OBSERVATION Isolated Relative Afferent Pupillary Defect Secondary to Contralateral Midbrain Compression Cheun Ju Chen, MD; Mia Scheufele, MD; Maushmi Sheth, MD; Amir Torabi, MD; Nick Hogan, MD, PhD; Elliot M. Frohman, MD, PhD Background: Relative afferent pupillary defects are typi- accounts for the relative afferent pupillary defect con- cally related to ipsilateral lesions within the anterior vi- tralateral to the described lesion. sual pathways. Result: Magnetic resonance imaging of the brain revealed a pineal tumor compressing the right rostral midbrain. Objective: To describe a patient who had a workup for headache and was found to have an isolated left relative Conclusion: While rare, a relative afferent pupillary de- afferent pupillary defect without any other neurological fect can occasionally occur secondary to lesions in the findings. postchiasmal pathways. In these circumstances, the pu- pillary defect will be observed to be contralateral to the Design: We review the neuroanatomy of the pupil- side of the lesion. lary light reflex pathway and emphasize the nasotem- poral bias of decussating fiber projections, which Arch Neurol. 2004;61:1451-1453 RELATIVE AFFERENT PUPIL- though retinal fibers concerned with this lary defect (RAPD) is char- reflex transmit information to both the ip- acterized by pupillary dila- silateral and contralateral midbrain, there tion upon illuminating the is a slight crossing bias, with about 53% of eye during the swinging the fibers crossing in the optic chiasm Aflashlight test. The presence of this sign sig- (chiefly derived from the nasal retina) and nifies an abnormality in the transmission 47% remaining ipsilateral. This anatomi- of light information within the pupillary cal organization of the pupillary constric- light constrictor pathway from the retina tor pathway results in the possibility of pro- to the rostral midbrain circuitry involved ducing an RAPD during illumination of the in this reflex. Relative afferent pupillary de- eye opposite to an optic chiasm, tract, or fects are most frequently associated with le- midbrain lesion (Figure). Here, we de- sions in the optic nerve. For example, pa- scribe a patient who had an isolated sign tients with unilateral optic neuritis have a of a left RAPD secondary to a pineal tu- slowing in conduction velocity in the af- mor compressing the right dorsal mid- fected nerve. During illumination of the un- brain at the level of the brachium of the su- affected eye, both direct and consensual pu- perior colliculus. pillary responses can be appreciated. The rapid transmission of this information re- sults in simultaneous innervation of the REPORT OF A CASE Edinger-Westphal nucleus, which ulti- mately provides parasympathetic innerva- A 27-year-old man with no medical his- tion to the sphincter fibers of the iris via the tory was referred to the neurology clinic oculomotor cranial nerve. However, dur- for evaluation of a headache. Results of his Author Affiliations: ing the rapid movement of the light source physical examination were normal with the Departments of Neurology to the affected side, the abnormality in op- exception of the presence of a left RAPD. (Drs Chen, Scheufele, Sheth, Torabi, and Frohman) and tic nerve conduction velocity (or the loss Visual acuity was 20/20 bilaterally with full Ophthalmology (Drs Hogan and of optic nerve axons) delays the arrival of visual fields by bedside testing. The pu- Frohman), University of Texas pupillary light information entering the pils were equal in size and reactivity to di- Southwestern Medical Center brainstem, and the examiner can identify rect light illumination. However, during at Dallas. an escape or dilation of the pupils. Al- the swinging flashlight test, we noted the (REPRINTED) ARCH NEUROL / VOL 61, SEP 2004 WWW.ARCHNEUROL.COM 1451 ©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 unmistakable presence of a left RAPD. Funduscopic ex- A amination revealed normal optic discs without evi- dence of papilledema, pallor, or atrophy. There was no evidence of head tilt, ptosis, internuclear ophthalmopa- resis, fourth nerve palsy, or skew deviation. Extraocular movements were full. There were normal ocular align- ment and normal ductions and versions. There was no evidence of vertical or oblique strabismus on alternate cover testing. Pursuit and vestibular eye movements were normal. There was no evidence of primary position, gaze evoked, rebound, or convergent retraction nystagmus. Magnetic resonance imaging of the brain with gado- linium infusion revealed a large pineal tumor. The mass was found to compress the right dorsal midbrain at the level of the brachium of the superior colliculus (Figure). Despite the apparent