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Objective: The quantitative assessment of spinal cord volume is still in the early stages of development. Recently, normative morphometric values of the cervical spinal cord have been reported. This study aimed to establish normative values for spinal cord morphometry, extending beyond the cervical region to include the thoracic and lumbar spinal cord, and to examine the influence of sex and ethnicity on these measurements., Materials and Methods: This prospective study included 28 young, healthy, East Asian volunteers (14 males and 14 females; mean age, 30.14 ± 4.07 years) who underwent spinal cord MRI using a 3T scanner. The cross-sectional areas (CSAs), anteroposterior (AP) and transverse diameters, and compression ratios of the entire spinal cord were calculated. Additionally, the effects of sex and ethnicity on spinal cord volumetry were evaluated, with the influence of ethnicity assessed by comparing the findings with a Caucasian dataset from the PAM50 study., Results: The CSAs demonstrated two enlargements at the cervical and lumbar levels. The cervical enlargement at C4-5 exhibited an elliptical shape, while the lumbar enlargement at T12 appeared more circular. The CSAs and AP and transverse diameters of the spinal cords in males were significantly larger than that of females ( P < 0.001). The spinal cord compression ratios in East Asians were significantly lower than those in Caucasians ( P < 0.001)., Conclusion: This study revealed that the two spinal cord enlargements exhibit different patterns and suggest significant differences in spinal cord morphometric values according to sex and ethnicity., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2025 The Korean Society of Radiology.)

The upper end of the central canal of the human spinal cord has been repeatedly implicated in the pathogenesis of various diseases, yet its precise normal position in the medulla oblongata and upper cervical spinal cord remains unclear. The purpose of this study is to describe the anatomy of the upper end of the central canal with quantitative measurements and a three-dimensional (3D) model. Seven formalin-embalmed human brainstems were included, and the central canal was identified in serial axial histological sections using epithelial membrane antigen antibody staining. Measurements included the distances between the central canal (CC) and the anterior medullary fissure (AMF) and the posterior medullary sulcus (PMS). The surface and perimeter of the CC and the spinal cord were calculated, and its anterior-posterior and maximum lateral lengths were measured for 3D modeling. The upper end of the CC was identified in six specimens, extending from the apertura canalis centralis (ACC) to its final position in the cervical cord. Positioned on the midline, it reaches its final location approximately 15 mm below the obex. No specimen showed canal dilatation, focal stenosis, or evidence of syringomyelia. At 21 mm under the ACC in the cervical cord, the median distance from the CC to the AMF was 3.14 (2.54-3.15) mm and from the CC to the PMS was 5.19 (4.52-5.43) mm, with a progressive shift from the posterior limit to the anterior third of the cervical spinal cord. The median area of the CC was consistently less than 0.1 mm 2 . The upper end of the CC originates at the ACC, in the posterior part of the MO, and reaches its normal position in the anterior third of the cervical spinal cord less than 2 cm below the obex. Establishing the normal position of the upper end of this canal is crucial for understanding its possible involvement in cranio-cervical junction pathologies., (© 2024 The Author(s). Clinical Anatomy published by Wiley Periodicals LLC on behalf of American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Scholars usually consider the Historia anatomica corporis humani , published in 1600 by André du Laurens, as an obsolete defense of Galenic principles against the novelty of Vesalian material. Although du Laurens's book plagiarized many illustrations from Vesalius's De humani corporis fabrica (1543), critics such as Choulant insisted that the Historia 's iconography had "no particular anatomical or artistic value." However, four of the Historia 's engravings appear to be original. One of these, the Tabula hæc veram spinalis medullae et nervorum ab ea prodeuntium effigiem exprimit , is now famous for depicting the intradural spinal nerves as a horsetail, leading to the addition of the term cauda equina to the anatomical lexicon. A less flamboyant figure from the same plate shows small blood vessels coursing over the surface of the cervical spinal cord. This drawing may be the first published depiction of anterior spinal arteries and veins.

