I ANATOMY            


II PHYSIOLOGY                 







When the head tilts in the roll plane (ear to shoulder), torsional eye movements are mainly driven by inputs from the semicircular canals.  However, the otoliths also respond to changes in the orientation of the head relative to gravity, and with a sustained lateral tilt, the eyes counter-roll in the opposite direction to the head tilt, which serves to maintain a constant, unaltered eye position in space (gaze). This static change in torsion, the otolith-driven tilt response, is mediated by inputs from the otoliths (mainly the utricle), which sense the pull of gravity1.

This otolithic reflex includes the generation of:

Normally, balanced signals from the utriculo-ocular pathway are used to align the head’s vertical axis and the eye’s vertical meridian with absolute earth-vertical (gravity) when stationary. For example, when the head is tilted counterclockwise statically, the eyes compensate for the head tilt by rotating clockwise, so that the eyes’ vertical meridian is realigned with earth-vertical. At the same time, the right eye depresses and the left eye elevates, so that the eyes’ horizontal meridian is realigned with earth-horizontal3.

Damage to the utriculo-ocular pathway lead to an erroneous internal estimate of absolute earth-vertical (gravity); that is, the brain erroneously computes that the head is tilted despite the fact that the head is actually in an upright position and that the utricles are still in the horizontal plane. The triad of head tilt, skew deviation, and abnormal torsion seen in the ocular tilt reaction (OTR) represents a righting response, the goal of which is to realign the vertical axes of both the head and the eyes to the internal estimate of absolute earth-vertical, even though this estimate is faulty. 

The OTR has been attributed to the emergence of a phylogenetically old response, best appreciated in lateral-eyed animals, such as rabbits, since in humans it has been largely superseded by mechanisms that are optimized for binocular, foveate, and frontal-eyed vision4. With an imbalance in otolith and especially utricular pathways, the OTR emerges, which represents the vestibular-ocular and vestibular-collic components of the righting reaction in response to lateral tilt of the head and body.  The physiological OTR depends on a crossed graviceptive (ie, sensitive to gravity) pathway which arises from excitation of the dependent utricle, and then projects via the ipsilateral vestibular nucleus to the contralateral interstitial nucleus of Cajal (INC) and then on to oculomotor and spinal motor neurons5.
The utriculo-ocular motor fibers which carry signals from the vestibular apparatus will decussate at the level of the pontomedullary junction and ascend as part of the contralateral MLF. The fibres reach the midbrain to supply the 3rd and 4th nuclei, as well as the INC6.

Vestibular syndromes are commonly characterized by a combination of phenomena involving four modalities: perrceptual, ocular motor, postural, and vegetative. These will manifest respectively as: vertigo, nystagmus, ataxia, and nausea.  Brainstem lesions typically affect the roll plane giving rise to symptoms and signs in three modalities9:

1. OTR

The OTR reflects an imbalance analogous to the spontaneous nystagmus that occurs when there is a tone imbalance between the semicircular canals in each labyrinth7.  In that case there is a static semicircular canal pathway imbalance, whereas in the case of the OTR, there is a static utricular pathway imbalance.

By definition, a rightward OTR comprises a:

-The left eye elevates from contraction of the left superior rectus (decussating fibers from the right third nucleus), and incycloducts from contraction of the right superior oblique (decussating fibers from the left fourth nucleus).
-The right eye depresses from contraction of the right inferior rectus (fibers from the right third nucleus), and excycloducts from contraction of the left inferior oblique (fibers from the left third nucleus).
-Some afferents from the utricle ascending in the right MLF will synapse in the right interstitial nucleus of Cajal, which is responsible for vertical and torsional gaze-holding. This ensures that the eyes will stay in the desired position while the head tilt is maintained.


Figure 1. Schematic drawing of a right ocular tilt reaction. There is a rightward head tilt, skew deviation (with right eye undermost),and torsion of both eyes to the right.

Redrawn from: Brandt T, Dieterich M. Vestibular syndromes in the roll plane: topographic diagnosis from brainstem to cortex. Ann Neurol. 1994;36(3):337-47.


Lesions giving rise to an OTR typically involve:

             - A left MLF lesion results in a right OTR with head tilt to the right, hypotropia of the right eye, counterroll of both eyes (top poles)                           towards the right ear, and SVV tilted to the right.

             - A right MLF lesion results in a left OTR with head tilt to the left, hypotropia of the left eye, counterroll of both eyes (top poles)                                towards the left ear, and SVV tilted to the left.



Tilt of the head toward the right or left shoulder is observed in patients with:

  1. Superior oblique palsy: the head is tilted towards the non-affected side to lessen diplopia.
  2. An ocular tilt reaction (OTR) due to a imbalance of the VOR in the roll plane10.  In the OTR the head is tilted to the side of the lower eye.

Tilt of the head indicates a lesion either:


Skew deviation is a vertical misalignment of the visual axes caused by a disturbance of supranuclear inputs as a result of lesions in the brainstem, cerebellum, or peripheral vestibular system (ie, the inner ear and its afferent projections). The vertical misalignment may be comitant or incomitant. Rarely, it alternates with eye position (eg, right hypertropia on right gaze and left hypertropia on left gaze).

