Muscle spindles of the multifidus muscle undergo structural change after intervertebral disc degeneration.

PURPOSE: Proprioceptive deficits are common in low back pain. The multifidus muscle undergoes substantial structural change after back injury, but whether muscle spindles are affected is unclear. This study investigated whether muscle spindles of the multifidus muscle are changed by intervertebral disc (IVD) degeneration in a large animal model. METHODS: IVD degeneration was induced by partial thickness annulus fibrosus lesion to the L3-4 IVD in nine sheep. Multifidus muscle tissue at L4 was harvested at six months after lesion, and from six age-/sex-matched naïve control animals. Muscle spindles were identified in Van Gieson's-stained sections by morphology. The number, location and cross-sectional area (CSA) of spindles, the number, type and CSA of intrafusal fibers, and thickness of the spindle capsule were measured. Immunofluorescence assays examined Collagen I and III expression. RESULTS: Multifidus muscle spindles were located centrally in the muscle and generally near connective tissue. There were no differences in the number or location of muscle spindles after IVD degeneration and only changes in the CSA of nuclear chain fibers. The thickness of connective tissue surrounding the muscle spindle was increased as was the expression of Collagen I and III. CONCLUSION: Changes to the connective tissue and collagen expression of the muscle spindle capsule are likely to impact their mechanical properties. Changes in capsule stiffness may impact the transmission of length change to muscle spindles and thus transduction of sensory information. This change in muscle spindle structure may explain some of the proprioceptive deficits identified with low back pain.

Late Deformity Following Fronto-Orbital Reconstructive Surgery for Metopic Synostosis: The Role of Temporalis Muscle.

ABSTRACT: Theories for late-developing deformity (LDD) following fronto-orbital reconstructive surgery (FOR) for metopic synostosis (MS) must explain both its delayed onset and its physical characteristics. This study examined whether FOR-related interference with the normal childhood expansion of temporalis is responsible for its soft tissue component.Three-dimensional reformats of preoperative and postoperative computed tomography scans of MS patients were reviewed. Measurements of vertical and horizontal reach of temporalis against those of the underlying skull (to allow for normal skull growth) were compared with normal subjects. The thickness of temporalis and the development of the temporal crests were also assessed.Mean age at FOR was 17.1 months; interval between surgery and first report of LDD 4.7 years; mean age at computed tomography scan for post-FOR LDD patients 8.8 years. There was a significant difference between vertical and horizontal reach of temporalis in pre-FOR MS patients compared to normal subjects ( P < 0.0017 and P < 0.05, respectively). The vertical age-related reach of temporalis in post-FOR patients after allowing for underlying skull growth was significantly reduced ( P = 0.0045) compared to normal subjects but not its horizontal reach ( P = 0.25). Temporal crests in LDD patients were absent or aberrantly formed while muscle thickness was similar to normal subjects at the 2 levels measured.This study supports the theory that failure of the normal childhood expansion of temporalis is responsible for the soft tissue element of LDD, accounting for both its delayed onset and physical characteristics. Aberrant temporal crest development suggests FOR-related damage as the probable cause.

Workflow Integration of Research AI Tools into a Hospital Radiology Rapid Prototyping Environment.

The field of artificial intelligence (AI) in medical imaging is undergoing explosive growth, and Radiology is a prime target for innovation. The American College of Radiology Data Science Institute has identified more than 240 specific use cases where AI could be used to improve clinical practice. In this context, thousands of potential methods are developed by research labs and industry innovators. Deploying AI tools within a clinical enterprise, even on limited retrospective evaluation, is complicated by security and privacy concerns. Thus, innovation must be weighed against the substantive resources required for local clinical evaluation. To reduce barriers to AI validation while maintaining rigorous security and privacy standards, we developed the AI Imaging Incubator. The AI Imaging Incubator serves as a DICOM storage destination within a clinical enterprise where images can be directed for novel research evaluation under Institutional Review Board approval. AI Imaging Incubator is controlled by a secure HIPAA-compliant front end and provides access to a menu of AI procedures captured within network-isolated containers. Results are served via a secure website that supports research and clinical data formats. Deployment of new AI approaches within this system is streamlined through a standardized application programming interface. This manuscript presents case studies of the AI Imaging Incubator applied to randomizing lung biopsies on chest CT, liver fat assessment on abdomen CT, and brain volumetry on head MRI.