Swedish neuroscientist Bror Anders Rexed lived between 1914 and 2002. He was a renowned neuroscientist and a politician who packed a lot into his 88-year life. Bror Rexed is best known for his works on the description of the cytoarchitectonic organization of the cat spinal cord. Rexed laminae as an eponym is a historical landmark for the spinal cord cytoarchitecture. Rexed's name (particularly his surname) has also been linked to the du-reform in Swedish. In this article, we focus on his works on the central and peripheral nervous systems and translational approaches for neurosurgery, as well as his influence on health policies in Sweden., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study aimed to evaluate the spinal morphometry of the thoracic and lumbar regions in normal Korean Shorthair cats using computed tomography (CT) and to investigate the relationship with variables such as sex, age and body weight. Fifteen clinically healthy Korean Shorthair cats (eight males, seven females) from Seoul National University Veterinary Medical Teaching Hospital were included in this retrospective study. Measurements of the height, width and area of the vertebral canal and spinal cord on CT images were taken at the cranial, middle and caudal points of the thoracic and lumbar vertebrae by three observers, and the ratios of the spinal cord area to the vertebral canal area were calculated. The significance of the differences in measurements between sexes and correlations with age and body weight were analysed. The mean age of the cats was 7 years (range: 2-12 years), with a mean weight of 5.27 kg (range: 2.6-8.3 kg). The height, width and area of the vertebral canal and spinal cord were significantly greater in males than in females (p < 0.05). The ratios of the spinal cord area to the vertebral canal area showed no significant difference between sexes (p > 0.05), and no significant correlations were found between the ratios of the spinal cord area to the vertebral canal area and age or body weight. This study provides useful reference intervals for spinal morphometry in the thoracic and lumbar regions of healthy Korean Shorthair cats and investigate the relationship with variables such as sex, age and body weight. This anatomical information may assist in the diagnosis and prognosis of thoracic, lumbar vertebral and spinal cord diseases using CT., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Rat strains differ in physiology, behavior, and recovery after central nervous system injury. To assess these differences, we compared the gross and local anatomy and neuromorphology of the lumbar spinal cord of the Wistar and Dark Agouti (DA) strains. The key findings include (i) distinct spatial relationships between vertebrae and spinal segments in the two strains; (ii) Wistar rats have larger volumes of spinal cord gray and white matter; (iii) DA rats have smaller total neuronal populations, thus indicating an expectation of smaller local neuronal populations; (iv) this expectation was confirmed for interneurons expressing calbindin 28 kDa. But contrary to expectations, (v) DA rats had more numerous populations of the interneurons expressing parvalbumin and a population of α-motoneurons. Consequently, these strains displayed divergent ratios in specific spinal neuronal populations. Researchers should consider these inter-strain differences when comparing data across different strains., (© 2024 Wiley Periodicals LLC.)

The study objective is to obtain normal morphology and morphometric data from Baladi goat spinal cord segments. Using Tompsett's technique for staining gray matter with a blue stain allowed us to calculate the quantity or area of gray and white matter and thus the total area of each segment. The spinal cord of the goat started at the extent of the middle-third of the occipital condyles, and the tapered end of the spinal cord terminated at the center of the first sacral vertebra. The total length of the spinal cord was 73.3 ± 2.5 cm on average. C3 was the longest spinal segment, measuring 3.95 cm. The gray matter area had a high value at the cervical and lumbar enlargements, with C8 having the highest value of gray matter cross sectional area at 12 mm 2 and C7 having the highest value of white matter cross sectional area at 42 mm 2 . The area of white matter of the cervical region was higher than that of the other spinal regions. At C7, the total cross section area reached its maximum of 53 mm 2 . The cervical enlargement included segments from C6 to T1, while the lumbar enlargement included L5 to S1. The dura mater is connected cranially to the dens of the axis and caudally to the fourth and fifth lumbar vertebrae. The epidural space height between lumbar vertebrae was 2 mm in all lumbar spaces and 3 mm in the lumbosacral space. The normal morphology and morphometric data of the goat spinal cord segments may be useful in pathological conditions of the spinal cord and during epidural anaesthesia technique., (© 2023 Wiley-VCH GmbH.)

Spatially charting molecular cell types at single-cell resolution across the 3D volume is critical for illustrating the molecular basis of brain anatomy and functions. Single-cell RNA sequencing has profiled molecular cell types in the mouse brain 1,2 , but cannot capture their spatial organization. Here we used an in situ sequencing method, STARmap PLUS 3,4 , to profile 1,022 genes in 3D at a voxel size of 194 × 194 × 345 nm 3 , mapping 1.09 million high-quality cells across the adult mouse brain and spinal cord. We developed computational pipelines to segment, cluster and annotate 230 molecular cell types by single-cell gene expression and 106 molecular tissue regions by spatial niche gene expression. Joint analysis of molecular cell types and molecular tissue regions enabled a systematic molecular spatial cell-type nomenclature and identification of tissue architectures that were undefined in established brain anatomy. To create a transcriptome-wide spatial atlas, we integrated STARmap PLUS measurements with a published single-cell RNA-sequencing atlas 1 , imputing single-cell expression profiles of 11,844 genes. Finally, we delineated viral tropisms of a brain-wide transgene delivery tool, AAV-PHP.eB 5,6 . Together, this annotated dataset provides a single-cell resource that integrates the molecular spatial atlas, brain anatomy and the accessibility to genetic manipulation of the mammalian central nervous system., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

This article describes the vascular anatomy of the spine and spinal cord, highlighting key structures and anatomical variations relevant to musculoskeletal radiologists. It covers the arterial and venous drainage systems, along with examples of vascular conditions affecting the spine. Understanding the vascular anatomy of the spine and spinal cord is crucial for accurate interpretation of imaging studies and safe spinal interventional procedures. Imaging techniques for evaluating vascular pathology of the spine are discussed and compared. Understanding vascular anatomy and the most common vascular disorders will lead to an accurate diagnosis and suggest the appropriate type of study needed for further characterization and/or patient management., Competing Interests: None declared., (Thieme. All rights reserved.)

