Journal of Neurology, Neurosurgery, and Psychiatry 1982;45:209-216

Intracranial pressure in patients with the empty sellasyndrome without benign intracranial hypertensionANDREW H KAYE, BRIAN M TRESS, DAVID BROWNBILL, JOHN KING

From the Department of Neurology and Neurosurgery, and the Department of Radiology,Royal Melbourne Hospital, Melbourne, Australia

SUMMARY The intracranial pressure was monitored continuously for at least 48 hours in five patientswith empty sella syndrome, who did not have clinical benign intracranial hypertension (BIH). It hasbeen suggested that the empty sella syndrome is a result of chronically elevated intracranial pressurein the presence of a congenitally deficient diaphragma sellae. However, whilst the intracranialpressure in two of the five patients was abnormally high, in three patients in whom it was monitored,the CSF pressure was normal. Although, these cases may represent "burnt out" forms of intra-cranial pressure problems, it might be that the normal pulsations of CSF are sufficient to produce theempty sella in the presence of a deficient diaphragma sellae.

"Empty sella" is a gross descriptive term introducedby Busch in 1951 to describe the appearance atnecropsy of the sella turcica when the diaphragmasellae is incomplete or forms only a small peripheralrim.' In 1924, Schaeffer described the gross appear-ance of the diaphragma sellae in 125 cases, and notedthat the diaphragm varied from being a completeroof which transmitted the infundibulum to, at theother extreme, a small peripheral rim.2 In 40 of the788 patients with no known pituitary disease studiedby Busch (an incidence of 5 5 %), the diaphragmasellae was a peripheral rim of tissue two millimetresor less, with the pituitary gland flattened to thebottom of the sella.The term "empty sella syndrome" originally

referred to the findings at surgical exploration inpatients who had received radiation for an intrasellartumour, and subsequently developed visual symp-toms.3 Primary (idiopathic) and secondary forms ofthe empty sella syndrome have been described.4 Theprimary empty sella has been defined as "that whichdid admit significant air at pneumoencephalo-graphy, in the absence of prior surgery or radiationtherapy".5 The role of a chronically elevatedcerebrospinal fluid (CSF) pressure in the patho-genesis of the so-called idiopathic empty sellasyndrome has been discussed.6-10

Address for reprint requests: Andrew H Kaye, Departmentof Neurosurgery, Radcliffe Infirmary, Oxford OX2 6HE, UK.

Received 28 January 1981 and in revised form 13 June 1981Accepted 25 October 1981

It has been suggested that the primary emptysella is caused by a combination of a congenitallydeficient diaphragma sellae and chronically elevatedCSF pressure.5 11 12There is a definite relationship between benign

intracranial hypertension (BIH) and the primaryempty sella syndrome'6 911-13 Although it has beensuggested that there must be a chronic elevation ofintracranial pressure (ICP) in addition to a deficientdiaphragma sellae to produce a prolapse of thesubarachnoid space into the sellae turcica,12 therehas been no adequate measurement of the ICP ofpatients with the empty sella syndrome who do nothave benign intracranial hypertension.

This is a report of a series of five patients all withradiologically proven empty sella syndrome, whodid not have benign intracranial hypertension. In allpatients the ICP was monitored continuously for atleast 48 hours.

Patients and methods

All five patients were adult females who presented to theRoyal Melbourne Hospital with a major complaint oflongstanding headaches. There was no significant neuro-logical deficit in any patient and all had normal visualfields on perimetry. A full clinical and laboratory endo-crine assessment was made in all patients and all patientshad a normal serum level of prolactin. No significantabnormality was found in any patient. All patients hadneuroradiological investigations proving the existence ofan empty sella. The diagnosis of empty sella was basedon a combination of an enlarged sella with characteristic

209

by copyright. on M

arch 1, 2020 by guest. Protected

http://jnnp.bmj.com

/J N

eurol Neurosurg P

sychiatry: first published as 10.1136/jnnp.45.3.209 on 1 March 1982. D

ownloaded from

by copyright.

