THE GROSS AND HISTOLOGI(rAL ANATOMY O F !I’HE: RR~BTNOF A C P C L ~ P S SIX FIGURES 1he coilgenital anomaly dcsignatcd by the term cylops cwiixists of a 1,ilateral symmctuical malformation of the hcatl r i ill wliicli there is ail absence of some of tlic mediaii striietures, or in which a t least these parts a r e poorly developed. I n more tliaii one hundred cases of this coiidition that liave been I-eported there has bceri suffic*icntindividual variation to make it at once apparent that this dcfiiiitioii of cyclops is hut partly applicable i r i specific instances. Perhaps, as suggested by ScI~.cr-alhe,~ a more inclusi\-e definition would be : that aiiomaly iii w-hic*hthe c y e s arc’ SO cle~sc~ly adjilwiit as to lie within a single orhit. The most strikiiig abnormality externally a p p e w s to he a single or ail apparent single eye u-liicli lies in the midline. This eye, l i o w c ~ e r ,is most common1;v produced 11y a fusion of two caompoiieiits and nxnally has two ~oriieae,hut thew may be N single cwriiea. Also, there caii be two separatc eyes lying iii a single orbit. The latter lies in a position where normally the root of the nose is present. Other structures , skull, showing some degree of malformation are the ~ i o s e the mid the brain. A careful liistologicd cxamiiiation of the brain in this iiistaiice lias revealed a number of interestiiig From t h r 1kp:irtiiic~t of Patliologp, Y;ile TJiiirersity School of Xedicinr, Tnstiiut tles :iIlpnc.ilicn Krankciih:tuses St. Cl(.org, 11:iniburg (Pi of. b’rietlricli Wolilwill, prowctoi ), tliroiigli the courtc.sy of Uoctor W c h r , of Mt:itlr, ( ~ r r i i i ~ i i i u, ~l i, o sul~initterltlir iii:it(~i:iI for study. ‘ Schmillw, E. 1913. Ilic. Morpliologic ( l e i Jlisshiltlnngc~itles 3lenxclirii uiid der Tiere, Tlieil 3, S. 205. :ind t h e I’:itliologisclics 19 ~iarro\vaiitl the posterior ~ v a l of l tlic sella is rather promincW. Anteriorly, tlie houiiclary of the sella is rounded ant1 COIICH\-~, ; i i i d ;IS ;I (wiiw(~iieiiw the anterior cliiioid processes are closei* together t l i ~ i ithey are normally. The middle fossae ant3 tlic petroiis portions of the ternpoi-a1 bones a r c normally formed. Tlw Iwstcbrior fossa is of a decidedly ronnd form, the diametei. ;it t l i v 1)tise lwiiig 5.6 cam. in lrlngth aiid 5 cm. in mitlth. Z i i tlic removal of tlic hraiii the vertehral arterics have h e i i cwt close to the basilar artery. The latter is large and well t l c ~ ~ c i l o p o ;uicl t l iiormally situated. Two arteries take origiii o i i citlici* sitlc from tlici hasilai* t o supply tlie a i i t c ~ ~ i omi(1 r Imstcrior parts of the inferior surfaces of tlic ceuc~lwllnm. Two very small pontiiie arteries arc also present b i l a t e r d l ~ . ?l I iisiinl siiperior cerebcllar artcries a r c present. Oil either sitlc a rathcr promiiiciiit tirtcrj- h a s ;iii m o m d o n s origin from t l i c h junction of the hasilnr aiid the posterior commiinicating aiatery, mtl tliese vessch also supply the inferior s u r f ~ c w of tlie ceidxlliim. l’lie postcirior c~~re1)ral arteries art‘ rJi*cs(wt, a s arc also t l i c b posterior communicating. The middlc c.erct,i.al artcries a r e both present ; thc right gives rise to t l i r aiiterioi. cerebral il1itl the left is ;m eiicl artery, ill t l i c b s(’iisc’ tlitit t1iei.c. arc 1 1 0 m t e r i o r communicating ~ i * t c ~ ito es cwmplctc! the circle of TVillis wiitcriorly. Iiiteriial c*ai*otid ;irtcbJ*icsciuiiiot he itlmtitiecl. 