Monocular elevation paresis and contralateral downgaze paresis from unilateral mesodiencephalic infarction.

A 26 year old woman presented with monocular elevation paresis of the right eye, contralateral paresis of downward gaze, and subtle bilateral ptosis. Magnetic resonance imaging disclosed a unilateral embolic infarction restricted to the mesodiencephalic junction involving the left paramedian thalamus. Preserved vertical oculocephalic movements and intact Bell's phenomenon suggested a supranuclear lesion. This rare "crossed vertical gaze paresis" results from a lesion near the oculomotor nucleus affecting ipsilateral downward gaze and contralateral upward gaze fibres, originating in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF).     

Vertical one-and-a-half syndrome. Supranuclear downgaze paralysis with monocular elevation palsy

A patient with bilateral infarction in the mesodiencephalic region showed impairment of all downward rapid eye movements (including vestibulo-ocular movements) and foveal smooth pursuit (nondissociated downgaze paralysis) associated with monocular paralysis of elevation (vertical one-and-a-half syndrome). Bell's phenomenon and all types of horizontal eye movements were preserved. The lesions may have affected the efferent tracts of the rostral interstitial nucleus of the medial longitudinal fasciculus bilaterally and the premotor fibers to the contralateral superior rectus subnucleus and ipsilateral inferior oblique subnucleus, either before or after decussation in the posterior commissure.     

Unilateral midbrain infarction causing upward and downward gaze palsy.

We report on a 47-year-old-woman who developed sudden complete loss of vertical saccades, smooth pursuit, and vestibular eye movements bilaterally. MRI revealed a unilateral midbrain infarct involving the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal (INC) and spared the posterior commissure (PC). The lesion is presumed to have interrupted the pathways involved in vertical gaze just before they decussate, inducing an anatomically unilateral but functionally bilateral lesion. Previous reports of bidirectional vertical gaze palsy have shown lesions involving the PC or both riMLFs. This case is the first to show that a unilateral lesion of the riMLF and the INC that spares the PC may cause complete bidirectional vertical gaze palsy.     

Vestibulo-ocular reflex deficits with medial longitudinal fasciculus lesions

The medial longitudinal fasciculus (MLF) is the final common pathway for all conjugate adducting horizontal eye movements, as well as for the vertical–torsional vestibulo-ocular reflex (VOR). MLF lesion causes adduction paresis of ipsilesional (adducting) eye with dissociated nystagmus of contralesional (abducting) eye—the well-known clinical syndrome of internuclear ophthalmoplegia (INO). We measured the VOR stimulation and also any catch-up saccades, from individual semicircular canal (SCC) evoked by the head impulse test (HIT), using head and binocular 3-dimensional scleral search coils in 27 multiple sclerosis (MS) patients, 8 with unilateral, 19 with bilateral INO. In unilateral INO, VOR gain (normal >0.90) from ipsilesional lateral SCC stimulation was 0.48 for the adducting eye and 0.81 for the abducting eye; 0.61 from contralesional anterior SCC stimulation and only 0.29 from contralesional posterior SCC stimulation. In bilateral INO, there were VOR gain deficits from all six SCCs: lateral SCC gains were asymmetrically reduced to 0.45 in the adducting eye and 0.66 in the abducting eye; anterior SCC gain was 0.48 and posterior SCC gain was only 0.19. Horizontal VOR versional dysconjugacy between adducting and abducting eyes at 0.66 was less severe than horizontal catch-up saccade versional dysconjugacy (0.44); normal >0.80. Unexpected partial preservation of horizontal VOR with greater catch-up saccade impairment from the adducting than abducting eye suggests that the ascending tract of Deiters (ATD), an extra-MLF pathway, also mediates the horizontal VOR, but not adducting horizontal saccades. Vertical VOR deficits will produce vertical oscillopsia with any vertical head movement and measurement of the vertical VOR could help with the diagnosis and quantitative evaluation of MLF lesions in suspected MS. Horizontal VOR deficits and catch-up saccade versional dysconjugacy in INO will cause gaze instability and horizontal oscillopsia during active horizontal head movements.     

