skew deviation revisited

SURVEY OF OPHTHALMOLOGY VOLUME 51 � NUMBER 2 � MARCH–APRIL 2006

MAJOR REVIEW

Skew Deviation RevisitedMichael C. Brodsky, MD,1 Sean P. Donahue, MD, PhD,2 Michael Vaphiades, DO,3

and Thomas Brandt, MD4

1Departments of Ophthalmology and Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA;2Department of Ophthalmology and Visual Sciences, Pediatrics, and Neurology, Vanderbilt University School of Medicine,Nashville, Tennessee, USA; 3Department of Ophthalmology, University of Alabama, Birmingham, Alabama, USA;and 4Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians University, Munich, Germany

Abstract. Skew deviation is a vertical misalignment of the eyes caused by damage to prenuclearvestibular input to ocular motor nuclei. The resultant vertical ocular deviation is relatively comitant innature, and is usually seen in the context of brainstem or cerebellar injury from stroke, multiplesclerosis, or trauma. Skew deviation is usually accompanied by binocular torsion, torticollis, and a tilt inthe subjective visual vertical. This constellation of findings has been termed the ocular tilt reaction. Inthe past two decades, a clinical localizing value for skew deviation has been assigned, and a cogentvestibular mechanism for comitant and incomitant variants of skew deviation has been proposed. Ourunderstanding of skew deviation as a manifestation of central otolithic dysfunction in different planesof three-dimensional space is evolving. The similar spectrum of vertical ocular deviations arising inpatients with congenital strabismus may further expand the nosology of skew deviation to includevergence abnormalities caused by the effects of early binocular visual imbalance on the developingvisual system. (Surv Ophthalmol 51:105--128, 2006. � 2006 Elsevier Inc. All rights reserved.)

Key words. ocular tilt reaction � skew deviation � vergence abnormalities � vision � visualimbalance

I. Introduction

According to Stedman’s Medical Dictionary,184 skewdeviation refers to ‘‘a hypertropia in which the eyesmove in opposite directions equally; an acquiredhypertropia, often fairly comitant, not fitting thecharacteristic pattern of trochlear nerve damage orof ocular muscle abnormality; often due to a brain-stem or cerebellar lesion.’’ For many years, skewdeviation was held to be a nonlocalizing sign anda diagnosis of exclusion.84,112 Skew deviation usuallypresents as a comitant hypertropia in a patient withposterior fossa disease.44 In rare cases, however, itcan increase in one horizontal direction of gaze,

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� 2006 by Elsevier Inc.All rights reserved.

manifest as a paroxysmal hyperdeviation of one eye,or produce alternating hyperdeviations in gaze toeither side.44,181 The purpose of this review is toacquaint the reader with advances in our under-standing of skew deviation as a clinical diagnosticentity, in terms of its clinical range of presentation,its underlying pathophysiology, and its clinicallocalizing value.

II. History

Skew deviation was first recognized experimentallyin animals by the experimental physiologist Francois

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106 Surv Ophthalmol 51 (2) March--April 2006 BRODSKY ET AL

Magendie in 1824.131 The following year, HenryHertwig described skew deviation in a cat followingan incision through the cerebellum into the me-dulla.100,182 In 1904, Stewart and Holmes observedskew deviation in a man with a cerebellar tumor, andin other patients following craniotomies for cerebel-lar tumors.186 During World War I, Gordon Holmesdocumented skew deviation in 5 of 40 patients whohad sustained cerebellar gunshot injuries.104 In1921, Holmes theorized that skew deviation wasobserved only in patients with extensive cerebellarlesions and otherwise had no localizing value.103 In1925, Potzl and Sittig described skew deviation ina patient with a lesion in the ventral caudal portionof the vestibular complex and referred to it as theHertwig-Magendiescher Schielstellung.155 In 1926,Brain reported skew deviation with head tilting ina patient with chronic otitis media.19

In his 1956 book Neurology of the Eye Muscles, Coganobserved that skew deviation was common withlesions of the cerebellum (tumors, abscesses, andvascular and post-surgical lesions) and in lesions ofthe vestibular nuclei, nerve, and end organ.44 Heobserved that the eye on the side of the lesion wasdirected downward and the opposite eye upward.Cogan attributed skew deviation to a lesion in-volving the vestibulo-ocular pathways but empha-sized that, ‘‘evidence is scanty for localization, otherthan the general region of the posterior fossa.’’44 In1961, Smith et al noted that skew deviation mayaccompany internuclear ophthalmoplegia, in whichcase the higher eye is usually on the side of thelesion.181,182 They considered skew deviation to fallinto three clinical subtypes: comitant, laterally comitant(actually an incomitant skew deviation in which thehyperdeviation increases in one lateral field ofgaze), and a laterally alternating skew deviation inwhich there is a hyperdeviation of the abducting eyein each lateral field of gaze.181

In 1975, Keane described 100 patients with skewdeviation. Most patients had unilateral lesionsinvolving the pons, but lesions within the medullaand midbrain were also common.116 As in previousreports, the hypotropic eye tended to be on the sideof the lesion except in cases of unilateral internu-clear ophthalmoplegia (INO), where the higher eyewas on the side of the lesion. Keane attributed skewdeviation to a lesion involving the otolithic path-ways, which can be injured at any site as they ascendwithin the brainstem.115 He also noted that thenatural history of skew deviation tended towardspontaneous resolution.

The role of the vestibular system and brainstem inthe control of head-eye posture in the roll plane hasbeen recognized for almost a century.19,89,102,132,143

In 1975, Westheimer and Blair provided what was to

be a unifying explanation for skew deviation whenthey electrically stimulated the brainstem tegmen-tum of alert monkeys and noted a vertical deviation(skew deviation) and rotation (cyclotorsion) of theeyes conjugately and equally in the direction of theinfraducted eye. They assigned the name ocular tiltreaction and stated that clinical skew deviation(Hertwig-Magendie phenomenon) and the oculartilt reaction were identical phenomena.215,216 Inretrospect, the ocular tilt reaction had been pro-duced by Muskins in 1914,143 documented indifferent species by Magnus et al,132 and describedlater by investigators in the scientific201 and veter-inary literature.171,214 These reports suggested thatwhen skew deviation is due to a lesion in the rostralend of the medial longitudinal fasciculus (MLF),the ipsilateral eye may be higher.133

In 1977, Rabinovitch et al provided the firstclinically recognized report of a human ocular tiltreaction.156 Two years later, Halmagyi et al docu-mented an ocular tilt reaction in a woman followingunilateral stapedectomy.91 They correctly attributedit to a compensatory response that followed unilateralinjury to the vestibular pathway that arises in the utricleof the dependent ear and projected to the oppositebrainstem. Numerous descriptions of the humanocular tilt reaction (Fig. 1) have since followed, and

Fig. 1. Ocular tilt reaction. Top Left: Facial photographshows mild left head tilt. Top Right: Fundus photographsshow intorsion of the right eye and extorsion of the lefteye. Bottom left: MR imaging shows focal lesion involving theright medial longitudinal fasciculus. Bottom right : Diagramdepicting causative lesion. (Reprinted from Vaphiades205

with permission of Wisconsin University Press.)

SKEW DEVIATION REVISITED

neuroimaging has provided exquisite anatomicalconfirmation of the site of injury.

In summary, skew deviation was, until recently,considered to be a vertical misalignment of the eyesthat was uncommon, usually seen in neurologicallydebilitated patients, and nonspecifically localizingexcept to the posterior fossa. In the past twodecades, however, dedicated studies have shownthat skew deviation is common, that its causativelesion can be focal, that it can be seen in otherwiseintact ambulatory patients, and that it occurs in themore general context of an ocular tilt reaction.

III. Causes

Skew deviation can result from any acute injurywithin the posterior fossa (ischemic infarction,multiple sclerosis, tumor, trauma, abscess, hemor-rhage, syringobulbia, or neurosurgical proce-dures).12,44,116,181 The majority of cases are seen inassociation with brainstem stroke.61,181 A lesionneed not involve the brainstem or cerebellum tocause skew deviation, however. Acute unilateralvestibular lesions can also cause skew devia-tion.61,63,90,91,113,116,167,219

Numerous rarer causes of skew deviation havebeen documented.116 Several reports have docu-mented skew deviation in patients with increasedintracranial pressure.9,76,134 Skew deviation mayaccompany paroxysmal hemiparesis of child-hood.66,97 Cogan described skew deviation in onepatient with Arnold-Chiari malformation and in twoindividuals with platybasia.45 Galimberti et al de-scribed paroxymal epileptic skew deviation ina patient who was otherwise neurologically intact.80

They attributed it to ictal activation of the vestibularcortex with secondary activation of descendingprojections to the vestibular nuclei. Suzuki et aldescribed three patients who developed diplopiaand skew deviation following cardiac catheteriza-tion.192 Negative neuroimaging studies were sugges-tive of minor ischemic damage to the brainstem.Yokota et al described skew deviation with alternat-ing hypertropia of the abducting eye in threepatients with Creutzfelt-Jakob disease.222

Ragge et al described an ocular tilt reaction in a5-year-old girl with a mesencephalic lesion andpolyarteritis nodosa.158 Skew deviation has also beenreported in multifocal encephalopathy,17 CNS cryp-tococcus,56 hepatic coma,74 following Mandraxoverdosage,151 from a unilateral cochleo-vestibulardamage due to herpes zoster oticus,206 in paraneo-plastic encephalomyelitis associated with benignovarian teratoma,196 and in adult Leigh disease.93

Chueng et al diagnosed skew deviation on prenatal

MR images in a fetus with association with glioblas-toma involving the brainstem.43

