Analysis of risk factors for seizures and short-term reoccurrence of seizures in febrile children with SARS-CoV-2 infection: an observational study

doi:10.21203/rs.3.rs-3009867/v1

Background:With the epidemic of the Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) variant Omicron, its accompanying neurological manifestations have gradually attracted attention.The main objective of this study was to compare seizures in febrile children with and without coronavirus disease 2019(COVID-19) and to conduct a short-term follow-up in the COVID-19 positive group to investigate the risk factors for short-term recurrence of seizures in children with febrile seizures(FS).

Methods: Retrospective analysis of patients admitted to the Children's Hospital of Chongqing Medical University for fever and seizures between October 1 and December 30, 2022.Based on the results of SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR), the patients were divided into a COVID-19 positive group and a COVID-19 negative group.Moreover,we followed up patients in the COVID-19-positive group for 3 months using outpatient or telephone follow-up, and the main content of follow-up included whether the patients had seizures after discharge and whether there were neurological abnormalities.

Results:Compared with the COVID-19-negative group, the COVID-19-positive group had a higher proportion of seizure duration ≥ 15 minutes(18.7%VS5.1%;P=0.001), seizure ≥ 2 time(54.4%VS41.0%;P=0.024), status epilepticus(15.4%VS5.1%;P=0.005), and Electroencephalogram (EEG) abnormalities(29.4%VS13.6%;P=0.016).Seizures ≥2 time[P=0.015,OR(95% CI)=4.632(1.347-15.928)], peak temperature ≤39°C[P=0.001,OR(95% CI)=6.296(2.059-19.254)], and history of convulsions[P=0.005,OR(95% CI)=5.628(1.707-18.550)] were risk factors for recurrence of seizures within a short period of time in children with covid-19 infected febrile convulsions.In the COVID-19 positive group, three patients died and four patients had residual cognitive or motor dysfunction.

Conclusions:The seizures were more severe in the COVID-19 positive group compared to the COVID-19 negative group.In addition, patients with COVID-19 who present with seizures and persistent impaired consciousness need to be alerted to serious neurological disorders such as acute necrotizing encephalopathy.

COVID-19

Seizures

Follow-up

Acute necrotizing encephalopathies

In the early stages of the COVID-19 epidemic, most SARS-CoV-2 infected children presented with fever and cough as the main manifestations and rarely had seizures[1]. With the gradual mutation of SARS-CoV-2, the Omicron variant dominates worldwide[2]. Recent studies have found an increase in the frequency of seizures in children during the Omicron epidemic [3–4]. In addition, a recent study reported severe neurological disease in several SARS-CoV-2 infected children with fever and seizures as the main clinical manifestations[5].However, the current studies on COVID-19 and seizures are few and mostly in febrile convulsions.Therefore, this study will not be limited to febrile seizures(FS), but will include patients who present with fever and seizures.This study will summarize the clinical features and severity of seizures in febrile children with SARS-CoV-2 infection, analysis of risk factors for recurrent seizures within a short period of time in children with SARS-CoV-2 infected febrile convulsions, and provide a detailed description of children with secondary severe neurological disease.

Study population and definition

This retrospective study was conducted at the Children's Hospital of Chongqing Medical University, one of the national pediatric medical centers in China. Inclusion criteria were patients hospitalized for fever and seizures from October 1, 2022, to December 30, 2022. Patients with a previous diagnosis of epilepsy were excluded because of the many factors that influence the presence of seizures in patients with epilepsy, in addition to the exclusion of patients with incomplete medical history taking.We reviewed the risk factors for recurrence of febrile convulsions when studying the risk factors for recurrence of seizures in the short term.Based on previous studies, risk factors for Febrile seizures recurrence in a distant febrile period included;age; family history; history of febrile convulsions; seizures ≥ 2 time;seizure duration≥ 15min;and peak fever temperature[6].Febrile status epilepticus is defined as any prolonged seizure or recurrent seizure lasting for more than 30 minutes without return to full consciousness[7].The diagnosis of febrile convulsions is made according to the International League Against Epilepsy (ILAE) criteria.

