Transient Bilateral Visual Loss as the Presenting Symptom of High-Altitude Ascent-Related Cytotoxic Lesion of the Corpus Callosum

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Transient Bilateral Visual Loss as the Presenting Symptom of High-Altitude Ascent-Related Cytotoxic Lesion of the Corpus Callosum Matthew Yang, MD, Subahari Raviskanthan, MBBS, Peter W. Mortensen, MD, Tanu Garg, MD, Andrew G. Lee, MD H igh-altitude ascent is a potentially dangerous human activity, and high-altitude cerebral edema (HACE) is a life-threatening disease. By contrast, less severe altitude-related illness includes acute mountain sickness (AMS). Typical clinical features for HACE include altered mental status, headaches, and other neurological symptoms, most commonly ataxia. Ophthalmic manifestations of HACE and AMS may include retinopathy and papilledema and can be seen in w 40% of patients in the literature (1). Imaging abnormalities in HACE most commonly show vasogenic or cytotoxic cerebral edema (1–3). We report a case of isolated episodic bilateral simultaneous vision loss in the setting of a cytotoxic lesion of the corpus callosum (CLOCC) after recent rapid high-altitude ascent. To the best of our knowledge, this is the first such reported case in the English language ophthalmic literature. A 25-year-old man with no medical history flew from his sea-level residence to 1,700 m elevation (Denver, CO) and undertook several local mountain hikes to no more than 2,500 m before a day hike to 4,287 m elevation. He experienced no adverse symptoms before or during his hikes, but 2 days later, having returned to the sea level, he experienced episodic vision loss. These were characterized by 20–30 seconds of vision loss that occurred approximately 15 times over 4 hours. Each episode was stereotyped and would have a gradual offset without intervention. The episodes ceased without any targeted intervention while the patient was admitted for observation. He denied any gastrointestinal, neurologic, Department of Ophthalmology (MT, AGL), University of Texas Medical Branch, Galveston, Texas; Department of Ophthalmology (SR, PWM, AGL), Blanton Eye Institute, Houston Methodist Hospital, Houston, Texas; Department of Neurology (TG), Houston Methodist Hospital, Houston, Texas; Departments of Ophthalmology, Neurology, and Neurosurgery (AGL), Weill Cornell Medicine, New York, New York; Department of Ophthalmology (AGL), University of Texas MD Anderson Cancer Center, Houston, Texas; Texas A and M College of Medicine (AGL), Bryan, Texas; and Department of Ophthalmology (AGL), The University of Iowa Hospitals and Clinics, Iowa City, Iowa. The authors report no conflicts of interest. Address correspondence to Andrew G. Lee, MD, Department of Ophthalmology, Blanton Eye Institute, Houston Methodist Hospital, 6560 Fannin Street, Ste 450 Houston, TX 77030; E-mail: aglee@ houstonmethodist.org e268 or pulmonary symptoms aside from dyspnea during strenuous exertion. He did not smoke and reported social alcohol intake. He reported previous use of marijuana 1 month before the onset of symptoms but denied the use of illicit substances before, during, or after his holiday. On examination, his visual acuity was 20/20 in both eyes (OU). External examination was unremarkable. His pupils were isocoric without relative afferent pupillary defect. His extraocular motility and confrontation visual fields were normal OU. Slit-lamp biomicroscopy and dilated fundus examination were unremarkable. Neurologic examination was normal. Automated perimetry (automated visual field 24-2) and optical coherence tomography of the optic nerve, macula, and ganglion cell layer were all within normal limits. Laboratory studies were within normal limits including complete blood count, comprehensive metabolic panel, lipid panel, urine drug screen, hypercoagulability panel, antineuronal antibody, antineutrophil cytoplasmic antibodies, vitamin B12, vitamin B9, homocysteine, and methylmalonic acid. Serology was negative for COVID19, QuantiFERON, HIV, syphilis serology, Lyme disease, angiotensin-converting enzyme, and lysozyme. Lumbar puncture was unremarkable except for culture growth of coagulase-negative Staphylococcus epidermidis deemed a contaminant by the infectious disease team. Imaging studies were unremarkable including chest x-ray, computed tomography (CT) of the head, CT angiography of the head and neck, transthoracic echocardiogram, and transcranial doppler. MRI of the brain and orbits with contrast the day of evaluation demonstrated a diffusion restricting lesion (bright on diffusion-weighted imaging and dark on apparent diffusion coefficient sequences) that was hyperintense on T2 fluid-attenuated inversion recovery (FLAIR) sequences, without contrast enhancement, consistent with a CLOCC within the splenium (Fig. 1A). Electroencephalography was within normal limits. On clinical review 1 month later, he had not had any further symptoms. Repeat MRI of the brain revealed resolution of the diffusion restricting lesion and decrease in T2 FLAIR hyperintensity, consistent with resolution of the CLOCC (Fig. 1B). Yang et al: J Neuro-Ophthalmol 2023; 43: e268-e270 