Faculty Collaboration Database

Differences in globus pallidus neuronal firing rates and patterns relate to different disease biology in children with dystonia. J Neurol Neurosurg Psychiatry 2016 Sep;87(9):958-67

Date

02/06/2016

Pubmed ID

26848170

Pubmed Central ID

PMC5013118

DOI

10.1136/jnnp-2015-311803

Scopus ID

2-s2.0-84958093532 (requires institutional sign-in at Scopus site)   41 Citations

Abstract

BACKGROUND: The pathophysiology underlying different types of dystonia is not yet understood. We report microelectrode data from the globus pallidus interna (GPi) and globus pallidus externa (GPe) in children undergoing deep brain stimulation (DBS) for dystonia and investigate whether GPi and GPe firing rates differ between dystonia types.

METHODS: Single pass microelectrode data were obtained to guide electrode position in 44 children (3.3-18.1 years, median 10.7) with the following dystonia types: 14 primary, 22 secondary Static and 8 progressive secondary to neuronal brain iron accumulation (NBIA). Preoperative stereotactic MRI determined coordinates for the GPi target. Digitised spike trains were analysed offline, blind to clinical data. Electrode placement was confirmed by a postoperative stereotactic CT scan.

FINDINGS: We identified 263 GPi and 87 GPe cells. Both GPi and GPe firing frequencies differed significantly with dystonia aetiology. The median GPi firing frequency was higher in the primary group than in the secondary static group (13.5 Hz vs 9.6 Hz; p=0.002) and higher in the NBIA group than in either the primary (25 Hz vs 13.5 Hz; p=0.006) or the secondary static group (25 Hz vs 9.6 Hz; p=0.00004). The median GPe firing frequency was higher in the NBIA group than in the secondary static group (15.9 Hz vs 7 Hz; p=0.013). The NBIA group also showed a higher proportion of regularly firing GPi cells compared with the other groups (p<0.001). A higher proportion of regular GPi cells was also seen in patients with fixed/tonic dystonia compared with a phasic/dynamic dystonia phenotype (p<0.001). The GPi firing frequency showed a positive correlation with 1-year outcome from DBS measured by improvement in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS-m) score (p=0.030). This association was stronger for the non-progressive patients (p=0.006).

INTERPRETATION: Pallidal firing rates and patterns differ significantly with dystonia aetiology and phenotype. Identification of specific firing patterns may help determine targets and patient-specific protocols for neuromodulation therapy.

FUNDING: National Institute of Health Research, Guy's and St. Thomas' Charity, Dystonia Society UK, Action Medical Research, German National Academic Foundation.

Author List

McClelland VM, Valentin A, Rey HG, Lumsden DE, Elze MC, Selway R, Alarcon G, Lin JP

Author

Hernan Gonzalo Rey PhD Assistant Professor in the Neurosurgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Child
Deep Brain Stimulation
Dystonia
Electrodes, Implanted
Globus Pallidus
Humans
Magnetic Resonance Imaging
Microelectrodes
Neural Inhibition
Neurons
Retrospective Studies
Severity of Illness Index
Tomography, X-Ray Computed