The LUMBAR FACET ARTHROSIS SYNDROME Clinical Presentation and Articular Surface Changes

8/3/2019 The LUMBAR FACET ARTHROSIS SYNDROME Clinical Presentation and Articular Surface Changes

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V OL . 69 -B , No . 1 , JANUARY 1987 3

THE LUM BAR FACET ARTHRO S IS SYNDROM ECL IN ICAL PRESENTAT ION AND ART ICULAR SURFACE CHANGES

S . M . E ISEN STE IN , C . R . PARRY

F rom the U n ive rs ity of the W itw ate rsrand

W e descr ib e a lum bar face t syndrom e in w h ich d isab lin g sym ptom s are asso cia ted w ith no rm a l o r n ea r-norm a l p la in rad io graph s. L o ca l sp ina l fu sion re lieved sym p tom s in 12 pa tien ts; the exc ised facet jo in tsu rfaces show ed som e o f the h is to lo g ica l changes seen in chondrom ala cia pate lla e and in os teoarth rit is o fo th er large jo in ts.

T he m ost frequen t change w as fo ca l fu ll-th ickness cartilage necro sis or lo ss of cartila ge w ith expo sure o fsubchond ral bone, bu t osteophy te form ation w as rem ark ab ly absen t in a ll specim ens. W e suggest th at the rea re both c lin ica l and h isto log ica l s im ila rit ie s b e tween th e face t arth rosis syndrom e and chond rom alac iapa te llae . F acet ar th ro sis m ay be a re la tive ly im portan t cau se o f in trac tab le back pa in in young and m idd le -ag ed ad u lts .

The design a tion non-sp ec ific low -back pa in im pliesfa ilu re to estab lish the pa tho log ica l chang es in m any ofthe pa tien ts w ho presen t w ith d isab lin g low back pa inand norm a l o r nea r-no rm al rad iog raphs. W e suggesttha t, am ong these pa tien ts , the re a re a t lea st tw osy ndrom es, each w ith a recog n isab le pa ttern o f pa in ;the se a re the face t ar th rosis sy ndrom e an d th e instab ility synd rom e. O u r inv estig a tio n a im ed top rov id e ev idence tha t pa tho log ica l changes in th ea rticu la r ca r tilag e o f th e lum bar facet jo in ts m ay b ere la ted to th e face t a r th ro sis sy ndrom e.

PA IN SYNDROM ESFacet a rth rosis syndrom e. In th is syn drom e pa in isag grav ated by re st in any pos tu re , inc lud in g recum bency ,an d is re lieved by repea ted o r co n tinu ous gen tlem ov em en t. R ising in th e m o rn ing is d iff icu lt becau se o fp ain and stif fn es s , w h ich ease as ph ysica l ac tiv ityinc rea se s. W hen rest is un av o idab le, pa in is comm onlyreduced by a pos ition o f lum bar f lex ion . B ackw ardb en d ing is restr ic ted by p ain ; fo rw ard b en d ing is u sua llyo f n o rm a l rang e and ch a rac ter , w ith little o r no p ain . W e

SM . E isenstein , P hD , FRC S, D irec torDep ar tmen t fo r Sp ina l D isorders, T he Rober t Jon es & A gnes H un tO rth opaed ic H osp ital, O sw estry , S alo p SY 1O 7AG , E ng land .CR . P arry, B Sc (H on s), R esearch F ellowUniversity of th e W itw ate rsrand M edical Schoo l, Y ork R oad ,Park tow n, Jo hannesb urg , Sou th A frica .Requests for rep rin ts sh ou ld b e sen t to M r S . M . E isens tein . 1987 B ritish Ed ito rial S ociety of Bone and Join t Su rge ry0301 -620X /87 /lO l 1 $2.0 0

have called these pa tien ts th e uppe rs b ecause of the irneed to be u p an d abou t o r con stan tly alte r ing pos tu re inord e r to reduce th eir p ain .

