Studies of cerebral circulation in brain injury

STUDIES

OF C E R E B R A L

CIRCULATION

IN BRAIN

INJURY

II. - - Cerebral c o n c u s s i o n 1 JOHN S. MEYER, M . D . a n d D. DENNY-BROWN, M . D . Neurological Unit, Boston City Hospital and the Department ol Neurology, Harvard Medical School, Cambridge, Mass. (Received for publication: May 10, 1955) INTRODUCTION

discharge followed by after discharge and extinction (Walker et al. 1944). Earlier theories of brain ischemia and hypoxia from cerebral compression as a cause of concussion seem unlikely in view of accumulated experimental data (Denny-Brown and Russell 1941; Denny-Brown 1945). It is generally agreed, that concussion is a traumatically induced transient derangement of the nervous system. I n the experimental animal loss of consciousness cannot be objectively evaluated but certain observable changes occur regularly. Immediately following a concussive blow there is abolition of respiration for some seconds, a steep rise in blood pressure with a gradual decline, extensor spasm aud loss of the corneal and other reflexes temporarily. This sequence of events occurs in the absence of demonstrable brain lesion. Associated with these manifestations are a deflection of the E E G pens due to blocking of the amplifiers at the time of the blow for 5-8 see., followed by diminished amplitude activity for a short interval before recovery (Denny-Brown and Russell 1941; Williams and Denny-Brown 1941; Walker et al. 1944). The diminished amplitude E E G activity is unrelated to electrical artifact caused by overloading the amplifiers since in man it has been shown to occur in boxers when the E E G records were made soon after the blow (Larsson et al. 1954). In the curarised, vinethene-novocaine anesthetised animal a marked increase in the frequency of the cortical activity with little i 1 This study was supported by a research grant decrease in amplitude has been reported rom the United States Navy. (Walker et al. 1944). Experimental concust~ Opinions expressed are those of the authors and sion also is accompanied by increased jugular not necessarily tel)resent those of the Department venous outflow shown by drop recorders the Navy. [ 529 ] Of all the phenomena arising from brain :rauma the most intriguing is that of the :ransient, reversible disorder of brain func;ion termed concussion, i n man, cerebral con~ussion has been well defined by Trotter ',1924), " a n essentially transient state due :o head i n j u r y which is of instantaneous )nset, manifests widespread symptoms of a )urely paralytic kind, does not as such tom)rise any evidence of structural cerebral n j u r y and is always followed by amnesia for :he actual moment of the accident." A phy;iological definition, encompassing all the ~nown clinical and experimental data is that )f Denny-Brown (1945), " a transitory and :eversible nervous reaction with i m m e d i a t e >nset following physical stress of sufficient ¢iolence and brevity, and characterized by orogressive recovery t h e r e a f t e r . " I n spite of many detailed experimental ;tudies of concussion opinion is still divided ~oncerning the underlying physiological nechanisms (Polls 1894; Denny-Brown and Russell 194]; Williams and Denny-Brown 1941; Merritt 1943; Walker et al. 1944; Den~ly-Brown 1945 ; Larsson et al. 1954). Theories ~oncerning the possible mechanisms in concussion have been reviewed in detail by Polls 1894) and more recently by Denny-Brown n d Russell (1941). Of the proposed mechmisms those that have been recently invoked ~re a transient neuronal paralysis (Demly[~rowu and Russell 1941; Williams and Denly-Brown 1941) and an excessive neuronal

530

JOHN S. MEYER and D. D E N N Y - B R O W N

(Polls 1894; K n a u e r and Enderlen 1922; Denny-Brown and Russell 1941) and increased carotid a r t e r y flow shown by the electromagnetic flow meter (Brown and Hines 1951 ; Brown and Brown 1954). In general, there are two main problems which have yet to be finally settled in concussion, the mechanisms of i n j u r y and the neuronal mechanisms underlying the transient interruption of function. B y analogy with the effect of ultrasound it is considered likely that the negative phase of the compression wave in the brain, by producing intracelhflar micro-vacua, is the effective mechanism of i n j u r y (Denny-Brown 1950). The present study has been directed toward elucidating neuronal mechalfisms involved in the transient loss of function. In the present experiments, we have elaborated methods we have previously employed at the Neurological Unit of the Boston City Hospital in a study of rapid local changes in cerebral circulation. We .have correlated these with DC recording which permits a wider understanding of the meaning of brain i n j u r y potentials (or steady potentials, or " S P " recently reviewed by Kempinsky, 1954). Using such methods we have critically studied experimental cerebral coneussion in order to attempt a clearer definition of the mechanisms involved. Such data may be of some practical importance in our understanding of the manifestations of head i n j u r y in man. During an extensive clinical and electrocncephalographic study - - by the U.S. Navy - - of head injuries during the Korean conflict one of the authors (J. S. M.) had personal experience with 140 cases of carefully studied brain injury. In that clinical study, initiated and directed by Dr. William F. Caveness (New York Neurological Institute), diminishcd E E G activity was commonly seen imme.diately after closed and penetrating bead injury, maximal higb voltage E E G abnormality usually being delayed for several hours to several days after injury. One of the objectives of the present experimental study was planned to examine the mechanisms underlying such early E E G changes.

METHODS

Observations have been made on 26 cats and on 32 monkeys (Macacus rhesus). Repeated concussive blows were made in the same animal. Records arc available of 117 concussive and subconcussive blows. Paralell data. on cerebral contusion, laceration, herniation and brain stein i n j u r y will be reported in a later paper (Meyer 1955). In the majority of experiments light pentobarbital anesthesia was used (0.4 to 0.6 g. per kg. of body weight). Similar results were found in a few animals anesthetised with ether or immobilized with dihydrobeta-erythroidin hydrobromide and local anesthesia (procaine 2 per cent). Concurrent records were made of local cortical oxygen availability, local blood flow (as illdicated by local changes in temperature) electro-corticogram ( E C G ) and E K G together with the femoral blood pressure and respirations. Ill some experiments the jugular venous pressure was recorded from the right jugular vein, and in others the eerebrospinal fluid pressure from the cisterna magna (Meyer et al. 1954; Meyer and DennyBrown 1955). Iu some experiments recordings were made of the local cortical p H and the SP (steady potential) of the brain, as it is now well established that damaged brain generates a negative i n j u r y potential (Kempinsky 1954). For control purposes we have frequently recorded the arterial oxygen saturation. For recording the latency of changes in cortical oxygen availability and SP with concussion in several experiments devised for this purpose we used a Westinghouse universal oscillograph ~ with a frequency response of less than a millisecond. For these experiments the output of the millivoltmeters was amplified with capacitor coupled amplifiers. The values of the parameters measured were therefore only valid for the first few seconds after the blow and the latency somewhat damped. A control of the response is shown in figure 3I where a 25 mV. square wave of 30 1 Type PA Universal Oscillograph, Westinghouse Electric Corporation, Newark, N.J.

