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Major Neurological Syndromes with COVID-19: Lessons to Learn

Neeraj Jain, Dnyaneshwar Jadhav, Akash Chheda, Sangeeta Ravat, Rahil Ansari, Mayur Thakkar, Rishikesh Joshi, A. Santosh Sriram, Vrug Durge

Abstract


Objective: Covid-19 is a highly infectious viral disease, and our understanding of the impact of this virus on the nervous system is limited. Therefore, we aimed to do a systematic analysis of the neurological manifestations. Methods: We retrospectively studied the clinical, laboratory, and radiological findings of patients with major neurological syndromes (MNS) in Covid-19 over 6 months. Results: We had 39 patients with major neurological syndromes (MNS). The most common MNS was cerebrovascular disease (CVD) (61.53%), in which ischemic stroke (83.33%), cortical sinus thrombosis (12.50%), and haemorrhagic stroke (4.16%) were seen. Among ischemic stroke patients, 50% had a large vessel occlusion, and 66.66% of patients with CVD had a significant residual disability. Cranial neuropathy (15.38%), GBS (10.26%), encephalitis (7.26%), and myelitis (5.12%) were the other MNS. Among the three encephalitis cases, two had CSF-Covid-19 PCR positivity and had severe manifestations and a poor outcome. Associated comorbidities included hypertension (30.76%), diabetes mellitus (12.82%), chronic kidney diseases (7.69%), and polycythaemia vera (2.56%). Lung involvement was seen in 64.1% of patients. Mortality was 17.94% in MNS with Covid-19. Conclusions: The most common major neurological syndrome associated with Covid-19 is CVD with increased frequency of large vessel occlusion causing significant morbidity and mortality. Simultaneous lung and other systemic involvement in MNS results in a deleterious outcome.

 

Doi: 10.28991/SciMedJ-2022-0401-02

Full Text: PDF


Keywords


Covid-19; Major Neurological Syndromes (MNS); Cerebrovascular Disease (CVD); Encephalitis; GBS; Cranial Neuropathy.

References


Wrapp, D., Wang, N., Corbett, K. S., Goldsmith, J. A., Hsieh, C.-L., Abiona, O., Graham, B. S., & McLellan, J. S. (2020). Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science, 367(6483), 1260–1263. doi:10.1126/science.abb2507.

World Health Organization. (2020). Coronavirus Disease (COVID-19) - Events as they happen. World Health Organization, Geneva, Switzerland. Available online: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/events-as-they-happen (accessed on January 2022).

Huang, C., Wang, Y., Li, X., Ren, L., Zhao, J., Hu, Y., Zhang, L., Fan, G., Xu, J., Gu, X., Cheng, Z., Yu, T., Xia, J., Wei, Y., Wu, W., Xie, X., Yin, W., Li, H., Liu, M., … Cao, B. (2020). Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet, 395(10223), 497–506. doi:10.1016/S0140-6736(20)30183-5.

Bhatraju, P. K., Ghassemieh, B. J., Nichols, M., Kim, R., Jerome, K. R., Nalla, A. K., Greninger, A. L., Pipavath, S., Wurfel, M. M., Evans, L., Kritek, P. A., West, T. E., Luks, A., Gerbino, A., Dale, C. R., Goldman, J. D., O’Mahony, S., & Mikacenic, C. (2020). Covid-19 in Critically Ill Patients in the Seattle Region — Case Series. New England Journal of Medicine, 382(21), 2012–2022. doi:10.1056/nejmoa2004500.

Paterson, R. W., Brown, R. L., Benjamin, L., Nortley, R., Wiethoff, S., Bharucha, T., Jayaseelan, D. L., Kumar, G., Raftopoulos, R. E., Zambreanu, L., Vivekanandam, V., Khoo, A., Geraldes, R., Chinthapalli, K., Boyd, E., Tuzlali, H., Price, G., Christofi, G., Morrow, J., … Zandi, M. S. (2020). The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings. Brain, 143(10), 3104–3120. doi:10.1093/brain/awaa240.

Tai, W., He, L., Zhang, X., Pu, J., Voronin, D., Jiang, S., Zhou, Y., & Du, L. (2020). Characterization of the receptor-binding domain (RBD) of 2019 novel coronavirus: implication for development of RBD protein as a viral attachment inhibitor and vaccine. Cellular and Molecular Immunology, 17(6), 613–620. doi:10.1038/s41423-020-0400-4.

Chen, R., Wang, K., Yu, J., Howard, D., French, L., Chen, Z., Wen, C., & Xu, Z. (2021). The Spatial and Cell-Type Distribution of SARS-CoV-2 Receptor ACE2 in the Human and Mouse Brains. Frontiers in Neurology, 11(573095). doi:10.3389/fneur.2020.573095.

Hamming, I., Timens, W., Bulthuis, M., Lely, A., Navis, G., & van Goor, H. (2004). Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. The Journal of Pathology, 203(2), 631–637. doi:10.1002/path.1570.

