psychiatric aspects of liver disease - postgraduate medical journal

487

PSYCHIATRIC ASPECTS OF LIVER DISEASEBy ESTHER A. DAVIDSON, M.B., M.R.C.P.(Edin), D.P.M., and*W. H. J. SUMMERSKILL, M.A., D.M.(Oxon), M.R.C.P.(Lond.)

From the Department of Medicine, Postgraduate Medical School of London, Harvard Medical School and the BostonCity Hospital, Boston, Massachusetts

The Babylonians (circa 2000 B.C.) attributedpowers of augury and divination to the liver,designating it by the term used also for ' soul' or'mood' (Baumann, 193 ), and clinical descrip-tions of an association between hepatic disease andmental disorders have been recorded since Hippo-cratic times. A patient with hepatitis' developed astate like rabies; he could not be held, said thingswhich could not be comprehended and barkedlike a dog' (Morbis Internis), and the fatal illnessof Hermocrates included a fluctuating delirium onthe fifth day, followed by the appearance of jaun-dice on the sixth (Hippocrates, 460-370 B.C.).

Hippocrates' concept of' madness on account ofbile' survived until recently in the term ' chol-aemia,' but failed to explain mental changes in thenon-jaundiced patient with liver disease. Galen(A.D. 13 -200) implicated excess liver secretions asconducing to choleric and melancholic person-alities and also contributed to a theory of hepaticfunction relevant to modern concepts of the liver-brain relationship. He considered that the liverprepared the blood from food in the stomach andthat this blood spread into all parts of the body.Various psychiatric syndromes have now beenrecognized as incident to liver disease (Zillig,1947) and certain neuro-psychiatric conditions canbe related to disorders of functional anatomy of theliver and portal system.The Concept of Portal-SystemicEncephalopathyThe significance of earlier observations that

ammonium salts might provoke mental changes inpatients with hepatic cirrhosis (Van Caulaert et al.,1932; Kirk, I936) was stressed by the descriptionof characteristic neuro-psychiatric findings inhepatic coma (Adams and Foley, 1953) and theirreproduction by various nitrogenous substances(Phillips et al., i952). The importance of derangednitrogen metabolism in the genesis of hepatic coma

*Rockefeller Travelling Fellow of the MedicalResearch Council.

is also evident from the observations of Sherlockand her colleagues (1954), who reported the charac-teristic syndrome occurring spontaneously inpatients with liver disease, either as an acute orchronic disorder, and responding to protein with-drawal.The term ' portal-systemic encephalopathy'

(Sherlock et al., 1954) was introduced to describethe neuro-psychiatric syndrome of which hepaticcoma is the ultimate and most severe manifestation.It is based on clinical and biochemical investiga-tions which relate the onset of neuro-psychiatricdisorders of the same basic pattern to a combina-tion of hepato-cellular disease of varied aetiology,shunting of portal blood to the systemic circulationand the presence of nitrogenous material in theintestines. Responsible factors vary in each patient,the route of toxic nitrogenous substances from theintestines to the brain being through a diseasedliver, through portal collateral channels or by bothroutes (Fig. i).Wagner-Jauregg (1896) launched the theory of

. : .... ...i, t;r .;..-.

**.

- Ii;~;.ti!i }r.. ^' ;~

S;.·~

Fig. I-The mechanism of portal-systemic encephalopathy.From Sherlock, et al., Lancet, ii, 453 (I954).

Protected by copyright.

on 29 Novem

ber 2018 by guest.http://pm

j.bmj.com

/P

ostgrad Med J: first published as 10.1136/pgm

j.32.372.487 on 1 October 1956. D

ownloaded from

http://pmj.bmj.com/

488 POSTGRADUATE MEDICAL JOURNAL October 1956

intestinal auto-intoxication in mental disease andit was related to liver disease by Quastel (i931),who believed that toxic amines resulting frombacterial action in the gut might produce con-fusional states because ofimpaired hepatic function.The nature of the substance producing portal-systemic encephalopathy and its effect on cerebralmetabolism remain to be demonstrated, but muchcurrent investigation is directed towards the possi-bility that ammonia may be incriminated.

Clinical FeaturesThe neuro-psychiatric disorder consists in an

organic reaction associated with neurological dis-turbance. The psychiatric features vary in acute-ness and therefore in symptomatology, dependingon the nature and intensity of aetiological and pre-cipitating factors, and its rate of progress to theonset of hepatic coma may vary from hours toyears. The associated neurological and E.E.G.findings are of importance as confirmation of thesignificance of the mental changes.