CERNBRAL CONCUSSION

reset, duration was applied to the cortex of a cat between the recording electrodes. The stimulus is recorded with a latency of less than 5 msec. In all other experiments the slower Rubicon type of galvanometer was used, compatible with the slow rate of recording speed. In these experiments the time of the concussive blow was recorded by two leads of the Grass Electroencephalograph conneeted to the head and forepaw ( H P in fig. 3) this recorded not only the blow but the EKG and elements of the electroencephalogram. The validity of these methods has been critically reviewed in an earlier paper (Meyer and Denny-Brown 1955). Concussion was caused by three methods. The importance of the method used in the production of concussion has been emphasized previously (Denny-Brown and Russell 1941, DennyBrown 1945) and differences in the resultant pattern of changes have been found in this study. (1) Acceleration Concussion was produced by a blow on the occipital protuberance using a pendulum designed after that of Denny-Brown and Russell (1941), causing an acceleration blow of 29 feet per second 1. We have verified our polarographic data by this method in 7 cats, but the movement of the head inherent in this method is undesirable for multiple recording techniques. (2) Percussion Concussion was produced after the method described by Walker et al. (1944). A weight of 70 g. was dropped into a column of saline on the exposed dura, from a maximum height of 4 feet 6 inches and rapidly withdrawn by a light cord and pulley. The measured duration of blow was 0.1 to 0.2 'seconds. Dropping the weight from a height of 4 feet 6 inches regularly but by no means invariably produced concussion. (3) Compression Concussion was prodneed by sharply striking the plunger of a syringe designed for this purpose. The syringe was of 2 c.c. capacity filled with air 1 Professor Hans Muehler, Department of Physics, Massachusetts Institute of Technology, kindly made the calculations.

531

or saline screwed into a suitable trephine hole in the skull, with a 1 cm. diameter outlet. The duration of the blow was limited by an adjustable spring attached to the handle (fig. 1). In percussion concussion and compression concussion it is important that the concussive stimulus is applied for less than 1/10 of a sec. Longer duration of stimulus results in herniation, brain stem compression and ischemic effects totally unrelated to concu~.sion. In the majority of experiments recording electrodes other than E E G electrodes were placed through twist drill holes into the cortex and sealed into the skull with dental cement. In others, the electrodes were placed through a small trephine opening. The E E G was recorded with brass screws threaded through the skull to make contact with the dura. Concussion was judged according to the reflex changes (especially transient loss of corneal reflex) described by Denny-Brown and Russell, in addition electroencephalographic signs were used (Williams and Denny-Brown 1941). At the end of each experiment the brain, brainstem and cervical cord were examined at necropsy, for absence of contusion or laceration is an essential criterion. RESULTS

In experimental concussion in the cat or monkey a blow, by any of the three methods used, sufficient to cause severe concussion, results in transient loss of the corneal reflex, momentary arrest of the respiration, a rise in blood pressure (10 to 180 sec.) and diminution in E E G activity lasting "10-80 sec. These changes are shown in the blood pressure, respiratory and E E G traces of fig. 2B. In the majority of experiments concussion was caused by the percussion or compression method. We verified the polarographic observations in 7 cats by acceleration concussion, but all other data relates to concussion caused by compression or percussion. The results from either method were similar. It was found that when a blow is sufficient to produce concussion there is consis-

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JOHN S. MEYER alld D. DENNY-BROWN

tently a rise in the oxygen availability of the cortex with a latency of 20-80 msec. levelling off or beginning to fall after 6-8 sec. (fig. 3B-D). This occured when the E P G electrodes were placed through a trephine hole or through twist drill holes in the skull, but was more evident when placed through a trephine hole. The rise did not occur with subconcussive blows in the living animal or

(30 msee., 30 msec., 20 msec.). A f t e r several blows the E P G latency may be as short as 20 msec. (fig. 3D). With progressively severe blows the degree of r.ise in E P G increases being in the order or 1 x 10-SA. with a mild blow and 5 x 10 -s A. with a severe blow (fig. 3H). If the exposed cortex is examined closely and photographed ill color before a~ld after

Fig. 1 Method of recording compression concussion in the monkey. EEG brass electrodes screwed into skull. Concussion syringe with return spring is screwed into left side of skull, intracranial pressure transducer is screwed into right. EPG and SP electrodes are placed through twist drill holes. A thoracic trochar is visible on the left for recording respirations. EKG electrode attached to right forelimb. concussive blows iu the dead or shocked animal (fig. 3H). With suitable recording techniques it may be shown that progressively severe concussive blows increase the degree of rise of cortical oxygen availability and decrease the latency. With the first concussive blow the E P G latency may be as long as 80 msec. (fig. 3F) but repeated severe blows shorten the latency as in 3G (60 msec.) and 3B, C, D

the concussive blow, there appears after a delay of 15-30 sec. (usually associated with the rise in blood pressure) a flushed appearance of the exposed cortex. The E P G electrode will show a persistent or secondary rise d u r i n g this phase. The cortical temperature electrodes also show a delayed rise after a concussive blow but it is not as consistent or as remarkable as the E P G rise (fig. 2 A,B,C). The rise

CEREBRAL CONCUSSION of T 1 i n f i g u r e 2A is of u n u s u a l l y r a p i d d e v e l o p m e n t a n d is p r e s u m e d to be due to the electrode r e s t i n g on a large vessel. W i t h the electrodes c e m e n t e d into the skull, the t e m p e r a t u r e electrodes a n d r a r e l y

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one t e m p e r a t u r e electrode showed a rise a n d the other a fall, a n d i n r e c o r d B one E P G showed a rise a n d the other a s m a l l fall. A rise ill all electrodes is c o m m o n l y seen with a h a r d e r blow ill a closed system, how-