Data collection

We collected the following information for patients: age, gender,number of seizures, duration of longest seizure, seizure types, accompanying symptoms, maximum temperature during the course of illness, neurological exam results, convulsion history, family convulsion history, blood tests, cerebrospinal fluid (CSF) test results, EEG results, and head CT(Computed Tomography) or MRI(Magnetic Resonance Imaging)imaging data.In addition, We followed up patients in the COVID-19 positive group for 3 months using telephone follow-up to collect data on whether patients had recurrence. Any differences in the data collection process were resolved through discussion.

Statistical analysis

The Statistical Package for Social Sciences version 26.0 for Windows (SPSS Inc., Chicago, IL, USA) was used.Continuous variables are described as median and quartile intervals or mean and standard deviations, and categorical variables are described by numbers and percentages. Results were compared between groups using a chi-square or Fisher exact test for categorical variables and an independent-sample T-test or Mann-Whitney U-test for continuous variables.p-value < 0.05 was considered statistically significant.Categorical variables with a p-value < 0.05 on univariate analyses were entered into multivariate logistic regression.

Patient cohort

A total of 299 patients were included in this study.Among them, 182 were in the COVID-19 positive group and 117 were in the COVID-19 negative group.Because 3 patients in the COVID-19 positive group died and 18 patients could not be contacted, our final follow-up number was 161(Figure 1).

Comparison of data between COVID-19 positive and COVID-19 negative groups.

Based on the results of SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) , the patients were divided into a COVID-19 positive group(n=182) and a COVID-19 negative group(n=117).Table 1 shows the differences between the two groups.Our findings showed a higher proportion of seizure duration ≥15 minutes, seizure ≥ 2 time, status epilepticus and EEG abnormalities in the COVID-19 positive group compared with the COVID-19 negative group.

Data related to COVID-19 positive group

Of the 182 patients infected with fever and seizures associated with COVID-19, 7 had a poor prognosis, including 3 patients who died (Table 2), 4 patients with residual partial cognitive or motor impairment. Notably all 7 patients presented with impaired consciousness lasting several hours, and three of them were diagnosed with a rare acute necrotizing encephalopathy (Table 3).

Neuroimaging (head CT or MRI) was performed in 60/182 (32.9%) patients, of whom 10 had significant abnormalities on MRI or CT.Out of 182 patients, 32 (17.6%) underwent routine cerebrospinal fluid analysis through a lumbar puncture. The analysis included appearance, pressure, protein, glucose, chloride ion, cell count, and cell classification. Of these, 28 patients had normal cerebrospinal fluid results, 2 patients had elevated glucose levels in the cerebrospinal fluid, 1 patient had elevated protein in the cerebrospinal fluid, and 1 patient had elevated leukocytes and protein in the cerebrospinal fluid.

Follow-up results

We followed a total of 161 patients for 3 months, of whom 2 developed intermittent dizziness and headache, 4 had residual partial motor or cognitive impairment, and 20 of 141 patients diagnosed with febrile convulsions had a recurrence of seizures.We compared hospitalization data for febrile convulsions patients with and without seizures during the follow-up period and showed statistically significant differences between the two groups in terms of peak temperature (≤39°C), seizure ≥ 2 time, and history of convulsions(Table4).Multivariate logistic regression results showed that peak temperature ≤39°C, history of convulsions, and seizures ≥2 time were risk factors for reoccurrence of seizures within a short period of time(Figure 2).

