924

THE LANcET, ocroBEl 30,L976

CEREBRAL VENTRICULIR SIZE AND TABLE I-NORI\{AL CONTROLS

COGNITTYE IMPAIRMENT IN CHRONIC
SCHIZOPHRENIA
EvB C. JouNsroNn T. J. Cnow 5lJ Technical supervisor 90
C. D. Fmrn J,rNrr HusaeNo 6l
67
Porter 80
L. Knnnr Messenger 88
62 Porter o/
Dioisions of Psychiatry and Radiologjt, Clinical Research 56 Maintenance engineer r02
Cenrre, lVatlord Road, Harrow, Middlesex ItAI 3IJJ 50 Porter t02
40 Engineer 109
Maintenance engineer
SumnarSr By comparison with age-matched con- 52
116

trols in employment, l7 institutionalised

schizophrenic patients were shown by computerised
axial tornography ofthe brain to have intreasej cerebral
in the group of schizophrenic pa_
cular size was highly significantly
gmuve lmpalrment.

Introduction

li:i il. 1

Methods :ai:r""' i

be unimpaired,T There are undoubredly patients in

whom an illness with a schizophrenic presintation is fol-
TABLE II-PATIDNTS
I'revious Ireatment
'l'ime in
No. of \-ognnr nvc
hospital No. of insulin I
)rev rous frrnccUon
Case no. Age (yr.) Leucotomy E.C.T. comas Pheno ( )ccupa t lon scol)re "
I 64 39 Wireless 3t)
engrneer
2 42 24 l4
8 + Warehouse +5
asslstant
J 66 4l Labourer 27
53 32 8 Nava! rating T2
5 66 42
Clerk 36
6 63 39 Violinist
7 52 23 + 40 55 + Commercial 79
artlst
8 47 25 47 + Labourer 33
3
9 69 38 >40 +0 Clerk 64
6
l0 66 40 + Salesman 4
ll 54 24 J + Upholsterer 2
t2 63 42
Dioing-car
l3 attendant
70 32 + Bus
t4 conductor
20 55 + Labourer 4
l5 5l 28 + o 68 Clerk 8
l6 64 28 8 77
l1 Coalman 4
54 29 28 48
Itl 46
Army driver 2E
27 8 58 +
R.A.F. 6(
servrceman

r l)hcrrothiazines given at any time

 tr-t24--Z-1--l-

rHE LANCET, OCTOBER 30, I976

Northwick Park Hospilal and Clinical Research Centre who 70

were matched with the index group for age, and as closely as o = teucotomised ootient
possible for premorbid occupational attainment. The mental 18
stales of the patienls and controls were assessed in terms of the
rating sca.le devised by Krawiecka et al.t0 A total score ofposi- t0
tive features of schizophrenia (delusions, hallucinations and
a
thought disorder) and negative features of schizophrenia
(retardation, flattening of affect, and muteness) was derived t4
from this rating. The cognitive functioning of the patients and oo
controls was assessed on the clinical tests devised by Withers
and rou-
, erythro-
N
17
! to.
10
a
o a
i.ri3'"'n' o
8 schizo- = aaa o
I
phrenics and from 8 controls. Tomographic sect;ons through C T a
rhe brain were taken beginning a!, and continuing parallel to, I rl
the orbitomeatal line, at 1 cm intervals to the vertex. Two im-
ages at comparable levels were selected for each patient. One tt
I
showed the body ofthe lateral ventricles and the other showed
the anterior and posterior horns of the lateral ventricles
rogether with the third ventricle. The images were photo-
graphed and the area ofthe ventricles in each photograph was
measured with a planimeter, an instrument which measures
the area contained within a circumference. These measure-
ments were made blindly on two separate occasions by two in- Normols SchtzoPhrenics
dependent investigators, giving four measurements on each Ventriculr size in patients and controls.
subject. No attempt was made in rhis study to assess the size Each point represents average of four measurements on
photographs,
TABLE III-RELATIONSHIP OF CLINICAL FEATURES TO
VENTRICULAR SIZE IN SCHIZOPHRENIC PATIENTS tion between the measurements obtained by the two sep
(LEUcoroMlsED cAsEs oMlrrED) arare observers (cut 1, r:0'96, e<<0'001; cut 2,
Correla tion No. of r:0.94, p<<0.001) and apparently this is a reliable
(,onrpa rrson coelllcien t paIlents S ign ific a nce method of measuring ventricular size' The correlation
between the measurements at the two levels in the same
v rcnLricular size r: 021 N.S. 1)Cll 2' r: 001)' and
Cognrtivc tunctionrr r:-0.70 p< 0.01
r variation ite of the
v ventricular size unlikely s to alTect
l'osrtive features
v, ventricular size
r- 0.2 4 NS !
r slze.
Negatrvc fcatures
fhe figure shows the mean of the four measurements
l rcntricular sizc r: 0.3 8 N.s I of ventricular size. Leucotomy is associated wirh in-
creased ventricular size and in some cases with distor-
tion of the ventricles. For this reason the leucotomised
of the sulci, in view of the difficulties of finding an obiective patients were omitted from all calculations except those
and reliable means of measurement. concerning the effects of leucotomy. Ventricular size in
the schizophrenic group, with leucotomised patients
Results excluded, is significantly greater than that in the control
There were no oblious discrepancies between the ages group (r<0.01). The relationship between ventricular
and occupations of the control (table r) and patient size and clinical features within the schizophrenic group
(table rr) groups. The mental states of the control group (leucotomised patients excluded) is shown in table tIt. In
showed no abnormality on lhe Krawiecka scale' The this group there is a significant association between in-
schizophrenics performed significantly less well than the creased ventricular size and poor performance on the
control group on the Withers and Hinton tests of cogni- Withers and Hinton test battery (p<0'01). This impair- -
tive function (n<0.001). ment emerges principally in those items in the batter,T
In the EMI-scan assessments there was a high correla- that place greatest demands on memory-e.g., serial

