Localization of Nerve Growth Factor Expression to Structurally Damaged Cartilaginous Tissues in Human Lumbar Facet Joint Osteoarthritis.

Purpose: Nerve Growth Factor (NGF) is a pivotal mediator of chronic pain and plays a role in bone remodelling. Through its high affinity receptor TrkA, NGF induces substance P (SP) as key downstream mediator of pain and local inflammation. Here we analysed NGF, TrkA and SP tissue distribution in facet joint osteoarthritis (FJOA), a major cause of chronic low back pain. Methods: FJOA specimens (n=19) were harvested from patients undergoing intervertebral fusion surgery. Radiologic grading of FJOA and spinal stenosis, followed by immunohistochemistry for NGF, TrkA and SP on consecutive tissue sections, was performed in ten specimens. Explant cultures (n=9) were used to assess secretion of NGF, IL-6, and SP by FJOA osteochondral tissues under basal and inflammatory conditions. Results: NGF was predominantly expressed in damaged cartilaginous tissues (80%), occasionally in bone marrow (20%), but not in osteochondral vascular channels. NGF area fraction in cartilage was not associated with the extent of proteoglycan loss or radiologic FJOA severity. Consecutive sections showed that NGF and SP expression was localized at structurally damaged cartilage, in absence of TrkA expression. SP and TrkA were expressed in subchondral bone marrow in both presence and absence of NGF. Low level NGF, but not SP secretion, was detected in four out of eighteen FJOA explants under both basal or inflammatory conditions (n=2 each). Conclusion: NGF is associated with SP expression and structural cartilage damage in osteoarthritic facet joints, but not with radiologic disease severity. NGF tissue distribution in FJOA differs from predominant subchondral bone expression reported for knee OA.

Origin, branching pattern, foraminal and intraspinal distribution of the human lumbar sinuvertebral nerves.

BACKGROUND CONTEXT: The lumbar sinuvertebral nerve (SVN) innervates the outer posterior intervertebral disc (IVD); it is thought to mediate discogenic low-back pain (LBP). Controversy, however, exists on its origins at higher (L1-L2) versus lower (L3-L5) lumbar levels. Additionally, lack of knowledge regarding its foraminal and intraspinal branching patterns and extensions may lead to iatrogenic damage. PURPOSE: To systematically describe the origins of the L2 and L5 SVNs, their morphological variation in the intervertebral foramen (IVF) and intraspinal distribution. STUDY DESIGN: Dissection-based study of 20 SVNs with histological confirmation in five embalmed human cadavers. METHODS: The origin, branching pattern and distribution of the L2 and L5 SVNs was investigated bilaterally in five human cadavers using dorsal and anterolateral dissection approaches. Parameters studied included somatic and/or autonomic SVN root contributions, foraminal SVN morphology and course, diameter, branching point, intraspinal distribution and IVD innervation pattern. Nerve tissue was confirmed by immunostaining for neurofilament and S100 proteins. RESULTS: The SVN and its origins was identified in all except one IVF at L2 and in all foramina at L5. At L2, the SVN arose in nearly 90% of sides from both somatic and autonomic roots and at L5 in 40% of sides. The remaining SVNs were formed by purely autonomic roots. The SVN arose from significantly more roots at L2 than L5 (3.1 ± 0.3 vs. 1.9 ± 0.3, respectively; p=.022). Four different SVN morphologies could be discerned in the L2 IVF: single filament (22%), multiple (parallel or diverging) filament (33%), immediate splitting (22%) and plexiform (22%) types, whereas the L5 SVN consisted of single (90%) and multiple (10%) filament types. SVN filaments were significantly thicker at L2 than L5 (0.48 ± 0.06 mm vs. 0.33 ± 0.02 mm, respectively; p=.043). Ascending SVN filaments coursed roughly parallel to the exiting spinal nerve root trajectory at L2 and L5. Branching of the SVN into ascending and descending branches occurred mostly intraspinal both at L2 and L5. Spinal canal distribution was also similar for L2 and L5 SVNs. Lumbar posterior IVDs were innervated by the descending branch of the parent SVN and ascending branch of the subjacent SVN. CONCLUSIONS: The SVN at L2 originates from both somatic and autonomic roots in 90% of cases and at L5 in 40% of cases. The remaining SVNs are purely autonomic. In the IVF, the L2 SVN is morphologically heterogeneous, but generally consists of numerous filaments, whereas at L5 90% contains a single SVN filament. The L2 SVN is formed by more roots and is thicker than the L5 SVN. Intraspinal SVN distribution is confined to its level of origin; lumbar posterior IVDs are innervated by corresponding and subjacent SVNs (ie, two spinal levels). CLINICAL SIGNIFICANCE: Our findings indicate that L5 discogenic LBP may be mediated both segmentally and nonsegmentally in 40% of cases and nonsegmentally in 60% of cases. Failure of lower lumbar discogenic pain treatment may be the result of only interrupting the nonsegmental pathway, but not the segmental one as well. Relating SVN anatomy to microsurgical spinal approaches may prevent iatrogenic damage to the SVN and the formation of postsurgical back pain.

