Isolated clinical syndrome with optic neuritis related to COVID-19: Etiological, laboratory and neuroimaging perspectives

An 11-years old female started with a flu-like clinical picture, using only symptomatic medications. After six days of evolution, presented pain in the right eye with decreased visual acuity. The ophthalmological evaluation showed signs of optic neuritis. RT-PCR was positive for COVID-19, and the medical team requested imaging evaluation.

Imaging demonstrated thickening and hypersignal on STIR in the retrobulbar portion of the right optic nerve (Fig. 1A), associated with avid contrast enhancement on T1 fat-suppressed sequence (Fig. 1B). Those findings were compatible with optic neuritis.

Also, brain and orbital Magnetic Resonance Imaging (MRI) demonstrated oval and elongated T2/FLAIR hyperintensities located in the periventricular white matter (Fig. 2) and callous-septal interface perpendicular to the ependymal axis (Fig. 3), without gadolinium enhancement. These findings could represent demyelinating lesions.  Spinal MRI did not demonstrate lesions in the spinal cord.

Neuro-ophthalmological manifestations have been reported in COVID-19, displaying a more profound association in severe disease and hospitalized patients [1-5].

The laboratory and imaging data were crucial to reach the diagnosis: positive polymerase chain reaction (PCR) nasal swab analysis and later serology with positive IgM and IgG identified the SARS-Cov-2 infection; MRI demonstrated right optic neuritis, supporting the clinical condition; besides, Cerebrospinal fluid evaluation aided in excluding bacterial and fungal infections, with negative oligoclonal bands. Finally, diagnostic criteria of primarily demyelinating diseases like optic neuromyelitis and Multiple Sclerosis could not be fulfilled with the data presented [6,7]. However, the follow up is crucial to define possible diagnostic criteria for multiple sclerosis, considering the distribution and morphology of the lesions, since SARS-CoV-2 can be the trigger of the disease [8].

Acute disseminated encephalomyelitis could be a presumptive diagnosis since some cases were described in post-COVID-19 patients [9]. The neurological symptoms and imaging findings could represent this condition, although they are not entirely typical. A viral infection could be the trigger factor; however, the time of evolution was not precise in this case [10]. This autoimmune disease requires additional time to establish the immune-mediated process, and the patient had less than a week of symptoms of COVID-19 [9].

SARS-CoV-2 uses the Angiotensin-converting-enzyme 2 receptor to enter cells [2,5,10]. This receptor is remarkably expressed in the central nervous system, including the retina and its vessels [5]. This association could explain why neurotropism is a regular feature of SARS-Cov-2, with neurons and glial cells potential cellular targets [5,10]. However, the vascular mechanism cannot be excluded since COVID-19 can cause a pro-thrombotic state, vasculopathy, and endotheliopathy, including in the CNS [2,11]. Also, the virus was found in tears and the lacrimal duct in COVID-19 patients, providing another option of ocular and neurological dissemination [5,12].

Considering neurotropism and immune-mediated aetiology association between SARS-Cov-2 infection and CNS involvement, and that this virus could modify the patient immune system [13], it is not clear in this case whether there was direct virus invasion causing optic neuritis.  The most likely mechanism is an isolated clinical syndrome triggered by the virus that does not meet the radiological criteria for multiple sclerosis.

The patient started treatment with pulse IV methylprednisolone therapy 30/mg/kg/day for three days and three sessions of plasmapheresis. After a substantial improvement of the symptoms, she was discharged with oral prednisone and neurologic follow-up.