In mild cases there may be no objective neuro-logical findings. A coarse 'flapping' tremor onsu§tained posture of the limbs is the most charac-teristic feature, but tremor is not infrequentlyatypical. Additional disorder of the motor systemincludes increased muscle tone and tendon reflexes,often with ankle clonus and normal plantarresponses, but, like other signs, these may bevariable or absent. The facies is often devoid ofexpression, except when broken by fatuousgrimaces, speech becomes slow and slurred, andsialorrhoea develops in more chronic cases. TheE.E.G. changes were well described by Adams andFoley (1953) and are based on the presence ofbilaterally synchronous, symmetrical, high-voltage,slow waves in the theta and delta ranges.

Clinical and biochemical stigmata of liver diseaseand portal hypertension should be searched for.Fetor hepaticus is a frequent finding.TreatmentTreatment of the established neuro-psychiatric

disorder, independent of its cause, aims at theelimination of nitrogenous substances from thegut and the improvement of hepatic function. Itcomprises bed rest, withdrawal of dietary protein,repeated enemata and the provision of the requisitefluid, glucose and electrolytes by mouth or parent-erally. A short course of oral chlortetracycline orneomycin inhibits bacterial action on nitrogenoussubstances in the intestines. Factors which mayhave precipitated the syndrome (gastro-intestinalhaemorrhage, intercurrent infection, etc.) aretreated immediately.

Sedation of the noisy, violent patient presentsproblems, as most sedatives in common use, par-

ticularly opiates, barbiturates and paraldehyde,have been incriminated as precipitants of hepaticcoma in patients with liver disease. Chlorpro-mazine may be of benefit; although it occasionallycauses jaundice, there is no evidence that patientswith liver disease are particularly susceptible. Inany case, the drug of choice should be exhibitedin small doses and withdrawn as soon as possible.Psychiatric Disorders Complicating VirusHepatitisAcute Liver Failure

In the fulminant form of the disease the psy-chiatric syndrome is an acute organic reaction,with delirium (disorientation and visual hallu-cinosis) and clouding of consciousness rapidlyprogressing to coma within hours or days. Psy-chiatric abnormalities may precede other clinicalfeatures of the disease and jaundice may be late inappearing. This sequence of events can lead todifficulties in diagnosis and the patient may beadmitted to a mental hospital or observation ward.There is little to add to the Hippocratic descrip-

tion that these patients ' are vociferous and viciousand do not keep quiet.' Nightmares, headacheand dizziness are inaugural, non-specific symp-toms, but even before complaints are forthcomingthe patient may show episodes of anti-socialbehaviour or character disturbance.A 49-year-old deaf-mute, epileptic and psycho-

pathic, behaved with sudden unprecedentedviolence on a return visit to a mental hospital.There was no overt confusion and no amnesia forthe episodes which were repeated following ad-mission. On the fifth day he was febrile, vomitedand passed rapidly into coma on the seventh dayand died on the ninth. Jaundice appeared ter-minally. Post-mortem examination confirmed thediagnosis of acute virus hepatitis.

Unco-operative behaviour often continues whileconsciousness is clouded. The delirium is of thenoisy, restless variety and attacks of screamingoccur spontaneously or may be induced by theslightest stimulus. Violent behaviour may not beprominent in adults, but is common in children(Spence and Ogilvie, 1927).An I -year-old girl in the fourth week of

hepatitis developed fever, anorexia, vomiting andincreasing jaundice and lapsed into coma, respond-ing only to noxious stimuli with all the manifesta-tions of extreme rage. Attacks of screamingoccurred every few minutes and penetrated beyondthe hospital confines. Deliberately obstructivebehaviour preceded the onset of coma and duringlighter phases she screamed at her attendants to' get out.'The neurological features are the same as those

found in portal-systemic encephalopathy from


on 29 Novem


j.bmj.com

/P


j.32.372.487 on 1 October 1956. D

ownloaded from

http://pmj.bmj.com/

October 1956 DAVIDSON AND SUMMERSKILL: Psychiatric Aspects of Liver Disease 489other causes. Diagnosis may be suggested, evenin the absence of jaundice, by the clinical features,which include fetor hepaticus, a palpable spleenand diminishing liver dullness.

Prognosis in fulminating hepatitis is poor, butmay be improved by appropriate treatment. Com-plete recovery of liver function is the rule in thosesurviving the attack.

DepressionInvasion by certain organisms, particularly the

viruses of infective hepatitis and influenza, appearsto be associated with the development of depressivestates (Mayer-Gross et al., I954). Depressionoccurs in the prodromal phase, during icterus ormay continue as a distressing symptom after moreobjective evidence of the disease has disappeared(Findlay and Martin, I943). Certain authors(Lichtman, I953; Ford, I943) stress that somedegree of mental depression occurs commonly inthe pre-icteric phase, usually disappearing with theonset of jaundice. Liebowitz and Gorman (1952)describe a psychotic reaction developing in thesixth week of severe infective hepatitis in a man of30 years. Depression, with conviction of impend-ing death and suicidal threats, was followed bysensorial clouding, defective memory, negativebehaviour, silent staring, nocturnal insomnia, slowspeech and agitated movements of the limbs. Theauthors stress the importance of categorizing eachcase according to whether the mental illness iscoincidental, reactive or dependent on infectivehepatitis.

