Vestibular Dysfunction Secondary to Reactivation of the Neurotropic Virus VZV After COVID-19: A Case Study

Background

The varicella zoster virus (VZV) is a neurotropic virus and a member of the Herpesviridae family of DNA viruses [1]. VZV establishes latency in the trigeminal ganglion, a phenomenon involving the retention of a functional viral genome without the production of infectious viral particles [1,2]. After establishing latency, the virus has the potential to reactivate, resume replication, and cause disease [1]. Primary infection affects the mucocutaneous surfaces of the human nervous system, which serve as a viral gateway to the peripheral nervous system [1,3]. Triggers such as stress or immunosuppression can cause these viruses to reactivate, resulting in recurrent infections that can invade other nervous system pathways [4–6].

The potential for VZV to wreak havoc on the human vestibular system has been documented for decades [7–9]. Reactivation of VZV can lead to vestibular symptoms through the development of Ramsay Hunt Syndrome, which is characterized by herpes zoster oticus, peripheral facial palsy, and eighth cranial nerve symptoms such as hearing loss and vertigo [10]. MRI studies have demonstrated enhancement of the superior vestibular nerve in the internal auditory canal, suggesting the superior vestibular nerve as an origin of vestibular symptoms after reactivation of VZV [10].

With immunosuppression acting as a trigger for the reactivation of neurotropic viruses that are known to have vestibular implications, it is plausible that COVID-19 could lead to a heightened reactivation of these viruses, resulting in the development of vestibular dysfunction after COVID-19 infection. Indeed, COVID-19 is known to decrease cell-mediated immunity by decreasing CD3+, CD4+, and CD8+ T cells and lymphocyte count [11]. Malayala and Raya (2020) described a case of possible COVID-19-induced acute vestibular neuritis in a female patient, presenting with intractable vertigo, nausea, and vomiting, and suggested that clinicians should consider COVID-19 in the differential diagnosis for patients with such symptoms [12]. Karimi-Galougahi et al suggested that the neurotropism of SARS-CoV-2 enables the virus to inflict an array of neuropathic effects, including effects on the neural networks that govern balance [13]. While case studies regarding vestibular neuritis following COVID-19 are limited at this time, case studies regarding vestibular dysfunction secondary to Ramsay Hunt Syndrome following COVID-19 infection and the prognosis of such patients following vestibular rehabilitation are also very limited.

Here, we present the case of a 67-year-old woman who began experiencing dizziness following a diagnosis of shingles in January 2021 after contracting COVID-19 in December 2020. Following a comprehensive balance evaluation in March 2021, the patient was diagnosed with an acute right peripheral vestibulopathy and otolith dysfunction, as well as mixed, moderate hearing loss in the right ear. The patient’s presenting symptoms, test findings, and recommended treatment are further discussed below, and may support the claim that COVID-19 puts patients at risk of reactivating neurotropic viruses, ultimately leading to vestibular neuritis.

The purpose of this article is to further promote evidence of a possible reactivation of VZV via recent COVID-19 and its effects on the vestibular system. Additionally, the paper aims to promote the benefit of vestibular treatment after onset of vestibular disorders.

Case Report

A 67-year-old woman was diagnosed with COVID-19 on December 28, 2020 based upon positive results from a PCR test performed at a local urgent care facility. She reported cold-like symptoms until completing a quarantine period of 2 weeks on January 14, 2021, denying hospitalization or any medical treatment at that time. She then reported a subsequent outbreak of shingles in the right ear on January 16, 2021, at which time she followed up with her provider and diagnosis was made based on case history and visual examination with the presence of blisters in the right ear (Figure 1). No Tzanck smear was performed at the time of diagnosis to confirm the findings. Symptoms of auditory and vestibular dysfunction began shortly after. The patient presented to our facility with chief concerns of vertigo, hearing loss, tinnitus, aural fullness, dizziness, and imbalance. The dizziness and imbalance occurred daily, lasted all day, and was especially pronounced when ambulating. Additional symptoms included right aural fullness, right-sided otalgia, hyperacusis, and VOR disturbances, described as inability to focus on objects, especially when in the car. She additionally reported that standing up too quickly would trigger her imbalance and dizziness.

