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Archives o f Disease i n Childhood, 1977, 5 2 , 844-849 Cerebrospinal fluid acid-base status a n d lactate a n d pyruvate concentrations after convulsions o f varied duration a n d aetiology in children H . SIMPSON, A . H . HABEL, AN D E . L . GEORGE From t h e Royal Hospital f o r Sick Children, Edinburgh, an d t h e Department of Child Life a n d Health, University o f Edinburgh SUMMARY Twenty-two infants a n d children were studied after convulsions o f varied cause a n d duration. Arterial a n d CSF acid-base variables, lactate a nd pyruvate concentrations, a n d lactate/ pyruvate ratios were measured between 3 a n d 1 8 hours after convulsive episodes. Biochemical signs o f cerebral hypoxia were found in 7 patients with prolonged (>30 minutes) o r recurrent short convulsions. These signs were absent i n patients with single short convulsions. These findings indicate that cerebral hypoxia a n d possible brain damage i s a hazard of prolonged o r rapidly recurring short convulsions. I n our accompanying paper (Simpson e t al., 1977) we that first-time febrile convulsions o f short duration i n children a r e unlikely t o result i n cerebral hypoxia. T h e questions arise whether brief (<30 minutes) single or multiple 'nonfebrile' convulsions o r prolonged convulsions (>30 minutes), with or without fever, cause cerebral hypoxia with t h e attendant risk o f structural brain damage. Patho- logical changes ma y occur i n t h e brains of adults after several hours o f status epilepticus (see review b y Corsellis, 1971), whereas in children damage h as been attributed t o seizures o f 1 - 2 hours' duration (Zimmerman, 1938; Fowler, 1957). T h e mechanism whereby recognized pathological changes (cerebro- cortical atrophy, cerebellar atrophy, a n d mesial temporal sclerosis) a r e produced i n t h e brains of chronic epileptics is n ot always certain, b u t there i s a growing suspicion that convulsive hypoxia, especially during prolonged febrile convulsions, gives rise t o permanent cerebral lesions (Falconer, 1971; Ounsted, 1971). T h e present investigation w a s undertaken t o measure t h e degree of postulated cerebral hypoxia b y determination of lactate a n d pyruvate con- centrations a n d lactate/pyruvate ratios in t h e cere- brospinal fluid (CSF) o f children after convulsions o f varied duration a n d aetiology (excluding patients with first febrile convulsions o f short duration). n increase i n C S F lactate a n d i n lactate/pyruvate ratio Received 3 1 March 1977 indicates impairment of cerebral oxidative metabol- i s m (Siesjb a n d Plum, 1971). Patients a n d methods Table 1 gives clinical details of t h e 2 2 patients i n t he series. T h e group comprised 6 females a n d 1 6 males (mean a g e 3 4 years). Patients with first-time febrile convulsions lasting <3 0 minutes were excluded. N o other selection criteria were adopted a n d t h e 6 children with febrile convulsions (Cases 5-7, 1 6 , 17, 1 9 ) are included because o f either prolonged con- vulsions (>30 minutes) o r a previous history o f similar episodes. T h e remaining 1 6 patients had convulsions of varied duration an d cause. A history o f a n immunization procedure o r contact with infectious illness i n th e preceding 4 weeks was noted i n 4 patients (Cases 15-17, 19). Convulsions were most often clonic i n type a n d i n 8 children (Cases 1-8) lasted > 3 0 minutes. O n e patient (Case 9 ) h a d recurrent short convulsions each lasting approximately 1 0 minutes over a period of several hours. I n 3 patients (Cases 19-21) t h e duration o f convulsions before admission t o hospital could n o t b e ascertained. T h e interval between con- vulsion a n d lumbar puncture w a s n o t always known precisely an d w a s most often between 4 a n d 8 hours. Viruses were isolated from throat o r nasal swabs o r virusinfection inferred serologically b y a fourfold rise i n titre i n paired samples i n 5 o f 2 0 patients investigated (Cases 3 , 7 , 1 4 , 16, 19). I n o n e patient 844

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A r c h i v e s o f D i s e a s e i n C h i l d h o o d , 1 9 7 7 , 5 2 , 8 4 4 - 8 4 9

C e r e b r o s p i n a l f l u i d a c i d - b a s e s t a t u s a n d l a c t a t e a n dp y r u v a t e c o n c e n t r a t i o n s a f t e r c o n v u l s i o n s o f v a r i e dd u r a t i o n a n d a e t i o l o g y in c h i l d r e n

H . SIMPSON, A . H . HABEL, AND E . L . GEORGE

F r o m t h e R o y a l H o s p i t a l f o r S i c k C h i l d r e n , E d i n b u r g h , a n d t h e D e p a r t m e n t o f C h i l d L i f e and H e a l t h ,U n i v e r s i t y o f E d i n b u r g h

SUMMARY T w e n t y - t w o i n f a n t s a n d c h i l d r e n were s t u d i e d a f t e r c o n v u l s i o n s o f v a r i e d cause a n dd u r a t i o n . A r t e r i a l a n d CSF a c i d - b a s e v a r i a b l e s , l a c t a t e a n d p y r u v a t e c o n c e n t r a t i o n s , and l a c t a t e /p y r u v a t e r a t i o s were m e a s u r e d b e t w e e n 3 a n d 1 8 h o u r s a f t e r c o n v u l s i v e e p i s o d e s . B i o c h e m i c a l s i g n s

o f c e r e b r a l h y p o x i a were f o u n d i n 7 p a t i e n t s w i t h p r o l o n g e d ( > 3 0 m i n u t e s ) or r e c u r r e n t s h o r tc o n v u l s i o n s . T h e s e s i g n s were a b s e n t i n p a t i e n t s w i t h s i n g l e s h o r t c o n v u l s i o n s . T h e s e f i n d i n g si n d i c a t e t h a t c e r e b r a l h y p o x i a a n d p o s s i b l e b r a i n d a m a g e i s a h a z a r d o f p r o l o n g e d or r a p i d l yr e c u r r i n g s h o r t c o n v u l s i o n s .

I n o u r a c c o m p a n y i n g p a p e r ( S i m p s o n e t a l . , 1 9 7 7 ) wes h o w e d t h a t f i r s t - t i m e f e b r i l e c o n v u l s i o n s o f s h o r td u r a t i o n i n c h i l d r e n a r e u n l i k e l y t o r e s u l t i n c e r e b r a lh y p o x i a . T h e q u e s t i o n s a r i s e w h e t h e r b r i e f ( < 3 0m i n u t e s ) s i n g l e o r m u l t i p l e ' n o n f e b r i l e ' c o n v u l s i o n so r p r o l o n g e d c o n v u l s i o n s ( > 3 0 m i n u t e s ) , w i t h o r

w i t h o u t f e v e r , c a u s e c e r e b r a l h y p o x i a w i t h t h e

a t t e n d a n t r i s k o f s t r u c t u r a l b r a i n d a m a g e . P a t h o -l o g i c a l c h a n g e s ma y o c c u r i n t h e b r a i n s o f a d u l t sa f t e r s e v e r a l h o u r s o f s t a t u s e p i l e p t i c u s ( s e e r e v i e wb y C o r s e l l i s , 1 9 7 1 ) , w h e r e a s i n c h i l d r e n d a m a g e h a sb e e n a t t r i b u t e d t o s e i z u r e s o f 1 - 2 h o u r s ' d u r a t i o n( Z i m m e r m a n , 1 9 3 8 ; F o w l e r , 1 9 5 7 ) . T h e m e c h a n i s mw h e r e b y r e c o g n i z e d p a t h o l o g i c a l c h a n g e s ( c e r e b r o -c o r t i c a l a t r o p h y , c e r e b e l l a r a t r o p h y , a n d m e s i a lt e m p o r a l s c l e r o s i s ) a r e p r o d u c e d i n t h e b r a i n s o fc h r o n i c e p i l e p t i c s i s n o t a l w a y s c e r t a i n , b u t t h e r e i sa g r o w i n g s u s p i c i o n t h a t c o n v u l s i v e h y p o x i a ,e s p e c i a l l y d u r i n g p r o l o n g e d f e b r i l e c o n v u l s i o n s ,g i v e s r i s e t o p e r m a n e n t c e r e b r a l l e s i o n s ( F a l c o n e r ,1 9 7 1 ; O u n s t e d , 1 9 7 1 ) .

