Characterize novel neural correlates of status dystonicus (SD) and assess their relation to clinical severity.
SD is an emergency with severe episodes of dystonia, necessitating urgent hospital admission. Deep brain stimulation (DBS) of the globus pallidus interna (GPi) is a treatment for refractory SD. Intracranial neural correlates to SD-states and corresponding clinical severity are unknown.
Methods:
Nine patients with SD (Hospital for Sick Children, Canada) were implanted with sensing-capable Medtronic Percept™GPi DBS (age: 7.8±3.6). Local Field Potentials (LFPs) were recorded at multiple time points during SD and after recovery in non-SD states longitudinally (6-36 months; range: 11-1155 days; average: 319±358 days) and Power Spectral Densities (PSDs) calculated (Welch-method). Analysis of PSD periodic and aperiodic components was performed using fitting-oscillations/one-over-f methods. Band-limited power (Theta: 3-7Hz; Alpha: 7-12.5Hz, Beta: 12.5-30Hz, Gamma: 30-60Hz) was calculated. Intra-pallidal functional connectivity in SD and non-SD was computed using magnitude squared coherence (MSC) between outer (contact 3-referenced-to-2) and inner (1-to-0) GPi. Mixed effects models (MEMs) assessed relations between LFP metrics and clinical scales, including Burke‐Fahn‐Marsden Dystonia Rating Scale (BFMDRS) and Pediatric Quality of Life Score (PedsQL).
Results:
Across all patient recordings at optimal contact points, the peak power of the periodic component of the LFP in the beta-band (p=0.01) and band-limited beta-band power (p<0.001) increased in SD compared to non-SD. GPi beta-band MSC (p<0.001) increased in SD (0.24±0.10) from non-SD (0.16±0.08). MEMs controlling for random effects of patient and time determined significant correlation (R2=0.80) between decreased PedsQL and increased beta power (p=0.004; intercept p=0.007). Results were beta-band specific with no significant associations with theta (p=0.793) or alpha-band power (p=0.877). Similar results were seen for PedsQL motor-subscores but not BFMDRS.
Excessive pallidal beta-band activity and functional connectivity are newly described biomarkers of SD, correlating with clinical severity.