Journal of Neuro- 15(4): 236-240, 1995. i 1995 Lippincott-Raven Publishers, Philadelphia

Lid as a Sign of Intrinsic Midbrain Disease

Michael C. Brodsky, M.D. and Frederick A. Boop, M.D.

A 6-year-old boy with signs and symptoms of ocular The terms "lid nystagmus," "upper lid jerks," had lid nystagmus evoked by hori­ and "lid hopping" have been applied to a rare zontal gaze. MR imaging demonstrated an intrinsic mid­ neuro-ophthalmic phenomenon in which a series brain lesion, which was diagnosed by biopsy as a low- grade astrocytoma. In the setting of ocular myasthenia of rapid, rhythmical, upward jerking movements gravis, the finding of lid nystagmus may serve as a use­ of the upper lids occur alone or in conjunction with ful clinical sign of intrinsic midbrain disease. specific movements of the eyes or head (1-14). Key Words: Lid nystagmus—Ocular myasthenia— Clinical reports suggest that this phenomenon oc­ Ophthalmoplegia—Midbrain tumor. curs in the setting of posterior fossa disease (1). We describe a child with bilateral and diffuse ophthalmoplegia suggestive of ocular myasthenia gravis in whom the atypical finding of lid nystag­ mus led to the diagnosis of midbrain astrocytoma.

CASE REPORT

A healthy 6-year-old boy was referred for eval­ uation of gradually progressive exotropia and bi­ lateral upper ptosis of 6 months duration. His mother stated that the ptosis was usually mild upon awakening and worse as the day progressed. There was no history of headaches, nausea or vomiting, mental status changes, decreased motor strength, or difficulty swallowing or chewing. There was no family history of ptosis or ophthal­ moplegia. Facial examination demonstrated a severe bilat­ eral ptosis and a large exotropia (Fig. 1). Corrected visual acuity was 20/20 in each eye. The were equal in size and normally reactive to light, with no afferent pupillary defect. Extraocular movements were mildly limited in all fields of gaze with a severe adduction deficit in the right eye as shown in Fig. 2. Horizontal and vertical sac- Manuscript received July 18, 1994. cades were slow in all directions. The patient was From the Department of Ophthalmology (M.C.B.), and Neu­ unable to converge his eyes. He had no nystagmus rosurgery (F.A.B.), University of Arkansas for Medical Sci­ when he looked straight ahead in his exotropic po­ ences, Little Rock, Arkansas, U.S.A. This study was supported in part by a grant from Research to sition of gaze, but developed a gaze-evoked Prevent Blindness, Inc. nystagmus in horizontal and vertical gaze. He usu­ Address correspondence and reprint requests to Dr. Michael ally fixated objects of interest with his left eye C. Brodsky, Arkansas Children's Hospital, 800 Marshall, Little Rock, AR 72202, U.S.A. which necessitated a compensatory right face

236 LID NYSTAGMUS 237

drift to the original ptotic position. During hori­ zontal pursuit movements, the lids jerked at a fre­ quency of approximately one cycle per second. Careful examination of videotapes disclosed no as­ sociated vertical movement of the eyes. In sus­ tained lateral gaze, the lid nystagmus continued as a horizontal gaze-paretic nystagmus supervened. During attempted upgaze, the lid nystagmus in­ creased in amplitude and coincided with a large- amplitude, synchronous upbeating nystagmus. Attempted upgaze produced no visible retraction movements of the globes. During fixation of a sta­ tionary object, an occasional spontaneous upward jerk of the lids was observed. The patient had a positive Cogan's lid twitch sign. He displayed equivocal levator fatigability; however, his ptosis improved noticeably after 30 minutes of sleep. In­ tramuscular injection of neostigmine 0.8 mg pro­ duced no visible change in his ptosis or ophthal­ FIG. 1. Facial photograph demonstrating bilateral up­ moplegia. Results of a neurological examination per eyelid ptosis and exotropia. were otherwise normal. A magnetic resonance (MR) scan of the head turn and a slight chin elevation. He had 45 diopt­ demonstrated a 2-cm mass with low signal inten­ ers of exotropia in all fields of gaze except for left sity on Tl -weighted images and high signal inten­ gaze where his exotropia increased to greater than sity on T2-weighted images within the midbrain 90 diopters. tegmentum (Fig. 3). There was mild enlargement Horizontal pursuit movements or saccades in ei­ of the ventricular system with sparing of the fourth ther direction evoked a large-amplitude upper lid ventricle secondary to compression of the aque­ nystagmus that lasted for the duration of horizon­ duct of Sylvius. Results of a stereotactic biopsy re­ tal gaze. Each abnormal lid movement consisted of vealed a low-grade astrocytoma. a rapid, conjugate, upward jerk of both lids that The patient was treated with radiation therapy was followed immediately by a slower downward consisting of 5,400 cGy over a 6-week period. Two

FIG. 2. Versions in secondary positions of gaze demonstrating diffuse ophthalmoplegia with marked adduction lag in the right eye.