Magnetic resonance imaging-guided lumbar nerve root infiltrations: optimization of an in-house protocol.

BACKGROUND: For the treatment of radicular pain, nerve root infiltrations can be performed under MRI guidance in select, typically younger, patients where repeated CT exams are not desirable due to associated radiation risk, or potential allergic reactions to iodinated contrast medium. METHODS: Fifteen 3 T MRI-guided nerve root infiltrations were performed in 12 patients with a dedicated surface coil combined with the standard spine coil, using a breathhold PD sequence. The needle artifact on the MR images and the distance between the needle tip and the infiltrated nerve root were measured. RESULTS: The distance between the needle tip and the nerve root was 2.1 ± 1.4 mm. The visual artifact width, perpendicular to the needle long axis, was 2.1 ± 0.7 mm. No adverse events were reported. CONCLUSION: This technical note describes the optimization of the procedure in a 3 T magnetic field, including reported procedure time and an assessment of targeting precision.

A comparison of three different surgery approaches and methods for neurologically intact thoracolumbar fractures: a retrospective study.

OBJECTIVES: The purpose of this study was to evaluate and compare the feasibility, safety, and efficacy of conventional open pedicle screw fixation (COPSF), percutaneous pedicle screw fixation (PPSF), and paraspinal posterior open approach pedicle screw fixation (POPSF) for treating neurologically intact thoracolumbar fractures. METHODS: We retrospectively reviewed 108 patients who were posteriorly stabilized without graft fusion. Among them, 36 patients underwent COPSF, 38 patients underwent PPSF, and 34 patients underwent POPSF. The clinical outcomes, relative operation indexes, and radiological findings were assessed and compared among the 3 groups. RESULTS: All of the patients were followed up for a mean time of 20 months. The PPSF group and POPSF group had shorter operation times, lower amounts of intraoperative blood loss, and shorter postoperative hospital stays than the COPSF group (P < 0.05). The radiation times and hospitalization costs were highest in the PPSF group (P < 0.05). Every group exhibited significant improvements in the Cobb angle (CA) and the vertebral body angle (VBA) correction (all P < 0.05). The COPSF group and the POPSF group had better improvements than the PPSF group at 3 days postoperation and the POPSF group had the best improvements in the last follow-up (P < 0.05). CONCLUSION: Both PPSF and POPSF achieved similar effects as COPSF while also resulting in lower incidences of injury. PPSF is more advantageous in the early rehabilitation time period, compared with COPSF, but POPSF is a better option when considering the long-term effects, the costs of treatment, and the radiation times.

Does the L5 spinal nerve move? Anatomical evaluation with implications for postoperative L5 nerve palsy.

PURPOSE: While palsy of the L5 nerve root due to stretch injury is a known complication in complex lumbosacral spine surgery, the underlying pathophysiology remains unclear. The goal of this cadaveric study was to quantify movement of the L5 nerve root during flexion/extension of the hip and lower lumbar spine. METHODS: Five fresh-frozen human cadavers were dissected on both sides to expose the lumbar vertebral bodies and the L5 nerve roots. Movement of the L5 nerve root was tested during flexion and extension of the hip and lower lumbar spine. Four steps were undertaken to characterize these movements: (1) removal of the bilateral psoas muscles, (2) removal of the lumbar vertebral bodies including the transforaminal ligaments from L3 to L5, (3) opening and removing the dura mater laterally to visualize the rootlets, and (4) removal of remaining soft tissue surrounding the L5 nerve root. Two metal bars were inserted into the sacral body at the level of S1 as fixed landmarks. The tips of these bars were connected to make a line for the ruler that was used to measure movement of the L5 nerve roots. Movement was regarded as measurable when there was an L5 nerve excursion of at least 1 mm. RESULTS: The mean age at death was 86.6 years (range 68-89 years). None of the four steps revealed any measurable movement after flexion/extension of the hip and lower lumbar spine on either side (< 1 mm). Flexion of the hip and lower lumbar spine revealed lax L5 nerve roots. Extension of the hip and lower lumbar spine showed taut ones. CONCLUSION: Significant movement or displacement of the L5 nerve root could not be quantified in this study. No mechanical cause for L5 nerve palsy could be identified so the etiology of the condition remains unclear.

