Chapter 18: Damage to the Intercalated Pretectal Neuron: Consensual Deficit

CHAPTER 18 Damage to the Intercalated Pretectal Neuron: Consensual Deficit CONTENTS A. Summary .......................... B. Appearance ........................ 945 945 C. Mechanism ........................ D. Clinical Occurrence and Significance ...... 949 952 A. Summary The intercalated neurons in the pretectal area redistribute the afferent impulses that reach them from the optic nerve and tract. In man and monkeys the pretectal neurons of each side send equal numbers of fibers to the sphincter nuclei on the same and on the opposite side. For this reason the two pupils constrict equally, even in the presence of lesions in the afferent path (see previous chapter and Chapter 3). Damage to the pretectal area or the fibers from there to the oculomotor nucleus disturbs this symmetry. In the unilateral pretectal syndrome the pupils, equal in darkness, will remain so when one eye is exposed to light, as in Figure 18-1,A3; but they become unequal when the light is shifted to the other eye (18-l,A2). The pupil of the stimulated eye then becomes smaller than the consensually reacting one. In the bilateral syndrome (Figure 18-1,8) the directly reacting pupil is always smaller than the consensually reacting one: the right pupil when the light is on the right side, and the left pupil when the light is on the left side. Because the anisocoria thus alternates, depending upon which eye is stimulated, we named this syndrome "alternating contraction anisocoria"; or, because the consensual re- sponse but not the direct one is defective, "consensual deficit." It should be stressed that the consensual reaction in this syndrome is never more extensive than the direct one. This kind of anisocoria is a fleeting phenomenon, usually of small extent, and it is fairly common. It generally escapes ordinary clinical observation, and can be revealed with certainty only with the help of bilateral pupillographic records. Once established, it persists without further change for many years, and rarely improves or disappears. In man it is more often unilateral than bilateral, and seldom symmetric, while in cats, who have this sign normally, it is always bilateral and symmetric. Its (unrecognized) presence may lead to faulty assumptions about anisocoria in various diseases. When found on routine pupillographic examination, it usually is of little pathologic significance because the time of onset is unknown. Occasionally it has been observed following acute virus infections in person who had not shown it before, suggesting that the infection included an element of central nervous system involvement. B. Appearance As mentioned in Chapters 3 and 17, many clinicians are convinced that uneven lighting of the patient's eyes will cause "physiologic anisocoria," due to a normally uneven fiber distribution in the afferent pathways. The pupil in the more intensely stimulated eye is said always to be smaller than the one in dimmer light. Reasons for this widespread belief are enumerated in the previous chapter. However, the majority of normal human subjects have equal pupils even when one eye is exposed to a bright light and the other eye remains in darkness.' Further, damage limited to the optic nerve or tract does not cause anisocoria, for the following reasons. The intercalated neurons in the pretectal area have the job of conducting the afferent impulses from the optic tract to the sphincter nuclei. In man and monkeys, with well-developed binocular vison, the fibers arising from the pretectal neurons on each side of midline are distributed evenly to the ipsilateral and the contralateral oculomotor nuclei, resulting in symmetric stimulation of the oculomotor nuclei (see Figure 17-12,B). When the symmetry of this central hemidecussation is disturbed, anisocoria will indeed develop during pupillary contractions to light. And this type of anisocoria differs from ordinary "contraction anisorcoria" associated with efferent parasympathetic impairment. In cases with efferent lesions (third nerve, ciliary ganglion, or ciJiary nerves) the same pupil always reacts poorly (the one on the side of the lesion), no matter which eye is exposed to light. In contrast, in cases with damage in the intercalated neuron only the consensual reaction is disturbed: in unilateral cases stimulation of one eye leaves the pupils equal, but they become unequal when the light is shifted I. Again and again, up to the present, "physiologic anisocoria" of very small amplitude has been said to result in n?rmal ma_nfrom unilateral light stimulation. This question is discussed m Chapters 3 and J7. For clinical purposes these statements can be ignored because the asymmetries mentioned are too small to be found in clinical tests. 