Sequential orbital apex syndrome following the COVID-19 vaccination: A case report

Abstract

Background

Many kinds of vaccines have been developed worldwide to bring the coronavirus disease 2019 (COVID-19) to an end. We report a case of recurrent orbital apex syndrome following the first and third doses of SARS-CoV-2 vaccination.

Case presentation

A 71-year-old woman presented with acute painless diplopia and visual disturbance for two days. She had received the first dose of the COVID-19 vaccine two weeks before. She showed decreased visual acuity and ophthalmoplegia in the right eye. An orbital magnetic resonance image (MRI) revealed a hyperintense lesion with enhanced bulging in the right cavernous sinus. Following the steroid pulse therapy, she fully recovered. However, six months after the first attack, painful ophthalmoplegia with decreased visual acuity recurred in her left eye after the booster vaccination for COVID-19. MRI also showed a well-enhanced hyperintense lesion in the left orbital apex. Fortunately, her visual acuity and ocular motility returned to normal after the steroid therapy.

Conclusions

Immunologic reactions from COVID-19 vaccines may cause multiple cranial neuropathies. Diverse individual immunologic states should be considered before any kind of vaccine.

Highlights

• •Orbital apex syndrome, a rare neurological condition, can be caused by COVID-19 vaccinations, even repeatably.
• •Our patient showed sequential inflammatory orbital apex syndrome induced by various COVID-19 vaccinations.
• •Individual immunologic pre-existing conditions should be considered as a side effect of vaccinations.

1. Background

The coronavirus disease 2019 (COVID-19) has spread worldwide and led to widespread social disruption. In order to end the unprecedented situation, the vaccination for COVID-19 has been developed actively around the world [1] and administrated over 10 billion doses (World Health Organization). Also, the inevitable side effects from vaccination have been reported, which is not uncommon involving the cranial nerves or the central nervous system (CNS). [2] We report a case of recurrent orbital apex syndrome following the first and third doses of SARS-CoV-2 vaccination. To our knowledge, this is the first report of sequential orbital apex syndrome after the COVID-19 vaccine and booster administration.

2. Case presentation

On June 19, 2021, a 71-year-old woman presented to the emergency department with acute onset of painless diplopia and visual disturbance for two days. She had a history of mitral valve replacements at 50 and well-controlled hypertension. She got vaccinated against influenza every year from age 65 without any side effects. She received the first COVID-19 Oxford/AstraZeneca vaccine on June 5, 2021. She denied headache, fever, nausea, vomiting, or other neurologic symptoms. Upon examination, her visual acuity was 20/40 in the right eye and 20/20 in the left. The pupils were round and equally responsive to light without rapid afferent pupillary defect (RAPD) or anisocoria. She had limited adduction, supraduction, and infraduction of her right eye with ptosis (Fig. 1-A and 1-B). Abduction of the right eye, all movements of the left eye, and corneal reflexes in both eyes were normal. A fundoscopy examination was also normal bilaterally. Complete blood counts, liver, thyroid, and renal function tests were normal. Antinuclear, anti-Smith, anti-cardiolipin, anti-dsDNA IgG antibodies, and lupus anticoagulant were negative. Angiotensin-converting enzyme, complement C3 and 4, were also normal. Only anti-dsDNA IgM was positive (37.4 U/ml). CSF study was unremarkable. An orbital magnetic resonance image (MRI) and brain magnetic resonance angiography showed a hyperintense lesion with enhanced protruding in the right cavernous sinus (Fig. 1-C). Following IV prednisolone 1 g/day for five days with tapering for one month, she fully recovered with 20/20 visual acuity in both eyes (Fig. 1-D).

Fig. 1.

