DOI: https://doi.org/10.21203/rs.3.rs-1888467/v1
Introduction: We report an adult man who developed an isolated long thoracic nerve palsy three days following vaccination against COVID-19. To the best of our knowledge this is the first well-documented case of this association.
Case presentation: A 46-year-old white man developed back pain, followed by pain in the right axilla and scapular region, clumsiness of the right arm and unusual position of his shoulder blade, three days after receiving a second dose of the Pfizer-BioNTech COVID-19 vaccine. When he consulted a neurologist six months later, the pain had subsided, but the other symptoms persisted despite physiotherapy. Main clinical findings were right scapular winging and marked amyotrophy of the serratus anterior, with preservation of the other muscles of the shoulder and scapula. Nerve conduction studies of the long thoracic nerve yielded a low amplitude with a slightly prolonged latency. Needle electromyography showed decreased compound motor action potentials on the right was normal with a few polyphasic waves on the left.
Main diagnosis and interventions: A diagnosis of post-immunisation long thoracic neuritis was made. The patient was treated with physiotherapy.
Conclusions: Clinicians should be aware of the possibility of neuritis of any nerve after COVID-19 vaccination.
Vaccination against COVID-19 has saved millions of lives. However, with millions of people vaccinated each month, enhanced surveillance and public scrutiny, rare adverse events are being increasingly identified. Several cases of facial nerve palsy, reactivation of herpes zoster, Guillain-Barre syndrome, other demyelinating diseases, and neuropathy have been described following COVID-19 vaccination [1]. Decreased tolerance of myeline sheath antigens due to type 1 interferon production, transient lymphopenia and immune dysregulation have been proposed as potential vaccine-induced pathophysiological mechanisms. Unilateral scapular winging is most often caused by serratus anterior dysfunction related to neuralgic amyotrophy of the long thoracic nerve (LTN) [2, 3]. Alternative causes include spinal accessory nerve (SAN) palsy, both LTN and SAN palsy, facioscapulohumeral dystrophy, trauma, cervical pathology, voluntary winged scapula, and iatrogenic injury. There are a few case reports of Parsonage Turner syndrome following COVID-19 and other vaccinations. A search with Pubmed of the keywords long thoracic nerve and COVID-19 vaccination did not yield any results. We describe the case of a man who developed an isolated long thoracic nerve palsy three days after receiving a COVID-19 vaccine, following the CARE Guidelines for case reports [4].
An adult white man developed thoracic back pain, followed by severe pain in the right axilla and scapular region, three days after receiving a second dose of the BNT162b2 messenger RNA (mRNA) COVID-19 vaccine (Pfizer-BioNTech). A few days later he noticed clumsiness of his right arm and an abnormal position of his right scapula, which he described as dislocation. The pain subsided after a few days and the clumsiness improved moderately with physiotherapy over the next weeks. However, the symptoms remained sufficiently invalidating to hamper his manual work, even though he was left-handed. This prompted him to consult a neurologist six months after the first symptoms. He had a medical history of hypercholesterolemia, chronic sinusitis, various fractures of the left wrist, bilateral inguinal hernia operation and a section of the tendon of the flexor of the thumb. He did not have any known allergies and didn’t take any medication. There was no family history. He did not smoke and did regularly drink alcohol. The timeline is summarized in Table 1.
Physical examination revealed a winged scapula on the right side and marked amyotrophy of the serratus anterior, with preservation of the other muscles of the shoulder. The tone, bulk and strength of the supraspinatus, infraspinatus, deltoid, triceps, and biceps were normal. Sensitivity was strictly normal. All reflexes were normal and symmetrical. The remainder of the examination was normal.
|
Day |
Event |
Findings |
|---|---|---|
|
0 |
COVID-19 vaccine |
2nd dose of BioNTech-Pfizer |
|
3 |
First symptoms |
Dorsal, axillar, and scapular pain |
|
5 |
Motor symptoms |
Winged scapula, weakness of the shoulder |
|
7 |
Resolution of pain |
Continuation of motor symptoms |
|
7–60 |
Physiotherapy |
Limited improvement of motor symptoms |
|
60 |
GP consultation |
Referral to neurologist |
|
90 |
MRI of the right shoulder |
Normal |
|
135 |
Orthopedist consultation |
Referral to neurologist |
|
180 |
Neurologist consultation |
Laboratory, ENMG, MRI cervical plexus |
Three months after the first symptoms his family physician prescribed magnetic resonance imaging (MRI) of the right shoulder, which was normal.
Three months later, electroneuromyography (ENMG) performed by the neurologist was highly suggestive of an isolated long thoracic axonal neuropathy. Bilateral ulnar and median nerve sensory conduction, motor conduction velocities, latencies, and F-wave incidence and latencies, were normal. Velocities were measured up to the level of the axilla. Stimulation of the right long thoracic nerve yielded a markedly reduced amplitude (1.0 mV) and slightly prolonged latency (4.1 m/s) compared to the left (5.7 mV and 3.9 m/s). Electromyographic needle examination of the right serratus anterior [5] showed decreased recruitment of compound motor unit action potential and maximum volitional activity; it was normal on the left.
Full blood count, iron studies, and vitamin B12 were normal. Serology was negative for cytomegalovirus IgM, HIV Ag p24, hepatitis B Ag HBs, hepatitis E virus IgM and IgG; it was positive for varicella zoster virus IgG, and borrelia IgM but not IgG. Western Blot confirmation of IgM was negative for proteins p17, p19, p21, p30, p31, p39, p83 and VLsE, but positive for p25 (= OspC), which is compatible for early infection or cross-reactions with herpes viruses. Given that symptoms were present for more than six months, borrelia is highly unlikely. Antibodies against SARS-CoV-2 were positive.
