Arq. NeuroPsiquiatr. vol.29 número4

RHEOENCEPHALOGRAPHIC OBSERVATIONS IN MIGRAINE

B. G. L. V O N A L M A Y * G. S. B A R O L I N * * F . L . J E N K N E R * * *

Amongst the various forms of headache migraine is differentiated by

three main criteria: (1) intense pain, hemicranic in type, of which (2)

beginning and termination are clearly defined (meaning pain occurs in

so-called fits or attacks) and which is (3) recurring periodically. It should

be distinguished from continuous headache (vasomotor cephalea) even if the

latter is only one-sided (hemicranic) and pulsating or of changing intensity

as in waves. Typical and rare symptoms accompanying migraine such as

vomiting, scotomata, vegetative disturbances and others we shall not discuss

here since they have been presented separately (Barolin

).

The pathophysiological concept of migraine originated in studies of

Graham and Wolff

and was supported and extended later by H e y k

and

Pichler

. Generally, one assumes a trifold vascular process consisting of

(1) initial vasoconstriction, (2) overshooting vaso-dilation causing (3) stasis

of blood in terminal vessels, occasionally accompanied by edematous

transu-dation into surrounding tissue. Some assume abnormal patency of

pre-capillary arterio-venous anastomoses to play a role in this mechanism.

Lately, several "vaso-neuro-active substances" have been described (mainly

by Sicuteri

and Saraiva

) and their role in the evolution of migraine

was stressed. Inspite of these new humoral aspects which are being studied,

the aforementioned aspect of vascular phenomena in the pathophysiology of

migraine remains to be regarded as the most pertinent and ascertained

concept at this time.

Therefore, it seems most convenient to have an indirect electrical method

available for observing cerebro-vascular changes; rheoencephalography (REG)

is a method which allows apparently to objectivate such changes. It should

F r o m t h e lst

D i v . of t h e N e u r o l . H o s p i t a l of t h e C i t y of V i e n n a " R o s e n h ü g e l " ( D i r e c t o r : P r o f . D r . H . R e i s n e r ) a n d t h e N e u r o l o g i c a l Clinic of t h e H o s p i t a l of P u b l i c E m p l o y e e s of t h e S t a t e of S ã o P a u l o ( H e a d : Prof. D r . R . M e l a r a g n o F i l h o ) : * F o r m e r h e a d of t h e S e c t i o n of R h e o e n c e p h a l o g r a p h y a t t h e N e u r o l o g i c a l Clinic, H o s p i t a l of P u b l i c E m p l o y e e s of t h e S t a t e of S ã o P a u l o , B r a s i l ; ** A s s i s t a n t a t t h e F i r s t D i v i s i o n of N e u r o l o g y H o s p i t a l of t h e C i t y of V i e n n a " R o s e n h ü g e l " ; *** N e u -r o s u -r g e o n a n d D o c e n t , G -r a z U n i v e -r s i t y , O e s t e -r -r e i c h .

be appropriate and interesting to compare the results obtained by this

method with EEG-tracings in cases of proven migraine. Should our present

concept of the pathophysiology of this disease be correct, one would expect

changes in the realm of cerebral circulation primarily and only secondarily

those relating to activity and metabolism of cerebral parenchyma. By its

properties and definition, REG then should give better indications of our

insight into pathology in cases of migraine than EEG may provide. Just

the opposite should apply to cases of primarily metabolic disorders.

EEG-findings in migraine have been reported extensively (Barolin

);

one may observe diffuse abnormality of bioelectrical activity of the brain

( e . g . dysrhythmia with interspersed sharp waves) as well as localized

changes, especially in recordings during an attack (focal character).

Obser-vations on REG also have been made (Orioli et a l .

) . In our study we

shall compare relative merits of REG and EEG after having determined the

value of REG as a diagnostic tool in cases of migraine.

