SMALL CASE SERIES Report of Cases. Case 1. A 19-year- pupil (eg, irregular shape, sector Unilateral Light-Near old Asian woman had symptoms of palsy, tonic near response, delayed Dissociation in Lesions headache and diplopia. Oculomo- redilation on looking back into the of the Rostral Midbrain tor examination findings demon- distance) or anterior segment patho- strated a vertical gaze palsy with con- logic conditions, nor were there any vergence-retraction nystagmus, clinical signs of a third cranial nerve Examination of the pupillary re- noncomitant skew deviation, and palsy. Her visual acuity and color vi- sponse to light and accommoda- convergence insufficiency but pres- sion were normal. Magnetic reso- tion can provide precise informa- ervation of all other eye move- nance imaging of the brain showed tion concerning the localization of ments. Examination of the pupils re- a hyperintense lesion at the level of a lesion within the sympathetic and vealed moderate anisocoria, with the the rostral midbrain immediately to parasympathetic pathways, the an- right pupil being 0.50 mm larger the right of the aqueduct of Syl- terior visual pathway, or the brain- than the left in both bright light and vius, within the periaqueductal gray stem (Table 1). Classical teaching has associated all lesions of the ros- in the dark (Table 2). The light re- (Figure 2A and B). tral midbrain with bilateral light- sponse (LR) and the near response Case 2. A 31-year-old man had a near dissociation (LND), defined as in the left eye were equally brisk and sudden-onset headache, vomiting, attenuation of the pupil light reflex normal; however, in the right eye and poor balance. He reported ver- (PLR) with relative sparing of the there was attenuation of the light re- tical diplopia and difficulty focus- near response, as one component of flex but preservation of a normal ing on near targets. Oculomotor ex- Parinaud syndrome. We describe 2 brisk near response (LND). These amination findings revealed a patients with rostral midbrain le- findings were confirmed by formal noncomitant skew deviation with sions in whom LND was clinically measurement of the amplitudes of right hypertropia on right gaze but present only in the eye ipsilateral to the LR and near response in each full horizontal eye movements. Pa- the lesion. To our knowledge, this eye, recorded separately under mon- resis of vertical eye movements and clinical phenomenon has not been ocular conditions, using infrared an up-gaze saccadic palsy with con- previously reported. We provide an video pupillometry.1 In the left eye vergence-retraction nystagmus was explanation for this observation and both the LR and the near response present. Visual acuity and color vi- its implications for our understand- were normal with no LND sion were normal. Examination of ing of the anatomy of the pupil light (Figure 1A). Slitlamp examina- the pupils under resting conditions pathway. tion showed no evidence of a tonic showed a small degree of anisoco- Table 1. Expected Pupil Examination Findings in Various Lesions of the Afferent, Central, and Efferent Limbs of the Pupillary Light Reflex Pathway Pupil Measurement Resting Pupil Diametera Direct Light Consensual Near Description Lesion Eye Dark Light Responseb Light Responseb Responseb of Pupil Sign Right optic nerve R Normal Normal ↓ Normal Normal Ipsilateral RAPD L Normal Normal Normal ↓ Normal Right optic tract R Normal Normal Normal ↓ Normal Contralateral RAPD L Normal Normal ↓ Normal Normal Dorsal midbrain-midline (PC) R Normal ↑↓ ↓ Normal Bilateral LND L Normal ↑↓ ↓ Normal Right ventral midbrain R Normal ↑↓ ↓ Normal Ipsilateral LND L Normal Normal Normal Normal Normal Ipsilateral unreactive pupil Right preganglionic P/S fibers R Normal ↑↓ ↓ ↓ L Normal Normal Normal Normal Normal Right postganglionic P/S fibers R ↓↑ ↓ ↓ ↑Ipsilateral tonic pupil (chronic) L Normal Normal Normal Normal Normal Abbreviations: LND, light-near dissociation; PC, posterior commissure; P/S, parasympathetic fibers; RAPD, relative afferent pupil defect. a The ↑ indicates an increase in mydriasis; ↓, decrease (myosis) in the size of the pupil. b The ↑ indicates an increase in the speed of the pupil response to that stimulus; ↓, a decrease in the speed of the pupil response to that stimulus. (REPRINTED) ARCH OPHTHALMOL / VOL 128 (NO. 11), NOV 2010 WWW.ARCHOPHTHALMOL.COM 1486 ©2010 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 ria in the dark (the right pupil being larger than the left) that increased Table 2. Pupillary Measurements From Both Right and Left Eyes of Patients 1 and 2 in bright light (Table 2). Clinically the right pupil showed an attenu- Resting Pupil Diameter, mm ated direct LR compared with that Direct Light Near measured in the left pupil, but the Patient No. Eye Dark Light Response, mm Response, mm near responses