The topographical neuroanatomy of the human spinal cord (SC) is currently based on the adjacent vertebrae. This morphometric study sought to develop a dataset allowing for statistical analysis of human SC segment characteristics. Overall, 32 human SCs were dissected (18 female and 14 male donors), and individual SC segments were identified. Anterior and posterior lengths, thicknesses and widths were measured by two examiners. Statistical analyses included t-tests, as well as intraclass and Pearson's correlation coefficients. The SC length was significantly shorter in females than males. The cranial (C4) and caudal (T1/T2) limits of the cervical enlargement, along with its maximal width (C6-C7), were identified by combining widths and thicknesses of the segments. The thoracic region, T2 to T12, could be identified using segments widths and thicknesses values. The length of the lumbosacral region, from segments L2 to S5, was particularly stable, independently of SC length and sex. The lumbar enlargement was characterized by a thickness increase between the segments L2 and S1 which reached its maximum at the level of L3, L4, and L5, whereas the width was not significantly increased. From the S2 to S5 segments, width and thickness were equal, with both decreasing of 1 mm per segment. The morphometrical analysis of 32 human SCs provided a dataset allowing for statistical analysis of segmental measures with significant results. A combined approach mostly using widths and thicknesses provided landmarks of potential interest for the localization of SC segments in a clinical MRI setting., (© 2023 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Secondary neurulation is a common feature of vertebrate development, which in non-mammalian and non-anuran vertebrates, results in the formation of a caudal spinal cord. The present study was undertaken to describe the terminal end of the caudal spinal cord in a crocodylian, a group chosen for their unique status of a living-tailed archosaur. The caudal spinal cord of Alligator mississippiensis terminates near the intervertebral joint between the fourth and fifth terminal vertebrae. Prior to this termination, the dorsal root ganglia get proportionately larger, then stop before the termination of the spinal cord; and the gray matter of the spinal cord is lost producing an unusual morphology in which an ependymal-lined central canal is surrounded by only white matter which is not divided into a cauda equina. The inner layer of the meninges (the pia-arachnoid) courses over the distal end of the spinal cord and forms a ventral attachment, reminiscent of a very short Filum terminale; there is no caudal cistern. The dura extends beyond the termination of the spinal cord, continuing for at least the length of the fourth terminal vertebra, forming a structure herein termed the distal meningeal sheath. During its course, the distal meningeal sheath surrounds a mass of mesothelial cells, then terminates as an attachment on the dorsal surface of the vertebra., (© 2022 The Authors. The Anatomical Record published by Wiley Periodicals LLC on behalf of American Association for Anatomy.)

The incidence of spinal cord (SC) injury in developed and undeveloped countries is alarming. The pig (Sus scrofa) has been recommended as a suitable research model for translational studies because of its morphophysiological similarities of organ systems with humans. There is a dearth of information on the SC anatomy of the large white and landrace crossbreed (LW-LC) pigs. We therefore aim to describe the gross morphology and morphometry of its SC. Twelve juvenile LW-LC pigs (six males and six females) were used. The skin and epaxial muscles were dissected to expose the vertebral column. The SC was carefully harvested by laminectomy, and 13 gross SC morphometric parameters were evaluated. Thirty-three spinal nerves were seen emanating from either side of the SC by means of dorsal and ventral spinal roots. The overall average of SC length and weight was 36.23 ± 1.01 cm and 16.60 ± 0.58 g, respectively. However, the mean SC length and weight were higher in females compared with males, with SC weight being statistically significant. A positive relationship between SC length and weight was significant for males (p = 0.0435) but not for females (p = 0.42). Likewise, the strength of the relationship between SC length and weight was significant in males (r = 0.82) but not significant in females (r = 0.41). Baseline data for the morphometric features of the spinal cord in the LW-LC pigs were generated, which will contribute to the knowledge of this species anatomy and useful information on regional anaesthesia that should further strengthen the drive in adopting the pig as a suitable research model for biomedical research., (© 2022 Wiley-VCH GmbH.)

The spinal cord of the tree pangolin is known to be very short compared to the overall length of the body and tail. Here, we provide a description of the tree pangolin spinal cord to determine whether the short length contributes to specific structural, and potentially functional, differences. The short spinal cord of the adult tree pangolin, at around 13 cm, terminates at the midthoracic level. Within this shortened spinal cord, we could identify six regions, which from rostral to caudal include the prebrachial, brachial, interramal, crural, postcrural, and caudal regions, with both the brachial and crural regions showing distinct swellings. The chemoarchitecture of coronal sections through these regions confirmed regional assignation, being most readily delineated by the presence of cholinergic neurons forming the intermediolateral column in the interramal region and the sacral parasympathetic nucleus in the postcrural region. The 10 laminae of Rexed were observed throughout the spinal cord and presented with an anatomical organization similar to that observed in other mammals. Despite the shortened length of the tree pangolin spinal cord, the regional and laminar anatomical organization is very similar to that observed in other mammals. This indicates that the functional aspects of the short tree pangolin spinal cord can be inferred from what is known in other mammals., (© 2022 The Authors. The Journal of Comparative Neurology published by Wiley Periodicals LLC.)

