Ann Child Neurol Search

CLOSE


Ann Child Neurol > Volume 32(3); 2024 > Article
Lee, Kim, and Koo: Analysis of Inflammatory Markers and Electroencephalogram Findings in Pediatric Patients with COVID-19: A Single-Center Study in Korea

Abstract

Purpose

The Omicron variant wave spread rapidly from February 2022 in South Korea following the initial management of the coronavirus disease 2019 (COVID-19) outbreak. This study examined electroencephalogram (EEG) findings and serological inflammatory markers in pediatric patients with COVID-19 (Omicron variant).

Methods

We retrospectively reviewed the medical records of 41 patients who presented at Gyeongsang National University Changwon Hospital between March and May 2022 and were diagnosed with COVID-19. All serological tests were performed within 24 hours of fever or seizure onset.

Results

The median patient age was 3.6 years (range, 0.08 to 14.00), and the average hospital stay was 3.7 days (range, 1.0 to 7.0). Interleukin-6 (IL-6) levels were elevated above the normal range in all patients (median, 43.18 pg/mL; range, 7.0 to 190.0) and were higher among those who experienced seizures. Of the 41 total patients, 17 (41.5%; mean age, 5.4 years) visited the clinic for seizure. Three patients experienced prolonged seizures (lasting longer than 30 minutes) and received intravenous lorazepam, while eight presented with complex febrile seizures. Nine patients underwent EEG, of whom five exhibited abnormal initial findings. Linear regression demonstrated correlations between prolonged seizure duration and both serum IL-6 level and blood lymphocyte count.

Conclusion

Numerous serological markers associated with the immune cascade were found to be elevated in children with COVID-19. Nevertheless, febrile seizures represent a relatively common neurological presentation among pediatric patients infected with Omicron variants. Consequently, COVID-19 infection exhibits both familiar and distinct characteristics regarding the mechanisms inducing seizures and fever in children.

Introduction

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the virus has undergone mutation, leading to a shift in clinical symptoms from primarily affecting the respiratory system to involving multiple organs. Neurological manifestations, known as “neuroCOVID,” have been noted in adults. Meanwhile, children, including those with no history of febrile seizures, have presented with seizures when infected with the Omicron variant [1-3]. Febrile seizures, which typically occur in children aged 6 months to 5 years, can arise during viral infection [4-6]. Seizures induced by fever associated with COVID-19 have been linked to status epilepticus or increased seizure frequency in patients with pre-existing epilepsy [7]. Several hypotheses have been introduced regarding the impact of COVID-19 on the brain, with evidence pointing to the role of inflammatory cytokines in causing coagulopathy [8,9]. Abnormalities in electroencephalograms (EEGs) have been detected, particularly in severe cases, with prognostic implications [10,11]. Marinelli et al. [12] observed attenuated EEG patterns in adult patients with severe COVID-19 and found elevated interleukin 6 (IL-6) levels in those who died from the virus. However, the relationship between serological markers and EEG findings in pediatric patients remains to be clarified. This study was performed to investigate this correlation and to establish baseline characteristics in such patients.

Materials and Methods

1. Study population and data collection

We conducted a retrospective review of the medical records of patients diagnosed with COVID-19 who attended Gyeongsang National University Changwon Hospital between March and May 2022. The study examined data from patients with COVID-19 who experienced seizures accompanied by fever. Febrile seizures are defined as seizures occurring with fever in children, typically between 6 months and 5 years old. Our study also included patients older than 5 years who presented with seizures and fever, which are classified as late-onset febrile seizures. None of the patients included in the study had a prior diagnosis of epilepsy or encephalopathy, nor did they exhibit clinical signs of encephalitis. We excluded patients over the age of 18 years, as well as those with incomplete data or who declined to provide laboratory measurements. To confirm the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we used real-time reverse-transcriptase polymerase chain reaction testing on nasopharyngeal swab specimens. EEG data were collected from patients who had fully recovered from their seizures. The inspection timing was within 1 day to 25 days after the fever started and resolved. The EEG recordings included phases of both wakefulness and sleep. All procedures were conducted in compliance with relevant guidelines and regulations, and informed consent was obtained from all participants and their legal guardians. The Institutional Review Board of Gyeongsang National University Changwon Hospital approved this research (IRB No: GNUCH 2022-04-022).