T h is typ e of pa in is recognisab ly sim ila r to tha t seenin degene rativ e o r in f lamm ato ry a rth r itis in o the rsyn ov ia l jo in ts , in clu d ing th e h ip , knee an d th ose o f thehand . A nky lo sing spo ndy litis in its ea r ly stages p rov ideson e c lin ica l m ode l fo r th is syn drom e ; in a yo ung adu ltw ith kn ow n d isease o f the sp ina l sy nov ial jo in ts , thep resen tatio n m ay be m uch as desc rib ed ab ove .L um bar ins tab ility . In th is syndrom e , by con tras t, th ep a tien ts are dow ners , w hose pa in is re liev ed b y re stan d recum ben cy an d in creases th ro ughou t the d ay .Forw ard bend ing is re s tricted by pain and charac terisedby sw ay in g or jerk in g m ov em en ts . T h is desc rip tion fitstho se p atien ts w ho have had som e sp rain o r s tra in ofsp ina l so f t tissues, th e re su lt o f un recogn ised or lo ng-fo rgo tten m inor in ju rie s . T his clin ical p attern m ayp rov ide a b e tter de fin itio n o f lum bar ins tab ility th an them ore ob jec tive d efin ition s w hich h ave fa iled in p rac ticalc lin ica l app lica tion (N ach em son 1985). O n e c lin ica lm ode l fo r th is sy ndrom e is sym p tom a tic spon dy lo lysis , inw h ich a sim ila r pa tte rn o f sym ptom s and sign s re su ltfrom th e unun ited fractu re.

T he diffe ren tia tio n o f these tw o pa tte rns is im po r-tan t and he lp fu l in bo th conse rva tive trea tm en t and pre -o pe ra tive investig atio n , bu t e lem en ts o f bo th pa tte rnsm ay be foun d in o ne pa tien t. T h e com bin atio nsyn drom e m ust be reco gn ised and no t allow ed to causeconfusio n . It re flec ts the fac t th a t an in te rve r teb ra lsegm en t m ay fa il in m ore than one o f its pa rts at the sam etim e . B o th pa in pa tte rns m ay be asso c iated w ith som erefe rred pa in in the low er lim bs, bu t th is can read ily be


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d is tin gu ished from the m ajor d isab ling pa in p roduced byne rve roo t com p ressio n .

W e have inv estig ated 1 2 pa tien ts w ith th e faceta rth ro sis sy ndrom e in an a ttem pt to re la te th is topa tho log ica l ch an ges.

PAT IENTS AND M ETHODSO f a ve ry la rge num ber o f pa tien ts seen fo r low backpa in , 1 2 p a tien ts w ith ch a rac te r is tic face t a rth ro sissy ndrom e and sign if ican t d isab ility w ere fu llyinvestig ated . N ine o f th e p a tien ts h ad h ad sym ptom s fo ran av e rage o f 1 5 m onth s b efo re refe rra l, an d th ree fo r 12to 20 years . A ll had failed to respond to conserv ativetrea tm en t g iven fo r an ave rag e o f fou r m on ths a fte rre ferra l. F o ur pa tien ts had som e low er lim b p ain bu t o f ales se r d eg ree than the ir low b ack pa in .

There w ere 1 1 w om en and one m an w ith agesrang ing from 24 to 6 0 y ea rs . T h e av erage age w as 4 0 ;on ly o ne p a tien t w as un de r 30 and one ove r 5 0 . Pain an dtende rness w ere localised to th e g en e ra l a rea o f thelum bosac ra l ju nc tion in all case s . Tw o pa tien ts had h adprev ious sp ina l op era tions : o ne an L5 lam in ec tom y andon e a lum bosacra l d iscec tom y .Investigations. P lain rad iog raphs o f th e lum bar sp inew ere he lp fu l on ly in exc lud ing oth er causes o f b ackache .In four pa tien ts they w ere no rm al, in th ree the re w as ade tec tab le dec rease in th e jo in t space o f the lum bosac ralface t jo in ts . M ild redu ctio n o f in te rve rteb ra l d is c he igh tw as seen a t on e or m o re lev els in six p atien ts , and on ep a tien t had a lum bar sco lio sis .

Osteophy tosis o f the lum bar face t jo in ts , comm onlyassoc ia ted w ith lum bar sp ondy los is, w as n o t seen .

