Altered levels of transthyretin in human cerebral microdialysate after subarachnoid haemorrhage using proteomics; a descriptive pilot study.

BACKGROUND: Subarachnoid haemorrhage (SAH) is one of the most severe forms of stroke in which delayed cerebral ischemia is one of the major complications. Neurointensive care aims at preventing and treating such complications and identification of biomarkers of early signs of ischemia might therefore be helpful. METHODS: We aimed at describing proteome profile in cerebral microdialysate in four patients with aneurysmal SAH using two dimensional gel electrophoresis in combination with mass spectrometry in search for new biomarkers for delayed cerebral ischemia and to investigate if there were temporal fluctuations in those biomarkers over time after aneurysmal bleed. RESULTS: The results showed transthyretin in nine different proteoforms (1001, 1102, 2101, 3101, 4101, 4102, 5001, 5101, 6101) in cerebral microdialysate samples from four patients having sustained SAH. Several proteoforms show highly differing levels and pooled analysis of all samples showed varying optical density related to time from aneurysmal bleed, indicating a temporal evolution. CONCLUSIONS: Transthyretin proteoforms have not earlier been shown in cerebral microdialysate after SAH and we describe differing levels based on proteoform as well as time from subarachnoid bleed. Transthyretin is well known to be synthetized in choroid plexus, whilst intraparenchymal synthesis remains controversial. The results need to be confirmed in larger studies in order to further describe transthyretin.

A more than 20-year follow-up of pain and disability after anterior cervical decompression and fusion surgery for degenerative disc disease and comparisons between two surgical techniques.

BACKGROUND: Follow-ups more than 20 years after neck surgery are extremely rare. No previous randomized studies have investigated differences in pain and disability more than 20 years after ACDF surgery using different techniques. The purpose of this study was to describe pain and functioning more than 20 years after anterior cervical decompression and fusion surgery, and to compare outcomes between the Cloward Procedure and the carbon fiber fusion cage (CIFC). METHODS: This study is a 20 to 24-year follow-up of a randomized controlled trial. Questionnaires were sent to 64 individuals, at least 20 years after ACDF due to cervical radiculopathy. Fifty individuals (mean age 69, 60% women, 55% CIFC) completed questionnaires. Mean time since surgery was 22.4 years (range 20,5-24). Primary outcomes were neck pain and neck disability index (NDI). Secondary outcomes were frequency and intensity of neck and arm pain, headache, dizziness, self-efficacy, health related quality of life or global outcome. Clinically relevant improvements were defined as 30 mm decrease in pain and a decrease in disability of 20 percentage units. Between-group differences over time were analyzed with mixed design ANOVA and relationships between main outcomes and psychosocial factors were analyzed by Spearman´s rho. RESULTS: Neck pain and NDI score significantly improved over time (p < .001), with no group differences in primary or secondary outcomes. Eighty-eight per cent of participants experienced improvements or full recovery, 71% (pain) and 41% (NDI) had clinically relevant improvements. Pain and NDI were correlated with lower self-efficacy and quality of life. CONCLUSION: The results from this study do not support the idea that fusion technique affects long-term outcome of ACDF. Pain and disability improved substantially over time, irrespective of surgical technique. However, the majority of participants reported residual disability not to a negligible extent. Pain and disability were correlated to lower self-efficacy and quality of life.

Neurological outcomes after surgery and postoperative rehabilitation for cervical radiculopathy due to disc disease: a 2-year-follow-up of a randomized clinical trial.

