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      COVID-19 associated cranial nerve neuropathy: A systematic review

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          Abstract

          The involvement of cranial nerves is being increasingly recognized in COVID-19. This review aims to summarize and discuss the recent advances concerning the clinical presentation, pathophysiology, diagnosis, treatment, and outcomes of SARS-CoV-2 associated cranial nerve mononeuropathies or polyneuropathies. Therefore, a systematic review of articles from PubMed and Google Scholar was conducted. Altogether 36 articles regarding SARS-CoV-2 associated neuropathy of cranial nerves describing 56 patients were retrieved as per the end of January 2021. Out of these 56 patients, cranial nerves were compromised without the involvement of peripheral nerves in 32 of the patients, while Guillain-Barre syndrome (GBS) with cranial nerve involvement was described in 24 patients. A single cranial nerve was involved either unilaterally or bilaterally in 36 patients, while in 19 patients multiple cranial nerves were involved. Bilateral involvement was more prevalent in the GBS group (n = 11) as compared to the cohort with isolated cranial nerve involvement (n = 5). Treatment of cranial nerve neuropathy included steroids (n = 18), intravenous immunoglobulins (IVIG) (n = 18), acyclovir/valacyclovir (n = 3), and plasma exchange (n = 1). The outcome was classified as “complete recovery” in 21 patients and as “partial recovery” in 30 patients. One patient had a lethal outcome. In conclusion, any cranial nerve can be involved in COVID-19, but cranial nerves VII, VI, and III are the most frequently affected. The involvement of cranial nerves in COVID-19 may or may not be associated with GBS. In patients with cranial nerve involvement, COVID-19 infections are usually mild. Isolated cranial nerve palsy without GBS usually responds favorably to steroids. Cranial nerve involvement with GBS benefits from IVIG.

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          Most cited references56

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          Neuropathology of patients with COVID-19 in Germany: a post-mortem case series

          Background Prominent clinical symptoms of COVID-19 include CNS manifestations. However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, gains access to the CNS and whether it causes neuropathological changes. We investigated the brain tissue of patients who died from COVID-19 for glial responses, inflammatory changes, and the presence of SARS-CoV-2 in the CNS. Methods In this post-mortem case series, we investigated the neuropathological features in the brains of patients who died between March 13 and April 24, 2020, in Hamburg, Germany. Inclusion criteria comprised a positive test for SARS-CoV-2 by quantitative RT-PCR (qRT-PCR) and availability of adequate samples. We did a neuropathological workup including histological staining and immunohistochemical staining for activated astrocytes, activated microglia, and cytotoxic T lymphocytes in the olfactory bulb, basal ganglia, brainstem, and cerebellum. Additionally, we investigated the presence and localisation of SARS-CoV-2 by qRT-PCR and by immunohistochemistry in selected patients and brain regions. Findings 43 patients were included in our study. Patients died in hospitals, nursing homes, or at home, and were aged between 51 years and 94 years (median 76 years [IQR 70–86]). We detected fresh territorial ischaemic lesions in six (14%) patients. 37 (86%) patients had astrogliosis in all assessed regions. Activation of microglia and infiltration by cytotoxic T lymphocytes was most pronounced in the brainstem and cerebellum, and meningeal cytotoxic T lymphocyte infiltration was seen in 34 (79%) patients. SARS-CoV-2 could be detected in the brains of 21 (53%) of 40 examined patients, with SARS-CoV-2 viral proteins found in cranial nerves originating from the lower brainstem and in isolated cells of the brainstem. The presence of SARS-CoV-2 in the CNS was not associated with the severity of neuropathological changes. Interpretation In general, neuropathological changes in patients with COVID-19 seem to be mild, with pronounced neuroinflammatory changes in the brainstem being the most common finding. There was no evidence for CNS damage directly caused by SARS-CoV-2. The generalisability of these findings needs to be validated in future studies as the number of cases and availability of clinical data were low and no age-matched and sex-matched controls were included. Funding German Research Foundation, Federal State of Hamburg, EU (eRARE), German Center for Infection Research (DZIF).
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            Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry

