Calpains at the Crossroads of Spinal Cord Physiology, Plasticity, and Pathology.

Objective ‒ to maintain the adequate sedation and analgesia without respiratory depression in children up to 4 years old with spinal cord pathology in early postoperative period (first 3 days) in inpatient department; to decrease digestive system motor function depression; to exclude aspiration possibility; to start early children’s natural feeding in postoperative period.Materials and methods. From October 2019 to January 2020 dexmedetomidine sedation was performed by the prolonged infusion administration to 10 children (6 children aged 6 month to 1 year and 4 children up to 4 years) with spinal cord and vertebral pathology (spina bifida, meningomyelocele, myelocele, teratoma, lipoma of lumbar spine) in early postoperative period at intensive observation ward of neurosurgical department. During the first three days after the surgery and dexmedetomidine prescription the vital functions monitoring was being performed for 24 hours. Arterial blood pressure, heart rate, blood saturation have been scheduled by one of the parents. The immediate access to oxygen and parent’s permission for using this sedation method were the obligatory requirements.Results. The appropriate sedation target was achieved after the dexmedetomidine prescription for the children with the spinal cord and vertebral pathology in early postoperative period at intensive observation ward of neurosurgical department; the dosage of opioid analgesics was successfully decreased by 50 %. The respiratory depression was not observed. The blood pressure and bradycardia were not haemodynamically significant. Swallowing reflex was saved, which led to early physiological nutrition and excluded aspiration risk. The following transfer of patients after the surgery to the neurosurgical department bypassing ICU reduced the financial expenditure of the hospital.Conclusions. Dexmedetomidine provides with the adequate sedation in early postoperative period and can be recommended for the usage in children with the spinal cord and vertebral pathology as the safest medication due to minimal cardio-respiratory complications during moderately prolonged prescribed period.

Background. Dexmedetomidine is a unique α2 -agonist medication which ensures sedation similar to physiological sleep without r espiratory depression. The dexmedetomidine’s characteristics determine the transfer of the patient with neurosurgical pathology in early postoperative period.The aims areto maintain the adequate sedation and analgesia without respiratory depression in children up to 4 years old with spinal cord pathology in early postoperative period (first 3 da ys) in inpatient department;to decrease digestive system motor function depression;to exclude aspiration possibility.Materials and methods. From October 2019 to January 2020, the dexmedetomidine sedations were performed by the prolonged infusion administration to 10 children (6 children aged 6 month to 1 year and 4 children up to 4 years) with spinal cord and vertebral pathology (spina bifida, meningomyelocele, myelocele, teratoma, lipoma of lumbar spine) in early postoperative period at the neurosogical department. During the first three days after the surgery and dexmedetomidine prescription the vital functions monitoring was being performed for 24 hours. The immediate access to oxygen was the obligatory requirement.Results. The appropriate sedation target was achieved after the dexmedetomidine prescription for the children with the spinal cord and vertebral pathology in early postoperative period at the neurosurgical department; the dosage of opioid analgesics was successfully decreased by 50%; the respiratory depression was not observed; the blood pressure and bradycardia were not haemodynamically significant. Swallowing reflex was saved, which led to early physiological nutrition and excluded aspiration risk. The following transfer of patient after the surgery to the neurosurgical department bypassing ICU reduced the financial expenditure of the hospital.Conclusion Dexmedetomidine provides with the adequate sedation in early postoperative period and can be recommended for the usage in children with the spinal cord and vertebral pathology as the safest medication due to the absence of cardio-respiratory complications and the influence on them during moderately prolonged period.

Histaminergic Receptors Modulate Spinal Cord Injury-Induced Neuronal Nitric Oxide Synthase Upregulation and Cord Pathology: New Roles of Nanowired Drug Delivery for Neuroprotection.

The possibility that a combination of neurotrophins induces long-lasting neuroprotection of the cord following spinal cord injury (SCI) was examined in a rat model. The SCI was performed by making a unilateral incision into the right dorsal horn of the T10-11 segments and the animals were allowed to survive 5 h after trauma. Different combination of neurotrophins, i.e., BDNF in combination with GDNF, NT-3, or NGF was applied topically over the traumatized spinal cord and motor dysfunction, blood-spinal cord barrier (BSCB) breakdown, edema formation, and cell injury were examined. Topical application of BDNF in combination with GDNF and NGF 30 min (but not 60 or 90 min) at high concentrations (0.5 microg each) after SCI significantly improved motor function and reduced BSCB breakdown, edema formation, and cell injury at 5 h. However, concurrent application of BDNF, IGF-1, and GDNF (but not with NT-3 or NGF) even 60 or 90 min after trauma induced a significant reduction in motor dysfunction and spinal cord pathology. These observations suggest that a combination of neurotrophins may have added therapeutic value in the treatment of SCI, not reported earlier.