M A T E R I A L A N D M E T H O D S

For e x a m i n i n g t h e problem a t hand, w e recorded r h e o e n c e p h a l o g r a m s (REG) of all p a t i e n t s w i t h s u s p e c t e d m i g r a i n e t h a t entered t h e n e u r o l o g i c a l s e r v i c e of t h e " N e u r o l o g i c a l H o s p i t a l of t h e City of V i e n n a — R o s e n h u g e l " d u r i n g a 2 - m o n t h s period. 54 p a t i e n t s w e r e s u b j e c t e d to REG d u r i n g t h e pain-free i n t e r v a l period; in s o m e of t h e s e c a s e s h e m o d y n a m i c o b s e r v a t i o n s w e r e a l s o possible d u r i n g a n a c u t e episode of p a i n . T h e s e p a t i e n t s w e r e part of a l a r g e g r o u p of persons s u f f e r i n g f r o m m i g r a i n e c o l l e c t e d a n d controlled f r e q u e n t l y in t h i s h o s p i t a l o v e r a n 11 y e a r period a s i n a n d o u t p a t i e n t s . W h i l e h o s p i t a l i z e d , t h e y w e r e c o m p l e t e l y and r e p e a -t e d l y e x a m i n e d p h y s i c a l l y and n e u r o l o g i c a l l y , i n c l u d i n g -t h e en-tire r a n g e of clinical w o r k - u p . EEG h a d b e e n recorded r e p e a t e d l y in all c a s e s . W h e n indicated, carotid o r / a n d v e r t e b r a l or 4 - v e s s e l - a n g i o g r a p h y and p n e u m o - e n c e p h a l o g r a p h y w e r e done. Therefore, a c c u r a c y of d i a g n o s i s m a y s a f e l y be said to be of t h e h i g h e s t s t a n d a r d possible to-day.

To j u d g e c h a n g e s in cerebral h e m o d y n a m i c s , indirect e l e c t r i c a l m o n i t o r i n g ( = REG) w a s c h o s e n b e c a u s e this special a p p l i c a t i o n of t h e i m p e d a n c e t e c h n i q u e w a s s e e n t o be d i a g n o s t i c a l l y v a l u a b l e a n d r e l i a b l e a c c o r d i n g to s t u d i e s of m a n y a u t h o r s in m a n y c o n d i t i o n s . B a s i c a l l y , t h e principle of REG m a k e s u s e of t h e c h a n g e s of i m p e d a n c e due to c i r c u l a t o r y e v e n t s w h e n a p p l y i n g a n a l t e r n a t i n g c u r r e n t t o p a r t s of t h e body. V a r i a t i o n s of i m p e d a n c e a r e d e p e n d i n g on h e m o d y n a m i c c h a -r a c t e -r i s t i c s s i n c e i m p e d a n c e of blood is s u f f i c i e n t l y b e t t e -r t h a n i m p e d a n c e of o t h e -r o r g a n s ( m u s c l e , adipose tissue, g l a n d s , bone, etc.) and t h e l a t t e r does not c h a n g e ( M a n n w h i l e t h e v o l u m e of blood does c h a n g e w i t h i n a body s e g m e n t w i t h t h e p r o p a g a t i o n of t h e p u l s e w a v e .

O b s e r v a t i o n s of t h e a c t u a l v o l u m e c h a n g e s are c a l l e d m e c h a n i c a l p l e t h y s m o g r a m s . F o r o b s e r v i n g c o r r e s p o n d i n g e l e c t r i c a l c h a n g e s , a s o p h i s t i c a t e d d o u b l e bridge circuit ( D o p p e l r h e o g r a p h Dr. Schuhfried) w a s used. T h e r e l e v a n c e of t h i s m e t h o d for o b s e r v i n g i n t r a c r a n i a l ( = cerebral) c i r c u l a t i o n u s i n g skin s u r f a c e e l e c t r o d e s h a s b e e n discussed and s h o w n p r e v i o u s l y ( J e n k n e r8

,9

) . T h e a d v a n t a g e of t h e t w o e l e c -trode s y s t e m o v e r o t h e r m o d e l s h a s b e e n d e m o n s t r a t e d ( S e i p e l2 5

) . E v i d e n c e of t h i s m a y a l s o be d e d u c e d f r o m a n o p h t h a l m o l o g i c a p p l i c a t i o n of t h e i m p e d a n c e t e c h n i q u e

( B e t t e l h e i ms

) .

