Symmetrical ataxia of gait and limbs—affecting arms and legs more or less equally—dysarthria, and nystagmus are the usual manifestations; some have vertigo. Striking in fully developed cases has been the severity of the ataxia, matched by few other diseases. Occasionally, myoclonus and opsoclonus or a fast-frequency myoclonic tremor may be associated (“dancing eyes–dancing feet,” as noted later). In addition, there are quite often symptoms and signs not strictly cerebellar in nature, notably diplopia, vertigo, Babinski signs (common in our cases), sensorineural hearing loss, disorders of ocular motility, and alteration of affect and mentation—findings that serve to distinguish paraneoplastic from alcoholic and other varieties of cerebellar degeneration. Lambert-Eaton syndrome is known to occur with cerebellar degeneration as paraneoplastic illnesses, generally in association with anti-voltage-gated calcium channel (VGCC) antibodies. These are well emphasized in the series of 47 patients collected by Anderson and colleagues and the 55 cases by Peterson et al, who tabulated these noncerebellar neurologic features.
The CSF may show a mild pleocytosis (up to 50 cells/mm3 in a few of our patients) and increased protein, or it may be entirely normal. Early in the course of the disease, CT and MRI show no abnormality, but after a few months, atrophy of the brainstem and cerebellum may appear. In a few cases, T2-weighted MRI discloses increased signal of the cerebellar white matter (Hammack et al), but this has not been uniform in our experience, and furthermore does not correlate well to the presence or degree of
Purkinje cell loss (Fig. 30-25). FDG-PET may show hypometabolism in the cerebellum before the MRI changes are detectable.
Pathologically, there are diffuse degenerative changes of the cerebellar cortex and deep cerebellar nuclei. Purkinje cells are affected prominently and all parts of the cerebellar cortex are involved. Degenerative changes in the spinal cord, involving the posterior columns and spinocerebellar tracts, have been found rarely. The cerebellar neuronal degeneration is frequently associated with perivascular and meningeal clusters of inflammatory cells. Henson and Urich regard the inflammatory changes as an independent process, part of a subacute paraneoplastic encephalomyelitis (see in the following text). This view is supported by the finding that the specific antibodies linked to cerebellar degeneration differ from those found in paraneoplastic inflammatory lesions in other parts of the nervous system.