key: cord-0828613-j7nsz6gu authors: Cellina, Michaela; D'Arrigo, Andrea; Floridi, Chiara; Oliva, Giancarlo; Carrafiello, Gianpaolo title: Left Bell's palsy following the first dose of mRNA-1273 SARS-CoV-2 vaccine: A case report date: 2021-11-04 journal: Clin Imaging DOI: 10.1016/j.clinimag.2021.10.010 sha: 809e97a6d707084867298bb33f0362ca1e58e480 doc_id: 828613 cord_uid: j7nsz6gu Even though no definitive link has been established, Bell's palsy has been described as a potential side effect of SARS-CoV-2 mRNA vaccines in a few reports, and the US Food and Drug Administration has recommended strict surveillance of its occurrence in the vaccinated general population. We present the case of a previously healthy 35-year-old female patient who developed Bell's palsy 12 h after receiving the first dose of the mRNA-1273 vaccine. Her general practitioner performed the diagnosis, and corticosteroid treatment was initiated, with slow symptoms improvement. The neurologist's evaluation and a contrast-enhanced brain Magnetic Resonance Imaging revealed a subtle enhancement of the left facial nerve, confirming the diagnosis of Bell's palsy. Two vaccines using mRNA technology are currently available against SARS-CoV-2 infection: BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna). Bell's palsy has been observed as a potential side effect of both, but without any defined causal relationship [1] . This disorder, also known as idiopathic peripheral facial paralysis, consists of rapid onset facial nerve paralysis. The peak age of presentation is between 15 and 50 years, with about 25 cases per 100,000 per year, without gender predominance [2] . It is currently a diagnosis of exclusion, supported by a typical presentation, and usually encounters spontaneous resolution within 6-8 weeks in 70% of the cases. Timely treatment with corticosteroids raises the chance of full recovery to more than 90% [2] . Two large phase-3 vaccine trials, based on data from 73,799 volunteers, 36,901 of whom got at least one vaccine dose, identified eight occurrences of probable Bell's palsy: seven from vaccinated participants and one from placebo recipients [3] : four incidences of Bell's palsy were recorded in the mRNA-1273 vaccine group, three in vaccine recipients and one in the placebo group [4] ; whereas, in the case of the BNT162b2 vaccine, four vaccinated participants developed Bell's palsy [1, 3] . A diagnosis of Bell's palsy was made by the general practitioner, and treatment with 50 mg of daily prednisone for two weeks was prescribed. The patient came to our attention 10 days after the onset of the symptoms for a neurological evaluation. At the clinical examination, the patient was alert and oriented. Vital parameters were within the normal range. Cranial nerve examination showed isolated left VII nerve palsy of lower motor neuron type; a slight asymmetry of the left corner of the mouth was detectable when smiling, and the patient was able to completely close the left eye only with maximum effort (House-Brackmann grade III). No objective weakness in all four limbs was observed, and the rest of her physical examination was unremarkable. Even though the symptoms were still present, J o u r n a l P r e -p r o o f they were described as improved since their onset. After 12 days from the vaccine injection, the patient underwent a contrast-enhanced brain MRI confirming the diagnosis of Bell's palsy and demonstrating only a subtle enhancement of the left facial nerve (Figures 1,2) . On a second neurological visit, performed seven days after the MRI, the patient showed complete resolution of the symptomatology. Bell's palsy is defined as an acute unilateral facial paralysis; the etiology is still unclear, but the potential mechanisms of development include immune, infective, and ischemic mechanisms. The most accredited hypotheses are the reactivation of latent Herpes Simplex Virus type 1 in the geniculate ganglia of the facial nerves, an autoimmune mechanism through the mimicry of host molecules by the antigens of the vaccines, or immunemediated demyelination analogous to Guillain-Barrè syndrome [5] . Regarding Bell's palsy, the authors stated that this disorder was disproportionately more frequently reported with COVID-19 vaccines than with other viral vaccines over the full database, with a higher frequency in males and the age subgroup 65-74 years and ≥75 years. The characteristics of the affected patients, as well as the incidence for the type of vaccine, are listed in Table 1 . According to this study, male patients