Perinatology PN Perinatology 2508-4887 2508-4895 The Korean Society of Perinatology 10.14734/PN.2016.27.3.168 Original Article Neonatal Seizures Accompanied by Cerebral White Matter Injury Associated with Rotavirus Infection Kim Hyun-A MD Jo Chae-Ku MD Kim Myo-Jing MD Department of Pediatrics, Dong-A University College of Medicine, Busan, Korea. Correspondence to: Myo-Jing Kim, MD. Department of Pediatrics, Dong-A University College of Medicine, 1,3-ga, Dongdaesin-dong, Seo-gu, Busan 602-714, Korea. Tel: +82-51-240-2589, Fax: +82-51-242-2765, myojing@dau.ac.kr 09 2016 30 09 2016 27 3 168 173 08 07 2016 19 09 2016 21 09 2016 Copyright © 2016 The Korean Society of Perinatology 2016 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Purpose

Few studies have investigated the neurological complications of rotavirus infection in newborns. This study reports on clinical characteristics of newborns with seizures during rotavirus infection period and the neurological complications through case reports of infants who experienced seizures during rotavirus infection and demonstrated deep white matter injury on brain magnetic resonance imaging (MRI).

 Methods

The study retrospectively investigated the medical records of newborn patients with positive rotavirus results who admitted to the neonatal intensive care unit of Dong-a University Hospital between January 2010 and May 2015. We analyzed the clinical characteristics of patients with seizures compared to without seizures among the patients of positive rotavirus results. The clinical characteristics of seizure patients according to the stool rotavirus antigen test results (positive vs. negative) and MRI results (normal vs. abnormal) were compared and analyzed.

 Results

Of the 144 infants with positive rotavirus results, 17 infants (11.8%) had the seizures. These 17 patients showed no other symptom except seizures, positive rotavirus results predominantly at 4-6 days after birth, and more abnormal MRI results compared to without seizures. These results investigated in the seizure infants with positive rotavirus and infants of abnormal MRI results with positive rotavirus in same trend. In 15 newborns who showed positive stool test results and abnormal MRI results, seizure symptoms occurred at 4-6 days after birth, mostly following a pattern of clonic seizures. On MRI, all these newborns showed cerebral deep white matter injury in areas including the corpus callosum (CC) and internal capsule. Six out of 15 newborns underwent follow-up MRI scans, and five of them showed porencephalic white matter disease or periventricular leukomalacia.

 Conclusion

In cases when a newborn shows seizures and cerebral deep white matter injury on diffusion-weighted MRI, rotavirus infection should be strongly suspected, and the patient should be subjected to long-term follow-up for neurological development.