Parcellation of the Human Cerebral Cortex Based on Molecular Targets in the Serotonin System Quantified by Positron Emission Tomography In vivo.

Parcellation of distinct areas in the cerebral cortex has a long history in neuroscience and is of great value for the study of brain function, specialization, and alterations in neuropsychiatric disorders. Analysis of cytoarchitectonical features has revealed their close association with molecular profiles based on protein density. This provides a rationale for the use of in vivo molecular imaging data for parcellation of the cortex with the advantage of whole-brain coverage. In the current work, parcellation was based on expression of key players of the serotonin neurotransmitter system. Positron emission tomography was carried out for the quantification of serotonin 1A (5-HT1A, n = 30) and 5-HT2A receptors (n = 22), the serotonin-degrading enzyme monoamine oxidase A (MAO-A, n = 32) and the serotonin transporter (5-HTT, n = 24) in healthy participants. Cortical protein distribution maps were obtained using surface-based quantification. Based on k-means clustering, silhouette criterion and bootstrapping, five distinct clusters were identified as the optimal solution. The defined clusters proved of high explanatory value for the effects of psychotropic drugs acting on the serotonin system, such as antidepressants and psychedelics. Therefore, the proposed method constitutes a sensible approach towards integration of multimodal imaging data for research and development in neuropharmacology and psychiatry.

Spatial analysis and high resolution mapping of the human whole-brain transcriptome for integrative analysis in neuroimaging.

The quantification of big pools of diverse molecules provides important insights on brain function, but is often restricted to a limited number of observations, which impairs integration with other modalities. To resolve this issue, a method allowing for the prediction of mRNA expression in the entire brain based on microarray data provided in the Allen Human Brain Atlas was developed. Microarray data of 3702 samples from 6 brain donors was registered to MNI and cortical surface space using FreeSurfer. For each of 18,686 genes, spatial dependence of transcription was assessed using variogram modelling. Variogram models were employed in Gaussian process regression to calculate best linear unbiased predictions for gene expression at all locations represented in well-established imaging atlases for cortex, subcortical structures and cerebellum. For validation, predicted whole-brain transcription of the HTR1A gene was correlated with [carbonyl-11C]WAY-100635 positron emission tomography data collected from 30 healthy subjects. Prediction results showed minimal bias ranging within ±0.016 (cortical surface), ±0.12 (subcortical regions) and ±0.14 (cerebellum) in units of log2 expression intensity for all genes. Across genes, the correlation of predicted and observed mRNA expression in leave-one-out cross-validation correlated with the strength of spatial dependence (cortical surface: r = 0.91, subcortical regions: r = 0.85, cerebellum: r = 0.84). 816 out of 18,686 genes exhibited a high spatial dependence accounting for more than 50% of variance in the difference of gene expression on the cortical surface. In subcortical regions and cerebellum, different sets of genes were implicated by high spatially structured variability. For the serotonin 1A receptor, correlation between PET binding potentials and predicted comprehensive mRNA expression was markedly higher (Spearman ρ = 0.72 for cortical surface, ρ = 0.84 for subcortical regions) than correlation of PET and discrete samples only (ρ = 0.55 and ρ = 0.63, respectively). Prediction of mRNA expression in the entire human brain allows for intuitive visualization of gene transcription and seamless integration in multimodal analysis without bias arising from non-uniform distribution of available samples. Extension of this methodology promises to facilitate translation of omics research and enable investigation of human brain function at a systems level.

