Primary Oblique Muscle Overaction the Brain Throws a Wild Pitch

CLINICAL SCIENCES Primary Oblique Muscle Overaction The Brain Throws a Wild Pitch

Michael C. Brodsky, MD; Sean P. Donahue, MD, PhD

Background: Sensorimotor and orbital anatomical inferior oblique overaction, which corresponds to a for- mechanisms have been invoked to explain primary ob- ward pitch in lateral-eyed animals, may result from vi- lique muscle overaction. sual disinhibition of central vestibular pathways to the extraocular muscle subnuclei that modulate upward ex- Methods: Review of primitive visuo-vestibular re- traocular muscle tonus. flexes and neuroanatomical pathways corresponding to vestibulo-ocular reflexes, and correlation with known Conclusions: Primary oblique muscle overaction reca- clinical abnormalities in patients with primary oblique pitulates the torsional eye movements that occur in lateral- muscle overaction. eyed animals during body movements or directional luminance shifts in the pitch plane. These primitive ocular Results: Bilateral superior oblique muscle overaction, motor reflexes become manifest in humans when early- which corresponds to a backward pitch in lateral-eyed onset strabismus or structural lesions within the poste- animals, can occur when structural lesions involving the rior fossa alter central vestibular tone in the pitch plane. brainstem or cerebellum increase central otolithic input to the extraocular muscle subnuclei that modulate downward extraocular muscle tonus. Bilateral Arch Ophthalmol. 2001;119:1307-1314

RIMARY oblique muscle over- tropia but no other overt neurologic ab- action is a common ocular normalities. Surgical weakening of the motility disorder character- overacting oblique muscles improves ver- ized by vertical incomitance sions, eliminates the associated A or V pat- of the eyes in lateral gaze.1 In tern, and reduces torsion. Pprimary inferior oblique muscle overac- In 1916, Ohm6-8 postulated that pat- tion, an upshoot of the adducting eye oc- tern strabismus and oblique muscle over- curs when gaze is directed into the field of action may be due to abnormal vestibu- action of the inferior oblique muscle, pro- lar innervation. Almost a century later, a ducing a greater upward excursion of the unifying neurologic mechanism to ex- adducted eye than of the abducted eye.1 The plain primary oblique muscle overaction opposite occurs in primary superior ob- remains elusive. This ocular motor phe- lique muscle overaction. Although duc- nomenon seems to defy fundamental prin- tions appear to be normal and there is no ciples of physiology since nowhere else in evidence of yoke muscle paresis, alternate the body do individual muscles bilater- cover testing discloses a vertical tropia of ally overact. similar magnitude in the abducting eye. Pri- The primary function of the oblique From the Departments of mary inferior oblique muscle overaction is muscles in lower vertebrates such as fish Ophthalmology and Pediatrics, usually associated with ocular extorsion and is to counterrotate the eyes torsionally in University of Arkansas for V-pattern strabismus, whereas primary su- response to pitch (fore-and-aft) move- Medical Sciences, Little Rock perior oblique muscle overaction is usu- ments of the body.9,10 As a fish pitches its (Dr Brodsky); and the ally associated with ocular intorsion and A- body to swim upward or downward, a Departments of Ophthalmology 2-5 and Visual Sciences, Pediatrics, pattern strabismus. Superior oblique compensatory “wheel” rotation of the eyes and Neurology, Vanderbilt muscle overaction is often accompanied by is produced by the oblique muscles in re- 9 University School other neurologic disease, whereas inferior sponse to vestibular stimulation. The ex- of Medicine, Nashville, Tenn oblique muscle overaction generally oc- istence of this physiologic oblique muscle (Dr Donahue). curs in children who have congenital eso- overaction in lower animals led us to ques-