Depression and incipient portal-systemic en-cephalopathy may closely simulate each other insymptomatology. The common features are thereduced psycho-motor activity, the fixed facialexpression and nocturnal insomnia. Anorexia is asprominent in infective hepatitis as in depressionand mood changes of a depressive kind may com-plicate the cerebro-toxic state. Only by carefulexclusion of the organic syndrome and its associ-ated neurological features can a diagnosis ofcoincidental or reactive depression be made. Thedistinction is important, since the treatment andprognosis varies. Temporary withdrawal of pro-tein from the diet may assist in distinguishing thetwo conditions. A history of a previous attack ofdepression does not necessarily favour a diagnosisof a coincidental or reactive depression.Post-Hepatitis Syndrome

This psychiatric syndrome is found almost ex-clusively in nursing personnel and doctors oramong Service patients warded together awaitingrepatriation (Sherlock and Walshe, 1946). Com-plaints are of fatigue, weight loss, anorexia andabdominal discomfort. The feature of this syn-

drome in the medical group is fear of chronic liverdisease as a sequel to virus hepatitis. Anxiety anddepression occur and the liver remains apparentlyenlarged with exaggerated tenderness due to muchanxious palpation by the patient himself. Sherlockand Walshe found that undue mobility of the liverand spleen through deep diaphragmatic respirationcould make the normal organs palpable. Symptomscan be induced or aggravated by the medicalattendant uncertain of the development of cirrhosisfollowing infective hepatitis, as the return tonormal values of flocculation tests of liver functionis often delayed and follows clinical recovery.Iatrogenic conditioning of this syndrome may beavoided by eliminating unnecessary palpation andvenepuncture in medical personnel convalescentfrom infective hepatitis.

In Service personnel the benefits of speedyrepatriation and eligibility for pension awaitedpatients with chronic liver disease, so that thefactors of gain through illness may have, con-sciously or unconsciously, determined the per-petuation of symptoms.

Treatment of the established syndrome is byreassurance following diagnostic liver biopsy; inthe great majority of cases no evidence of cirrhosisis found.

Psychiatric Disorders Complicating HepaticCirrhosisThe Acute Organic ReactionThe features of the acute organic reaction may

arise de novo in the patient with cirrhosis or, lesscommonly, they may occur as episodes punc-tuating a chronic state. The hallmark of the acuteorganic reaction is delirium characterized by cloud-ing of consciousness, disorientation and visualhallucinosis. In the cirrhotic patient the suddenappearance of this syndrome associated with in-creasing neurological disorder demands investiga-tion of its cause and treatment based on the con-cept of portal-systemic encephalopathy. Thefactors of liver cell function, portal-systemic venousshunting and nitrogen content of the gut must beassessed individually and in relation to each other.Acute deterioration in liver cell function may occurthrough haemorrhage, shock, deprivation of bloodsupply or from the action of drugs, poisons,anaesthetics or alcohol. Portal-systemic shuntingof blood may become maximal from thrombosis ofthe portal vein, the construction of a surgical porta-caval anastomosis or through liver cell failure.Paracentesis abdominis with resulting decrease inintra-abdominal pressure may accelerate the bloodflow through intra- or extra-hepatic portal-systemicshunts. Nitrogenous substances in the gut may beincreased directly by protein feeding, gastro-intestinal haemorrhage or treatment with am-


on 29 Novem


j.bmj.com

/P


j.32.372.487 on 1 October 1956. D

ownloaded from

http://pmj.bmj.com/


monium salts or indirectly by bacterial action. Thefinal result of all precipitating factors is an increasein the amount of toxic nitrogenous substancesdelivered to the brain and this is reflected usuallyin a rise in arterial ammonia levels.

Treatment of acute portal-systemic encephalo-pathy is, as already outlined, modified accordingto the precipitants found.

Rigid selection of patients for surgical porta-caval anastomosis is made by their ability to with-stand, without neuro-psychiatric deterioration orelectroencephalographic change, a diet containingI20 g. protein for 10 days. The construction of anadequate minimal functioning shunt, together withprotein withdrawal and sterilization of the gut overthe period of operation, help to prevent neuro-psychiatric complications which may otherwiseoccur in as many as 33 per cent. of patients, par-ticularly in the elderly (Wooler, 1955).

Delirium and coma in cirrhotic patients is oftenattributable to cerebral intoxication by nitrogenoussubstances, but where the clinical picture is atypicalother causes or additive factors must be sought.Such causes may include drug intoxications, febriledeliria from coincidental infections or from abscessformation in the surgical patient, or disturbance ofcerebral function due to water intoxication orelectrolyte imbalance. The threshold for deliriummay be reduced in children or in patients withprevious disease of the central nervous system.The particular problems associated with alcoholismare discussed later.