Assessment of Ketamine Binding of the Serotonin Transporter in Humans with Positron Emission Tomography.

Background: Comprehensive description of ketamine's molecular binding profile becomes increasingly pressing as use in real-life patient cohorts widens. Animal studies attribute a significant role in the substance's antidepressant effects to the serotonergic system. The serotonin transporter is a highly relevant target in this context, because it is central to depressive pathophysiology and treatment. This is, to our knowledge, the first study investigating ketamine's serotonin transporter binding in vivo in humans. Methods: Twelve healthy subjects were assessed twice using [11C]DASB positron emission tomography. A total of 0.50 mg/kg bodyweight ketamine was administered once i.v. prior to the second positron emission tomography scan. Ketamine plasma levels were determined during positron emission tomography. Serotonin transporter nondisplaceable binding potential was computed using a reference region model, and occupancy was calculated for 4 serotonin transporter-rich regions (caudate, putamen, thalamus, midbrain) and a whole-brain region of interest. Results: After administration of the routine antidepressant dose, ketamine showed <10% occupancy of the serotonin transporter, which is within the test-retest variability of [11C]DASB. A positive correlation between ketamine plasma levels and occupancy was shown. Conclusions: Measurable occupancy of the serotonin transporter was not detectable after administration of an antidepressant dose of ketamine. This might suggest that ketamine binding of the serotonin transporter is unlikely to be a primary antidepressant mechanism at routine antidepressant doses, as substances that facilitate antidepressant effects via serotonin transporter binding (e.g., selective serotonin reuptake inhibitors) show 70% to 80% occupancy. Administration of high-dose ketamine is widening. Based on the positive relationship we find between ketamine plasma levels and occupancy, there is a need for investigation of ketamine's serotonin transporter binding at higher doses.

Macrophage polarization contributes to local inflammation and structural change in the multifidus muscle after intervertebral disc injury.

PURPOSE: Intervertebral disk (IVD) lesion and its subsequent degeneration have a profound effect on the multifidus muscle. The subacute/early chronic phase of multifidus remodeling after IVD lesion has been proposed to be regulated by inflammatory processes. The balance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages plays an important role in maintaining tissue integrity after injury. The localization, polarization of macrophage subtypes and their mediation of the pro-inflammatory cytokine tumor necrosis factor (TNF) are unknown in paraspinal muscles during IVD degeneration. A sheep model of IVD degeneration was used to investigate the role of macrophages and TNF in the structural alterations that occur within the multifidus muscle. METHODS: Anterolateral lesions were induced at L3-4 IVD in sheep. Multifidus muscle tissue at L4 was harvested 3 and 6 months after lesion and used for immunofluorescence assays to examine total macrophage number, macrophage polarization between M1 and M2, and to assess the localization of TNF expression in muscle, adipose and connective tissues from injured and naïve control animals. RESULTS: A greater proportion of M1 macrophages is present in muscle at both 3 and 6 months after IVD lesion, and adipose tissue at 6 months. Total number of macrophages is unchanged. At 6 months, expression of TNF is increased in adipose and connective tissue and the proportion of TNF expressed by M1 macrophages is increased. CONCLUSIONS: These data support the proposal that macrophages and TNF (pro-inflammatory cytokine) play an active role in the subacute/early chronic phase of remodeling in muscle, adipose and connective tissues of the multifidus during IVD degeneration. This presents a novel target for treatment. These slides can be retrieved under Electronic Supplementary Material.

Altered interregional molecular associations of the serotonin transporter in attention deficit/hyperactivity disorder assessed with PET.