COVID-19, like previous coronaviruses, has the ability to enter the nervous system and cause neurological symptoms. The virus may enter the central nervous system through the olfactory pathway and angiotensin receptor-2[8], leading to astrocytosis and microglial activation. This, in turn, triggers the release of pro-inflammatory cytokines (TNF-α, IL-6, IL-1B), which play a key role in the seizure mechanism.However, pro-inflammatory factors in the central nervous system are not derived solely from astrocytes. When the blood-brain barrier is damaged or underdeveloped, it becomes another route for pro-inflammatory factors to enter the brain. This may also explain the fact that seizures occur even in the absence of infection of the central system. Secondly, high fever after new crown infection is also a cause of seizures. Studies have shown that hyperthermia not only has a negative effect on neurons, but also induces the release of inflammatory mediators and increases the permeability of the blood-brain barrier [9–11]. In our study, the peak fever of 39.5 ± 0.7°C in the COVID-19-positive group was higher than the average peak fever of 38.9 ± 0.6°C in Omicron-infected children [12], which supports that hyperthermia after COVID-19 infection is a cause of convulsive episodes.

Another possible cause of seizures in COVID-19 patients is direct damage to the central nervous system by the virus. However, a recent systematic review of cerebrospinal fluid testing in seizure patients with COVID-19 found little evidence to support this theory, as the virus was detected in only a small percentage of patients [13]. In our study, 32 (17.6%) patients in the COVID-19 positive group completed routine cerebrospinal fluid (CSF) examination.Only four of these patients had abnormal cerebrospinal fluid.Such results do not support seizures caused by viral encephalitis.However, since we have not performed COVID-19 PCR tests on cerebrospinal fluid, it cannot be ruled out that COVID-19 invades the brain and causes seizures. Therefore, in the future, it is crucial to conduct a more comprehensive neurological evaluation and test for COVID-19 in cerebrospinal fluid for patients suspected of having central nervous system invasion by the COVID-19, instead of relying solely on routine CSF tests.

Although cerebrospinal fluid examination does not support seizures due to direct invasion of the central nervous system by COVID-19, we must emphasize the possibility of severe neurological disorders secondary to COVID-19 infection. In the present study 9 patients with COVID-19 infection developed severe neurological manifestations in the form of impaired consciousness lasting several hours and recurrent seizures or persistent status epilepticus.Of these 3 died, 2 of them in just 2 days from fever to death.Due to the seriousness of these 2 patients, lumbar puncture cerebrospinal fluid examination and neurological MRI auxiliary examination could not be completed, and the family refused to authorize an autopsy. As a result, the final etiology could not be determined at this time. Although it remains unclear whether COVID-19 directly caused these deaths, these cases should be highlighted to draw the attention of physicians and researchers, in order to suggest more effective treatment measures.

In addition, 2 patients were definitively diagnosed with acute necrotizing encephalopathy (ANE), a rare and severe encephalopathy usually triggered by a viral infection.The clinical presentation, imaging, and laboratory findings of these 2 patients met the diagnostic criteria for ANE, namely seizures, impaired consciousness, and imaging manifestations of symmetrical thalamic and multisite lesions.It is worth discussing the other patient in this study. This patient presented with seizures and impaired consciousness, and MRI of the head suggested abnormal signal shadows in the bilateral thalamus, internal capsule, and cerebral hemispheres; such clinical presentation and imaging findings led the physician to consider necrotizing encephalopathy, but cerebrospinal fluid examination in this patient suggested slightly elevated white blood cells, which was inconsistent with the previous diagnostic criteria for ANE.However, a recent study reported a case of COVID-19 infection with typical clinical and imaging manifestations of ANE, but the patient's cerebrospinal fluid examination suggested leukocytosis, and the patient was finally diagnosed with ANE anyway after pathological examination of the thalamus and metagenomic next-generation sequencing (mNGS) of the cerebrospinal fluid[14].The prognosis of all three patients considered for ANE in this study was poor, with one patient dying, one patient left with motor dysfunction, and one patient whose guardian ultimately chose to abandon treatment due to little hope of cure. Therefore, in patients who develop seizures after COVID-19 infection, physicians need to be alert to the possibility of secondary necrotizing encephalopathy in the children, especially those who develop persistent impairment of consciousness.

