PREFRONTAL LEUCOTOMY A CLINICOPATHOLOGICAL REPORT

PREFRONTAL LEUCOTOMY A CLINICOPATHOLOGICAL REPORT

23 PREFRONTAL LEUCOTOMY A CLINICOPATHOLOGICAL REPORT ALICK ELITHORN M.A., M.B. Camb., M.R.C.P., D.P.M. MEMBER, M.R.C. NEUROLOGICAL RESEARCH UNIT AND...

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23

PREFRONTAL LEUCOTOMY A CLINICOPATHOLOGICAL REPORT

ALICK ELITHORN M.A., M.B. Camb., M.R.C.P., D.P.M. MEMBER, M.R.C. NEUROLOGICAL RESEARCH UNIT AND CLINICAL ASSISTANT, DEPARTMENT OF PSYCHIATRY, NATIONAL HOSPITAL,

QUEEN SQUARE, LONDON

With

a

pathological report by E. BECK

RESEARCH ASSISTANT, NEUROPATHOLOGICAL DEPARTMENT, INSTITUTE OF PSYCHIATRY, MAUDSLEY HOSPITAL, LONDON

FOR most of the mentally ill patients who come into the neurosurgeons’ hands a restricted leucotomy or topectomy is now the operation of choice. Clearly preferences for different forms of leucotomy should ultimately depend on a large series of detailed clinicopathological correlations, but not enough of such material is available. In these circumstances the publication of a single clinicopathological study is justified. Not only will it make a small contribution to the evidence available for a later analysis, but the difficulties of interpretation which become apparent when the clinicopathological correlations are discussed may usefully draw attention to those deficiencies in our present knowledge which most require investigation. Careful analysis of published cases does not provide evidence sufficient to sustain the widespread and enthusiastic belief that a bimedial inferior cut is always the modified operation of choice. In this operation the section of the white fibres is in the usual plane but is limited as far as possible to the ventromedial quadrant of each lobe. It is sometimes called an orbital leucotomy. Further, in the present case full recovery from a nonpsychotic mental illness followed a leucotomy in which these ventromedial segments virtually escaped damage. The clinical findings suggest that the improvement in this patient depended on personality changes. These were of a type which, in other patients, might bear no causal relationship to therapeutic success. In such patients they would be an irrelevant defect : in the present case, it is argued, they were essential to recovery.

gaiety. Although an extremely active woman. who was alwayss bottling. preserving. and knitting, she was inclined to be

excessively anxious over small matters and would arrive over early for trains. She was meticulous with her clothes and fussy about the house and would get upset if her routinewere Liable to headaches she was careful of her health. out. She had few interests outside her home and family. and her friends were chiefly those of her youth. Gardening, singing, and sketching were her hobbies. Present Illnes8.-At the age of 2.3 an attack of iiu left her with a ringing noise in the head. mainly in the left ear. This noise gradually lost its intensity and after a time became so faint that she could only hear it if she especially listened. for it. 27 years later, at the age of .’)2, she had an attack of gastric flu with diarrhoea and vomiting, and after this the noises increasecl in intensity. They became worse and 4 intolerable. years later were On adllli8sion she descrihed them as yarying-sonletL.>nes like the reverberations of beaten iron. at others like clanging cymbals or the dragging of heavy chains. Often the noises were so loud that she could feel something hitting the inside of her head, which at times seemed to be jerked about. For a year or two she had felt weak, lifeless, and depressed, with the result that she could not attend to her normal household duties. Her legs were weak and tremulous. Palpitations were accompanied by a dreadful pain in the chest. Although she was constipated, her appetite remained good. On examination she was well nourished, neat, and selfcomposed. She told her story with a wealth of circumstantial detail, and the house-officer noted that her mood was characterised by complacency rather than severe depression or emotional distress. Physically, apart from a chronic lesion of the right inner ear, there was no evidence of organic disease of the nervous system. She had hypertension (blood-pressure 250/130 mm. Hg) and arteriosclerosis. Operation.-On Nov. 12. 1948, Mr. Harvey Jackson carried out a standard prefrontal leucotomy. Postoperative State.-]Immediately after the operation the patient was grossly confused. She had urgency and incontiHer confusional state resolved rapidly, and after a nence. short convalescence she returned home much less worried by her noises but distinctly apathetic.

put

..