t h e cerebrum, t h e normal t i m e p a s s i n g from R - w a v e of EKG to i n i t i a l rise of REG is a b o u t 0,10 sec. and from R - w a v e to m a i n ( = first) p e a k n o r m a ' l y e q u a l s a b o u t 0,25 sec. T h e s e t i m e i n t e r v a l s do not s h o w s i g n i f i c a n t d i f f e r e n c e s w i t h s e x b u t do c o r r e l a t e w i t h t h e p h y s i o l o g i c a l a g e of cerebral v e s s e l s in t h e n o r m a l s u b j e c t . N o t u n l i k e blood pressure recordings it h a s 2 p e a k s ( t h e first one h i g h e r t h a n t h e second o n e ) s e p a r a t e d by a notch.

A m o n g t h e m a n y criteria ( J e n k n e r " ) w h i c h h a v e been used for e v a l u a t i n g R E G - t r a c i n g s t w o h a v e s h o w n to be i n t e r e s t i n g in respect to our q u e s t i o n h e r e and s h a l l be m e n t i o n e d in s o m e detail. First of all there are t e m p o r a l r e l a t i o n s . T h e t i m e at w h i c h t h e m a i n (first) peak of t h e t r a c i n g o c c u r s in r e l a t i o n to e i t h e r initial rise of c u r v e or R - w a v e of EKG m a y be c o m p a r e d to t h e n o r m a l v a l u e s or b e t w e e n c u r v e s of t h e t w o h e m i s p h e r e s . T e m p o r a l r e l a t i o n s of t h e t w o p e a k s of t h e REGt r a c i n g ( i . e . REGt i m e i n REGt e r v a l from firsREGt REGto second p e a k ) m a y be i n d i c a REGt i v e of p a REGt h o -logy also. T h e second c h a r a c t e r i s t i c v a l u e u s e f u l for us h e r e is t h e so-called r e l a t i v e p u l s e - ( w a v e - ) v o l u m e ( K a i n d l " ) . This is an i n d e x c a l c u l a t e d from a m p l i t u d e of c u r v e ( e x p r e s s e d in O h m s ) , basic v a l u e of o v e r a l l r e s i s t i v e i m p e d a n c e ( e x p r e s s e d in O h m j ) and p u l s e r a t e / m i n . This i n d e x g i v e s a good r e l a t i v e ( s e m i q u a n t i t a t i v e ) v a l u e for e s t i m a t i n g pulse w a v e v o l u m e . I t s m e a n i n g for cerebral a p p l i c a t i o n (REG) h a s been clarified o n l y r e c e n t l y ( J e n k n e r " ) .

B e c a u s e of s i g n i f i c a n t r e s u l t s from a p p l i c a t i o n of REG d u r i n g an o r t h o s t a t i c stress t e s t ( J e n k n e r1 0

) it w a s decided to include t h i s t e s t i n g in t h e d i a g n o s t i c p r o g r a m of o u r p a t i e n t s . 43 of 54 p a t i e n t s w e r e s u b j e c t e d t o t h i s procedure. Recor-d i n g of REG anRecor-d EKG w a s Recor-done by m e a n s of a three c h a n n e l Recor-direct recorRecor-ding a p p a r a t u s . I n t h e c o n t i n u o u s t r a c i n g s of t h e o r t h o s t a t i c s t r e s s test, o n l y original R E G - l e a d s u s i n g one frontal ( = g r o u n d ) a n d o n e m a s t o i d ( = a c t i v e ) e l e c t r o d e for e a c h h e m i s p h e r e w e r e r e g i s t e r e d w i t h s i m u l t a n e o u s EKG, w h i l e for t h e short r o u t i n e recordings t h e s e w e r e followed by r e g i s t e r i n g d e r i v a t i v e c u r v e s t o g e t h e r w i t h EKG.

