Neurological complications after first dose of COVID-19 vaccines and SARS-CoV-2 infection.

Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns. We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280). There was an increased risk of Guillain-Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15-3.92 at 15-21 days after vaccination) and Bell's palsy (IRR, 1.29; 95% CI: 1.08-1.56 at 15-21 days) with ChAdOx1nCoV-19. There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12-1.71 at 15-21 days) with BNT162b2. An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain-Barré syndrome (IRR, 2.32; 95% CI: 1.08-5.02 at 1-28 days). There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain-Barré syndrome (IRR, 5.25; 95% CI: 3.00-9.18). Overall, we estimated 38 excess cases of Guillain-Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test. In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test.

A systematic review of Bell's Palsy as the only major neurological manifestation in COVID-19 patients.

BACKGROUND: Bell's palsy is an acute idiopathic paralysis of the facial nerve. The disease is caused by many viruses like Herpes simplex virus-1, Varicella zoster, Epstein-bar virus, Cytomegalovirus, Usutu virus, Human immunodeficiency virus, etc. Literature has reported few cases of COVID-19 patients with Bell's palsy as the only major neurological manifestation indicating the possible role of another virus in the etiopathogenesis of Bell's Palsy. This paper aims to evaluate the reported cases of COVID-19 positive patients, presented with Bell's palsy as the only major neurological manifestation from March 2020 to December 2020, and to investigate the association of SARS-CoV2 and Bell's palsy. MATERIALS AND METHODS: A systematic review of the published literature was performed using an electronic search in PubMed/Medline, Science Direct, Web of Science, Embase, J- STAGE, Google Scholar, China National Knowledge Infrastructure (CKNI) and Scopus databases, from March 2020 to Dec 2020 using keywords like 'COVID-19', 'SARS-CoV-2', 'Coronavirus', 'Bell's palsy', 'Facial nerve', 'First', 'Only',' Neurological', 'Manifestation'. The studies reviewed were case series and case reports regarding the subject. RESULTS: Search strategy revealed thirteen articles from March 2020 to Dec 2020 with a total of 20 cases of COVID-19 with Bell's palsy as the only major neurological manifestation. CONCLUSION: Evidence of Bell's palsy as the only major neurological manifestation in COVID-19 patients signifies an important clinical finding but robust research is needed to investigate their association and the exact mechanisms by which SARS-CoV2 causes Bell's Palsy.

Can isolated sudden sensorineural hearing loss (SSNHL) and idiopathic acute facial paralysis (Bell's palsy) be symptoms of COVID-19?

OBJECTIVES: The symptoms of COVID-19 at the time of presentation mainly include fever, cough, respiratory distress and myalgia. On the other hand, as neurological symptoms, disruption of taste and smell and cerebrovascular pathologies are well-known, whereas other neurological symptoms and signs are being newly recognized. Sudden-onset sensorineural hearing loss (SSNHL) and idiopathic acute facial paralysis (Bell's palsy) are otologic emergencies that are frequently encountered by otorhinolaryngology specialists. Although there are many articles describing SSNHL and Bell's palsy in the literature, the literature describing their relationship to COVID-19 is limited. In our study, we aimed to present the neuro-otologic relationship of SSNHL and Bell's palsy with COVID-19. MATERIAL AND METHODS: The pretreatment real-time oronasopharyngeal PCR tests, COVID-19 symptomatology and COVID-19 infection statuses of patients who presented to our clinic with isolated SSNHL and Bell's palsy between April 2020 and April 2021 were questioned, and the data of the patients were collected. Throughout their treatment, the patients were followed-up in terms of COVID-19 infection. This is a prospective study. Moreover, to observe the change in the incidence, the data of patients visiting between January 2019 and January 2020 were also collected. The data of the patients were statistically analyzed using SPSS. RESULTS: The study included a total of 177 patients. The SSNHL group consisted of 91 patients, and the Bell's palsy group consisted of 86 patients. Neither group showed a statistically significant difference in comparison to the year without the pandemic in terms of the patient numbers (incidence), sex, age, morbidity, response to treatment or social habits. There was a statistically significant difference in age only in the Bell's palsy group, but this difference was not medically significant. CONCLUSION: As a result of our study, we did not observe a relationship between COVID-19 and cases of SSNHL and Bell's palsy. It is recommended to apply standard otologic treatment to isolated SSNHL and Bell's palsy patients whose association with COVID-19 is not determined.

