Correlation of Malondialdehyde (MDA) and C-reactive Protein (CRP) Level to Neurodevelopmental Outcome in Children After the Episode of Convulsive Type Status Epilepticus

Sintha Restuningwiyani, Ariani Ariani, Hidayat Sujuti, Masruroh Rahayu, Krisni Subandiyah


Refractory and mortality associated with status epilepticus (SE) were correlated with the degree of inflammation-induced neuronal cell death. This study was aimed to investigate the correlation of oxidative stress (Malondialdehyde, MDA) and inflammation (C-reactive protein, CRP) process with neurodevelopmental outcome in children after the episode of convulsive type SE. This study was designed as cross sectional which included 26 convulsive type SE subjects and 15 control subjects. MDA level was measured by thiobarbituric acid (TBA) method, while CRP level was measured by ELISA method. Neurodevelopmental outcome was measured by Bayley-III Scale of Infant and Toddler Development 3 month after the convulsive type SE episode. Results showed that both MDA (independent t-test, p < 0.05) and CRP (Mann-Whitney test, p < 0.05) level was significantly higher in convulsive type SE group as compared to control group. Further analysis also showed that MDA (Spearman correlation test, p = 0.000, r = 0.756) and CRP (Spearman correlation test, p = 0.000, r = 0.835) level was positively correlated with convulsive type SE. In convulsive type SE group, MDA level was negatively correlated with neurodevelopmental outcome but CRP was not. We concluded that MDA level was negatively correlated with neurodevelopmental outcome in children with convulsive type SE, but CRP was not.


C-reactive protein, malondialdehyde, neurodevelopmental outcome, status epilepticus

Full Text:



Ng YT, Maganti R (2013) Status epilepticus in childhood. Journal of Paediatrics and Child Health 49 (6): 432 - 437. doi: 10.1111/j.1440-1754.2012.02559.x.

Nair PP, Kalita J, Misra UK (2011) Status epilepticus: Why, what, and how. Journal of Postgraduate Medicine 57 (3): 242 – 252. doi: 10.4103/0022-3859.81807.

Tekgul H, Gauvreau K, Soul J et al. (2006) The current etiologic

profile and neurodevelopmental outcome of seizures in-term newborn infants. Pediatrics 117 (4): 1270 – 1280. doi: 10.1542/peds.2005-1178.

Sarhan AA, Ayouty MM, Elsharkawy AA, Elmagid DSA (2015) Neurodevelopmental and neurobehavioral aspects of childhood epilepsy. Benha Medical Journal 32 (1): 13 – 19. doi: 10.4103/1110-208X.170553.

Saz EU, Karapinar B, Ozcetin M et al. (2011) Convulsive status epilepticus in children: Etiology, treatment protocol and outcome. Seizure 8 (2): 115 – 118. doi: 10.1016/j.seizure.2010. 10.034.

Hussain N, Appleton R, Thorburn K (2007) Aetiology, course and outcome of children admitted to paediatric intensive care with convulsive status epilepticus: A retrospective 5-year review. Seizure 16 (4): 305 – 312. doi: 10.1016/j.seizure.2007.01.

Sandarangani M, Seaton C, Scott JAG et al. (2008) Incidence and outcome of convulsive status epilepticus in Kenyan children: a cohort study. The Lancet Neurology 7 (2): 145 – 150. doi: 10.1016/S1474-4422(07)70331-9.

Ayala A, Munoz MF, Arguelles S (2014) Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxidative Medicine and Cellular Longevity. doi: 10.1155/2014/360438.

Maestra SL, Kisby GE, Micale RT et al. (2011) Cigarette smoke induces DNA damage and alters base-excision repair and tau levels in the brain of neonatal mice. Toxicological Sciences 123 (2): 471 – 479. doi: 10.1093/toxsci/kfr187.

Rahardjani KB (2010) Hubungan antara malondialdehyde (MDA) dengan hasil luaran sepsis neonatorum. Sari Pediatri 12 (2): 82 – 87. doi: 10.14238/sp12.2.2010.82-7.

Li F, Yang Z, Lu Y et al. (2010) Malondialdehyde suppresses cerebral function by breaking homeostasis between excitation and inhibition. PLoS ONE 5 (12): e15325. doi: 10.1371/journal.pone.0015325.

Pepys MB, Hirschfield GM (2003) C-reactive protein: A critical update. The Journal of Clinical Investigation 111 (12): 1805 – 1812. doi: 10.1172/JCI18921.

Holtman L, van Vliet EA, Aronica E et al. (2013) Blood plasma inflammation markers during epileptogenesis in post-status epilepticus rat model for temporal lobe epilepsy. Epilepsia 54 (4): 589 – 595. doi: 10.1111/epi.12112.