Altered serotonergic neurotransmission has been found to cause impulsive and aggressive behavior, as well as increased motor activity, all exemplifying key symptoms of ADHD. The main objectives of this positron emission tomography (PET) study were to investigate the serotonin transporter binding potential (SERT BPND ) in patients with ADHD and to assess associations of SERT BPND between the brain regions. 25 medication-free patients with ADHD (age ± SD; 32.39 ± 10.15; 10 females) without any psychiatric comorbidity and 25 age and sex matched healthy control subjects (33.74 ± 10.20) were measured once with PET and the highly selective and specific radioligand [11 C]DASB. SERT BPND maps in nine a priori defined ROIs exhibiting high SERT binding were compared between groups by means of a linear mixed model. Finally, adopted from structural and functional connectivity analyses, we performed correlational analyses using regional SERT binding potentials to examine molecular interregional associations between all selected ROIs. We observed significant differences in the interregional correlations between the precuneus and the hippocampus in patients with ADHD compared to healthy controls, using SERT BPND of the investigated ROIs (P < 0.05; Bonferroni corrected). When correlating SERT BPND and age in the ADHD and the healthy control group, we confirmed an age-related decline in brain SERT binding in the thalamus and insula (R2 = 0.284, R2 = 0.167, Ps < 0.05; Bonferroni corrected). The results show significantly different interregional molecular associations of the SERT expression for the precuneus with hippocampus in patients with ADHD, indicating presumably altered functional coupling. Altered interregional coupling between brain regions might be a sensitive approach to demonstrate functional and molecular alterations in psychiatric conditions. Hum Brain Mapp 38:792-802, 2017. © 2016 Wiley Periodicals, Inc.

Effects of norepinephrine transporter gene variants on NET binding in ADHD and healthy controls investigated by PET.

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous disorder with a strong genetic component. The norepinephrine transporter (NET) is a key target for ADHD treatment and the NET gene has been of high interest as a possible modulator of ADHD pathophysiology. Therefore, we conducted an imaging genetics study to examine possible effects of single nucleotide polymorphisms (SNPs) within the NET gene on NET nondisplaceable binding potential (BPND ) in patients with ADHD and healthy controls (HCs). Twenty adult patients with ADHD and 20 HCs underwent (S,S)-[18F]FMeNER-D2 positron emission tomography (PET) and were genotyped on a MassARRAY MALDI-TOF platform using the Sequenom iPLEX assay. Linear mixed models analyses revealed a genotype-dependent difference in NET BPND between groups in the thalamus and cerebellum. In the thalamus, a functional promoter SNP (-3081 A/T) and a 5'-untranslated region (5'UTR) SNP (-182 T/C), showed higher binding in ADHD patients compared to HCs depending on the major allele. Furthermore, we detected an effect of genotype in HCs, with major allele carriers having lower binding. In contrast, for two 3'UTR SNPs (*269 T/C, *417 A/T), ADHD subjects had lower binding in the cerebellum compared to HCs depending on the major allele. Additionally, symptoms of hyperactivity and impulsivity correlated with NET BPND in the cerebellum depending on genotype. Symptoms correlated positively with cerebellar NET BPND for the major allele, while symptoms correlated negatively to NET BPND in minor allele carriers. Our findings support the role of genetic influence of the NE system on NET binding to be pertubated in ADHD.

Syncope Secondary to Concomitant Ingestion of Tizanidine and Alcohol in a Patient With Alcohol Use Disorder.

Syncope is the transient loss of consciousness due to cerebral hypoperfusion. A significant number of individuals experience a syncopal attack at one stage of their lives. The common causes of syncope include vasovagal syncope, orthostatic hypotension, and cardiac causes. Drugs are also associated with causing syncope. The drugs involved are mostly those that depress the central nervous system, and concomitant use of more than one of such drugs increases the risk of syncope even further. Tizanidine and alcohol individually can cause hypotension and combining both drugs is not advised due to heightened central nervous system depression and profound hypotension. We present a case of a 53-year-old female with alcohol use disorder who presented with a first-time syncopal attack due to postural hypotension after ingesting both tizanidine and alcohol concurrently. Co-administration of tizanidine and alcohol is not advised, however, cases of syncope have been rarely reported with concomitant use. This case will enlighten physicians to counsel patients about the need to abstain from alcohol consumption when taking tizanidine.

