Deep brain stimulation (DBS) of the globus pallidus internus (GPi) can be an effective intervention for severe refractory dystonia. Nonetheless, outcomes are often variable and unpredictable. To improve and predict outcomes, further development of physiomarkers can be useful. In contrast to more established β (±13–30 Hz) local field potential (LFP) oscillations in Parkinson's disease, low‐frequency (4–12 Hz) oscillations (LFOs) are present in dystonia. 1 LFP recordings perioperatively demonstrate suppression of LFOs related to clinical improvement. 2 , 3 Furthermore, LFOs have been used as a physiomarker for adaptive DBS (aDBS). 3 , 4 Although it is understood that LFOs evolve, longitudinal evolution of LFOs and their relation to symptoms are not yet established. Here, we describe a 22‐day recording of LFOs with clinical correlations in a pediatric patient with generalized dystonia, who first received bilateral GPi DBS in a status dystonicus (SD) in 2019. 5
Patients and Methods
A 10‐year‐old patient with GNAO1‐related dystonia was presented at our emergency department with an impending SD, triggered by left lead malfunctioning. He underwent DBS revision surgery (day 0) and received a sensing‐enabled rechargeable device (Medtronic Percept RC, Minneapolis, MN) and a new left lead on the same position as the former lead. The neurostimulator was activated perioperatively with the following stimulation parameters: bilateral monopolar case (+), contacts 2 (right) and 9 (left), pulse width (90 μs), stimulation frequency 130 Hz, and stimulation amplitude 2.2 mA (right) and 2.7 mA (left). Brain sensing was activated, and a periodogram of LFPs was analyzed to identify a frequency band of interest to record every 10 minutes. Presence of dystonia (0 = absent, 1 = present) was assessed four times daily for each body part (arm, leg, face, and torso) and side (left/right). On day 7 the new left lead needed to be repositioned because his symptoms, predominantly right sided, did not improve sufficiently. LFPs were analyzed, and the periodogram underwent bandpass filtering from 1 to 100 Hz and bandstop filtering at 40 Hz for artifact removal. Subsequently, fitting oscillations and one‐over‐F 6 was applied. Longitudinal LFP band powers were normalized using z scores. After lead replacement on day 7, separate z scores were calculated pre‐ and postoperatively. Postoperative computed tomography imaging confirmed lead localization. Clinical scores and LFPs were plotted with a 5‐day moving average. Spearman's correlation was performed on dystonia severity estimation and mean LFP power.
Results
During a 1‐minute rest recording (day 0), a clear LFO peak was visible for the left GPi (Fig. 1A). The surrounding 5‐Hz spectrum (7.27–12.27 Hz) was used for chronic LFP recording for 22 days. No major mechanical movement artifacts were visible in the signal. Figure 1B shows the relation between severity for right‐sided dystonia and left GPi‐LFP power, with a significant correlation of −0.69 (P < 0.001). The right GPi is not shown because no clear LFP peak could be detected.
FIG. 1.
(A) Periodogram of a 1‐minute recording of local field potentials (LFP) on the first day, after preprocessing and applying fitting oscillations and one‐over‐F (FOOOF). The blue band represents the frequency of interest that was selected for the longitudinal LFP recording. (B) The relation between dystonia symptoms in green and the LFPs in blue, with a moving average of 5 days. [Color figure can be viewed at wileyonlinelibrary.com]
Discussion
Here, we demonstrated a strong correlation between LFOs and severity of dystonia, which further illustrates the importance of this physiomarker. 1 , 2 With sensing‐enabled DBS systems, LFO dynamics might function as a physiomarker to help titrating DBS for dystonia and guide treatment, potentially applied as aDBS in dystonia. 3 , 4
Full financial disclosures of all authors for the previous 12 months
J.M.D. received funding for research from the Netherlands Organisation for Health Research and Development (ZonMW), Medtronic, and Amsterdam Neuroscience, all paid to the institution. L.A.P. received a research grant from the ForWhishdom Foundation. P.R.S. received TKI‐PPP grants from the Ministry of Economic Affairs, Brainlab, and Boston Scientific, and support grants from the Dutch Brain Foundation. R.M.A.B. received research grants from Medtronic, Bial, ZonMw, AMC Foundation, ROMO Foundation, and Stichting ParkinsonFonds, all paid to the institution. M.B received research funding from the EU Joint Programme—Neurodegenerative Disease Research (JPND) project (2020 call), the Amsterdam UMC TKI‐PPP grant (2021 and2023 call), Stichting ParkinsonFonds (2023), and Medtronic (2023, 2024).
Author Roles
(1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical Analysis: A. Design, B. Execution, C. Review and Critique; (3) Manuscript Preparation: A. Writing of the first draft, B. Review and Critique.
D. H: 1A, 1B, 1C, 2A, 2B, 3A
L.R.H: 1A, 1B, 1C, 2C, 3A, 3B
M.J.S: 1C, 2C, 3B
J.M.D: 2C, 3B
P.R.S: 2C, 3B
R.M.A.B: 2C, 3B
L.A.P: 1B, 2C, 3B
M.B: 1A, 1B, 2C, 3B
Supporting information
Data S1. Supporting Information.
Deborah Hubers and Larissa R. Heideman have contributed equally to this study.
Funding agency: No specific funding was received for this work.
Potential conflict of interest: The authors declare that there are no conflicts of interest relevant to this work.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.
References
- 1. Piña‐Fuentes D, van Dijk JMC, Drost G, et al. Direct comparison of oscillatory activity in the motor system of Parkinson's disease and dystonia: a review of the literature and meta‐analysis. Clin Neurophysiol 2019;130:917–924. [DOI] [PubMed] [Google Scholar]
- 2. Barow E, Neumann WJ, Brücke C, et al. Deep brain stimulation suppresses pallidal low frequency activity in patients with phasic dystonic movements. Brain 2014;137:3012–3024. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3. Piña‐Fuentes D, Beudel M, Van Zijl JC, et al. Low‐frequency oscillation suppression in dystonia: implications for adaptive deep brain stimulation. Parkinsonism Relat Disord 2020;79:105–109. [DOI] [PubMed] [Google Scholar]
- 4. Johnson V, Wilt R, Gilron R, Anso J, et al. Embedded adaptive deep brain stimulation for cervical dystonia controlled by motor cortex theta oscillations. Exp Neurol 2021;345:113825. [DOI] [PubMed] [Google Scholar]
- 5. Beudel M, Dijk JM, Bakker DP, Strijbis EMM, Buizer AI, Schuurman PR, van de Pol LA. Dieper hersenstimulatie bij een kind met een status dystonicus. J Neurol Neurosurg 2022;123:327–333. [Google Scholar]
- 6. Donoghue T, Haller M, Peterson EJ, et al. Parameterizing neural power spectra into periodic and aperiodic components. Nat Neurosci 2020;23:1655–1665. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data S1. Supporting Information.
Data Availability Statement
The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.