A. M. A•AIlCIlIVES o F

NEUROI.OGY AND PSYCIIIATRY

EDITOHIAL BOAHD

TIIACY .1. I'l:T;".\M, Chi •.r Edll" •.

4,;1) "'"rlh B,.<lr",.<! I),.; •.•.• UPV"";)- lillIs, C"lir"rni"

lHHOUI (;. \YOU:F, "",.,, York

H,\:-ILE\' COHIl, lI",I,,"

JiJH:'i WHI'J'EII()III'. 1I"ltim",..'

UL\Ill.ES I). AI\I~(;. Cilldnll"tl

!lOY ll. (il\lI\"KElI, U"""l':"llEH~AIlIl .1. AI.I'EIIS, l'hll"<I •.lI'1I1,,

I'I-:I\(:IVAI. 1l,\II.EY, ClIi•."W'

\\'11.1)1':11 ]'E:>;FlELlI, (:,,"t<"i!lutill;.( ~kllll,..t, Mm,lr,",,1

mCI/Alm .1. I'Lt.:xr{ETT, .\1.1)., Chic"llo, ~la""I!I"lo( Edtl",.

YOU:!'>H: {j;"j

1 !J;''il

1't:IIUSJIEllS

A\IEIII(;,\:-; MI-:r);(:.\!. ASS()(:lAT10:'\

CIIICM;(l 101, ILL.

CONTENTS OF VOLUME 65

JANUARY 1951. );"u~mER I.

Poliomye1iti,: IV. i\ Study of til'.' :>Udbrain. Howard A. !llatzkc,1[,0., ).lilllwallOlis.. . .

I'.~GF.

ph.n., and A. B. BahT,

I'i~urolol1:icalCOlllplicationsof Rabie, Vacrine: Report "f Two Ca~cs. F. R Latimer. I\LD.;J. E. W",bstt'T, 1I1.D" and E. S. {il1fdjian, 1LD., Iktroit... . .

Ce!~bralCirculation in l'os\cllC'.,phaliticPara!y,i, A~itans. Henry A. Sb<:llkin,),LD., andlOSt'l,hC. Yaskin, lILD., l'bila,k1I'hi'l.

\btivatinllSin th(, Hchahilitatioll of Parap1cgic>. ~Iors<: 1'. \[anson, Ph,D., Long Beach,Calif. .•.....•..

Te,tingVi'ual Fields by Flirk"r Fmion.

LooutolllY and P~y<:hopathol()gy. Ell;"tWorccsln, )"Iass.

Paul \V. ).,[i\es, ).1.D., SI. Louis.

I{. Rcin~r, ILD., and Sidnty L. Sands, !lI.D..

16

34

39

Vahleof COllvu],iveTherapy in Juvenile Schizophrenia. Sol 1.evy, \I.D., ~iIldI,. II. South-(olllbe.~,".1l.,I,lcdieal L,ke, \\'ash..... 54

Pneumocnl"tphalo~raphicChanges Following Pr..,frontal 1.cukotolllY(FT\'eman-\Vatts Ttch-nic). ba,lore "ltleschan. ;"1.1).,amI Joe n. Scruggs. ;.,,1.D.,I.ittle Hl)l"k..\rk... 60

Yi;ualFunction in Perinwtric;,l1y Blind Fields. ~1()rris H. Ben'\(,r, ~Ln., alld Howard P.Krieger, ;."LD.,Xew York. 72

90103120127

the New York AcadcnlYof '\lec1icille,Section of

Al,;tradsfrolll Current I.iterature. 80

SudetyTran~actio1lS:Chicago.t\eurological Society..NewYork Kellrulogiral Society a!HI

Neurulo~y and Psychiatry ...Philaddphia Psychiatric Society..PhiladelphiaNeurol"gical Socidy.

FEBkUAI,Y 1951. XW,IBER 2.

189

PQ,theqwtieTrigeminal Keuralgia. Oscar Sugar, ~I.D., and Paul C. Hucy, !lLIl., Chicag-u 131

Tuberculoma,of the Brain: Report of Olle Hundred and Fifty-Xinc Cas,'S. A. Ascujo,~1.I).;H. Valladares, .!ILD.,and J. Fiura, !,I.D., Santiago, Chile 146

EncephaliticForm of IIlctastatic Carcinoma. Lco ;."fadow,~1.D., and Bernard J. Alper~,"'l.D., Philadelphia.............. 161

Effeet,of Decamethonium Hromid~ (C HI) awl d-TulJorurarine Oil Elertrocom-ulsiollS.Lester II. Margolis, .\l.lJ_: Alexaw1cr Simon. lI1.11.,awl Karl :\1. Bowman, ;."I.D..~an Francisco...... li4

Clinicaland Physioh)~;("al Studie, in a Case of Myokymia. II. HollalHl de Jon,!!;,1I1.ll.;Irvin;;-A. ~Iat7.llcr, .\1.D., ami Arthm A. C"llger,:\1.1).,Van Xu)'", Calif 181

Retrob\llbar~euriti, Assoriatcd with Ilyjll'fthyroidi"1l1. ~fax A. Coldzieher. :\l.D.; Thoma,II. )'lcGavack. M.D.; Carl A. Peterson, ~I.D.: Jos~ph \V. (,oldziehcr, M.ll., and HaroldR. Miller, .'I.l.D.,New york .

Effoctof Prefrontal Lohotomy on Temperature Regulation in Schiwphr~llic Patient,C.W. Buck, /I-~.D.,Ph.D.; H. n. Carscalkn, u.n., and (i. I':. Hobbs, :\I.D., .'Il.P.H.:J.tmdotl,Ont., Canada......... . . 197

Oink'llami.Psyehological. IIlVc.stig~,ti(11lof Prefrontal LohotOlll?,h.1Chronic Schizophrenia.H. B. Carscatlen, .!ILl).: C. \\. Buck, ;."LD.,Ph.D., atld G. h. Hobhs. .'I1.D.,!II.P.HLondon,Ont., Canada. .,

iii200

,~ CONTENTS OF V01.UME 65

FEB RU,\RY -Colltillued

Abstracts from C\lrr~1\t 1.iterature.

So,-,j",y Transaction,:Chicago Neurolog;cal S(Je;dy.......... . .Philaddphia Psychiatric S"";d} .Philadelphia Neur"logiGt! Society. . .Philadelphia Neurological So('iety ami :\t\\' York l\curological Socidy.

Xcws and CornlJlcnt.

Book Rcvi<.,ws.

IIfA]{CII 1'JS1. NU.\IIH:r;: 3.

238246249lSi263

2("

Third VentriculostolllY ;n Tn'atmcllt of Ohstrurtivc Jlydroccphallls in Childn'l1. HaroldC. Voris, .\J.D., Chicago, ,... . ,........................... 265

EE(; and Cortical Elcctrof);Tams in Patients with Tem]>ora! Loh" Sdzun's, Herhert J",I''-'',"II!.D.; Bernard Pcrlnisst'(, \1.])., and Jlnman Flal1igin, :1.1.1).,!llontr,:"I. Can,«la ..... 272

l'ennam'llry of Clut:!lnir Acid Tn'atment. Fre(krick T. Zimmermau . .\1.1> .. and Hessie H,Hur.:ellldstu, Ph.D., :\n\ york.... . 2~1

The Syndrome of Croco,lile Tears. Ju?y Choroh,ki . .\1.D .. \Varsa'l, Poland.......... 299

Pain Btl"w t!I<.'Level of Injury of tlie Spinal Cord. 1-"wi, J. Polhlt'k, 1I.D.: /I!eyer Brown,.\1.1>.; B,'ujamill Ilosh(., . .\l.ll.; Isidore Finkdman, .\1.1>.' Ikrman Chor . .\1.]).; AlexJ. Arleff, .\L])., aml John I~. Finkk . .\Ln .. Chica.:o ,..... 319

Prt'l{llo,is III TO!J''I'tomks and l.obotomies Hdatlve to nodv Tyl"'. Nathan S. Kline, .\LD ..\\")rcl',tn, Mass" ami Ashton .\1. T"lHWy. .\!.S., Shre'wslmry, .\lass 323

Studies on the Iron C(lInen! of CeT!'hrOSplllal Fluid in Different Psychotic CUllditions. II. E.l"duuall!1 .• \1.ll .. ami V. A. Kral. .\1.1> \I'lI1tn:al. Canada.. . , 326

The l'almomt:nt"l Ref]'.x: A Pbyslologica! and Clinical Analv,is. John R Blake Jr., .\LD.,Clevdand. and E. Charles Kunkk, /11ll., llurham, N. C ,.,........ 337

Oc.-!u,iun of the Internal Carotid Artery . .\lill<:r Fi,lwr, 1I.ll .. FY.C.I'. (Canada), \\ont-real, Canada.