The aim of the present systematic review and meta-analysis was to identify when the ascent of the conus medullaris occurs in human foetuses considering differences in evaluation methods and sample characteristics. Five databases were searched for relevant articles using different combinations of keywords. Article selection and data extraction were performed independently by two reviewers. Disagreements were resolved by a third reviewer. The variables were distributed into four groups according to the gestational age of the specimens: I (13-18 weeks); II (19-25 weeks); III (26-32 weeks); IV (33 weeks to the probable date of birth). Eighteen articles were included. The majority used imaging exams as the evaluation method. Cadaveric dissections were reported in the remaining articles. Only morphological studies were included in the meta-analysis. Significant ascent occurs between groups I and III as well as groups II and IV. Despite the considerable heterogeneity among the studies included in the present review, the findings enabled the determination that the conus medullaris reaches its normal birth level by the 26th week. Further analyses should be performed based on nationality and ethnicity to diminish the heterogeneity of the data., (© 2022. The Author(s).)

Most of our knowledge about the human spinal ascending (sensory) and descending (motor) pathways comes from non-invasive electrophysiological investigations. However, recent methodological advances in acquisition and analyses of functional magnetic resonance imaging (fMRI) data from the spinal cord, either alone or in combination with the brain, have allowed us to gain further insights into the organization of this structure. In the current review, we conducted a systematic search to produced somatotopic maps of the spinal fMRI activity observed through different somatosensory, motor and resting-state paradigms. By cross-referencing these human neuroimaging findings with knowledge acquired through neurophysiological recordings, our review demonstrates that spinal fMRI is a powerful tool for exploring, in vivo, the human spinal cord pathways. We report strong cross-validation between task-related and resting-state fMRI in accordance with well-known hemicord, postero-anterior and rostro-caudal organization of these pathways. We also highlight the specific advantages of using spinal fMRI in clinical settings to characterize better spinal-related impairments, predict disease progression, and guide the implementation of therapeutic interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Inc.)

Objective: This study aimed to explore the migration process of the conus medullaris (CM) in early infancy using infant MRI and to evaluate the application of MRI for locating the infant CM level., Methods: The authors retrospectively analyzed the CM level on the lumbosacral MR images of 26 term infants aged < 3 months who were classified into three groups according to age. The authors numbered the CM level in each patient and analyzed the range and average of the CM level of the cohort. The authors studied the linear correlation between CM level and postnatal days with linear regression analysis, 1-way ANOVA, and the least significant difference test., Results: The CM level ranged from the superior border of the L1 vertebra to the top third of the L3 vertebra. About 96.2% of infants had CM higher than the superior border of the L3 vertebra. On average, CM was located between the L1-2 intervertebral disc and the inferior border of the L2 vertebra (mean ± SD score 1.64 ± 1.14). The three groups had no significant statistical difference in CM level (F = 1.071 and p = 0.359; groups 1 and 2, p = 0.408; groups 1 and 3, p = 0.170; groups 2 and 3, p = 0.755). CM level had no linear regression correlation with postnatal days within the first month (r2 = 0.061, F = 0.654, p = 0.438) or within the first 3 months (r2 = 0.002, F = 0.056, p = 0.816)., Conclusions: The CM level reaches the normal adult level by birth in term infants and does not ascend during childhood. On average, the CM was between the L1-2 intervertebral disc and the inferior border of the L2 vertebra in term infants. Considering the possibility of physiologically low-lying CM, the authors agree that normal CM is located above the L3 level in term infants and CM at the L3 level could be equivocal and should be investigated with other clinical data. The study data suggest that MRI is an accurate and valuable method for determining the CM level in term infants.