T h e p r e s e n t i n v e s t i g a t i o n w a s u n d e r t a k e n t om e a s u r e t h e d e g r e e o f p o s t u l a t e d c e r e b r a l h y p o x i ab y t h e d e t e r m i n a t i o n o f l a c t a t e a n d p yr u v a t e c o n -c e n t r a t i o n s a n d l a c t a t e / p y r u v a t e r a t i o s i n t h e c e r e -b r o s p i n a l f l u i d ( C S F ) o f c h i l d r e n a f t e r c o n v u l s i o n so f v a r i e d d u r a t i o n a n d a e t i o l o g y ( e x c l u d i n g p a t i e n t sw i t h f i r s t f e b r i l e c o n v u l s i o n s o f s h o r t d u r a t i o n ) . Ani n c r e a s e i n CSF l a c t a t e a n d i n l a c t a t e / p y r u v a t e r a t i o

R e c e i v e d 3 1 M a r c h 1 9 7 7

i n d i c a t e s i m p a i r m e n t o f c e r e b r a l o x i d a t i v e m e t a b o l -i s m ( S i e s j b a n d P l u m , 1 9 7 1 ) .

P a t i e n t s a n d m e t h o d s

T a b l e 1 g i v e s c l i n i c a l d e t a i l s o f t h e 2 2 p a t i e n t s i n t h e

s e r i e s . T h e g r o u p c o m p r i s e d 6 f e m a l e s a n d 1 6 m a l e s

( m e a n a g e 3 4 y e a r s ) . P a t i e n t s w i t h f i r s t - t i m e f e b r i l ec o n v u l s i o n s l a s t i n g <30 m i n u t e s w e r e e x c l u d e d . N oo t h e r s e l e c t i o n c r i t e r i a w e r e a d o p t e d a n d t h e 6c h i l d r e n w i t h f e b r i l e c o n v u l s i o n s ( C a s e s 5 - 7 , 1 6 , 1 7 ,1 9 ) a r e i n c l u d e d b e c a u s e o f e i t h e r p r o l o n g e d c o n -v u l s i o n s ( > 3 0 m i n u t e s ) o r a p r e v i o u s h i s t o r y o fs i m i l a r e p i s o d e s . T h e r e m a i n i n g 1 6 p a t i e n t s h a dc o n v u l s i o n s o f v a r i e d d u r a t i o n a n d c a u s e .A h i s t o r y o f a n i m m u n i z a t i o n p r o c e d u r e o r

c o n t a c t w i t h i n f e c t i o u s i l l n e s s i n t h e p r e c e d i n g 4w e e k s w a s n o t e d i n 4 p a t i e n t s ( C a s e s 1 5 - 1 7 , 1 9 ) .C o n v u l s i o n s w e r e m o s t o f t e n c l o n i c i n t y p e a n d i n8 c h i l d r e n ( C a s e s 1 - 8 ) l a s t e d >30 m i n u t e s . One

p a t i e n t ( C a s e 9 ) h a d r e c u r r e n t s h o r t c o n v u l s i o n se a c h l a s t i n g a p p r o x i m a t e l y 1 0 m i n u t e s o v e r a p e r i o do f s e v e r a l h o u r s . I n 3 p a t i e n t s ( C a s e s 1 9 - 2 1 ) t h ed u r a t i o n o f c o n v u l s i o n s b e f o r e a d m i s s i o n t o h o s p i t a lc o u l d n o t b e a s c e r t a i n e d . T h e i n t e r v a l b e t w e e n c o n -v u l s i o n a n d l u m b a r p u n c t u r e w a s n o t a l w a y s knownp r e c i s e l y a n d w a s m o s t o f t e n b e t w e e n 4 a n d 8 h o u r s .

V i r u s e s w e r e i s o l a t e d f r o m t h r o a t o r n a s a l s w a b so r v i r u s i n f e c t i o n i n f e r r e d s e r o l o g i c a l l y b y a f o u r f o l dr i s e i n t i t r e i n p a i r e d s a m p l e s i n 5 o f 2 0 p a t i e n t si n v e s t i g a t e d ( C a s e s 3 , 7 , 1 4 , 1 6 , 1 9 ) . I n o n e p a t i e n t

8 4 4

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C e r e b r o s p i n a l f l u i d a c i d - b a s e s t a t u s a n d l a c t a t e a n d p y r u v a t e c o n c e n t r a t i o n s 8 4 5

T a b l e 1 C l i n i c a l d e t a i l s o f c h i l d r e n w i t h c o n v u l s i o n s o f v a r i e d a e t i o l o g y a n d d u r a t i o n

A p p r o xd u r a t i o n I n t e r v a l

C a s e n o . S e x Ag e ( y r s ) H i s t o r y F i n a l d i a g n o s i s C o n vu ls i on * ( m i n) ( h ) EEG

I M 4 C e r e b r a l b i r t h i n j u r y - 2 n d S t a t u s e p i l e p t i c u s ; C 2 7 0 4 N

c o n v u l s i o n t r a n s i e n t l e f t h e m i p l e g i a2 M 4 R e t a r d e d c h i l d ; 2 p r e v i o u s S t a t u s e p i l e p t i c u s C 1 5 0 6 Nf e b r i l e c o n v u l s i o n s

3 M 0 9 V o m i t i n g a n d d i a r r h o e a ; H y p e r n a t r a e m i c d e hy d ra t i o n, T 1 5 0 7 Ar e c u r r e n t f i t s f o r 2 h , a d e n o v i r u s i s o l a t e du n re s p o n s i ve t h r o u g h o u t

4 F 0 9 R e c u r r e n t c o n v u l s i o n s f o r 4 S t a t u s e p i l e p t i c u s F 1 4 0 8 A

m; a f e b r i l e5 M 1 V o m i t i n g a n d f e v e r f o r 1 8 h P r o l o n g e d f e b r i l e c o n v u l s i o n C 9 0 3 N6 F 4 N o p r o d r o m a l f e a t u r e s P r o l o n g e d f e b r i l e c o n v u l s i o n C 7 0 4 N7 F 1 N o p r o d r o m a l f e a t u r e s P r o l o n g e d f e b r i l e F >60 4 A

c o n v u l s i o n ; p a r a i n f l u e n z a 3

v i r u s i s o l a t e d8 F 3 R e c u r r e n t c o n v u l s i o n s f o r 3 m; S t a t u s e p i l e p t i c u s ; t r a n s i e n t C 6 0 1 2 A

a f e b r i l e r i g h t h e m i p l e g i a9 M 4 M i l d a t a x i c d i p l e g i a ; r e c u r r e n t K e t o t i c h y p o g l y c a e m i a w i t h C lOx4 S t N

c o n v u l s i o n s ; h y p o g l y c a e m i a c o n v u l s i o n s1 0 M 3 R e c u r r e n t c o n v u l s i o n s f o r 4 m; N o n f e b r i l e c o n v u l s i o n s M 1 N K$ N

a f e b r i l e r e p e a t e d

1 1 F 1 1 B i z a r r e b e h a v i ou r , r e c ur re n t T o x o p l a s m a e n c e p h a l i t i s ; M 1 NKt As e i z u r e s f o r 1 m r i s i n g t o x o p l a s m a d y e t e s t r e p e a t e d