Increased incidence of idiopathic paediatric facial palsy during the coronavirus disease 2019 pandemic.

BACKGROUND: Bell's palsy is a lower motor neurone facial weakness of unknown aetiology, although reactivation of a virus within the facial nerve has been proposed. METHODS: A prospective study was conducted of Bell's palsy cases presenting to our paediatric ENT unit over a 19-week period, from February to June 2020. Patients were invited for severe acute respiratory syndrome coronavirus-2 antibody testing. A text-message questionnaire was sent to other ENT centres to determine their observational experience. RESULTS: During the study period, 17 children presented with Bell's palsy, compared with only 3 children in the same time period in the previous year (p < 0.0001). Five patients underwent severe acute respiratory syndrome coronavirus-2 antibody testing, the results of which were all negative. Four out of 15 centres questioned perceived an increased incidence in paediatric Bell's palsy. CONCLUSION: Clinicians are encouraged to be vigilant to the increase in paediatric Bell's palsy seen during the coronavirus disease 2019 pandemic, which may represent a post-viral sequela of coronavirus disease 2019.

Does the SARS-CoV-2 pandemic really increase the frequency of peripheral facial palsy?

PURPOSE: Publications about increased number of peripheral facial paralysis in the COVID-19 pandemic emerged in the literature. However, these studies comprised of an estimate rather than a broad analysis of exact numbers. In this study, we planned to investigate whether the pandemic really resulted in an increase in facial paralysis cases admitted to the hospital by evaluating the cases who applied to our hospital due to facial paralysis in the COVID-19 pandemic year and in the previous 4 years. MATERIALS AND METHODS: Patients who applied to our hospital due to facial paralysis between March 2016-February 2017 (Group 1), between March 2017-February 2018 (Group 2), between March 2018-February 2019 (Group 3), between March 2019-February 2020 (Group 4), and between March 2020-February 2021 (Group 5) were investigated and detailed data were noted. RESULTS: 156, 164, 149, 172 and 157 patients were admitted to the hospital due to peripheral facial paralysis in Group 1, 2, 3, 4, and 5, respectively. Of these patients, 155, 164, 145, 169, and 153 were Bell's palsy, respectively. SARS-CoV-2 RT-PCR test was positive in only 2 of the 153 patients who were diagnosed in the year of the pandemic. CONCLUSIONS: This study showed that the number of peripheral facial paralysis detected during the COVID-19 pandemic was similar to previous years. Very few number of positive SARS-CoV-2 RT-PCR test results may have been found incidentally in Bell's palsy patients. Theses stating that SARS-CoV-2 causes peripheral facial paralysis should be supported by laboratory studies and postmortem research.

Otolaryngological symptoms in COVID-19.

PURPOSE: The aim of this study was to evaluate the frequency of various otolaryngological symptoms in patients with COVID-19 with regard to age, gender and pneumonia-related thorax CT characteristics. METHODS: This is a retrospective study conducted between March 25, 2020 and April 25, 2020. The anamnesis and medical files of 155 patients who applied to our outpatient COVID-19 clinic were evaluated. Patients with positive PCR tests for COVID-19 who were aged between 18-72 years were divided into groups according to the presence of otolaryngological symptoms. The differences between the two groups were examined. RESULTS: Of the 155 patients, 89 (57.4%) had otolaryngological symptoms. The mean age of the patients was 36.3 ± 8.1 years. Ninety-one (58.7%) patients were female, and 64 (42.2%) were male. Fifty-eight (37.4%) patients had received a clinical diagnosis of viral pneumonia with ground glass findings in tomography. The frequency of otolaryngological symptoms was higher in females than males (p: 0.029). The otolaryngological symptoms were also observed to be more frequent in the 18-30 age group (p: 0.013) compared to other age groups. CONCLUSIONS: Tinnitus, gingivitis, sudden hearing loss, Bell's palsy, and hoarseness can be seen in COVID-19, albeit rarely. Revealing the otolaryngological symptoms of COVID-19, and obtaining more information about the extent of disease will be useful in managing patients and their complaints associated with otolaryngology.

