Pediatrics 1969 Menkes 1 3

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1969;44;1Pediatrics

John H. MenkesANOTHER LOOK

THE CAUSES FOR LOW SPINAL FLUID SUGAR IN BACTERIAL MENINGITIS:

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\ ‘o i r’ 44NUMBER 1

COMMENTAR I E S

SUGAR

LOOK

1

P ed fa t r icsJU LY 1969

THE CAUSES FOR LOW SP INAL FLU ID

IN BACTER IAL M EN ING IT IS : ANO THER

Q Ni : of th e m ost charac te ristic abno r-

m alities o f ce reb rosp in al flu id (CSF)

in p atien ts w ith bac te ria l and tubercu lo iism enin g itis is a dec rease in its g lucose co n-

ten t. T h is find ing , firs t observed by L ich-

the im, was in itia lly a ttribu ted to u tiliza tio n

of g lu cose by the l)acte ria g row in g in the

flu id . T h is exp lana tion , as m any sub se -

quen t on es , has b een abandon ed in th e

l igh t of conf lic ting ex perim en tal ev idence ,

an d at presen t the m echan ism s induc’ing a

low C SF sug ar ar e en igm atic . R ecen t pub ii-

ca tion s bearing au th is P rO l)lem Pr0 IBP t a

rev iew of the fac to rs invo lved in low erin g

ce i’eb rosp in a l flu id sug ar .

G o id ring and H arfo rd it foun d tha t the

u tiliza tion of g lucose 1w concen tra tions of

pn eum ococc i equa l to o r h igher than those

usu ally seen in m en ing itis w as too sm all to

be measu red and cou ld , the re fo re, no t a f-

fec t the sp in a l flu id sug ar in th e face of a

norm a l m ech an ism for its rep len ishm en t.

Th is s tudy , and one by m o ,’ w ho d em on-

stra ted th at u nder norm al co nd itio ns g lu -

cose w as transpo rted in to the C SF m o re

rap id ly than its u tiliz atio n by lym phocy te s,

sug gested to P c te rsdorf and H arte r# {176 } tha t

the decrease in CSF sugar w as du e to its

enhanced u tiliza tion b y phag ocy tiz ing po ly -

m orph onu clea r leuko cy te s in th e ireseu ice

of l)ac te ria . W ork ing with dogs , P e tersdorf,

e t a !. #{176}‘ show ed th at 1 )0 th in civo an d in

citr() the in trodu ction of bac te ria in to CSF

con tain ing po lym orp honuc lea r ee l Is in -

du ced a low ering of CSF sugar. T h is d id

no t occur w hen live b ac te ria w ere in jec ted

in to n orm al CSF , o r in to f lu id of an im als inw hom th e ce llu la r respon se to the in jec tio n

o f s te rile sa line h ad been in h ib ited by irra -

d ia tion -ind uced leukop en ia . Two ob jections

can be ra ised to the hy po thesis tha t the

low ered CSF sug ar is the resu lt o f the com -

b in ed presen ce of b ac te ria and phago cy tes .

First, it fails to exp la in the low C SF sugar

seen in tub ercu lo us m en ing itis and in o ther

m en in g itides ch arac te rized b y a s ligh t m o-

n onuc lea r resp onse. T he secon d ob jection is

th a t, even w hen the m etabo lism of leuko-

cy tes is enhanced th rough the presence of

bac te ria , bac ter ia l g lu co se up take is bu t a

frac tion o f the am oun t m etabo lized by the

bra in .

A ssum ing th at a ty p ica l ch ild w ith b ac te -

ria l m en in g itis has a CSF vo lum e of 100 m l

and u sing the da ta o f P e te rsdo rf and

H arde r,# {17 6} 75 m g of g lu cose is consum ed iw

C SF po lym orphonuc lear ce lls in 2 hours.

S im ila r resu lts a re ob ta ined w hen w e us e

v alu es fou nd by C ohn and M orse fo r gh i-

cose u tiliza tion by endo tox in -s tim u la ted

p o lym orp honuc lea r leukocy tes . T h is co n-

trasts with the u tiliza tion of a l)o u t 75 rug

g luco se per m inu te by the res ting adu lt

b rain . F or these reasons an im p a irm en t in

th e tran sfe r o f g lu co se be tw een b lood and

C SF and bra in an d CSF h as been sug -

gested as con tribu ting to the redu c tion of

sp ina l flu id sug ar .

PEDIAT II I ( ; s , Vo l . 44 , No . 1 , Ju ly 1969








2 SPIN AL FLU ID SUGAR

Fishmant and Crone’#{ 176 } have found that,

under physio lo g ical conditions, the transfer

o f g lucose from blood to CSF and brain is

dependent on tw o fac to rs : s imple diffus io n

and carrier-fac ilitated diffusion. In bacterial

mening itis , bo th mechanism s may func tion

abnormally . S ifontes, et hav e found

that g lucose transport from blood to CSF is

usually inhibited o r de layed in tuberculous

m ening itis , and a number o f o ther clinical

studie s hav e since confirm ed this defect in

non-v iral m ening itide s.