[ntralll<:dullary Tumors of Spinal ConI aml CEcl11as of Intradural Portion of Filnlll Tn.minale: Fak of Patil'lIts \Vh" Ilavl' Tlws" Tumors. Ht'nry \V. \Voltlllan, .\l.Il.;James \V. Knnolian, !ll.ll,: Alfr"d \V. Ad,on . .\1.0 .. and \\'inchl'il .\lcK. Craig:. }I.D.,Ruchestl'f, Minn . .

Abstracts from Currtllt !,itrratur",

Society T ra11sa•.ti"ns :Chi<',,~o Neurolog:i •.al Society ...

News and CO!l1m"nt.

APRIL 1951. XU.\lI\ER 4.

346

m396

'03

'0)

412

Sta1l<ling: l'uttntial Corrtiat"sHaven, C011n....

of Hypnosi, :11111Xarm.'is, L"onard]. Ravitz. ,\1.D., N(,w413

Vi,ual and ~lotor Changes il\ Patients with .\lllltiplc Sdl'fosis: i\ R"s\!!t of InducedChange, ill Environmelltal Tempt:rature. Thoma" C. (;utIJrie, .\1.1l., N"w york 437

Tremor ill Parkinso,,', Discase awl Its Inhihition by Amy! Nitrite.:-'U~.c.P.. !.oudon. England .

Oli,l'f (;arai, .\t.D.,452

Death" Related to 1'1lI'ullloenn'phalogral'hy I luring a Six Year Period. Joh" [~. \\'bittier,III,D., Xcw york, , ,. 463

COST/,NT.'> OF VOf.(I.lfJi 65

Interadion in RilaterallyIldhesda, ;..!d...

A l' I~Ir.-Cmlli/l1""f

Sil1\ult;\IWousVoluntary ~Iotor FUlldion.P.\l;t:

Rolwrt Cohn, ~LD.,

!llij\rainea11(1Other Head Pain.\\' ashinj\ton, D. C

I.ester S. H1llmtllthal, l\I,D .. and ~lanin Fuchs, 11.D.,4i7

An A"e,;,rntnt of Therapy in Parkinson's I)i-'l'ase. Robcrt S. Schwab, ;..1.D.,Hoston, amiJohn S. Prichard, 11.H., ~r.KC.P., London, England........... 489

A l\l'w Procedure for Activat<:dEledrocnccphalography. Juau lSiegrinJr., 11.D., Xew York 502

An Improvcd Technic for P(,reutancous Cerebral Angiography: A Prdiminary Rcport.Dan C. Donald Jr., 1r.D.: Karl F. KeslJ]o{l\.1Jr., !l1.Il.: Stacy L l{ollins Jr., !lI.D.,and Richard ;"1. Paddison, 1\1.1).. Philadelphia... 508

The ~[~hanism uf C1wostek's Sign. Eric Kllgclherg, 11 D., Stockholm, Sweden...... 511

Ab,traets from Cllrrl",t Literature.

SocietyTransactions:Chicag-oXellrolog-iealSocidy................. . .Philadelphia N•.,urological Society... . .l\ell"York ~l,l1rological Socidy and the Ne\\ York Acadcmy of :'fedidne, Section

Xeurology and Psychiatrj'.... . .

Book Reviews...

~fAY 1951. XU11BER 5.

518

525530

of533

542

Intdkctual and Emotional :llfakeupof the Epileptic. Frednic T. Zimnl(,rtllall, )'I.D.: BessieB. Burj\emeisler, Ph.D., and Traq J. Putnam, )'I.D., X<.,\\' york.............. 545

P,,}'cholog-i•..al Effe~tsLexington, Ky

of Chf()]llc Barbiturate Intoxication. COllan H. KOrllttsky, A.B.,557

Sturlie,on Headache: 1\1C(.hanisllloj Headache aud Observation, on Other Effeds Inducedby Distention of Bladder ;",,1 Hectuill in Subjects with Spinal Coni Injuries. G"orge A.Scll\lInadler,11.11.,and Thomas C. Guthric, ~1.1l., Xew York. . . . . . .. . .. . . . 568

EXl'lTirnclltal1'1Iy"iologic;t1Stu<li~s with I.yscrgic Acid Di<.othylamide(I.SD-25). GordonR. Forrn, "'Ln., ami Hich;tnl D. Gohlnn, ),1.D., Yp,;il;lIlti, ~1ich............. 581

SignifICanceof !~ise in BI"od Sug;ar 1.•..\.,.1After Injr".tion of Epinephrine in ~fent;tl Disease.~Iark D. A\t,dlU1e, 1I.D.: Elaine Sicgel, ;tlld Fe,lcrieo 1\1nra-Castaneda, ;..I.D.,Boston. 589

Traumatic.r\eurosis, COlllpell,;ationXellro,;i~or ,\ttitudiual Pathosi~? Gordon R. Kamman,M.Il .. St. Paul. 593

A Dynamic Factor Corrc1ah,,1 with th(, Progllosi, in !'aran"i,1 Schizophrenia. PhilipDurham Seitz, 11.D.. im\ianapoli,..... . .

The l'hellCHllenon"f Sensory Displac.:ment. ),{orris B. Bender, ~r.j)., Kcw '{ork .

ReAcxe.\Evoked I,y Cold Stimuli iu Injuri"s of the Spinal Cord. Lewis J. 1'ollock, )'LD.;Benjamin Boshes, ~LD.: Hnman Chor, ~I.D.: hi<1ore Finh'lm;tn, ~I.J).; Alex J.Aridf, M.D.: Mey•.-r Brown. lo.f.D.,awl John l{. Finkle, 11.ll., Chicago........... 622

Subaradl1loidHemorrhage ill !lfclanoma of tl,.., Brain. "'I. J. ~Iadonirk. )'L\) .. and XathanSavit,ky. I\f.!l .. X,,'w York. .. .. .. .. . 628

:\b",rarl~ from Current Literature .

SocietyTramartions:Philadelphia I'syd,iatri~ Society .Xew York Aea,\<omyof )'Iediritw, Section of Ketlro!ogy and l',;ychiatry, ;tnd the Xew

York Keurologieal Society..... . .

:\'ewsand COlllnlt'llt .

637

(j..Ji

649

657

Obituaries:Oliver Smith Stroug. Ph.D ...........•........................................ 658

vi CO,\"fEVTS OF VOU,'JlJ:' 65

JL'NE 195\. NU:\IIlEI~ 6.

Dandy', Striatal Theory oi "The Centcr of Comciouslless": ."l1r~it'alEvidellct' andAnalysis [ndicatin~ Its Improbability. Russell :\!t')Trs. "III.D.,Iowa City.

I'AG~

Lo~ical659

""port of a Case.I)" [[OU.'tOIl.T('xas

Ralph W. Aim'll),

EllCepha!opathy Associated with Acute IJiffuse Platel"t Thronlho,is:A. Han.'er, ).,1.]),;Alvin Beya Jr., /II D" amlI{ohcrt A. Burger, :\1

Effects of ACTH 011 Cerebral Blood FIOI\,'atul Oxy~cn Consumption.!II.D., and Joscph F. Fazekas, )"l.D., \Vashin~toll, fl.C..

Familial Occurrence of Tuherolls ."c!('rosis, \Villard \V. Dickenoll, ).,1.1).,Can>, ':>!ich..

672

600(iR3

XeuruloJ.\icalComplications of Tmul\n Shock Therapy with Eleclwencephalo~raphic Stud-ies: Ca;c Studie,. \.ouic Halle, ':>1.1).,and J. F. I<o"s, /I\.Il" Uen'!alld. 71).1

nabinski l\ctlex and .\larie.Foix Flexor \\'ithdrawal ",'Ikx: Hi;torical :\OIC'. Rohert\Vartenh'ir~> /I\.D., San Fra1H:i;w, 71,1

Gluco,,, Tolerance in ChWlli" St,hi7.ophrelliaand Senile Statts. \Vann Simon, ).,!D" andJam,,; T. Garvcy, ':>1.0_,!lliruwapolis , 717

Po,tpartum Necro"i, of th" A(knohypophysi, with Hypoglyrt'lllic Conntl,iun,.. Edward C.Clark,M.Il,: ::IIurnlYFranklin, :\I.D., '11HlAdulph L. ~ahs, ::11.]).,[owa City. 72-f

EE(; Progno,is in Vascular II('lllip!tg-ia I<dlahilitatiull. (harks \'an Buskirk, ':>1.]).,amIV. ". %ariillg, .\I.D., )"lirll](''1poli;. 7J~

Efftct of E!cetro,h,,..-k on the Blood I'n"'un, in Psychotic Patients. Walt"r \\'. 19t:r;hei-Iller, :\!.l)., alld Jame, A. F. StnTl1sml, .\I.D.. );t\\' Han'n, C"ntl. 7-fO

Anti"onl'ulsant Dru~ Thnal'Y of lkhavior Prubl"m Childr,," wit11:\hnnrlll;tin.phalograrm. H,'njamin Pa,amanick, .!Il.D., Arm Arbor, )"Jil-h..