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 organs).12,13 This hypothesis explains how sensory in- formation collected by the eyes can help to govern extraocular muscle tonus. The bilateral positioning of the eyes and ears permits them to function as balance organs. Visual and graviceptive input are yoked together A B within the central vestibular system to determine opti- mal postural orientation. In his early pioneering studies of vision-dependent tonus responses in fish, von Holst14 found that a posterior shift of a dorsal light source induces a pitch-up movement of the body, whereas an anterior shift induces a pitch-down movement, as if the animal is programmed to position the body so that the light source retains a dorsal orientation (Figure 1). With the body stabilized in C D the upright position, an overhead light moving fore-and- aft evokes a wheel-turning movement of both eyes, which rotate to maintain torsional alignment with the light source (Figure 1).14-16 Since light normally comes from overhead when a fish is upright, a posterior movement of the light is registered as a pitch forward movement of the body (ie, a movement of the body away from the light). This change in visual input evokes increased tonus to the in- E F ferior oblique muscles, which extort the eyes (Figure 1). Figure 1. Physiologic effects of gravistatic (postural) and visual input to the The observation that visual and vestibular input can al- oblique muscle tonus in fish. These bilateral torsional eye movements function ter postural and extraocular muscle tonus to produce a to align the eyes with the perceived visual vertical by modulating oblique muscle physiologic bilateral oblique muscle overaction in lower tonus. A, A pitch-down body movement evokes increased inferior oblique muscle tonus and extorsion of the eyes. B, A pitch-up movement evokes animals suggests that similar excitatory stimuli may be increased superior oblique muscle tonus and intorsion of the eyes. C, In the operative in strabismic humans with primary oblique unrestrained fish, an anterior light source evokes a pitch-down body movement. muscle overaction. D, In the unrestrained fish, a posterior light source evokes a pitch-up body movement. E, In the restrained fish, anterior movement of overhead light evokes increased superior oblique muscle tonus and intorsion of both eyes. VESTIBULAR INTERACTIONS WITH F, In the restrained fish, posterior movement of overhead light evokes THE OCULAR MOTOR SYSTEM increased inferior oblique muscle tonus and extorsion of both eyes. To understand why primary oblique muscle overaction so tion whether a central vestibular imbalance in the pitch often accompanies early-onset strabismus, it is instruc- plane might offer an explanation for the occurrence of tive to examine the components of central vestibular tone primary oblique muscle overaction in humans. Clinical that influence eye position. The primary function of the observations suggest that an imbalance in central ves- vestibuloocular system is to maintain eye position and sta- tibular premotor output to the extraocular muscle sub- bilize fixation during head movements.16 Vestibulo- nuclei can produce the primary oblique muscle overac- ocular movements are the most primitive of all extraocu- tion that accompanies congenital strabismus. This central lar movements. As expounded by Walls, vestibular imbalance develops when early loss of binocular vision or neurologic disease alters central vestibu- . . . the primitive function of the eye muscles was not to aim lar output in the pitch plane to produce excessive tonus the eyes at all. Their original actions were all reflex and invol- of the extraocular muscles that elevate the eyes (in the untary, and were designed to give the eyeball the attributes of a gyroscopically-stabilized ship, for the purpose of maintain- case of congenital esotropia and inferior oblique muscle ing a constancy of the visual field despite chance buffetings and overaction) or depress the eyes (in the case of neuro- twistings of the animals body by water currents.9(p303) logic disease and superior oblique muscle overaction). In the rabbit, for example, a rightward body tilt along CENTRAL TONUS MECHANISMS FOR its long axis causes the right eye to be lower in space than PRIMARY OBLIQUE MUSCLE OVERACTION the left eye. This tilt elicits a compensatory vertical divergence of the eyes to elevate the right eye and depress the The term tonus was originally coined by Ewald11 to de- left eye, thereby stabilizing the eyes in space.17-19 A pitch scribe the state of excitation of a living muscle during forward of the body would produce a compensatory ex- rest. In 1977, Meyer and Bullock12 advanced their tonus torsional movement of both eyes.14,15,20 hypothesis, which states that neuronal tonus pools within Now consider the same pitch-down body movement the central nervous system receive multisensory input and in a rabbit that is fixating with the right eye maximally ab- that tonus asymmetries between antagonistic pools can ducted and the left eye maximally adducted (Figure 2). produce tonic motor responses. According to this hy- Since the eyes are laterally placed in the rabbit, this posi- pothesis, the eyes are not merely sensory organs but tion of gaze would direct the left visual axis anterior to its components of a multimodally driven tonus pool that neutral position and the right visual axis posterior to its calibrates baseline muscle tone (ie, tonus-inducing neutral position. A forward pitch in the body plane with