1 2 M 4 R e c u r r e n t c o n v u l s i o n s f o r 6 N o n f e b r i l e c o n v u l s i o n s C 1 NK$ Nm; a f e b r i l e r e p e a t e d

1 3 M 8 I m i p r a m i n e i n g e s t i o n I m i p r a m i n e t o x i c i t y C 1 5 , 4 4 t N1 4 M 2 V o m i t i n g ; r e c u r r e n t b r i e f P a r a - i n f e c t i o u s e n c e p h a l o - F 7 , 3 7 t A

s e i z u r e s f o r 4 8 h p a t h y ; r i s i n g t i t r e t o p a r a -i n f l u e n z a I v i r u s

1 5 M 0 3 F i r s t t r i p l e i m m u n i z a t i o n 7 d P o s t i m m u n i z a t i o n c o n v u l s i o n C 1 0 9 N

b e f o r e c o n v u l s i o n ; a f e b r i l e1 6 M 3 P r e v i o u s f e b r i l e c o n v u l s i o n ; F e b r i l e c o n v u l s i o n ; mumps C 1 0 5 N

mumps c o n t a c t v i r u s i s o l a t e d1 7 F 1 M e a s l e s v a c c i n a t i o n 2 w b e f or e ; F e b r i l e c o n v u l s i o n ( r e c u r r e n t ) C 3 4 N

u p p e r r e s p i r a t o r y t r a c ti n f e c t i o n , f e b r i l e

1 8 M 0 3 M u l t i f o c a l c o n v ul s i o ns f o r 2 w H y p s a r r h y t h m i a ; d i f f u s e C 3 5 A

c e r e b r a l a t r o p h y1 9 M 4 P r e v i o u s f e b r i l e c o n v u l s i o n ; F e b r i l e c o n v u l s i o n ; i n f l u e n z a T NK 5 A

i n f l u e n z a c o n t a c t A v i r u s i s o l a t e d2 0 M 2 3 p r e v i o u s f e b r i l e c o n v u l s i o n s ; N o n f e b r i l e c o n v u l s i o n J NK 1 7 N

a f e b r i l e2 1 M 1 0 Known e p i l e p t i c ; f o u n d E p i l e p s y NK NK 1 8 N

u n c o n s c i o u s i n s t r e e t2 2 M 3 S p i n a b i f i d a , h y d r o c e p h a l u s , C o n v u l s i o n a f t e r r e v i s i o n o f C <1 N

b l o c k e d s h u n t s h u n t

* C = c l o n i c ; T t o n i c ; F = f o c a l ; M = m y o c l o n i c , m u l t i f o c a l ; J = j i t t e r i n e s s .t A f t e r l a s t f i t .$ F r e q u e n t s e i z u r e s t h r o u g h o u t e a c h 2 4 - h o u r p e r i o d .N = n o r m a l ; A = a b n o r m a l .M e d i c a t i o n b e f o r e l u m b a r p u n c t u r e :K e t a m i n e 5 m g / k g IM: C a s e s 4 , 6 , 8 , 1 0 , 1 6 , 1 7 , 1 9 .T h i o p e n t o n e 2 2 m g / k g r e c t a l l y : C a s e 1 1 .C h l o r p r o m a z i n e 2 5 m g IM: C a s e 1 2 .C h l o r a l h y d r a t e 5 0 0 m g o r a l l y : C a s e 2 0 .

( C a s e 1 1 ) t o x o p l a s m o s i s was t h e f i n a l d i a g n o s i s .Abnormal e l e c t r o e n c e p h a l o g r a p h i c r e c o r d i n g s were

o b t a i n e d i n 8 p a t i e n t s i n v e s t i g a t e d a t l e a s t 2 w e e k s

a f t e r c o n v u l s i v e e p i s o d e s .B e f o r e i n v e s t i g a t i o n a l l b u t 4 p a t i e n t s ( C a s e s 7 ,

1 5 - 1 7 ) had r e c e i v e d a n t i c o n v u l s a n t s , u s u a l l y d i a z e -

pam 0 - 1 - 0 3 m g / k g i m m e d i a t e l y , f o l l o w e d b yp h e n y t o i n 3 - 8 m g / k g per 2 4 h o u r s or p h e n o b a r b i t o n e

3 - 7 m g / k g per 2 4 h o u r s . R e d u c t i o n i n i n t r a c r a n i a l

pressure was a c h i e v e d w i t h 5 m l / k g 20% m a n n i t o l

( C a s e s 1 , 2 ) and d e x a m e t h a s o n e 2 - 4 mg f o u r t i m e s

d a i l y ( C a s e s 2 a n d 5 ) . T h e l a t t e r a l s o r e c e i v e d m u s c l e

r e l a x a n t s a n d i n t e r m i t t e n t p o s i t i v e p r e s s u r e v e n t i l a -t i o n w i t h o x y g e n e n r i c h e d a i r .

T h e p r o c e d u r e f o r o b t a i n i n g CSF s a m p l e s a n d

a n a l y t i c a l m e t h o d s are d e s c r i b e d i n o ur accompany-

i n g p a p e r ( S i m p s o n e t a l . , 1 9 7 7 ) . A d d i t i o n a l

measurements i n 1 1 p a t i e n t s i n c l u d e d serum a l a n i n ea m i n o t r a n s f e r a s e or a s p a r t a t e a m i n o t r a n s f e r a s e ,m e a s u r e d i n venous s a m p l e s o b t a i n e d some 1 2 t o

2 4 h o u r s a f t e r c o n v u l s i o n s . S e r u m a l a n i n e t r a n s f e r a s ewa s r a i s e d ( 7 4 U / I ) i n on e p a t i e n t ( C a s e 2 ) . T r a n s -

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846 S i m p s o n , H a b e l , a n d G e o r g e

a m i n a s e l e v e l s were l e s s t h a n 4 0 U / l i n t h e r e m a i n i n g

10 cases.

R e s u l t s

Th e 2 2 p a t i e n t s i n t h i s s e r i e s a l l s u r v i v e d . T h e i r

c l i n i c a l s t a t u s was r e v i e w e d p e r i o d i c a l l y a f t e rd i s c h a r g e f r o m h o s p i t a l f o r a t l e a s t one year. T h eprogress a n d s u b s e q u e n t n e u r o l o g i c a l s t a t u s o f t h e s eand our f i r s t f e b r i l e c o n v u l s i o n p a t i e n t s w i l l b e

r e p o r t e d s e p a r a t e l y ( H a b e l a n d S i m p s o n , 1 9 7 7 ) .

A c i d - b a s e v a r i a b l e s . T a b l e 2 g i v e s i n d i v i d u a l a n dgroup v a l u e s f o r a c i d - b a s e v a r i a b l e s i n a r t e r i a lb l o o d a n d C S F . A r t e r i a l b l o o d d a t a s h o w s pH a t or

n e a r n o r m a l i n most c a s e s . A r t e r i a l pH i s <7 * 3 6 i n3 p a t i e n t s ( C a s e s 1 , 3 , 2 0 ) a n d > 7 4 3 i n a f u r t h e r 3