fABL!t IV--RgLArroNSHrp Br..rwgtN pREvrOUs TREATMENT AND tvL.NTRICULAR SIZE IN SCHIZOPHRENICS (LEUCOTOMISED PATIIINTS
EXCLUDED FROM COMPARISONS EXCEPT THAT CONCERNING LEUCOTOMY)

Mean ventricular
size 29 cm Nr) o[ cases

Irornr of Wirh Without !(ithout

t rcatlrcDt lrca Imenl trea t men I trcatmen t

t2.3 s o 0.70 9.9 s o. 20 IJ 2.06 <0'05

(1 tailed)
9.9 s.o.2.96 9.97 s.o. 57 b 7 0.04 N.S,
q.-1.D 1.76 11.3 so 76 + 1.57 N.S,
8.i s.o.1,45 11.2 s.o 0 7 2.71 <o.05

'
 xT- --l--r
-r-
926
lt
sevens and delayed recall. The relationship between ven-
I tricular size and previous treatment is shown in table rv.
Leucotomy is associated with increased ventricular size
(n<0.05, 1 tailed), but no other physical treatment
seems to be positively associated with increased ventric-
ular size. There is a signifivant tendency for the patients
who have had insulin-coma treatment to have smaller
ventricles than those who have not (P<0'05). Vithin the
normal-control group there was no relationship between
ventricular size and cognitive functioning or age. There
was a tendency for the age-disoriented patients to have
larger ventricles, poorer cognitive function, fewer posi-
tive schizophrenic features, and more negative schizo-
phrenic features than those without age disorientation,
but none of these trends achieved statistical significance'
Physical examination and hamatological, chemical, and
serological tests revealed no abnormalities in the patient
group.
Discussion
The results show that the ventricles of a group of
chronic institutionalised schizophrenic patients are
larger than those of a group of age-matched normal con-
trols and that, within the schizophrenic group, increased
ventricular size is associated with poor performance on
cognitive testing. An association has previously been
reported betu,een dementia and increased ventricular
size as assessed by computerised axial tomography.r2
Our findings raise the question' is cognitive impair-
ment, related to a demonstrable abnormality in the
brain, a feature of schizophrenia? Two earlier
groupsrr ra who employed pneumoencephalography con-
cluded that there are patients with schizophrenia in
whom ceiebral ventricular size is increased, but
neither of these studies included normal controls. The
difficulties of selecting an appropriate control group for
this type of study are considerable. For this reason we
are inclined to place more emphasis upon the finding
that within the patient group there is a relationship
between increased ventricular size and cognitive impair-
ment, than upon the finding of large diflerences in ven-
tricular size between the patients and controls. A pos-
sible explanation for our results is that we have selected
a group of schizophrenic patients who fortuitously
suffer from an unrelated dementing illness and that we
have compared them with a group of people who, since
they are in employment, are unlikely to be disabled in
this way. However, our 18 patients were selected from
a population of 60 and th.is implies a prevalence of
dementia greatly in excess of rhe 3-57o seen in the
general population aged 60 and over.15
An alternative hypothesis is that amongst the severely
incapacitated schizophrenic patients requiring inpatient
care there is a group in which the disease is associated
with increased ventricular size and impaired cognitive
capacity. The question obviously arises as to whether in-
creased ventricular size is a consequence of the patho-
logical process or whether increased ventricular size may
in some way predispose to a severe and cognitively inca-
pacitating form of the disease. Tbe existence and pos-