945 946 I rv. Pupillary Pathology: Symptomatology to the other eye, as shown in Figures 18-1,A and 18-2 to 18-6). In bilateral cases the pupil of the stimulated eye is always mallcr than the consensually reacting one (Figures 18-1,B, 18-7, and 18-8). Becau e the anisocoria thus alternates we have named the phenomenon' alternating contraction anisocoria." H.S. Thompson suggested the name "consensual deficit" because the consensual reaction alone i impaired (uni- or bilaterally). Both terms de cribe the syndrome well. "Alternating contraction ani ocoria" tre ses what the pupils are doing, while "con en ual deficit' explains the nature of the defect. Since it i , furthermore, the horter term, I prefer it. Pupillary reflexes in per ons with marked consensual deficit often have "low-in ten ity" form. In bilateral cases timulation of either eye will result in "low-intensity" reaction , but in unilateral cases only reactions with ani ocoria show this afferent loss (see, for example, Figure 18-6,A and B). Near-vision responses may be entirely ymmetric even in unilateral cases (see Figure 1 -5), while in others the pupil that lags during the light reflex also lag during contractions to near vision (see Figure 18-4). P ychosensory reactions and drug reponse are normal. R A L &iii :ii 2 ~ • R B L I 2 3 3 ~ ·~ •l ~i 5 Figure 18-1. Consensual deficit (diagram). A, unilateral and B, bilateral phenomenon. The eyes are in darkness, with equal pupils, in frames 1. In frames 2 and 3 one eye is stimulated by light (as indicated), and in frames 4, both eyes are exposed to light. The patient looks far away, except in frames 5, the near-vision reaction (see text). 8 --------,--,--------==-----, 7 6 t t 5 f: ~ t-----•~~~-1----------------1-.--,~'-----------~ t:'. ·~ ,.. 3 ..., "q, f: 7 ----------------:_:;;;;;;_-_-_--_~!_;;;_-~ (j "i __ ;_;;:;;;::;.,.;:;_;:; __,,_.,_ ..._, 6 ~s -~¥ ::113 Time i.n. O.l,St!C'Ond-+ Figure 18-2. Post-convulsive disorder with unilateral consensual deficit. At the age of 12 the patient had been seriously ill with typhoid fever. He had generalized convulsions and was unconscious for several days. Since that time he had had about three grand mal seizures per year, each with about 45 minutes of post-ictal coma. At the time of examination he was 27 years old. He was morose and irritable, and had increasing trouble with his memory. There was hyperreflexia in this lower extremities, more pronounced on the left than on the right side. His pupils showed unilateral consensual deficit: they were equal in darkness and remained equal when the right eye was exposed to light. But when the left eye was stimulated the consensual reaction of the right pupil (solid line) was less extensive than the direct reaction of the left pupil (broken line), so that transient anisocoria developed. Similar behavior was shown in the darkness reflexes: when the right eye was adapted to light the pupils remained equal, but anisocoria developed when the light was shifted to the left eye. Note the "lowintensity" shape of the darkness reflex when the left eye was stimulated. (From 0. Lowenstein, Arch. Neural. Psychiat., Chicago, 72 [1954]: 742; 0 1954, American Medical Association) 18. Damage to the Intercalated Pretectal Neuron / 947 i--~-1 41---1---1----------1--1 3 81=---------=------------1 7 6 5 I I \----------------, I I t4 e3--=-·-------~-=------.--a~-~ a2 0.1sec.-+ Figure 18-3. Consensual deficit followed over a long time. A 22year-old woman came to the laboratory as experimental subject. She was neurologically and ophthalmologically normal, with corrected vision 20/20 in each eye. She had had many minor infections but had not been seriously ill except when, as a child of 2, she had fallen from her high chair and had been unconscious for several hours. Her pupils were normal except for slight but consistent "alternating anisocoria": in darkenss they were equal, and when the right eye was stimulated by light they contracted equally (LR in A and R in B). But when the left eye was exposed to light the left pupil contracted more extensively than the right one (LL in A and Lin B). During the following 4-year period the subject was tested on 160 separate occasions. In all records the alternating syndrome was shown with great fidelity. It never changed in extent, demonstrating that consensual deficit, once established, may continue permanently wihtout further development or regression. I t 7 (-i-------- :-__ -____ ---- • 5 -- I -----------< ~ ---=-------- 31--FV-;0.1sec. ~ L:iI!W!JimII;IlIIIII!miNmVIilt:::rm::!:!JliJJJI;:!IIIllIJ!!IC=:IJJ:El:±n::::::::Ii:riI!:!