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Fig. 2 A. Cat, compression concussion. Light blow, electrodes placed through drill holes. EEG shown below record showed transient diminisked amplitude. Respirations slowed, blood pressure minimal rise. T 1 rises, T 2 adjacent to area struck shows fall. EPG and ICP rises. Time intervals 6 sec. B. Monkey, percussion concussion. Transient arrest of respirations with slowing, rise in BP. Diminished amplitude EEG except right frontal region (below record) EPG I and CSF immediate rise, T falls with delayed rise, EPG 2 fall. Electrodes placed through drill holes. C. Monkey, percussion concussion, heavy blow, loss of corneal reflex 30 sec. EEG diminished amplitude (below record) T, EPGs, and CSF and BP all show rise. Respirations irregular after blow. Electrodes placed throygh drill holes. Time intervals marked in vertical lines at top of each record in 6 see. intervals. T _-- Temperature electrode. EPG ~-- Oxygen electrode. ICP _-- Intraeranial pressure. CSF _-- Cerebrospinal fluid pressure. a n E P G electrode occasionally show a slight fall. F i g u r e 2A is a n e x a m p l e of m i n i m a l concussion i n which the blood p r e s s u r e a n d r e s p i r a t o r y c h a n g e s were m i n i m a l b u t the E E G c h a n g e s were m a r k e d . Ill this record

ever, as i n f i g u r e 2C. The fact t h a t with a t r e p h i n e hole the electrodes show a more c o n s i s t e n t rise we take to i n d i c a t e t h a t the t h r e s h o l d for increase i n the cortical oxygen a v a i l a b i l i t y a n d cortical blood flow m a y n o t

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J O H N S. M E Y E R and D. D E N N Y - B R O W N

be u n i f o r m f r o m point to point with minimal blows owing to variation in local forces. Rarely, other evidences of concussion occur without a remarkable rise in blood pressure, as in figure 2A, the t e m p e r a t u r e and E P G electrodes still show a rise, indicating that the increased cortical blood flow m a y occur independently of a n y rise in blood

3 and 4A). Following a concussive blow there is frequently a biphasic rise in the E P G , the initial immediate rise and a secondary fluctuation a f t e r a latency of 1.2 sec. or longer, coinciding with the m a x i m u m rise in blood pressure (fig. 5D); W i t h a blow localized to the posterior fossa by percussing the exposed d u r a overlying the cerebellum,

Fig. 3 l'wo exl)eriments (A-D and E-I) recorded at f a s t speed with capacitor coupled amplifiers to show latency of EPG and SP changes with concussion. Electrode positions shown. Time interval at bottom of figure. Upward deflection of SP indicates cortex negative to white matter, tt.P. Head to paw record to show electrostatic effect of the blow and components of E K G and EEG. All blows by compression concussion method. A. Subconcussive blow. B. Mild concussive blow, loss of corneal 8 sec. C. and D. Progressively severe blows with arrest of respiration for 8 sec. and 15 sec. respectively. E. Localized percussive paralysis of cortex with 4 mV. i n j u r y potential mmccompanied by E P G rise in another area of cortex. Blow to opposite hemisphere shown in diagram. F. and G. Progressively severe blows with temporary loss of corneal reflex and respiration. H. Same animal, control blow after sacrifice. I Same animal, 25 inV. square wave stimulus of 30 lnsee, duration applied near the electrodes for control of latency mid condenser effect.

the concussive effects m a y be limited to the pressure. As shown by D e n n y - B r o w n and Russell (1941) percussion concussion less con- brain stem (fig. 5B and 6A) and then the E P G rise is almost purely confined to the sistently shows a rise of blood pressure. I n severe or fatal concussion the rise in second phase and follows the t e m p e r a t u r e the oxygen availability of the cortex is of rise a f t e r a latent interval of a p p r o x i m a t e l y 12 see. more r a p i d development, greater t h a n with Multiple E P G electrodes dispersed over less severe blows and clearly indepeudant of a n y increase in cortical blood flow (fig. • the cortex do not invariably give a sinmlta-

CEREBRAL CONCUSSION neons rise w i t h concussion. I n f i g u r e 5C a n u n u s u a l l y l o n g d e l a y is seen in t h e r i g h t m o t o r r e g i o n while t h e r i g h t p a r i e t a l r e g i o n sh6ws a n i m m e d i a t e rise f o l l o w i n g a blow to t h e l e f t o c c i p i t a l lobe. This N o w p r o d u c e d a diminished amplitude EEG over the left hemisphere and posterior right hemisphere and, therefore, was a localized rather than a diffuse concussion which probably accounts

535

close a n a l y s i s . The t o t a l d u r a t i o n of t h e i n c r e a s e in c o r t i c a l o x y g e n a v a i l a b i l i t y is u s u a l l y of 1-2 min. d u r a t i o n a l t h o u g h in m i n i m a l a n d localized c o r t i c a l concussion i t m a y last o n l y 30 see. a n d in severe concussion with p r o l o n g e d e l e v a t i o n of t h e blood p r e s sure and cortical temperature it may persist for m a n y m i n u t e s . The m o r e i m m e d i a t e rise in the E1)G occurs a f t e r c e r v i c a l s y m p a t h e c -

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Fig. 4 A. Cat. Fatal compression concussion. After the blow there is arrest of respiration which returns transiently, only to fail again. The blood pressure rises and the EKG slows, the blood pressure falls following the apnea and is transiently restored by artificial respiration (AR). The ICP and EPG rise, as apnea continues the EPG falls off the record. The cortical temperature shows a delayed rise. The EEG is at first diminished in amplitude then disappears in the apneie phase. B. Cat. Severe compression concussion after 2 subeoncussive blows (SUB). Loss of corneal reflex 30 sec. Immediate cortical injury potential of 7 mV. (SP) EEG shows diminished amplitude and delta activity. EPG falls after apneic phase. Respirations irregular, cease •tnd return. Secondary SP fall due to respiratory anoxia. for the d i f f e r e n c e in r e s p o n s e of t h e o x y g e n electrodes. The s e c o n d a r y E P G rise, a f t e r a l a t e n c y of 12 see. a p p e a r s to be d u e to a n i n c r e a s e d cortical b l o o d f l o w a c c o m p a n y i n g c e r e b r a l v a s o d i l a t i o n a n d t h e blood p r e s s u r e rise. I t is co.mmonly a c c o m p a n i e d b y f l u c t u a t i o n s in the c e r e b r o s p i n a l a n d i n t r a c r a n i a l p r e s s u r e s (fig. 5A, D ) , a n d is most c l e a r l y seen a f t e r Io~,al blows to t h e p o s t e r i o r fossa. The i n i t i a l i m m e d i a t e E P G rise a p p e a r s to Ire of a d i f f e r e n t n a t u r e a n d r e q u i r e s

t o m y a n d v a g o t o m y so t h a t it does n o t seem to be d e p e n d e n t on a n y n e u r o g e n i c r e f l e x m e c h a n i s m i n v o l v i n g these s t r u c t u r e s . The e l e c t r o p o l a r o g r a p h i c a n d c o r t i c a l t e m p e r a t u r e c h a n g e s do n o t a p p e a r w h e n a s i m i l a r blow is a d m i n i s t r a t e d to a n a n i m a l with a deficient cerebral circulation (when the b l o o d p r e s s u r e is below 50 nun. of m e r c u r y ) n o r do t h e y a p p e a r in t h e d e a d a n i m a l . R e p e a t e d concussive blows w i t h i n a few seconds of each o t h e r cause a p o l y p h a s i c rise ill E P G e l e c t r o d e s w i t h s u m m a t i o n (fig.