.\bstracb irom Cuntnt Literatmc.

~-,"-71,7

Sod,,!y Transactions:Xew York l\radlOmy"f \It'dirillt" S,'rtion of Neurul"gy and Psychiatry, and .'\lOwYurk

J'\turological S"cidy 7SOPhiladdpbia .'JlOurol(l~kalSori"ty 7&3

XtWS and Cornlll•..nt ...

Obituaries:Law-rence l\aylllOlul \!"rri,,,", ,\1 IJ.

Duok "el'iew,

iSi

7SS792

NEUROLOGICAL COMPLICATIONS OF RABIES VACCINEReport of Two Cases

F. R. LATIMER, M.D.

J. E. WEBSTER, M.D.

'"E. S. GURDJIAN, M.D.DETROIT

WHES LOllis J'astel1f 1 Sl\cccs."flllly prevellted the appearance of rahies inJoseph l\Jei"tt'r (1885) following the hite of a rabid dog, new hope was offered

to persOlls who previously would have heen condemned to certain Jeath. However,in the years that followed it hecame apparent that the lise of rahies vaccines was notwithout risk. Hepofb of various reactions, SOllle fatal, Leg-an to accu1JIulate in thelittrature, and the etiologic factors in these complications became it subjeet ofdispute, which continues until the present day, some 64 years after the Ikve10pl1lcntof Pastenr's treatment.

The rurrt'llt literature reveals the diHil'l1ltiesill colllplf'te1y reporling" each ca~e ofcomplications iollowing antirabies ther:apy. Certain (j(>tailsare l1sua11ylacking"; i. e.,permission for necropsy Illay ha,'e bet'1\ refused, lhe hiting" animal Illay not haveheen caught, the type of vaccine or the dosage may tlOt have heen ktl0w11or anadequate history of the illness may 110thave hee11available, Therefore, when twocases of ll{'uroparalytic acci(lent associated with the prophylactic use of rahies\'accinc L". S. 1'. occurred in Drtroit withll1 four 111onths,we were prompted toreport these cases as {~01npletelyas was possible in the circllm~tances. !{egn:ttably,certain particulars wefe bcking" in thesc cases also.

REPORT OF CASES

CIISE I.-History of car!ier c(Jursc of antirabies injcctions in child/Wilt!; develop",ent oftYimSl'erse myclitis after 10 in"clliatimts, ~(.;.thuri""ry rclc"tion, p(lralysi-r of loa'cr (x/remiticsand unsor}' loss IIp to ten/h thoracic dcrllhltome; almost full rt'C()l'<'rywitllin 2-/ months.

A 1i year old white youth, a student, was :ulmitte,1 to the Grace }-jo,pital on Jan. 19, 1948,complaininl{ of paralysis of hoth lower {,xtn'llliti(". On De", JI, 1947 he had been bitten onthe ril'ht cheek by a stray dog, whid, was not captuT<:d. First aid, consisting of 1000~alapplicationof phenol after cleansing of the wound, was administered shortly after the bite. A course ofantirahies treatment was advised, lmt the llaticnt <.1eferredreporting ior the injedions nntilJallu:try 5, when the first of daily injediolls of 1.5 cc. of rabi{,s vaccine (S{'mp1e), preparedby the Uichil'(an Departmcnt of Health, was givcn into the deltoid muscles. Aftcr the eighthconsecutive daily injection, the patient began to complain of headache and stated that he felt"fevnish." He received injections for tlw succeeding two days, and on January 16 urinar~'

From the D'.partment uf N•.•urosurl{ccy, the Grace Hospital. Dr. Latimer is Resident illXe\lrosurl{ery, 1Jivision of NCUHNlrgery, Grace Hospital.

1. Vallery-Radot, R: The Life of Louis Pasteur, translated by ]{, L, Devonshire, GardenCity,~. Y, Garden City Puhlishing Company, Tnc.,1926, PI'. 414-41i.

1(,

LATIMER 1:'1' .1L_CO,lfPl,ICJT/ONS OF HARIES f"ACClNE 17

retentiondn"doped. Tbereafter, he received uu antirahi~s therapy. An indwelling eathderU5 inserted,amI antibiuties \H,re gh"cn. On Jauuary IS, ';numlm•.'" and tingling" in bulhkg,werenoted, and the lJalicnt aPI'",ared somcwhat lethargic. The ucxt day the abdomenb/canlcdi\knded, and h", lost all vuluntary control uf his kgs. \Vith the Oll>ctof these symptums,thepaticntwas transfcrrcd to tI,c Grace Hu,pital.

Onadmission to the hospital, the g('nnal physical examinatiun reveai<.,da "ell d"",doped,wel1llouri,hed,whitt' yuuth. wh" appeared dehydrat"d and lethargic, with a blood prcssurc 01III/tiS,a pulsc rate of 94 per minute, a rcspiratioll rate uf 16 per minute and an oral~l>tratureof lOO.2F. Thc h~art, lungs and ahdomen appearcd norma!. Xellr()l"gi(~alexami-I13tioorevealed inequality of the pupils, the right pupil h•.,in)o\,lightly larger than thc left, anduakne,sof both upper cxtremities with l,ypoactive hieeps and triceps reflcxe, bilaterally" Therens complete.!lan'id paraly,is of huth 1"')0\'"ilh ab,,,n~e of the patdlar and ac\,i1les rcfl~xe"U!ss of pain and tempnature sensations wa~ apparcnt up to the tenth thoracic dermatome. .Adiolgno;i,of "acute postvaccinal el",~phalumyditis" was made, and lumhar ptlllctun, r"veakd aninitiall'ressureof 150 mm. of water, with a nCKativerea"t;ol\ to the Qut'ck"mtedl test. \Vebmlmati,,"wa, noted ill tIl\' fluid aft{'r 30 minut•.".

Thepatient had recei\'ed a l,re\'ious s('rie, of antiral)ies injections at thc age of 7 yean.,\Ilergyof any type in tlw immediak family or the pcrsonal history was denicd.

L~!It'mto'.vVatn 0» .'ld~,,;.\'.riOJ~.-TIII::results of a comp1<.-tehlood count IHre within normal:imits;the urine containnl a trac", of albumin, a "few" white ],lood cells and 4 + rcd bloodctlls.Theccrehrospinal fluid wa, "bhxxly" and rolllaincd (,29red hlood cells and 1,181leukocytes~ cubicmillimeter, of whirh 98 per ('('nt W""T ,c",llwnt"',1granulocytes and 2 per cent wcrel)lnphocyles.The fluid showcd a trac~ of ",lobuli" and a I + reaction for alhumin '111,1containc,l58 mg.of Slll(arand 69 mg. of total prokin, lJer 100n'. The fluid was ckar on centrif\1/o(atioll.

HosPital Co"'.re,-Pellicillin and sulfadiazine therapy was instituted. The patient's neuro-logicalstatus remained unchanged for two days, awl strength in the hands tbell b('gan toimprol'C,so that he could grasp objects fIrmly. By January 24 th", deep r",f1exes in the UI'P"r!ltreTnitie5were artiw and I,.,rcepti"n "f pain and light tonch wa' acutc down to the knees.Thepatellar reflex was absent, although the achilles reflex was pre,ent on both sides. and\herewas a bilatt'ral Babinski sign. The patient's tClllpl'ratur", wa, normal and remaincd soduringthe rest 01 his hospital stay. On January 26 daily ph)'sical thcrapy, consisting of massagel.lldpossi\"emotion of both lower extr"mitics, was b"'l(nn, Threc days lakr the patient wasab:eto movc all to('S of the ri)o\htfoot. At th,' time of his discharge fwm thc hospital, onFebruary12, there was rOlllplcte return of sensation throu",hou\. Slight weakness of the lowerextremities,with fecal incontinellc"" remain•.,d. Fluid ohtained by lumbar puncture prior todi\fhorgere\'ealed 9 wbite blood cells per cubic mi1lilllct"r, a negati;c reaction for globulin, aIplusreaction for albumin and a total protcin of (jQ mg".per 100ce.