2. Variables and analysis groups

The data extracted from electronic medical records comprised baseline demographic details such as age, sex, body weight, and medical history. Additionally, body weight was categorized into quartiles based on the 2017 Korean National Growth Chart [13]. Blood samples were collected upon admission and within 24 hours following the onset of fever or seizure. All serological tests were conducted within 2 hours of sample collection.
Several clinical hematology and chemical auto-analyzers were utilized to estimate serological markers as follows: the XN-9000 (Sysmex Co., Kobe, Japan) for the total white blood cell count and the proportions of neutrophils and lymphocytes; the Alifax Test 1 (Alifax Srl, Polverara, Italy) for the erythrocyte sedimentation rate; the AU5800 (Beckman Coulter Inc., Brea, CA, USA) for C-reactive protein levels; and the STA-R MAX coagulometer (Stago, Paris, France) for D-dimer levels. Additionally, the ADVIA Centaur XPT immunoassay analyzer (Siemens Healthineers, Milano, Italy) was employed to measure serum procalcitonin and ferritin levels. Finally, an automated immunoassay using the Cobas 8000 device (Roche Diagnostics, Basel, Switzerland) was used to quantify IL-6 concentrations.
The EEG data were recorded using a NicoletOne EEG device (Natus Medical Inc., Middleton, WI, USA) in accordance with the International 10-20 system for a minimum duration of 30 minutes. Seizure descriptions employed terminology from the classification system of the International League Against Epilepsy [14]. Clinical neurophysiologists and medical college professors (SL and CK) independently reviewed the EEG tracings and reached a consensus on their interpretations. The revised terminology version [15] was utilized to interpret the EEG findings.

3. Statistical analysis

Statistical analyses were conducted using R version 4.1.2 (R Foundation for Statistical Computing, Vienna, Austria, 2021). Analysis of variance and the t-test, along with the Kruskal-Wallis test and the Mann-Whitney U test, were employed to examine the quantitative data of the participants. Furthermore, the chi-square and Fisher exact tests were utilized to compare groups categorized by seizure presentation and EEG findings. Finally, linear regression analysis was performed to assess the relationships between fever peak or seizure duration and inflammatory markers. A P value of 0.05 was considered to indicate significance for all statistical calculations.

4. Availability of data and materials

The authors confirm that the data supporting the findings of this study are presented within the article and its supplementary materials. Anonymized data from this study are available upon reasonable request to Chungmo Koo, the corresponding author.

