Supranuclear Paralysis of Downgaze

Supranuclear Paralysis of Downgaze; Vertical Oculocephalic Reflex Normal; Absent Convergence; Skew Deviation; Ocular Tilt ReactionPowerPoint Presentation: Supranuclear Paralysis of Downgaze: http://library.med.utah.edu/NOVEL/Wray/PPT/Supranuclear_Paralysis_of_Downgaze.ppt Shirley H. Wray, M.D., Ph.D., FRCP, Harvard Medical SchoolSomnolenceJohn Trojanowski and I published this case in Neurology in 1980.(12) At that time, it was one of the first of five reports in the literature of the pathological localization of lesions in the midbrain that are responsible for selective supranuclear paralysis of downgaze. This case is of particular interest because serial ocular motility examinations over five years documented full recovery of his eye movements two years prior to death. The patient was a 58 year old man who was admitted to the Massachusetts General Hospital with dyspnea and a heart murmur. Cardiac catheterization revealed moderately severe mitral regurgitation attributed to a ruptured chorda tendineae. After the procedure, the patient was somnolent and lethargic. Seven days later, I did the first neuro-ophthalmic consultation. Neuro-ophthalmological findings: Pupils 3 mm, equal, sluggish to light and near (no light-near dissociation) Global paralysis of downgaze (saccades and pursuit) Absent convergence Slow saccades on upgaze Deviation of the eyes up under forced eye closure (Bell phenomenon) Horizontal gaze nystagmus to the right Optokinetic nystagmus absent with vertical rotation of the drum Normal vertical oculocephalic reflex (Doll's head maneuver) and Skew deviation, right hypertropia (6-8 diopters) Slight left head tilt - a left ocular tilt reaction (OTR) Neurologic examination was unremarkable except for periods of somnolence during which the eyes diverged up. When aroused, the patient was oriented with normal speech and without other neurological deficits. Diagnosis: Cardio-embolic midbrain infarct Spinal Tap: Normal pressure and cerebrospinal fluid. The patient was discharged home . Ocular motility one month later : • Improved downgaze • Absent convergence • Persistent skew deviation • Full horizontal gaze without nystagmus Six weeks later a Starr-Edwards ball valve was implanted. Ocular motility eleven weeks post stroke: • Complete recovery of downgaze • Convergence insufficiency • Persistent skew deviation Ocular motility two years prior to death: • Age related limitation of upgaze • Absent Bell phenomenon • Normal downgaze • Convergence insufficiency • Persistent skew deviation, right hypertropia The patient entered the hospital for the last time at age 63 with fever and right hip pain. Despite extensive evaluation and antibiotic therapy, he developed septic shock and died on the tenth hospital day. The etiology of the fever and hip pain was a right psoas abscess caused by perforation of the duodenum. Details of the last admission and general autopsy findings were the subject of a clinicopathological (CPC) report in the New England Journal of Medicine 1979;301:370-377. In preparation for the CPC John Trojanowski found very fortuitously a drawing of the midbrain that I had placed in the patient's record at the time of my first consultation. The drawing indicated the probable location of the midbrain infarct. As a result John retrieved the patient's brain from its place on a shelf and sections of the brainstem showed the localization of the midbrain infarct. This case should be reviewed alongside ID944-7.This 58 year old man with a midbrain infarct had acutely a: • Global paralysis of downgaze (saccades and pursuit) • Absent convergence • Slow saccades on upgaze • Deviation of the eyes up under forced eye closure (Bell phenomenon) • Horizontal gaze nystagmus to the right • Optokinetic nystagmus absent with vertical rotation of the drum • Normal vertical oculocephalic reflex (Doll's head maneuver) • Skew deviation, right hypertropia (6-8 diopters) • Slight left head tilt - a left OTR The global supranuclear downgaze palsy is attributed to bilateral infarction of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) in the prerubral area of the ventral midbrain due to embolic occlusion of the artery of Percheron. 