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ACUTE APPENDICITIS IN PREGNANCYFrom the Department of Obstetrics and Gynaecology

The Middlesex Hospital

By A. L. T. EASTON, M.B., B.Chir., F.R.C.S., M.R.C.O.G.Late Senior Registrar

In I892, Lawson Tait described a case in whichfour years previously he had successful diagnosedand removed the first acutely inflamed appendix(Shepherd, I956). In the same year Wigginsreported a case of perforated appendix with athree-month foetus in utero in which he advisedremoval of the appendix, only to have his counselrejected by the patient's relatives. She died ofperitonitis and the pregnancy was found post-mortem. Munde, in I894, appears to havereported the first successful American case to betieated by operation. 13ahler (I908), and laterMarbury (1953), both quote Hancock (I848) ashaving reported a case of perityphlitic abscessdrained surgically in the puerperium, but it isdoubtful from the history if this was in fact such acase. It seems more probable that he was dealingwith a strangulated Richter's hernia.The occurrence of five cases, in the past two

years at the Middlesex Hospital, of this compli-cation of pregnancy, has prompted a further studyof the condition. A search through the recordsof the last ii years revealed only three others,making a total of eight cases in the period 1946-1956 inclusive. It is emphasised that only casesof acute appendicitis, confirmed by the operativefindings and the histological report, have beenincluded. One, case No. 7, was treated con-servatively whilst pregnant, but was subsequentlyfound at laparotomy to have incontestable evidenceof a recent attack of acute appendicitis. Six otherpatients, in which appendicectomy was performedfor symptoms and signs suggesting appendicitisbut where chronic disease or evidence of pastinflammation only was found, have not beenincluded.These eight cases are related to a total number of

deliveries in the same period of 8,6o8 patients, anincidence ofone case in i,078 deliveries. However,as only two cases occurred among patients alreadybooked for delivery at the Middlesex Hospital thetrue incidence is obviously much lower. Rosner,quoted by Bahler (I908), found 22 cases in 15,000

pregnancies, whereas Van Gordt also cited byBahler, gave an incidence of three cases in io,ooopregnancies. More recently Cosgrove (1937)counted i8 cases in 25,000 live births and Smithand Bartlett (I940), found 20 cases in 66,431 livebirths, an incidence of i in 1,389 and i in 3,322respectively. Differing criteria as to the diagnosisaccounts for much of this variation, and thepresent series more nearly approaches that ofCosgrove (I937). Others approaching the matterdifferently, have stated that from 1.9 per cent. to2 per cent. of all women who have appendicitis arealso pregnant (Baer, Reis and Arens, I932, andJohnson, I944). The total number of appendi-cectomies performed at the Middlesex Hospitalduring the period under consideration on womenbetween the ages of i6 to 45 years was i,288, ofwhom 14 were pregnant, and of whom only eighthad acute appendicitis and were pregnant as well.This gives a figure of I.I per cent. which is notdissimilar to the aforementioned ones.

In the series under review three cases occurredin the last trimester, whilst of the remaining five,two occurred at 26 weeks maturity, and the rest(three cases), between i6 and 2o weeks maturity.The number is, however, small and therefore littlecan be inferred from these figures. Because of itsrarity, few are likely to be seen even during thelifetime of a busy practising obstetrician.

Case HistoriesCase No. 4: Mrs. S.G., aged 34 years; Gravida 2L.M.P. October 5, I950. Admitted on June 7,

I95I. During her pregnancy her blood pressurehad tended to rise slightly. She was admitted atapproximately 36 weeks maturity with a diagnosisof pre-eclamptic toxaemia. Blood pressure I90/I20 mm. Hg. No albuminuria but slight ankleoedma. On the following day she began to vomit.This continued into the second day, when shecomplained, in addition, of abdominal pain, whichwas worse on the right than on the left.

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On Examination. There was very markedtenderness on the right side of the uterus, and theloins were also tender. Her blood pressure waswas i8o/iI0 mm. Hg. The foetal heart was heard.The vertex was presenting with the fundus at36 weeks. That evening the temperature, whichhad been normal, rose to 99.60F., and the pulse toI32 beats per minute. The blood pressure wasnow I40/90 mm. Hg. A diagnosis of concealedaccidental haemorrhage was made, and it wasdecided to treat her by caesarean section.