 Newborns Seizures Rotavirus Brain magnetic resonance imaging Choi UY Lee SY Ma SH Jang YT Kim JY Kim HM Epidemiological changes in rotavirus gastroenteritis in children under 5 years of age after the introduction of rotavirus vaccines in Korea Eur J Pediatr 2013 172 947 952 Kim CR Neonatal rotavirus infection Neonatal Med 2013 20 389 401 Park DK Chung JY The changes in the outbreak of rotavirus gastroenteritis in children after introduction of rotavirus vaccines: a retrospective study at a tertiary hospital Korean J Pediatr Infect Dis 2014 21 167 173 Sohn TY Lee CJ Kim YJ Kang MJ Kim SH Lee SY Clinical and epidemiological study of 1,165 hospitalized cases of rotaviral gastroenteritis before and after the introduction of rotavirus vaccine, 2006-2013 Korean J Pediatr Infect Dis 2014 21 174 180 Langley JM LeBlanc JC Hanakowski M Goloubeva O The role of Clostridium difficile and viruses as causes of nosocomial diarrhea in children Infect Control Hosp Epidemiol 2002 23 660 664 Gurwith M Wenman W Hinde D Feltham S Greenberg H A prospective study of rotavirus infection in infants and young children J Infect Dis 1981 144 218 224 Santosham M Yolken RH Quiroz E Dillman L Oro G Reeves WC Detection of rotavirus in respiratory secretions of children with pneumonia J Pediatr 1983 103 583 585 Park MK Park JO Kim CH Comparison of clinical manifestation of rotaviral gastroenteritis between neonates and infants Korean J Pediatr Gastroenterol Nutr 2006 9 153 161 Lynch M Lee B Azimi P Gentsch J Glaser C Gilliam S Rotavirus and central nervous system symptoms: cause or contaminant? Case reports and review Clin Infect Dis 2001 33 932 938 Shiihara T Watanabe M Honma A Kato M Morita Y Ichiyama T Rotavirus associated acute encephalitis/encephalopathy and concurrent cerebellitis: report of two cases Brain Dev 2007 29 670 673 Lee KY Oh KW Weon YC Choi SH Neonatal seizures accompanied by diffuse cerebral white matter lesions on diffusion-weighted imaging are associated with rotavirus infection Eur J Paediatr Neurol 2014 18 624 631 Salmi TT Arstila P Koivikko A Central nervous system involvement in patients with rotavirus gastroenteritis Scand J Infect Dis 1978 10 29 31 Riedel F Kroener T Stein K Nuesslein TG Rieger CH Rotavirus infection and bradycardia-apnoea-episodes in the neonates Eur J Pediatr 1996 155 36 40 Verboon-Maciolek MA Truttmann AC Groenendaal F Skranes J Døllner H Hunt RW Development of cystic periventricular leukomalacia in newborn infants after rotavirus Infection J Pediatr 2012 160 165 168 Wong CJ Price Z Bruckner DA Aseptic meningitis in an infant with rotavirus gastroenteritis Pediatr Infect Dis 1984 3 244 246 Ushijima H Bosu K Abe T Shinozaki T Suspected rotavirus encephalitis Arch Dis Child 1986 61 692 694 Keidan I Shif I Keren G Passwell JH Rotavirus encephalopathy: evidence of central nervous system involvement during rotavirus infection Pediatr Infect Dis J 1992 11 773 775 Diffusion-weighted images of the patients. Diffusion-weighted images of the 3 patients (A; patient 8, B; patient 9, C; patient 10) of the group of positive rotavirus and abnormal MRI. Note the high signals on deep white matter, corpus callosum and internal capsule. Follow-up magnetic resonance image (MRI) after 2 weeks from seizure onset of patients A shows porencephaly and cerebromalacia in both frontal and parietal white matter, periventricular leukomalacia around occipital horn (A-1, A-2; patient 8). Likewise, porencephaly in frontal and parietal white matter is demonstrated in follow-up MRI of patient B (B-1, B-2; patient 9). Comparison of the Clinical Characteristics between Infants with Seizures and without Seizures in Rotavirus Group
Rotavirus+Seizure (+) (n=17) Rotavirus+Seizure (−) (n=127) P value
Gestational age (weeks) 37.6±1.0 35.8±4.2 0.09
Male, n (%) 12 (70.6) 67 (52.8) 0.11
Birth weight (kg) 3.1±0.4 2.7±0.9 0.06
Cesarean section, n (%) 7 (41.2) 73 (57.5) 0.42
Apgar score (1'/5') 8.3±0.8/9.1±0.9 7.4±1.9/9.2±0.9 0.12/0.48
Age at positive rotavirus (days) 4.8±0.6 14.3±17.2 0.03
NICU screening, n (%) 0 34 (26.8) 0.01
Vomiting, n (%) 0 14 (11.0) 0.37
Poor feeding, n (%) 0 32 (25.2) 0.02
Diarrhea, n (%) 1 (5.9) 20 (15.7) 0.13
Fever, n (%) 0 19 (15.0) 0.13
Abnormal MRI, n (%) 15/17 (88.2) 1/19 (5.3) <0.01

Values are expressed as number (percent) or mean±standard deviation

Abbreviations: 1', one minute; 5', five minutes; NICU, neonatal intensive care unit; MRI, magnetic resonance imaging

 Comparison of the Clinical Characteristics between Infants with Positive Rotavirus and Negative Rotavirus in Seizure Group
Seizure+Rotavirus (+) (n=17) Seizure+Rotavirus (−) (n=14) P value
Gestational age (weeks) 38.2±1.0 39.2±1.2 <0.01
Male, n (%) 13 (76.5) 6 (42.9) 0.08
Birth weight (kg) 3.2±0.5 3.1±0.4 0.54
Cesarean section, n (%) 8 (47.1) 9 (64.3) 0.47
Apgar score(1'/5') 8.3±0.8/9.1±0.9 7.9±1.4/8.9±1.2 0.54/0.59
Age at seizure onset (days) 4.9±0.8 5.0±3.3 0.85
Seizure onset between 4 and 6 days of life, n (%) 16 (94.1) 2 (14.3) <0.01
Abnormal findings in MRI, n (%) 15 (88.2) 9 (64.3) 0.20
Abnormal findings in EEG, n (%) 5 (29.4) 2 (20.0) 0.68

Values are expressed as number (percent) or mean±standard deviation

Abbreviations: 1', one minute; 5', five minutes MRI, magnetic resonance imaging; EEG, electroencephalography