Reports on neurological outcomes in patients with cervical radiculopathy (CR) undergoing surgery and postoperative rehabilitation are important to inform prognosis. This 2-year-follow-up of a randomized clinical trial aimed to compare secondary neurological outcomes between structured postoperative rehabilitation and a standard approach after surgery for CR. A secondary aim was to increase knowledge about recovery of neurological impairments in relation to patient-reported neck disability. Neurological outcomes included assessment of sensibility, motor function, arm reflexes and the Spurling test. A total of 153 and 135 participants (> 70% response rate) completed the clinical examination. Between-group differences, changes over time, and associations between persistent neurological impairments and the Neck Disability Index were investigated. No between-group differences were reported (p > 0.07), and neurological impairments in sensibility, motor function, and a positive Spurling test decreased over time in both groups (p < 0.04). Persistent impairments in sensibility and reflex arm were most frequent at follow-up, whereas, a persistent positive Spurling test, and impairments in motor function were associated with higher NDI score. Neurological outcomes improved over time in patients undergoing surgery for CR with no between-group differences., However, persistent neurological impairments were common, and associated with poorer outcome for patient-reported neck disability.Clinical registration: clinicaltrial.gov NCT01547611, 08/03/2012, Title: Outcome of physiotherapy after surgery for cervical disc disease: a prospective multi-centre trial.

Fatty infiltrate and neck muscle volume in individuals with chronic whiplash associated disorders compared to healthy controls - a cross sectional case-control study.

BACKGROUND: The underlying pathophysiological mechanisms of chronic Whiplash Associated Disorders (WAD) are not fully understood. More knowledge of morphology is needed to better understand the disorder, improve diagnostics and treatments. The aim was to investigate dorsal neck muscle volume (MV) and muscle fat infiltration (MFI) in relation to self-reported neck disability among 30 participants with chronic WAD grade II-III compared to 30 matched healthy controls. METHODS: MV and MFI at spinal segments C4 through C7 in both sexes with mild- to moderate chronic WAD (n = 20), severe chronic WAD (n = 10), and age- and sex matched healthy controls (n = 30) was compared. Muscles: trapezius, splenius, semispinalis capitis and semispinalis cervicis were segmented by a blinded assessor and analyzed. RESULTS: Higher MFI was found in right trapezius (p = 0.007, Cohen's d = 0.9) among participants with severe chronic WAD compared to healthy controls. No other significant difference was found for MFI (p = 0.22-0.95) or MV (p = 0.20-0.76). CONCLUSIONS: There are quantifiable changes in muscle composition of right trapezius on the side of dominant pain and/or symptoms, among participants with severe chronic WAD. No other statistically significant differences were shown for MFI or MV. These findings add knowledge of the association between MFI, muscle size and self-reported neck disability in chronic WAD. TRIAL REGISTRATION: NA. This is a cross-sectional case-control embedded in a cohort study.

Dizziness and balance outcomes after two different postoperative rehabilitation approaches following neck surgery: analyses of a multicenter randomized controlled trial.

BACKGROUND: Dizziness and balance problems are common symptoms in patients with cervical radiculopathy. OBJECTIVE: To evaluate the effect of neck surgery postoperatively combined with either structured rehabilitation or standard approach in patients with cervical radiculopathy and dizziness and/or balance problems, and investigate factors influencing dizziness and balance at 6-month follow-up. METHODS: Individuals (n = 149) with cervical radiculopathy and dizziness and/or balance problems were randomized preoperatively to structured postoperative rehabilitation or standard postoperative approach. Outcomes were intensity of dizziness and subjective balance, and clinical measures of balance. RESULTS: Self-reported measures improved at three months (p ˂ 0.001 to p = .007) and the standing balance at six months (p = .008). No between-group differences. Baseline values, neck pain, and physical activity level explained 23-39% of the variance in 6-month outcomes for self-reported measures. Baseline values and physical activity level explained 71% of the variance in walking balance, and lower baseline scores were significantly associated with standing balance impairments (OR 0.876). CONCLUSION: Patients improved significantly in dizziness and subjective balance intensity shortly after surgery, and in standing balance at 6 months, independent of postoperative rehabilitation. Neck pain, physical activity, and neck muscle function influenced dizziness and balance, although preoperative values and neck pain were of most importance for 6-month outcomes.

Determining the level of cervical radiculopathy: Agreement between visual inspection of pain drawings and magnetic resonance imaging.