on March 1, 2020 by guest. P

rotectedhttp://jnnp.bm

j.com/

J Neurol N

eurosurg Psychiatry: first published as 10.1136/jnnp.45.3.209 on 1 M

arch 1982. Dow

nloaded from

by copyright. on M

arch 1, 2020 by guest. Protected

http://jnnp.bmj.com

/J N

eurol Neurosurg P

sychiatry: first published as 10.1136/jnnp.45.3.209 on 1 March 1982. D

ownloaded from

Kaye, Tress, Brownbill, King

"symmetrical ballooning" or globular appearance onplain skull radiograph5 and the detection of CSF densitywithin the sella by computed tomography (CT) per-formed with slice widths collimated to five millimetres andoverlapped in both transverse axial and direct coronalplanes.The diagnosis was confirmed in one case by pneumo-

encephalography and another by CT metrizamidecisternography.14 15CT has been successful in diagnosing the presence of an

empty sella in up to 100% of cases.14 16 17 False positivediagnoses have been produced by prolactin secretingtumours with necrotic centres,16 18 a possibility whichwas excluded in this series by pituitary function tests.The ICP was monitored continuously in all patients

for a minimum of 48 hours by a subarachnoid screwinserted in the right frontal position (just in front of thecoronal suture). This was connected by a 150 cm saline-filled tube to a Hewlett Packard transducer and then toa Hewlett Packard amplifier which was connected to acontinuous paper recorder. A Hewlett Packard 1208Ctransducer was attached to a Hewlett Packard 78200series patient monitor which houses a 78205B amplifier.This was attached to a Hewlett Packard 7803B monitor-scope and to a Rikadenki single channel recorder,modified by the Royal Melbourne Hospital ElectronicsDepartment, for two channel multiplex operation. Thezero reference point for the transducer was taken as apoint three centimetres anterior to the external auditorymeatus, with the patient lying supine.19 The zero driftand gain drift of the system was checked, and if necessarycorrected, at least every six hours. Very little correctionwas required at any time. Antibiotics (cloxicillin andampicillin) were administered during the monitoringperiod.

Case I This 67-year-old obese woman, referred forinvestigation of the cause of two months' constant head-ache, had been previously reported by one of the authors20(AHK). Neurological and general examination wasnormal. The plain skull radiographs revealed an enlargedglobular sella (fig la). CT showed normal size ventricles,but also an enlarged sella with density consistent with thatof CSF. A pneumoencephalogram showed air enteringthe anterior and mid portions of the sella, and thepituitary flattened against the dorsum and posteriorportion of the floor of the sella. During the follow-upexamination three months after presentation, she devel-oped intermittent CSF rhinorrhoea. Continuous ICPmonitoring revealed a generally raised baseline pressurewith intermittent high plateau waves up to 34 mm Hg(fig 2). On the basis of the elevated ICP and its presumedcausal relationship with the empty sella syndrome andCSF rhinorrhoea, it was decided to perform a lumbarperitoneal shunt as an initial procedure rather than adirect intracranial attack on the fistula itself. Afteroperation, the patient was initially free of CSF rhinor-rhoea and the ICP, measured again by the above tech-nique, demonstrated a normal baseline pressure and theelimination of wave forms. However, after 10 weeks therewas a recurrence of the CSF rhinorrhoea. She wasreadmitted to hospital and the sella was explored through

a) Case 1

c) Case 3 d) Case 4

e) Case 5Fig 1 Tracings of the sella turcicas of each of the fivecases, as seen in a standard lateral skull radiograph.In all cases the volume of the sella was increased. Inparticular the depth was increased, being in the range

15-16 mm (upper level normal 14 mm).

1 Tine (hours) 2

Fig 2 Intracranial pressure recording of Case 1,showing a moderately raised baseline pressure withplateau waves up to 34 mm Hg.

a right subfrontal craniotomy. At surgery an empty sellawas found and a fold of arachnoid was noted to extenddown into and occupy the sella. A hole, present at thejunction of the floor with the anterior wall of the sella,was packed with crushed muscle and covered with fascialata.She has subsequently been followed for two years and

has had no further CSF rhinorrhoea.