1 f o ~ ~ ii ~dl i t l (ii*ossl>-,tllc 0111;~criillid II~YVC’Y t h t ~ ~ 1 1be iclthiitifietl ar(1 the fifth, sixth, s i ~ e i i t l i ,and niiith, aiid tlicsc Iiavch a normal origin. Tlie olfi1dor:- and optic nerves (’ailiiot Iw fouiicl. Tlii~optic. cliiasm is iiot present. ‘lllio groatcist al~ioi~malities lie in the pallinm (fig. 3). This is i*epi*eseiitedby ti somcwliat c2ircular flattciiied tlisc 3.5 em. i i i tlimieter. It is slightly coiivcs oii tlic inferior surface aiitl (*oll(’i\\.e 011 the siipcrior, prescwt iiig the appearaace of tlie Ii~’ii(1 of a i l iiivci~leclin11s1i~wom.T1iei-e is 110 sepnmtion i n t o c * c ~ I . P ~ I .Iic~mispliercs. ~I~ Small clcvatioiis are present on 1~0th t lie superior a i d inferior surfaces and tliese rcpi-eseiit t tie of cercihr.al corivolutioiis. Tlie aiitcro-infcrior siii*faw of this disc>-likv sti*nctiii.cASIIOW‘R il gi*oo\--c~ iii tlic mitl- liiic which probably i*eprescnts the iiiideveloped loiigitiitlinal fissure. The mitlhraiii as a whole appears to bc wcll tlevelopccl and c~oi*respoiitls iii this clcvelopmciit to the stagc rcachcd I)? an Pig. 3 Brain of ryelops. Fig. 4 Longitudinal seetion of brain of cyclops. T H E RHAIN O F A CTCLOTS 25 Microscopic Beneath the pia of the cerehrum (fig. 5) is present a i i a r r o ~ ham1 of deiisely placed a i d dark-staining small rouiid cells, three o r four in thickness. Beneath these cclls is preseiit a Fig. .i I h w i n g of c*erc.l,r:il c o r t r x of cgrlops, t o sliow c!.to-;Lrcliitectul.nl structure. X o t e distinct lay%% Delafield 's hematorplin without counttrst:rin. X 65. wide, pale, and accllular zone wliich forms tlie molecular layer. Next can he seen a fairly continuous hand of small, round, dark-staining cells which correspoiitls to the external graiiular layer. The third layer coiltailis relatively few cells, which a r c of a lilrg-ci- size than those of the second layer, these cells biaiiig more numerous in tlie zone adjacent to thc second arid l t w Iiiimerous 11eai-the fourth layer. These cells liave amplc cytoplasm aiitl large pale iiiiclci, hut thtq7 a r c still round in sliapc~. The fourth 01'iiiiicr granular layer is composed of' small rouiid cchlls similar to those forming the S C C O I ~layvr, ~ oiiJ>- these (*ellsdo not form a continuous haiid a s do the cells of t l l P scco11tl layw. Tllc fourth lH!'er has a11 app"ar;iilcc~ similar to thc glomcrular zoiic in tlic hippocampal cortcx. r i 1 IIC. iicst, 0 1 - fifth, layer is composed of a mixture of t l i c w l9g. f i 1 ' l i o t o n i i ~ ~ ~ c ~ g r :of i ~ ~wrtrl)elltiii~ Ii of c y ~ l o p . Uel:ifidtl 'S Iicwi;itos\ l i t 1 cells and tlic iieurolhsts of the thin1 liiyw, aitli the smaller cells predominating. Tliis last layer, together n.itli tlic hixth, forms ii hmid of cells which is i * t i t I i ~ i wider than m y of tlic other laycrs a i d gradiially fuses with t l w ~iilworticalwhite matter. Tlic eiitire cortical cellular wri*aiigemeiit corrcsponds to this description, writ11 ti f e w minor ant1 iuiesscmtial variations iii diffcrent parts of the cortex. In the (:erebellum (fig. G ) , immediately bencatli the r)iii, is w haiid of small, dark, round cells. Then follows a n ncellnlar h i i ( 1 cwrrcymidiiig t o tlw molmilar