Metabolic disorders and disorders caused by exposure to a toxic agent portend a good prognosis, leading most of the time to a full recovery when recognized and treated promptly. Despite significant advances in critical care in the last 30 years, leading to improved survival of affected patients, little advance has been made in the treatment of acute neurological problems in the pediatric population. Metabolic disorders represent an exception to this statement, due to the development of new diagnostic techniques combined with a better understanding of the pathophysiology of such disorders, which have lead to the application of life-saving therapeutic tools and reducing the severity of brain injury. Examples include hemodialysis for the treatment of urea cycle disorders1 (eg, citrulinemia). In addition, significant advances in communication have made more readily available consultative expertise through academic centers worldwide. Access to the Internet has allowed most practitioners managing patients with a toxic or metabolic encephalopathy to maintain the highest standards of treatment, reduce injury, improve survival, and reverse changes in the penumbra zone of the affected areas of the brain.
This chapter is an approach to the different etiologies causing a metabolic derangement leading to a toxic or metabolic encephalopathy, and classified according to the age of the patient. Also, this chapter provides a wide overview of the pathogenesis, clinical approach, and treatment of patients affected with such disorders.
Toxic and metabolic encephalopathies refers to a group of disorders characterized by changes in the level of consciousness due to an exogenous or endogenous substance causing a metabolic derangement in the normal neuronal activity and leading to a transient or permanent damage of neuronal pathways (see Figure 20-1). The source of the injurious substrate can be from (1) a malfunctioning organ such as the liver or kidney, (2) an outside source such as a poisoning, or (3) deregulation of internal homeostasis as seen in primary or secondary electrolyte disturbances. Either pathway leads to compromise of autoregulation of the blood-brain barrier or internal brain homeostasis. Several etiologies are included in this syndrome and classified in two groups: congenital and acquired disorders.2 Causes of acquired disorders are listed in Table 20-1 and include exogenous poisoning (eg, methanol, ethanol, and ethylene glycol), diabetes mellitus, uremia, and late-onset congenital enzymatic deficiencies. Causes of congenital disorders leading to a toxic metabolic encephalopathy can be divided into early and late onset, based on the clinical presentation, and include organic acidurias, congenital glycosylation disorders, and neurotransmitter deficiencies3 (Table 20-2). For better understanding, definitions of several terms used when describing patients with altered mental status have been summarized in Table 20-3.
Pathogenesis of ischemic neuronal death. Ischemia deprives the brain of metabolic substrates, especially glucose, making it impossible for cells to carry out energy-dependent functions such as the maintenance of trans-membrane ion gradients. Loss of these gradients depolarizes cell ...