CORPUS CALLOSUM STIMULATION AND STEREOTACTIC
CALLOSOTOMY IN THE MANAGEMENT OF REFRACTORY
GENERALIZED EPILEPSY
P R E L I M I N A R Y C O M M U N I C A T I O N
RAUL MARINO JR.* — GARY GRONICH *
S U M M A R Y — Corpus callosum stimulation produced by c h r o n i c a l l y i m p l a n t e d electrodes, placed e i t h e r b y c r a n i o t o m y o r s t e r e o t a c t i c a l l y , f a i l e d to control r e f r a c t o r y g e n e r a l i z e d e p i l e p s y i n humans a n d also i n e x p e r i m e n t a l l y p r o d u c e d p e n i c i l l i n e p i l e p s y i n cats. H o w e v e r , the p a t i e n t s that suffered, c r a n i o t o m y , frontal l o b e r e t r a c t i o n or p n e u m o e n c e p h a l o g r a m s , w i t h o u t callosal section, s h o w e d r e m a r k a b l e i m p r o v e m e n t of t h e i r seizure c o n d i t i o n due to these, unspecific m a n i p u l a t i o n effects. Stereotactic a n t e r i o r c a l l o s o t o m y e m e r g e d as a sequel of these functional n e u r o s u r g i c a l f i n d i n g s , a n d as an a l t e r n a t i v e p r o c e d u r e to preclude undesirable n e u r o p s y c h o l o g i c a l and n e u r o l o g i c a l side effects of split brain s y n d r o m e and of b r a i n retraction, associated t o c o n v e n t i o n a l c a l l o s o t o m y . T e n patients w i t h v a r i o u s d i s a b l i n g convulsive d i s o r d e r s h a v e u n d e r g o n e this n e w operation, w h i c h s h o w e d to be less traumatic and better t o l e r a t e d than o p e n c a l l o s o t o m y .
Estimulação do corpo caloso a calosotomia estereotáxica nas epilepsias generalizadas refratá-¬ rias: comunicação preliminar.
R E S U M O — A e s t i m u l a ç ã o crônica d o corpo caloso, o b t i d a p e l a i m p l a n t a ç ã o de marca-passo e e l e t r o d o s i m p l a n t a d o s , c o l o c a d o s a t r a v é s d e c r a n i o t o m i a ou e s t e r e o t a x i c a m e n t e , não controla, em humanos, ou em animais e x p e r i m e n t a i s , a e p i l e p s i a g e n e r a l i z a d a refratária. P o r outro lado, e m pacientes c r a n i o t o m i z a d o s , a r e t r a ç ã o d o l o b o frontal ou a r e a l i z a ç ã o d e pneumen-¬ c e f a l o g r a m a s , sem secção calosa, resultou em i m p o r t a n t e m e l h o r a do q u a d r o c o n v u l s i v o , em r a z ã o d e e f e i t o s inespecíficos de m a n i p u l a ç ã o do encéfalo. A c a l o s o t o m i a e s t e r e o t á x i c a a n t e r i o r e m e r g i u c o m o conseqüência desses achados n e u r o c i r ú r g i c o s funcionais e c o m o p r o c e d i m e n t o a l t e r n a t i v o p a r a p r e v e n i r e f e i t o s colaterais i n d e s e j á v e i s , tanto n e u r o p s i c o l ó g i c o s c o m o neuro-lógicos, tais c o m o : ' s p l i t brain s y n d r o m e ' e r e t r a ç ã o c e r e b r a l , associados à calosotomia convencional. D e z pacientes c o m v á r i o s t i p o s d e s í n d r o m e s convulsivas incapacitantes foram submetidos a esta n o v a i n t e r v e n ç ã o , q u e se m o s t r o u menos t r a u m á t i c a e m e l h o r t o l e r a d a q u e a c a l o s o t o m i a convencional a céu a b e r t o .
Based on a significant series of 35 micro-surgical E E G guided callosotomies, operated upon under scalp E E G and mesial electrocorticographic monitoring, w e have, in previous publications 10,12 described a disruption of the bilateral synchrony after g r a d e d section of the anterior portion of the corpus callosum and, in t w o instances, of a section exclusively of the callosal trunk. During these functional operations, in which the extent of the callosal section w a s determined by the operative E E G findings, w e have also performed callosal stimulation as a part of the intra-operative studies in the latter cases, thus observing that stimulation with pulses of 1 msec duration, 2 to 3 v o l t amplitude and frequencies in the range of 100 Hz up to 200 Hz w e r e able to modify the spread of the secondary bilateral discharges. Based on this
* D i v i s i o n of F u n c t i o n a l N e u r o s u r g e r y , U n i v e r s i t y of São P a u l o M e d i c a l School.