Results

We retrieved the medical chart data of 585 patients with confirmed COVID-19. We excluded a total of 544 patients aged 18 years and older, as well as those with missing data or who declined to provide laboratory measurements. Consequently, 41 patients with COVID-19 were included in the study. Among these individuals, we conducted further analysis of 17 patients who visited our clinics with seizures, as well as nine patients with available EEG results (Fig. 1). None of the study participants had a history of multisystem inflammatory syndrome in children, nor had they received treatment in intensive care units. All patients had unremarkable perinatal and birth histories, and their neurodevelopmental examinations were normal for their age.
The mean age of the patients was 3.6 years, with an average hospital stay of 3.7 days (range, 1.0 to 7.0) and a predominance of male patients. Among those with seizures, boys were also more prevalent than girls, and the mean age was higher compared to the non-seizure group. Patients with seizures experienced higher peak fever temperatures than those without seizures. Serum IL-6 concentrations were elevated in all enrolled patients, with the seizure group displaying levels about twice as high as those not exhibiting seizures. Additionally, D-dimer levels were higher in the seizure group, while both the proportion and counts of lymphocytes were lower compared to the non-seizure group. No significant difference was observed between groups in white blood cell or neutrophil counts. Similarly, no significant differences were noted in body weight proportions, although a higher percentage of patients in the seizure group were above the 75th percentile for body weight (Table 1).
Of the total patients, eight children experienced complex febrile seizures. Within this group, three children had focal seizures, two experienced seizures more than twice a day, and three exhibited prolonged seizures lasting over 30 minutes, for which they received intravenous lorazepam. Four patients had a family history of febrile seizures, three patients had previous febrile seizures, and all these patients presented simple types of febrile seizures. Seven patients underwent brain magnetic resonance imaging (MRI). Of these, two exhibited abnormal findings, namely choroidal fissure cyst and delayed myelination. The remaining MRI results were non-specific, with no evidence of encephalitis . All patients achieved complete control of seizure activity, maintained an alert mental status, and were discharged from the clinic without the need for anti-seizure medications.
Furthermore, patients with available EEG findings were categorized by the presence or absence of theta burst. The serum IL-6 level was approximately twice as high in the group with theta burst (84.2 pg/mL) compared to the group without such theta activity (42.6 pg/mL). However, this relationship was not statistically significant (Table 2).
Using the results of a linear regression model based on fever peak, we found that a high serum IL-6 level was correlated with a high fever peak (β=0.01; 95% confidence interval [CI], 0.004 to 0.016; P=0.002). However, we observed no significant correlation between fever peak and serum ferritin level (β=−0.004; 95% CI, −0.006 to 0.001; P=0.014) or total lymphocyte count (β=−0.099; 95% CI, −0.192 to −0.006; P=0.038). In the multivariate linear regression model examining the relationship between seizure duration and inflammatory markers, IL-6 levels were associated with prolonged seizure duration, although the association weakened after adjustment (crude: 0.175 [95% CI, −0.032 to 0.382; P=0.09]; adjusted: 0.131 [95% CI, −0.024 to 0.287; P=0.087]).Conversely, only lymphocyte counts were correlated with prolonged seizure duration (crude: 10.951 [95% CI, 3.490 to 18.411; P=0.007]; adjusted: 17.783 [95% CI, 5.224 to 30.341; P=0.011]).