The patient denied a history of aural drainage, otitis media, or otologic surgery. She reported that everything in the right ear sounded “muffled,” and reported a long-standing history bilateral tinnitus, which became significantly worse in the right ear following the shingles outbreak. She also reported a significant history of noise exposure secondary to shooting guns without hearing protection. She underwent an audiologic evaluation approximately 2 years prior, at which time results were reportedly normal. While the patient did report a history of headache described as a “constant head pressure,” she denied any history of head injury, concussion, pulmonary issues, cardiac issues, or a formal diagnosis of migraine, and denied any prior history or episodes of dizziness or imbalance. The patient’s family history was negative for hearing loss, vertigo, or migraine. Prior to the arrival at our facility, she reported being seen by a physician at an urgent care clinic, her primary care physician, and an otolaryngologist. She was prescribed neomycin, polymyxin B, hydrocortisone combination ear drops, and Meclizine. At that time, vaccinations against COVID-19 had not yet been approved by the Food and Drug Administration and were not readily available to the general public. She reported taking 25 mg of Meclizine approximately every 8hours and reported using the ear drops for approximately 1 week but denied any significant relief from otalgia or dizziness. She then stopped taking the treatment for shingles. She denied any prior imaging or vestibular testing, and was referred to Newport Mesa Audiology Balance & Ear Institute for a comprehensive diagnostic audiological, dizziness, and balance evaluation.

The patient was seen at Newport Mesa Audiology Balance & Ear Institute in March 2021 for a comprehensive diagnostic audiological, dizziness and balance evaluation. This comprehensive test battery included the following: the Dizziness Handicap Inventory (DHI), tympanometry, acoustic reflex thresholds, distortion product otoacoustic emissions (DPOAEs), the Romberg test, the vertebral artery screening test (VAST), computerized dynamic posturography (CDP), the Epley Omniax evaluation, a comprehensive audiologic evaluation, cervical vestibular evoked myogenic potentials (cVEMP), ocular vestibular evoked myogenic potentials (oVEMP), video head impulse test (vHIT), NeuroKinetics rotational chair studies (NOTC), tasks of subjective visual vertical (SVV), tasks of subjective visual horizontal (SVH), unilateral centrifugation (UC), and videonystagmography (VNG). The patient received a score of 54 on the DHI, placing her in the severe range of self-perceived handicap due to dizziness.

VNG bithermal closed-loop calorics produced a total vestibulo-ocular reflex (VOR) of 0 degrees/second in the right ear and 45 degrees/second in the left ear, resulting in a right unilateral caloric weakness of 100%, indicating right canal paresis. High-frequency video head impulses were obtained for all 6 semicircular canals, including right and left horizontal semi-circular canals, right anterior left posterior (RALP), and left anterior right posterior (LARP). Impulses were abnormal for the right lateral, anterior, and posterior canals, with evidence of low gain, covert, and overt saccades. Pure tone air, bone, and speech audiometry was performed with insert earphones from 125 through 8000 Hz. Hearing thresholds revealed a mild high-frequency sensory hearing loss in the left ear and a mixed moderate sensory hearing loss in the right ear. There was a significant asymmetry noted, with the right ear being worse. Speech testing revealed excellent word discrimination ability bilaterally: 100% at 75 dBHL. All other testing was unremarkable. Conductive components in hearing can limit VEMP findings when an air-bone gap is present in the low frequencies. Audiometric results for this patient revealed an air-bone gap at 4000 Hz, eliminating the possible conductive effect for absent VEMP responses. The typical cVEMP P13-N23 waveform complex responses were obtained for the left ear and were absent for the right ear. The typical oVEMP N10-P16 waveform complex responses obtained for the left ear were absent for the right ear, suggesting possible utricular and saccular dys-function. Within the NOTC, optokinetic pursuit at 60 degrees per second revealed a significant right asymmetry. The patient then adjusted a series of 6 lines presented at random angles to their perception of horizontal and vertical (SVV/SVH tasking). The mean adjusted line angle indicated a significant rightward tilt in both the horizontal and vertical planes. Lastly, the patient underwent unilateral centrifugation testing and was rotated at a constant velocity of 300 degrees/second with the chair center and at 3.5 cm to the right and left to isolate otolith function of each utricle. Unilateral centrifugation results were consistent with right utricular dysfunction.

