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Show Journal of Neuro- Ophthahnology 15( 1): 26- 30, 2995. ) 1995 Raven Press, Ltd., New York Possible Mechanisms for Horizontal Gaze Deviation and Lateropulsion in the Lateral Medullary Syndrome David Solomon, Ph. D., M. D., Steven L. Galetta, M. D., and Grant T. Liu, M. D. We report a patient who developed conjugate horizontal gaze deviation and ipsipulsion of saccades from a lateral medullary infarction. Recent evidence suggests that the gaze deviation may result from increased inhibition of the ipsilateral vestibular nucleus and ipsipulsion of sac-cades from decreased excitation of the contralateral ocular premotor areas of the brainstem reticular formation. Interruption of the olivocerebellar pathways may account for both of these ocular motor abnormalities. Key Words: Lateral medullary ( Wallenberg) syndrome- Gaze deviation- Lateropulsion. Conjugate horizontal gaze deviation frequently suggests a destructive lesion of one cerebral hemisphere or the pons. Unilateral hemispheric damage typically results in transient ipsilateral deviation and is most commonly observed with posterior right- sided lesions ( 1). In contrast, lesions involving the paramedian pontine reticular formation ( PPRF) cause an ipsilateral gaze palsy and consequently, contralateral eye deviation. Ipsilateral horizontal conjugate eye deviation may also occur in the lateral medullary ( Wallenberg) syndrome, and in these instances it is usually most obvious upon removal of visual fixation ( 2- 4). We report a patient with ipsipulsion and prominent horizontal gaze deviation from a dorsolateral medullary infarction and speculate on the possible underlying mechanisms. From the Division of Neuro- ophthalmology, Departments of Neurology and Ophthalmology, Hospital of the University of Pennsylvania, Scheie Eye Institute, and Children's Hospital of Philadelphia; University of Pennsylvania School of Medicine; Philadelphia, Pennsylvania, U. S. A. Address correspondence and reprint requests to Dr. Steven L. Galetta, Division of Neuro- ophthalmology, Dept. of Neurology, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104, U. S. A. CASE HISTORY A 40- year- old woman with hypertension developed acute vertigo, headache, and postural instability. She had a slight right head t u rn and left head tilt on examination. There was no dysarthria or aphasia. There was a left gaze preference with the eyes open ( Fig. 1A); however, voluntarily versions were full ( Fig. IB). There was a spontaneous torsional nystagmus beating toward the right shoulder with a horizontal right beating component in primary and left gaze. Saccades were hypermetric to the left and hypometric to the right, and pursuit was saccadic bilaterally. A right hypertropia greater in left gaze, consistent with a skew deviation, was present. The pupils measured 5 mm OD, 4 mm OS in the dark and 4 mm OD, 3.5 mm OS in the light, and both were briskly reactive. There was 2 mm of 26 GAZE DEVIATION IN MEDULLARY SYNDROME 27 W < B> FIG. 1. ( A) Spontaneous conjugate gaze deviation to the left observed with the eyes open in light. The left eye is hypotropic, ipsilateral to the lesion. ( B) Voluntary conjugate gaze to the right was complete, with decreased skew deviation. left ptosis and decreased sweating over the left face. Following instillation of 10% cocaine eyedrops, the right pupil dilated to 8 mm, with no change OS, confirming a left Horner syndrome. Corneal reflexes were symmetric, but there was decreased pinprick and cold sensation over the left face in an onion- skin distribution; body sensation was intact. Facial strength, hearing, and gag were normal, and the uvula and tongue were midline. Motor strength was normal with brisk symmetric reflexes and flexor plantar responses bilaterally. Rapid alternating and fine motor movements were performed normally. She was unable to stand independently due to leftward lateropulsion. Electronystagmography ( bandpass DC to 25 Hz) recorded hypometric calibration saccades to the right, left- beating horizontal nystagmus present only with the eyes closed ( maximum velocity 8 deg/ s), and direction changing positional nystagmus ( leftward with left ear down, rightward with right ear down). Transient up- beating nystagmus was also noted. Peak calorics responses were asymmetric with right slow phase velocities predominating ( 32 deg/ s from left ear warm and 22 deg/ s from right ear cold) versus 14 and 12 deg/ s for leftward slow phase eye velocities. Fixation suppression of caloric responses was impaired bilaterally. MRI showed hyperintensity in the upper left medulla on long TR, TE images consistent with infarction ( Fig. 2). Angiography demonstrated a hypoplastic but patent left vertebral artery. Six days after onset, the horizontal gaze deviation had improved, and by 17 days the ipsipulsion of saccades had resolved. According to