Dynamic functional changes upon thalamotomy in essential tremor depend on baseline brain morphometry.

Patients with drug-resistant essential tremor (ET) may undergo Gamma Knife stereotactic radiosurgical thalamotomy (SRS-T), where the ventro-intermediate nucleus of the thalamus (Vim) is lesioned by focused beams of gamma radiations to induce clinical improvement. Here, we studied SRS-T impacts on left Vim dynamic functional connectivity (dFC, n = 23 ET patients scanned before and 1 year after intervention), and on surface-based morphometric brain features (n = 34 patients, including those from dFC analysis). In matched healthy controls (HCs), three dFC states were extracted from resting-state functional MRI data. In ET patients, state 1 spatial stability increased upon SRS-T (F1,22 = 19.13, p = 0.004). More frequent expression of state 3 over state 1 before SRS-T correlated with greater clinical recovery in a way that depended on the MR signature volume (t6 = 4.6, p = 0.004). Lower pre-intervention spatial variability in state 3 expression also did (t6 = - 4.24, p = 0.005) and interacted with the presence of familial ET so that these patients improved less (t6 = 4.14, p = 0.006). ET morphometric profiles showed significantly lower similarity to HCs in 13 regions upon SRS-T (z ≤ - 3.66, p ≤ 0.022), and a joint analysis revealed that before thalamotomy, morphometric similarity and states 2/3 mean spatial similarity to HCs were anticorrelated, a relationship that disappeared upon SRS-T (z ≥ 4.39, p < 0.001). Our results show that left Vim functional dynamics directly relates to upper limb tremor lowering upon intervention, while morphometry instead has a supporting role in reshaping such dynamics.

Successful MRI-Guided Focused Ultrasound Thalamotomy after Ipsilateral Gamma Knife Radiosurgery for Essential Tremor: A Case Report with Video.

We report the case of a 67-year-old left-handed female patient with disabling medically refractory essential tremor who underwent successful right-sided magnetic resonance-guided focused ultrasound (MRgFUS) of the ventral intermediate nucleus after ipsilateral gamma knife radiosurgery (GKRS) thalamotomy performed 3 years earlier. The GKRS had a partial effect on her postural tremor without side effects, but there was no reduction of her kinetic tremor or improvement in her quality of life (QoL). The patient subsequently underwent a MRgFUS thalamotomy, which induced an immediate and marked reduction in both the postural and kinetic tremor components, with minor complications (left upper lip hypesthesia, dysmetria in her left hand, and slight gait ataxia). The MRgFUS-induced lesion was centered more medially than the GKRS-induced lesion and extended more posteriorly and inferiorly. The MRgFUS-induced lesion interrupted remaining fibers of the dentatorubrothalamic tract (DRTT). The functional improvement 1-year post-MRgFUS was significant due to a marked reduction of the patient's kinetic tremor. The QoL score (Quality of Life in Essential Tremor) improved by 88% and her Clinical Rating Scale for Tremor left hand score by 62%. The side effects persisted but were minor, with no impact on her QoL. The explanation for the superior efficacy of MRgFUS compared to GKRS in our patient could be due to either a poor response to the GKRS or to a better localization of the MRgFUS lesion with a more extensive interruption of DRTT fibers. In conclusion, MRgFUS can be a valuable therapeutic option after unsatisfactory GKRS, especially because MRgFUS has immediate clinical effectiveness, allowing intra-procedural test lesions and possible readjustment of the target if necessary.

[Assessing occipital nerve stimulation efficacy for chronic refractory headaches]. / Efficacité de la stimulation du nerf occipital pour les céphalées chroniques réfractaires - Une étude prospective lausannoise.

We prospectively followed a cohort of 26 subjects for an average period of 41 months who benefited from occipital nerve stimulation (ONS) in the context of chronic refractory headaches. In 17 patients treated, the frequency of headache decreased, and quality of life scores improved significantly. Among these patients, the "very good" response rate was 34 %. In this cohort, treatment-related adverse events are relatively common (42 %) but not severe. While it is difficult to anticipate the risk factors for non-response to treatment, we estimate that the risk of failure may not be related to the duration of the disease, but rather to the number of different preventives attempted prior to ONS.