Operation. The abdomen was opened througha mid-line sub-umbilical incision, when pus wasfound on opening the peritoneum. The uteruswas quite normal. A second incision, a McBurneywas made, and a gangrenous perforated appendixwas found lying retro-caecally and removed.Both incisions were closed with drainage to thewounds only. She was given a blood transfusionand was treated post-operatively by gastric suctionand intravenous electrolytes together with systemicpenicillin and streptomycin. Her recovery wassteady, and three weeks later, was delivered of alive child.

Case No. 5: Mrs. P.H., aged 22 years; PrimigravidaHer expected date of delivery was January 25,

1957. She was admitted to Hospital when 26weeks pregnant on October I9, with a history ofupper abdominal pain followed by vomiting forthree days. The pain was referred to the back aswell, and occurred in spasms. On the second dayof her illness, she complained of diarrhoea whichwas soon followed by constipation. Foetal move-ments were felt.On Examination. She looked ill. Her tempera-

ture was 99.60F., pulse ioo. The tongue wasmoist and slightly coated and there was somefoetor. Per abdomen the uterus was consistentwith a pregnancy of 26 weeks. The epigastriumwas somewhat distended.and there was markedtenderness and rebound tenderness in the rightiliac fossa. The foetal heart was heard and thefoetal movements felt.

Investigations. C.S.U. No pus cells or organ-isms. Blood count: W.B.C., 17,000 per c.mm.;polymorphs, 92 per cent.; lymphocytes, 5 percent; and monocytes, 3 per cent. X-ray ofabdomen: no fluid levels seen.

Operation. A right paramedian incision. Agangrenous retro-caecal appendix containing afaecolith was found and removed. The abdomenwas closed without dlrainage. Post-operativelyshe was given pethidine I00 mg. four-hourly,streptomycin j g. b.d. A Ryles tube was passedand an intravenous drip set up. She made asteady recovery but on the third day after operationshe aborted. The foetus weighed 2 lb. 6 oz. and

died five hours later. Culture of peritoneal swabshowed a moderate growth of coliforms insensitiveto penicillin, erythromycin and sulphanilamide.Case No. 6: Mrs. M.L., aged 26 years; Gravida 3L.M.P. June 20, 1956. Maturity i6 weeks.

Admitted October 2I, 1956, complaining ofanorexia, nausea and vomiting for some days.At first she considered her symptoms no worsethan she had experienced in her previous preg-nancies. For two days she had lower abdominalpain which became referred to the right flank onthe day before admittance, and more recently wasfelt in the shoulder. She further stated that thiswas aggravated by deep breathing and wasassociated with a rigor.On Examination. She looked ill aiXd was in

pain. The respirations were shallow and rapid.Temperature ioi0F., pulse 140. There was nocyanosis and the alae nasae were working. Thechest was normal. Blood pressure 130/80 mm.Hg. Per abdomen the uterus was consistent withher dates. There was marked tenderness andguarding in the right loin, and the right iliac fossaand lower abdomen. Rectal examination showeda very tender pouch of Douglas.

Investigations. Chest X-ray normal. C.S.U.No pus cells or organisms. Diagnqsis of generalperitonitis resulting from acute appendicitis wasmade.

Operation. The abdomen was opened througha McBurney's incision without delay. Free pusappeared on opening the peritoneum. A gangre-nous perforated retro-caecal appendix was removedand the abdomen closed with drainage to thewound. The post-operative treatment consistedof gastric suction, an intravenous drip andparenteral penicillin and streptomycin. Cultureof peritoneal swab grew profuse B. Coli sensitiveto chloromycetin. A coliform wound infectionwhich developed on the ioth day, causing atemperature of ioo0F. was insensitive tochloromycetin.She was discharged three weeks after operation,

but aborted i i days later a macerated foetus. Onthis occasion she had a rigor and a temperature ofIo°F., but culture of a vaginal swab showed nopathogenic organism.

Case No. 7: Mrs. J.P., aged 28 years; PrimigravidaAdmitted in 1946. Maturity 36 weeks. She

gave a history of vomiting followed by lowerabdominal pain which localized to the right iliacfossa on the day after its onset. Total duration ofsymptoms before admission: 72 hours. Thesymptoms, however, had been preceded byanorexia and diarrhoea for some days.On Examination. Temperature IoO.40F., pulse

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274 POSTGRADUATE MEDICAL JOURNAL June I957rA BLE /.