==l Figure 18-5. O.lsec. ➔ Figure 18-4. Consensual deficit with asymmetric near-vision contraction. The patient was 42 years old. Although she had many ~eurotic complaints her neurologic and ophthalmologic examinat~onswere negative. The pupils were equal in darkness. When the nght eye was stimulated by light, the consensual contraction of the left pupil (broken line) lagged and anisocoria developed (A). When the left eye was stimulated instead, the two pupils remained equal (B). The left pupil lagged also during the near-vision response (C). ---Nv·-.---1-----F-v.-.-----~ ➔ Consensual deficit with symmetric near-vision contraction. The patient was 43 years old. At the age of 12 he had had encephalitis, and at 14 he had to drop out of school because of a "nervous breakdown." Ten year before examination he had trouble with droopiness of his lids and inability to turn his eyes upward. These symptoms were worse when he was tired and improved with prostigmine treatment. However, the condition cleared after a few months. Recently he had spells of dizziness and paresthesias in his right foot. The tendon reflexes were symmetrically hyperactive in the lower extremities, with bilateral foot clonus. His pupils showed unilateral consensual deficit: when the right eye was exposed to light the pupils remained equal (A), but when the left eye was stimulated they did not (B). In contrast to the patient of Figure 18-4, the near-vision responses were symmetric in the two eyes. 948 IV. Pupillary Pathology: Symptomatology .. ,----~Al :: ,/. ,1 ,1- -\ J l ~l~~th '1= ~I ,- ,1-- s • i-- 3 ,l / - • ~•t~i,hk -- K -\ -- / ------ ff - , ... .:;. / Si- 11-- - ~ \~~ 3' ~ m ~ ..,/ iW[,. -- m ,,,-- ..... IC ~---✓-~ }~ ........ --- ', \ /,,_- l<9{!~. ~ ~----- iY' __• T" -- T."..ln• irt -~ '9,",,$, 1,~~t. 0.IS~~OtU:t ➔ Figure 18-6. Acute development of consensual deficit with recovery. The patient, a 27-year-old pianist, was the mother of 2 healthy children, 2 and I years old. She had been an experimental subject in the laboratory 8 and 4 years before she became ill. On both occa ions her pupils were large, equal, and normally reactive. After a 5-day period of low-grade fever with headaches and malaise he had a hard time recovering. She felt constantly weak and tired. She could not do her daily housework, and when she tried to play the piano her arms and fingers would not move properly and she had pain in her fingertips. Neurologic examination showed bilateral radial and medial neuropathy, more so on the right than on the left side. Vision was unimpaired. A: The pupils showed unilateral consensual deficit worse with repeated stimulation. B: 6 weeks later the general condition was unchanged and the pupillary defect had become worse. Stimulation of the left eye now elicited distinctly reduced "low-intensity" reactions with marked contraction anisocoria. C: 6 weeks after the second test the pupillary condition had improved greatly. The sole remaining pathologic sign was slight unilateral consensual deficit, with the right pupil lagging on stimulation of the left eye. The patient recovered gradually, and her pupillary reactions returned to normal (D, recorded a year after onset of the condition). (From 0. Lowenstein,Arch. Neural. Psychiat., Chicago, 73 [1955]: 302; '"1955, American Medical Association) Figure 18-7. Bilateral consensual deficit. The patient was a 26year-old woman. She had never been ill, had married at 21, and had a healthy 2-year-old son. Three months before examination she had a "bad cold" with a temperature of l00°F. She was not sick enough to stop work, but after the fever had subsided she did not recover for months. She continued to feel exhausted, and her right arm and leg felt weak. She was sleepy in the daytime but could not go to sleep at night; and when she finally did so, she awoke unrested. She also felt vague, unable lo make up her mind about trifling matters. Al the time of examination the motor weakness had cleared, and there were no neurologic or ophthalmologic signs. The patient was still tired, excitable, and slightly depressed. Her pupils showed bilateral consensual deficit: when the right eye was exposed to light the right pupil (solid line) became smaller than the left, and the opposite happened when the light was shifted to the left eye (broken line). (From 0. Lowenstein, Arch. Neural. Psychiat., Chicago, 75 [ 1955j: 302; I 955, American Medical Association) :$ 5 ~ "~-------- 3 c!onstcvi.t tight Tim.e right in 0.1 .fec!ortct-+ . 