Intermuscular coherence as a biomarker of subthalamic nucleus deep brain stimulation efficacy in Parkinson's disease.

OBJECTIVE: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an established treatment in advanced Parkinson's disease (PD). However, the clinical outcome after STN-DBS is variable. The aim of this study was to explore the coherence of antagonistic muscles measured with electromyography (EMG) as novel biomarker of STN-DBS efficacy in PD. METHODS: EMG of bilateral wrist and upper arm antagonistic muscles of 21 PD patients was recorded during three standardized motor tasks. Patients were measured one day prior to DBS surgery (pre-DBS) and 6 months afterwards (post-DBS). Coherence analyses were performed on the antagonistic muscle pairs. Pearson correlations between intermuscular coherence and clinical performance were calculated. RESULTS: Intermuscular coherence during each of the different co-contraction tasks significantly correlated to UPDRS-III bradykinesia scores (p < 0.01). In other words, higher intermuscular coherence is associated with more severe PD symptoms. Moreover, coherence changes (pre-DBS - post-DBS coherence) correlated to clinical score changes after DBS (p < 0.01) and pre-DBS coherence correlated to this clinical score change as well (p < 0.01). CONCLUSIONS: Higher pre-DBS coherence of antagonistic arm muscles is correlated to worsening of clinical PD state and higher intermuscular coherence predicts enhanced clinical improvement. SIGNIFICANCE: We propose that pre-DBS intermuscular coherence could be developed into a predictor of STN-DBS clinical outcome. It could aid patient selection and adaptive stimulation algorithms for DBS.

Low-frequency oscillation suppression in dystonia: Implications for adaptive deep brain stimulation.

BACKGROUND: Low-frequency oscillations (LFO) detected in the internal globus pallidus of dystonia patients have been identified as a physiomarker for adaptive Deep Brain Stimulation (aDBS), since LFO correlate with dystonic symptoms and are rapidly suppressed by continuous DBS (cDBS). However, it is as yet unclear how LFO should be incorporated as feedback for aDBS. OBJECTIVES: to test the acute effects of aDBS, using the amplitude of short-lived LFO-bursts to titrate stimulation, to explore the immediate effects of cDBS on LFO-modulation and dystonic symptoms, and to investigate whether a difference in the resting-state LFO is present between DBS-naïve patients and patients with chronic DBS. METHODS: seven patients were assessed during either DBS-implantation (n = 2) or battery replacement surgery (n = 5), and pseudorandomized in three conditions: no stimulation, cDBS, and aDBS. Additionally, resting-state LFP-recordings from patients undergoing battery replacement were compared to those obtained during DBS-implantation; LFP-recordings from a previous cohort of six dystonia patients undergoing DBS-implantation were incorporated into this analysis (total n = 8 newly implanted patients). RESULTS: we corroborated that a mild LFO-suppression rapidly occurs during cDBS. However, no acute changes in clinical symptoms were observed after cDBS or aDBS. Remarkably, we observed that resting-state LFO were significantly lower in patients who had been effectively treated with chronic cDBS compared to those of newly implanted patients, even when stimulation was suspended. CONCLUSIONS: our results indicate that LFO-suppression in dystonia, similar to symptom response to cDBS, might be gradual, and remain after stimulation is suspended. Therefore, tracking gradual changes in LFO may be required for aDBS implementation.

Intermuscular coherence as biomarker for pallidal deep brain stimulation efficacy in dystonia.

OBJECTIVE: Finding a non-invasive biomarker for Globus Pallidus interna Deep Brain Stimulation (GPi-DBS) efficacy. Dystonia heterogeneity leads to a wide variety of clinical response to GPi-DBS, making it hard to predict GPi-DBS efficacy for individual patients. METHODS: EEG-EMG recordings of twelve dystonia patients who received bilateral GPi-DBS took place pre- and 1 year post-surgery ON and OFF stimulation, during a rest, pinch, and flexion task. Dystonia severity was assessed using the BFMDRS and TWSTRS (pre- and post-surgery ON stimulation). Intermuscular coherence (IMC) and motorcortex corticomuscular coherence (CMC) were calculated. Low frequency (4-12 Hz) and beta band (13-30 Hz) peak coherences were studied. RESULTS: Dystonia severity improved after 1 year GPi-DBS therapy (BFMDRS: 30%, median 7.8 (IQR 3-10), TWSTRS: 22%, median 6.8 (IQR 4-9)). 86% of IMC were above the 95% confidence limit. The highest IMC peak decreased significantly with GPi-DBS in the low frequency and beta band. Low frequency and beta band IMC correlated partly with dystonia severity and severity improvement. CMC generally were below the 95% confidence limit. CONCLUSIONS: Peak low frequency IMC functioned as biomarker for GPi-DBS efficacy, and partly correlated with dystonia severity. SIGNIFICANCE: IMC can function as biomarker. Confirmation in a larger study is needed for use in clinical practice.