Muscle responses to radicular stimulation during lumbo-sacral dorsal rhizotomy for spastic diplegia: Insights to myotome innervation.

OBJECTIVE: Most of knowledge on muscle radicular innervation was from explorations in root/spinal cord pathologies. Direct and individual access to each of the lumbar-sacral -ventral and dorsal- nerve roots during dorsal rhizotomy for spastic diplegia allows precise study of the corresponding muscle innervation. Authors report the lumbo-sacral segmental myotomal organization obtained from recordings of muscle responses to root stimulation in a 20-children prospective series. METHODS: Seven key-muscles in each lower limb and anal sphincter were Electromyography (EMG)-recorded and clinically observed by physiotherapist during L2-to-S2 dorsal rhizotomy. Ventral roots (VR), for topographical mapping, and dorsal roots (DR), for segmental excitability testing, were stimulated, just above threshold for eliciting muscular response. RESULTS: In 70% of the muscles studied, VR innervation was pluri-radicular, from 2-to-4 roots, with 1 or 2 roots being dominant at each level. Overlapping was important. Muscle responses to DR stimulation were 1.75 times more extended compared to VR stimulation. Inter-individual variability was important. CONCLUSIONS: Accuracy of root identification and stimulation with the used method brings some more precise information to radicular functional anatomy. SIGNIFICANCE: Those neurophysiological findings plead for performing Intra-Operative Neuromonitoring when dealing with surgery in the lumbar-sacral roots.

Direct anterior decompression of L4 and L5 nerve root in sacral fractures using the pararectus approach: a technical note.

PURPOSE: To describe a new surgical technique for neurolysis and decompression of L4 and L5 nerve root entrapment after vertical sacral fractures via the pararectus approach for acetabular fractures, and to present four case examples. PATIENTS AND METHODS: We retrospectively evaluated four patients suffering radiculopathy from entrapment of the L4 or L5 nerve root in vertical sacral fractures between January and December 2016. The mean follow-up period after surgery was 18 (range 7-27) months. All patients underwent direct decompression and neurolysis of the L4 and L5 nerve roots via the single-incision, intrapelvic, extraperitoneal pararectus approach. RESULTS: In all patients, the L4 and L5 nerve root was successfully visualized and decompressed, proving feasibility of the pararectus approach for this indication. No patient presented with a neural tear. Complete neurologic recovery was present in one patient at last follow-up; two patients had incomplete recovery of their radiculopathy; and one patient had no improvement after nerve root decompression. CONCLUSIONS: The pararectus approach allows for sufficient visualisation and direct decompression and neurolysis of the L4 and L5 nerve root entrapped in vertical sacral fractures. Although neurologic recovery was not achieved in all patients in this small case series, the approach may be a suitable alternative to posterior approaches and other anterior approaches such as the lateral window of the ilioinguinal approach.

BMSCs-Derived Exosomes Ameliorate Pain Via Abrogation of Aberrant Nerve Invasion in Subchondral Bone in Lumbar Facet Joint Osteoarthritis.

Lumbar facet joint osteoarthritis (LFJ OA) is regarded as one of the common causes of low back pain (LBP). The pathogenesis and underlying mechanism of this disease are largely unknown, there is still no effective disease-modifying therapy. This study aims to investigate the efficacy of exosomes derived from bone marrow mesenchymal stem cells (BMSCs) on the pathogenesis and behavioral signs of LBP in the LFJ OA mouse model. The pathogenetic change in cartilage and aberrant nerve invasion in the subchondral bone of LFJ in a mouse model after treatment with BMSC-exosomes was evaluated. BMSC-exosomes could relieve pain via abrogation of aberrant CGRP-positive nerve and abnormal H-type vessel formation in the subchondral bone of LFJ. Moreover, BMSC-exosomes attenuated cartilage degeneration and inhibited tartrate-resistant acid phosphatase expression and RANKL-RANK-TRAF6 signaling activation to facilitate subchondral bone remodeling. These results indicated that BMSC-exosomes could relive behavioral signs of LBP and pathological processes in LFJ OA. BMSC-exosomes have a prominent protective effect and might be a potential therapeutic option for the treatment of LFJ OA causing LBP. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:670-679, 2020.

