key: cord-0919801-ikkm1rv1 authors: Saeed, Amir; Shorafa, Eslam title: Status epilepticus as a first presentation of COVID-19 infection in a 3 years old boy; Case report and review the literature date: 2020-09-03 journal: IDCases DOI: 10.1016/j.idcr.2020.e00942 sha: d83032014910211e729232615f7519484d7787f8 doc_id: 919801 cord_uid: ikkm1rv1 It was December 2019 that china reported series of patients with respiratory symptoms, a disease that later named COVID-19; and from there spread to other countries around the world; and in February 2020, the world health organization declared COVID-19 as a pandemic. From the beginning, it was assumed that COVID-19 occurrence in pediatric patients is less and has less severity but nowadays; there are a reports that shows severe cases with multiple organ involvement. The most manifestation symptom is fever but convulsion is rare as the first manifestation symptom. Here we describe a 3 years old; previously healthy boy that presented with repeated fever induced seizure and status epilepticus and positive RT-PCR for COVID-19 that in the first day; brain CT scan revealed brain edema and 5 days later, there was intracerebral hemorrhage in brain MRI. It was December 2019 that in Wuhan, China series of patients presented with respiratory symptoms (1) , a disease that its cause, the novel coronavirus (SARS-COV-2), was identified in samples of bronchoalveolar lavage fluid from a patient in Wuhan and named COVID-19 and from China rapidly spread to other countries all around the world so that in February 2020 the world health organization declared it as a pandemic. (2, 3, 4) The rate of infection with covid-19 in children is low and the first pediatric case reported on January 20, 2020 was a 10 years old boy in Wuhan (4) and in the early phase of pandemic; those whom infected had relatively milder clinical symptoms compared with infected adults (5) ; but as the time passed and the number of infected pediatric patients increased, there were several reports of multiple organ involvement in pediatric COVID-19 patients and according to the last reports (6, 7, 8, 9) ;WHO developed a new definition :" multisystem inflammatory syndrome in children with COVID-19 (MIS-C)" (10) . MIS-C definition criteria are: Children and adolescents 0-19 years of age with fever > 3 days, and two of the following: a) Rash or bilateral non-purulent conjunctivitis or muco-cutaneous inflammation signs (oral, hands or feet). b) Hypotension or shock. And; elevated markers of inflammation such as ESR, C-reactive protein, or procalcitonin. And; No other obvious microbial cause of inflammation, including bacterial sepsis, staphylococcal or streptococcal shock syndromes. And; evidence of COVID-19 (RT-PCR, antigen test or serology positive), or likely contact with patients with COVID-19 (10) . In this case report; we describe a 3 years old with MIS-C that his first presentation was: repeated seizures induced by fever (status epilepticus). A 3 years old boy that was previously healthy, taken to emergency room (ER)of Namazi Hospital due to abnormal movement;(Namazi Hospital ;the largest hospital in south of Iran with 750 beds is located in Shiraz city that is the main tertiary referral center in south of Iran which has 18 bed general pediatric intensive care unit (PICU) and 9 bed surgery PICU).He was well up to 12 hours prior to admission that presented with high grade fever (39.5 °C) so visited by a pediatrician that found no abnormal sign and just acetaminophen was prescribed for fever relief, but fever didn't subside. He presented with oral foamy discharge and jerky movement of hands and feet about 30 minutes before admission in the hospital (he had history of contact in a ceremony, a day before, but no one that were there, had fever nor contact to suspected patients). On arrival to ER, his initial vital signs were: Glasgow coma score(GCS) :10/15 Heart rate(HR):160, respiratory rate(RR):45, blood pressure:110/78. In ER; the patient had two episodes of tonic colonic convulsions that lasted one minute with about 5 minutes interval that stopped with parenteral midazolam and due to repeated convulsions so phenobarbital started and transferred to PICU. In PICU, his GCS was 10/15 and had another tonic-clonic seizure so phenobarbital (5 mg/kg) in addition to levetiracetam 30 mg/kg was given; but convulsions didn't stop so intubated and phenobarbital 1mg/kg/hour and midazolam 1 mg/kg/hour intravenous infusion started and neuroprotection strategies were employed for him. In his initial laboratory data (listed in Table 1 ), WBC:6800 with 70% neutrophil and 23% lymphocyte, CRP: 105 were detected. Meropenem, vancomycin and acyclovir