Thepatient was la,t ,,,,enon April 21, 1950. Hc was walking I!llaid"d, and his only complaintu,that of urinary incoutinclJcc, particularly atllight. llis gait \Ias normal, although the lcitlowerextremity was slightly weaker than the right. Ther", was no atrophy. The deep reflcxes1Ttreall hytJeractive, and an equivocal B,,],imki sign was ohserw,1 hilaterally, There were 110srn'orydeficits,

CA,f. 2."-!1ist"ry of predol!,I' an/ira/,ics """"hllltio» i'l childhood .. systemic reacli(IJ1immedi.altl, afler first antin/llies ;""cltlatio", with d(~'('/()p1Jlent af enccpllalomyc!iti.l' and ;nterco,rtalp~ralj'sisafter "ighth injat;OII, terminal;nH in death withill 21 hallrs.

A white man, aged about 25, a laborer, was billcn on the right ankle by a stray dog OilSqll.12,1947. Tlw animal was Ilc\'",r apprehcndrd. PendinK rapture of the animal, antirabicstr.erapywas lJostpol1ed until S{'ptember Hi, when furtl'ef delay was thought inadvi,abk.Accordingly,on tlmt date a "')\lrse of rallies vaccine (Scmple), frolJl the 11ichigan State Depart-mentof Health, \Ia, begun, and daily injections uf f:5'"CC:-oftIl<.'vacdne werc given into thedeltoidmuscles. Almost immediately afkr the f,rst illj('cliol1,the pati•..ut cOlllplailwdof head-l(heamI "fe\'Cr" and became nauseated. After each inoculation the r",adio!l l,ceame worsc,

2. Case 2 is prcs<.'ntedthrough tl,.., comtesy of Dr. Joseph G" Uolll~r. Commissioner,Departmentof Health, Detroit.

18 .1. M. A. .-iNClillEr;; OF NF./iJ<()UJ(;V ,.ISI> l'S}"CllIATRV

and at the time of the f,fth injectioll the sit{, of administration became indurakd, red and painfili.On Stptemher 2Dthe t[(,atment was discontinued, and tlw symptoms disappeared i"r the ensuingtll"O ,lays. Treatment was [("umed on Septemher 23, 24 a",1 25, and the following day thtpati""t had s"rell('SS ill the hack of th{, neck, numhness in the hands, fed and gum~ and severalepisodes of \"lllniting. On Septemher 27, he lx'Kan to "hurt all over," ,'ontinu"d to vomit, withrep,'ated hiccuping, and pnspired profusely. TI,,, l<.'mperature at this time rose to 10! F,\ lumhar pUlIcture was dOl"'. Tlw tTrehrospinal tluid was found to contain 8 white blood celli]J<.'rcuhie millimder and 81 mg. of sugar and (,4,7 mg, of total protein, per 100 cc. On th!morning of Sl'ptemh,,'r 29 tbe patit'llt was ldhargk all,l had respiratory diffinlity. He wa,1"lSpitalized at 2: ¥I p. Ill., bl'came comat"se at 7: 00 p. m. and died at 8: .15.

On admission the patient appeared morihund and cyanotic. 1{espiratioll was labored anddiapbragmatk in type, with complete paralysis of the intercostal nHlseles, Tbere was no nnchalriKidity, and he rcsponded but feehly to the spoken word. Ill' was imnlediatt'ly placed in thert'spirator, an,l oxygen was given throllRh a nasal catheter. Supportive measun:s, in tl,., formof 1,0110cc, of 10 per cent dextrosl' in salille solution and frl'<ju,,'nt aspirations of the throat, wenof no avail.

Th", past hi,tory of the patient revealed that he had heen in the military ~I'f\'ice and hadreceiH'd all routine inondations without ""''1uclae. There was no history of allergic readi,,!l'"f all\, tYlW, bllt the patient had received more than 10 injections of rahies vaccine as a child.Hay iever was ]!resent in the patient's relatin's.

Xecrop.•y.-Thert' w,.'re tWI} H'"ent linear ~ean on tIlt' rip;ht ankle alK've awl bdow th~,,'xtema! malleolus, [('ddish in colur, the result of the animal hilt'. Th" lungs w,,'re darhrthan normal and \H[(' soggy', having the appearance of passi\'c ('ongestion, Rdle,.tion of th~dura reveale,1 diffuse, grayish thickening- of the !eptom"ning{'s over the \"erltx. This wa,e,pecial1y prol10111lCedll{'ar the midline of 1K)th parktal lol){,s. Dissectioll of the nlellinge,showed this process to be an lnnea~e in cOTlnectj,'e tissue, J)ot exudative. TIlt' brain was S()g~y,and th", blood vesscls of tIll, leptomeninges and cnebral parenchyma Were moderalt'ly collgested,The cortex and gray 'nattn of the medulla aplwared darkn thall "ormaL Then' was SOlW","n-olulional ilaU,'ning- over the convexitit's of tIlt' hemisplwres. Both sphenoid sinust's containednwderate anl<lUtl!~of thick, grayish yellow, IllnCOl'Ur\llelit nlalerial with reddening and thiekcnil1Rof the lllllCOUSm('ll1!Jralil'. .-\ cultUre of this di,<charge produc"d "1'1lt'U1l10e'",Tus type :\IIl,diphtheroid bacilli and IW'l)olytie Stal'hylo"oCCl1S pY"~l'nes vOIr. albus." Tlie ~pinal cord helm\the UPPtT cer •.i"al ~eln,wnts was not r{,lIIo'Td.

One-half the brain was submitted to the Hun'au of Lahoratories of the :'I.-\ichiR-auIkpartlll('ntof Ikalth f"r e.,amination. Dr. G, D. Cummings, llir •.dor, reported that .'\CJ<ri 1)<){lic~\\'{'rc1I0t ~t'en on dirtct ""';lIninatioli. Test animals inoculat,'d for rahit,s, poliomyelitis and eneel,haliti,exhihit"d no nid"lIce "f illness during the trial periods,

TIll' otlier hali of tl", hraill, tb,' thoracic ,ympatlwti(" truub, major portious of tht \"a~ll'nerve. lumbar pItX1L"'~ and hl""ks frOll) the l"oas, rectus abdolIlillis, pectora! and intucmtaimuseks were .'ent to the Brain Disl'ast Registry of tIlt' \Yayne University College of ~Iedkinc,The Detroit Departllltnt of Htalth received the following description of the pathologicalexamination from Ilr. (;ahriel Steiller, neuropathologist.

:'I.ficros"opie Study: There is widespread inflammation in tbe hrain itself, the I'roc,'ss 1J.cin~much less intense ill the !eptoltll'nillges. Th" inflammatory respOllse consists of adn'ntitiaiinfiltration with lymphocyte" plasma cells and a few segllwnttd granulocyks (I'olyn,orpho-lluclear leukocytes) in thick cuffs. ThlTe is also a perivascular reaction in the sllrmundin~parl'llebYlIIal IL'~nt's, es]""cial1y in the wbitt matttr. II"re the edlular in"rl'<lse consists chidlyof microglial celk Tlw gray malter, except the eortn, IlIay he somewhat 1II0rt, in"o];,,'d thatlthe ,,-hilt' nlattl'r. 1'1'<"nin"l1t inf1all1ll1:ltory 1<>siot"ar,,' ,_t.",uill II", liipl'ocamlnl.' and around Ihealjll"'t!Llc!, till' posterior hom and the floor oi tIll' fourth ",'ntricit'. An eSlwei;']I" illtertstillgol"ervation is lhat of inflammatory lesions in l""ri1'lwral llern's (vagus). "hkh cO'bi4 "f diffuseiufiltrati"11 "ilh st'gl1lt'llted g:ranul"cyte~. Th", sY111patlwtic g:allj.\lia and tl<'rHS sl\O,,," scantyIYl1wh"cylic illfiitration. :'\'egri l)<,dies are not H"ted.

Th", diag11",i, is cnct'llhalitis f"lIowing: thl, f'a'!<,\Ir Irt'atnwl1t, with l,",lllo\1lw"d IY111phorytkinfiltratioll, alld purulclIt diifll'" end01l<'\Iriti~ "fth" vagus nern'.

L4.TIJ/ER WI' AL._COMI'UCAT/ONS OF NAntES F,,!eelN!' 19

(;E;>;ElnL CO",STDERATlO:-;S

r~('actiolls to antirahies therapy have heen completrly described and cla~~ifiedby J[orack~ His seven groUJlS lIlay he comhined under two main head~: theextraneural and the neural type, Extralleural complications, which do not primarilyinrolw the nervous systelll. arc of two types:

1. The appearance ill selL~itize(1j:wrsOllsSOOI1after the institution of treatmentofa g-etleraliz('(lurticarial rash, which responds to epinephrim'.