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51°

Superior Rectus

23°

41°

Semicircular Canals

56°

Posterior Top View

Figure 2. Overhead view of a rabbit fixating an object in the right posterior Figure 3. The close anatomical relationship of the semicircular canals and visual field. Solid lines correspond to the visual axis of the abducted right eye the extraocular muscles in humans is shown. Figure modified with and the adducted left eye. When the rabbit pitches forward (as when starting to permission from Simpson and Graf.17 run down a hill), the head rotates downward and the tail rotates upward. Although both eyes move downward in space, the left visual axis (which is directed toward the nose) rotates downward, while the right visual axis (which ticular plane, a semicircular canal within the labyrinth is directed toward the tail) rotates upward (curved arrows). This divergence of detects acceleration and sends excitatory innervation to the visual axes corresponds to a right hypertropia that must be neutralized by vestibular innervation to elevate the lower left eye and depress the higher right the extraocular muscle(s). Within the brainstem and cer- eye. The compensatory vertical divergence for a pitch-forward position ebellum, peripheral vestibular input is summated to pro- corresponds to primary inferior oblique muscle overaction. duce appropriate innervation to the extraocular muscle subnuclei and maintain the position of the eyes in space the eyes in this position would tilt the left visual axis to a (Figure 4).18-22 Each anterior semicircular canal pro- lower position in space than the right visual axis (Figure vides excitatory innervation to the ipsilateral superior rec- 2). This tilt would necessitate compensatory vestibulo- tus and the contralateral inferior oblique muscles while ocular innervation to increase upward tonus in the left eye inhibiting the yoked ipsilateral inferior rectus and con- and increase downward tonus in the right eye, while ex- tralateral superior oblique muscles (Figure 4). Like- torting both eyes in response to the body pitch. Con- wise, each posterior semicircular canal system provides versely, if the body were pitched back during dextrover- excitatory innervation to the ipsilateral superior ob- sion, the higher visual axis of the adducted left eye would lique and the contralateral inferior rectus muscles while necessitate increased downward tonus in the left eye and inhibiting the ipsilateral inferior oblique and the contra- increased upward tonus in the right eye to stabilize the po- lateral superior rectus muscles. In humans, a pitch-up sition of the eyes in space. The necessary vestibulo-ocular movement of the head (as occurs when raising the chin) movements, which correspond to the vertical divergence activates both posterior semicircular canals, which send in lateral gaze seen in humans with primary oblique muscle excitatory innervation to both depressors in both eyes. overaction, are programmed at an early evolutionary stage Like their target extraocular muscles, the semicircular ca- to assure stability of the visual field in all fields of gaze. In nal pathways have a push-pull (yoke) relationship, so that 1996, Zee18 formulated this hypothesis to explain how the activation of one canal inhibits the antagonist canal.19 alternating skew deviation in lateral gaze that occurs in hu- Thus, the pitch-up movement that excites both poste- mans could be a reversion to a phylogenically old otolith- rior canals also inhibits both anterior semicircular ca- mediated righting reflex in lateral-eyed animals. Zee’s hy- nals, which send inhibitory innervation to the ocular el- pothesis also explains how superior oblique muscle evators. The result is an equal contraversive movement overaction with alternating hypotropia of the adducting eye of both eyes to adjust for the pitch-up head movement. reflects a pitch-up otolithic bias and a downward tonus bias Injury to or inhibition of anterior canal pathways sub- to the extraocular muscle plant, whereas inferior oblique serving upward eye movements causes a functional ac- muscle overaction with alternating hypertropia of the ad- tivation of the posterior canal downgaze pathways and ducting eye would result from a pitch-down otolithic bias produces downward eye movements.22 and an upward tonus bias to the extraocular muscle plant. In addition to the semicircular canals, each laby- In lateral-eyed animals and in humans, the semicir- rinth contains otolithic sensors consisting of the utricle cular canals are roughly aligned with the extraocular and the saccule.19 While the semicircular canals re- muscles (Figure 3).17 When the head is rotated in a par- spond to angular acceleration and produce dynamic ves-

