In all forms of hypoglycemic encephalopathy, the major damage is to the cerebral cortex. Cortical nerve cells degenerate and are replaced by microglia cells and astrocytes. The distribution of lesions is similar, although probably not identical to that in hypoxic encephalopathy. The cerebellar cortex is less vulnerable to hypoglycemia than to hypoxia. Auer has described the ultrastructural changes in neurons resulting from experimental hypoglycemia; with increasing duration of hypoglycemia and EEG silence, there are mitochondrial changes, first in dendrites and then in nerve cell soma, followed by nuclear membrane disruption leading to cell death.
Treatment of all forms of hypoglycemia obviously consists of correction of the hypoglycemia at the earliest possible moment. It is not known whether hypothermia or other measures will increase the safety period in hypoglycemia or alter the outcome. Seizures and twitching may not stop with antiepileptic drugs until the hypoglycemia is corrected.
Two syndromes have been defined, mainly in diabetics: (1) hyperglycemia with ketoacidosis and (2) hyperosmolar nonketotic hyperglycemia.
In diabetic acidosis, the familiar picture is one of dehydration, fatigue, weakness, headache, abdominal pain, dryness of the mouth, stupor or coma, and Kussmaul type of breathing. Usually the condition has developed over a period of days in a patient known or proven to be diabetic. Often, the patient had failed to take a regular insulin dose. The blood glucose level is found to be more than 400 mg/dL, the pH of the blood less than 7.20, and the bicarbonate less than 10 mEq/L. Ketone bodies and b-hydroxybutyric acid are elevated in the blood and urine, and there is marked glycosuria. The prompt administration of insulin and repletion of intravascular volume correct the clinical and chemical abnormalities over a period of hours.
A small group of patients with diabetic ketoacidosis, such as those reported by Young and Bradley, develop deepening coma and cerebral edema as the elevated glucose is corrected. Mild cerebral edema is commonly observed in children during treatment with fluids and insulin (Krane et al). Prockop attributed this condition to an accumulation of fructose and sorbitol in the brain. The latter substance, a polyol that is formed during hyperglycemia, crosses membranes slowly, but once it does so, is said to cause a shift of water into the brain and an intracellular edema. However, according to Fishman (1974), the increased polyols in the brain in hyperglycemia are not present in sufficient concentration to be important osmotically, though they may induce other metabolic effects related to the encephalopathy. These are matters of conjecture, as the increase of polyols has never been found. The brain edema in this condition is probably a result of reversal of the osmolality gradient from blood to brain, which occurs with rapid correction of hyperglycemia.
The pathophysiology of the cerebral disorder in diabetic ketoacidosis is not fully understood. No consistent cellular pathology of the brain has been identified in the cases we have examined. Factors such as ketosis, tissue acidosis, hypotension, hyperosmolality, and hypoxia have not been identified. Attempts at therapy by the administration of urea, mannitol, salt-poor albumin, and dexamethasone are usually unsuccessful, though recoveries are reported.