Steroid dependent changes in human visual evoked potentials

LIFE SCIENCFS Vol. 6, pp . 327-334, 1967 . Printed in Great Britain.

aTSSOm

Pergamon Press Ltd .

n=rsmDrr aaex~ras zrt awes vzauer. ava~n roaalel, George e. Oje>ta~ and Scbart I. Sankia

~fational Institutws of Health, Dsthasda, Marylead (Received 6 September 1966 ; in final form 28 November 1966)

Prsrviow studies have demoostratad that patients with untreated adrenal corti-

cal insufficiency poasass iacrsaaed sensitivity for a nus~bar of sensory systeos ~aste, wll, hearing, (1-3~ . Treatment of thaw patients with xa-L active

steroids does not altar this incrwad sensory sensitivity while trsatmeat with carbohydrate-active steroids (Cee) stares sensitivity tarards normal . Other studies have indicated that psriphsral atonal conduction velocity is sigaifi-

caatly increased in patients with uatrewtad adrenal cortical insufficiency (4) while conduction across the a
altared after treatment xith lla; active agroids but rsturn to nomal after treatment with Cea . Bateau of thaw results it yard plausibL that the

pattsrn of visual avoloed potentials is patients with untreated adrenal cortical insufficiency might also ba steroid dependant,

äaterials and Methods

Svoked potentials for visual stisuli ware studied in 6 patients with adranal~cortical insufficiency (age 18 to 56) wader various conditions of staroad replacement . ties of thaw patients had eddisoa~s disease, ans had pan

hypopituitarism, ell patients with eddisonss disease had clinical features of this disuse, urinary 17-hydr~yeortieostaroids that ware belay 2 ng par 24

hears and did not increase with adrenocorticotropin (/1CTa), 40 II=givan intra-

venously over 8 hours, each day for 9 days . Tha pedant with panhypopituitar.ism had hypothyroidisa, hypogonadism and adrenal insufficiency, with urinary 327

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VISUAL EVOKED POTEniTIALS

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17-hydroaycorticostaroide bslop 2 mg per 24 hours, rising to 12 mg per day with ACTH .

All patiente ramaiaad on an air-conditioned metabolic ward and ate a

normal diet, which was wall tolsratsd swan when they were not receiving trsatmeat,

Sodium intakes was 100-200 mßq per day .

thrss conditions :

The patients ware studied under

1) Untreated for 4 or morn days, 2) treated with dssoaycort ~

costarona acstats (DOCA), 20 m8 per day for 2 to 7 days, and 3) traatsd with prsdaieolona (p1F), 20 mg par day or cortisone acetate 37 .5 mg par day for 4 to 9 days . $lectrosncephalographic response were recorded from scalp slectrodae from the O1 and 02 positions (International 1020 system) oa as Offner type TC Light flashes, at 2 snc intervals ware delivered from

slactrosncsphalograph .

a Gras~ Modal PS-2 photic stimulator at intensity 4, with the light 12 inches abwa the patisnt~s faces .

The patient was recumbent with his head stationary

and ayes closed throughout the recording period of 15 minutes,

Averaged evoked

responses to thane flashes were obtained from magnetic tape recordings of the occipital SSG by means of a program oa the LLNC computer l .

Averaged responses

for 500 mast periods after each flash were obtained for the initial and the final 45 flashes in sach 15-minute recording period under each condition of trsatmaat .

Sach sample of averaged responses from a patient in the untrsatsd

states was compared to an analogous samples from the same patient in the two treated statae (Fig . 1) .

Comparison of the uatrsatad state with traatmsat

with DOCA was made in each of the three patients so treated . wars treated with p1F or cortisone acstata .

All six

The camparisone ware based upon

similarl.tise is the peaks of the first 7 positive and aagativs deflections (waves) of the evoked response .

Thssa waves wre groupsd with respect to the

time of their appearances after the visual stimulus (Table I) . 1

J .S . Bryan, Unpublished puter, This program also respones . In the present meet) satsaded beyond the

For each wave

avsragsd evoked raspones program for the LILAC comprovides standard error maasuraments for each nvokad study waves 5-7 (waves with latencies of 163-267 two standard error limits in all casse .

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VISUAL EVOKED PDTENTL4IS

O,

Oz

FIG . 1 Averaged responses for 500 msac periods after each flash in one patient with panhypopituitariem . Tha uatraatnd condition is indicated by the solid 1~}s, treatment with cortisone acntata, by the dotted line . O1 and "2 indicate left and right occipital electrode placements, respectively . Initial sample represents the average of the first 45 flashes, the final sample, the avsraga of the last 45 flashna (after 15 miautea of continuous rhythmic flaahea) .

32 9

330

VISUAL EVOKED POTENTIALS

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Tabla I .