Erdheim-Chester disease mimicking lumbar nerve schwannoma: case report and literature review.

Introduction: Erdheim-Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis. The clinical spectrum of ECD is diverse, varying from asymptomatic focal lesion to life-threatening multisystem infiltration. Neurological manifestations of ECD are common, mostly due to the involvement of the central nerve system. However, spinal nerve or peripheral nerve involvement has rarely been mentioned. Case presentation: Herein, we present a case of a 32-year-old female patient complaining about radiating pain on the front and lateral side of her left thigh for 2 months. Spinal MRI with contrast enhancement showed a space-occupying lesion on the left L3/L4 intervertebral foramen, indicating an initial diagnosis of lumbar nerve schwannoma. The patient underwent surgery to remove the mass and decompress the lumbar nerve. Postoperative histological examination revealed the diffuse infiltration of foamy histiocytes that were CD68+, CD163+, and CD1a- on immunostaining, which confirmed the diagnosis of Erdheim-Chester disease. The radiating pain was gradually alleviated and PET-CT was performed but showed no further involvement of ECD. Discussion: To the best of our knowledge, this is the first case of ECD demonstrated as an infiltrative mass on the spinal nerve, with imaging manifestations and compression symptoms similar to those of peripheral nerve schwannoma.

Prevalence of benign osseous lesions of the spine and association with spinal pain in the general population in whole body MRI.

BACKGROUND: Benign osseous lesions of the spine are common but precise population prevalence estimates are lacking. Our study aimed to provide the first population-based prevalence estimates and examine association with back and neck pain. MATERIALS AND METHODS: We used data from the population-based Study of Health in Pomerania (SHIP). Whole-body MRI examinations (1.5 Tesla: T1, T2, and TIRM weightings) were available from 3,259 participants. Readings of the spinal MRI images were conducted according to a standardized protocol by a single reader (JS). The intra-rater reliability was greater than Kappa values of 0.98. Pain measures included the seven-day prevalence of spine pain and neck pain, and average spine pain intensity due to spine pain during the past three months. RESULTS: We found 1,200 (36.8%) participants with at least one osseous lesion (2,080 lesions in total). Osseous lesions were less common in men than in women (35.5% vs 38.9%; P = .06). The prevalence of osseous lesions was highest at L2 in both sexes. The prevalence of osseous lesions increased with age. Up to eight osseous lesions were observed in a single subject. Hemangioma (28%), and lipoma (13%) occurred most often. Sclerosis (1.7%), aneurysmal bone cysts (0.7%), and blastoma (0.3%) were rare. Different osseous lesions occurred more often in combination with each other. The association with back or neck pain was mostly negligible. CONCLUSION: Osseous lesions are common in the general population but of no clinical relevance for spinal pain. The prevalence of osseous lesions varied strongly across different regions of the spine and was also associated with age and gender. Our population-based data offer new insights and assist in judging the relevance of osseous lesions observed on MRIs of patients.

Management of lumbar radiculopathy due to disc herniation with interlaminar epidural steroid injection in the presence of multilevel Tarlov cysts in the neural foramina: A case report.

RATIONALE: Perineural cysts, commonly referred to as Tarlov cysts, are cerebrospinal fluid-filled dilations between the perineurium and endoneurium typically arising at the junction of posterior and dorsal root ganglia in the neural foramina. This anatomical location is in close proximity to usual needle trajectory during performing transforaminal epidural injection, and therefore presents a potential risk of dural puncture and associated complications. PATIENT CONCERNS: Severe lower extremity pain interfering with activities of daily living. DIAGNOSES: Lumbar radiculopathy secondary to left-sided L4-5 disc herniation in the presence of multilevel Tarlov cysts in the neural foramina. INTERVENTIONS: Posterior interlaminar epidural steroid injection technique was preferred, as opposed to transforaminal approach, to avoid potential risk of dural puncture and associated complications in the presence of multilevel Tarlov cysts in the neural foramina. OUTCOMES: The patient responded favorably to epidural steroid injection via interlaminar approach with complete resolution of pain, symptoms, and signs. There were no complications. The patient was able to tolerate physical therapy, wean pain medications, and achieve normal activities of daily living without any significant limitations. LESSONS: In patients presenting with an MRI report of "Tarlov cysts", meticulous evaluation of diagnostic images should be an essential first step before considering invasive spinal procedures. Should there be any presence of Tarlov cyst in close proximity to planned needle trajectory, we recommend appropriate modification of spinal intervention to avoid potential complications.