Recently , Prockop and Fishma&2 have

found both the fac ilitated diffusio n o f g lu-

co se from blood to CSF and the fac ilitated

outw ard diffusion o f g lucose from CSF to

blood to be impaired in bacterial meningitis

and, significantly , that a nonspec ific in-

crease in the perm eability o f the m em-

branes betw een blood and CSF, as m ea-

sured by the rates o f mannito l entry and

disappearance , allow ed more hexose to

enter the CSF than w ould be exc luded by

the inhibitio n o f the carrier sys tem .

It is there fore like ly that facto rs aside

from those already c ited contribute to the

reduced CSF sugar in mening itis . One of

these is the greater utilization of g luco se by

the brain as a consequence o f an increase in

the rate o f cerebral g ly co lysis re lative to

g lucose o x idatio n.U nder normal conditions, brain ox idize s

about 85% o f the g lucose it utilizes, while

but 15 % is converted to lac tic acid. S ince ,

theoretically , g ly co lysis y ie lds 2 mo les and

g lucose ox idation 36 mo les of high energy

phosphates per mo le o f g luco se utiliz ed, a

decrease [as fo r instance from 85% to 45% in

the re lativ e amount o f g lucose ox idized by

the tricarhoxy lic ac id (Krebs) cy c le] w ill

increase l)y 78% the amount o f g lucose re -

quired to maintain a constant rate o f en-

e rg y pro duc tio n.

The ev idence for a s ignif icant decrease in

cerebral g lucose ox idatio n, and an increase

in g lyco ly sis in bac terial m ening itis may be

summarized as fo llow s:

1 . A n increased CSF lactic ac id concen-

tratio n has been noted in patients w ith bac-

terial and tuberculous , but not w ith v iral,

mening itis.1 4 ’1 ’ A lthough lac tic ac id has

been cons idered to arise from the metabo-

lism of g luco se by phagocytiz ing leuko-

cy te s, a consideratio n of lac tic acid trans-

po rt mechanism s makes this highly unlike ly .

Po sner and Plum15 have show n that, in al-

te red phy sio lo g ic s tates , CSF lac tic ac id

concentratio ns paralle l those in the brain

rather than those in arterie s o r cerebral

ve ins. Therefore , the increased CSF lac tate

in bacterial mening itis re flec ts a propo rtio n-

al increase in brain lac tate . In the absence o f

impaired brain-CSF-brain transpo rt o f lac -

tic ac id, it is highly unlike ly that lac tic ac i-

dosis o f the CSF could be maintained so lely

through the anaerobic g lyco lysis by po ly -

morphonuc lear leuko cy tes, but it also re-

quires participatio n by the brain in lac tic

ac id production. The productio n of 12 mg of

lac tic ac id per m inute by the normal resting

adult brain, and 0 .06 0 mg lactic ac id by 1 X

10 endotox in stimulated po lymorphonu-

c lear ce lls per hours emphas ize s the re lativ e

dimens ions of the tw o sources fo r lactic ac id

production. W hile increased lactic ac id pro-

duc tion also occurs in status epilepticus and

fo llow ing experimentally induced se i-

zures,1 6 increased g lucose utilizatio n o ccur-

ring under these conditio ns is compensated

fo r by a tenfo ld increase in g lucose uptake

by the brain, and no chang e in CSF glucosew ould be expected.

2 . Reduction in the activ ity o f ox idativ e

enzymes in the neutrophil occurs w ith m ini-

m al degrees o f tissue damage , such as fo l-

low ing anox ia or head trauma, and is de -

tec table by histo chem ical techniques in the

absence o f any obv ious anatom ical or his-

to log ic alte rations. S Converse ly , w hole

body radiatio n has l)een shown to increase

g luco se o x i( latio n and decrease g lyco ly sis o f

adult rat cortex .1 9 The experiments o f Pc -

tersdorf, et a l.e show ing that a low ering of

CSF gluco se can be prevented by prior ir-

radiation of animals should perhaps be in-

terpreted in light o f this most recent find-

ing.

3 . Increased brain g lycogen has been

noted in anox ia and in a varie ty o f infec-

tious conditions, inc luding mening itis . In








COMMENTARIES 3

experimental injurie s the increased g lycogen

finding corre lates w ell w ith a decrease in

the ac tiv ity o f enzymes partic ipating in the

ox idation of g lucose ,2#{ 17 6} a nd w ith the slow ing

of e lec trical ac tiv ity o f the e lectroencephalo -

gram which o ccurs w hen g lucose o x idation

has been reduced by 50 % or more . These

finding s sugg es t that g lycog en fo rmation,

proceeding v ia g lucose 6 -phosphate (an in-

termediate in the g ly co ly tic pathw ay ), m ay

be re lated to decreased func tion o f the tn-

carboxy lic ac id cy cle , and that it is a rela-

tiv ely common response to m ino r degrees o f

rev ersible cerebral damage .

To sun# { 238} marize, a combination o f in-

creased g lucose utilizatio n by the brain due

to increased g lyco lysis and a defec tive g lu-

cose transpo rt appears at present to repre-

sent the prim ary fac tors fo r the low spinal

f luid sugar in bacterial mening itis .

J O H N H. MENKES, M.D .

D iv ision of Pediatric N euro lo gy

UCLA S choo l o f M edicine

Los Angeles, California 90024

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1969;44;1Pediatrics

John H. MenkesANOTHER LOOK

THE CAUSES FOR LOW SPINAL FLUID SUGAR IN BACTERIAL MENINGITIS:

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