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An Unusual Case of Multiple Sclerosis Presenting with Skew Deviation Following COVID Vaccination

Anupama Janardhanan, Shashikant Shetty*

Head of the Department, Department of Paediatric Ophthalmology and Adult Strabismus, Aravind Eye Hospital, Madurai, India

Abstract: Ocular tilt reaction is an uncommon phenomenon. It is usually misdiagnosed as superior oblique palsy. One of the rare oculomotor presentations of multiple sclerosis is ocular tilt reaction. Large number of people get affected by multiple sclerosis every year. Prompt diagnosis and timely intervention helps in long term rehabilitation and prevents irreversible sequele. We report a case of a young girl with no prior history of any co morbidity, presented with double vision and was diagnosed with ocular tilt reaction. The only attributable history was of receiving COVID vaccine. On further evaluation and literature review the case was differentiated from an adverse reaction of COVID vaccination. A diagnosis of multiple sclerosis was determined that enabled early initiation of appropriate systemic therapy for her. In our knowledge, this becomes the first case report that describes, an ocular tilt reaction as a manifestation of multiple sclerosis following COVID vaccination.

Keywords: skew deviation, ocular tilt reaction, COVID vaccine, multiple sclerosis, vertical deviation

Received February 10, 2022; Revised March 13, 2022; Accepted March 20, 2022

Citation: Anupama Janardhanan, Shashikant Shetty, An Unusual Case of Multiple Sclerosis Presenting with Skew Deviation Following COVID Vaccination. Neuro Ophthalmology & Visual Neuroscience, 7 (1). 1-4. January 2022. doi:10.12691/novn-7-1-1

1. Introduction

In the uncertain times of Covid-19 pandemic, discovering vaccination has been evolutionary. We have an array of well-engineered vaccines as on date, that has been tested in a variety of systemic conditions in smaller groups. Yet they continue to surprise us with their heterogenous effects.

Multiple sclerosis (MS) is a demyelinating disease of central nervous system. [1] Many ocular motor manifestations have been identified to occur in MS [1]. So far, ocular motor manifestation of a new onset MS has not been reported following COVID vaccination.

Ocular tilt reaction is one of the uncommon presenting features of MS [2]. It is characterized by skew deviation, head tilt and ocular torsion. Since most common presentation of multiple sclerosis in young individuals is optic neuritis. Ocular tilt reaction becomes challenging to diagnose and arduous to trace back to a demyelinating disorder, when presenting in a young healthy individual. [1] Since skew deviation presents with a unilateral hypertropia and contralateral hypotropia, sometimes it may mimic superior oblique paresis. [7] This case is reported in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed written consent of the patient to publish clinical picture and information has been obtained.

2. Case Report

We report a case of a 22-year-old female patient who presented to us with complaints of sudden onset double vision of 3 days duration. She was perceiving two images with horizontal and vertical separation which was worsening in left gaze. It was associated with deviation of right eye. She had received first dose of ChAdOx-1 nCov-19 (COVISHIELD) corona virus vaccine a day before onset of symptoms. Also reported tingling and numbness along both her legs, noted shortly after the onset of double vision. She mentioned about similar episode of tingling and numbness over legs about an year back. It had resolved spontaneously and was not investigated. There was no complaint of any pain/diminution of vision/ head trauma/ febrile illness.

General physical examination was unremarkable. Neurological assessment revealed reduced sensations over both lower extremities.

On ophthalmic evaluation she was found to have a Best corrected visual acuity of 20/20 both eyes and J6 Jaegar’s for near vision. Slit lamp biomicroscopy of anterior segment of both eyes and pupil examination were normal. Posterior segment evaluation of both eyes did not reveal any pathology.

Figure 1. Nine gaze collage of patient showing Right hypertropia with exotropia and right adduction deficit

On orthoptic evaluation she had a small head tilt (~ 10 degrees) to right side. (Figure 3a) Hirschberg’s test showed 10 degrees Right eye (RE) hypertropia (HT). On cover test there was Alternating exotropia (XT) with RE HT. Prism Bar Cover test for distance showed a 16 prism dioptres (PD) XT with 10 PD RE HT for distance and for near 20 PD XT with 8 PD RE HT. (Figure 1)

Park Bielchowsky three step test showed a 12 PD RE HT with 12 PD XT on right head tilt and 16 PD XT with no HT in left head tilt. Her nine gaze measurements are as in (Figure 2).