JOHN S. MEYER and D. DENNY-BROWN

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W e have, in one e x p e r i m e n t w i t h t h e nmnkey, u s e d t h e same s t i m u l u s to p r o d u c e perc. cone. b e f o r e a n d a f t e r c u t t i n g t h e edge of the t e n t o r i u m . T h i s d i d n o t l o w e r t h e concussion t h r e s h o l d as m i g h t be a n t i c i p a t e d f r o m a r e l a t i v e l y u n p r o t e c t e d p o s t e r i o r fossa, however, the most r e l i a b l e e x p e r i m e n t a l s i g n s of concussion a r e u n d o u b t e d l y d u e to b r a i n stem p e r c u s s i o n b y the base of t h e skull r a t h e r thai1 at the i n c i s n r a t e n t o r i i since t h e y a p p e a r

8B). This finding confirms the quantitative e f f e c t of b o t h t h e e l e c t r i c a l c h a n g e a n d its associated defect in oxygen consumption, and m a k e s t h e p h e n o m e n o n d i f f i c u l t to e x p l a i n b y a n y process o t h e r t h a n b r e a k d o w n of n e u r o n a l m e m b r a n e charge. The rise in E P G o x y g e n levels occurs w h e n t h e a n i m a l is a r t i f i c i a l l y r e s p i r a t e d so t h a t i t is n o t p r i m a r i l y d u e to a n i n s p i r a t o r y g a s p w i t h its related increased venous return and cortical COitT, CO~C e~T~m4[jl A IIIIIIIIIIIli~'UllllII' IIII~

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Fig. 5 Cat. A. Predominantly cortical concussion. EEG diminished amplitude, blood pressure and respiratory effects minimal. Drill holes. B. Cat. Local posterior fossa percussion concussion. Marked brain stem effects, no EEG change. Nol:e delayed rise after T rises. Trephination. C. Monkey. Percussion concussion. Delayed EPG rise in EPG 2. Trephination. 1). Monkey. Percussion concussion. Trepllin,~tion. Same experiment as C. Cabs. CP ~ Corneal at)selLLand present. Cbl Cone. ~ Posterior fossa blow. blood flow ( M e y e r a n d D e n n y - B r o w n 1955) a l t h o u g h this m e c h a n i s m m a y p l a y a ]>art since t h e j u g u l a r v e n o u s p r e s s u r e shows a r a p i d , i n i t i a l n e g a t i v e d e f l e c t i o n of less t h a n a s e e o , d b e f o r e it shows a c u s t o m a r y rise. It is t h e r e f o r e c o n c l u d e d t h a t /he :immed i a t e rise in t h e E I ' G represe~lts .all ess,,,utial a u d v i t a l fa(.tor i1~ the whole me(,ha~lism of ~.oneussion, n a m e l y a t r a n s i t o r y decrease in u(,uroual o x y g e u n t i l i z a t i ( m or p a r a l y s i s .

ill the d e c e r e b r a t e a n i m a l ( D e n n y - B r o w l l a n d R u s s e l l 1941) a n d a r e m o r e r e a d i l y elicited b y p e r c u s s i n g t h e c e r e b e l l u m ill t h e i n t a c t preparation.

SI' cha,gcs i1~ e.rpcrimeJ~tal conc,,~'.~io,. V a r i o u s p a r t of t h e c o r t e x m a y ;~h(!w a t r a , s i e n t S1 ) n e g a t i v e s h i f t of 1-2 inV. w i t h r e s p e c t to a l m t h e r p a r t ( t u r i u g (.olwussion p r o ( h w e d by l)er(.ussion or ~,Oml)r(,ssion.

C E R E B R A L CONCUSSION

W a l k e r et al. (1944) mentioned t h a t following concussion the motor area remained negative for several seconds with respect.to the posterior parietal region. W i t h a posterior placed concussive blow over the left occipital d u r a we have also observed the right parietal cortex to show a 2 mV. negative shift with respect to the motor area and take this to indicate t h a t the cortex is not always homogc-

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3-9 inV. I n figure 4B the sequence of events are illustrated in the cat. Two progressively severe subconcussive blows (compression concussion method) marked SUB on the record, fail to abolish t h e corneal reflex ( C P ) or affect SP, E E G , E P G or blood pressure tracing. However, a near f a t a l concussive blow causes irregular respirations and apnea for 2 rain., a r a p i d l y developing cortical in-

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Fig. 6 Upper figure. Localized percussion concussion posterior fossa. Note absence of E E G change (above record) marked brain stem signs. Prolonged loss of corneal reflex, delayed rise of E P G after T. At P H O T O colored picture showed flushing of the cortex (compared to control taken prior to coneussiml). Lower figure. F a t a l brain stem contusion by rapid increase in extradural pressure for comparison with brain stem concussion. The EEG shows delta and some spike activity after injury (below record). Blood pressure shows enormous rise, respirations are first stimulated then slowed. Terminally, blood pressure falls, cortical T and EPG fall, EEG then disappears.

nously concussed, but that there m a y be a p r e d o m i n a n t l y localized concussive effect in the region of the blow. B y placing one SP electrode on the cortex and the other ill the subcortieal white m a t t e r we were able to show t h a t with a severe concussive blow the cortex shows a rapidly developing i a j u r y potential, all p a r t s of the cortex beeomillg ]wgative to white matter by

j u r y potential and a large rise in the E P G off the record followed by a fall in the apneic phase. The corneal reflex is abolished for 42 see., the E E G shows diminished activity followed by slow activity. The SP shift began to r e t u r n to resting levels a f t e r 54 see. and then showed a transient secondary fall. This secondary SP shift is unusual but this was a severe concussion a f t e r repeated blows,

JOHN S. MEYER and D. DENNY-BROWN

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a n d r e s p i r a t o r y h y p o x i a is b e l i e v e d to h a v e m o d i f i e d t h e S P shift. I n g e n e r a l , t h e m o r e severe t h e concussion t h e m o r e p r o l o n g e d t h e S P shift. More c o m m o n l y i n less severe concussive blows of b r i e f d u r a t i o n t h e S P s h i f t of c o r t e x .with r e s p e c t to w h i t e m a t t e r is m o r e r a p i d in r e v e r s a l . I n f i g u r e 7A, t h e a c t u a l m i l l i j~