"

.

"

Case-report A married woman, aged 59, diagnosed as suffering from (i) tinnitus due to middle-ear disease, and (ii) a hypochondriasis with hysterical features, complained mainly of terrible head noises, palpitation, and weakness of the

legs. F’ew!!7
’-

Fig. 1-Slood-pressure

at rest and under sodium-amytal sedation and electrical resistance of palmar skin before and after leucotomy.

24 the operation a home visit alive and interested. She was using make-up again and planning her future wardrobe in a sensible manner. Only once had she been incontinent, but she had been troubled by some urgency. Her husband and her daughter were both very pleased with her progress, finding her unworried and placid but very lazy. She was helping little with household tasks and mostly sat about doing nothing. She had done some shopping in" a competent slower on the manner, but she herself noticed that she was uptake," and her daughter found her distinctly forgetful. Her appetite was excessive. A year after the operation her husband reported that she was still improving. She concentrated better and was taking the initiative in such matters as altering her own clothes and mending her husband’s. Her cooking was good but plainer, and she still occasionally forgot to put salt in the potatoes. She found it difficult, moreover, if she was put out of her routine-e.g., if someone extra came to a meal, or if her daughter tried to persuade her to try a new recipe. She enjoyed going out more than she had done for the past 6 or 7 years, but in the cinema she became lost if the plot was complex. Of her tinnitus she said : " I have those noises but I can’t be bothered with them." Her husband thought that her personality was improved and she was not an invalid in any way: " If she could sleep more and eat less, she would be no problem at all." 6 months later she was still happy-go-lucky, did not appear to bother about anything, and when warned by her husband about leaving her bag in the shops she replied " If I lose it I lose it." In June, 1950, she had what was probably a small cerebrovascular accident, which was followed by an increase in her apathy and a further impairment of her powersof memory and concentration. In December, 1952, she died of cardiac rupture.

Follou’-up.-3 months after

disclosed that she

was more

substitution subtests. 3 months later her performance had definitely improved, but 19 months after the operation it was still below her preoperative level. 4 years after the operation there was evidence that further deterioration had taken place. Her performance on all subtests was consistently below what it had been before the operation : she could not reproduce the Terman designs, her performance at Weigl’s sorting test was poor, and she failed to learn the Babcock sentence after nine attempts. Autonomic Functions.-On admission her blood-pressure was 250/130 mm. Hg. Her urine was normal, blood-urea 40 mg. per 100 ml., and 1trea clearance 102%. Intravenous pyelography revealed no functional or anatomical abnormality. Her heart showed some left ventricular enlargement. The blood-pressure was recorded morning and evening in the right arm. Though the evening values tended to be higher than the morning values, leucotomy affected both in a similar manner, and only the evening values are presented here (fig. 1). It will be seen that there was no pronounced fall in either the systolic or diastolic pressures even in the immediate postoperative period. A year after the operation (Nov. 30, 1949) the patient’s blood-pressure was recorded in the outpatient department. It was then 220/125 mm. Hg. After 15 minutes’ rest the mean of three readings was 192/112 mm. Hg. In November, 1952, the blood-pressure was 230/125 mm. Hg. These values were essentially the same as those found preoperatively. In addition to the resting blood-pressure observationsSodium amytal ’ sedation tests were done both before and after operation. The results of these are given

digit symbol

Electro-enceplwlography.-B e fore the operation the electro-encephalogram was symmetrical, with a normal alpha rhythm. The record was dom-

inated

by a generalised high-voltage rhythm of 20 cycles per sec. Twenty days after the operation distinct changes were observed. The alpha rhythm at 10-11 cycles per sec. was of greater amplitude and spread further forward. The fast rhythm of 20 cycles per sec. was no longer apparent but may have been masked. Irregular slow activity of 1-3 cycles per see. was seen bilaterally in the prefrontal regions but was much more extensive on the right, where it was seen as a focus. A year after the operation the only abnormality was a small amount of low-voltage slow activity in the frontal regions, now greater on the left than on the right. 4 years after the operation (Nov. 6, 1952) the frontal slow activity was only just discernible, but the record showed

abnormality :a bilateral theta rhythm at about 7-8 cycles per sec. predominantly in the left frontotemporal area. There were also, on overbreathing, suggestions of spikes in the left frontotemporal region. Psychological Tests.-The patient a new

tested with the Wechsler-Bellescale before the operation and 1 4, 19, and 48 months after it. She scored an intelligence quotient of 110 before the operation, and her results showed no significant evidence of intellectual deterioration. A month after the operation there was clear evidence of intellectual impairment. Her scores on all subtests except picture completion, similarities, and

was vue

design showed not only no practice effect but even a definite

block loss.