ACUTE APPENDICIT/S IN PREGNAACYP/IYS/C4RL SeGNS

Dur-Ae A4t- Pls oitFwr opeGuard- Rov Re - otion. TernQ6rS s Ph MhrCilAge uity Tmp.A/N Voit Pator Tngue Ing sing bound (hrs) ns.CS. Ptooy AoM ~/

not/ 2/ 2 98 94 # . ./ A.rnfnd - + f- 36 AR/.F sted Gangrenous A ND

;2 30 26 /004 /20 f none clean - - 4/ 72 R/F ELC. Gangrenous A Cs

3 36 /6 /0/ /30 + m//d fured - - - 48 SIF EC. Perforated A AS

not not Perforated4 34 36 99 /30 + stated stated - - - 46 R/F (C. P A NA.5 Z 26 99 6 /00 * mowd furred - - - 72 RIF EC. Gongrenous A AS

6 26/6 /04 /40 * none ckon| - -|Lo46 (C. |erfrocor A ABShouft Retrocaeca/ Anot 'w - - - 2 Subsequnt

7 28 6 0 1 stotwe stated 7 |FR RBCC Appendiceomy A |S7 ~ 3 /00 /46Witc Obilterative ____

8 2/ 32 994 |/4 |+ |vht c/eo + + +/ RIFR EC Eo/y ocute A N

RIPF=Right iliac fosso A = Ab4B F Both Avc fosse C.S. s COaOesn sectionEIC= (pthe//al ce/Is SB. = St/I/bornND =Nwo d"very N = Pren,cy continues

f- iWb cowt SC- Wte blood courtA = AlIve

130. The uterus was enlarged to 36 weeks.There was tenderness on the right side of theabdomen. C.S.U. showed R.B.C. and W.B.C.,but no organisms. A diagnosis of acute appendi-citis was made, and it appears from the notes thatit was decided to treat her conservatively. Shewas given penicillin 50,000 units and sulphathiazolei g. four-hourly. The temperature rangedbetween 99 and ioo.60F.Four days after admission she went into

premature labour and was delivered with forcepsof a stillborn macerated infant. It appears thatthe foetal heart was not heard for some time beforedelivery, but the precise moment is not known.A fortnight after admission her temperature againrose to IoI.40F. and the notes state that a tendermass became palpable below the right costalmargin. This subsided without treatment and,before her discharge from Hospital, an X-rayBarium enema showed no filling of the appendix.Four months later she was readmitted for aninterval appendicectomy. This was done througha grid-iron incision, when a completely fibroticappendix, whose tip had vanished, was removed.There were few adhesions.

DiagnosisAcute appendicitis in pregnancy differs little in

history and physical signs from the non-pregnantsave in one or two of the abdominal findings.Table I shows the relevant details of each case,and from it one can see that guarding is absent in

all cases except one. Rebound tenderness, a signof parietal peritoneal irritation, was noted in halfthe cases only. Nausea and vomiting always occurand the cases presented show no exception to thisrule.

However, it should be remembered that suchsymptoms are not infrequently associated withnormal pregnancy and this may lead the unwaryinto errors in diagnosis.The absence of guarding over the right iliac

fossa due to the presence of an enlarged uterus hasbeen noted by some, but others speak of rigiditybeing present (Browne, I95I). It must beremembered that the abdominal wall relaxesconsiderably to accommodate the increase in itscontents during pregnancy without rise in tension,and possibly an alteration in muscle tone orfunction may be added to the anatomical change.This is, of course, purely speculative but mayaccount for the lack of guarding. One fact iscertain, and that is that tenderness, often acute, ispresent on the right side of the abdomen in everycase.There is another factor that will alter the picture.