Figure 2. Depicting measurement of deviation in all nine gazes and on head tilts

Double maddox rod results showed absence of torsional diplopia. Ocular motility showed -1 adduction deficit of right eye. An abducting nystagmus was noted in the left eye on levoversion. However, no restriction of adduction was observed on convergence. Her fundus evaluation was normal except for incyclotorsion of Right eye and excyclotorsion of left eye. (Figure 3b & c)

She was clinically diagnosed to have right sided Internuclear ophthalmoplegia with left skew deviation.

In view of sudden onset vertical diplopia, Magnetic resonance imaging (MRI) of Brain and orbit was advised. MRI brain depicted multiple hyperintensities in brain parenchyma, suggestive of demyelination involving corpus callosum, peri callosal regions, calloso-septal interface, brainstem, middle cerebellar peduncle and cervico thoracic cord. (Figure 3d-f)

On Neurologist consultation and further investigations, she was confirmed to have active lesions of multiple sclerosis and was started on systemic treatment.

Six days from the initiation of treatment, her symptoms started resolving. She was explained regarding her eye condition being secondary to the underlying systemic disorder and advised to follow up regularly.

3. Discussion

Multiple sclerosis causes widespread inflammation of myelin, axons, white matter, blood vessels and neurons. Missing diagnosis and delay in treatment lead to persistent deficits after each attack. [3] Due to extensive possibilities of anatomical involvement, clinical presentation is usually diverse. [1]

Incidence of skew deviation and unilateral INO is about 13.5 % and 14.7 %, but combination of both is infrequent. [2]

Skew deviation is an ocular manifestation characterised by vertical misalignment caused due to disruption of prenuclear vestibular input to oculomotor nucleus. When skew deviation is accompanied by torticollis, ocular torsion and subjective visual field tilt it is termed as ocular tilt reaction. [4] It is a phrase coined by Westheimer and Blair in 1975. [5]

Presentation of skew deviation can be identical to trochlear nerve palsy at first. Park’s 3 Step test may give equivocal results depending on whether it is a comitant or an incomitant type of skew deviation. [6] On a detailed orthoptic evaluation they both can be differentiated.

Figure 3. a) Right head tilt of ocular tilt reaction. b) Right eye Fundus photograph demonstrating Incyclotorsion. c) Left Eye Fundus photograph demonstrating Excyclotorsion d-f) MRI of brain showing multiple hyperintensities (red arrows) diffusely noted across brain parenchyma in sagittal (d), axial (e) and coronal sections (f)

On dilated fundus examination, in trochlear nerve palsy, excyclotorsion is noted in comparison to incyclotorsion that is found in the hypertropic eye of skew deviation (excyclotorsion of hypotropic eye). [7]

In case if vertical misalignment is not evident, double Maddox rod testing, blind spot mapping and settings of subjective visual vertical can be helpful. [4]

Recently, Upright-supine test has been found to be diagnostic to skew deviation. Wong et al demonstrated that in case of skew deviation, more than 50 % resolution of vertical misalignment occurs in supine position in comparison to upright position. Whereas, no such postural difference is noted in trochlear nerve palsy. [8]

Skew deviation can be classified into comitant- same deviation in all gazes, incomitant-deviation varies with each gaze, laterally comitant deviation that has hyperdeviation worsening in lateral position and alternating skew deviation which has alternating hyperdeviation of either eyes. [4] Also, rarely identified are paroxysmal intermittent skew deviation and neonatal skew deviation. Underlying pathophysiology depends on the area of insult. It can be either central (brainstem or cerebellum) or peripheral (vestibular nerve). [4]

Finer details and associated neurological features help in localizing the site of affliction. [4] Such as, when skew deviation results from lateral medullary infarction there is a difference between amount of ocular torsion of either eyes. Wallenberg’s syndrome presents with an associated torsional nystagmus. [4] Medial medullary lesions demonstrate an upbeating nystagmus along with skew deviation. [4] When associated with INO, pathology can be traced back to medial longitudinal fasciculus as evidenced in our case. [1]

Acute episode of multiple sclerosis manifesting as ocular tilt reaction and unilateral internuclear ophthalmoplegia within few days of receiving COVID vaccine has not been reported till now.

