From off-period dystonia to peak-dose chorea. The clinical spectrum of varying subthalamic nucleus activity

P. Krack
Brain. 1999-06-01; 122(6): 1133-1146
DOI: 10.1093/brain/122.6.1133

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1. Brain. 1999 Jun;122 ( Pt 6):1133-46. doi: 10.1093/brain/122.6.1133.

From off-period dystonia to peak-dose chorea. The clinical spectrum of varying
subthalamic nucleus activity.

Krack P(1), Pollak P, Limousin P, Benazzouz A, Deuschl G, Benabid AL.

Author information:
(1)Department of Clinical and Biological Neurosciences, Joseph Fourier
University, Grenoble, France.

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.

DOI: 10.1093/brain/122.6.1133
PMID: 10356065 [Indexed for MEDLINE]

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