IV. Evolutionary Underpinnings

Classical skew deviation occurs in the context ofan ocular tilt reaction, in which bilateral otolithicinput is leveraged by the central vestibular system tomodulate extraocular muscle and postural tonus inthe roll plane (the plane in which the head or bodytilts from side to side).136,176,223 The ocular tiltreaction in humans is probably a vestigial remnantof the primitive otolithic righting reflex that isreleased only under pathological conditions.136 Therelative preponderance of the individual compo-nents of head tilt, ocular torsion, and vertical eyemovements, is dependent upon species differencesin the range of head movement and the orientationof the optic axes.136 The head tilt component ismost prominent in animals with little eye move-ments, such as owls.136,185 The skew eye movement ismost prominent in animals with mobile, laterallyplaced eyes, but no head movement in roll, such asfish.136 In these lateral-eyed animals, a body tiltaround the long axis produces a rotation of the eyesthat is purely vertical.11,204 In the fish or a rabbit, forexample, a rightward body tilt along its long axiscauses the right eye to be lower in space than the lefteye, which results in a compensatory skew deviationwith upward rotation of the lowermost right eye anddownward rotation of the uppermost left eye.89 Thetorsional eye movement (known as the ocularcounter roll) is most prominent in frontal-eyedanimals such as cat and humans.136

In humans, the head tilt is the major componentof the physiological ocular tilt reaction (Fig. 2).Thus, motorcycle riders or skiers reflexively reorient

Fig. 2. Figure showing physiologic and pathologic skewdeviation. In the physiologic ocular tilt reaction (left), thecompensatory head tilt predominates, with only a smallskew deviation or static ocular counterroll. In thepathologic ocular tilt reaction (right), all three compo-nents of the ocular tilt reaction are present. (Reprintedfrom Brodsky37 with permission of the American MedicalAssociation.)

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the head back to the gravitational vertical duringsharp turns that induce body tilt (Fig. 3). Inhumans, the gain of the static ocular counterroll(the torsional component of the ocular tilt reaction)is only about 0.1, as the need for a compensatory eyetorsion reflex is reduced by a compensatory head tiltreflex.49,59 Pansell et al found that humans showa transient skew deviation at the initiation of a headtilt that is opposite to the final skew deviation (i.e.,right hypertropia during the initiation of a left headtilt).152 The subsequent dynamic skew deviation(left hypertropia during leftward tilt) is robustduring whole body oscillations around the naso-occipital axis,113 but only a trace static skew de-viation can be detected during static head or bodytilt (on the order of 0.3 degrees).15,119,188 In thenormal individual, for example, prism alternatecover testing during head tilt will not evokea measurable hyperphoria.39 Given the magnitudeof asymmetrical otolithic innervation evoked bya static head tilt, the virtual absence of a physiologicskew deviation must be taken as evidence that thefrontal-eyed system has evolved to inhibit this reflexin the interest of single binocular vision.

V. Neuroanatomy

The primary functions of the vestibulo-ocularsystem are to maintain eye position and stabilize

Fig. 3. Physiologic ocular tilt reaction in a motorcyclerider when tilted in the roll plane. (Reprinted withpermission from Bike magazine, p 74, August 2001.)

fixation during head movements. The labyrinthinereceptors transduce the forces associated with headacceleration into a biological signal.136 The semi-circular canals sense angular acceleration, while theotoliths (the saccules and utricles) respond to linearacceleration (i.e., head translation and the mostpervasive form of linear acceleration, the pull ofgravity).136 In lateral-eyed animals and in humans,the semicircular canals are roughly aligned with thelong axis of the extraocular muscles (Fig. 4).176

When the head is rotated in a particular plane, thesemicircular canal that lies in the plane of rotationdetects acceleration and sends excitatory innerva-tion to its corresponding extraocular muscles. Inaddition to serving to stabilize gaze, the vestibulo-ocular pathways also provide ascending input tothe thalamo-cortical projections of spatial percep-tion as well as descending input to vestibulo-spinal

Fig. 4. Figure showing close anatomical correspondencebetween semicircular canals and extraocular muscles inman. (Reprinted from Simpson and Graf176 with permis-sion of the New York Academy of Sciences.)

SKEW DEVIATION REVISITED 109

projections for adjustments of head and bodyposture (vestibulo-spinal reflexes).21

The ocular tilt reaction and its associated skewdeviation represent a fundamental pattern of eye-head coordination in the roll plane.29,61,64 Theotolith-ocular response to rotation is impaired inpatients with skew deviations due to brainstemlesions.198 The ocular tilt reaction can be observednot only in patients with peripheral vestibulardysfunction but also in those with lesions of thegraviceptive pathways, which run from the medullato the mesencephalon.21,24,26--29,60,63,64,89 Unilateraldysfunction due to either a peripheral or centralvestibular pathway lesion results in a clinical syn-drome characterized by a combination of phenom-ena involving perceptual (tilt in the subjective visualvertical) ocular motor (ocular torsion, skew de-viation), and postural (head tilt) manifestations,which together constitute the ocular tilt reaction.29

Consequently, skew deviation is usually associatedwith lesions in the posterior fossa, particularly thoseinvolving the brainstem tegmentum from the di-encephalon to the medulla.26 It is also seen clinicallyin lesions of the utricle or vestibular nerve.28

Each anterior semicircular canal provides excit-atory input to the ipsilateral superior rectusand contralateral inferior oblique muscles(Fig. 5).48,124,190 Each posterior semicircular canalsystem provides excitatory innervation to the ipsilat-eral superior oblique and the contralateral inferiorrectus muscles while inhibiting the ipsilateral in-ferior oblique and the contralateral superior rectusmuscles (Fig. 5). Like their target extraocularmuscles, the semicircular canals have a push--pull(yoke) relationship, so that activation of one canalinhibits the antagonist canal.48,124,190 Thus, injury toor inhibition of an anterior canal pathway causesfunctional activation of the ipsilateral posteriorcanal pathway.24

Fig. 5. Vesitibulo-ocular connections showing showingextraocular muscles activated by individual semicircularcanals (I 5 ipsilateral; c 5 contralateral). Centralconnections through the vestibular nucleus are notshown.

In addition to the semicircular canals, eachlabyrinth contains otolithic sensors consisting ofthe utricle and the saccule.25,124 Although someoverlap exists,170 the semicircular canals respond toangular acceleration and produce dynamic vestibulo-ocular movements (phasic ocular deviations andnystagmus), whereas the parallel otolithic systemresponds to linear acceleration and is sensitive tochanges in static head position.25,63,82,124,197 Theotolithic pathways are not as well studied, but arebelieved to have similar projections to the corre-sponding canal pathways.124 Static eye positions, theocular counterroll, sensory input for subjectivevertical orientation, and conjugated vertical devia-tions such as skew deviation are mediated mainly bythe utricles,25 although recent evidence suggests thata semicircular canal imbalance may contribute to thecyclotropia in unilateral vestibular patients.170 Grav-iceptive input from the otoliths converges with thatfrom the vertical semicircular canals at the level of thevestibular nuclei.5,8,20,85,86,172 Mathematical modelsof biological systems have recently been applied tothe tonic and dynamic aspects of vestibulo-ocularfunction.20,81,82

VI. Symptomatology

Unilateral lesions or stimulation of the utricles orvertical semicircular canal pathways cause an imbal-ance of vestibular tone in the roll plane, whichresults either in a complete (tonic or paroxysmal)ocular tilt reaction or in single components of theocular tilt reaction such as cyclorotation of the eyesor skew deviation.64

In the pathological ocular tilt reaction, the eyes,head, and body are continuously adjusted to whatthe central nervous system erroneously computes asbeing vertical.29 This compensation causes a synki-netic rotation of the eyes, interpupillary axis, andhead in the roll plane to realign with the perceivedvertical (Fig. 6).27 When the patient’s head is movedto the true vertical, the patient may perceive it astilted in the opposite direction.29 However, theocular torsion and head tilt are easily overlookedunless specifically sought.

The fundamental association of skew deviationwith ocular torsion and torticollis was overlooked formany years.25,79 Although Trobe202 found no cyclo-deviation in patients with skew deviation,79 theexclusion of patients with positive head tilt tests inthis study may have foreordained that result.115 Thisclassic triad of findings is absent in some pa-tients.23,90 The ocular tilt reaction rarely causessymptoms by itself; it does not cause disequilibriumand may only induce vertical diplopia.90


A skew deviation is usually comitant in differentpositions of gaze but can occasionally show hori-zontal incomitance and skew vertically in one lateralfield of gaze.44,182 The Bielschowsky Head Tilt Test isgenerally negative in comitant skew deviation, butcan be positive in incomitant skew deviation andthereby simulate isolated oblique muscle pare-sis.7,165 Skew deviation may be associated witha torsional jerk nystagmus. When this occurs, theupper poles of the eyes tend to beat away from theside of a medullary lesion and toward the side ofa midbrain lesion.14,63,88,92,128 The ocular tilt re-action and its associated skew deviation tend torecover spontaneously over weeks to months.18,115

Fig. 6. Graviceptive pathways from the otoliths andvertical semicircular canals mediating the vestibularreactions in the roll plane. The projections from theotoliths and the vertical semicircular canals to the ocularmotor nuclei (trochlear nucleus IV, oculomotor nucleusIII, abducens nucleus VI), and the supranuclear centers ofthe interstitial nucleus of Cajal (INC), and the rostralinterstitial nucleus of the medial longitudinal fasciculus(riMLF) are shown. They subserve vestibuloocular reflex(VOR) in three planes. The VOR is part of a morecomplex vestibular reaction that also involves vestibulo-spinal connections via the medial and lateral vestibulospi-nal tracts for head and body posture control. Note thatgraviceptive vestibular pathways for the roll plane cross atthe pontine level. Ocular tilt reaction is depictedschematically on the right in relation to the level of thelesion (i.e., ipsiversive with peripheral and pontomedul-lary lesions, and a contraversive with pontomesencephaliclesions). In vestibular thalamus lesions, the tilts of thesubjective visual vertical may be contraversive or ipsiver-sive. (Reprinted from Brandt and Dieterich25 withpermission of Wiley.)

