Exploring Inflammatory Status in Febrile Seizures Associated with Urinary Tract Infections: A Two-Step Cluster Approach

Raluca Maria Costea; Ionela Maniu; Luminita Dobrota; Rubén Pérez-Elvira; Maria Agudo; Javier Oltra-Cucarella; Andrei Dragomir; Ciprian Bacilă; Adela Banciu; Daniel Dumitru Banciu; Călin Remus Cipăian; Roxana Crișan; Bogdan Neamtu

doi:10.3390/brainsci11091168

Exploring Inflammatory Status in Febrile Seizures Associated with Urinary Tract Infections: A Two-Step Cluster Approach

Brain Sci. 2021 Sep 3;11(9):1168. doi: 10.3390/brainsci11091168.

Authors

Raluca Maria Costea^{1

2

3}, Ionela Maniu^{1

4}, Luminita Dobrota³, Rubén Pérez-Elvira⁵, Maria Agudo⁵, Javier Oltra-Cucarella⁶, Andrei Dragomir⁷, Ciprian Bacilă³, Adela Banciu⁸, Daniel Dumitru Banciu⁸, Călin Remus Cipăian³, Roxana Crișan³, Bogdan Neamtu^{1

3

9}

Affiliations

¹ Pediatric Research Department, Pediatric Clinical Hospital Sibiu, 550166 Sibiu, Romania.
² Pediatric Neurology Department, Pediatric Clinical Hospital Sibiu, 550166 Sibiu, Romania.
³ Faculty of Medicine, Lucian Blaga University of Sibiu, 550024 Sibiu, Romania.
⁴ Research Center in Informatics and Information Technology, Mathematics and Informatics Department, Faculty of Sciences, Lucian Blaga University of Sibiu, 550024 Sibiu, Romania.
⁵ Neuropsychophysiology Laboratory, NEPSA Rehabilitación Neurológica, 37003 Salamanca, Spain.
⁶ Department of Health Psychology, Universidad Miguel Hernández de Elche, 03202 Elche, Spain.
⁷ N.1 Institute for Health, National University of Singapore, Singapore 117575, Singapore.
⁸ Department of Bioengineering and Biotechnology, Faculty of Medical Engineering, Politechnic University of Bucharest, 011061 Bucharest, Romania.
⁹ Computer and Electrical Engineering Department, Faculty of Engineering, Lucian Blaga University of Sibiu, 550024 Sibiu, Romania.

Abstract

Background: Urinary tract infections (UTIs) are considered common facilitating factors, along with other infections, in triggering febrile seizures (FS). The main purpose of our study was to identify specific inflammatory patterns of UTI cases from other infections in a specific cluster, using a combination of inflammatory biomarkers to differentiate UTIs from other bacterial diseases triggering FS.

Method: This prospective study included a number of 136 patients with 197 distinct FS events, from patients hospitalized in the Pediatric Clinical Hospital Sibiu, among which 10.2% were diagnosed with UTIs.

Results: In one-third of the patients with UTIs (20 cases), the symptoms were limited to fever and FS. Using two-step cluster analysis, a distinct UTI inflammatory pattern has emerged: highest platelet values (PLT), median value 331 × 103/mm³ and intermediate C-reactive protein (CRP), median value 15 mg/dL, platelet distribution width (PDW), median value 9.65%, platelet-large cell ratio (P-LCR), median value 14.45%, mean platelet volume (MPV), median value 8.60 fL and neutrophil-to-lymphocyte values (NLR), median value 3.64. Furthermore, higher PDW (median value 12.25%), P-LCR (median value 28.55%), MPV (median value 10.40 fL), CRP (median value 74.00 mg/dL) and NLR values (median value 4.11) were associated mainly (85.7%) with bacterial lower respiratory infections. UTIs were highly unlikely in these patients with significantly increased CRP values and normal values of platelet indices.

Conclusions: Considering the nonspecific clinical picture of UTIs at an early age, to optimize the management of FS, a fast diagnosis of UTI is mandatory. The analysis of the inflammatory biomarker clusters (rather than individual parameters) correlated with urine leukocyte and nitrite stick evaluation for specific age groups could help in identifying even oligosymptomatic UTIs patients. The study limitation (20 UTI cases) recommends future multicentric trials on larger datasets to validate the model.

Keywords: CRP; cluster analysis; cut-off values; febrile seizures; inflammatory biomarkers; laboratory data; urinary tract infections; urine leukocyte and nitrite stick test.