2. Local reactions, with or without systemic im'olvell1ent, varying frolll simpleredness.swelling and induration at the site of injection to a severe local response,attendedwith hcadachc. Illaiaise, fe\'er alHllympha(lenopathy. 1t is eutirrly possihlethatJoseph ::\Ieister had this type (Ii rcaction nmkr Louis Pasteur's treatment, sincerallery-Hadot' quotes I'ash'ur's obsel"\.ati()l1~on the child:The la,t three inoculations hilVt' kit some pink marks onder II", skin, graduallv Idd •.ning :m,lm~at all tender. Tlwr.., is S01ll<.'acti"". Idlieh is Ill'eO!lliogmore intense as we a"proach tlwfinalinoculatio1\,which will take place "n Thursday, July ](,.

TAULEl._lllcid.'lIcc of SCl(ro!,,,raiyli,. COIII!,ii,,"lioliS /<oll/till!! ir"m USC "I Habits I'aai",.

2,:lI<li 1:1,,~1

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n"l,ort ••.,Ca."" of

Patieot. l'eurol,atalj'!i,'Trpal••,1 1\".1.1"01.

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Alal>ultla , , •.........•••.(ile"l"o", O. ,\., and Po,..lln).[, .J. n ..• 1 .\. )1. A.

113::l\~'-~V.,I.Jnly 2('] \\~')1.0' .\nl(eIP" County .•......................

(R"I"wliJ. F. II .•. lc .• "n.1 Vn.l"""<l'''J, I•.. 1,' Croll!""nla-'1••1. 66: :~.I.:ll)~ [.In'','] ]flj7)

~."rlh Caroll""s ..........• ,.. ,Col,,,,,,,,,".Ohio...................... . , .

(I'hiJlips, J. 'I.; Jlt'T'Y. F .• an,l ~nouk .. 1. II f.lolept ..Hi,. 29: 9;.1():'C !.Jul~'J1it21)

G,01(~:~Ja.c~>i::~;:: .1. M, ,I. (;;,:;t~j;.:is;.f.:;~~i.:;;llApell] 1!1l6)

'f<ltal

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Cainit'll"Cord ",,,thodDHmlon,,,,,tho,1

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The neural type of reaction, afTectillg the nervous systelll, nsnally falls lIm1erolleof thrre forms:

1. The peripheral form, nmllllonly involving the facial nerve. Completc recow'ryisusual.

2. The spinal form, occurring aiter a preliminary ~e\'('re local reaction andmanifesting" itsei( either as dor~ol\lmhar mye1iti~, with pare~thesias, sphincterdisturb;lnce an(l paralysis of the lower extremities, or as an ascen(ling paralysis ofthe I.andry type.

3. The cerebral form, without paralysis, characterized hy a prodrome of aden-opathy, malaisl', heartache allII inflammation at the site of injection and the suhse-quentdeH']oplllent of dr()\\,,~ilH'~s.1111chalrigidity and signs of increased intmcranialpr<,ssure,i. e" hra(lycart1ia and papilledema.

The incidence of neltroparalytic accidents complicating the use of rabies vaccinehas becll \'arionsly reported hy American authors as ranging from I : 2RO treatedpati('nt~, ill a small series, 10 1: K2H7 l"1.tients receiving the vaccine (tahle 1).

3, Burack, II 111.' Alkrgy as a Factor in the IkvciOl'nwllt oi R<.'actionsto Amirahic Trcat-m~nl,Am, J. ~L :"e. 197:fi72-fi1\2 Ora)") 19,19.

4. \'allt'fy-I~;ulot.' p.. -111,.

20 A. M. A.• -lNClIlI'ES OF NPJ,)IWI.OCF .LV]) l'SYCllfATH}'

On the other hand. worldwide statistic~, reported hy (;reeuwood," place the incidenaat 1: 5,814 in a series of 1.2W.758 treated patienb, with a lllortality of 25 per cent

In 22 ca~es oj neurological reactioIls to rahies vaccine colledcd frolll the litera.ture 6 the large majority of the p<"1tientswere betwccn 20 ami 40 years of age, anathe males outlll1ull)('re<\the females hy more than 2: I. The mortality iu this groupwas -10per ceul.

[n .:'.Iichigan, approximately 6,000 paticnts receivcd 84,122 doses of rabiesvaccine from July 1, 1945 through .:'.farch 31, 1949. During this Jleriod, 12 casesof reactions of all types to rabies vaccine, inclt1(ling"four cases of lleuroparalyticaccident with one death, were reported to the l\lichigan Department of Health,'This represents I ca~e of postvaccinal involn'llWllt of the lIernJUs system for 1,500patients treated (table 2),

Of the many theories l'OlKCming the etiology of reaclioll~ to antirahin treat.Illent," those with current support may he divided into two groups: those \\.hid.implicatc tIlt' Ilen'e tissuc in the vaccine a~ the eausati\"l' agent and those whicha~st1l1l('a culpable virl1~.

Proponcnts of the former holJ that the reactions are due to the toxic effect ofa constituent of l1erve tissue in the inoculant Oil the nervous systelll of the n~eipient,or that they are anaphylactic or al1l~rg"icresponses to repeated injectiou of neneproteins in the vaccine. It is the helief oj Stuart amI Krikorian On that the aceidentsarc due to the injected brain tis~l1e,and they postulate the presence of a "cytotoxin"in normal hrain tissue, To support their views, they offer experimental studics withallimal~ in which p...1.ralyses were pro(ll1tcd by the injection of hoth homolog-ous

5. Greenwood, 1f.: Tenth Report Oil Data of Allti-Rabi~ Trealmenb Supplied by Pastt'UfInstitutes, null. Health Organ., LeaRucof Nations 12:301-364, 1945-1940.

6. (11) Hora~k." (/,) Ansell. I.: A Fat'll Case of :\Iyelitis After .-\ntiraLi~ Va~dlw, Brit. )'1,J. 2:338-340 (Aug. 14) 1948. (c) Bas"""" V., and (;r;nker, K: Human Ral,ies and Rabi~!Vaccinc Ence[Jhaiomyl'1itis: A Clinicopathological Study, Arch. Xcurol. & Psychia\. 23:1138.1160 (June) 1930. (d) nreed, \V. II.. Paralysis Following Antirabi~ Treatment with Cal!Report, New England J, ~[cd. 202:15/-153 (Jan. 23) 1930. (r) Hussell, L. J.: ~!yelitis .-\fterAntir~,bie Va,Tine: I-kport of Fatal Casc, I.ancd 2:820-827 (Ike. 7) 1946. (f) Halle, S.:Post-Rahics Vaccine Paralysis, Xew Ori<.'ans:\f. & S.. 1. 101:47-52 (Aug.) 1948. (y) Herron.P,: Fatal Paralysis Following Antirabie Treatment, ihid. 93:446-450 O\'Iarch) 1941, (h)Imrie, A.. A Case of Paraplegia FollowillR Anti-Rahi,. Vaccination, J. Roy. Army :/If.Corp!83:196-198 (Oct.) 1944. (i) Kiely, C. E.. Paralytic Accidents of Anti-Rahic Treatment. J.Med. 15:68-78 (April) 1934. (j) Koenigsf,'ld, E.. NCl1ruparalytic Accident Following c\nti.Hahic Vaccination, J. Roy. Army U, Corps, 85:254-255 (Xov.) 1945. (k) LirHlctnulder,F. G.:Paraly~is Followin,l:' thc l'rophylactic Inonllation of Rabies Va"cinc and Tdarms Antitoxill.I. Nerv. & ~I{,llt.Dis. 86:284-291 (Sept.) 1937. (I) :\Illrphy, w. H.. I'aralysi~ Induced h)'Anti-Rahie Tn'atment, South, "led. & Surg. 94: 150-157 (I\lareh) 1932. (m) Pickar, D., andKramcr, H.: Ene,'phalitis Complicating Vaccination for Rahies, South. ~1. J. 42:127-129(Feb.) 1949. (II) Smith, ],' and Murphy, J .. Fatal Paralysi, Followiug Antirahic Treatment.New England ], :/lIed. 202:/53-154 (Jan, 23) 193U. (0) Stuart, G., and Krikorian, K. S,;Keuro-ParalYlic Acdd"nts of Antiral,i,'s Tn,atment, Anti. Troll. /lIed. 22:327-377 (Nov.)1928; (t) A Fatal X,'uroparalytic Accident of Antirahies Treatment, I.anfd 1:1123-1125(May 24) ]l).lO: ('I) ~,'uropar:1l".tic Ac,.ideuts COlllpliralillRAntirahic Treatmcnt, Brit. :\1.J.1:501-504 o.fardl 25) 1933. (r) Thomas, C. R,' Compli,.ations Following Usc of AnlirabkVaccine with Sugg:cstiom as to Treatment, South:\1. .I, 37:539-543 (Oct.) 1944.

