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Up until fairly recently, it was thought that sciatic pain in the lumbar herniated disc was caused by compression on the nerve root. However, the lumbar herniated disc shows mixed pictures which are difficult to explain by simple mechanical compromise. In recent years various immunology, immunohistochemistry and molecular biology studies have shown that the herniated tissue is not an inert material, but rather it Is biologically very active with the capability of expressing a series of inflammatory mediators: cytokines such as interleukin-1, interleukin-6, interleuquin-8 and tumor necrosis factor being the ones which stand out. The inflammation is not only induced by the chemical irritation of the bioactive substances released by the nucleus pulposus but also by an autoimmune response against itself. Thus, in addition to the mechanical factor, the biomechanical mediation plays an important role in the pathophysiology of sciatic pain and of radiculopathy. Through a review of a wide range of literature, we researched the cellular molecular mediators involved in this inflammatory process around the lumbar herniated disc and its involvement in sciatic pain., (Copyright © 2020 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background Context: Back pain is a highly prevalent health problem in the world today and has a great economic impact on health-care budgets. Intervertebral disc (IVD) degeneration has been identified as a main cause of back pain. Inflammatory cytokines produced by macrophages or disc cells in an inflammatory environment play an important role in painful progressive degeneration of IVD. Mesenchymal stem cells (MSCs) have shown to have immunosuppressive and anti-inflammatory properties. Mesenchymal stem cells express a variety of chemokines and cytokines receptors having tropism to inflammation sites., Purpose: This study aimed to develop an in vitro controlled and standardized model of inflammation and degeneration of IVD with rat cells and to evaluate the protective and immunomodulatory effect of conditioned medium (CM) from the culture of MSCs to improve the conditions presented in herniated disc and discogenic pain processes., Study Design: This is an experimental study., Methods: In this study, an in vitro model of inflammation and degeneration of IVD has been developed, as well as the effectiveness of CM from the culture of MSCs., Results: Conditioned medium from MSCs downregulated the expression of various proinflammatory cytokines produced in the pathogenesis of discogenic pain such as interleukin (IL)-1β, IL-6, IL-17, and tumor necrosis factor (TNF)., Conclusion: Mesenchymal stem cells represent a promising alternative strategy in the treatment of IVD degeneration inasmuch as there is currently no treatment which leads to a complete remission of long-term pain in the absence of drugs., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The intervertebral disc (IVD) is noted for its low cell content, and being the largest avascular structure of human body. The low amount of cells in the disc have to adapt to an anaerobic metabolism with low oxygen pressure and acidic pH. Apart from surviving in an adverse microenvironment, they are exposed to a high level of mechanical stress. The biological adaptation of cells to acidosis and hyperosmolarity conditions are regulated by mechanoproteins, which are responsible for converting a mechanical signal into a cellular response, thus modifying its gene expression. Mechanobiology helps us to better understand the pathophysiology of IVD and its potential biological repair., (Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.)

The cells of the intervertebral disc (IVD) have an unusual acidic and hyperosmotic microenvironment. They express acid-sensing ion channels (ASICs), gated by extracellular protons and mechanical forces, as well as neurotrophins and their signalling receptors. In the nervous tissues some neurotrophins regulate the expression of ASICs. The expression of ASIC2 and TrkB in human normal and degenerated IVD was assessed using quantitative-PCR, Western blot, and immunohistochemistry. Moreover, we investigated immunohistochemically the expression of ASIC2 in the IVD of TrkB-deficient mice. ASIC2 and TrkB mRNAs were found in normal human IVD and both increased significantly in degenerated IVD. ASIC2 and TrkB proteins were also found co-localized in a variable percentage of cells, being significantly higher in degenerated IVD than in controls. The murine IVD displayed ASIC2 immunoreactivity which was absent in the IVD of TrkB-deficient mice. Present results demonstrate the occurrence of ASIC2 and TrkB in the human IVD, and the increased expression of both in pathological IVD suggest their involvement in IVD degeneration. These data also suggest that TrkB-ligands might be involved in the regulation of ASIC2 expression, and therefore in mechanisms by which the IVD cells accommodate to low pH and hypertonicity.