Nous avons suivi prospectivement durant une période d'en moyenne 41 mois une cohorte de 26 patients romands qui ont bénéficié d'une stimulation du nerf occipital (ONS) dans le cadre de céphalées chroniques réfractaires. Chez 17 patients non explantés, la fréquence des céphalées a diminué et les scores de qualité de vie se sont améliorés de façon significative. Parmi ces patients, le taux de « très bonne ¼ réponse est de 34 %. On constate dans cette cohorte que les effets indésirables liés au traitement sont relativement courants (42 %) mais non sévères. Même s'il est difficile d'anticiper les facteurs de risque de non-réponse au traitement, nous estimons que la probabilité d'échec ne serait pas corrélée à la durée de la maladie mais plutôt au nombre de traitements préventifs tentés avant l'ONS.

Improved susceptibility-weighted imaging for high contrast and resolution thalamic nuclei mapping at 7T.

PURPOSE: The thalamus is an important brain structure and neurosurgical target, but its constituting nuclei are challenging to image non-invasively. Recently, susceptibility-weighted imaging (SWI) at ultra-high field has shown promising capabilities for thalamic nuclei mapping. In this work, several methodological improvements were explored to enhance SWI quality and contrast, and specifically its ability for thalamic imaging. METHODS: High-resolution SWI was performed at 7T in healthy participants, and the following techniques were applied: (a) monitoring and retrospective correction of head motion and B0 perturbations using integrated MR navigators, (b) segmentation and removal of venous vessels on the SWI data using vessel enhancement filtering, and (c) contrast enhancement by tuning the parameters of the SWI phase-magnitude combination. The resulting improvements were evaluated with quantitative metrics of image quality, and by comparison to anatomo-histological thalamic atlases. RESULTS: Even with sub-millimeter motion and natural breathing, motion and field correction produced clear improvements in both magnitude and phase data quality (76% and 41%, respectively). The improvements were stronger in cases of larger motion/field deviations, mitigating the dependence of image quality on subject performance. Optimizing the SWI phase-magnitude combination yielded substantial improvements in image contrast, particularly in the thalamus, well beyond previously reported SWI results. The atlas comparisons provided compelling evidence of anatomical correspondence between SWI features and several thalamic nuclei, for example, the ventral intermediate nucleus. Vein detection performed favorably inside the thalamus, and vein removal further improved visualization. CONCLUSION: Altogether, the proposed developments substantially improve high-resolution SWI, particularly for thalamic nuclei imaging.

Pretherapeutic Functional Imaging Allows Prediction of Head Tremor Arrest After Thalamotomy for Essential Tremor: The Role of Altered Interconnectivity Between Thalamolimbic and Supplementary Motor Circuits.

OBJECTIVE: To correlate pretherapeutic resting-state functional magnetic resonance imaging (rs-fMRI) measures with pretherapeutic head tremor presence and/or further improvement 1 year after stereotactic radiosurgical thalamotomy (SRS-T) for essential tremor (ET). METHODS: We prospectively collected head tremor scores (range, 0-3) and rs-fMRI data for a cohort of 17 consecutive ET patients in pretherapeutic and 1 year after SRS-T states. We additionally acquired rs-fMRI data for a healthy control (HC) group (n = 12). Group-level independent component analysis (n = 17 for pretherapeutic rs-fMRI) was applied to decompose neuroimaging data into 20 large-scale brain networks using a standard approach. Through spatial regression, we projected 1 year after SRS-T and HC rs-fMRI time points, on the same 20 brain networks. RESULTS: Pretherapeutic interconnectivity (IC) strength between the network including bilateral thalamus and limbic system with left supplementary motor area predicted head tremor improvement at 1 year after SRS-T (family-wise corrected P < 0.001, cluster size Kc = 146). For the statistically significant cluster, IC strength was strongest in HCs (mean, 4.6; median, 3.8) compared with pre- (mean, 0.1; median, 0.2) or posttherapeutic (mean, -0.2; median, 0.09) states. CONCLUSIONS: Baseline measures of IC between bilateral thalamus and limbic system with left supplementary motor area may predict head tremor arrest after thalamotomy. However, procedures such as SRS-T, for this particular clinical feature, do not align patients to HCs in terms of functional brain connectivity. We postulate that supplementary motor area is modulating head tremor appearance, by abnormal connectivity with the thalamolimbic system.