18. Damage to the Intercalated Preteclal Neuron / 949 C. Mechanism Since "alternating anisocoria" appears during contractions to light and the pupils are equal in darkness, the defect must be situated within the light reAex arc. And since neither afferent nor efferent lesions will produce the alternating pattern, the intercalated pretectal neuron remains the only possible site. This appears plain enough. But a few calculations showed that the matter is not quite a simple: asymmetries limited to the pretectal neuron will not cause "alternating anisocoria." We tabulated all theoretically possible lesions and combinations of lesions that could affect this neuron (Figure 18-9): -damage to crossed fibers or to uncrossed fibers arising from one pretectal area (see small diagrams in columns A and B); -involvement of crossed and of uncrossed fibers from one side (column C); or -involvement of all crossed fibers in the posterior commis ure (column D); --damage to uncrossed fibers from both pretectal areas (column E); or -impairment of crossed and uncrossed fiber past the commissure, where they approach the motor nucleus (column F); or -combinations of lesions that would leave only one crossed or one uncrossed bundle intact (column G and H). ' 7 -- -,------------I \ 6 We assigned arbitrary values to the afferent volleys that reach the pretectal area when one or the other eye is expo ed to light, and we assumed (a) a normal 50-50 distribution between crossed and uncrossed pretectal fibers, and (b) a "lesion" to mean reduction of fibers in a bundle to half of normal, a in Figure 18-10, or to one-fourth or to three-fourths of normal (calculations not shown). To our surprise we found that anisocoria could be produced by certain lesion (Figure 18-9,A, B F, and G, and H) but that the "alternating" feature would not occur in any combination of defect . ff, then, asymmetries in the pretectal neuron cannot explain "alternating" anisocoria, how can it be brought about? Nature itself indicated this. Normal cats have imperfect con ensual light reAexes: when you take a cat into your arms and stand near a window, the cat's pupil nearest the window will become smaller than the other. When you now turn so that the cat's other eye is nearest the window, the anisocoria will reverse and again, the eye nearest the window will have the smaller pupil. Cat have many more eras ed than uncrossed fibers in their pretectal hemidecu sation and in the optic chiasm. When the same calculations as in Figures 18-9 and 18-10 are ~ \-----~ ' '- 5 ., ----~ - _s_______ __ '\\ J ' 7 6 t s .... ""E: J" \, tj ·~ "3 7 ~6 tj ....., .....5 ::s Q.. T,me in o tsecond-+ Figure 18-8. Bilateral consensual deficit. This patient was examined at the ages of 10 and 15 years, and had the same pupillary responses on both occasions. He was nervous and obese and had behavior problems, but neurologic and eye examinations were negative. His pupils showed bilateral, almost symmetric consensual deficit: when the right eye was exposed to light, the right pu- pil (solid lines) became smaller that the left one (broken lines), and the left pupil became the smaller one when the light was placed on the left eye. (From 0. Lowenstein, Arch. Neural. Psychiat., Chicago, 72 [1954]: 742; 1954, American Medical Association) A B C D R. L I lo(ation of luion. z Strong light /~ft Strong light ri9M light r~'ln l1l E R..P"'I'! l:l..pu.p,l:-- I I I ' • > 16. • <11.• ll. . <. •>· ll. " L ,-~A./ \..,,.... \;t ,, / 11 " V:l\i' \ \ \ ,, I l L I loeation oF luio,i JI stro,r9 li9Ml,ft llI /i.9'1t rigJrl Ir ✓tron.9 •=•/1 • =. L •=-. 11. 11. ll. \ "'" \I\/ V:r►\/11. .. ~ R. H R. L •>· I " •>· I " .