With advancing pregnancy there goes an alterationin the position of the caecum and appendix. Anupward displacement of the viscera has been ablydemonstrated radiologically by Baer and hisassociates (I932). They have shown that aprogressive upward movement of the caecumoccurs and that the appendix, in addition, isrotated in a counter-clockwise direction. This

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EASTON: Acute Appendicitis in Pregnancy

results in the appendix becoming an upperabdominal organ and leads to confusing physicalsigns when it is inflamed. Its distinction fromcholecystitis then becomes a matter for somecircumspection, particularly when, as occurred incase No. 6, perforation had occurred and shouldertip pain was present on the right side.The presence of a coated tongue and oral

foetor, so often relied on, can be seen to have beenan inconstant finding, though in two instances nomention of this is made in the records. Thepulse-rate proved to be a more reliable guide thanthe temperature, though it should be emphasisedthat with fluctuations in the latter, a normalreading should be repeated after an interval beforebeing accepted as such.

Vaginal and rectal examinations are seldomhelpful, the less so as the pregnancy matures,though where generalized peritonitis has occurredthe pouch of Douglas will be felt to be tender.This was found in case No. 6. With advancingpregnancy the recto-uterine pouch becomesreduced and its contents become displaced by thefoetal head.An analysis of i6 incorrectly diagnosed cases

has shown that pyelitis, torsion of the pedicle of anovarian cyst, and acute gastroenteritis were amongthe commonest errors, whilst salpingitis orruptured pyosalpinx are also reported (Child andDouglas, i944; Evans, 1955). Again, right basalpneumonia, cholecystitis and intestinal obstructionhave been mistaken in the past for appendicitis(Browne, 1951).More commonly, the diagnosis must be made

from ruptured tubal pregnancy, in the earlymonths, torsion of a pedunculated fibroid ordegeneration in an intramural or pedunculatedmyoma. In ectopic gestation the pain of tubalcolic, together with signs of peritoneal irritationfrom the leakage of blood through the abdominalostium, may closely simulate acute appendicitis.Such pain, however, is more paroxysmal in natureand the temperature, if raised, is only very slightlyso.

In late pregnancy the possibility of the casebeing one of concealed accidental ante-partumhaemorrhage must be borne in mind while at alltimes pyelitis should be excluded. In the latter,the pain tends more to the loin, there is frequencyof micturition and rigors are seldom absent. Acatheter specimen of urine should in all cases beexamined for pus cells and organisms. Never-theless, a gangrenous perforated retro-caecalappendix may closely simulate pyelitis, as in caseNo. 6. Red blood cells may also appear in theurine, as in case No. 7, which is attributed toproximity of an inflamed appendix to the uretercausing ureteritis (Bahler, I908), whilst the urine

of normal pregnant women is said to grow BacillusColi in ii per cent. of cases (Dodds, I93I).The passage of a ureteric calculus may also

mimic the disease, particularly as there will befrequent vomiting. I have seen such a caseelsewhere when this proved to be so.

Other InvestigationsThe leucocyte count would seem to be of even

less value than in the uncomplicated case becauseof the physiological leucocytosis of pregnancy.A high total count, over 14,000, with a dominanceof young polymorphonuclear leucocytes, will besignificant, but a negative finding does not excludeappendicitis. Radiological examination of theabdomen is seldom of value and is probably contra-indicated on the grounds of unnecessary delay anddisturbance to the patient.

DiscussionA maternal mortality of 0.71 per cent. when

the disease is confined to the appendix, 30 per cent.when there is peritonitis, and 50 per cent. when theappendix is perforated is to be found (Meiling,1947). These figures are largely based on pre-warcases and are alarming. But the recently collectedresults of nine authors show a maternal death rateof 5.8 per cent. in all of 2o6 cases. Of evengreater significance is the fact that cases occurringin the last three months of pregnancy show amortality of 20.7 per cent. (Parker, 1954). Clearlypatients with this disease are worse off than if theyhad not been pregnant.What are the results as far as the pregnancy is

concerned ? All are agreed that the patient witha perforated appendix stands something in theregion of a 50 to 8o per cent. chance of abortion orpremature labour, while the acute non-perforatedcase may show a 30 per cent. chance of abortion.Lower estimates occur in the first trimester andinclude many normal and chronic appendicitiscases. These show little variation from theexpected incidence of abortion in uncomplicatedpregnancy. Most workers can point to a markedincrease in abortion rate in the perforated asdistinct from the non-perforated case (Bahler,I908; Child and Douglas, I944; Hoffman andSuzuki, 1949). In the series under review,50 per cent of the foeti were lost and in six casesthe appendix was known to be gangrenous orperforated. In one instance, case No. 7, a stillborninfant was delivered after being allowed to remainseveral days in the presence of an acute attack thatprobably did not result in perforation. Of thethree patients who perforated their appendix,cases 3, 4 and 6, two aborted and one was deliveredof a live child at term. Of the four other cases ofnon-perforated appendicitis, subjected to im-