layer of m o w mwtulxb s i i ~ i i vsmall ro11iici T H E BRAIN O F A CYCLOPS 27 brains, and this is followed 1i;v an inner granular layer of small round cells. I n the zone of transitioii between tlie molecular and the granular layers are present large cells which resemble somewhat the Purkiiije cells. The cores of white matter projecting into the granular zones are primitire i n their development. I n the regions of the brain corresponding to tlie central gray matter sire found large cells witli abwitlant cytoplasm which represent the primitive ganglion cells of these zones. However, tlie iiormal cellular architectiire of the ceiitixl gray matter is still lacking in development. 111 tlir pons tinti medulla are also fourid nests of ganglion cells represent iiig the arilagcn of the nuclear masses found in normal lmiiis, but the apparent lack of orderly arraiigement of these groups of cells makes it quite impossible to identify any of them. The ventricular ependyma is well formed aiid is composed of tall columnar cells. The leptomcningcs show no abnormalities. COMMENT I n commoii with the many cases collected by Schwalbe, the case prcseiitecl liere litis t i single orbital cavity in which is pi-eseiit oiie eyehall with one cornea. This rcpresciits the nsual fiiidiiig iii cyclops, though the eye map h ~ v eso man:variations as to make a siiigk descriptioii iiivalid for all cases. The iiose or proboscis in this monster is a small structure placed in the midline above the eye-a coiidition fo1111d in the majority of instances. The proboscis may be a doiihlc organ, hoxrever, or oiie having a diameter of a centimeter or two. There is a complete absciice of the nasal holies aid a malformatioil of the ethmoid bone, with flattciiiiig of the anterior cranial fossa. The sella turcica is slightly malformed. These a r c ratlier coilstant findings in all the reported cases. The cerebral malformatioiis a r e limited in tlie majority of instances to the forebrain aiid tlie midlortiin. The mesencephalon, met enccphalon, and myeleiiceplialoii may be normal. The forebrahi is never divided into hemispheres, and consists of a single mass that is of horxeslioe shape with the coiicavi t p upward and posteriorly. I t coiitaiiis ail niidividcd cda\.it- wliich corr.espontls to thc two lateral ventriclc~s. Tl1e cwrpus <:a110siim, septum pellucitlum, and fornix a r e a1)sent. is iilmost coiistaiitl?- aloscnt. ( )lily rarel?‘l’li(3 rlii~icnce~~lialon is tliei-t: prcwiit a single mcditilly placcxl olfnctory iierw, of i*iidimeiitar?-clevelopmcnt, rcprcsenting a fusion of the two olfwt ory ii(~rvcs. If the corpora striata arc at all prcsz~c~~t, t lioy a r c poorly clcvelopecl. Tlic thalami optici arc oftcin fusetl into a single structure. The base of the dicnc*cphaloii 1;icks a n y tliff’circiitiatioii. 111 plaw of the (wi.i)orti mwmillaria, iiifuiiclibulum, and the suhstantia yc~rforwtii t1ic.w is Inwent H pear-sliapetl mass ~vliose apex gives rise to a siiigle optic. iiervc. ()ccasioiially two defiiiite iierve 1~1~1itllcs form a i l optic cliiasm that gives rise to two separate optic. iwi-ves. At times the optic iicrws arc absent. A ixtlier conxtaiit aiitl ~uiiisual fiiitiiiig is prcseiit iii tlie iwof of the mesciiccphaloii. Normally, it is a thiii structure 1~1iic.l~ is reflcc*ted o v e r ;uid covers tlic clioroitl plcsiiscs. 