Discussion

In this study, we analyzed inflammatory markers and EEG findings associated with COVID-19, observing several changes in serological markers among patients with the disease. Notably, a significant correlation was observed between increased serum IL-6 levels and peak body temperature. C-reactive protein and IL-6 levels have been shown to be significantly elevated in patients who died from COVID-19 [16]. Furthermore, a dramatic rise in IL-6 has been associated with COVID-19-related severe pneumonia and bilateral interstitial lung disease [17]. However, previous research has also suggested that specific cytokines, including interferon-α/β/γ, tumor necrosis factor-α, and various interleukins (IL-1α/β, -2, -6, -12, -13, and -18), are implicated in the antiviral response, with IL-6 playing a pivotal role in the survival and proliferation of CD4 T cells [18,19]. Therefore, in light of our findings and a review of the literature, IL-6 can be considered a key immunological mediator involved in the COVID-19 immune response.
Additionally, our findings revealed a markedly higher level of cytokines in the group experiencing seizures, with serum IL-6 level displaying a significant correlation with seizure duration. While the exact mechanism by which COVID-19 may trigger seizures remains unconfirmed, several studies have proposed that inflammatory cytokines are crucial neuromodulators that become elevated following epileptic events, both in vivo and in vitro [8,20-22]. Specifically, the increased levels of circulating cytokines seen in patients with COVID-19 can increase the permeability of the blood-brain barrier [23,24] and activate additional inflammatory mediators, triggering a cascade of immune responses [25]. Moreover, inflammatory cytokines may stimulate activity in the developing brain, aligning with the evidence-based theory of epileptic events [26]. Animal studies of febrile seizures have demonstrated elevated cytokine levels in the hippocampus [27]. Our findings indicate that cytokines associated with COVID-19 could represent a crucial marker for understanding the mechanisms underlying fever-induced seizures in children. Additionally, our results suggested a relationship between increased total lymphocyte count and the duration of seizure. This correlation is particularly interesting in that it mirrors the early immune response to viral infection observed in studies of immunocompromised patients. For instance, a moderate rise in lymphocyte count is evident in the initial phase of human immunodeficiency virus infection, followed by a gradual decline [28]. Traditional febrile seizures in children are associated with a variety of viral infections that cause high fever [29]. Significant lymphocytopenia is indicative of an “immunological burst” involving circulating cytokines, which can influence the severity of viral infections, including COVID-19 [30]. However, our findings reveal an unexpected pattern, as lymphocytosis was significantly associated with prolonged seizures in patients with COVID-19. Thus, extended seizures induced by fever in the context of COVID-19 may be linked to lymphocytosis during the early stages of infection [31], offering a different perspective from the mechanisms associated with high fever in other viral infections.
Our findings indicate that patients exhibiting theta burst activity on EEG had IL-6 levels approximately twice as high as those without such activity. Theta burst activity is noteworthy, as it can signify focal abnormalities in brain function and is indicative of prolonged seizures in otherwise healthy children with febrile seizures [32,33]. Furthermore, the presence of theta burst activity is linked to an increased risk of recurrent febrile seizures and adverse outcomes in childhood epilepsy [34,35]. This leads us to consider the potential relationship between theta rhythm and seizure triggered by fever associated with COVID-19 in children. It is plausible that COVID-19 infection may provoke theta burst activity in the brain. Supporting this hypothesis, anosmia was a prominent and widely examined neurological symptom during the initial wave of the COVID-19 pandemic [36]. Autopsy findings suggest a direct pathway for SARS-CoV-2 entry, in which the virus interacts with angiotensin-converting enzyme 2 receptors in the olfactory mucosa [37]. Although the olfactory cortex is situated near the frontal lobe, it has anatomical connections with the hippocampus [38], a primary site of the generation of theta rhythms [39]. In vitro studies using a mouse model injected with SARS-CoV-2 RNA have demonstrated viral aggregation in the hippocampus [40]. Consequently, we propose that the mechanism underlying fever-induced seizures associated with COVID-19 may involve the neuronal invasion route through the hippocampal network.
This study had several limitations. First, the sample size was small, with relatively few patients enrolled. Second, the research was based on retrospective observational data obtained over a short period that did not include laboratory data, such as cerebrospinal fluid analysis. Lastly, the evaluation of developmental milestones relied on questionnaires completed by parents, and the study did not consider other prospective neurological outcomes, such as underlying susceptibility to epilepsy or encephalopathy. Despite these limitations, our research provides current insights into the relationship between serological markers and specific EEG features in healthy pediatric patients. Further follow-up studies should, therefore, be conducted to monitor the neurological outcomes of the enrolled patients, thereby gaining a deeper understanding of latent neurological complications. Additionally, larger populations and extended longitudinal studies are needed to investigate the long-term neurocognitive effects and the pathophysiology of seizures triggered by COVID-19-related fever. Such studies should include postmortem examinations and experimental animal models, along with cerebrospinal fluid analysis or brain biopsy.

Conflicts of interest

No potential conflict of interest relevant to this article was reported.

Notes

Author contribution

Conceptualization: SL. Data curation: SL and KRK. Formal analysis: SL and CK. Funding acquisition: SL and CK. Methodology: SL. Project administration: SL and CK. Visualization: SL. Writing - original draft: SL. Writing - review & editing: SL.

Acknowledgments

The authors express their gratitude to all staff members, doctors, and statistical consultants who were involved in this study.

