Motor Control in Childhood Onset Dopa-Responsive Dystonia (Segawa Syndrome)*

Abstract

To elucidate the pathophysiological features of childhood onset dopa-responsive dystonia (DRD) we used a variety of quantitative analysis techniques to evaluate aspects of reflex- and voluntary motor control in two brothers with this disorder. The observed patterns were compared with those obtained in patients with adult onset Parkinson's disease (PD) and Huntington's disease (HD). In both brothers onset of the disease was in the first decade. Both responded either to treatment with L-Dopa or a combination of L-Dopa with trihexiphenidyl. Neurophysiological studies revealed slowing of different upper extremity voluntary motor activities and a low frequency postural tremor similar to results in other basal ganglia disorders including PD. In contrast to adult onset PD, fastest isometric voluntary index finger contractions did not show the typical kinetic tremor oscillations superimposed on the force trajectories. Also, different to adult PD, no impairment of stance regulating reflexes or saccadic and smooth pursuit eye movements was found in DRD. Magnetoelectrical stimulation of motor cortex showed normal efferent cortical spinal activity. Data indicate that like in other basal ganglia diseases slowing of voluntary motor activity is also a constant feature in DRD. DRD patients show, however, a clear difference to the pattern of motor abnormalities obtainable in PD. Both the pattern of motor control abnormalities is different, and the longlasting effect. In contrast to PD the pathophysiological mechanism in DRD possibly involves a lack of maturation of dopaminergic substantia nigra neurons rather than a degenerative process.

Dopa-responsive dystonia simulating spastic paraplegia due to tyrosine hydroxylase (TH) gene mutations

“…2,8 The paternally transmitted mutant allele with the deletion (296 del T) cannot produce any functional TH protein due to a lack of the whole catalytic and tetramerization domains in a C-terminal region of the enzyme. Our index patient was initially diagnosed as having spastic paraplegia.…”

Convergent mechanisms in etiologically-diverse dystonias

“…Segawa disease, or DOPA-responsive dystonia (DRD) [14-20] is characterized by childhood-onset generalized dystonia, in which symptoms are mild in the morning and worsen throughout the course of the day (diurnal fluctuation) [21,22]. This disorder is defined by the dramatic improvement in symptoms upon administration of low doses of L-DOPA.…”

Familial levodopa‐responsive parkinsonian‐pyramidal syndrome

“…Dopa-responsive dystonia (DRD) may begin with gait disturbances due to dystonia and parkinsonian features, and all patients described to date were 12 years old or younger at onset (13); none of our four patients had the diurnal fluctuations frequently seen in DRD. In some DRD patients, spasticity, tendon hyperreflexia, and extensor plantar responses were noted; because the corticospinal tracts were functionally normal in studies by stimulation of motor cortex as they are in idiopathic parkinsonism, the origin of these pyramidal signs is not clear (14,15). No dystonic posture was ever found in our patients during the long follow-up.…”