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.     

Palsy of upward and downward saccadic, pursuit, and vestibular movements with a unilateral midbrain lesion: pathophysiologic correlations

Upward and downward gaze palsy was measured by a magnetic search coil technique and correlated with neuropathologic findings in a patient with a unilateral midbrain infarct. Oculography demonstrated (1) saccadic palsy above primary position and slow, limited vertical saccades below; (2) low-gain, restricted vertical pursuit; and (3) low-gain, abnormal phase lead, and restricted range of the vertical vestibulo-ocular reflex (VOR). Bidirectional palsy of vertical saccades is attributed to unilateral loss of burst cells in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and interruption of burst cell fibers from the opposite riMLF. Pathways mediating vertical pursuit and integration of the vertical VOR also traversed the infarct, which included the interstitial nucleus of Cajal.     

Localizing value of torsional nystagmus in small midbrain lesions

BACKGROUND: The topodiagnostic value and specificity of nystagmus in patients with mesencephalic lesions and its relation to tonic torsional deficits and vertical saccade deficits is controversial and anecdotal. METHODS: The authors examined 11 patients with vascular MRI-identified mesencephalic lesions and clinical evidence of vertical-torsional nystagmus on gaze straight ahead, focusing on the three-dimensional nystagmus components recorded with the three-dimensional search coil technique. RESULTS: Combined lesions of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal (iC) are much more frequent than riMLF and, in particular, iC lesions alone. Eight patients showed contralesional torsional nystagmus with a conjugate vertical component on gaze straight ahead and had anatomic (MRI) and clinical evidence (slowing of vertical saccades) for riMLF involvement. Tonic ocular torsion and the subjective visual vertical were shifted to the contralesional side (n = 7). Torsional nystagmus to the ipsilesional side was uncommon (n = 3) and found in patients with midbrain lesions involving the iC, all of whom also had decreased time constants of the slow phases of gaze-evoked nystagmus. CONCLUSIONS: Contrary to previous proposals, contralesional torsional nystagmus was the most frequent direction and is probably not compensatory for contralesional tonic ocular torsion. Small amplitude vertical saccades with normal velocities in association with ipsilesional torsional nystagmus may indicate isolated iC lesions. Torsional nystagmus following mesencephalic lesions may last for years and may help to distinguish rostral (riMLF) from caudal (iC) midbrain lesions.     

Vertical gaze palsy and selective unilateral infarction of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF).

We report a clinico-pathological correlation study in a patient with basilar artery thrombosis, who developed tetraplegia and combined up- and downgaze palsy involving voluntary saccades and visually-guided movements, but sparing the oculocephalic responses. At necropsy, apart from bilateral infarction in the basis pontis, there was a single unilateral infarct selectively destroying the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) on the right. The posterior commissure and its nucleus, the nucleus of Cajal, the nucleus of Darkschewitsch and the pontine tegmentum were spared. We suggest that the unilateral riMLF lesion may have disrupted bilateral upgaze excitatory and inhibitory inputs and unilateral downgaze excitatory inputs. The functional anatomy of inhibitory and excitatory vertical gaze circuitry, which remains speculative, may explain why a unilateral lesion of the upper midbrain tegmentum may be sufficient to generate an upgaze palsy or a combined up- and downgaze palsy, while an isolated downgaze palsy requires bilateral lesions.     

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.     

Premotor circuits controlling eyelid movements in conjunction with vertical saccades in the cat: I. The rostral interstitial nucleus of the medial longitudinal fasciculus

