Journal of Neuro-Ophthalmology, March 1986, Volume 6, Issue 1

Dilantin-induced long-term bilateral total external ophthalmoplegia.

A young, healthy woman underwent craniotomy for the resection of a corpus callosum arteriovenous malformation. She was slow to awaken from anesthesia and was later noted to have a total external ophthalmoplegia. Her mental status quickly improved but the total ophthalmoplegia showed only minimal improvement for 2 weeks. After ruling out possible cerebrovascular and anesthetic complications, we concluded that the oculomotor impairment was due to postoperative toxic levels of Dilantin. Toxic Dilantin levels are known to rarely produce total ophthalmoplegia. In previously reported cases, this has always resolved with normalization of the serum Dilantin levels. This case represents the first report of Dilantin-induced ophthalmoplegia that took at least 3 months to resolve; it provides a detailed documentation of the course of ocular findings.

Dilantin-Induced Long-Term Bilateral Total External OphthCllnloplegia Craig A. Fredericks, M.n., Stevl'11 I.. Ci,111110U,l, M.D., and AlirL'dl) A. Sadull, M.D., I'hD. A nlullg. IW,IIII1\' '\'llm.lI1 Ulldl'J'\'TIlI Lr,lllillh'm,' Ipr Ilw rl'sl'dillil 111.1 Cllrpus c.IIII,~um ,Hll'ri,"'I'Il11lh m,llI"rm,l­tillll, ~hl' \\-.lS Slll\\' tll .1\\',IKI'1l Iwm ,ml'~thl',i,1 ,md \\',l~ 101 tl'r llllll'd t,l h,l \'1' a tlll,ll I" krn,ll "ph Ih,llmllpll'gl,1 Hl'r nWllt,ll st<ltus quicKI\' imprlln'd bul the Illl.11 "ph­thillm'lplq~ i,l shll\\'l'd lInh' minim,11 imprll\'l'll1l'nl I"r 2 1I'1'l'Ks. Alter ruling oul p,,,,ibll' cl'I'l'brll\',l,CuloH ,md ,m­estl1l'tic cOlllplications, \\'l' ClllKludl,d th,lt till' "nd,,· motllr ill1p<lirment \\',l~ dul' III pIl~h'pl'r,lli\'l' Ill,1( Il,,'d~ oi Dil<llllin. To:-..ic Dil.lI1till Il'\'d~ .Hl' KIHl\\'I1 III r.Hl'h· pnlduCI' total Ilphthallllllpll'gi,l, III prl"'lllu~l\' rl'pllrll'~j cases, this has al\\'a\'s rl'~llh'l'd \\'ith llllrlll,lli/,ltioll III thl' serum Dilalliin I~'\'l'b Thi~ C,bl' rl'pn'sl'nh Ihl' lir~l repllrllll Dilanlin-inducl'd llphlh,111l111pll'gi'1 lh,ll tllllK ,II least ~ lllllnths tI' rl',<ll\'l'; It pnll'idl'~ a dl'l,ldl'd dll'"­mentatilln lli the course III llcul.H t'Jlldlllg" F'(l1ll 1111' 1l<'p",tl11l'l1h "I ~l'lll'"I"hl,',,1 ~lIrh,'n' Il'.'\f', ~l C, AA<.,) '1I1d Ilphlh,oInhll"h" (AA"). L:I1lI'l"~II\' "I ~,,"II1l'rn C.lh· l(lrIll,1 ~,h",,1 "' t\h-diu,1\', I ,,~ '\IIgl'l,'~. C"I,I<'rlll,1. Addn·........ l"tlrn· .... pondl·Il"..l· tlnd n'prlJlt n·qul".. t.... III Dr. :\. :\. Sddul1 "I I )q'"rlllll'l1h (II I )phth,oIlll"I"h" 'Illd I\:"l",,'"r~l'n' E~ll'II,' I )"h"I1" h',' F(llIl1d"IIl'". 11;; ",Ill I'"bl•• "I , I,,~ .-\11: hdl'~, ( A '1111111. U.s, A Oilantin I\'a~ iir.... t introduced ior the treatment lli ~eizures in IY:1S (I) It" I\'idespread use is testi­mllll\' tll its eiiecti\"L'ne"" and relati\'e saiety; hol\'­l'\" L'r. it is not \\'ithout tll'l.icit\', bllth acute and chn'nic. Cllmmnn ocular eiiech lli acute Dilantin intll'l.icatilln include blurring lli \'ision. diplopia, ll\·~t,lgIl1US, and \Mi,lble pupillan' changes. One l1i thL' mLlre unnlmnhln tll'l.ic reactions is that oi tLlt,ll l''I. te rna I Ilphth,llmLlplegl,l, In the past, this h,lS been repllrtt-d ,1-- an acutl' reactillll to high ~erum le\'els ~lf Dilantin that resLlh'ed soon after till' drug '\'as \\'lthdr,l\\'n and serum le\'els jell. rhe pre"ent repllrt dl"cnbes a case oi acute bilat­t'r, ll tLlta! ~lphthaln1l1plt-gia that did nllt quickl\' re­SIll\'(, \\'ith discLlntinu,ltiLln lli the Dilantin, CASE REPORT A :1-!-\'ear-11Id \\'llm,ln \\'as ,1dmitted to Hunt­ingtlln \lenlllrtal Hllspital l'n June 2, 1985, for surgiC,ll t''l.cisi~ln lIt ,1 (llrpuS c,lllosum arterio\'e­IlllUS m.1IiLlrmdtil1fl In 1470. tht' patient had had a singl,'. Sl'\'t're hl',h.i.1c11t' dssllciated I\'ith phllto­pllllbi. l .1I1d ned. stiffness lasting 10 days, for \\'hich she did nllt Sl'l'\... medi(al attention, She did I\'ell until IlJ82. I\'I1t'n she began ha\'ing recurrent 11l'.ld.Klll's :\ I\'Llr\...up b\' her iamil\' ph~'sician in­c1udl'd .1 C~lmpult'd ll\Jllllgraphk (CT) scan, which l'l'\'l',lkd the Mlt'rill\'enOUS maliormation. She SUbSI''1Ut'nth' underl\'ent angillgraph~' that delin­t'. llt'd the lesilln lLlc,lted in the middle one-third of the cllrpus (,lllL'sum (Fig. 1). The patient had no histlln' Ili seizures l'r neuroIL1gic symptoms. Her p,lst medical history was not remarkable and the llnh' medications she took were mild analgesics illr the headaches, Results of her admission phys­ical t"amination and preoperative studies were nLlrmdl. The patient declined the options of watchful P/L·\NTlN-/NPun/) ( W/ ITI I,.