Our study showed that COVID-19 variant Omicron infection was accompanied by more severe seizures, as evidenced by a higher proportion of seizure duration ≥ 15 minutes, seizure ≥ 2 time, persistent status epilepticus, similar to the results of a related study [4].Previous studies have shown that fevers may trigger febrile seizures via the inflammatory pathway, but different pathogens do not cause the same inflammatory mediators, combined with studies suggesting that inflammatory mediators may be associated with status epilepticus [15]. Therefore, we hypothesize that this more severe seizure may be closely related to the inflammatory response after COVID-19 infection, which of course needs to be confirmed by more relevant studies.In addition,our findings showed that peak temperature (≤ 39°C), seizure ≥ 2 time, and history of convulsions were risk factors for recurrent seizures in the short term. Such results suggest that the risk factors for reoccurrence of seizures in febrile convulsions associated with COVID-19 infection are not significantly altered.Based on these characteristics, it is necessary for medical personnel to actively inform patients' family members of the risk of recurrent seizures, provide education on emergency seizure management, and conduct regular follow-up visits for this patient population in order to ensure patients' safety and well-being.

There were several limitations in our study. First, this is a single-center study, but given that our hospital is the largest children's hospital in southwest China, our patients are somewhat regionally representative.Secondly, to ensure the reliability and integrity of our data, we only included inpatients and excluded outpatients.Lastly, due to various factors, some patients have not completed relevant examinations, resulting in possible deviations in the results, but the clinical data on seizures are perfect.

Although a higher proportion of the COVID-19 positive group experienced seizure duration ≥ 15 minutes, seizure ≥ 2 time, status epilepticus, the vast majority of patients have a good prognosis.However, in patients with persistent impairment of consciousness after COVID-19 infection, the prognosis may be poor and requires vigilance for secondary serious neurological disease.Additionally,education of guardians about epilepsy management is critical because some patients may have recurrences within a short period of time, especially those with multiple seizures and a prior history of convulsions.

SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2

COVID-19

Coronavirus disease 2019

FS

Febrile seizures

RT-PCR

reverse transcription-polymerase chain reaction

EEG

Electroencephalogram

CSF

cerebrospinal fluid

CT

Computed Tomography

MRI

Magnetic Resonance Imaging

WBC

White blood cell count

HB

Hemoglobin

PLT

Blood platelets

CRP

C-reactive protein.

NS

Not significant in terms of statistics

ANE

Acute necrotizing encephalopathies

PCT

Procalcitonin

PRO

Protein

EBV

Epstein-Barr virus

HSV

Herpes simplex virus

CMV

Cytomegalovirus

mNGS

metagenomic next-generation sequencing;

ALT

Alanine aminotransferase

AST

Aspartate aminotransferase

SF

Serum ferritin

IL-6

Interleukin-6

Data Availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Acknowledgments

None

Funding

None.

Author information

Authors and Affiliations

Jipeng Jiang^{1 2 3},Zhengsong Shen¹,Jie Cao(Corresponding author)^{1 2 3}

1.Department of General Medicine Childrens Hospital of Chongqing Medical University,Nation Clinical Research Center for Child Health and Disorders,Ministry of Education Key Labiratory of Child Development and Disorders,Chongqing,China.No.136 Zhongshan 2nd Road, Yuzhong District, Chongqing, China.

2.China International Science and Technology Cooperation base of Child development and Critical Disorders,Chongqing, China.No.136 Zhongshan 2nd Road, Yuzhong District, Chongqing, China.

3.Chongqing Key Laboratory of Pediatrics,Chongqing, China.No.136 Zhongshan 2nd Road, Yuzhong District, Chongqing, China.

Authors' contributions

Conception and design: JpJ, JC,ZsS;Provision of study materials or patients: JpJ;Collection and assembly of data:ZsS,JpJ; Data analysis and interpretation:JpJ,JC,ZsS; Manuscript writing: All authors; All authors approved the final manuscript.

Corresponding author

Corresponding author：Jie Cao,[email protected],Children's Hospital of Chongqing Medical University,Chongqing, China.

Ethics approval and consent to participate

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).This study was approved by the Medical Ethics Committee of the Children's Hospital of Chongqing Medical University(NO.2023-73).Informed consent forms were obtained from the parents of the patients.

