Arq Neu ro p siq u iat r 2003;61(4):942-945
CORPORA AM YLACEA IN TEM PORAL LOBE EPILEPSY
ASSOCIATED WITH HIPPOCAM PAL SCLEROSIS
M arlise de Cast ro Ribeiro, Lígia Barbosa-Cout inho, Fabiana M ugnol, Arlet e Hilbig,
André Palmini, Jaderson Cost a da Cost a, Eliseu Paglioli Net o, Eduardo Paglioli
ABSTRACT - Hip p ocam p al sclerosis (HS) is the com m onest p athology in ep ilep tic p atients und ergoing tem p oral lob e ep ilep sy surg ery. Besid e, there are an increased d ensity of corpora amylacea (CA) found ed in 6 to 63% of those cases. Objective: verify the p resence of CA and the clinical correlates of their occurrence in a consective series of p atients und erg oing tem p oral surg ery w ith d iag nosis of HS. Method: We review ed 72 hip p ocam p us sp ecim ens from January 1997 to July 2000. Stud ent’s t test for ind ep end ent, sam p les, ANOVA and Tukey test w ere p erform ed for statistical analysis. Results: CA w ere found in 35 p atients (49%), w hose m ean ep ilep sy d uration (28.7 years) w as sig nificantly long er than that g roup of p atients w ithout CA (19.5 years, p = 0.001). Besid es, when CA were found , d uration was also significantly correlated with d istrib ution within hip p ocam p us: 28.7 years w ith d iffuse d istrib ution of CA, 15.4 w ith exclusively sub p ial and 17.4 years w ith d istrib ution sub p ial p lus p erivascular (p = 0.001). Conclusion: Our find ing s corrob orate the p resence of CA in p atients w ith HS and sug g est that a long er d uration of ep ilep sy correlate w ith a m ore d istrib ution of CA in hip p ocam p us. KEY WORDS: hip p ocam p al sclerosis, corp ora am ylacea, tem p oral lob e ep ilep sy.
Corpos amiláceos associados à esclerose hipocampal na epilepsia do lobo temporal
RESUMO - A esclerose hip ocam p al (EH) é a p atolog ia m ais ob servad a em lob ectom ias tem p orais d e p acientes com ep ilep sia intratável. Além d os achad os histop atológ icos clássicos existe a p resença d e corp os am iláceos (CA) em até 60% dos hipocam pos ressecados. Objetivo: Verificar a presença de corpos am iláceos em hipocam pos d e p acientes sub m etid os a cirurg ia p ara tratam ento d e ep ilep sia e verificar se havia d iferenças clínicas entre p acientes q ue ap resentavam CA e aq ueles em q ue eles não foram encontrad os. Método: Foram revisad os 80 hip ocam p os ressecad os entre janeiro d e 1997 a d ezem b ro d e 2000 e, p osteriorm ente, os p rontuários d e 72 d os p acientes. Foi realizad o o teste t d e Stud ent p ara am ostras ind ep end entes, ANOVA e p osteriorm ente o teste d e Tukey. Resultados: Dos setenta e d ois p acientes estud ad os, 40 eram hom ens (55,6%) e trinta e d ois m ulheres (44,4%). Trinta e cinco (48,6%) ap resentavam CA e em trinta e sete (51,4%) não foram encontrad os. Houve d iferença estatisticam ente sig nificativa entre a m éd ia d e tem p o d e evolução d a ep ilep sia: o g rup o com CA ap resentava tem p o m aior d e evolução (28,97 anos) em relação ao g rup o q ue não ap resentava CA (19,54 anos), com p = 0,001. Tam b ém ob servou-se d iferença sig nificativa q uand o foi com p arad a a localização d e corp os am iláceos com o tem p o d e evolução d a ep ilep sia: os p acientes com CA p resentes d ifusam ente no hip ocam p o ap resentavam m aior tem p o d e ep ilep sia (p = 0,001). Conclusão: Ob servam os q ue o nosso estud o confirm a a p resença d e corp os am iláceos em hip ocam p os d e p acientes com EH e sug erim os q ue q uanto m aior o p eríod o d e ep ilep sia m aior é a d istrib uição d e CA no hip ocam p o
PALAVRAS-CHAVE: esclerose hip ocam p al, corp ora am ylacea, ep ilep sia d e lob o tem p oral.