( C a s e s 1 7 , 1 8 , 2 2 ) . N e g a t i v e v a l u e s o f b a s e excess

g r e a t e r t h a n - 5 m m o l / l i n d i c a t e s i g n i f i c a n t m e t a -

b o l i c a c i d o s i s ( C a s e s 3 , 8 , 1 9 , 2 0 ) p a r t i a l l y c o m p e n -

s a t e d b y a r e d u c t i o n i n P c o , b e l o w 3 5 mmHg( 4 . 6 7 k P a ) . R e s p i r a t o r y a l k a l o s i s ( C a s e s 1 8 a n d 2 2 )was p r o b a b l y d u e t o t r a n s i e n t d i s t u r b a n c e d u r i n g

s a m p l i n g or p o s t i c t a l h y p e r v e n t i l a t i o n . T r a n s i e n td i s t u r b a n c e i s t h e most l i k e l y e x p l a n a t i o n w h e nt h e r e i s a m a r k e d d i f f e r e n c e b e t w e e n a r t e r i a l a n dCSF P c o , ( F i s h e r a n d C h r i s t i a n s o n , 1 9 6 3 ) . MeanCSF pH, P c o , , a n d b i c a r b o n a t e d o n o t d i f f e r s i g n i f i -

c a n t l y f r o m c o nt r o l v a lu e s g i v e n i n our accompany-

i n g paper ( S i m p s o n e t a l . , 1 9 7 7 ) .When c o r r e s p o n d i n g v a r i a b l e s i n b l o o d a n d CSF

are c o m p a r e d ( p a i r e d t t e s t ) t h e mean CSF pH o f

7 - 3 2 i s s i g n i f i c a n t l y l o w e r (P<0 0 0 1 ) a n d t h e mean

P c o 2 f o f 4 5 mmHg ( 6 H 0 0 k P a ) h i g h e r (P<0 0 0 1 )t h a n t h e r e s p e c t i v e mean a r t e r i a l pH o f 7 - 3 9 a n d

P c o 2 o f 3 4 m m H g ( 4 5 3 k P a ) . T h e s e are t h e r e l a t i o n -s h i p s n o r m a l l y f o u n d i n a d u l t s ( B r a d l e y a n d S e m p l e ,1 9 6 2 ) . T h e mean CSF b i c a r b o n a t e o f 2 2 - 0 m m o l / ld o e s n o t d i f f e r s i g n i f i c a n t l y f r o m t h e mean b i c a r -b o n a t e o f 2 0 5 m m o l / l i n a r t e r i a l b l o o d .

L a c t a t e a n d p y r u v a t e . T a b l e 3 g i v e s i n d i v i d u a l a n d

group v a l u e s f o r l a c t a t e a n d p y r u v a t e c o n c e n t r a t i o n s

a n d l a c t a t e / p y r u v a t e r a t i o s i n a r t e r i a l b l o o d and

C S F . A r t e r i a l l a c t a t e c o n c e n t r a t i o n e x c e e d s 2 - 0

m m o l / l ( 1 8 m g / 1 0 0 m l ) i n 4 p a t i e n t s ( C a s e s 3 , 5 , 9 ,1 5 ) a n d l a c t a t e / p y r u v a t e r a t i o e x c e e d s 1 6 0 i n 7

( C a s e s 1 - 3 , 8 , 9 , 1 6 , 2 0 ) . F o r e a c h v a r i a b l e v a l u e s are

s c a t t e r e d w i t h i n a w i d e r a n g e .

CSF l a c t a t e e x c e e d s 2 -

1 m m o l / l ( 1 8 * 9 m g / 1 0 0 m l )i n 8 p a t i e n t s ( C a s e s 2 - 5 , 9 , 1 0 , 1 3 , 2 2 ) a n d l a c t a t e /p y r u v a t e r a t i o e x c e e d s 1 8 - 0 i n 9 ( C a s e s 2 - 5 , 9 , 1 0 ,1 6 , 1 7 , 2 0 ) . H o w e v e r , group mean v a l u e s f o r e a c h do

n o t d i f f e r s i g n i f i c a n t l y ( W i l c o x o n n o n p a r a m e t r i ct e s t ) f r o m c o nt r o l v a l u e s g i v e n i n our a c c o m p a n y i n gpaper ( S i m p s o n e t a l . , 1 9 7 7 ) .

T a b l e 2 A r t e r i a l b l o o d a n d CSF a c i d - b a s e v a r i a b l e s i n c h i l d r e n w i t h c o n v u l s i o n s

B l o o d C SF

C a s e P 0 2 P c o 2 HCO; B a s e e x c e s s H+ P c o 2 HCO;n o . (mmHg) pH (mmHg) ( m m o / l l ) ( m m o l / l ) ( n m o l l l ) pH ( m m H g ) ( m m o l / l )

1 - 7 - 3 3 3 9 2 0 - 0 -4-8 4 9 - 0 7 - 3 1 5 2 2 4 - 42 7 6 7 - 4 3 3 5 2 3 - 0 -1-0 5 1 - 3 7 - 2 9 5 2 2 3 - 63 - 7 - 2 3 3 2 1 4 - 5 -14-0 4 4 - 7 7 - 3 5 - -4 - - - _ - - - - _5 - - - - - - _ _ -

6 - - - - - 4 7 - 9 7 - 3 2 4 4 2 1 - 07 - - - - - _ - _ _8 8 7 7 - 3 8 3 1 1 8 - 0 -6-5 4 6 - 8 7 - 3 3 4 8 2 4 - 09 - - - _ _ _ _ - -

1 0 9 2 7 - 3 8 3 6 2 1 - 0 -3-4 5 2 - 5 7 - 2 8 5 4 2 4 - 01 1 - - - - - 4 9 - 0 7 - 3 1 5 1 2 4 - 41 2 -- - - --1 3 - - - - - 4 9 - 0 7 - 3 1 5 1 2 4 - 81 4 -1 5 - 7 - 4 1 3 4 2 1 - 2 -2-8 4 3 - 7 7 - 3 6 4 2 2 2 - 61 6 - 7 - 3 6 3 6 1 9 - 8 -4-5 4 9 - 0 7 - 3 1 4 5 2 1 - 31 7 1 0 2 7 - 4 4 4 3 2 9 - 0 + 5 - 0 4 6 - 8 7 - 3 3 4 0 2 0 - 21 8 9 6 7 - 4 4 2 9 1 9 - 3 -3-5 4 5 - 7 7 - 3 4 3 4 1 7 - 51 9 9 3 7 - 4 1 2 9 1 8 - 1 -5-8 4 7 - 9 7 - 3 2 4 5 2 2 - 02 0 7 2 7 - 3 2 3 4 1 7 - 1 - 8 * 5 4 5 - 7 7 - 3 4 3 7 1 9 - 12 1 - 7 - 4 1 3 9 2 4 - 4 0 4 9 - 0 7 - 3 1 4 4 2 1 - 02 2 8 7 7 - 4 9 2 7 2 0 - 8 - 2 5 4 6 - 8 7 - 3 3 4 0 2 0 - 6Mean 8 8 7 - 3 9 3 4 2 0 - 5 -4 -0 4 7 - 8 7 - 3 2 4 5 2 2 - 0±S D 1 0 - 0 2 0 - 0 7 4 - 5 8 3 - 6 1 4 - 4 8 2 - 3 1 0 - 0 2 6 - 0 1 2 - 1 8±S E 3 . 5 4 0 - 0 2 1 - 2 7 1 - 0 0 1 - 2 4 058 0 - 0 1 1 - 5 5 0 - 5 6R a n g e 7 2 - 1 0 2 7 - 2 3 - 7 - 4 9 2 7 - 4 3 1 7 - 1 - 2 9 - 0 -14 -0-+ 50 4 3 - 7 - 5 2 5 7 - 2 8 - 7 - 3 7 3 4 - 5 4 1 7 - 5 - 2 4 - 8n 9 1 3 1 3 1 3 1 3 1 6 1 6 1 5 1 5

C o n v e r s i o n : S I t o t r a d i t i o n a l u n i t s - P o , , P c o , : 1 k P a - 7 . 5 mmH g . H C O , b a s e e x c e s s : 1 m m o l / 1 = I m E q / l .

