key: cord-1011881-np13h8ja authors: Asadi-Pooya, Ali A.; Farjoud Kouhanjani, Mohsen; Nemati, Hamid; Emami, Amir; Javanmardi, Fatemeh title: A follow-up study of patients with COVID-19 presenting with seizures date: 2021-07-02 journal: Epilepsy Behav DOI: 10.1016/j.yebeh.2021.108207 sha: 5147f1e36b810b288953c90a98f0031e1f6fbb4a doc_id: 1011881 cord_uid: np13h8ja Objective We performed a follow-up study of patients with COVID-19 presenting with seizures. Methods All consecutive patients with seizures, who were referred to Namazee Hospital, Shiraz, Iran, with a diagnosis of COVID-19, from 10 August 2020 until 20 October 2020 were included in this longitudinal study. The clinical data were collected by the admitting physician. In a follow-up phone call to the discharged patients (after eight weeks or more), we inquired their seizure outcome. Results In total, 32 patients were studied; 28 patients were followed. Twelve patients (37.5%) presented with a single tonic-clonic seizure and nine (28.1%) had convulsive status epilepticus; one patient had functional (psychogenic) seizures. Ten patients (31.3%) had pre-existing epilepsy, eight others (25%) had pre-existing CNS problems (without epilepsy), one person (3.1%) had pre-existing functional seizures, and 13 individuals (40.1%) neither had epilepsy nor had other CNS problems. Eight patients (28.6%) reported experiencing seizure(s) after being discharged from the hospital; six of these had pre-existing epilepsy and one had pre-existing functional seizures. One patient, who had a newly developed ischemic brain infarction, reported experiencing recurrent seizures. Conclusion Seizures in patients with COVID-19 are either acute symptomatic (in about two-thirds) or an exacerbation of a pre-existing epilepsy/functional seizures (in about one-third). A thorough investigation of the underlying etiology of seizures in patients with COVID-19 is necessary. Seizure outcome in patients, who are hospitalized with COVID-19 and seizures, is generally good. Objective : We performed a follow-up study of patients with COVID-19 presenting with seizures. Methods: All consecutive patients with seizures, who were referred to Namazee Hospital, Shiraz, Iran, with a diagnosis of COVID-19, from 10 August 2020 until 20 October 2020 were included in this longitudinal study. The clinical data were collected by the admitting physician. In a follow-up phone call to the discharged patients (after eight weeks or more), we inquired their seizure outcome. In total, 32 patients were studied; 28 patients were followed. Twelve patients (37.5%) presented with a single tonic-clonic seizure and nine (28.1%) had convulsive status epilepticus; one patient had functional (psychogenic) seizures. Ten patients (31.3%) had preexisting epilepsy, eight others (25%) had pre-existing CNS problems (without epilepsy), one person (3.1%) had pre-existing functional seizures, and 13 individuals (40.1%) neither had epilepsy nor had other CNS problems. Eight patients (28.6%) reported experiencing seizure(s) after being discharged from the hospital; six of these had pre-existing epilepsy and one had pre-existing functional seizures. One patient, who had a newly developed ischemic brain infarction, reported experiencing recurrent seizures. Previous case series have provided evidence that seizure is rarely a presenting manifestation of COVID-19; it happens in less than 1% of these patients 1 . However, considering the high number of patients with COVID-19 worldwide, this may translate to thousands of patients with COVID-19 and seizures globally. Furthermore, seizure is an important and serious manifestation that may complicate the course of illness in any critically ill patient. In severely ill patients, isolated seizures may quickly escalate to generalized convulsive status epilepticus or non-convulsive status epilepticus (NCSE) which are associated with a high morbidity and mortality 2 . In such circumstances, a comprehensive investigation of the etiology of the seizure should be performed immediately 3 . The etiology of seizure(s) in many previously reported COVID-19 patients was most likely multifactorial, as many of them had multi-organ failure, metabolic derangements, hypoxemia, fever, etc 4 . However, some of the patients had specific neurological problems (e.g., encephalitis or cerebrovascular events) [5] [6] [7] [8] [9] [10] . New-onset seizures in patients with COVID-19 have often