most evident on the arrangement, digit span, and

This

picture

was

Pig. 2-Greatest extent of surgical

lesion in frontal lobes (hatched areas). Numerals indicate BrodC, caudate nucleus ; P, putamen ; Ra, area

mann’s cyto-architectonic fields in each section : recta anterior.

25

Fig.3-Retrograde degeneration in thalamus (hatched areas) : A, nucleus anterior thalami ; C, nucleus caudatus ; DM, nucleus medialis dorsalis thalami ; LP, nucleus lateral is posterior thalami ; MB, corpus mammillare ; R, nucleus ruber ; Sb, corpus subthatamieum ; SN, substantia nigra ; VA, nucleus ventralis anterior thalami ; VL, nucleus ventralis lateralis thalami ; VPL, nucleus ventralis posterolateralis thalami ; III ventriculus tertius.

graphically in fig. 1. In the second test, 29 days after the operation, the fall in both systolic and diastolic pressures was much less than preoperatively, the initial readings being much lower and the lowest reading very slightly higher. The nsistance of the palmar skin was measured on several occasions before and after the operation. This technique has been described elsewhere, together with the results obtained with patients undergoing prefrontal leucotomy (Elithorn et al. 1954). Recordings were made from both hands. No consistent difference between the two hands was observed, and in fig. 1 the mean values for the two hands are given. It is apparent that all except one of the immediately postoperative values are higher than those found before the operation. The postoperative reduction in palmar sweating which generally follows prefrontal leucotomy has been shown to be independent of thermoregulatory requirements. It is probably related to the relief of anxiety which normally follows the operation. After the operation there was a considerable change in cceight. In February, 1949, the patient weighed 9 st. 71/2 lb. ; 2 years later she weighed 13 st. 5 lb. Strenuous attempts were made to keep her to a diet, and her weight fell to 11st. 10 lb. On her last visit, in November, 1952, she she weighed 11 st. 43/4 lb. Throughout the follow-up continued to complain of insomnia, which, however, was adequately controlled with hypnotics. Pathology.-The brain weighed 1430 g. and showed considerable atheroma of all the arteries at the base, especially the vertebral, basilar, and carotid arteries. There was a slight bilateral tonsillar pressure cone. Both frontal lobes, particularly on their anterior and dorsal aspects, were somewhat atrophic. The leucotomy entry-marks were in the pars triangularis of the inferior frontal convolution on either side. A coronal section through these entry-marks at the level of the genu corporis callosi passed through the greatest extent of the leucotomy sear (fig. 2a and c). This occupied almost the entire white matter of both frontal lobes, extending to the wall of the lateral ventricle, which was pierced on the right side ; the two scars communicated through the dorsal half of the corpus callosum. Only the most medial dorsal and orbital regions had escaped. The cortex of both inferior frontal convolutions was extensively damaged. More posteriorly, at the level of the head of the caudate nucleus, the lesion in the left hemisphere (fig. 2b) was much smaller and terminated in a central and ventral position, slightly involving the caudate nucleus. The lesion in the right hemisphere at this level (fig. 2d) was still extensive, and occupied, in addition to those structures mentioned above, parts of the striatum, the claustrum, and the capsulae externa and extrema. It terminated 5 mm. further posteriorly in a similar position. Anteriorly the lesions extended within the central white matter to the level of the pregenual gyrus cinguli on either side. Histological investigation of serial sections through the thalamus (fig. 3) showed substantial retrograde degeneration