Ventrolateral Motor Thalamus Abnormal Connectivity in Essential Tremor Before and After Thalamotomy: A Resting-State Functional Magnetic Resonance Imaging Study.

OBJECTIVE: To evaluate functional connectivity (FC) of the ventrolateral thalamus, a common target for drug-resistant essential tremor (ET), resting-state data were analyzed before and 1 year after stereotactic radiosurgical thalamotomy and compared against healthy controls (HCs). METHODS: In total, 17 consecutive patients with ET and 10 HCs were enrolled. Tremor network was investigated using the ventrolateral ventral (VLV) thalamic nucleus as the region of interest, extracted with automated segmentation from pretherapeutic diffusion magnetic resonance imaging. Temporal correlations of VLV at whole brain level were evaluated by comparing drug-naïve patients with ET with HCs, and longitudinally, 1 year after stereotactic radiosurgical thalamotomy. 1 year thalamotomy MR signature was always located inside VLV and did not correlate with any of FC measures (P > 0.05). This suggested presence of longitudinal changes in VLV FC independently of the MR signature volume. RESULTS: Pretherapeutic ET displayed altered VLV FC with left primary sensory-motor cortex, pedunculopontine nucleus, dorsal anterior cingulate, left visual association, and left superior parietal areas. Pretherapeutic negative FC with primary somatosensory cortex and pedunculopontine nucleus correlated with poorer baseline tremor scores (Spearman = 0.04 and 0.01). Longitudinal study displayed changes within right dorsal attention (frontal eye-fields and posterior parietal) and salience (anterior insula) networks, as well as areas involved in hand movement planning or language production. CONCLUSIONS: Our results demonstrated that patients with ET and HCs differ in their left VLV FC to primary somatosensory and supplementary motor, visual association, or brainstem areas (pedunculopontine nucleus). Longitudinal changes display reorganization of dorsal attention and salience networks after thalamotomy. Beside attentional gateway, they are also known for their major role in facilitating a rapid access to the motor system.

Clinical response to Vim's thalamic stereotactic radiosurgery for essential tremor is associated with distinctive functional connectivity patterns.

INTRODUCTION: Essential tremor (ET) is the most common movement disorder. Drug-resistant ET can benefit from standard surgical stereotactic procedures (deep brain stimulation, thalamotomy) or minimally invasive high-intensity focused ultrasound (HIFU) or stereotactic radiosurgical thalamotomy (SRS-T). Resting-state fMRI (rs-fMRI) is a non-invasive imaging method acquired in absence of a task. We examined whether rs-fMRI correlates with tremor score on the treated hand (TSTH) improvement 1 year after SRS-T. METHODS: We included 17 consecutive patients treated with left unilateral SRS-T in Marseille, France. Tremor score evaluation and rs-fMRI were acquired at baseline and 1 year after SRS-T. Resting-state data (34 scans) were analyzed without a priori hypothesis, in Lausanne, Switzerland. Based on degree of improvement in TSTH, to consider SRS-T at least as effective as medication, we separated two groups: 1, ≤ 50% (n = 6, 35.3%); 2, > 50% (n = 11, 64.7%). They did not differ statistically by age (p = 0.86), duration of symptoms (p = 0.41), or lesion volume at 1 year (p = 0.06). RESULTS: We report TSTH improvement correlated with interconnectivity strength between salience network with the left claustrum and putamen, as well as between bilateral motor cortices, frontal eye fields and left cerebellum lobule VI with right visual association area (the former also with lesion volume). Longitudinal changes showed additional associations in interconnectivity strength between right dorsal attention network with ventro-lateral prefrontal cortex and a reminiscent salience network with fusiform gyrus. CONCLUSIONS: Brain connectivity measured by resting-state fMRI relates to clinical response after SRS-T. Relevant networks are visual, motor, and attention. Interconnectivity between visual and motor areas is a novel finding, revealing implication in movement sensory guidance.