Saccadic eye movements in the vertical plane are controlled by the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and the interstitial nucleus of Cajal. Eye movements in the vertical direction are accompanied by concurrent upper eye lid movements. These gaze-related lid movements are produced by the levator palpebrae superioris muscle, whose motoneurons are located in the caudal central subdivision (CCS) of the oculomotor nucleus. The neural circuits that direct such gaze-related lid movements were examined by use of both conventional and dual neuronal tracing methods in the cat. Injections of wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) into the area of the CCS revealed a distinctive subset of retrogradely labeled neurons located in the caudomedial portion of the riMLF. This subset of riMLF neurons was not labeled when injections were localized within the oculomotor nucleus proper, without involving the CCS. Injections of biotinylated dextran amine (BDA) that included this caudomedial riMLF region anterogradely labeled axons that projected profusely throughout the CCS. Labeled terminals were seen in close association with retrogradely labeled levator palpebrae motoneurons, which were primarily found contralateral to WGA-HRP muscle injections. Ultrastructural examination revealed that most BDA-labeled terminals contained clear spherical vesicles and formed asymmetrical synaptic contacts, primarily on the proximal dendrites of WGA-HRP-labeled motoneurons. A few had pleiomorphic vesicles. In summary, these results strongly suggest that the caudomedial part of the cat riMLF is a premotor center that monosynaptically controls lid movements in conjunction with vertical saccades.     

Premotor neurons for vertical eye movements in the rostral mesencephalon of monkey and human: Histologic identification by parvalbumin immunostaining

In the monkey, premotor neurons for vertical gaze are located in the mesencephalic reticular formation: the rostral interstitial nucleus of the medial longitudinal fascicle (riMLF) contains medium-lead burst neurons, and the interstitial nucleus of Cajal (iC) acts as integrator for the eye-velocity signals to eye-position signals. Both nuclei lie adjacent to each other and are similar in appearance at the transition zone in Nissl-stained sections, which makes a delineation of the functionally different nuclei difficult in human. For a neuropathologic analysis of degenerative changes in saccadic disorders of patients, the histologic identification of the riMLF and the iC is important. The aim of this study is to identify both nuclei in human by using parvalbumin as a histologic marker. First, in monkeys the premotor neurons in riMLF and iC were identified by trans-synaptic labelling after injections of tetanus toxin fragment C into vertical-pulling eye muscles. Premotor neurons were found in the riMLF mainly ipsilateral to the corresponding eye muscle motoneurons and on both sides within the iC, but here the labelled cell populations differed: the contralateral side contained more medium-sized cells compared with the mainly small-sized cell population on the ipsilateral side. Double labelling showed that almost all premotor neurons in the iC and all premotor neurons in the riMLF were parvalbumin-immunoreactive. The immunocytochemical staining of human brainstem sections revealed the riMLF as a cluster of medium-sized, elongated parvalbumin-positive cells, with a similar appearance and at a similar location as that in monkey: a wing-shaped nucleus dorsomedial to the red nucleus, rostral to the traversing tractus retroflexus, dorsally bordered by the thalamo-subthalamic paramedian artery. The adjacent iC could be distinguished easily by its more densely packed, round parvalbumin-immunoreactive neurons. The exact identification of premotor neurons of the vertical system in the normal human brain provides a reference basis for the neuropathologic analysis of vertical gaze disorders at a cellular level. J. Comp. Neurol. 392:413–427, 1998. © 1998 Wiley-Liss, Inc.     

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).     

Vestibular syndromes in the roll plane: Topographic diagnosis from brainstem to cortex