BACKGROUND AND AIMS: Pain drawings are commonly used in the clinical assessment of people with cervical radiculopathy. This study aimed to assess (1) the agreement of clinical interpretation of pain drawings and MRI findings in identifying the affected level of cervical radiculopathy, (2) the agreement of these predictions based on the pain drawing among four clinicians from two different professions (i.e., physiotherapy and surgery) and (3) the topographical pain distribution of people presenting with cervical radiculopathy (C4-C7). METHODS: Ninety-eight pain drawings were obtained from a baseline assessment of participants in a randomized clinical trial, in which single-level cervical radiculopathy was determined using MRI. Four experienced clinicians independently rated each pain drawing, attributing the pain distribution to a single nerve root (C4-C7). A post hoc analysis was performed to assess agreement. OUTCOME MEASURES: Percentage agreement and kappa values were used to assess the level of agreement. Topographic pain frequency maps were created for each cervical radiculopathy level as determined by MRI. RESULTS: The radiculopathy level determined from the pain drawings showed poor overall agreement with MRI (mean = 35.7%, K = -0.007 to 0.139). The inter-clinician agreement ranged from fair to moderate (K = 0.212-0.446). Topographic frequency maps revealed that pain distributions were widespread and overlapped markedly between patients presenting with different levels cervical radiculopathy. CONCLUSION: This study revealed a lack of agreement between the segmental level affected determined from the patient's pain drawing and the affected level as identified on MRI. The large overlap of pain and non-dermatomal distribution of pain reported by patients likely contributed to this result.

Morphology and composition of the ventral neck muscles in individuals with chronic whiplash related disorders compared to matched healthy controls: a cross-sectional case-control study.

BACKGROUND: OBJECTIVE: Studies of cross-sectional area (CSA) (morphology) and muscle fat infiltration (MFI) (composition) in ventral neck muscles is scarce in patients with chronic whiplash associated disorders (WAD), especially for men and those with severe WAD compared with matched healthy controls. The aim was to compare CSA and MFI of sternocleidomastoid (SCM), longus capitis (LCA) and longus colli (LCO) in patients with chronic right-sided dominant moderate (Neck Disability Index: NDI < 40) or severe WAD (NDI ≥ 40), compared to age- and sex-matched healthy controls. METHODS: Cross-sectional case-control study with blinded investigators. Thirty-one patients with chronic WAD (17 women and 14 men, mean age 40 years) (SD 12.6, range 20-62)) and 31 age- and sex-matched healthy controls underwent magnetic resonance imaging of ventral neck muscles segmental level C4. RESULTS: Unique to the severe group was a larger magnitude of MFI in right SCM (p = 0.02) compared with healthy controls. There was no significant difference between the groups with regards to the other muscles and measures. CONCLUSIONS: Individuals with severe right-sided dominant WAD have a higher MFI in the right SCM compared to healthy controls. No other differences were found between the groups. The present study indicates that there are changes in the composition of muscles on the side of greatest pain.

Deep Brain Stimulation: Emerging Tools for Simulation, Data Analysis, and Visualization.

Deep brain stimulation (DBS) is a well-established neurosurgical procedure for movement disorders that is also being explored for treatment-resistant psychiatric conditions. This review highlights important consideration for DBS simulation and data analysis. The literature on DBS has expanded considerably in recent years, and this article aims to identify important trends in the field. During DBS planning, surgery, and follow up sessions, several large data sets are created for each patient, and it becomes clear that any group analysis of such data is a big data analysis problem and has to be handled with care. The aim of this review is to provide an update and overview from a neuroengineering perspective of the current DBS techniques, technical aids, and emerging tools with the focus on patient-specific electric field (EF) simulations, group analysis, and visualization in the DBS domain. Examples are given from the state-of-the-art literature including our own research. This work reviews different analysis methods for EF simulations, tractography, deep brain anatomical templates, and group analysis. Our analysis highlights that group analysis in DBS is a complex multi-level problem and selected parameters will highly influence the result. DBS analysis can only provide clinically relevant information if the EF simulations, tractography results, and derived brain atlases are based on as much patient-specific data as possible. A trend in DBS research is creation of more advanced and intuitive visualization of the complex analysis results suitable for the clinical environment.

Work Ability After Anterior Cervical Decompression and Fusion Followed by a Structured Postoperative Rehabilitation: Secondary Outcomes of a Prospective Randomized Controlled Multi-Centre Trial with a 2-year Follow-up.