Berth, S. H., Leopold, P. L., & Morfini, G. (2009). Virus-induced neuronal dysfunction and degeneration. Frontiers in Bioscience, 14(14), 5239–5259. doi:10.2741/3595.

Li, Y., Li, M., Wang, M., Zhou, Y., Chang, J., Xian, Y., Wang, D., Mao, L., Jin, H., & Hu, B. (2020). Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke and Vascular Neurology, 5(3), 279–284. doi:10.1136/svn-2020-000431.

Radmanesh, A., Raz, E., Zan, E., Derman, A., & Kaminetzky, M. (2020). Brain imaging utilization and findings in COVID-19: A single academic center experience in the epicenter of disease in the United States. American Journal of Neuroradiology, 41(7), 1179–1183. doi:10.3174/AJNR.A6610.

Varga, Z., Flammer, A. J., Steiger, P., Haberecker, M., Andermatt, R., Zinkernagel, A. S., Mehra, M. R., Schuepbach, R. A., Ruschitzka, F., & Moch, H. (2020). Endothelial cell infection and endotheliitis in COVID-19. The Lancet, 395(10234), 1417–1418. doi:10.1016/S0140-6736(20)30937-5.

Wu, Y., Xu, X., Chen, Z., Duan, J., Hashimoto, K., Yang, L., Liu, C., & Yang, C. (2020). Nervous system involvement after infection with COVID-19 and other coronaviruses. Brain, Behavior, and Immunity, 87, 18–22. doi:10.1016/j.bbi.2020.03.031.

Zhang, Y., Xiao, M., Zhang, S., Xia, P., Cao, W., Jiang, W., Chen, H., Ding, X., Zhao, H., Zhang, H., Wang, C., Zhao, J., Sun, X., Tian, R., Wu, W., Wu, D., Ma, J., Chen, Y., Zhang, D., … Zhang, S. (2020). Coagulopathy and Antiphospholipid Antibodies in Patients with Covid-19. New England Journal of Medicine, 382(17), e38. doi:10.1056/nejmc2007575.

Avula, A., Nalleballe, K., Narula, N., Sapozhnikov, S., Dandu, V., Toom, S., Glaser, A., & Elsayegh, D. (2020). COVID-19 presenting as stroke. Brain, Behavior, and Immunity, 87, 115–119. doi:10.1016/j.bbi.2020.04.077.

Tsivgoulis, G., Palaiodimou, L., Zand, R., Lioutas, V. A., Krogias, C., Katsanos, A. H., ... & Tsiodras, S. (2020). COVID-19 and cerebrovascular diseases: a comprehensive overview. Therapeutic advances in neurological disorders, 13, 1756286420978004. doi:10.1177/1756286420978004.

Mao, L., Jin, H., Wang, M., Hu, Y., Chen, S., He, Q., Chang, J., Hong, C., Zhou, Y., Wang, D., Miao, X., Li, Y., & Hu, B. (2020). Neurologic Manifestations of Hospitalized Patients with Coronavirus Disease 2019 in Wuhan, China. JAMA Neurology, 77(6), 683–690. doi:10.1001/jamaneurol.2020.1127.

Morassi, M., Bagatto, D., Cobelli, M., D’Agostini, S., Gigli, G. L., Bnà , C., & Vogrig, A. (2020). Stroke in patients with SARS-CoV-2 infection: case series. Journal of Neurology, 267(8), 2185–2192. doi:10.1007/s00415-020-09885-2.

Jain, R., Young, M., Dogra, S., Kennedy, H., Nguyen, V., Jones, S., Bilaloglu, S., Hochman, K., Raz, E., Galetta, S., & Horwtiz, L. (2020). COVID-19 related neuroimaging findings: A signal of thromboembolic complications and a strong prognostic marker of poor patient outcome. Journal of the Neurological Sciences, 414. doi:10.1016/j.jns.2020.116923.

Romero-Sánchez, C. M., Díaz-Maroto, I., Fernández-Díaz, E., Sánchez-Larsen, Ã., Layos-Romero, A., García-García, J., González, E., Redondo-Peñas, I., Perona-Moratalla, A. B., Del Valle-Pérez, J. A., Gracia-Gil, J., Rojas-Bartolomé, L., Feria-Vilar, I., Monteagudo, M., Palao, M., Palazón-García, E., Alcahut-Rodríguez, C., Sopelana-Garay, D., Moreno, Y., … Segura, T. (2020). Neurologic manifestations in hospitalized patients with COVID-19: The ALBACOVID registry. In Neurology (Vol. 95, Issue 8, pp. E1060–E1070). doi:10.1212/WNL.0000000000009937.

Baig, A. M., Khaleeq, A., Ali, U., & Syeda, H. (2020). Evidence of the COVID-19 Virus Targeting the CNS: Tissue Distribution, Host-Virus Interaction, and Proposed Neurotropic Mechanisms. ACS Chemical Neuroscience, 11(7), 995–998. doi:10.1021/acschemneuro.0c00122.

