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Neurologic Manifestations of the World Health Organization's List Of REVIEW published: 22 February 2021 doi: 10.3389/fneur.2021.634827 Neurologic Manifestations of the World Health Organization’s List of Pandemic and Epidemic Diseases Caleb R. S. McEntire 1, Kun-Wei Song 1, Robert P. McInnis 1, John Y. Rhee 1, Michael Young 1, Erika Williams 1, Leah L. Wibecan 2, Neal Nolan 1, Amanda M. Nagy 2, Jeffrey Gluckstein 1, Shibani S. Mukerji 3 and Farrah J. Mateen 3* 1 Massachusetts General Hospital (MGH)-Brigham Neurology Residency Program, Boston, MA, United States, 2 Massachusetts General Hospital (MGH)-Brigham Pediatric Neurology Residency Program, Boston, MA, United States, 3 Department of Neurology, Massachusetts General Hospital, Boston, MA, United States The World Health Organization (WHO) monitors the spread of diseases globally and maintains a list of diseases with epidemic or pandemic potential. Currently listed diseases include Chikungunya, cholera, Crimean-Congo hemorrhagic fever, Ebola virus disease, Hendra virus infection, influenza, Lassa fever, Marburg virus disease, Neisseria meningitis, Edited by: Peter R. Williamson, MERS-CoV, monkeypox, Nipah virus infection, novel coronavirus (COVID-19), plague, National Institutes of Health (NIH), Rift Valley fever, SARS, smallpox, tularemia, yellow fever, and Zika virus disease. The United States associated pathogens are increasingly important on the global stage. The majority of Reviewed by: these diseases have neurological manifestations. Those with less frequent neurological Sophie Cho, National Institutes of Health Clinical manifestations may also have important consequences. This is highlighted now in Center (NIH), United States particular through the ongoing COVID-19 pandemic and reinforces that pathogens with Veronique Nussenblatt, National Institutes of Health (NIH), the potential to spread rapidly and widely, in spite of concerted global efforts, may affect United States the nervous system. We searched the scientific literature, dating from 1934 to August *Correspondence: 2020, to compile data on the cause, epidemiology, clinical presentation, neuroimaging Farrah J. Mateen features, and treatment of each of the diseases of epidemic or pandemic potential as [email protected] viewed through a neurologist’s lens. We included articles with an abstract or full text Specialty section: in English in this topical and scoping review. Diseases with epidemic and pandemic This article was submitted to potential can be spread directly from human to human, animal to human, via mosquitoes Neuroinfectious Diseases, a section of the journal or other insects, or via environmental contamination. Manifestations include central Frontiers in Neurology neurologic conditions (meningitis, encephalitis, intraparenchymal hemorrhage, seizures), Received: 29 November 2020 peripheral and cranial nerve syndromes (sensory neuropathy, sensorineural hearing loss, Accepted: 25 January 2021 Published: 22 February 2021 ophthalmoplegia), post-infectious syndromes (acute inflammatory polyneuropathy), and Citation: congenital syndromes (fetal microcephaly), among others. Some diseases have not McEntire CRS, Song K-W, McInnis RP, been well-characterized from a neurological standpoint, but all have at least scattered Rhee JY, Young M, Williams E, case reports of neurological features. Some of the diseases have curative treatments Wibecan LL, Nolan N, Nagy AM, Gluckstein J, Mukerji SS and available while in other cases, supportive care remains the only management option. Mateen FJ (2021) Neurologic Regardless of the pathogen, prompt, and aggressive measures to control the spread of Manifestations of the World Health Organization’s List of Pandemic and these agents are the most important factors in lowering the overall morbidity and mortality Epidemic Diseases. they can cause. Front. Neurol. 12:634827. doi: 10.3389/fneur.2021.634827 Keywords: epidemic, pandemic, neuroviral epidemics, clinical neurology, tropical medicine Frontiers in Neurology | www.frontiersin.org 1 February 2021 | Volume 12 | Article 634827 McEntire et al. Neurological Manifestations of Epidemics INTRODUCTION palsy, sensorineural deafness, optic neuritis, and more (4, 5). Approximately 75% of adult and pediatric cases have a pure The World Health Organization (WHO) provides guidance on central nervous system (CNS) phenotype, while ∼13% have a diseases that are international threats to populations with a pure peripheral nervous system (PNS) disorder. Approximately focus on diseases of epidemic and pandemic potential (1). Close 9% have disorders of both the CNS and PNS. observation of these infectious diseases is required to ensure The time course of neurologic signs varies by the syndrome; prevention, foster early detection, mitigate further spread, and encephalopathy