Po rt o Aleg re Ep ilep sy Su rg ery Pro g ram , Ho sp it al São Lu cas d a Po n t ificia Un iversid ad e Cat ó lica (PUC), Po rt o Aleg re RS, Brazil. Received 26 Feb ru ary 2003, received in fin al fo rm 7 Ju ly 2003. Accep t ed 18 Ju ly 2003.
Dra. Arlet e Hilbig - Rua Quint ino Bocaiuva 283 / 401 - 90440-051 Port o Alegre RS - Brasil.
Hippocampal sclerosis (HS) is the commonest histo-pathological substrate in epileptic patients undergoing tem poral lobe epilepsy (TLE) surgery1. Characteristic
features include neuronal loss in Am m on’s horn fields CA1, CA3 and CA4, with relative sparing of neurons in CA2 and in the subiculum2, associated with
axo-dendritic reorganization. In addition, hippocam pal tis-sue resected in patients with TLE have an increased
density of corpora amylacea (CA), reported to be found in 6 to 63% of the cases3-6. These are spherical,
baso-philic structures which normally accumulate in perivas-cular and subpial regions of the central nervous system as a result of aging7-9. However, although CA are seen
in the context of neurodegenerative disorders2,3,8, their
Arq Neu ro p siq u iat r 2003;61(4) 943
We h ave b een syst em at ically exam in in g h ip p o -cam p al t issu e o f ep ilep t ic p at ien t s u n d erg o in g su r-g ery fo r TLE in t h e last 10 years11. Th u s, w e d ecid ed
t o st u d y b o t h t h e p resen ce o f CA an d t h e clin ical co rrelat es o f t h eir o ccu rren ce in a co n secu t ive series o f p at ien t u n d erg o in g t em p o ral lo b e su rg ery w it h h ip p o cam p al resect io n in m o re recen t years.
M ETHOD
We review ed t h e h ist o p a t h o lo g ica l fin d in g s fo r t h e p resen ce o f CA in 88 co n secu t ive h ip p o cam p al sp ecim en s
in w h ich a d iag n o sis o f HS h ad b een p revio u sly est ab lis-hed11. Tissue was resected as p art of the surg ical treatm ent o f p at ien t s w it h refract o ry TLE, fro m Jan u ary 1997 t o Ju ly 2000. All p atients und erw ent com p rehensive p reop erative evalu at io n as p revio u sly rep o rt ed12. We exclu d ed 16 p a-t ien a-t s w ia-t h d u al p aa-t h o lo g y (5 p aa-t ien a-t s), fro m a-t h o se w ia-t h m ore than 60 years of age (3 p atients) and also incom p lete m ed ical reco rd s (8 p at ien t s).Hist o p at h o lo g ical an alysis o f 72 hip p ocam p al sp ecim ens consisted ofneuronal loss and g lio sis fo r d iag n o sis o f HS at least in CA1 an d CA w ere ch a ra ct eriza d ed m o rp h o lo g ica lly: sp h erica l, la m in a t ed ,
Fig 1. a) Dif f use dist ribut ion of CA in hippocampus (PAS, object ive 20X). b) CA in subpial and perivascular t hrough PAS st ain (obj 20X).
A
944 Arq Neu ro p siq u iat r 2003;61(4)
h yalin e b o d ies, st ain ed w it h p erio d ic-acid -Sh iff (PAS) an d Gro cco t (Fig 1a an d 1b ).