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FIG. 3. MR images demonstrating intrinsic midbrain lesion. Left: T2-weighted (TR = 2500; TE = 90) axial MR image demonstrating large intrinsic hyperintense midbrain glioma. Right: T1-weighted (TR = 700; TE = 11) sagittal image (postgadolinium) demonstrating the rostrocaudal extent of the tumor. years after initial presentation, he is attending ers and coworkers (4) described convergence- public school and appears to be functioning nor­ induced lid nystagmus induced by convergence in mally except for mild speech impairment. His par­ a patient with a cerebellar sarcoma that filled the ents state that his ptosis has resolved, but his ex- fourth ventricle. Safran and coworkers (5) de­ otropia persists. scribed convergence-induced lid nystagmus in two patients cerebellar system disease and speculated DISCUSSION that a phasically initiated instability of cerebellar origin might disrupt the normal physiological in­ Upper lid nystagmus is considered pathological crease in levator tonus that occurs during conver­ when it occurs in the absence of synchronous ver­ gence. As an alternative hypothesis, they sug­ tical movements of the globes. Nystagmus-like gested that convergence-evoked lid nystagmus jerking of the upper lids has been described in nu­ might also represent the effect of gaze-evoked merous pathological conditions. In each case, the nystagmus of cerebellar origin upon the normal abnormal lid movements have been evoked by physiological eyelid retraction evoked by conver­ specific movements of the eyes or head. Most pre­ gence. Salisachs and Lapresle (6) noted conver­ viously reported cases can be subdivided into lid gence-evoked lid nystagmus in patient with Miller nystagmus evoked by convergence (Pick's sign) Fisher syndrome. Howard described the same and lid nystagmus evoked by horizontal gaze. phenomenon in a patient with a pontomedullary Convergence-evoked lid nystagmus was first re­ angioma (7). ported in 1916 by Pick (2) in a patient who had Gaze-evoked lid nystagmus was first reported in and spastic quadriparesis. The 1916 by Popper (8) in an alcoholic patient with a lid nystagmus was observed in primary gaze in the left-beating vestibular nystagmus. Sittig (9) and absence of bulbar nystagmus. The lid movements Wilbrand and Saenger (10) subsequently described became accentuated during convergence and also gaze-evoked lid and ocular nystagmus in patients upgaze, where a synchronous upbeating nystag­ clinical signs of brainstem dysfunction without fur­ mus appeared. Pick (2) hypothesized that lid ther clinical or pathological localization. Daroff and nystagmus may reflect abnormal excitation within colleagues (11) described a patient with lateral the oculomotor nuclei radiating to the cell bodies medullary syndrome who had lid nystagmus that that control levator function. Rohmer and col­ was evoked by lateral gaze and inhibited by con­ leagues (3) noted convergence-induced lid nystag­ vergence. mus in a patient with a posttraumatic dorsal mid­ The fact that our patient's lid nystagmus oc­ brain syndrome and a left third nerve palsy. Sand­ curred in the absence of any visible vertical move-

/ Neuro-Ophthalmol, Vol. 15, No. 4, 1995 LID NYSTAGMUS 239 ment of the globes led us to conclude that the ab­ was characterized by a momentary elevation or normal lid movements somehow resulted from the fluttering of the ptotic eyelid as the patient visually abnormal innervational milieu created by his pursued an object from one position of lateral gaze slowly growing tegmental tumor. In upgaze, the to another. The ptosis resolved following radiation amplitude of the lid nystagmus increased as a therapy to the tumor. Ragge and Hoyt (23) attrib­ large-amplitude upbeating nystagmus super­ uted the patients neuro-ophthalmic signs to "mid­ vened, suggesting that the observed lid move­ brain myasthenia" and hypothesized that tumor ments in upgaze were, at least in part, secondary infiltration within the midbrain may have critically to the ocular nystagmus. reduced levels at centrally located The pathophysiology of lid nystagmus in un­ acetylcholine synapses (most likely at the synapses known. In this case, however, its neuroanatomical between supranuclear pathways in the brainstem substrate can clearly be localized to the midbrain and the nuclear complex of the third nerve), result­ tegmentum. Our patient's neuroophthalmic find­ ing in fatigable ptosis. The similar myasthenic pre­ ings suggest a combined disturbance of supranu­ sentation of a midbrain tegmental tumor in our clear (periodic firing of paretic levator muscles dur­ case raises the possibility that lid nystagmus may ing lateral and upward pursuit movements), nu­ be a neuro-ophthalmic sign of "midbrain myasthe­ clear (bilateral upper eyelid ptosis), and possibly nia." Conceivably, lid nystagmus in the setting of internuclear (selective impairment of adduction) an intrinsic midbrain lesion could require a combi­ pathways. His bilateral ptosis was similar to that nation of (a) an intermittent conduction block at described in previous reports of "midbrain pto­ the synaptic junction of supranuclear neurons of sis," which is attributable to a dorsal midbrain le­ the posterior commissure with the central caudal sion involving cell bodies of neurons that bilater­ nucleus (midbrain myasthenia), and (b) nuclear in­ ally innervate the levator muscles in the central volvement at the level of the central caudate nu­ caudal nucleus (12-16). Midbrain ptosis can occur cleus. Why intermittent levator activity should as an isolated finding or in combination with dif­ somehow be potentiated by horizontal gaze is un­ fuse ophthalmoplegia, internuclear ophthalmople­ clear. gia, or third nerve palsy (17,18). Our patient's slow The finding of lid nystagmus in the setting of abducting saccades suggested that descending ocular myasthenia gravis may serve as a useful pathways for horizontal gaze were also affected, clinical sign of intrinsic midbrain pathology. Atten­ albeit to a lesser degree (17,18). tion to this clinical sign may help the clinician se­ Intracranial compressive lesions involving the lect out those patients who have underlying cen­ brainstem and cavernous sinus can occasionally tral nervous system disease. present with clinical findings indistinguishable from myasthenia gravis (19-22). Our patient had signs and symptoms of ocular myasthenia gravis (a REFERENCES history of minimal ptosis upon awakening with 1. Schmidtke K, Buttner-Ennever JA. Nervous control of eye­ worsening as the day progressed, absence of pain, lid function: a review of clinical, experimental, and patho­ absence of pupillary involvement, and a positive logical data. Brain 1992;115:227-47. 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