C om pute rised tom og raph y fa iled to sh ow anyadd ition a l pa tho lo g ical ch an ge in the face t jo in ts an dshow ed no o the r segm en tal sou rces o f pa in . M orespec ific loca lisa tio n o f th e cause o f sym p tom s w asach iev ed by face t a r th rog rap hy or by d iligen t p alp atio nfo r po in ts o f m axim um tende rness fo llow ed by rad io -grap hs w ith sk in m ark ers . A rth rog raphy w as con side redto be po sitiv e on ly w hen the in jec tion reproduced som eor a ll o f th e u su al sym p tom s, and when som e re lie f w asp ro v ided by sub sequen t in f iltra tion w ith ligno cain e.S evera l o f th e pa tien ts had negative lum bar m ye log raphyan d d is co grap hy in the search fo r o th e r causes o f th eirpain .O peration . A ll 1 2 patien ts had po stero latera l andin te rtransve rse fusio n ope ration s. B o th L4-5 and L5 -S lw ere fu sed in seven pa tien ts , L 5 -S l a lo ne in fou rpa tien ts , w h ile fusio n from L 2 to the sac rum w ithH arr ing ton in strum en ta tion w as requ ired fo r a 32-yea r-o ld w om an w ith p ro g re ss ive sco lio sis and in trac tab lefacet pa in a t th e lum bosac ra l jun ction .

D u ring the opera tion s the face t jo in ts w ere exc isedand pre served fo r h is to log ica l ex am ina tion . S ec tio nsw ere cu t p e rpend icu la r to the p lane o f th e jo in t ands tain ed w ith e ithe r haem a toxy lin and eosin o r to lu id in e

b lu e. T he face t jo in t cap su le s had necessa r ily beend am aged or destroy ed and cou ld n o t be stu d iedh isto log ical ly .

To provide som e contro l m a teria l w ith ou t to o m uchpo stm o rtem ch an ge the low lum bar face t jo in ts w ereexc ised from fo ur fresh cadave rs w hose k idn ey s w erebe ing taken fo r tran sp lan ta tion . D eath had o ccurred a tages rang ing from 1 7 to 48 yea rs and the spec im ens w ereexam in ed in th e sam e w ay as th ose o f the p a tien ts . I tcou ld no t be estab lished w he the r o r no t the se sub jec tshad su ffered backache .

RESULTSFacetjo in ts. T here w as som e ev idence o fea r ly d am ag e toarticu la r ca r tilag e in th e face t jo in ts o f a ll I 2 p a tien ts .T h e m ost frequ en t f ind ing w as a fo cu s o f fu ll-th ick nesscar tilage nec ro sis , bu t w e a lso saw u lce ratio n , f ib r illa tionan d ebu rn atio n (F igs 1 to 4 ) . W e susp ec t th a t theca r tilag e u lce r is the re su lt o f sloug h ing of a p lug o fn ec ro tic car tilage .Chondrocy te c lus te rs , fo c i o f fib rocarti lag e (F ig . 5 )and in creased pe richo ndrocy te m e tach rom asia p ro v idedev id en ce o f rep air . T he o n ly no tew o rthy chang e in thesu bchondra l bon e w as ea rly subchond ra l cy st fo rm a tion(F ig . 2 ). N o spec ific p a rt of th e face t su rface appea red tob e pa rticu la rly in vo lved and , s trik in g ly , th ere w as noo steo ph y te fo rm a tion in an y specim en .

The comm on fea ture o f all spec im ens w as theexpo su re o f sub ch ond ra l bo ne , som etim es in an u lce r, o re lse po ten tia lly p re sen t in an a rea o f fu ll- th icknesscar tilage nec ro sis .

The contro l sp ec im en s w ere com ple te ly norm a l inth ree sub jec ts aged 1 7 , 17 an d 26 yea rs , b u t in a 48 -yea r-o ld m an k illed in a m oto r v eh icle accid en t the re w assu rface fib rilla tion o f th e ar ticu la r ca r tilag e and m inorperiph era l o steophyto sis in all lum bar face t jo in ts ,w ith ou t ev idence o f an y focal ca rtilage nec ro sis .Clinical re su lts . O ne pa tien t requ ired rev ision of h isfu sion fo r pseu da rth ros is , bu t a ll pa tien ts ach iev edgratify ing p ain re lie f in an av erage o f 3 .5 m on th s af te roperation.

