Supranuclear Paralysis of Upgaze;
Convergence Retraction Nystagmus;
Vertical Oculocephalic Reflex Normal;
Wray, Shirley H.
Shirley H. Wray, MD, PhD, FRCP, Professor of Neurology, Harvard Medical School; Director, Unit for Neurovisual Disorders, Massachusetts General Hospital
Supranuclear Paralysis of Upgaze Hemorrhage;
Convergence Retraction Nystagmus;
Vertical Oculocephalic Reflex Normal;
Light/Near Dissociation of the Pupils;
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The patient is a 49 year old woman who was in good health until January 17, 1991. When, at work one morning, she had an acute attack of light headedness and double vision and collapsed on the floor without loss of consciousness. She developed a severe retro-orbital headache.
She was taken to the local hospital and admitted. After five days she was transferred to the Massachusetts General Hospital (MGH) for cerebral angiography.
Negative for hypertension or recent trauma.
On no medications.
Negative for CNS disease or bleeding dyscrasias
On admission to the MGH, she had mild headache and vertical double vision.
Blood pressure 120/80, pulse 84 regular.
Normal mental status
Visual acuity 20/20 OU
Pupils 5 mm OU reacting sluggishly to light and brisk to accommodation.
Supranuclear paralysis of upgaze
The remainder of the cranial nerves normal
Strength 5/5 bilaterally
Reflexes: 2+ symmetrical with flexor plantar responses down.
1/22/91 Neuro-Ophthalmology Consult:
Visual acuity J2 OU with reading glasses.
Visual fields and fundus examination normal
Pupils 5 mm OU, sluggish to light, brisk to near.
Light/near dissociation of the pupils.
No lid retraction
Supranuclear saccadic upgaze palsy
Full horizontal and downgaze
Normal vertical pursuit
Convergence retraction nystagmus on upgaze
Convergence retraction nystagmus in primary gaze when the eyes return to central position from gaze right, left or down.
Skew deviation - right eye hypotropic. No head tilt
Vertical oculocephalic reflex normal
Deviation of the eyes up under closed lids (Bell’s phenomenon)
Hematocrit, white blood cell count
PT and PTT normal.
1/28/91 Brain MRI:
Axial T2W images showed a high signal intensity in the right dorsal midbrain immediately adjacent to the cerebral aqueduct.
Axial GRE (T2* scan) showed the lesion ‘blooms’ and contains blood degradation products extending from the midline to the right lateral colliculus area.
(Figures 1 and 2)
Impression: Subacute hemorrhage with bright signal arising from met-hemoglobin products.
1/25/91 A right cerebral angiogram was done, with selective injections of the left internal carotid artery (ICA) and right vertebral artery (VA).
The right VA showed no evidence of arteriovenous shunting or focal vascular abnormality.
The left ICA demonstrated a fetal type posterior cerebral artery without any focal abnormalities.
By January 31, 1991 the skew deviation had resolved and the patient had no double vision. She was also headache free and ready to go home.
She was cautioned never to take aspirin or other medications that might impair coagulation of the blood.
The residual neurological findings were:
1. Supranuclear saccadic upgaze palsy
2. Convergence retraction nystagmus
3. Light/near dissociation of the pupils
She was followed up at six monthly intervals for two years and then annually.
In 1993 following a syncopal attack at work, she returned for repeat imaging studies.
12/8/93 MRI pre and post gadolinium and axial magnetic susceptibility images were performed. Within the posterior right midbrain there was a 5 mm heterogeneous focus of signal abnormality manifested by low T1 signal intensity and central bright T2 signal intensity with a peripheral rim of dark signal intensity. A subtle area of enhancement was noted at the anterior medial margins suggesting granulation tissue.
Old right midbrain hemorrhage without interval change consistent with a cavernous angioma.
In Jan 1994 in an effort to prevent a second midbrain bleed, a consultation was obtained from the MGH Intervention Neuroradiologist, Dr. In Sup Choi.
Dr. Choi reviewed the radiological studies and found no dilated blood vessels surrounding the lesion and suspected that the patient hemorrhaged from a small cavernous angioma (CA) as the CA was deep and the patient asymptomatic apart from the inability to look up, he recommended no further studies or procedures.
In 1996, at her last visit, the neuron-ophthalmic signs were unchanged.