LATENCY CHAIfGâS I1( VISUAL EVO~EED RESPONSES IN YAT1ElTf8 WITH ADRENAL CORTICAL INSUl1rICIENCY APTES THEATM6NT WITH CARBOH7~$ATE-dCTIVE 8TbY0IDS (A) AND WTTH Na-F, ACTIVE STEROIDS (B) . LATENCY CHANC$

WAVE

Number 1

Mann latency from flesh in msac

30±3 .3+

S

la

67±2 .3

91±2 .8

3

4

5

123K+ .4

164±3 .1

210±3 .2

6

26714 .1

7

(1)

(2)

Untraatad vs . B Moan diff . in maeD

average

- 5 .6~ .7~

0 .2±1 .

initial (1)

- 4 .1+_4 .2

0 .0+_0 .0

- 5 .8+4 .2

O .Ofi1 .4

average

-10 .8±3 .6*

-2 .8±3 .9

initial

-10 .53 .6*

-0 .8+2 .2

final

- 7 .4+3 .8

-5 .8+7 .1

average

- 6 .2±2 .2*

3 .7±1 .2

initial

-10 .5+4 .1*

2 .5+7 .5

final

- 1 .9+4 .4

5 .0+5 .0

average

- 8 .$F4 .8

2 .7±1 .0

initial

- 2 .5+3 .8

-1 .2+1 .2

final

-15 .OF9 .0

6 .2+8 .4

average

-U+ .7±5 .6*

0 .8±4 .1

initial

-17 .06 .3*

-13 .7+6 .2

final

-13 .OF6 .1*

6 .3i-8 .8

average

-17 .1±2 .1~`

9 .2±5 .5

initial

-22 .1+1 .9~

3 .3+8 .8

final

-12 .1+4 .0*

15 .01-5 .0 *

avsraga

-26 .1±6 .8`

6 .7±1 .6

initial

-33 .5F7 .7~`

-3 .SF8 .7

final

-1ß .0F8 .0*

11 .2+12 .0

final

2

Uatraatad vs . A Maaa diff . in msnc

(2)

Avaraga of firnt 45 flashes . Avsraga of last 45 fluhae (aftsr 15 minutes of continuous rhythmic flashes)

* p,s .03, ** p .s .O1

+ Mesa ± S .E .M . (ia the untreated condition) * Msaa + standard error of düferencn

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VISUAL EVOKED POTENTIALS

33 1

diffanacas in latency and amplitude batwena the uatnatad and the two treatment conditions were calculated independently by each investigator .

Thasa sap-

~rate datnrmiaetioas of latency differences van found to agree within 5 mans or lees for each patiaat .

Thass latency diffsnncaa for the four samples of

each vava (O1 initial, O1 final, 02 initial, 02 final) free each patiaat van than averaged (Table I), Diffanacaa bagman the untreated a~ the two traatmeat conditions for the initial 45 flashes and the final 45 flashes (after 15 minutas) van also e~parataly determined for each vava is sash patiaat (Table I~ ëaaa and standard error of the mane of these diffsrancas van thaw canpu4d and T taste performed to evaluate dagra of significance (Tabls I) . Yaaults A dacnasn is latency vas obssrvad for each vava of the visual evoked rasponsa after treatment with CAS .

This decrees vas significant at the 1T. Lval

for the two wowa found at a latency of 210 sad 267 mans is the untreated casdi tion (Table I) .

Caaparisoa of the visual evoked responses obtained initially

and after a 15rminuta aaposurs to the rhythmic flashes indicated that the latansy dncraasas batvnaa the untreated sad CAS treated conditions van more marked, and achieved significance at the 1X level, only in the initial rasponsas, Responses from the 3 patients treated with DOG did not shw any coasisteat latency changes as compared to those obtained in the untreated state although comparison of the untreated responses to those after treatment with CAS is these three patients alone shwad significantly dacraassd latencies 2, This abssncs of consistent change is latency of visual evoked responses after traatmeat vith.DOG occurred is spite of the return of the hyparkalamia and hyponatremia observed in these patients towards normal and is apita of gains is aztracallular fluid volume . 2 Latency differences for vava 6, after treatment with CAS, vas -17 .9 ± 2 .5 mass, (p- .O1) for the 3 patients who received treatment with DOG .

VISUAL EVOKED POTENTIALS

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Comieteat changes is amplitude of visual evoked responses could not be clearly demonstrated under aithar treatment condition . Discussion The observed dacraaeee is latency of visual evoked responses after trnacwant with 011.8 lnpresaat additional evideaca relating changes in brain function to changes is CAS concentration.

Prwious data have daa metrated that datacticn

thresholds for taste, smell and boating in patients with untreated adrenal cortical insufficiency ware significantly lover than normal

(1-3) .