Central vestibular syndromes may be classified according to the three major planes of action of the vestibuloocular reflex, secondary to a lesional tone imbalance in either the horizontal yaw plane or the vertical pitch or roll plane. The clinical signs, both perceptual and motor, of a vestibular tone imbalance in the roll plane are ocular tilt reaction (OTR), ocular torsion, skew deviation and tilts of the perceived visual vertical (SVV). Either complete OTR or skew torsion without head tilt indicates a unilateral peripheral deficit of otolith input or a unilateral lesion of graviceptive brainstem pathways from the vestibular nuclei (crossing midline at the pontine level) to the interstitial nucleus of Cajal (INC) in the rostral midbrain. SVV tilts are the most sensitive sign of a vestibular tone imbalance in roll and occur with peripheral or central vestibular lesions from the labyrinth to the vestibular cortex. All tilt effects, perceptual, ocular motor and postural, are ipsiversive (ipsilateral eye undermost) with unilateral peripheral or pontomedullary lesions below the crossing of the graviceptive pathways. All tilt effects are contraversive (contralateral eye undermost) with unilateral pontomesencephalic brainstem lesions and indicate involvement of the medial longitudinal fasciculus or the rostral midbrain (INC). Unilateral lesions of vestibular structures rostral to the INC typically manifest with deviations of perceived vertical without concurrent eye–head tilt. OTR in unilateral paramedian thalamic infarctions indicates simultaneous ischemia of the paramedian rostral midbrain including the INC. Unilateral lesions of the posterolateral thalamus can cause thalamic astasia and moderate ipsiversive or contraversive SVV tilts, thereby indicating involvement of the vestibular thalamic subnuclei. Unilateral lesions of the parietoinsular vestibular cortex cause moderate, mostly contraversive SVV tilts. An SVV tilt found with monocular but not with binocular viewing is typical for a trochlear or oculomotor palsy rather than a supranuclear graviceptive brainstem lesion.     

Slow vertical saccades in motor neuron disease: Correlation of structure and function

We studied eye movements and brainstem pathology in 2 patients with slow vertical saccades and autopsy-proven amyotrophic lateral sclerosis (ALS). In both patients, the main ocular motor finding was supranuclear vertical gaze impairment with slow vertical saccades. The second patient had difficulty opening his eyes on command, with preserved spontaneous eyelid opening. Postmortem examination in both patients demonstrated cell loss in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and substantia nigra, along with histopathological findings consistent with ALS. The extent of the pathological changes in the riMLF corelated well with the degree of functional impairment as reflected in the slow vertical saccades. We suggest that motor neuron disease with early involvement of vertical saccades represents a distinct clinicopathological entity.     

Impairment of vertical motion detection and downgaze palsy due to rostral midbrain infarction

Summary We present two cases with acute onset of vertical gaze palsy, mainly consisting of impaired downgaze and apraxia of downward head movements, together with neuropsychological deficits (hypersomnia, impaired attention and disorders of memory and affective control). CT and MRI revealed bilateral post-ischaemic lesions in the dorsomedial thalamus and the mesodiencephalic junction, dorsomedial to the red nucleus, thus being restricted to the territory of the posterior thalamosubthalamic paramedian artery, which includes the region of the rostral interstitial nucleus of the medial longitudinal fascicle as the main premotor nucleus for the generation of vertical saccades. In our patients, oculographic examination with electro-oculography and magnetic search coil recording showed severe impairment of downward more than upward saccades and only minor deficits of vertical pursuit and the vestibulo-ocular reflex. Visual functions were normal, with one exception: a psychophysical test of motion perception revealed a significant deficit in the detection of vertical movements. This could be due to a central adaptive mechanism which, in order to minimize oscillopsia, might elevate thresholds for vertical motion perception in cases of vertical gaze palsy. As an alternative explanation, lesions within the midbrain tegmentum could have damaged subcortical visual pathways involved in motion perception.     

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.     

Rapid eye movement generation in the primate. Physiology, pathophysiology, and clinical implications

The trajectories of rapid eye movements are usually described in a Cartesian coordinate frame with a horizontal, vertical and torsional component. The sensory to motor coordinate transformations for horizontal components of rapid eye movements can be localized to neurons of the paramedian pontine reticular formation (PPRF), where long-lead and short-lead burst neurons are found. The equivalent area for recoding of vertical and torsional movement components is situated in the rostral interstitial nucleus of the MLF (rostral iMLF). Pause cells in caudal midline structures of the PPRF help to coordinate the various movement components. Experimental inactivation of these different neuron population lead to palsies of rapid eye movement generation. A unilateral PPRF lesion leads to a loss of all horizontal rapid eye movements towards the ipsilateral side. A bilateral PPRF lesion involving caudal midline structures leads to a bilateral horizontal gaze palsy in addition to a severe disruption of vertical and torsional eye movements. A bilateral rostral iMLF lesion leads to a loss of all rapid eye movements with a vertical or torsional movement component. A unilateral iMLF lesion leads to a loss of all rapid eye movements with an ipsilateral torsional component.     