\IAH Wile/I' ':3 FIG. 1. Right internal carotid an­giogram. sagittal view, Straight arrows depict boundaries of the middle one-third corpus callosom arteriovenous malformation Curved arrows show dilated draining veins waiting t)r ftlcu~ed beam radiation therapy and elected ttl ha\'e the artt'ritl\'t'IWU~ maliormation surgically remtl\'ed, On June 3, 1985, the artt'rill\'enuu~ maliorma­lion was re~ected under general anesthesia, The patient was given 500 mg Dilantin intravenuuslv at the start oi the procedure and anutlwr 500 mg -l h later. A right parietal craniutunw was per­iormed, Prior ttl opening the dura, 20 mg iurose­mide and 50 g mannitol were administered intra­wnously, Two dural bridging veins were divided on entrance into the sagittal sinus, The arteriove­nous malformation \\'as approached through the interhemispheric fissure and was removed un­even tfull v, Immediately postuperativdv the patient did nut awaken irom anesthesia, She had "'pontanl'ou", respirations but muved her right -;idl' onlv tu deep pain; the pupils were irregular and sluggishl\' rt\1C­tive to light. A CT ~can ~howl'd on'" a small amount of blood in the ventricle and ..,onw air over the convexity, both oi which wert' to be npected after the surgery, Twu hou r.., iollo\\'i ng ..,u rgen' she became slightly more respon..,in', Tlwre W,l'" ,1 left arm paresis felt to be attribut,lbll' to injun' 10 parietal bridging \'eins and/or the IWllli"'plwric n'­traction, Complete bilateral l'xkrnal (lphth,lIIllO­plegia, including absence oi oculovt"il ibul,H n'­flexes, was noted. Over the next 24 h the patil'nt's nwnl,ll ..,t,llus improved and she was extubakd, On the Illorning of the second postoperative da\' the p,ltil'nt COlll­plained of diplopia. The serum Dil,1I1lin level \\..1.., found to be 35,2 f.l.g/ml (therapeutic r,lngl' C;-211 f.l.g/ml), The Dil,mtin wa.., then discontinued and she was given pht'nob,Hbita!. 30 mg three times per da\" ior seizure prophvlaxi~, On the iourth da\' ,liter surgen', the patient's serum Dilantin Il'vel wa.., l-l,h f.l.g m!. vt'! minima!. ii anv, eve movements clluld be elicited and her lids remained closed, Her mental statu~ was normal. On day 6, the ~erum Dilantin le\'el \\',]s less than 2,5 f.l.g;ml and there wa~ impn,\'ed strength in her leit arm and iace, She had bilateral ptosis and her pupils were llll\\' briskly reactin' tll light and near. The e\'l' nhl\'l'ment exalllinatilln demonstrated approximateh' 211 dil'pkr~ Ili eXIl­tropia on straight gaze with Illl e\'e ele\'ation and minimal depression, She \\'a~ able to ,lbduct and adduct her eves onIv ,lbllut 20-30'; , There \\',l~ nil nvslagJllu~ a wed. aikr surgcrv; her C\'C Jllo\'e­nwnh h,ld iJllpw\'l'd (lllh' Jllinilll.lllv, She delllon­slr, lll'd ,ln exolropi,l ,lnd "',lS ,lblc III Jlltl\'l' ht'r evcs on horiztllll,ll g,lIt' ,lblllit 50', ,lnd 11Il \'l'rtlc,ll g,Ut' 20-30'; , She still h,ld ,1 nlllderatl' ,llllllllnl lli pll'sis, This renl,lined hcr statu~ tln di~ch.Hge inlJll Ihl' hospit,ll 2 wl'l'b ,ltlcr surgt'rv, Otlwr studics dOlw whilc ~Iw was in the ho~­pit, ll included a illllll\v-up high-rt'~l)lutilln CT scm Ih,ll slwwcd nil structur,ll ksilln. ,ln ,lngiogr,lnl th,lt coniirnwd the tllt,ll rl'nll)\..ll lli the ,uterill\'e­IlIlUS Jll,llfllrtll,ltillll, ,1Ild l'kctwphv~iologic studit'~ (l'lt'cI rlll'nceph,llllgr,l Jll ,lnd bra instenl a ud itory t'\'oked plllt'nti,lls) th,lt wert' alsl) normal. The p,llit'nt W,]S seen I Il1llnlh after surgery, at which tillle silt' had nl) t'\'idt'nce of the previous It'lt .Hill ,llld iacl' p,lresis, SIlt' cllntinued to com­pl, lin of dipillpia. An l'x,lminatioll showed mild bi- ,\ 11,11 JII\I( "" II :1/ 1,lllT,11 l'I,I"j", ,1111"u,'uri,1, \I'i1h II", 11-11 pllpil 2 111111 I,H,~,'r Ih,111 1111' IIghl. dlld .I IIII111l1l1l"l11il.llll ,'\U' Irupid with .1 p.lrll'lIl.lrh' \1'('.11, 1"'1 I1lt'di.1I rt',lu" (hg 2), I hI' 1'.111"111 r"I'I'I"'d 111.11 Ih,' dlJ,IIII'I,\ ,llld l'll",i" ,"'.I"l'd .II'ulIl 2 11IUlllh" ,"1<'1' "lIr~,'1'\ :\11 '" .1111111,111"11 d"l1lt'II"Ir.J1l'll '\I'lhlll'IIIII'I.I III "lr.lI,I~hl ~,I/" bill ,,1i~hl"\Ullh\'II,1 III II~hl i~d/" IIU\\','I"', Ih,' ",It\,ld,'" ,lil1l"lIh ""I'llIl'd .I litll,' ,,111\1 III" Irt1I'h\"II.I"~I',11 111",\"1111'111,'111" "'IIIIII11I'd th,''''' ,lbI1lIrl11,II,'\',' II1U\"'l1lt'I1I'-, 1111" "llId\' ,1I"u "hu\\'('d Ih,11 \11lt'11 ,I "1111111111" '.Il1""d 111'1' til ".Ill .Id,' Iu tl", 11-11. Ilt'r I'Ighl ,'\'" wUlIld lI1,d,,' ,I hq'UIIlt'tll' ",II' ,',Idl' \\'Ilh 1111'11",'111.11' \l'r,~"11II' rl'lI'\"I'\', h,'r ''''I 1'\',' \I'111l1d 1'll'r"h,','1 ,lI1d 1"1 "I ,'I Wllh Il\T,'l11l'1I11 ","',',hlt·", DISCUSSIO\l Ihl' 1',llIl'111 1II1d,'r\\"'111 1','11111\,11 III ,I '"ITlI" (,II, 1""L1I11 ,lrl''I'II'I,'I1Ulh 1I1.1llurl1l.1tlllll, \\'\" ,,1,,\\ til ,1\\',Ih.1'11 Inll11 ,1Ilt'''lh''''I,I, ,1I1d 1111,111\ ,1\1'.