Genetic dissection of neural circuits has been accelerated by recent advances in viral-based vectors. This protocol describes an effective approach to performing intraspinal injections of adeno-associated viruses, which can be used to label, manipulate, and monitor spinal and supraspinal neurons. By avoiding invasive laminectomies and restrictive spinal-clamping and by adopting injectable anaesthetics and tough quartz glass micropipettes, our protocol presents a time-saving and efficient approach for genetic manipulation of neural circuits nucleated in the spinal cord. For complete details on the use and execution of this protocol, please refer to Sathyamurthy et al. (2020)., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Transient opening of the blood-spinal cord barrier has the potential to improve drug delivery options to the spinal cord. We previously developed short-burst phase-keying exposures to reduce focal depth of field and mitigate standing waves in the spinal canal. However, optimal short-burst phase-keying parameters for drug delivery have not been identified. Here, the effects of pressure, treatment duration, pulse length, burst repetition frequency and burst length on resulting tissue effects were investigated. Increased in situ pressures (0.23-0.33 MPa) led to increased post-treatment T 1 -weighted contrast enhancement in magnetic resonance imaging (p = 0.015). Increased treatment duration (120 vs. 300 s) led to increased enhancement, but without statistical significance (p = 0.056). Increased burst repetition frequency (20 vs. 40 kHz) yielded a non-significant increase in enhancement (p = 0.064) but corresponded with increased damage observed on histology. No difference was observed in enhancement between pulse lengths of 2 and 10 ms (p = 0.912), corresponding with a sharp drop in the recorded second harmonic signal during the first 2 ms of the pulse. Increasing the burst length from two to five cycles (514 kHz) led to increased enhancement (p = 0.014). Results indicate that increasing the burst length may be the most effective method to enhance drug delivery. Additionally, shorter pulse lengths may allow more interleaved targets, and therefore a larger treatment volume, within one sonication., Competing Interests: Conflict of interest disclosure The authors have no conflicts of interest to declare., (Copyright © 2021 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objective: To provide precise description of the dorsal and ventral roots orientation along with the main spinal cord anatomical measurements and their segment-specific variations., Patients and Methods: We collected and analyzed the measurements of the spines, spinal cords, and dorsal and ventral roots (C2-L5) of nine adult cadavers (five males and four females)., Results: This study for the first time provides analysis of the dorsal and ventral roots orientation along with spinal cord anatomical measurements and their segment-specific distribution. The results of this study showed less variability in rostral root angles compared with the caudal. Dorsal and ventral rootlets were oriented mostly perpendicular to the spinal cord at the cervical level and had more parallel orientation to the spinal cord at the thoracic and lumbar segments. The number of rootlets per root was greatest at dorsal cervical and lumbar segments. Spinal cord transverse diameter and width of the dorsal columns were largest at cervical segments. The strongest correlation between the spinal cord and vertebrae structures was found between the length of intervertebral foramen to rostral rootlet distance and vertebral bone length., Conclusion: These results demonstrate consistent variation in spinal cord anatomical features across all tested subjects. The results of this study can be used to locate spinal roots and main spinal cord landmarks based on bone marks on computed tomography or X-rays. These results could improve stereotactic surgical procedures and electrode positioning for neuromodulation procedures., (Copyright © 2020 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Functional magnetic resonance imaging (fMRI) of the spinal cord relies on the integrity of neurovascular coupling (NVC) to infer neuronal activity from hemodynamic changes. Astrocytes are a key component of cerebral NVC, but their role in spinal NVC is unclear. The objective of this study was to examine whether inhibition of astrocyte metabolism by fluorocitrate alters spinal NVC. In 14 rats, local field potential (LFP) and spinal cord blood flow (SCBF) were recorded simultaneously in the lumbosacral enlargement during noxious stimulation of the sciatic nerve before and after a local administration of fluorocitrate (N  = 7) or saline (N  = 7). Fluorocitrate significantly reduced SCBF responses (p  < 0.001) but not LFP amplitude (p  = 0.22) compared with saline. Accordingly, NVC was altered by fluorocitrate compared with saline (p  < 0.01). These results support the role of astrocytes in spinal NVC and have implications for spinal cord imaging with fMRI for conditions in which astrocyte metabolism may be altered.

Non-human primates are most suitable for generating cervical experimental models, and it is necessary to study the anatomy of the cervical spine in non-human primates when generating the models. The purpose of this study was to provide the anatomical parameters of the cervical spine and spinal cord in long-tailed macaques (Macaca fascicularis) as a basis for cervical spine-related experimental studies. Cervical spine specimens from 8 male adult subjects were scanned by micro-computed tomography, and an additional 10 live male subjects were scanned by magnetic resonance imaging. The measurements and parameters from them were compared to those of 12 male adult human subjects. Additionally, 10 live male subjects were scanned by magnetic resonance imaging, and the width and depth of the spinal cord and spinal canal and the thickness of the anterior and posterior cerebrospinal fluid were measured and compared to the relevant parameters of 10 male adult human subjects. The tendency of cervical parameters to change with segmental changes was similar between species. The vertebral body, spinal canal, and spinal cord were significantly flatter in the human subjects than in the long-tailed macaques. The cerebrospinal fluid space in the long-tailed macaques was smaller than that in the human subjects. The anatomical features of the cervical vertebrae of long-tailed macaques provide a reference for establishing a preclinical model of cervical spinal cord injury.

Purpose of Review: This article focuses on clinically relevant teaching points in spinal anatomy and localizing the lesion in myelopathy., Recent Findings: The principles underlying spinal cord lesion localization are well established, but improvements in MRI and the discovery of pathologic antibodies associated with causes of transverse myelitis distinct from multiple sclerosis, such as aquaporin-4 IgG and myelin oligodendrocyte glycoprotein IgG, have assisted in diagnosis., Summary: The spinal cord has a highly organized neuroanatomy of ascending and descending tracts that convey sensory, motor, and autonomic information. Using integration of clues from the patient's history and neurologic examination, the effective clinician can distinguish spinal cord from peripheral nerve or brain pathology, often determine the level and parts of the spinal cord affected by a lesion, and focus on a likely diagnosis. The advent of MRI of the spine has revolutionized investigation of spinal cord disorders, but an important place for strong clinical acumen still exists in assessing the patient with a myelopathy., (Copyright © 2021 American Academy of Neurology.)