 Comparison of the Clinical Characteristics between Infants with Abnormal MRI and Normal MRI in Seizure Group
Seizure+Abnormal MRI (n=24) Seizure+Normal MRI (n=7) P value
Gestational age (weeks) 38.6±1.1 39.0±1.5 0.25
Male, n (%) 16 (66.7) 3 (42.9) 0.38
Birth weight (kg) 3.1±0.5 3.0±0.4 0.56
Cesarean section, n (%) 13 (54.2) 4 (57.1) 1.0
Apgar score(1'/5') 8.0±1.2 / 8.9±1.1 8.4±0.8 / 9.3±0.8 0.38/0.53
Age at seizure onset (days) 4.8±2.2 5.3±2.4 0.95
Positive rotavirus antigen, n (%) 15 (62.5) 2 (28.5) 0.20

Values are expressed as number (percent) or mean±standard deviation

Abbreviations: 1', one minute; 5', five minutes MRI, magnetic resonance imaging

 Comparison of the Clinical Characteristics between Infants with Positive Rotavirus and Negative Rotavirus in Abnormal MRI Group
Abnormal MRI+Rota (+) (n=15) Abnormal MRI+Rota (−) (n=9) P value
Gestational age (weeks) 38.0±0.9 39.4±0.8 <0.01
Male, n (%) 12 (80) 4 (44.4) 0.10
Birth weight (kg) 3.2±0.5 3.1±0.5 0.73
Cesarean section, n (%) 7 (46.7) 6 (66.7) 0.42
Apgar score(1'/5') 8.2±0.8 / 9.0±1.0 7.5±1.6 / 8..6±1.4 0.34/0.55
Age at seizure onset (days) 5.0±0.7 4.6±3.6 0.68
Seizure onset between 4 and 6 days of life, n (%) 15 (100) 0 (0) <0.01
Abnormal findings in EEG, n (%) 4 (36.3) 0 (0) 0.26

Values are expressed as number (percent) or mean±standard deviation

Abbreviations 1', one minute; 5', five minutes MRI, magnetic resonance imaging; EEG, electroencephalography

 Clinical Characteristics, Seizure Type, MRI and EEG Findings of the Group of Positive Rotavirus and Abnormal MRI
Pt. No. GA/Sex Bwt. (g) Del. A/S (1'/5') Onset (days) Seizure type Abnormal brain DWI EEG Stool rotavirus antigen Follow-up brain MRI
1 38+4/M 3,820 NSVD 8/9 5 Clonic, F Deep white matter, CS NS + Porencephalic change in white matter
2 35+5/M 2,420 NSVD 9/10 5 Clonic, M Deep white matter NS +
3 38+3/M 3,220 NSVD 7/8 4 Clonic, M Deep white matter NS +
4 38+2/M 3,700 C/S 9/10 5 Clonic, G Deep white matter, CS, IC Multifocal sharp wave, predominant frontal +
5 37+5/F 2,410 C/S 8/9 6 Clonic, G Deep white matter, T NS +
6 39+3/M 3,270 NSVD 8/9 5 Clonic, M Deep white matter, CS, IC Encephalopathic pattern + Cerebromalacia in white matter
7 38+4/M 3,720 C/S 8/9 5 Clonic, G Deep white matter, CS, IC, T Infrequent multifocal sharp wave +
8 38+0/F 2,520 C/S 9/10 5 Clonic, M Deep white matter, CS, IC, T NS + Cystic PVL, Cerebromalacia in white matter
9 37+3/M 3,100 NSVD 9/10 5 Clonic, M Deep white matter, CS, IC Multifocal sharp wave + Porencephalic change in white matter
0010 36+6/M 3,200 C/S 9/10 5 Clonic, M Deep white matter NS +
0011 38+0/F 2,760 NSVD 8/9 5 Clonic, M Deep white matter, CS NS +
0012 38+1/M 2,970 NSVD 7/7 4 Rigidity BG NS + Normal
0013 37+6/M 2,780 NSVD 9/9 4 Pedaling Deep white matter, CS ,IC, EC NS + Porencephaly in white matter
0014 38+2/M 3,390 C/S 7/8 6 Clonic, M Deep white matter, CS, IC, T NS +
0015 39+3/M 3,120 C/S 9/10 6 Clonic, F Deep white matter, CS, IC NS +

Abbreviations: GA, gestatioanal age; Bwt, birth weight; Del, delivery method; A/S, apgar score; DWI, diffusion-weighted imaging; EEG, electroencephalography; F, focal; M, multifocal; G, generalized; CS, corpus callosum; IC, internal capsule; EC, external capsule; T, thamus; BG, basal ganglia; NS, non-specific