Purpose Information on work ability after ACDF and postoperative rehabilitation is lacking. The aim of the present study is therefore to investigate the work ability benefits of a structured postoperative treatment (SPT) over a standard care approach (SA) in patients who underwent anterior cervical decompression and fusion (ACDF) for cervical radiculopathy and factors important to the 2-year outcome. Methods Secondary outcome and prediction model of a prospective randomized controlled multi-centre study with a 2-year follow-up (clinicaltrials.gov NCT01547611). The Work Ability Index (WAI) and Work Ability Score (WAS) were measured at baseline and up to 2 years after ACDF in 154 patients of working age who underwent SPT or SA after surgery. Predictive factors for the WAI at 2 years were analysed. Results Both WAI and WAS significantly improved with SPT and SA (p < 0.001), without any between-group differences. Thoughts of being able to work within the next 6 months, Neck Disability Index (NDI), and work-related neck load explained 59% of the variance in WAI at the 2-year follow-up after ACDF. Conclusions Patients improved over time without group differences, suggesting the improvement to be surgery related. Expectation to work within the next 6 months, self-reported neck functioning and work-related neck load were important to work ability and are central factors to ask early after ACDF, to identifying further interventions promoting return to work.

Comparison between patient-specific deep brain stimulation simulations and commercial system SureTune3.

Objective. Software to visualize estimated volume of tissue activated (VTA) in deep brain stimulation assuming a homogeneous tissue surrounding such as SureTune3 has recently become available for clinical use. The objective of this study is to compare SureTune3 with homogeneous and heterogeneous patient-specific finite element method (FEM) simulations of the VTA to elucidate how well they coincide in their estimates.Approach. FEM simulations of the VTA were performed in COMSOL Multiphysics and compared with VTA from SureTune3 with variation of voltage and current amplitude, pulse width, axon diameter, number of active contacts, and surrounding homogeneous grey or white matter. Patient-specific simulations with heterogeneous tissue were also performed.Main results. The VTAs corresponded well for voltage control in homogeneous tissue, though with the smallest VTAs being slightly larger in SureTune3 and the largest VTAs being slightly larger in the FEM simulations. In current control, FEM estimated larger VTAs in white matter and smaller VTAs in grey matter compared to SureTune3 as grey matter has higher electric conductivity than white matter and requires less voltage to reach the same current. The VTAs also corresponded well in the patient-specific cases except for one case with a cyst of highly conductive cerebrospinal fluid (CSF) near the active contacts.Significance. The VTA estimates without taking the surrounding tissue into account in SureTune3 are in good agreement with patient-specific FEM simulations when using voltage control in the absence of CSF-filled cyst. In current control or when CSF is present near the active contacts, the tissue characteristics are important for the VTA and needs consideration.Clinical. trial ethical approval: Local ethics committee at Linköping University (2012/434-31).

Influence of Virchow-Robin spaces on the electric field distribution in subthalamic nucleus deep brain stimulation.

Patient MRI from DBS implantations in the subthalamic nucleus (STN) were reviewed and it was found that around 10% had Virchow-Robin spaces (VRS). Patient-specific models were developed to evaluate changes in the electric field (EF) around DBS leads. The patients (n = 7) were implanted bilaterally either with the standard voltage-controlled lead 3389 or with the directional current-controlled lead 6180. The EF distribution was evaluated by comparing simulations using patient-specific models with homogeneous models without VRS. The EF, depicted with an isocontour of 0.2 V/mm, showed a deformation in the presence of the VRS around the DBS lead. For patient-specific models, the radial extension of the EF isocontours was enlarged regardless of the operating mode or the DBS lead used. The location of the VRS in relation to the active contact and the stimulation amplitude, determined the changes in the shape and extension of the EF. It is concluded that it is important to take the patients' brain anatomy into account as the high conductivity in VRS will alter the electric field if close to the DBS lead. This can be a cause of unexpected side effects.

Larger pain extent is associated with greater pain intensity and disability but not with general health status or psychosocial features in patients with cervical radiculopathy.

