Status epilepticus after a massive intravenous N-acetylcysteine overdose leading to intracranial hypertension and death

Bailey, Benoît; Blais, René; Letarte, Anne

doi:10.1016/j.annemergmed.2004.05.014

Cited by 53 publications

(35 citation statements)

References 20 publications

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“…Mice pretreated with N-Ac were more susceptible to limbic seizures in both the pilocarpine model and 6 Hz corneal stimulation model. These proconvulsant effects are supported by clinical case reports of status epilepticus induced by intravenous N-Ac administration (Hershkovitz et al, 1996;Bailey et al, 2004). Here, we provide conclusive evidence for the role of system x c Ϫ in these proconvulsive effects of N-Ac given that its effect on pilocarpine-induced seizure susceptibility was abolished in xCT Ϫ/Ϫ mice.…”

Section: Discussionsupporting

confidence: 71%

Loss of System x_c⁻Does Not Induce Oxidative Stress But Decreases Extracellular Glutamate in Hippocampus and Influences Spatial Working Memory and Limbic Seizure Susceptibility

Bundel¹,

Schallier²,

Loyens³

et al. 2011

J. Neurosci.

168

195

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System x cϪ exchanges intracellular glutamate for extracellular cystine, giving it a potential role in intracellular glutathione synthesis and nonvesicular glutamate release. We report that mice lacking the specific xCT subunit of system x c Ϫ (xCT Ϫ/Ϫ ) do not have a lower hippocampal glutathione content, increased oxidative stress or brain atrophy, nor exacerbated spatial reference memory deficits with aging. Together these results indicate that loss of system x c Ϫ does not induce oxidative stress in vivo. Young xCT Ϫ/Ϫ mice did however display a spatial working memory deficit. Interestingly, we observed significantly lower extracellular hippocampal glutamate concentrations in xCT Ϫ/Ϫ mice compared to wild-type littermates. Moreover, intrahippocampal perfusion with system x c Ϫ inhibitors lowered extracellular glutamate, whereas the system x c Ϫ activator N-acetylcysteine elevated extracellular glutamate in the rat hippocampus. This indicates that system x c Ϫ may be an interesting target for pathologies associated with excessive extracellular glutamate release in the hippocampus. Correspondingly, xCT deletion in mice elevated the threshold for limbic seizures and abolished the proconvulsive effects of N-acetylcysteine. These novel findings sustain that system x c Ϫ is an important source of extracellular glutamate in the hippocampus. System x c Ϫ is required for optimal spatial working memory, but its inactivation is clearly beneficial to decrease susceptibility for limbic epileptic seizures.

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Section: Discussionsupporting

confidence: 71%

Loss of System x_c⁻Does Not Induce Oxidative Stress But Decreases Extracellular Glutamate in Hippocampus and Influences Spatial Working Memory and Limbic Seizure Susceptibility

Bundel¹,

Schallier²,

Loyens³

et al. 2011

J. Neurosci.

168

195

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“…79 Whereas NAC appears to be antiepileptic at low doses, 80 seizures are reported with overdose. 81 Vigilance is necessary. Given that many of these disorders have many interacting potential pathophysiological pathways, further research is required to determine how NAC is exerting benefits.…”

Section: Discussionmentioning

confidence: 99%

N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action

Dean

Giorlando

Berk

2011

J Psychiatry Neurosci

421

314

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There is an expanding field of research investigating the benefits of alternatives to current pharmacological therapies in psychiatry. N-acetylcysteine (NAC) is emerging as a useful agent in the treatment of psychiatric disorders. Like many therapies, the clinical origins of NAC are far removed from its current use in psychiatry. Whereas the mechanisms of NAC are only beginning to be understood, it is likely that NAC is exerting benefits beyond being a precursor to the antioxidant, glutathione, modulating glutamatergic, neurotropic and inflammatory pathways. This review outlines the current literature regarding the use of NAC in disorders including addiction, compulsive and grooming disorders, schizophrenia and bipolar disorder. N-acetylcysteine has shown promising results in populations with these disorders, including those in whom treatment efficacy has previously been limited. The therapeutic potential of this acetylated amino acid is beginning to emerge in the field of psychiatric research.

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“…acetylcysteine have been published. 44,45 A previously healthy 30-month-old girl developed status epilepticus after receiving more than a 10-fold cumulative overdose of i.v. acetylcysteine.…”

Section: Bailey and Mcguiganmentioning

confidence: 99%

“…acetylcysteine. 44 She was administered 44 mL/kg of 5% dextrose injection during the acetylcysteine infusion. She developed intracranial hypertension and subsequently died.…”

Section: Bailey and Mcguiganmentioning

confidence: 99%

Comparison of oral and i.v. acetylcysteine in the treatment of acetaminophen poisoning

Kanter

2006

American Journal of Health-System Pharmacy

101

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Status epilepticus after a massive intravenous N-acetylcysteine overdose leading to intracranial hypertension and death

Cited by 53 publications

References 20 publications

Loss of System x_c⁻Does Not Induce Oxidative Stress But Decreases Extracellular Glutamate in Hippocampus and Influences Spatial Working Memory and Limbic Seizure Susceptibility

Loss of System x_c⁻Does Not Induce Oxidative Stress But Decreases Extracellular Glutamate in Hippocampus and Influences Spatial Working Memory and Limbic Seizure Susceptibility

N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action

Comparison of oral and i.v. acetylcysteine in the treatment of acetaminophen poisoning

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Status epilepticus after a massive intravenous N-acetylcysteine overdose leading to intracranial hypertension and death

Cited by 53 publications

References 20 publications

Loss of System xc−Does Not Induce Oxidative Stress But Decreases Extracellular Glutamate in Hippocampus and Influences Spatial Working Memory and Limbic Seizure Susceptibility

Loss of System xc−Does Not Induce Oxidative Stress But Decreases Extracellular Glutamate in Hippocampus and Influences Spatial Working Memory and Limbic Seizure Susceptibility

N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action

Comparison of oral and i.v. acetylcysteine in the treatment of acetaminophen poisoning

Contact Info

Product

Resources

About

Loss of System x_c⁻Does Not Induce Oxidative Stress But Decreases Extracellular Glutamate in Hippocampus and Influences Spatial Working Memory and Limbic Seizure Susceptibility

Loss of System x_c⁻Does Not Induce Oxidative Stress But Decreases Extracellular Glutamate in Hippocampus and Influences Spatial Working Memory and Limbic Seizure Susceptibility