R E S U L T S

A s a second point of i m p o r t a n c e t h e r e s u l t s of c a l c u l a t i n g v a l u e s for r e l a t i v e p u l s e w a v e v o l u m e s ( = PR) d u r i n g a n o r t h o s t a t i c s t r e s s t e s t ( s l i g h t l y modified)

s h a l l be presented. I t b e c o m e s e v i d e n t t h a t i r r e s p e c t i v e of t h e t i m e course of c h a n g e s in blood p r e s s u r e a n d p u l s e r a t e s , v a l u e s of PR d e v i a t e d m a r k e d l y and in

a m o n o t o n o u s l y c h a r a c t e r i s t i c w a y from t h o s e t y p i c a l c u r v e s t h e s e v a l u e s s h o w in e i t h e r n o r m a l s or s u b j e c t s w i t h h y p o t e n s i v e (or h y p e r t e n s i v e ) d y s r e g u l a t i o n w h e n p e r f o r m i n g e x a c t l y t h e s a m e type of o r t h o s t a t i c s t r e s s t e s t ( S c h e l l o n g " ) . A c o m p a r i s o n of t h e r e p r e s e n t a t i v e course of PR- v a l u e s d u r i n g a S c h e l l o n g - t e s t a s s e e n

in p a t i e n t s d i s p l a y i n g o r t h o s t a t i c h y p o t e n s i o n w i t h t h e course of v a l u e s for a p a t i e n t w i t h m i g r a i n e is s h o w n d i a g r a m m a t i c a l l y in fig. 2. Here, t h e 27 yr. old p a t i e n t is t h e one w i t h h y p o t e n s i v e d y s r e g u l a t i o n w h i l e t h e 52 yr. old s u b j e c t ( G . H . ) suffers from m i g r a i n e . I n t h e c a s e of t h e l a t t e r p a t i e n t PR- v a l u e s i n c r e a s e d u r i n g

s t a n d i n g u p ( e v e n s i t t i n g ) and d e v i a t e from a d e c r e a s e of t h e s e v a l u e s a s is u s u a l l y s e e n in h y p o t e n s i v e s u b j e c t s . T h e y a l s o differ from t h e m i n i m a l t e n d e n c y t o w a r d s d e c r e a s e s e e n in n o r m a l s u b j e c t s . T h e s e differences w i l l h a v e to be e x p l a i n e d .

H a v i n g observed REG c h a n g e s r e p r e s e n t i n g d i s t u r b a n c e s in h e m o d y n a m i c s in c a s e s of m i g r a i n e t o o c c u r in a fairly l a r g e p e r c e n t a g e of c a s e s ( j u s t a s h a d b e e n o b s e r v e d by others, e . g . 6 5 % : Orioli e t a l .1 8

(or v i c e - v e r s a ) and h o w t h e s e c o r r e l a t e w i t h o t h e r i n v e s t i g a t i o n s a n d t h e clinical picture. We t h o u g h t it r e l e v a n t e n o u g h to c o m p a r e l a t e r a l i z i n g p a t h o l o g y by EEG a n d REG and u s e d t h e c o r r e c t n e s s (or i n c o r r e c t n e s s ) of t h e d e t e c t e d side of p a t h o l o g y a s our criterion. A s s e e n from d a t a in t h e t a b l e 1, R E G - t r a c i n g s a g r e e d three t i m e s a s w e l l w i t h t h e correct c l i n i c a l condition t h a n did E E G - t r a c i n g s . I n 3 c a s e s both e x a m i n a t i o n s d e v i a t e d from t h e c l i n i c a l picture.

F i n a l l y it m a y be i n t e r e s t i n g to c o m p a r e EEG and REG r e s u l t s of t h i s group of m i g r a i n e p a t i e n t s w i t h p a t i e n t s h a v i n g s i m i l a r a f f e c t i o n s of cerebral c i r c u l a t i o n . A group of p a t i e n t s w i t h Meniere's d i s e a s e a n d s y n d r o m e a n d a group of p r o v e n arteriosclerotic c h a n g e s in cerebral v e s s e l s both studied a t a p r e v i o u s o c c a s i o n

( J e n k n e r a n d V o j a c e k1 2

) w a s used. The r e s u l t s of t h i s c o m p a r i s o n i s p r e s e n t e d a s t h e t a b l e 2.