VII. Subjective Visual Tilt

The ocular tilt reaction is associated with a tilt inthe subjective visual vertical. This term is oftenconfusing to the uninitiated reader because thepatient remains asymptomatic, and even whenasked, states that his or her surroundings do notappear tilted. However, the patient’s subjectivevisual world (which he or she perceives as upright)is indeed tilted with respect to the true earthvertical. In this sense, the patient can be said toexperience a subjective visual tilt. It is as if you tilteda television set to one side and then imagined whatthe television characters perceived. Because theirentire visual world is tilted together, they would tendto perceive themselves and their surroundings asnormal. Despite their tilt, all visual cues would tellthem that their internal world corresponds to trueearth coordinates.

Such is the case in the patient with an ocular tiltreaction. In normal structured environments, ourlife-long experience persuades us as to horizontaland vertical orientations of rooms, houses, trees, andso on. For this reason, in the ocular tilt reaction theexaminer can only determine the perceived tilt ifa straight line is adjusted to ‘‘vertical’’ in darkness, orin surroundings which provide no cue for truevertical. A patient with a left ocular tilt reaction, forexample, will experience a tilt in the subjective visualvertical that is counterclockwise (from the patient’sperspective) because diminished input from the leftutricle causes the brain to perceive the head ashaving been tilted to the right (Fig. 6). Underclinical conditions the patient’s head reflexivelyrotates to align with the internally perceived vertical.Under testing conditions, the patient would adjusta vertical line in a counterclockwise direction until itcorresponds to this altered internal sense of vertical.The subjective visual tilt can be identified usingDouble Maddox rods209 or by placing the patient’shead in a half-spherical dome and instructing him orher to adjust a potentiometer to vertically situate anobserved line.29 Either test must be performedseparately with each eye occluded, and severalmeasurements must be averaged. A tilt in thesubjective visual vertical can also be suspected byobserving the slant of personal photographs beingtaken or by observing the slant of handwriting withthe eyes closed.29 In the ocular tilt reaction, theobserved errors in tilt orientation are always in thesame direction as the observed ocular torsion.

The ocular tilt reaction strives to realign the eyesand head to a tilted position that the brainerroneously computes as vertical (note that theensuing cyclorotation of the eyes counterrotate thetilted subjective visual vertical back to true vertical


(Fig. 6). With this disturbance, the patient’s sub-jective sense of true vertical is rotated in the samedirection as the ocular torsion, suggesting that thetilted perception of vertical provides the drivingforce for all components of the ocular tilt reaction,which strives to realign the eyes and body with theperceived vertical. This mechanism for torticollisdiffers from the more common contralateral headtilt in superior oblique palsy, which recruits otolithicinnervation to restore vertical ocular alignment, allthree components of the ocular tilt reaction realignthe eyes and head to the tilted perception of true vertical.In the ocular tilt reaction, correction of the verticalocular misalignment by prisms or by strabismussurgery should not eliminate the torticollis.

Following vestibular stimulation, some patientswith skew deviation may experience a room-tiltillusion in which a room is perceived to be tilted onits side or even upside down.199 Slavin andLoPinto178 described an exceptional patient whoexperienced subjective visual tilt. Examination dis-closed a bilateral rightward cyclodeviation anda corresponding tilt in the subjective visual vertical,but no hypertropia or head tilt in this patient whohad compression of the left lateral medulla bya dolichoectatic carotid artery. These findings wereconsistent with a partial ocular tilt reaction (withoutskew deviation). Conversely, Strupp et al recentlydescribed a patient with unilateral anterior semi-circular canal dehiscence who experienced oculartorsion but no displacement of the subjective visualvertical, suggesting that subjective visual tilt specif-ically requires asymmetrical otolithic input.189

To examine the effect of unilateral brainsteminjury on perception of vertical in the roll plane,Dieterich and Brandt examined ocular torsion andtilt in the subjective visual vertical in 111 patientswith acute vascular brainstem stroke.61 Of thesepatients, 104 (94%) showed a direction specificpathologic tilt of the static subjective visual vertical.Seventy-one of 86 patients (83%) exhibited a path-ological static ocular torsion of one (47%) or both(36%) eyes. The tilt in the subjective visual verticaland ocular torsion were generally in the samedirection. Caudal brainstem lesions caused ipsiver-sive tilts of the subjective visual vertical, whereasupper brainstem lesions caused contraversive tilts.Tilts in the subjective visual vertical were greatestwith mesodiencephalic lesions and with lateralmedullary lesions (i.e., Wallenberg syndrome). Themean tilt angle was 8.1 degrees, with a range of 2 to26 degrees. All lesions caudal to the upper ponscaused ipsiversive ocular torsion of one or both eyes,with concurrent ipsiversive tilts of the subjectivevisual vertical, whereas all lesions rostral to thispontine level cause contraversive tilts of ocular

torsion and the subjective visual vertical. Somepatients had significant tilts of the subjective visualvertical but no concurrent ocular torsion. Whenocular torsion was present, it was always accompa-nied by a tilt of the subjective visual vertical in thesame direction. The quantitative dissociation be-tween a tilt in the subjective visual vertical and thecorresponding ocular torsion shows that deviationsin the subjective visual vertical are not simply thesensory consequence of the rotation of the eye, butrepresent the perceptual correlate of a vestibulartone imbalance in the roll plane.61 Some patientswith brainstem injury can also experience brief,episodic tilting of the visual world as an apparentlyisolated phenomenon.163

In addition to brainstem injury, acute peripheralvestibular loss can also cause an ipsiversive tilt of thesubjective visual vertical and ocular torsion, asshown by Friedman following labyrinthectomy,75

and by Curthoys following unilateral vestibularneurectomy.52 Curthoys et al found a high correla-tion between the direction and magnitude ofchanges in ocular torsion and the subjective visualvertical one week after unilateral vestibular neurec-tomy in many patients,52 suggesting that peripherallesions cause a tilt of the subjective visual verticalwith an ocular torsion of similar magnitude while, incentral vestibular lesions, the magnitude of theeffect on these two parameters may differ, witha tendency of the subjective visual vertical to beaffected to a greater degree.

VIII. Localizing Value

To ascertain the localizing value of skew deviation,Brandt and Dieterich reviewed 155 patients with theclinical diagnosis of acute unilateral brainsteminfarction.26 Fifty-six (36%) of these patients dem-onstrated skew deviation. Skew deviation was alwaysassociated with ocular torsion, which affected botheyes in 50%, the lowermost eye in 31%, and theuppermost eye in 19%. The direction of the oculartorsion inevitably corresponded to the direction ofskew (i.e., intorsion of the right eye and/orextorsion of the left eye with a left hypotropia, andintorsion of the left eye and extorsion of the righteye with a right hypotropia). Skew deviation wasassociated with a complete ocular tilt reactiontoward the lowermost eye in 61%. In all cases,unilateral pontomedullary lesions induced ipsiver-sive skew deviations (toward the side of the lowereye) which were probably caused by injury to themedial or superior vestibular nucleus, while unilat-eral pontomesencephalic and mesodiencephaliclesions all caused contraversive skew deviations,probably from involvement of the interstitial


nucleus of Cajal in the rostral midbrain tegmentumor the medial longitudinal fasciculus along itspontomesencephalic route. These findings con-firmed that skew deviation usually occurs as a com-ponent of the ocular tilt reaction. It also identifiedthe localizing value of skew deviation in patientswith acute brainstem infarction. If the level ofbrainstem damage is known from the clinicalsyndrome, then skew deviation indicates the sideof the lesion. Conversely, if the side of the lesion isevident from the clinical syndrome, then the level ofthe brainstem injury is indicated by the direction ofskew, ipsiversive with caudal and contraversive withrostral brainstem lesions.26

From these studies,26 the following conclusionscan be drawn:

1. The clinical signs, both perceptual and motor,of a vestibular tone imbalance in the roll planeare ocular tilt reaction, ocular torsion, skewdeviation, and tilts of the perceived visualvertical.

2. Either a complete ocular tilt reaction (OTR) ora skew deviation (as one component of theocular tilt reaction) indicates a unilateral pe-ripheral deficit of otolith input or a unilaterallesion of graviceptive brainstem pathways fromthe vestibular nuclei (crossing the midline atthe pontine level) to the interstitial nucleus ofCajal in the rostral midbrain.

3. All tilt effects—perceptual, ocular motor, andpostural—are ipsiversive (ipsilateral eye under-most) with unilateral peripheral or pontome-dullary lesions below the crossing of thegraviceptive pathways.

4. All tilt effects are contraversive (contralateraleye undermost) with unilateral pontomesence-phalic brainstem lesions. Contraversive tilteffects indicate involvement of the mediallongitudinal fasciculus or the rostral midbrain(interstitial nucleus of Cajal).

IX. Sites of Injury

The ocular tilt reaction indicates a unilateralperipheral deficit of otolithic input or a unilaterallesion of graviceptive brainstem pathways from thevestibular nucleus (crossing midline at the pontinelevel) to the interstitial nucleus of Cajal in therostral midbrain.25 The resultant head tilt, torsion ofthe eyes, skew deviation, and tilt of the subjectivevisual vertical are the postural, ocular motor, andperceptual manifestations of a single lesion of thosevestibular pathways subserving the vestibulo-ocularreflex in the roll plane.25 Because these pathwaysare difficult to injure in isolation, lesions along each

site of the vestibulo-ocular pathways may be associ-ated with specific clinical disorders depending ontheir location which determine the contiguous areasof injury. Lesions causing the ocular tilt reaction canbe subdivided in to peripheral and central injuriesto the otolithic pathways.

