Congenital Oculomotor Nerve Paresis With Isolated Cyclic Pupillary Spasms

Original Contribution Congenital Oculomotor Nerve Paresis With Isolated Cyclic Pupillary Spasms Michael S. Salman, MBBS, BSc, MRCP, MSc, PhD, Samantha F. Klassen, BSc, MD, Ian H. Clark, MA, MB BChir, FRCSEd, FRCSC Abstract: Cyclic oculomotor nerve paresis is a rare and usually congenital disorder. It is characterized by unilateral third nerve paresis with periodic spasms causing eyelid elevation, miosis, and contraction of 1 or more of the extraocular muscles innervated by the third nerve. We report a 20-month-old girl who presented initially with a congenital partial right third nerve paresis without ptosis. She subsequently developed isolated cyclic spasms of the pupil followed several months later by permanent partial ptosis. Journal of Neuro-Ophthalmology 2015;35:371-373 doi: 10.1097/WNO.0000000000000285 © 2015 by North American Neuro-Ophthalmology Society M onocular cyclic oculomotor nerve paresis is a rare disorder. It typically presents at birth or within the first 2 years of life (1-5). In 1975, Loewenfeld and Thompson (5) published an extensive review and summarized many of its features, primarily consisting of 2 alternating phases involving paralysis and spasm of 1 or more muscles innervated by the third nerve. In the majority of cases, ptosis and a dilated pupil are present during the paralytic phase, whereas during the spastic phase, the eyelid elevates and the pupil constricts. On average, the paralytic phase lasts approximately 1 minute, and the spastic phase lasts half as Sections of Pediatric Neurology (MSS) and Pediatric Ophthalmology (IHC), Children's Hospital, Winnipeg, Manitoba, Canada; and Departments of Pediatrics and Child Health (MSS) and Ophthalmology (IHC), College of Medicine (SK), Faculty of Health Sciences, University of Manitoba, Winnipeg, Manitoba, Canada. The authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the full text and PDF versions of this article on the journal's Web site (www. jneuro-ophthalmology.com). Address correspondence to Michael S. Salman, MBBS, BSc, MRCP, MSc, PhD, Section of Pediatric Neurology, Children's Hospital, AE 308, 820 Sherbrook Street, Winnipeg, MB R3A 1R9, Canada; E-mail: [e-mail] Salman et al: J Neuro-Ophthalmol 2015; 35: 371-373 long. However, the duration of the full cycle (paralytic and spastic phases) varies among patients and ranges from 1- 3 minutes. The affected pupil is typically nonreactive to light and accommodation. The rhythmic cycling is involuntary and persists throughout the day and during sleep (1,2,5). Amblyopia and strabismus commonly occur (2- 6). The fourth and sixth cranial nerves are spared. The cyclic spasms involve the sphincter pupillae in all cases, the levator palpebrae superioris muscle frequently, and the medial rectus muscle less commonly (5). We present a case of isolated cyclic spasm of the pupil in a toddler with congenital partial right third nerve paresis, who developed ptosis as a relatively late sign. CASE REPORT A 4-month-old girl was referred for assessment of congenital strabismus. Her mother's pregnancy had been unremarkable, and there was no exposure to alcohol, tobacco, or illicit drugs. She was born after a planned cesarean section because of breech presentation. Labor and delivery were otherwise unremarkable. The patient had a right exotropia of 70-80 prism diopters. There were adduction and elevation deficits of the right eye. Incyclotorsion of the right eye was observed on ophthalmoscopy suggesting inferior oblique muscle involvement. Hypertropia of the right eye was noted intermittently, which was not detected on subsequent clinic visits. There was no ptosis and pupils were equal, round, and reactive to light. A congenital partial right third nerve paresis was suspected. At 6 months of age, cycling of the right pupil was observed but periodicity was not measured. There was no ptosis. There were variable limitations in elevation and adduction of the right eye. The patient would fixate reliably with the right eye when the left was covered. At 8 months of age, she demonstrated photophobia of the right eye. There was marked limitation of adduction and 371 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution elevation of the right eye, and a right hypotropia was noted. Motility of the left eye was normal. Brain magnetic resonance imaging (MRI) with thin cuts (0.8 mm) was normal. At 9 months of age, a depression deficit of the right eye was noted for the first time. The child now showed a clear fixation preference for the left eye and would only hold gaze with the right eye for a few seconds. To treat amblyopia, patching of the left eye was recommended. By 11 months of age, adduction, elevation, and depression of the right eye were impaired. Intermittent noncyclic twitching of the right upper eyelid was noted, which occurred independently of the intermittent partial ptosis that was now present. By 15 months of age, partial noncyclic right ptosis was constant. Repeat brain MRI was normal. At 18 months of age, periodicity of right pupillary cycling was measured for the first time. There was pupillary constriction to a diameter of 2 mm for 30 seconds followed by dilation to 4 mm for 30-60 seconds. The right pupil was not reactive to light. No cycling spasms of the right extraocular muscles were seen. A 2-mm right ptosis and complete paresis of right eye elevation, depression, and adduction were evident while abduction remained intact (Fig. 1). Random and brief right upper eyelid twitches were noted intermittently. They occurred at the onset of the spastic phase when