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.     

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.     

Dorsal midbrain syndrome: clinical and oculographic findings

We report clinical and oculographic findings in seven patients with the dorsal midbrain syndrome (Parinaud's syndrome). All presented with limited upward voluntary gaze and convergence nystagmus with attempted upward voluntary gaze. Quantitative analysis of vertical eye movements documented characteristic abnormalities of saccades with relative preservation of reflex eye movements (ie, vestibular, optokinetic, and visual-vestibular). Vertical saccade velocity was only slightly decreased in five patients with tumors, indicating that the vertical burst neurons in the mesencephalic reticular formation and their efferent pathways to the oculomotor neurons were minimally damaged. On the other hand, two patients with probable brainstem encephalitis exhibited marked slowing of vertical saccades, indicating that the burst neurons, or their efferent pathways to the oculomotor neurons, were severely damaged.     

Immunohistochemical localization of neurotransmitters utilized by neurons in the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) that project to the oculomotor and trochlear nuclei in the cat

The rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) contains excitatory and inhibitory burst neurons that are related to the control of vertical and torsional eye movements. In the present study, light microscopic examination of the immunohistochemical localization of amino acid neurotransmitters demonstrated that the riMLF in the cat contains overlapping populations of neurons that are immunoreactive to the putative inhibitory neurotransmitter γ-aminobutyric acid (GABA) and the excitatory neurotransmitters glutamate and aspartate. By using a double-labelling paradigm, GABA-, glutamate-, and aspartate-immunoreactive neurons in the riMLF were retrogradely labelled by transport of horseradish peroxidase (HRP) from the oculomotor and trochlear nuclei. Electron microscopy showed that the oculomotor and trochlear nuclei contain synaptic endings that are immunoreactive to GABA, glutamate, or aspartate. Each neurotransmitter-specific population of synaptic endings has distinctive ultrastructural and synaptic features. Synaptic endings in the oculomotor and trochlear nuclei that are anterogradely labelled by transport of biocytin from the riMLF are immunoreactive to GABA, glutamate, or aspartate. Taken together, the findings from these complimentary retrograde and anterograde double-labelling studies provide rather conclusive evidence that GABA is the inhibitory neurotransmitter, and glutamate and aspartate are the excitatory neurotransmitters, utilized by premotor neurons in the riMLF that are related to the control of vertical saccadic eye movements. © 1996 Wiley-Liss, Inc.     

Gaze holding defect induced by injections of ketamine in the cat brainstem.

The signal responsible for horizontal gaze holding is known to be generated, at least in part, by the prepositus hypoglossi (PH) nucleus, whereas that responsible for vertical gaze holding is known to be generated by the interstitial nucleus of Cajal (INC). An intramuscular injection of ketamine was recently demonstrated to induce a gaze holding failure. The aim of the present study was to analyse if ketamine produced this effect by acting, at least in part, on the PH nucleus. We found that a unilateral injection of a small amount of ketamine in the PH nucleus could cause either bilateral horizontal gaze holding failure or a vertical gaze holding failure or both an horizontal and a vertical gaze holding failure.     

Brainstem findings in Huntington's disease. Possible mechanisms for slow vertical saccades

Quantitative, morphometric studies of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) were performed on the brains of four patients with Huntington's disease (HD) who had shown slow vertical saccades, and on the brains of three control subjects. Only one HD brain showed a statistically significant decrease in the number of larger neurons in the riMLF though all four brains showed non-specific gliosis. Taken with results from physiological and other clinical studies, the present data suggest that slow vertical saccades in HD are due, at least in part, to disordered inputs to the riMLF.