A. PERIPHERAL INJURY TO OTOLITHIC

PATHWAYS

1. Utricle

In the cat, stimulation of one utricular nerveproduces conjugate ocular torsion and verticalskewing of the eyes.191 In humans, inadvertentdamage to one utricle52,90,91 or lesions of the humanlabyrinth91 and vestibular nerve produce a tonicipsiversive ocular tilt reaction.53 In rare patients withTullio phenomenon (sound-induced nystagmus),acoustic stimulation of one labyrinth can producea controversive ocular tilt reaction.31,54,65 Brandt etal described a sound-induced ocular tilt reaction(Tullio phenomenon) in a professional horn playerwho complained about distressing attacks of oscil-lopsia as well as postural imbalance elicited by loudsounds applied to the involved ear.31 Surgicalexploration of the middle ear revealed a subluxatedstapes footplate with the hypertrophic stapediusmuscle causing pathologically large amplitudemovements during the stapedius reflex, compress-ing the adjacent utricle.

2. Vestibular Nerve

A phasic (i.e., paroxysmal) contraversive OTR isproduced in the cat by electrical stimulation of oneutricular nerve.191 In humans, skew deviation canresult from chronic nonsuppurative otitis media,19

peripheral vestibular neurectomy, labyrinthectomy,stapedectomy complicated by an otolithic dysfunc-tion,89,92,166,209--211 vestibular neuritis,167,208,209 andvestibuloacoustic nerve surgery.161,209,219 In thissetting, skew deviation generally disappears withinseveral days while the conjugate cyclotorsion andtilting of the static visual vertical may persist for weeksto months.208,209 Skew deviation is also seen incochleo-vestibular loss (viral labyrinthitis),210 andvestibular neuritis.166,167 Tiliket et al induced a roomtilt illusion by vestibular stimulation in three patientswith skew deviations, suggesting that this symptomresults from a perceptual manifestation of a dynamicmismatch between the inappropriate otolith inputsand the correct visual inputs.199

B. CENTRAL INJURY TO OTOLITHIC PATHWAYS

1. Medulla

Clinical29 and experimental203 unilateral medullarylesions can produce a tonic ipsiversive OTR.142 Skew


deviation is a frequent accompaniment of Wallenberg(lateral medullary) syndrome.63,73,114,138,139,175,197 Pa-tients with Wallenberg syndrome present with ipsi-lateral impairment of pain and temperature sensationover the face, ipsiversive lateropulsion (a compellingsensation of being pulled toward the side of thelesion), skew deviation, saccadic eye movements thatare larger toward the side of the lesion (causingvertical saccades to have an oblique configuration),Horner syndrome, limb ataxia, and bulbar distur-bance causing dysarthria and dysphagia.13,33,197 Con-tralateral pain and temperature sensation is impairedover the limbs and trunk. Some patients experiencea room tilt illusion, in which the entire room is tiltedon its side or even upside down.33,105 The disorder isusually caused by occlusion of the intradural segmentof the ipsilateral vertebral artery, or occlusion of theperforating branches which supply the dorsolateralmedulla and cause injury to the vestibular nucleusor its cerebellar, semicircular canal, or otolithicconnections.

In patients with lateral medullary infarction, theocular torsion is usually unequal, with greaterextorsion of the ipsilateral eye than incyclotorsionof the contralateral eye.79,90 In a study of 36 patientswith Wallenberg syndrome, Dieterich and Brandt63

noted ipsiversive cyclorotation of one or both eyes inmost patients, especially extorsion of the eyeipsilateral to the brainstem lesion (suggesting anisolated lesion of posterior canal pathways) (Fig. 7).Only one third of patients had a complete ocular tiltreaction but all patients had a tilt of the subjectivevisual vertical.28,139 Torsional nystagmus is alsocommon in Wallenberg syndrome, with the upperpoles of the eyes beating away from the side of thelesion.33 In Wallenberg syndrome, the deviation inthe subjective visual vertical, lateropulsion of thebody, and cyclorotation of the eyes are the percep-tual, ocular motor, and postural consequences ofa common lesion of central vestibulo-ocular path-ways that subserve graviceptive tone in the rollplane.33 The disconjugate ocular torsion in thissyndrome presumably reflects selective injury tootolithic pathways corresponding to the posteriorsemicircular canals.23,29,33 Medial medullary lesionsthat cause skew deviation can be associated withupbeating nystagmus.142

2. Cerebellum

Otolith input to the cerebellum has been dem-onstrated extensively.10,42,47,83 Animal studies havedemonstrated pathways not only from the vestibularnuclei via the inferior olive to the cerebellar vermis(uvula-nodulus), but also primary otolith projec-tions to the uvula-nodulus via mossy fibers.11

Furthermore, single-cell recordings suggest thatthe otoliths influence neural activity in the rostralfastigial nucleus.42 The otolith signals are relayedfrom the vestibular nuclei, medullary reticularformation, inferior olive, and lateral reticularnucleus to the cerebellar nodulus and uvula, andinfluence the deep cerebellar nucleus.42 Skewdeviation has been produced experimentally inanimals by lesions of the cerebellum,104,149,217 resti-form body,212 and inferior and middle cerebellarpeduncle.2,44,149 Burde and colleagues found lateralalternating skew deviation in two monkeys after totalcerebellectomy;41 however, most studies of ocularmotor function following stimulation or destructionof the cerebellum in humans116,145 and mon-keys47,162,218 have not noted skew deviation.

Because early reports of skew deviation in humanswere so frequently associated with large cerebellar

Fig. 7. Figure showing different types of skew deviationthat can result from selective unilateral injury to otolithiceither the anterior or posterior semicircular canals. Theseasymmetric injuries provide an explanation for incomitantforms of skew deviation.


lesions,41,103,153,181,207 it is curious that the causalassociation of skew deviation with cerebellar diseasehas been a matter of some controversy. As discussedbelow, lateral alternating skew deviation (resultingfrom bilateral injury to the vestibulo-oculartracts)140,141,207,224 is recognized in patients withArnold Chiari malformation and other types ofcerebellar disease, but clinical reports of unilateralskew deviation in patients with pure cerebellardisease are surprisingly rare.140 In retrospect, mostcerebellar lesions purported to cause skew deviationwith comitant hypertropia have been large,181 andhave probably involved adjacent brainstem vestibulo-ocular pathways, and this was the cause of theobserved skew deviation.115,157

Recent evidence has confirmed that isolatedcerebellar lesions can indeed cause skew deviation.Mossman and Halmagyi documented two patientswith tonic contraversive partial ocular tilt reactionsattributable to unilateral cerebellar lesions. Radtkedescribed paroxysmal alternating skew deviation ina patient who underwent biopsy of the inferiorcerebellar vermis resulting in destruction of theuvula. The localization of these lesions suggestedthat the ocular tilt reaction may be under inhibitorycontrol of the ipsilateral caudal cerebellum.140

Wong and Sharpe described five patients withprobable skew deviations caused by focal cerebellarlesions involving the vermis or hemisphere.220

3. Medial Longitudinal Fasciculus

Because focal lesions of the medial longitudinalfasciculus can also produce an ocular tilt reaction,careful examination for skew deviation is especiallyimportant in patients with demyelinating disease.225

When skew deviation accompanies internuclearophthalmoplegia, the higher eye is usually on theaffected side, suggesting a rostral lesion of themedial longitudinal fasciculus after it crosses inthe pons.84,182 Patients with an unilateral internu-clear ophthalmoplegia should also be examined forocular torsion and a head tilt to the contralateralside.46,180,200,225 In a retrospective series, Smith et alidentified skew deviation in 43% of patients withunilateral internuclear ophthalmoplegia (mostlysecondary to ischemic vascular disease) and in13% of patients with bilateral internuclear ophthal-moplegia (mostly secondary to multiple sclero-sis).182 In 10 of 12 unilateral cases, the higher eyewas on the side of the MLF lesion.

Patients with unilateral internuclear ophthalmo-plegia may also have a conjugate torsional nystag-mus in which the upper poles of the eyes cyclorotateso as to beat toward the side of the lesion.55 Wheninternuclear ophthalmoplegia is associated with

diplopia, it is often incorrectly assumed that thediplopia is horizontal secondary to deficient adduc-tion. In this setting, a patient may have a clinicallynonevident skew deviation that is sufficient toprevent fusion. Placement of a small vertical prismmay be all that is necessary to relieve the diplopiaand restore binocular vision.

4. Midbrain

It was noted long ago that skew deviation can beproduced in monkeys by unilateral electrolyticlesions in the midbrain tegmentum.58 In experi-mental animals, electrical stimulation of the meso-diencephalon in the region of the interstitialnucleus of Cajal elicits a phasic (i.e., transient)ipsiversive head tilt and eye torsion, whereas lesionsin the region of the interstitial nucleus of Cajalproduce tonic (i.e., persistent) contraversive headtilt and eye torsion.3,70,89,96,101,102,109--111,130,201 Elec-trical stimulation in the region of the INC producesa phasic ipsiversive OTR.77,78,96,129,169 Patients withunilateral stereotactic midbrain lesions have alsodeveloped skew deviation.144

In humans, mesodiencephalic lesions involvingthe interstitial nucleus of Cajal produce an oculartilt reaction that is contraversive if the lesion isinhibitory and ipsiversive and paroxysmal if thelesion is excitatory.89 The interstitial nucleus ofCajal is the most rostral midbrain structure inwhich a unilateral lesion induces the ocular tiltreaction or skew deviation.25 It is an importantstructure in the control of vertical and torsionalhead and eye position,193 and an essential compo-nent of the neural (velocity-to-position) integratorfor both vertical and torsional eye move-ments.3,4,25,51,77,99,117

The current functional concept is that there aretwo distinct and separate brainstem structurescontrolling eye--head coordination in roll and pitch:the bilateral caudal vestibulo-ocular reflex withinputs from the otoliths and the vertical semi-circular canals, and the bilateral rostral integrationcenter (the interstitial nucleus of Cajal). If theascending medullary graviceptive pathways arelesioned at the pontomesencephalic level, rostralto the downward branching of the vestibulo-spinaltracts, skew deviation and ocular torsion can occur inthe absence of a head tilt.23 This mechanism explainssome partial forms of ocular tilt reaction that areseen. Other mesencephalic lesions selectively affectdescending pathways for eye--head coordination andproduce a complete ocular tilt reaction with conju-gate ocular torsion. These lesions involve descendingpathways such as the tectoreticulospinal neurons thatoriginate in the interstitial nucleus of Cajal and run


through the medial longitudinal fasciculus to coupleeye and head roll motion by excitatory projections.