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C e r e b r o s p i n a l f l u i d a c i d - b a s e s t a t u s a n d l a c t a t e a n d p y r u v a t e c o n c e n t r a t i o n s 8 4 7

T a b l e 3 A r t e r i a l b l o o d a n d CS F l a c t a t e a n d p y r u v a t e c o n c e n t r a t i o n s a n d l a c t a t e / p y r u v a t e r a t i o s i n c h i l d r e n w i t hc o n v u l s i o n s

B l o o d C SF

L a c t a t e P y r u v a t e L a c t a t e L a c t a t e P y r u v a t e L a c t a t e

C a s e n o . ( m m o l / l ) ( m m o l / l ) P y r u v a t e ( m m o l / l ( m m o l / l ) P y r u v a t e

1 1 - 2 2 0 - 0 6 4 1 9 . 1 1 - 8 5 0 - 1 2 9 1 4 - 32 1 * 7 1 0 - 1 0 0 1 7 - 1 2 - 7 1 0 - 1 4 3 1 8 93 3 - 6 4 0 - 1 4 7 2 4 - 8 3 - 1 8 0073 4 3 54 - - - 2 - 2 9 0 - 1 2 7 1 8 - 15 3 - 0 6 0 - 1 9 6 1 5 - 6 4 0 7 0 - 2 1 9 1 8 - 66 - - - 1 - 8 5 0 - 1 1 8 1 5 - 77 - - - 1 * 5 9 0 - 1 0 2 1 5 - 58 1 - 4 6 0 - 0 7 9 1 8 - 5 1 - 6 6 0 - 1 1 3 1 4 - 79 2 - 0 2 0 - 0 9 8 2 0 - 6 2 - 4 2 0 - 1 1 8 2 0 - 5

1 0 1 - 7 4 0 - 1 6 4 1 0 - 6 2 - 3 7 0 - 1 1 9 1 9 - 81 1 - - - 1 - 4 7 0 - 0 9 6 1 5 31 2 1 - 6 2 0 - 1 2 4 1 3 - 0 1 - 2 8 0 0 7 4 1 7 31 3 - - - 1 * 4 3 0 . 1 0 1 1 4 - 21 4 - - - 2 - 3 7 0 - 2 0 0 1 1 * 91 5 2 - 2 8 0 - 1 6 9 1 3 - 5 1 - 3 9 0 - 0 9 2 1511 6 1 - 4 4 0 - 0 8 1 1 7 - 8 1 - 5 7 0 - 0 7 0 2 2 - 41 7

1 - 1 2 0 - 0 9 8 1 1 - 4 1 - 3 3 0 - 0 7 2 1 8 - 51 8 1 * 3 3 0 - 1 3 8 9 - 7 1 . 5 9 0 1 0 2 1561 9 1 . 5 0 0 - 1 1 6 1 2 - 9 1 - 8 3 0 - 1 3 8 1 3 - 32 0 0 - 9 9 0 - 0 6 1 1 6 - 2 1 * 3 2 0 - 1 2 9 1 0 - 22 1 - - - 1 - 6 1 0056 2 8 - 82 2 1 . 0 9 0 - 0 9 2 1 1 * 8 2 - 8 0 0 1 7 6 1 6 0Mean 1 - 7 5 0115 1551 2 0 0 0 - 1 1 7 1 8 - 1±SD 0 - 7 4 0 - 0 3 9 4 - 2 1 0 - 7 1 0 - 0 4 0 6 - 8 8±S E 0 . 1 9 0 . 0 1 0 1 - 0 9 015 0 - 0 0 9 1 - 4 7R a n g e 0 - 9 9 - 3 * 6 4 0 - 0 6 1 - 0 * 1 9 6 9 7 - 2 4 - 8 1 2 8 - 4 - 0 7 0 - 0 7 0 - 0 - 2 1 9 1 0 - 2 - 4 3 * 5n 1 5 1 5 1 5 2 2 2 2 2 2

No s i g n i f i c a n t d i f f e r e n c e s w e r e f o u n d o n c o m -p a r i n g CSF a n d b l o o d w i t h r e s p e c t t o l a c t a t e a n dp y r u v a t e c o n c e n t r a t i o n s a n d l a c t a t e / p y r u v a t e r a t i o s

( p a i r e d t t e s t ) . T h e r e w a s n o s i g n i f i c a n t c o r r e l a t i o nb e t w e e n CSF l a c t a t e a n d CSF p H , P c o 2 , o r b i c a r -b o n a t e .

D u r a t i o n o f c o n v u l s i o n s . I n t h e p r e s e n t s e r i e s , 8c h i l d r e n ( C a s e s 1 - 8 ) h a d c o n v u l s i o n s e x c e e d i n g 3 0m i n u t e s a n d i n 4 ( C a s e s 2 - 5 ) CSF l a c t a t e c o n c e n -t r a t i o n s a n d l a c t a t e / p y r u v a t e r a t i o s w e r e r a i s e d .N o r m a l v a l u e s f o r t h e s e v a r i a b l e s w e r e o b t a i n e d i no n e p a t i e n t ( C a s e 1 ) t h o u g h t t o h a v e ' c o n v u l s e d ' f o ro v e r 4 h o u r s b e f o r e a r r i v a l i n h o s p i t a l .

S i x p a t i e n t s ( C a s e s 9 - 1 4 ) h a d s h o r t r e p e a t e d c o n -v u l s i o n s a n d 2 s h o w e d e v i d e n c e o f c e r e b r a l h y p o x i a

b y t h e s a m e c r i t e r i a ( C a s e s 9 a n d 1 0 ) . Of t h e r e -m a i n i n g 8 ( C a s e s 1 5 - 2 2 ) , 5 w e r e k n o w n d e f i n i t e l y t oh a v e h a d s i n g l e c o n v u l s i o n s o f s h o r t d u r a t i o n a n dn o n e s h o w e d a n i n c r e a s e i n b o t h CSF l a c t a t e c o n -c e n t r a t i o n a n d l a c t a t e / p y r u v a t e r a t i o . T a b l e 4s u m m a r i z e s o u r m a i n f i n d i n g s , i n c l u d i n g p a t i e n t s i nt h e f i r s t f e b r i l e c o n v u l s i o n s e r i e s ( S i m p s o n e t a l . ,1 9 7 7 ) . When c o n v u l s i o n s a r e r e c ur r e n t o r p r o l o n g e dt h e r e i s a s i g n i f i c a n t i n c r e a s e i n t h e p r o p o r t i o n o fp a t i e n t s w i t h a r a i s e d CSF l a c t a t e c o n c e n t r a t i o n ,l a c t a t e / p y r u v a t e r a t i o , a n d w i t h b o t h , c o m p a r e d w i t h

s i n g l e s h o r t c o n v u l s i o n s . T h e s e f i n d i n g s s u p p o r t t h e

v i e w t h a t c e r e b r a l h y p o x i a f o l l o w i n g c o n v u l s i o n s i sr e l a t e d t o t h e i r d u r a t i o n a n d i s m o s t l i k e l y a f t e rp r o l o n g e d o r r e p e a t e d c o n v u l s i o n s , w h a t e v e r t h e

a e t i o l o g y .

D i s c u s s i o n

S t u d i e s a b o u t s y s t e m i c a n d c e r e b r a l m e t a b o l i c

c h a n g e s f o l l o w i n g b r i e f e p i l e p t i c s e i z u r e s a r e

m e n t i o n e d i n o u r a c c o m p a n y i n g p a p e r ( S i m p s o n e ta l . , 1 9 7 7 ) . C o r r e s p o n d i n g i n f o r m a t i o n a b o u t s e i z -u r e s s u f f i c i e n t l y l o n g a n d s e v e r e t o p r o d u c e b r a i nd a m a g e i s a l s o a v a i l a b l e f o r b a b o o n s ( M e l d r u m a n dH o r t o n , 1 9 7 3 ; M e l d r u m a n d B r i e r l e y , 1 9 7 3 ) , b u t

u n d e r s t a n d a b l y n o t f o r e x p e r i m e n t a l s e i z u r e s i nh u m a n s . T h e r e i s a l s o l i t t l e i n f o r m a t i o n a b o u t t h e

m e t a b o l i c c h a n g e s d u r i n g s p o n t a n e o u s g r a n d m a lc o n v u l s i o n s e i t h e r i n a d u l t ma n ( B r o o k s a n d A d a m s ,1 9 7 5 ) o r c h i l d r e n ( B l e n n o w a n d S v e n n i n g s e n , 1 9 7 4 ) ,a n d i t s e e m s i m p o r t a n t t o d e t e r m i n e w h e t h e r t h ec h a n g e s w h i c h o c c u r p a r a l l e l t h o s e s e e n e x p e r i -m e n t a l l y .