D I S C U S S I O N

To judge changes in cerebral hemodynamics the indirect electrical

moni-toring (REG) was selected because this special application of the impedance

technique was seen to be diagnostically valuable and reliable according to

the studies of many authors in the following conditions: determining the

biological age of cerebral vessels; cerebral arteriosclerosis; arterial stenosis

and occlusion (except of minute vessels; Schreiber

and distinction of it from hematoma) ; cerebral compression (also from

abscess) ; clarifying causes of stroke (with of without occlusion/stenosis of

vessels or hemorrhage); objectivating causes of cerebro-vascular insufficiency;

testing of various physiological and pathological conditions such as carotid

compression (for determining latéralisation of dependence on carotid blood

supply and sufficiency of collateral flow), lack of O 2 (athletic stress, e . g .

diving) and increase of g (by increasing acceleration in a human centrifuge)

It must be mentioned that few authors have reported the method not to

be suitable for some of these purposes ( e . g . Perez-Borja and M e y e r

) .

However, in most of these circuiting of apparatus and "selection" of patients

may be subject to criticism and the approximate relation of affirmatory to

negative reports in the literature is about 350 to one at this time.

At first let us regard the deviation of the shape of an REG-tracing from

a normal record seen in a routine REG of only 7 migrainous patients. The

later occurrence of the second peak ( i . e . lower on the catacrote slope; fig.

1) was not seen in any other well defined clinical condition studied. Such a

shape may be postulated mathematically only (applying the theory of REG

to a practical problem; R o t h

) if there are existing certain criteria of

damping (within the skull) of the pulse wave (initiated by cardiac action*)

as they should be present in cases of low CSF-pressure or decreased amount

of CSF within the intracranial space. Because of the small number of

cases in which this shape was observed one should not specify this as a

typical shape.

The control of the mathematically postulated condition comes when we

regard the later (and lower on the catacrote branch of the tracing) occurring

notch and second peak as a correlate of decreased peripheral vascular

resis-tance, contrary to earlier (i.e. higher on declining slope of REG occurring

notch in cases of increased peripheral vascular resistance, which was

mathe-matically postulated by K e n n e r

) . Thereby a slower propagation of the

pulse wave in cases of migraine would have to be postulated. To judge this

with the slightest degree of significance our number of observations is far

too small. However, we did compare the respective time intervals from our

7 cases with the same values of 178 average normal REG-tracings (evaluated

by computer) using 100 phases of each subject and the values for migraine

patients were higher, meaning the impression of a slower propagation of

pulse wave was conveyed.

Comparing the average of 100 phases of each of 246 arteriosclerotic

pa-tients, which should have a higher speed of propagation of pulse wave the

mean of this same time interval was shorter (even though not significantly

so) than in 178 normal REG's.

Summarizing this part of our results it seems that there is a group of

migraine patients in which the mathematical analysis of REG suggests that

they have decreased peripheral vascular resistance. We could see only one

case where increased peripheral vascular resistance was deduced from

REG-analysis. Another group showed arteriosclerotic changes which might of

course cover up and thereby make impossible to detect other REG-changes.

To correlate the respective changes seen in peripheral vascular resistance with

the diagnosis of migraine would require confirmation of our results on a

much larger number of cases. After this discussion of abnormal findings in

the timing of details of an REG-record we proceed to regarding findings of

REG-tracings during an orthostatic stress test on our patients.

First of all, it should be mentioned that the values for relative pulse

wave volume ( P R ) calculated from routine REG (short time registration) of

our migraine patients were found to be subnormal. This supplements the

low incidence of rather abnormal shape of REG observed but must be and

can be differentiated from the decrease of P R found in cases of CVI of

varying causes. A good means of such differentiation is calculating and

diagrammatically sketching the PR-values for the various parts of a

conti-nuous tracing obtained during performance of an orthostatic stress test.

Migraine patients show a very much different type of course of the PR-values

during such a test than is seen in all other pathological states and normals.

43 of our 54 patients were submitted to this test and the following courses

of PR-values were seen: 13 times the course could be called normal, 4 times

it was judged as pointing to hypotensive dysregulation and 26 times a course

was found which is shown in fig. 2 and could be termed "migrainoid".

Since not only the latter cases but also those 4 showing hypotensive trends

belonged to the group of proven migraine, 2/3 of the courses of PR-values

showed what was called "migrainoid" characteristics and this asks for further

discussion and explanation.