$yoked re-

spons~ latencies from sciatic nerve to thalamus have been found to be eignificandy laagthaned is adrenalectamisnd cats

(5-7) .

Ia each of thane experiments

there was a return toward normal values after treatment with CAB . this ie also the caea with human evoked responses,

Thus the

Presumably,

raepoasae "off

treatment" would be coneidarad unusually long and the decrease with treatment represents a return towards normal latency.

CAS action on visual evoked ra-

aponees appears to ba independent of changes is Na or & concaatration in the satracallular fluid,

for treatment with DOCA does not produce any consistent

change is lataacy . The effect of traatmaat with CAB is most pronounced on the two late waves of the visual evoked response .

These waves am coneidarnd to ba part of the

secondary portion of the evoked reaponsa, non-specific for a particular sensory modality and probably reflecting reticular activation system activity (8,9) . A dacreasa in lataacy after CAS treatment was also obsarvad in the auditory evoked potentials recorded from the temporal areas after s standard click in ilro of the patiente in this satins (G .A . Ojamana and S.I . Hankie, unpublished obsarvationa) .

The sensitivity changes in patients with adrenal cortical in-

sufficiency involve multiple sensory systems .

One explanation for all these

observations would be that withdrawal of CAB produces similar changes in the non-epacific portion of the sensory system . It has been previously recognised that visual evoked response latencies

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VISUAL EVOI~D POTQiTIALS

increase rith adaptation (10),

Ia tha prasent atudy, CA6 trutmant had a

333

greater affect on latencies in the "utudaptad state" (initial sample) than is the "adapted state" (final sample) .

Thus, ~ effect on the non-specific sea-

sort' system may ba more evident is the "uaadaptad responses" theta the affects of the non-apacific sensory system on cortical electrical activity are thought to play an important rota (11) . Cortisol has bann ahwn to ba present is the brain of acta (12) rhils both Cortisol and corticostarona have basa chain to be present in the brain of the cat (13) .

hollering adreaalactamy, concentrations of Cortisol and Cortico-

ataraie decrease significantly is cat brain (13) . The latency Changes obssrvad is this study may tall ba related to change in co~eatratioa of brais atero~,ds, This may occur through the direct action of Corticostaroids on braie tiasua or through their actions on ion balance across call mnsiranes,

Ia these respects,

the visual evoked rupoase could mirror change is brain metabolism . Summar~ Carbohydrata~activa steroid treatment of siz patienta rith untreated adrenal cortical insufficiency dscrusad the latency of visual evoked rasponass . Thasa change rare most pronounced in the secondary, aonvpscific portion of the evoked raspanse,

This decrease is latency ras not observed after treatoaat

rith lfa-[ activa staroids, Lfarencas 1.

~.I . ~lXß1I, J .H, QILL, JA . aad l .C, DAORj1, J. Clin . Iawat. 4-'2 (1963) .

2.

l.I . I9ZIQIR and 1r .C . BAaT'al, J . Clin . Invest , 4_,5

3.

t.I . ~lOZIDi, ~.~ . McGLOlR sad y,C . sAII'rit, FropL, ~adocr . 3oc ,, 47th Meating~p.. 9] (1965) .

4.

11 .I, ~~f.IX, J,1. GILL, JR ., J .Z, iTAgl6pLTZ, A.A . CA11 sad y,C, àAII~I, J . Clin . Invest . 42, 941 (1963) .

5.

8, 1rELaëAä, J .C . TOUT sad L.ü, POSE, Heurolo¢y 1~1

6.

8 . liIDàW~, Arch, lieurol.

7

460 (1962) .

721

1631 (1966) .

109 (1961) .

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VISUAL EVOKED POTENTIALS

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6, No .

7.

R .F . CHA1fl1EB8, B .L . FREBDMAti and C .H . SAi15~$, Eaperimaatal 1Tnurology 548 (1963) .

8.

L . CIGAR&, BEG . ,_3 1

9.

G . GOBE and D .B . LIl®SIaY, Scianca 148, 1244 (1965) .

10 .

M . HAIDEli, P . SPO$G aad D .B . LI~SLEY, Scianca 145, 180 (1964) .

11 .

D .B . LIBDSLEY, Haadbook of Physiology, Sac . 1, Nauro h siolo pp . 1570-78 . Amer . Phyaiol . Soc ., pashington, D .C ., (1960 .

12 .

J .C . TOUCHBT01~, ä . iABPA$Qi, P .A . HUG~S and M .B . HO$iITZ, etaroids 7~ 205 (1966) .

13 .

B .I . HE1~IN and F,C . BAlt1~8, Prog . Endocr . 8oc ., 48th Maating, p . 37 (1966) .

165 (1961) .

v . III,

3