ABSTRACT: Pain as a result of cervical radiculopathy (CR) can be widespread, nondermatomal and individually specific, but the association between pain extent and other clinical features has never been explored. The objective of this study is to investigate whether pain extent relates to clinical variables including pain intensity in addition to health indicators including disability, general health, depression, somatic anxiety, coping strategies or self-efficacy.An observational cohort study was conducted. Participants were recruited from 4 hospital spinal centres in Sweden. Pain extent was quantified from the pain drawings of 190 individuals with cervical disc disease, verified with magnetic resonance imaging (MRI) and compatible with clinical findings (examined by a neurosurgeon), that show cervical nerve root compression. Pain extent was evaluated in relation to neck pain, arm pain, and headache intensity. Multiple linear regression analysis were then used to verify whether pain extent was associated with other health indicators including disability, health-related quality of life, depression, somatic anxiety, coping strategies and self-efficacy.Pain extent was directly related to neck, arm and headache pain intensity (all P < .01). Multiple linear regression revealed that pain extent was significantly associated only to the level of perceived disability (P < .01).Increased pain extent in people with CR is associated with higher headache, neck and arm pain intensity, and disability but not measures of general health, depression, somatic anxiety, coping strategies or self-efficacy.

Postoperative Lead Movement after Deep Brain Stimulation Surgery and the Change of Stimulation Volume.

INTRODUCTION: Lead movement after deep brain stimulation may occur and influence the affected volume of stimulation. The aim of the study was to investigate differences in lead position between the day after surgery and approximately 1 month postoperatively and also simulate the electric field (EF) around the active contacts in order to investigate the impact of displacement on affected volume. METHODS: Twenty-three patients with movement disorders underwent deep brain stimulation surgery (37 leads). Computed tomography at the 2 time points were co-fused respectively with the stereotactic images in Surgiplan. The coordinates (x, y, and z) of the lead tips were compared between the 2 dates. Eleven of these patients were selected for the EF simulation in Comsol Multiphysics. Postoperative changes of EF spread in the tissue due to conductivity changes in perielectrode space and due to displacement were evaluated by calculating the coverage coefficient and the Sørensen-Dice coefficient. RESULTS: There was a significant displacement (mean ± SD) on the left lead: x (0.44 ± 0.72, p < 0.01), y (0.64 ± 0.54, p < 0.001), and z (0.62 ± 0.71, p < 0.001). On the right lead, corresponding values were: x (-0.11 ± 0.61, ns), y (0.71 ± 0.54, p < 0.001), and z (0.49 ± 0.81, p < 0.05). The anchoring technique was a statistically significant variable associated with displacement. No correlation was found between bilateral (n = 14) versus unilateral deep brain stimulation, gender (n = 17 male), age <60 years (n = 8), and calculated air volume. The simulated stimulation volume was reduced after 1 month because of the perielectrode space. When considering perielectrode space and displacement, the volumes calculated the day after surgery and approximately 1 month later were partly overlapped. CONCLUSION: The left lead tip displayed a tendency to move lateral, anterior, and inferior and the right a tendency to move anterior and inferior. The anchoring technique was associated to displacement. New brain territory was affected due to the displacement despite considering the reduced stimulated volume after 1 month. Postoperative changes in perielectrode space and small lead movements are reasons for delaying programming to 4 weeks following surgery.

Clinical predictive modelling of post-surgical recovery in individuals with cervical radiculopathy: a machine learning approach.

Prognostic models play an important role in the clinical management of cervical radiculopathy (CR). No study has compared the performance of modern machine learning techniques, against more traditional stepwise regression techniques, when developing prognostic models in individuals with CR. We analysed a prospective cohort dataset of 201 individuals with CR. Four modelling techniques (stepwise regression, least absolute shrinkage and selection operator [LASSO], boosting, and multivariate adaptive regression splines [MuARS]) were each used to form a prognostic model for each of four outcomes obtained at a 12 month follow-up (disability-neck disability index [NDI]), quality of life (EQ5D), present neck pain intensity, and present arm pain intensity). For all four outcomes, the differences in mean performance between all four models were small (difference of NDI < 1 point; EQ5D < 0.1 point; neck and arm pain < 2 points). Given that the predictive accuracy of all four modelling methods were clinically similar, the optimal modelling method may be selected based on the parsimony of predictors. Some of the most parsimonious models were achieved using MuARS, a non-linear technique. Modern machine learning methods may be used to probe relationships along different regions of the predictor space.

