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©2021 American Academy of Pediatrics

Stridor Due to Cranial Nerve X Palsy Progressing to Polyneuropathy in a Teenager With COVID-19

Andrea Dean, MD; Amira Said, MD; Kavitha Marri, MD; Daniel Chelius, MD

DOI: 10.1542/peds.2021-051534

Journal: Pediatrics

Article Type: Case Report

Citation: Dean A, Said A, Marri K, Chelius D. Stridor due to cranial nerve X palsy progressing to polyneuropathy in a teenager with COVID-19. Pediatrics. 2021; doi: 10.1542/peds.2021-051534

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Stridor Due to Cranial Nerve X Palsy Progressing to Polyneuropathy in a Teenager With COVID-19

Andrea Dean, MDa; Amira Said, MDa; Kavitha Marri, MDa; Daniel Chelius, MDb

Affiliations: aDepartment of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030 bDepartment of Otolaryngology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas, 77030

Corresponding Author: Andrea Dean, 1102 Bates Street, Suite FC.1860, Houston, TX 77030 Phone: 832.824.5447 Fax: 832.825.0341 [email protected]

Conflict of Interest Disclosures: The authors have no conflicts of interest and no financial relationships relevant to this article to disclose.

Funding/Support: No external or internal funding was received for this study.

Clinical Trial registry: NA .

Abbreviations COVID-19, coronavirus disease 19; CN, cranial nerve; dL, deciliter, EC, emergency center; ENT, otolaryngology; GBS, Guillain-Barre Syndrome, GBS; Ig, immunoglobulin; IVIG, intravenous immunoglobulin; mmol/L, millimoles per liter; kg/m2, kilogram per meter squared; MRI, magnetic resonance imaging; NIF, negative inspiratory force; PCB, pharyngeal-cervical-brachial; PCR, polymerase chain reaction; PHM, Pediatric Hospital Medicine; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Article Summary: A SARS-CoV-2 infected teenager presented with stridor due to a cranial nerve X palsy and progressed to a polyneuropathy suggesting a COVID-19-associated neuritis.

Contributors Statement:

Dr. Dean conceptualized the study, obtained consent from the patient and guardian for participation, collected data from the electronic medical record, drafted the initial manuscript, and reviewed and revised the manuscript.

Dr. Said, Dr. Marri and Dr. Chelius collected data from the electronic medical record and reviewed and revised the manuscript.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.




Abstract

The neurological manifestations of coronavirus disease 19 (COVID-19) are wide-ranging,

including various cranial neuropathies, beyond anosmia and dysgeusia, the exact

neuropathological mechanism of which are yet unknown. Acute cranial nerve (CN) X neuritis

with vocal cord paralysis has not been reported in COVID-19 and is a rare presentation of

neuropathy in general.

A 14-year-old female was admitted with stridor. She was diagnosed with symptomatic COVID-

19 eight days prior. By presentation, fever had resolved, but she had developed stridor, sore

throat with dysphagia, chest, shoulder, and back pain, and generalized weakness. Neurological

exam and laryngoscopy were consistent with isolated left CN X palsy. Steroids were started, but

neurological disease progressed with subjective pain, right lower face numbness, and eye

fatigability. Respiratory distress increased and she was intubated for airway protection. MRI

showed abnormal enhancement of CNs III, V, XII and X. CSF studies were normal.

Nasopharyngeal SARS-CoV-2 PCR testing was positive. She was treated with intravenous

immunoglobulin (IVIG), a total of 2 g/kg and steroids were continued. She made a full

neurological recovery and was discharged after 9 days of hospitalization.

This is a case of a teenager who presented with an acute life-threatening CN X palsy and

development of a progressive polyneuropathy in the setting of COVID-19. Though there was

concern for Guillain-Barre Syndrome, a definitive diagnosis could not be made, and the unusual




features of this case, including presentation with stridor and predominate CN involvement seem

to indicate a separate symptomatic COVID-19-associated polyneuritis.

Introduction

Coronavirus disease 19 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2

(SARS-CoV-2) typically presents with respiratory illness in adults and is asymptomatic in

majority of children. However, a wide range of neurological manifestations has been described

since the start of the COVID-19 pandemic. Headache and dizziness are commonly associated

with the flu-like illness caused by SARS-CoV-2 and serious cerebral vascular events,

dysautonomia, delirium, seizures, movement disorders, and encephalitis have all occurred [1-6].

Anosmia and dysgeusia are frequently recognized symptoms [1-5, 7, 8] and several other

COVID-19-associated cranial neuropathies have been reported in the literature [6, 9-21].

Guillain-Barre Syndrome (GBS), a syndrome of acute immune-mediated radiculo-

polyneuropathy, has been increasingly recognized in relation to COVID-19[2, 4, 5, 22-28],

including pediatric cases [29-31].