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. 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 nucleus of Cajal in the midbrain. Lesions in the midbrain and interstitial nucleus of Cajal may present with a sustained contralesional 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 two previous cases including one reported by Cogan. (For full discussion of the OTR review ref (11)). The significance of the nystagmus on horizontal gaze to the right is difficult to access, but it was present also on right and left 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 our findings and 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 the cases reported. Nevertheless, the present case differed 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: When this patient came to autopsy 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. (Figure 1-4) 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 in our case suggests 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 publication of this report, Trojanowski and Lafontaine published another autopsy case 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 previous reports of selective vertical gaze 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. This is likely to be the location of the human analogue of the monkey "nucleus of the prerubral fields', a supranuclear structure which is thought to mediate vertical gaze and especially downgaze.Embolic infarction of the midbrain1. André-Thomas, H. Schaeffer, I. Bertrand. Paralysie de l'abaissement du regard, paralysie des inférogyres, hypertonie des supérogyre et des reveleurs des paupiéres. Rev Neurol (Paris) 1933;40:535-542. 2. Büttner U, Büttner-Ennever JA, Henn V. Vertical eye movement related unit activity in the rostral mesencephalic reticular formation of the alert monkey. Brain Res 1977;130:239-252. http://www.ncbi.nlm.nih.gov/pubmed/406969 3. Büttner-Ennever JA, Büttner U. A cell group associated with vertical eye movements in the rostral mesencephalic reticular formation of the monkey. Brain Res 1978;151:31-47. http://www.ncbi.nlm.nih.gov/pubmed/98208 4. Büttner-Ennever JA, Acheson JF, Büttner U, Graham EM, Leonard TJK, Sanders MD, Russell RR. Ptosis and supranuclear downgaze paralysis. Neurology 1989;39:385-389. http://www.ncbi.nlm.nih.gov/pubmed/2927647 5. Case records of the Massachusetts General Hospital, N Engl J Med 1979;301:370-377. http://www.ncbi.nlm.nih.gov/pubmed/460326 6. Cogan D. Paralysis of downgaze. Arch Ophthalmol 1974;912:192-199. http://www.ncbi.nlm.nih.gov/pubmed/4814966 7. Graybiel AM. Organization of oculomotor pathways in the cat and rhesus monkey. In Baker R, Be rthoz A, Eds. Control of Gaze by Brainstem Neurons: Developments in Neuroscience. Amsterdam, Elsevier 1977:1:79-889. 8. Halmagyi GM, Evans WA, Hallinan JM. Failure of downward gaze: The site and nature of the lesion. arch Neurol 1978;35:22-26. http://www.ncbi.nlm.nih.gov/pubmed/304343 9. Jacobs L, Anderson PJ, Bender MB. The lesions producing paralysis of downward but not upward gaze. Arch Neurol 1973; 28:319-323. http://www.ncbi.nlm.nih.gov/pubmed/4696014 10. Jenkyn LR, Margolis G, Reeves AG. Reflex vertical gaze and the medial longitudinal fasciculus. J Neurol Neurosurg Psychiatry 1978;41:1084-1091. http://www.ncbi.nlm.nih.gov/pubmed/731253 11. Kompf D, Pasik T, Pasik P. Critical structures for downward gaze in monkeys. Neurosci Abstr 1977;3:156. 12. Leigh RJ, Zee DS. Diagnosis and Management of Vestibular Disorders. Chp 11:559-598. In: The Neurology of Eye Movements, 4th Edition, Oxford University Press, New York, 2006. 13. Trojanowski JQ, Wray SH. Vertical gaze ophthalmoplegia: Selective paralysis of downgaze. Neurology 1980;30:605-610. http://www.ncbi.nlm.nih.gov/pubmed/7189837 14. Trojanowski JQ, LaFontaine MH. Neuroanatomical correlates of selective downgaze paralysis. J Neuro Sci 1981;52:91-101. http://www.ncbi.nlm.nih.gov/pubmed/729941