Fast eye movement initiation of ocular torsion in mesodiencephalic lesions

Three patients with episodic ocular torsion and skew deviation due to mesodiencephalic lesions were studied by using binocular three-dimensional scleral search coils. The conjugate ocular torsion (upper pole of each eye rotating toward the side of the brainstem lesion) was initiated by a torsional fast eye movement. During prolonged episodes, torsional nystagmus was also present. Cessation of the ocular torsion and skew deviation occurred by slow eye movements with exponentially decreasing velocities in 2 patients, and by multiple fast torsional movements in 1 patient. In 1 patient, the abnormal eye movements were temporally linked to dystonic movements in the limbs on the side opposite the brainstem lesion. The occurrence of skew deviation with conjugate ocular torsion in brainstem lesions has been attributed to functional asymmetry in vestibular pathways responsible for the slow-phase compensatory eye movement response to roll. In comparison, the findings in our patients show that in mesodiencephalic lesions conjugate ocular torsion with skew deviation may be generated by torsional fast eye movements, indicating activation of the burst cells of the rostral interstitial nucleus of the medial longitudinal fasciculus.     

Eye movement related neurons in the cat pontine reticular formation: projection to the flocculus

This study examines projection to the cerebellar flocculus of eye movement-related neurons in the median and paramedian part of the cat pontine tegmentum between the trochlear and the abducens nucleus. They were identified by rhythmic activity related to horizontal vestibular nystagmus induced by sinusoidal rotation. These neurons were classified into several groups by their discharge patterns during nystagmus, using criteria of earlier studies on saccadic eye movements and vestibular nystagmus in the monkey. Electrical stimulation of the ipsilateral flocculus elicited antidromic spike responses in a number of burst-tonic neurons and long-lead and medium-lead burst neurons. These neurons were located in and around the medial longitudinal fasciculus, the nucleus raphe pontis and the nucleus reticularis tegmenti pontis. A few neurons tested were also activated antidromically by stimulation of the contralateral flocculus. In contrast, no pauser neurons were activated from the ipsi-lateral flocculus. It is concluded that eye movement-related neurons in the medial pontine tegmentum, except for pauser neurons, directly project to the flocculus and may convey information about eye movements of visual and vestibular origins to the flocculus.     

A case of left third nerve palsy and contralateral vertical gaze palsy with medial midbrain infarction]

An 81-year-old man developed oculomotor nerve palsy of the left eye and vertical gaze palsy of the right eye due to left medial midbrain infarction. His left eyelid was ptotic and the pupil was dilated. His right eye showed normal horizontal movement and Bell's phenomenon was preserved although the oculocephalic reflex was incomplete. There were no other abnormal neurological findings. The brain MRI revealed a high-intensity lesion in left medial midbrain on T2 weighted image. This lesion involved the oculomotor nerve nucleus, the interstitial nucleus of Cajal, and the rostral intersititial nucleus of the medial longitudinal fasciculus (riMLF). We thought that upward gaze palsy of the right eye was resulted from the infarction of the left riMLF or disruption of the axonal collateral of upward gaze fibers in the left oculomotor nucleus. Downward gaze palsy was resulted from the damage of the downward gaze fibers before their decussation, or the damage of the left interstitial nucleus of Cajal. This case provides evidence that unilateral lesion of the midbrain could cause contralateral vertical gaze palsy.     

Ocular motor abnormalities in progressive supranuclear palsy

Eleven patients, 7 males and 4 females, of progressive supranuclear palsy (PSP) were examined neuro-otologically for the purpose of elucidating the characteristics of ocular motor abnormalities. All cases were admitted to our hospital and age at onset was from 52 to 71 years old, duration of illness was 2 to 11 years. Range of voluntary eye movements and abnormal eye movements including nystagmus were examined on naked eyes and with electronystagmography (ENG). Smooth pursuit movements and saccadic eye movements were tested both horizontally and vertically by using visual tracking method with ENG recordings. Optokinetic nystagmus test and caloric test with visual suppression test were also performed. These neurotological examinations were made repetitively in 5 cases and their progressions were observed. Vertical gaze palsy and convergence palsy were observed in all cases as the initial symptom. In this study downward gaze was more severely disturbed than upward gaze. Using ENG, saccadic eye movements (saccades) were disturbed earlier than smooth pursuit movements. Hypometric saccades and decreased saccadic velocity were common abnormalities. In the later stage of the disease, horizontal eye movements were also disturbed. In four cases bilateral adduction palsy was added to vertical gaze paralysis so that the lesion of the MLF to oculomotor nucleus was suggested to exist. These voluntary eye movements were worsened gradually as the disease progressed. By using ENG we could find so called abnormal eye movements more frequently than the previous reports. Eight patients demonstrated horizontal gaze nystagmus, and rebound nystagmus were observed in four cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Selective saccadic palsy caused by pontine lesions: clinical, physiological, and pathological correlations