Following the analysis of the histopathological m aterial, t h e m ed ical reco rd s w ere review ed t o co llect d at a o n sex, ag e at seizu re o n set , ag e at o p erat io n , p reo p erat ive d u rat io n o f rat h e ep ilep rat ic d iso rd er, ap p ro xim arat e an n u al p reo -p era t ive seizu re freq u en cy, -p revio u s e-p iso d es o f st a t u s epilepticus, and the occurrence of secondary generalization o f t h e co m p lex p art ial seizu res (Tab le 1). Fo r an alysis o f t h e d a t a , t h e p a t ien t s w ere t h en g ro u p ed o n t h e b a sis o f the p resence or ab sence of CA. The g roup of p atients who-se h ip p o ca m p i d isp la ye d CA w a s fu rt h e r su b d ivid e d according to their intrahippocam pal localization into those in w h o m CA w ere o b served (i) d iffu sely in t h e h ip p o cam -p u s, (ii) o n ly in t h e su b -p ial reg io n , (iii) an d in b o t h t h e sub p ial and p erivascular reg ions (Tab le 2). A SPSS softw are p ackag e (SPSS In c, Ch icag o , IL, USA) w as u sed t o p erfo rm st at ist ical calcu lat io n s. St u d en t ’s t t est fo r in d ep en d en t sam p les were ap p lied to com p are p ossib le d ifferences b et-w een g ro u p s. In ad d itio n , th e th ree su b g ro u p s o f p atien ts harb oring CA w ere com p ared throug h analysis of variance (ANOVA) an d t h e Tu key t est .
RESULTS
Fo rt y o f t h e 72 p at ien t s (56%) w ere m ale. Ag e at recu rren t seizu re o n set ran g ed fro m 1 t o 30 years (m ean , 6.7) an d p reo p erat ive ep ilep sy d u rat io n va-ried b et w een 3 an d 58 years (m ean , 24.1). CA w ere fo u n d in 35 p at ien t s (49%), w h o se m ean ep ilep sy d u rat io n (28.9 years) w as sig n ifican t ly lo n g er t h an t h at fro m t h e g ro u p o f p at ien t s w it h o u t CA in t h e h ip p o cam p u s (19. 5 years, p = 0.001). Fu rt h erm o re, w h en CA w ere fo u n d , ep ilep sy d u rat io n w as also sig nificantly correlated w ith their d istrib ution w ithin t h e h ip p o cam p u s. Mean d u rat io n o f ep ilep sy w as
22.7 years in p at ien t s w it h a d iffu se d ist rib u t io n o f t h e CA, w h ile t h o se w it h exclu sively su b p ial o r su b -p ial -p lu s -p erivascu lar d ist rib u t io n h ad seizu res fo r a m e a n o f 1 5 .4 a n d 1 7 .4 ye a rs b e fo re o p e ra t io n (p= 0.001, Table 2). In contrast, gender, age at seizure o n set , ag e at o p erat io n , seizu re freq u en cy, h ist o ry o f st at u s ep ilep t icu s an d o ccu rren ce o f seco n d ary g en eralizat io n d id n o t sig n ifican t ly d iffer b et w een t h e g ro u p s (Tab le 1).
DISCUSSION
CA are roughly round , lam inated , structures com -posed of glucose polym ers and a plethora of different p ro t ein s, in clu d in g h eat sh o ck p ro t ein s (HSP). Th ey u su a lly o rig in a t e w it h in a st ro cyt ic p ro ce sse s, although neuronal and oligod end roglial origins have o ccasio n ally b een rep o rt ed13,14. Th e p resen ce o f CA
in t h e resect ed h ip p o cam p u s o f p at ien t s w it h TLE u n d erg o in g su rg ery h as b een recen t ly rep o rt ed b y d if f e r e n t g r o u p s2 , 4 , 9 , 1 5 . Like w is e , Lo is e a u a n d Table 1. M ean epilepsy durat ion w as signif icant ly longer on t he group of pat ient s w it h
CA and t he demonst rat ion of ot hers st udied variables.