A r t e r i a l b l o o d f i n d i n g s s h o w t h a t m i l d t o m o d e r a t em e t a b o l i c a c i d o s i s o c c u r s i n many p a t i e n t s i n t h ep o s t i c t a l p e r i o d w i t h m i n i m a l c h a n g e i n CSF a c i d -b a s e s t a t u s . T h e CSF a r t e r i a l b l o o d d i f f e r e n c e f o rb i c a r b o n a t e i s c o n s i s t e n t w i t h m e t a b o l i c a c i d o s i s .S i m i l a r f i n d i n g s a r e r e p o r t e d b y B r o o k s a n d Adams

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8 4 8 S i m p s o n , H a b e l , a n d G e o r g e

T a b l e 4 CSF l a c t a t e a n d p y r u v a t e c o n c e n t r a t i o n s a n d l a c t a t e / p y r u v a t e r a t i o s i n r e l a t i o n t o d u r a t i o n o f c o n v u l s i o n s( i n c l u d i n g d a t a f r o m a c c o m p a n y i n g p a p e r o n f e b r i l e c o n v u l s i o n s )

L a c t a t e L a c t a t e / p y r u v a t e L a c t a t e a n d l a c t a t e l p y r u v a t eD u r a t i o n * N o . >2 1 ( m m o l / l ) >18-0 >2 1 ( m m o l l ) > 1 8 0

S i n g l e <30min 3 1 4 4 1

R e p e a t e d 9 4 3 3P<005 N S P < 0 0 1

S i n g l e >30min 8 4 4 4P < 0 - 0 2 5 P < 0 - 0 2 5 P <0 0 0 0 5

R e p e a t e d a n d 1 7 8 7 7

s i n g l e > 3 0 m m i n P<0-01 P < 0 0 5 P < 0 0 0 1

* E x c l u d e s c a s e s 1 9 - 2 1 ( T a b l e 1 ) w h e r e d u r a t i o n o f c o n v u l s i o n s w a s u n c e r t a i n .P v a l u e s f r o m 2 x 2 c o n t i n g e n c y t a b l e s u s i n g X 2 d i s t r i b u t i o n .

( 1 9 7 5 ) f o r a d u l t p a t i e n t s s t u d i e d 3 a n d 6 h o u r s a f t e ri d i o p a t h i c s e i z u r e s .

T h e b l o o d l a c t a t e c o n c e n t r a t i o n w a s r a i s e d i ns e v e r a l o f o u r p a t i e n t s ( T a b l e 3 ) . T h i s c o u l d r e s u l t

n o t o n l y f r o m h y p o x a e m i a a n d i n c r e a s e d m u s c l ea c t i v i t y , b u t a l s o f r o m h y p e r v e n t i l a t i o n , l i v e r d y s -f u n c t i o n , c a t e c h o l a m i n e r e l e a s e , t h e u s e o f a n a e s -

t h e t i c a g e n t s , o r i n f u s i o n o f s o d i u m b i c a r b o n a t e( O l i v a , 1 9 7 0 ) . A r t e r i a l b l o o d l a c t a t e w a s n o t i n -c r e a s e d i n t h e o n e p a t i e n t w i t h a b n o r m a l l i v e rf u n c t i o n ( C a s e 2 ) o r i n t h o s e c h i l d r e n g i v e n k e t a m i n eb e f o r e l u m b a r p u n c t u r e ( T a b l e 1 ) . S o d i u m b i c a r -b o n a t e i n f u s i o n d i d n o t p r e c e d e s a m p l i n g o f b l o o do r CSF i n t h e p a t i e n t s s t u d i e d .CSF l a c t a t e e x c e e d e d 2 a 1 m m o l / l ( 1 8 - 9 m g / 1 0 0 m l )

( t h e u p p e r l i m i t o f n o r m a l f o r c o n t r o l s ) i n 8 p a t i e n t s .T h i s i n c r e a s e c o u l d h a v e r e s u l t e d d i r e c t l y f r o m

c e r e b r a l m e t a b o l i c c h a n g e s d u r i n g t h e s e i z u r e , i c t a lo r p o s t i c t a l h y p e r v e n t i l a t i o n , o r t h e t r a n s f e r o fl a c t a t e f r o m b l o o d t o C S F . I f t h e h y p o t h e s i s i sc o r r e c t t h a t a n i n c r e a s e i n b o t h CSF l a c t a t e c o n -

c e n t r a t i o n a n d i n l a c t a t e / p y r u v a t e r a t i o i n d i c a t e sc e r e b r a l h y p o x i a ( S i e s j o a n d P l u m , 1 9 7 1 ) , t h i s w a sp r e s e n t i n o n l y 6 o f o u r p a t i e n t s . Our i n d i v i d u a lm e a s u r e m e n t s ( T a b l e 3 ) a r e n o t s t r i c t l y c o m p a r a b l ea s t h e y w e r e made b e t w e e n 3 a n d 1 8 h o u r s a f t e rc o n v u l s i o n s . T h i s v a r i a t i o n i n t i m i n g w a s u n a v o i d a b l ea s m o s t c o n v u l s i v e e p i s o d e s o c c u r r e d o u t s i d e

h o s p i t a l a n d a v a r y i n g p e r i o d h a d e l a p s e d b e fo re

h o s p i t a l a d m i s s i o n a n d s u b s e q u e n t l u m b a r p u n c t u r e .

H o w e v e r , m o s t o f o u r s a m p l e s w e r e t a k e n b e t w e e n4 a n d 8 h o u r s a f t e r c o n v u l s i o n s when a n i n c r e a s e d

CSF l a c t a t e may p e r s i s t e v e n when b l o o d l a c t a t ec o n c e n t r a t i o n h a s r e t u r n e d t o n o r m a l ( P o s n e r a n dP l u m , 1 9 6 7 ) . Lumbar p u n c t u r e w a s a v o i d e d i n t h e

f i r s t 3 h o u r s a f t e r c o n v u l s i o n t o p e r m i t t i m e f o re q u i l i b r a t i o n b e t w e e n b r a i n , c i s t e r n a l , a n d l u m b a rCSF l a c t a t e a n d p y r u v a t e . N o a t t e m p t w a s made t or e p e a t t h e l u m b a r p u n c t u r e s d u r i n g t h e s t u d y a n dt h e o p t i m a l t i m e f o r s a m p l i n g r e m a i n s u n c e r t a i n .

T h e i n t e r - r e l a t i o n s h i p b e t w e e n h y p o x a e m i a ,h y p e r c a p n i a , a n d i s c h a e m i a o n t h e e n e r g y s t a t e o f

t h e b r a i n i n n o n c o n v u l s i n g e x p e r i m e n t a l a n i m a l s h a s

b e e n i n v e s t i g a t e d b y S i e s j o a n d h i s c o l l e a g u e s( S i e s j o , 1 9 7 1 / 7 2 ; S i e s j o a n d P l u m , 1 9 7 1 ) . H y p o x -a e m i a p e r s e ma y r e s u l t i n an i n c r e a s e d l a c t a t e a n d

l a c t a t e / p y r u v a t e r a t i o i n b r a i n t i s s u e w i t h o u t c o n -c o m i t a n t r e d u c t i o n i n t h e e n e r g y s t a t e o f t h e b r a i n .H o w e v e r , a c o m b i n a t i o n o f i s c h a e mi a a n d h y p o x -a e m i a l e a d s t o p r o n o u n c e d l a c t a t e a c i d o s i s a n d a f a l li n e n e r g y p o t e n t i a l . E v e n t h e n , t h e c o m b i n e d

h y p o x a e m i c / i s c h a e m i c i n s u l t h a s t o b e g r e a t b e f o r e

h i s t o l o g i c a l c h a n g e s a r e p r o d u c e d ( S a l f o r d e t a l . ,1 9 7 1 / 7 2 ) .