A pilot study of essential tremor: cerebellar GABA+/Glx ratio is correlated with tremor severity.

OBJECTIVE: Essential tremor is a common movement disorder with an unclear origin. Emerging evidence suggests the role of the cerebellum and the thalamus in tremor pathophysiology. We examined the two main neurotransmitters acting inhibitory (GABA+) and excitatory (Glx) respectively, in the thalamus and cerebellum, in patients diagnosed with severe essential tremor. Furthermore, we also investigated the relationship between determined neurotransmitter concentrations and tremor severity in the essential tremor patients. METHODS: Ten essential tremor patients (prior to deep brain stimulation surgery) and six healthy controls, were scanned using a 3 T MR system. GABA+ and Glx concentrations were measured using magnetic resonance spectroscopy (MRS) performed using single voxel MEGA-PRESS. For the purpose of assessing the tremor severity, the essential tremor rating scale (ETRS) was used in accordance with Fahn, Tolosa, and Marin. RESULTS: We demonstrated that the cerebellar GABA+/Glx ratio was positively correlated to the ETRS (r = 0.70, p = 0.03) in essential tremor. Cerebellar and thalamic GABA+ and Glx concentrations did not show any significant difference when comparing essential tremor patients with healthy controls, at the group level. CONCLUSION: We demonstrated a positive correlation between increasing tremor disability and the ratio of GABA+/ Glx in the cerebellum of essential tremor patients. This highlights the impact of an altered balance of the excitatory and inhibitory neurotransmitters in tremor severity. Rather than a change in GABA+, which was constant, we attribute this finding to an overall decrease of Glx.

Neck-Related Headache in Patients With Cervical Disc Disease After Surgery and Physiotherapy: A 1-Year Follow-up of a Prospective Randomized Study.

STUDY DESIGN: A prospective randomized multicenter trial. OBJECTIVE: To investigate the effects of surgery with either structured postoperative physiotherapy or standard postoperative approach on neck-related headache in patients with cervical radiculopathy. Secondary, to investigate associations between change in neck-related headache and change in neck muscle endurance, neck mobility, or neck pain. SUMMARY OF BACKGROUND DATA: The effect of physiotherapy on individuals with neck-related headache after surgery for cervical radiculopathy due to magnetic resonance imaging-verified disc disease is unknown. METHODS: One hundred six patients with neck-related headache and participating in a randomized controlled trial evaluating the additional effects of physiotherapy after surgery for cervical radiculopathy were included. Patients were randomized preoperatively to structured postoperative physiotherapy (n = 51) or the standard postoperative approach (n = 55). Outcome measures were headache intensity and neck pain intensity, neck muscle endurance, and neck mobility. Measures were obtained preoperatively and at 6 weeks, 3 months, 6 months, and 1 year postoperatively. RESULTS: Headache intensity significantly changed from baseline to 1 year postoperatively (P < 0.001) in both groups. Post-hoc tests showed a significant difference between baseline and 6 weeks (P ≤ 0.05). No significant differences were found between groups (P > 0.05) or between-group differences in changes over time (P > 0.05). The change in current headache intensity over time was associated with a change in current neck pain intensity over time (P = 0.003, ß = 0.40). CONCLUSION: There was a significant improvement in headache intensity 1 year postoperatively in patients with cervical radiculopathy and neck-related headache, but there were no differences between groups over time. Change in current headache intensity was only associated with a change in current neck pain intensity. LEVEL OF EVIDENCE: 2.

Optical Measurements during Asleep Deep Brain Stimulation Surgery along Vim-Zi Trajectories.