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to w h i t e m a t t e r ) , n o r do t h e y a p p e a r w i t h s u b c o n c u s s i v e blows (fig. 3A, H ) . T h e i n j u r y p o t e n t i a l of c o n c u s s i o n h a s a l a t e n c y of 10-40 msec. (fig. 3). T h i s l a t e n c y is a l w a y s s h o r t e r t h a n the a s s o c i a t e d E P G rise b y 10-40 msec. b u t follows t h e same p a t t e r n of r e s p o n s e as the E P G , i.e. w i t h r e p e a t e d blows t h e l a t e n c y is s h o r t e r (10-15 msec.) w i t h t h e f i r s t blow it is l o n g e r (40 msec.). The m o r e severe t h e blow the l a r g e r t h e i n j u r y p o t e n t i a l , t h u s a l i g h t b l o w (fig. 3 E ) m a y cause a n i n j u r y p o t e n t i a l of o n l y 3 inV. while a severe blow will cause a n i n j u r y pot e n t i a l of 7 mV. or more. The l i g h t blow in fig. 3E was u n a c c o m p a n i e d b y a n E P G rise in a n e a r b y electrode. R a p i d l y r e p e a t e d concussive blows, as in f i g u r e 8B, cause a s u m m a t i o n e f f e c t on t h e

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Fig. 7 Monkey, Nembutal anesthesia. Comparison of (A) injury potentials produced by minimal compression concussion (MIN. CONC.) and (B) nitrogen breathing. Electrode placement shown in diagram. In mild concussion there is a rapid surface negativity and return to the steady state. Nitrogen breathing causes slow development of surface negativity. Time intervals at bottom of chart are 30 sec. AR _Artificial respiration. v o l t m e t e r r e a d i n g s h a v e been p l o t t e d o u t f o r a m i n i m a l concussive blow ( c o m p r e s s i o n concussion) i n a cat, w h i c h p r o d u c e d d i m i n i s h e d a m p l i t u d e E E G a c t i v i t y a n d s l o w i n g of t h e r e s p i r a t i o n s f o r 5 sec. ( p r e d o m i n a n t l y cortical c o n c u s s i o n ) . T h e m i l l i v o l t m e t e r shows a r a p i d d e v e l o p m e n t a n d r e s o l u t i o n of S P in the course of 10-240 sec. F i g u r e 7B is a c o n t r o l in t h e s a m e e x p e r i m e n t i n w h i c h d e a t h was c a u s e d b y n i t r o g e n b r e a t h i n g . T h e c o r t e x shows t h e same t y p e of i n j u r y p o t e n t i a l as o c c u r e d in concussion b u t i t is m u c h slower i n . d e v e l o p m e n t r e q u i r i n g 2 min. f o r t h e s a m e p o t e n t i a l to develop. S u c h i n j u r y p o t e n t i a l s w i t h concussive blows do n o t a p p e a r in t h e d e a d a n i m a l , or a n a n i m a l in w h i c h the blood p r e s s u r e is below 50 mm. of m e r c u r y ( w h e n t h e c o r t e x has a l r e a d y become n e g a t i v e w i t h r e s p e c t

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Fig. 8 To show summation of EPG and SP with repeated concussive blows in cat (artificial respiration). Electrode positions shown in diagram. Downward deflection of SP is cortex negative. Time marker at top of record indicates 5 sec. intervals. Concussive blow at arrow. At X the corneal was tested in figure B. ICP ~ Intracranial pressure. A. Control concussive blow with loss of corneal reflex for 10 see. B. Two concussive blows 4 sec. apart SP and EPG show summation of effects. Loss of corneal reflex for 20 sec. S P c h a n g e as well as oil t h e E P G rise. T h e d e g r e e of i n j u r y has a t h r e s h o l d v a l u e a n d w h e n t h e t h r e s h o l d is p r o g r e s s i v e l y e x c e e d e d the time of r e v e r s a l is c o r r e s p o n d i n g l y p r o longed. R e p e a t e d concussive blows t e n d to p r o l o n g the e f f e c t a n d l o w e r the t h r e s h o l d , not o n l y of the S P c h a n g e s b u t also of t h e

CEREBRAL CONCUSSION

539

There are certain similarities of the brain stem effects of concussion to ischemia of the brain stem by vertebral a r t e r y occlusion, Local Percussive Paralysis. which we have illustrated in a previous p a p e r We have confirmed the observations of (Meyer and D e n n y - B r o w n 1955) and brain Williams and D e n n y - B r o w n (1941) that with stem i n j u r y (fig. 6). However, at necropsy a local blow on an E E G electrode screwed in the experiments illustrated in figures 5B into the skull there is p u r e l y local diminution and 6A there was no lesion of brain stem or in the E E G , indicating t h a t the paralytic cervical cord. The m a j o r differences are effect without vascular i n j u r y m a y be local- that in local brain stem concussion there are ized. F r e q u e n t l y a light blow administered ilo E E G changes and the phenomenon is by the percussion concussion or compression completely reversible, whereas in brain stem concussion method causes a greater diminucontusion and vertebral a r t e r y occlusion there tion of the E E G over the side of the head are E E G effects, and either m a y be rapidly struck and little if a n y rise in the blood pres- fatal or incompletely reversible. sure, loss of corneal reflex or other signs of Duratio~ of stimulus. W i t h the return brain stem concussion, l~igure 4A is an ex- spring attachment of the compression conample of such p r e d o m i n a n t l y cortical effects. cussion syringe the duration of the stimulus There is an immediate rise in E P G but little could be ('ontrolled from less than 0.1 sec. change in the cortical t e m p e r a t u r e of either to longer tinle intervalls. Concussion can hemisphere suggesting that the increased cort- be readily aml cousisteutly produced by a ical blood flow in concussion m a y be mediated blow of duratiou less than 0.1 sec. Itowever, by the brain stem effects. Light blows may a similar blow with a less powerful return produce local SP effects in another a~ea spriu~' (compression of longer duration) (fig. 3 E ) . Such differences indicate that it is caused more signs of brain stem concussion. I f the generalization of the physical stimulus iutracranial pressure was already increased that results in the generalization of the neu- at the time of the eoncussive blow then the ronal changes, and not the spread of neuronal blow was more likely to be fatal or unusually effect from a n y p a r t i c u l a r focus. prolonged. We have also been able to produce all E E G changes in concussions. In 72 records the criteria of experimental concussion, ex- of experimental concussion diminished E E G cept the cortical E E G effects by a blow amplitude of 10-80 sec. duration occurred. In administered to the d u r a overlying brain sever(, concussion slow waves in the delta stem and cerebellum. Such blows are illus- range of moderate amplitude precede the trated in figure 5B and 6A. In figure 6A returt~ to normal activity for 10-160 see. In there was arrest of respiration for 10 :~ee., only one experiment was concussion associated absence of the corneal reflex for 90 see. (the with spike activity, and this was focal, arising longest loss we have recorded) a rise in the from a small area of cortex which at autopsy cortical t e m p e r a t u r e and a delayed rise in showed no area of contusion. It is possible the E P G . There was ~o change in the course that in this one experiment a minute contusion of the E E G . This shows that the medullary was not observed at necropsy which seems effects of concussion are the results of con- likely in view of the consistent p a t t e r u of cnssion of the medullary centers themselves, E E G chauges in concussion, in contusion, and the cortical effects are effected by direct however, focal spike activity ix extremely eortieal concussion r a t h e r than by i n j u r y to ('ommon Meyer 1955). a n y neuroanatomieal structures such as the DISCUSSION reticular activating system. This also would E x p e r i m e n t a l concussion without visible be in keeping with the more regular production of the entire syndrome of concussion by brain hemorrhage, is readily produced by a the acceleration method, which would tend to traumatic stimulus of brief duration. The affect all p a r t s of the brain and brain stem. stimulus requires a threshold of change in

other signs of concussion (apnea, hypertension, loss of corneal reflex and E E G change).