\'(' \\'llh .I II-It Mill .Il1d 1,lll,11 I'.H""I" ,md ,I 11I1,11 bil,1ll'r,1I ,'\­krn" I,'phlh,lIllwpll'gi,l.ll1\' "'11'''ldl'd pMl'''''' \\'.1" allnbukd 1" rl'lr,l11illll "I II1\' rlghl hl'll1I"plll'r,' 111 ,unillndiun "'ilh thl' di\'j"ion of two cortical hlldgil1g 1"'il1'" bLlt Illl' bil,lkro1l 1'\ Il'rn,1 I ophthal­lI1ul'l,' giol "till fl'qLlin'd 1'\pl,1I1,ltion, EIlll'rgl'nt and 1,>111'\\"111' ( I "'oll1" rull'd "ut "m,l11 hl'lllorrhagl's III 1111.11'1 I'- '-,ll1ll' 1111' olrll'nU\'I'I1'llI" lll,111"rmatilln dr,III1"d 1111" lilt' d"'T \,'n"ll" "\',,tl'l11, 01 postorl'ra­111' 1' Ihrtllllhll'-I" 1I11,~hl h,l\'(' "'llhl'd "1l111l' stasis 01 1I'IIt'lI" "lIltl,,\\ Ir"lll th,' dor",,1 111l'''l'nll'pho1lon, IIII\\'I'Il'J', IU"I'\I,ul' .Ill,~ll,,~ro1pll\' shuwed normal d,',,1' \ ,'I1"U" .Il1dlllll1\ lilt' 1'"..,..,iI'II,,\, "' oll1 intr,II'pl'r,lti\'I' ,Hteridl dir ('111hullI" \\ .I" n'II'1 tl'll b"l,ILl"I' ul Ihl' lalk "I h"mo­, hl1olll1l' ,holl1g"" Il1lr,II'l'l'r,lli\'I'I\' ,1l1d the diqri­bllllllil ,o! tilt' 1I\'lIrlllll,~ll ddll'll It "trLlllLlral. thl' f'.III"I1t'" "f'hlhdI111'''"~ll Ilndlng" ""'Llld mtls! 11h."h 111, rlll1ln,",' .I 1""I"1l In 1111' middll' and upper bl.l,n"t"1ll 11,,\\ ,'I ,'r, Ihl' ,1b"I'ncl' "f l"ng tract "Ign" ,Illd 1Ilhl'r, r,ll1loll Ill'r\'(' ,lbn,'rl11,llitil'" in C(1n· '1I11l111111 \\Ith n'dl til I' pUI'J!" ,1I1d a n,,rl1101l ml'ntdl "1.llu,, \\,,.., It'll tl' Il1ltl~olk ",~,lIn"t "lIlh ,1 lesilln, Ih,III1"ll'1ll 1'1 tll..l'd l'tlll'llll,ll" ~,l\l' 11" 1'\'ldl'nCI' III ol !'r,11I1"1I'1ll 1111lJrl 1111' l'rtltr,lLIl'li ,\\\ ,Ih.l'nllh: Ir,lm ,1nl,,,thl'sia \\'as ,11'l'oHl'nth Iwl l,llhl'd b\' ,111\' "trllllural changes rl'''lIllin,~ t[(lm thl' "I'l'roltl\ln llr llthl'r drug interac- FIG, 2. Nine cardinal lields 01 gaze Patient (1 month postoperat I)' h ' , lId ' Ive Y IS S own to have several Itmlta- Ions 0 ucllons, In particular, she shows poor adduction (00 worse than OS) and abduction OS, [) II. \N r L\' I,\j [) Ill' I /) l )1'/ I I II. \ /;\ Il l/'II l ;/,\ 25 tion. To>.ic k'vt'ls lII DiI,lIl till C,lIl h,l \l' ,1 111.1 r"l'd efiect on cunsciuusnl'ss. I'hrl'l' III lin' l"llil'l1h with uIKllmpliC,ltl'd DiI,1I1Iil1-il1dul'l'd lll'hlh,dl1lll­ple~ ia discussl'd bv Spl'dllr l'l ,11. (2) \\l'll' II1IlI,dh Unrt'Sp,'nsin' tll nll,\illUS sti111uIi II is II"l'h Ih,1l l)Ur p,ltit'nt's pllstl)pl'r,llin' l'll111,l 11',1'" lhll' III .1 tl),\ic Il'n'l ul Dil,1I1 tI 11, \Ve bt'lil'\'l' this C,lSl' rl'pn''''l'l1h ,1 tll'\ll rl',ldlllil tl) DiI,1I1tin. m,1I1itl'stl'd b\ tllt,ll l''\lt'rI1,d llphlh.1l­n1l1pll'~ i,l, \\'h,lt is rl'l11,lr",lblc' III lhis II1 ... t,lllll· I'" the