Case 2 This 70-year-old obese Italian lady presentedafter 12 months of moderately severe continuous head-ache. On examination there was no neurological abnor-mality and endocrine studies were normal. Lumbarpuncture pressure was 12 cm of CSF. A plain skullradiograph showed an enlarged globular sella (fig lb).

'E

Z.C 0

c40- C:) 'oa.

-4-44

0

210

by copyright. on M

arch 1, 2020 by guest. Protected

http://jnnp.bmj.com

/J N

eurol Neurosurg P

sychiatry: first published as 10.1136/jnnp.45.3.209 on 1 March 1982. D

ownloaded from

Intracranial pressure in patients with the empty sella syndrome without benign intracranial hypertension 211

CT using the above technique showed normal sizedventricles with an enlarged sella containing intrasellarattenuation values of CSF (fig 3).The ICP monitoring for 56 hours showed a slightly

elevated baseline pressure, with plateau waves rising to30 mm Hg and Lundberg "B" waves21 up to 35 mm Hg(fig 4). These "B" waves were present during 20% of themonitoring time and there was no particular predilectionfor them to occur during the sleeping period.

Case 3 This 28-year-old obese female presented aftersome years of headaches. Neurological examination andendocrine studies were normal. Plain skull radiographsshowed the characteristically enlarged globular sella(fig 1c), and CT, using the above technique, showednormal size ventricles with an enlarged sella containingCSF density material (fig 5).The ICP was monitored for 48 hours. The baseline ICP

I

E

E

a-

20

.t-

:vio F4

i - -. '', '

: ,.,

1-t -dt -'

-v+!$

i i T

a,_I-I*V.....- - 1

1~2:F -111 2

Time (hours)Fig 4 ICP trace of Case 2, showing a slightly elevatedbaseline pressure, with plateau waves rising to 30 mmHg and Lundberg "B" waves up to 35 mm Hg.

aLi. h. c (Ca%c 2. Over/appiulgl 5 /lilt/ IhickIViIt'sIX At/ nyXX 1ir/1of/I Ifluidcu%iJI ithIIi inimalerial "Itverchrmpin t (/R{lillXfif/ wfithsir1 [r1isi

kML-W:_lrtP,'-'IJLL-.Ljl L.' 111;"Jul

kw - ,-.

by copyright. on M

arch 1, 2020 by guest. Protected

http://jnnp.bmj.com

/J N

eurol Neurosurg P

sychiatry: first published as 10.1136/jnnp.45.3.209 on 1 March 1982. D

ownloaded from

Kaye, Tress, Brownbill, King

Fig 5 a, b Ccase 3. Two5 mm thick transverse axialscans through sella turcica,showing low density contents.

was within normal limits. Lundberg "B" waves occurredfor approximately 5% of the monitoring time, particularlyduring sleep, and rose to as high as 20 mm Hg (fig 6a andb).

Case 4 This 34-year-old rather thin female, with a pasthistory of asthma and a hysterectomy for menstrualirregularity, presented following some years of moderately

20i (i c,

Ii .~0 L~~~~~~~u0

E

Time (hours)

severe headache. There was no significant neurologicalabnormality and endocrine studies were normal.A plain skull radiograph showed the characteristic

features of scaphocephaly. Convolutional impressionswere marked particularly in the upper third of the vault,and the sella was symmetrically enlarged in a globularfashion (figs Id and 7). CT performed in transverse axialand direct coronal planes confirmed the presence of CSFdensity material in the sella (fig 8).The ICP was monitored for 48 hours. The baseline ICP

pressure was within normal limits and there was no

significant wave formation (fig 9).

Case 5 This 41-year-old obese female presented fol-lowing many years of constant headache. There was no

neurological abnormality and a full endocrinologicalassessment was normal.A plain skull radiograph showed an enlarged globular

0Lu

>

--o

E

Time (minutes)

Fig 6 a, b ICP trace of Case 3, showing normal

baseline pressure (a) and Lundberg B waves

occurring during sleep (b), being present for

approximately 5% of the monitoring time.