Superior Hypogastric Plexus and Its Surgical Implications During Spine Surgery: A Review.

The superior hypogastric plexus (SHP) is a complex nervous collection located at the lumbosacral region below the level of the aortic bifurcation. As a part of the autonomic nervous system, it is an extension of the preaortic plexuses and continues bilaterally as the hypogastric nerves that ultimately contribute to the inferior hypogastric plexus. Although commonly described as a plexiform structure, several morphologic variations exist. Damage to the SHP can occur during anterior and anterolateral approaches to the lumbosacral spine leading to dysfunction of the abdominopelvic viscera. Visceral afferents travel in the SHP and are responsible for transmitting pain. Management therapies such as SHP blockade or presacral neurectomy can reduce pelvic pain caused by cancer and nonmalignant etiologies. This review highlights some of the recent findings regarding the nature of the SHP.

Chemical lumbar sympathectomy in the treatment of recalcitrant erythromelalgia.

OBJECTIVE: Erythromelalgia is highly disabling and treatment is often very challenging. There have been solitary case reports that it might benefit from sympathectomy. This study sought to evaluate the short-term and long-term efficacy of chemical lumbar sympathectomy (CLS) for treatment of recalcitrant erythromelalgia and try to identify a CLS-responsive subset. METHODS: Patients with recalcitrant erythromelalgia were recruited from a tertiary hospital over a 10-year period. L3 to L4 CLS was performed using 5% phenol. The pain intensity score (visual analog scale [VAS] 0-10) was assessed before CLS and at 1 day, 1 week, 3 months, 6 months, 1 year, and 2 years after CLS. A VAS decrease of 90%-100% is defined as complete response, 60%-89% as major partial response. Relapse was defined by a return of a VAS score of 5 or higher. SCN9A gene mutations were screened. RESULTS: Thirteen patients were enrolled, with a median age of 15 years. The mean follow-up was 6.2 ± 3.8 years. SCN9A gene mutation was identified in five patients having family histories. The VAS was 8.2 ± 2.0 at baseline; it decreased to 4.9 ± 2.7 at 1 day and 1.9 ± 3.0 at 1 week after CLS. Nine patients (69.2%) achieved complete response at 1 week after CLS, including three patients with SCN9A gene mutation. Among the three complete response patients having the gene mutation, two reverted to major partial response and one relapsed at 2 years after CLS. Among the six complete response patients without mutation, five maintained complete response and one relapsed. Among the four patients who did not achieve complete response, one patient died at 3.5 months and one patient had an amputation performed at 4 months after CLS. CONCLUSIONS: CLS provides a valid option for the treatment of recalcitrant erythromelalgia. It takes about 1 week to achieve full efficacy. Relapse may occur, especially in patients with an SCN9A gene mutation.

Radiographic Study of Lumbar Sympathetic Trunk in Oblique Lateral Interbody Fusion Surgery.

BACKGROUND: Oblique lateral interbody fusion (OLIF) surgery provides a convenient and minimal access to the lesion disc with few complications; however, the left lumbar sympathetic trunk (LST) lies in the surgical field with a certain incidence of injury. The aim of this study was to describe the anatomic structures of the left LST at risk for injury during OLIF at different lumbar segment levels based on radiologic evaluations. METHODS: Forty-four healthy young people (22 men and 22 women) were recruited, and routine lumbar magnetic resonance radiograph was performed. The LST, abdominal aorta (AA), and psoas muscle (PM) were observed, and all parameters were acquired using axial T2-weighted turbo spin echo sequence images. Independent-samples t test, 1-way analysis of variance test, and Least significant difference test were used to explore the LST's tract and the anatomic relationship with the adjacent anatomic landmarks at different levels. RESULTS: The distance from the left lateral border of the AA to the anterior medial border of the left PM was significantly narrowing from the L2-3 to L4-5 segment levels (13.72 ± 3.00, 11.78 ± 2.69, and 9.18 ± 3.43 mm). The distance from the left lateral border of the AA to the left LST was also significantly decreased from the L2-3 to L4-5 segment levels (11.14 ± 2.89, 9.36 ± 2.79, and 6.63 ± 2.94 mm). However, the distance from the leading edge of the left PM to the left LST had no statistical differences among all adjacent segment levels (2.96 ± 0.62, 2.83 ± 0.62, and 3.07 ± 0.86 mm). The location of the left LST is more backward and lateral at level L2-3, whereas it is inside front at levels L3-4 and L4-5. CONCLUSIONS: The practical risk of LST injury in different segment levels varied with specific anatomic conditions. The segment level L2-3 could provide a safer surgical space for OLIF, and the risk of the left LST injury might be greater during OLIF at level L4-5.