When skew is accompanied by dorsal midbrainsyndrome the lesion can be localized to the mesen-cephalon.50,89,148,159,168,180,213 Medially situated orbilateral midbrain lesions can produce lateral alter-nating skew deviation.118,164,165 Because the halfcycles of see-saw nystagmus are identical to the eyemovement abnormalities of the ocular tilt reaction,92

it is not surprising that jerk see-saw nystagmus and theocular tilt reaction sometimes occur concomitantly inpatients with midbrain lesions involving the intersti-tial nucleus of Cajal.14,88,92,159 Rambold et al de-scribed a patient with congenital nystagmus whodeveloped intermittent see-saw nystagmus with visi-ble head oscillations that were synchronized to thenystagmus, suggesting a common oscillating signalfor the generation of head and eye movements.159

Unilateral mesodiencephalic lesions that activate therostral interstitial nucleus of the medial longitudinalfasciculus can produce an ocular tilt reaction or a jerksee-saw nystagmus with torsional fast phases thatrotate the upper poles of the eyes toward the side ofthe lesion.14,88

5. Thalamus

Reports of skew deviation in patients with thalamicinjury reflect injury to subthalamic structures.71,121

Ischemic lesions involving the interstitial nucleus ofCajal often occur in association with paramedianthalamic infarctions. When a skew deviation occursin association with pretectal extension of a thalamichemorrhage, the higher eye is usually ipsilateral.72

Kumral et al found skew deviation in 17 of 55 (31%)patients with posterior thalamic hemorrhage, 14 ofwho had a large thalamic hemorrhage.120

In 1993, Brandt and Dieterich examined 35patients with acute thalamic infarctions and foundthat 8 of 14 patients with paramedian infarctionshad a complete ocular tilt reaction.60 The ocular tiltreaction in these patients was due to ischemia of therostal midbrain tegmentum (including the intersti-tial nucleus of Cajal) and not to thalamic injury perse. Eleven of 17 patients with posterolateral in-farctions of the thalamic nuclei exhibited tilts of thesubjective visual vertical that were either ipsiversiveor contraversive. Anteromedial infarctions did notaffect vestibular function in the roll plane. Theseresults indicate that the interstitial nucleus of Cajaland the rostral interstitial nucleus of the MLF arethe most rostral brainstem structures mediatingeye-head coordination in roll.60 Unilateral lesionsof vestibular structures rostral to the interstitialnucleus of Cajal manifest with deviations of per-ceived vertical without concurrent eye-head tilt.25,60

6. Vestibular Cortex

Unilateral lesions of vestibular structures rostralto the INC (i.e., the vestibular thalamus andvestibular cortex) cause mostly contraversive tilts inthe subjective visual vertical without concurrent eye-head tilt.22,25 Tilts in the subjective visual verticalcaused by lesions in the vestibular cortex may beassociated with a compulsory lateropulsion.22 Theoverlapping areas of infarction centered on theposterior insula, suggesting that the parieto-insularvestibular cortex seems to represent the integrationcenter of the multisensory vestibular cortex areaswithin the parietal lobe.30

X. Clinical Subtypes

Smith et al divided skew deviation into threeclassic subtypes (comitant, laterally comitant, andlateral alternating skew deviation).181 Additionalforms such as paroxysmal skew deviation, alternat-ing skew deviation, and transient neonatal skew havesince been recognized.

A. COMITANT SKEW DEVIATION

Most cases of skew deviation are comitant,44,182

meaning that the size of the hyperdeviation remainsabout the same in each field of gaze.44 Comitantskew deviation arises from a lesion that knocks outunilateral otolithic input corresponding to pathwaysof the anterior and posterior semicircular canals toequal degrees.25,28 Consider a left-sided utricularlesion, which would produce a right hypertropia bystimulating the right superior oblique and superiorrectus muscles and the left inferior oblique and theleft inferior rectus muscles. In right gaze, the rightsuperior rectus and left inferior rectus activationwould produce a right hypertropia that would bereduced slightly by the vertical action of theactivated left inferior oblique muscle. In left gaze,the same muscles would produce a hypertropia thatwould be reduced slightly by the vertical action ofthe activated right superior oblique muscle. Thus,the skew deviation would remain relatively comitantin different horizontal positions of gaze. Thebinocular torsion would be produced by therelatively greater oblique muscle contribution tocyclorotation in each eye.

It is more difficult to explain why a comitant skewdeviation is generally associated with a negativeBielschowsky Head Tilt test.7,165 In skew deviationwith a right hypertropia, for example, tilting thehead to the right would stimulate the right otolith toactivate the right superior rectus and superioroblique muscles and the left inferior rectus andinferior oblique muscles. Because the vertical rectus


muscles have a stronger vertical action, this maneu-ver should slightly increase the size of the verticaldeviation. Conversely, a left head tilt would activatethe right inferior rectus and inferior obliquemuscles and the left superior rectus and superioroblique muscles, and thereby reduce the existingvertical deviation. In skew deviation, this effect isminimal, perhaps because these muscles are moreor less fully recruited by disinhibition from thelesioned left utricular system.

B. INCOMITANT SKEW DEVIATION

Some forms of skew deviation may be greater inone horizontal field of gaze and minimal in theopposite field of gaze.84,181 Smith et al dubbed thisform of skew deviation laterally comitant meaningthat, in each lateral field of gaze, the deviationremains fairly comitant whether the patient islooking up or down.182 Because the hyperdeviationis greater in one lateral field of gaze than the other,this form of skew deviation is actually incomitant. Insuch cases, prism alternate cover testing maydisclose only a residual hyperphoria in the normalfield of gaze, although small tropias are oftenpresent. In our experience, a large vertical deviationin one lateral field of gaze with no vertical deviationin the contralateral field of gaze may often be a signof isolated or associated oblique muscle palsy, andshould be accompanied by a positive BielschowskyHead Tilt test and a corresponding extorsion of thehypertropic eye.

Incomitant skew deviation may arise from asym-metric injury to otolithic pathways corresponding toeither the anterior or posterior canals are selectivelyinjured.68 Using known vestibulo-ocular connec-tions, the examiner can often postulate whichpathways have been injured (Fig. 7). Consider, forexample, a lesion that selectively injures theotolithic projections corresponding to the leftanterior semicircular canal (which excite the leftsuperior rectus and right inferior oblique muscles,and inhibit the left inferior rectus and right superioroblique muscles). In left gaze, the hyperdeviationwill be fairly minimal, because the action of both ofthese elevators is diminished. In right gaze, thevertical effect of the weak right inferior obliquemuscle is minimal while the inhibited left superiorrectus muscle (which is still the main elevator) willproduce a right hypertropia, causing the eyes toskew in right gaze. Thus, if the lesion is known fromassociated clinical findings or neuroimaging to beon the left side, the examiner can infer that theotolithic pathways corresponding to the anteriorcanal are selectively injured. Conversely, injury tothe left posterior canal pathways would inhibit the

left superior oblique and right inferior rectusmuscles. Because both depressors have a strongvertical action in right gaze there would be minimalvertical deviation in this position of gaze. In leftgaze, however, the left superior oblique has minimalvertical action while the right inferior rectus muscleis still the major depressor. Thus, inhibiting bothmuscles will result in a right hypertropia in left gaze,causing the eyes to skew apart in left gaze.

C. PAROXYSMAL (INTERMITTENT) SKEW

DEVIATION

Whereas a tonic ocular tilt reaction is due toa decrease in tonic neural activity, a phasic (i.e.,paroxysmal or intermittent) ocular tilt reaction is dueto a transient lesion-induced increase in neuralactivity. 89 Tilt effects caused by paroxysmal activa-tion are opposite in direction to those caused bylesional inhibition such as unilateral infarc-tion.24,89,98,129,156 Most reports of paroxysmal skewdeviation have involved patients with irritative mid-brain lesions. Intermittent forms of skew deviationin which one eye drifts up episodically have beendocumented in other patients with irritative mid-brain lesions.87,115 Hedges and Hoyt describeda patient who experienced episodes of contralateralhypertropia and head tilt due to a lesion close to theright interstitial nucleus of Cajal.98 The paroxysmalhead tilt and vertical divergence were coupled totonic conjugate torsional movements of the eyes,suggesting an irritative mechanism.