Consent for publication

Not applicable.

Competing Interest

The authors declare that they have no competing interests.

Dong Y, Mo X, Hu Y, et al. Epidemiology of COVID-19 Among Children in China[J]. Pediatrics, 2020,145(6). doi:10.1542/peds.2020-0702.
Tian D, Sun Y, Xu H, et al. The emergence and epidemic characteristics of the highly mutated SARS-CoV-2 Omicron variant[J]. J Med Virol, 2022,94(6):2376-2383. doi:10.1002/jmv.27643.
Pascarella A, Maglione M, Lenta S, et al. Seizures in Children with SARS-CoV-2 Infection: Epidemiological, Clinical and Neurophysiological Characterization[J]. Children (Basel), 2022,9(12). doi:10.3390/children9121923.
Joung J, Yang H, Choi YJ, et al. The Impact of Omicron Wave on Pediatric Febrile Seizure[J]. J Korean Med Sci, 2023,38(3):e18. doi:10.3346/jkms.2023.38.e18.
Chen CS, Chang CN, Hu CF, et al. Critical pediatric neurological illness associated with COVID-19 (Omicron BA.2.3.7 variant) infection in Taiwan: immunological assessment and viral genome analysis in tertiary medical center[J]. Int J Infect Dis, 2022,124:45-48. doi:10.1016/j.ijid.2022.09.001.
Sawires R, Buttery J, Fahey M. A Review of Febrile Seizures: Recent Advances in Understanding of Febrile Seizure Pathophysiology and Commonly Implicated Viral Triggers[J]. Front Pediatr, 2021,9:801321. doi:10.3389/fped.2021.801321.
Tintinalli J, Ma OJ, Yealy D, Meckler G, Stapczynski J, Cline D, et al. In: Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. 9th ed. New York, NY, USA: McGraw-Hill Education; 2019.
Steardo L, Steardo L Jr, Zorec R, et al. Neuroinfection may contribute to pathophysiology and clinical manifestations of COVID-19[J]. Acta Physiol (Oxf), 2020,229(3):e13473. doi:10.1111/apha.13473.
Nikbakht F, Mohammadkhanizadeh A, Mohammadi E. How does the COVID-19 cause seizure and epilepsy in patients? The potential mechanisms[J]. Mult Scler Relat Disord, 2020,46:102535. doi:10.1016/j.msard.2020.102535.
Kiyatkin EA, Sharma HS. Permeability of the blood-brain barrier depends on brain temperature[J]. Neuroscience, 2009,161(3):926-939. doi:10.1016/j.neuroscience.2009.04.004.
Reid AY, Galic MA, Teskey GC, et al. Febrile seizures: current views and investigations[J]. Can J Neurol Sci, 2009,36(6):679-686. doi:10.1017/s0317167100008246.
Wang X, Chang H, Tian H, et al. Epidemiological and clinical features of SARS-CoV-2 infection in children during the outbreak of Omicron variant in Shanghai, March 7-31, 2022[J]. Influenza Other Respir Viruses, 2022,16(6):1059-1065. doi:10.1111/irv.13044.
Carroll E, Melmed KR, Frontera J, et al. Cerebrospinal fluid findings in patients with seizure in the setting of COVID-19: A review of the literature[J]. Seizure, 2021,89:99-106. doi:10.1016/j.seizure.2021.05.003.
Rettenmaier LA, Abdel-Wahed L, Abdelmotilib H, et al. COVID-19-associated necrotizing encephalopathy presenting without active respiratory symptoms: a case report with histopathology[J]. J Neurovirol, 2022,28(1):172-176. doi:10.1007/s13365-021-01042-3.
Dono F, Nucera B, Lanzone J, et al. Status epilepticus and COVID-19: A systematic review[J]. Epilepsy Behav, 2021,118:107887. doi:10.1016/j.yebeh.2021.107887.

Table1:Comparison of data between COVID-19 positive and COVID-19 negative groups.