Only two isolated reports in similar line were found. Fujimori et al came across a 40-year-old with right arm paraesthesia two weeks following Pfizer-BioNTech COVID-19 vaccine and was diagnosed to have MS. [9] Maniscalco et al reported an exacerbation and development of fresh MRI evident lesions along with clinical worsening in an already diagnosed case of MS after 2 days of receiving COVID-19 BNT162b2 vaccine. [10] COVISHIELD is one of the most effective vaccines. It has been evaluated widely and found to have a fair safety profile as per all clinical trials. [11]

Few underlying mechanisms have been suggested regarding development of an autoimmune disease following vaccination. Maniscalco et al suspected a strong B and T cell response that may precipitate the autoimmune activity by increasing migration and placement of autoreactive T cells to central nervous system. [10] According to Mainland et al, epitope spreading, cytokine upregulation and polyclonal activation of lymphocytes cause immune reactions leading to an autoimmune response. [12] Another mechanism proposed by Farez et al is the presence of Angiotensin converting enzyme in the endothelium of blood brain barrier which precipitates an inflammatory response on encountering viral spike proteins. [13] Additionally, a study has noted that immunological interaction with myelin basic protein and interaction between Covid 19 spike protein and host proteins effects in re /activation of demyelinating diseases. [14]

However, a mass study conducted on 200 MS patients that received Pfizer-BioNTech COVID-19 vaccine showed that only around 2 % patients developed myelitis. It was finally concluded to be the same relapse rate that would be noted in a population without vaccination. [15]

4. Conclusion

This case was an uncommon presentation of MS. It adds to the variety of neuro ophthalmic presentations related to COVID vaccines. Ocular tilt reaction must be identified and differentiated from trochlear nerve palsy. An early diagnosis and timely management may prevent long term debility. We strongly believe that the lifesaving benefits of the COVID vaccine outweighs the rare risks associated with it. There is a need to study the impact of vaccination over demyelinating diseases.

5. Statements and Declarations

The authors have no relevant financial or non-financial interests to disclose. The authors have no competing interests to declare that are relevant to the content of this article.

This case is reported in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed written consent of the patient to publish clinical picture and information has been obtained.

References

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[2]   | Servillo G, Renard D, Taieb G. Bedside Tested Ocular Motor Disorders in Multiple Sclerosis Patients. Multiple Sclerosis International, 1-4, Apr 2014.
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[5]   | Westheimer G, Blair SM. The ocular tilt reaction--a brainstem oculomotor routine. Investigative Ophthalmology 14(11): 833-9. Nov 1975.
[6]   | Kushner BJ. Errors in the Three-step Test in the Diagnosis of Vertical Strabismus. Ophthalmology. 96(1): 127 32. Jan 1982.
[7]   | Donahue SP, Lavin PJ, Mohney B. Skew deviation and inferior oblique palsy. American Journal of Ophthalmology 132(5):751-6. Nov 2001.
[8]   | Wong AMF. Understanding skew deviation and a new clinical test to differentiate it from trochlear nerve palsy. Journal of American Association for Pediatric Ophthalmology and Strabismus. 14(1): 61-7. Feb 2010.
[9]   | Fujimori J, Miyazawa K, Nakashima I. Initial clinical manifestation of multiple sclerosis after immunization with the Pfizer-BioNTech COVID-19 vaccine. Journal of Neuroimmunology 15; 361: 577755. Dec 2021.
[10]   | Maniscalco GT, Manzo V, Di Battista ME. Severe Multiple Sclerosis Relapse After COVID-19 Vaccination: A Case Report. Frontiers in Neurology, 12:721502. Aug 2021.
[11]   | Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. The Lancet. 397(10269). Dec 2020.
[12]   | Mailand MT, Frederiksen JL: Vaccines and multiple sclerosis: a systematic review, J Neurol., 264: 1035-50. Jun 2017.

[13]  
Farez MF, Correale J, Armstrong MJ, et al.: Practice guideline update summary: vaccine-preventable infections and immunization in multiple sclerosis: report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology. Neurology, 93: 584-94, Sep 2019.

[14]   | Langer-Gould A, Qian L, Tartof SY, et al.: Vaccines and the risk of multiple sclerosis and other central nervous system demyelinating diseases. JAMA Neurol, 71:1506-13, Dec 2014.
[15]   | Achiron A, Dolev M, Menascu S, Zohar D-N, Dreyer-Alster S, Miron S, et al. COVID-19 vaccination in patients with multiple sclerosis: What we have learnt by February 2021. Multiple Sclerosis Journal. 15; 27(6): 864-70. Apr 2021.