Postmortem examination of patients, originally reported by Rebeiz and colleagues, disclosed a combination of findings that differentiated the disease process from other neurodegenerative conditions. Cortical atrophy (mainly in the frontal motor–premotor and anterior parietal lobes) was associated with degeneration of the substantia nigra and, in one instance, of the dentatorubrothalamic fibers. The loss of nerve cells was fairly marked, but there was no gross lobar atrophy, as occurs in Pick disease. The neuronal degeneration was more on one side of the brain than the other. There was moderate gliosis in the cortex and underlying white matter. The disease is now clearly considered to be related to tau deposition in specific brain structures; however, the original authors were more impressed with ballooned and chromatolytic neurons with eccentric nuclei, a state that was called neuronal achromasia. The presence of these achromatic cells in posterior frontal and parietal neurons continues to be considered an essential feature of the disease, although the rounded areas within neurons stain for tau and resemble globose tangles that are found occasionally in Alzheimer disease (corticobasal bodies); in this way, CBGD is connected to the other tau-related neurodegenerative diseases, or “tauopathies.” In addition, adjacent glia are filled with various configurations of tau protein, thereby linking the disease to frontotemporal lobar degeneration and PSP. Our colleague Feany, with Dickson, has identified one type of these as “plaques” in the cortex that are composed of tau aggregates within the distal processes of astrocytes.
Both CT and MRI have demonstrated asymmetrical cerebral and pontine atrophy, and PET studies have revealed thalamoparietal metabolic asymmetries—a greater reduction of glucose metabolism on the side of the most extensive lesion (Riley et al).
There are no clues as to the pathogenesis of this disease. There are rare familial types but no definite genetic cause has been identified. No organ other than the CNS is affected. The progression is relentless. None of the drugs in common use for spasticity, rigidity, and tremor has been helpful.
Included in this category are a heterogeneous group of degenerative diseases in which the symptoms of parkinsonism and corticospinal degeneration are present in various combinations. Some of the diseases that make up this group have not been sharply delineated and are difficult to separate from one another. Moreover, the relationship of this process to the better defined corticobasal degeneration, explained above, is indeterminate.
Under the title “Spastic Pseudosclerosis,” Jakob, in 1921, described a chronic disease of middle to late adult life, characterized by abnormalities of behavior and intellect; weakness, ataxia, and spasticity of the limbs (chiefly the legs); extrapyramidal symptoms such as rigidity, slowness of movement, tremors, athetotic postures, and hesitant, dysarthric speech; and normal spinal fluid. The pathologic changes were diffuse and consisted mainly of an outfall of neurons in the frontal, temporal, and central motor gyri, striatum, ventromedial thalamus, and bulbar motor nuclei. In one of Jakob’s cases, there were also prominent changes in the anterior horn cells and corticospinal tracts in the spinal cord like those of ALS. The latter finding gave rise to Wilson’s concept of the disease as a corticostriatospinal degeneration. Some restricted cases bear a resemblance to the type of frontotemporal dementia that occurs with motor neuron disease.