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IR MR III N I S O IO MLF M BC BC

III

BC VTT IV MLF

SVN MLF SVN AC MVN PC VTT HC VI AC AC

LVN HC HC MVN Cerebellum PC PC Figure 4. Neuroanatomical projections from the labyrinths to the extraocular muscles. The orientation of the anterior semicircular canal corresponds to that of the ipsilateral superior rectus and contralateral inferior oblique muscles. The orientation of the posterior semicircular canals corresponds to that of the ipsilateral superior oblique and contralateral inferior rectus muscles. The orientation of each horizontal canal corresponds to that of the horizontal rectus FLO NOD FLO muscles. Turning the head to the right stimulates the right horizontal canal to increase excitatory innervation to the right medial rectus muscle and left lateral rectus muscle so that the eyes rotate equally and opposite to the direction of Figure 5. Segregation of pathways controlling anterior and posterior canal head rotation. HC indicates horizontal canal; AC, anterior canal; PC, posterior tone. Only the anterior canal pathways receive inhibitory innervation by the canal; LVN, lateral vestibular nucleus; MVN, medial vestibular nucleus; VI, cerebellar flocculus. A loss of modulation from the cerebellar flocculi could abducens nucleus; MLF, medial longitudinal fasciculus; IV, trochlear nucleus; disinhibit the anterior canals and produce an upward tonus imbalance, III, oculomotor nucleus; SR, superior rectus muscle; MR, medial rectus muscle; leading to bilateral inferior oblique muscle overaction, bilateral extorsion, and LR, lateral rectus muscle; and IO, inferior oblique muscle. Data modified with V-pattern strabismus. FLO indicates flocculus; NOD, nodulus; AC, anterior permission from Tusa.21 canal; PC, posterior canal; HC, horizontal canal; SVN, superior vestibular nucleus; V T T, ventral tegmental tract; MVN, medial vestibular nucleus; MLF, medial longitudinal fasciculus; BC, brachium conjunctivum; III N, oculomotor tibuloocular movements, the parallel otolithic system re- nucleus (S, I, O, and M represent the oculomotor subnuclei); SR, superior rectus muscle; and IR, inferior rectus muscle. Data modified with permission sponds to linear acceleration and is sensitive to changes from Tusa.21 in static head position.19 Damage to the semicircular canal pathways produces phasic ocular deviations and nystagmus, while damage to the otolithic projections cor- tion of the eyes.21 Conversely, bilateral lesions of the responding to the semicircular canal pathways causes tonic ventral tegmental tract or brachium conjunctivum can ocular deviations (strabismus).19,23-25 The otolithic path- injure central pathways from the anterior semicircular ways are not as well studied, but are believed to have simi- canals and produce a posterior canal predominance, re- lar projections to the corresponding canal pathways.19 For sulting in tonic downgaze. Maturation of cerebellar floc- the sake of simplicity, we refer to the otolithic pathways cular inhibition to anterior canal pathways may be de- corresponding to a particular canal pathway simply as pendent on normal visual experience early in life. Ocular the anterior canal or posterior canal system, recognizing stabilization is normally modulated by visual and ves- the similarity in projections between the otoliths and semi- tibular input. When binocular visual input is pre- circular canals. Likewise, we also use the term anterior empted, this multisensory mechanism may fall under (or posterior) canal predominance to mean “predomi- greater weight of labyrinthine control, allowing excit- nance of the otolithic pathways corresponding to those atory anterior canal output to predominate.28 of the anterior (or posterior) semicircular canals.” The otolithic pathways corresponding to the ante- SUPERIOR OBLIQUE rior and posterior semicircular canals are under differ- MUSCLE OVERACTION ent inhibitory control (Figure 5).19,21,22,26,27 The ante- AND A-PATTERN STRABISMUS rior canals receive inhibitory connections from the IN NEUROLOGIC DISORDERS cerebellar flocculi, while the posterior canals do not. Thus, a structural lesion or metabolic abnormality that inhib- A bilateral lesion that injures both anterior canal path- its output from the cerebellar flocculi can also disin- ways or disinhibits both posterior canal pathways will inhibit the anterior canals, resulting in an upward devia- crease prenuclear innervation to the superior oblique and

