Partial ocular tilt reaction due to unilateral cerebellar lesion

Ocular tilt reaction (OTR) is a postural synkinesis consisting of head and conjugate eye torsion, all to the same side, as well as skew deviation with the hypotropia ipsilateral to the direction of the head and eye torsion, due to disordered function of one utricle or its brainstem connections.^1,2 For example, a rightward OTR consists of rightward torsion of the upper poles of both eyes, a right hypotropia, and a rightward head tilt. It can be due to a destructive lesion of the right utricle, the right vestibular nerve, the right vestibular nucleus, the left medial longitudinal fasciculus, or its rostral interstitial nucleus, or of the left interstitial nucleus of Cajal. An OTR can be tonic-that is, it can persist for days or weeks, or it can be paroxysmal and last only for seconds or minutes. Here we report on two patients with tonic partial OTRs due to unilateral cerebellar lesions demonstrating that the OTR is under cerebellar control and can be the sole manifestation of an acute unilateral cerebellar lesion.

Case 1. A 73-year-old man presented with persistent vertical diplopia. Four months previously he had suddenly developed vertigo, vomiting, and a combined vertical-horizontal diplopia. Examination elsewhere had shown bilateral gaze-evoked horizontal nystagmus, dysarthria, gait ataxia, and left upper and lower limb appendicular ataxia. CT had revealed a left caudal cerebellar hemorrhage involving the left side of the nodulus(figure 1); a vertebral angiogram was normal. He was treated conservatively and improved. On examination he still had mild gait and left upper limb ataxia as well as prominent ocular motor abnormalities: a right hypotropia of 7 degrees in the primary position, bilateral gaze-evoked horizontal nystagmus, and defective horizontal and vertical smooth pursuit. Vestibulo-ocular reflexes in response to rapid passive head rotations and voluntary saccades were normal. Fundus photographs showed conjugate rightward ocular torsion (i.e., clockwise from the patient's point of view): 23 degree extorsion of the right eye and 18 degree intorsion of the left (figure 1).

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Figure 1. Fundus photographs and noncontrast CT scan from Patient 1. There is conjugate rightward torsion of the eyes (i.e., clockwise from the patient's point of view); a 23-degree extorsion of the right eye and an 18-degree intorsion of the left, indicating a partial rightward ocular tilt reaction. This was due to the left caudal cerebellar hemorrhage involving the left side of the nodulus.

Case 2. A 58-year-old man presented with sudden imbalance, without vertigo, vomiting, or any other neurologic symptom. On examination, the only neurologic abnormality was that he was unable to stand or to walk without support. Unsupported, he tended to fall to the left. There was no strabismus, no spontaneous, head-shaking, gaze-evoked or positional nystagmus, and no deficiency of vestibulo-ocular reflexes in response to rapid passive head rotations, and no deficiency of horizontal or vertical smooth pursuit. There was no appendicular ataxia and no dysarthria. Tests of the subjective visual horizontal² showed conjugate rightward deviation of the settings (i.e., clockwise from the patient's point of view): 6.9 ± 0.7 (1 SD) degrees with the right eye, 8.4 ± 0.9 degrees with the left eye (normal = 2.0 degrees). Fundus photographs showed 20-degree extorsion of the right eye and 5-degree extorsion of the left. MRI showed a recent infarct in the territory of the medial branch of the left PICA, involving the left tonsil and biventer lobules and the left side of the inferior vermis, including the left side of the nodulus(figure 2). Magnetic resonance angiography showed normal vertebral arteries; a transthoracic echocardiogram was normal but a transesophageal "bubble" study showed a patent foramen ovale. Within 3 days the patient was able to walk normally and was discharged and advised to take an oral anticoagulant. A month later, the subjective visual horizontal was normal: 1.7 ± 1.4 degrees to the left with either eye viewing. Fundus photographs now showed 7-degree extorsion of the right eye indicating that the right eye had been extorted by 13 degrees at the first examination (i.e., by 20 minus 7 degrees) and 13 degrees of extorsion of the left eye indicating that at the first examination, the left eye had in fact been intorted by 8 degrees (i.e., by 5 minutes 13 degrees) with respect to its recovered, and thus presumably its near normal, torsional position.