Two patients suffered a selective deficit of voluntary saccades and quick phases of nystagmus after hypoxic-ischemic insults during open-heart surgery. All voluntary saccades, in both horizontal and vertical planes, were slow, and quick phases of vestibular and optokinetic nystagmus were absent. Smooth pursuit, the vestibuloocular reflex, the ability to hold steady eccentric gaze, and vergence eye movements were all preserved. Pathological studies in 1 patient confirmed neuronal necrosis and gliosis, consistent with ischemic lesions involving the median and paramedian pontine reticular formation and median basis pontis but sparing the rostral mesencephalon and rostral interstitial nucleus of the medial longitudinal fasciculus. These findings, taken with data from experimental studies, support the hypothesis that each functionally defined class of horizontal eye movements is controlled by a separate neural substrate that projects independently to the abducens nuclei. In addition, these data suggest that the rostral interstitial nucleus of the medial longitudinal fasciculus is dependent on inputs from the paramedian pontine reticular formation for the programming of normal vertical saccades.     

A case presenting vertical one-and-a-half syndrome and seesaw nystagmus due to thalamomesencephalic infarction]

A 58-year-old woman presented, conjugate upgaze palsy and monocular paresis of downward gaze in the ipsilateral eye (vertical one-and-a-half syndrome; VOHS) as well as seesaw nystagmus (SSN). Vertical oculocephalic response and conjugate horizontal gaze were preserved. Magnetic resonance imaging revealed a right thalamo-mesencephalic infarction including the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal. On the 22nd hospital day SSN was disappeared, and then on the 32nd day VOHS was improved. The lesions of VOHS may have affected the efferent tracts of riMLF and the descending fibres to the ipsilateral subnucleus of the inferior rectus and contralateral subnucleus of the superior oblique. Furthermore, it was assumed that SSN was caused simultaneously by a lesion in the interstitial nucleus of Cajal existing in the adjacent area of riMLF.     

Eye movements evoked by electrical stimualtion of the brain in anesthetized fishes.

Several eye movements were evoked by electrical stimulation of the brain in anesthetized sunfish and goldfish. Conjugate lateral rolling movements, similar to eye movements observed when an unoperated fish is rotated about its long axis, were evoked from the acoustico-lateral area of the medulla and the eminentia granularis and an adjacent medial portion of the cerebellum. Bilateral and unilateral backward rotations, similar to the eye movements observed when unoperated fish are rotated forward about the interpupillary axis, were evoked from the medial longitudinal fasciculus and areas related to the oculomotor nerve. Bilateral forward rotations, comparable to the eye movements resulting when unoperated fish are rotated backward about the interpupillary axis, were elicited by stimulation near the trochlear nerve roots in the valvula of the cerebellum; unilateral responses resulted from stimulation near the exiting trochlear nerves. Convergence was elicited by stimulation in the midline near the oculomotor complex and the medial longitudinal fasciculus while unilateral vergence responses were triggered by stimulation in the medial longitudinal fasciculus and areas lateral to the oculomotor nucleus. Conjugate eye movements in the horizontal plane were frequently evoked but were not studied in detail.     

Paresis of lateral gaze alternating with so-called posterior internuclear ophthalmoplegia. A partial paramedian pontine reticular formation-abducens nucleus syndrome

Summary A patient with multiple myeloma developed gaze paresis to the left with slowed saccades and gaze-paretic nystagmus, which alternated with abduction palsy in the left eye (with preserved oculocephalic deviation) and dissociated adducting nystagmus in the right eye, suggesting so-called posterior internuclear ophthalmoplegia. At autopsy multiple small infarcts were found with partial destruction of the left paramedian pontine reticula formation (PPRF) extending towards the abducens nucleus, which was involved only in its inferior pole. The medial longitudinal fasciculus and other oculomotor structures were spared. It is suggested that slowing of all ipsilateral saccades with gaze-paretic nystagmus corresponded to partial destruction of the PPRF, and that intermitted abduction palsy in the ipsilateral eye with adduction nystagmus in the fellow eye was due to intermittant dysfunction of the abducens nucleus. Involvement of voluntary saccades, pursuit movements and vestibulo-ocular responses may be dissociated in partial lesions of the abducens nucleus.     