One week later an MRI of the cervical plexus did show integrity of the brachial plexus without hypersignal, contrast enhancement or compression, symmetrical muscles of the shoulder and scapula, without amyotrophy or oedema, normal and symmetrical serratus anterior, and moderate uncus and disk arthritis from C5 to C7 without spinal or foraminal narrowing or myelopathy. MRI of the brachial plexus is rarely abnormal in brachial plexus neuropathy or isolated long thoracic nerve palsy [6] although more recent analyses suggest that positive EMG findings can often be confirmed by MRI [7].
The clinical history, physical examination and neurophysiological findings strongly suggest an isolated neuropathy of the long thoracic nerve following vaccination against COVID-19. It could be a post-vaccine neuritis or a plexitis. Although the clinical history evokes a Parsonage-Turner syndrome or idiopathic brachial plexus neuropathy, typical signs of plexitis were absent and physical and electrophysiological abnormal findings were confined to the long thoracic nerve and the serratus anterior muscle. The patient didn’t present any signs or symptoms suggestive of a viral or bacterial infection known to be associated with post-infectious auto-immune neuritis (borrelia burgdorferi, cytomegalovirus, mycoplasma pneumoniae etc.). A discal prolapse or spondylolysis at the level of C5-C6 with compression of the anterior spinal cord or another cause of compression was excluded by MRI. The temporal sequence was highly suggestive of an adverse event following immunization (AEFI).
The prognosis of long thoracic nerve palsy is relatively good, with a third of patients recovering partially after one year and more than 50% after two years [8].
This patient was treated with physiotherapy and will be followed up every three months by the treating neurologist.
This is the first well-documented case report of long thoracic nerve palsy as an adverse event following immunisation with an mRNA vaccine against SARS-CoV-2, to the best of our knowledge. As for other adverse events, a causal effect would need to be confirmed by additional case reports and case-control studies. Strengths of this case report include its novelty, and the well-documented clinical history, physical examination, ENMG, MRI and laboratory testing. The main limitation is the time elapsed between the onset of symptoms and the assessment by a neurologist. While the history, signs and symptoms are well described, earlier and sequential MRI and ENMG would have been useful to document the evolution of the illness. Nevertheless, it remains critical to publish the first occurrence of an adverse event, for pharmacological surveillance, to sensitize clinicians, and to stimulate research of causal association and pathophysiological explanation.
Isolated serratus anterior palsy caused by a long thoracic nerve lesion is the most common cause of scapular winging [9]. Most cases are right-sided, for an unknown reason. Causes, ranked by frequency, include strenuous physical activity, acute trauma, idiopathic, invasive procedures, infection, after injections, pregnancy, anesthesia and miscellaneous (sleeping position or cold). A clinical presentation of acute onset severe shoulder pain followed by weakness and scapular winging one or two weeks later has been ascribed to either repeated minor trauma or neuralgic amyotrophy, also known as Parsonage-Turner syndrome or brachial plexus neuritis.
Several cases of Parsonage-Turner syndrome have been reported after immunisation against SARS-CoV-2, with the ChAdOx1-S (Vaxzevria, AstraZeneca) [10, 11] and BNT162b (Comirnaty, Pfizer-BioNtech) vaccines [12]. All were after a first dose of vaccine and involved several muscles innervated by nerves of the brachial plexus. A recent pharmacovigilance review of the World Health Organization’s (WHO) global database of suspected adverse drug reactions (ADRs) found that up to 16 May 2021 there were 57 (0.01%) cases of neuralgic amyotrophy out of 808,906 COVID-19 vaccine-related safety reports [13]. COVID-19 associated NA was rare and wasn’t higher than with other viral vaccines. Another recent, two-year extensive review of the literature concluded that there isn’t sufficient epidemiological and pathological evidence to confirm a causal link suggested by the temporal association between vaccination and peripheral nerve pathology [14]. The authors found several reports of neuralgic amyotrophy after COVID-19 mRNA and adenovirus-based vaccines, most involving the brachial plexus and less frequently the lumbosacral plexus. The incidence of post vaccine NA was very low, with the most reliable data reporting 18 cases during the 2018–2020 influenza vaccination campaign in the United States. A systematic review of neurological immune related events after vaccination concluded that given the rarity of events compared to the number of vaccines administered, and the similar incidence of events between COVID-19 vaccines and other more common vaccines, there was little evidence to support a causal relationship between COVID-19 vaccines and adverse neurological events [1]. We did not find any case report of isolated long thoracic nerve palsy after COVID-19 vaccination.
In summary, we describe a well-documented case of isolated long thoracic nerve palsy following immunisation with the BNT162b vaccine. This may be a very rare adverse event or a chance finding. Clinicians and researchers should be encouraged to report rare potential adverse events. Accumulation of global pharmacovigilance data over many years is necessary to verify causality of rare events.
Funding
No funding was received to assist with the preparation of this manuscript.
Competing Interests
The authors have no relevant financial or non-financial interests to disclose.
Ethical standards
This case report was reviewed and deemed exempt by the Comité National D’Ethique de Recherche (CNER) of Luxembourg (CE 2022-EA-6) and is in line with the principles of the Declaration of Helsinki. The person gave informed consent and all details that might disclose the identity of the subject have been omitted.
Standards of reporting
The authors adhered to the minimum reporting guidelines for case reports (CARE) hosted by the EQUATOR Network.
Data Availability
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
Author contributions
SB and GVC contributed to conceptualization, data curation, methodology and writing – review and editing of the final draft. SB conducted the investigation and provided supervision. GVC wrote the original draft.