operative finding w e have tried to reproduce it in cats with experimental penicillin epilepsy 3, and at the same time have selected t w o patients, w h o o b e y e d all our previously reported criteria for callosotomy 10.12, and submitted them to implantation of a chronic stimulation device: a flat 8-lead bipolar platinum electrode which w a s placed over the anterior convexity of the corpus callosum, and connected to a receiver under the skin of the infra-clavicular region, using the same craniotomy approach as in our previously operated cases 10.12. T h e rationale for this operation, in opposi-tion to cerebellar stimulaopposi-tion devices, which seek only stimulaopposi-tion, w a s to produce a "functional" or non-surgical "interruption" of the callosal fibers, b y depolarizing or inhibiting transmission of epileptic discharges from one hemisphere to the other, as an attempt to prevent spread of the epileptic activity and its clinical consequences. Our w o r k i n g hypothesis w a s to spare the callosal fibers from surgical d a m a g e and also to prevent the undesirable sequelae of the "split-brain" syndrome, using a more conservative procedure, w h o s e effects, if not effective, could be immediately reversed. Both cases w e r e operated upon on January 14 and 28, 1986, respectively. No cons-picuous adhesions w e r e found between the cingulate g y r i in either case, as may usually be observed, and both procedures w e r e carried out smoothly, without excessive re-traction over the mesial surface of the brain ( F i g . 1 ) .
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v e r y g e n t l e r e t r a c t i o n was utilized, s u g g e s t i n g that some brain d a m a g e of vascular o r i g i n m i g h t h a v e occurred u n d e r the r e t r a c t e d tissue o v e r the r i g h t h e m i s p h e r e mesial c o r t e x : a funnel-like « t o r n a d o » — shaped i m a g e w a s o b s e r v e d in the t e r r i t o r y of the pericallosal a r t e r y , p r o b a b l y r e p r e s e n t i n g some of the a n a t o m i c a l substrate of our electrical and n e u r o p s y c h o l o -gical ( * ) f i n d i n g s ( F i g . 2 ) .
I n o r d e r t o e x p l a i n our u n e x p e c t e d l y o b t a i n e d « s h a m o p é r a t i o n » m o d e l , and by-pass its p o s s i b l e m e c h a n i s m s w h i c h , in o u r opinion, could c h e c k m a t e o u r r o u t i n e c a l l o s o t o m y operations, w e d e c i d e d to c r e a t e t w o n e w r e b u t t a l m o d e l s : 1. A t r a u m a t i c stereotactic i m p l a n t a t i o n o l an i n d w e l l i n g e l e c t r o d e f o r c h r o n i c callosal stimulation, thus b y - p a s s i n g the m e s i a l c o r t i c e s ; 2. G r a d e d s t e r e o t a c t i c lesion o f t h e corpus callosum, thus p r e v e n t i n g c e r e b r a l manipulation. H o w e v e r , a n e w v a r i a n t c a m e into p l a y d u r i n g the callosal l o c a l i z a t i o n and « r e p é r a g e » s t u d i e s : b i s y n c h r o n y w o u l d disappear and the clinical picture w o u l d i m p r o v e after injection of a i r f o r t h e p n e u m o e n c e p h a l o g r a m s , a n o t h e r unspecific effect r e p o r t e d to affect seizures b y e a r l y a u t h o r s : F o e r s t e r in 1924, C l o v i s V i n c e n t in 1933, c i t e d b y J. D e l a y ( 4 ) , in 1950; P e n f i e l d (Jfi), in 1954, has also r e p o r t e d on the therapeutic use of subarachnoid air injections as a d e l i b e r a t e f o r m of t r e a t m e n t for e p i l e p s y . D u e to this fact, candidates f o r stereotactic c a l l o s o t o m y o p e r a t i o n s w e r e s u b m i t t e d t o a P E G b e f o r e the p r o c e d u r e , in o r d e r t o d e t e r m i n e the d u r a t i o n o f the d i s a p p e a r a n c e of the b i s y n c h r o n i e s , t h r o u g h r e p e a t e d E E G s . A s an a v e r a g e , this a m e l i o r a t i o n t o o k 10 to 20 d a y s to r e g r e s s , and w h e n t h e clinical picture d e t e r i o r a t e d a g a i n and t h e E E G r e t u r n e d t o its p r e v i o u s a b n o r m a l i t i e s , i m p l a n t or stereotactic c a l l o s o t o m y w a s u n d e r t a k e n . O n l y one case ( M P ) d i d not s h o w s i g n i f i c a n t a m e l i o r a t i o n of his s e v e r e E E G a b n o r m a l i t i e s after t h e P E G , and w a s s u b m i t t e d to a stereotactic pace-m a k e r ipace-mplantation, f o r chronic callosal stipace-mulation.
