cerebral blood-volume due to passive distension of the intracranial veins is uncertain. Other experiments have shown, howeyer, that sagittalsinus and cortical-vein pressures may behave quite independently in states of raised intracranial

pressure.3o

Increase

factors

in

RA.v.-It

associated with

seems

the

likely that several benign intracranial

may act to increase the resistance to C.S.F. flow across the arachnoid villi. Thus, vitamin-A deficiency has been shown to cause marked morphological changes in the villi 31 Further, acute steroid withdrawal was shown, in the experiments described earlier, to cause an increase in RA.v., and perhaps the apparently spontaneous cases of the syndrome may be due to the same mechanism as there is some evidence to suggest an underlying abnormality of steroid metabolism in these patients.32 Indeed, an increase in RA.v. may be the link between many of the astiological agents so far related to this

hypertension syndrome

syndrome. CONCLUSIONS

A reduced c.s.F. absorption syndrome has been defined by considering the factors which control the transfer of c.s.F. across the arachnoid villi. These factors are incorporated in the relationship:

Thus any factor which acts to reduce Fe.smay produce the syndrome. Reduced c.s.F. absorption results in an increase in c.s.F. volume which may lead to an increase in intracranial pressure. This syndrome corresponds to the conditions previously included under a variety of titles: benign intracranial hypertension, otitic hydrocephalus, pseudoIn a majority of cases the intumour cerebri, &c. creased c.s.F. volume can be accommodated in a distended subarachnoid space and there is no ventricular dilatation, for the reasons considered above. Several setiological factors may cause the syndrome through their action either on sagittalsinus pressure or on the resistance to flow across the arachnoid villi. If this concept is confirmed and accepted then the term " reduced c.s.F. absorption syndrome " should replace the previous names, since it states the basic pathophysiology of the condition which may then be related to any identifiable astiological agent. Requests for reprints should be addressed to 1. J., Departof Neurosurgery, Victoria Hospital, London, Ontario,

ment

Canada. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8. 9.

10. 11. 12. 13. 14. 15. 16. 17. 18. 19.

Gowers, W. R. Br. med. J. 1881, i, 796. Quincke, H. Dt. Z. Nervenheilk. 1897, 9, 149. Nonne, M. ibid. 1904, 27, 169. Foley, J. Brain, 1955, 78, 1. Johnston, I. H., Paterson, A. ibid. (in the press). Greer, M. Clin. Neurosurg. 1968, 15, 161. Feldman, M. H., Schlezinger, N. S. Archs Neurol. 1970, 22, 1. Bercaw, B. L., Greer, M. Neurology, Minneapolis, 1970, 20, 787. Johnston, I. H., Paterson, A., Hendrick, E. B. Proc. Am. Ass. neurol. Surg. Los Angeles, 1973. Davidoff, L. M. Neurology, Minneapolis, 1956, 6, 605. Siegel, N. J., Spackman, T. J. Clin. Pediat. 1972, 11, 580. Greer, M. Pediat. Clins N. Am. 1967, 14, 819. Gardner, W. J. Archs Otolar. 1939, 30, 253. Symonds, C. P. Neurology, Minneapolis, 1956, 6, 681. Sahs, A. L., Joynt, R. J. ibid. p. 791. Dandy, W. E. Ann. Surg. 1937, 106, 492. Ray, B. S., Dunbar, H. S. ibid. 1951, 134, 376. Gills, J. P., Kapp, J. P., Odom, G. L. Archs Ophthal. 1967,78, 592. Frigeni, G., Gaini, S. M., Paoletti, P., Villani, R. Acta neurochir. 1971, 25, 145.

421

Reviews of Books Neurology of Ear, Nose and Throat Diseases

xtiology and treatment, but the soundness of theory is always tested by the acid of clinical practice, of which Dr Edwards has clearly had a lot. Clinical

CHARLES HAROLD EDWARDS, F.R.C.P., consultant physician, St. Mary’s Hospital, London. London: Butterworths. 1973. Pp. 305. E6.

GENERAL practitioners not only provide the backbone the National Health Service but also help to shape the work of hospital doctors by the manner in which they refer patients. Patients complaining of headache, giddiness, and facial pain are often referred to E.N.T. surgeons (or otorhinolaryngologists as they are called in the European Economic Community), and as a result much of these surgeons’ work has a medical flavour. The primary purpose of this book is to help E.N.T. surgeons to form a balanced view of the investigation and treatment of patients with acoustic neuroma, vertebrobasilar ischmmia, trigeminal neuralgia, and other similar conditions which are usually considered to be the province of the neurologist or general physician. Dr Edwards is not seeking to produce budding neurologists, and he describes his material as no more than the simplest alphabet and his aim as purely clinical. But to be effective the Law needs to know the sort of thieves they are trying to catch, and surgeons need to know the runners in the diagnostic field if they are to give good advice to their patients and to the practitioners who refer them. Most of the book is clear and to the point

