The effect of chronic bilateral high-frequency stimulation of the subthalamic nucleus (STN) on
levodopa-induced dyskinaesias was investigated in eight patients with fluctuating
Parkinson's disease complicated by functionally disabling off-period
dystonia. All of the patients also had severe diphasic and peak-dose
chorea, so that it was possible to study the effect of high-frequency stimulation on the different types of
levodopa-induced dyskinaesias. Off-period fixed
dystonia was reduced by 90% and off-period
pain by 66%. After acute
levodopa challenge, high-frequency stimulation of the STN reduced diphasic mobile
dystonia by 50% and peak-dose choreic dyskinaesias by 30%. The effect of bilateral high-frequency stimulation of the STN on the Unified Parkinson's Disease Rating Scale motor score had the same magnitude as the preoperative effect of
levodopa. This allowed the
levodopa dose to be reduced by 47%. The combination of reduced medication and continuous high-frequency stimulation of the STN reduced the duration of on-period diphasic and peak-dose dyskinaesias by 52% and the intensity by 68%. Acute high-frequency stimulation of the STN mimics an acute
levodopa challenge, concerning both
parkinsonism and dyskinaesias, and suppresses off-period
dystonia. Increasing the voltage can induce repetitive dystonic dyskinaesias, mimicking diphasic
levodopa-induced dyskinaesias. A further increase in voltage leads to a shift from a diphasic-pattern
dystonia to a peak-dose pattern choreodystonia. Chronic high-frequency stimulation of the STN also mimics the benefit of
levodopa on
parkinsonism and improves all kinds of
levodopa-induced dyskinaesias to varying degrees. Off-period
dystonia, associated with neuronal hyperactivity in the STN is directly affected by stimulation and disappears immediately. The effect of chronic high-frequency stimulation of the STN on diphasic and peak-dose dyskinaesias is more complex and is related directly to the functional inhibition of the STN and indirectly to the replacement of the pulsatile dopaminergic stimulation by continuous functional inhibition of the STN. Chronic high-frequency stimulation of the STN allows a very gradual increase in stimulation parameters with increasing beneficial effect on
parkinsonism while reducing the threshold for the elicitation of stimulation-induced dyskinaesias. In parallel with improvement of
parkinsonism, the
levodopa dose can be gradually decreased. As diphasic dystonic dyskinaesias are improved to a greater degree than peak-dose dyskinaesias, both direct and indirect mechanisms may be involved. Peak-dose choreatic dyskinaesias, associated with little evidence of
parkinsonism and thus with low neuronal activity in the STN, are improved, mostly indirectly. Fixed off-period
dystonia, mobile diphasic
dystonia and peak-dose choreodystonia seem to represent a continuous clinical spectrum reflecting a continuous spectrum of underlying activity patterns of STN neurons.