The emergence of diffusion, structural, and functional neuroimaging methods has enabled major multi-site efforts to map the human connectome, which has heretofore been defined as containing all neural connections in the central nervous system (CNS). However, these efforts are not structured to examine the richness and complexity of the peripheral nervous system (PNS), which arguably forms the (neglected) rest of the connectome. Despite increasing interest in an atlas of the spinal cord (SC) and PNS which is simultaneously stereotactic, interactive, electronically dissectible, scalable, population-based and deformable, little attention has thus far been devoted to this task of critical importance. Nevertheless, the atlasing of these complete neural structures is essential for neurosurgical planning, neurological localization, and for mapping those components of the human connectome located outside of the CNS. Here we recommend a modification to the definition of the human connectome to include the SC and PNS, and argue for the creation of an inclusive atlas to complement current efforts to map the brain's human connectome, to enhance clinical education, and to assist progress in neuroscience research. In addition to providing a critical overview of existing neuroimaging techniques, image processing methodologies and algorithmic advances which can be combined for the creation of a full connectome atlas, we outline a blueprint for ultimately mapping the entire human nervous system and, thereby, for filling a critical gap in our scientific knowledge of neural connectivity., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To explore the optimal b value setting for diffusion tensor imaging of rats' spinal cord at ultrahigh field strength (7 T)., Methods: Spinal cord diffusion tensor imaging data were collected from 14 rats (5 healthy, 9 spinal cord injured) with a series of b values (200, 300, 400, 500, 600, 700, 800, 900, and 1000 s/mm 2 ) under the condition that other scanning parameters were consistent. The image quality (including image signal-to-noise ratio and image distortion degree) and data quality (i.e., the stability and consistency of the DTI-derived parameters, referred to as data stability and data consistency) were quantitatively evaluated. The min-max normalization method was used to process the calculation results of the four indicators. Finally, the image and data quality under each b value were synthesized to determine the optimal b value., Results: b = 200 s/mm 2 and b = 900 s/mm 2 ranked in the top two of the comprehensive evaluation, with the best image quality at b = 200 s/mm 2 and the best data quality at b = 900 s/mm 2 ., Conclusion: Considering the shortcomings of the ability of low b values to reflect the microstructure, b = 900 s/mm 2 can be used as the optimal b value for 7 T spinal cord diffusion tensor scanning., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2021 Shu-Sheng Bao et al.)

Background: Nusinersen is the only approved treatment for all spinal muscular atrophy (SMA) subtypes and is delivered intrathecally. Distorted spinal anatomy and instrumentation preclude standard approaches for intrathecal access, necessitating alternative techniques for delivery. The purpose of this study is to report technical success and adverse events of transforaminal intrathecal delivery of nusinersen., Methods: 28 patients, mean age 24.1±9.8 years (range 10.0-51.0 years), with intermediate or late onset SMA, underwent a combined 200 transforaminal nusinersen injections. All patients had osseous fusion or spinal instrumentation precluding standard posterior access routes. Patients who underwent nusinersen injections using a technique other than transforaminal lumbar puncture (n=113) were excluded. Technical success, adverse events (AEs) and radiation exposure were recorded., Results: 200 (100%) procedures were technically successful; 6 (3%) required a second level of attempt for access. 187 (93.5%) interventions were completed using cone beam computed tomography (CBCT) with two-axis fluoroscopic navigational overlay. 13 (6.5%) procedures were performed with fluoroscopic-guidance only at subsequent sessions. There were 8 (4.0%) mild AEs and 2 (0.5%) severe AEs; one patient received antibiotics for possible traversal of the large bowel but did not develop meningitis, and one patient developed aseptic meningitis. Mean air kerma was 74.5±161.3 mGy (range 5.2-1693.0 mGy)., Conclusion: Transforaminal intrathecal delivery of nusinersen is feasible and safe for gaining access in patients with distorted spinal anatomy. The use of CBCT delineates anatomy and optimizes needle trajectory during the initial encounter, and may be used selectively for subsequent procedures., Competing Interests: Competing interests: EJM discloses scientific advisory and speaking for Biogen, Inc. NN receives research support for studies for Biogen, Inc., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background Modern high-spatial-resolution radiologic methods enable increasingly detailed volumetric postmortem investigations of human neuroanatomy for diagnostic, research, and educational purposes. Purpose To evaluate the viability of postmortem x-ray phase-contrast micro-CT to provide tissue-conserving, high-spatial-resolution, three-dimensional neuroimaging of the human spinal cord and column by comparing quality of x-ray phase-contrast micro-CT images of nondissected Thiel-embalmed human spines with images of extracted formalin-fixed human spinal cords. Specific focus was placed on assessing the detection of micrometric spinal cord soft-tissue structure and vasculature. Materials and Methods In this study from August 2015 to August 2019, three Thiel-embalmed human spinal column samples, unilaterally perfused with an iodinated vascular contrast agent, and three extracted formalin-fixed spinal cord samples were imaged postmortem at a synchrotron radiation facility. Propagation-based x-ray phase-contrast micro-CT was used with monochromatic 60-keV x-rays and a detector with either 46-µm or 8-µm pixel sizes. A single-distance phase-retrieval algorithm was applied to the acquired CT projection images in advance of filtered back projection CT reconstruction. The influence on image quality of Thiel versus formalin embalming was examined, and images were qualitatively evaluated in terms of the value of their anatomic representations. Results The x-ray phase-contrast micro-CT of Thiel-embalmed samples resulted in soft-tissue contrast within the vertebral canal, despite evident nervous tissue deterioration after Thiel embalming. Gross spinal cord anatomy, spinal meninges, contrast agent-enhanced spinal vasculature, and spinal nerves were all well rendered alongside surrounding vertebral bone structure. The x-ray phase-contrast micro-CT of formalin-fixed boneless cords led to much higher gray versus white matter contrast and to microscale visualization of deep medullary vasculature and neuronal perikarya. Conclusion This work demonstrated the use of x-ray phase-contrast micro-CT for detailed volumetric anatomic visualization of embalmed human spines. The method provided three-dimensional display of bone, nervous tissue, and vasculature at microscale resolutions without exogenous contrast agents. © RSNA, 2020 Online supplemental material is available for this article.

