key: cord-1031757-1iqa77av
authors: Pascual-Goñi, Elba; Fortea, Juan; Martínez-Domeño, Alejandro; Rabella, Nuria; Tecame, Mario; Gómez-Oliva, Cristina; Querol, Luis; Gómez-Ansón, Beatriz
title: COVID-19-associated ophthalmoparesis and hypothalamic involvement
date: 2020-06-25
journal: Neurol Neuroimmunol Neuroinflamm
DOI: 10.1212/nxi.0000000000000823
sha: c0c947d52dd2b3a8f6652f008ea1c418c39e640a
doc_id: 1031757
cord_uid: 1iqa77av

nan

thiamine and pyridoxine despite normal vitamin levels. The patient's mental status partially improved during the following days. A control MRI (1 week after) also demonstrated partial improvement of the MRI findings. After 1 month, ophthalmoparesis and paraparesis as well as her mental status improved, but she had persistent episodic memory loss and depression.

To our knowledge, these are the 2 first patients with COVID-19 presenting with ophthalmoparesis and involvement of the hypothalamus and mesencephalic tegmentum with some radiologic features resembling those of WE. 2 However, thiamine levels in both our patients were normal, and there was no condition leading to thiamine deficiency in patient 1 and some radiologic features in case 2 (limbic involvement) were not typical of WE. Concurrency of both patients, both diagnosed with COVID-19, and the important hypothalamic involvement suggested a relationship with the underlying infection. Other cases of ophthalmoparesis associated with COVID-19 have recently been reported, 3,4 one of them with enlargement and contrast enhancement of the oculomotor nerve that we did not observe in our patients. Acute hemorrhagic necrotizing encephalopathy has also been reported in association with confirmed COVID-19 on MRI. 5 Similarly, encephalomyelitis associated with SARS-CoV-2 has been recently reported in a patient with unconsciousness and epileptic seizures in which SARS-CoV-2 was detected in the CSF, and MRI demonstrated T2-HI in the right medial temporal lobe. 6 Our current cases show prominent hypothalamus and pituitary stalk involvement on MRI. Indeed, SARS-CoV (a related coronavirus causing the 2002-2004 SARS outbreak) has also been detected in hypothalamic neurons of SARS autopsies, 7 and hypothalamic-pituitaryadrenal axis dysfunction has been observed in almost 40% of SARS survivors, suggesting that SARS-CoV could cause hypophysitis and/or hypothalamic damage. 8 Furthermore, animal models have shown that after intranasal inoculations, SARS-CoV enters the brain through the olfactory bulb and via the olfactory nerve with subsequent trans-synaptic spread, causing selective neuronal infection and death in the absence of inflammation in the amygdala, raphe nuclei, and paramedial hypothalamus, a topographic distribution of lesions similar to that from our cases. 9 The olfactory bulb involvement is supported by the high rates of hyposmia in patients with COVID-19 and would enable the trans-synaptic spread hypothesis. However, other mechanisms, arising from the inflammatory response or the metabolic demands to the susceptible regions, could also be playing a role in the development of our patients' lesions.

In conclusion, we report 2 cases of COVID-19-associated neurologic manifestations with abducens palsy, encephalopathy, and characteristic MRI findings that suggest selective vulnerability of the involved regions. Whether this vulnerability is related to 

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