D I SCUSS IONM any o f the h is to lo g ical changes w hich w e found haveb een desc r ibed in c la ssic and standa rd tex ts a s those o fosteoa rth ritis o r a rth r itis d e fo rm ans (A y ers 1 935 ;L eubn er 1 936 ; O ppenh eim er 1 938 ; B adg ley 1 94 1 ; P u ttian d Logr#{2 44} sc ino 1952 ; L ew in 1964 ; S chm orl and Ju ngh -an ns 1 971 ; V erno n-R ob erts 19 80) . A ll th ese stud ies a rean atom ical desc rip tio ns on ly an d the re fo re cann o t re lateth e abn orm a lities to the cau ses o f low b ack pa in . A ye rs(1935) d escrib es w ha t is p ro bab ly the f irs t exam ina tiono f a lum bar face t jo in t ex c ised a t ope ratio n , b u t th eh isto logy sugg es ts in flamm atio n rath er thandegenerat ion .


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T hese stu d ie s do , how eve r , a ll em phasise osteop hy-to sis or bony spurrin g as an im portan t fea tu re of th epa tho logy of os teo arth r itis . A fin d ing w h ich d oes no tappea r to have been desc r ib ed prev iou sly is the fu ll-th ickn es s nec ros is-in -situ show n in F igu re 1 , bu t th is isno t a ssoc ia ted w ith osteo phy tes and re sem ble s the in te rm ed iate stage destruc tion w hich M each im ( 1980)reported in h is s tudy o f ex cised fem ora l head s , and th ebasa l degene ratio n desc ribed by G ood fe llow , H ung er-fo rd and W ood s (1 976 ) in ch ond rom a lac ia p ate llae .

T he atrop h ic fea tu re s w e fou nd in the a rticu la rca rtilage o f o u r re la tive ly yo ung pa tien ts ra ise s th eq uestion w hich is cu rren tly ex e rc is ing th e m in ds o f those

H isto lo gic al section s of face t jo in ts exc ised from patien ts w ith face tarthro sis syndrom e . F igu re 1 - Full-th ickness cartilage necros is,betw een the sh ort arrow s. Th is sh ow s ligh ter s ta in in g and no viab lechond rocyte s. The re is som e separatio n at th e ca rtilage -bone junc tio n(lo ng a rrow ) and th e sp ace is f illed w ith exud ate (to lu id ine blue, x 7) .F ig ure 2 - A n articu la r car tila ge u lc er w h ich exp ose s bone . T his ispre sum ed to rep re sen t a sta ge beyond the n ecrosis -in -situ in F igure 1.An ea rly cy st in subchondral b on e is arrow ed (to lu id ine b lu e, x 3).Figure 3 - A fibr illa tion cle ft w ith adja cen t car tila ge necro sis dow n tobon e. C hond rocyte clu ste rs are arrow ed (to lu id in e b lu e x 1 2). F igure 4- To sh ow groov ed eburna tion expo sin g sub chond ra l b on e. Afibroca rtilag inou s plug (b etw een arrow s) fi lls a cy st (to lu id ine b luex 3 ). F igu re 5 - Full- th ickn ess fib rocarti lag e (b etw een arrow s) at th eed ge o f an u lc er wh ich expo se s sub chond ral b one (to lu id ine b lu e,

x 12) .

Fig. 5

eng ag ed in the stu dy o f ch ond rom a lac ia pa te llae (G ood -fel low C t al. 19 76 ; Insa ll 19 82 ; B en tley and D ow d 1984 ;B en tley 1985 ): w he th er th is is m ere ly a stag e in th ecou rse o f c las sic sp ondy lo tic osteoa rth r itis (O u te r-b r idge 1 961 ) o r a pecu lia rly sym ptom a tic v arian t o f it.There are s im ilarit ies be tw een the face t a rth ro sissy ndrom e and chondrom alac ia p ate llae . T h ese sim ilar i-tie s a re fo und no t on ly in th e h isto log ical chang es o f fu ll-th ickn ess car tilage nec ro sis , s ep ara tion o f car tilage frombone , chond rocy te c lu ste rs and m etach rom asia (G ood-fe llow e t al. 1 976 ) bu t a lso in the c lin ica l p re sen ta tion ; inbo th condition s rela tiv ely young pa tien ts m ay presen tw ith sev ere d isab ility from pain , assoc ia ted w ith lo ca l