they were seen but without periodicity (See Supplemental Digital Content, Video, http://links.lww.com/WNO/A166). Her development was normal and the remainder of her neuro-ophthalmological and neurological examinations were unremarkable. At 19 months of age, the patient had strabismus surgery. Two months later, the visual acuity equivalent was estimated to be 20/80 in the right eye and 20/20 in the left eye using Cardiff cards. Her right pupil was still cycling with the same periodicity. The effect of gaze on pupillary cycling could not be ascertained due to her young age. She had a small right hypotropia and a small right exotropia. The right eyelid was still twitching intermittently but without periodicity and right partial ptosis was still present. DISCUSSION Our patient was unusual since her ptosis was partial, appeared later during infancy, and never demonstrated any cyclic spasms. In a large case series, only 8 of 54 patients with cyclic oculomotor paresis lacked cyclic spasms of the eyelid (5). Another interesting finding in our patient was the evolution of weakness of the muscles innervated by the third nerve, starting with the medial rectus, superior rectus, and inferior oblique muscles, progressing to cyclic spasms of the pupil and inferior rectus weakness, followed by the development of partial ptosis. Such progression has rarely been documented in the literature, and unlike our case, ptosis appeared first in both of the reported patients with documented progression (2,7). Lowenfeld and Thompson (5) found that 19 of 54 patients had cyclic spasms and third paresis documented at the same time, although 29 of 54 patients were presumed to have had the cyclic spasms occur at the same time as the paresis. Only 6 patients developed cyclic spasm "some time" after the onset of third nerve paresis. This delay of months to several years between the onset of third nerve paresis and cyclic spasms has been described previously (2,4,6). The mechanism underlying cyclic oculomotor paresis is unknown. A number of theories have been proposed. First, combined prenatal partial damage to the third nerve, a secondary third nucleus lesion, and impaired supranuclear connections with the oculomotor nucleus have been proposed (5). The cyclic nature is seen because only a summation of many impulses would have enough capacity to pass through the damaged area and cause a spasm. Second, the lesion may reside in the peripheral third nerve. This is supported by evidence on electromyography, muscle histology, and electron microscopy (8,9). Third, there may be aberrant regeneration of the third nerve with intermittent conduction block in the regenerated fibers (10). Fourth, the cyclic spasms might be related to the pathophysiology of ocular neuromyotonia (11). However, the contractions in neuromyotonia occur randomly (nonrhythmically) or are induced by sustained eccentric eye movement. A nuclear site for the lesion is unlikely (5,7). Friedman et al (7) reported a 39-month-old child with cyclic spasms of the left pupil and eyelid, who had partial FIG. 1. Partial right third nerve palsy. In the primary gaze, there is a large right exotropia, partial ptosis, and dilated right pupil. On downgaze (not shown due to lack of cooperation), the patient had limited ability to depress the right eye. Constriction of the right pupil, which occurred in a cyclic manner, is evident on upgaze. 372 Salman et al: J Neuro-Ophthalmol 2015; 35: 371-373 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution extraocular muscle involvement but with intact adduction, mildly affected infraduction, and partial ptosis. The authors argued that a lesion of the central nucleus would not have spared these functions. We also propose that the lesion in our patient is peripheral and is likely located before the point where the third nerve divides into superior and inferior divisions, because all muscles supplied by the nerve were affected. In addition, since the contralateral superior rectus muscle was spared, a lesion in the right third nerve nucleus is unlikely (7). The variability in the degree of extraocular muscles weakness noted in our patient is intriguing. It may be due to periods of intermittent spasms akin to the intermittent eyelid twitching described in our patient. However, this remains speculative. Treatment for this condition is limited. Surgery to correct ptosis may lead to the risks of corneal exposure (2,6). Currently, there is no proven treatment for the cyclic spasms. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: M. S. Salman and I. H. Clark; b. Acquisition of data: M. S. Salman, S. Klassen, and I. H. Clark; c. Analysis and interpretation of data: M. S. Salman, S. Klassen, and I. H. Clark. Category 2: a. Drafting the manuscript: M. S. Salman, S. Klassen, and I. H. Clark; b. Revising it for intellectual content: M. S. Salman, S. Klassen, and I. H. Clark. Category 3: a. Final Salman et al: J Neuro-Ophthalmol 2015; 35: 371-373 approval of the completed manuscript: M. S. Salman, S. Klassen, I. H. Clark. REFERENCES 1. Susac JO, Smith JL. Cyclic oculomotor paralysis. Neurology. 1974;24:24-27. 2. Price DM, Trounce DQ. Cyclic oculomotor paralysis. Arch Dis Child. 1973;48:881-884. 3. McGregor IS. Cyclic oculomotor palsy. J Neurol Neurosurg Psychiatry. 1945;8:22-23. 4. Clarke WN, Scott WE, Cyclic third nerve palsy. J Pediatr Ophthalmol. 1975;12:94-99. 5. Loewenfeld IE, Thompson HS. Oculomotor paresis with cyclic spasms. A critical review of the literature and a new case. Surv Ophthalmol. 1975;20:81-124. 6. Yazici B, Ünal M, Köksal M, Özdek SC. 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