Update on Neurological Manifestations of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2, the source of COVID-19, causes numerous clinical findings including respiratory and gastrointestinal findings. Evidence is now growing for increasing neurological symptoms. This is thought to be from direct in-situ effects in the olfactory bulb caused by the virus. Angiotensin-converting enzyme 2 receptors likely serve as a key receptor for cell entry for most coronaviridae as they are present in multiple organ tissues in the body, notably neurons, and in type 2 alveolar cells in the lung. Hematogenous spread to the nervous system has been described, with viral transmission along neuronal synapses in a retrograde fashion. The penetration of the virus to the central nervous system (CNS) allows for the resulting intracranial cytokine storm, which can result in a myriad of CNS complications. There have been reported cases of associated cerebrovascular accidents with large vessel occlusions, cerebral venous sinus thrombosis, posterior reversible encephalopathy syndrome, meningoencephalitis, acute necrotizing encephalopathy, epilepsy, and myasthenia gravis. Peripheral nervous system effects such as hyposmia, hypogeusia, ophthalmoparesis, Guillain-Barré syndrome, and motor peripheral neuropathy have also been reported. In this review, we update the clinical manifestations of COVID-19 concentrating on the neurological associations that have been described, including broad ranges in both central and peripheral nervous systems.

Metagenomic next-generation sequencing of viruses, bacteria, and fungi in the epineurium of the facial nerve with Bell's palsy patients.

Bell's palsy (BP) represents a major cause leading to facial paralysis in the world. The etiology of BP is still unknown, and virology is the prevailing theory. The purpose of this study is to explore the pathogenic microorganisms that may be related to BP, and it is of great significance to study the pathogenesis and treatment of BP. Metagenomic next-generation sequencing (mNGS) detection was performed in the epineurium of the facial nerve of 30 BP patients who underwent facial nerve epineurium decompression. A total of 84 pathogenic microorganisms were detected in 30 clinical samples, including 4 viruses, 10 fungi, and 70 bacteria. The species with the highest detection frequency in virus was human betaherpesvirus 7 (HHV-7). The species with the highest detection frequency in Fungi was Malassezia restricta. The species with the highest detection frequency in Bacteria was Pseudomonas aeruginosa. In this study, mNGS method was firstly used to detect the pathogenic microorganisms in the epineurium of the facial nerve with BP patients. We have for the first time identified HHV-7 and aspergillus in the epineurium of the facial nerve of BP patients. These results suggest that these two pathogenic microorganisms should be considered in the pathogenesis of BP.

The presence of herpes simplex-1 and varicella zoster viruses is not related with clinical outcome of Bell's Palsy.

Bell's Palsy is the most frequent acute neuropathy of cranial nerves; it has been associated in various reports to herpes viruses. In a prospective study we searched the presence of DNA from five herpes viruses (HSV-1 and 2, VZV, EBV and HHV-6) in 79 patients at the acute phase of Bell's Palsy. Results were related with various parameters; age, gender and clinical outcome. We found the significant presence (p˂0.001) of HSV-1 and VZV in 39% and 42% of patients. However, a large percentage of cases were negative. When comparisons were made between subgroups according to gender and age no differences were found with viral findings nor with clinical outcome of palsy, which was of clinical remission in most cases (78%). Our results suggest that herpes viruses might participate in the complex mechanisms of autoimmunity of Bell's Palsy but not as determinant etiological element.

Herpes viruses in optic neuritis: Similar to Bell's palsy.