This 49 year old woman with the pretectal syndrome from a right dorsal midbrain hemorrhage had:
• Supranuclear saccadic upgaze palsy
• Full horizontal and downgaze
• Normal vertical pursuit
• Convergence retraction nystagmus on attempted upgaze
• Convergence retraction nystagmus in primary gaze when the eyes returned to central position
• Prominent lid retraction on upgaze
• Convergence normal.
• Optokinetic nystagmus (OKN) with stripes down provoked bursts of convergence retraction nystagmus
• Normal oculocephalic reflex tested by passive head flexion and extension whilst fixating on a near target.
The pretectal dorsal midbrain syndrome is known by a variety of names, Parinaud’s syndrome, Koeber-Salus-Eischnig syndrome, and the Sylvian aqueduct syndrome and is due to a lesion of the posterior commissure and the nucleus of the posterior commissure (nPC).
Parinaud’s syndrome is characterized by:
1. Supranuclear upgaze palsy
2. Light/near dissociation of the pupils and
3. Paralysis of convergence
Classic descriptions of nystagmus in the pretectal syndrome report :
1. Pure retraction nystagmus (nystagmus retractorius,)
2. Pure convergence nystagmus and
3. The two combined
Barrani reported a case with unilateral retraction nystagmus associated with convergent nystagmus of the contralateral eye. Both phenomena have been reported to occur intermittently in the same eye with lesions in the rostral midbrain.
Convergence retraction nystagmus is perhaps the most distinctive pretectal phenomenon. Convergence retraction nystagmus may be present before upward gaze becomes grossly limited. With every attempt to make an upward saccade, the eyes first jerk inward several times then diverge again. When the phenomenon is pronounced, any saccadic attempt, horizontal or vertical, causes a convergent jerk of the eyes followed by a slower divergent drift back to the parallel position.
Atkin and Bender used the term lightening eye movements to describe bursts of rapid, small amplitude movements seen on attempted upgaze. Patients with such signs complain of slowness in focusing and difficulty reading.
When convergent eye movements distort horizontal saccades, the result in limitation of abduction mimics partial abducens nerve palsy, so called pseudo-abducens palsy of upper midbrain lesions. Oculocephalic or caloric stimulation usually produces full abduction and thereby resolves the question of paresis.
Gowers was the first to report pupillary areflexia and upgaze palsy from a pathologically confirmed case of pinealoma.
Interestingly, in Parinaud’s report two years later, the pupils were small and recorded as nonreactive to convergence, while light reactions were retained.
In our experience, and in the reports of others, light-near dissociation of the pupillary light reflexes occurs frequently.
The pupils are moderately dilated and poorly reactive to direct light while pupillary constriction to near is retained. This type of pupil abnormality has been called Argyll-Robertson, but it differs from classic Argyll-Robertson pupils by virtue of lack of miosis and the normal response to atropine.
The afferent fibers of the pupillary light reflex pass from the optic tract to the pretectum, where they decussate, in part, through the posterior commissure before reaching reticular cells surrounding the Edinger-Westphal nucleus. Light reflex abnormality is frequently present in patients with pineal tumors. Control signals for accommodation coming from the striate and peristriate cortex, are usually spared as they transverse the posterior capsule, and reach the EW nucleus from below.
Electronic infrared pupillographic studies, however, have shown that pineal region tumors impair both light and near responses and that true light-near dissociation is rare.
Impaired sympathetic pupillary control is equally rare.
Alternating contraction anisocoria is another pupillary syndrome of the anterior midbrain. This syndrome is characterized by greater pupillary constriction in the directly stimulated eye than in the consensually reacting pupil a subtle sign of minimal pretectal impairment.
Corectopia or displaced pupil may be a permanent or transient sign.
Selhorst et al in a case of midbrain corectopia with bilateral rostral midbrain infarction observed the pupils to dilate spontaneously, independently and eccentrically. Sporadic cycles of dilation and constriction, each lasting 5 to 15 minutes, occurred during the last 3 days of the patient’s life. The aperture expanded irregularly to an oval shape. The pupils independently shifted off-center, upward and outward in the right eye and downward and outward in the left eye. Then the pupils reconstricted, became round, and returned to the center.
Autopsy in this case disclosed isolated but intact EW nuclei and the explanation of midbrain corectopia by the authors centered on the segmental innervation of the pupil by the EW nucleus. In the presence of a paralyzed dilator muscle, select, central inhibition of sphincter tone resulted in oval and eccentric pupils.