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 inferior rectus subnuclei, resulting in a posterior canal pre- associated with tonic downgaze early in life.29-38 Children dominance and increased downward tonus to both eyes. with myelomeningocele not only have hydrocephalus but This downward tonus must be overcome by fixational in- also frequently have an associated Chiari II malforma- nervation (Figure 6). Since the inferior rectus muscles re- tion.35,36 Since prenuclear input to the vestibular system tain their vertical field of action in adduction while the su- from the vestibulocerebellum is primarily inhibitory, bi- perior oblique muscles have minimal vertical action in lateral compression of or injury to those vestibulocerebel- abduction, this downgaze predominance would produce lar pathways activating the anterior canals would disin- a relative overdepression of the adducting eye in lateral gaze hibit the posterior canals and increase extraocular muscle (Figure 7). Activation of both superior oblique muscles tonus in their target muscles. produces bilateral intorsion in the primary position and an Previous investigators35-40 have speculated that bi- A pattern due to the tertiary abducting action of the supe- lateral superior oblique muscle overaction may be su- rior oblique muscles in downgaze. In addition, binocular pranuclear or prenuclear in nature, citing the frequency intorsion rotates the inferior rectus insertions laterally and with which it accompanies defective upgaze. Biglan37,38 reduces the adducting action of the inferior rectus muscles attributed the overacting superior oblique muscles, A pat- in downgaze. tern, and chronic downward deviations of the eyes in chil- The vestibuloocular pathways pass through the pos- dren with myelomeningocele to defects in the vertical gaze terior fossa and are susceptible to injury when structural pathways producing either a failure to inhibit the down- abnormalities involve the brainstem or the cerebellum. In gaze pathways or excessive stimulation of downward gaze. children with hydrocephalus and myelomeningocele, the Acute comitant esotropia caused by neurologic disease constellation of A-pattern strabismus, bilateral superior ob- such as hydrocephalus or Chiari malformation is often lique muscle overaction, and bilateral intorsion is often associated with bilateral superior oblique muscle overaction.39 Although orbital anatomical factors have also been implicated as a cause of superior oblique muscle 1,29 Right Labyrinth Vestibular Innervation Left Labyrinth overaction in hydrocephalus, the high frequency of PC PC A structural abnormalities within the posterior fossa led Hamed35,36 and colleagues to propose that superior ob- HC HC lique muscle overaction and alternating skew deviation AC AC in lateral gaze may share a common neuroanatomical sub- 41 Vestibular and Fixational Innervation strate. Recently, Hoyt has observed that premature in- PC PC fants with periventricular leukomalacia or intraventricu- B lar hemorrhage may initially manifest a tonic downgaze HC HC that evolves into an A-pattern esotropia and bilateral su- AC AC perior oblique muscle overaction.

