Format

Send to

Choose Destination
See comment in PubMed Commons below
J Neurol Neurosurg Psychiatry. 2016 Sep;87(9):958-67. doi: 10.1136/jnnp-2015-311803. Epub 2016 Feb 4.

Differences in globus pallidus neuronal firing rates and patterns relate to different disease biology in children with dystonia.

Author information

  • 1Department of Clinical Neurophysiology, King's College Hospital NHS Foundation Trust, London, UK Department of Basic and Clinical Neuroscience, King's College London, London, UK.
  • 2Department of Clinical Neurophysiology, King's College Hospital NHS Foundation Trust, London, UK Department of Basic and Clinical Neuroscience, King's College London, London, UK Department of Human Physiology, Faculty of Medicine, Complutense University, Madrid, Spain.
  • 3Centre for Systems Neuroscience, University of Leicester, Leicester, UK.
  • 4Rayne Institute, King's College London, London, UK Complex Motor Disorder Service, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.
  • 5Department of Statistics, University of Warwick, Coventry, UK.
  • 6Department of Functional Neurosurgery, King's College Hospital NHS Foundation Trust, London, UK.
  • 7Complex Motor Disorder Service, Evelina Children's Hospital, Guy's and St Thomas' NHS Foundation Trust, London, UK.

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.

PMID:
26848170
PMCID:
PMC5013118
DOI:
10.1136/jnnp-2015-311803
[PubMed - in process]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center