the patient, the head turn and lateral gaze deviation resolved completely after approximately 1 year. DISCUSSION Our patient's left gaze deviation initially might suggest a lesion of the left cerebral hemisphere or right PPRF; however, the full horizontal eye movements, left facial sensory loss, left Horner syndrome, right hypertropia, ipsipulsion of saccades and counterclockwise torsional nystagmus all support a left medullary localization ( 5). Neuroimag-ing confirmed infarction within the distribution of the left posterior inferior cerebellar artery ( PICA), involving the lateral medulla but sparing the inferior cerebellum. Lateropulsion of saccades, characterized by overshoot of ipsilaterally directed saccades, undershoot of contralaterally directed saccades and ipsilateral oblique trajectories during vertical refix-ation, is often a prominent ocular finding in the lateral medullary syndrome ( 6,7). Ipsilateral conjugate eye deviation, on the other hand, is less common but may manifest if fixation is removed. Hornsten ( 8), in his review of 14 patients with Wallenberg syndrome, noted that 4 patients had this finding with eyelids open. One patient had a persistent horizontal gaze deviation and contralateral FIG. 2. T2- weighted axial MRI ( TR = 3000, TE = 90, 1.5 T) through the caudal brainstem demonstrating a wedge- shaped area of increased signal in the left lateral medulla { arrow) without cerebellar involvement. ] Ncuro- Ophtlmimol, Vol. 25, No. 1, 1995 Inferior Cerebellar Peduncle Lateral Medullary Infarct ( Weinberg) ( B) Uncinate Fasciculus ( Hook Bundle of Russell} Superior Cerebellar Peduncle Dentate Nucleus Cerebellar Vermis *' i VH inferior Cerebellar Peduncle Lateral Medullary Infarct ( Wallenberg) Paramedian Pontine Reticular Formation ( EBN) Medullary Reticular Formation ( IBN> FIG. 3. ( A) Schematic of connections responsible for conjugate horizontal gaze deviation following disruption of olivary projections to the contralateral vestibulocerebellum by an infarct involving the inferior cerebellar peduncle in the dorsolateral medulla. Without climbing fiber input, floccular Purkinje cells increase their activity, thereby inhibiting the ipsilateral vestibular nucleus. The relatively increased contralateral vestibular tone results in a horizontal drift of the eyes toward the side of the lesion via vestibulo- ocular pathways and the medial longitudinal fasciculus. ( B) Same lesion as in Fig. A; diagram for saccadic ipsipulsion and contrapulsion. Increased Purkinje cell firing in the cerebellar vermis causes tonic inhibition of caudal fastigial nucleus cells. These neurons pass over the contralateral superior cerebellar peduncle in the uncinate fasciculus before making excitatory connections onto the paramedian pontine reticular formation ( PPRF) and rostral medullary reticular formation ( MRF). Horizontal saccades toward the side of the lesion are hypermetric ( saccadic ipsipulsion), and saccades away from the lesion are hypometric due to lack of fastigial facilitation of the contralateral excitatory and inhibitory burst neurons in the PPRF and MRF, respectively. This mechanism could also contribute to horizontal conjugate gaze deviation. Interruption of the same circuit due to a lesion in the distribution of the superior cerebellar artery causes saccadic contrapulsion because of uncinate fasciculus involvement and ipsilateral limb dysmetria due to dentatorubral pathway interruption. GAZE DEVIATION IN MEDULLARY SYNDROME 29 face turn. With eyelids closed, 12 of 14 patients showed moderate or marked conjugate eye deviation toward the side of the lesion. However, no patient had a gaze palsy, and horizontal eye movement in the opposite direction was full. The exact mechanism for these ocular motor abnormalities remains unclear because few studies have correlated these findings with neuroanatomic data ( 9). Some evidence suggests the conjugate gaze deviation in Wallenberg syndrome results from an imbalance of vestibular tone ( 9). Damage to the inferior cerebellar peduncle may interrupt climbing fibers projecting from contralateral inferior olive to cerebellar cortex. Experimental removal of inhibitory climbing fiber input results in a transient ( 1- 3 weeks) doubling of Purkinje cell simple spike frequency ( 10). Inhibitory projections from Purkinje cells of the flocculus to the ipsilateral vestibular nucleus travel along the dorsolateral aspect of the inferior cerebellar peduncle ( 11). Lesions in the inferior cerebellar peduncle may cause increased inhibition of the ipsilateral vestibular nucleus, resulting in a relative increase in contralateral vestibular activity ( Fig. 3A). The vestibular nuclei generate slow phase eye velocity in the contralateral direction, so that our patient's gaze preference toward the lesion with compensatory head turn may have been due to a central vestibular imbalance favoring the contralateral