Deterioration of Vocal Cord Paralysis after COVID-19 Infection in Multiple System Atrophy

Abstract

Multiple system atrophy (MSA) is a progressive neurodegenerative disease that often causes vocal cord paralysis (VCP), Parkinsonism, cerebellar ataxia, and autonomic dysfunction. VCP is the most fatal symptom that affects the prognosis of patients with MSA. Coronavirus disease 2019 (COVID-19) is often associated with neurological complications and it has recently been reported to induce VCP in patients without neurodegenerative diseases. We herein present two cases of patients with MSA in whom VCP worsened after COVID-19 and this led to the need to perform emergency tracheostomies. As VCP may deteriorate after COVID-19 in patients with MSA, it is important to prevent COVID-19 in these patients and closely monitor such patients for any signs of VCP deterioration post-infection to improve their prognosis.

Introduction

Multiple system atrophy (MSA) is a sporadic neurodegenerative disease that induces cerebellar ataxia, parkinsonism, and autonomic dysfunction. Patients with MSA more frequently have vocal cord dysfunction than those with Parkinson's disease or other Parkinsonian syndromes. A progression of vocal cord paralysis (VCP) causes airway obstruction with severe respiratory failure, which can lead to sudden death and often requires tracheostomy. As VCP is associated with a poor survival in patients with MSA (1), early VCP detection and appropriate management may improve the prognosis of patients with MSA.

Several cases of VCP triggered by coronavirus disease 2019 (COVID-19) have been reported in patients without neurodegenerative diseases (2-9), and the cause is thought to be recurrent laryngeal nerve dysfunction. Therefore, VCP is a rare but noteworthy complication in COVID-19 patients.

We herein report two cases of patients with MSA whose VCP deteriorated rapidly after COVID-19 and led to emergency tracheostomies.

Case Reports

Case 1

A 76-year-old woman diagnosed with MSA was admitted to our emergency department with dyspnea. Three years earlier, she had experienced dysuria, and one year ago, she also began to experience occasional stridor on inhalation. When she visited our hospital three months previously, a neurological examination revealed parkinsonism, cerebellar ataxia, and severe autonomic dysfunction, including orthostatic hypotension with a fall in systolic blood pressure of approximately 30-40 mmHg, urinary retention requiring catheterization, and constipation. Laryngoscopy revealed moderate bilateral VCP. Brain magnetic resonance imaging (MRI) showed cerebellar atrophy without pontine atrophy and an abnormal signal intensity lesion. Dopamine transporter (DAT) imaging revealed bilateral striatal dopaminergic depletion. She was diagnosed with clinically probable MSA parkinsonian type (MSA-P) based on these criteria (10). Before admission, she was able to walk using a senior rollator walker.

In the emergency room, she developed frequent stridor on inhalation, a fever of 37.8°C, respiratory failure with SpO₂ (peripheral O₂ saturation) of 88% on room air, and polymerase chain reaction (PCR) positivity for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). She had got the vaccine against SARS-CoV-2 within the past year. Laryngoscopy revealed that bilateral vocal cords were fixed at the midline during the inspiration phase; however, no edema was evident (Fig. 1). Chest computed tomography (CT) showed no signs of pneumonia (Fig. 2A). Other than a worsening of VCP, there were no new neurological deficits suggestive of any other neuromuscular diseases such as a disturbance of consciousness, cranial nerve palsy, or limb weakness. At the time of admission, the MSA type was MSA-P. We performed emergency tracheal intubation to secure the airway at the time of admission, and tracheotomy on day 16 of hospitalization. The COVID-19 infection improved with remdesivir treatment, and after consultation with the patient, the tracheal cannula was not removed because of the risk of respiratory failure associated with bilateral VCP. The patient was transferred for rehabilitation on day 99 of hospitalization.

Figure 1.

Laryngeal endoscopic findings in Case 1. A laryngeal endoscopy revealed bilateral vocal cord paralysis. No edema was observed in the vocal cord. (A) Inspiration phase. (B) Exhalation phase.

Figure 2.

Chest computed tomography (CT). Chest CT showed no pneumonia in Case 1 (A) and slight pneumonia in Case 2 (B).

