Abstract
Brainstem auditory evoked potentials (BAEPs) are a sensitive indicator of bilirubin neurotoxicity. Somatosensory evoked potentials (SEPs) have been proposed as another measure of toxicity, though the lemniscal pathways that generate the SEP are not involved in kernicterus. In 16 to 17-d-old jaundiced (jj) Gunn rats, serial BAEPs and SEPs were obtained up to 8 h after acute bilirubin toxicity. jjs were injected with 150 mg/kg sulfadimethoxine to displace bilirubin into brain tissue (n = 8); littermate controls were jjs given saline (n = 4) and nonjaundiced given sulfadimethoxine or saline (n = 7). After anesthesia, BAEP and SEP recordings were obtained at baseline and serially after injection. SEPs to median nerve stimulation were recorded from surface electrodes over the brachial plexus (Erb's) and contralateral parietal cortex, and subtracted to obtain central conduction time (CCT). There were no statistically significant different baseline values between groups. Baseline BAEP I, I-II, and I-III were 1.22 ± 0.13, 1.11 ± 0.12, and 2.10 ± 0.15 ms, and SEP Erb's and CCT were 1.48 ± 0.20 and 5.59 ± 0.50 ms, respectively (n = 19). At 6.8 ± 1.5 h after injection BAEP I, I-II, and I-III increased 0.10 ± 0.08, 0.18 ± 0.17, and 0.56 ± 0.33 ms over baseline, respectively (p = 0.005, 0.01, and 0.001, respectively, paired, 1-tailed t-tests), in experimental but not control groups. SEP Erb's decreased slightly, −0.06 ± 0.04 ms in experimental and −0.08 ± 0.08 ms in control groups, while CCT did not change significantly. BAEPs were completely abolished in two jjs with no SEP changes. When injection of sulfonamide induced significant peripheral and central BAEP abnormalities in jaundiced rats, no SEP abnormalities occurred. SEPs assess proprioception but not other somatosensory function or sensory integration. The results demonstrate the selectivity of acute bilirubin toxicity for the auditory nervous system.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- BAEP:
-
brainstem auditory evoked potential
- SEP:
-
somatosensory evoked potential
- CCT:
-
central conduction time
- jj:
-
homozygous jaundiced Gunn rat
- Nj:
-
heterozygous nonjaundiced Gunn rat
- sulfa:
-
sulfadimethoxine
- MRI:
-
magnetic resonance imaging
- PET:
-
positron emission tomography
- CNS:
-
central nervous system
References
Wennberg RP, Ahlfors CE, Bickers R, McMurtry CA, Shetter JL 1982 Abnormal auditory brainstem response in a newborn infant with hyperbilirubinemia: improvement with exchange transfusion. J Pediatr 100: 624–626
Perlman M, Fainmesser P, Sohmer H, Tamari H, Wax Y, Pevsmer B 1983 Auditory nerve-brainstem evoked responses in hyperbilirubinemic neonates. Pediatrics 72: 658–664
Nwaesei CG, Van Aerde J, Boyden M, Perlman M 1984 Changes in auditory brainstem responses in hyperbilirubinemic infants before and after exchange transfusion. Pediatrics 74: 800–803
Lenhardt ML, McArtor R, Bryant B 1984 Effects of neonatal hyperbilirubinemia on the brainstem electrical response. J Pediatr 104: 281–284
Nakamura H, Takada S, Shimabuku R, Matsuo M, Matsuo T, Negishi H 1985 Auditory nerve and brainstem responses in newborn infants with hyperbilirubinemia. Pediatrics 75: 703–708
Gupta AK, Raj H, Anand NK 1990 Auditory brainstem responses (ABR) in neonates with hyperbilirubinemia. Indian J Pediatr 57: 705–711
Levi G, Sohmer H, Kapitulnik J 1981 Auditory nerve and brain stem responses in homozygous jaundiced Gunn rats. Arch Otolaryngol 232: 139–143
Uziel A, Marot M, Pujol R 1983 The Gunn rat: an experimental model for central deafness. Acta Otolaryngol 95: 651–656
Shapiro SM 1988 Acute brainstem auditory evoked potential abnormalities in jaundiced Gunn rats given sulfonamide. Pediatr Res 23: 306–310
Shapiro SM, Hecox KE 1988 Developmental studies of brainstem auditory evoked potentials in jaundiced Gunn rats. Brain Res 469: 147–157
Shapiro SM, Hecox KE 1989 Brain stem auditory evoked potentials in jaundiced Gunn rats. Ann Otol Rhinol Laryngol 98: 308–317
Bongers-Schokking JJ, Colon EJ, Hoogland RA, Van den Brande JL, de Groot CJ 1990 Somatosensory evoked potentials in neonatal jaundice. Acta Paediatr Scand 79: 148–155
Ahdab-Barmada M, Moossy J 1984 The neuropathology of kernicterus in the premature neonate: diagnostic problems. J Neuropath Exp Neurol 43: 45–56
Claireaux AE 1961 Pathology of human kernicterus. Montreal: University of Toronto Press
Haymaker W, Margles C, Pentschew A 1961 Pathology of kernicterus and posticteric encephalopathy. In: Swinyard CA (ed) Kernicterus and Its Importance in Cerebral Palsy. Springfield, IL: Charles C Thomas, pp 21–229).