\R.,,· L •<•I ·<• 11. I •>•ll. ' •>•11. • ~~f(., I ... \ \,' R. ~~~ ll. " l ,, ~\r WV:t Figure 18-9. Calculations mentioned in the text, with different kinds of lesion a sumed to be limited to the pretecal neurons. Lines I show the location of the assumed defects (black bars). In line II and Ill the dot indicate pupillary size in steady light to the left or to the right eye and lines IV the diagrams show anisoco- ll. 11 ll. \ l.,pu.p,l1-- /1 I I I • =.11. .at.pu.pjl:- I '~ ll. F fl. ll. light,,,,,. \ • =. ·=· /1 " ,''' W-tf_,<,-· ~ ria during light reflexes. Note that none of all possible defects limited to the intercalculated neurons would result in "alternating" anisocoria. (From 0. Lowenstein,Arch. Neural. Aychiar., Chicago, 72 [1954): 472; 1954, American Medical Association) • > lb lb lb 16 AJI Figure 18-10. Method of calculation for Figures 18-9, 18-11, and 18-12. An assumed lesion is shown by black bars, as in Figure 189,A. It was thought to involve the crossed fibers from the right pretectal area to the left oculomotor nucleus. Upon light stimulation of the left eye, or of the right eye, each retinal half was assumed to generate 16 (arbitrary) afferent stimulation units. Normally these would be distributed symmetrically by the right and left pretecal neurons, each sending 8 units to the ipsilateral and 8 to the contralateral sphincter nucleus. The lesion was postulated to cut these afferent units in half, so that the left oculomotor nucleus would receive a total of only 12 units, compared to the normal 16 of the right nucleus. The arrows show which eye was assumed to be exposed to light. (From 0. Lowenstein,Arch. Neural. Psychiat., Chicago, 72 [ I954): 742; 0 1954, American Medical Association) 950 Figure 18-11. Calculations as in Figures 18-9 and 18-10 for cats, with preponderantly crossed chiasmal and pretectal fibers. In cats less than one-fourth of the optic fibers are uncrossed while the majority cross to the opposite pretectal area. Note that this double asymmetry (afferent and pretectal) leads to "alternating" behavior of the pupils: upon unilateral stimulation the directly reacting pupil receives more innervation than the consensually reacting one. (From 0. Lowenstein,Arch. Neural. Psychiat.,Chicago, 72 [1954): 742; 01954, American Medical Association) 18. Damage to the Intercalated Pretcctal Neuron done, using the approximate fiber distribution for cats, it can be seen how the "alternating" pattern develops. Upon stimulation of one retina-say, the left, as in Figure 18-11-the majority of optic impulses cross in the optic chiasm and reach the pretectal area on the right side; and fewer impulses ascend to the left pretectal area uncrossed. The pretectal neurons on each side, again, send more crossed than uncrossed fibers to the oculomotor nucleus; and since (in this example) the right pretectal area has more impulses to distribute than the left one, the left oculomotor nucleus will receive more stimulation, and the left pupil will become smaller than the right one. When the light is shifted to the right eye, the situation reverses, and the right pupil will become the smaller one. In order not to overlook any possible combinations of afferent with intercalated asymmetries that might be responsible for the consensual deficit, we ran through all theoretically possible combinations of afferent plus intercalated defects (one hundred in all), assuming different degrees of relative impairment (Lowenstein and Loewenfcld, 1954). The result was that only two combinations of afferent plus intercalated deficit could result in "alternating" anisocoria as it occurs in nature. For all others, there was either no anisocoria at all; or the direct reaction was worse than the consensual one; or there were other traits not encountered in reality. Only the series in Figure 18-9,D and E could be combined with afferent defects to lead to unilateral or to bilateral alternating behavior (Figure 18-12). In Figure 18-9,D, only crossed and Figure 18-9,E only uncrossed elements were involved. Which is the more likely combination? The answer is suggested by the fact that in primates as well as in cats the chiasmal fiber distribution distinctly favors crossed over uncro sed elements. 2 It appears reasonable to assume that this natural asymmetry sets the stage for "alternating" pupillary behavior to occur if the uncrossed fiber contingent from the pretectal neuron should develop imperfectly or should be injured at a later time. In summary, then, consensual deficit results from asymmetry in the intercalated (pretectal) neuron of the light reflex arc, but not from this asymmetry alone: there is additional inequality of afferent impulses from the optic chia m to the pretectal region. The existence of a natural asymmetry in the afferent neuron in primates, as in lower species (though not as marked), makes it possible for lesions confined to the uncrossed pretectal neurons to bring about consensual deficit. And since the uncrossed pretectal fibers are relatively new phylogenetically, selective sensitivity to toxic or other adverse conditions would not be surprising. 