M o d e l 1 case r e p o r t ( M P ) — T h i s w a s a 17 y . o . h e l m e t - w e a r i n g b o y w i t h a 16 y e a r h i s t o r y of m u l t i f o r m seizures and s e v e r e d a i l y countless absences that g a v e h i m t h e false appearance of b e i n g m e n t a l l y r e t a r d e d and m a d e h i m untestable to r o u t i n e n e u r o p s y c h o l o g i c a l tests. H e s h o w e d a s e v e r e b i l a t e r a l s y n c h r o n y and b e h a v i o r p r o b l e m s , d u r i n g his p e r i o d s of a w a k e n i n g f r o m his a l m o s t p e r m a n e n t state of absences. N o a m e l i o r a t i o n w a s obtained f r o m m e t i c u l o u s l y c o n t r o l l e d anticonvulsant m e d i c a t i o n , d u r i n g m a n y w e e k s of h o s p i t a l i z a t i o n .
324 Arq Neuro-Pttiqumt (Sao Pernio) 47(3) 1989
R E S U L T S
T h i s d e s c r i p t i v e account w a s h o w b e i t n e c e s s a r y to establish the c h a i n i n g of events, w h i c h led us t o p r o p o s e t h i s a t r a u m a t i c i n t e r v e n t i o n as a n e w and r e l i a b l e s u r g i c a l t r e a t m e n t f o r r e f r a c t o r y e p i l e p s y . T e n cases have been s u b m i t t e d , up t o t h e t i m e of this r e p o r t , t o s t e r e o t a c t i c a n t e r i o r c a l l o s o t o m y , u s i n g r a d i o f r e q u e n c y and a special s i d e outlet t h e r m o c o u p l e e l e c t r o d e . A l l 5 cases h a d s i g n i f i c a n t i m p r o v e m e n t , a c c o r d i n g t o t h e d e g r e e o f s e v e r i t y of their p r e o p e r a t i v e e l e c t r o g r a p h i c f i n d i n g s , as w e have r e p o r t e d e l s e w h e r e (.10,12) in our adopted selection c r i t e r i a . D e c r e a s e o f t h e i r n u m b e r of seizures and absences, b e t t e r c o n t r o l w i t h anticonvulsants, i m p r o v e m e n t of b e h a v i o r and f e w e r e p i s o d e s o f consciousness loss w e r e o b s e r v e d . H o w e v e r , m o r e m a r k e d r e s u l t s w e r e o b s e r v e d in n e u r o b e h a v i o r a l f i n d i n g s : d i f f e r e n t l y f r o m c r a n i o t o m y patients, the s t e r e o t a c t i c cases s h o w e d less f i n d i n g s in r e l a t i o n t o their i m m e d i a t e p o s t - o p e r a t i v e d i s c o n n e c t i o n s y n d r o m e , no a d i n a m i a o f the left side of the b o d y , found in p a t i e n t s s u b m i t t e d t o open c a l l o s o t o m y ( c o n s i d e r e d as p a r t of t h e callosal disconnection s y n d r o m e ) , less p e r s e v e r a t i o n and increased attention w e r e a l s o noticed after stereotactic c a l l o s o t o m y . N o o t h e r f o r m a l n e u r o p s y c h o l o g i c a l ( ~ ) data could be e v a l u a t e d due t o the e x t r e m e l y l o w - l e v e l of intelectual and c o g n i t i v e functions of these s e v e r e l y i l l patients.
C O M M E N T S
W e soon realized that the present findings would originate many questions yet to be answered. Stimulation of the corpus callosum, either in humans 11 or experi-mentally 3, has led us to apparently negative results, which forced us to abandon its use for the time being, until more experimental data, it possible in monkeys, as well as other clinical correlations, are established, before w e attempt to draw any further conclusions. In our experimental m a t e r i a l s , 12 cats w e r e submitted to callosal stimu-lation: 2 had direct stimulation after craniotomy and 10 stereotactically. T h e epileptic activity w a s produced by topic penicilin, placed over the convexity of the neocortex, after extensive bilateral craniotomies. T h e results indicated that callosal stimulation w a s not able to modify the m o r p h o l o g y , frequency and synchrony of the epileptic bursts, at least in this model. T i n s mignt be in agreement with the fact that tnalamic and callosal afferents to the cortex do not share the same topographic distribution. Thus, our results are n o w Deing rechecked in focal epilepsy models. '1 he most difficult question yet to be answered will be the disappearance ot bilateral synchrony and the clinical improvement of seizures in our t w o patients submitted to a simple placement of a flat electrode over the surface of the anterior corpus callosum. T h i s unspecific effect of craniotomy and frontal lobe retraction has not disappeared in our t w o pa-tients up to tne present time, more than a year and a half after electrode implantation. Conversely, this unspecific effect has not appeared in our single case submitted to insertion of a callosal indwelling electrode, stereotactically placed atraumatically, after a frontal twist-drill hole ( F i g . 3 ) . T h i s third case had to be submitted, 6 months later, to a stereotactic callosotomy (after removal of the stimulation e l e c t r o d e ) , since his clinical picture continued to deteriorate. T h e MR1 scanning finding of a right sided funnel-skaped lesion in the territory of the pericallosal artery in craniotomy cases, may thus represent the anatomical substrate of vascular damage or gliosis under the retracted area of mesial frontal lobe and corresponding callosal fibers, that may account for an unspecific effect of craniotomy and manipulation of brain commisures ( F i g . 2 ) .