S t u d i e s o f p r o l o n g e d e p i l e p t i c s e i z u r e s i n p r i m a t e s( M e l d r u m a n d B r i e r l e y , 1 9 7 3 ) h a v e s h o w n i s -c h a e m i c c h a n g e s a f t e r b i c u c u l l i n e - i n d u c e d s e i z u r e sl a s t i n g b e t w e e n 1 a n d 5 h o u r s . B r a i n d a m a g ea p p e a r e d t o o c c u r a f t e r t h e f i r s t h a l f h o u r a t a s t a g e

i n t h e s e i z u r e w h e n t h e r e wa s a s s o c i a t e d h y p e r -p y r e x i a , a r t e r i a l h y p o t e n s i o n , s y s t e m i c h y p o x a e m i a ,a c i d o s i s , a n d o c c a s i o n a l l y s e v e r e h y p o g l y c a e m i a .G e n e r a l i z e d s e i z u r e s l a s t i n g u p t o 5 h o u r s s o m e t i m e s

l e d t o b r a i n d a m a g e o r d e a t h . M u s c l e p a r a l y s i s a n da r t i f i c i a l v e n t i l a t i o n p r o t e c t a g a i n s t c o r t i c a l a n d

h i p p o c a m p a l d a m a g e d u r i n g p r o l o n g e d s e i z u r e s a n d

p r e v e n t c e r e b e l l a r d a m a g e w h i c h i s t h o u g h t t o b e

r e l a t e d t o h y p e r p y r e x i a a n d a r t e r i a l h y p o t e n s i o n( M e l d r u m e t a l . , 1 9 7 3 ) . I t i s u n l i k e l y t h a t o u r p a t i e n t ss u f f e r e d h y p o x i c i n s u l t o f t h i s d e g r e e . A l l w e r e

t r e a t e d w i t h a n t i c o n v u l s a n t s a n d e v e r y a t t e m p t w a smade t o m a i n t a i n o x y g e n a t i o n a n d c o r r e c t m e t a b o l i c

u p s e t s d u r i n g o b s e r v e d s e i z u r e s . O n l y a c a r e f u lf o l l o w - u p o f s i n g l e s h o r t a n d p r o l o n g e d f e b r i l e c o n -

v u l s i o n s w i l l s h o w w h i c h p a t i e n t s h a v e r e c u r r e n c e s

a n d p o s s i b l e ' h y p o x i c ' b r a i n d a m a g e . H o w e v e r , o u rr e s u l t s s u p p o r t t h e v i e w t h a t p r o l o n g e d o r r e c u r r e n t

c o n v u l s i o n s o f w h a t e v e r a e t i o l o g y ma y c a u s e c e r e -b r a l h y p o x i a , w h i c h i n t u r n m i g h t c o n t r i b u t e t o t h ep r o d u c t i o n o f l o c a l o r d i f f u s e s t r u c t u r a l c h a n g e s . T h e3 0 - m i n u t e ' s a f e ' p e r i o d s u g g e s t e d i s n e c e s s a r i l ys o m e w h a t a r b i t r a r y , b u t t h e r e i s i n c r e a s i n g a g r e e -ment t h a t more p r o l o n g e d c o n v u l s i o n s ( > 3 0m i n u t e s ) a r e p o t e n t i a l l y h a r m f u l ( A i c a r d i a n d C h e v -

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C e r e b r o s p i n a l f l u i d a c i d - b a s e s t a t u s a n d l a c t a t e a n d p y r u v a t e c o n c e n t r a t i o n s 8 4 9

r i e , 1 9 7 0 ; A i c a r d i a n d B a r a t o n , 1 9 7 1 ) . I t m i g h t a l s ob e i n f e r r e d f r o m t h e e x p e r i m e n t a l w o r k o f W a s t e r l a i n

a n d P l u m ( 1 9 7 3 ) a n d W a s t e r l a i n ( 1 9 7 6 ) i n i m m a t u r er a t s t h a t t h e d e v e l o p i n g human b r a i n , e s p e c i a l l y i ni n f a n c y , i s p a r t i c u l a r l y v u l n e r a b l e t o c o n v u l s i v e

h y p o x i a . T h u s i n c h i l d r e n u n d e r o n e y e a r t h e ' s a f e 'p e r i o d m i g h t b e l e s s t h a n 3 0 m i n u t e s .W e h a v e g i v e n e v i d e n c e o f c e r e b r a l h y p o x i a i n

c h i l d r e n f o l l o w i n g r e c u r r e n t o r p r o l o n g e d c o n -

v u l s i o n s a n d m e t a b o l i c t r e n d s s i m i l a r t o t h o s e s e e n

e x p e r i m e n t a l l y . T h e c l i n i c a l i m p l i c a t i o n s s e e m c l e a r .E v e r y a t t e m p t s h o u l d b e m a d e t o s t o p g e n e r a l i z e ds e i z u r e s a s e a r l y a s p o s s i b l e . O x y g e n a t i o n s h o u l d b em a i n t a i n e d t h r o u g h o u t c o n v u l s i o n s a n d m e t a b o l i ca n d a c i d - b a s e d e r a n g e m e n t s c o r r e c t e d . I f a n t i -c o n v u l s a n t s a r e i n e f f e c t i v e ( e . g . o v e r a 3 0 - m i n u t ep e r i o d ) m u s c l e p a r a l y s i s a n d m e c h a n i c a l v e n t i l a t i o ns h o u l d b e c o n s i d e r e d i n f u r t h e r m a n a g e m e n t .

W e t h a n k P r o f e s s o r J . 0 . F o r f a r f o r h i s s u p p o r t , a n dc o n s u l t a n t c o l l e a g u e s f o r a l l o w i n g u s t o i n c l u d ep a t i e n t s u n d e r t h e i r c a r e ; D r . J . M. I n g l i s a n d h i ss t a f f wh o c a r r i e d o u t v i r o l o g i c a l i n v e s t i g a t i o n s a tt h e C i t y H o s p i t a l , E d i n b u r g h ; a n d M r s . D . T e r v i twh o t y p e d t h e m a n u s c r i p t s .

R e f e r e n c e s

A i c a r d i , J . , a n d B a r a t o n , J . ( 1 9 7 1 ) . A p n e u m o e n c e p h a l o -g r a p h i c d e m o n s t r a t i o n o f b r a i n a t r o p h y f o l l o w i n g s t a t u se p i l e p t i c u s . D e v e l o p m e n t a l M e d i c i n e a n d C h i l d N e u r o l o g y ,1 3 , 6 6 0 - 6 6 7 .

A i c a r d i , J . , a n d C h e v r i e , J . J . ( 1 9 7 0 ) . C o n v u l s i v e s t a t u s e p i l -e p t i c u s i n i n f a n t s a n d c h i l d r e n . A s t u d y o f 2 3 9 c a s e s .E p i l e p s i a , 1 1 , 1 8 7 - 1 9 7 .

B l e n n o w , G . , a n d S v e n n i n g s e n , N . W. ( 1 9 7 4 ) . C e r e b r o s p i n a lf l u i d l a c t a t e / p y r u v a t e r a t i o i n c h i l d r e n w i t h f e b r i l e c o n -v u l s i o n s . N e u r o p a e d i a t r i e , 5 , 1 5 7 - 1 6 1 .