Paroxysmal skew deviation can also be a feature ofepilepsy, presumably resulting from spread ofexcitation from the cerebral hemisphere to theportions of the brainstem that mediate otolith-ocular reflexes.80 Straube and Brandt describeda patient with paroxysmal skew deviation, torsionalnystagmus, and contraction of the frontalis musclesince childhood (probably due to neurovascularcross-compression of the vestibular and facialnerves).187 Allerand described a paroxysmal rightskew deviation lasting 40--50 sec in a patient withbrainstem glioblastoma that was infiltrating fromthe midbrain to the medulla.2 Brandt et al docu-mented noise-induced paroxysmal ocular tilt re-action resulting from a perilymph fistula (Tulliophenomenon).31,65 Bentley et al described episodicskew deviation and ocular torsion in three patientswith mesodiencephalic lesions. These patients wereunusual in that they exhibited fast phase movementsin the direction of the ocular tilt reaction.14 In onepatient, the abnormal eye movements were tempo-rally linked to dystonic movements in the limbs onthe side opposite the brainstem lesion.14


D. PERIODIC OR SLOWLY ALTERNATING SKEW

DEVIATION

Numerous patients have been described withslowly alternating skew deviation or, less commonly,periodic alternating skew deviation that alternates orvaries in magnitude over the course of a fewminutes.50,137 The great majority have been attribut-able to midbrain lesions.116 Most of these cases hadno documented torsion or head tilt. However, somehad intorsion of the higher eye and extorsion of thelower eye, suggesting a pathophysiologic overlapwith seesaw nystagmus. Causative lesions includea bilateral cryptococcal lesion at the mesodience-phalic junction,56 biopsy injury to the uvula ina patient with suspected glioma involving the leftvestibular nucleus and cerebellar peduncle,157 ste-reotactic pretectal lesion,144 cerebellar degeneration(which also caused periodic alternating skew de-viation in phase with horizontal periodic alternatingnystagmus,126 Leigh disease, Mandrax (methaqua-lone and diphenhydramine HCL) overdosage,151

third ventricular cyst,118,164 ischemia,71,218 glioma ofthe brainstem,2 and a discrete lesion lateral to therostral aqueduct.116 As noted above, Radtke de-scribed a patient with suspected brainstem gliomawho developed a paroxysmal alternating skew de-viation after biopsy of the inferior cerebellar vermisresulting in destruction of the uvula.157 Rarely slowlyalternating skew deviation and lateral alternatingskew deviation (see below) can coexist.50

E. LATERAL ALTERNATING SKEW DEVIATION

Lateral alternating skew deviation refers to a re-versing hypertropia that is present in each lateralposition of gaze. Most commonly the abducting eyeis higher but sometimes the adducting eye can behigher.115,141 It has long been suspected thatlaterally alternating skew deviation results frombilateral rather than unilateral involvement ofcentral otolithic pathways.24,84,115,116,144 Only re-cently, however, has evidence accumulated toexplain the specific ocular motor effects of bilateralbrainstem lesions.

Cogan first reported bilateral abduction hyper-tropia in a patient with downbeating nystagmus andbasilar invagination.45 In 1985, Keane examined 408patients with skew deviation and found that 47(12%) had a skew deviation that alternated on gazeto either side.115 Pretectal lesions were responsiblefor 29 cases and lower brainstem lesions were seen in5 cases. Acute hydrocephalus, tumors, strokes, andmultiple sclerosis were the most common causes,followed by spinocerebellar disease and tectalherniation. In 23 patients the adducting eye washigher, in 22 it was lower, and in 2 it reversed on

repeat examination. This suggested that bilateralalternating skew deviation may localize to thepretectal area.115 In 1988, Moster et al described53 patients with alternating skew deviation in lateralgaze with hypertropia of the abducting eye.141 Mostpatients had associated downbeating nystagmus andataxia and were diagnosed as having lesions of thecraniocervical junction. The localization of theselesions contrasted sharply with those in Keane’sreport, where lesions were found mainly in themidbrain pretectum. It is now established thatlateral alternating skew deviation results from bi-lateral injury to central graviceptive pathways whichextend from the medulla to the midbrain.24 Becausethese pathways can be injured at any point alongtheir course, it should be expected that bilaterallesions at many positions along the brainstem canproduce this ocular motility disorder.24

In 1995, Brandt and Dieterich suggested thatoverlapping pathways modulate roll and pitchfunction of the vestibulo-ocular reflex, makingefficient use of the vestibular network.24 Accordingto their hypothesis, a unilateral skew deviationreflects a central graviceptive imbalance in the rollplane, while bilateral paramedian lesions or bilateraldysfunction of the cerebellar flocculus producesa tone imbalance in the pitch plane. The principlebehind this operation resembles the guidancesystem of airplanes, in which unilateral activationof a brake flap causes the plane to roll but bilateralactivation results in downward pitch. In a bilateralocular tilt reaction, the vertical components sum-mate to produce the slow phase vertical drift of botheyes while the torsional components cancel eachother. Thus, a unilateral roll imbalance manifests asan ocular tilt reaction, while bilateral otolithicimbalance produces vertical nystagmus in conjunc-tion with an alternating skew on lateral gaze.24

Because central otolithic pathways correspondingto the anterior and posterior semicircular canals(which subserve forward and backward body pitch)are segregated in the brainstem, the clinicalcharacteristics of bilateral alternating skew devia-tion may simply reflect the pattern of injury to thesepathways. A bilateral neurologic lesion that selec-tively inhibits those otolithic pathways correspond-ing to the anterior semicircular canals would lead toa predominance of output from otolithic pathwayscorresponding to the posterior semicircular canals(Fig. 8). 24 Brandt and Dieterich coined the termposterior canal predominance for this type of centralvestibular imbalance, which would increase tonus tothe inferior rectus and superior oblique musclesof both eyes.67 Because the vertical action ofthe superior oblique muscles is more prominentin adduction, the abducting eye would display


a hypertropia on gaze to either side (Fig. 8). A recentevolutionary hypothesis by Zee similarly invokes theinnervational effects of body pitch during lateralgaze in lateral eyed animals to similarly explain whylateral alternating skew deviation could result froma central pitch imbalance.224

F. TRANSIENT NEONATAL SKEW DEVIATION

Hoyt et al found skew deviation in 22 neonateswith no other signs of brainstem dysfunction.108 Theskew deviation resolved by 3 days of age in 15 cases.Five infants subsequently developed congenitalesotropia. The authors emphasized that neonatalskew deviation may be a precursor of congenitalesotropia, and that some of these infants may havehad dissociated vertical divergence.

XI. Differential Diagnosis

A. GENERAL

Skew deviation and its associated ocular tiltreaction are usually readily differentiated from thevertical ocular misalignment caused by restriction(blow out fracture, congenital fibrosis syndrome,Brown syndrome, orbital fibrous bands, pareticdisease—some forms of double elevator palsy,superior or inferior division third nerve palsy,

Fig. 8. Lateral alternating skew deviation. Top: Diagramdepicting the ocular motor affects of bilateral prenuclearlesions affecting otolithic pathways corresponding to theanterior semicircular canals. These lesions would activatethe posterior semicircular canals which excite all fourdepressors. The greater torsional actions of the superioroblique muscles in primary position also produces staticintorsion of the globes. Bottom: Because the verticalactions of the oblique and rectus muscles summate inadduction (the oblique muscles have mainly a torsionaleffect in abduction), this disorder results in laterallyalternating skew deviation with overdepression of theadducting eye. (Reprinted from Brodsky and Donahue38

with permission of the American Medical Association.)

etc.), neuromuscular junction disease (myastheniagravis), innervational disorders (dissociated verticaldivergence), and rare disorders such as extraocularmuscle aplasia1,32,183 (Table 1). In the patient withacute neurologic disease, however, the prenuclearocular tilt reaction must be carefully distinguishedfrom nuclear or peripheral oculomotor and troch-lear lesions, especially when the midbrain tegmen-tum is involved.62,150 In a cranial nerve palsy, anyperceived tilt in the subjective visual vertical issecondary to the ocular torsion, whereas in theocular tilt reaction, the ocular torsion is secondaryto the subjective visual tilt (or both may besecondary to the underlying central vestibulardisturbance). Unilateral oculomotor or trochlearpalsy should be suspected when ocular torsion andtilt in the subjective visual vertical are measurable inone eye only.62 In bilateral fourth nerve palsy,monocular measurements show subjective visualtilts for both eyes in opposite directions.25 Aprenuclear tegmental lesion can rarely injure thecranial nerve nucleus or nerve fascicle and producea combined prenuclear and fascicular lesion,62

resulting in a skew deviation plus an oblique musclepalsy. These disorders produce complicated ocularmotility findings depending upon the relativedamage to each structure.

B. SKEW DEVIATION SIMULATING SUPERIOR

OBLIQUE PALSY

Kushner has noted that skew deviation cansometimes simulate superior oblique palsy during

TABLE 1

Skew Deviation: Differential Diagnosis

Neurologic� Superior Oblique Palsy� Inferior Oblique Palsy� Superior Division 3rd Nerve Palsy� Third Nerve Palsy� Ocular NeuromyotoniaNeuro-Muscular� Myasthenia Gravis� Systemic Botulism� Lambert-Eaton SyndromeRestrictive (positive forced ductions)� Thyroid Eye Disease� Monocular Elevation Deficiency� Congenital Fibrosis Syndrome� Acquired Brown Syndrome� Chronic Progressive External Ophthalmoplegia� Orbital Fibrous BandsCongenital� Brown Syndrome� Superior Oblique Palsy� Monocular Elevation Deficiency� Extraocular Muscle Aplasia


Bielschowsky Three-step testing.122 Because bothdisorders can result from traumatic or neurologicalinjury to the posterior fossa,32,184 skew deviationshould always be a diagnostic consideration inpatients with apparent superior oblique palsy.Superior oblique palsy with spread of comitancecan also mimic a comitant skew deviation since bothconditions are associated with a head tilt that isdirected toward the side of the lower eye. In thissetting, the positive Bielschowsky Head Tilt test andthe ocular torsion, as measured by fundus observa-tion, must be used to distinguish the two disorders(Table 2).

