The non-decussating and decussating trigeminothalamic tracts in humans: A combination of connectome-based tractography and histological validation.

BACKGROUND: Functional anatomical research proposed the existence of a bilateral trigeminal ascending system although the anatomy trajectories of the trigeminothalamic connections cranial to the pons remain largely elusive. This study therefore aimed to clarify the anatomical distributions of the trigeminothalamic connections in humans. METHODS: Advanced deterministic tractography to an averaged template of diffusion tensor imaging data from 1065 subjects from the Human Connectome Project was used. Seedings masks were placed in Montreal Neurological Institute standard space by use of the BigBrain histological dataset. Waypoint masks of the sensory thalamus was obtained from the Brainnetome Atlas. RESULTS: Tractography results were validated by use of the BigBrain histological dataset and Polarized Light Imaging microscopy. The trigeminothalamic tract bifurcated into a decussating ventral and a non-decussating dorsal tract. The ventral and dorsal tracts ascended to the contralateral thalamus and ipsilateral thalamus and reflected the ventral trigeminothalamic tract and the dorsal trigeminothalamic tract, respectively. The projection of the ventral trigeminothalamic tract and the dorsal trigeminothalamic tract to both thalami confirm the existence of a bilateral trigeminothalamic system in humans. CONCLUSIONS: Because our study is strictly anatomical, no further conclusions can be drawn with regard to physiological functionality. Future research should explore if the dorsal trigeminothalamic tract and the ventral trigeminothalamic tract actually transmit signals from noxious stimuli, this offers potential in understanding and possibly treating neuropathology in the orofacial region.

Spinal Cord Stimulation in Failed Back Surgery Syndrome: An Integrative Review of Quantitative and Qualitative Studies.

BACKGROUND: Spinal cord stimulation (SCS) is an established therapy of failed back surgery syndrome (FBSS), although the effects on daily functioning, quality of life (QoL), and patients' expectations, experiences, and satisfaction remain elusive. The current integrative review aimed to summarize the overall effects of SCS in patients with FBSS on pain relief, health-related QoL, and daily activities. MATERIALS AND METHODS: PubMed, CINAHL, Embase, ClinicalTrials.gov, gray literature, and reference lists of relevant articles were searched for additional papers. All included studies were assessed for risk of bias using the Mixed Methods Appraisal Tool. Following the methods of Whittemore and Knafl, an integrative review and a meta-analysis were performed. RESULTS: In total, 16 articles were included; 11 articles presented quantitative outcomes, and five articles presented qualitative data. Lower back pain, leg pain, overall pain, Oswestry Disability Index, EuroQol Five Dimensions Health Questionnaire three-level/five-level, and the physical component score of Short Form Health Survey (SF-36) significantly improved during all follow-up moments. Only the mental component score of the SF-36 did not significantly improve, compared with baseline. Heterogeneity was diversely present among the studies. Patients' expectations and goals were disparate, although patients seemed to desire a return to their pre-FBSS state. Experiences with regard to the outcomes showed that patients largely recuperated after SCS, although limitations were still present. Patients also expressed inconvenience with regard to the trial period, implantation location, and recharging of the implantable pulse generator. CONCLUSIONS: SCS showed beneficial effects on different domains of life in patients with FBSS. The quantitative analyses suggest an overall improvement in most domains, although patients' experiences show that limitations in daily life and living with the SCS system persist. Multiple extensive preoperative counseling sessions and discussions with patients are deemed necessary to improve patient satisfaction and meet their expectations. Shared decision-making and provision of complete information are key factors for success.

Experiences From the Patient Perspective on Spinal Cord Stimulation for Failed Back Surgery Syndrome: A Qualitatively Driven Mixed Method Analysis.