            The coronavirus disease 2019 (COVID-19) has spread worldwide since December 2019. Neurological symptoms have been reported as part of the clinical spectrum of the disease. We aim to determine whether neurological manifestations are common in hospitalized COVID-19 patients and to describe their main characteristics. We systematically review all patients diagnosed with COVID-19 admitted to hospital in a Spanish population during March 2020. Demographic characteristics, systemic and neurological clinical manifestations, and complementary tests were analyzed. Of 841 patients hospitalized with COVID-19 (mean age 66.4 years, 56.2% men) 57.4% developed some form of neurological symptom. Nonspecific symptoms such as myalgias (17.2%), headache (14.1%), and dizziness (6.1%) were present mostly in the early stages of infection. Anosmia (4.9%) and dysgeusia (6.2%) tended to occur early (60% as the first clinical manifestation) and were more frequent in less severe cases. Disorders of consciousness occurred commonly (19.6%), mostly in older patients and in severe and advanced COVID-19 stages. Myopathy (3.1%), dysautonomia (2.5%), cerebrovascular diseases (1.7%), seizures (0.7%), movement disorders (0.7%), encephalitis (n=1), Guillain-Barré syndrome (n=1), and optic neuritis (n=1) were also reported, but less frequent. Neurological complications were the main cause of death in 4.1% of all deceased study subjects. Neurological manifestations are common in hospitalized COVID-19 patients. In our series, more than half of patients presented some form of neurological symptom. Clinicians need to maintain close neurological surveillance for prompt recognition of these complications. The investigation of the mechanisms and emerging consequences of SARS-CoV-2 neurological involvement require further studies.
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              Miller Fisher Syndrome and polyneuritis cranialis in COVID-19

              To report two patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) who acutely presented with Miller Fisher syndrome and polyneuritis cranialis, respectively. Patient data were obtained from medical records from the University Hospital “Príncipe de Asturias”, Alcalá de Henares, Madrid, Spain and from the University Hospital “12 de Octubre”, Madrid, Spain. The first patient was a 50-year-old man who presented with anosmia, ageusia, right internuclear ophthalmoparesis, right fascicular oculomotor palsy, ataxia, areflexia, albuminocytologic dissociation and positive testing for GD1b-IgG antibodies. Five days before, he had developed a cough, malaise, headache, low back pain, and a fever. The second patient was a 39-year-old man who presented with ageusia, bilateral abducens palsy, areflexia and albuminocytologic dissociation. Three days before, he had developed diarrhea, a low-grade fever, and a poor general condition. The oropharyngeal swab test for coronavirus disease 2019 (COVID-19) by qualitative real-time reverse-transcriptase–polymerase-chain-reaction assay was positive in both patients and negative in the cerebrospinal fluid. The first patient was treated with intravenous immunoglobulin and the second, with acetaminophen. Two weeks later, both patients made a complete neurological recovery, except for residual anosmia and ageusia in the first case. Our two cases highlight the rare occurrence of Miller Fisher syndrome and polyneuritis cranialis during the COVID-2 pandemic. Neurological manifestations may occur because of an aberrant immune response to COVID-19. The full clinical spectrum of neurological symptoms in patients with COVID-19 remains to be characterized.
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                Author and article information

                Journal
                Bosn J Basic Med Sci
                Bosn J Basic Med Sci
                Bosnian Journal of Basic Medical Sciences
                Association of Basic Medical Sciences of Federation of Bosnia and Herzegovina (Bosnia )
                1512-8601
                1840-4812
                February 2022
                11 August 2021
                : 22
                : 1
                : 39-45
                Affiliations
                [1 ]Clinic Landstrasse, Messerli Institute, Vienna, Austria
                [2 ]Department of Neuroscience, Federal University of São Paulo/Paulista School of Medicine
                [3 ]Department of Speech Therapy, Pontifical Catholic University of São Paulo, Paulista School of Medicine/Federal University of São Paulo, São Paulo, Brazil
                Author notes
                [* ] Corresponding author: Joseph Finsterer, Clinic Landstrasse, Messerli Institute, Vienna, Austria. E-mail: fifigs1@ 123456yahoo.de
                Article
                BJBMS-22-39
                10.17305/bjbms.2021.6341
                8860318
                34392827
                0f1b4af5-abbb-48b0-8b4d-7dc659cf40da
                Copyright: © The Author(s) (2022)

                This work is licensed under a Creative Commons Attribution 4.0 International License

                History
                : 24 July 2021
                : 05 August 2021
                Categories
                Review Article

                cranial nerves,nerve conduction,neuropathy,sars-cov-2,covid-19,guillain barre syndrome

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