Supranuclear Paralysis of Downgaze

Bilateral Ptosis; Supranuclear Paralysis of Downgaze; Vertical Oculocephalic Reflex Normal; Absent ConvergencePowerPoint Presentations: Thalamic Infarct: http://library.med.utah.edu/NOVEL/Wray/PPT/Thalamic_Infarct.ppt Shirley H. Wray, M.D., Ph.D., FRCP, Harvard Medical School Thalamic Stroke and Disordered Sleep: http://library.med.utah.edu/NOVEL/Wray/PPT/Thalamic_Stroke_and_Disordered_Sleep_guest_lecture.ppt Kenneth C. Sassower, M.D. Massachusetts General HospitalSomnolenceThe patient is a 64 year old man with no major past medical history who, on the day of admission, suddenly developed loss of vision in both eyes and then was unable to open his eyes on his own unless he used his hands. Holding his eyelids open his vision was very blurry. Within minutes he lost consciousness and his wife was unable to arouse him. In the emergency room he was described as unresponsive to pain, with 8 mm sluggish reacting pupils, moving all four extremities with bilateral decorticate posturing and bilateral upgoing toes. A non-contrast Brain CT was read as normal. The patient was admitted to the Intensive Care Unit. Diagnosis: ‘Top of the basilar syndrome'. Neurological examination: Over the next two hours, his level of consciousness fluctuated, ranging from impairment of arousal to occasionally conversing with yes and no to asking questions. When awake he was oriented x3 and then he would drift back to sleep. Repetition, naming and comprehension were intact. He had bilateral ptosis Pupils 6 mm OU, sluggish to light. Eyes straight in primary gaze Normal horizontal and vertical oculocephalic reflex Motor system: Left hemiplegia involving face, arm and leg with normal tone. Reflexes 2+ symmetric with bilateral upgoing toes. Sensory examination: Left hemi-sensory loss. On day 1, the patient was heparinized and placed on pressors to keep the systolic blood pressure greater than 180 as his level of alertness fluctuated markedly with his blood pressure and was dependent on maintaining a systolic blood pressure over 180. On day 3, he was awake and alert and fully oriented. The left sided weakness and hemi-sensory loss had completely resolved and he had no ptosis. On day 5, he tried to get out of bed, which resulted in a drop of systolic blood pressure to 120. Almost immediately he became confused, dysarthric and hemiparetic. As soon as his systolic blood pressure was greater than 180, he was alert and his signs resolved. 2/7/94 CT of the Brain with contrast: 1. Acute right thalamic infarct with the possibility of involvement of the left thalamus not completely excluded. 2. No intracranial hemorrhage or mass 3. Appearance of an old left cerebellar hemispheric infarct. 2/10/90 Brain MRI: Axial T2 WI images show 1. An area of T2 bright signal within the right medial thalamus suggestive of an infarct. 2. Abnormal signal within the left cerebellar hemisphere and punctate areas within the right anterior cerebellar hemisphere, both consistent with infarction. (Figures 1 and 2) Brain MR Angiogram: On MRA the right vertebral artery was segmentally visualized and diminutive in size. probably representing a small hypoplastic vertebral artery with slow flow. However, the possibilities of thrombus and/or dissection could not be excluded. 2/15/94 Cerebral Angiogram: Showed no evidence of vertebral artery dissection or of a basilar tip aneurysm. The basilar artery was normal. A Holter monitor demonstrated some sinus node dysfunction, but cardiology felt that in the absence of syncable symptoms the patient did not require a pacer. On 2/17/94, 13 days post stroke, Neurovisual Consult: The patient was fully alert. He complained that he could not look down and he was unable to read his menu. He had intermittent vertical double vision watching TV, one image being slightly higher than the other, but at the time of the examination this was improving. He mentioned that he was sleeping a lot. He denied headache, vertigo and confusion and he emphasized that his memory "was good". On examination: Visual acuity OD: 20/25 OS: 20/40, pinhole 20/25 Confrontation fields full OU and normal fundus exam. Pupils 4 mm OU reacting normally to light and near Ocular motility: Eyes straight in primary gaze Full horizontal gaze right and left with gaze evoked nystagmus. Full upgaze, no nystagmus Supranuclear paralysis of downgaze Saccades limited to 5 to 10 degrees. Pursuit 20 to 30 degrees down. Intact vertical oculocephalic reflex Absent convergence Intact horizontal optokinetic nystagmus Absent vertical optokinetic nystagmus No skew deviation. Diagnosis: 1. Isolated global supranuclear paralysis of downgaze 2. Right medial thalamic infarct extending into the right mesencephalic reticular formation (MRF) 3. Embolic cerebellar infarcts Etiology: Embolic infarction of the thalamus and MRF supplied by the posterior thalamosubthalamic paramedian artery (Artery of Percherson) Top of the basilar artery syndrome A transthoracic echo cardiogram