The Chronic Organic Reaction with AcuteExacerbations

In a small proportion of patients with liverdisease the characteristic neuro-psychiatric andE.E.G. findings of hepatic coma present as achronic disorder with periodic exacerbations(Summerskill et al., 1956). An extensive portal-systemic collateral circulation can be demon-strated by transplenic portal venography (Atkinsonet al., I955) and the syndrome may follow portal-systemic anastomosis operations (McDermott andAdams, 1954). Fluctuations in the condition arerelated to the nitrogenous content of the diet anddiagnosis can be confirmed by noting the effect ofa precipitant, such as ammonium chloride (io g.daily), or by demonstrating improvement onprotein withdrawal.

Clinical and biochemical evidence of liverdisease may be equivocal or absent and mentaldisorder dominates the clinical picture.A 67-year-old housewife, admitted as a certified

patient to a mental hospital, had for one year showna lack of her usual reticence and modesty with afailing memory, faulty habits and a gluttonousappetite. She had no recollection of' bad turns'

during which she was confused and disorientatedwith incomprehensible speech and manifest diffi-culty in dressing. She learned to retire to bed whenshaking hands and an unsteady gait announced theonset of another blank spell. Previous health hadbeen good apart from a three-weeks episode ofjaundice at the age of 30. There was no history ofalcoholism or malnutrition.The diagnosis of cirrhosis with portal-systemic

encephalopathy was suggested by the diminishedawareness, upward gazing with perseverated dys-phasic utterance and marked grimacing of theacute episode. It was supported by the findings offetor hepaticus, hepato-splenomegaly, flappingtremor and exaggerated tendor reflexes and con-firmed by the demonstration of 'nitrogen in-tolerance ' with typical E.E.G. changes. Occlusionof the portal vein with a collateral circulationthrough a large inferior mesenteric vein wasdemonstrated on venography.An intake of 50 g. protein daily was compatible

with good mental health. On 60 g. daily she wasinert, garrulous and reminiscent with minor defectsin organic mental functions and minimal neuro-logical signs. 80 g. protein daily reproduced theacute episode with rapid advancement to coma.

Intelligent co-operation in the management ofher own diet allowed this patient to resume hernormal life and activities. When her family, un-convinced of her recovery, refused to accept hershe took up new responsibilities as housekeeper toa relative, a position she has discharged efficientlyfor over one year.The clinical psychiatric picture conforms with

that of any chronic organic reaction in the featuresof personality change, intellectual deterioration andlability of mood, and with any chronic intoxicationin its fluctuating character. Although intermittentcharacter changes occur (such as childishness,irritability, loss of concern for family), manypatients present in remission similar personalityfeatures. They are co-operative, pleasant peoplewith an ease in social relationships and frequentlya jocular, euphoric mood. Emotional lability is lessfrequently observed than persisting alterations inmood.

Intellectual deterioration varies from slight im-pairment of organic mental functions to gross con-fusion and daily fluctuations may be observed.Focal defects, appearing in a setting of clear con-sciousness, relate to disturbances in visual-spatialgnosis and are most easily elicited in the motorsphere as constructional apraxia, shown by in-ability to reproduce simple designs with blocksor matches (Fig. 2a). Symptoms of this defect aremanifest in various difficulties. Writing is typicallyoblivious of rulings (Fig. 2b); dressing presentsproblems to some patients, one cannot fill up a


on 29 Novem


j.bmj.com

/P


j.32.372.487 on 1 October 1956. D

ownloaded from

http://pmj.bmj.com/

October 1956 DAVIDSON AND SUMMERSKILL: Psychiatric Aspects of Liver Disease 491

I. EI.//

X X 1·US-9( ?S

FIG. 2.-Focal disorders in chronic portal systemic encephalopathy elicited in patientswith full consciousness and minimal intellectual defect, in the absence of grosstremor or visual disorder.(a) Constructional apraxia.(b) Writing difficulty. 'Hello dear. How are you ? Better I hope. That goes forme too.'

cheque, another has difficulty in following lines ofprint, some lose themselves in familiar surround-ings (sometimes neglecting the left half of space).Failure to distinguish objects of similar size, shape,function or position leads to the frequently ob-served symptom of micturating and defaecating ininappropriate places. Insight into such anomaliesof behaviour is frequently preserved. Benhamouet al. (I955) tell of a patient micturating in a cornerof the room who murmured, ' C'est degoutant.'One of our patients described her dressing andundressing difficulty as the funniest experience ofher life.

' Confusion' of this type is usually episodic,since the condition is never static. It may be aprelude to 'coma' in which clouding of con-sciousness exists with language disorder character-ized by dysphasia with perseveration and loss ofpropositional speech.