Case 2

A 54-year-old woman presented to our hospital with dyspnea and newly emerging stridor. At the time of admission, she had a fever (body temperature, 38.3°C), SpO₂ of 90% on room air, and PCR-positivity for SARS-CoV-2. She had been vaccinated against SARS-CoV-2 within the past one year. She presented with progressive gait disturbance nine years previously and exhibited orthostatic hypotension with a drop of at least 40 mmHg, Parkinsonism, and urinary dysfunction at her first visit to our hospital five years prior to this presentation. Brain MRI revealed cerebellar and pontine atrophy, abnormal intensities in the bilateral middle cerebellar peduncles, and a hot cross-bun sign. DAT imaging showed bilateral dopaminergic deficits. She was diagnosed with clinically probable MSA-P based on these criteria (10). Two years previously, she became bedridden due to truncal ataxia and severe autonomic dysfunction, including orthostatic hypotension with syncope, urinary retention requiring catheterization, and constipation. Subsequently, her diagnosis was revised from MSA-P to MSA cerebellar type, with disease progression. Four months earlier, she noticed mild hoarseness but no dyspnea, and laryngoscopy showed slight bilateral VCP. Chest CT revealed mild pneumonia on admission (Fig. 2B). Although the pneumonia improved with remdesivir administration, an emergency tracheostomy was performed on day 16 to manage her respiratory failure that had been caused by a rapid deterioration of the bilateral VCP despite no new neurological findings. Laryngoscopy did not reveal vocal cord edema, and her respiratory failure improved. However, the tracheal cannula was not removed for the same reason as that noted in Case 1.

Discussion

We here describe two cases of MSA in which VCP deteriorated following COVID-19 which led to the performance of emergency tracheostomies. VCP is a complication of MSA that occurs at a frequency of approximately 10% and it is particularly concerning because of its prognostic significance (11). VCP is commonly present in the advanced stages of MSA and sometimes in the early stages (12). In both the patients presented in this report, autonomic dysfunction was prominent from the beginning and it may have contributed to the appearance of VCP, as previously reported (13). Considering that the underlying disease was MSA, we opted not to remove the tracheal cannula; therefore, it remains unclear whether the deterioration of the VCP following COVID-19 was temporary or permanent.

SARS-CoV-2, the causative agent of COVID-19, causes various neurological complications such as anosmia, Bell's palsy, and Guillain-Barré syndrome (14-16). VCP develops following COVID-19 and it often requires tracheostomy in patients without neurodegenerative diseases (2-9). In several patients, long-term tracheal intubation is required to treat severe pneumonia, and vocal cord injury caused by intubation may induce VCP (17). However, VCP also occurs in patients who are not intubated, which suggests that other mechanisms may also contribute to this condition.

How does VCP manifest after COVID-19? One possible explanation for this is that SARS-CoV-2 directly infects the nervous system. It has been hypothesized that SARS-CoV-2 can enter the host cell by binding to the angiotensin-converting enzyme 2 receptor (ACE2-R) and cleavage by transmembrane protease serine 2 (TMPRSS2) (18). Both TMPRSS2 and ACE2-R are expressed in the laryngeal mucosal epithelium of rats (19), thus suggesting invasion of the nervous system from the laryngeal mucosa in humans. Previous reports have shown that needle electromyography reveal denervation potentials in the laryngeal muscles of patients with VCP following COVID-19 infection (9). These findings indicate that SARS-CoV-2 may damage the recurrent laryngeal nerve, thus resulting in VCP. In patients with MSA who originally had VCP, dysfunction of the recurrent laryngeal nerve caused by COVID-19 may facilitate a greater manifestation or severity of VCP than infections in otherwise healthy individuals.

Another possibility is that the COVID-19 infection triggered the progression of neurological manifestations in MSA. Previous reports have indicated that infections other than COVID-19, such as pneumonia and urinary tract infections, may exacerbate the motor function and activities of daily living in patients with Parkinson's disease (20) and patients in need of medical care (21). Recently, the adverse effects of COVID-19 on motor and non-motor symptoms in Parkinson's disease have been reported (22,23). In addition, cerebellar ataxia has been reported to transiently worsen after COVID-19 in patients with MSA (24). To our knowledge, this is the first report of worsening VCP following COVID-19 in patients with MSA. Therefore, it is unclear how COVID-19 affects VCP deterioration in patients with MSA. Additional case evaluations are needed to reveal the association between VCP deterioration and COVID-19 in patients with MSA.

In conclusion, we herein presented two cases of worsening VCP after COVID-19 in patients with MSA. Thus, VCP, a fatal manifestation of MSA, may occasionally worsen in the event of COVID-19 infection. Preventing various infections, including COVID-19, is particularly important for improving the prognosis and quality of life of patients with MSA. Clinicians should therefore pay special attention to VCP in patients with COVID-19.

The authors state that they have no Conflict of Interest (COI).

Yosuke Takeuchi and Teruaki Masuda contributed equally to this work.