MULTIPLE SCLEROSIS WITH EARLY CHILDHOOD ONSET
A C A S E R E P O R T
MARIA ISABEL CAMPOS VERGANI * — RUBENS REIMÃO ** — ANA MARIA CAMARA SILVA * — MAURO MUSKAT * — SANDRO ESPÓSITO * — ARON DIAMENT ***
S U M M A R Y — A 2 y e a r o l d b o y w a s a d m i t t e d o w i n g t o a s u b a c u t e e p i s o d e o f a t a x i c g a i t a n d h e a r i n g d e f i c i t . C o m p u t e r i z e d t o m o g r a p h y ( C T ) w a s n o r m a l a n d c e r e b r o s p i n a l f l u i d ( C S F ) a n a l y s i s r e v e a l e d g a m m a g l o b u l . n s l e v e l o f 1 5 . 4 % ( n o r m a l 7 t o 1 4 % ) . T h e r e w a s s p o n t a n e o u s r e m i s s i o n a f t e r 7 m o n t h s . A t 5 y e a r s o f a g e t h e b o y i n c u r r e d a s e c o n d e p i s o d e w i t h p r e d o m i n a n t l y r i g h t a p e n d i c u l a r a t a x i a a n d t o n i c g a z e d e v i a t i o n t o t h e r i g h t s i d e . C T s h o w e d a l o w - d e n s i t y l e s i o n i n t h e w h i t e m a t t e r a d j a c e n t t o t h e r i g h t f r o n t a l h o r n . V i s u a l a n d a u d i t o r y e v o k e d p o t e n t i a l s w e r e a b n o r m a l . C S F r e v e a l e d a m i l d i n c r e a s e i n g a m m a g l o b u l i n s l e v e l o f 1 4 . 5 % w i t h a n a b n o r m a l T l y m p h o c y t e s u b s e t s s t u d y . T h e c o m b i n a t i o n o f v i s u a l , c e r e b e l l a r , b r a i n s t e m a n d p a r a v e n t r i c u l a r l e s i o n s w i t h c l e a r r e m i s s i o n s a n d e x a c e r b a t i o n s , s u p p o r t e d b y C T , C S F a n d e v o k e d p o t e n t i a l s f i n d i n g s s u g g e s t s t h e d i a g n o s i s o f m u l t i p l e s c l e r o s i s e v e n a t t h i s e a r l y a g e .
Esclerose múltipla na infância: relato de um caso.
R E S U M O — O s a u t o r e s r e l a t a m o c a s o d e u m m e n i n o c o m p r o v á v e l e s c l e r o s e m ú l t i p l a , d e
i n í c i o a o s 2 a n o s d e i d a d e , c o m u m s e g u n d o s u r t o a o s 5 a n o s . O a c o m e t i m e n t o f o i p r e d o m i n a n t e m e n t e d e t r o n c o c e r e b r a l , c e r e b e l o , n e r v o ó p t i c o e p a r a v e n t r i c u l a r . T o m o g r a f i a c o m p u -t a d o r i z a d a , e x a m e d o l í q u i d o c e f a l o r r a q u e a n o c o m e l e -t r o f o r e s e d e p r o -t e í n a s e e s -t u d o d e s u b p o p u l a ç õ e s l i n f o c i t á r i a s T , b e m c o m o a a v a l i a ç ã o d o s p o t e n c i a i s e v o c a d o s v i s u a i s , a u d i t i -v o s e s ô m a t o - s e n s i t i -v o s s u g e r i r a m o d i a g n ó s t i c o .
The prevalence of multiple sclerosis ( M S ) is 50:1000CO, depending on
geogra-phical area and ethnic origin 14. It rarely occurs before 10 years of age, comprising
some 0.2 to 0.4% of the total patients 14. The present paper reports a case starting
early in childhood and emphasizes that such a diagnosis should be considered even
at such an early age.
C A S E R E P O R T
Li B L ( R G 2 2 G 7 4 6 9 J ) a 2 y e a r s 3 m o n t h s o l d b o y w a s a d m i t t e d t o t h e h o s p i t a l a u e
t o a s u b a c u t e e p i s o d e o f a t a x i c g a i t a n d h e a r i n g d e f i c i t f o r t w o m o n t h s . T h e r e w a s n o
p r e v i o u s r e m a r k a b l e d i s e a s e . H e h a s h e a l t h y p a r e n t s w i t h n o c o n s a n g u i n i t y o r n e u r o l o g i c a l
d i s e a s e s i n t h e f a m i l y . G e n e r a l p h y s i c a l e x a m i n a t i o n w a s n o r m a l . N e u r o l o g i c a l e x a m i n a t i o n
— A x i a l c e r e b e l l a r s i g n s , w i t h a t a x i c g a i t , f a l l i n g f r e q u e n t l y ; h y n o a c u s i a . L a b o r a t o r y
e x a m i n a t i o n s — C o m p u t e d t o m o g r a p h i c ( T C ) s c a n w a s n o r m a l . C e r e b r o s p i n a l f l u i d ( C S F ) :
0 c e l l s / m m 3 , a t o t a l p r o t e i n s 2 2 m g % , g l u c o s e 5 2 m g % ; V D R L , W a s s e r m a n n a n d W e i n b e r g
D i v i s i o n o f C h i l d N e u r o l o g y , D e p a r t m e n t o f N e u r o l o g y , U n i v e r s i t y o f S ã o P a u l o S c h o o l o f M e d i c i n e : * R e s i d e n t ; * * A s s i s t a n t P r o f e s s o r ; * * * H e a d , D i v i s i o n o f C h i l d N e u r o l o g y .