Zimmerman HH, Yannet H 1933 Kernicterus: Jaundice of the nuclear masses of the brain. Am J Dis Child 45: 740–759
Yokochi K 1995 Magnetic resonance imaging in children with kernicterus. Acta Paediatr 84: 937–939
Strebel L, Odell GB 1971 Bilirubin uridine disphosphoglucuronyltransferase in rat liver microsomes: genetic variation and maturation. Pediatr Res 5: 548–559
Johnson L, Sarmiento F, Blanc WA, Day R 1959 Kernicterus in rats with an inherited deficiency of glucuronyl transferase. Am J Dis Child 97: 591–608
Johnson L, Garcia ML, Figueroa E, Sarmiento F 1961 Kernicterus in rats lacking glucuronyl transferase. Am J Dis Child 101: 322–349
Diamond I, Schmid R 1966 Experimental bilirubin encephalopathy. The mode of entry of bilirubin- 14C into the central nervous system. J Clin Invest 45: 678–689
Conlee JW, Shapiro SM 1991 Morphological changes in the cochlear nucleus and nucleus of the trapezoid body in Gunn rat pups. Hear Res 57: 23–30
Shapiro SM, Conlee JW 1991 Brainstem auditory evoked potentials correlate with morphological changes in Gunn rat pups. Hear Res 57: 16–22
Desmedt JE, Brunko E 1980 Functional organization of far-field and cortical components of somatosensory evoked potentials in normal adults. Prog Clin Neurophysiol 7: 27–50
Desmedt JE, Cheron G 1983 Spinal and far-field components of human somatosensory evoked potentials to posterior tibial nerve stimulation analyzed with oesophageal derivations and non-cephalic reference recording. Electroencephalogr Clin Neurophysiol 56: 635–651
Fagan ER, Taylor MJ, Logan WJ 1987 Somatosensory evoked potentials: Part I. A review of neural generators and special considerations in pediatrics. Pediatr Neurol 3: 189–196
Weiderholt WC, Iragui-Madoz VJ 1977 Far field somatosensory potentials in the rat. Electroencephr Clin Neurophysiol 42: 456–465
Silver S, Sohmer H, Kapitulnik J 1996 Postnatal development of somatosensory evoked potential in jaundiced Gunn rats and effects of sulfadimethoxine administration. Pediatr Res 40: 209–214
Silver S, Sohmer H, Kapitulnik J 1995 Visual evoked potential abnormalities in jaundiced Gunn rats treated with sulfadimethoxine. Pediatr Res 38: 258–261
Blanc WA, Johnson L 1959 Studies on kernicterus; relationship with sulfonamide intoxication, report on kernicterus in rats with glucuronyl transferase deficiency and review of pathogenesis. J Neuropath Exp Neurol 18: 165–189
Rose AL, Wisniewski H 1979 Acute bilirubin encephalopathy induced with sulfadimethoxine in Gunn rats. J Neuropathol Exp Neurol 38: 152–165
Schutta HS, Johnson L 1969 Clinical signs and morphologic abnormalities in Gunn rats treated with sulfadimethoxine. J Pediatr 75: 1070–1079
Shapiro SM 1993 Reversible brainstem auditory evoked potential abnormalities in jaundiced Gunn rats given sulfonamide. Pediatr Res 34: 629–633
Hebel R, Stromberg MW 1986 Anatomy and embryology of the laboratory rat: Worthsee, Biomed Verlag
Keppel G 1982 Design and Analysis: A Researcher's Handbook, 2 Ed, Englewood Cliffs, NJ, Prentice-Hall
Jew JY, Sandquist D 1979 CNS changes in hyperbilirubinemia. Functional implications. Arch Neurol 36: 149–154
Jew JY, Williams TH 1977 Ultrastructural aspects of bilirubin encephalopathy in cochlear nuclei of the Gunn rat. J Anat 124: 599–614
Sturrock R, Y JJ 1978 A quantitative histological study of changes in neurons and glia in the Gunn rat. Neuropath Appl Neurobiol 4: 209–223
Kumada S, Hayashi M, Umitsu R, Arai N, Nagata J, Kurata K, Morimatsu Y 1997 Neuropathology of the dentate nucleus in developmental disorders. Acta Neuropathol Berl 94: 36–41
Ahdab-Barmada M, Moossy J 1983 Kernicterus reexamined. Pediatrics 71: 463–464
Harris MC, Bernbaum JC, Polin JR, Zimmerman R, Polin RA 2001 Developmental follow-up of breastfed term and near-term infants with marked hyperbilirubinemia. Pediatrics 107: 1075–1080
Martich-Kriss V, Kollias SS, Ball WS 1995 MR findings in kernicterus. AJNR Am J Neuroradiol 16: 819–821