Consciousness and sleep are disturbed in variousways. The acute disturbances which punctuate thecourse of the chronic disorder are expressed in theclouded sensorium of delirium advancing to coma,the episodes being covered by amnesia. Less acutedisturbances are shown by drowsiness and con-fusion, while in the chronic state diurnal som-nolence from which the patient is easily rousedpresents the most common pattern of disturbance.Other manifestations which have been observed

are nocturnal insomnia, narcolepsy, fugues andtwilight states.

Disturbances of sensation include blurred ordouble vision, loss of visual acuity, simple visualhallucinations (lights and stars), paraesthesias andnumbness. Perceptual anomalies also occur(macropsia, distortion and prolongation of theimage, synaesthesia).

Psychomotor disturbance is shown in the dis-inclination for activity and poverty of spontaneousmovement, which are almost constant. Fixity ofexpression, staring, stupor and catatonic posturingare observed. Forced activity has been observedto lead to deterioration and neurasthenic syndromessometimes complicate the chronic state.

Neurological signs usually develop and regressin association with the psychiatric manifestations,but may be dissociated.

Psychiatric ' functional' reactions complicatethe clinical picture in about half the patients andmay mislead by reason of their lack of relationshipto the intensity of the organic reaction or theneurological signs. Usually transient, they com-prise mainly manic-depressive and paranoid re-actions and can be related to the previous per-sonality type. Their occurrence as incipient mani-festations may not be regarded as symptomatic ofportal-systemic encephalopathy. We know of two


on 29 Novem


j.bmj.com

/P


j.32.372.487 on 1 October 1956. D

ownloaded from

http://pmj.bmj.com/


patients who failed to show any good response toelectroplexy.

Treatment is modified to include long-termdietary restriction of protein within the limits ofthe individual nitrogen tolerance (usually 20 to60 g. protein daily). Education of the patient andhis relatives in the management of the disorderand in the recognition of symptoms of impendingdeterioration is important. Prognosis depends onthe extent and activity of hepato-cellular disease,the incidence of complications, such as gastro-intestinal haemorrhage, and the intelligence withwhich the patient applies himself to the regime oftreatment.

Liver Disease, Alcoholism and MalnutritionIn the ' civilized' world the commonest type of

chronic liver disease is cirrhosis occurring inindividuals habituated to the intemperate use ofalcohol. Associated nutritional deficiency is woveninto the clinical pattern, but the inter-relationshipof cirrhosis, alcoholism and malnutrition remainsunsettled. Cirrhosis of the alcoholic is oftenassociated with parotid enlargement, Dupuytren'scontracture, peripheral neuritis and other nu-tritional stigmata, an increased incidence of pepticulcer and pancreatitis and macrocytic anaemia.Relapses sometimes occur with very deep jaundicemore suggestive of acute hepatitis. Neuro-psychiatric disorder in such patients may beattributable to portal-systemic encephalopathy, thesyndromes associated with alcoholism and mal-nutrition or to combinations of these factors.The effects of alcohol on the nervous system are

well reviewed by Victor and Adams (I953) and theirclassification has been employed. Acute inebriationaccounted for 59 per cent. of the comatoseadmitted in a year to the Boston City Hospital(Solomon and Aring, I934); careful diagnosis byexclusion is necessary in the patient with cirrhosis.Delirium tremens, the most severe and dangerous ofthe tremulous - hallucinatory- epileptic - deliriousconditions associated with alcohol withdrawal,may follow a drinking 'spree' or appear duringunrelated illness in the ' steady' drinker. Con-tinuous motor and autonomic over-activity, totalinsomnia, terrifying hallucinations and a finer,more rapid tremor differentiate this syndromefrom the delirium of impending hepatic coma.Alcoholic tremulousness (the ' shakes' or 'jitters ')occurs more frequently. The patient is flushed,agitated, inattentive and perfunctory in his replies.Tremor, absent at rest, becomes coarse andirregular on activity. Profound anorexia, oftenwith retching and vomiting, is common. Treat-ment, as for delirium tremens, is based on sedationby chlorpromazine or reserpine and the prognosisis relatively good. Atypical states include periods

of quiet confusion and bizarre behaviour on cessa-tion of drinking and Kraepelin's acute auditoryhallucinosis, in which behaviour dictated by 'voices'occurs in a setting of clear consciousness and fullorientation. Alcoholic epilepsy (' rum fits') maycomplicate delirium tremens.