pt'rsistl'ncl' lIt such ,1 Clll11~1klt' dl'tll'll. whllh shl)\\'t'd Si~l1itic,ll1t i111I'rl1\l'111l'lll 1111" ,ll"'r 2 \\·t't'''s, In ,1dditIl111. thl' p.1tll·l1t· ... llll11l'll'll' 1'1'­Cl1l't'rV r,ln ,1 ClIlII'Sl' III ,It 11',1st 3 I11llI11h .... qUill' UI1­lik. t' prl'vil)US rt'pllrh III such rl',ldlllIlS. I'hls .11 ... ll represt'nts thl' lirst dl't,likd d,'scnpti' ll1 .1l1d dllCU­l11enl. ltil)n lIt llcul,H lil1din~s ,1I1d tlwir rl· ...lliutilln 111 this UnCl)l11ml)n Dil,lntin l'tkd In ,1 C,lSl' UI1Clll11­plicated Q\' l)tlwr dru~s lJr !1l'UWlllh ic disl',lSl' .... ()cul.1r paisI' as ,1 l11anitt'st,ltilln III Dil,1I1tin in­tl),\ lcatil)n \\',lS fIrst r,'pl1rtl'd bv r-.1,lIll,lp,lI (3) in 14:;4. Ht' discuSSl'd llnl' child \\'Ith bil,ltl'r,ll ,1b­ducens palsit'''' and ll!1l' \\'ith ,1 unilatl'ral ddicit, Ql1th LIt \\,hl)111 rl'ClI\·t'rt'd cl1mpll'tl'lv within 2 \\·eek.s. In 19(14, Orth t't a!. (-!) rl'pllrtl'd Illur C,l"'l'S l)1 partial l'r tl)tal ')phthaln1l1pll'hia in p,lt1l'nh rl'­ceiving Dilantin and primid'lJ1l', ,111 III 11'1111111 rl'­clwered within b davs, A simil.H C,hl' l1t I11I'\l·d In­to'\ ication \\'as rt'pllrtl'd bv RI,lir ,1I1d Cll-\\·llr"l'r... I:;) in 1%8, RusenQl'rg l't .11 (h) n1l'ntilln tIl'll 1',1­tients \\'ith supratl'ntllrialll'sillnS \\'1111 1\'l'rL' ta"in h Dilantin and \\'hll transient"· Il)St call1nc,ll''' in­duced e;.e mm'ements, In respunsl' tll that .Hticlt" Posner and Plum (7) indicatl'd that thl'\' felt this was due to Dilantin's l't'stibul.H dl'prl'ss,lIlt dll'c!. This proposed central n'... tibul.H rl'fll''\ dhruplilln was documented b\' I'll'dn1lwstagl11llhr,lplw in .1 Dilantin-to>.jc patient \\'ith intad \(llunl.n\' l'\l' movements but nll rl'SpllnSI' tll l'\lld call1nc... (:-I). Incomplete efiech III Dilantln lln lllUl.H I11ll\'l'l11l'nt have been describl'd a ... \\'1'11 b\' Bitll'nlllurt l'l ,11. (9) and Thurstun d a!. (10) In thl' fl'll'nt lill'r,l­ture, total externalllphthaln1l1p!l'gi,1 l,llIsl'li b l ' Di­lantin has bl'en rl'pllfll'd in li\l' p,ltll'nh b\' Spector et a!. (2) and in ll!1l' p,ltil'nl b\' ",1I1dv" (11). In all uf thl'sl' lasl· ... , till' p.1til'nt .... dl'lil'lh cleared soon after thl' dfUg \\',h \\'llhlll'ld llr lhl' dosage decreased, There is a spectrum llf llllll.H l'lklh III DiI,lnlin toxicity, from total extl'rnal uphth.11111l1pll'hi,1 tll partial deficits and uncllmplicatl'd Iwst,lgI11US. There may be a selective l'fied llt