period

in both dorsomedial nuclei (the right more than the left), moderate degeneration in the right anterior nucleus, and slight changes in the left anterior nucleus. There was considerable nerve-cell loss, shrinkage, and a dense compensatory gliosis. From the site of the degeneration within the thalamic nuclei and from the histological investigation of the surgical lesions one can conclude that the thalamic connections with Brodmann’s areas 8, 9, 10, 46, 45, 47, lateral 11 and 24 were severed. All these areas were more severely involved on the right side than on the left. Further, a few fibres to the left medial orbital gyrus rectus were interrupted. In addition to the thalamofrontal projection, the fasciculus cinguli, the superior longitudinal and uncinate fasciculi, and Arnold’s bundle were cut bilaterally. Representative blocks from various cortical regions showed no gross damage but some increase of the marginal glia and of the fibrous glia in the white matter. Most blood-vessels, both of the brain and the meninges, showed adventitial fibrosis: the larger and mediumsized arteries showed various degrees of’ arteriosclerosis. Discussion

In view of the current preference for selective " bimedial incisions this case is of considerable interest. It is clear that the operation aborted a severe hypochondriasis occurring at the involutional age. Pathological investigation has shown that this result was achieved in the absence of significant damage to, or involvement of, the medial orbital regions, and with only unilateral involvement of the cingulate areas. In the light of these findings it seems worth while to examine the evidence on which the current preference for bimedial operations is based. In doing so it becomes necessary to consider whether an operation which statistically " maximal improvement with minimal personality change ’’ is necessarily the operation of choice in any "

produces

given patient. lluch of the enthusiasm for the bimedial stems from the results of the Massachusetts

operation lobotomy

studies (Greenblatt and Solomon 1952). These workers have, in fact, only shown that in schizophrenics this operation produces results which are more satisfactory than either a standard bilateral operation or a unilateral one. They do not themselves provide any evidence on which the different symmetrical modified cuts can be compared. Their original preference for this operation is perhaps based on the earlier work of Scoville et al. (1951), who reported the results obtained in an investigation which compared the effects of three selective undercuts : superior, medial cingulate, and orbital.

26 terised by a reduction in anticipatory and preoccupative These workers, the majority of whose patients were also Such a change, if not too extensive, may sometimes schizophrenic, concluded that there was little to chooseactivity. be in all ways beneficial, and is then sought deliberately in the between the three areas from the point of view of theratreatment of psychoneurotic disturbances of personpeutic effect, but claimed that there were definite surgical In other cases it might be necessary to produce these ality. differences between the postoperativesyndromes characchanges to an excessive degree so that a diminished personality teristic of each area. The superior-convexity operation, should react with less emotional disturbance to an otherwise they stated, was associated with the most striking intolerable strain-e.g., excessive pain, and the experiences of personality changes, in particular emotional blunting a schizophrenic psychosis (Frankl and Mayer-Gross 1947). The and apathy. After an orbital cut the personality showed surgeon seeking to obtain solely an alteration in personality structure would wish to cause the least structural damage less change, this being in the direction of hyperactivity and restlessness. compatible with achieving the desired effect-i.e’., he would lTedial cingulate operations they ’



causing postoperatively a severe physical " knock out," again with little personality change. These results contrast strongly with those of Le Beau (1952), whose patients also underwent various forms of topectomy and undercutting. Le Beau agrees that operations on the convexity tend to produce the greatest personality change ; in his cases, however, this was in the direction of overactivity-" the hypomanic syndrome of the convexity "-whereas orbital cuts produced apathy. Similar inconclusive findings have also been reported after clinicopathological investigations. Thus, reviewing the results obtained from their study at the Institute of Psychiatry, Meyer and Beck (1954) conclude :

reported

as

The dorsal and, in particular, the dorso-lateral sectors of white matter do not appear to be as significant for improveOn ment as the midcentral, orbital and cingulate sectors. the other hand, involvement of the dorso-lateral and lateral white matter, and particularly cortex, appears to be one of the "

factors

responsible for severe personality change." However, full social recovery was obtained they point out that provided the cut was quantitatively adequate without consistent involvement of medial, orbital, and cingular segments." ,.