Direct comparison of oscillatory activity in the motor system of Parkinson's disease and dystonia: A review of the literature and meta-analysis.

OBJECTIVE: To outline the current knowledge of (sub)cortical oscillations in Parkinson's Disease (PD) and dystonia, and to quantitatively summarize the results of direct comparisons of local oscillatory power between both diseases in the resting state, without medication or stimulation, in both the low-frequency (LF, ±4-12 Hz) and beta (±13 to ∼30 Hz) range. METHODS: Eight relevant studies were included. Recordings from 127 dystonia-, and 144 PD-patient hemispheres were analyzed. Ratios of LF and beta power between diseases were obtained. RESULTS: Beta oscillations in dystonia were lower when compared to beta oscillations in PD, ratio = 0.72, Z = 3.56, p = 0.0004, 95% CI [0.60, 0.86]. Subgroup analyses showed significant differences only in the GPi, whilst conflicting evidence was shown in the STN. LF oscillations in PD were lower when compared to LF oscillations in dystonia, ratio = 0.77, Z = 2.45, p = 0.01, 95% CI [0.63, 0.95]. Subgroup analyses showed significant differences in the GPi and the STN, but not in the M1. CONCLUSIONS: LF and beta oscillations are present in the resting-state motor network of both PD and dystonia patients. However, the power distribution of those oscillations differs between diseases. SIGNIFICANCE: This meta-analysis provides high-level evidence which supports the presence of exaggerated oscillations across the parkinsonian/dystonic motor networks.

The presence of depression and anxiety do not distinguish between functional jerks and cortical myoclonus.

INTRODUCTION: Functional movement disorders are accompanied by a high occurrence of psychopathology and cause serious impairments in quality of life. However, little is known about this in patients with functional jerks and no comparison has been made between patients with functional jerks and organic myoclonus. This case control study compares the occurrence of depression, anxiety and quality of life (HR-QoL) in patients with functional jerks and cortical myoclonus. METHODS: Patients with functional jerks and cortical myoclonus, consecutively recruited, were compared on self-rated anxiety (Beck Anxiety Inventory), depression (Beck Depression Inventory), health-related quality of life (RAND-36), and myoclonus severity (UMRS and CGI-S rating scales). RESULTS: Sixteen patients with functional jerks and 23 with cortical myoclonus were evaluated. There was no significant difference in depression (44% vs. 43%) or anxiety (44% vs. 47%) scores between groups. The HR-QoL was similarly impaired except that functional jerks patients reported significantly more pain (p < 0.05). Only in the functional jerks group myoclonus severity correlated with depression and anxiety. CONCLUSION: Depression and anxiety scores are high and do not discriminate between functional jerks and cortical myoclonus. Quality of life was equally impaired in both sub-groups, but pain was significantly worse in patients with functional jerks.

Electroencephalographic Findings in Posthypoxic Myoclonus.

The physical examination findings of early posthypoxic myoclonus (PHM) are associated with poor prognosis. Recent findings indicate that patients with multifocal PHM, assumed to have a cortical origin, have a comparable outcome to resuscitated patients without PHM. Generalized PHM, assumed to have a subcortical myoclonus origin, is still associated with a bad clinical outcome. It is not known whether the electroencephalographic (EEG) findings differ between the multifocal and generalized myoclonus groups nor is the clinical significance clearly defined. Forty-three patients with PHM were retrospectively derived from an EEG database. Patients were categorized as having multifocal (i), generalized (ii), or undetermined (iii) PHM. Outcome was expressed in cerebral performance category scores. The EEG background was categorized into isoelectric (I), low voltage (II), burst suppression (III), status epilepticus (SE; IV), diffuse slowing (V), and mild encephalopathic or normal (VI). 17 patients had generalized PHM and 23 had multifocal PHM (3 undetermined). The EEG showed more SE in generalized compared to multifocal PHM (64% vs 13%, P< .001). Diffuse slowing was more often present in multifocal PHM (52% vs 17%, P < .05). Early-onset myoclonus occurred significantly more often in generalized PHM, and early generalized PHM was invariantly associated with poor outcome. In conclusion, patients with generalized PHM showed more SE. These EEG findings might be either subcortical corollaries or primarily cortical phenomena. Our retrospective results conflict with currently used clinical criteria for myoclonus classification, and we suggest that more refined difference may be needed for accurate assessment of PHM. To better understand PHM, prospective research with standardized clinical assessment and quantitative EEG analysis is needed.