COVID-19 Symptoms: New Documented Case Shows That SARS-CoV-2 Can Cause Cranial Nerve Palsy With Resulting Double Eye Vision (Diplopia)

COVID-19 Symptoms: Moroccan medical researchers have reported a documented case of a COVID-19 patient manifesting double vision (Diplopia) and misalignment of her left eye (Strabismus). Investigations showed that the conditions were a result of third cranial nerve palsy caused as a result of SARS-CoV-2 infection.


Restricted upgaze (A), adduction (B), and downgaze (C) of the left eye in ocular motility examination
 
The report and study findings were published in the American Journal of Case Reports. https://www.amjcaserep.com/abstract/index/idArt/925897
 
The manifestation of such symptoms was not unique as cross checks with physicians and databases around the world indicated that such incidences had occurred but not properly documented.
 
In this documented case, a previously healthy 24-year-old woman was admitted to an emergency department at Mohammed VI University Hospital Center at Caddy Ayad University, Marrakesh-Morocco reporting double vision and misalignment of her left eye.
 
Her symptoms have worsened since starting about 3 days earlier, but she has no eye pain or redness.
 
Accordingly about 4 days prior, she had developed a fever (38.5°C) and dry cough, and lost her sense of smell, and notes that her father whom she sees regularly tested positive for COVID-19 the day before.
 
The hospital clinicians confirmed strabismus and diplopia of the patient's left eye. Her medical history was excellent and included no risk factors for ischemic ophthalmoplegia (i.e., diabetes, high blood pressure, dyslipidemia, vasculitis, smoking, obesity, or familial neurological disease).
 
Detailed clinical examination shows her blood pressure and hemodynamic state are within normal ranges: Blood pressure-110/70 mm Hg, Oxygen saturation-95%,Heart rate -67 bpm, Respiratory rate-21 bpm.
 
The doctors performed an ophthalmological exam, which showed visual acuity of 0.1 logMAR in both eyes. Palpebral examination notes no ptosis. Both pupils were of equal in size and reactive to light and accommodation, with no afferent pupillary defect.
 
Further assessment of the patient's ocular motility revealed restricted upgaze, adduction, and downgaze of the left eye. The diplopia increased in adduction, and findings of the slit lamp and fundus examinations were unremarkable.
 
All results of the rest of the physical exam were unremarkable and did not identify any neurological impairment.
 
The doctors diagnosed the patient with incomplete palsy of the third cranial nerve.
 
Importantly results of a nasopharyngeal swab for SARS-CoV-2 by reverse transcription polymerase chain reaction come back positive, and the patient was admitted to the COVID-19 ward.
 
Further subsequent laboratory workup and radiological investigations were performed on the patient's first day in the hospital.
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The magnetic resonance angiography of the brain and orbits showed no evidence of lesions or aneurysmal compression of the third left cranial nerve.
 
Further blood test results suggested mild normocytic regenerative anemia, with no evidence of inflammation, thrombophilia, or renal or hepatic impairment. The corrected QT interval was 380 ms on electrocardiogram.
 
The doctors started the patient on the following standard treatment recommended for COVID-19 in Morocco: ie Chloroquine (500 mg BID for 10 days) Azithromycin (500 mg once a day for the first day, then 250 mg once daily for 6 days) Vitamin C (1 g BID for 10 days) Zinc (90 mg BID for 10 days).
 
Interestingly the patient's fever resolved on the second day and her overall clinical status shows improvement, as does the exotropia and diplopia of her left eye.
 
It was found that on the sixth day, her ocular motility returned to normal, and she showed complete recovery.
 
Also four days later, the patient's hemoglobin levels returned to within the normal range, and she showed no signs of any treatment adverse effects. She was discharged home.
 
Physicians reporting this case of a patient who develops incomplete unilateral palsy of the third cranial nerve during the acute phase of COVID-19 infection noted that ophthalmological manifestations of COVID-19 are relatively rare compared with the typical clinical features of fever, dry cough, dyspnea, myalgia, and fatigue.
 
Despite various disorders including cerebral aneurysms, vascular disorders, tumors, and diabetes mellitus can lead to unilateral oculomotor nerve palsy, this patient had no clinical, laboratory, or imaging evidence of an underlying structural etiology. This led the team to suspect COVID-19 infection as the cause of the transient oculomotor nerve palsy.
 
The doctors involved in this case explain that although COVID-19 infection has been associated primarily with respiratory symptoms, the variety of organs affected appears to be expanding to involve different body systems.
 
The extensive range of affected organs is thought to reflect the common expression of the major SARS-CoV-2 entry-receptor angiotensin-converting enzyme 2 (ACE2), which appears to be the gateway for the virus into the cell. Given the overexpression of ACE2 receptors in the lungs, the typical respiratory presentation of COVID-19 infection is not surprising.
 
Interestingly in a 2004 analysis of autopsy tissue samples from patients who died of SARS, researchers reported that while the virus (SARS-CoV) was found predominantly in the lungs, trachea, and bronchus, it was also detected in many other organs and tissues, including the stomach, small intestine, kidney, adrenal glands, skin, and parathyroid, which harbored 25-49% positive cells. https://onlinelibrary.wiley.com/doi/full/10.1002/path.1560
 
The physicians for the current patient noted that penetration of SARS-CoV-2 through the cribriform lamina of the ethmoid bone may damage the olfactory bulb, causing loss of sense of smell and that this can be the entry route to the nervous system.
 
Furthermore, the expression of ACE2 receptors in nerve cells explains the neurological damage that can occur with COVID-19 infection.

Pertaining to the hypothetical neurotropic nature of the virus, the doctors point to a study of 214 cases, which found neurological manifestations in over one-third of COVID-19 patients. Such neurological lesions can be secondary to neuronal damage without inflammation or caused by direct action of the virus on the nerves or vessels in particular in the setting of a necrotizing hemorrhagic encephalopathy. https://jamanetwork.com/journals/jamaneurology/fullarticle/2764549
 
So far the ophthalmological effects of coronavirus infection generally present in the form of conjunctivitis in some cases as the initial manifestation of COVID-19 infection before development of respiratory symptoms.
 
Also COVID-19 has been linked with inflammatory neuropathies, and the case doctors cite a report of a patient with a complete isolated third oculomotor nerve palsy, who ultimately died of respiratory failure 12 days later. Two other cases of ophthalmoplegia associated with neurological impairment were slower to improve, and in this case the patient had no headache or other signs of central nervous system involvement.
 
The physicians in this case conclude that as shown in this patient, unilateral palsy of the third cranial nerve can be a sign of COVID-19 in adults, and can occur in patients with mild symptoms and without other central nervous system involvement.
 
Hence double vision (Diplopia) and misalignment of her left eye (Strabismus) can also be symptoms of COVId-19 disease.
 
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