Fig. 1.
Schematic diagram sorting of enrolled patients. COVID-19, coronavirus disease 2019; EEG, electroencephalogram.
acn-2023-00416f1.jpg
Table 1.
General characteristics of pediatric patients with COVID-19 infection
Characteristic Febrile seizure All patients (n=41) P value
No (n=24) Yes (n=17)
Sex 0.381
 Female 13 (54.2) 6 (35.3) 19 (46.3)
 Male 11 (45.8) 11 (64.7) 22 (53.7)
Age (yr) 2.4±4.0 5.4±3.9 3.6±4.2 0.002
Fever peak (℃) 38.5±0.8 39.1±0.5 38.8±0.7 0.019
Inflammatory markers
 ESR (mm/hr) 6.8±6.2 3.4±2.2 5.3±5.1 0.18
 CRP (mg/dL) 5.6±9.5 3.1±3.1 4.5±7.5 0.671
 D-dimer (μg/mL) 0.6±0.4 2.9±9.7 1.7±6.7 0.024
 Procalcitonin (ng/mL) 0.3±0.6 0.1±0.1 0.2±0.5 0.389
 IL-6 (pg/mL) 29.1±30.0 60.3±50.9 44.2±43.6 0.044
 Ferritin (ng/mL) 169.1±112.7 40.4±17.9 109.3±104.9 0.001
 WBC (/μL) 7,822.3±5,171.9 6,937.6±1,493.0 7,446.3±4,024.9 0.265
 Neutrophil count (/μL) 3,379.6±2,755.1 4,950.6±1,770.9 4,047.2±2,487.4 0.005
 Lymphocyte count (/μL) 3,275.1±2,959.9 1,059.8±929.6 2,333.6±2,554.7 <0.001
Body weight (kg) 0.635
 >75 11 (45.8) 5 (29.4) 16 (39.0)
 50-75 6 (25.0) 4 (23.5) 10 (24.4)
 25-50 2 (8.3) 3 (17.6) 5 (12.2)
 <25 5 (20.8) 5 (29.4) 10 (24.4)

Values are presented as number (%) or mean±standard error.

COVID-19, coronavirus disease 2019; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; IL-6, interleukin 6; WBC, white blood cell.

Table 2.
Comparison of serological markers in patients according to theta bursts on EEG
Variable Theta burst in EEG Patients who underwent EEG (n=9) P value
No (n=4) Yes (n=5)
Sex 0.444
 Female 0 2 (40.0) 2 (22.2)
 Male 4 (100.0) 3 (60.0) 7 (77.8)
Age (yr) 5.5±4.5 6.6±3.4 5.4±3.9 0.684
Fever peak (℃) 38.8±0.4 39.0±0.7 39.1±0.5 0.611
ESR (mm/hr) 3.5±3.0 2.0±0.0 3.4±2.2 0.371
CRP (mg/dL) 5.0±2.5 2.4±2.2 3.1±3.1 0.139
D-dimer (μg/mL) 10.0±18.6 0.3±0.1 2.9±9.7 0.125
Procalcitonin (ng/mL) 0.2±0.1 0.1±0.0 0.1±0.1 0.344
IL-6 (pg/mL) 42.6±18.4 84.2±80.9 60.3±50.9 0.433
Ferritin (ng/mL) 46.6±21.0 33.7±5.3 40.4±17.9 0.279
WBC (/μL) 7,405.0±1,686.9 5,962.0±1,296.6 6,937.6±1,493.0 0.189
Neutrophil count (/μL) 5,437.5±2,242.3 4,332.0±1,628.3 4,950.6±1,770.9 0.418
Lymphocyte count (/μL) 1,255.0±1,439.7 1,025.1±959.0 1,059.8±929.6 1.000

Values are presented as number (%) or mean±standard error.

EEG, electroencephalogram; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; IL-6, interleukin 6; WBC, white blood cell.