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POSTGRADUATE MEDICAL JOURNAL

mediate operation, cases i, 2, 5 and 8, only oneaborted. Case No. 8 was operated on afterminimal delay from the onset of symptoms, andhad not progressed beyond the stage of acutecatarrhal inflammation; the pregnancy continuesnormally.

In the eight cases presented no mother died,four infants were lost, three were delivered of livechildren, one by caesarean section for foetaldistress at term 14 weeks later. The most recentpatient, case No. 8, at the time of writing is stillpregnant and expects to be confined after March i,1957. These show an overall foetal loss of50 per cent.That the patient who was treated conservatively

at 36 weeks maturity survived to have an intervalappendicectomy, is a tribute to the effectivenessof chemotherapy. She was delivered, four daysafter admission, of a stillborn macerated child andsubsequently ran a pyrexial course developing amass on the right side of the abdomen. Later anobliterated appendix with evidence of pastinflammation was removed. The remaining sevencases were treated by immediate appendic'ectomy.

Attention has been drawn to the increase inmortality in the later months of pregnancy, andthis is attributed in part to delay in treatment dueessentially to difficulty in diagnosis. Three factorsconspire to bedevil the picture and, by the subse-quent delay, place the patient in special hazard.Mention has already been made of the displace-ment of the appendix upward into the abdomen.This alters the position of the signs and varies thesymptoms and thus confuses the picture. Next,the appendix, now an upper abdominal organ, liesin contact with coils of upper intestine and along-side a large globe-shaped contractile organ, theuterus. Should perforation occur, localization ofan abscess is made difficult or impossible for thefollowing reason. Whereas, in the presence ofperitonitis the alimentary viscera cease movement,the uterus does the reverse. All attempts atadhesion formation to localize the infection will benullified by such movement. Labour and delivery,because of the associated rapid diminution in theuterine volume, will further aggravate the condi-tion as the inner wall of the abscess cavity will betorn away and all adhesions broken.When localization has occurred, removal of the

appendix, the centre of the infection, is done at theprice of breaking down many adhesions. If anexpectant policy is advocated, it should be done inthe full knowledge that the patient will almostcertainly abort and reproduce the operativeinterference without the benefit of having theappendix removed first.'

Lastly, another factor which may contributeto the delay is the clinician's disinclination to

perform laparotomy at, or near, term in thepresence of an otherwise normal pregnancy.The penalties of a missed appendicitis justify theoccasional unnecessary laparotomy. Most authorsagree that pregnant women tolerate even majorsurgical procedures quite as well as the non-pregnant, though under ordinary circumstances,operation at the 12th week is best avoided for fearof precipitating miscarriage.Any disagreement with the view that immediate

appendicectomy should be done dates largely fromthe time when the controversy centred round thetreatment of acute appendicitis in general. Sincethis issue is now settled, there seems little point indifferentiating the pregnant from the non-pregnant.The earliest observations on the high mortality

of the disease attributed this entirely to the highposition of the appendix and consequent poorpowers of localization. This prompted a movetowards immediate evacuation of the uterusirrespective of the maturity. Instead of treatingthe disease on its merits and allowing the pregnancyto remain undisturbed, a spate of caesarean sec-tions, caesarean hysterectomies, and surgicalinductions were done with disastrous results(Cosgrove, I937; Priddle and Heseltine, I95i).