111 (*yelops tliis i*oof is I)allooiietl out to form i~ vclsicl(h \vliicli i i t times reaches ail estraorc1iiiar;v- size and ca11, indeed, co\-er most of the foi*chlniiii 2111tl fill tlic grcater part of tlie crmiial w v i t y . I t s will is quite thin iiiid not iiifrequeiitlp is uiiitctl I I ~ torn in the removal of tlie with tlie durw, ~ C C H S ~ O I I ; Ibeing 1)riiiii. Tliv cpiphysis ;iiicl liywpliysis ai’c a s often a1)seiit ;is they are present. The craiiial nerres from the third to tlic twcilfth are usiia11;\. preseiit. (‘hangcs in the cwrd d i c i i 1I i t h y oc(wi* pi*rsciit no iuiif‘orm picturc. The vesicle iisua11;v- produced by an outpouching of the roof o f tlic mcsr.iiceplialori, iii tlie prescnt instance, is pi~odiic~vl hy a similar outponchiiig of the IT” of tlic tlicllcei)litiloi~. Iiitleecl, tliis vesicle simply represents H dilated tliirtl reiitriclc. r l ’ l i ~ h c*ei*ehi.alaqiicvliic t appears quite iioi.ma1. Iii 11011e of tlic cases reported hitherto has any titlequnte tlcscription heeii giveii of the histological structiire of tlic hrtiiii. I t is ;I mattchi. of some iiitowst, t h c ~ c f o r c t, o f i r i d i i i ii hrttin which grosslv presents so man?- anomalies it r a t l i c ~ iiormnl, if immature, cyto-arcliitcctiiri~lstructui.e in Ilie eoi*tex. THE B R A I S OF A CYCLOPS 29 There is a defiiiite arrangement of the cortical iicuronal clemeiits into six layers, and although the different cortical R ~ C H S lack the usual differentiatioil, it is nevcrtheless snrprisirig to fiiitl tlie fundamental and characteristic six-layer arrangement so sharply defined. To be sure, the individual ganglion cclls a r e not as maturely dcvcloped as is to be expected iii a n eight-month fetus. Oil the otlier hand, the histologic picturc of thc ccrcbcllum is quite in keeping with that of a normal fetus of the same age. The architectural disposition of the garigliori cells formiiig the central grap matter as well a s of those forming the iiuclcar structures in the poiis a i d meclnlla is of sncli a nature as to maltc impossiblch tlic positivc idciitificat ion of the structnrcs iiivolved. S U l l l Y A Ill' Tlrc cyclopic monster was the product of the tliird pregiiaiicy in a iiormal woman of thirty years and was clelivered 11y cesarean sectioii in the eighth moiitli because of placenta previa. The child lived two hours. I t pre~ciitedtlic usual malformation of the head, coiisisting of R single orbital e a ~ i t y placed in the mitlliiie aiicl cwntaiiiing oiic eyeball with on? cornea. il rudimentary pro1)oscis occurred in the midliiie above the eye. The skull \\-as malformed to the extent that thcrc was hit a single flat anterior cranial fossa produced by a maltlclevclopcd ethmoid hone. The brain presented the iisual liorseshoe-sliape~~,uiipaircd prosencephalon aiitl a greatly tlilatctl third veiitriclc. Tlie olfactory and the optic nerves, as well as tlie optic cliiasm, were not present. Positirelv ideiitified were oiily tlic fifth, sixth, seventli, a i d ninth cranial nerves. Histologically, thc cerebral cortex WIS the normal six-layer type, though the individiial ganglion cells x-erc immature in thcir dcvclopment. The cellular arcliitecture of tlic cerebellar cortex was that of a normal fetus of eight months. Thc basal ganglia and tlic nuclca~.miisses of tlicl pons niid mcdulla were poorly developed.