Goldstein and associates compared a cohort of POTS patients with a group that experienced recurrent postural near-syncope and found that in the former group there was increased myocardial epinephrine release from intact cardiac sympathetic nerves. The basis for this is not known, although the researchers did exclude the possibility of defects in the cardiac norepinephrine transporter membrane and in norepinephrine synthesis.
This presents in two forms. In one, there is a selective degeneration of neurons in the sympathetic ganglia with denervation of smooth muscle vasculature and adrenal glands. The pathology has not been fully delineated, but lesions in other parts of the nervous system are not evident. In the second type, there is a degeneration of preganglionic neurons in the lateral columns of gray matter in the spinal cord, leaving postganglionic neurons isolated from spinal control. The latter lesion is often associated with degeneration of other systems of neurons in the CNS, particularly the basal ganglia but also the cerebellum. These processes are subsumed under the term multiple system atrophy, as discussed in Chap. 38. Parkinson disease and Lewy-body dementia may be associated with the same type of central loss of sympathetic neurons, but orthostatic hypotension and a variety of other features of autonomic insufficiency are early, more pronounced, and progressive in multiple system atrophy than in the other diseases named. Most of the dopaminergic drugs used in the treatment of Parkinson disease can exaggerate the hypotension. There are cases in which neuronal degeneration is limited to the sympathetic neurons of the intermediolateral cell columns—the Shy-Drager syndrome. All of these forms of degenerative disease have their onset in adult life, and the associated hypotension and syncope are usually part of a more widespread autonomic dysfunction that includes other features such as a fixed cardiac rate, vocal cord paralysis, a loss of sweating in the lower parts of the body, redness of the digits, atonicity of the bladder, constipation, and erectile dysfunction.
Syncope of Cardiac Origin
This is caused by a sudden reduction in cardiac output, usually because of an arrhythmia. Normally, a heart rate as low as 35 to 40 beats per minute or as high as 150 beats per minute is well tolerated, especially if the patient is recumbent. Changes in heart rate beyond these extremes impair cardiac output and may lead to syncope. Upright posture, anemia, and coronary, myocardial, and valvular disease all render the individual more susceptible to these alterations in heart rate and rhythm. Detailed discussions of the various valvular and myocardial abnormalities and arrhythmias that may compromise cardiac output and lead to syncope are to be found in the articles by Lipsitz, and by Kapoor and colleagues.