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

• Published in: Journal of neurology, neurosurgery and psychiatry Vol. 87; no. 9; pp. 958 - 967
• Main Authors: McClelland, V M, Valentin, A, Rey, H G, Lumsden, D E, Elze, M C, Selway, R, Alarcon, G, Lin, J-P
• Format: Journal Article
• Language: English
• Published: England BMJ Publishing Group LTD 01.09.2016; BMJ Publishing Group
• Series: Research paper
• Subjects: Anesthesia; Child; Deep Brain Stimulation - methods; Dystonia; Dystonia - physiopathology; Dystonia - therapy; Electrodes; Electrodes, Implanted; Globus Pallidus - physiology; Humans; Kinases; Magnetic Resonance Imaging; Medical imaging; Microelectrodes - statistics & numerical data; Movement Disorders; Neural Inhibition - physiology; Neurodegeneration; Neuroimaging; Neurons - physiology; Pathophysiology; Patients; Retrospective Studies; Severity of Illness Index; Tomography, X-Ray Computed; Wavelet transforms
• ISSN: 0022-3050; 1468-330X
• DOI: 10.1136/jnnp-2015-311803

BackgroundThe 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.MethodsSingle 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.FindingsWe 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).InterpretationPallidal 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.FundingNational Institute of Health Research, Guy's and St. Thomas’ Charity, Dystonia Society UK, Action Medical Research, German National Academic Foundation.