Fig 7 Plain skull radiograph of Case 4, showingmarked convolutional impressions, particularly in theupper third of the vault, and an enlarged globular sella.

212

by copyright. on M

arch 1, 2020 by guest. Protected

http://jnnp.bmj.com

/J N

eurol Neurosurg P

sychiatry: first published as 10.1136/jnnp.45.3.209 on 1 March 1982. D

ownloaded from

lIltracrallijal prc.ssiire il paitielnt%s lit/i thc cimptl scllai sYnldronic it7tlout /)bcnign,}u iuitr-ticrciiliaitlhypcrtcisioni 21 3

Fig 8 Case 4 (a, b, c) ()Oerlapping 5 n1un1 t/ick transverse axial Scans thlrioug/i sella tlecica a11d(d) 5 min thick coronal slice tlinaug/i sella, demon storcting the sella to coantaill cerebro.spinalfluicdden sit, ;niatel ial.

sella (fig le). CT in transverse axial and coronal planes,with and without intravenous contrast medium, showedCSF density material within the sella (fig 10). CT per-formed in the same planes after the introduction ofintrathecal metrizamide showed a marked increase in thedensity of the intrasellar contents, confirming the presenceof an empty sella (fig I 1).The ICP was monitored continuously for 56 hours. The

baseline ICP was within normal limits and there was nosignificant wave formation (fig 12).

Discussion

I

_EE0-

c E OO, 22 C

;t t t

e t - ... . .._LLu i, ,.1,1, !, i ., s 1 .. 1Il 1.

EfTime (hours)

2

The most commonly accepted aetiologic hypothesis Fig 9 ICP trace of Case 4, demnionstratiuig n0ortm1alfor the empty sella concerns transmission of elevated pr-essires.

I

by copyright. on M

arch 1, 2020 by guest. Protected

http://jnnp.bmj.com

/J N

eurol Neurosurg P

sychiatry: first published as 10.1136/jnnp.45.3.209 on 1 March 1982. D

ownloaded from

Kaye, Tress, Brownbill, King

Fig 10 Case 5. Overlapping S mm thick scans in transverse axial (a, b) and coronal (c, d)planes, showing cerebrospinal fluid density material in sella.

CSF pressure through a congenitally deficientdiaphragma sellae.5 1112 There is a definite relation-ship between benign intracranial hypertension anddevelopment of the empty sella syndrome.6 11-13However, those patients with benign intracranialhypertension form a minority in any series of patientswith empty sella syndrome, ranging from 8% ofcases,12 to 13 %5 and 158 %.6 Normal CSF pressurehas been recorded in patients with emptysella.5 101122 However, in no study was continuousICP monitoring performed. The importance ofcontinuous versus static measurements of ICP hasbeen shown in normal pressure hydrocephalus,where intermittent high pressure peaks have beendemonstrated.23 Neelon argues that longstandingmild elevation of CSF pressure in the setting ofincomplete sella diaphragm can bring about intru-

sion of the subarachnoid space into the sella cavitywith enlargement and remodelling of the sellaturcica and flattening of the pituitary contentsagainst the floor.5However, intermittent raised ICP cannot be

adequately evaluated without using continuous ICPmonitoring.

In this series of five patients with empty sella, noneof whom had benign intracranial hypertension onclinical grounds and in whom continuous ICPrecordings had been performed over at least a 48hour period, a spectrum of ICP was seen from thedefinitely abnormal, as in the patient (Case 1) whohad marked wave formation, to those patients(Cases 3, 4 and 5) who had normal ICP. Althoughsome Lundberg "B" wave activity has been reportedas being normal,24 that seen in Case 2 was probably

214

by copyright. on M

arch 1, 2020 by guest. Protected

http://jnnp.bmj.com

/J N

eurol Neurosurg P

sychiatry: first published as 10.1136/jnnp.45.3.209 on 1 March 1982. D

ownloaded from

Intracranial pressure in patients with the empty sella syndrome without benign intracranial hypertension 215

Fig 11 Case 5. After introduction of intrathecal metrizamide the density of the sellacontents is markedly increased, shown in both transverse axial (a, b) and coronal (c, d)planes.