vestibular nuclei ( 9). Others have speculated that the horizontal gaze deviation may be due to faulty processing of corollary discharges causing errors in the central representation of eye position in the orbit ( 6,7). Disruption of a pathway involving the deep cerebellar nuclei may explain lateropulsion ( Fig. 3B). Noda and associates ( 12) have demonstrated that ipsilateral saccadic eye movements generated by stimulation of lobule VII of the cerebellar vermis result from inhibition of the ipsilateral caudal fastigial nucleus. When these fastigial nuclear cells were directly stimulated, contralateral saccades were generated. Projections from these neurons cross the midline and course through the contralateral fastigial nucleus to exit the cerebellum in the uncinate fasciculus ( hook bundle of Russell) ( 13). The fibers of the uncinate fasciculus loop around the superior cerebellar peduncle before projecting to brainstem structures, including the paramedian pontine reticular formation and adjacent rostral medullary reticular formation ( MRF) ( 14). Caudal fastigial cells have been implicated in accelerating contralateral saccades and decelerating ipsilateral ones via these projections ( 15). Exictatory burst neurons ( EBNs) in the PPRF project to ipsilateral abducens motorneurons and provide the pulse necessary for horizontal saccades. Inhibitory burst neurons ( IBNs) in the MRF project to the contralateral abducens nucleus, providing inhibition of the antagonist muscles ( contralateral lateral rectus and ipsilateral medial rectus, via the medial longitudinal fasciculus) during an ipsilateral saccade. Thus the increase in Purkinje cell activity following inferior cerebellar peduncle disruption ( 10) would inhibit the ipsilateral fastigial neurons that ultimately excite the contralateral PPRF ( EBNs) and MRF ( IBNs) and create a bias toward ipsilateral saccades ( ipsipulsion). Because many fastigial cells fire for purely vertical eye movements ( 15), this bias may also result in oblique vertical saccades. Experimental inhibition of the fastigial nucleus by the GABA agonist muscimol creates the typical pattern of saccadic lateropulsion seen in lateral medullary infarcts ( 16). When this same pathway is interrupted by a lesion in the distribution of the superior cerebellar artery, uncinate fasciculus fibers that have already crossed are involved, as well as output projections from the dentate nucleus. This results in the syndrome of contrapul-sion of saccades and ipsilateral limb ataxia described by Ranalli and Sharpe ( 17). A similar patient with contrapulsion from a rostral cerebellar infarction has been recently documented by Straube and Biittner. They attributed their findings to a lesion involving the crossed outflow pathway from the caudal fastigial nucleus ( 18). Although speculative, an interruption in this pathway ( Fig. 3B) may also account for gaze deviation with eyes closed. During fixation, burst neurons are inhibited by omnipause neurons, which cease firing during saccades and eye blinks ( 19). Therefore, eyelid closure could unmask a tonic imbalance in burst neurons associated with unilateral fastigial nucleus dysfunction. Sato and Noda ( 20) induced saccadic dysmetria in monkeys by functional decortication of the cerebellar vermis. Unilateral decortication of the vermis produced by bicuculline injections eliminates Purkinje cell inhibition and leads to increased tonic activity of the ipsilateral fastigial nucleus and ultimately increased activity of the contralateral pontine and medullary reticular formations. This resulted in ipsilateral hypometric saccades and contralateral gaze deviation, and established the role of the vermal Purkinje cells in saccadic ipsi- and contrapulsion as well as in conjugate gaze deviation. Our patient demonstrates that horizontal gaze deviation with eyes open may occasionally complicate the lateral medullary syndrome. Separate mechanisms may account for the conjugate eye de- / Nciiw- OpMlmlmol, Vol. 15, No. 1, 1995 30 D. SOLOMON ET AL. viation and ipsipulsion of saccades, although each could result from damage to the inferior cerebellar peduncle and interruption of climbing fibers: ( a) conjugate gaze deviation either from increased inhibition of the ipsilateral vestibular nucleus or possibly from decreased tonic excitation of the contralateral reticular formation, and ( b) ipsipulsion of saccades from increased inhibition of the ipsilateral fastigial nucleus. Acknowledgment: The authors would like to thank Dr. David Zee for his helpful comments. REFERENCES 1. De Renzi E, Colombo A, Faglioni P, Milena G. Conjugate gaze paresis in stroke patients with unilateral damage. Arch Neurol 1982; 39: 482- 6. 2. Baloh RW, Yee RD, Honrubia V. Eye movements in patients with Wallenberg's syndrome. Ann NY Acad Sci 1981; 600- 13. 3. Estanol B, Lopez- Rios G. 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