The metabolic encephalopathies comprise a series of neurological disorders not caused by primary structural abnormalities; rather, they result from systemic illness, such as diabetes, liver disease, renal failure and heart failure (Table 38-1). Metabolic encephalopathies usually develop acutely or subacutely and are reversible if the systemic disorder is treated. If left untreated, however, metabolic encephalopathies may result in secondary structural damage to the brain.

Table 38-1

Classification of the Major Metabolic Encephalopathies.

There are two major types of metabolic encephalopathies, namely those due to lack of glucose, oxygen or metabolic cofactors (which are usually vitamin-derived) and those due to peripheral organ dysfunction (Table 38-1).

Abnormalities of brain chemistry sufficient to cause encephalopathy and coma are numerous and represent a wide array of disorders. Vitamin deficiencies (Chap. 33), inherited disease, (Chaps. 40, 41 and 44) and some neuroendocrine disorders (Chap. 49) may at some stage disrupt brain metabolic processes and result in encephalopathy. Exposure to various heavy metals and organic solvents also may cause a toxic encephalopathy. Of particular significance is ethanol because it is widely used and, in excessive amounts, can produce permanent brain damage, particularly in association with avitaminoses and malnutrition (see Chap. 33). Clinically, hepatic encephalopathy secondary to alcoholic cirrhosis is not infrequently associated with brain damage resulting from previous acute alcoholic episodes.

Clinical signs and symptoms of metabolic encephalopathies consist of a generalized depression of cerebral function, including consciousness. The effects on consciousness may be a consequence of decreased integrative capacity of the neocortex [1]. Arousal of the neocortex and other forebrain structures involved in cognition is mediated by specific brainstem nuclei and their projecting fiber tracts, which together constitute the ascending reticular activating system (ARAS). Activating pathways ascend from the ARAS via thalamic synaptic relays to the neocortex. Metabolic encephalopathies result from alterations of brain chemistry at both neocortical and brainstem ARAS centers. Respiration may be diminished and pupils appear small but reactive. As encephalopathy progresses, asterixis, also termed “flapping tremor,” is encountered, particularly in hepatic disease, uremia and sedative intoxication. Asterixis results from the loss of postural tone in voluntary muscles of the limbs, trunk, head or tongue. More advanced stages of metabolic encephalopathy may be characterized by seizures, for example, in hypoglycemia, acute liver failure and, ultimately, Cheyne-Stokes pattern of respiration resulting from loss of brainstem respiratory control. In addition, many metabolic encephalopathies, including those caused by vitamin deficiencies and ingestion of toxic substances, are characterized by focal metabolic changes in basal ganglia and cerebellar structures, resulting in disorders of movement control and coordination. Vitamin deficiencies and their effects on CNS function are discussed in Chapter 33.