aged ≥65 years has a higher risk of post-vaccine Bell's palsy. The authors instead observed an incidence of neuralgic amyotrophy and Guillain-Barrè post-COVID-19 vaccine like that previously observed for other viral vaccines, without any sex or age predisposition [9] . Most of the neurological adverse effects were related to the BNT162b2 (Pfizer-BioNTech) [9, 10] and mRNA-1273 (Moderna) [9, 11] , and the COVID-19 Vaccine Vaxzevria (ex-COVID-19 AstraZeneca), whilst less frequently were associated with the Ad26.COV2.S (Janssen) vaccination [9, 12] , A case report described Bell's palsy after mRNA-1273 vaccine administration, reporting the case of a 36-year-old male who developed facial palsy after one day from the second vaccine dose; in this case, brain MRI was unremarkable [7] . In our case, the patient complained of symptoms at 12 hours from the injection. We can assume that the timing of Bell's palsy onset after mRNA vaccine administration varies, with early manifestation occurring as early as 5 hours after vaccination, as reported in a male patient who received BNT162b2 and developed recurrent Bell's palsy after the second dose of vaccine [8] . In this case, the first episode occurred 5 hours after the first dose was administered, and the second occurred 2 days later. The mechanism of post-vaccination Bell's palsy remains unclear. The first hypothesis is an autoimmune reaction occurring via either mimicry of host molecules by the vaccine antigen or activation of dormant auto-reactive T-cells [13] . A second theory is that the vaccine causes an innate immune activation by a combination of mRNA and lipids, which could include interferon synthesis exceeding the peripheral tolerance [14, 15] [16] . Moreover, in a study comparing Bell's palsy patients treated with acyclovir-prednisone versus patients treated with placebo-prednisone, the first treatment was significantly more effective in returning volitional muscle motion and in preventing partial nerve degeneration than placebo-prednisone treatment [17] . If this hypothesis is confirmed by future studies, previous Herpes Simplex Virus 1 infection should be considered as a risk factor for the development of post-vaccine Bell's palsy. Contrast-enhanced brain MRI can help confirm the diagnosis or exclude other anomalies, through the assessment of the morphology and normal enhancement pattern of the facial nerve along its course, including the geniculate ganglion and mastoid segments. The normal facial nerve faintly enhances in the geniculate ganglion, tympanic, and mastoid segments, but not in the cisternal, intracanalicular, labyrinthine, or parotid portions. In Bell's palsy, increased nerve enhancement has been reported at a variable rate, ranging from 57 to 100 % [18] ; the affected segments of the facial nerve enhance linearly, more intensely than the contralateral non-affected side. The mastoid and extratemporal segments are less frequently involved [19] . The enlargement or thickening of the facial nerve should be instead considered suspicious for a neoplastic process. The treatment is based on steroids administration. Patients presented to the Emergency Departments are usually treated with intravenous methylprednisolone (500 mg) twice daily for three days plus 400 mg of acyclovir four times daily, followed by prednisone per os associated with 400 mg of acyclovir three times daily, as for idiopathic Bell's Palsy [20] . Patients who directly refer the general practitioner are usually treated with 50-60 mg of daily oral prednisolone for one week associated or not with acyclovir with the abovereported dosage [7] . For what concerning the prognosis of these patients, Noseda et al reported a recovery in 16 .4% of patients, a recovery with sequelae in 0.6% of patients, and an absent recovery in 19 .5% of patients [9] . Renoud et al in an analysis of the data collected in the VigiBase on March 9, 2021, described recovery in 19.8% of patients, a recovery with sequelae in 0.3%, and an absent recovery in 23.9% of patients [21] . Reports of Bell's palsy following mRNA SARS-CoV-2 vaccines in the general population are emerging in the literature. The exact causal relationship between the mRNA vaccines and the onset of Bell's palsy needs to be investigated further. Our case emphasizes the importance of collecting vaccine history in patients with Bell's palsy. Brain MRI can be used to confirm a diagnosis and rule out other disorders. The authors declare that they have no conflict of interest. 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