References

1. Fotuhi M, Mian A, Meysami S, Raji CA. Neurobiology of COVID-19. J Alzheimers Dis 2020;76:3-19.
crossref pmid pmc
2. Nakra NA, Blumberg DA, Herrera-Guerra A, Lakshminrusimha S. Multi-system inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection: review of clinical presentation, hypothetical pathogenesis, and proposed management. Children (Basel) 2020;7:69.
crossref pmid pmc
3. Ludvigsson JF. Convulsions in children with COVID-19 during the Omicron wave. Acta Paediatr 2022;111:1023-6.
crossref pmid pmc pdf
4. Capovilla G, Mastrangelo M, Romeo A, Vigevano F. Recommendations for the management of “febrile seizures”: Ad Hoc Task Force of LICE Guidelines Commission. Epilepsia 2009;50 Suppl 1:2-6.
crossref pmid
5. Tso WW, Kwan MY, Wang YL, Leung LK, Leung D, Chua GT, et al. Severity of SARS-CoV-2 Omicron BA.2 infection in unvaccinated hospitalized children: comparison to influenza and parainfluenza infections. Emerg Microbes Infect 2022;11:1742-50.
crossref pmid pmc
6. Mewasingh LD, Chin RF, Scott RC. Current understanding of febrile seizures and their long-term outcomes. Dev Med Child Neurol 2020;62:1245-9.
crossref pmid pdf
7. Thongsing A, Eizadkhah D, Fields C, Ballaban-Gil K. Provoked seizures and status epilepticus in a pediatric population with COVID-19 disease. Epilepsia 2022;63:e86-91.
crossref pmid pmc pdf
8. Vohora D, Jain S, Tripathi M, Potschka H. COVID-19 and seizures: is there a link? Epilepsia 2020;61:1840-53.
crossref pmid pmc pdf
9. Jensen MP, Le Quesne J, Officer-Jones L, Teodosio A, Thaventhiran J, Ficken C, et al. Neuropathological findings in two patients with fatal COVID-19. Neuropathol Appl Neurobiol 2021;47:17-25.
crossref pmid pdf
10. Singh A, Jain S, Dutta V, Dutta S, Gaind R, Sharma S. Role of inflammatory markers and clinical correlate in children infected with the novel SARS-CoV-2: a prospective observational study. J Clin Diagn Res 2023;17.
crossref
11. Tsai C, Wilson SE, Rubinos C. SARS-CoV-2 infection and seizures: the perfect storm. J Integr Neurosci 2022;21:115.
crossref pmid
12. Marinelli L, Pappalardo I, Robba C, Saitta L, Cabona C, Battaglini D, et al. The value of EEG attenuation in the prediction of outcome in COVID-19 patients. Neurol Sci 2022;43:6159-66.
crossref pmid pmc pdf
13. Kim JH, Yun S, Hwang SS, Shim JO, Chae HW, Lee YJ, et al. The 2017 Korean National Growth Charts for children and adolescents: development, improvement, and prospects. Korean J Pediatr 2018;61:135-49.
crossref pmid pmc pdf
14. Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia 2017;58:512-21.
crossref pmid pmc pdf
15. Kane N, Acharya J, Benickzy S, Caboclo L, Finnigan S, Kaplan PW, et al. A revised glossary of terms most commonly used by clinical electroencephalographers and updated proposal for the report format of the EEG findings: revision 2017. Clin Neurophysiol Pract 2017;2:170-85.
crossref pmid pmc
16. Mahat RK, Panda S, Rathore V, Swain S, Yadav L, Sah SP. The dynamics of inflammatory markers in coronavirus disease-2019 (COVID-19) patients: a systematic review and meta-analysis. Clin Epidemiol Glob Health 2021;11:100727.
crossref pmid pmc
17. Samprathi M, Jayashree M. Biomarkers in COVID-19: an up-to-date review. Front Pediatr 2021;8:607647.
crossref pmid pmc
18. Guidotti LG, Chisari FV. Cytokine-mediated control of viral infections. Virology 2000;273:221-7.
crossref pmid
19. Dienz O, Rincon M. The effects of IL-6 on CD4 T cell responses. Clin Immunol 2009;130:27-33.
crossref pmid pmc
20. Jankowsky JL, Derrick BE, Patterson PH. Cytokine responses to LTP induction in the rat hippocampus: a comparison of in vitro and in vivo techniques. Learn Mem 2000;7:400-12.
crossref pmid pmc
21. Kalueff AV, Lehtimaki KA, Ylinen A, Honkaniemi J, Peltola J. Intranasal administration of human IL-6 increases the severity of chemically induced seizures in rats. Neurosci Lett 2004;365:106-10.