We present a case of a teenage girl infected with SARS-CoV-2 who presented with stridor due to

acute cranial nerve (CN) X palsy, which, unlike other isolated cranial neuropathies, has not been

described in association with COVID-19. She developed progressive focal neurological

symptoms with involvement of multiple CNs on imaging. She was treated for presumed GBS

pharyngeal-cervical-brachial (PCB) variant, but a definitive GBS diagnosis could not be made,

and a COVID-19-associated polyneuritis was suspected. We discuss her challenging diagnosis,




which illustrates the need for further investigation of the neuropathogenic mechanism of SARS-

CoV-2, and urges clinicians to remain vigilant as our understanding of COVID-19 morbidities

expands.

Presentation

An obese 14-year-old girl presented to the emergency center (EC) with difficulty breathing.

Eight days prior to presentation, she developed fever, malaise, myalgias, sore throat and cough

and was diagnosed with COVID-19 by polymerase chain reaction (PCR). On day 4 of illness,

she sought care for shortness of breath at a community EC and was treated with albuterol and

prednisone 20 mg daily for 3 days without improvement of difficulty breathing. By the day of

presentation to the EC, her fever had resolved, but breathing had become more difficult and

increasingly noisy. Her sore throat had worsened with swallowing difficulty. She had bilateral

shoulder, chest and upper back pain and reported generalized weakness. She denied ageusia and

anosmia, vision changes, sensory deficit, facial asymmetry or gastrointestinal symptoms.

In the EC, she was afebrile, with oxygen saturation 99% on room air and tachypnea to 26 breaths

per minute. Vital signs were otherwise normal. BMI was 35 kg/m2. Her exam was remarkable

for biphasic stridor with mild tracheal tugging on each breath and she was not distractible. Lungs

were otherwise clear. Oropharynx revealed mild erythema without exudate. Neck was supple

without lymphadenopathy. She had diffuse tenderness to palpitation over the ribs, shoulders and

upper back. Mentation was normal.




Nasopharyngeal SARS-CoV-2 PCR testing was positive. Chest X-ray and electrocardiogram

were unremarkable. She showed no improvement after dexamethasone, albuterol, ipratropium or

nebulized epinephrine and was admitted to the Pediatric Hospital Medicine (PHM) service.

Otolaryngology (ENT) performed bedside flexible naso-laryngoscopy which revealed a paretic

and medialized left vocal fold that only abducted with cough. The right vocal fold seemed

normal by comparison, but on post-hoc video review, was likely also weaker than normal (Figure

1).

The following day, neurological exam revealed intact cognitive function and language. The

patient complained of extremity weakness, but objective tone and strength were normal in all

extremities. Reflexes were normal. There was decreased sensation to light touch on the left

lower extremity. Coordination was intact. CNs I-IX, XI and XII were intact.

These findings were most consistent with isolated left CN X palsy. Neurology, ENT and PHM

agreed on treatment with steroids and patient was started on dexamethasone 10 mg orally every 8

hours for 24 hours and, subsequently, switched to methylprednisolone intravenously 80 mg

daily.

Over the next 24 hours into hospital day 3, stridor persisted with otherwise stable respiratory

status including negative inspiratory force (NIF) of -85 mmHg and normal oxygen saturations.

However, she described increasing weakness of her upper and lower extremities as well as

“shooting” and “stinging” pains mostly in her upper extremities with sensitivity to touch,




different from the myalgias she experienced earlier in her COVID-19 illness. She had numbness

of right lower face, and complained of eye fatigability in which she “lost focus” and had to close

her eyes when holding horizontal gaze, though denied diplopia at the time. She also described a

sense of impending doom. As intensified evaluation was underway, she attempted to lay flat in

anticipation of an MRI and developed acute respiratory distress with tachypnea and decreased

NIF to -20 mmHg. She was sedated and intubated by ENT with direct visualization of her

airway, which showed bilateral medialized vocal folds and no other anatomic obstruction.

Complete blood count, complete metabolic panel, sedimentation rate and C-reactive protein were

unremarkable. SARS-CoV-2 antibody panel was IgM positive, IgG negative.

Subsequent brain MRI showed abnormal enhancement bilaterally in cranial nerves III, V, VII, X

(Figure 2). There was equivocal enhancement of the left olfactory bulb without enlargement.

There was mild swelling of the right hippocampal head with abnormal T2 signal. Spinal MRI

showed equivocal faint enhancement of the ventral and dorsal cauda equina nerve roots without

thickening and with no additional signal abnormality in the spinal canal (Figure 3).

Cerebrospinal fluid (CSF) examination revealed an opening pressure of 32 cm H2O, likely

increased due to sedation and ventilation. CSF was clear with white blood cell count 2

(lymphocyte and monocyte), 1 RBC, protein 37 mg/dL, albumin 18.4 mg/dL, glucose 69 mg/dL

and sterile cultures. Viral and bacterial PCR were negative, but SARS-CoV-2 testing of CSF was




unavailable. CSF demyelinating panel (AQP4, MOG), autoimmune encephalopathy panel and

CSF anti-ganglioside antibody panel (GM1, GD1b, GQ1b) were all negative except very mild

elevated glutamic acid decarboxylase 65 antibody of 0.09 mmol/L (normal is <0.02 mmol/L)

which was considered insignificant as the finding is prevalent in general population and the

profile did not align with her clinical findings.