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tend erness and norm a l p la in rad io g rap hs.A s in cho nd rom alac ia pa te llae , the rela tio nsh ip

be tw een th e h is to lo gy and the sym p tom s in face ta rth ro sis is no t c lear . C lin ic ian s m ay fee l in tu itiv e ly tha tthe deg ree o f pa in in bo th co nd itio ns is d isp rop ortiona teto the phy sica l changes w h ich can be dem onstra ted . W ehave prop osed th e term ch ondrom a lacia face tae , ifo n ly to con fe r a d eg ree o f re spec tab ility u pon thosepa tien ts w ho do no t qu alify fo r a d iag nosis o f sp ina la rth ritis and a re som e tim es un ju stly c lass ified aspsy ch o log ica lly susp ec t. F if ty years ag o H ugo L eubne r(1 936 ) ap pealed to co lleagu es to consid er a d iagno sis o fea r ly a rth ritis de fo rm an s in p atien ts p resen ting w ithlow back pa in b u t no rm a l rad iog raphs. W e sugg est tha tth is appea l is n ow supported b y a lin k be tw een sym ptom sand p ath o log y . W e a lso su spec t tha t a sim ila r synd rom em ay presen t in the tho rac ic sp in e , th at it c an b ed istin gu ish ed from m yofasc ia l pa in and tha t it m aysim ila rly req u ire sp ina l a r th ro desis if o th er trea tm en tfai ls .

T he cau ses fo r the a r ticu la r chang es w e hav edesc ribed a re o bscu re, bu t n o les s so th an tho seco n jectu red fo r ch ond rom a lac ia pa te llae , w h ich in clu dev aria tions o f no rm al b iom echan ic s , traum a and gene ticp red isp ositio n . It is poss ib le th at a sym m etric ang u la tiono f lef t an d righ t face t jo in ts co u ld p rodu ce stre sse ssu ff ic ien t to cause ea rly a rticu la r ca r tilag e in ju ry , bu ta symm etry w as n o t a p rom inen t fea tu re in o ur pa tien tsand ye t is so com m on (B adg ley 1941) tha t it m ay beco nside red to be a va ria tion o f no rm a l ana tom y . P u tti(19 27) o rig ina lly d escr ibed these anom alie s o f face tang u la tion as a p ossib le cause o f ne rv e ro o t com p ressio nand sc ia tic p ain rath er th an low back p a in . L os s o f h eig h to f an in te rv er teb ral d isc can b e exp ec ted to p rod uceinc rea sed p re ssu re o n the facetjo in t su rfaces p oste rio r toit (D un lop , A dam s and Hu tto n 1984; Y ang and K ing1984 ) b u t in m ost o f ou r p a tien ts the d isc spaces w ere o fnorm al h e igh t or on ly sligh tly redu ced . W e found littlechang e in th e su bchondral bo ne of the face t jo in ts ,ce rta in ly no th ing like the p ate lla r osteo porosis desc rib edby D arraco tt and V ernon -R obe rts (197 1) .

The obviou s a rgum ent ag ains t an a ttem p t to relatem inor chang es in ar ticu la r su rfaces to m a jo r pa insym p tom s is tha t the se changes are p rob ab ly a lm o stun ive rsa l in m idd le-aged adu lts y et few have d isab lin glum bar pa in . Th e purpo se o fo u r lim ited study of cadave rm ate r ial w as to attem p t to d iscov er if th e desc ribeda rticu la r changes w ere in deed u n ive rsa l. T he resu lts sofar a re un satis fac to ry ; m os t o f th e few rena l tran sp lan tdonors ava ilab le fo r s tudy a re young adu lts and noaccu ra te h is to ry o f sp in a l pa in is ava ilab le. W e have tofall back o n the find in gs o f P u tti and Logr# {2 44} sc ino (19 52 )th at sub jec ts unde r 30 yea rs o f age had norm a ljo in ts andth e v ast m a jority o f th ose unde r 40 had only m ilda rth ritic changes.

The m echan ism w hereby th ese p a tho log ica lchang es m ay p ro duce p a in is no t kn ow n . T he con cep t

tha t inc reased jo in t p ressu re is tran sm itted to p ain-s en sitive subchondra l bo ne th roug h foc i o f n ec ro ticca r tilag e, a s desc rib ed fo r th e p a tella by G oodfe llow e t a l.(19 76) , is p lausib le. A ny attem p t to exp la in m a jo r p ainb y rela tive ly m inor changes co nfined to a rticu la rca r tilag e is confro n ted by th e fac t, w e ll kn ow n toc lin ic ians in th is f ie ld , tha t m any pa tien ts p re sen t w ithm inor sym ptom s in th e p resence o f advanced jo in td es tru ctio n , sc leros is and os teo phy tosis . E xp lana tion sfo r th is opposite s itu ation a re a lso con jectu ral . It ispossib le th at w id esp read lo ss o f ca r tilag e allow s arela tive ly even d iffu sion of jo in t p re ssu re in to thesubchondra l bo ne , p rod uc ing le ss pa in than tha t resu lt-ing from hig h con cen tra tions o f p re ssu re actin g th rou ghsm all a rea s o f ca rtilage los s .