OBJECTIVE: Optic Neuritis (ON) might unfold either as a single intracranial neuritis or as multiple sclerosis, a widespread demyelinating disorder. Different herpes viruses have been proposed as potential participants in the etiology of multiple sclerosis (MS). To analyze the potential presence of herpes viruses in blood and subarachnoid area at the time of ON and contrast the findings according to long-term evolution either as intracranial neuritis or as progression to multiple sclerosis. PATIENTS AND METHODS: In a prospective investigation we searched the presence of DNA from 5 herpes viruses (HSV-1, HSV-2, VZV, EBV and HHV6) in CSF and blood lymphocytes from 54 patients with ON, patients were followed 62 ±â€¯3 months; those who developed MS were separated from those with ephemeral ON. Long-term prognosis of ON was related to DNA findings. RESULTS: As compared with controls, DNA from HSV-1 was significantly more frequent in CSF and blood from cases with ON; VZV and HSV-2 were found only in CSF; EBV was found only in blood samples (p < 0.006). CONCLUSIONS: Our results point out the potential participation of HSV, VZV and EBV in ON; suggesting the intervention of various herpes viruses as triggering agents of autoimmunity. However, the number of positive cases was minor than negative cases. Also, our results suggest that the etiological mechanisms in ON could be similar to those of neuritis of the facial nerve (Bell's palsy).

Antiviral treatment for Bell's palsy (idiopathic facial paralysis).

BACKGROUND: Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. This review was first published in 2001 and most recently updated in 2015. Since a significant benefit of corticosteroids for the early management of Bell's palsy has been demonstrated, the main focus of this update, as in the previous version, was to determine the effect of adding antivirals to corticosteroid treatment. We undertook this update to integrate additional evidence and to better assess the robustness of findings, taking risk of bias fully into account. OBJECTIVES: To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy. SEARCH METHODS: We searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS in July 2019. We reviewed the bibliographies of the identified trials and contacted trial authors to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) or quasi-RCTs of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that followed-up participants for less than three months. DATA COLLECTION AND ANALYSIS: We independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures. We performed sensitivity analyses excluding trials at high or unclear risk of bias in at least five domains, and reported these data as the primary analyses. MAIN RESULTS: Fourteen trials, including 2488 participants, met the inclusion criteria. Most were small, and most were at high or unclear risk of bias in multiple domains. We included four new studies at this update.Incomplete recoveryA combination of antivirals and corticosteroids may have little or no effect on rates of incomplete recovery in people with Bell's palsy compared to corticosteroids alone (risk ratio (RR) 0.81, 95% confidence interval (CI) 0.38 to 1.74; 3 trials, N = 766; random-effects; low-certainty evidence). We excluded 10 trials that were at high or unclear risk of bias in several domains from this analysis and limited all analyses to studies at lower risk of bias. Recovery rates were better in participants receiving corticosteroids alone than antivirals alone (RR 2.69, 95% CI 0.73 to 10.01; 2 trials, N = 667; random-effects), but the result was imprecise and allowed for the possibility of no effect. The rate of incomplete recovery was lower with antivirals plus corticosteroids than with placebo or no treatment (RR 0.56, 95% CI 0.42 to 0.76; 2 trials, N = 658; random-effects). Antivirals alone had no clear effect on incomplete recovery rates compared with placebo, but the result was imprecise (RR 1.10, 95% CI 0.87 to 1.40; 2 trials, N = 658; fixed-effect). For people with severe Bell's palsy (House-Brackmann score of 5 and 6, or equivalent on other scales), we found that the combination of antivirals and corticosteroids had no clear effect on incomplete recovery at month six compared to corticosteroids alone, although the result was again imprecise (RR 0.82, 95% CI 0.57 to 1.17; 2 trials, N = 98; random-effects).Motor synkinesis or crocodile tearsAntivirals plus corticosteroids reduced the proportion of participants who experienced these long-term sequelae from Bell's palsy compared to placebo plus corticosteroids (RR 0.56, 95% CI 0.36 to 0.87; 2 trials, N = 469; fixed-effect; moderate-certainty evidence). Antivirals plus corticosteroids reduced long-term sequelae compared to placebo but there was no clear difference in this outcome with antivirals alone compared to placebo.Adverse events Adverse event data were available in four studies providing data on 1592 participants. None of the four comparisons showed clear differences in adverse events between treatment and comparison arms (very low-certainty evidence); for the comparison of antivirals plus corticosteroids and corticosteroids alone in studies at lower risk of bias, the RR was 1.17 (95% CI 0.81 to 1.69; 2 trials, N = 656; fixed-effect; very low-certainty evidence). AUTHORS' CONCLUSIONS: The combination of antivirals and corticosteroids may have little or no effect on rates of incomplete recovery in comparison to corticosteroids alone in Bell's palsy of various degrees of severity, or in people with severe Bell's palsy, but the results were very imprecise. Corticosteroids alone were probably more effective than antivirals alone and antivirals plus corticosteroids were more effective than placebo or no treatment. There was no clear benefit from antivirals alone over placebo.The combination of antivirals and corticosteroids probably reduced the late sequelae of Bell's palsy compared with corticosteroids alone. Studies also showed fewer episodes of long-term sequelae in corticosteroid-treated participants than antiviral-treated participants.We found no clear difference in adverse events from the use of antivirals compared with either placebo or corticosteroids, but the evidence is too uncertain for us to draw conclusions.An adequately powered RCT in people with Bell's palsy that compares different antiviral agents may be indicated.