196 Arq. Neuro-Psiquiat. (Sao Paulo) Jt6(2) 1988
w e r e n o n r e a c t i v e . C S F p r o t e i n e l e c t r o p h o r e s i s s h o w e d a s l i g h t g a m m a g l o b u l i n s i n c r e a s e
o f 1 5 . 4 % ( n o r m a l 7 t o 1 4 % ) ; n o o l i g o c l o n a l b a n d i n g w a s p r e s e n t . T h e b o y w a s d i s c h a r g e d
w i t h t h e d i a g n o s t i c h y p o t h e s i s o f c e r e b e l l a r s y n d r o m e a n d h y p o a c u s i a o f u n d e t e r m i n e d
e t i o l o g y . N o s p e c i f i c t r e a t m e n t w a s g i v e n ; h i s c e r e b e l l a r s i g n s n o r m a l i z e d o v e r a t w o
m o n t h p e r i o d w h i l e a m o d e r a t e i m p r o v e m e n t i n h y p o a c u s i a o c c u r r e d o v e r a 7 m o n t h p e r i o d .
A t t h e a g e o f 5 y e a r s 1 m o n t h h e w a s r e h o s p i t a l i z e d w i t h t h e o n s e t o f a c u t e g a z e
d e v i a t i o n t o t h e r i g h t , s t a r t i n g t w o w e e k s p r e v i o u s l y . N e u r o l o g i c a l e x a m i n a t i o n — A p e n d i
-c u l a r a t a x i a g r e a t e r o n t h e r i g h t s i d e ; t e n d e n -c y t o a t o n i -c g a z e d e v i a t i o n t o t h e r i g h t ,
w i t h u n i m p a i r e d f i x a t i o n a n d t r a c k i n g c a p a c i t i e s ; o c u l a r f u n d i a n d o p t i c d i s c s w e r e n o r m a l .
L a b o r a t o r y e x a m i n a t i o n — C T s h o w e d a l o w - d e n s i t y l e s i o n i n t h e w h i t e m a t t e r a d j a c e n t
t o t h e r i g h t f r o n t a l h o r n w i t h n o m a s s e f f e c t a n d n o c o n t r a s t e n h a n c e m e n t a f t e r i n t r a v e n o u s
c o n t r a s t m e d i u m . A u d i o m e t r y c o n f i r m e d b i l a t e r a l h y p o a c u s i a . C S F : 9 c e l l s / m m a ( 6 0 %
l y m p h o c y t e s , 3 0 % r e t i c u l o m o n o c y t e s , 5 % n e u t r o p h i l i s , 2% p l a s m o c y t e s , 3 % m a c r o p h a g e s ) ,
t o t a l p r o t e i n s 1 8 m g % , g l u c o s e 5 8 m g % ; V D R L , W a s s e r m a n n a n d W e i n b e r g w e r e n o n r e a c t i v e .
C S F g a m m a g l o b u l i n s w e r e s l i g h t l y i n c r e a s e d ( 1 4 . 5 % ) a n d n o o l i g o c l o n a l b a n d i n g w a s p r e s e n t .
T h e C S F T l y m p h o c y t e s u b s e t s s t u d y s h o w e d a d e c r e a s e i n t h e T - a c t i v e s u b s e t a n d a n
i n c r e a s e i n t h e T - s e n s i t i z e d s u b s e t w h i c h s u g g e s t s l o c a l l y m p h o c y t e s i g n a l i n g i n t h e C S F
s y s t e m (10,11). E l e c t r o e n c e p h a l o g r a m w a s n o r m a l . S o m a t o s e n s o r y e v o k e d p o t e n t i a l ( S E P )
w a s n o r m a l ; p a t t e r n - r e v e r s a l v i s u a l e v o k e d p o t e n t i a l ( V E P ) r e v e a l e d r i g h t o p t i c n e r v e
i m p a i r m e n t . T h e b r a i n s t e m a u d i t o r y e v o k e d p o t e n t i a l w a s s u g g e s t i v e o f a b i l a t e r a l
i m p a i r m e n t o f t h e a u d i t o r y p a t h w a y a t t h e p o n t o m e s e n c e p h a l i c l e v e l . T h e c h i l d w a s t r e a t e d
w i t h p r e d n i s o n e 1 m g / k g / d a y w i t h r e m i s s i o n o f t h e o c u l o m o t o r d e f i c i t o v e r a t w o m o n t h
p e r i o d .