sible size of the subpopulation of schizophrenic patients
with enlarged ventricles will require further investiga-
tion with respect to a welldefined base population.
These further investigations must also be conducted at
different srages of the disease.
--r:Y. r -
THE LANcET, ocroBER 3Q,1976
We thank the patients and controls who participated in the study
for their cooperationl the medical and nursing staffs of Shen-
ley and Northwick Park Hospitals for their assistance; Dr M- V. P.
Carney and Dr H. I. Hershon for their kindness in allowing us to
study patients under their care; and Mrs Aviva Gold for social-work
assistance. Our thanks are due also lo the Department of Health and
Social Security whose far-sighted and generous help has assisted
greatly in the development of the computerised-tomography proiect
(EMI scan). Lasrly, we thank Mr John Twydle who has been manag-
ing the EMI scanner and Mrs P. Wright for secretarial assistance.
REFERENCE S
1. Kraepelin, E iz Dementia Praecox and Paraphrenia (translated by
R. E. Krieger); p 17 New York, 1971.
2. Blculer, E.J ment Path,N.Y. 1902, 3, 113
3. Vogt, C., Yogt, O. Ptoc. L int. Congr. Neuropath. 1952,l' 515.
4. David, G. B., n Schizophrenia, Somatic Aspects (edited by D. Richter); p
93. hndon, 1957.
5. Nieto, D., Escobar, A, iz Pathology of the Nervous System, vol. 3 (edited by
J. Minckler); p. 2654, Ncw York, 1972.
6 Fisman, M. Br. J Psychiat. 197 5' 126' 414.
7 Payne, R. W. u Handbook of Abnormal Psychology (edited by H. J
Eyscnck); p. 424, bndon' 1973.
8. Feighner, J. P., Robios, E., Guze, S. B, Woodruff, R A.' Vinokur' G,
Munoz, R. Archs get Psychiot. 1972' 26' 57.
9. Crcw, T. J., Mitchell, W. S.8r./. Psychiat 1975,126'360
10. Krawiecka, M., Goldberg, D., Vaughan, M. Unpublished.
I l. Withcrs, E., Hinron, l. Br. J. Psychiat. 197 l, ll9, 1
12. Huckman, M. S., Fox, J., Topel, J . Radiology, l9'l 5, 116,85.
13. Haug, J. O Acta psychiat scand. 1962, tA,Suppl 165, p I 1.
14. Young, I. J., Crampton, A. R. Biol Psychiat 1974,8,281.
I 5. Gunner-Svensson, F., Jensen, K Acta psychiot scond 79'l 6, 51, 283
DOI.]BLE BLIND CROSSOVER TRIAL OF
LEVAMISOLE IN RECTJRRENT APHTHOUS
ULCERATION
T. LBHNTn J. M. A.rJfltlroN
L. IveNyr
Department of Oral Immunology and Microbiologt, Gult's
Hospital Medical and Dental Schools, London SE I 9RT
Sumtnar1 A double blind crossover trial of levamt-
sole has been carried out in 47 Patients
with recurrent oral ulceration. Significant decreases in
thc number of ulcers and ulcer days were found after 2
months of intermittent administration of levamisole.
About 64/o of patients responded to the drug by a de-
crease in the number of ulcers of more than 50%, for
two or more months. The remaining 367o of patients
failed to respond to levamisole and237o of these had an
increased number of ulcers. The side-effects recorded in
patients taking levamisole were comparable with those
in patients on placebo, except for a flu-like syndrome in
1 patient and urticaria in another, necessitating with-
drawal of the drug. The mechanism of action of levami-
sole in recurrent oral ulceration is not known, but it is
suggested that levamisole may correct a deficiency of
suppressor cells, or potentiate the cellular responses to
crossreacting microbial agents.
Introduction
Lnr,ruNosuppnEssIvE and anti-inflammatory drugs,
such as corticosteroids and to a lesser extent azathio-
prine and cyclophosphamide have been used in the trebt-
ment of recurrent aphthous ulcers (n.,t.u.) and Behqet's
syndrome (n.s.). The response is varioble but topl-al
ctrticosteroids are effective in the managemet( of