A Neurophysiological Study in Children and Adolescents with Crigler-Najjar Syndrome Type I

Abstract

We studied the neurophysiological features of five patients (age range: 4-20 years) suffering from Crigler-Najjar syndrome type I (CNsI) by means of multimodal (brainstem, somatosensory, motor) evoked potentials and periodic EEG-polygraphic recordings (follow-up: 3 months-4.5 years). Two patients presented with neurological disturbances, consisting mainly of mental slowing, motor impairment and seizures. Both of them presented an abnormal EEG, characterized by slowing of background activity associated with paroxysmal discharges. Liver transplantation was performed in one of these two patients and was followed by improvement of both the neurological picture and EEG activity. In a third patient, clinically normal, after two years of follow-up, the EEG started to show paroxysmal activity during sleep or when evoked by intermittent photic stimulation. In these three patients, multimodal evoked potentials were unremarkable. The remaining two younger subjects did not show any clinical or EEG abnormality. Our findings suggest that, whereas in newborns and infants evoked potentials have been demonstrated as reliable techniques to monitor bilirubin neurotoxicity, in children and adolescents with CNsI, EEG seems to be more sensitive in evaluating patients for neurological damage and effectiveness of therapeutic strategies adopted.

Nerve Growth Factor Protects against 6-Hydroxydopamine-induced Oxidative Stress by Increasing Expression of Heme Oxygenase-1 in a Phosphatidylinositol 3-Kinase-dependent Manner

“…This led to the assumption that HO-1 overactivity might not protect, but rather contribute to the development of parkinsonism because iron accumulation in dopaminergic neurons may contribute to chronic oxidative damage, leading to neurodegeneration in Parkinson's patients. A protective role for HO catabolism in the nervous system has been also challenged by the fact that hyperbilirubinemia is commonly associated with nerve cell injury and brain damage during severe neonatal jaundice and CriglerNajjar type II syndrome (41,42). Consistent with these obser- vations, we could not obtain high constitutive levels of HO-1 expression either in HO-1-overexpressing cells (2.3-fold) or in myr-EGFP-Akt1 cells (2.5-fold).…”

The Mitochondrial Connection in Auditory Neuropathy

“…Consequently, in those infants having an accelerated bilirubin production, a reduced or impaired capability to conjugate bilirubin, reduced hepatic uptake, increased enterohepatic circulation, and/or a limited ability to eliminate bilirubin from the body, potentially toxic levels of this substance can develop in the circulation [Bancroft et al, 1998;Rubboli et al, 1997]. Thus, hyperbilirubinemia ( 1 17 mg/dl, 291 mol/l) [American Academy of Pediatrics, 1994] can create a particular concern for infants because of the potential for cellular and neuronal toxicity, which can lead to bilirubin encephalopathy or kernicterus.…”

Bilirubin directly disrupts membrane lipid polarity and fluidity, protein order, and redox status in rat mitochondria

“…Accumulation of unconjugated bilirubin (UCB) in the central nervous system contributes to cell damage during severe neonatal hyperbilirubinemia and Crigler-Najjar type I syndrome leading to bilirubin encephalopathy [1,2]. In fact, numerous crucial aspects of cell function are impaired by UCB [3][4][5][6][7][8][9][10][11], perhaps resulting in apoptotic processes [11][12][13].…”