showed no embolic source from the heart. A transesophageal echo cardiogram showed a small patent foramen ovale. Lower extremity arterial non-invasive study showed no evidence of deep venous thrombosis. Discharge: At the time of discharge the patient was doing very well. The residual neurological findings were: 1. Supranuclear paralysis of downgaze 2. Absent convergence and 3. Increased somnolence. He was discharged home on Coumadin. Follow-Up: The patient's stroke occurred on February 4, 1994. On follow-up on March 23, 1994 he had full vertical gaze down and normal convergence. His wife reported that "he was very sleepy and lethargic in mid-afternoon and generally sleeps a lote and takes frequent naps".This 64 year old man with a right medial thalamic infarct involving the MRF had, acutely, bilateral ptosis which recovered after 3 days. He had a constellation of motility signs: • Global paralysis of downgaze (saccades and pursuit) • Absent convergence • Normal deviation of the eyes up under forced eye closure (Bell phenomenon) • Horizontal gaze evoked nystagmus to right and left • Optokinetic nystagmus absent with vertical rotation of the drum • Normal vertical oculocephalic reflex (Doll's head maneuver) A second video recorded four months later shows: • Full vertical saccades and pursuit • Normal convergence The global supranuclear downgaze palsy is attributed to bilateral ischemia in the region of the thalamic-mesencephalic junction involving the supranuclear pathways and rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) mediating downgaze. Impaired convergence is sometimes associated with lesions in the mesodiencephalic region and was present in two of the four previously reported cases of selective downgaze palsy. Bilateral ptosis was one of the most striking ocular signs in this patient acutely. According to Warwick this could result from a single lesion damaging the central caudal nucleus of the third nerve nuclear complex. The central caudal nucleus lies in the midline at the caudal end of the nucleus just ventral to the cerebral aqueduct. It provides bilateral innervation to the levator palpebrae. Total recovery of bilateral ptosis can occur, however, despite extensive neuron loss in the caudal portions of the oculomotor nucleus, a finding that we reported in a case of Midbrain ptosis with clinicopathologic correlation in 1975 (Growdon JH, Winkler GF, Wray SH. Arch Neurol 1974;30:179-181.) The unusual combination of a supranuclear downgaze palsy and midbrain ptosis in another autopsy case was found to be due to a single midbrain glioma growing around the third ventricle, the aqueduct and the M-group of neurons involved in eye lid control. The M-Group of neurons lie immediately dorsal to the third nerve nucleus and adjacent, medial, and caudal to the riMLF. The M-group neurons receive inputs from riMLF and project to both the elevator subnuclei of the eye (superior rectus, inferior oblique) and the motor neurons of levator palpebrae superioris in the central caudal nucleus of the third nerve nucleus. We suspect the transient midbrain ptosis in our patient resulted from ischemia of M-group neurons Intermittent stupor is a logical neuroanatomical accompaniment to focal thalamomesencephalic infarcts including the area of the riMLF, and consequently can be seen in cases of Parinaud's syndrome and in those cases with both supranuclear paralysis of up and downgaze. (ID207-1) In 1995 Beversdorf's et al reported the case of a woman with intermittent impairment of arousal with elevated blood pressure during the episodes, and reviewed several other cases in the literature with similar features. The authors found that the only report in the literature featuring waxing and waning consciousness, as in their case, was that of Büttner-Ennever et al 1978. The approximate locations of many of the cited lesions in cases with prominent alterations in consciousness were diagramed and, as would be expected, the lesions with the greatest involvement of the reticular activating system correlated with the greatest alterations in consciousness. In our case, the infarct involved a portion of the territory supplied by the posterior thalamosubthalamic paramedian artery. The significance of the nystagmus on horizontal gaze to the right is difficult to access, but it was also present on horizontal gaze in the case described by Jacobs et al in 1973.Neuroimaging studies are not available in this patientThree neural structures in the midbrain reticular formation are involved in the generation of vertical eye movements: 1. The posterior commissure (PC) 2. The interstitial nucleus of Cajal (INC) 3. The rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) 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. With respect to the supranuclear structure mediating downgaze in humans, only four autopsy cases (André-Thomas et al 1933; Jacobs et al 1973; Cogan 1974; Halmagyi et al 1978) were available when we published an autopsy case in 