Skew deviation is the hallmark of an imbalance in the tonic levels of activity underlying otolith-ocular reflexes.  Skew deviation is a naturally occurring component of the righting reflex that occurs in lateral-eyed animals (ie, rabbits) in response to lateral tilt of the body so that they can keep their eyes aligned with the horizontal meridian and the head and body upright.  Presumably in frontal-eyed animals (ie, humans) this pattern of eye deviation only emerges when otolith inputs become unbalanced in a non-physiological manner.  Patients with a skew deviation complain of a vertical and sometimes torsional (one image tilted with respect to the other) diplopia. 

Skew deviation is often the initial manifestation of diseases that affect the brainstem, cerebellum, or peripheral vestibular system11. Acutely, torsional nystagmus is commonly present.

Skew deviation may be detected by alternate cover testing.  With the alternate cover test, a vertical corrective movement on switching the cover from one eye to the other is looked for, as an index of vertical misalignment.  The effect of the position of the eye in the orbit and of left and right head tilt on the skew should also be recorded, particularly to exclude a 4th nerve palsy.

In contrast to a 4th nerve palsy, the vertical misalignment in skew deviation does not typically follow any set patterns; Although usually comitant ( as opposed to superior oblique palsy), it may be non-comitant, or may even alternate with gaze direction.
Note that vertical misalignment in skew decreased by at least 50% when the patients changed from an upright to a supine position ( a helpful feature to distinguish skew from superior oblique palsy)11.

Figure 3. Pontomedullary lesions cause ipsilateral SVV tilts, whereas pontomesencephalic lesions cause contralateral SVV tilts. 
The graviceptive pathways cross at the level between the vestibular and the abducens nuclei.





Normally, the subjective visual vertical (SVV) is aligned with the gravitational vertical12, and a tilt of the SVV is a sensitive sign of a disturbance in the otolith-ocular pathways, and is the most sensitive sign of vestibular tone imbalance in the roll plane11
Body lateropulsion is correlated with SVV tilt, ie, the more pronounced the lateropulsion, the greater the SVV tilt13.

Tilt of the SVV occurs in lesions of central and peripheral vestibular pathways, and, in particular, is seen in the majority of patients with acute unilateral brainstem lesions that affect the central graviceptive pathways (running from the vestibular nuclei via the medial longitudinal fasciculus to the midbrain)4. For example, marked image tilting (ranging from 90 to 180 degrees) may be seen in the lateral medullary syndrome.

Lesions of the more rostral pathways, including the thalamus and notably the cortex in the posterior region of the insula will produce the same distrubance of SVV. In thalamic lesions, the tilts of SVV may be contraversive or ipsiversive; in vestibular cortex lesions they are most often contraversive. OTR is not induced by supratentorial lesions above the level of the INC15.

Most patients with acute vestibular neuritis show a small and transient ipsilateral deviation of the SVV.
More central lesions can produce larger and longer lasting tilts of the SVV. In the rostral medullary tegmentum and caudal pons the tilt of the SVV is usually ipsilateral to the lesion; in the rostral pons and caudal mesencephalic tegmentum the tilt of the SVV is usually contralateral to the lesion.

The SVV can be measured at the bedside using the bucket method14. The subject estimates verticality by aligning a dark straight line visible on the bottom of a bucket that is rotated to the right or left by the examiner. On the outside, there is a plumb line on the bottom of the bucket that originates from the center of a semicircle divided into degrees with the zero line adjusted to the dark line inside. In this way the deviation from true vertical can be measured by averaging a few trials.

Figure 4. The bucket method for determining monocular and binocular visual vertical14.
Patients sit upright looking into a translucent plastic bucket so that the bucket rims prevent any gravitational orientation clues. On the bottom inside the bucket there is a dark line. On the outside there is a perpendicular that originates from the center of a quadrant divided into degrees with the zero line corresponding to the true vertical. For measurement, the examiner rotates the bucket clockwise or counterclockwise to an end position and then slowly rotates it back toward the zero degree position. Patients indicate the position where they estimate the inside bottom line to be truly vertical by signaling stop. The examiner reads off the degrees on the outside scale. 

Redrawn from: Zwergal A, Rettinger N, Frenzel C, Dieterich M, Brandt T, Strupp M. A bucket of static vestibular function. Neurology. 2009;72(19):1689-92.

Ocular counter-roll is difficult to detect clinically without photography; however, if there is a large amount of counter-roll, it can be shown by the tilt of the imaginary line that connects the macula with the optic disc.

In most skew deviations except for those caused by a lesion in the lateral medulla, ocular torsion is binocular and conjugate (ie, excyclotorsion of the hypotropic eye and incyclotorsion of the hypertropic eye). In patients with lateral medullary syndrome, the ocular torsion is monocular (ie, the hypotropic eye is excyclotorted, but the hypertropic eye has normal torsion or is slightly incyclotorted)11. The pathological ocular counter-roll arising in an OTR is signficantly greater than the normal counter-roll6.

Figure 2. Schematic drawing from fundus photograph, in a patient with a mesodiencephalic infarction on the left involving the region of the interstitial nucleus of Cajal7

Redrawn from: Dieterich M, Brandt T. Ocular torsion and tilt of subjective visual vertical are sensitive brainstem signs. Ann Neurol. 1993;33(3):292?299. doi:10.1002/ana.410330311





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