In 1999, Donahue et al described 5 patients withhypertropia and contralateral head tilt, in whom theBielschowsky Head Tilt test suggested superioroblique palsy68 (Fig. 9). Although extorsion of thehigher eye characterizes superior oblique palsy,these patients had extorsion of the lower eye and/or intorsion of the higher eye, indicating an oculartilt reaction. All patients had other neurologicfeatures consistent with more widespread brainstemdisease. The authors interpreted the findings fromthe three-step test to be indicative of selective injuryto the otolithic pathways corresponding to theanterior semicircular canals, and cautioned thatexamination of objective fundus torsion in both eyesis necessary to rule out an ocular tilt reaction anddifferentiate the incomitant hypertropia of apparentsuperior oblique palsy from skew deviation. Me-chanical anomalies within the orbital pulley system(a lower lateral rectus muscle pulley on one side)can also manifest as unilateral superior obliquepalsy.57

C. SKEW DEVIATION SIMULATING INFERIOR

OBLIQUE MUSCLE PALSY

In 2001, Donahue et al described 5 patients withocular motility disorders and Bielschowsky Head Tilttests suggestive of inferior oblique palsy.69 All hadassociated neurologic disease referable to the

TABLE 2

Ocular Tilt Reaction Versus Superior Oblique Palsy

Prenuclear Lesion(Ocular Tilt Reaction) Superior Oblique Palsy

Intorsion of higher eye/extorsion of the lowereye

Extorsion of higher eye

Binocular tilt ofsubjective visualvertical

Monocular tilt ofsubjective visual vertical

Head tilt compensatoryfor altered subjectivevisual vertical

Head tilt compensatoryfor vertical diplopia

posterior fossa. Five patients had extorsion of thelower eye and four had intorsion of the higher eye.The authors concluded that an ocular tilt reactioncan simulate inferior oblique palsy when otolithicpathways corresponding to the posterior semicircu-lar canal pathways on the side of the hypotropic eyeare selectively injured. Because the original papersdescribing isolated inferior oblique muscle paralysisdid not directly measure ocular torsion,154,173 somepreviously reported cases of isolated inferior obliquemuscle overaction may have actually representedskew deviation.

D. SKEW DEVIATION ACCOMPANYING SIXTH

NERVE PALSY

Patients with sixth nerve palsy may present witha small coexistent hyperdeviation which may beattributable to physiologic hyperphoria (probablydissociated vertical divergence), superior obliquepalsy, or skew deviation. In 1989, Slavin examined 16patients with isolated unilateral sixth nerve palsyusing Maddox rods, and found that a large amount

Fig. 9. Ocular tilt reaction simulating superior obliquepalsy. Top left: Facial photograph demonstrates a left headturn and a slight head tilt. Top right: Field measurementsare consistent with right superior oblique palsy (HT 5hypertropia). Bottom left and right: Retinal photographsshow intorsion of the higher eye and extorsion of thelower eye which signifies an ocular tilt reaction. (Re-printed from Donahue et al68 with permission of theAmerican Medical Association.)


of hyperdeviation, up to 16 prism diopters, could bedetected in these patients in different gaze positionsas well as in head tilt.177 Wong et al recentlyexamined 20 patients with unilateral sixth nervepalsy with scleral search coil recordings and foundthat 75% had a vertical deviation in at least one eyeposition.221 They found that patients with periph-eral palsies had greater hyperdeviations of the eyeipsilateral to the tilt (suggesting possible disinhibi-tion of otolith-ocular reflexes by loss of binocularvision). Conversely, patients with central palsiesmaintained the same hypertropia on tilt to eitherside (suggesting unilateral injury to otolith-ocularpathways leading to skew deviation).

XII. Expanding the Definition of SkewDeviation

Our traditional application of the term skewdeviation to patients with neurologic disease leavesus with a hemianopic view of this disorder and itsunderlying physiology. In lower animals, the centralvestibular system uses weighted graviceptive inputfrom the two labyrinths and weighted visual inputfrom the two eyes to establish subjective verticalorientation in the roll and pitch plane.38 Theseprimitive reflexes can be detected in normalhumans, wherein a cycloversion movement (aconjugate torsional rotation of both eyes as occursin the ocular tilt reaction) is evoked by visual orgraviceptive imbalance in the roll plane, whilea cyclovergence movement (a disconjugate torsionalrotation of both eyes resulting in intorsion orextorsion of both eyes) is evoked by a visual orgraviceptive imbalance in the pitch plane.35 Al-though the binocular visual system is normallysubordinate to the peripheral vestibular system inestablishing extraocular muscle tone, these primi-tive reflexes manifest in the setting of congenitalstrabismus.38 Thus, a unilateral or asymmetrical lossof otolithic tone secondary to brainstem, cerebellar,or utricular injury causes a skew deviation, whileasymmetrical visual input in the setting of congen-ital strabismus evokes dissociated vertical diver-gence.36,37 The same interrelationship is evident inthe pitch plane, where a bilateral loss of otolithictone causes lateral alternating skew deviation whileasymmetrical visual input can produce primaryinferior oblique muscle overaction.35,38

A. DISSOCIATED VERTICAL DIVERGENCE

Dissociated vertical divergence (DVD) is an ocularmotor disorder characterized by a slow upward driftof either eye, followed, after a variable period oftime, by a slow descent of the higher eye back to the

neutral position (Fig. 10). The hyperdeviating eyeextorts during its ascent and intorts as it descends toresume fixation. Dissociated vertical divergencemost commonly accompanies congenital esotropia,but is also seen with rarer forms of congenitalstrabismus.37

Dissociated vertical divergence recapitulates theprimitive dorsal light reflex, wherein asymmetricalvisual input to the two eyes evokes a verticaldivergence movement.37 Like the otolithic oculartilt reaction, this visuo-vestibular reflex also func-tions as a righting reflex in lateral-eyed animals torestore vertical orientation by equalizing visual inputto the two eyes.37 Brodsky has proposed thatdissociated vertical divergence is a human dorsallight reflex, which is normally suppressed exceptwhen early onset strabismus precludes the develop-ment of single binocular vision in infancy(Fig. 10).36,37 In this setting, the two eyes revert totheir primitive ancestral function as sensory balance

Fig. 10. Dissociated vertical divergence. In the patientwith congenital strabismus, unequal binocular visual inputexerts the same physiologic effect as unbalanced utricularinput, producing a combined vertical divergence andcycloversion of the eyes. In DVD, however, the cyclo-version movement is opposite in direction to that seenwith the utricular ocular tilt reaction. (Reprinted fromBrodsky36 with permission of the American MedicalAssociation.)


organs. Dissociated vertical divergence appears to bea second type of ocular tilt reaction that producesa vertical divergence with intorsion of the lower eyeand extorsion of the higher eye.37 This verticaldivergence can be conceptualized as an inverse skewdeviation that is driven by unequal visual input tothe two eyes rather than unequal graviceptive inputto the two labyrinths.37 Vertical divergence of theeyes with these inverse torsional characteristicsseems to be a signature of abnormal binocularvision.37 Dissociated vertical divergence may alsocontribute to the physiologic hyperphoria that isevoked in normal individuals by occlusion orMaddox rod testing.127,147,179

B. PRIMARY OBLIQUE MUSCLE OVERACTION

Central vestibular mechanisms that are operativein the pitch plane may explain the clinical overlapbetween primary oblique muscle overaction andlateral alternating skew deviation.25,35,38,67 By view-ing a pencil slanted forward or backward in thepitch plane, then closing one eye and the other, thereader can see that each image appears tilted inopposite directions when viewed monocularly. Thus,the monocular correlate of slant is disconjugatetilt.35 In the same way that a roll plane imbalanceevokes an ocular tilt reaction, a pitch planeimbalance evokes a compensatory cyclovergence ofthe eyes. In the setting of congenital strabismus, thiscompensatory cyclovergence manifests as primaryoblique muscle overaction.35

Like DVD, primary inferior oblique overactiongenerally accompanies congenital strabismus.38 Pri-mary inferior oblique overaction corresponds toa forward pitch imbalance.38 Conversely, structuralneurologic disease within the brainstem or cerebel-lum produces the intorsion and superior obliquemuscle overaction so commonly seen in childrenwith Chiari malformations, meningomyelocele, orhydrocephalus.38,94,95 Hamed et al have argued thatprimary superior oblique overaction and lateralalternating skew deviation are phenomenologicallyindistinguishable.94,95 Brodsky and Donahue pro-posed that both disorders represent a centralvestibular pitch imbalance.38,67,224 Instead of thesubjective tilt that leads to skew deviation withcomitant hypertropia, a subjective backward pitchwould be necessary to drive the eyes downward andproduce the motility dysfunction seem with primarysuperior oblique muscle overaction and laterallyalternating skew deviation. Indeed, many childrenwith A-pattern esotropia and bilateral superioroblique overaction have tonic downgaze duringinfancy.38 A bilateral neurologic lesion that selec-tively inhibits those otolithic pathways correspond-

ing to the anterior semicircular canals would lead toa predominance of output from otolithic pathwayscorresponding to the posterior semicircular ca-nals.25 As noted above, a posterior canal imbalancewould cause the abducting eye to display a hyper-tropia on gaze to either side since the verticalactions of the activated superior oblique muscles aregreater in adduction (Fig. 8).38

Humans display an inherent upward tonus pre-dominance of the eyes which correlates withanatomical differences in the orientation of thesemicircular canals.16 Using a Maddox rod, Slavin etal found a bilateral physiologic hyperdeviationcorresponding to inferior oblique muscle over-action, (i.e., right hyperdeviation in gaze up andto the left, and left hyperdeviation in gaze up and tothe right) in 22 of 61 normal subjects.178 Liesch andSimonsz127 and Neikter147 have performed pro-longed patching of one eye in normal subjects andelicited either unilateral (same eye) or bilateralinferior oblique muscle overaction. Brodsky andDonahue38 have proposed that early binocularvisual loss could alter input to the cerebellarflocculus and thereby disinhibit otolithic pathwayscorresponding to the anterior canals. The verticalactions of the elevators (which are activated byanterior canal pathways) would then summate inadduction (where both the superior rectus andinferior oblique muscles have a primarily verticalaction). The finding of a normal anterior canalpredominance in humans could explain the smallphysiologic inferior oblique muscle overaction de-scribed by Slavin, and its clinical manifestationfollowing unilateral patching. Physiologic inferioroblique muscle overaction may also contribute tophysiologic hyperphoria.221

C. ACQUIRED COMITANT ESOTROPIA

Acquired comitant esotropia is a perplexingdisorder that is also produced by structural lesionswithin the posterior fossa. Because these lesionsaffect neurologic pathways subserving horizontalrather than vertical vergence mechanisms, they beara pathophysiologic resemblance to skew deviation.Acquired comitant esotropia can be produced bystructural lesions localized to the posterior fossasuch as cerebellar vermal tumors or Arnold Chiarimalformations.106,107,125,218 Some patients may alsohave divergence insufficiency.44,125 Because theseprenuclear lesions presumably disrupt central ves-tibular pathways subserving horizontal rather thanvertical vergence, the resulting esodeviation can beby conceptualized as a horizontal skew deviation,recognizing its mechanistic overlap with other formsof skew deviation.34