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. A. MRI of the brain, axial sequences, at the time of initial presentation showing hyperintense lesion at the splenium of the corpus callosum on diffusion-weighted imaging (left—arrow), with corresponding hypointensity on apparent diffusion coefficient sequence (right—arrow), consistent with cytotoxic edema, and associated hyperintensity on T2 fluid-attenuated inversion recovery sequence (middle—arrow), suggestive of a cytotoxic lesion of the corpus callosum (CLOCC). B. MRI of the brain, axial sequences, at subsequent review 4 weeks later showing resolution of the previously seen lesion on diffusionweighted imaging (left) and apparent diffusion coefficient sequence (right). There is still mild hyperintensity on T2 fluidattenuated inversion recovery sequence, overall consistent with the resolution of the CLOCC. Our patient’s recent exposure to high-altitude, negative laboratory testing, lack of systemic symptoms, and lack of medical history suggests he had altitude-related CLOCC causing episodic vision loss, possibly HACE, although he had no other neurological symptoms. AMS and HACE are often viewed as a spectrum of illnesses with high-altitude exposure as the common precipitant for neurologic pathology. However, bilateral transient vision loss secondary to cerebral edema is not among the previously reported ophthalmic symptoms. In previous reports, anterior segment corneal edema or tear film changes have led to various visual disturbances (1). In other cases of HACE, optic disc edema, retinal hemorrhages, and cotton-wool spots have been associated with exposure to moderate altitudes 3,000 m (w9,800 ft) (1,3). Contrary to these reports, our patient only presented 2 days after returning to the sea level from an elevated altitude and had a normal ophthalmologic examination around the time of the symptoms (but not during an episode). Also, presumed mechanisms of neurological manifestations in HACE include disruption of the blood–brain barrier causing microhemorrhages, and susceptibility weighted imaging performed on our patient did not reveal any evidence of microhemorrhage (3). The largest series of patients with HACE reported in the literature showed that all 8 patients had MRI abnormalities in the corpus callosum, with at least 6 of them involving Yang et al: J Neuro-Ophthalmol 2023; 43: e268-e270 the splenium of the corpus callosum, suggesting this structure is likely involved in HACE (3). Restricted diffusion and vasogenic edema were the most common MRI abnormalities in the splenium, similar to our patient’s CLOCC (3). There has only been one previously reported case of episodic vision loss in a patient with a CLOCC, although with very similar symptoms to our patient. A 24-year-old 3month postpartum woman had multiple episodes of bilateral painless vision loss w 30 seconds in duration over 2 hours, with a CLOCC lesion on MRI and no other abnormalities on workup except an isolated fever. Her only active intervention included intravenous saline, and her symptoms and MRI lesion subsequently resolved (4). There is no clear hypothesis in the literature as to why a lesion in the corpus callosum might cause transient bilateral vision loss. To the best of our knowledge, this is the first case reported in the English language ophthalmic literature of bilateral simultaneous transient episodic loss of vision as the presenting symptom of CLOCC in the setting of recent high-altitude ascent. Clinicians should be aware that neurological and ophthalmologic manifestations of high altitude may manifest during the ascent, but also may present after the patient has returned to the sea level, and full workup should be considered to exclude other potential causes. e269 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence REFERENCES STATEMENT OF AUTHORSHIP Conception and design: M. Yang, S. Raviskanthan, P. W. Mortensen, T. Garg, A. G. Lee; Acquisition of data: M. Yang, S. Raviskanthan, P. W. Mortensen, T. Garg, A. G. Lee; c. Analysis and interpretation of data: M. Yang, S. Raviskanthan, P. W. Mortensen, T. Garg, A. G. Lee. Drafting the manuscript: M. Yang, S. Raviskanthan, P. W. Mortensen, T. Garg, A. G. Lee; Revising it for intellectual content: M. Yang, S. Raviskanthan, P. W. Mortensen, T. Garg, A. G. Lee. Final approval of the completed manuscript: M. Yang, S. Raviskanthan, P. W. Mortensen, T. Garg, A. G. Lee. e270 1. Willmann G, Gekeler F, Schommer K, Bärtsch P. Update on high altitude cerebral edema including recent work on the eye. High Alt Med Biol. 2014;15:112–122. 2. Starkey J, Kobayashi N, Numaguchi Y, Moritani T. Cytotoxic lesions of the corpus callosum that show restricted diffusion: mechanisms, causes, and manifestations. Radiographics. 2017;37:562–576. 3. Hackett PH, Yarnell PR, Weiland DA, Reynard KB. Acute and evolving MRI of high-altitude cerebral edema: microbleeds, edema, and pathophysiology. AJNR Am J Neuroradiol. 2019;40:464–469. 4. Gunaydin M, Ozsahin F. Transient visual loss: transient lesion in the splenium of the corpus callosum. Turk J Emerg Med. 2018;18:128–130. Yang et al: J Neuro-Ophthalmol 2023; 43: e268-e270 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.