Sensitivity of Computed Tomography Compared With that of Magnetic Resonance Myelography in the Presurgical Diagnosis of Foraminal or Extraforaminal Entrapment at the Lumbosacral Junction.

STUDY DESIGN: This is a retrospective analysis. OBJECTIVE: To investigate and compare the sensitivities of computed tomography (CT) and magnetic resonance myelography (MRM) in the presurgical diagnosis of foraminal or extraforaminal entrapment of the L5 nerve. SUMMARY OF BACKGROUND DATA: CT is more clinically available than MRM. Foraminal or extraforaminal entrapment at the lumbosacral junction may cause L5 radiculopathy but is difficult to diagnose. Asymmetric enlargement of the anterior primary division (APD) of the L5 nerve on preoperative CT and dorsal root ganglion (DRG) swelling and abnormal L5 nerve course on MRM coronal images have been examined in cases of foraminal or extraforaminal L5 nerve entrapment, but have not been compared directly. MATERIALS AND METHODS: Ninety-five patients (mean age 63 y; 28-85 y) with L5 nerve entrapment at the lumbosacral junction who underwent preoperative CT and MRM, and microsurgical decompression by a single surgeon (K.-H.M.) from January 2010 to June 2014 were included. Symptomatic sites were diagnosed by confirming L5 nerve entrapment intraoperatively. Two spinal surgeons independently compared the bilateral APD diameters of the L5 nerve on CT and the L5 nerve courses and DRG swelling on MRM coronal images. RESULTS: The interobserver agreement of asymmetric APD swelling on CT and abnormal nerve course and DRG swelling on MRM were excellent (κ=0.808, 0.811, and 0.849, respectively), and the sensitivities were 81%, 84%, and 82% on the right, and 86%, 92%, and 90% on the left sides, respectively. There was no statistically significant difference in the sensitivity between APD swelling on CT and an abnormal nerve course or DRG swelling on MRM on the right (P=1.000 and 0.789) and left (P=0.727 and 1.000) sides, respectively. CONCLUSIONS: CT has comparable sensitivity to MRM for the presurgical diagnosis of L5 nerve entrapment at the lumbosacral junction. LEVEL OF EVIDENCE: Level II.

Biomechanical Simulation of Stresses and Strains Exerted on the Spinal Cord and Nerves During Scoliosis Correction Maneuvers.

STUDY DESIGN: Biomechanical analysis of the spinal cord and nerves during scoliosis correction maneuvers through numerical simulations. OBJECTIVE: To assess the biomechanical effects of scoliosis correction maneuvers and stresses generated on the spinal nervous structures. BACKGROUND DATA: Important forces are applied during scoliosis correction surgery, which could potentially lead to neurologic complications due to stresses exerted on the nervous structures. The biomechanical impact of the different types of stresses applied on the nervous structures during correction maneuvers is not well understood. METHODS: Three correction techniques were simulated using a hybrid computer modeling approach, personalized to a right thoracic adolescent idiopathic scoliotic case (Cobb angle: 63°): (1) Harrington-type distraction; (2) segmental translation technique; and a (3) segmental rotation-based procedure. A multibody model was used to simulate the kinematics of the instrumentation maneuvers; a second comprehensive finite element model was used to analyze the local stresses and strains on the spinal cord and nerves. Average values of the internal medullar pressure (IMP), shear stresses, nerve compression, and strain were computed over three regions and compared between techniques. RESULTS: Harrington distraction maneuver generated high stresses and strains over the thoracolumbar region. In the main thoracic region, the segmental translation maneuver technique induced 15% more shear stress, 25% more strain, and 62% lower nerve compression than Harrington distraction maneuver. The segmental rotation-based procedure induced 25% lower shear stresses and 18% more strain, respectively, at the apical level, as well as 72%, 57%, and 7% lower IMP, nerve compression, and strain in the upper thoracic region, compared with Harrington distraction maneuver. CONCLUSION: This study quantified the relative stress induced on the spinal cord and spinal nerves for different correction maneuvers using a novel hybrid patient-specific model. Of the three maneuvers studied, the Harrington distraction maneuver induced the most important stresses over the thoracolumbar region.

