36 The Reticular Formation and Clinical Neurology GEOFFREY JEFFERSON (Manchester, England) Tt has given me great pleasure to be present at an exciting conference, cone which must have delighted Ds. Magoun in particular, and those thers of the Ranson school, always instigators of fruieful research. “This has been a real symposium, a school for the exchange and for the pooling of ideas, and further, what was best about it was its tentative ness, as if to say of some things, "This we know" and “That we know,” but of others, “The most that it would be wise to say at this stage is this..." Yet all our concepts, certain or conjectural, are beginning to make a pattern. I confess that three or four years ago I thought that T understood the concept of the reticular formation, but now T find that i has turned into a syseem which, like a big flourishing and expanding business, has boughe up all its competitors. Dr. Scheibel, after presenting his beautiful histologic preparations, came out fiat with the remark that “This” (the reticular formation) “is the central nezyous system.” ‘The way things are going —and nut unly tat Lut the exctavndnary: increase in che volunie of information and the speed with which things are moving —it could be true that some part of a wide integration is taking place. I have watched parts of the temporal Tobes, the red nuclei, the pituitary, parts of the cerebellar function, disappear into the reticular system —and there are some indications that the sympathetic nervous system too is in danger of a merger, perhaps only as 2 subsidiary. Te would ‘not be too absurd to say that wherever any really interesting fun was going on in brain research, chat part was immediately claimed as pare of the reticulac formation, And yet, as one who hes to make what he can of the complex human nervous system, its subjective disturbances exprewed in the sufferer’s own ‘words, his behavior noted as unit in his natural environment — these are two great differences from laboratory experiments —a neurosurgeon cannot resist the tempration to raise some protest, It is a plea on behalf of the vast dumb millions, the cells in the cerebral cortex, which, i aP~ pears, are the poor relations of the reticular system, pensioners living its bounty. I has, T have iong realized, one important funetion, to sigaal no0 Reticular Formation of the Brain what sort of night the reticular system is having. Does it sleep or is it restless? Is an uncomfortable bed putting in a barrage of painful impulses to disturb it and goad it to insure the cortex’s insomnia? Poor cortex, to be reduced so low that it is now no more than a conveniently shaped article for electrode placements! Thave almost done with teasing vou, for ie was very: right and proper chat a symposium on the reticular formation should be aboue that subjece and not about anything else, I know well that all of you are conscious of the unlimited importance of the cortex and grateful, 2s we all should be, to the great pioneers who worked so devotedly in building up our ‘knowledge of the structure and functions of the nervous system over the past cighty or ninety years And yet, and yet again, of course, we were dae for a change, for although che cerebral hemispheres still have their secrets these were becoming increasingly difficult to solve without some further aid. The easy ciddles were long ago guessed. Research work, sometimes think, has something in common with isotopes wich their different expectations of life before they completely decay. Some last “only for days, some for a very long time, and so itis with original work. Only the great survives. And what was learned of the cercbral hemisphere ‘was this —_mose chings except one only —che vital one that would re- veal so much move — how it r2a5 integrated. We leamed that isolated portions of the cortex still retained their electrical activity —a fact which proved the need for some better in- sight into the way it was federated. It was not until we tured back again to the brain stem that at last 2 recognizable meaning came about, largely through the work of Ranson, Magoua, Gerard, Dempsey. Morison, and Lindsley, and of Penfield and Jasper in another location. Yet L should remind you that others have been there before. In 1830 Sir Charles Bell in his book on the nervous system published a plate and wrote of it, "He who makes himself master of this plate can have no diffculey in compre hending the whole nervous system. He holds the Key to it in hie hand.” ‘The plate was a drawing of the brain stem from the upper cervical cord fon to the thalamic and optic chiasma. The reason that he attached so och significance to this portion of the brain was because it was the area through which the messages from the spinal cord Howed; and be- sides—and this was important-—all the cranial nerves were attached to it. Bell knew for the first time ‘what those of earlier times had not known: that chese nerves were sensory or motor. It was because of the colossal traffic of input and of ouput that passed theough this streech of brain that Bell choughe it so important, It was much more important than he knew, for we must nor credit him with clairvoyance. So much for that. As for the reticular formation itself, Sherrington was well aware that it played some pare in decerebrate rigidity. He The Rericular Formation and Clinical Neurology a also knew that there was something more in the brain than the classical input and output tracts. As long ago as 1897 Sherrington wrote these. words Even the higher psychical events cannot be truly spoken of as a function of the cortex in the sense that chey are simply the outcome of molecular ‘changes in the grey matter; they are rather to be regarded as the onteome ‘of complex processes in which the parts of the brain below the cortex play a pare no less an essential chan the cortex itself. The fibres passing down from the cortex to the mid-brain have probably functions by which they take par even jn our psychical fe, funetions for which the words neither motor or sensory are fiting, 1 repeae those last words, “functions for which the words neither motor nor sensory are fitting” — for whac in paraphrase could becter describe in pare the reticular system? Iris high time that 1 passed on from this already’ top long introduction to speak of my own experience. What | suppose the pure physiologists want to know is, how far does the kind of work they are currently doing fit with clinical observations? Is it in line with it, is it explanatory? ‘The answer is broadly “ves,” hut the conclusions that che clinician has ar= rived at a8 to neural causes of depressed states of consciousness must be inferential. What I propose to do is to speak very briefly of those con- ditions which would fit accurately with the concept of « diffuse arousal mechanism, Tn order co contribute properly. attention must be drawn to some clinicopathologic evidence which akthough not necessarily antagonistic to the proposition does not positively