1980. (Trojanowski JQ, Wray SH. Vertical gaze ophthalmoplegia: Selective paralysis of downgaze. Neurology 1980;30:605-610). Destruction of fiber tracts and neurons in the region bordering the dorsomedial portion of the red nucleus, i.e. the riMLF was a feature common to all five cases. The autopsy case we reported (ID907-3) differed, however, from previous cases in three significant ways: First, our patient lived longer than any of the others and afforded an opportunity for follow-up ocular motility examinations for 3 years. All the previous patients died from 1 week to 1 year after the onset of symptoms, and in three cases death occurred within 4 months. Second, although improvement was noted in some patients, our patient was the only one who fully recovered vertical downgaze. Full or more complete recovery might have eventuated in the other patients had they lived longer. Finally, the lesion in our patient was smaller than three of the lesions in the previously reported cases. The lesion in the fourth case is difficult to evaluate, since it was illustrated with only one section through the midbrain, although it was said to extend rostrally into the thalamus. Furthermore, the exact duration of the downward gaze paralysis is not stated, although the patient did survive 1 year after the onset of his deficit.Pathological correlation: Trojanowski and Wray reported the fifth autopsy case of a patient with isolated supranuclear paralysis of downgaze (17). The brainstem and ventral diencephalon were step-sectioned in the horizontal plane. At the level of the rostral midbrain, two irregularly shaped, slit-like old cavitary infarcts were observed on either side of the cerebral aqueduct where it originates from the third ventricle. They extended from immediately subjacent to the ependymal surface laterally to the red nucleus and from the dorsomedial surface of the red nucleus dorsolaterally into the ventral portion of the pretectum. In the rostral direction, the infarct did not grossly extend beyond the red nucleus; caudally, it disappeared above the point of exit of the fibers of the third nerve. A similar cavitary infarct, 0.8 cm. in greatest dimension, was seen in the right posterior cerebellar cortex. The bilateral rostral midbrain infarcts were cavitary on microscopic examination, with fibrillary gliosis around and within the cavities along with a few capillaries and hemosiderin-laden macrophages indicating infarcts of considerable age. The lesions were almost completely symmetric. In the rostrocaudal axis, they began just rostral to the oculomotor complex and INC without involving either of these structures and extended through the midbrain in the rostral direction to barely encroach upon the medial dorsal nucleus. In the mediolateral plane, the infarcts extended from the ependymal lining of the ventricular surface laterally to the region of the most lateral edge of the red nucleus while largely sparing this structure. Finally, in the dorsoventral plane, the infarcts extended from the most ventral portion of the pretectum to the most ventral limit of the cerebral aqueduct. The following structures were damaged bilaterally: • riMLF • Periaqueductal gray • Ventral fibers of the PC and a portion of its nuclei • Dorsomedial red nucleus and adjacent midbrain • Ventromedial edge of the medial dorsal nucleus, fasciculus retroflexus, dorsal and medial longitudinal fasciculi and • Nucleus of Darkshevich It can be concluded, therefore, that either axons or neurons in the riMLF nuclei where the fasciculus retroflexus passes the dorsomedial portion of the red nucleus are vital for mediating downgaze. The recovery of vertical downgaze in this case suggested that not all the fibers originating from neurons subserving this function were destroyed or that the neuronal population itself was only partially involved. Following the report of this case, Trojanowski and Lafontaine published another autopsy case (number six) which can be considered the first clinicopathological study of an unambiguously permanent downgaze paralysis. The patient was a 56-year-old woman who had the sudden onset of a selective paralysis of downgaze associated with a partial third nerve paralysis on the right. On numerous examinations over the ensuing 3 and ¾ years, these deficits were observed to persist. At autopsy, bilateral somewhat asymmetrical cavitated lesions were seen in the region of the thalamo-mesencephalic junction. Because this patient's selective downgaze paralysis was permanent, the authors concluded that the supranuclear neural elements mediating downgaze are situated within the confines of these lesions. A consideration of this case together with the five previous reports of selective vertical downgaze paralysis permits the relevant region to be further localized to an area extending from the oculomotor nucleus to the rostral pole of the red nucleus and immediately dorsomedial to the latter. 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