Face t syndrom es h ave been desc ribed p rev iou sly ,bu t w ith d iffe ren t fea tu re s on each occasio n . G horm ley(193 3) p ion ee red the asso cia tion o f low back pa in w ithrad io g rap h ic ev id en ce o f ad vanced d egene ra tivechan ges in the face t jo in ts . H e d id no t d is ting u ishbe tw een a rth ritis and in stab ility , bu t ven tured to suggest,w ith som e d iff idence , tha t sp ina l a rth rod esis p ro ducedsym ptom atic re lie f. M oon ey and R ob e rtso n (197 6) a lsofa iled to m ake th is d is tinc tion bu t m ade a m a jo rcon tr ibu tio n by d escr ib ing jo in t in jec tio n fo r th e id en tifi-catio n o f sym ptom a tic face t jo in ts and fo r trea tm en t o fpain .

Our patien ts m ost c lose ly resem ble the respondersto lo ca l in filtra tio n describ ed by Fa irbank (1981 ) excep tth a t o u r p atien ts ex pe rienced m ore pa in w ith th e ir jo in tsunder com press io n (lum bar sp ine in ex tension), andre lief w ith jo in t su rfaces sepa ra ted (lum bar sp ine inf lex ion ) .

Fo r a pa tien t d isab led by pa in re frac to ry toco nse rv ativ e m easu res w ho is fac ing ope ratio n fo r sp in alfusio n , d iag nosis o f the respon sib le segm en ta l lev el o rlev els is c ruc ia l. C om pu ter ised tom og raph y offe rs nom ore th an pla in rad iograph s, un less the re is adv anceddegene ration (C arrera e t a l. 1 980). Face t arth rog raphy ,w hile in vasive and p ain fu l, rem a in s the b es t p re -o pe ra tive inv estiga tion by v ir tue o f th e p rov oca tion o fp ain in the a ffec ted jo in ts (P a rk an d M cC a ll, pe rso na lcomm unicatio n 19 76 ; F a irbank et a l. 19 81) . T hea rth rograph ic abno rm a lit ies d esc ribed by D o ry (1981)a re o f seco nda ry im portance bu t m ay prov id e usefu lcon firm a tion o f a p ositive pa in re spo nse .

CONCLUS IONSW e have describ ed lin ks be tw een a c lin ica l synd rom e oflow back pa in , lo ca lisa tion o f th e so urce o f pa in in facetjo in ts , h is to log ica l ab no rm a litie s in the exc ised jo in tsu rfaces and c lin ica l relie fob ta ined th rou gh fus ion of th ea ffected segm en ts .

The causes fo r the face t jo in t abnorm alities rem ainunknow n and the asso cia tio n be tw een th ese a rticu la rsu rface chang es an d p ain has no t b een proved ; i t rem a insa m atte r o f con jec tu re .


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THE LUMBAR FACET ARTHRO SIS SYNDROME 7

VOL . 69-B , N o. 1 , JANUARY 1987

A t th is s tage , it is im po ssib le to b e dogm aticas to w h eth er the facet sy ndrom e w e have desc rib ed(ch ond rom alac ia face tae ) is a d is tinc t n on-os teo phy tica rth rosis , o r m erely a stage (po ssib ly reve rs ib le ) in th ep rog re ssion of age -re lated h ype rtro ph ic o steoa rth ritis . I tis im portan t th at the cond ition sho u ld be reco gn ised sotha t pa tien ts w ho a re d is ab led by the syn drom e m ayrece ive ap pro priate trea tm en t ra the r than b e con side redneuro t ic .The auth ors a re g rate fu l to D r F . Sp iro and D r I. V an N iek erk for therad io lo gic al in ves tig atio ns, to M rs Co leen W aith er for the h isto logypreparatio ns, to D r Je rem y Fa irb ank for m aking available theex ce llen t trans la tion by J. H art o f the paper by Putti and Logr#{244}sc in o ,and to M s D olo res Rokos for th e illustrations .

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