Alcoholic tremulousness or delirium tremensmay arise during decompensation of liver diseaseor hepatic coma, thus causing real diagnosticdifficulty.A 34-year-old fireman, drinking heavily until the

day of admission, entered hospital following agastro-intestinal haemorrhage. He showed stig-mata of liver disease and was drowsy and confusedwith limb rigidity and a flapping tremor. Haemor-rhage was arrested and after three days' treatmentwith protein withdrawal and glutamic acid therewas no residual neuro-psychiatric abnormality.The next day he became noisy, violent and con-fused with a coarse tremor, in the absence ofrecurrent bleeding or deterioration in liver function.Chlorpromazine, 12.5 mg.b.d., was followed by areturn to normal within 48 hours.The 'steady' drinker commonly has a poor

nutritional background from which no specificdeficiency can be isolated and clinical findingsusually indicate more than one disease entity.Wernicke's encephalopathy is of fairly acute onset.Varying delirium with drowsiness is associatedwith ocular disturbance (nystagmus and paresis)and ataxia. The condition responds well to thia-mine treatment, but the amnesia for recent eventsand confabulation of Korsakow's syndrome maypersist and are frequently associated with peri-pheral neuritis. The diagnosis may be difficult,especially when the condition arises in the courseof liver disease or hepatic coma.A 44-year-old male alcoholic with cirrhosis was

admitted to hospital deeply jaundiced and inhepatic coma. He had been drinking until ad-mission, but had been drowsy and unco-operativein the previous three days. A year earlier he hadbeen treated for beri-beri heart disease. On proteinwithdrawal he regained consciousness the followingday and three days later he was alert, orientatedand free from tremor and other residual neuro-logical signs. It was not for several days that it wasappreciated that the patient had no memory forrecent events and that gross confabulation waspresent. This state persisted for more than twoweeks and remained unchanged despite proteinwithdrawal, enemata and chlortetracycline. Deaththen occurred following a massive gastro-intestinalhaemorrhage.

Portal-systemic encephalopathy in the alcoholicpatient differs from that in the non-alcoholic incertain features. Mental changes more often in-clude excitement and violence and the additional


on 29 Novem


j.bmj.com

/P


j.32.372.487 on 1 October 1956. D

ownloaded from

http://pmj.bmj.com/

October 1956 DAVIDSON AND SUMMERSKILL: Psychiatric Aspects of Liver Disease 493

possibility of the clinical picture being clouded bythe onset of alcoholic tremulousness, deliriumtremens or Korsakow's psychosis, all of which arelikely to occur in the course of unrelated illnesses,creates special diagnostic problems. Neurologicalfeatures are identical with those in the non-alcoholic, save for the frequent absence of rigidity,hyper-reflexia and ankle clonus due to coincidentperipheral neuritis.

Differential diagnosis of the alcoholic or mal-nutritional states may be easy in the well-developedcase, but less characteristic examples, especiallythose arising under circumstances in which hepaticcoma might be anticipated, may cause difficulty.Correct diagnosis is important, since the nutritiousdiet and sedation prescribed for the one group isso much at variance with the regime of minimalsedation and protein deprivation demanded by theother.A detailed alcoholic and nutritional history,

particularly relative to the period before mentaldisorder appeared, should be obtained. Possibleprecipitating factors of hepatic coma must be ex-cluded while the presence and significance ofassociated neurological abnormalities is deter-mined. The nature of the tremor and the relativeprominence of mental excitement, convulsions,complex hallucinations, confabulation, ocular para-lysis (all of which are relatively uncommon inportal - systemic encephalopathy) and fetorhepaticus must be considered.Where doubt still remains the diagnosis may be

clinched by finding E.E.G. changes of hepaticcoma or observing the favourable response ofpatients with this condition to a trial of proteinwithdrawal and chlortetracycline.Subdural HaematomaA high incidence of trauma and increased bleed-

ing tendencies expose the alcoholic with hepaticcirrhosis to the hazard of subdural haematoma.The injury may have been relatively light andfrequently cannot be recalled. In the acute formloss of consciousness is usually preceded by head-ache, confusion, irritability and localizing signs,of which hemiparesis is the most common. Per-sonality changes, intellectual deterioration, inter-mittent headache and localizing signs, which in-clude evidence of an upper motor neurone lesion,papilloedema, or inequality of the pupils, shouldraise the possibility of chronic subdural haematomain the susceptible subject.

Examination of the cerebrospinal fluid (whichshows no abnormal routine findings in hepaticcoma) for inconstant changes in pressure andprotein level and E.E.G. records help differentiatesubdural haematoma from the various types ofhepatic coma. Nevertheless, many clinical features

are common to both conditions and difficulty mayarise, as is illustrated in the following case:A 50-year-old tavern worker, a known alcoholic,

was found lying unconscious in the road. Friendsreported that during the previous day alteredbehaviour and incoherence of speech were evident.On examination he responded only to painfulstimuli and had generalized hyperreflexia andextensor plantar reflexes. Fetor hepaticus, vascularspiders and hepato-splenomegaly were present.On protein withdrawal he became alert and orient-ated, exhibiting a transient non-specific tremor,but with persistent hyper-reflexia and a left-sidedextensor plantar response. Soon afterwards hebecame drowsy and inattentive. Emergency burrholes revealed a large right temporo-parietal sub-dural haematoma; he made a satisfactory recoveryfollowing its evacuation.