540

JOHN S. MEYER and D. DENNY-BROWN

intensity to induce signs of reversible neuronal injury. The t e r m concussion is best reserved for generalized reversible neuronal i n j u r y of this type. Localized percussive paralysis which m a y be demonstrated to result from the local effects of a t r a u m a t i c stimulus has the same neuronal mechanism as occurs in concussion but it is restricted to one or other region of the brain. I f a minimal threshold stimulus is applied by the compression or percussion method over the exposed d u r a the concussive effects are p r e d o m i n a n t l y local in their manifestations. B y this means the effects of cortical concussion m a y be separated f r o m brain stem effects. In the experimental animal the cortical effects are diminished amplitude of the cortical E E G , an i n j u r y potential ( S P ) which arises f r o m the cortical g r a y matter and diminished cortical neuronal utilization of oxygen. All these changes are reversible at different rates. The cortical i n j u r y potential is rapid in onset having a latency of 30-40 msec. and the recovery curve is steep at first a n d tends to level off as the steady state is reached. The more severe the concussion the longer the duration of i n j u r y potential. Repeated blows tend to shorten the latency to 10-20 msec. Rapidly repeated blows summate these effects. The brain stem effects are transient loss of the corneal and other reflexes, a rise in blood pressure and arrest of respirations. The cortical blood flow increases as the blood pressure rises usually a f t e r a latency of 10-20 sec. This increase in cortical blood flow occurs a f t e r cervical s y m p a t h e c t o m y and vagotomy. Acceleration concussion with a p e n d u l u m blow causing an acceleration of 29 feet/see. or compression or percussion blows of sufficient intensity consistently produce concusSive effects of both brain stem and cortex. F u r t h e r increases in intensity of the stimulus cause concussion of longer duration until death m a y occur from a concussive blow either due to vasomotor or r e s p i r a t o r y collapse. In the absence of visible lesions these effects indicate severe neuronal paralysis of the brain stem.

I n . experimental concussion positive evidence of a transient neuronal paralysis is shown by reversibly diminished E E G activity, reversible cortical i n j u r y potential ( S P ) of cortex with respect to white matter, and associated rise in the cortical oxygen availability of slightly longer latency. These changes can be dissociated f r o m the changes accompanying the r e s p i r a t o r y gasp a n d the rise in blood pressure and cortical blood flow by the brief latency of their onset. The rise in E P G is consistent with decreased neuronal consumption of oxygen. Percussion or concussion blows m a y cause localized concussive effects in the area of the cortex struck. Local E E G diminution m a y occur and local SP shifts of one area of cortex with respect to another and local increases in cortical oxygen availability. W h e n the brain stem is struck isolated brain stem effects m a y occur. The fact that the SP negative potential arises from cortex rather than white m a t t e r suggests that the nerve cell body is more disposed to the traumatic i n j u r y than its dendrites or axones. Our experimental data are supported by the experimental data of others. Walker, Kollross and Case mention cortical SP shifts of brief duration recorded with direct coupled amplifiers but do not discuss their significance. Spiegel et al. (1946), found that in acceleration concussion there was a decrease in the polarizability of the brain which they measured by recording the conductivity of the cortex at high and low frequencies with a testing alternating current. They found t h a t in subconeussive blows a significant, reversible i n j u r y to nerve cells occurred, which they believe was an i n j u r y to the cell membranes. Groat, Magoun, Dey and Windle (1944) studied the steady thresholds of excitation for brain stem nuclei, supranuclear p a t h w a y s and tracts. They found that either acceleration concussion or compression concussion sufficient to abolish the corneal reflex raised the threshold momentarily in motor nuclei and for hmg periods in supranuclear pathways. The motor cortex, for example, showed a very liigh rise ill threshold during concussion.

CEREBRAL CONCUSSION Spiegel et al. 1947, have shown that the threshold for Metrazol convulsions in rats is temporarily raised immediately following concussion. Indeed, a concussive blow abolished Metrazol convulsions for 30 sec. to 1 min. and the recorded frequency of clonic movements was reduced for a longer time interval. A less consistent rise in threshold for electrically induced convulsions in the rat and cat was also found. Comparison of our data with that of Groat et al. and Spiegel et al. show a remarkable similarity of the properties of the cortical i n j u r y potential during concussion with that of the cortical stimulation threshold of Groat et al., and the " p o l a r i z a b i l i t y " and convulsion thresholds of Spiegel et al. (1946, 1947). Groat et al. found that the stimulation threshDld of cell groups but not their fibers were affected. The rise of stimulation threshold, concussion threshold and polarizability change is very rapid in onset and the recovery roughly proportional to the intensity of the concussion. Recovery curves of the stimulation threshold were usually steep at first and then tended to level off as the values approach control levels. Groat et al. also compared the effects of anoxia with those of concussion on the stimulation threshold. The threshold did not begin to rise until 2.5 to 5 rain. after obstructing the air way. We found a comparable latent interval of the SP shift with asphyxia. These authors also found evidence of differential functional alterations in the brain during concussion. Spiegel et al. (1947), mentioned that hypoxia has a similar effect on the polarizability as concussion. We have previously shown (Meyer and Denny-Brown 1955) that in rapid cerebral anoxia produced by nitrogen breathing, only when the cortical hypoxia is maximum does the cortical SP show a rapidly reversible shift with respect to white matter. There is a latent interval of approximately two minutes before the cortical i n j u r y potential develops after the cortical oxygen availability has begun to fall. In concussion, a similar i n j u r y potential develops within 10-40 msec. The rise in the oxygen electrode with concussion is therefore presumed to be significant evidence against anoxia as its cause.

