A sporadically occurring disorder closely resembling the Holmes type of cortical cerebellar degeneration but with additional features of brainstem atrophy was described in 1900 by Dejerine and André-Thomas, who named it olivopontocerebellar atrophy (OPCA). As more cases of this type were collected, an autosomal dominant hereditary pattern was evident in some, and one or more long tracts in the spinal cord were found to have degenerated. About half the cases later developed the parkinsonism with degeneration of nigral cells and, in a few, of striatal cells, thereby marking the disease as a form of striatonigral degeneration that is essentially a type of multiple system atrophy (MSA-C) as discussed in detail in an earlier section and also below. The main distinction from the Holmes type is that MSA-C involves degeneration of the ponto-cerebellar and olivocerebellar fibers.
Notable findings in both the sporadic and the familial forms of many of the variants of cerebellar atrophy are extensive degeneration of the middle cerebellar peduncles, cerebellar white matter, and pontine, olivary, and arcuate nuclei; loss of Purkinje cells has been variable. Most likely this degeneration represents a “dying back” of axons of the cerebellar, pontine, and olivary nuclei with secondary myelin degeneration. Extreme atrophy of the medullary olivary nuclei may be evident on MRIs but is usually more subtle (Fig. 38-9). In a personally observed series of 12 definite cases and a larger number of probable cases of MSA-C, our colleague Schmahmann (Lin et al) described autonomic features and REM-sleep behavior disorder and an older age of onset, and a faster disease progression as distinguished from idiopathic-sporadic late onset forms of cerebellar ataxias; both categories can have associated extrapyramidal features. Their series had a mean age of onset of symptoms of approximately the middle of the sixth decade and urinary dysfunction and erectile were particularly common.
Other complex forms of cerebellar degeneration Certain clinical constellations are recognizable and clinically useful. They were denominated by the person who described them or by a particular clinical feature but they are now classified as spinocerebellar ataxias (degenerations) and their genetic source (Table 38-5). For example, Konigsmark and Weiner subdivided these disorders into several types, including a dominantly inherited OPCA (of Menzel); a recessive type (of Fickler-Winkler); a dominant type with retinal degeneration; one with spastic paraplegia and areflexia; and with dementia, ophthalmoplegia, and extrapyramidal signs. To these had been added cases of OPCA with neuropathy and slowed eye movements (Wadia type), of which we have seen 2 cases, and cases with dystonia and a variety of other clinical findings, most in single families (hemiballismus, athetosis, contractures of the legs, fixed pupils, ophthalmoplegia, ptosis, gaze palsy, deafness, retinal degeneration, mental retardation and epilepsy, claw foot and scoliosis, incontinence, parkinsonian symptoms and signs, plethora of presentations including a neonatal type). Some of these are detailed below.
Cases of sporadic olivopontocerebellar atrophy are more common than the familial variety and tend to occur at an older age; nystagmus, optic atrophy, retinal degeneration, ophthalmoplegia, and urinary incontinence are generally not observed. However, there are numerous cases that include mild extrapyramidal and neuropathic signs, slow eye movements, dystonia, impairment of vertical saccadic eye movements (thus simulating progressive supranuclear palsy), vocal cord paralysis, all of which mark the process as multiple system atrophy (MSA-C) or Machado-Joseph-Azorean disease (SCA3, discussed below), and some cases with deafness.