INTRODUCTION: When neither pharmacological therapies nor alternative interventions provide sufficient pain relief, spinal cord stimulation (SCS) can be used to treat Failed Back Surgery Syndrome (FBSS). Although it seems reasonable that quality of life (QoL)- and psychosocial-related factors contribute to the outcome of SCS since pain is a multidimensional experience, few qualitative studies have explored the expectations of SCS and experiences on SCS to treat FBSS from the patient perspective. OBJECTIVES: The aim of this study was to qualitatively and quantitatively map the FBSS patients' experiences with SCS and the effects of SCS on low back pain caused by FBSS. MATERIALS AND METHODS: A qualitative study with in-depth semi-structured interviews, assisted by the Brief Pain Inventory (BPI)-questionnaire. RESULTS: Seven themes regarding patients' experiences, subdivided into 15 categories, were identified, including an understudied theme within this field of research, Spiritual Well-Being. "Acceptance" and "coping" emerged as pre-eminent motifs throughout these themes. Moreover, the realization of patients' expectations were variable throughout the presented themes. According to the BPI Questionnaire, four out of 13 patients (31%) had significant pain relief (≥50%). Seven out of 13 (54%) reported a ≥50% increase regarding enjoyment of life. CONCLUSION: Multiple QoL- and psychosocial-related themes are related to SCS-outcomes. In order to improve SCS-outcomes for both short- and long-term, these themes should be implemented as a multidimensional approach, both prior to implantation as during follow-up.

Motor cortex stimulation in chronic neuropathic orofacial pain syndromes: a systematic review and meta-analysis.

Invasive motor Cortex Stimulation (iMCS) was introduced in the 1990's for the treatment of chronic neuropathic orofacial pain (CNOP), although its effectiveness remains doubtful. However, CNOP is known to be a heterogeneous group of orofacial pain disorders, which can lead to different responses to iMCS. Therefore, this paper investigated (1) whether the effectiveness of iMCS is significantly different among different CNOP disorders and (2) whether other confounding factors can be impacting iMCS results in CNOP. A systematic review and meta-analysis using a linear mixed-model was performed. Twenty-three papers were included, totaling 140 CNOP patients. Heterogeneity of the studies showed to be 55.8%. A visual analogue scale (VAS) measured median pain relief of 66.5% (ranging from 0-100%) was found. Linear mixed-model analysis showed that patients suffering from trigeminal neuralgia responded significantly more favorable to iMCS than patients suffering from dysfunctional pain syndromes (p = 0.030). Also, patients suffering from CNOP caused by (supra)nuclear lesions responded marginally significantly better to iMCS than patients suffering from CNOP due to trigeminal nerve lesions (p = 0.049). No other confounding factors were elucidated. This meta-analysis showed that patients suffering from trigeminal neuralgia and patients suffering from (supra)nuclear lesions causing CNOP responded significantly more favorable than others on iMCS. No other confounding factors were found relevant.

Invasive Motor Cortex Stimulation Influences Intracerebral Structures in Patients With Neuropathic Pain: An Activation Likelihood Estimation Meta-Analysis of Imaging Data.

OBJECTIVE: Invasive motor cortex stimulation (iMCS) has been proposed as a treatment for intractable neuropathic pain syndromes. Although the mechanisms underlying the analgesic effect of iMCS remain largely elusive, several studies found iMCS-related changes in regional cerebral blood flow (rCBF) in neuropathic pain patients. The aim of this study was to meta-analyze the findings of neuroimaging studies on rCBF changes to iMCS. METHODS: PubMed, Embase, MEDLINE, Google Scholar, and the Cochrane Library were systematically searched for retrieval of relevant scientific papers. After initial assessment of relevancy by screening title and abstract by two investigators, independently, predefined inclusion and exclusion criteria were used for final inclusion of papers. Descriptive results were statistically assessed, whereas coordinates were pooled and meta-analyzed in accordance with the activation likelihood estimation (ALE) methodology. RESULTS: Six studies were included in the systematic narrative analysis, suggesting rCBF increases in the cingulate gyrus, thalamus, insula, and putamen after switching the MCS device "ON" as compared to the "OFF" situation. Decreases in rCBF were found in for example the precentral gyrus and different occipital regions. Two studies did not report stereotactic coordinates and were excluded from further analysis. ALE meta-analysis showed that, after switching the iMCS electrode "ON," increased rCBF occurred in the (1) anterior cingulate gyrus; (2) putamen; (3) cerebral peduncle; (4) precentral gyrus; (5) superior frontal gyrus; (6) red nucleus; (7) internal part of the globus pallidus; (8) ventral lateral nucleus of the thalamus; (9) medial frontal gyrus; (10) inferior frontal gyrus; and (11) claustrum, as compared to the "OFF" situation. Reductions in rCBF were found in the posterior cingulate gyrus when the iMCS electrode was turned "OFF." CONCLUSIONS: These findings suggested that iMCS induces changes in principal components of the default mode-, the salience-, and sensorimotor network.