BACKGROUND: Optics can be used for guidance in deep brain stimulation (DBS) surgery. The aim was to use laser Doppler flowmetry (LDF) to investigate the intraoperative optical trajectory along the ventral intermediate nucleus (VIM) and zona incerta (Zi) regions in patients with essential tremor during asleep DBS surgery, and whether the Zi region could be identified. METHODS: A forward-looking LDF guide was used for creation of the trajectory for the DBS lead, and the microcirculation and tissue greyness, i.e., total light intensity (TLI) was measured along 13 trajectories. TLI trajectories and the number of high-perfusion spots were investigated at 0.5-mm resolution in the last 25 mm from the targets. RESULTS: All implantations were done without complications and with significant improvement of tremor (p < 0.01). Out of 798 measurements, 12 tissue spots showed high blood flow. The blood flow was significantly higher in VIM than in Zi (p < 0.001). The normalized mean TLI curve showed a significant (p < 0.001) lower TLI in the VIM region than in the Zi region. CONCLUSION: Zi DBS performed asleep appears to be safe and effective. LDF monitoring provides direct in vivomeasurement of the microvascular blood flow in front of the probe, which can help reduce the risk of hemorrhage. LDF can differentiate between the grey substance in the thalamus and the transmission border entering the posterior subthalamic area where the tissue consists of more white matter tracts.

Probing the mechanisms underpinning recovery in post-surgical patients with cervical radiculopathy using Bayesian networks.

BACKGROUND: Rehabilitation approaches should be based on an understanding of the mechanisms underpinning functional recovery. Yet, the mediators that drive an improvement in post-surgical pain-related disability in individuals with cervical radiculopathy (CR) are unknown. The aim of the present study is to use Bayesian networks (BN) to learn the probabilistic relationships between physical and psychological factors, and pain-related disability in CR. METHODS: We analysed a prospective cohort dataset of 201 post-surgical individuals with CR. In all, 15 variables were used to build a BN model: age, sex, neck muscle endurance, neck range of motion, neck proprioception, hand grip strength, self-efficacy, catastrophizing, depression, somatic perception, arm pain intensity, neck pain intensity and disability. RESULTS: A one point increase in a change of self-efficacy at 6 months was associated with a 0.09 point decrease in a change in disability at 12 months (t = -64.09, p < .001). Two pathways led to a change in disability: a direct path leading from a change in self-efficacy at 6 months to disability, and an indirect path which was mediated by neck and arm pain intensity changes at 6 and 12 months. CONCLUSIONS: This is the first study to apply BN modelling to understand the mechanisms of recovery in post-surgical individuals with CR. Improvements in pain-related disability was directly and indirectly driven by changes in self-efficacy levels. The present study provides potentially modifiable mediators that could be the target of future intervention trials. BN models could increase the precision of treatment and outcome assessment of individuals with CR. SIGNIFICANCE: Using Bayesian Network modelling, we found that changes in self-efficacy levels at 6-month post-surgery directly and indirectly influenced the change in disability in individuals with CR. A mechanistic understanding of recovery provides potentially modifiable mediators that could be the target of future intervention trials.

Proteomic Analysis of the Cerebrospinal Fluid in Patients With Essential Tremor Before and After Deep Brain Stimulation Surgery: A Pilot Study.

OBJECTIVE: Electrical neuromodulation by deep brain stimulation (DBS) is a well-established method for treatment of severe essential tremor (ET). The mechanism behind the tremor relieving effect remains largely unknown. Our aim of this study was to evaluate alterations in proteomics pre- and post-DBS in patients diagnosed with severe ET. MATERIALS AND METHODS: Ten right-handed ET patients were included in this study. Cerebrospinal fluid (CSF) was obtained by lumbar puncture preoperatively (N = 10) and six months postoperatively (N = 7). The samples were analyzed by high sensitive liquid chromatography tandem mass spectrometry. RESULTS: Twenty-two proteins were statistically significantly altered in the CSF of ET patients before and after DBS treatment. Downregulated proteins were involved in regulatory processes of protein activation, complement activation, humoral immune response as well as acute inflammatory response. The upregulated proteins were involved in pathways for cell secretion, adhesion as well as response to axon injury. CONCLUSIONS: DBS in ET patients effects the neurochemical environment in the CSF. These findings further elucidate the mechanisms of DBS and may lead to new biomarkers for evaluating the effect of DBS treatment.