The physiologic underpinnings of horizontal skewdeviation may lie in the translational vestibulo-ocular reflex. During fore-and-aft translation, vestib-ularly driven eye movements use radial optic flowand binocular disparity vergence to minimize headmovement induced modulation of the fixationplane.135 Visual tracking mechanisms that addresstranslational disturbances are most accurately tunedfor headings in the fore-aft axis (i.e., the surgeplane) (Table 3).6 Disconjugate vergence move-ments during fore-and-aft translations exhibit muchhigher gains (at or above unity) than conjugateversion movements during lateral translation in thelateral plane (approximately 0.5), suggesting thatthe translational vestibulo-ocular reflex is tuned tostabilize binocular gaze in the same depth planeduring translational movements.6

While prenuclear lesions that disrupt verticalvergence generally localize to the brainstem, thosethat disrupt horizontal vergence tend to localize tothe cerebellum.207 Although little is known about theneurologic substrate of the translational vestibulo-ocular reflex, monkeys with lesions involving thedorsal cerebellar vermis develop an esotropia that isgreater at distance than at near fixation.194,195 Similarobservations are made clinically in adults withcerebellar disease who develop a divergence in-sufficiency-type esotropia. The dorsal vermis projectsto the fastigial oculomotor region, which has beenimplicated in the control of vergence.195 Neuronshave been identified within the cerebellar vermis thatmodulate with convergence alone (Zhang HY,Gamlin PDR: Single-unit activity within the posteriorfastigial nucleus during vergence and accommoda-tion in the alert primate. SocNeurosci Abstr 1996:22)Humans with global cerebellar dysfunction can haveanesophoria duringmonocular viewinganda smalleresotropia during binocular viewing, suggesting anincrease in esotonus to the extraocular muscles witha relatively preserved ability to use horizontaldisparity cues to drive motor fusion.194 Further studywill be necessary to determine whether patients withacquired comitant esotropia or divergence insuffi-ciency experience an altered internal representationof proximity (Table 3).34

XIII. Prognosis and Treatment

Becausemost ocular tilt reactions are transient andspontaneous recovery is the rule,18,123 surgicaltherapy should be deferred for several months.During this period, prismatic treatment or botulinumtherapy can provide adequate symptomatic relief ofvertical diplopia. Prisms, botulinum toxin, andvertical rectus muscle recession have all been toutedas effective treatments for vertical diplopia secondaryto persistent skew deviation.40,123,146,160,174 The reso-lution of the ocular tilt reaction after unilateralvestibular deafferentation may be an index ofvestibular compensation.90

It is important to recognize that these treatmentswill not eliminate the head tilt component (which issecondary to a central tilt in the subjective visualvertical and not compensatory for the verticaldiplopia). As noted above, the patient is usuallyunaware of the head tilt and grateful to be relievedof vertical diplopia following successful treatment.Treatment of a persistent head tilt poses a paradox-ical therapeutic dilemma. Because the head tiltserves to realign the head to a tilted subjectivevertical, any effort to simultaneously treat the headtilt would require surgically augmenting the tor-sional deviation to rotate the eyes further in thedirection of the head tilt. This surgical cyclorotationof the eyes would serve to counter-rotate the visualworld in the opposite direction (i.e., back towardthe true earth vertical) and thereby eliminate theneed for a compensatory head tilt. This therapeuticprinciple also underlies the use of horizontal trans-position of the vertical rectus muscles or obliquemuscle surgery in children with idiopathic torticollisand head tilts associated with congenital nystagmus.In patients with ocular tilt reactions, this procedurecould be combined with vertical rectus musclerecessions to treat both components of the oculartilt reaction.

XIV. Questions

Our enormous progress in elucidating the patho-physiology of skew deviation raises a number of

TABLE 3

The Three Dimensions of Skew Deviation

Clinical Disorder Plane Laterality Pathways

Skew deviation Roll plane Unilateral Brain stem graviceptivepathways modulating otolithic tone

Lateral alternating skew deviation Pitch plane Bilateral Brain stem graviceptivepathways modulating otolithic tone

Horizontal skew deviation Surge plane ? Midline Cerebellar pathways mediatingtranslational VOR


new questions. Because skew deviation is oftenassociated with conjugate ocular torsion, are somepatients with unilateral otolithic dysfunction usinga combination of horizontal and vertical conver-gence to fuse a hyperphoria? Perhaps patients withmanifest hypertropia represent the most severe endof the spectrum. Is the subjective visual tiltnecessarily the cause of the skew deviation, oculartorsion, and head tilt? Although these three ocularmotor phenomena accompany subjective visual tiltin the context of an ocular tilt reaction, recovery ofall these ocular motor phenomena is not necessarilycoincident with normalization of the subjectivevisual vertical. It is therefore possible that neuro-logic disease causes the ocular tilt reaction and thesubjective visual tilt together, with the subjectivesense of vertical the most easily disrupted and thelast to return to normal. Why is there so littlephysiologic skew deviation? What are the antivestib-ular forces independent of fusion that minimizephysiologic skew deviation during physiologic headtilt? Do some idiopathic head tilts (without strabis-mus) result from a central or peripheral otolithicimbalance? It is well to remember that, when wetreat idiopathic head tilts by torsional rotating theeyes in the direction of the head tilt, we aresurgically inducing a contraversive subjective visualtilt to neutralize the head tilt.

XV. Conclusions

Skew deviation has evolved from a descriptiveterm to a precise physiological mechanism of injury.Skew deviation results from a unilateral lesion thatunilaterally injures the otolithic pathways andthereby causes the brain to perceive the world astilted. The resulting vertical deviation is but one partof an ocular tilt reaction which rotates the eyes andhead toward the tilted visual world to restore verticalorientation. Skew deviation can be caused by a lesionto utricular pathways anywhere from the utricle tomidbrain. Partial injury that involves only thosepathways corresponding to the anterior or posteriorsemicircular canals produces incomitant skew de-viation, while lateral alternating skew deviationresults from symmetric bilateral lesions involvingthese same pathways. While unilateral skew de-viation corresponds to central graviceptive dysfunc-tion of otolithic pathways in the roll plane, lateralalternating skew deviation corresponds to a centralgraviceptive dysfunction of otolithic pathways in thepitch plane. A developmental imbalance in visualinput between the two eyes produces a constellationof ocular motility abnormalities that is strikinglysimilar to those produced by the two labyrinths,suggesting that our eyes retain their primitive

evolutionary function as balance organs. By expand-ing our clinical definition of skew deviation toinclude those central vestibular imbalances inducedby binocular imbalance, we can broaden ourphysiologic perspective of skew deviation.

Several challenges face the ophthalmologist whois evaluating a vertical ocular deviation of neuro-logic origin. First, the clinician must look forassociated signs and symptoms of skew deviation(tilt of the subjective visual vertical, head tilt,torsion). Second, the clinician must measure thehyperdeviation in different fields of gaze to not onlyidentify clinical subtypes of skew deviation, but torecognize incomitant forms of skew deviation thatare due to selective patterns of injury to the anterioror posterior semicircular canals, and to distinguishthem from isolated superior or inferior obliquemuscle palsy. Third, it should be remembered thatlesions producing skew deviation can also compro-mise ocular motor nerve function to producea complex clinical picture. Finally, developmentalaberrations in binocular alignment can produceequivalent ocular motility disturbances and must beconsidered in the differential diagnosis.

XVI. Method of Literature Search

References were obtained from English and non-English references for skew deviation, and ocular tiltreaction. English references from 1966 to 2005 wereobtained from MEDLINE, and older English andnon-English references were obtained from neuro-ophthalmology textbooks and major articles thataddressed the topic of skew deviation. Due to thelarge number of experimental animal studies in-vestigating the ocular motor consequences ofbrainstem or cerebellar lesioning on vertical ocularalignment, only the seminal neurophysiologic stud-ies that related directly to the mechanism of skewdeviation and the ocular tilt reaction were cited.

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Supported in part by a grant from The Pat and Willard WalkerFoundation, Jones Eye Institute, and Research to PreventBlindness, Inc. The authors reported no proprietary or commer-cial interest in any product mentioned or concept discussed inthis article.

Reprint address: Michael C. Brodsky, M.D., Arkansas Children’sHospital, 800 Marshall, Little Rock, Arkansas 72202. E-mail:[email protected]

Outline

I. IntroductionII. HistoryIII. CausesIV. Evolutionary underpinningsV. NeuroanatomyVI. Symptomatology

VII. Subjective visual tiltVIII. Localizing valueIX. Sites of injury

A. Peripheral injury to otolithic pathways

1. Utricle2. Vestibular nerve

B. Central injury to otolithic pathways

1. Medulla2. Cerebellum3. Medial longitudinal fasciculus4. Midbrain5. Thalamus6. Vestibular Cortex

X. Clinical Subtypes

A. Comitant skew deviationB. Incomitant skew deviationC. Paroxysmal (intermittent) skew deviationD. Periodic or slowly alternating skew devia-

tionE. Lateral alternating skew deviationF. Transient neonatal skew deviation

XI. Differential diagnosis

A. GeneralB. Skew deviation simulating superior oblique

palsyC. Skew deviation simulating inferior oblique

palsyD. Skew deviation accompanying sixth nerve

palsy

XII. Expanding the definition of skew deviation

A. DVDB. Primary oblique muscle overactionC. Acquired comitant esotropia

XIII. Prognosis and treatmentXIV. QuestionsXV. ConclusionsXVI. Method of Literature Search

mailto:[email protected]

skew deviation revisited

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