Variab les To t al Wit h CA Wit h o u t CA
To tal 72 35 37
Men 40 18 22
Wo m en 32 17 15
Ag e at seizu re o n set (m ean ) 6,71 6,04 7,34
Ag e at o p erat io n (m ean ) 32,81 35,42 28,01
Du rat io n o f ep ilep sy (years)* 24,13 28,97 19,54
Seizu re freq u en cy/an n u al (m ean ) 464,63 490,85 425,72
Previo u s St at u s 0 0 0
Gen eralizat io n seco n d ary 12 7 5
* p = 0,001
Table 2. Dist ribuit ion of CA w it hin t he hippocampus subdivided in t hree groups,it s f requences and mean epilepsy durat ion.
Dist rib u it io n o f CA Freq u en ce Mean ep ilep sy d u rat io n (years)
To t al 35 28,97
Hip p o cam p u s 16 (22,2%) 22,7
Su b p ial 9 (12,5%) 15,4
Arq Neu ro p siq u iat r 2003;61(4) 945
co lleag u es5 rep o rt ed ab u n d an t CA in t h e su b co rt ical
w h it e m at t er o f a w o m an o p erat ed fo r refract o ry CA in sim ilar series of patients, all showing that about h alf t h e p at ien t s h ave t h ese st ru ct u res in t h e res-sect ed sclero t ic h ip p o cam p u s4,6 . Fu rt h erm o re, t h e
lack o f co rrelat io n b et w een t h e p resen ce o f CA an d m o st ep ilep t ic variab les like ag e o f seizu re o r ag e at o p erat io n w as also p revio u sly rep o rt ed16. In co n t rast
w it h t h e la t t er st u d y fro m Belg iu m h o w ever, w e actually found that ep ilep sy d uration w as sig nifican-t ly relanifican-t ed nifican-t o nifican-t h e p resen ce o f CA, w h ich m ay b e a p at h o g en ically relevan t fin d in g .
Desp it e t h eir co m m o n o ccu rren ce in sclero t ic h ip p o ca m p i, t h e p a t h o g e n e sis o f CA is la rg e ly ig n o red , d esp it e rep o rt s su g g est in g t h at HSP9,17 o r
so m e p ro t ein s o f t h e S100 fam ily m ay b e in vo lved18.
Erd am ar an d co lleag u es9 rep o rt ed a sig n ifican t in
-crease o f an HSP su b t yp e in t issu e resect ed fo rm p at ien t s w it h TLE, b u t t h e ab n o rm al p ro t ein accu -m u lat ed o u t sid e t h e CA. St u d yin g n o n -ep ilep t ic t is-su e, Bo t ez et al.8 fo u n d ab u n d an t CA in t h e h ip p o
-cam p i an d d en t at e g yri o f p at ien t s w it h a h ist o ry o f recu rren t ep iso d es o f cereb ra l h yp o xem ic in su lt s. Th ey su g g est ed t h at t h e g en esis o f CA m ay b e p art o f a t issu e react io n t o b u ffer t h e accu m u lat io n o f free ra d ica ls a n d o t h er p o t en t ia lly d a m a g in g ele-m e n t s re su lt in g fro ele-m ele-m e t a b o lic d e ra n g e ele-m e n t s seco n d ary t o rep eat ed cellu lar st resses d u rin g life. Ou r fin d in g o f a sig n ifican t ly h ig h er o ccu rren ce o f CA in the hip p ocam p us of exactly those p atients who exp erienced recurrent seizures for long er p eriod s b e-fo re su rg ery su p p o rt t h is m et ab o lic h yp o t h esis o f t h e g en esis o f CA. In ad d it io n , w e sh o w ed t h at a lo n g er d u rat io n o f ep ilep sy sig n ifican t ly co rrelat ed with a m ore d iffuse d istrib ution of CA in the resected hippocam pi, which also suggest that repeated insults m ay p lay a role in the g eneration of these structures. If o u r fin d in g s are in d ep en d en t ly co n firm ed , t h ey a d d a n o t h e r p o t e n t ia l m e t a b o lic re a so n t o t h e
g ro w in g b o d y o f evid en ce su g g est in g t h a t ea rly rat h er t h an lat e su rg ery fo r m ed ically refract o ry TLE m ay ach ieve b et t er o verall resu lt s.
Acknow ledgements - To st at ist ic Alan Birck.
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