cm20 _ XLI: ----_a-:'- L

10 '2

Time (hours)

Fig 12 ICP time of Case 5, showing normal pressures.

abnormal, in that it occurred for a large percentageof the monitoring time with a high amplitude. Withthe exception of Case 1,20 ICP recordings have notbeen previously reported in patients with empty sellasyndrome who do not have benign intracranial

hypertension. The recordings in those patients whoseICP is raised (Cases 1 and 2), help in the under-standing of aetiology of the empty sella syndrome.Benign intracranial hypertension has been describedin the absence of papilloedema,25-27 and Cases 1 and2 may well represent examples of either benignintracranial hypertension without papilloedema or a"forme fruste". The ICP traces in both cases arecomparablenot onlywith those reported by Johnstoneand Paterson,28 in patients with papilloedema andbenign intracranial hypertension, but also with thosecases of Spence et al,27 having the disorder withoutpapilloedema. Alternatively it has been suggestedthat obesity itself may cause a chronic elevation of

by copyright. on M

arch 1, 2020 by guest. Protected

http://jnnp.bmj.com

/J N

eurol Neurosurg P

sychiatry: first published as 10.1136/jnnp.45.3.209 on 1 March 1982. D

ownloaded from

Kaye, Tress, Brownbill, King

ICP.5 11 Whatever the cause of the pressure waves,the resulting raised ICP may be sufficient to prolapsethe arachnoid into the sella.The normal ICP found in Cases 3, 4 and 5 does

not necessarily negate the hypothesis of raised ICPcontributing in the aetiology of empty sella syn-drome. The headache occurring in these patients isnot readily explainable. In the patient (Case 4) whohad a scaphocephalic skull with marked copperbeating, it is interesting to speculate on the relevanceof the convolutional markings in the presence of theempty sella syndrome, and at the present time nor-mal ICP. These skull radiograph changes mayrepresent evidence of previously raised ICP. TheICP levels of the other two normal patients (Cases 3and 5) may represent "burnt out" intracranialhypertension. That is, those patients with normalICP have had at some time in the development of theempty sella a high CSF pressure. Alternatively, theconcept of the raised ICP being necessary for thedevelopment of the empty sella syndrome may haveto be reconsidered. It may be that the normalpulsations of CSF29 are sufficient in the presence ofan incomplete diaphragna sellae, to produce in somepatients the empty sella syndrome.

The authors thank Mr David Wallace, AssistantNeurosurgeon, Royal Melbourne Hospital forpermission to report Case 5. This work was under-taken with help from a grant from the VictorHurley Medical Foundation.

References

Busch W. Die morphologia der sella turcica and ihrbeziehungen zur hypophyse. Virchows Arch PatholAnat 1951;320:437-58.

2 Schaeffer JP. Some points in the regional anatomy ofthe optic pathways with especial reference totumours of hypophysis cerebri and resulting ocularchanges. Anat Rec 1924;28 :243-79.

3 Colby MY, Kearns TP. Radiation therapy of pituitaryadenomas with associated visual impairment. MayoClin Proc 1962;37:15-24.

4 Weiss SR, Raskind R. Non neoplastic intrasellar cysts.Inter Surg 1969;51:282-6.

Neelon FA, Goree JA, Lebovitz HE. The primaryempty sella. Clinical and radiographic characteristicsand endocrine function. Medicine 1973;52:73-92.

6 Berke JP, Buxton LF, Kokmen E. The "empty" sella.Neurology 1975 ;25:1137-43.

7 Garcia-Uria J, Carrillo R, Serrano P et al. Empty sellaand rhinorrhoea. J Neurosurg 1979;50:466-71.

8 Mortara R, Norrell H. Consequences of a deficientsella diaphragma. J Neurosurg 1970;32:565-73.

9 Weisberg LA, Zimmerman EA, Frantz AG. Diagnosisand evaluation of patients with an enlarged sellaturcica. Am J Med 1976;61:590-6.