The gray matter of the spinal cord is the seat of somata of various types of neurons devoted to the sensory and motor activities of the limbs and trunk as well as a part of the autonomic nervous system. The volume of the spinal gray matter is an indicator of the local neuronal processing, and this can decrease due to atrophy associated with degenerative diseases and injury. Nevertheless, the absolute volume of the human spinal cord has rarely been reported, if ever. Here, we use high-resolution magnetic resonance imaging, with a cross-sectional resolution of 50 × 50 μm and a voxel size of 0.0005 mm 3 to estimate the total gray and white matter volume of a post mortem human female spinal cord. Segregation of gray and white matter was accomplished using deep learning image segmentation. Furthermore, we include data from a male spinal cord of a previously published study. The gray and white matter volumes were found to be 2.87 and 11.33 mL, respectively, for the female and 3.55 and 19.33 mL, respectively, for the male. The gray and white matter profiles along the vertebral axis were found to be strikingly similar, and the volumes of the cervical, thoracic, and lumbosacral sections were almost equal. NEW & NOTEWORTHY Here, we combine high-field MRI (9.4 T) and deep learning for a post mortem reconstruction of the gray and white matter in human spinal cords. We report a minuscule total gray matter volume of 2.87 mL for a female and 3.55 mL for a male. For comparison, these volumes correspond approximately to the distal digit of the little finger.

Area prostriata in primates has recently been found to play important roles in rapid detection and processing of peripheral visual, especially fast-moving visual information. The prostriata in rodents was not discovered until recently and its connectivity is largely unknown. As a part of our efforts to reveal brain-wide connections of the prostriata in rat and mouse, this study focuses on its commissural projections in order to understand the mechanisms underlying interhemispheric integration of information, especially from peripheral visual field. Using anterograde, retrograde and Cre-dependent tracing techniques, we find a unique commissural connection pattern of the prostriata: its layers 2-3 in both hemispheres form strong homotopic commissural connections with few heterotopic projections to bilateral medial entorhinal cortex. This projection pattern is in sharp contrast to that of the presubiculum and parasubiculum, two neighbor regions of the prostriata. The latter two structures project very strongly to bilateral medial entorhinal cortex and to their contralateral counterparts. Our results also suggest the prostriata is a distinct anatomical structure from the presubiculum and parasubiculum and probably plays differential roles in interhemispheric integration and the balancing of spatial information between two hemispheres., (Copyright © 2020 Chen, Hu, Chen, Liu and Ding.)

Phoenixin (PNX) is a newly described peptide found in both neural and non-neural tissues. Until now, no attempts have been made to investigate the expression of PNX in the nervous system of animals other than laboratory rodents, in which an enzyme immunoassay revealed the highest quantity of the substance in the spinal cord. Since the domestic pig, due to its anatomical and histological resemblance to humans, is often used as an animal model in biomedical investigations, the present study was designed to examine PNX-immunoreactivity in the spinal cords of female pigs (n=5). The spinal cords were dissected and divided into the cervical, thoracic, lumbar, sacral and coccygeal segments, which were sectioned transversally into 10-μm-thick serial sections. The sections from each spinal cord segment were processed for double-labelling immunohistochemistry using antibodies against PNX in a mixture with those against calcitonin gene-related peptide (CGRP), substance P (SP) or choline acetyltransferase (CHAT). The PNX-immunoreactivity had a similar distribution in the grey matter of all the spinal cord sections examined and was mainly observed in varicose nerve fibres (NF) that formed a dense plexus in laminae I and II of the dorsal horn. Nearly all of the PNX-immunoreactive NF stained also for CGRP or SP and, interestingly, many of them were CHAT-positive. The present study has provided for the first time the detailed information on the arrangement and chemical features of nerve structures expressing PNX-immunoreactivity in the spinal cord of a large mammal. The exact function of PNX in the spinal cord is not known yet. However, the distribution pattern and immunohistochemical characteristics of PNX-IR NF clearly suggest that this peptite most likely plays a role in spinal noxious signalling., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

