Box 2.

Subcortical atrophy group, comprising subforms described and named by Alzheimer and Binswanger (condensed excerpts).

Arteriosclerotic brain degeneration (arteriosklerotische Hirndegeneration). Described by both Alzheimer and Binswanger, macro- and microscopically7. Course of months or years, with periodic attacks, progressing to severe dementia. Reminiscent personality, insight and judgement, ordered behavior, consciousness of disease, maintained until later stages (as opposed to Paralysis [neurolues]). Neurologic signs (absence or late appearance of pupillary rigidity, slowing of speech, cephalic, truncal and appendicular paresis, hemiparesis, and following attacks, ataxia and aphasia) helpful for diagnosis7. Brain weight loss, ventricular enlargement, widened vessel holes [perivascular spaces], discoloration and atrophy of adjacent tissue, especially of the basal ganglia and internal capsule, on gross examination. Microscopy with focal changes in the white matter and cortex, degeneration and loss of numerous ganglion cells; myelinated cortical fibers (tangential layer), radiations and deep white matter greatly decreased. Alzheimer indicated diseased long vessels of the white matter, with resulting secondary medullary [white matter] degeneration, as the main cause7,8.

Chronic progressive subcortical encephalitis (Encephalitis subcorticalis chronica progressiva). Described by Binswanger (1894), and named after him by Alzheimer (1902). Binswanger’s text partially quoted by Alzheimer (1898)7, emphasizing prominent atrophy of the white matter attributed to nourishment disturbance due to severe arteriosclerosis, affecting one or several gyri, and when marked, an entire brain lobe, preferentially of posterior brain slices, with inferior and posterior horn enlargement, on macroscopy7. Theme revisited by Alzheimer (1902), with some divergent gross findings, and addition of microscopic examination9. Mildly narrowed, but deeply sunken gyri, well preserved cortex, shrunken and discolored white matter, enlarged ventricles, on gross neuropathology. Scarcely affected cortex (Nissl preparations), even in advanced stages, deep white matter lacking or highly pale in many places, with gyral core white matter, and short subcortical association fibers preserved, on microscopy. Alzheimer indicated severe arteriosclerosis of the long vessels of the deep white matter, causing the highest atrophic changes, as the underlying cause9. Clinical course, according to Binswanger, as quoted by Alzheimer, characterized by slow decline of mental strength, difficulty and finally loss of the associative linking between certain cortical sensory areas or motor regions, with varied symptoms (hemianopia, hemiparesis with sensory loss, decline of the intellect). Protracted evolution, and in the terminal stage the patients becoming comparable to brainless experimental animals7. Later, Alzheimer added the emergence of a difficulty of association of ideas, followed by gradual language deficits, and often linguistic association difficulties. Spells (dizziness, epileptic, apoplectic), with related symptoms (visual field constriction, asymbolia, sensory and motor aphasia, agraphia, monoparesis, hemiparesis, among others) might occur, often disappearing, but tending to recur and remain stable; consciousness of disease maintained for a long period, despite deep mental decay; appearance of severe dementia, lasting for years, or progressing to death within months9.

Arteriosclerotic atrophy of hemispheric white matter (arteriosklerotische Atrophie des Hemisphärenmarkes). Alzheimer presented and named a short account of this subform. The cause lay in arteriosclerotic degeneration of the long vessels of the white matter, associated with loss of myelinated fibers, and vanished white matter replaced by glial proliferation. White matter atrophy could eventually reach severe degrees, the cerebral cortex, in pure cases, being only secondarily affected8.