involvement of the cerebral aque- duct, there was no evidence of hydrocephalus. No ab- normalities of the optic nerves were identified. The pa- tient’s headache subsequently resolved spontaneously, and he was referred to the departments of neurosurgery and neuro-oncology for further evaluation. COMMENT B 1 The size of the resting pupil is controlled by the amount of light falling on the retina and depends on the integ- rity and relative activity of these discrete autonomic path- ways. The axons of the ganglion cells of the nasal retina 2 decussate in the optic chiasm to join the fibers derived from the temporal retina from the other eye. Collec- tively, these fibers constitute the optic tract. Photore- ceptors have been identified to be more densely distrib- 3 uted in the nasal vs the temporal portion of the retina. 4 Given this anatomical arrangement, there is a corre- 5 sponding asymmetric parcelling of nerve fibers within 6 the optic tracts arising from the nasal and temporal retina. 7 In particular, it has been estimated that the ratio of crossed 8 9 1 10 to uncrossed afferent pupillary fibers is 53:47 (Figure). 11 13 14 12 The majority of retinal axons provide afferent informa- 15 tion to the lateral geniculate nucleus en route to the pri- 16 mary visual areas on the calcarine cortex. However, ap- proximately 10% of the fibers bypass the lateral genicu- 17 18 latenucleusandarerelayedtothepretectalareaoftherostral midbrain. These fibers travel through the brachium to syn- 19 20 apse at the level of the superior colliculus. Second-order 17 neurons subsequently relay pupillary light information to 21 Edinger-Westphal nuclei bilaterally. This dual and near- simultaneous innervation provides the anatomical basis 22 for both the direct and the consensual light reflexes. From the Edinger-Westphal nucleus, tertiary parasympathetic neurons travel in the superficial dorsomedial aspect of the Figure. A, A T1-weighted axial magnetic resonance image of a pineal tumor ipsilateral occulomotor nerve to reach the ciliary ganglion. compressing the right dorsorostral midbrain (arrows). B, The corresponding axial illustration shows the components of the pupillary light reflex pathway. The ganglion then gives rise to 8 to 10 short ciliary nerves, There is asymmetry in the crossing pattern of this pathway, with 53% of the which subdivide into 16 to 20 branches. The majority of retinal projections (derived predominantly from the nasal retina) decussating thesebranchessupplytheciliarymuscletocontroltheshape in the optic chiasm, whereas 47% remain ipsilateral. Retrochiasmally, these pupillary light projections course with the optic tract (number 4) until they of the lens. Approximately 3% of these fibers ultimately enter the brachium of the superior colliculus (number 13, arrow). The converge upon and innervate the pupillary sphincter nasotemporal bias of crossing pupillary light reflex fibers results in a muscles (promoting constriction), thereby contributing contralateral left relative afferent pupillary defect. Reprinted with permission to the regulation of pupil size. from Nieuwenhuys R, Voogd J, and van Huijzen C. The Human Central Nervous System: A Synopsis and Atlas. Heidelberg, Germany: Relative afferent pupillary defects have been classi- Springer-Verlag; 1988:182. cally associated with lesions in the ipsilateral retina or op- (REPRINTED) ARCH NEUROL / VOL 61, SEP 2004 WWW.ARCHNEUROL.COM 1452 ©2004 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/02/2021 tic nerve. Because of the asymmetric distribution of pho- ment of Neurology, University of Texas Southwestern toreceptors in the nasal and temporal retina and the ratio Medical Center at Dallas, 5323 Harry Hines Blvd, Dal- of crossed to uncrossed fibers in the chiasm, an RAPD can las, TX 75235 ([email protected]). also result from contralateral optic tract and midbrain le- Author Contributions: Study concept and design: Chen sions. The pretectal afferent pupillary pathway is a con- and Frohman. Acquisition of data: Chen, Scheufele, tinuation of the fibers within the optic tract. As such, a Sheth, Torabi, and Frohman. Analysis and interpretation lesion affecting those fibers that have branched off from of data: Chen, Hogan, and Frohman. Drafting of the manu- the optic tract during their trajectory to the dorsal mid- script: Chen and Frohman. Critical revision of the manu- brain can also result in a contralateral RAPD. Unlike reti- script for important intellectual content: Scheufele, Sheth, nal, optic nerve, and optic tract lesions, no visual field de- Torabi, Hogan, and Frohman. Administrative, technical, fect should be produced when the lesions affect this and material support: Torabi, Hogan, and Frohman.