C O M M E N T S
At the first occurrence, clinical diagnosis of M S is generally impossible to
establish as there are no specific signs, symptoms or laboratory t e s t s
1 4. Ghezzi and
M a n a r a ? reported 58 childhood cases of M S ; Gall et a l .
6described 4 0 children and
adolescents with M S , reviewed from 1920 to 1952; Bye et a l .
4reported 5 cases in
childhood, most of these patients
4- G > 7
with first episode studied retrospectively. The
case discussed here underwent clinical and laboratorial evaluation in both episodes.
Initial bouts in childhood 6 , n , i 7 are usually accompanied by visual or brainstem
impairment followed, in order of frequency, by hemiparesis, paraparesis, ataxia and
difuse encephalopathy. Our patient had predominantly ataxia and brainstem signs
while visual impairment was not clinically detectable but revealed by V E P . The
course of the disease in children
2' 8 > 9
is mainly of the relapsing-remitting type as in
adults. An initially progressive course occurs in only 2 2 % 5 while complete recovery
after the first attack is found in 6 8 % 5 . In the patient discussed here, the two
episodes with a remissive course supports the diagnosis of M S . Onset before the age
of 10 years occurred in 7 of Gall et al's.6 4 0 cases with none before 7 years old.
In the large series reported by Ghezzi and M a n a r a
7, M S was not encountered prior
to 6 years of age; in the 125 cases of M S prior to 16 years of age analysed by
Duquette et al.5, 5 years was the earliest age at onset. Besides the case discussed
here, the onset of M S at 2 years of age has been described by Bejar et al.
1, Brandt
and Ziegler 2 , and Hauser and Bresnan 8. Brandt et a l .
2mentioned another case
with onset at the same age, with clinical evaluation and necropsy by Nobel, in 1912.
The diagnostic difficulties are well exemplified by our patient who at the first
bout was suspected of having a posterior fossa tumour ruled out by C T and the
clinical course. After the first hospitalization, the etiology of his cerebellar signs
and hypoacusia remained unclear. During the second episode, a relapsing-remitting
course was established, M S was suspected and supported by laboratory findings.
CSF gamma globulins levels are elevated in 50 to 6 5 % of MS patients and in the
case discussed here, a mild increase was detected. Lymphocyte subsets with a
decrease in T-active cells and increase in T-sensitized cells were present in our case
which is the most frequent pattern in the chronic, repetitive, inflammatory model
of which MS is a typical example, as pointed out by Livramento et al.io. V E P
demons-trated unilateral but otherwise undetected optic nerve impairment in the patient here
described which occurs in 14% of children with M S is. V E P and SEP are established
as superior to clinical routine evaluation in demonstrating lesions in these pathways,
in MS
3 .nerve lesions evidenced by C T and VEP supported by CSF pattern suggest the
diagnosis 9 of M S despite the early age of onset. These characteristics fulfill all
the necessary criteria of Schumacher et al.ie with the exception of the precipitate age
of onset. For this same reason, the case here reported does not fit into the
'definite MS' category using the guidelines of Rose et al.is but would be better
considered as 'probable MS'.
Acknowledgement — T h e a u t h o r s w i s h t o t h a n k A . S p i n a - F r a n ç a , M . D . , J . A . L i v r a m e n t o ,
M . D . a n d L . R . M a c h a d o , M . D . , f o r k i n d l y p r o v i d i n g t h e C S F s t u d i e s .
R E F E R E N C E S
1. B e j a r J M , Z i e g l e r D K — O n s e t o f m u l t i p l e s c l e r o s i s i n a 2 4 - m o n t h - o l d c h i l d . A r c h N e u r o l 4 1 : 8 8 1 , 1 9 8 4 .
2 . B r a n d t S , G y l d e n s t e d C , O f f n e r H , M e l c h i o r J C — M u l t i p l e s c l e r o s i s w i t h o n s e t i n a t w o - y e a r - o l d b o y . N e u r o p e d i a t r i c s 1 2 : 7 5 , 1 9 8 1 .
3. B u g g e n h o u t E , K e t e l a e r P , C a r t o n H — S u c c e s s a n d f a i l u r e o f e v o k e d p o t e n t i a l s i n d e t e c t i n g c l i n i c a l a n d s u b c l i n i c a l l e s i o n s i n m u l t i p l e s c l e r o s i s p a t i e n t s . C l i n N e u r o l N e u r o s u r g 8 4 : 3 , 1 9 8 2 .