to

and argument follows argument in an analytical and scientific manner that is stimulating to read. It is a pity that the author is occasionally long-winded: for instance, he sensibly thinks that it is bad if someone who is about to faint is not allowed to lie down, but you might be forgiven for not realising this when you read that environmental circumstances such as encumbrances in a bathroom and well-meaning bystanders may deprive the fainting subject of levelling of the heart and brain. However, it is churlish to criticise the occasional lapse in a book that is mostly easy to follow and which is full of nicely phrased comments " on the clinical scene; allergy next to injury must be the most uncritically blamed association in medicine "; and, speaking of the 10% of patients with anxsthesia dolorosa after injection of the gasserian ganglion for tic douloureux, " surgery has nothing whatever to offer them unless it be further sorrow ". There are chapters on some of the commoner symptoms to be met within medical practice such as pain in the head, face, and neck, disorders of balance, tinnitus and head noises, facial paralysis, disorders of speech, and other familiar problems. When seen in the busy practice or clinic, patients complaining of these symptoms often produce a sinking feeling in the doctor’s stomach, and the author’s clear account and common-sense approach to their management will help to cure this. The author is aware of current thinking on

Application

of Blood Gases

BARRY A. SHAPIRO, M.D., assistant professor of anesthesiology, North-Western University Medical School, and medical director, division of respiratory therapy and associate director, North-Western Memorial Hospital. Chicago: Year Book. London: Lloyd-Luke. 1973. Pp. 210.$10; E5.

THE tended "

worthy to

aim of

accomplished

here innurse " and

maximising the audience,

encompass both " critical

physician ",

always

care

poses

problems.

Dr Shapiro’s dilemma is apparent, for his didactic style, with exhortations to master one section before proceeding further, leaves him open to inevitable doubt as to the evidence for some of his didactic certainty, for he gives no references throughout his text. Much in this book is good, with clear practical advice, yet also much controversy is concealed. To most English readers ventilatory insuffi-

ciency

means

not

enough ventilation, but Dr Shapiro

defines it as too much, or hyperventilation-a confusing difference which could lead to misunderstanding of literally lethal proportions. One senses that his experience is mainly with postoperative critical care, for the common medical emergencies where blood-gas estimations are invaluable, such as chronic bronchitis, cor pulmonale, pneumonia, and pulmonary oedema, receive scant attention. Thus he fails to stress the important differences between acute and chronic CO2 retention, and he omits entirely any reference to the invaluable delineation of the significance bands of in-vivo acid/base relationships described by Schwartz and his colleagues. Some of the statements on oxygen therapy are equally questionable, from the insistence " on dead space " as mechanisms of hypoxshunt " or amiia, with little or no attempt to explain the far more ubiquitous ventilation/perfusion imbalance, to resurrection of the 1925 Lundsgaard hypothesis on recognition of cyanosis, ignoring modern investigations on the accuracy of detection of this sign or even the distinction between central and peripheral cyanosis. How can oxygen therapy " manipulate the ventilatory status " except by changing the arterial P02 sufficiently to effect chemoreceptor drive ? These criticisms are of little concern to the accomplished physician, for his experience will allow him to form his own judgment; but this book appears to cater principally for the nurse and paramedical technician, for it includes a brief description of cardiopulmonary physiology, of bloodgas electrodes, and of the gas laws, and a glossary of medical terms (where, strangely enough, respiratory failure is not defined in terms of blood-gas tensions). Regrettably, this book raises doubts as to the wisdom of the instruction in too many places for it to be recommended wholeheartedly to the uncritical student. "

Immunotherapy of Cancer in Man 20. 21. 22. 23. 24.

Johnston, I. H., Gilday, D., Hendrick, E. B. Unpublished. Walker, A. E., Adamkiewicz, J. J. J. Am. med. Ass. 1964, 188, 779. Cohn, G. A. J. Neurosurg. 1964, 20, 784. Davson, H., Hollingsworth, G., Segal, M. B. Brain, 1970, 93, 665. Schurr, P. H., McLaurin, R. L., Ingraham, F. D. J. Neurosurg. 1953, 10, 515. 25. Marr, W. G., Chambers, R. G. Am. J. Ophthal. 1961, 51, 605. 26. Fitz-Hugh, G. S., Robins, R. B., Craddock, W. D. Laryngoscope, 1966, 76, 893. 27. Kinal, M. E., Jaeger, R. M. J. Neurosurg. 1960, 17, 81. 28. Martin, J. P. Br. med. J. 1955, ii, 467. 29. Beller, A. J. J. Neurol. Neurosurg. Psychiat. 1964, 27, 149. 30. Johnston, I. H., Rowan, J. O. ibid. (in the press). 31. Hayes, K. C., McCombs, H. L., Faherty, T. P. Brain, 1971, 94, 213. 32. Oldstone, M. B. A. J. clin. Endocr. 1966, 26, 1366.

EVAN M. HERSH, M.D., JORDAN U. GUTTERMAN, M.D., and GIORA MAVLIGIT, M.D., department of developmental therapeutics, University of Texas, M. D. Anderson Hospital and Tumor Institute, Houston, Texas. Springfield, Illinois: Charles C. Thomas. 1973. Pp. 141.$9.50.

THE authors of this small book set out to provide " a review of the current status of immunotherapy in the context of advances of the past two decades ". The literature is vast, and the coverage is sensibly confined to a few topics. First, a chapter on immunological deficiency in cancer: the approach is critical, and the distinction between tumour-specific and non-specific immunodeficiency is a useful one. A section on tumour antigens follows, dealing with the cell surface and describing the factors that