DiI,1I1tin p.HtilU­larly localized to the vestibul,H-visu,ll S\'stl·l11. I'hl' anatomic and physiulogic basis III vl'stibul.H-\'isu,ll il1ll'r,lltil'l1 h.1'" bl'l'l1 \\TII lit- ...cribl'd (12). Ell'ctro­pll\ · ... iulllgil .1l1d .1l1d 1ll1111C stud iI'S propllSL' I'X tl'n­... i\'l' bil,lll'l',lI Llln l1\'ll iun ... bl't \\'l'L'n thl' llculumlltur 11lIlll'i, II1\' l\'l1tr,i1 \'l· ... ,ibul.n S\'Stl'lll, and the Cl'fe­bl'lIu 111 , Il1l"l'l'rJl111'I1I,d dl1il11,d stud iI'S, thl' \'l'stib­ul, lI' I1l'unlll i111I'ul ...l· ... f,rllduCl' Inhibituf\' p"shvn­dl'liL pUll'111ldis III tlw l'cullll1ll1tur ,1I1d abducens 111lltur I1l'Urlll1'" 1111·dlall'd b\' (,;\13;\ (11). Oilantin I... "l1ll\\'11 lu l'llhdllll' (,;\();\ dllilln, \\'hich has led Spl'dur l'l ,d. (2) dlld l,tlwr... (I-!) tll p"... tlliatl' this .1 ... tlw 1111·l'hdlll ... 111 tl'r llw Pl'l uli.n tU'\ll fL'actiuns bl'il1g dl· ...lrJbl'd. I lU\\'l'\Tr, uur p,llll'nt had .1 llllllh lllUrl' prll­IUl1 h L'd rl'ad illn th,lt ld 11 nut "'1111 I'll' bl' ,1 ...cril1L'd tll tU'\il- DiI,1I1tll1 !l'n·l ... nwdlatlng enhaIllL'ml'nl uf C;\B;\ inhibltlun un till' \·isu,ll-\'l· ... tibul.u S\'stem, Our patient's lllllditiun pL'r...lskd t"r munths, de­spitt' therL' bl'in h nu dl'tL'ctabiL' amuunh uf Di­lantin in llL'r "'efum. ['t'rmallL'nt central nen'uus SVstL'1ll chanhL's pruduc,'d b\' Oilantin include Pur­" inIL' cl·1I dnlp-uut In till' cL'rL'bL'llum in buth an­im, lls and hUl11ans, ,IS \\'1'11 as sL'hIllL'ntal dL'm\'elin­atiun uf perJpllL'ral nL'nL'S in patiL'nts un chfllnic Oilantin t Ill' r,l 1'\' (I 'i, Ih) Althuugh a full e>.plana-tiun ut the pathugelwsi... is nut "nu\\'n, l\'l' pre ent this fl'puft tu dl'IllUnstr,ltl' Oilantin as a pl,s ible cause ul a pl'lllunhL'd tlltal L''\lt'rnal uphthalm,)­plegia. Acknowledgment: J11l' ,1lI1llllrs Ih,1n\.. \b :\nn D,lll',,'n 1(11' 11\'1' 11\'lf1 1\llh II1\' m,1I111scJ'lpl REFERENCES \kmlt. II II .1I1d !'1I11l,1I11 r I ""d,ul11 dl,'lwf1\ I h\­d, lll(llll1,ltV In till' trl',ltml'nt lIt l-l)l1\ul .... I\' ... • dl ....... )rdl'r.., 1.\ .11\ Ill: Illh.S lie,. I"" 2 ",'''li", R Ii I),llId, ," I, .. \ ,1I1d "',h\\ .HI/I11,l11 R I 1111l'I1\tlll11 llldllll'd ll~lhth,lll1llIF'lll'.~I,l \t'llll'll'\'1I 2b: ! 11\ I ! In~. 1"~I' 1, '1.11l1.1~),1/. 1"'" \l"dllll·n .... IltT'\.' ~),d .... \ III (1t!.11l111l1Iltll\ll-,1- tltlll I 1'((//1111 55: -;-1 -- jq;q ~ ll'lh 1):\ \IIlH',d,1 II I\''''h II ,11,,1 I h,"d,l \1 l )phlh,""1"1,1"hl,1 ,,·,ulllll h 1"'111 d','I"'1l1 1111 d.1I11""1 .1I1d prll1l1dlllh' Inhl\l\.dthlll l\l'~'"lrt llt tllur (,l ....l' .... 