4 . B y e A M E , K e n d a l l B , W i l s o n J — M u l t i p l e s c l e r o s i s i n c h i l d h o o d : a n e w l o o k . D e v e l o p M e d C h i l d N e u r o l 2 7 : 2 1 5 , 1 9 8 5 .
5. D u q u e t t e P , M u r r a y T J , P l e i n e s J , E b e r s G C , S a n d w i c k D , W e l d o n P , W a r r e n S , P a t y D W , U p t o n A , H a d e r W , N e l s o n R , A u t y A , N e u f e l d B , M e l t z e r C — M u l t i p l e s c l e r o s i s i n c h i l d h o o d : c l i n i c a l p r o f i l e i n 1 2 5 p a t i e n t s . J P e d i a t r 1 1 1 : 3 5 9 , 1 9 8 7 .
6. G a l l J C , H a y e s A B , S i e k e r t R G , K e i t h H M — M u l t i p l e s c l e r o s i s i n c h i l d r e n : a c l i n i c a l s t u d y o f 4 0 c a s e s w i t h o n s e t i n c h i l d h o o d . P e d i a t r i c s 2 1 : 7 0 3 , 1 9 5 8 .
7 . G h e z z i A , M a n a r a F — M u l t i p l e s c l e r o s i s i n c h i l d h o o d . A c t a N e u r o l ( N a p o l i ) 3 3 : 1 5 7 , 1 9 7 8 . 8. H a u s e r S L , B r e s n a n M J — C h i l d h o o d m u l t i p l e s c l e r o s i s : c l i n i c a l f e a t u r e s a n d d e m o n s
-t r a -t i o n o f c h a n g e s i n T c e l l s s u b s e -t s w i -t h d i s e a s e a c -t i v i -t y . A n n N e u r o l 1 1 : 4 6 3 , 1 9 8 2 . 9. K e l l y R — C l i n i c a l a s p e c t s o f m u l t i p l e s c l e r o s i s . I n K o e s t i e r J C ( e d ) : H a n d b o o k o f
C l i n i c a l N e u r o l o g y . E l s e v i e r , A m s t e r d a m , 1 9 8 5 , v o l 4 7 .
1 0 . L i v r a m e n t o J A , M a c h a d o L R , S p i n a - F r a n ç a A — S i n a l i z a ç ã o d o l í q ü i d o c e f a l o r r a q u e a n o e m d o e n ç a s i n f l a m a t ó r i a s c r ô n i c a s d o s i s t e m a n e r v o s o c e n t r a l . A r q N e u r o - P s i q u i a t ( S ã o P a u l o ) 4 4 : 3 5 1 , 1 9 8 6 .
1 1 . L o w N L , C a r t e r S — M u l t i p l e s c l e r o s i s i n c h i l d r e n . P e d i a t r i c s 1 8 : 2 4 , 1 9 5 6 .
1 2 . M a c h a d o L R — S u b p o p u l a ç õ e s l i n f o c i t á r i a s d o l i q ü i d o c e f a l o r r a q u e a n o : I I . T é c n i c a . A r q N e u r o - P s i q u i a t ( S ã o P a u l o ) 4 1 : 1 3 2 , 1 9 8 3 .
1 3 . M a c h a d o L R — S u b p o p u l a ç õ e s l i n f o c i t á r i a s n o l í q ü i d o c e f a l o r r a q u e a n o : I I I . V a l o r e s n o r m a i s . A r q N e u r o - P s i q u i a t ( S ã o P a u l o ) 4 1 : 1 3 7 , 1 9 8 3 .
1 4 . P o s e r C M — D i s e a s e s o f t h e m y e l i n s h e a t . I n B a k e r A B , B a k e r L H ( e d s ) : C l i n i c a l N e u r o l o g y . H a r p e r & R o w , P h i l a d e l p h i a , 1 9 8 2 , v o l 2 , p g 2 1 .
1 5 . R o s e A , E l l i s o n G , M i y e r s L , T o u r t e l l o t t e W — C r i t e r i a f o r t h e c l i n i c a l d i a g n o s i s o f m u l t i p l e s c l e r o s i s . N e u r o l o g y 2 6 : 2 0 , 1 9 7 6 .
1 6 . S c h u m a c h e r G , B e e b e G , K i b l e r R , K u r l a n d L , K u r t z k e J , M c D o w e l l F , N a g l e r B , S i b l e y W , T o u r t e l l o t t e W , W i l l m o n R — P r o b l e m s o f e x p e r i m e n t a l t r i a l s o f t h e r a p y i n m u l t i p l e s c l e r o s i s . A n n N Y A c a d S c i 1 2 2 : 5 5 2 , 1 9 6 5 .
