1. The combination of raised cerebral blood pressure and ruptured blood-brain barrier often causes another problem, cerebral edema. The high pressure forces proteins and other substances out of the now "leaky" vessels into the brain tissue. As noted earlier, fluid tends to follow these substances and the tissue begins to swell. This process once started can become disastrous because a "vicious circle" is started. As the pressure inside the skull rises from the swelling, capillaries are closed. Their linings are damaged by anoxia making them even more leaky. This leads to more edema and damage (Fishman, 1975; Klatzo and Seitleberger, 1967). Edema has been noted in the human retina, an easily visible part of the brain, as a consequence of shock (Winnik, et al., 1966). Patients cannot be protected from this process by drugs that lower blood pressure, because the extra pressure is needed to supply the brain's huge metabolic needs during the seizure. It has been noted in experimental animals and man that rises in blood pressure accelerate the spread of edema (Fishman, 1975; Shutta, et al., 1968; Klatzo and Seitleberger, 1967) and the leakage of trace materials from the blood-brain barrier (Lee and Olszewski, 1961; Klatzo and Seitleberger, 1967). It has also been noted that individuals with high blood pressure "have a significant predisposition to cerebral edema" (Klatzo and Seitleberger, 1967, P.148). Where the swelling is great enough to block the blood supply to neurons .-- or even to slow it below the extreme needs of the active tissue -- nerve cells will become anoxic and die.

2. Even where there is adequate oxygen, neurons may die because they use up the metabolites that they need to function, It has been demonstrated that during a seizure, the "respiratory quotient" of the brain shifts markedly. This shift indicates a change in cerebral metabolism away from the use of glucose as fuel. Here is what a prominent neurology group had to say about the changes in cerebral metabolism that they measured during ECT-induced seizures in man:

   If endogenous substances essential to normal cerebral metabolism are depleted during seizures, one might expect post-ictal brain dysfunction until repletion even without hypoxia. At some point during repeated seizures, depletion of cerebral substances might become irreversible and permanent brain damage ensue. Thus, post ictal EEG flattening and coma need not imply cerebral hypoxia (Posner, et al., 1969, P.394).

   Translated into English, this means that even if the brain receives enough oxygen during a seizure. the brain may exhaust its sources of nutrients and be irreversibly damaged. It means that the abolition of electrical activity and the coma that sometimes follows a seizure can occur even though adequate oxygen is supplied.

3. There are changes in a host of brain chemicals as the result of ECT (reviewed by Essman, 1973). Synthesis of protein and RNA are inhibited within five minutes of ECS, with the decrease persisting for a number of hours. The levels of neural transmitters (acetylcholine, norepinephrine, serotonin) and their related enzymes also change. For example, acetylcholine and the enzyme that destroys it, acetyicholinesterase, fall after ECT but rise above normal levels within 2 hours. These changes are reflected in the choline levels in the cerebrospinal fluid, which in man and monkey are increased 24 hours following a single ECT and remain elevated for at least a week after multiple ECT. Changes in serotonin, an important neural transmitter, last up to 5 months. The time courses of these changes are very complex, and their meaning is not yet understood. Nevertheless, each of the chemicals listed has been shown to play some role in memory, and I would anticipate that significant changes in any one of them might contribute to the changes in memory that have been demonstrated to follow ECT.

4. Following ECT, there is a marked rise-in cerebral levels of arachidonic acid (Essman, 1973; Bazan, N.G., 1970, 1971). This compound has been shown to cause aggregation of blood platelets when injected d into the cerebral blood supply, resulting in small "strokes" throughout the brain (Furlow, T.W., Jr. and Bass, N.H., 1975). Conceivably the rise. in arachidonic acid associated with ECT could be a source of the brain damage to be described later.

Changes in the Electroencephalogram (E.E.G.)

The EEG changes markedly during and following ECT. Before describing these changes, it is necessary to explain what the EEG represents. The electrical activity of neurons can be studied in two ways -- either by recording the electrical activity of one neuron at a time to see how it responds to particular environmental events -- or by recording outside the skull from a large population of neurons and their supporting "glial" cells. It is something like pushing a microphone close to one member of an orchestra (single neuron) and listening to his theme or withdrawing the microphone in order to listen to the whole (EEG). In the first case, one can make out the individual notes; in the second, one hears the overall rhythm, pitch, and loudness, but blended in such a way that the detailed contributions cannot be discerned.. When the rhythms of millions of individual nerve cells are merged in the EEG, the resulting broader rhythms have fairly characteristic features in normal and pathological states. When something is wrong, one cannot identify precisely what it is -- especially since glial cells as well as nerve cells contribute to the EEG rhythm -- but one can be sure that something is wrong. In awake adults, a beta-rhythm is normally seen with a frequency of about 15-60/ sec. and an amplitude of 5-10uV (low voltage-fast activity). If the person closes his eyes, the rhythms, particularly over the visual area, may slow a little and increase in amplitude, changing to an alpha-rhythm of 8-10 sec., 5OuV. In sleep the rhythm slows to a delta-rhythm, still slower (1-5/sec.) and higher in amplitude (20-200uV).

These slow delta rhythms are rarely recorded in normal, awake adults. They do appear, however, in various pathological states and are interpreted as evidence of pathology such as tumor, epilepsy, raised intracranial pressure, mental deficiency, depression of consciousness by toxic or other factors. For example, lack of oxygen and lack of glucose in the brain both cause the appearance of these large, slow delta waves. Again, we cannot say precisely what these rhythms mean or how they arise from the individual elements, but they do seem to convey the overall "mood" of the brain.

It is not at all surprising that the EEG is altered during the ECT seizures because the seizure itself is an interruption of the normal electrical rhythms. Furthermore, it is to be expected that the EEG would be abnormal for some time after a seizure because of the outpouring of potassium ions from neurons. It is significant, however, that in many patients the EEG remains abnormal for many months. Here, I should like to cite several studies in some detail.