crossref pmid
22. Alapirtti T, Lehtimaki K, Nieminen R, Makinen R, Raitanen J, Moilanen E, et al. The production of IL-6 in acute epileptic seizure: a video-EEG study. J Neuroimmunol 2018;316:50-5.
crossref pmid
23. Solomon T. Neurological infection with SARS-CoV-2: the story so far. Nat Rev Neurol 2021;17:65-6.
crossref pmid pmc pdf
24. Huang X, Hussain B, Chang J. Peripheral inflammation and blood-brain barrier disruption: effects and mechanisms. CNS Neurosci Ther 2021;27:36-47.
crossref pmid pmc pdf
25. Nikbakht F, Mohammadkhanizadeh A, Mohammadi E. How does the COVID-19 cause seizure and epilepsy in patients?: the potential mechanisms. Mult Scler Relat Disord 2020;46:102535.
crossref pmid pmc
26. Innes RF. Understanding the pathophysiology behind febrile convulsions. Nurs Child Young People 2015;27:20-3.
crossref
27. Heida JG, Pittman QJ. Causal links between brain cytokines and experimental febrile convulsions in the rat. Epilepsia 2005;46:1906-13.
crossref pmid
28. Itescu S, Brancato LJ, Buxbaum J, Gregersen PK, Rizk CC, Croxson TS, et al. A diffuse infiltrative CD8 lymphocytosis syndrome in human immunodeficiency virus (HIV) infection: a host immune response associated with HLA-DR5. Ann Intern Med 1990;112:3-10.
crossref pmid
29. Francis JR, Richmond P, Robins C, Lindsay K, Levy A, Effler PV, et al. An observational study of febrile seizures: the importance of viral infection and immunization. BMC Pediatr 2016;16:202.
crossref pmid pmc pdf
30. Lalueza A, Folgueira D, Munoz-Gallego I, Trujillo H, Laureiro J, Hernandez-Jimenez P, et al. Influence of viral load in the outcome of hospitalized patients with influenza virus infection. Eur J Clin Microbiol Infect Dis 2019;38:667-73.
crossref pmid pmc pdf
31. Ulich TR, del Castillo J, Guo KZ. In vivo hematologic effects of recombinant interleukin-6 on hematopoiesis and circulating numbers of RBCs and WBCs. Blood 1989;73:108-10.
crossref pmid pdf
32. Santoni JR, Santoni-Williams C. Abnormal theta response to nociceptive stimuli during sleep EEG in children with febrile convulsions and control children. Neurophysiol Clin 1996;26:164-9.
crossref pmid
33. Yamatogi Y, Ohtahara S. EEG in febrile convulsions. Am J EEG Technol 1990;30:267-80.
crossref
34. Doose H, Volzke E, Petersen CE, Herzberger E. Fever cramps and epilepsy. II. Electroencephalographic study of the course of so-called fever or infection cramps. Arch Psychiatr Nervenkr (1970) 1966;208:413-32.
pmid
35. Daute KH, Klust E. The abnormal theta-rhythm and its relation to febrile convulsions. Z Kinderheilkd 1969;105:108-18.
crossref pmid
36. Hosseini N, Nadjafi S, Ashtary B. Overview of COVID-19 and neurological complications. Rev Neurosci 2021;32:671-91.
crossref pmid
37. Meinhardt J, Radke J, Dittmayer C, Franz J, Thomas C, Mothes R, et al. Olfactory transmucosal SARS-CoV-2 invasion as a port of central nervous system entry in individuals with COVID-19. Nat Neurosci 2021;24:168-75.
crossref pmid pdf
38. Aqrabawi AJ, Kim JC. Hippocampal projections to the anterior olfactory nucleus differentially convey spatiotemporal information during episodic odour memory. Nat Commun 2018;9:2735.
crossref pmid pmc pdf
39. Nunez A, Buno W. The theta rhythm of the hippocampus: from neuronal and circuit mechanisms to behavior. Front Cell Neurosci 2021;15:649262.
crossref pmid pmc
40. Glass WG, Subbarao K, Murphy B, Murphy PM. Mechanisms of host defense following severe acute respiratory syndrome-coronavirus (SARS-CoV) pulmonary infection of mice. J Immunol 2004;173:4030-9.
crossref pmid pdf


ABOUT
ARTICLE CATEGORY

Browse all articles >

BROWSE ARTICLES
EDITORIAL POLICY
AUTHOR INFORMATION
Editorial Office
101, Daehak-ro, Jongno-gu, Seoul 03080, Korea
Tel: +82-2-2072-2364    Fax: +82-2-743-3455    E-mail: editor@annchildneurol.org                

Copyright © 2024 by Korean Child Neurology Society.

Developed in M2PI

Close layer
prev next