This process is discussed here because its main characteristic is a dystonia that is responsive to l-dopa, but most cases also have features of parkinsonism, which is why it was also mentioned in the earlier discussion of hereditary forms of Parkinson disease, especially in young patients. Following the description of the syndrome by Segawa and colleagues in 1976, others drew attention to this unique form of hereditary dystonia (Allen and Knopp; Deonna; Nygaard and Duvoisin). The pattern of inheritance is autosomal dominant and there is no ethnic predilection. Nygaard and colleagues found a linkage to the gene on chromosome 14q for the protein GTP cyclohydrolase 1 (GCH1 gene) that is implicated in the synthesis of tetrahydrobiopterin, a cofactor for tyrosine hydroxylase. It is likely that the mutation impairs the generation of dopamine, a prediction that accords with responsiveness of the parkinsonian and dystonic features to l-dopa. In one autopsied case (an accidental death), there was a reduction in the amount of tyrosine hydroxylase in the striatum and depigmentation but no cell loss in the substantia nigra (Rajput et al). The affected enzyme was reduced in the striatum, as was the level of dopamine.
The dystonic manifestations usually become evident in childhood, usually between 4 and 8 years of age; females outnumber males in a ratio of 3:2. Often the legs are first affected by intermittent stiffening, with frequent falls and peculiar posturing, sometimes the feet assuming an equinovarus position. The arms become involved as well as the truncal muscles; retrocollis or torticollis may appear. Within 4 to 5 years, all parts of the body, including the bulbar muscles, are involved. Mild parkinsonian features (rigidity, bradykinesia, postural instability) can usually be detected early in the course of the illness, but more characteristically they are added to the clinical picture several years later. In our own patients, and in several of those of Deonna, there was rigidity of the limbs as well as slowness of movement and a tremor at rest, all aspects more parkinsonian than dystonic. In still others, the clinical picture has been one of cerebral spastic diplegia.
The special feature of this juvenile dystonia-parkinsonism syndrome is the dramatic response of both the dystonic and parkinsonian symptoms to treatment with l-dopa. As little as 20-200 mg/d may eliminate the movement disorder and permit normal functioning. Unlike idiopathic
Parkinson disease, the medication can be continued indefinitely without the development of tolerance, wearing-off effects, or dyskinesias. Segawa disease accounts for some cases that had in the past been reported as juvenile
Parkinson disease. Another feature is the disappearance or marked subsidence of the symptoms after a period of sleep and worsening as the day progresses. This diurnal variation is shared with many of the inherited (and sporadic) forms of Parkinson disease listed in Table 38-3. Fluctuations of symptoms with exercise and menses and in the first month of pregnancy have been observed in some cases.
Torticollis and Other Restricted Dyskinesias and Dystonias (See Chap. 4)
With advancing age, a large variety of focal or regional movement disorders come to light. Various neurophysiologic abnormalities, summarized in Chap. 4, have been implicated. In the common restricted dystonias, localized groups of adjacent muscles manifest arrhythmic cocontracting spasms (i.e., agonist and antagonist muscles are activated simultaneously). The patient’s inability to suppress the dystonia and the recognition that it is for the most part beyond voluntary control distinguishes it from tics, habit spasms, and mannerisms described in