541

The p r i m a r y event we have observed is an SP cortex negative shift of 3 to 9 mV. with a latency of 10-40 msec. It is not an all-ornone phenomenon, but can be quantitatively related to the intensity of stimulus. This has all the characteristics of an injury potential, due to breakdown of membrane polarization. It appears to effect nerve cells rather than axons. It can be repeated and summated within periods as brief as 1 sec., when synaptic transmission is abolished. It cannot therefore be explained by reflex or synaptic discharge. The associated defect in neuronal utilization of oxygen recorded by the E P G with approximately twice the latency is quantitatively related to the intensity of the SP change, and is f u r t h e r evidence of reversible neuronal damage of extremely rapid onset and gradual recovery. These changes relate concussion directly to the cell membrane and are compatible with rise in convulsion and stimulation threshold and alteration in the impedance properties of the cortex to alternating currents. The direct membran~ change in the neurone f u r t h e r fully accounts for the peculiar and enigmatic limitation of all the late stage of concussion paralysis to defects in synaptic transmission pointed out by Denny-Brown and Russell (1941) and accurately measured by Groat et al. (1944). It appears logical that this i n j u r y potential better accounts for the large potentials r0corded by Walker et al. with a voltage divider, after a concussive blow, rather than true neuronal excitation and this large potential .may account in part, at least, for the momentary blocking of the E E G amplifiers. Furthermore, it has been shown by Goldring and O ' L c a r y (1947) and Kempinsky (1954) that in cortical paroxysmal activity the SP shows a surface positive rather than a surface negative shift. If severe neuronal discharge does in fact occur with concussion a fall rather than a rise in the cortical oxygen availability would be expected. It is possible, however, that the breakdown of ionization of the cell membrane expressed by the i n j u r y potential, if particularly severe, may be associated with generation of one or two impulses giving instantaneous signs of excitation, for Krems, Schoepfle and Erlanger have shown

542

J O H N S. M E Y E R and D. D E N N Y - B R O W N

a transmitted potential ix~ distal segments of " c o n c u s s e d " peripheral nerve at the time of the blow and Walker et al. (1944) have shown similar potential in peripheral nerve at the time of a concussive blow to the head. The ability to summate the SP and E P G change within 1 to 5 sec. after the blow, when neuronal transmission is not possible indicates that nerve impulses play no part in the p r i m a r y mechanism. Such transmitted impulses therefore do not appear to play any essential part in concussion and may be related to the phenomenon of "seeing s t a r s " with a subconcussive blow in man. Stone, Webster and Gurdjian (1945) in a s t u d y of gasometric and cerebral metabolic changes in dogs following experimental head injuries found that the arterial blood oxygen was raised 14 to 180 rain. after i n j u r y in the majority and decreased in a few. This study is difficult to interpret because degrees of head i n j u r y were classified as minimal, moderate and p r o f o u n d rather than clearly divided" into groups with concussion, contusion, brain stem i n j u r y and other complications. The changes of blood gases within the first few minutes of i n j u r y were not examined. In the present study we have controlled this factor either by continuous artificial respiration or recording the respirations. The transitory arrest of respiration in concussion would tend to lower rather than raise the arterial oxygen saturation within the first few minutes of injury. Similarly, the failure of these investigators to show a cerebral arterio-venous oxygen and carbon dioxide difference after head i n j u r y in the dog is not relevant to the present study since their samples were drawn 18 minutes or longer after i n j u r y and the sample is contaminated with extra cerebral blood. Their data on cerebral lactic acid content indicated no evidence of cerebral hypoxia after head i n j u r y except in severely contused zones. Our data would be in agreement with this finding. The possibility of a transient disturbance in cerebral oxidation is not excluded by their experiments. The observations of Spiegel et al. (1947) are of special interest in relation to neuronal oxygen consumption during concussion. They

reported that studies of oxygen uptake of rat brain by the W a r b u r g technique failed to demonstrate significant differences between normal and concussed brain. However, we have found that the cortical rise in E P G oxygen is a rapidly reversible phenomenon, even the secondary change is too brief for the interval of time required for W a r b u r g determinations. The trauma to the brain necessary for removal of samples for such estimations may well conceal a transient reduction of neuronal oxygen utilization. The rise of the cortical p H to the alkaline side in concussion is probably due to the associated increase in cerebral blood flow (Weil 1945). A similar rise or cortical p H occurs regularly when cortical blood flow is increased (Jasper and Erickson 1941; ]V[eyer and Denny-Brown 1955). F r o m these data, the general principle arises that the immediate effect of brain trauma of concussion intensity is a transient paralysis of neurones, and that in concussion this is the only effect. Possible clinical significance in man. It has been shown in another series of experiments (Meyer 1955) that localized percussive paralysis is frequently associated with contusion, however, it may occur independently of visible injury. While localized percussive paralysis is differentiated from concussion this does not imply that it may not also have wide clinical significance in man. Localized, transient, reversible impairment of neuronal function is occasionally seen in high velocity missile wounds (Denny-Brown 1942) and is particularly common following tangential wounds of the skull (Dodge an5 Meirowsky 1952; Russell 1945). One of the authors had personal experience with 16 cases of tangential missile wounds during the Korean conflict. Several electroencephalograms in these cases showed transient focal diminished electi'ical activity in the region of i n j u r y for a few hours or days following injury. The rapidity of recovery in many of these examples of motor, sensory and E E G disturbance is more readily accountable by a localized percussive paralysis than by contnsion alone.

CEREBRAL CONCUSSION I t a p p e a r s probable f r o m clinical experience t h a t local percussion paralysis m a y occur in spinal cord i n j u r y a n d in peripheral ndrve injury. E x p e r i m e n t a l studies have shown t h a t the time course of blocked excitability of nerve is similar to t h a t of experimental concussion ( K r e m s et al. 1942). I n man, the most reliable criterion of concussion is a brief, permanent, retrograde amnesia without a n y p e r m a n e n t sign of cortical damage suggesting a r a p i d l y reversible cortical paralysis. Recently, evidence of decreased amplitude E E G activity in m a n a f t e r concussion has been demonstrated (Larsson et al. 1954). Local percussion paralysis of the brain stem m a y account for the transient syncope of boxers " g o i n g down for the c o u n t " where there is no amnesia for the event, while concussion occurs more r a r e l y in those boxers " k n o c k e d s t i f f " who remain unconscious for several minutes and who show amnesia for the event. CONCLUSIONS 1. The E E G , SP, cortical temperature, oxygen availability, i n t r a c r a n i a l a n d j u g u l a r venous pressure, blood pressure a n d respirations have been recorded in experimental cerebral concussion produced b y percussion concussion, compression concussion and acceleration concussion. 2. I n experimental concussion there is a r a p i d l y reversible cortical i n j u r y potential ( S P ) followed by a r a p i d rise in cortical oxygen availability ( E P G ) preceding a n y effects referable to changes in respiration and circulation. The intensity of this p r i m a r y change is proportional to the objective signs of concussion (loss of corneal reflex, respira t o r y paralysis, rise in blood pressure and diminished E E G activity). Following the blow there is a rise in cortical temperature. I t is concluded that this p r i m a r y change occurs in all nerve cells t h a t are affected, and that generalization of the phenomenon is due to the affection of all neurones b y the stimulus. The essential process can be localized in one region by limiting the adequate physical stimulus to that region. 3. There is a threshold for the stimulus necessary to produce concussion. Progres-