been considered as acute symptomatic seizures 3, 4 . Patients with acute symptomatic seizures do not need long-term anti-seizure medication (ASM) therapy after the period of their acute illness (i.e., about six weeks in COVID-19 patients), unless a subsequent seizure occurs 11 . However, no study has ever followed these patients to determine their seizure outcome and whether these patients experience any further unprovoked recurrent seizures after the period of their acute illness. The aim of the current study was to investigate the seizure outcome in patients who were hospitalized with COVID-19 and seizures. We also investigated the etiology of seizures (as a presenting manifestation) in patients with COVID-19. These two objectives (i.e., clarifying the etiology and more importantly the seizure outcome) may add to the existing literature on this important issue. In this study, all consecutive patients with seizures, who were referred to and admitted at For any patient, who was admitted with a diagnosis of COVID-19, the following data were collected at the emergency room by the admitting physician: age, sex, and presence of fever. Other collected data were included after reviewing the patients' medical records: In a follow-up phone call interview to the discharged patients (after eight weeks or more), we inquired their seizure outcome (whether they have experienced unprovoked recurrent seizures), drug history, and any other enduring problems. Values were presented as mean ± standard deviation (SD) for continuous variables and as number (percent) of subjects for categorical variables. This is a descriptive study. Shiraz University of Medical Sciences Review Board approved this study as a minimal-risk research using the data that were collected for routine clinical practice and waived the requirement for written informed consent; however, patients orally consented to be interviewed during the phone call (approval number: 22383). The data are confidential and will not be shared as per the regulations of Shiraz University of Medical Sciences. During the study period, 32 patients [20 (62.5%) women and 12 (37.5%) men] were hospitalized with seizure(s) and a diagnosis of COVID-19. The mean age (± standard deviation) of the patients was 22.8 (± 20.4) years (range: one month to 65 years; median: 14.5 years; interquartile range: 33 years). In total, three patients died at the hospital (case fatality rate = 9.4%); these were not included in the follow-up phase of the study. One other patient did not answer the phone calls and was not included in the follow-up phase of the study. Table 1 shows all the details of the studied patients. Among 13 patients without any pre-existing CNS problems the presenting seizures were as follows: tonic-clonic (4), tonic (3), febrile seizure (3), status epilepticus (2), focal clonic (1). All patients had available data on their body temperature (at admission), arterial blood oxygen saturation, and routine laboratory test results (i.e., blood sugar and electrolytes). Twenty-eight patients had available brain imaging and five patients had CSF analyses data. Eleven patients (34.4%) had exacerbation of their pre-existing seizures; among these, seven patients had fever and six had hypoxemia. Among eight patients with pre-existing CNS problems (without epilepsy) (3 with tumors, 2 with old CVA, one with old ischemic (vascular) changes, one with hypoxic brain damage at birth, and one with cerebral palsy and normal brain imaging), five had fever and six had hypoxemia. Electroencephalography was available in 23 patients. Twelve patients had either status epilepticus (N = 9) or clusters of seizures (N = 3); two of these died and three reported recurrent seizures after being discharged. Twenty patients had isolated seizures; one of them died (p = 0.540) and five others reported recurrent seizures after being discharged (p = 0.852). Twenty-eight patients were interviewed after being discharged from the hospital. The mean duration of their follow-up was 87 (± 23) days In the current study, we observed that seizures (as a presenting manifestation) in patients with there is no need for long-term ASM therapy in patients with COVID-19 and seizure, after the period of the acute illness, unless a subsequent seizure happens. Since the period from the onset of COVID-19 symptoms to death may range from 6 days to 6 weeks, it is reasonable to continue the ASM for about 6 weeks