2. When we worked on thi problem in 1954 we were not aware of the uneven fiber distribution in the primate chiasm and thus could not decide the que lion. DZ DI R. L I lot'ation of lt.<ion II J'tron9 l i91tt ltft Ill J'trDn9 ligM rigM N li91tt r-efln "pr.,pil·L.pupll·-- •<•, •, >•ID lo(atiott of tesiott 1l st,Dn9 light lrft 1ll Strong_ l tgltt r-tgltt l£ l i91t t refter R. pupil L p 1-<pil,-- \ ... -,L I ~ •>• -,,. V Vv I ~R. \../ loc-atio11 lesion .Jr Stron9 li9ht {rlt J.II stro,r9. l19ht r-tgltt .u li9lrt ul/u II. pupil:L.pupil. - - b➔ I location of Inion J[ rtro,r9 light {,1/1 .Ill rtro,r9 li9ht ,-i9ltf u l,91tt ,ellu 11.pu,oj/oL.,ou,o,I:-- I I 10 •=• •=• ' ' ' 6 \., ...... \ ,," " •>• •<. JO 10 -,11.., DB L ~~ 10 <• 10 \/ It I., •>• • •>• , 10 I Dl ll \F' \,,/ ei. \Y,R., ~ ' V -'L ;v H 0 I~i I I 1t L L It I -v,ll,, ~ '/' ,/ V\/ D6 f./ of ,.J L ll L I \\p'lt \ ,...~ .., V "VW ' • ' ' 10 R., •<• •>• ID ID ll, fl. "- I • = • tL ll, D5 I L ' '•=• IL L D't ll L • = • • = • IL D3 ll L I 951 / L It ll . •=• • = • 12 ll. I •>. I •<. 10 •>• • = • ,. IL /l. 10 I /J. •=• ' ' JO •<. , /0 \J~ Vv .. \rv V~ lt \ I ,, ll. \.,, ,,' ~ \ l5 l6 (7 ll \ , ..' I ,' (8 ,.. ..~ ~ ~ ~ I~><v It L L •<. •>• I /0 ',,...., \., ..... \1/-"~ 10 JO -,ll, •_1 I ..., I \ ID L ll •<. I~ I •=• •=• ' • • • •<. I •>• \ ~v L •<. , I /0 It ,.., I Vv )l ', , ~-v,.. \_/ l Figure 18-12. Combinations of afferent plus pretectal deficit that could bring about "alternating" pupillary behavior. Calculations and plotting as in Figures 18-9 and 18-10. ln the D series (top) only crossed paths are involved (unilateral defect in DI and bilateral in D4); and in the E series, only uncrossed fibers (unilateral m E2 and bilateral in ES). Note that in all species, including primates, the uncrossed fiber contingent of the optic chiasm is less well de~eloped than the crossed fibers (see text). (From O. Lowenstem,Arch. Neural. Psyclziat.,Chicago, 72 [ 1954): 742; OJ 954, American Medical Association) , 952 IV. Pupillary Pathology: Symptomatology D. Clinical Occurrence and Significance The significant question is whether consensual deficit should be regarded as physiologic, resulting from normally a ymmetric fiber di tribution in the afferent and intercalated neurons; or as pathologic; or as a developmental anomaly without pathologic significance. The fir t of the e po sibilitie can, in our opinion, be di carded, for the following reasons. (1) in cats, with normally uneven pretectal fiber di tribution, "alternating ani ocoria" is always pre ent; and it i alway bilateral and always symmetric. In contra t, only a minority of human ubjects show the trait, and in tho e who do, the condition is much more often unilateral than bilateral; and bilaterally symmetric deficit i a rarity (Table 18-1). (2) In a phy iologically a ymmetric fiber system one would expect a ide preference (as, for example, in hemi pheric dominance). But there is no such thing here: among unilateral ca es just about half show their ani ocoria when the right eye is stimulated, and the other half when the left eye i stimulated (Table 18-1). (3) In patient with marked consensual deficit it is quite obviou that afferent conduction is diminished when the eye that cause the anisocoria is exposed to light: both the light reflexes and the darkness reactions have reduced amplitude and an unmistakable "lowinten ity" form. (4) These characteristic would be expected if consenual deficit were caused by a pathologic process. And 15 14 13 A 1 1 12 t 8 i II ~i AGE DISTRIBUTION / ,N "OOC,_,e, 10 C, 9 () 8 <( I u<( 7 6 i 5 ~ 4 Ii :::-, I'~-? ::: :::\ 3;:: 3 ~ 2 01 "#- . . 0 10 20 30 AGE IN YEARS ➔ 40 I.