Variable

COVID-19 positive group

COVID-19 negative group

P

N

Male

Age(years)

≤1years

1-5years

≥5years

Time from fever onset to seizure

<24 hours

≥24hours

Seizure duration ≥ 15min

Status epilepticus

History of convulsions

Family history of convulsions

Seizure ≥ 2 time

Peak body temperature,℃

Abnormal EEG

Simultaneous phenomenon

Pharyngodynia

Cough

Vomiting

Diarrhoea

Dizziness/Headache

Labiratory results

WBC(*109/L)

HB(g/dl)

PLT(*109/L)

CRP(mg/L)

182

107(58.8%)

2.3(1.3-3.8)

25(13.7%)

130(71.4%)

27(14.8%)

163(89.6%)

19(10.4%)

34(18.7%)

28(15.4%)

82(45.1%)

42(23.1%)

99(54.4%)

39.5(39.0-40.0)

20/68(29.4%)

10(5.5%)

79(43.4%)

52(28.6%)

9(4.9%)

8(4.4%)

5.9(4.7-7.6)

12.1(11.6-12.7)

212(183-258)

5.2(1.8-11.2)

117

67(57.3%)

2.1(1.2-3.5)

17(14.5%)

85(72.6%)

15(12.8%)

101(86.3%)

16(13.7%)

6(5.1%)

43(36.8%)

29(24.8%)

48(41.0%)

39.5(39.0-40.0)

12/88(13.6%)

6(5.1%)

51(43.5%)

20(17.1%)

8(6.8%)

2(1.7%)

8.7(6.3-12.8)

12.1(11.4-12.8)

239(205-309)

9.0(2.8-30.7)

NS

0.001

0.006

NS

0.024

NS

0.016

NS

0.023

NS

0.000

NS

0.000

WBC: White blood cell count; HB: Hemoglobin; PLT: Blood platelets; CRP: C-reactive protein. NS:Not significant in terms of statistics.

Table 2:Data related to the three deceased patients.

Variable

Patient 1

Patient 2

Patient 3

Age

Sex

Main symptoms

Time of onset

Admission Time

Time of death

Seizure forms

Underlying Diseases

State of consciousness

With or without shock

EEG

Hematology tests

WBC(*10⁹/L)

CRP(mg/L)

PCT(ng/ml)

Main treatment

Ventilator

Drugs

Head CT

3 years and 9 months

Female

Fever, seizures, impaired consciousness

2022.12.21

2022.12.22 06:23

2022.12.23 12:30

GTCS

None

Coma

Shock

None

5.7

7.2

None

Invasive ventilator

Methylprednisolone

Gammaglobulin

Vasoactive drugs

None

2 years and 2 months

Female

Fever, seizures, impaired consciousness

2022.12.18

2022.12.20 20:47

2022.12.21 00:05

GTCS

None

Coma

Shock

None

3.89

0.5

43.24

Invasive ventilator

Gammaglobulin

Vasoactive drugs

The thalamus was enlarged and hypodense bilaterally, with hypodense changes in the brainstem, and the remaining brain parenchyma showed no significant abnormalities. The size of the ventricular pool system was in the normal range.

2 years and 2months

Female

Fever,seizures,impaired consciousness,double inspiration

2022.12.22

2022.12.23 23:10

2022.12.31 13:04

GTCS

None

Coma

Shock

Background diffuse low voltage changes

9.72

10.51

38.23

Invasive ventilator

Methylprednisolone

Gammaglobulin

The brainstem was hypointense, the bilateral cerebellar hemispheres and the thalamus were seen to be symmetrically lamellar hypointense,, the cerebellar curtain and the longitudinal fissure pool were slightly increased in density, the third and fourth ventricles and the cerebral sulci were narrowed at different levels.

EEG:Electroencephalogram;GTCS:generalized tonic-clonic seizure;WBC:White blood cell count;CRP:C-reactive protein;PCT:Procalcitonin.