INFERIOR OBLIQUE Figure 6. Superior oblique muscle overaction. A, Vestibular innervation. A central vestibular tonus imbalance corresponding to bilateral posterior MUSCLE OVERACTION canal predominance would produce tonic downgaze, divergence, and AND V-PATTERN STRABISMUS intorsion of the eyes if unopposed by fixational innervation. B, Vestibular IN CONGENITAL ESOTROPIA plus fixational innervation. Fixational innervation, which conforms to the Hering law, recruits bilateral innervation to the superior rectus and inferior Clinical observations and eye movement recordings have oblique muscles to negate the vertical component of the downward tonus bias. Fixational innervation allows a disconjugate intorsional bias to persist. documented abnormal ocular responses to vestibular PC indicates posterior canal; HC, horizontal canal; and AC, anterior canal. stimulation in children with strabismus.42-45 Gait and pos-

Figure 7. Superior oblique muscle overaction. The observed eye movements in different fields of gaze are a summation of fixational innervation that conforms to Hering’s law, and an underlying central vestibular imbalance that does not. All 4 depressors are receiving excessive vestibular innervation. Since the vertical action of the superior oblique muscles is maximal in adduction, the adducting eye exhibits a downshoot in adduction relative to the abducting eye. The tertiary abducting effects of the overacting superior oblique muscles are maximized by vestibular innervation in downgaze and minimized by fixational intervation in upgaze, producing an A pattern.

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 tion. The “neurologic lesion” that induces this central ves- Right Labyrinth Vestibular Innervation Left Labyrinth tibular imbalance is loss of binocular visual input. PC PC A PRIMARY OBLIQUE HC HC MUSCLE OVERACTION AC AC AND HERING’S LAW

Vestibular and Fixational Innervation Primary oblique muscle overaction appears to defy Heri- 56 PC B PC ng’s law, which dictates that, in any volitional conjugate movement, both eyes receive equal innervation. As HC HC summarized by Bielschowsky, “all of the muscles of both AC AC eyes always participate in each movement; one half ex- periences an increase in tonus and the other half a de- 57(p178) Figure 8. Primary inferior oblique muscle overaction. A, Visuovestibular crease.” This control system optimizes binocular innervation. Failure to develop normal binocular vision is associated with vision in all positions of gaze.56-58 Although Hering’s law increased upward tonus to the eyes, perhaps through reduced anterior canal requires that the ocular motor system synthesize a con- inhibition from the cerebellar flocculi. A central vestibular tonus imbalance corresponding to bilateral anterior canal predominance would produce tonic jugate signal to the motor neurons involved in the ex- upgaze, horizontal divergence, and extorsion of the eyes if unopposed by ecution of any ocular movement, it should be evident from fixational innervation. B, Visuovestibular plus fixational innervation. Fixational the previous discussion that equal innervation to any set innervation recruits equal innervation from the inferior rectus and superior of vertical yoke muscles would produce dissociated move- oblique muscles to negate the vertical component of the upgaze bias, and allows the disconjugate extorsional bias to persist. PC indicates posterior ments of the 2 eyes. To execute conjugate vertical eye canal; HC, horizontal canal; and AC, anterior canal. movements, the extraocular muscles of both eyes must receive appropriate innervation to move the eyes equally rather than receiving equal innervation. tural control have also been studied in children with dif- Hering56 made reference only to voluntary eye move- ferent kinds of strabismus, and a defect of postural sta- ments as conforming to his law of equal innervation. Since bility has been demonstrated in esotropic but not exotropic the semicircular canals and their corresponding oto- children.46,47 The high