~,~--50 60 70 80 & 70 90 100 ~ 80 90 indeed, we have observed the development of the pupillary syndrome in patients with infectious diseases who had not shown this sign before they fell ill (Figure 18-6). While we therefore consider consensual deficit a pathologic condition, its clinical significance is often questionable. The anisocoria is small and fleeting: it rarely exceeds half a millimeter at the peak of contractions to light, so that usually it cannot be demonstrated with certainty without bilateral recording of the pupillary movements. And when it is found, the time of onset usually is uncertain. Once established, consensual deficit is permanent in most cases (see Figures 18-3 and 18-8). ln a given individual, therefore, it need not be related to the patient's presenting illness. Unless previous normal pupillograms exist, it may have been acquired at an earlier time, or may have been present from birth. These facts prompted us to look whether a relationship between age and the incidence of consensual deficit might exist. If this sign were always acquired, it should occur more often in older than in young patient groups. However, we did not find such an age trend in our unselected eighteen hundred cases (Figure 18-13). Nor was there an age trend in the large population survey of 1969-1972. It has been our impression that consensual deficit has become more common during the decades since the end of World War II, when international air travel increased greatly, and when antibiotic treatment of infectious diseases became available. During the same period the incidence of relatively benign but protracted "virus flu" appears to have increased. In any case, patients like the one described in Figure 18-6, who developed consensual deficit after a low-grade fever, malaise, headaches, nausea, and so forth, followed by a protracted period of exhaustion, nervousness, polyneuritis, and depression, were not observed in our laboratory before the 1950s. In apparently healthy subjects, also, "alternating" anisocoria appears to be encountered more often today than was the case until recent decades. These clinical impressions find some support in the statistics of our laboratory, which show a sudden jump of almost 100% in the incidence of consensual deficit immediately after the war (Table 18-2). Further, among 195 experimental sub- 100 Figure 18-13. Age distribution of consensual deficit among our unselected patient group. A: Each column shows the percentage of patients with consensual deficit in each successive 5-year age group. The thin broken line shows the same percentage for the entire 1,800-patient group. B: The circles and solid line show relative frequency of consensual deficit for each age group, compared with the total patient group. Each circle shows the value for a decade. Note that there was no age trend: all values were close to 1, that is, the age distribution of the total group. 18. Damage to the Intercalated Pretectal Neuron Table 18-1. Laterality of alternating contraction anisocoria Number of patients with ACA in unselected Among these: (1) anisocoria (2 ) 11 (3) tt upon stimulation " " 11 " 1800 cases: 520 of either eye. • • • 106 of right eye only ... 201} 414 of left eye only. . . . 213 Table 18-2. The incidence of alternating contraction anisocoria 1935-1960 YEARS TOTAL counted 1935-40 1941-45 1946-50 1951-55 1956-60 277 350 658 321 359 NOACA 230 293 444 2.44 256 ACA 47 57 214 77 103 % ACA 17.0 16.3 32.5 24.0 28.7 Table 18-3. The incidence of alternating contraction anisocoria among 1800 unselected clinical cases NUMBER OF CASES DISEASE E TITY u SELECTED cases (total) CNS syphilis nons:eecific CNS infections multiple sclerosis traumatic brain lesion post - concussion syndrome space - taking processes degenerative CNS conditions cerebral arteriosclerosis cerebro - vascular accidents parall'.sis agitans essential hypertension diabetes mellitus hn~erthl'.roidism autonomic nervous attacks schizophrenia } non-specific manic depressive psychoses psychoneuroses endogenous nervousness glaucoma experimental subjects TOTAL in above diseases cystic fibrosis (1964-66 study) NUMBER ACA % ACA IN ENTITY 28. 9 1800* 520* 177 137 115 55 51 34 82 93 29 34 119 28 55 81 63 57 64 16 23 6 39 34 10 9 27 8 16 26 35.6 41.6 55.7 29.1 45.1 17.7 47.6 36.6 34.5 26.5 22.7 28.6 29.1 32.1 53 21 39.6 204 43 74 195 59 10 21 4 28.9 23.3 28.4 2.1 513 30.9 69 65.1 1659* ote that only the maJor disease entities are tabulat d so that the total group is larger than the tabulated total. e ' / 953 954 IV. Pupillary Pathology: Symptomatology Table 18-4. The incidence of alternating contraction anisocoria versus age among I 07 patients with cystic fibrosis, and among 191 normal children tested during the same time span, 1964-1966 A. CYSTIC FIBROSIS AGE GROUP (YEARS) PERCENTAGE 0 0 - 5 6 - 13 14 - 29 ALTERNATING CONTRACTION ANISOCORIA + ++ +++ 88.2 51. 6 32.1 5.9 27.4 46 .4 5.9 19 .4 7.2 0 1. 6 14.3 87.0 84.7 97.4 11.1 14.3 0 1. 9 1. 0 2.6 0 0 0 B. NORMAL 0 - 5 6 - 13 14 - 29 65.1 65 60 55.7 55 50 47.6 ~ 45 0 (.) 0 40 a: (/) z ex: z 35 0 30 ~ a: f-z 25 ~ 0 20 (!) 