Acid-sensing ion channels (ASICs) are a family of H(+)-gated voltage-insensitive ion channels that respond to extracellular acidification by regulating transmembrane Ca(2+) flux. Moreover, ASICs can also be gated by mechanical forces and may function as mechanosensors. The cells of the intervertebral disc (IVD) have an unusual acidic and hyperosmotic microenvironment. Changes in the pH and osmolarity determine the viability of IVD cells and the composition of the extracellular matrix, and both are the basis of IVD degeneration. In this study, the expression of ASICs (ASIC1, ASIC2, ASIC3 and ASIC4) mRNAs and proteins in human healthy and degenerated IVD was evaluated by quantitative reverse transcription-quantitative polymerase chain reaction and Western blot. The distribution of ASIC proteins was determined by immunohistochemistry. The mRNAs for all ASICs were detected in normal human IVD, and significantly increased levels were found in degenerated IVD. Western blots demonstrated the presence of proteins with estimated molecular weights of approximately 68-72 kDa. In both the annulus fibrosus (AF) and nucleus pulposus (NP) of normal IVD, ASIC2 is the most frequently expressed ASIC followed by ASIC3, ASIC1 and ASIC4. In the AF of degenerated IVD, there was a significant increase in the number of ASIC1 and ASIC4 positive cells, whereas in the NP, we found significant increase of expression of ASIC1, ASIC2 and ASIC3. These results describe the occurrence and localization of different ASICs in human healthy IVD, and their increased expression in degenerated IVD, thus suggesting that ASICs may be involved in IVD degeneration.

Leiomyoma are slowly growing lesions arising from smooth muscle. Orbital location has been reported in 25 cases. Histological findings and no recurrence after total resection support their benign behaviour. We report an intraconal orbital haemangioleiomyoma in a 55-year-old female treated by total resection through fronto-orbital craniotomy, with no recurrence after 15 months of follow-up. Radiological and pathological features are discussed, emphasising the prognostic role of the surgery., (Copyright © 2012 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.)

Until very recently, intervertebral disc innervation was a subject of considerable debate. Nowadays, the introduction of inmunohistochemical techniques associated to specific antibodies and studies with retrograde tracers in nerves have allowed greater understanding of disc innervation in physiological and pathological conditions and also endings characteristics and their patterns of distribution in both situations. The existing controversies regarding structural basis of discogenic pain, have raised the interest of knowing the influence of innervation in back pain from discal origin and its characteristics. Today, we know that pathologic neoinnervation accompanying radial fissures is an important factor in the genesis of discogenic pain; within a complex mechanism in which other neurobiomechemical, inflammatory and biomechanical factors are involved., (Copyright © 2012 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.)

Giant-cell granuloma is a benign and nonneoplastic lesion with an expansive and locally destructive behavior. It typically involves the mandible and the maxilla. Only 1 case arising from the odontoid process of the axis has been reported previously. The authors report on a 64-year-old man with a giant-cell granuloma of the axis. They review this uncommon entity, emphasizing the complexity of differentiating between this lesion and other giant-cell tumors.

After the great enthusiasm generated in the '70s and '80s in brachial plexus surgery as a result of the incorporation of microsurgical techniques and other advances, brachial plexus surgery has been shaken in the last two decades by the emergence of nerve transfer techniques or neurotizations. This technique consists in sectioning a donor nerve, sacrificing its original function, to connect it with the distal stump of a receptor nerve, whose function was lost during the trauma. Neurotizations are indicated when direct repair is not possible, i.e. when a cervical root is avulsed at its origin in the spinal cord. In recent years, due to the positive results of some of these nerve transfer techniques, they have been widely used even in some cases where the roots of the plexus were preserved. In complete brachial plexus injuries, it is mandatory to determine the exact number of roots available (not avulsed) to perform a direct reconstruction. In case of absence of available roots, extraplexual nerve transfers are employed, such as the spinal accessory nerve, the phrenic nerve, the intercostal nerves, etc., to increase the amount of axons transferred to the injured plexus. In cases of avulsion of all the roots, extraplexal neurotizations are the only reinnervation option available to limit the long-term devastating effects of this injury. Given the large amount of reports that has been published in recent years regarding brachial plexus traumatic injuries, the present article has been written in order to clarify the concerned readers the indications, results and techniques available in the surgical armamentarium for this condition. Since the choice of either surgical technique is usually taken during the course of the procedure, all this knowledge should be perfectly embodied by the surgical team before the procedure. In this first part extraplexual nerve transfers are analyzed, while intraplexual nerve transfers will be analyzed in the second part of this presentation.

