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.

Is remaining intervertebral disc tissue interfering with bone generation during fusion of two vertebrae?

STUDY DESIGN: laboratory research. BACKGROUND: Through the increasing number of minimally invasive procedures in spinal fusion surgery, the complete removal of intervertebral disc (IVD) tissue has become more a challenge. Remaining IVD may interfere with the biological process of bone formation. OBJECTIVE: In order to establish whether complete removal of IVD tissue will improve or inhibit the fusion process, the effects of different concentrations of extracts of inflamed disc tissue on the mitochondrial activity of mesenchymal stem cells (MSCs), and the capacity to mineralize their extracellular matrix by osteoblasts and differentiated MSCs were tested in vitro. METHODS: A MTT assay was conducted to measure the mitochondrial activity of MSCs, and an Alizarin Red S staining quantification assay to measure the deposition of calcium by osteoblasts and differentiated, bone marrow-derived MSCs. RESULTS: A significantly higher mitochondrial activity was shown in MSCs co-cultured with extracts of IVD tissue (10%, 50%, and 100%) compared with the control group after 48 hours of incubation, indicating that the IVD tissue extracts stimulated the mitochondrial activity of MSCs. This effect appeared to be inversely proportional to the concentration of IVD tissue extract. No significant differences in mineralization by human osteoblasts or differentiated MSCs were found between the samples incubated with IVD tissue extracts (3% and 33%) and the control samples. CONCLUSION: Our findings indicate that remaining IVD tissue has more of a stimulating than inhibiting effect on the activity of MSCs. Even if inflammatory cytokines are produced, these do not result in a net inhibition of cellular activity or osteogenic differentiation of MSCs.

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.

[Diagnosis and treatment of patients with spinal epidural metastases]. / Diagnostiek en behandeling van patiënten met spinale epidurale metastasen.

Three patients with a medical history of malignancy were referred for back pain: two women aged 53 and 43 years respectively, with breast cancer, and a woman of 85 years with rectal carcinoma. All patients suffered from spinal metastasis. Considerable delay occurred between the initial complaint of back pain and the diagnosis. This adversely influenced the outcome after treatment. A reliable differentiation, based on symptoms and signs, between widely occurring non-malignant back pain and back pain due to spinal metastasis is impossible. This confronts physicians with the dilemma of overexposing their patients to diagnostic tests on the one hand and the risk of missing an important diagnosis on the other. Early recognition of warning signs, i.e. previous medical history of malignancy, onset of back pain above 50 years of age, continuous pain not related to posture or movement and nocturnal pain, should alert physicians.