1.0Zatz LM, Janon EA, Newton TH. The enlarged sella

and the intrasellar cistern. Radiology 1969;93:1085-91.

11 Kaufman B. The "empty" sella turcica-a manifesta-tion of the intrasellar subarachnoid space. Radiology1968;90:931-41.

12 Foley KM, Posner JB. Does pseudotumour cerebricause the empty sella syndrome? Neurology(Minneap) 1975;25:565-9.

13 Davis S, Tress B, King J. Primary empty sella syndromeand benign intracranial hypertension. Clinical andexperimental neurology. Proc Aust Assoc Neurol1978 ;15:248-57.

14 Bajraktari X, Bergstrom M, Brismar K, Goulatia R,Greitz T, Grepe A. Diagnosis of intrasellar cisternalherniation (empty sella) by computer assisted tomo-graphy. J Comput Assist Tomogr 1977;1:105-16.

15 Manelfe C, Pasquini V, Banks WO. Metrizamidedemonstration of the subarachnoid space surround-ing the optic nerve. J Comput Assist Tomogr 1978;215:545-7.

16 Rozaria R, Hammerschlag SB, Post KD, Wolpert SM,Jackson I. Diagnosis of empty sella with C.T. scan.Neuroradiology 1977;13 :85-8.

17 Sage MR, Chan ES, Reilly PL. The clinical andradiological features of the empty sella syndrome.Clin Radiol 1980;31:513-9.

1 Hsu TH, Shapiro JR. Hyperprolactinaemia associatedwith empty sella syndrome. JAMA 1979;235:2002-4.

19 Azevedo Filho HRC. Clinical applications of intra-cranial pressure monitoring. Oxford University,1975;76-7. (MSc thesis.)

20 Davis S, Kaye AH. A dynamic pressure study ofspontaneous CSF rhinorrhoea in the empty sellasyndrome. J Neurosurg 1980;52:103-5.

21 Lundberg N. Continuous recording and control ofintracranial pressure in neurosurgical practice.Acta Psychiatr Neurolog Scand 1960;36:(suppl 149):1-193.

22 Bemasconi V, Giovanelli MA, Papo I. Primary emptysella. J Neurosurg 1972;36:157-61.

23 Symon L, Dorsch NWC, Stephens RJ. Pressure wavesin so called low pressure hydrocephalus. Lancet1972;2:291-2.

24 Martin G. Lundberg's B waves as a feature of normalintracranial pressure. Surg Neurol 1978;9(6):347-8.

25 Cooper PR, Moody S, Skear F. Chronic monitoring ofintracranial pressure using an in vivo calibratingsensor. Experience in patients with pseudotumourcerebri. Neurosurgery 1979;5 :666-70.

26 Scanarini M, Mingrino S, d'Avella D, Della Corte V.Benign intracranial hypertension without papill-oedema. Case report. Neurosurgery 1979;5:376-7.

27 Spence JD, Amacher AL, Willis NR. Benign intra-cranial hypertension without papilloedema. Role of24 hours cerebro spinal fluid pressure monitoringin diagnosis and management. Neurosurgery 1980;7(4) :326-36.

28 Johnstone I, Paterson A. Benign intracranial hyper-tension II CSF pressure and circulation. Brain 1974;97:301-12.

29 Du Bourlay GH. Pulsatile movements of CSF path-ways. Br J Radiol 1966;39 :255-62.

216

by copyright. on M

arch 1, 2020 by guest. Protected

http://jnnp.bmj.com

/J N

eurol Neurosurg P

sychiatry: first published as 10.1136/jnnp.45.3.209 on 1 March 1982. D

ownloaded from

Book reviews

CorrectionIn the article "Intracranial pressure inpatients with the empty sella syndromewithout benign intracranial hypertension"Kaye, Tress, Brownbill, King, J NeurolNeurosurg Psychiatry 1981;45:209-16figure 10(d) was incorrect. The correctfigure 10(d) is reproduced here.

Book reviews

Psychotropic Drugs. Plasma Concentrationand Clinical Response. Edited by GrahamD Burrows and Trevor R Norman. (Pp544; SFr. 150.) New York: Marcel DekkerInc, 1981.