Right Brodmann area 18 predicts tremor arrest after Vim radiosurgery: a voxel-based morphometry study.

INTRODUCTION: Drug-resistant essential tremor (ET) can benefit from open standard stereotactic procedures, such as deep-brain stimulation or radiofrequency thalamotomy. Non-surgical candidates can be offered either high-focused ultrasound (HIFU) or radiosurgery (RS). All procedures aim to target the same thalamic site, the ventro-intermediate nucleus (e.g., Vim). The mechanisms by which tremor stops after Vim RS or HIFU remain unknown. We used voxel-based morphometry (VBM) on pretherapeutic neuroimaging data and assessed which anatomical site would best correlate with tremor arrest 1 year after Vim RS. METHODS: Fifty-two patients (30 male, 22 female; mean age 71.6 years, range 49-82) with right-sided ET benefited from left unilateral Vim RS in Marseille, France. Targeting was performed in a uniform manner, using 130 Gy and a single 4-mm collimator. Neurological (pretherapeutic and 1 year after) and neuroimaging (baseline) assessments were completed. Tremor score on the treated hand (TSTH) at 1 year after Vim RS was included in a statistical parametric mapping analysis of variance (ANOVA) model as a continuous variable with pretherapeutic neuroimaging data. Pretherapeutic gray matter density (GMD) was further correlated with TSTH improvement. No a priori hypothesis was used in the statistical model. RESULTS: The only statistically significant region was right Brodmann area (BA) 18 (visual association area V2, p = 0.05, cluster size Kc = 71). Higher baseline GMD correlated with better TSTH improvement at 1 year after Vim RS (Spearman's rank correlation coefficient = 0.002). CONCLUSIONS: Routine baseline structural neuroimaging predicts TSTH improvement 1 year after Vim RS. The relevant anatomical area is the right visual association cortex (BA 18, V2). The question whether visual areas should be included in the targeting remains open.

Combination of functional magnetic resonance imaging-guided neuronavigation and intraoperative cortical brain mapping improves targeting of motor cortex stimulation in neuropathic pain.

OBJECTIVE: To evaluate, regardless of the clinical results, the contribution of combining functional magnetic resonance imaging (fMRI) with intraoperative cortical brain mapping (iCM) as functional targeting methods for epidural chronic motor cortex stimulation (MCS) in refractory neuropathic pain. METHODS: Eighteen neuropathic pain patients (central stroke in six; trigeminal neuropathy in six; syrinx or amputation in six) who underwent operations for epidural MCS were studied with preoperative fMRI and iCM. fMRI investigated motor tasks of hands (as well as foot and tongue, when painful). fMRI data were analyzed with Statistical Parametric Mapping99 software (University College London, London, England; initial analysis threshold corresponding to P < 0.001), registered in a neuronavigation system, and correlated during surgery with iCM. The primary aim of this study was to improve the topographical precision of MCS. Matching of fMRI and iCM specifically was examined. RESULTS: Correspondence between the contour of the fMRI activation area and iCM in precentral gyrus (mean distance, 3.8 mm) was found in 17 (94%) of 18 patients. Eleven of them showed correspondence for more restrictive values of the analysis threshold (P < 0.0001); in six patients, the quality of the iCM was reduced by somatosensory wave attenuation and general anesthesia. In this group of six patients, a combination of both techniques was used for the final targeting. Correspondence was not found in one patient as the result of image distortion and residual motion artifact. At follow-up (4-60 mo), MCS induced significant pain relief in a total of 11 patients (61%). CONCLUSION: This study confirms the functional accuracy of fMRI guidance in neuropathic pain and illustrates the usefulness of combining fMRI guidance with iCM to improve the functional targeting in MCS. Because appropriate targeting is crucial to obtaining pain relief, this combination may increase the analgesic efficacy of MCS.