prevalence of incoordination and lithic pathways segregate innervation to each set of yoke balance disorders in children with “isolated” congenital muscles, it is not surprising that dissociated eye move- esotropia also supports the notion that early loss of single ments of central origin are generally associated with ves- binocular vision associated with congenital esotropia may tibular disease. Paradoxically, these dissociated move- affect central vestibular tone.47 ments may reflect the fact that the vertical yoked muscles Humans display an inherent upward tonus predomi- receive roughly equal innervation rather than the nec- nance of the eyes, which correlates with anatomical dif- essary innervation to rotate the eyes equally in one plane. ferences in the orientation of the anterior and posterior Our model of primary oblique muscle overaction as canals.28 This inherent up-down asymmetry in central a pitch plane imbalance predicts that oblique muscles over- pathways may explain why vertical vestibular optoki- act bilaterally in conjunction with rather than relative to their netic responses normally favor upward rather than down- yoke vertical rectus muscles. In primary gaze, the torsional ward slow phases.48-51 It may also explain why a slight action of the overacting oblique muscles predominates in downbeat nystagmus may be seen in individuals attempt- both eyes, producing the bilateral extorsion observed in pri- ing to fixate an imaginary target in darkness28,52 and why mary inferior oblique muscle overaction and the bilateral a hyperphoria of the adducting eye can often be elicited intorsion observed in primary superior oblique muscle over- in individuals fixating in lateral upgaze with a Maddox action. When both sets of elevators or depressors receive rod covering one eye.53 The development of single bin- excessive central vestibular innervation, adduction of ei- ocular vision serves to increase downward tonus to the ther eye produces excessive vertical excursion of the ad- extraocular muscles and hold this inherent upward bias ducting eye as it moves into the vertical field of action of in check. Conversely, the disruption of single binocular the overacting oblique muscle (Figure 7). In this context, vision associated with congenital esotropia reduces down- an upward tonus imbalance to both eyes manifests as bi- ward tonus to the extraocular muscles, perhaps by dis- lateral overelevation of the adducting eye, and a down- rupting maturation of inhibitory pathways from the cer- ward tonus imbalance manifests as bilateral overdepres- ebellar flocculi to the anterior canals. The resulting sion of the adducting eye. Volitional gaze out of the vertical anterior canal predominance would increase upward to- field of action of the overacting yoke muscles recruits physi- nus in the extraocular muscles and predispose to bilat- ologic innervation to counterbalance the vertical tonus im- eral inferior oblique muscle overaction (Figure 8). balance, while gaze into the vertical field of action of the Prolonged occlusion of one eye can also induce in- overacting yoke muscles allows this underlying tonus im- ferior oblique muscle overaction in nonstrabismic hu- balance to predominate, producing the A and V patterns mans with normal stereopsis,54,55 suggesting that either observed clinically (Figure 7). The ocular torsion pro- prolonged interruption or early loss of single binocular duced by primary oblique muscle overaction also initiates vision may also be registered as forward pitch (ie, away a cascade of secondary mechanical events, including rota- from the light). The retention of this primitive vision- tional displacement of the rectus muscle insertions, ob- dependent tonus mechanism in humans would explain lique muscle length adaptation, and mechanical tighten- why poor sensory fusion leads to inferior oblique muscle ing of the oblique muscles, as detailed elegantly by Guyton overaction rather than superior oblique muscle overac- and Weingarten.5 These peripheral responses augment the