Optimising cylinder model dimensions for VARSKIN to simulate a droplet of radionuclide skin contamination using Geant4 Monte Carlo code.

AIM: VARSKIN provides a convenient way of calculating skin dose from predefined geometries but the models are limited to concentric shapes such as discs, cylinders and point sources. The aim of this article is to use the Geant4 Monte Carlo code to independently compare the cylindrical geometries available in VARSKIN to more realistic droplet models obtained from photography. It may then be possible to recommend an appropriate cylinder model that can be used to represent a droplet within acceptable accuracy. METHOD: Geant4 Monte Carlo code was used to model various droplets of radioactive liquid on the skin based on photographs. The dose rates were then calculated to the sensitive basal layer 70 µm beneath the surface for three droplet volumes (10, 30 and 50 µl) and 26 radionuclides. The dose rates from the cylinder models were then compared against the dose rates from the 'true' droplet models. RESULTS: The table gives the optimum cylinder dimensions that best approximate a true droplet shape for each volume. The mean bias and 95% confidence interval (CI) from the true droplet model are also quoted. CONCLUSION: The evidence from the Monte Carlo data suggests that different droplet volumes require different cylinder aspect ratios to approximate the true droplet shape. Using the cylinder dimensions in the table in software packages such as VARSKIN, dose rates from radioactive skin contamination are expected to be within ± 7.4% of a 'true' droplet model at 95% CI.

Methods for Culturing Anaerobic Microorganisms.

Anaerobic microorganisms (anaerobes) proliferate in diverse oxygen-free environments. They inhabit Earth's soils and aquatic sediments, the rumen and gut of mammals, and the gut of insects among many other oxygen-free environments. Anaerobes impact biotechnological, biomedical, ecological, and astrobiological fields. Sensitivity to oxygen is of prime consideration for successful culturing which is essential to understand function. Although cultivated for many years, the protocols and media components have been modified and adapted to the special needs of species, as well as conditions and variables for experimental evaluations. Here we describe a revised method used in our laboratories for the growth of methane-producing anaerobes (methanogenic archaea) which are among the most oxygen sensitive. The method is an example for the preparation of more specific media to cultivate a wide diversity of anaerobes.

Spring-assisted posterior vault expansion: a parametric study to improve the intracranial volume increase prediction.

Spring-assisted posterior vault expansion has been adopted at the London Great Ormond Street Hospital for Children to treat raised intracranial pressure in patients affected by syndromic craniosynostosis, a congenital calvarial anomaly causing the premature fusion of skull sutures. This procedure involves elastic distractors used to dynamically reshape the skull and increase the intracranial volume (ICV). In this study, we developed and validated a patient-specific model able to predict the ICV increase and carried out a parametric study to investigate the effect of surgical parameters on that final volume. Pre- and post-operative computed tomography data relative to 18 patients were processed to extract simplified patient-specific skull shape, replicate surgical cuts, and simulate spring expansion. A parametric study was performed to quantify each parameter's impact on the surgical outcome: for each patient, the osteotomy location was varied in a pre-defined range; local sensitivity of the predicted ICV to each parameter was analysed and compared. Results showed that the finite element model performed well in terms of post-operative ICV prediction and allowed for parametric optimization of surgical cuts. The study indicates how to optimize the ICV increase according to the type of procedure and provides indication on the most robust surgical strategy.

Comparison of two capillary gel electrophoresis systems for Clostridium difficile ribotyping, using a panel of ribotype 027 isolates and whole-genome sequences as a reference standard.