often appears concurrently with initial systemic provide supportive care to those affected. To date, of all of the symptoms, occasionally lagging by 1 to 2 days. Spinal disease, millions of pathogens globally, only ∼20 infections are listed with weakness and occasional paresthesias of multiple limbs, can as having epidemic or pandemic potential by the WHO. While appearatsymptomaticonsetorwithadelayofupto3weeks.GBS some may be familiar to the neurologist, others may be only appears weeks after the initial illness, consistent with its usual known to practitioners in tropical settings or locations where few presentation (5). neurologists practice. Here we synthesize the available knowledge The exact proportion of individuals infected with on the neurological manifestations of the WHO’s listed diseases Chikungunya who exhibit neurologic involvement is unclear, of epidemic and pandemic potential by pathogen. but it appears to be the most common “atypical” involvement in severe disease. Case series during epidemics have reported MATERIALS AND METHODS neurologic involvement ranging from 0.1% (5) to 16.3% (6). A neurological disorder was the primary issue in 61% (7) and 79% Searches were performed using the keywords of the disease and (8) of more severely affected patients in intensive care units. infectious organism (if different) as well as the terms “neurology,” Diagnosis of chikungunya is with real-time reverse- “brain,” “nervous system,” and related terms for each of the listed transcription polymerase chain reaction (RT-PCR) or disease of epidemic or pandemic potential on the WHO website enzyme-linked immunosorbent assay (ELISA) of the serum as of April 1, 2020. Search engines included PubMed, Google depending on the timing of testing. Within 5 days of initial Scholar, and the reference lists of articles found through those symptom onset, serum RT-PCR for viral RNA has up to 100% searches. All searches took place in spring 2020 with updates sensitivity and 98% specificity, while ELISA for immunoglobulin continuing as more information became available, particularly on M (IgM) is appropriate for patients who have shown clinical evolving pandemics, such as SARS-CoV-2, influenza, Ebola Virus symptoms for at least 6–8 days (9, 10). Viral RNA has not been disease, and Neisseria meningitidis meningitis until September shown in the CSF of affected individuals, although viral particles 2020. Articles in English or with an abstract in English were have been found in glial cells of infected mice (11). Treatment included, using data sources dating from 1934 until present. of the disease is supportive care, including rest and fluids, as well as acetaminophen or non-steroidal anti-inflammatory drugs Data Availability Statement to alleviate arthralgias. Corticosteroids have been used in some Data sharing is not applicable to this article as no new data were published case reports but with no data for their efficacy (5). GBS created or analyzed in this study. should be treated as per its standard protocols with intravenous immunoglobulins (IVIg) or plasmapheresis. RESULTS Cholera Epidemic and Pandemic Diseases Cholera was classified as a pandemic by the WHO in 2010 in Chikungunya light of the disease causing an estimated 28,800–130,000 deaths Chikungunya virus is a positive-sense alphavirus most often per year and affecting 3–5 million individuals globally (12). The spread by Aedes mosquitos as a direct infection to humans, causative organism Vibrio cholerae is a gram-negative, comma although it can rarely pass through maternal-fetal transmission shaped bacterium most commonly found in seawater and known or blood products. Chikungunya presents with a systemic course to have a number of serogroups. Specifically, serogroups O1 and that is relatively uniform across individuals, but neurologic O139 have been implicated in the majority of intestinal infections manifestations can be more heterogeneous. Its systemic course that are most common worldwide (13). Non-O1 serotypes have begins with an incubation period from 1 to 12 days and long been associated with more invasive disease phenotype and then progresses to fever, malaise, and headache, as well as a extraintestinal involvement (14). characteristic symmetric arthralgia in as many as 90% of patients Infants and neonates make up the majority of cholera cases (2). Chikungunya means “that which bends up” in Kimakonde, with neurologic sequelae, presenting with V. cholerae meningitis, the language of the ethnic group in whom the disease was first abscess, or both. In some cases there appears to have been a identified (3), referring to the stooped posture individuals with specific causative risk factor, as in one case where an individual the disease adopt due to joint pain (Tables 1, 2). had eviscerated fish from a nearby reservoir
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