Hepato-Lenticular DegenerationHepato-lenticular degeneration (Wilson's dis-

ease) is a condition in which deranged metabolismof copper results in disease of the central nervoussystem and hepatic cirrhosis. The salient psy-chiatric features are a progressive organic dementia-mild in juvenile cases-emotional lability andcharacter changes expressed as behaviour disordersin children. The open-mouthed grin and drooling,alert eyes with corneal rings and disorders of move-ment, posture and speech are characteristic.Tremor, in late cases, has no 'flapping' qualityand the neuro-psychiatric changes lack the fluc-tuations and relationship to dietary protein whichcharacterize portal - systemic encephalopathy.Patients with this disease may also experienceportal-systemic encephalopathy if the liver diseaseis sufficiently severe or the portal collateral circula-tion sufficiently great.SummaryThe occurrence of mental disorder in association

with hepatic disease has been observed fromantiquity and various psychiatric syndromes in-cident to liver disease can now be recognized. Theconcept of cerebral intoxication by nitrogenoussubstances derived from the intestine to accountfor a neuro-psychiatric syndrome (portal-systemicencephalopathy) provides a rational basis for effec-tive therapy. This syndrome may occur as anacute or chronic organic reaction with an associatedneurological disorder and E.E.G. abnormalitiesand may be modified by the concurrence ofalcoholic and malnutritional syndromes. Func-tional reactions, which include depression in virushepatitis and the post-hepatitis syndrome, mayalso complicate the chronic organic reaction. Aprogressive organic dementia characterizes hepato-lenticular degeneration.


on 29 Novem


j.bmj.com

/P


j.32.372.487 on 1 October 1956. D

ownloaded from

http://pmj.bmj.com/


AcknowledgmentsWe are grateful to Dr. Sheila Sherlock and Dr.

Charles S. Davidson for allowing us to studypatients under their care. We wish to thank theMedical Research Council for a personal grant toone of us (E.A.D.).

BIBLIOGRAPHYADAMS, R. D., and FOLEY, J. M. (I953), Res. Publ. Assn. Res.

Nerv. Ment. Dis., 32, 198.ANON., 'De Morbis Intemis,' 27.ATKINSON, M., BARNETT, E., SHERLOCK, S., and

STEINER, R. E. (I955), Quart. J. Med., n.s. 24, 77.BAUMANN, E. D. (1931), Janus 35, 153 and I85.BENHAMOU, J. P., HARTMANN, L., and FAUVERT, R. (I955),

Presse medicale, 63, 1451.FINDLAY, G. M., and MARTIN, N. H. (1943), Lancet, i, 678.FORD, J. C. (1943), Ibid., x, 675.GALEN (A.D. 131-200), quoted by Baumann, E. D.HIPPOCRATES (460-370 B.C). 'Epidemiorum,' 3: 'Hippocrates

with an English Translation,' W. H. S. Jones, I, 219, Heine-mann, London.

HIPPOCRATES (460-370 B.C). 'The Sacred Disease,' x8:'Hippocrates with an English Translation,' W. H. S. Jones, 2177, Heinemann, London.

KIRK, E. (1936), Acta. med. Scand., 77, suppl. p. I.LICHTMAN, S. S. (I953), 'Diseases of Liver, Gall Bladder and

Bile Ducts,' I, 484, 3rd Ed., Klimpton, London.LEIBOWITZ, S., and GORMAN, W. F. (1952), New Engl. J.

Med. 246, 932.MAYER-GROSS, W., SLATER, E., and ROTH, M. (i954),

'Clinical Psychiatry,' p. 299. Cassell & Co. Ltd., London.McDERMOTT, W. V., Jr., and ADAMS, R. D. (I954), J. clin.

Invest., 33, I. ,PHILLIPS G. B., SCHWARTZ, R., GABUZDA, G. J., Jr.,

DAVIDSON, C. S. (I952), New Engl. J. Med., 247, 239.QUASTEL, J. H. (1932), Lancet, ii, I417.SOLOMON, P., and ARING, C. D. (1934), Amer. J. med. Sci.,

I88, 805.SPENCE, J. C., and OGILVIE, A. G. (1927), Arch. Dis. Childh.

2, 41.SHERLOCK, S., SUMMERSKILL, W. H. J:, WHITE, L. P.,

and PHEAR, E. A. (1954), Lancet, ii, 453.SHERLOCK, S., and WALSHE, V. (1946), Lancet, ii, 482.SUMMERSKILL, W. H. J., DAVIDSON, E.A., SHERLOCK 'S.,

and STEINER, R. E. (x956), Quart. J. Med. n.s. 25, 245.VAN CAULAERT, C., DEVILLER, C., and HALFF,

(1932), C. R. Soc. Biol., Paris, III, 735.VICTOR, M., and ADAMS, R. D. (1953), A. Res. Nerv. and Ment.