B r a d l e y , R . D . , a n d S e m p l e , S . J . G . ( 1 9 6 2 ) . A c o m p a r i s o no f c e r t a i n a c i d - b a s e c h a r a c t e r i s t i c s o f a r t e r i a l b l o o d ,j u g u l a r v e n o u s b l o o d a n d c e r e b r o s p i n a l f l u i d i n m a n , a n dt h e e f f e c t o f t h e m o n some a c u t e a n d c h r o n i c a c i d - b a s ed i s t u r b a n c e s . J o u r n a l o f P h y s i o l o g y , 1 6 0 , 3 8 1 - 3 9 1 .

B r o o k s , B . R . , a n d A d a m s , R . D . ( 1 9 7 5 ) . C e r e b r o s p i n a lf l u i d a c i d - b a s e a n d l a c t a t e c h a n g e s a f t e r s e i z u r e s i nu n a n e s t h e t i z e d m a n . N e u r o l o g y , 2 5 , 9 3 5 - 9 4 2 .

C o r s e l l i s , J . A . N . ( 1 9 7 1 ) . T h e n e u r o p a t h o l o g y o f humane p i l e p s y w i t h p a r t i c u l a r r e f e r e n c e t o s t a t u s e p i l e p t i c u s .B r a i n H y p o x i a , p p . 2 6 3 - 2 6 5 . E d . b y J . B . B r i e r l e y a n d

B . S . M e l d r u m . C l i n i c s i n D e v e l o p m e n t a l M e d i c i n e 3 9 / 4 0H e i n e m a n n , L o n d o n .

F a l c o n e r , M. A . ( 1 9 7 1 ) . G e n e t i c a n d r e l a t e d a e t i o l o g i c a lf a c t o r s i n t e m p o r a l l o b e e p i l e p s y . E p i l e p s i a , 1 2 , 1 3 - 3 1 .

F i s h e r , V . J . , a n d C h r i s t i a n s o n , L . C . ( 1 9 6 3 ) . C e r e b r o s p i n a lf l u i d a c i d - b a s e b a l a n c e d u r i n g a c h a n g i n g v e n t i l a t o r y s t a t e

i n m a n . J o u r n a l o f A p p l i e d P h y s i o l o g y , 1 8 , 7 1 2 - 7 1 6 .F o w l e r , M. ( 1 9 5 7 ) . B r a i n d a m a g e a f t e r f e b r i l e c o n v u l s i o n s .A r c h i v e s o f D i s e a s e i n C h i l d h o o d , 3 2 , 6 7 - 7 6 .

H a b e l , A . H . , a n d S i m p s o n , H . ( 1 9 7 7 ) . N e u r o l o g i c a l a n db i o c h e m i c a l c o r r e l a t i o n a t f o l l o w - u p o f c h i l d r e n s u f f e r i n gf e b r i l e c o n v u l s i o n s . I n p r e p a r a t i o n .

M e l d r u m , B . S . , a n d B r i e r l e y , J . B . ( 1 9 7 3 ) . P r o l o n g e de p i l e p t i c s e i z u r e s i n p r i m a t e s : i s c h e m i c c e l l c h a n g e a n di t s r e l a t i o n t o i c t a l p h y s i o l o g i c a l e v e n t s . A r c h i v e s o fN e u r o l o g y , 2 8 , 1 0 - 1 7 .

M e l d r u m , B . S . , a n d H o r t o n , R . W. ( 1 9 7 3 ) . P h y s i o l o g y o fs t a t u s e p i l e p t i c u s i n p r i m a t e s . A r c h i v e s o f N e u r o l o g y , 2 8 ,1 - 9 .

M e l d r u m , B . S . , V i g o u r o u x , R . A . a n d B r i e r l e y , J . B . ( 1 9 7 3 ) .S y s t e m i c f a c t o r s a n d e p i l e p t i c b r a i n d a m a g e . A r c h i v e s o fN e u r o l o g y , 2 9 , 8 2 - 8 7 .

O l i v a , P . ( 1 9 7 0 ) . L a c t i c a c i d o s i s . A m e r i c a n J o u r n a l o fM e d i c i n e , 4 8 , 2 0 9 - 2 2 5 .O u n s t e d , C . ( 1 9 7 1 ) . Some a s p e c t s o f s e i z u r e d i s o r d e r s .

R e c e n t A d v a n c e s i n P a e d i a t r i c s , 4 t h e d . , p p . 3 6 3 - 4 0 0 . E d .b y D . G a i r d n e r a n d D . H u l l . C h u r c h i l l , L o n d o n .

P o s n e r , J . B . , a n d P l u m , F . ( 1 9 6 7 ) . I n d e p e n d e n c e o f b l o o d a n dc e r e b r o s p i n a l f l u i d l a c t a t e . A r c h i v e s o f N e u r o l o g y , 1 6 ,4 9 2 - 4 9 6 .

S a l f o r d , L . G . , B r i e r l e y , J . B . , P l u m , F . , a n d S i e s j 6 , B . K .( 1 9 7 1 / 7 2 ) . E n e r g y m e t a b o l i s m a n d h i s t o l o g y i n t h e b r a i nd u r i n g c o m b i n e d h y p o x e m i a a n d i s c h e m i a . E u r o p e a nN e u r o l o g y , 6 , 3 2 9 - 3 3 4 .

S i e s j o , B . K . ( 1 9 7 1 / 7 2 ) . M e t a b o l i s m a n d f l o w i n t h e h y p o x i cb r a i n . E u r o p e a n N e u r o l o g y , 6 , 4 3 - 4 8 .

S i e s j o , B . K . , a n d P l u m , F . ( 1 9 7 1 ) . C e r e b r a l e n e r g y m e ta b o l -i s m i n n o r m o x i a a n d i n h y p o x i a . A c t a A n a e s t h e s i o l o g i c a

S c a n d i n a v i c a , S u p p l . 4 5 ,8 1 - 1 0 1 .

S i m p s o n , H . , H a b e l , A . H . , a n d G e o r g e , E . L . ( 1 9 7 7 ) .C e r e b r o s p i n a l f l u i d a c i d - b a s e s t a t u s a n d l a c t a t e a n dp y r u v a t e c o n c e n t r a t i o n s a f t e r s h o r t ( < 3 0 m i n u t e s ) f i r s tf e b r i l e c o n v u l s i o n s i n c h i l d r e n . A r c h i v e s o f D i s e a s e i nC h i l d h o o d , 5 2 , 8 3 6 - 8 4 3 .

W a s t e r l a i n , C . G . ( 1 9 7 6 ) . E f f e c t s o f n e o n a t a l s t a t u s e p i l -e p t i c u s o n r a t b r a i n d e v e l o p m e n t . N e u r o l o g y , 2 6 , 9 7 5 - 9 8 6 .

W a s t e r l a i n , C . G . , a n d P l u m , F . ( 1 9 7 3 ) . V u l n e r a b i l i t y o fd e v e l o p i n g r a t b r a i n t o e l e c t r o c o n v u l s i v e s e i z u r e s . A r c h i v e so f N e u r o l o g y , 2 9 , 3 8 - 4 5 .

Z i m m e r m a n , H . M. ( 1 9 3 8 ) . The h i s t op a t h o l o g y o f c o n v u l s i v ed i s o r d e r s i n c h i l d r e n . J o u r n a l o f P e d i a t r i c s , 1 3 , 8 5 9 - 8 9 0 .

C o r r e s p o n d e n c e t o D r . H . S i m p s o n , D e p a r t m e n t o fC h i l d L i f e a n d H e a l t h , U n i v e r s i t y o f E d i n b u r g h ,H a t t o n P l a c e , E d i n b u r g h .