INTRATHECAL infusion of baclofen is a Food and Drug Administration-approved treatment for spasticity. Although animal studies indicate that baclofen has analgesic properties when injected spinally, there are few reports of intrathecal baclofen use for the treatment of pain in humans, and most of those studies have examined its use in patients with central pain associated with spinal cord injury.24 We have found that intrathecal baclofen provides persistent analgesia in some patients with chronic pain not associated with spasticity. The drug has been effective in multiple clinical situations when other treatments have failed or produced intolerable side effects. As in animal studies, 5 it is effective in patients who have become tolerant to intrathecal morphine and provides analgesia at doses that do not produce motor dysfunction. Here we present a series of case reports. Table 1 provides a summary of these cases.

Deep Learning based Convolutional Neural Networks (CNNs) are the state-of-the-art machine learning technique with medical image data. They have the ability to process large amounts of data and learn image features directly from the raw data. Based on their training, these networks are ultimately able to classify unknown data and make predictions. Magnetic resonance imaging (MRI) is the imaging modality of choice for many spinal cord disorders. Proper interpretation requires time and expertise from radiologists, so there is great interest in using artificial intelligence to more quickly interpret and diagnose medical imaging data. In this study, a CNN was trained and tested using thoracolumbar MR images from 500 dogs. T1- and T2-weighted MR images in sagittal and transverse planes were used. The network was trained with unremarkable images as well as with images showing the following spinal cord pathologies: intervertebral disc extrusion (IVDE), intervertebral disc protrusion (IVDP), fibrocartilaginous embolism (FCE)/acute non-compressive nucleus pulposus extrusion (ANNPE), syringomyelia and neoplasia. 2,693 MR images from 375 dogs were used for network training. The network was tested using 7,695 MR images from 125 dogs. The network performed best in detecting IVDPs on sagittal T1-weighted images, with a sensitivity of 100% and specificity of 95.1%. The network also performed very well in detecting IVDEs, especially on sagittal T2-weighted images, with a sensitivity of 90.8% and specificity of 98.98%. The network detected FCEs and ANNPEs with a sensitivity of 62.22% and a specificity of 97.90% on sagittal T2-weighted images and with a sensitivity of 91% and a specificity of 90% on transverse T2-weighted images. In detecting neoplasms and syringomyelia, the CNN did not perform well because of insufficient training data or because the network had problems differentiating different hyperintensities on T2-weighted images and thus made incorrect predictions. This study has shown that it is possible to train a CNN in terms of recognizing and differentiating various spinal cord pathologies on canine MR images. CNNs therefore have great potential to act as a “second eye” for imagers in the future, providing a faster focus on the altered image area and thus increasing workflow in radiology.

Spinal Cord Monitoring Data in Pediatric Spinal Deformity Patients With Spinal Cord Pathology

Chapter 20 - Spinal cord lesions and disorders

Spinal cord pathology is a diverse topic with a broad range of causes. Etiologies include trauma, inflammatory processes, infections, vascular disease, neoplasm, degenerative conditions and toxin exposure. Regardless of etiology, spinal pathology often presents as rapidly progressive paraparesis. Transverse Myelitis (TM) is a rare, acute segmental inflammatory spinal cord disorder characterized with motor, sensory, and/or autonomic dysfunction. This process usually occurs post-infection, but may also be related to acute neuro-inflammatory disorders. This paper will present a case of TM refractory to medication and describe the diagnosis of Spinal Dural Arteriovenous Fistula (SDAVF). SDAVF is a rare condition in which there is an arteriovenous fistula formed on the dural surface of the spinal cord which typically drains via retrograde flow through the medullary vein, thereby causing enlargement of coronal venous plexus.

The possibility that spinal cord pathology following trauma can be assessed with early changes in the spinal cord evoked potentials (SCEPs) was examined in a rat model. Spinal cord injury (SCI) was produced in Equithesin-anesthetized (3 ml/kg, i.p.) rats through a longitudinal incision into the right dorsal horn at the T10-11 segments. The SCEPs were recorded with epidural electrodes placed over the T9 (rostral) segment of the cord. The SCEPs consisted of a small positive amplitude and a broad and high negative amplitude (NA). SCI resulted in an instant depression of the rostral NA that lasted for 1 h. However, the latency of NA continued to increase over time. At 5 h, spinal cord blood flow declined by 30% in the T9 segment, whereas the spinal cord water content and the permeability of the blood-spinal cord barrier (BSCB) were markedly increased. Damage to the nerve cells, glial cells, and myelin was quite common in the spinal cord, as seen by light and electron microscopy. Pretreatment with p-chlorophenylalanine, indomethacin, ibuprofen, and nimodipine attenuated the SCEP changes immediately after trauma and resulted in a marked reduction in edema formation, BSCB permeability, and blood flow changes at 5 h. However, pretreatment with cyproheptadine, dexamethasone, phentolamine, and propranolol failed to attenuate the SCEP changes after SCI and did not reduce the cord pathology. These observations suggest that early changes in SCEP reflect secondary injury-induced alterations in the cord microenvironment. Obviously, these changes are crucial in determining the ultimate magnitude and severity of cord pathology.

