About a Peculiar Disease of the Cerebral Cortex

Case Report

A reports about the case of a patient that had been observed in the insane asylum in Frankfurt a. M.; and whose central nervous system was let to him for examination by Director Sioli. The inherent clinical presentation of the case had already yielded such a deviant clinical picture that it could not be subsumed under any previously known disease; anatomically a divergence from all previously known disease processes emerged.

A woman of 51 years presented with ideas of jealousy toward her husband as the first apparent illness sign. Soon, a rapidly worsening memory weakness was noticeable; she could no longer negotiate her way around her dwelling; dragged objects back and forth and hid them; and at times she believed she was about to be murdered and started yelling loudly.

Her overall presentation in the institution bore the mark of complete perplexity. She is entirely disoriented to time and place. Once in a while she makes comments that she does not understand anything going on; or has lost track of things.^a Occasionally she welcomes the doctor as if he were visiting, and apologizes that she is not yet finished with her chores; occasionally she loudly yells that he would proceed to cut her;^b or she dismisses him full of outrage with phrases indicating she dreads some action of his against her “female honour.” Intermittently she is completely delirious; drags her bedclothes around; calls for her husband and her daughter; and appears to have auditory hallucinations. Oftentimes she yells for many hours with horrible voice.

As soon as one tries to undertake an examination of her, she always reverts to loud yelling upon her inability to comprehend the situation. Only through numerous repetitive efforts was it eventually possible to elicit some information.

Her ability to retain information is impaired to the profoundest degree. When shown objects, she mostly labels them correctly; but soon thereafter she has forgotten everything again. While reading out loud she slips from one line to another; reads by spelling single characters or with senseless accentuation; while writing she repeats single syllables many times while omitting others; her efforts generally cease very rapidly. While speaking, she frequently uses awkward structure; single paraphasic terms (i.e., milk pourer instead of cup); sometimes one observes that the patient remains stuck altogether. Apparently, she does not comprehend some questions at all. She does not seem to recall the use of various individual objects. The gait is undisturbed; she uses her hands both equally well. The patellar reflexes are present. The pupils react. Slightly rigid radial arteries, no enlargement of cardiac dullness, no protein.^c

During further illness course, the phenomena to be interpreted as focal symptoms appear to wax and wane; overall they are always mild only. In contrast, the general loss of intelligence makes progress.^d Death occurs after four and one-half years of illness duration. The patient was eventually completely dull; lying in bed with legs pulled up; had let go under her^e and developed decubitus despite all care.

The section yielded an evenly atrophic brain without macroscopic foci. The larger brain vessels show atherosclerotic changes. In preparations that are stained according to the silver method of Bielschofsky, very peculiar changes of neurofibrils are observable. Initially, through their particular thickness and particular stainability, a single one or a few fibrils come to prominence on the inside of an otherwise still “normal” appearing cell. Then, during further progression, many such fibrils running next to each other show changes in the same way. They subsequently fold together into dense bundles and move towards the cell surface. Eventually the nucleus and the cell disintegrate, and only a tangled bundle of fibrils indicates the place which had formerly been occupied by a ganglion cell.

Since these fibrils are stainable with other dyes than normal neurofibrils, a chemical transformation of the fibril substance must have taken place; which appears to be the cause for the fibrils' persistence after demise of the cell. The transformation of the fibrils seems to go hand in hand with the deposition of a not yet more closely examined pathological metabolic product into the ganglion cell. Around one-fourth to one-third of all ganglion cells in the brain cortex show such changes. Numerous ganglion cells, particularly in the upper cell layers, have completely disappeared.

Dispersed over the entire cortex and especially numerous in the upper layers, one finds miliar foci; which are due to storage of a peculiar matter into the cortex. It^f can be detected even without staining; but remains very refractory to dyes.

The glia have produced abundant fibers; concurrently many glia show large fatty sacks. Infiltration of vessels is completely absent. Conversely, one is able to see signs of excess proliferation in the endothelium; here and there also a neovascularization.

All in all recaptured, we apparently appear to have in front of us a peculiar disease process. In recent years, such peculiar disease processes have been detected in growing numbers. This observation will have to suggest to us that we should not let ourselves satisfied with trying to include—with mobilization of many an effort—any clinically unclear illness case into one of the diagnostic entities known to us. There are without any doubt many more psychic illnesses than listed in our textbooks. In some of these instances a later histological examination will subsequently reveal peculiarities of the specific case. Then, we will gradually arrive at a stage, when we will be able to separate out individual disease from the large illness categories of our textbooks; to delineate them clinically more accurately.

Discussion

There are already two excellent English translations of Alzheimer's original article.^2,3 The quest of this translation, performed by the first author, was to capture even more of the content and structure set forth in the original case report. Occasionally, English grammar conventions, such as those requiring the use of certain tenses or singular/plural, had to be omitted in the interest of capturing an accurate picture of what was originally said; similarly, sentence structure has been kept as close to the original as possible. Previous translations, including that of Jarvik and Greenson's,⁴ are faithful to content, but have assumed a less literal technical standpoint than we have. For example, these authors, while writing coherently and fluently, have lost subtle nuances in their translation, i.e., the patient is described in English as presenting as “suspicious of her husband” when in fact phenomenologically, in the original German translation, she is jealous of him; or “using her hands well” when she is rather using her hands both equally well, referring to the absence of focal or lateralizing signs. Similar minor misconceptions appear in other translations.⁵ This author for example describes that “… the patient's central nervous system was examined by Director Sioli,” when it was factually examined by Alzheimer himself; or “… the peculiar matter (i.e., the amyloid) … was much more evident when stained,” when Alzheimer originally had reported, quite to the contrary, that “…it is very refractory to dyes.” By rendering an English version closer to the original German, we trust we have contributed toward preserving its historical accuracy. In doing so, we pay our own tribute to Professor Alzheimer and his patient, Auguste, almost 100 years since her demise and his landmark publication. We continue to be inspired by his recommendation that we strive to constantly improve disease classification by means of accurate description.