PCR ribotyping is the most commonly used Clostridium difficile genotyping method, but its utility is limited by lack of standardization. In this study, we analyzed four published whole genomes and tested an international collection of 21 well-characterized C. difficile ribotype 027 isolates as the basis for comparison of two capillary gel electrophoresis (CGE)-based ribotyping methods. There were unexpected differences between the 16S-23S rRNA intergenic spacer region (ISR) allelic profiles of the four ribotype 027 genomes, but six bands were identified in all four and a seventh in three genomes. All seven bands and another, not identified in any of the whole genomes, were found in all 21 isolates. We compared sequencer-based CGE (SCGE) with three different primer pairs to the Qiagen QIAxcel CGE (QCGE) platform. Deviations from individual reference/consensus band sizes were smaller for SCGE (0 to 0.2 bp) than for QCGE (4.2 to 9.5 bp). Compared with QCGE, SCGE more readily distinguished bands of similar length (more discriminatory), detected bands of larger size and lower intensity (more sensitive), and assigned band sizes more accurately and reproducibly, making it more suitable for standardization. Specifically, QCGE failed to identify the largest ISR amplicon. Based on several criteria, we recommend the primer set 16S-USA/23S-USA for use in a proposed standard SCGE method. Similar differences between SCGE and QCGE were found on testing of 14 isolates of four other C. difficile ribotypes. Based on our results, ISR profiles based on accurate sequencer-based band lengths would be preferable to agarose gel-based banding patterns for the assignment of ribotypes.

Hydrodynamic force on a microparticle approaching a wall in a nanoparticle dispersion: observation of a separation-dependent effective viscosity.

Colloid probe atomic force microscopy was used to measure the hydrodynamic force exerted on a 30-µm-diameter silica particle being moved toward or away from a silica plate in aqueous dispersions of 22-nm-diameter silica nanoparticles (6 or 8 vol %). Upon comparing the measured force to predictions made using the well-known expression of Cox and Brenner (Cox, R. G.; Brenner, H. Chem. Eng. Sci.1967, 22, 1753-1777) assuming a constant viscosity equal to that of the bulk dispersion, the measured drag force was found to become significantly less than that predicted at smaller particle-plate separation distances (e.g., <500 nm). A recent theoretical paper by Bhattacharya and Blawzdziewicz (Bhattacharya, S.; Blawzdziewicz, J. J. Chem. Phys.2008, 128, 214704) predicted that in a solution of dispersed nanoparticles the effective viscosity characterizing the hydrodynamic force on the particle should vary from that of the solvent at contact to that of the bulk dispersion at large separations. By adjusting the viscosity in the Cox and Brenner expression to make the predicted hydrodynamic force match that measured (i.e., the effective viscosity), a curve showing these exact characteristics was obtained. The effective viscosity profile was not a function of particle speed, and changes in the effective viscosity extended to separation distances of as large as 2 µm (nearly 100 times the hard diameter of the nanoparticles). These results suggest that in the range of typical colloidal forces (on the order of 100 nm), the dynamics of particle motion in such systems are determined by the viscosity of the solvent and not that of the bulk dispersion.

Dynamic tire pressure sensor for measuring ground vibration.

This work presents a convenient and non-contact acoustic sensing approach for measuring ground vibration. This approach, which uses an instantaneous dynamic tire pressure sensor (DTPS), possesses the capability to replace the accelerometer or directional microphone currently being used for inspecting pavement conditions. By measuring dynamic pressure changes inside the tire, ground vibration can be amplified and isolated from environmental noise. In this work, verifications of the DTPS concept of sensing inside the tire have been carried out. In addition, comparisons between a DTPS, ground-mounted accelerometer, and directional microphone are made. A data analysis algorithm has been developed and optimized to reconstruct ground acceleration from DTPS data. Numerical and experimental studies of this DTPS reveal a strong potential for measuring ground vibration caused by a moving vehicle. A calibration of transfer function between dynamic tire pressure change and ground acceleration may be needed for different tire system or for more accurate application.

Multifidus Muscle Fiber Type Distribution is Changed in Mouse Models of Chronic Intervertebral Disc Degeneration, but is not Attenuated by Whole Body Physical Activity.