This review covers recent advances in identifying conventional and quantitative neuroimaging spinal cord biomarkers of lesion severity and remote spinal cord pathology following traumatic spinal cord injury (SCI). It discusses the potential of the most sensitive neuroimaging spinal cord biomarkers to complement clinical workup and improve prediction of recovery. At the injury site, preserved midsagittal tissue bridges - based on conventional sagittal T2-weighted scans - can be identified in the majority of SCI patients; its width being predictive of recovery. Remote from the injury, diffusion indices, and myelin/iron-sensitive neuroimaging-based changes are sensitive to secondary disease processes; its magnitude of change being associated with neurological outcome. Neuroimaging biomarkers reveal focal and remote cord pathology. These biomarkers show sensitivity to the underlying disease processes and are clinically eloquent. Thus, they improve injury characterization, enable spatiotemporal tracking of cord pathology, and predict recovery of function following traumatic SCI. Neuroimaging biomarkers, therefore, hold potential to complement the clinical diagnostic workup, improve patient stratification, and can serve as potential endpoints in clinical trials.

Diffusion tensor imaging (DTI) provides a measure of the directional diffusion of water molecules in tissues. The measurement of DTI indexes within the spinal cord provides a quantitative assessment of neural damage in various spinal cord pathologies. DTI studies in animal models of spinal cord injury indicate that DTI is a reliable imaging technique with important histological and functional correlates. These studies demonstrate that DTI is a noninvasive marker of microstructural change within the spinal cord. In human studies, spinal cord DTI shows definite changes in subjects with acute and chronic spinal cord injury, as well as cervical spondylotic myelopathy. Interestingly, changes in DTI indexes are visualized in regions of the cord, which appear normal on conventional magnetic resonance imaging and are remote from the site of cord compression. Spinal cord DTI provides data that can help us understand underlying microstructural changes within the cord and assist in prognostication and planning of therapies. In this article, we review the use of DTI to investigate spinal cord pathology in animals and humans and describe advances in this technique that establish DTI as a promising biomarker for spinal cord disorders.

The spinal cord accounts for the main communication pathway between the brain and the peripheral nervous system. Spinal cord injury is a devastating and largely irreversible neurological trauma, and can result in lifelong disability and paralysis with no available cure. In vivo spinal cord imaging in mouse models without introducing immunological artifacts is critical to understand spinal cord pathology and discover effective treatments. We developed a minimally invasive intervertebral window by retaining the ligamentum flavum to protect the underlying spinal cord. By introducing an optical clearing method, we achieve repeated two-photon fluorescence and stimulated Raman scattering imaging at subcellular resolution with up to 15 imaging sessions over 6–167 days and observe no inflammatory response. Using this optically cleared intervertebral window, we study neuron-glia dynamics following laser axotomy and observe strengthened contact of microglia with the nodes of Ranvier during axonal degeneration. By enabling long-term, repetitive, stable, high-resolution and inflammation-free imaging of mouse spinal cord, our method provides a reliable platform in the research aiming at interpretation of spinal cord physiology and pathology.

© 2016 John Wiley & Sons, Ltd. This chapter discusses the common interest with the sub-specialities of neuro-rehabilitation, neuro-inflammation, neuro-infection, neuro-genetics and neuro-muscular disorders. It broadly divides into four sections: spinal embryology anatomy and physiology; diagnosis of spinal column and cord disorders; specific diseases of the spinal column and spinal cord, and clinical management including medical and surgical approaches. The chapter discusses conditions that have yielded insight into spinal cord maldevelopment. Consideration of the details of Klippel-Feil syndrome, X-linked Kallmann syndrome and congenital hemiplegia pathophysiology has led to a wider appreciation of corticospinal tract development. The chapter focuses on symptoms and physical signs that are of particular value in helping the experienced clinician achieve an accurate and timely diagnosis and an assessment that allows a coherent plan of management to be formulated. Surgical detethering may treat a tethered cord in a patient with progressive neurological symptoms.

Spinal cord injury (SCI) is a serious clinical disorder that leads to lifetime disability for which no suitable therapeutic agents are available so far. Further research is needed to understand the basic mechanisms of spinal cord pathology that results in permanent disability and poses a heavy burden on our society. In the past, a lot of effort was placed on improving functional outcome with the help of various therapeutic agents, however less attention has been paid on the development and propagation of spinal cord pathology over time. Thus, it is still unclear whether improvement of functional outcome is related to spinal cord pathology or vice versa. Few drugs are able to influence functional outcome without having any improvement on cord pathology. Some drugs, however, can lessen cord pathology but fail to influence the functional outcome. The goal of future treatment options for SCI is therefore to find suitable new drugs or a combination of existing drugs and to use various cellular transplants, neurotrophic factors, myelin-inhibiting factors, tissue engineering and nano-drug delivery to improve both the functional and the pathological outcome in the inured patient. This review deals with the key aspects of the latest treatments for SCI and suggests some possible future therapeutic measures to enhance healthcare in clinical situations.