support it. It will in the second case be proper to mention factors which might explain the discrepancy. Je seems unlikely that with such highly complex mechanisms as comprise the nervous system there is only one cause for luck of consciousness, namely a lesion in the brain stem, and here perhaps we have the best immediate alternative in the action of anesthetics which are not so focally selective a5 t0 pick out one area alone or, if not alone, with absolute dominance. Another curiously negative picce of evidence comes from ‘tumors in the posterior fossa, which in spite of vecy high pressure rarely produce even somnolence, let alone coma Although everybody adinits that full and complete states of conscious ress require an intact cortes, one has immediately ro qualify that by adding that the subcortical structures which energize the correx: must be infact too. Doubts as to the importance of intrinsic faults in the cortex itself first came to my mind many years ago in my observations on head injury, and especially those on the effects of acute compression by epidural clos. ‘Why was it, T asked, that if, as everybody thought, the stupor of com-mm Reticular Formation of the Brain pression wes caused by cerebral anemia, the patient frequently did not return to a wakeful seate for hours or even days after che clot had been removed and intracranial pressure had retumed to normal? L said in to43: “Is it the clot by reason of its position or the clot by reason of its size which leads to stupor? We know, for example, that pressure alone docs not cause stupor except in che last tension far in advance of anything seen in head presure in cerebellar tumors exceeds considerably any so far recorded in trauma and yet these patients are never ordinarily unconscious.” ‘That it was the position of the clot that was the dominant factor became apparent soon after in thar these clots led to temporal lobe shifts — the brain stem compressions and che “eoning” produced by clots as well as by tumor and abscesses, That was a new chapter opened by Clovis Vincene " and his collaborators and by myself? when 1 drew attention particularly co the deformity of the midbrain which these lesions could produce. In 1944. returned again to the question of the brain stem as the site of the primary disturbance in concussion. It seemed to me that the instantaneous and symmetrical inhibitions produced by head injury could be collated with the obscrved sites at which the smallest, the most economical lesions produced depressions of consciousness. These were either in che brain stem or in the floor and walls of the 3d ventricle. Furthermore, it was surely significant that loss of che comeal and pinna reflexes had been taken by all experimenters as the surest sign that con- cussion had been produced. These reflexes are at pontomedullary: level, Another impressive feature was the fact chae 4 patient, although quite un- rouable, would perform highly skillful acts, such as rubbing his nose, patting himself rapidly, or pulling up the bedclothes. The retention of these motor skills did not mean for certain that the patient would re cover, but they did indicate co me thae the corcex was little damaged, a fact that autopsy very likely would confirm. The conclusion was that traumatic stupor was caused in a relatively focal manner and chat the focus was not, as had generally been believed, in the cortex. Te seemed to me clear that an injury could set going a self-propagating chain of events, “a traumatic disease,” which led eventually to death, and [ sure mised that time would probably show that ehe trauma had damaged the deep structures, that intracellular enzymes had been altered or destroyed, sesulting in loss of integration, Some support for the brain stem theory of concussion has again come feom the experimental side, I refer to the work of Eldon Foltz and R. P. Schmidt (1956) in Arthur Ward's department. They compared the a¢- tivity in the reticular formation with conductivity in the medial ler niscus after an accelerating blow on the monkey's head. They concluded The Reticular Formation ond Clinical Newrology ny that “sensory evoked responses in the RF. were selectively, uniformly and dramatically absent after a sufficient blow on the head, responses in ‘the lemniseus remaining unchanged.” And since that was the case, that removed the possibility or even the probability that the cause of traumatic stupor was a temporary block of sensory input. A reduction of sensory input is well known to be an effective inducement to sleep, made moze conducive still if muscle relaxation reduces the captive barrage as well, ‘There was 2 famous case of Scrtinpell’s where the sensory input was reduced to one eye and one ear and where sleep followed rapidly in two or three minutes on these sources of information being cut off. Te may be interposed here chat the enteroceptors (e.g. from the bladder) play’ a large part in wakening from normal sleep, and cause restlesmess in semicoma. Bur before we settle too comforeably down to a belief that che cause of the stupor of concussion will be found in the cessation of the normally induced activity of the reticular formation not necessarily with any even immediate microscopic evidence of a lesion of lesions there — we have to consider the evidence in cases of very prolonged stapor. Here there might have been gross damage from contusional hemorthage in the brain stem. Autopsy’ evidenee, on the other hand, shows more often atcophy of the basal ganglia and cortex and in some cases the diffuse degeneration of the white matter which Sabina Strich * found in Oxford in 7 patients: who came to postmortem after a coma or near-coma of up to a year's duration Such massive degenerations a5 she has shown in the white matter of the corona radiata are very diffcule to understand when attempts are made to reconseruct the cause, Iris noteworthy that the white matter in these subjects did not appear to be particularly abnormal co the naked eye; it ‘was only when ie was stained by the Marchi method that the degeneration was seen. Dr, Strich suggests that the cause isa subcortical shearing of the white matter such as was suggested as a theoretical cause many years ago and in a more limited sense by Hothourn.* A demyelinization on chis seale wislst presumably blocking both input and outpet must include the diffuse projection system of cortical energizers. Sa that in that sense these observations are neither for nor against the evidence of a brain stem szousal mechanisn, What they do show is that chere is more then one ‘cause for stupor— unless the subcortical changes were, as brain stem hemorrhages commonly are in chronic cases, secondary. Ar the same time they would explain the mental damage seen too often for comfort in those who have sucvived, thanks to tracheotomy and antibioties, long periods of stupor. Signs of old hemorrhages in the midbrain and elsewhere in che brain stem and cerebellar peduncles were only the rule in this materi) if there