Amongst the possible mechanisms responsible for such a course the one

most likely to provide an explanation presupposes that the sensitivity of

reflexes regulating hemodynamics is very high in patients suffering from

migraine. These patients most commonly are hypotensive. Because of this

hypersensitivity, a further small drop in (brachial artery) blood pressure will

be overcompensated and an increase of relative pulse wave volume is resulting.

Otherwise P R would decrease or at least stay stable during the orthostatic

period of the test. Therefore it does not surprise to find initial PR-values

low as is true for all hypotensive subjects.

EEG. Of course, one clearly understands that 50% of EEG's were

patholo-gical in arteriosclerotic patients because of longer standing of the organic

pathology. In this condition, 100% of REG records were pathological. On

the other hand, in Meniere's attacks, only a 25% rate of pathological

EEG-findings was seen while no REG tracings were normal. Our study of REG

pathology in these 2 last conditions therefore is confirmed in its differential

diagnostic value by the observations in cases of migraine, where 73,6% of

EEG and 82,7% of REG were pathological.

This study then shows that REG as a technique supplying insight into

an aspect of cerebral circulatory events provides a better basis for diagnostic

evaluation of cases of migraine than does EEG. The small number of

our interval tracings on routine REG examinations (1/8 of total number

of cases studied) expresses the complexity of the problem: the supply areas

of both carotid and vertebral arteries as well as possibly the extracranial

vascular bed (Anthony et

)

may be involved in the pathophysiology of

migraine.

Our observations on the course of relative pulse wave volume during a

certain circulatory stress and their explanation by overshooting reflex

regula-tion provides a basis for understanding of the largely unsatisfactory therapeutic

effect sympathomimetic drugs have in cases of migraine. Generally, it is

regarded as typically for migraine that in the many hypotensive migrainous

patients derivatives of synephrine usually are of little avail and fail to

norma-lize blood pressure. This study gives an experimentally founded explanation

why this is so.

From these empirical observations alone one should not deviate too

much into theoreticizing suppositions; however, it is very satisfying that

REG apparently allows to objectivate the cerebrovascular state also in

migraine. Our results are ascertained by comparison with series of

studies in similar conditions. Now it seems that such studies may also be

applicable to and useful in following and evaluating therapeutic results

espe-cially in view of their harmlessness which invites repetition.

S U M M A R Y

According to the results of this study, it should be interesting to include

REG in the work-up of migrainous patients. In these and under similar

conditions, REG will be of diagnostic value.

R E S U M O

Reoencefalografia: observações na enxaqueca

No conceito fisiopatológico da enxaqueca atribui-se grande importância

às alterações vasculares. Por esta razão empregamos a reoencefalografia, mé¬

todo simples e inócuo que nos pareceu o mais adequado para estudar a hemo¬

dinâmica cerebral em casos de hemicrania. Nossas conclusões foram as

seguintes: (1) nos traçados reoencefalográficos de rotina encontramos, em

apenas 1/7 dos casos, alterações qualitativas e quantitivas significantes no

período intercrítico da enxaqueca, ao passo que mais de 2/3 dos traçados

po-diam ser classificados como patológicos e característicos, desde que utilizásse¬

mos o teste ortostático de Schellong; (2) a reoencefalografia parece ser mais

precisa do que a eletrencefalografia para o diagnóstico de hemicrania; este

fato é compreensível pois o reoencefalograma registra diretamente a hemo¬

dinâmica cerebral, enquanto que o eletrencefalograma registra a atividade

bioelétrica do parênquima a qual, por sua vez, apenas secundariamente depen¬

de de circulação sangüínea; (3) resultados semelhantes foram, também,

obser-vados em casos de síndrome de Menière nos quais a eletrencefalografia seria,

também, menos útil que a reoencefalografia.

De acordo com estes resultados, parece-nos ser lícito sugerir a inclusão

la reoencefalografia na rotina e no controle terapêutico de pacientes com

íemicrânia. Nesta e em outras condições similares a reoencefalografia é

im método paraclínico de alto valor.

R E F E R E N C E S

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