7. CUlllmiuRs,(;. D.. l'ersonal communication to tl", authors.8, Van Rooyen, C. E., an,\ Hhodes, A. ) Virus Di,eases of ~f;m,XCIV '{ork, Thos. Nd,on

& Sons, 1948, pp. 876-887. •

LATlJfliN. liT AL-COJfPLlC.IF/O.vS OF H.'W//;", I "ICC/Xli 21

,

="

"

~t~

•

.;:

20 A. J1 . .1.• 1/<ClilVl~S OF NliUJ<OU)GV ANIJ l'SYC1I1AT/<Y

On the other hand. worldwide statistics, reported by (;reenwood," place the incidenceat 1: 5,814 in a series of 1.2c,x)]5S treated patients, with a mortality of 25 per cent.

In 22 cases of neurolog-ical reactions to rabies vaccine collected frolll the litcra~ture 6 the large majority of the patients wen~ betwecn 20 <It1(140 years of age, andthc males out1l\llul,ered the females by lllor(' than 2: I. The lllortality in this groupwas 40 per ccnt.

In tlichigan, approximately (i,OOD paticnts recei\'ed H4.l22 doses of rabiesvaccine froIll July I, 1945 throug-h )'larch 31, 1949. During this period, 12 casesof reactions of all types to rabies vaccine. including- fOllr cases of llcuroparalytieaccident with one death, ,vere reported to the )'Iichigan Dcpartment of Health.T

This represents 1 case of posh'accinal involvetlK'nt of the nervous system for 1,500patients treated (tahle 2).

Of the many theories ('oncel"lling tlw etiolog-y oj reactious to antirahies treat-luent,8 thosc with current support may he divided into two groups: those whichimplicate thc nerve tissue ill the vaccine as the cal1sative agent and those whichassume a culpah1e virus.

Proponellts of the fonner hold tbat the reactions are due to the toxic dfect ofa constituent oi nerve tissue in the inoculant on the nervo\ls systelll of the r~cipicnt,or that they are anapbylactic or allergic responses to repeated injection of nerveproteins in the vaccine. It is the helief of Stuart ami Krikorian 0" that the accidentsare dne to the injected brain tissne, amI they postulate the presence of a "cytotoxin"in normal hrain tissue. To support their views. they offer experinlClltal studies withanimals in which paralyses were pr()(hK~edby the injection of hoth homologous

5. Gf<.>enwood.),1.: Tenth Repurt on Data of Anti-Hallie Treatnwnh Supplied hy I'asteurInstitut('s. Bull. H('alth Organ., Leagne of Nations 12:301-:Yi4.1945-194(,.

6. (a) H"racka (b) Ansell. I.: A Fatal Case of ~lyelitis After Antiral,ie Vaccine. Brit. :\1.J. 2;338-340 (Aug. l.f) 1<)4K (e) Bass"'" P.• atJ(L(;rillker, R: Human Ra.bk, alld RabiesVaccine Encephalomyditis: A Clinicopathological Study, Arch, ~('urol. & Psyclliat. 23;1138-1160 (June) 1930. (d) Bn'("l. \Y. B.' Paralysis Following Antirahi(' Tr •..atmcnt with Casel{cport. N('w England J.. \I('d. 202::151-153 (Jan. 23) 19.m. (r) Bussell. L. J.: :\Iyditis AfterAlltirahic Vaccinc: Report oi Fatal Case. l.ancd 2:82('~R27 (Ike. 7) 1946. (I) HaHe, S.:Po,t-Rahies Vacciru, Paralysis. Xcw Orleans .\L & S. J. 101:47.52 (Aug.) 1948. (9) Herron,1'.' Fatal Paralysis Fol1owinl!;.Alltirabic Treatnwnt. ibid. 93:446-450 (Sfareh) 1941. (h)Imri"" A.' A Casc of Paf<l.I'1c,l!;iaFollowing Anti-Rahie Vaccination, J. Roy_ Army ),1. Corps83;196-1911(Oct.) 1944. (i) Kiely. C. E.' Paralytic Aeclr1cntsof Anti-Rahie Treatm('nt, J.:\fcd. lS:o.'\-n (ApriO 1934. (j) Koclllgsf(.ld. E.' Neuroparalytic A(,ci<1entFollowin,l!;Anti-Rabie Vaccination, J. Roy. Army 1If.Corl'g. .'\5:254-255 (Nov.) 1945. (k) Lirl<1cmulder,F. G.:Paralysis Following the Prophylactic Inoculation of Habies Vaccine ami Tdantls Antitoxin,J. Kerv. $:. !\f"tlt. Dis. 86:284-291 (Sept.) 1937. (I) ~Iurphy, \Y. B.: Paralysis Inouc('d byAnti-Rabie Treatment, South. \fe,1. & Surg:. 94:15(,-157 (/llarch) 1932. (m) Pickar. D., andKr:ulln. IT.: Encephalitis Complicating' Vaccination for \{a1Jies,South. ),1. J. .:12:127-129(Feb.) EN'>. (,,) Smith, J., and ),,[urphy, J.: Fatal Paralysis Fol1owiul!;Antirabie Treatment,New Enj!;land ]. \fed. 202:153-154 (Jan. 23) 1930. (0) Stuart, G., and Krikorian. K. S.:Keuro-Paralytic .-\reidcll1s of Antirabies Treatment. Ann. Trop. :\fcd. 22:327-377 (Nov.)I92R: (I') A Fatal !\('uroparalytic ,-\cci,knt oi Antirabies Tn:atmcnt. Lancet 1:1l23-1125(),fay 24) 193(1: ('I) N{,urol'aralytic .\cri,l\onts Complirating Alltirahic Tn'atment, Brit. :\1. J.1:501.504 (:\Iarch 25) 193.1. (rl Thomas, C. R.: COllll'li{-atiollsFollowing Usc of AntirabicVaccine with Sugl!;estiUlrsas to Treatment. South :\[. J. 37:539-543 (Oct.) 1<)44.

7. CUIllmings,(;. D.' P"rson;,,1communkatimi to the authors.8. Van 1{ooycn,C. E.. awl Rho,\cs, A. J.' Virus Discases of Han. New York, Thos. XcI,on

& Sons. 194R,l'P. 876-887. •

22 .1. ,If. .1. .-IN(:jlJVl:'S OF NI:TJ<OI,OGl' AND PSYCIIIATRY

alJ(l heterolog"Oll~normal hrain substance. They concede, however, that an indi\'idualidio~ynrrasy on the part of the paticnt Illay he important. On the other ham!' Hur~t 9

concludes from his inve~tigatiol1~that the evidellce is insufficient to prove that theinjected brain tissue pcr ~c is n:spollsihle for the syndrome.

Schwentker and I{iver~ ''': Kallat. \Volf and Bezer," and )'Iorri~on 12 state thattheir laboratory researche~ have Icd them to believe that a serologic re~JlO1lSe,theproduction of antihodie~ against an antigen, takes place to the injection of emulsionsof Herve tissue, Kirk and Ecker,'" in transposing tlw work to human subjects, reportthat they found an increased antihrain antibody titer in the ~erum of a patient inwhOlll encephalitis developed after antirabies therapy. The~e findings lend credenceto the theory that reactions to rabies raccines arc anaphylactic or allergic. Horack 8

reports that the incidence of a personal or a familial history of allcrgy was sig~nilicantly greater in a group of patients who exhibited reactions to rahie~ vaccinethan in a control g-ronp wIll) tolerated the injections withollt complication.

Jt cannot be denil~d that anaphylactic rcadio)]s to the prophylactic IlSCof rabiesvaccine do occur. Dorfman a describes one case in \vhich a syncopal attack with apseudopodial wlwal ami gencralized urticaria appeared within a short time afterthe injectioll of SClllple vaccine. Epinephrine was :l(lministered. and the symptomsdisappl.:ared. It was proved that the patient was hYJler;;ell~itiveto rabbit dander.

Pickar and Kramcr I.' and Slipyall '6 report ~\lcce~sfI11treatment of reactionsto rabies vaccine with alltihi~tamine drngs. Sellars 17 fecls that the history of previouscourses of antirabic~ therapy in five of seven of his cases with reactiom to thevaccine is a "frequency which i~ beyond the realm of pure chance."