The patient was continued on methylprednisolone 80 mg daily for acute COVID-19-associated

neuritis. Intravenous immunoglobulin (IVIG) was initiated for treatment of GBS, possible PCB

variant, which was considered due to development of hyporeflexia in upper extremities after

sedation and intubation taken in conjunction with subjective weakness prior to intubation.

Areflexia was never noted throughout her 3-day intubation. Immediately post-extubation, she

had resolution of her stridor, though laryngoscopy revealed ongoing mild adduction of the left

vocal cord. She reported diplopia on horizontal gaze bilaterally and ongoing decreased sensation

on lower right face. Neurological exam did not identify other CN palsy; the remainder of exam

was normal including strength and reflexes.

She completed a 5-day course of IVIG 40 gram daily and remained on methylprednisolone 80

mg IV daily throughout hospital admission with an oral prednisone taper at discharge. She was

discharged after a 9-day inpatient stay with resolution of focal neurological symptoms. At

outpatient ENT follow up 10 days after discharge, naso-laryngoscopy was normal (Figure 4).




She reported ongoing fatigability. At 4-week neurology follow up, she was back to baseline with

full recovery.

Discussion

This is a case of a progressive polyneuritis involving CNs in a teenager with acute SARS-CoV-2

infection. Early in her illness, CN X palsy, causing stridor, appeared to be isolated. Cranial

neuropathies during COVID-19 infection are common, most notably, anosmia and dysgeusia,

which can occur in otherwise asymptomatic persons [4, 7, 8]. Isolated optic neuritis [10, 11],

acute sensorineural hearing loss[12], vestibular neuritis [13], CN III palsy[14] and CN VI palsy

[15-17] and CN VII [18-20] as well as post-mortem CN X involvement [21] have been reported.

Despite these reports, there was little guidance on treatment for this patient’s potentially life-

threatening CN X palsy, which is rare outside of direct disturbance of the nerve.

Methylprednisolone dosing was derived from case reports of COVID-19-associated cranial

neuropathies [10, 12, 18-20] and recommendations for Bell’s palsy, a common but incompletely

understood neuropathy of CN VII presumed to have a viral trigger [32]. However, it should be

noted that the patient worsened despite steroid treatment.

After an initial period of stability, she complained of worsening symptoms which, despite a lack

of objective findings, were concerning in the setting of her life-threatening neuropathy of poorly

understood etiology. Neuroimaging revealed involvement of the oculomotor, trigeminal, and

vagus nerves which was consistent with eye fatigability and eventual diplopia, facial numbness,

stridor, and dysphagia. She did not have facial weakness or anosmia corresponding with facial




nerve or olfactory bulb enhancement. Cranial nerve enhancement in the absence of

corresponding symptoms has been described in children with suspected COVID-19 [6].

The extent of peripheral nerve involvement in our patient’s process remains unclear. Her

decreased NIF was thought to reflect upper airway obstruction and decreased effort secondary to

anxiety, as opposed to weakness of inspiratory muscles. However, hyperalgesia suggestive of

neuropathic pain as well as her weakness and hyporeflexia may point to early peripheral nerve

involvement. However, weakness was not objective and her hyporeflexia was only seen after

sedation.

The patient’s imaging in conjunction with reported upper extremity weakness and hyporeflexia

triggered concern for GBS PCB variant. PCB is characterized by acute weakness of the

oropharyngeal, neck, and shoulder muscles with swallowing dysfunction and presentations can

be atypical [33-36]. However, in retrospect, her constellation of signs and symptoms were not

consistent with GBS including polyneuritis cranialis or overlapping variants [37, 38]. Notably,

she did not have cytoalbuminologic dissociation or anti-ganglioside antibodies in her CSF,

though these findings can be absent, especially early in the disease course [39] such as when our

patient’s investigation took place. Electrodiagnostic studies may have delineated her diagnosis

and their absence limits this case study. Ultimately, at the time of respiratory failure, GBS could

not be excluded at the time and triggered treatment with IVIG. However, steroids, which play no

role in the treatment of GBS, were continued throughout her illness.




While the tendency for SARS-CoV-2 to affect a variety of cranial nerves is now recognized, this

patient’s unusual presentation with stridor due to CN X palsy represents a previously

undescribed neurological manifestation of COVID-19. While variants of GBS deserve

consideration, a non-GBS polyneuritis is more likely and is consistent with other reports of

COVID-19-associated cranial neuropathies [6, 9]. This case, including her ultimately imprecise

diagnosis, illustrates the lack of understanding of the pathogenic mechanisms of SARS-CoV-2

neurologic dysfunction. Importantly, her acute presentation with isolated, symptomatic CN X

palsy, which is rare and required life-saving interventions even after a period of stability, serves

as reminder that clinicians must remain vigilant for unique manifestations and unpredictable

illness progression of COVID-19.

Acknowledgments

Thank you to Brandon Tran, M.D., Department of Radiology, Baylor College of Medicine.

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originally published online September 9, 2021; Pediatrics Andrea Dean, Amira Said, Kavitha Marri and Daniel Chelius

With COVID-19Stridor Due to Cranial Nerve X Palsy Progressing to Polyneuropathy in a Teenager

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