1.\.\1 ,.\ 201: ~S'i ~,S~. 1"h~ 1I1.lll ,\ .\ 11 . 11."11',k,·. I I 1""-"11,". I' 1 ,1Ild 1\'\11­h" iL'. I) 1 .\, uiL' dll,IH'1l1111ld,1I11""1 .11ld ,'"l11ld'liW plli­.... lllllll,l~ (n'.Iil'd b\ ~)l'rltllllt,.d dl,lh .... \.... I \t'llIll! .\t'lIll).,~l/I.\ 1\1/1/1/111111 .~I: ~~(l ;2"), jqhS " 1''''''·III>I''.h 1\1 sh,lIf"', I .llld 11",1. 1\ .,\l"l·nt \'"slll'- 1I1,n-lllld.lr n'lll'\l, ,Ind ,IlLIte .... lIpr,ltl'l1tl)t"\,ll Il' ... il)n"" ,. ,\'I'I(/I~1 .\r·II/(I"'/lI:~ j lltllldflll 38: t, Ill, Ilj~::; '7 l'lhlll'l. I I~ ,Ind 1)11I1ll. t ()\,lhl1l1 .... ti( ",ihllitic,ll1l-l' l)f \'e~- tlblllll-lllllldr n' .... F'llll .... l' .... (ll'tll'r) , \'(j{/(JI .\'(·II/(I~III".\. f\.I1(/I1­11" 1(3H:~2~ ~2K. Iq~~ S 1\,,1>111. I, 1\' 1111,1n11l1 "lIf'f""""I"n (INC "I till' I\h'nth). \/1/1 (llll! H7:2S4 2,"'1\ Iq~K 'I Ilill,·n'''lI't. I' I, 1\1 en·"tl·. 1\1 A. ,)J)d Rlclll'ns, A 0u,lnlll.ltl\'l' ,1 ........ l' ........ ll11'l1t lIt .... ll11)llth·pur.... uit L'~'l' 111l)\'t'- C /I. /RLDL!,/CI\S /J AL. Ilwllh III 11l..,llh\· .lIld l'plll'pill subl"lh, I N,'III"I, N,'III" '/I'.~ J"II'/II"'III~J: 111<1 11~4, 1<1,"11 1\1 I htU'slllll. S I I "Igh. 1\ I I\[,,'I. I ;\, dlld 1),,11'( )"", f· Sl{l\\' '-i,ll·l,llil· ... ,llld h\'P{lIlH'lrl.l til .llltllIHl\'td .... dllt Ill\­Il'lt, \'1'11I(1/1),\1/.1-l: 1:,l/1 I ")lJh, IlJS~ II S.lIllh~. 1\ 1,11.11 ,'\ll'lI1.11 lIphlh.III1H'f,I,'gld I1ldu'I'd b\ f'h"llI'!l'111 :\ \.1,,' "'pllil S "'II ;\"''' I os: 141 I,~~, ILIK4 12 Il.dllh. I, \\' dlhi 11\lIHlIbld, \' (lll1lt'IIII!Olilfll S, 'lIfO/O.\' l/ ~1·11t'.., \ (II 1,'1' ('/111/( III ,\'('//1(1/11,1/"/0/1':\1/ (If f!I,. l"",/I!I/ili/J .... 1/"'·/11 :\ 1\I\'IS ( 1I. l'hll.lLh-lphl.l, 1<l7ll, pp 7'1 7l) 11, Ubala, K, dnd Highstein, S. M.: Blocking by picrotoxin of both I"'stibuldr inhibition and GABA action on rabbit OCll­11InwI", Ill'urllnes. Aralll Res. 18: 538-543, 1970. 14 NlI/lIl', M , MizlInll, M" and Kaga, K.· Neurological findlllgs in diphenvllwdantoin intoxication. Ann, 0101. 82: lKY l L14, IY71 1'1 Il,rfflldlm, IV Cerl'bl'lldr il'sions after parenteral Dilantin ddrlllnisirdlilln !Vellrol"Xlf 8: 210-214, 1958, Ii> f'ls"", I S, dnd Pl'nn', J, K Adverse effect'> of phenytoin lin f"'r1ph,'rdl n,'n','S and nl'uromuscular lunction: A re­\' 1"11' '/'II"/hll/ 22: 407-471, 19K]