Despite this, the perforated appendix in the lastmonth of pregnancy where a viable child with areasonable chance of extra-uterine survival exists,merits special consideration. Quite apart from thelikelihood of premature labour, there exists aspecial risk of intra-uterine foetal death if theinfant is allowed to remain in utero in the presenceof peritonitis. It is recognized that this may occurin any severe constitutional disease, and is probablydue to the continuation of high pyrexia togetherwith bacterial toxaemia. It is not quite clear whythis should occur, but perhaps it would not be outof place to indulge in a little speculation. Theprolonged rise in temperature must increase themetabolic rate and therefore the oxygen require-ments of the fast developing tissues. It is possiblethat a point is reached when the demand outstripsthe supply, and this at a time when the placentalefficiency is diminishing. In addition, it isrecognized that fast growing tissues are especiallysusceptible to noxious stimuli. One authorsuggests that acidosis occurring in a case ofperforated appendicitis post-operatively was re-sponsible for an intra-uterine death and recom-mends early infusion with 5 per cent. sodiumbicarbonate (De Voe, 1947).How then can the infant be spared this risk of

intra-uterine death, whatever its cause ? Ingeneral, operative manoeuvres to terminate thepregnancy'are contra-indicated, save where forcepsdelivery can the more rapidly complete the second

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June 1957 EASTON: Acute Appendicitis in Pregnancy 277

stage of a spontaneous labour, and where lowersegment caesarean section is done for an overidingobstetrical reason.The view that, where peritonitis is present,

caesearean section should be performed, is roundly,condemried by several authors (Bahler, I908;Hoffman and Suzuki, 1949; Cosgrove, I937;.De Voe et al., I947) though caesarean hysterectomyin the more severe cases of abscess formation mayprove life saving.There seems little doubt that the best way to

save the child is to remove the appendix before,perforation and peritonitis occur. Furthermore,it is doubtful if, even with modern powerful anti-biotics, it is ever justifiable to incise the uterus inthe presence of such peritonitis, though there isroom for legitimate differences of opinion here,especially at term.

WVhere abscess formation 'has already occurred,a special case for early drainage exists, since thepatient here is in very grave danger. The abscess,as has been pointed out, will surely rupture whenabortion or premature labour occurs.

In general, removal of the appendix should besupplemented by anti-biotic treatment with carefulregulation of fluid and electrolyte balance, if thefoetal as well as maternal death rates are to befurther reduced. A significant improvement inthe mortality from perforated appendicitis may,in part, be due to the use of antibiotics. Whilethis may be true, the improvement must also bedue to increase in awareness of the condition by thepractitioner and improvement in therapeuticstandards and efficiency in general. A greaterwillingness on the part of the patients to seek earlytreatment, improved nutrition and living standards,all play their part.Where there is severe respiratory, embarrass-

mnent, as occasionally occurs, induction of labourby surgical rupture of membranes after appendi-cectomy provides the quickest relief (Parker,1954).

IncisionOpinion is divided, but both from experience of

these recent cases and from general considerationsit is obvious that, provided no attempt at caesareansection is to be made, a high McBurney incisionprovides the best access to the appendix. Itslevel is dictated by the maturity of the pregnancyand its use results in minimal disturbance to theuterus itself. Its only drawback would seem to bewhen the diagnosis is in error. However, it is tobe hoped that this will seldom prove to be the case.Midline and paramedian incisions result indifficulty of access and much pressure and handlingof the uterus in order to reach the appendix.

Drainage of the peritoneum is, on the whole, lessimportant than drainage of the wound itself.The post-operative treatment includes intra-

venous drip and gastric suction when ileus occurs.Appropriate antibiotics should be used and of evengreater importance is prolonged and adequatesedation to minimise the chance of abortion orpremature Ilabour. Morphine,' or allied drugs,given 4 to 6 hourly for up to three days, isdesirable. It is probable that insufficient attentionhas been paid to this aspect in the cases presentedand this may in part have contributed to the highabortion rate.

ConclusionIt seems that Bahler's precept of I908, con-

cerning the dangers of delay has not, in the light ofrecent advances in technique, knowledge andtherapy, been in any way modified. The earlyremoval of the appendix provides the best chanceboth to mother and infant of survival. A diseasewhich carries with it a maternal mortality of over20 per cent. in the last trimester of pregnancy, andan overall foetal loss of 50 per cent. deserves themost strenuous efforts at improvement.

Summaryi. Eight cases 'of acute appendicitis compli-

cating pregnancy are reviewed.2. No mother died and four infants were lost;3. A higher foetal loss occurred in those cases

of perforated appendix than in the non-perforated.4. Attention is drawn to the, dangers both to

mother and infant of peritonitis resulting from poorlocalization of the infection.