15 (.) z ~ z a: UJ 10 ~ 5 ~ 0 ex: 0 0 0 ~ ...J ~ 0 I- - .,_ C QJ Cl en QJ en en en u en en UC "' -c en en en -c > C ~-en Q) ::, -zo -~ 0 .!!? .Q E C Q) ·; 0 ::, Q) '.:? ,,, 0 :..: gi cu-; .o c·rn Q)= ~~ ~-Q Uu Q) C E ~ t, .o~~ en•~ ·o, ::,U ~~ ~~ Q) u "'u ::,...J 0. "' Q) CJ C >, cc ro< "'"'t:Q) a'.:? lo (.) en > u en.l!! ~ C C >, Q) Q) 0 Cl) w Q) CC .Q I < ll. I- 'iij oen CJll. o0. g,0 0 Cl) >, r~ ,,,~ ~ e ~ z (.) ZC/l z(.) ai (.) I o5 0 a. "' en 0. oen z (.) 2 15 <{ Q) ai Figure 18-14. Relative incidence of consensual deficit in patients with various clinical conditions among our 1,800 unselected patients. The shaded column at the left shows the incidence of consensual deficit among the entire 1,800-patient group (28.9% ). The (.) I E u ·-:,: en .!!! Eu u 0"' '6 C:::: >, 2< ::, :: :;; < 0. >, I ·c "' ~ .c 0. QJ en .?'tn ,,, 0 ,,, .c Q) ~ u >, o. en 0 N L:. i11. I CJ en CJ ·2 "' en Q) en e::, Q) C 0 .c §/. "' en en ::, en 0 Q) CC ., en Cl::, oo u> c~ w Q) z ,,, -en .,_ 'cii "' co E -u 0 C Q) Q),_ 0(0 a"' ·-::, LL I 0. ~~ u::, :e~ :;;cn E.o )( w CJ st ,.._ (.) ll. '.:? black columns show the frequency (in%) among different clinical subgroups, as indicated. Note the outstandingly frequent occurrence of this pupil sign among children with cystic fibrosis (large black column on the right). 18. Damage to the Intercalated Pretcctal Neuron jects used in the laboratory before 1960, only seven had consen ual deficit, while almost a third of the subjects in the 1969-1972 population survey showed it. In part, the low incidence in the earlier group may reflect selection, because the subjects were deliberately cho en for extensive physiologic studies and were healthy young adults with equal pupils that looked normal on clinical examination. In contrast, the criterion for selection for the population tudy was only that the subjects should not be ill at the time of examination, and should have no hi tory of yphilitic, neurologic, psychiatric, or eye disease. everthele s, in the past it was unusual that we would reject an experimental subject becau e con ensual deficit was found in a screening pupillogram, while this occurs frequently today. If indeed the kind of illne s likely to precipitate consensual deficit has become more common in recent decades, a lack of increase of the pupil sign with advancing age would be explained: while these subjects have lived longer, they would have been exposed to such diseases relatively seldom in their earlier years. As seen in Table 18-3 and Figure 18-14 consensual deficit was observed in all disease entities among our eighteen hundred unselected cases. In a few pathologic groups it appeared to occur more often than in the "normal" populations. These were conditions affecting relatively young patients: multiple sclerosis, trauma, and heredodegenerative conditions. This tendency may have tilted the age curve further toward younger groups. / 955 The "alternating" sign was found with outstanding frequency among 107 children with cystic fibrosis of the pancreas. Fully 65% of these children had this pup!I sign (69 children); and in 48 of thes~, consensual d_efi~1twas the sole pathologic pupillary sign (70% ), while in the unselected patients a mere 10% had consensual deficit without other pupillary signs. Further, among the children with cystic fibrosis an age trend appeared to exist (Table 18-4): in the youngest group, "alternating" anisocoria was no more frequent than in a control group of normal children examined during the same time span. But with increasing age both the frequency and the severity of the pupil sign increased among the children with cystic fibrosis while in the normal children this was not true. Children with cystic fibrosis are, from birth, prone to all kinds of viral and other infectious diseases as well as hypoxic episodes. In view of their pupillary findings one might think of the possibility that the uncrossed pretectal fiber system might be especially vulnerable to noxious influences suffered so often by these children. For all these reasons we regard consensual deficit as a neurologic "mini-sign," often without clear pathologic significance. In rare patients in whom it appears during the course of infectious or other diseases, it proves that the disease involved the central nervous system. An important point to remember is that consensual deficit sufficiently marked to be detectable clinically is not found in the majority of healthy people (see further discussion in Chapter 3).