key: cord-0856790-ew9ghz53 authors: Kuroda, Naoto title: Epilepsy and COVID-19: Associations and important considerations date: 2020-04-22 journal: Epilepsy Behav DOI: 10.1016/j.yebeh.2020.107122 sha: 698643400837c1e66b66c5126b13c9770d21ab7f doc_id: 856790 cord_uid: ew9ghz53 Abstract Coronavirus disease 2019 (COVID-19) outbreak, which initially occurred in Wuhan, China in late 2019, is now rapidly spreading globally. Epilepsy, a disease characterized by a spontaneous recurrence of unprovoked seizures, is a common chronic neurological condition. Associations between epilepsy and COVID-19 have not been reported. Here, we discuss the important considerations for epilepsy patients by reviewing known facts of COVID-19 and suggestions from medical societies associated with epilepsy, as well as inferences from past experiences of infectious diseases. We discuss the risk of COVID-19 for epilepsy patients, the effect of COVID-19 on epilepsy patients, and the importance of maintaining seizure control. We also consider suggestions for epilepsy monitoring units or surgery, what caregivers should know, and the importance of public awareness. The effect of COVID-19 on individuals with epilepsy remains unclear due to the lack of enough evidence. Clinicians and researchers need to share case information, continue investigations, and provide known facts to epilepsy patients and their families. J o u r n a l P r e -p r o o f Coronavirus disease 2019 (COVID-19) is a novel infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the outbreak which initially occurred in Wuhan, China in late 2019, is now rapidly spreading globally [1] . The world is expected to implement early precautionary measures to control the spread of COVID-19 through restriction of activities. Epilepsy, a disease characterized by a spontaneous recurrence of unprovoked seizures, is one of the most common chronic neurological conditions. Its prevalence rate is reported to be 0.7-1.0 % with high incidences in elderly people and children [2] ; additionally, some patients have comorbidities. Associations between epilepsy and COVID- 19 have not been reported. Here, we discuss the important considerations for epilepsy patients by reviewing known facts of COVID- 19 and suggestions from medical societies associated with epilepsy, as well as inferring from past experiences of infectious diseases. The Center for Disease Control and Prevention (CDC) suggests that neurological comorbidities, including epilepsy, may be a risk factor for COVID-19, despite the lack of evidence. Presently, a medical history of epilepsy has not been reported to be a risk factor for developing COVID-19. Moreover, past experiences with infectious diseases do not suggest any associations. Considering the experience with previous infectious diseases, some societies suggest that epilepsy itself seems unlikely to represent a risk J o u r n a l P r e -p r o o f factor for COVID-19. (Table 1 ) However, certain pre-existing conditions (such as smoking, obesity, diabetes, heart disease, lung disease, and cancer) are recognized as risk factors [3, 4] . Therefore, epilepsy patients with these comorbidities may adopt a more cautionary approach regarding COVID-19. Conversely, children infected with COVID-19, including those just with well-controlled epilepsy and no other health conditions, are generally asymptomatic or present with mild symptoms [5] . COVID-19 prevention strategies recommended by the CDC are applicable to all individuals, including those with epilepsy. Baig et al. suggested that the central nervous system could be a potential target of SARS-CoV-2 as the angiotensin-converting enzyme two receptors have been detected on the surface of glial cells and neurons [6, 7] . However, the effects of COVID-19 on epilepsy patients and the prevalence of newonset epilepsy cases remain unclear. Reported symptoms of COVID-19 are primarily associated with respiratory or gastrointestinal issues and have not been commonly related to seizures [8] . According to previous data, the rate of neurological comorbidity has not been assumed to be greater for COVID-19 than other respiratory viral infectious diseases. Conversely, epilepsy patients infected with COVID-19 or any other infectious diseases may have fever, which may possibly trigger seizures. Additionally, the association between anti-epileptic drugs (AEDs) and medications for COVID-19 requires consideration. Currently, no specific medications have been Certain epilepsy medications may affect the immune system, including everolimus and steroids that are used for tuberous sclerosis complex and autoimmune epilepsy, respectively. However, according to some studies, everolimus may prevent viral infections [9] . Meanwhile, the usage of corticosteroids is correlated with the risk of infectious diseases [10] . Hence, medications need to be chosen on an individual basis in clinical settings. Furthermore, some societies do not recommend changing the AEDs of patients with well-controlled seizures, as seizure exacerbations or status epilepticus may increase the risk of COVID-19 infections. It is also important in clinical settings to inform patients that they should not discontinue AEDs without the advice of a