Insanity in its initial stage does not, as a rule, involve a recognizable deviation from the normal structure of the brain, and the patient may die before such pathological changes are so manifest that we can detect them. But if the disease has been of long standing, in the majority of cases the brain shows evident marks of disease, and there may be found no striking indication to the naked eye of deviation from a healthy condition, when a microscopic examination reveals signs of advanced cerebral disease. The limited knowledge of the cerebral structure and function which pathologists possess, and the consequent difficulty in detecting changes from the healthy state, indicate that the failure to find them is attributable in not a few instances to the fault of the investigator rather than to the nature of the disease. Certain it is that the better acquainted we have become with the anatomy of the brain and with its functions and sensible qualities, and the more thorough and painstaking we have been in our examinations, the rarer it has become to find a case of insanity where no organic changes are observed after death, although it is true that we do not understand all the relations between these changes and the symptoms observed during life. A large abscess of the brain, a hemorrhage, a tumor, or a wound of the cortex or other portion of the brain, various degrees of inflammation, {122} meningitis, are sometimes followed by insanity and sometimes not; and we do not yet understand the reason for the difference. Indeed, nearly every pathological condition of the brain known in insanity—in kind, if not in extent and degree—may be found in diseased or injured brains where there has been no mental disease in consequence. There is only one disease, general paralysis of the insane, in which the morbid appearances discoverable after death with our present knowledge bear a definite relation to the most constant manifestations during life. And yet, with pathological changes so similar that we are not able to detect their essential difference, the mental symptoms of the first stage of general paralysis may be most various. Rosenbach has found in the brains of starved dogs and guinea-pigs as extensive changes as in well-marked primary dementia, in which the pathological conditions are more extensive than in any other form of acute insanity.[7] That is to say, when we have discovered and described all the morbid appearances in the brain of an insane person we have taken only the first step in accounting for his insanity. [Footnote 7: _Centralblatt für Nevr. Psych. und ger. Med._, 1884, p. 33.]