Sugama S, Soeda A, Eto Y 2001 Magnetic resonance imaging in three children with kernicterus. Pediatr Neurol 25: 328–331
Anziska B, Cracco RQ 1980 Short latency somatosensory evoked potentials: Studies in patients with focal neurological disease. Electroencephr Clin Neurophysiol 49: 227–239
Cracco RQ, Cracco JB, Anziska BJ 1979 Somatosensory evoked potentials in man: cerebral, subcortical, spinal, and peripheral nerve potentials. Am J EEG Technol 19: 59–81
Malamud N 1961 Pathogenesis of kernicterus in the light of its sequelae. In: Swinyard CA (ed) Kernicterus and Its Importance in Cerebral Palsy. Springfield, IL, Charles C Thomas, pp 230–246
Ibanez V, Deiber MP, Sadato N, Toro C, Grissom J, Woods RP, Mazziotta JC, Hallett M 1995 Effects of stimulus rate on regional cerebral blood flow after median nerve stimulation. Brain 118: 1339–1351
Coghill RC, Talbot JD, Evans AC, Meyer E, Gjedde A, Bushnell MC, Duncan GH 1994 Distributed processing of pain and vibration by the human brain. J Neurosci 14: 4095–4108
Burton H, Videen TO, Raichle ME 1993 Tactile-vibration-activated foci in insular and parietal-opercular cortex studied with positron emission tomography: mapping the second somatosensory area in humans. Somatosens Mot Res 10: 297–308
Boecker H, Ceballos-Baumann A, Bartenstein P, Weindl A, Siebner HR, Fassbender T, Munz F, Schwaiger M, Conrad B 1999 Sensory processing in Parkinson's and Huntington's disease: investigations with 3D H(2)(15)O-PET. Brain 122: 1651–1665
Conlee JW, Shapiro SM 1997 Development of cerebellar hypoplasia in jaundiced Gunn rats treated with sulfadimethoxine: a quantitative light microscopic analysis. Acta Neuropathol 93: 450–460
Gibson NA, Brezinova V, Levene MI 1992 Somatosensory evoked potentials in the term newborn. Electroencephalogr Clin Neurophysiol 84: 26–31
Gilmore R 1992 Somatosensory evoked potential testing in infants and children. J Clin Neurophysiol 9: 324–341
Aiminoff MJ, Eisen A 1999 Somatosensory Evoked Potentials. In: Aiminoff MJ (ed) Electrodiagnosis in Clinical Neurology, 4th Ed. Churchill Livingston, New York
Dumitru D, Robinson LR, Zwarts MJ 2002 Somatosensory Evoked Potentials. In: Dumitru D, Robinson LR, Zwarts MJ (eds) Electrodiagnostic Medicine, 2nd Ed. Hanley & Belfus, Inc., Philadelphia
Dumitru D, Robinson LR, Zwarts MJ (Eds) 2002 Electrodiagnostic Medicine, 2nd Ed. Hanley & Belfus, Inc., Philadelphia
Chiappa KH 1997 Evoked Potentials in Clinical Medicine, 3rd Ed. Lippincott-Raven, Philadelphia
Levy SR 1997 Somatosensory Evoked Potentials in Pediatrics. In: Chiappa KH (ed) Evoked Potentials in Clinical Medicine, 3rd ed. Lippincott-Raven, Philadelphia, pp 453–469
George SR, Taylor MJ 1991 Somatosensory evoked potentials in neonates and infants: developmental and normative data. Electroencephalogr Clin Neurophysiol 80: 94–102
Desmedt JE, Brunko E, Debecker J, Carmeliet J 1974 The system bandpass required to avoid distortion of early components when averaging somatosensory evoked potentials. Electroencephalogr Clin Neurophysiol 37: 407–410
Guideline nine: guidelines on evoked potentials. American Electroencephalographic Society. 1994 J Clin Neurophysiol 11: 40–73
Acknowledgements
Preliminary experiments and determination of optimal recording technique were performed by Laurie Coggins Han.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was supported by National Institutes of Health-NIDCD grant R01 DC00369.
Rights and permissions
About this article
Cite this article
Shapiro, S. Somatosensory and Brainstem Auditory Evoked Potentials in the Gunn Rat Model of Acute Bilirubin Neurotoxicity. Pediatr Res 52, 844–849 (2002). https://doi.org/10.1203/00006450-200212000-00006
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-200212000-00006
This article is cited by
-
Models of bilirubin neurological damage: lessons learned and new challenges
Pediatric Research (2023)
-
Experimental models assessing bilirubin neurotoxicity
Pediatric Research (2020)
