It is impossible in every instance to decide whether a given state of wakefulness is the result of cerebral hyperæmia or anæmia. In the one case the persistence of wakeful activity of the mind is due to excitement of the cerebral cells, accompanied by a lavish irrigation of their substance with the plasma of the blood. In the other case the excitement is occasioned, not so much by increased afflux of the blood, as by a morbid instability of the nervous substance. The outcome in both cases is very similar--mental excitement and wakefulness. In a third class of cases the agitation of the brain is produced by the direct action of certain chemical agents upon the cortical substance. Tea and coffee are familiar examples of such agents. The caffeine, by virtue of which they produce their effect, when transported to the brain, enters into combination with its protoplasm in such a way as to stimulate molecular movement. Perception is thus quickened, and the mind is aroused. Sleep is postponed until the effect of the stimulant has subsided. This form of wakefulness is quite different from that produced by alcoholic drinks. These operate, when taken in small quantities, to favor cerebral equilibrium--and consequent equanimity--by producing a general dilatation of the smaller blood-vessels. Their anæsthetic influence is favorable to sleep, under such circumstances. But, if frequently repeated, these doses of alcohol modify the nutrition of the nervous system until, at last, a condition of irritable weakness is reached, in which wakefulness of a most distressing character is experienced. _Inflammations, degenerations, and neoplasms._--The early stages of inflammation involving the central nervous organs are marked by that form of insomnia which is associated with active hyperæmia. The headache and painful delirium which accompany the different varieties of meningitis, are causes of a wakefulness that persists until the brain is merged in the coma of compression. The interstitial changes which cause the various forms of insanity, are in like manner causes of wakefulness. Local injuries and degenerations of brain-substance, tubercular deposits upon the meningies, and all the different forms of intra-cranial tumor, are causes of wakefulness, both by reason of the direct irritation which they produce, and by reason of the circulatory disturbances which arise in their neighborhood.