Table 3:Data from 2 patients diagnosed with ANE and 1 patient with highly suspected ANE.

Variable

Patient3

Patient 4

Patient 5

Sex

Age

Main symptoms

Seizure forms

Primary Diagnosis

Cerebrospinal fluid

WBC(*10⁶)

GLU(mmol/L)

PRO(g/L)

EBV(PCR)

HSV(PCR)

CMV(PCR)

Cultivation

mNGS

Hematology tests

WBC(*10⁹/L)

CRP(mg/L)

PCT(ng/ml)

ALT(U/L)

AST(U/L)

SF(ng/ml)

IL-6(pg/ml)

CT or MRI of the head

Main treatment

Ventilator

Drugs

Female

2 years and 2months

Fever,seizures,impaired consciousness,double inspiration

GTCS

ANE

None

9.72

10.51

38.23

222

241

907.4

None

The brainstem was hypointense, the bilateral cerebellar hemispheres and the thalamus were seen to be symmetrically lamellar hypointense,, the cerebellar curtain and the longitudinal fissure pool were slightly increased in density, the third and fourth ventricles and the cerebral sulci were narrowed at different levels.

Invasive ventilator

Methylprednisolone

Gammaglobulin

Male

11 months

Fever, seizures, impaired consciousness

GTCS

ANE

1

2.85

4.04

Negative

9.06

17.66

>100

1307

1970

None

109.1

Deep brain white matter, thalamus, basal ganglia area and brainstem, cerebellum symmetrical large lamellar hypointense shadow. The rest of the brain parenchyma showed no obvious abnormalities. The bilateral ventricles were slightly full, and the four ventricles were slightly narrow.

Invasive ventilator

Methylprednisolone

Gammaglobulin

Male

2 months

Fever, seizures, impaired consciousness

GTCS

Highly suspicious of ANE

12

2.34

3.01

Negative

None

5.94

0.71

0.17

32

48

None

Long T1 and long T2 signals can be seen in the cerebral hemispheres, thalamus, internal capsule and brainstem bilaterally. Enhancement scans showed line like enhancement in the sulcus region, which was obvious in the frontal lobes bilaterally.

None

Methylprednisolone

Gammaglobulin

ANE:Acute necrotizing encephalopathies;WBC: White blood cell count;CRP: C-reactive protein;PCT:Procalcitonin;

PRO:Protein;EBV:Epstein-Barr virus;HSV:Herpes simplex virus;CMV:Cytomegalovirus;mNGS:metagenomic next-generation sequencing;ALT:Alanine aminotransferase;AST:Aspartate aminotransferase;SF:Serum ferritin;IL-6:Interleukin-6.

Table 4:A univariate analysis of short-term reoccurrence of seizures in covid-19-related FS.

Variable

Recurrence of seizures

No recurrence of

seizures

χ2

P

Number

Male

Age

≤1years

1-5years

≥5years

Seizure ≥ 2 time

Seizure duration ≥ 15min

History of convulsions

Family history of seizure

Peakbody temperature(≤39℃)

20(14.2%)

14(70.0%)

2(10.0%)

13(65.0%)

5(25.0%)

16(80.0%)

1(5.0%)

15(75.0%)

3(15.0%)

13(65%)

121(85.8%)

76(62.8%)

14(11.6%)

92(76.0%)

15(12.4%)

59(48.8%)

18(14.9%)

53(43.8%)

30(24.8%)

36(29.8%)

0.384

0.042

1.099

2.240

6.727

0.714

6.691

0.453

9.404

0.535

0.837

0.295

0.135

0.009

0.398

0.010

0.501

0.002

Analysis of risk factors for seizures and short-term reoccurrence of seizures in febrile children with SARS-CoV-2 infection: an observational study

Status:

Version 1

Abstract

Figures

Background

Methods

Study population and definition

Data collection

Statistical analysis

Result

Discussion

Conclusions

Abbreviations

Declarations

Authors and Affiliations

Ethics approval and consent to participate

Competing Interest

References

Tables

Status:

Version 1