Another unspecific effect: amelioration after pneumoencephalography, reported by other authors some years a g o 4.16, also came into play in our cases to c o r r o D o r a t e tne fact that other unspecific manoeuvers like subarachnoid air injection 16, reduction of the cerebral mass or resection of brain tissue unrelated to tne epileptogenic area 5
-1 3
may reduce seizure activity. T h e mechanisms that underlie these unspecific findings remain to be elucidated as well. Stereotactic anterior callosotomy w a s a logical conse-quence of the findings that f o l l o w e d each other in the models w e used, in our endeavour to control generalized refractory epilepsy by a less traumatic and safer functional neu-rosurgical technique. Experimental demonstration by Marcus and W a t s o n 9, Naquet et a l .1 5
and M u s g r a v e and G l o o r 14
, that section of the corpus callosum, even when
incomplete, will partially prevent the bilateral synchronization of discharges in cat and monkey has also been demonstrated in our clinical cases, w h e r e marked disruption of bisynchrony w a s found after partial section of the callosum subsequent to cranioto-my i O -1 2
. T h e introduction of the stereotactic approach to the corpus callosum, in our
experience, has produced less neuropsychological findings as compared to previously operated craniotomy c a s e s2
that w e r e associated to satisfactory seizure control, improvement in behavior and better response to anticonvulsant medication.
W e consider that the number of cases operated upon and their follow-up are still limited for further conclusions. H o w e v e r , w e feel that w e have opened the w a y to less d a m a g i n g , more limited and more functional interventions on the cerebral commissures destined to have less side effects to unrelated adjacent structures and other extraneous brain mechanisms. Extensive c o r r o b o r a t i v e technical, electrophysiolo-gical, neuro-psychological and neuro-imaging data which have been collected in this o n g o i n g study, w i l l be the subject of future publications. Meanwhile, this new functional neurosurgical approach to the corpus callosum seems w o r t h y of immediate notice.
Acknowledgments — We are deeply indebted to the Hospital Albert Einstein of São Paulo, who provided the Magnetic Resonance exames; to C.H.P. Camargo for the Neuropsy-c h o l o g i Neuropsy-c a l t e s t i n g , and a l l o u r h o s p i t a l staff w h o h e l p e d i n t h e t r e a t m e n t o f patients.
R E F E R E N C E S
1. A v i l a J O , R a d v a n y J, H u c k F R , C a m a r g o C H P , M a r i n o R Jr, R a g a z z o P C , R i v a D , A r l a n t P A — A n t e r i o r c a l l o s o t o m y as a substitute f o r h e m i s p h e r e c t o m y . A c t a N e u r o c h i r u r 30 ( S u p p l ) : 137, 1980.
2. C a m a r g o C H P , M a k r a y R M A , R a d v a n y J, M a r i n o R J r — P a r t i a l frontal c a l l o s o t o m y : a n e u r o p s y c h o l o g i c a l f r o n t a l l o b e s y n d r o m e d e t e c t e d in t h e b a c k g r o u n d of i m p r o v e m e n t of e p i l e p s y . I n R e e v e s A G ( e d ) : E p i l e p s y a n d the Corpus Callosum. P l e n u m , N e w Y o r k , 1985, p g 435.
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induced convulsion and electronarcosis. A r c h N e u r o l 2 : 55, 1960.
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F u n c t i o n a l A n a t o m y of t h e H u m a n B r a i n . L i t t l e , B r o w n a n d Co, B o s t o n , 1954, p g 564. 17. Sussman N M , Scanlon M , G a r f i n k l e W , Callana M , O ' C o n n o r M J , H a r n e r R N — M a g n e t i c