Human dorsal root ganglion in vivo morphometry and perfusion in Fabry painful neuropathy.

OBJECTIVE: To evaluate functional and morphometric magnetic resonance neurography of the dorsal root ganglion and peripheral nerve segments in patients with Fabry painful neuropathy. METHODS: In this prospective study, the lumbosacral dorsal root ganglia and proximal peripheral nerve segments of the lower extremity were examined in 11 male patients with Fabry disease by a standardized 3T magnetic resonance neurography protocol. Volumes of L3 to S2 dorsal root ganglia, perfusion parameters of L5-S1 dorsal root ganglia and the spinal nerve L5, and the cross-sectional area of the proximal sciatic nerve were compared to healthy controls. RESULTS: Dorsal root ganglia of patients with Fabry disease were symmetrically enlarged by 78% (L3), 94% (L4), 122% (L5), 115% (S1), and 119% (S2) (p < 0.001). In addition, permeability of the blood-tissue interface was decreased by 53% (p < 0.001). This finding was most pronounced in the peripheral zone of the dorsal root ganglion containing the cell bodies of the primary sensory neurons (p < 0.001). Spinal nerve permeability showed no difference between patients with Fabry disease and controls (p = 0.7). The sciatic nerve of patients with Fabry disease at the thigh level showed an increase in cross-sectional area by 48% (p < 0.001). CONCLUSIONS: Patients with Fabry disease have severely enlarged dorsal root ganglia with dysfunctional perfusion. This may be due to glycolipid accumulation in the dorsal root ganglia mediating direct neurotoxic effects and decreased neuronal blood supply. These alterations were less pronounced in peripheral nerve segments. Thus, the dorsal root ganglion might play a key pathophysiologic role in the development of neuropathy and pain in Fabry disease.

Estrogen deficiency accelerates lumbar facet joints arthritis.

Dramatic increase in the prevalence of lumbar facet joint (LFJ) arthritis in women around the age of menopause indicates a protective role for estrogen in LFJ arthritis. To date, there is no evidence for this indication and the mechanism of such an effect remains poorly understood. In this study, ovariectomized (OVX) mice were used to mimic the estrogen-deficient status of post-menopausal women. Micro-CT and immunohistochemistry was employed to assess the morphological and molecular changes in ovariectomy-induced LFJ arthritis. The results show that the LFJ subchondral bone mass was significantly decreased in OVX mice, with increased cavities on the interface of the subchondral bone. Severe cartilage degradation was observed in ovariectomy-induced LFJ arthritis. Increased blood vessels and innervations were also found in degenerated LFJ, particularly in the subchondral bone area. 17ß-Estradiol treatment efficiently suppressed LFJ subchondral bone turnover, markedly inhibited cartilage degradation, and increased blood vessel and nerve ending growth in degenerated LFJ in OVX mice. Our study reveals that estrogen is a key factor in regulating LFJ metabolism. Severe LFJ degeneration occurs when estrogen is absent in vivo. Collapsed subchondral bone may be the initiation of this process, and estrogen replacement therapy can effectively prevent degeneration of LFJ under estrogen-deficient conditions.

The Subcostal Nerve During Lateral Approaches to the Lumbar Spine: An Anatomical Study with Relevance for Injury Avoidance and Postoperative Complications Such as Abdominal Wall Hernia.

