In fully developed cases, the MRI findings are of reduced width of the superior and middle cerebellar peduncles, atrophy of the frontal and temporal lobes, and smallness of the pons and globus pallidus (Murata et al). There is no treatment of proven value.
Dentatorubropallidoluysian Atrophy (DRPLA, ATN1)
This is a rare familial disorder, described mostly in Japan and in small European pockets, in which symptoms of cerebellar ataxia are coupled with those of choreoathetosis and dystonia and, in some instances, parkinsonism, myoclonus, epilepsy, or dementia. Pathologically there is degeneration of the dentatorubral and pallidoluysian systems. The main consideration when chorea is a prominent feature is the separation of this disorder from Huntington disease. The gene defect in DRPLA is an unstable CAG trinucleotide repeat in ATN1, which codes for the protein atrophin 1. This same mutation has been defined in affected families from throughout the world (e.g., Warner et al). Clinical manifestations are usually associated with 48 to 93 repeat triplets as compared to 7 to 35 in the general population. As with Huntington chorea (where the expanded polyglutamine sequence is in the protein huntingtin), this disease is inherited as an autosomal dominant trait and shows an inverse correlation between the age of onset and the size of the gene expansion (anticipation). When chorea predominates early in the illness, there may be difficulty distinguishing DRPLA from Huntington disease. The pathology has been summarized by Iizuka and colleagues. The diagnosis is confirmed by sequencing of the affected gene.
Dentatorubral degeneration This is a rare and still nebulous entity but it may be distinct from DRPLA. There are several instructive features and is listed here partly for historical reasons. In 1921, Ramsay Hunt published an account of 6 patients (2 of whom were twin brothers) in whom myoclonus was combined with progressive cerebellar ataxia. The age of onset in the 4 nonfamilial cases was between 7 and 17 years, and the cerebellar ataxia followed the myoclonus by an interval of 1 to 20 years. Hunt named the disorder dyssynergia cerebellaris myoclonica. There were signs of Friedreich ataxia in the twin brothers; postmortem examination of one showed cerebellar atrophy, degeneration of the posterior columns and spinocerebellar tracts but not of the corticospinal tracts. In 1947, Louis-Bar and van Bogaert reported a similar case and noted, in addition to the above findings, degeneration of the corticospinal tracts and loss of fibers in the posterior roots. Thus, the pathology was identical to that of Friedreich ataxia in their case except for the more severe atrophy of the dentate nuclei.
Earlier (1914), under the title dyssynergia cerebellaris progressiva, Hunt had drawn attention to a progressive disease in young individuals manifest by what he considered to be a pure cerebellar syndrome but one of his cases was revealed at autopsy to be Wilson disease. Hunt’s reports emphasize the hazard of classifying cerebellar ataxias on the basis of clinical findings alone, a point made effectively by Holmes.
Paroxysmal Ataxias (See Also Chap. 5)
Two adult forms of hereditary cerebellar ataxia are paroxysmal in nature. In one (EA-2 for “episodic ataxia, type 2”), the episodes occur without explanation and last several hours; vertigo is the prominent feature of the attacks. Between attacks the patient is normal or has only minimal ataxia and nystagmus (Griggs et al). These ataxic episodes are prevented strikingly by the administration of oral acetazolamide. The disorder has been found to be a mutation of the calcium channel gene on chromosome 19 as listed in Table 38-5.