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©2001 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/30/2021 overelevation or overdepression of the adducting eye and nystagmus might be similarly driven by a central vestibu- the corresponding A and V pattern observed clinically. lar tonus imbalance in the yaw (axial) plane. This neurologic model would also explain why pri- NONNEUROLOGIC CAUSES OF OBLIQUE mary oblique muscle overaction is usually associated with MUSCLE OVERACTION a negative Bielschowsky head-tilt test.1,59 A head tilt to either side recruits ipsilateral otolithic innervation to stimu- Most of the mechanisms invoked to explain the exist- late 1 of the 2 overacting vertical muscles in each eye while ence of A and V patterns with oblique muscle overac- inhibiting the other. The net result for each eye is a mini- tion have described orbital anatomical abnormalities that mal change in vertical tonus in the primary position. How- could account for the abnormal movements on a biome- ever, this model would predict that pitching the head for- chanical basis.64-75 It is beyond the scope of this article ward and backward (ie, a vertical head-tilt test) would to review and critique all of them. In some patients, neu- superimpose a physiologic tonus imbalance on the under- rologic and anatomical causes of oblique muscle over- lying central vestibular tonus imbalance in the pitch plane action may coexist. Children with hydrocephalus and and thereby alter the amplitudes of an existing A or V pat- tonic downgaze, for example, may also have frontal boss- tern and the amplitudes of the associated hyperdevia- ing with anterior displacement of the trochlea, which can tions in lateral gaze. Accordingly, the clinical practice of increase tension on the superior oblique muscles and pro- pitching the patient’s head forward and backward duce a mechanical superior oblique muscle overac- to obtain strabismus field measurements in upgaze and tion.1,29 Recently, Clark76 and Demer77 and their col- downgaze would augment an existing A or V pattern. leagues have used magnetic resonance imaging to demonstrate that heterotopia of extraocular muscle pul- OBLIQUE MUSCLE OVERACTION AND leys within the orbits can also produce overelevation or DISSOCIATED VERTICAL DIVERGENCE overdepression of the adducting eye and simulate ob- Dissociated vertical divergence may coexist with primary lique muscle overaction. Orbital pulley malposition may oblique muscle overaction.60 Dissociated vertical divergence account for some children who have superior oblique has been attributed to a central vestibular tonus imbalance muscle overaction and A-pattern strabismus in the in the roll plane induced by fluctuations of binocular visual absence of neurologic disease. Since orbital anatomical input.60,61 This hypothesis is based on physiologic studies60,61 abnormalities can produce excessive vertical excursion in fish that show that unequal visual input to the 2 eyes in- of one or both eyes in the field of action of the oblique duces a reflex body tilt in the roll (frontal) plane toward the muscles, many authorities advocate use of the descrip- side with greater visual input. This dorsal light reflex is a bal- tive terms overelevation and overdepression of the adduct- ancing movement that uses light from the sky as a visual ing eye rather than the diagnostic term overaction of the reference to maintain vertical orientation by equalizing lu- oblique muscles to characterize these movements.1,76 minance input to the 2 laterally placed eyes. In a vertically restrained fish, unequal visual input induces a vertical di- CONCLUSIONS vergence of the eyes, with depression of the eye that has greater visual input and elevation of the eye that has lesser Lower lateral-eyed animals use light from the sky above visual input. This vertical divergence of the eyes corresponds and gravity from the earth below as major sources of sen- to the dissociated vertical divergence seen in humans who sory input to neuronal tonus pools within the central ves- fail to develop single binocular vision secondary to early- tibular system. These neuronal tonus pools calibrate ex- onset strabismus. traocular muscle and postural tonus to maintain vertical In humans with dissociated vertical divergence, sup- orientation. In lower animals, oblique muscle tonus is pression or mechanical occlusion of one eye increases up- determined by luminance and gravitational input in the ward tonus to the extraocular muscles of that eye and pitch plane. In humans, the brain leverages visual and downward tonus to the extraocular muscles of the oppo- gravistatic sensory input to calibrate extraocular muscle site eye.60,61 Simultaneous recruitment of central vestibu- tonus in the pitch plane. Early loss of single binocular lar innervation to both elevators in the visually deprived vision is treated by the central vestibular system as for- eye has been invoked to explain the spontaneous overel- ward pitch, necessitating increased upward tonus to the evation in adduction that can be observed with dissoci- extraocular muscles and manifesting as primary ob- ated vertical divergence, when no V pattern or baseline ex- lique muscle overaction. Neurologic lesions within the torsion is present.60 The observation that decreased visual posterior fossa can produce the opposite central input increases upward tonus to one eye (in the case of vestibular imbalance, in which a backward pitch evokes dissociated vertical divergence) and to both eyes (in the increased downward tonus to the extraocular muscles and case of inferior oblique muscle overaction) attests to the produces primary superior oblique muscle overaction. retention of primitive vision-induced tonus mecha- This duality reflects an ancestral bimodal tuning of cen- nisms62,63 in humans, and to the atavistic resurgence of these tral vestibular output to the extraocular muscles that is primitive subcortical reflexes when strabismus precludes subordinate to binocular vision in humans. the development of binocular vision. Our neurologic model of primary oblique muscle overaction as a central vestibu- Accepted for publication January 12, 2001. lar tonus imbalance in the pitch plane complements the This study was supported in part by a grant from Re- recently proposed theory of dissociated vertical diver- search to Prevent Blindness Inc, New York, NY. Dr Donahue gence as a central vestibular tonus imbalance in the roll is a recipient of a career development award from Research (frontal) plane, and begs the question of whether latent to Prevent Blindness Inc.

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