Eie (1954) reports the macroscopic necropsy findings in 29 cases and claims that his results show that

4. aggressive, hyperactive, restless patients may improve after lesions limited to the connections of the granular areas of the convexity and of the cingulate gyrus." One important difference between various workers is that the selection of patients differs widely from one investigation to another. Both pathological investigations were undertaken largely on patients who died in mental hospitals. The Maudsley material was diagnostically mixed, whereas those of Eie’s patients who were suitable for clinicopathological analysis were all overactive and aggressive before operation. In the two clinical series discussed the contrast is even greater : most of Scoville’s patients were schizophrenics, whereas most of Le Beau’s were operated on for intractable pain. The striking contradictions between the results found by these and other workers suggest that ablations of anatomically corresponding areas need not produce similar defects in different patients. Indeed, most clinicians will agree that their expectations of the sort of defects which may follow any individual leucotomy are coloured by the previous personality of the patient. The conception that there exists an operation which will produce the greatest improvement together with the smallest personality change is based on the belief that

choose to operate on the region known to be most likely to produce the type of personality alteration which was desired.

Applying this type of analysis to the present clinicopathological case-report one may argue that the successful results were closely associated with, and dependent on, the alterations in personality which followed the operation. There was in the history and on examination little evidence that the illness might be an endogenous depressive one. Although the onset was during the involutional period and followed a minor physical illness, there was no diurnal variation of symptoms, no retardation, and no objective sign of depression. The clinical picture was essentially one of preoccupation with, and elaboration of, most

disturbance of sensation. It can be economically as a reactive development

a

explained of the patient’s premorbid personality tendency to anxious preoccupation of the obsessional type. This excessive reaction may perhaps have been partly precipitated by arteriolar and psychological stresses associated with the involutional period. The changes in personality which followed leucotomy, and which justifiably came to be characterised as defects-i.e., her laziness, her placidity and her lack of concern for herself, her property, and her relations-can be seen as a reduction in her tendency to ruminative and anxious preoccupation. Two main qualitative differences between her bothering less about her symptoms and her bothering less about her cooking and her finances seem to be (1) that the stimulus of the tinnitus was always present, and (2) that taking thought about the noises would not reduce their intensity.

Failure to habituate to a constant and irreducible source of emotional distress is characteristic of the neurotic personality and especially of the obsessional neurotic. It is therefore likely that the change of personality involving a reduction in preoccupative anxiety was essential to the success of this operation, and that this personality change was undesirable only in so far as it was excessive. As regards the involvement of the orbital and cingulate regions, it appears that, since the operation was both successful and excessive, a further extension of the lesion would only have increased the defects. To have cut the orbital and cingulate sections in place of an equal amount of dorsal tissue would (according to most workers) have produced less personality change. But (most authorities would again agree) a similar effect would have been produced more economically by reducing the amount of dorsal tissue cut. Later experience with modified leucotomies in non-psychotic patients crippled by a improvement and personality change are two independent morbid preoccupation with a tinnitus has in fact shown On theoretical grounds, and these are variables. that operations restricted to the convexity, as well as supported by clinical observations—in particular Part- bimedial cuts can produce relief with only minor personridge’s (1949) important observations on depressive ality changes. These changes may in their own right be illnesses treated by leucotomy-it may be presumed that regarded by close relations as beneficial (Elithorn 1953). two major effects may be expected from frontal ablations : We may conclude that the search for an operation which is statistically most satisfactory for all patients (1) Such a lesion may abort a functional psychosis (e.g., an endogenous depressive illness) which in other circumstances is sterile. Both the relevant published reports and the might be expected to resolve spontaneously or to be resolved analysis of the present clinicopathological report support by treatment (e.g., electric shock). For this effect the surgeon Fulton’s (1951) contention that restricted leucotomies would seek to damage the area which would produce the should be adapted " to the nature of the mental illness." greatest shock " effect together with the smallest persisting Fulton suggests that "depressed patients should have the disturbance of personality and intellect. bimedial type of operation, and that those who are overmain effect of a prefrontal- ablation is to second The (2) produce a change of personality which is generally charac- active or agitated might benefit most from a dorsal "

27 It is only necessary to point out that a causal clinical analysis is more important and relevant than an observational correlation which will depend on the sample of patients examined. Many patients are and overactive because they have a " depresagitated sive " illness.

topectomy.

BLOOD A_BTD

PER

CONCEVTRATIO_1‘S GLUCOSE

100

I5

OF

FORMAL

PYTtUVATE, L"’BD

K-EETOGLUTARATE,

DIABETIC

SUBJECT3

(MG.

ML.)