A hypothetical scheme for the brainstem control of vertical gaze

OBJECTIVES: To develop a hypothetical scheme to account for clinical disorders of vertical gaze based on recent insights gained from experimental studies. METHODS: The authors critically reviewed reports of anatomy, physiology, and effects of pharmacologic inactivation of midbrain nuclei. RESULTS: Vertical saccades are generated by burst neurons lying in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). Each burst neuron projects to motoneurons in a manner such that the eyes are tightly coordinated (yoked) during vertical saccades. Saccadic innervation from riMLF is unilateral to depressor muscles but bilateral to elevator muscles, with axons crossing within the oculomotor nucleus. Thus, riMLF lesions cause conjugate saccadic palsies that are usually either complete or selectively downward. Each riMLF contains burst neurons for both up and down saccades, but only for ipsilateral torsional saccades. Therefore, unilateral riMLF lesions can be detected at the bedside if torsional quick phases are absent during ipsidirectional head rotations in roll. The interstitial nucleus of Cajal (INC) is important for holding the eye in eccentric gaze after a vertical saccade and coordinating eye-head movements in roll. Bilateral INC lesions limit the range of vertical gaze. The posterior commissure (PC) is the route by which INC projects to ocular motoneurons. Inactivation of PC causes vertical gaze-evoked nystagmus, but destructive lesions cause a more profound defect of vertical gaze, probably due to involvement of the nucleus of the PC. Vestibular signals originating from each of the vertical labyrinthine canals ascend to the midbrain through several distinct pathways; normal vestibular function is best tested by rotating the patient's head in the planes of these canals. CONCLUSIONS: Predictions of a current scheme to account for vertical gaze palsy can be tested at the bedside with systematic examination of each functional class of eye movements.     

Supranuclear vertical gaze palsy and convergence nystagmus caused by unilateral riMLF lesion]

We report a case showing supranuclear vertical gaze palsy and convergence nystagmus caused by a unilateral lesion of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). The patient was a 54-year-old female with mitral stenosis and regurgitation and atrial fibrillation, who suddenly developed vertigo and double vision. She was admitted to our hospital because of persisting diplopia 4 days after onset, although vertigo had resolved within 1 hour. On admission she was alert, but presented with supranuclear vertical gaze palsy and convergence nystagmus. Other cranial nerves were intact and motor strength, deep tendon reflexes, sensations were also normal. There were no cerebellar signs. Cranial MRI demonstrated a unilateral ischemic lesion at the left thalamo-mesencephalic junction that involved the unilateral riMLF. Cerebral angiography revealed no abnormalities. Vertical gaze palsy has been reported to be caused by a lesion involving bilateral riMLF or unilateral posterior commissure, and convergence nystagmus usually by a lesion near or within the dorsal mesencephalon. However, recent reports have demonstrated a histopathologic evidence that vertical gaze palsy was caused by unilateral riMLF lesion. The present case confirms clinically that both vertical gaze palsy and convergence nystagmus can be developed by a lesion of unilateral riMLF.     

Supranuclear vertical gaze palsy: bilateral thalamo-mesencephalic lesions demonstrated by MRI

The exact location for the major control center of the vertical gaze, which is referred to as rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF), has been documental in a few autopsy studies. However, CT in some of the case reports of vertical gaze palsy have not clearly delineated this nucleus and its nearby complex anatomical structures. Discrete small, bilateral, symmetric infarcts in the thalamo-mesencephalic junction were demonstrated by MRI in a 59-year-old female patient who had sustained vertical gaze palsy over a period of nine years. Neurological examination revealed severe supranuclear combined downward and upward vertical gaze palsy, incomplete convergence, and slight limitation in adduction of the right eye. There was neither ptosis, pupillary disturbance, nor any further abnormalities of horizontal eye movements. The vertical vestibulo-ocular reflex was maintained, being similar to the other reported cases of vertical gaze palsy. MRI has advantages over CT in demonstrating lesions in the thalamo-mesencephalic junction in the cases of vertical gaze palsy, because clearer sagittal images can be obtained.     