were brisk and of 1 normal amplitude in both eyes. As Initially R 7.20 6.00 1.23 2.60 a result, LND was found on the right L 6.70 5.50 2.04 1.48 side but not on the left side 1 y later R 7.40 5.35 2.50 2.36 (Figure 1B). There were no signs of L 7.65 5.52 3.00 2.60 2 R 6.25 4.20 1.60 2.00 a tonic pupil or third cranial nerve L 5.95 3.15 2.10 1.60 palsy. A magnetic resonance image of the brain revealed a small hem- orrhage secondary to a midbrain ar- teriovenous malformation on the A B right of the aqueduct of Sylvius (Figure 2C). He slowly recovered with a minor residual vertical eye movement deficit. Comment. The patients described demonstrate the novel finding of unilateral LND in association with some other components of a dorsal midbrain syndrome, namely, supra- nuclear up-gaze palsy, impaired con- vergence, and convergence- retraction nystagmus on attempted up gaze. This finding was clinically apparent. We were careful to ex- clude infranuclear causes of unilat- eral LND, including aberrant regen- Figure 1. Pupillograms recorded from patients 1 (A) and 2 (B) using an infrared pupillometer (series eration of the third cranial nerve (eg, 1800; Whittaker Corporation, Simi Valley, California). (See Fison et al1 for methods of eliciting and miosis associated with attempted ad- recording the light and near responses). The recordings were made under monocular conditions, with the pupil response being recorded in all cases from the eye that was stimulated (ie, consensual responses duction, elevation, or depression of were not recorded). Upper traces are of the right eye; lower traces, the left eye. The responses to light the eye), a chronic postganglionic (standardized 1 second square-wave pulse under Maxwellian optics) are shown on the left; the responses parasympathetic lesion (eg, irregu- to an accommodative effort are shown on the right. Scale bars indicate vertical measure of 0.5 mm; lar pupil shape, sector palsy, exag- horizontal, 2 seconds (A; also B right-hand trace) or 1 second (B, left hand trace). gerated but tonic response to an ac- eral pupil under bright lighting con- Alternatively, it may simply be that commodative effort), or local ditions because the light signal can- any effect of the lesion on anisoco- pathologic features within the an- not reach the ipsilateral EWN from ria is being swamped by the many terior segment of the eye (eg, uve- either eye; in the dark, however, other central influences that affect itis, iris ischemia, and others), but when EWN output is not affected by the tonic output of EWN cells (eg, neither of these cases showed signs the PON projections, there should projections from the locus ceruleus). of a peripheral lesion. Given the lat- eralized and rostral location of the be less (or no) anisocoria. Only pa- In contrast, a lateralized and ros- midbrain lesions identified by neu- tient 2 showed the expected in- trally placed midbrain lesion is not roimaging in these cases, it is likely crease in anisocoria in the light, with expected to cause asymmetry in the that the asymmetric pupil signs were patient 1 showing an insignificant pupillary miosis that accompanies an instead caused by supranuclear dis- degree of anisocoria under all light- accommodative effort, yet both pa- ruption to the projections of the pre- ing conditions. It is hard to inter- tients showed larger amplitude near tectal olivary nuclei (PON) to the pret this lack of asymmetry in rest- responses in the ipsilateral eye. Pe- Edinger-Westphal nucleus (EWN) ing pupil size in patient 1. One ripheral (postganglionic) lesions are, on only one side, with relative spar- possibility is that the identified le- of course, often characterized by ex- ing of the PON projections to the sion may also be disrupting the cen- aggerated near responses, but nei- other EWN. tral inhibitory projections to the ther of the near responses in these Such lateralized dorsal mid- EWN, resulting in relative disinhi- patients were tonic or exaggerated; brain lesions might also be ex- bition and miosis of the pupil that therefore, a supranuclear mecha- pected to cause anisocoria. The rest- would counteract any mydriatic ef- nism must be invoked by way of ex- ing diameter of the ipsilateral pupil fects of removing the excitatory light planation. It is unfortunate that the should be larger than the contralat- signal projections from both PON. near responses in both patients were (REPRINTED) ARCH OPHTHALMOL / VOL 128 (NO. 11), NOV 2010 WWW.ARCHOPHTHALMOL.COM 1487 ©2010 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/27/2021 A B C Figure 2. A, Patient 1. Sagittal T2-weighted brain magnetic resonance image showing a hyperintense lesion at the level of the rostral midbrain. B, Axial sectionin patient 1 shows that the lesion is located to the right of the aqueduct of Sylvius within the periaqueductal gray.