Several toxic and pharmacologic agents such as cocaine and phenylpropanolamine are capable of producing abrupt overactivity of the sympathetic and parasympathetic nervous systems—severe hypertension and mydriasis coupled with signs of CNS excitation—sometimes including seizures. Tricyclic antidepressants in excessive doses are also known to produce autonomic effects, but in this case cholinergic blockade leads to dryness of the mouth, flushing, absent sweating, and mydriasis. The main concern with tricyclic antidepressant overdose is the development of a ventricular arrhythmia, also on an autonomic basis, presaged by prolongation of the QT interval on the ECG. Poisoning with organophosphate insecticides (e.g., Parathion), which have anticholinesterase effects, causes a combination of parasympathetic overactivity and motor paralysis (see discussion of poisonings in Chap. 41). A severe autonomic disturbance involving both postganglionic sympathetic and parasympathetic function is produced by ingestion of the rodenticide N-3-pyridylmethyl-N′-p-nitrophenylurea (PNU, Vacor). The exaggerated sympathetic state that accompanies tetanus—manifest by diaphoresis, mydriasis, and labile or sustained hypertension—has been attributed to circulating catecholamines.
Among the most dramatic syndromes of unopposed sympathetic-adrenal medullary hyperactivity occur in cases of severe head injury and with hypertensive cerebral hemorrhage. Three separate mechanisms of the hypersympathetic state are observed at different times after the injury or cerebral hemorrhage: an outpouring of adrenal catecholamines at the time of the ictus with acute hypertension and tachycardia; a brainstem-mediated vasopressor reaction (Cushing response, described in the following pages); and a later chronic phenomenon, consisting of episodes of extreme hypertension, profuse diaphoresis, and pupillary dilatation, usually arising during episodes of several minutes’ duration of rigid extensor posturing (the “diencephalic autonomic seizures” of Penfield, described later and in Chap. 34 in relation to head injury). Most patients who exhibit such paroxysms are decorticate from traumatic lesions of the deep cerebral white matter or from acute hydrocephalus (the likely explanation of Penfield’s and Jasper’s cases); in any case, they are clearly not epileptic. These attacks may be the result of the removal of inhibitory influences on the hypothalamus, creating, in effect, a hypersensitive decorticated autonomic nervous system.
Regarding the acute sympathetic reaction, experimental evidence suggests that nuclei in the caudal medullary reticular formation (reticularis gigantocellularis and parvocellularis) can precipitate severe hypertensive reactions. These nuclear centers are tonically inhibited by the NTS, which receives afferent input from arterial baroreceptors and chemoreceptors. Bilateral lesions of the NTS therefore produce extreme elevations in blood pressure, and this abrupt rise plays a role in the genesis of “neurogenic” pulmonary edema. These sympathetically mediated effects are eliminated by sectioning of the cervical spinal cord and by alpha-adrenergic blockade.