In a series of experiments with monkeys, Ranson demonstrated a number of autonomic effects upon stimulation of the hypothalamus. Subsequently, Byer and colleagues described large, upright T waves and prolonged QT intervals in patients with stroke, and since then it has been appreciated that other acute lesions of the brain—particularly subarachnoid hemorrhage and head trauma—may be accompanied by supraventricular tachycardia, ectopic ventricular beats, ventricular fibrillation, and other changes in the electrocardiogram. Cropp and Manning found that the changes seen in the ECG, particularly “cerebral T waves” and other reversible repolarization abnormalities, could occur almost instantaneously (too quickly for attribution to circulating factors) during surgery for a cerebral aneurysm. Most of the same effects can also be induced by very high levels of circulating norepinephrine and corticosteroids. Extreme emotional states can also provoke arrhythmias and other changes in the ECG. The hypothalamus, with its limbic connections and ability to mount a massive sympathoadrenal discharge, is the likely source of the autonomic changes in these various clinical situations.
Gastric Complications of Hypothalamic Dysfunction
In experimental animals, lesions placed in or near the tuberal nuclei induce superficial erosions or ulcerations of the gastric mucosa in the absence of hyperacidity (Cushing ulcers). Gastric lesions of similar type are seen in patients with several types of acute intracranial disease (particularly subdural hematoma and other effects of head injury, cerebral hemorrhages, and tumors). In seeking causative lesions in patients, for example those with head injury or subarachnoid hemorrhage, one searches in vain for a lesion in the various hypothalamic nuclei. An organic disorder in this region is nonetheless suspected.
Following the original observations by Maire and Patton in humans, numerous cases of massive and often fatal pulmonary edema have been described in relation to catastrophic intracranial lesions—most commonly head injury, subarachnoid and intracerebral hemorrhage, bacterial meningitis, or status epilepticus. A sudden elevation in intracranial pressure is involved in most cases, usually accompanied by a brief bout of extreme systemic hypertension without obvious left ventricular failure—which is one reason the pulmonary edema has been attributed to a “neurogenic” rather than a cardiogenic cause. Also, it has been shown that experimental lesions in the caudal hypothalamus are capable of producing this type of pulmonary edema, but almost always with the interposed event of brief and extreme systemic hypertension.
Both the pulmonary edema and hypertensive response can be prevented by sympathetic blockade, suggesting that the adrenergic discharge and the hypertension it causes are essential for the development of pulmonary edema. The rapid rise in vascular resistance and systemic blood pressure is similar to the pressor reaction obtained by destruction of the nucleus of the tractus solitarius, as described in Chap. 25, making understandable the few instances of neurogenic edema that have followed acute lesions in the medullary tegmentum (Brown). At issue is whether the hypothalamus exerts a direct sympathetic influence on the pulmonary vasculature, allowing a leakage of protein-rich edema fluid, or if the edema is the result of sudden and massive overloading of the pulmonary circulation by a shift of fluid from the systemic vasculature. The latter theory, essentially one of momentary right-heart failure, is currently favored but does not explain all aspects of the syndrome. Likewise, the role of circulating catecholamines and adrenal steroids has not been fully elucidated. These issues have been summarized in the text on neurologic intensive care by Ropper and colleagues.
Disorders of Consciousness and Personality