and then tapper and discontinue the drug rapidly in 1-2 weeks 3 . In spite of this, we observed that many patients continued to take their ASM(s) for longer times. It is necessary to educate the treating healthcare professionals to limit the use of unnecessary ASMs and to avoid their many adverse effects. In rare instances, seizures in patients with COVID-19 could be attributed to specific CNS pathologies; one of our patients had encephalitis and three others had cerebrovascular events. Neurotropic and neuro-invasive capabilities of coronaviruses have been described before. Severe acute respiratory syndrome (SARS)-coronavirus-2 (SARS-CoV2) RNA was detected in the CSF in a few patients before 6,10 ; however, many other studies that tested for this had negative results 4 . Furthermore, a recent systematic review revealed a pooled incidence of 1.7% for ischemic CVA in the setting of COVID-19 infection 15 . Another systematic review concluded that cerebral venous thrombosis in the context of COVID-19 is rare, but there seems to be an increased relative risk of the condition 16 . In any patient with COVID-19 and seizures it is necessary to request a brain imaging study, as soon as possible, to detect any potentially life-threatening condition such as CVT. It is also desirable to have CSF analyses of patients with COVID-19 and seizures; however, how a diagnosis of encephalitis might change the disease course and also the management plan in these patients should be investigated and clarified in future studies. In a recent study, we observed that patients with epilepsy were not susceptible to contracting COVID-19 more than that in other individuals. Furthermore, COVID-19 in patients with epilepsy was not associated with a poorer prognosis 17 . In the current study, the seizure outcome in patients, who were hospitalized with COVID-19 and seizures, were generally good. Only rarely the presenting seizure may herald the development of epilepsy in the future (in one patient with CVA in the current study). However, patients with epilepsy, who contract COVID-19, may experience an exacerbation of their seizures for a variety of reasons (e.g., fever, hypoxemia, etc.). It may be necessary to order a Real-Time polymerase chain reaction testing of nasopharyngeal and oropharyngeal samples for COVID-19 in any patient who comes to the emergency department with pre-existing epilepsy and seizure exacerbation during this pandemic. This was a single center study with a small sample size. We acknowledge that subtle, nonconvulsive seizures, in patients presenting with alteration of mental status, may have been missed without EEG monitoring. Another limitation was the nature of the follow-up (selfreported outcome); some patients might have missed minor seizures or even severe unwitnessed seizures. Finally, the length of the follow-up was short.  Seizures in patients with COVID-19 are often acute symptomatic (in about twothirds).  Seizures may be exacerbation of a pre-existing epilepsy/functional seizures (in about one-third).  A complete investigation of the underlying etiology of seizures is necessary.  Seizure outcome is generally good. Seizure is a rare presenting manifestation of COVID-19 Seizures in the critically ill Seizures Associated With Coronavirus Infections COVID-19, de novo seizures, and epilepsy: a systematic review Seizure with CSF lymphocytosis as a presenting feature of COVID-19 in an otherwise healthy young man A first case of meningitis/encephalitis associated with SARS-Coronavirus-2 Cerebral venous thrombosis: A typical presentation of COVID-19 in the young Focal EEG changes indicating critical illness associated cerebral microbleeds in a Covid-19 patient Extensive cerebral venous sinus thrombosis: a potential complication in a patient with COVID-19 disease Encephalopathy and seizure activity in a COVID-19 well controlled HIV patient Management of a First Seizure Outcomes of seizures, status epilepticus, and EEG findings in critically ill patient with COVID-19 Seizure in patients with COVID-19 The Incidence and Mortality Ratio of Ischemic Cerebrovascular Accidents in COVID-19 Cases: A Systematic Review and Meta-Analysis Cerebral venous thrombosis and severe acute respiratory syndrome coronavirus-2 infection: A systematic review and meta-analysis COVID-19 presentations and outcome in patients with epilepsy Acknowledgments: Shiraz University of Medical Sciences supported this study.