An interesting oh~ervati011is the fact that prior to the development of oettermethods of epileptic control, injections of brain elll\1lsions were given to epilepticpatients to reduce thl~ seizure rate. Sta\'rov~kaya '" reports the treatment of 60epileptic patients with it1jectiol1~of 1 cc. of spinal cord emulsion which was allO\vedto ~tand 2~ hours prior to use. He states that illjectiou of the cord emulsion for as,

'). Hurst, E, }V,: Tbe Effects of the Injertioll of ;\ormal Brain Emulsion into Rabhits,with Special Reference to the Aetiology of the Paralytk Accidents of Antirabic Treatment,J, Hyg. 32:33-44 (Jan,) 1932.

10. Schwentker, F. F., and Riwrs, T. 11.' The Antih')lly Response "f Rabbits to Injectionsof Emulsions and Extracts of Homl,logou, Rrain. J. EXlwr. ),fed. 60:559-574 C';ov.) 1934.

II. Kabat, F. A.; \Volf. A., and Bal.T, i\. A.' The Rapid Productio" of AClll~Dis~eminatedEIlCephalomyc1itisin Rhesus .\lonkeys hy Injection of Heterologous and Homolog'ous BrainTissue with Adjuvants. J. Exper . .\ted. 85:117-1.)() (Ja1l. I) 1947.

12. )"forrison, L. R.: Disseminated Encephalumyelitis EX1,erimclltally Produced by Useof Homologous Antigen. i\rch. ::\Il.'urn!.& Psychiat. 58:319.416 (Oct.) 1947.

13. Kirk. H. C. and Ecker, E. E.: Time of App,'arance of Antibodies to Brain in theHuman Heceivinl{ Anti-I{abies Vaccirw. I'roc. Soc. Exp,..r. BioI. & !\.fed. 70:734-737 (April)194').

14. Dorfman, \V.' HYl'erscnsitil'ity to Rabies Vardtw, ;\('w York State J. ),fed. 4.0:215-216 (Feh. 1) 194().

15. Pickar, I). N., and Kramer, If. 11.' Encq,halitis Complicating Vaccination for Rabies,~ol1th. ),1. J. 4.2:127-129 (Feb.) 1949.

16. S!il'yan, A.: Control of Allergy to Antiral,ic Vaccine, Ann. Allergy 6:428-430 (July-Aug.) 1948.

17. Sdlar,. T. F. I.imitations of Antirahk Treatnl('llt, ]. M. A. Georgia 35:l.12-133(April) 1946.

18. Stavrovskaya. IlL ::\I.: Treatll'ellt "f Epilepsy with Brain Extract, Klin. med. 6:1187-11%, 1928.

LATIMER ET .:lL-COJIPLlCATlONS OF H.1BlJiS V.ICCIXl.:' 23

longas three years pro(luce(lno undesirable complicatiolls. Kimball ami (;t\(..lakllnst19

placed 106 patiellts with cOllvl1lsire (Iisorr!ers under a reg-imell collsisting of dailyintramuscular injt'ctiolls of 2 Cl~.of a 10 per cent suspension of lipids frolll sheepbraill. Five injections a week for six \\"('eks comprise(1 olle course of treatment.;\n interval of one month was allowed to elapse, and the treatment was thenresumer!. In 10 per ct'nt of the patiellts a slig-ht loca! reaction devc10ped at the siteof inoculation ami disappeare(1 in two to three days, althoug-h 110neexhibited atlY,('wn' rt'action.

Admittedly, these snies are sill'llI. It w0111dseem reasonable, however, that ifthecomplications of rabies vaccine therap)' are due to tilt' injected nen'e tissue per se,these patients would 1)(' likely candidates for s('vere reactions, sinct' they receivediar greater doses than the a\'erag-e person who is heing treatt'd after an animal bite .

.\tlother group oi investigators stthscrihe to the hypothesis that the reactionsto the vaccine arc caused by a virtts. Hassoe and (;rinker ,", conrhvle that the Iixedvirus present in the iuonthtm is responsihle. They base their dedttctions on similari-tiesin the microscopic ami gross pathology of rabies vaccine encephalomyelitis, truerabies awl llonvaceinal encephalomyelitis ~~otllplic.alit1g-smallpox. \Vhile filteringphenolizerlvaccines through a wire sieve, Kdscr 2u recovered some rdativdy coarseIh1rlicles,which were snspell(\e(l in saline solution ami injected intracerehrally intorahhits. Fi:-;l'(]virtts rahies was produced in these animals. 1t is his cOlltention thatphenoliztllg the van'int' "seared" the partieles amI protected the virus in the deeperportio1ls. Tlwrdort', he reasons, viahle Iixe(1 virns can, anrl oftetl does, hecomepathog-enic.

Bahol11lei:-;and Sigw,l1rl"' postulate that the fixed virtts in the varcinc activatesa latent micro-organism pn'sent in the m'fVUI1S,~ystemof the recipient of the vaccine.They rlraw a parallel hehn'l'll this action a!HI that of the \'irns in smallpox vaccine,which, according to Le\'aditi and Xico!ai. sensitizes the nervous system of theperson inocl1late(1to the virus of herpes encephalitis,

Marsden am! Hurst 22 lwlit've that 1lJ('ash.s,smallpox and ant'rabies vaccinationare predisposing factors to an inr1epenr1ent exanthem, whidl til'y term "acuteperivascular myelinoclasis." As proof, they cite ohserW'u dinical and patholog-icalTl:semblancesin the so-called nenfol(lgical complications of these diseases.

PATHOLOGYIkscriptiolls of patholog-ical changes were found accompanyillg the recent

reports of iatal nenroparalytic accidents.2" There is almost complete agreement

19. Kimhall. 0, p" alld (;mlaku1\st, D. \V.: A ~h1tly of Epilepsy in Detroit. :\ Pn'liIllinaryReport. J. :'Ilichij!;an:'II. Soc. 35:641-644 (Oct.) 1936.

20. Kclsn, H. A.' The Epidemiolo~y ami Prophylaxis of Rabies, in Virus and Hickt-ttsilllDi,eases with Especial Cnnsid.'ration of Their 1'uhli" Health SiKnifi"alle,', Cambridge, :-"fass.,Harvard l:niHrsity !'r~ss, 1940, pp. 642-659.

21. HahoIllwix, L" lind Si!,:\\al<l,J.' Paral,1t"!,:ieI1aS'lIlCau conrs <In lraitement antirabique,AlIl1.dr' !l1l'd.26:114-130 (July) 1929.

22. :'Ilarsden, J. 1'.. and Hurst, E, \V.' Acute Perivascular :Myclinoclasis ("Acute Dissemi-nall'd Etl("ephalomyclitis") in Snlallpox, Brain 55:1Rl-22$ (June) 1932.

23. (II) .\nseH."1o (b) Has"l" ami C;rinkt'r,"" (c) 1\lI",ell."" (d) Herron.">: (e) Smithand :\lurphy."n (f) Getzowa, S.; Stuart, G .• a'1l1 Krikorian, K. 5.' Pathological ChangesObserved in Paralysis of the Landry Type: A Contribution to the HistoloKYof Neuroparalytiel\cci'\(,nts Complicating Antirahic Treatnwnt. J, Path . ."::Bact. 37:4&1-500 (Nov.) 1933.,

o \~\ '

24 A. JI. A.• lNCII1VHS OF NF.UNOI.Oc;}' AND l'SVCIfIATNJ'

among the authors regarding the g-ross alterations of the nervous system. Thechanges. when present, were minor, consisting of injection of the vessels of the pia,brain or spinal cord. together with an occasioual .~Itlall hemorrhage. Herron,',galone, (k~crihes a thin, clowly exudate at the hase of the hrain.

1licroscflpically, the meninges were usually swollen, and occasionally round celland erythrocyte infiltration was seen. Altaations in ganglion cells were ohservedin six of the seven cases, TIK's(' changes varied from simple swelling and earlynuclear chang-es to karyolysis and karyorrhexis. llassoe alld Grinker"e notedcapillary abnormalities ranging from mild swelling of the endothelial cclls to markedswtlling with ohliteration of the capillary lumens. They also ohserved pronouncedproliferation of oligmlendroglia in the cortex and cerehral white matter with areasof complete demyelination sl1rwwHling- the hl()()(l\'('ssels.

Perivascular "cuffing-" with lymphocytes and erythrocytes was seen in threeof the cases. lmt Cctzowa, Stuart and Krikorian "Of state that there were noillfiltrations of the adventitial lymphatics; there was, howen.:r. cnlargement of thepcrivascular slJaces.