started for him and also reverse transcriptase-polymerase chain-reaction (RT-PCR) assay for COVID-19 with nasopharyngeal swan taken. In a brain CT scan in day 1; it showed a severe brain edema ( Figure 1 ) and chest CT scan was suspicious to COVID-19( Figure 2) . A 24 hours later; lumbar puncture (LP) was done that revealed: no cell, protein: 14 and sugar was 125 and cerebrospinal fluid (CSF) pressure was 33 centimeter of water(cmH2O). The patient also fulfilled the criteria of "multi-system inflammatory syndrome associated with COVID-19(his initial RT-PCR was negative but the other one that sent 3 days later was positive). In day two, the patient became hypotensive so inotrope started but echocardiography was normal. In the following 2 days, inotrope increased to maintain normal mean arterial pressure and still the J o u r n a l P r e -p r o o f patient was febrile so intravenous globulin (IVIG) was given. (hydrocortisone, ascorbic acid and thiamine(HAT) had been started before) After IVIG infusion; we could decrease inotrope but still he had intermittent fever so brain MRI was done that revealed intracerebral hemorrhage in the right occipital lobe (Figure 3 ). In the 8 th day, the patient extubated from ventilator and tolerated; his GCS was 15/15 with normal neurologic exam. On the 14 th day, the patient discharged home with good condition. In the beginning; the rate of infected pediatric patients were less so it was believed that they are less susceptible and the most common symptoms in severe pediatric patients were; tachypnea, fever, cough, nausea/vomiting and diarrhea ,fatigue/myalgia and headache(11); but as the disease spread to other countries, there were reports that the first presentation were liver failure (9) In SARS, the first cases with neurological manifestations presented with seizure (13, 14) . In MERS, the most neurological presentations were seizure and encephalopathy (15) but intracerebral hemorrhage also have been reported (16) . In a retrospective study that Mao L et al. did in China; it showed: Patients with more severe infection had neurologic manifestations, such as acute cerebrovascular diseases (5.7%), impaired consciousness (14.8%), and skeletal muscle injury (19.3%) but in their study mean age was 52.7 years (17). Coronaviruses has capability the neuroinvasion (12) and the presence of ACE2 receptors in the nervous system and in skeletal muscle are the suggesting a mechanism for SARS-CoV-2-related neuromuscular injury (25, 26) . In kawasaki disease ;altered mental status, seizures, and hemiplegia had been reported that was thought to be due to vasculitis (27) Apart from ACE2, COVID-19-associated nervous system damage may also be caused by septic shock, hypoxic injury, fever (in children), metabolic derangements and immune responses. In our patient; RT-PCR of CSF was negative so one possibility of the repeated convulsions was autoimmune reaction and another was fever although direct invasion of virus cannot be excluded even with negative PCR but ICH that had been reported before (22) , that could be co-incidence and related to his old age, but in our patient might be due to direct invasion of CNS by COVID- The above data indicate that SARS-CoV-2 may infect the nervous system and skeletal muscle as well as the respiratory tract especially in severe cases that have MIS-C; thus, clinicians should consider COVID-19 as a differential diagnosis for patients with neurological manifestations. In pediatric cases, it is important to emphasize that COVID19 could be another risk factor for febrile seizures (taking into account that other types of coronaviruses could also be involved) although it is known that influenza virus and enterovirus are the most frequently associated to this condition (28, 29) . And even in the absence or respiratory symptoms, occurrence of neurologic symptoms might be the first presentation of COVID-19 and MIS-C and should be assessed for, especially in the critically ill pediatric patients. Funding/Support: The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors This study was approved by the ethics committee of Shiraz University of Medical sciences. Written informed consent was obtained from the parents and sent to the ethics committee. Dr.Saeed planned the study and wrote the manuscript. Dr.Shorafa gathered patients' data and submitted the manuscript. Drs Saeed and Shorafa edited the manuscript. Both authors discussed the results and contributed to the final manuscript. Outbreak of pneumonia of unknown etiology in Wuhan China: the mystery and the miracle China Novel Coronavirus Investigating and Research Team. 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