Paralysis of Convergence:
Paralysis of convergence is the third sign completing the triad of Parinaud’s syndrome. The syndrome of convergence palsy is characterized by failure of convergence with crossed diplopia when the eyes view a near target but with absence of paresis of the medial recti and lateral gaze. Although the anatomic substrates for convergence, vertical gaze, and pupillary reaction lie in the same vicinity in the midbrain, convergence is often retained when only supranuclear upgaze is involved. Convergence is usually absent when supranuclear downgaze palsy is added.
Skew deviation has been attributed to unilateral or incomplete bilateral destruction of the medial longitudinal fasciculus (MLF) and the disruption of the otolith-ocular pathway from the utricle in the inner ear to the INC in the midbrain.
Lesions in the midbrain and interstitial nucleus of Cajal may present with a sustained contralesional ocular tilt reaction (OTR). Eye movement abnormalities in OTR are:
1. Skew deviation (e.g. hypotropia of the right eye in right OTR)
2. Ocular torsion with upper poles of the eyes rotated towards the lower ear (e.g. in right OTR, excyclotorsion of the right eye and incyclotorsion of the left eye) and
3. Head tilt (e.g. right head tilt in right OTR).
Acutely, there may be associated torsional nystagmus. Deviation of the subjective visual vertical (e.g. tilting of the subjective visual vertical to the right in right OTR).
Skew deviation was present in 5 of 22 of my cases of pinealoma and in one reported by Dr. Cogan.
Figures 1 and 2.
The neural structures in the mesencephalic reticular formation involved in the generation of vertical eye movements are:
1. The posterior commissure (PC) and the nucleus of the PC (nPC)
2. The interstitial nucleus of Cajal (INC)
3. The rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF)
The pretectal dorsal midbrain syndrome is due to a lesion of the posterior commissure and the nucleus of the posterior commissure (nPC). Cells in the nPC project through the posterior commissure to the rostral interstitial nucleus of the MLF, (riMLF), the interstitial nucleus of Cajal (INC) and the M-group of neurons, which relays to the central caudal subdivision of the oculomotor nucleus and coordinates vertical eye and lid movements.
Unilateral lesions of the mesencephalic reticular formation create the same bilateral oculomotor syndrome by interrupting both projections through the posterior commissure.
The interstitial nucleus of Cajal is frequently involved in lesions producing supranuclear gaze palsies and the INC lesion is not just one of vertical gaze evoked nystagmus but also of restriction in the range of vertical eye movements although saccades are not slowed.
Bilateral lesions of INC affect vertical gaze whereas unilateral lesions produce the ocular tilt reaction and ipsilesional torsional nystagmus with quick phases moving the top poles of the eyes towards the side of the lesion.
The rostral interstitial nucleus of the MLF (riMLF) is a cluster of neurons which lie adjacent to, but are distinct from the INC. The riMLF is situated rostral to the latter nucleus among the fibers of the MLF and ventral to the nucleus of Darkshevich within a few millimeters of the midline. It also lies near the fasciculus retroflexus and the rostral pole of the red nucleus.
Büttner-Ennerver and Büttner gave this region the name rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) in the monkey, whereas Graybiel referred to it as the nucleus of the prerubral field in the cat.
In the riMLF approximately equal numbers of neurons are activated by upward and downward gaze, but none are activated by horizontal movements.
Leigh and Zee reported a patient with a unilateral midbrain hemorrhage, who came to autopsy.
Their patient was a 38 year old woman with monocytic leukemia in blastic crisis. She became acutely stuporous and developed a right hemiparesis.
The ocular motility signs were:
• A left third nerve palsy
• Continuous square-wave jerks during attempted fixation
• Complete paralysis of vertical eye movements above the
• Below the horizontal meridian, downward pursuit was
abnormal and saccades, both up and down, appeared
slow and with
• Downbeating nystagmus on attempting to look down
• Absent convergence
• Horizontal gaze evoked nystagmus
Computed tomography of the brain demonstrated a hemorrhage in the left midbrain.
The patient died. The autopsy examination of the brain confirmed the presence of the midbrain hemorrhage with compression and displacement of the aqueduct and posterior commissure.
The important finding, however, was that although the CT indicated a unilateral midbrain lesion, at autopsy the posterior commissure was compressed and more over, the hemorrhage was located so as to affect fibers crossing into and out of the posterior commissure.
Unilateral Midbrain Hemorrhage;
Blood pressure control
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