After the great enthusiasm generated in the '70s and '80s in brachial plexus surgery as a result of the incorporation of microsurgical techniques and other advances, brachial plexus surgery has been shaken in the last two decades by the emergence of nerve transfer techniques or neurotizations. This technique consists in sectioning a donor nerve, sacrificing its original function, to connect it with the distal stump of a receptor nerve, whose function was lost during the trauma. Neurotizations are indicated when direct repair is not possible, i.e. when a cervical root is avulsed at its origin in the spinal cord. In recent years, due to the positive results of some of these nerve transfer techniques, they have been widely used even in some cases where the roots of the plexus were preserved. In complete brachial plexus injuries, it is mandatory to determine the exact number of roots available (not avulsed) to perform a direct reconstruction. In case of absence of available roots, extraplexual nerve transfers are employed, such as the spinal accessory nerve, the phrenic nerve, the intercostal nerves, etc., to increase the amount of axons transferred to the injured plexus. In cases of avulsion of all the roots, extraplexal neurotizations are the only reinnervation option available to limit the long-term devastating effects of this injury. Given the large amount of reports that has been published in recent years regarding brachial plexus traumatic injuries, the present article has been written in order to clarify the concerned readers the indications, results and techniques available in the surgical armamentarium for this condition. Since the choice of either surgical technique is usually taken during the course of the procedure, all this knowledge should be perfectly embodied by the surgical team before the procedure. In a previous paper extraplexual nerve transfers were analyzed; this literature review complements the preceding paper analyzing intraplexual nerve transfers, and thus completing the analysis of the nerve transfers available in brachial plexus surgery.

Intraneural cysts are benign lesions filled with mucinous content and located inside the epineurum of the peripheral nerves. Peroneal nerve is the most affected nerve. The entity is rare and its ethiopathology still remains to be definitely elucidated. In 2003 Spinner et al published their articular theory, implicated in the formation and frequent recurrence of these lesions after surgical treatment. The practical application of this theory, nowadays almost universally accepted, generated an important diminution in the recurrence rate after surgical evacuation of this lesions, previously very elevated. Most of the cases of this entity are described in adults. In the present paper we describe two pediatric cases and analyze the clinical aspects of these cysts in pediatric and adults patients. Peroneal intraneural cysts are one of the differential diagnoses in foot drop, and an adequate treatment concludes in a complete remission of the symptoms.

Purpose: Nonlinear dynamics has enhanced the diagnostic abilities of some physiological signals. Recent studies have shown that the complexity of the intracranial pressure waveform decreases during periods of intracranial hypertension in paediatric patients with acute brain injury. We wanted to assess changes in the complexity of the cerebrospinal fluid (CSF) pressure signal over the large range covered during the study of CSF circulation with infusion studies., Methods: We performed 37 infusion studies in patients with hydrocephalus of various types and origin (median age 71 years; interquartile range 60-77 years). After 5 min of baseline measurement, infusion was started at a rate of 1.5 ml/min until a plateau was reached. Once the infusion finished, CSF pressure was recorded until it returned to baseline. We analysed CSF pressure signals using the Lempel-Ziv (LZ) complexity measure. To characterise more accurately the behaviour of LZ complexity, the study was segmented into four periods: basal, early infusion, plateau and recovery., Results: The LZ complexity of the CSF pressure decreased in the plateau of the infusion study compared to the basal complexity (p=0.0018). This indicates loss of complexity of the CSF pulse waveform with intracranial hypertension. We also noted that the level of complexity begins to increase when the infusion is interrupted and CSF pressure drops towards the initial values., Conclusions: The LZ complexity decreases when CSF pressure reaches the range of intracranial hypertension during infusion studies. This finding provides further evidence of a phenomenon of decomplexification in the pulsatile component of the pressure signal during intracranial hypertension.

Brown tumors appear in advanced stages of hyperparathyroidism. Only 17 cases have been documented in the orbit. We report a case of a young woman with a brown tumor in the orbital roof. Secondary hyperparathyroidism due to chronic renal disease was detected during the preoperative study. The pathogenesis, diagnosis and management of the brown tumor are discussed.

The normal intervertebral disc (IVD) is a poorly innervated organ supplied only by sensory (mainly nociceptive) and postganglionic sympathetic (vasomotor efferents) nerve fibers. Interestingly, upon degeneration, the IVD becomes densely innervated even in regions that in normal conditions lack innervation. This increased innervation has been associated with pain of IVD origin. The mechanisms responsible for nerve growth and hyperinnervation of pathological IVDs have not been fully elucidated. Among the molecules that are presumably involved in this process are some members of the family of neurotrophins (NTs), which are known to have both neurotrophic and neurotropic properties and regulate the density and distribution of nerve fibers in peripheral tissues. NTs and their receptors are expressed in healthy IVDs but much higher levels have been observed in pathological IVDs, thus suggesting a correlation between levels of expression of NTs and density of innervation in IVDs. In addition, NTs also play a role in inflammatory responses and pain transmission by increasing the expression of pain-related peptides and modulating synapses of nociceptive neurons at the spinal cord. This article reviews current knowledge about the innervation of IVDs, NTs and NT receptors, expression of NTs and their receptors in IVDs as well as in the sensory neurons innervating the IVDs, the proinflammatory role of NTs, NTs as nociception regulators, and the potential network of discogenic pain involving NTs.