A 17-Year-Old Boy With Right Face Palsy, Left Leg Weakness, and Lytic Skull-Bone Lesions.

Human T-cell lymphotropic virus (HTLV), an infection that is endemic in certain parts of Asia, Africa, and South America, has been associated with malignancy and neurological deficits. Here, we describe a pediatric patient with chronic HTLV-I infection who developed complications associated with HTLV-I (ie, adult T-cell leukemia/lymphoma and HTLV-I-associated myelopathy/tropical spastic paraparesis). To our knowledge, this presentation in a child has never been described. The patient underwent a bone marrow transplant and, at the time of this writing, was in remission. This case report highlights the fact that HTLV-related complications, previously expected to occur after decades of infection, also can occur in pediatric patients, particularly those who acquired HTLV-I perinatally.

PML-IRIS in an HIV-2-infected patient presenting as Bell's palsy.

We present the case of an HIV-2-infected patient who developed progressive multifocal leukoencephalopathy (PML) in the setting of immune reconstitution inflammatory syndrome (IRIS) presenting as Bell's palsy. The brain MRI showed a single lesion in the facial colliculus considered initially to be ischemic in nature. This case report should alert clinicians that PML can occur in the setting of HIV-2 infection. It also illustrates the difficulty of establishing the diagnosis of PML.

Concurrent pityriasis rosea and Bell's palsy.

Pityriasis rosea is a dermatological disease with a well-documented clinical appearance, but less is known about causes and treatment. Bell's palsy is a neurological condition leading to acute idiopathic hemifacial paralysis. Recent studies indicate that human herpesvirus (HHV) 6-7 reactivation may be a contributing factor to both conditions. We report a case of the 2 concurrent diagnoses that supports a common contributing factor and suggests further awareness and research into the role HHV 6-7 may play in the aetiology of both conditions.

Acoustic Reflex and House-Brackmann Rating Scale as Prognostic Indicators of Peripheral Facial Palsy in Neuroborreliosis.