Correlation of drug effect with plasmalevels is of use in many disease states. Oneof the most difficult areas, however, is thatof psychiatric illness. The variety of meansof assessing or classifying mental illness,the poor understanding of underlyingpathology and the changes in brain func-tion that occur, explain why this area hasnot seen more widespread implementationof plasma level monitoring. The volumeedited by Burroughs and Norman, how-ever, is a significant contribution to the lit-erature on this topic. It is a comprehensivevolume dealing with many aspects of drugmonitoring in the psychiatric field. The ini-tial chapter by Lang on the mechanism ofaction of psychotropic drugs, provides aninteresting introduction to the pharmacol-ogy of these compounds. Two interestingchapters follow, on methods for the meas-urement of psychotropic drugs-anti-depressants, antipsychotics and anti-anxiety agents-which deal comprehen-sively with all modern techniques. Thechapter by Graham shows application ofthese techniques to the measurement of thepharmacokinetics of tricyclic anti-depressants. This is followed by an excel-lent chapter by Burroughs and Normandealing with the relationship betweenplasma levels and clinical response in theanti-depressant field. The authors concludethat no consistent relationship exists bet-ween plasma levels and clinical responsefor tiicyclic anti-depressants and thatroutine monitoring of plasma levels is notwarranted. This contrasts with the meas-urement of serum lithium levels dealt withby Annitto and Gershon where only be-nefit is derived from determining correcttherapeutic dosage and prevention in toxic-ity. Excellent chapters also follow on anti-psychotic agents, Curry dealing with chlor-promazine in considerable depth, Sakalusand Traficante reporting on fluphenazine,Crammer on thioridazine and Evans onbutyrophenones. It must be said, however,that the overall conclusion from these in-depth appraisals is that little relationshipexists between efficacy and plasma orblood antipsychotic levels. Sedvall andGrimm contribute on sampling CSF and

plasma as tools for obtaining biochemicaland pharmacokinetic data in neuroleptictherapy. They suggest some relationshipexists between chlorpromazine treatmentand clinical effect, at least in the earlyphases of treatment. Fulton and otherscontribute extensively on the phar-macokinetic of benzodiazepines. Justifi-ably, diazepam is given pride of place butfurther sections deal with other individualbenzodiazepine compounds. Sedatives andhypnotics are dealt with by Wade butagain the conclusion is that plasma con-centrations of hypnosedatives correlatepoorly with their effects, both at dosagesused clinically and in overdosage. Eadiedemonstrates the value of anticonvulsantdrug plasma levels but concludes that thepatient's clinical state should always be thefinal criterion in management and thatplasma anticonvulsant levels should beseen only as a means to an end. The book isadmirably finished by an overview by Hol-lister who concludes that there is littledoubt that monitoring plasma levels oflithium and of anticonvulsants has madesuch treatme-nt both safer and moreeffective. However, he is less certain of therole of tricyclic antidepressant monitoringand argues that there is little to favourmonitoring of plasma concentrations ofantipsychotic drugs. Hollister concludesthat anti-anxiety and hypnotic drugs, whichgenerally have a large margin of safety andsuitable clinical criteria of response, shouldnot be monitored. I find this overall to be aremarkably good book that is thoroughlyrecommended. I found much of interestand much new information and the editorsmust be congratulated for the productionof such a volume. I would imagine, how-ever, that at 150 Swiss francs many poten-tial customers will be frightened away.

PG JENNER

Prevention and Treatment of Depression.Thomas A Ban, Rene Gonzalez, Assen SJablensky, Norman A Sartorius and FelixE Vartanian. (Pp 300; £19.50.) Baltimore,University Park Press. Distributor: MTPPress Ltd. Lancaster, 1981.

This is the proceedings of a conference ondepression organised by WHO and held inWashington in June 1980. Despite its titleits 31 chapters embrace most aspects ofdepressive illness-epidemiology,classification, symptomatology, the role ofbiological and psychological factors inaetiology, various forms of treatment andmodels of care delivery from various partsof the world. The proceedings of confer-

763