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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:Y. r -
-r-

926 THE LANcET, ocroBER 3Q,1976


lt
sevens and delayed recall. The relationship between ven- We thank the patients and controls who participated in the study
I tricular size and previous treatment is shown in table rv. for their cooperationl the medical and nursing staffs of Shen-
ley and Northwick Park Hospitals for their assistance; Dr M- V. P.
Leucotomy is associated with increased ventricular size Carney and Dr H. I. Hershon for their kindness in allowing us to
(n<0.05, 1 tailed), but no other physical treatment study patients under their care; and Mrs Aviva Gold for social-work
seems to be positively associated with increased ventric- assistance. Our thanks are due also lo the Department of Health and
ular size. There is a signifivant tendency for the patients Social Security whose far-sighted and generous help has assisted
greatly in the development of the computerised-tomography proiect
who have had insulin-coma treatment to have smaller (EMI scan). Lasrly, we thank Mr John Twydle who has been manag-
ventricles than those who have not (P<0'05). Vithin the ing the EMI scanner and Mrs P. Wright for secretarial assistance.
normal-control group there was no relationship between
ventricular size and cognitive functioning or age. There REFERENCE S

was a tendency for the age-disoriented patients to have 1. Kraepelin, E iz Dementia Praecox and Paraphrenia (translated by
larger ventricles, poorer cognitive function, fewer posi- R. E. Krieger); p 17 New York, 1971.
2. Blculer, E.J ment Path,N.Y. 1902, 3, 113
tive schizophrenic features, and more negative schizo- 3. Vogt, C., Yogt, O. Ptoc. L int. Congr. Neuropath. 1952,l' 515.
phrenic features than those without age disorientation, 4. David, G. B., n Schizophrenia, Somatic Aspects (edited by D. Richter); p
93. hndon, 1957.
but none of these trends achieved statistical significance' 5. Nieto, D., Escobar, A, iz Pathology of the Nervous System, vol. 3 (edited by
Physical examination and hamatological, chemical, and J. Minckler); p. 2654, Ncw York, 1972.
serological tests revealed no abnormalities in the patient 6 Fisman, M. Br. J Psychiat. 197 5' 126' 414.
7 Payne, R. W. u Handbook of Abnormal Psychology (edited by H. J
group. 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.
Discussion 9. Crcw, T. J., Mitchell, W. S.8r./. Psychiat 1975,126'360
10. Krawiecka, M., Goldberg, D., Vaughan, M. Unpublished.
The results show that the ventricles of a group of I l. Withcrs, E., Hinron, l. Br. J. Psychiat. 197 l, ll9, 1
chronic institutionalised schizophrenic patients are 12. Huckman, M. S., Fox, J., Topel, J . Radiology, l9'l 5, 116,85.
larger than those of a group of age-matched normal con- 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.
trols and that, within the schizophrenic group, increased I 5. Gunner-Svensson, F., Jensen, K Acta psychiot scond 79'l 6, 51, 283
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 DOI.]BLE BLIND CROSSOVER TRIAL OF
brain, a feature of schizophrenia? Two earlier LEVAMISOLE IN RECTJRRENT APHTHOUS
groupsrr ra who employed pneumoencephalography con- ULCERATION
cluded that there are patients with schizophrenia in
whom ceiebral ventricular size is increased, but T. LBHNTn J. M. A.rJfltlroN
neither of these studies included normal controls. The L. IveNyr
difficulties of selecting an appropriate control group for
this type of study are considerable. For this reason we Department of Oral Immunology and Microbiologt, Gult's
Hospital Medical and Dental Schools, London SE I 9RT
are inclined to place more emphasis upon the finding
that within the patient group there is a relationship Sumtnar1 A double blind crossover trial of levamt-
between increased ventricular size and cognitive impair- sole has been carried out in 47 Patients
ment, than upon the finding of large diflerences in ven- with recurrent oral ulceration. Significant decreases in
tricular size between the patients and controls. A pos- thc number of ulcers and ulcer days were found after 2
sible explanation for our results is that we have selected months of intermittent administration of levamisole.
a group of schizophrenic patients who fortuitously About 64/o of patients responded to the drug by a de-
suffer from an unrelated dementing illness and that we crease in the number of ulcers of more than 50%, for
have compared them with a group of people who, since
two or more months. The remaining 367o of patients
they are in employment, are unlikely to be disabled in failed to respond to levamisole and237o of these had an
this way. However, our 18 patients were selected from
increased number of ulcers. The side-effects recorded in
a population of 60 and th.is implies a prevalence of patients taking levamisole were comparable with those
dementia greatly in excess of rhe 3-57o seen in the in patients on placebo, except for a flu-like syndrome in
general population aged 60 and over.15
1 patient and urticaria in another, necessitating with-
An alternative hypothesis is that amongst the severely
drawal of the drug. The mechanism of action of levami-
incapacitated schizophrenic patients requiring inpatient
sole in recurrent oral ulceration is not known, but it is
care there is a group in which the disease is associated
suggested that levamisole may correct a deficiency of
with increased ventricular size and impaired cognitive suppressor cells, or potentiate the cellular responses to
capacity. The question obviously arises as to whether in-
crossreacting microbial agents.
creased ventricular size is a consequence of the patho-
logical process or whether increased ventricular size may
Introduction
in some way predispose to a severe and cognitively inca-
pacitating form of the disease. Tbe existence and pos- Lnr,ruNosuppnEssIvE and anti-inflammatory drugs,
sible size of the subpopulation of schizophrenic patients such as corticosteroids and to a lesser extent azathio-
with enlarged ventricles will require further investiga- prine and cyclophosphamide have been used in the trebt-
tion with respect to a welldefined base population. ment of recurrent aphthous ulcers (n.,t.u.) and Behqet's
These further investigations must also be conducted at syndrome (n.s.). The response is varioble but topl-al
different srages of the disease. ctrticosteroids are effective in the managemet( of