S ummarySummary

of a patient incapacitated by preoccupation with severe tinnitus and who was treated successfully by a standard prefrontal leucotomy is reported, together with a description of the primary lesions and the retrograde degeneration in the thalamic The clinical

history "

"

nuclei. The

concept

that there is

a

single

selective

operation

which will provide in each case the greatest improvement with the smallest personality change is dismissed as

unlikely.

The relative roles of " improvement " and " personality change " in producing a satisfactory therapeutic result are discussed.

grouping, and also because the derivatives tend to give rise to multiple spots during paper-chromatography, from separation of geometrical isomerides.7 The first objection is of particular relevance when specimens from diabetic patients with ketosis are examined, because interference from aceto-acetic acid may occur when high concentrations of this substance are present.8

We are particularly indebted to Dr. Eliot Slater and Mr. Harvey Jackson, under whose care this patient was, and we

would also like to thank Dr. E. A. Carmichael and Prof. A.

for encouragement and advice. Miss M. A. Crosskey assisted with the autonomic investigations. We are also indebted to Dr. W. A. Cobb and Prof. O. L. Zangwill, in whose departments the electro-encephalographic and psychological studies were made.

Meyer

We have devised a method for the separation and estimation of pyruvic and x-ketoglutaric acids in blood REFERENCES using 1 : 2-diamino-4-nitrobenzene, which was introduced Eie, N. (1954) Acta psychiat., Kbh. suppl. 90. by Hockenhull and Floodgate9 as a specific reagent for Elithorn, A. (1953) Proc. R. Soc. Med. 46, 832. oc-keto acids, with which it forms stable derivatives Piercy, M. F., Crosskey, M. A. (1954) J. Neurol. Neurosurg. & Neuropsychiat. 17, 186. separable by paper-chromatography. The reagent is Frankl, L., Mayer-Gross, W. (1917) Lancet, ii, 820. Fulton, J. F. (1951) Frontal Lobotomy and Affective Behaviour. allowed to react with the deproteinised blood-filtrate for London. 12-16 hours, and the derivatives are extracted with ethyl H. C. Amer. J. 262. (1952) Greenblatt, M., Solomon, Psychiat. 109, Le Beau, J. (1952) J. ment. Sci. 98, 12. acetate and removed from the organic solvent with Meyer, A., Beck, E. (1954) Prefrontal Leucotomy and related 5% -nB"- sodium carbonate solution. After acidification operations : Anatomical aspects of success and failure. Edinof the sodium carbonate solution, the derivatives are burgh. Partridge, M. (1949) J. ment. Sci. 93, 795. re-extracted with ethyl acetate, which is then evaporated W. E. A. J. K., Pepe, Scoville, B., Wilk, (1951) Amer. J. Psychiat. to dryness ; the residue is dissolved in acetone and the 107, 730. derivatives are separated by paper-chronia,tography-1-0° Communication The separated derivatives are eluted with 30% ethanol, and the optical densities of the resulting solutions BLOOD CONCENTRATIONS OF PYRUVIC measured at 280 m[1.. The blood pyruvate, fx-ketoglutarate, and glucose AND &agr;-KETOGLUTARIC ACIDS IN concentrations in 7 normal people and 8 ambulant NORMAL PEOPLE diabetic outpatients are given in the table. All the AND DIABETIC PATIENTS patients were receiving insulin, and were healthy apart THE blood-levels of
Preliminary

.

2. Seligson, D., Shapiro, B. Analyt. Chem. 1952, 24, 754. 3. Gey, K. F. Hoppe-Seyl. Z. 1953, 294, 128. Biochim. biophys. Acta, 1952, 4. Von Marken, L., Florijn, E. 8, 349. 5. Fidanza, A., Laviano, F. Boll. Soc. ital. Biol. sper. 1951,

27, 1468. 6. Frohman, C. E., 1951, 193, 803.

Orten, J. M., Smith, A. H.

J. biol. Chem.

London, S.E.5 7.

Isherwood, F. A., Cruikshank, D. H. 173, 121.

B.A. Camb.

Nature, Lond, 1954,

8. Markees, S. Biochem. J. 1954, 56, 703. 9. Hockenhull, D. J. D.. Floodgate, G. D. Ibid, 1952, 52, 38. 10. Smith, M. J. H., Taylor, K. W. Ibid, 1953, 55, xxx.