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Figure 2. T2-weighted MRI scans from Patient 2 with a partial rightward ocular tilt reaction due to an infarct in the territory of the medial branch of the left posterior inferior cerebellar artery. In the most rostral section (a), the infarct is shown to involve the left side of the nodulus (*): a rim of intact nodulus (N) is evident on the right side (curved arrow). The more caudal sections (b and c), show involvement of the left uvula (U) and pyramis (P), as well as the left biventer (B) and gracilis lobules (G), and the medial part of the tonsil (T). The dentate nucleus (D) appears spared. The fourth ventricle is compressed and distorted by edema (arrows). The vestibulocochlear nerve (8, panel a) and adjacent vestibular nucleus appear normal.

Discussion. OTR appears to be due to asymmetry in the bilateral tonic resting rates of peripheral or central otolithic neurons. Although there are no single cell neurophysiologic data to support this view, the circumstantial evidence is convincing.^1,2 The concept of a partial OTR is not universally accepted: for example Brandt and Dieterich³ prefer the term skewtorsion if head tilt is absent. However, in the 17 years since we reported the first case of OTR due to a peripheral vestibular lesion,⁴ we have only found conjugate ocular torsion in patients who have had unilateral lesions of the peripheral of central vestibular system. In our view, the mechanism of conjugate ocular torsion is the same as that of the complete OTR and that conjugate ocular torsion is not only necessary, but also sufficient, for the diagnosis of OTR.

Previous evidence indicates that cerebellum is involved in the OTR: skew deviation⁵ and contraversive head tilt occur with cerebellar lesions,^6,7 and ipsiversive head tilt occur with cerebellar stimulation.⁷ In contrast, conjugate ocular torsion has not been previously reported with cerebellar lesions, almost certainly because its recognition requires techniques not regularly used in neurologic evaluation, that is, fundus photography to measure the torsion directly, or settings of the subjective visual horizontal or vertical to measure torsion indirectly.²

Although both primary and secondary semicircular canal and otolith neurons project to the cerebellum, especially to flocculus, nodulus, and fastigial nucleus, little is known about projections from the cerebellum to secondary otolith neurons, cerebellar modulation of otolith function, or the effects of cerebellar lesions on otolith function. There is, nevertheless, a potential anatomic and physiologic substrate for a cerebellar OTR. For example, vermis Purkinje cells monosynaptically inhibit Deiters' (lateral) vestibular nucleus neurons.⁸ Electrical stimulation of the nodulus and uvula inhibits descending vestibular nucleus neurons projecting to the contralateral cerebellum, as well as the utricular activation of vestibular axons in trochlear nucleus.⁸ Lesions of the nodulus alone, or of the nodulus and uvula together, impair otolith-ocular reflexes and otolithic modulation of semicircular canal vestibulo-ocular reflexes. In the monkey, there is inability to reorient vertical semicircular signals on the basis of gravitoinertial signals;⁹ loss of the steady-state nystagmus response to off-vertical axis rotation;¹⁰ and unilateral nodulus lesions cause a contraversive head tilt.⁶ In the cat, there is persistent positional nystagmus¹¹ with lesions of the nodulus.

Which part of the cerebellum is involved in producing a tonic contraversive OTR? The only cerebellar structures with known functional vestibular connections that appeared to be involved in both these patients were the nodulus and the uvula. The vessel that was occluded in patient 2, the medial branch of PICA, usually supplies both these structures.¹² In contrast, the flocculus is usually supplied by the anterior inferior cerebellar artery, and the fastigial nucleus by the superior cerebellar artery.¹³

We propose that the mechanism of a tonic contraversive OTR with a unilateral cerebellar lesion is an increase in tonic resting activity of secondary otolithic neurons in the ipsilesional vestibular nucleus, due to loss of inhibition from the lesioned nodulus. The OTR is opposite in direction to that occurring with unilateral peripheral vestibular lesions,^2,4 which decrease tonic resting activity, and thus produce an ipsiversive OTR, due to the unopposed activity of the intact, contralesional vestibular nucleus.

Our second case shows that a tonic partial OTR can be the only specific finding in a patient presenting with an acute unilateral cerebellar lesion. Tests of the subjective visual horizontal or vertical are easy to do² and can be the only clue to the diagnosis in a patient with a recent medical PICA territory infarct.

Acknowledgment

The assistance of Dr. Peter Herrick is gratefully acknowledged.