Natoli, S., Oliveira, V., Calabresi, P., Maia, L. F., & Pisani, A. (2020). Does SARS-Cov-2 invade the brain? Translational lessons from animal models. European Journal of Neurology, 27(9), 1764–1773. doi:10.1111/ene.14277.

Zhang, T., Rodricks, M. B., & Hirsh, E. (2020). COVID-19-Associated Acute Disseminated Encephalomyelitis – A Case Report. Medrxiv, 1-7. doi:10.1101/2020.04.16.20068148.

Zanin, L., Saraceno, G., Panciani, P. P., Renisi, G., Signorini, L., Migliorati, K., & Fontanella, M. M. (2020). SARS-CoV-2 can induce brain and spine demyelinating lesions. Acta Neurochirurgica, 162(7), 1491–1494. doi:10.1007/s00701-020-04374-x.

Filatov, A., Sharma, P., Hindi, F., & Espinosa, P. S. (2020). Neurological Complications of Coronavirus Disease (COVID-19): Encephalopathy. Cureus, 7352. doi:10.7759/cureus.7352.

Siow, I., Lee, K. S., Zhang, J. J. Y., Saffari, S. E., & Ng, A. (2021). Encephalitis as a neurological complication of COVID-19: A systematic review and meta-analysis of incidence, outcomes, and predictors. European Journal of Neurology, 28(10), 3491–3502. doi:10.1111/ene.14913.

Poyiadji, N., Shahin, G., Noujaim, D., Stone, M., Patel, S., & Griffith, B. (2020). COVID-19-associated acute hemorrhagic necrotizing encephalopathy: Imaging features. Radiology, 296(2), E119–E120. doi:10.1148/radiol.2020201187.

Zhang, C., Wu, Z., Li, J. W., Zhao, H., & Wang, G. Q. (2020). Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality. International Journal of Antimicrobial Agents, 55(5), 105954. doi:10.1016/j.ijantimicag.2020.105954.

Ahmed, M. U., Hanif, M., Ali, M. J., Haider, M. A., Kherani, D., Memon, G. M., Karim, A. H., & Sattar, A. (2020). Neurological Manifestations of COVID-19 (SARS-CoV-2): A Review. Frontiers in Neurology, 11, 518. doi:10.3389/fneur.2020.00518.

Baud, D., Qi, X., Nielsen-Saines, K., Musso, D., Pomar, L., & Favre, G. (2020). Real estimates of mortality following COVID-19 infection. The Lancet Infectious Diseases, 20(7), 773. doi:10.1016/S1473-3099(20)30195-X.

Zhao, K., Huang, J., Dai, D., Feng, Y., Liu, L., & Nie, S. (2020). Acute myelitis after SARS-CoV-2 infection: a case report. Medrxiv, 1-13. doi:10.1101/2020.03.16.20035105.

Román, G. C., Gracia, F., Torres, A., Palacios, A., Gracia, K., & Harris, D. (2021). Acute Transverse Myelitis (ATM): Clinical Review of 43 Patients with COVID-19-Associated ATM and 3 Post-Vaccination ATM Serious Adverse Events with the ChAdOx1 nCoV-19 Vaccine (AZD1222). Frontiers in Immunology, 12. doi:10.3389/fimmu.2021.653786.

Blackburn, K. M., & Wang, C. (2020). Post-infectious neurological disorders. Therapeutic Advances in Neurological Disorders, 13. doi:10.1177/1756286420952901.

Zhao, H., Shen, D., Zhou, H., Liu, J., & Chen, S. (2020). Guillain-Barré syndrome associated with SARS-CoV-2 infection: causality or coincidence? The Lancet Neurology, 19(5), 383–384. doi:10.1016/S1474-4422(20)30109-5.

Toscano, G., Palmerini, F., Ravaglia, S., Ruiz, L., Invernizzi, P., Cuzzoni, M. G., Franciotta, D., Baldanti, F., Daturi, R., Postorino, P., Cavallini, A., & Micieli, G. (2020). Guillain–Barré Syndrome Associated with SARS-CoV-2. New England Journal of Medicine, 382(26), 2574–2576. doi:10.1056/nejmc2009191.

McGonagle, D., Sharif, K., O’Regan, A., & Bridgewood, C. (2020). The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease. Autoimmunity Reviews, 19(6). doi:10.1016/j.autrev.2020.102537.

Qin, C., Zhou, L., Hu, Z., Zhang, S., Yang, S., Tao, Y., Xie, C., Ma, K., Shang, K., Wang, W., & Tian, D. S. (2020). Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clinical Infectious Diseases, 71(15), 762–768. doi:10.1093/cid/ciaa248.


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DOI: 10.28991/SciMedJ-2022-0401-02

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Copyright (c) 2023 Neeraj Jain, Dnyaneshwar V Jadhav, Sangeeta H Ravat, Akash Chheda, Rahil Ansari, Mayur D Thakkar, Rishikesh S Joshi, Andugulapati Santosh Sriram, Vrujkumar L Durge