On June 19, 2021, after 14 days from Oxford/AstraZeneca vaccine, the right oculomotor nerve palsy showed in 9 gaze photos (A) and the Lancaster red-green test (B). Orbital MRI (C) revealed an enhanced focal lesion in the right cavernous sinus (Red arrow). Her extraocular muscle limitations fully recovered on July 21, 2021 (D). After 25 days from the third dose of the Pfizer-BioNTech vaccine on January 7, 2022, the follow-up orbital MRI (E) was conducted for painful ophthalmoplegia and decreased visual acuity on the left eye and revealed a hyperintense focal inflammation on the left orbital apex (Red arrow). The follow-up Lancaster red-green test also showed the limitation of adduction, supra- and infraduction on the left eye (F).

O.D. = oculus dexter, O.S. = oculus sinister. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

After confirming that there was no recurrence and sequelae, she received the second COVID-19 Oxford/AstraZeneca vaccine on August 21 and the third Pfizer-BioNtech vaccine on December 13, 2021. Then nine days later, the patient developed painful diplopia and severe visual disturbance, which was in the opposite (left) eye from the previous one. When she attended the emergency department again on January 7, 2022, she could see only the hand motion on the left eye with dilated pupil and RAPD. The visual acuity in the right eye was 20/20. She had limited adduction, supraduction, and infraduction of the left eye with ptosis (Fig. 1-F). Abduction of the left eye, all eye movements of the right eye, corneal reflexes, and fundus in both eyes were normal. Chest and abdominal CT for hidden malignancy or inflammatory diseases did not show any abnormal findings. All blood tests were the same as the previous results (anti-dsDNA IgM antibody: 41.2 U/ml). The follow-up orbital MRI revealed a well-enhanced hyperintense lesion in the left orbital apex, which was more prominent than the previous right focal lesion. Fortunately, her visual acuity and ocular motility returned to normal after IV prednisolone 1 g/day for five days with tapering for one month.

3. Discussion

Recently, Tolosa-Hunt syndrome after seven days from mRNA-1273 COVID-19 vaccination was published as a hypothesized consequence of auto-immune responses or coincidence. [3] However, neurological inflammatory side effects involving CNS after SARS-CoV-2 vaccination have been reported one after another. [4,5] Furthermore, isolated cranial neuropathies after several days of vaccination have been more frequently published [[6], [7], [8], [9]] and they assumed the possibility of an immunogenic demyelinating or microvascular process triggered by the vaccine in susceptible individuals. [2,4,5]

Interestingly, our patients showed repeated orbit apical lesions in the opposite eye sequentially after receiving different types of vaccines. Although each Oxford/AstraZeneca and Pfizer-BioNTech vaccine has a different target strategy, both elicit S-protein-specific IgG and neutralizing antibodies in humans. [1] Therefore, these recursive inflammatory CNS lesions may be derived from the final antibodies of the acquired immunization process by vaccination. Her immunologic predisposition associated with anti-dsDNA IgM antibody can contribute to that, although she could not have met the diagnostic criteria for systemic lupus erythematosus. [10]

4. Conclusion

COVID-19 vaccinations can be an indispensable option for escaping this catastrophe worldwide. Even if it is possible that an unexpected CNS inflammation and COVID-19 vaccinations are concurrent in the present case, the immunologic reaction from these vaccines may cause multiple cranial neuropathies. Also, diverse individual immunologic states should be considered before any kind of vaccine.

Author contribution

Dr. S. Choi conducted the conceptualization of the study, analyzed and interpreted the data, and wrote the manuscript.

Dr. J. Choi, and Dr. E. H. Oh analyzed and interpreted the data.

Dr. K. Choi, the first author, conducted the experiments, analyzed, and interpreted the data.

Ethical standard

This study followed the tenets of the Declaration of Helsinki and was performed according to the guidelines of Institutional Review Board of Pusan National University Hospital (2203–028-113). The patient gave written informed consent for participation in the trial.

Study funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT). (No. 2021R1F1A1051464).

Availability of data and materials

The datasets used the current study are available from the corresponding on reasonable request.

Declaration of Competing Interest

No conflicting relationship exists for the authors.