Objective: Deep brain stimulation (DBS) of the globus pallidus internus (GPi) is a highly effective symptomatic therapy for dystonia in X-linked dystonia-parkinsonism (XDP). A deeper understanding of pallidal neuronal activity in XDP may provide new insights into therapeutic strategies and basal ganglia function.

Background: XDP is a genetically determined neurodegenerative basal ganglia disorder with a sequential development of adult-onset dystonia and subsequent parkinsonism in most patients. The dystonic phase is characterised by substantial loss of spiny projections neurons in the striatal striosome compartment, which provide inhibitory control of dopaminergic neurons in the substantia nigra pars compacta. Conceptually, this loss of striosomal inhibition is discussed to increase dopamine levels in the striatum resulting in preponderance of the direct pathway, and thus causing a hyperkinetic state. In the subsequent Parkinsonian phase, the neurodegenerative process additionally involves the matrix components and striatal interneurons presumably leading to hypokinetic symptoms.

Method: We performed microelectrode recordings (unit activity and local field potentials (LFP)) in the globus pallidus externus (GPe) and GPi in 12 XDP patients undergoing DBS surgery under general anaesthesia. For disease controls, we obtained data from 10 patients with isolated dystonia and exploratory data from a patient with Parkinson’s disease (PD).

Results: LFP power spectra of XDP patients as well as patients with isolated dystonia were characterised by a prominent peak in the alpha-frequency range (~ 10 Hz). While the peak frequency was similar for XDP and dystonia, alpha power was significantly lower in the XDP group. Discharge rates of GPi single units were ~ 20 Hz and mean values were lowest for isolated dystonia followed by XDP and PD. A similar trend was observed for GPe firing rates. GPi units were significantly phase-locked to pallidal LFPs in a wide range of frequencies mainly below 10 Hz with a trend of more frequent phase-locking to frequencies >10 Hz in XDP patients.

Conclusion: The electrophysiological profile of GPi discharge characteristics was not different between patients with XDP and isolated dystonia under general anaesthesia, but confirms the firing rate model with lower firing rates in comparison to PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/characterization-of-pallidal-neuronal-activity-in-x-linked-dystonia-parkinsonism-a-model-disease-for-compartment-degeneration-in-the-striatum/