Oculomotor function is subtly affected in most patients (Leigh et al; Lasker et al). Particularly characteristic are impaired initiation and slowness of both pursuit and volitional saccadic movements and an inability to make a volitional saccade without movement of the head. Excessive distractibility may be noticed during attempted ocular fixation. The patient feels compelled to glance at extraneous stimuli even when specifically instructed to ignore them. Upward gaze is often impaired as the illness progresses.
As Wilson stated, the relation of the choreic to the mental symptoms “abides by no general rule.” Most often the mental symptoms precede the chorea but they may accompany or follow it, sometimes by many years. Once the movement disorder is fully established, there is nearly always some degree of cognitive abnormality. Exceptional cases have been reported in which the movement disorder existed for 10 to 30 years without mental changes (Britton et al); this would be most characteristic of patients with fewer CAG repeats. More typically, after 10 to 15 years of symptoms, most patients deteriorate to a vegetative state, unable to stand or walk and eating little; in this late stage, a mild amyotrophy may appear. Noteworthy is the high suicide rate, as pointed out by Huntington himself (see also Schoenfeld et al). Because there is a higher-than-normal incidence of head trauma, chronic subdural hematoma is another common finding at autopsy.
The first signs of the disease may appear in childhood, before puberty (even younger than the age of 4 years), and several series of such early-onset cases have been described (Farrer and Conneally; van Dijk et al). Mental deterioration at this early age is more often accompanied by cerebellar ataxia, behavior problems, seizures, bradykinesia, rigidity, and dystonia than by chorea (Byers et al). However, this rigid form of the disease (Westphal variant) also occurs occasionally in adults as mentioned above, in some cases because of HDL2. Functional decline is much faster in children than it is in adults (Young et al).
The dementia is generally more severe in cases of early onset and with correspondingly longer repeat lengths (15 to 40 years of age) than in those of later onset (55 to 60 years of age). In adult patients with early onset, the emotional disturbance tends to be more prominent initially and precedes the chorea and intellectual loss by years; with older age of onset, choreiform features are more often the initial components; in the middle years, dementia and chorea have their onset at nearly the same age. At the other extreme of age, the first features may become evident in the eighties, with orofacial or other dyskinesias that are mistakenly attributed to an exposure to neuroleptic drugs or called “senile chorea” (see Chap. 4).
Gross atrophy bilaterally of the head of the caudate nucleus and putamen is the characteristic abnormality, usually accompanied by a moderate degree of gyral atrophy in the frontal and temporal regions. The caudate atrophy alters the configuration of the frontal horns of the lateral ventricles in that the inferolateral borders do not show the usual bulge formed by the head of the caudate nucleus. In addition, the ventricles are diffusely enlarged (Fig. 38-4); in CT scans, the bicaudate-to-cranial ratio is increased, which corroborates the clinical diagnosis in the moderately advanced case.