Systematic Review and Neural Network Analysis to Define Predictive Variables in Implantable Motor Cortex Stimulation to Treat Chronic Intractable Pain.

Implantable motor cortex stimulation (iMCS) has been performed for >25 years to treat various intractable pain syndromes. Its effectiveness is highly variable and, although various studies revealed predictive variables, none of these were found repeatedly. This study uses neural network analysis (NNA) to identify predictive factors of iMCS treatment for intractable pain. A systematic review provided a database of patient data on an individual level of patients who underwent iMCS to treat refractory pain between 1991 and 2017. Responders were defined as patients with a pain relief of >40% as measured by a numerical rating scale (NRS) score. NNA was carried out to predict the outcome of iMCS and to identify predictive factors that impacted the outcome of iMCS. The outcome prediction value of the NNA was expressed as the mean accuracy, sensitivity, and specificity. The NNA furthermore provided the mean weight of predictive variables, which shows the impact of the predictive variable on the prediction. The mean weight was converted into the mean relative influence (M), a value that varies between 0 and 100%. A total of 358 patients were included (202 males [56.4%]; mean age, 54.2 ±13.3 years), 201 of whom were responders to iMCS. NNA had a mean accuracy of 66.3% and a sensitivity and specificity of 69.8% and 69.4%, respectively. NNA further identified 6 predictive variables that had a relatively high M: 1) the sex of the patient (M = 19.7%); 2) the origin of the lesion (M = 15.1%); 3) the preoperative numerical rating scale score (M = 9.2%); 4) preoperative use of repetitive transcranial magnetic stimulation (M = 7.3%); 5) preoperative intake of opioids (M = 7.1%); and 6) the follow-up period (M = 13.1%). The results from the present study show that these 6 predictive variables influence the outcome of iMCS and that, based on these variables, a fair prediction model can be built to predict outcome after iMCS surgery. PERSPECTIVE: The presented NNA analyzed the functioning of computational models and modeled nonlinear statistical data. Based on this NNA, 6 predictive variables were identified that are suggested to be of importance in the improvement of future iMCS to treat chronic pain.

Motor Cortex Stimulation in Patients Suffering from Chronic Neuropathic Pain: Summary of Expert Meeting and Premeeting Questionnaire, Combined with Literature Review.

BACKGROUND: Motor cortex stimulation (MCS) was introduced in the early 1990s by Tsubokawa and his group for patients diagnosed with drug-resistant, central neuropathic pain. Inconsistencies concerning the details of this therapy and its outcomes and poor methodology of most clinical essays divide the neuromodulation society worldwide into "believers" and "nonbelievers." A European expert meeting was organized in Brussels, Belgium by the Benelux Neuromodulation Society in order to develop uniform MCS protocols in the preoperative, intraoperative, and postoperative courses. METHODS: An expert meeting was organized, and a questionnaire was sent out to all the invited participants before this expert meeting. An extensive literature research was conducted in order to enrich the results. RESULTS: Topics that were addressed during the expert meeting were 1) inclusion and exclusion criteria, 2) targeting and methods of stimulation, 3) effects of MCS, and 4) results from the questionnaire. CONCLUSIONS: Substantial commonalities but also important methodologic divergencies emerged from the discussion of MCS experts from 7 European Centers. From this meeting and questionnaire, all participants concluded that there is a need for more homogenous standardized protocols for MCS regarding patient selection, implantation procedure, stimulation parameters, and follow-up-course.