BACKGROUND: Lateral approaches to the spine are increasing in popularity. However, details of the innervation pattern of the abdominal oblique muscles with the initial dissection have not been well studied. METHODS: Ten adult fresh-frozen cadavers (20 sides) were placed in the lateral position. On each side, the region in which transpsoas approaches are performed, between the iliac crest and the 12th rib, was dissected. The nerves, their course, and their muscular supply were studied. RESULTS: The subcostal nerve is the predominant nerve supply for the anterolateral abdominal muscle innervation. It is larger and has a wider field of distribution and more branches (8 on average) compared with the L1 (4 on average) and 11th intercostal nerves (2 on average 2). The proximal 6-10 cm of each nerve has few if any branches. The subcostal nerve is often (75%) located up to 5 cm inferior to the 12th rib in its initial course. The area of least concentration ("safe zone") is located at an approximate midpoint between the lower edge of the 12th rib and the superior-most aspect of the iliac crest. A previously undescribed branch of the subcostal nerve was found traveling posterior to the quadratus lumborum and joining the remaining subcostal nerve in an anastomosis at or near the lateral position. CONCLUSIONS: Knowledge of the innervation and nerve dominance patterns might help decrease postoperative complications such as sensory deficits or abdominal wall hernias. The subcostal nerve is the dominant nerve in both size and innervation of the oblique muscles in the lateral position, transpsoas approach.

Periprosthetic UHMWPE Wear Debris Induces Inflammation, Vascularization, and Innervation After Total Disc Replacement in the Lumbar Spine.

BACKGROUND: The pathophysiology and mechanisms driving the generation of unintended pain after total disc replacement (TDR) remain unexplored. Ultrahigh-molecular-weight polyethylene (UHMWPE) wear debris from TDRs is known to induce inflammation, which may result in pain. QUESTIONS/PURPOSES: The purpose of this study was to determine whether (1) periprosthetic UHMWPE wear debris induces immune responses that lead to the production of tumor necrosis factor-α (TNFα) and interleukin (IL)-1ß, the vascularization factors, vascular endothelial growth factor (VEGF) and platelet-derived growth factor-bb (PDGFbb), and the innervation/pain factors, nerve growth factor (NGF) and substance P; (2) the number of macrophages is associated with the production of the aforementioned factors; (3) the wear debris-induced inflammatory pathogenesis involves an increase in vascularization and associated innervation. METHODS: Periprosthetic tissues from our collection of 11 patients with contemporary TDRs were evaluated using polarized light microscopy to quantify UHMWPE wear particles. The major reason for revision (mean implantation time of 3 years [range, 1-6 years]) was pain. For control subjects, biopsy samples from four patients with degenerative disc disease with severe pain and autopsy samples from three normal patients with no history of back pain were also investigated. Immunohistochemistry and histology were used to identify secretory factors, macrophages, and blood vessels. Immunostained serial sections were imaged at ×200 magnification and using MATLAB and NIH ImageJ, a threshold was determined for each factor and used to quantify positive staining normalized to tissue sectional area. The Mann-Whitney U test was used to compare results from different patient groups, whereas the Spearman Rho test was used to determine correlations. Significance was based on p < 0.05. RESULTS: The mean percent area of all six inflammatory, vascularization, and innervation factors was higher in TDR tissues when compared with normal disc tissues. Based on nonparametric data analysis, those factors showing the most significant increase included TNFα (5.17 ± 1.76 versus 0.05 ± 0.03, p = 0.02), VEGF (3.02 ± 1.01 versus 0.02 ± 0.002, p = 0.02), and substance P (4.15 ± 1.01 versus 0.08 ± 0.04, p = 0.02). The mean percent area for IL-1ß (2.41 ± 0.66 versus 0.13 ± 0.13, p = 0.01), VEGF (3.02 ± 1.01 versus 0.34 ± 0.29, p = 0.04), and substance P (4.15 ± 1.01 versus 1.05 ± 0.46, p = 0.01) was also higher in TDR tissues when compared with disc tissues from patients with painful degenerative disc disease. Five of the factors, TNFα, IL-1ß, VEGF, NGF, and substance P, strongly correlated with the number of wear particles, macrophages, and blood vessels. The most notable correlations included TNFα with wear particles (p < 0.001, ρ = 0.63), VEGF with macrophages (p = 0.001, ρ = 0.71), and NGF with blood vessels (p < 0.001, ρ = 0.70). Of particular significance, the expression of PDGFbb, NGF, and substance P was predominantly localized to blood vessels/nerve fibers. CONCLUSIONS: These findings indicate wear debris-induced inflammatory reactions can be linked to enhanced vascularization and associated innervation/pain factor production at periprosthetic sites around TDRs. Elucidating the pathogenesis of inflammatory particle disease will provide information needed to identify potential therapeutic targets and treatment strategies to mitigate pain and potentially avoid revision surgery. LEVEL OF EVIDENCE: Level III, therapeutic study.