COClfME..t>.:T

Se\'eral points in the foregoing presentation merit further comment. 1\s maybe seen from tahle 2, eight of 12 reporterl reactions of aU types were to the samelot of vaccille, and all were ohserved withill one month. All these complicationswere similar and \vere extr;l1lellral in type.

The explanation for this occurrel1ce may lie in one of several factors. It mayrellect the periodicity of appearance of all independent exanthem, as pointed outhy Greenlirld 2. and .:\Iarsden and Hurst.°2 This would seem unlikely, however,since ill none of the cases did the condition progress to a typical encephalitic ormyelitic syndrome.

On the other hand. it is cOllceivable that some constitlltent of that lot of vaccinewas responsihle fur the complications, since recovery followed discontinuation of theinoculation series ill every case. As is the usual procedure, this vaccine had heentested fur toxicit:-, viahility, sterility, safety and potency in accordance with therequirements of the l\ational Institute of Health. ::-.Jothing-unusual was recordedfrom these lahoratory assays.

Case 1 follows rather closely thc established pattern of the spinal form ofcomplications following use of rallies vaccine. The patient. after eight consecutiveinjections, noted headache and malaise. Aftcr the tenth inoculation he comphinedof urinary retention, and there subsequently developed a typical tranverse thoracicmyelitis with no further antirabies propilyJaxis. After a protracted convalescence,there was almost complete recovery. It should he reemphasized that this patient hadreceived rabies vaccine on a previous occasion. This, in conjunction with a similarhistory in case 2. offers further suhstantiation of Halle's Of statement that g-ravedanger accomp."llliesa second course of antirabies inoculations,

Case 2 reveals details \rhich warrant discussion. The patient's first injectionwas followed almost immediately by a severe systemic reaction, The rapinity ofappearance would seem to indicate that this was the response of a previously sensi-tized person. The patient as a child had received a course of 10 injections of rahies

24. Gn'cl1fidd, J. G.: The Pathology of ~r('a"lt's Enccphalomyditis, Brain 52;171-195(July) 1929.

'.'.

~.' ,' .... "••

.,• ••l.;.•••

..

. '. vinl" (X (,OU)J) Illgh])()\\tr 11.'<1,,1<1Fig. !. (ra'(' - i~lll'h()c\'te". pla'lll<l rc s .inti1tratin'('d!~~rc ) _

lI11ckar I,'nkol)t<,j. 2~

1 hgule 1 Thl'", the .'n,t llId",ltu .1~1, (I'"hlllorpho-I "'-a'ml,)()!" _I,,, scgnl('ll!c< "

21> •.1. Jf. "1. •.INCIlt/'/:.'>' OF NI;'UNOU)(,T .1.\']) I'SrC"I •.1TNI'

,"accine, Coupk(l with this fact i" the temporary disappearance of the "y'mptollbwith intl'fruption of the treatmcllt course. Ii tilt' n",KtioIl had been produccJ hy avinls, as has hCCllpostu!att'(l, it docs not appear reasonahle that there should haveheen cOlllplete rClIIission ill the "Y1Hlrolllcl1Iltil the adtllinistration of the yaecinewas again hcgun.

The disriosure at llC("f0PSYoj a sphenuid sillusiti" in case 2 I11l1stnot he ov{'r~looked as a possihle rallsati\'e agent. ~eVt'fal tinditlgs, however, militate against thediagnmis of intracranial ext elision of "pheuoi(l Sillt\siti", First, the spinal fluiJ('ontaitll'd (lnly 1'1cells per rullie lIlillillleter, and 111("sugar level \\~L~.-:I Illg. per100 cco ~eeond, there wa,.; cOI11pleteahsence of gros" meningeal n;udate, and

Fif<.3 (('ase 2).-Vagus llen',', showing diffl1S{,inflitration with segmented j.:ralllliocytes.II"matoxylin and ('()Sillstaill: X ll~J.

lIIirrusropiral!y the leptolllellillg(',d infiltrak was "parse and COlliposed prilllarilyof lymphocytes. The probability is that if lite organisul"; cultured frolll the spheuoidsinlls (l'netlJ1HlCocCt\S,type \:111, diphtl](,f<li(l hacil1i atl(lltclllo\ytie Staph. corcuspyogenes vaf. aUms) were responsible for the (jisea"e ill this patient. the gross a11(1ltlicroscopic changes in the tllellillges \\'OI11r\han: beell oi the acute type and tltealterations ill the ccrebrospinal tlaid profollnd.

The pathologICal changes obervcd ill case 2 arc in accord, in general, withIhose (lescrilwd pre\.iollsly.~" TI\t're were no prominent gross alterations of thenervo\ls syste111.The microscopic dlangcs were characterize(1 by cerebral a(lventitia!illiiltratiotl, or "ctlffing," with f<l1111(\cclls and a few segtlll'lltcd grallulliCytes (fig. 2).

L.nnfliN hI' .lr._CO.,lf!'f.{C.rno.vs OF N.JfI/liS F"ICU,\/;' 27

l'tril'<lsrlllar lllirf('g-iial reartioll I\-a,~ ill evidl'tlrt~ throllJ,:lFllll tlte \lraill alill Ilrain,,,t('1ll(fig. 1), i'\egri hOllies werc l10t foulld.

OJ particular Iliterest was infiltration of thc vaglh ncnT with segllK'lltcll grallll-iocytes (figs.':; alHl..J.). I'Ilarillescll «ttl\ ])ragancsul ",-,(\escrilK' IYlllllhl,cytic il\tiltra-lious iu cl.rtai!l peripheral !lenTS, i. e .. the po,~kri()f tihial. ill ntH' oj tlll'ir cases.Illlt aPllarelltly 11Ilf(II('llt ("lH\OIleuriti,; ill rOlllllliratiolls of alltiral)i('s varcitlatil)\l hasIlut pn~l'io\lsly Iwen seen. Perhaps the vagn,; infiltration was in SOllte ll1alllWrattrilllltahk to the sphell(,il\ sinusitis and II-as. therefore, jlcC\lliar to this case.

Fig-, -t (<"a"l' 2),-.\tagllitiratiull "f till' fidd ;"dicall,d I" figure 3: X (,1111.

However. silln' tIll' presence or ail,"{'t1ce of patlHllogical challges 11l jll'riplwral alH\rrallialnrfu's was not rccorlit'd ill the Illajority of reportcd rases oi fatal rcactionsto tilt I'askur treatllll'nt. it is llifflcnlt to cvalnate thc frequency of this finding-.Consequelltly, an exalllination of the cranial anrl})('riplK'ralltcl"l'{,s wou\d ,"{'('Ill to he

indicat"d III fllture rases.

25. ~lari'w'ct1, (;., a\ld ]Jragan,"u), ~.' Contributioll " l'etllde ,ie-s <trddellb jlo,t-,'accill"-railiqm', (iL1''''Ta,iou <1'm, ca, al'<"<.'(.'''l11ll'\1allat<llll().ditlique), .\11\1. In.st, l'askl1r GO,-ti7--t'JROlay) 19.18.

21:\ .1. JI. .-/. .INCf{fJE~ OF SfTNOU)(,T .'ixn l'srCllf.fU{)"

;;1; I\I ~I.\II.Y

Two ca~l'S of neuroparalytic accid<,!lt ;\re rqllHted. III hoth cases thcre was ahistory of prc\.iolls antinlhies treatnwnt. In case I the condition was lllyelitic intype. with the aplH'arance of thoracic transn'rse myelitis afler the tellt1] inoculationand suhst'qlll'tlI recon'ry. In cast~ 2 it was cllcephalitic in character. with a systemi(~reaction following the first injection and the development of enccphalomyelitis withintt:rcostal paralysis after the eighth inoculatioll, the process termin,lting- in tkathwithin 2..J-hours. I'atholligical changes illc1lt(kd at1ventitial infiltratioll of cerchral\"("ssels with Tllltlld cells. llt'rivasclllar microglial n'artioll and infiltratioll of thevagus Iwr\(' wit II segnlente(! granultJCytes (pol )'lllOf]lhollltc1ear leuk, lCytcS).

The ,~tatistics of the :\lichigall Departmcnt of Il('alth rq~af(lil1g complications ofantirahi(~s therapy for the period 1~..J-5to 19..J-9are presented.

8-10David \Vllihwy Hldg. (26).The ma\{'rial ill Ihi, pap("r Irom the 1I1ichigall Departlllent of Ih'alth was made "vailable

to II' by I)r. (;. Il. CUlllllling', llired"r, BUH'all "f Lab"ratories. Translation of the arlirlt 11YStavro",kaya" was Ill"de hy Dr. I'eter G. Shifrin, Chief, lJi"j,i"n of Ortl1otwt!iu, (;ra""11""p;\al, !ktn,il,