physician, even if it would affect to immune systems. Some societies suggest that COVID-19 could increase the risk of sudden unexpected death in epilepsy (SUDEP). There are some reports which indicate that infection or viral J o u r n a l P r e -p r o o f infectious disease might increase the risk of SUDEP [11, 12] . However, there are still no data on the association between COVID-19 and SUDEP. Many societies recommend that patients should avoid running out of AEDs. The state of increased or uncontrollable seizures could cause some problems. One is the effect of seizure on the patient's body condition. Mortality associated with epilepsy is higher in patients with uncontrollable seizures than in those with controllable seizures [13, 14] . Frequent seizures would cause malnutrition and the state of nutrition is associated with the immune system [15] . The second problem is that going to emergency rooms due to increased or uncontrollable seizures could expose the patient to coronavirus. Epilepsy foundation does not recommend going to emergency room unless there is an actual emergency. Finally, uncontrollable seizures, especially status epilepticus, would need sedation and ventilators. However, in clinical settings at regions with many COVID-19 patients, clinicians face the shortage of mechanical ventilators [16] . Increase in the number of patients with status epilepticus would aggravate this problem. Therefore, it is very important to maintain the control of seizures, as well as the prevention of COVID-19. However, visits to doctors and periodic filling of prescriptions account for the greater difficulty encountered by epilepsy patients in avoiding crowded situations. Previous experience with SARS evidently shows that emerging infectious diseases can potentially prevent epilepsy patients from keeping up with their routine appointments [17] . This can be mitigated through the introduction of telemedicine and purchase of prescription medications lasting a minimum of a few J o u r n a l P r e -p r o o f months. Telemedicine allows consultations with doctors without exposure to crowded conditions, and thus prevents the spread of COVID-19 among patients. Hence, introduction and implementation of telemedicine should be given further consideration. Intractable epilepsy may be assessed and diagnosed by video-monitoring encephalograms and hospitalization. Elective surgical treatments for epilepsy, along with other non-urgent surgical procedures, may be postponed to prevent further spread of COVID-19 among medical staff and patients [18] . Hospitals should rather prepare for the increasing number of COVID-19 patients who will require critical care. Epilepsy patients who require urgent interventions, along with their families and medical staff, should adhere to thorough prevention and protection protocols against COVID-19. Some patients do not have emergency but progressive conditions of epilepsy. As for these cases, the real risk of proceeding and the real risk of delay on intervention should be considered case by case. Epilepsy patients may be dependent on caregivers. Epilepsy patients suspected to be infected with COVID-19 should be isolated; the caregiver should seek treatment, especially through oral care or aspirations, for prevention and protection against J o u r n a l P r e -p r o o f COVID-19. Protection against COVID-19 also necessitates the treatment of COVID-19 carriers. Caregivers infected or suspected to be infected with COVID-19 should stop providing care to their patients and isolate themselves. They may also find replacements for their clients for the time being. As for epilepsy patients who live alone, it is suggested to keep regular contact with someone to inform that they are alright while self-isolating, especially patients with uncontrolled seizures. It is important to provide this information to epilepsy patients and their families so that they may be prevented from being infected with COVID-19. Additionally, the spread of correct information will reduce unnecessary anxiety and stress. According to Hu M. et al., educating epilepsy patients would reduce seizure frequency and accidental injuries caused by seizures [19] . Conversely, internet and social media can be a source of informal, uncertain, or misleading information that may cause people to respond erroneously or panic unnecessarily. A system for disseminating reliable resources of information needs to be established. A few medical associations and societies have provided useful information regarding epilepsy and COVID-19 ( Table 1 ) that may be shared. Translations and subsequent dissemination of these resources can also aid epilepsy patients globally. Moreover, the American epilepsy society have also provided information and attention points for clinicians. This article reviewed known facts of COVID-19 associated with epilepsy and the suggestions from medical societies. The effect of COVID-19 on individuals with epilepsy remains unclear. Clinicians need to share case information, continue investigations, and provide known facts to epilepsy patients and their families. This work did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. 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