key: cord-0701872-fyqdxoud authors: Anilkumar, Aishwarya; Tan, Elizabeth; Cleaver, Jonathan; Morrison, Hamish D title: Isolated Abducens Nerve Palsy in a Patient with Asymptomatic COVID-19 Infection date: 2021-04-19 journal: J Clin Neurosci DOI: 10.1016/j.jocn.2021.04.011 sha: f1311a3b99c0d84530633f39f723f0ff5d81a829 doc_id: 701872 cord_uid: fyqdxoud The neuro-ophthalmological complications of SARS-CoV-2 infection are emerging but the spectrum of presentations and pathophysiological mechanism underpinning the association remains to be fully determined. We describe the case of a 44-year-old female who presented with a 12-hour history of diplopia preceded by a mild headache and was found to have an isolated right abducens nerve palsy. Initial vital signs were normal but she developed a fever and nasopharyngeal swab confirmed SARS-CoV-2 infection by RT-PCR. All other investigation results were normal including blood tests, chest X-ray, MRI brain and cerebrospinal fluid analysis. She remained systemically well, and there was complete resolution of the abducens palsy and diplopia at two week follow up. In the absence of any underlying cause or risk factors identified, the aetiology was presumed to be microvascular and potentially related to the underlying viral infection. We add to the growing literature on neuro-ophthalmological associations of SARS-CoV-2, consider possible causal mechanisms and suggest considering asymptomatic SARS-CoV-2 infection in cases of isolated abducens palsy without clear risk factors. Abducens nerve palsy is the most common isolated ocular motor palsy and has a wide range of potential aetiologies. In children, whilst most commonly associated with neoplasm, it has been associated with viral infections and following immunisations (1) . In older adults the most frequent cause is microvascular disease (2) . It is a rare presentation in younger adults, where the aetiology includes vasculopathies, neoplasia, multiple sclerosis and other inflammatory disease, with viral aetiologies responsible for 1-10% of cases. (3) There are emerging cases of abducens nerve palsies related to SARS-CoV-2 infection -both isolated and in association with other ocular and central nervous system (CNS) manifestations -but the incidence and pathophysiological mechanisms behind these associations is yet to be fully established. We present a case of isolated abducens nerve palsy in an individual with otherwise asymptomatic SARS-CoV-2 infection. A 44-year-old right-handed female attended her local Emergency Department after she awoke with persistent diplopia. The preceding day, she had a mild right-sided headache and blurred vision, which had significantly improved at the time of presentation. There were no additional features of migraine or raised intracranial pressure. She denied recent history of fever, malaise, cough or anosmia. There was no antecedent history of trauma, rash, insect bites or foreign travel. Her past medical history included migraine with aura, without previously associated cranial nerve palsies. She had no known vascular risk factors. On admission, she was afebrile with stable observations and no respiratory symptoms. Examination was notable for isolated, complete abduction failure of the right eye with associated horizontal diplopia which persisted on primary gaze and was exacerbated by distance fixation. All other extraocular movements were full, fundal and pupil examination was normal with no evidence of ptosis, proptosis, chemosis or fatigable weakness. The remainder of the neurological examination was normal. Repeat routine observations on the neurology ward revealed a pyrexia of 39.5C with otherwise normal vital signs. The patient's admission nasopharyngeal swab subsequently confirmed SARS-CoV-2 infection by real-time reverse transcription polymerase chain reaction (RT-PCR). Routine blood tests including lymphocyte count, C-reactive protein and urea and electrolytes were normal, as was the chest X-ray. HbA1C, cholesterol, plasma viscosity, thyroid stimulating hormone, anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, angiotensin-converting enzyme and acetylcholine receptor antibodies later returned normal. Magnetic resonance imaging (MRI) of the brain with gadolinium and dedicated venogram was normal. Lumbar puncture revealed a normal opening pressure and normal cerebrospinal fluid (CSF) constituents (WCC <1 mm3, RBC <1 mm3, protein 0.2 g/L, glucose 3.7 mmol/L), negative oligoclonal bands and a negative viral PCR for enterovirus, varicella zoster and herpes simplex type 1 and 2. CSF analysis for SARS-CoV-2 RNA was not available at our centre. The patient's isolated pyrexia resolved; she remained systemically well and was discharged 48-hours post admission with a persisting ophthalmoparesis. No treatment was required other than paracetamol for the pyrexia. At two week follow up, there was complete resolution of the abducens nerve palsy and diplopia. She reported the double vision had resolved five days after discharge and she remained systemically well. COVID-19 is associated with a broadening range of neuro-ophthalmological complications (4). These 4)(7) We discuss possible mechanisms behind the abducens palsy described in this case below. There is widespread evidence that COVID-19 is associated with vascular and thrombotic complications. Virus-mediated immune response is another proposed mechanism within the literature, with documented cases of Miller Fisher Syndrome in the context of SARS-CoV-2 infection(4). However, this is typically a post-infectious phenomenon, therefore the timing of abducens palsy during the active stage of SARS-CoV-2 infection in this case would be atypical. Furthermore, the lack of other neurological signs, such as ataxia or areflexia, together with the normal CSF protein level would be unusual for a Guillain-Barre syndrome variant. However, anti-ganglioside antibodies were not tested in this case and a viral induced immune-mediated neuropathy cannot be excluded as a potential mechanism. Whilst we acknowledge the occurrence of isolated abducens palsy and SARS-CoV-2 infection could be coincidental and unrelated, here we postulate a causative link due to the otherwise rare occurrence of abducens palsy young adults without risk factors. We add to the literature of emerging neuroophthalmological associations of COVID-19 infection and evaluate published cases to date of abducens nerve palsy associated with SARS-CoV2, considering potential mechanisms. Further work is required to more confidently support causality and to elucidate the proposed mechanisms. Early follow-up suggests a full recovery is possible without specific treatment. As the pandemic continues across the globe, we suggest considering asymptomatic COVID-19 infection in patients presenting with ocular motor palsies without other risk factors. Benign Recurrent Sixth Nerve Palsies in Childhood Isolated Sixth-Nerve Palsies in Younger Adults Cause and prognosis of nontraumatic sixth nerve palsies in young adults A Review of Neuro-Ophthalmological Manifestations of Human Coronavirus Infection. Eye Brain COVID-19 presenting with ophthalmoparesis from cranial nerve palsy Neurol -Neuroimmunol Neuroinflammation Acute abducens nerve palsy in a patient with the novel coronavirus disease (COVID-19) Miller Fisher syndrome and polyneuritis cranialis in COVID-19 Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis The Emerging Threat of (Micro)Thrombosis in COVID-19 and Its Therapeutic Implications Coagulation Abnormalities and Thrombosis in Patients Infected With SARS-CoV-2 and Other Pandemic Viruses Pain in ischaemic ocular motor cranial nerve palsies Clinicians and researchers confirmed for the first time that SARS-CoV-2 can cause central nervous system infection Status of SARS-CoV-2 in cerebrospinal fluid of patients with COVID-19 and stroke A first case of meningitis/encephalitis associated with SARS-Coronavirus-2 The authors declare no conflict of interest.This research did not receive any specific grant from funding agencies in the public, commercial, or notfor-profit sectors. SARS-CoV-2 is associated with a range of neuro-ophthalmological complications  Isolated abducens nerve palsy may be the presenting feature of SARS-CoV-2 infection  We review published cases to date of abducens nerve palsy associated with SARS-