STUDY DESIGN: Case-controlled animal study. OBJECTIVE: The aim of this study was to investigate whether multifidus muscle fiber type distribution changes in models of interverbal disc (IVD) degeneration and whether this is resolved by physical activity (PA). SUMMARY OF BACKGROUND DATA: The loss of slow type I muscle fibers in the multifidus muscle in people with low back pain is contentious. Data from animal models of IVD degeneration suggest some discrepancies in human studies might be explained by the dependence of slow muscle fiber changes and their underlying mechanisms, on the time since injury and progression of IVD degeneration. It is not yet resolved what changes are apparent once the chronic phase is established. It is also not known whether muscle fiber changes can be resolved by whole body PA. This study aimed to examine slow fiber distribution in the multifidus muscle in models of IVD injury or spontaneous degeneration in animals with or without exposure to PA. METHODS: Two models of IVD degeneration were used. The first model used a genetically modified mouse (SPARC-null) that spontaneously develops IVD degeneration. The second model involved a surgically induced IVD lesion to induce degeneration. Mice in each study were allocated to housing with or without a running wheel for PA. At 12 months of age, the multifidus muscle was harvested. Slow muscle fiber distribution and the mRNA expression of genes associated with muscle fiber type transformation were examined. RESULTS: The proportion and cross-sectional area of slow muscle fibers were reduced in both models of IVD degeneration compared to controls, without evidence of ongoing fiber transformation. Whole-body PA did not attenuate these alterations. CONCLUSION: Results confirmed slow muscle fiber loss in the multifidus in the chronic phase of IVD degeneration induced spontaneously and by injury. Whole-body PA did not attenuate changes to muscle fiber distribution. More specific approaches to muscle activation might be required to achieve more complete reversal of muscle fiber changes, with potential implications for therapy in humans.Level of Evidence: N/A.

Do Markers of Inflammation and/or Muscle Regeneration in Lumbar Multifidus Muscle and Fat Differ Between Individuals with Good or Poor Outcome Following Microdiscectomy for Lumbar Disc Herniation?

STUDY DESIGN: Observational study. OBJECTIVE: The aim of this study was to evaluate whether inflammatory and/or muscle regeneration markers in paraspinal tissues (multifidus muscle/fat) during microdiscectomy surgery in patients with lumbar disc herniation (LDH) with radiculopathy, differ between individuals with good or poor outcome. SUMMARY OF BACKGROUND DATA: Structural back muscle changes, including fat infiltration, muscle atrophy, and fiber changes, are ubiquitous with LBP and are thought to be regulated by inflammatory and regeneration processes. Muscle changes might be relevant for recovery after microdiscectomy, but a link between expression of inflammatory and muscle regeneration genes in paraspinal tissues and clinical outcome has not been tested. METHOD: Paraspinal tissues from deep multifidus muscles and fat (intramuscular, sub-cutaneous, epidural) were harvested from twenty-one patients with LDH undergoing microdiscectomy surgery. Quantitative polymerase chain reaction (qPCR) measured expression of 10 genes. Outcome was defined as good (visual analogue scale (VAS) low back pain (LBP)+) or poor (VAS LBP-) by an improvement of >33% or ≤33% on the pain VAS, respectively. Good functional improvement was defined as 25% improvement on the physical functioning scale (PFS). RESULTS: Brain-derived neurotrophic factor expression in deep multifidus was 91% lower (P = 0.014) in the VAS LBP- than VAS LBP+ group. Expression of interleukin-1ß in subcutaneous fat was 48% higher (P = 0.026) in the VAS LBP- than VAS LBP+ group. No markers differed based on PFS. CONCLUSION: Results show a relationship between impaired muscle regeneration profile in multifidus muscle and poor outcome following microdiscectomy for LDH. Inflammatory dysregulation in subcutaneous fat overlying the back region might predict poor surgical outcome.Level of Evidence: 4.