Lyme borreliosis is a vector-borne infectious disease characterized by three disease stages. In the areas endemic for borreliosis, every acute facial palsy indicates serologic testing and implies specific approach to the disease. Th e aim of the study was to identify and confirm the value of acoustic refl ex and House-Brackman (HB) grading scale as prognostic indicators of facial palsy in neuroborreliosis. Th e study included 176 patients with acute facial palsy divided into three groups based on serologic testing: borreliosis, Bell's palsy, and facial palsy caused by herpes simplex virus type 1 (HSV-1). Study patients underwent baseline audiometry with tympanometry and acoustic reflex, whereas current state of facial palsy was assessed by the HB scale. Subsequently, the same tests were obtained on three occasions, i.e. in week 3, 6 and 12 of presentation. Th e patients diagnosed with borreliosis, Bell's palsy and HSV-1 differed according to the time to acoustic refl ex recovery, which took longest time in patients with borreliosis. Th ese patients had the highest percentage of suprastapedial lesions at all time points and recovery was achieved later as compared with the other two diagnoses. Th e mean score on the HB scale declined with time, also at a slower rate in borreliosis patients. Th e prognosis of acoustic refl ex and facial palsy recovery according to HB scale was not associated with the length of elapsed time. The results obtained in the present study strongly confirmed the role of acoustic reflex and HB grading scale as prognostic indicators of facial palsy in neuroborreliosis.

Facial palsy after dental procedures - Is viral reactivation responsible?

OBJECTIVES: Herpes labialis viral reactivation has been reported following dental procedures, but the incidence, characteristics and outcomes of delayed peripheral facial nerve palsy following dental work is poorly understood. Herein we describe the unique features of delayed facial paresis following dental procedures. MATERIALS AND METHODS: An institutional retrospective review was performed to identify patients diagnosed with delayed facial nerve palsy within 30 days of dental manipulation. Demographics, prodromal signs and symptoms, initial medical treatment and outcomes were assessed. RESULTS: Of 2471 patients with facial palsy, 16 (0.7%) had delayed facial paresis following ipsilateral dental procedures. Average age at presentation was 44 yrs and 56% (9/16) were female. Clinical evaluation was consistent with Bell's palsy in 14 (88%) and Ramsay-Hunt syndrome in 2 patients (12%). Patients developed facial paresis an average of 3.9 days after the dental procedure, with all individuals developing a flaccid paralysis (House Brackmann (HB) grade VI) during the acute stage. 50% of patients developed persistent facial palsy in the form of non-flaccid facial paralysis (HBIII-IV). CONCLUSION: Facial palsy, like herpes labialis, can occur in the days following dental procedures and may also be related to viral reactivation. In this small cohort, long-term facial outcomes appear worse than for spontaneous Bell's palsy.

Facial paralysis induced by ear inoculation of herpes simplex virus in rat.

OBJECTIVE: Bell's palsy is caused by the reactivation of herpes simplex virus type 1 (HSV-1). Using Balb/c mice inoculated with the KOS strain of HSV-1, we previously developed an animal disease model that simulated mild Bell's palsy. The current study developed an animal disease model of more severe facial palsy than that seen in the mouse model. METHODS: Three-week-old female Wister rats weighing 60-80g were inoculated on the auricle with HSV-1 and acyclovir was administered intraperitoneally to deactivate the infected HSV-1. Instead of HSV-1, phosphate-buffered saline was used for inoculation as a negative control. Quantitative polymerase chain reaction (PCR), behavior testing (blink reflex), electroneuronography, histopathology of the peripheral nerve, and immunohistochemistry of the facial nerve nucleus were evaluated. RESULTS: Facial palsy occurred 3-5 days after virus inoculation, and the severity of the facial palsy progressed for up to 7 days. Quantitative PCR showed an increase in HSV-1 DNA copies in the facial nerve from 24 to 72h, suggesting that HSV-1 infection occurred in the nerve. Electroneuronography values were 33.0±15.3% and 110.0±18.0% in HSV-1-inoculated and control rats, respectively. The histopathology of the peripheral nerve showed demyelination and loss of the facial nerve, and the facial nerve nucleus showed degeneration. CONCLUSION: Facial palsy developed in Wister rats following inoculation of the KOS strain of HSV-1 onto the auricles. The behavioral, histopathological, and electroneuronography data suggested that the severity of facial palsy was greater in our rats than in animals in the previous mouse disease model.