From the abducens nucleus to spatial memory: an ocular motor journey

Advances in our knowledge on eye movements over the last 25 years are reviewed, focusing on the author's experience. First, the advantages of binocular frontal vision, which is a common characteristic of all predator mammals, are compared to those of lateral vision, characterizing their preys. Binocular frontal vision implies a perfect parallelism of both eyes, which is ensured in the pons by means of the abducens nucleus, controlling abduction as well as adduction. The pathological example of the "one-and-a-half" syndrome, in which the abducens nucleus and the adjacent medial longitudinal fasciculus are simultaneously impaired, is described. The main brainstem syndromes involving vertical eye movements are also reviewed: in particular, the third nerve nucleus syndrome, in which both ipsilateral third nerve paralysis and contralateral superior rectus paralysis (with hypotropia) result from a unilateral third nerve nucleus lesion. A case of upbeat nystagmus (in the primary position of gaze) due to a small upper pontine lesion, probably affecting the ventral tegmental tract (VTT) is also reported. This is an opportunity to emphasize that, although a number of cases of upbeat nystagmus due to focal brainstem lesions affecting the upward vestibular pathway (UVP)--either at the upper pontine (VTT) or caudal medullary level--exist in the literature, no convincing cases with downbeat nystagmus (in the primary position of gaze) due to a focal brainstem lesion have been reported. Downbeat nystagmus could result from a UVP hyperactivity (secondary to a floccular lesion) and the notion that this pathway is physiologically predominant compared to the downward pathway, maybe due to gravity, is developed. A new hypothesis about the role of the caudal medulla in UVP is also proposed. Next, the cortical control of saccadic eye movements is reviewed, with a reminder that reflexive saccades are mainly triggered by the parietal eye field whereas intentional saccades depend upon the frontal eye field. The inhibition of reflexive saccades is mainly controlled by the dorsolateral frontal cortex (DLPFC), i.e. area 46 of Brodmann. A few examples of the use of saccades as a research tool and model in cognitive neurosciences are given. The use of memory-guided saccades allowed us to study spatial memory and led us to propose a relatively original conception of the cortical control of spatial memory in which the DLPFC, the parahippocampal cortex and the hippocampal formation could be involved successively according to specific periods of time. An experiment using functional magnetic resonance imaging in a paradigm studying decision is described, again with the involvement of the DLPFC in the decisional process. Lastly, the usefulness of eye movements in clinical neuro-ophthalmology at the bedside as well as in neurophysiological or even neuropsychological research in the laboratory is emphasized.     

Reflex vertical gaze and the medial longitudinal fasciculus

Extraocular movements were investigated in a patient with bilateral vascular lesions of the medial longitudinal fasciculus. The patient showed voluntary and reflex horizontal gaze consistent with his lesion, but had absent reflex vertical gaze. Voluntary vertical gaze was present. Necropsy was performed, and the findings suggest that the medial longitudinal fasciculi in the pons conveys impulses for reflex vertical gaze, but are not required for voluntary vertical gaze.     

The one-and-a-half syndrome--a unilateral disorder of the pontine tegmentum: a study of 20 cases and review of the literature

The one-and-a-half syndrome is a clinical disorder of extraocular movements characterized by a conjugate horizontal gaze palsy in one direction plus an internuclear ophthalmoplegia in the other. The syndrome is usually due to a single unilateral lesion of the paramedian pontine reticular formation or the abducens nucleus on one side (causing the conjugate gaze palsy), with interruption of internuclear fibers of the ipsilateral medial longitudinal fasciculus after it has crossed the midline from its site of origin in the contralateral abducens nucleus (causing failure of adduction of the ipsilateral eye). Twenty cases are reported; 14 had multiple sclerosis.     

Complete bilateral horizontal gaze paralysis disclosing multiple sclerosis

Two women presented with bilateral internuclear ophthalmoplegia evolving in a few days to complete bilateral horizontal gaze paralysis. Convergence and vertical eye movements were normal. Cerebral MRI showed a few small white matter lesions in the lateral ventricle regions, and, at the brainstem level, a single, small, bilateral lesion affecting the posterior part of the medial pontine tegmentum and responsible for the clinical syndrome. The condition gradually improved in both patients, following a similar progression as at the onset: improvement first involved the adduction movements in both eyes, whereas bilateral abduction paresis still persisted for a few weeks, before complete recovery of eye movements. Bilateral damage to the medial longitudinal fasciculus and subsequent lateral extent of damage to the region of the two abducens emerging fibres may explain the clinical findings. In both cases, the cause was probably multiple sclerosis.     

Failure of downward gaze: the site and nature of the lesion.

We report four patients with paralysis of downward gaze but with intact upward gaze, including one with detailed clinico-pathological studies and another with a focal computerized axial tomographic (CT) scan abnormality confirming the presence of bilateral lesions of the dorsomedial red nucleus, including the fasciculus retroflexus. It is suggested that sudden, permanent selective failure of downward gaze accompanied by transient disturbance of consciousness is an embolic syndrome of the posterior thalamosubthalamic or rubral artery.