This comprehensive vestibular test battery evaluates the function of all 10 end-organs in the inner ear and their corresponding branches of the vestibulocochlear nerve (cranial nerve VIII). These end-organs and branches of the nerve contribute to the 3 main reflexes responsible for balance: the VOR, the vestibulo-spinal reflex (VSR), and the otolith ocular reflex (OOR). Patients diagnosed with a peripheral vestibulopathy exhibit dysfunction of the VOR, VSR, OOR, or a combination of the 3 [14]. The patient’s clinical history, as well as the results of the diagnostic balance evaluation, were suggestive of an acute right peripheral vestibulopathy and otolith dysfunction secondary to Varicella Zoster (shingles) virus following COVID-19, as well as mixed, moderate sensorineural hearing loss in the right ear. This diagnosis was supported by results of the VNG, vHIT, cVEMP, oVEMP, and the NOTC rotational chair studies.

After diagnosing the vestibulopathy, the patient was recommended to initiate a patient-specific treatment plan known as advanced vestibular treatment (AVT) to promote central compensation and improve subjective symptoms, with the overall goal of reducing the frequency, severity, and duration of the patient’s symptoms. Additional recommendations from the evaluation included 5000 IU of vitamin D3 daily and 50 mg of zinc daily. AVT was recommended for 12 sessions 2 times per week, with concurrent home treatment.

Discussion

COVID-19 has exhibited a wide range of clinical manifestations, ranging from respiratory dysfunction such as COVID-19 Acute Respiratory Distress Syndrome (CARDS), to neurological dysfunction, such as migraine, myalgia, and even encephalitis [15,16]. Recent findings and case studies describe patients presenting with vestibular symptoms following COVID-19, which include vertigo, nausea, and imbalance. Recent research demonstrating the development of vestibular dysfunction after reactivation of VZV following periods of immunosuppression, and additional research also demonstrating that COVID-19 lowers cell-mediated immunity, it is plausible that COVID-19 puts individuals at higher risk of developing vestibular symptoms [13,15]. We suggest that this 67-year-old woman seen at our facility is an example of vestibular dysfunction secondary to COVID-19. She presented to the facility with chief concerns of vertigo, hearing loss, tinnitus, aural fullness, dizziness, and imbalance after experiencing shingles following a confirmed diagnosis of COVID-19. The results of a comprehensive vestibular evaluation were indicative of an acute right peripheral vestibulopathy and otolith dysfunction in the right ear. We propose that the patient’s vestibular dysfunction was linked to VZV reactivation secondary to immunosuppression caused by COVID-19, and that this is an example of a much larger population of patients with dizziness.

While the central vestibular system is sometimes able to adapt in instances like this through the process of central compensation, the present case serves as an example of the limited ability of the system to fully adapt to such anomalies on its own without the use of formal treatment intervention [16]. Following discussion of the patient’s results, a program of AVT was implemented at our facility. To date, the patient has received 12 sessions of AVT and showed improvement in both subjective and objective data. Initial patient data indicated abnormal results on computerized dynamic posturography, sinusoidal harmonic acceleration testing (SHAs), optokinetic testing, and SVV and SVH tasking. After her 12th session, the patient’s objective data were revaluated and revealed improvement in the previously-mentioned tests. The patient’s subjective data were monitored via the Inventory DHI and revealed significant improvement, reducing the patient’s perception from a “severe handicap” to values within normal limits. We suggest that this patient’s outcomes support the potential for significant benefit from vestibular treatment as the primary strategy.

Conclusions

It is plausible that COVID-19 can put individuals at a higher risk of developing vestibular symptoms. This can be caused by the reactivation of VZV following a period of immunosuppression in conjunction with the lowered cell-mediated immunity brought upon by COVID-19 [12,17,18]. Furthermore, interventions such as AVT could be used as an aid to help further promote central compensation in a linear and controlled manner as seen in this patient’s subjective data over the past 12 months. This type of intervention is minimally invasive, and we believe it contributes to improved quality of life for the patient, as documented with standardized questionnaires.