As discussed above, vertical gaze occurs after stimulation of both cerebral hemispheres and later activation of midbrain nuclei and pathways. Therefore, abnormalities of vertical gaze should raise the question of a midbrain lesion or bilateral cerebral hemisphere dysfunction. Unilateral or bilateral lesions in the midbrain may result in abnormal vertical gaze. Elderly people may have difficulty with up gaze in a nonspecific manner; if this symptom occurs in isolation, without other neurologic signs or symptoms, it does not require further evaluation.
In general, lesions of the dorsal midbrain can result in up-gaze paresis, and lesions in the ventral midbrain preferentially affect down gaze. Examples of bilateral cerebral dysfunction that result in vertical-gaze palsies include Parkinson's disease, progressive supranuclear palsy, and certain lipidosis.
Dorsal Midbrain Syndrome (Parinaud Syndrome)
The dorsal midbrain contains pathways for both up gaze and pupillary constriction to light. The dorsal midbrain syndrome con. sists of (a) poor-to-absent up gaze, (b) position pupils with light-near dissociation, and (c) convergence-retraction nystagmus, The most common cause of this syndrome in compression, occurring either from mass lesions in the pineal region (Fig. 15.6) or dilation of the third ventricle from hydrocephalus. Increased intracranial pressure is usually present, causing papilledema. Other causes of this syndrome include midbrain infarction, multiple sclerosis, arteriovenouti malformation, and infections.
Figure 15.6. Meningioma of the pineal gland causing indentation of the dorsal midbrain. Compression of the dorsal midbrain leads to Parinaud syndrome. (From Schochet SS Jr, Nelson J. Atlas of Clinical Neuropathology. Norwalk, CT: Appleton & Lango, 1989. Used with permission of the publisher.)
Convergence-retraction nystagmus, it unique part of Parinaud syndrome, is seen best when the patient attempts to saccade up. On attempted fast up-gaze, the eyes pull in and the globes retract. Electromyography of the eye muscles in patients with this disorder has shown cocontraction of the oculomotor innervated muscles, resulting in retraction of the globes. Rarely, divergence-retraction nystagmus is seen instead of convergence-retraction nystagmus. The easiest way to bring out convergence-retraction nystagmus is to ask the patient to follow down-going stripes on an optokinetic drum; this maneuver will elicit convergence-retraction nystagmus in place of up-going saccades.
Other signs of dorsal midbrain dysfunction are lid retraction (Collier's sign) and conjugate down-gaze in the primary position ("setting-sun sign"). Neurosurgeons see these signs most commonly in patients with failed ventriculoperitoneal shunts with rapid reappearance of hydrocephalus.
Any patient with the dorsal midbrain syndrome should have a neuroimaging scan to look for an anatomic lesion. If a lesion is present, surgical treatment may result in resolution of the ocular findings.
Progressive: Supranuclear Palsy
Progressive supranuclear palsy (PSP) is a disorder of the basal ganglia resembling Parkinson's disease, with bradykinesia and rigidity. PSP patients differ in that they have marked rigidity of the trunk and neck, very little tremor, and a lack of response to parkinsonian drugs. They initially have difficulty with vertical eye movements, down more than up; the disorder progresses to involve horizontal gaze. The end-stage of PSP is a global ophthalmoplegia. Oculocephalic maneuvers or calorics can drive the eye movements, confirming the supranu-clear origin of this gaze palsy.
Vertical-gaze abnormality is common in patients with Parkinson's disease. This is usually an up-gaze palsy affecting saccades first and pursuit later. Saccades in other gazes can be slow, and the smoothness of pursuit disrupted, causing "cogwheel pursuit" in which the movement breaks into observable small saccades. Usually the gaze palsies in Parkinson's disease do not progress to total ophthalmoplegia as in PSP.
Vertical supranuclear ophthalmoplegia has been observed in patients with a lipid-storage disease that is a variant of Niemann-Pick disease. The patients present with a history of a progressive dementia beginning in late childhood, choreoathetosis, and hepatosplenomegaly. Ocular motility testing reveals inability to move the eyes vertically using saccades. Pursuit may remain until later. Intact vertical oculocephalic maneuvers confirm the supranuclear location.
Involvement of the central nervous system by Whipple's disease can lead to supranuclear gaze paralysis that is initially vertical. The patients develop a progressive dementia, hypersomnia, and ataxia. Uveitis has been seen in some patients. A history of malabsorption and diarrhea may or may not be present. Patients with acquired immunodeficiency syndrome (AIDS) have an increased incidence of Whipple's disease.
Magnetic resonance imaging (MRI) reveals areas of increased signal on T2-weighted images in the diencephalic-midbrain region. Occasionally, the spinal fluid will contain PAS-positive macrophages. If Whipple's disease is suspected, a small-bowel biopsy should be done. Recommended treatment of Whipple's disease is either chloramphenicol or trimethoprim-sulfamethoxazole.
Monocular Elevation Paresis
In monocular elevation paresis, the patient has no ocular deviation in primary gaze but has an inability to elevate one eye. The lesion, in the pretectum, involves the connection of the riMLF to the oculomotor nuclei. The oculocephalic maneuver is normal; forced ductions and Tensilon tests are negative, confirming the supranuclear origin. This condition may be congenital or acquired and may be mimicked by muscle diseases such as thyroid ophthalmopathy, myasthenia gravis, and chronic progressive external ophthalmoplegia.
The patient with a skew deviation has a vertical deviation of the eyes in primary gaze and notices vertical diplopia. The vertical tropia may be comitant or noncomitant, but unlike acute cranial nerve palsies, no primary or secondary deviations are present. Skew deviation denotes posterior fossa disease and is nonspecific for etiology and location. If an internuclear ophthalmoplegia (INO) is also present, the lesion causing the skew is usually ipsilateral to the INO, with the ipsilateral eye being hypertropic. In cases without an INO, the hypotropic eye usually is ipsilateral to the lesion (84% in one study). Isolated skew deviation in neonates may be a harbinger of horizontal strabismus.
Ocular Tilt Reaction
In ocular tilt reaction—a rare disorder related to skew deviation—the patient has a skew deviation, torsion of the eyes in the direction of the hypotropic eye, and a head tilt in the same direction. This condition may occur episodically or persist. Reported causes include lesions in the subthalamus, midbrain, and medulla, and, less commonly, peripheral vestibular disease. The otolith pathways appear to be involved, producing this unique triad of findings. Baclofen has been used in some patients with benefit.
An isolated inability to look down can occur in patients with infarcts in the pretectum affecting the riMLF. Some patients with basal ganglia disorders, such as progressive supranuclear palsy, initially have down-gaze paresis. In progressive supranuclear palsy, the extrapyramidal findings are the clue that bilateral hemispheric dysfunction is responsible.
Conjugate Downward Deviation of the Eyes
The patient who presents with acute onset of conjugate downward deviation of the eyes has dysfunction in the pretectum. The level of consciousness often is impaired as the result of involvement of the reticular activating system. Transient downward gaze can occur as a benign condition in neonates. A careful neurologic evaluation of these babies should be done to eliminate more serious conditions.