Dis. Proc., 32, 526.VON JAUREGG, W. (1896), Wien Klin. Wochenschr., 9, i65.WOOLER, G. (1955), Personal communication.ZILLIG, G. (1947), Nervenarzt, 18, 297.

RUTHIN CASTLE, NORTH WALESA Clinic for the diagnosis and treatment of Internal Diseases (except Mental or Infectious Diseases). The

Clinic is provided with a staff of doctors, technicians and nurses.The surroundings are beautiful. The climate is mild. There is central heating throughout. The annual

rainfall is 30.5 inches, that is, less than the average for England.The Fees are inclusive and vary according to the room occupied.

For particulars apply to THE SECRETARY, Ruthin Castle, North Wales.Telegrams: Castle, Ruthin. Telephone: Ruthin 66

Bibliography continued from page 48--Michael Atkinson, M.D. (Lond.). M.R.C.P.AXELRAD, B. J., CATES, J. E., JOHNSON, B. B., and

LUETSCHER, J. A. (1955), Brit. med. J., i, I96.BJORNEBOE, M., BRUN, C., and RAASCHOU, F. (I949),

Arch. Int. Med., 83, 539.CHART, J. J., SHIPLEY, E. G. (1953), J. clin. Invest., 32, 560.CHART, J. J., GORDON, E. S., HELMER, P., and LESHER, M.

(1956), J. clin. Invest., 35, 254.DAVIDSON, C. S. (1955), J. Amer. med. Ass., 159, 1257.EISENMENGER, W. J., BLONDHEIM, S., BONGIOVANNI,

A. M., and KUNKEL, H. G. (1950), J. din. Invest., 29, 1491.FALOON, W. W., ECKHARDT, R D., MURPHY, T. L.,

COOPER, A. M., and DAVIDSON, C. S. (1949), J. din.Invest., 28, 583.

GIGES, B., and KUNKEL, H. G. (1954), J. din. Invest., 33, 257.GOODYER, A. V. N., RELMAN, A. S., LAWRASON, F. D.,

and EPSTEIN, F. H. (1950), J. din. Invest., 29, 973.HILTON, J. G. (1952), Am. J. Med., 12, 3II.HYATT, R. E., LAWRENCE, G. H., and SMITH, J. R. (1955),

J. Lab. Clin. Med., 45, 274.JONES, R. A., MCDONALD, G. O., and LAST, J. H. (1952),

7. din. Invest., 31, 326.KLATSKIN, G., and YESNER, R. (x949), J. din. Invest., 28, 723.NELSON, W. P., and WELT, L. G. (1952), J. din. Invest., 31, 392.NELSON, W. P., ROSENBAUM, J. D., and STRAUSS, M. B.

(951), J. clin. Invest., 30, 738.

PATEK, A. J., MANKIN, H., COLCHER, H., LOWELL, A.,and EARLE, J. R. (1948), J. clin. Invest., 27, I35.

PHILLIPS, G. B., SCHWARTZ, R., GABUZDA, G. J., andDAVIDSON, C. S. (1952), New Engl. J. Med., 247, 239.

PREEDY, J. R. K., and AITKEN, E. H. (1956), J. clin. Invest., 35,430.

PRENTICE, T. C., SIRI, W., and JOINER, E. E. (1952), Am.J. Med., 13, 668.

RALLI, E. P., ROBSON, J. S., CLARKE, D., and HOAGLAND,C. L. (1945), J. din. Invest., 24, 316.

RATNOFF, O. D., and PATEK, A. J. (1942), Medicine, 21, 207.SCHOENBERGER, J. A., KROLL, G., SAKAMOTO, A., and

KARK, R. M. (1952), J. Lab. din. Med., 40, 941.SHERLOCK, S. (1955), 'Diseases of the Liver and Biliary System,

Blackwell Scientific Publications, Oxford.STARLING, E. H. (1896), J. Physiol., 19, 312.STRUB, I. H., TALSO, P. J., and KIRSNER, J. B. (x955),

Gastroenterology, 28, x63.TALSO, P. J., SPAFFORD, N., FERENZI, G., and JACKSON,

H. 0. (1956), Metabolism, 5, 58.VOLWILER, W., GRINDLAY, J. H., and BOLLMAN, J. L.

(1950), Gastroenterology, 14, 40.WHITE, A. G., RUBIN, G., and LEITER, L. (1951), J. clin.

Invest., 3x, 392.


on 29 Novem


j.bmj.com

/P


j.32.372.487 on 1 October 1956. D

ownloaded from

http://pmj.bmj.com/

psychiatric aspects of liver disease - postgraduate medical journal

Documents