Acute Convergence and Divergence Paralysis in HIV-Related Rhombencephalitis

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Gour Wang, MD Acute Convergence and Divergence Paralysis in HIVRelated Rhombencephalitis Ana I. Martins, MD, André F. Jorge, MD, Orlando D. Galego, MD, César P. Nunes, MD, Raquel S. Gonçalves, MD, João M. Lemos, MD, PhD V ergence eye movements change the angle between the visual axes, aligning both foveae with an object of interest and allowing for depth perception (1). An ocular vergence premotor network includes the supraoculomotor area (SOA) in the midbrain, nucleus reticularis tegmenti pontis and dorsolateral pontine nuclei (NRTP/DLPN) in the pons, frontal eye field, and the fastigial/globose/ emboliform nuclei (FN/GL/EM) and superior/middle cerebellar peduncles (SCP/MCP) in the cerebellum (1–3). Importantly, this network seems to be functionally segregated into convergence-related and divergencerelated neurons/pathways, which might explain why an acute damage of aforementioned circuit most often impairs either ocular convergence or divergence alone (1–4). We present a unique case of acute and simultaneous convergence and divergence paralysis in a patient with HIV-related rhombencephalitis involving both NRTP/DLPN and the left SCP/MCP. A 50-year-old man recently diagnosed with HIV presented with a 2-week history of horizontal binocular diplopia, dysarthria, imbalance and right-sided limb weakness, and paresthesia. He was currently on emtrici- Neurology Department (AIM, AJ, JL), Coimbra University Hospital Centre, Coimbra, Portugal; Neuroradiology Department (OG, CN), Coimbra University Hospital Centre, Coimbra, Portugal; Infectious Diseases Department (RG), Coimbra University Hospital Centre, Coimbra, Portugal; and Faculty of Medicine (JL), Coimbra University, Coimbra, Portugal. This work has been presented as a poster presentation at the 46th Annual Meeting of the North American Neuro-Ophthalmology Society, March 7–12, 2020, Amelia Island, FL. 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 HTML and PDF versions of this article on the journal’s Web site (www. jneuro-ophthalmology.com). A. I. Martins and A. Jorgethese co-first authors contributed equally to this manuscript. This study has been approved by the hospital ethics committee (no. 271/CES) and has therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Written informed consent was obtained from the patient for the anonymized information to be published in this article. Address correspondence to João Lemos, MD, PhD, Coimbra University Hospital Centre, Neurology Department, Praceta Professor Mota Pinto, 3000-075, Coimbra, Portugal. E-mail: merrin72@hotmail. com Martins et al: J Neuro-Ophthalmol 2021; 41: e197-e199 tabine, tenofovir, and cotrimoxazole. He had a normal distance and near visual acuity, color vision, visual fields, pupils, and ocular fundi. Ocular motor examination showed left-beating nystagmus on primary gaze, gazeevoked nystagmus, a hypoactive left head impulse, saccadic horizontal pursuit, and horizontal hypometric saccades. Ocular ductions were full, and there was no relative adduction lag. Ocular alignment using prism cover test showed comitant strabismus at near (1/3 m) (4-prism diopters exotropia) and distance (3 m) (4-prism diopters esotropia) (See Supplemental Digital Content, Video E1, http://links.lww.com/WNO/A430). The remaining examination showed dysarthria, central right facial palsy, right hemiparesis (grade 4) and hemihypoestesia, and generalized ataxia. On the following day, the ability to maintain binocular single vision (BSV) in the presence of increasing vergence demands (i.e., by using increasing strengths of prism power over one eye, with base-in and then base-out, for calculating fusional divergence and convergence amplitudes, respectively) was assessed. There was no ability to fuse the exodeviation at near and esodeviation at far, at the commencement of fusional convergence testing, and therefore fusional divergence and convergence amplitudes’ break point was recorded as 0. Near point of convergence (NPC; i.e., by slowly moving an isolated letter E of 20/30 size toward the eyes of the patient, initially placed at 50 cm in the midplane of the patient’s head; the patient was then asked to maintain fixation on the letter; the distance at which the patient reported diplopia and/or one of the eyes lost fixation and turned out after 5 consecutive trials was recorded as the NPC) was 48 cm. BSV (i.e., no diplopia) was in fact only possible when the fixation target was placed between 48 and 54 cm from the eyes, not being able to converge or diverge the eyes beyond these points, respectively. This was consistent with simultaneous ocular convergence and divergence paralysis. Written informed consent was obtained from the patient. This study was performed according to the Declaration of Helsinki and was approved by our hospital ethics committee. Binocular video-oculography (VO425; Interacoustics, Assens, Denmark; 105 Hz) and digital Hess test (Thomson Software Solutions, Hatfield, United Kingdom) performed at distance (130 cm) (Fig. 1A) e197 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Strabismic and imaging findings. A. Hess test at distance (130 cm). There is an esodeviation that is relatively equal in all fields of gaze, both when the right (left segment) and left eye (right segment) is fixating. The 9 cardinal positions of gaze in the left segment are represented by black dots (left eye) and gray dots (right eye), and in the right segment by gray dots (left eye) and black dots (right eye). B. Hess test at near (30 cm). There is an exodeviation that is relatively equal in all fields of gaze, both when the right (left segment) and left eye (right segment) is fixating. C. T2 sagittal and coronal FLAIR MRI. There is a hyperintense lesion involving the pons bilaterally and extending to the left superior (SCP) and middle cerebellar peduncles (MCP). FN, fastigial nucleus; FLAIR, fluid-attenuated inversion recovery; SOA, supraoculomotor area; NRTP/DPLN, nucleus reticularis tegmenti pontis/dorsolateral pontine nuclei; GL/EM, globose/emboliform nuclei. and near (30 cm) (Fig. 1B) confirmed the aforementioned signs. Extensive investigation, including serologies, cerebrospinal fluid analysis, autoimmune panel, and antineuronal antibodies, was unrevealing. Brain MRI 1.5 T showed a diffuse pontine enhancing lesion probably involving both the NRTP/DLPN and extending to the left SCP and MCP, whereas sparing the SOA and FN/GL/EM (Fig. 1C). Empirical treatment with methylprednisolone 1g/day was ineffective, and the patient died of respiratory failure associated with pneumonia 4 days later. Acute ocular vergence deficits due to central nervous system (CNS) focal lesions most often manifest as either isolated divergence or convergence deficits, possibly due to the selective injury of segregated convergence-related and divergence-related centers/pathways within the vergence network (3,4). Isolated acute divergence insufficiency has been associated with CNS lesions disrupting inhibitory convergence fibers connecting the FN/GL/ EM and thalamus with the SOA, including those e198 running through the NRTP/DLPN, ultimately leading to an imbalance between convergence and divergence tone (1,4). Isolated acute convergence insufficiency on the other hand has been mainly associated with lesions of the convergence pathway before (e.g., frontal eye field) and after its passage through SOA (e.g., NRTP/ DLPN and their output/input fibers running through the SCP and MCP), including the SOA itself (4). Interestingly, acute diplopia/strabismus in our case was strictly due to the simultaneous impairment of ocular divergence and convergence in probable association with damage of the NRTP/DLPN and/or its output/input fibers running through the SCP/MCP. Indeed, the NRTP seems to have neurons related with both ocular convergence and divergence (2). An exclusive injury of the SCP/MCP cannot also be excluded in our case because the FN/GL/EM is reciprocally connected with the SOA and the NRTP/DLPN by convergence-related and divergence-related fibers running through the SCP/ MCP (2). To the best of our knowledge, acute and Martins et al: J Neuro-Ophthalmol 2021; 41: e197-e199 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence simultaneous central paralysis of convergence and divergence manifesting as diplopia/strabismus at near and distance has not been reported before. In 2 other patients with a NRTP lesion, there was impairment of slow (i.e., pursuit) and fast (i.e., saccades) convergence and divergence movements, but these deficits were not associated with strabismus either at far or distance (5). As a limitation of this study, accommodative convergence assessment was not performed, which could have provided further insights. Acute and concurrent paralysis of ocular convergence and divergence as the only cause for binocular diplopia is a rare event. In our case, the simultaneous involvement of neurons mediating ocular convergence and divergence within the NRTP might have caused complete vergence paralysis. The use of standardized strabismic assessment both at near and distance together with formal eye movement recording is critical to accurately detect the presence of comitant strabismus, often associated with ocular vergence abnormalities, and to further rule out associated or alternative and far more common causes of acute diplopia, which usually lead to incomitant strabismus, including nuclear and internuclear eye movement disturbances. Martins et al: J Neuro-Ophthalmol 2021; 41: e197-e199 STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: A. I. Martins, A. Jorge, O. Galego, C. Nunes, R. Gonçalves, and J. Lemos, b. Acquisition of data: A. I. Martins, A. Jorge, O. Galego, C. Nunes, R. Gonçalves, and J. Lemos, c. Analysis and interpretation of data: A. I. Martins, A. Jorge, O. Galego, C. Nunes, R. Gonçalves, and J. Lemos. Category 2: a. Drafting the manuscript: A. I. Martins and A. Jorge, b. Revising it for intellectual content: R. Gonçalves and J. Lemos. Category 3: a. Final approval of the completed manuscript: A. I. Martins, A. Jorge, O. Galego, C. Nunes, R. Gonçalves, and J. Lemos; b. Critical revision of manuscript for intellectual content: J. Lemos and R. Gonçalves. REFERENCES 1. Brune AJ, Eggenberger ER. Disorders of vergence eye movements. Curr Treat Options Neurol. 2018;20:42. 2. Gamlin PDR, Yoon K, Zhang H. The role of cerebro-pontocerebellar pathways in the control of vergence eye movements. Eye. 1996;10:167–171. 3. Garcia AM, Egido JA. The chameleon syndrome: acute convergence paralysis. J Neurol Neurosurg Psychiatry. 2013;84:587. 4. Ghasemi M, Riaz N, Bjornsdottir A, Paydarfar D. Isolated pseudoabducens palsy in acute thalamic stroke. Clin Imaging. 2017;43:28–31. 5. Rambold H, Sander T, Neumann G, Helmchen C. Palsy of “fast” and “slow” vergence by pontine lesions. Neurology. 2005;64:338–340. e199 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.