5. Appendicectomy in pregnancy, even whenthe diagnosis is in- doubt, will help to avoid thelethal combinati'on in the last trimester.

6. There is no place "for the conservativetreatment of acute appendicitis in pregnancy.

AcknowledgmentsI wish to thank Mr. R. V. Hudson, Mr. W. R.

Winterton, Mr. Ian Jackson and Mr. R. S.Handley for permissiori to publish these cases.Also I would like to thank Mr. F. W. Roques,Mr. W. R.'Winterton and Mr. L. P. Le Quesne'for their kind help and guidance in preparing thisarticle. Also Miss Fisher, of the Records Depart-ment, The Middlesex Hospital, who prepared thetable.

BIBLIOGRAPHYBAER, J. L., REIS, R. A., and ARENS, R. A. (1932), J. Amer.

med. Ass., 98, 1359.BAHLER, E. A. (I908), Ibid 51, I310.BERKELEY, C., BONNEY, V., and MacLEOD, D. (1938),

'Abnormal in Obstetrics,' Arnold, London, p. i5.BROWNE, F. J. (i95I), 'Ante-natal and Post-natal care,' Churchill,

London, p. 435.Bibliography continued on page2z86 -

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286 POSTGRADUATE MEDICAL JOURNAL June I957present in 87 per cent. at the knees and in 56 percent. at the ankle in the age-group 60-75 years.The neurological findings in our patients over6o years were specially scrutinized, and wherepossible those considered to be due to senilitywere excluded.

TABLE I

Type of Neurological PerDisorders Males Females Total cent.

Myelopathy 7 24 31 28S.C.D. J Myelopathy40% 1 and Neuro-

pathy .. 0 13 13 12Neuropathy .. . 3 1I0 1I3 12Pernicious anaemia

alone . .. 20 33 53 48

Totals .. 30 8o I IO 0OOi io cases of pernicious anaemia:With neurological signs .. .. 7Without neurological signs .. ..

As will be seen from Table i neurological signswere present in 57 of our I IO cases. In 13(I2 per cent.) the picture was one of uncompli-cated neuropathy, whilst in the remaining 44there was unmistakable evidence of cord damageof postero-lateral column type, either pure (3Icases (28 per cent.)), or mixed with peripheralnerve lesions (13 cases (12 per cent.)). Thus40 per cent. of our series of i io cases of perniciousanaemia had definite evidence of subacute com-bined degeneration of the cord. No correlationwas apparent between the severity of the anaemiaand the presence of neurological signs of any sort.In fact six patients with S.C.D. had red bloodcell counts of 4.5 million or over.

Examination of the age of onset of symptomsshowed that the majority (36 of a total of 53) withpernicious anaemia alone were over 55, and thatthose with neurological signs were again morenumerous over this age (37 of a total of 57).These figures suggest that the incidence of neuro-logical complications is no higher in the young

than in the old. Lastly, an attempt was made tocorrelate the length of history of illness with theappearance of neuropathy or myelopathy. Statis-tical analysis showed no significant differencebetween the group with pernicious anaemia andthose with nervous semeiology.The efficacy of therapy in those with neuro-

logical signs could not be assessed, for duringthe period under study there was a great influx ofnew liver preparations, and vitamin B12 becameavailable during the latter years. However, onlyone case of S.C.D. relapsed after reachingmaximal improvement. This patient had stoppedliver therapy for six months and at the end of thisperiod both the anaemia and the S.C.D. hadprogressed markedly.

This series shows a preponderance of female(80) over male (30) cases. No satisfactory explana-tion could be found for this bias of case selection,but it is of interest that this trend is a constantfeature of the analysis of all case-records of theUnited Birmingham Hospitals, I950-55 (Water-house personal communication).SummaryA survey of iio cases of pernicious anaemia is

presented. Subacute combined degeneration ofthe cord was present in 40 per cent. All casesof senile neurological degeneration were excluded.The signs of S.C.D. were not related to length ofsymptoms of B12 deficiency, the age of the patientor the degree of anaemia. This high figurestresses the need for careful neurological examina-tion in the diagnosis and follow-up of perniciousanaemia.

AcknowledgmentsWe wish to thank Dr. Michael Jefferson and

Dr. J. Waterhouse for their advice and criticism,and Miss Ellis for her secretarial assistance.

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