543

sively severe blows over the threshold stimulus produce more severe concussion. Repeated concussive blows tend to lower the threshold. A severe concussive blow m a y be fatal without signs of brain injury. 4. The cortical i n j u r y potential, r a t h e r than neuronal excitation, accounts for the large potentials recorded immediately following a concussive blow, The rise in cortical E P G and the surface negative SP potential are c o n t r a r y to the changes induced b y cortical paroxysmal activity, and their ability to summate with r a p i d repetition negates their origin f r o m nerve impulses whether reflex or not. 5. The effect of localized percussive p a r alysis of the brain stem is contrasted with localized percussive paralysis of the cortex. 6. I t is concluded that in cerebral concussion transient t r a u m a t i c paralysis of neurones due to membrane damage is the essential effect. This membrane damage accounts for the prolonged after-effect on synaptic transmission. REFERENCES BROWN, G. W. and BROWN, M. L. Cardiovascular responses to experimental cerebral concussion in the rhesus monkey. Arch. Neurol. Psychiat., Chicago, 1954, 71: 707-713. BROWN, G. W. and HINES, H. 1~. Cardiovascular and respiratory changes associated with experimental concussion in dogs. Air Force. Tech. Rep, Oct. 1951, No. 6-7-37. DENNY-BROWN,D. The sequelae of war head injuries. New Eng. J. Med., 1942, 227: 771-780, 813-821. DENNY-BRowN, D. Cerebral concussion. Physiol. Rev., 1945, 25: 296-325. DENNY-BRowN, D. Blast injury. Medical Physics, Edited by O. Glasser, Chicago, 1950, Year Book Publications, 2: 127-129. DENNY-BROWN,D. and RUSSELL,W. R. Experimental cerebral concussion. Brain, 1941, 64: 93-164. DODGE, P. R. and MEIR0WSKY, A. M. Tangential wounds of scalp and skull. J. Neurosurg., 1952, 9 : 472-483. GROAT, R. A., MAGOUN, H. W., DEY, F. L. and WINDLE, W. F. Functional alterations in motor supranuclear mechanisms in experimental concussion. Amer. J. Physiol., 1944, 141: 117-127. GOLDRING, S. and O'LEARY, J. L. Experimentally derived correlates between ECG and steady potential. J. Neurophysiol., 1951, 14: 275-288. JASPER, H. and ERICKSON, T. Cerebral blood flow and pH in excessive cortical discharge induced by Metrazol and electrical stimulation. J. Neurophysiol., 1941, 4: 333-347. KEI~PINSKY, W. H. Steady potential gradients in experimental vascular occlusion. EEG Clin. Neurophysiol., 1954, 6: 315-402.

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J O H N S. M E Y E R and D. DENNY-BROWN

KNAUER, A. and ENDERLEN, E. Die patholigische physiologie der hirnerschutterung nebst bemerkungen uber verwandte zustande. J. Psychol. Neurol., 1922, 29 : 1-54. KREMS, A. D., SCHOEPI~LE, G . M. and ERLANGER, ,T. Nerve concussion. Proc. Soc. Exper. Biol. Med., 1942, 49: 73-75. LARSSON, L. E.~ MELIN, K. A., NORDSTROM-OHRBERG, G., SILFVERSKIOLD,B. P. and (~HRBERG, g . Acute head injuries in boxers. Clinical and electroencephalographie studies. Acta Psych. Nenrol. Scand. Supp., 1954, 95: 1-42. MERRITT, H. H. Head injury, Review of the literature. War Med., 1943, 4: 61-215. MEYER, J. S. Studies of cerebral circulation in brain injury. I I I Cerebral contusion, laceration and brain stem injury. (To be published 1955.) MEYER, J. S. and DENNY-BROWN, D. Studies of cerebral circulation in brain injury. I Validity of combined local cerebral electropolarography, thermometry and steady potentials as an indication of local circulatory and functional changes. EEG Clin. Neurophysiol., 1955, 7: 511-528. MEYER, J. S., FANG, H. C. and DEN SV-BRowN, D. Polarographic study of cerebral collateral circulation. Arch. Neurol. Psychiat., Chicago, 1954, 72: 296-312. MEYER, J. S. and MARTEL, E. Experimental studies of brain injury. Abstract of the Proceedings of the Boston Society of Psychiatry and Neurology. Arch. Nc~trol. Psychiat., Chicago, 1955 (in press).

POLIS, A. Recherches exp~rimentales sur la commotion c~r~brale. Rev. Chir., 1994, 14: 273-319, 645-730. RUSSELL, W. R. Transient disturbances following gunshot wounds of the head. Brain, 1945, 68: 79-97. SPIEGEL, E. A., HENNY, G. C., WYCIS, H. T. and SPIEGEL-ADOLF, M. Effect of concussion upon the polarizability of the brain. Amer. J. Physiol., 1946, 146: 12-20. SPIEGEL, E. h., SPIEGEL-ADOLF, M., WYCIS, H. T. and MARKS, M. Cerebral concussion and convulsive reactivity. Rcs. Publ. Ass. herr. ment. Dis., 1947, 26: 84-97. STONE, W. E., WEBSTER, J. E. and GURDJIAN, E. S. Chemical changes in brain and gasometric studies of the blood in experimental head injury. Res. Pub. Ass. ncrv. merit. Dis., 1945, 24: 226253. TROTTER, W. Certain minor injuries of the brain. Lancet, 1924, 1: 935-939. WALKER,A. E., KOLLROSS, J. J. and CASE, T. J. The physiological basis of concussion. J. Neuros~rg., 1944, 1: 103-116. WEIL, A. Discussion of "Chemical changes in the brain and gasometric studies of the blood in experimental head i n j u r y " . Res. Publ. Ass. herr. ment. Dis., 1945, 24: 250. WILLIAMS, D. and DENNY-BROWN, D. Cerebral electrical changes in experimental concussion. Brain, 1941, 64: 223-238.

Refcre~*cc: MEYER, JOHS S. and DENNY-BROWN, D. Studies of cerebral circulation in brain injury. ] I . --Cerebr.d concussion. EEG Clin. Nenrophysiol., 1955, 7: 529-544.