Sattler JM (2001) Assessment of children: Cognitive applications. 4th ed. California, Jerome M, Sattler, Publisher, Inc.

Bayley N (2006) Bayley scales of infant and toddler development. San Antonio, USA: Psych Corp.

Bedford H, Suzanne W, Jane A (2013) Policy research unit in the health of children, young people and families. Accessed date: December 2017.

Sleven H, Gibbs JE, Heales S et al. (2006) Depletion of reduced

glutathione precedes inactivation of mitochondrial enzymes fol-

lowing limbic status epilepticus in the rat hippocampus. Neurochemistry International 48 (2): 75 – 82. doi: 10.1016/j.neuint.2005.10.002.

Jarrett SG, Milder JB, Liang LP, Patel M (2008) The ketogenic diet increases mitochondrial glutathione levels. Journal of Neurochemistry 106 (3): 1044 – 1051. doi: 10.1111/j.1471-4159.2008.05460.x.

Tejada S, Sureda A, Roca C et al. (2007) Antioxidant response and oxidative damage in brain cortex after high dose of pilocarpine. Brain Research Bulletin 71 (4): 372 – 375. doi: 10.1016/j.brainresbull.2006.10.005.

Tsai HL, Chang CN, Chang SJ (2010) The effects of pilocarpine-induced status epilepticus on oxidative stress/damage in developing animals. Brain and Development 32 (1): 25 – 31. doi: 10.1016/j.braindev.2009.02.013.

Freitas RM, Vasconcelos SM, Souza FC et al. (2005) Oxidative stress in the hippocampus after pilocarpine-induced status epilepticus in Wistar rats. Federation of European Biochemical Societies Journal 272 (6): 1307 - 1312. doi: 10.1111/j.1742-4658.2004.04537.x.

Nobre Junior HV, de Franca Fonteles MM, de Freitas RM (2009) Acute seizure activity promotes lipid peroxidation, increased nitrite levels and adaptive pathways against oxidative stress in frontal cortex and striatum. Oxidative Medicine and Cellular Longevity 2 (3): 130 – 137. doi: 0.4161/oxim.2.3.8488.

Muzayyanah NL, Hapsara S, Wibowo T (2013) Kejang berulang dan status epileptikus pada ensefalitis sebagai faktor resiko epilepsi pascaensefalitis. Sari Pediatri 15 (3): 150 – 155. doi: 10.14238/sp15.3.2013.150-5.

Kovac S, Domijan AM, Walker MC, Abramov AY (2014) Seizure activity results in calcium- and mitochondria-independent ROS production via NADPH and xanthine oxidase activation. Cell Death and Disease 5: e1442. doi: 10.1038/cddis.2014.390.

Frantseva MV, Perez Velazquez JL, Tsoraklidis G et al. (2000) Oxidative stress is involved in seizure-induced neurodegeneration in the kindling model of epilepsy. Neuroscience 97 (3): 431 – 435. doi: 10.1016/S0306-4522(00)00041-5.

Kovacs R, Schuchmann S, Gabriel S et al. (2002) Free radical-mediated cell damage after experimental status epilepticus in hippocampal slice cultures. Journal of Neurophysiology 88 (6): 2909 – 2918. doi: 10.1152/jn.00149.2002.

Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiological Reviews 87 (1): 245-313. doi: 10.1152/physrev.


Tekgul H, Gauvreau K, Soul J et al. (2006) The Current etiologic profile and neurodevelopmental outcome of seizures in term newborn infants. Pediatrics 117 (4): 1270 – 1280. doi: 10.1542/peds.2005-1178.

Vezzani A, Aronica E, Mazarati A, Pittman QJ (2013) Epilepsy

and brain inflammation. Experimental Neurology 244: 11 – 21. doi: 10.1016/j.expneurol.2011.09.033.

Ishikawa N, Kobayashi Y, Fujii Y, Kobayashi M (2015) Increased interleukin-6 and high-sensitivity C-reactive protein levels in pediatric epilepsy patients with frequent, refractory generalized motor seizures. Seizure 25: 136 – 140. doi: 10.1016/j.seizure.2014.10.007.

Sutter R, Marsch S, Fuhr P, Ruegg S (2013) Mortality and recovery from refractory status epilepticus in the intensive care unit: A 7-year observational study. Epilepsia 54 (3): 502 – 511. doi: 10.1111/epi.12064.

Maegaki Y, Kurozawa Y, Tamasaki A et al. (2015) Early predictors of status epilepticus-associated mortality and morbidity in children. Brain and Development 37 (5): 478 – 486. doi: 10.1016/j.braindev.2014.08.004.


Copyright (c) 2018 Journal of Tropical Life Science