The course of spinal nerves and the corresponding cutaneous areas are fundamental for numerous therapeutic approaches used in complementary veterinary medicine. Positive effects of these methods are primarily based on segmental reflex arcs which are associated with the course of the spinal nerves. In this morphological study, the lateral cutaneous branches of the thoracolumbar dorsal branches from Th9 to L7 were examined in cats with special regard to their anatomical course. A four-layer dissection was carried out to reveal the course of nerves between the intervertebral foramina and their point of entry into the skin, starting in the dorsal midline. Dorsal branch courses and covered distances were documented and measured in each layer. The covered distance was evaluated by the Caudal Shift Index (CSI n ) on both body sides and within each layer. The 'back region' was used as relative dimensional unit, describing the distance between the cranial tips of two consecutive spinous processes. Overall, the mean CSI n for dorsal branches of Th9 to L7 amounted to three back regions from the intervertebral foramen to the skin entry point of a dorsal nerve branch. This provides therapists with clues and should be put into practice, by extending the treatment area up to three segments caudally from the nerve exit point. Furthermore, the results of this study present new data on inferred lumbar dermatomes in cats, data which until now have only been transferred from other species. These results may serve as an anatomical foundation for manual therapies., (© 2020 Wiley-VCH GmbH.)

Detecting the ultrastructure of brain tissue in human archaeological remains is a rare event that can offer unique insights into the structure of the ancient central nervous system (CNS). Yet ancient brains reported in the literature show only poor preservation of neuronal structures. Using scanning electron microscopy (SEM) and advanced image processing tools, we describe the direct visualization of neuronal tissue in vitrified brain and spinal cord remains which we discovered in a male victim of the AD 79 eruption in Herculaneum. We show exceptionally well preserved ancient neurons from different regions of the human CNS at unprecedented resolution. This tissue typically consists of organic matter, as detected using energy-dispersive X-ray spectroscopy. By means of a self-developed neural image processing network, we also show specific details of the neuronal nanomorphology, like the typical myelin periodicity evidenced in the brain axons. The perfect state of preservation of these structures is due to the unique process of vitrification which occurred at Herculaneum. The discovery of proteins whose genes are expressed in the different region of the human adult brain further agree with the neuronal origin of the unusual archaeological find. The conversion of human tissue into glass is the result of sudden exposure to scorching volcanic ash and the concomitant rapid drop in temperature. The eruptive-induced process of natural vitrification, locking the cellular structure of the CNS, allowed us to study possibly the best known example in archaeology of extraordinarily well-preserved human neuronal tissue from the brain and spinal cord., Competing Interests: The authors have declared that no competing interests exist.

Background: The regenerating blastema of the tail in the lizard Podarcis muralis contains numerous macrophages among the prevalent mesenchymal cells. Some macrophages are phagocytic but others are devoid of phagosomes suggesting that they have other roles aside phagocytosis., Methods: The presence of healing macrophages (M2-like) has been tested using autoradiographic, immunohistochemical and ultrastructural studies., Results: Autoradiography shows an uptake of tritiated arginine in sparse cells of the blastema and in the regenerating epidermis. Bioinformatics analysis suggests that epitopes for arginase-1 and -2, recognized by the employed antibody, are present in lizards. Immunofluorescence shows sparse arginase immunopositive macrophages in the blastema and few macrophages also in the apical wound epidermis. The ultrastructural study shows that macrophages contain dense secretory granules, most likely inactive lysosomes, and small cytoplasmic pale vesicles. Some of the small vesicles are arginase-positive while immunolabeling is very diffuse in the macrophage cytoplasm., Conclusions: The presence of cells incorporating arginine and of arginase 1-positive cells suggests that M2-like macrophages are present among mesenchymal and epidermal cells of the regenerative tail blastema. M2-like macrophages may promote tail regeneration differently from the numerous pro-inflammatory macrophages previously detected in the scarring limb. The presence of M2-like macrophages in addition to hyaluronate, support the hypothesis that the regenerative blastema of the tail in lizards is an immuno-privileged organ where cell proliferation and growth occur without degenerating in a tumorigenic outgrowth., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Study Design: Continuous measurements and computation of absolute metrics of cervical subarachnoid space (CSS) and spinal cord (SC) geometries proposed are based on in vivo magnetic resonance imaging and 3D reconstruction., Objective: The aim of the study is to offer a new methodology to continuously characterize and to quantify the detailed morphology of the CSS and the cervical SC in 3D for healthy subjects in both neutral supine and flexion., Summary of Background Data: To the best of our knowledge, no study provides a morphological quantification by absolute indices based on the 3D reconstruction of SC and CSS thanks to in vivo magnetic resonance imaging. Moreover, no study provides a continuous description of the geometries., Methods: Absolute indices of SC (cross-sectional area, compression ratio, position in the canal, length) and of CSS (cross-sectional area, occupational ratio, lengths) were computed by measures from 3D semi-automatic reconstructions of high resolution in vivo magnetic resonance images (3D T2-SPACE sequence) on healthy subjects (N = 11) for two postures: supine neutral and flexion neck positions. The variability induced by the semi-automatic reconstruction and by the landmarks positioning were investigated by preliminary sensitivity analyses. Inter and intra-variability were also quantified on a randomly chosen part of our population (N = 5)., Results: The length and cross-sectional area of SC are significantly different (P < 0.05) in flexion compared with neutral neck position. Spinal cord stays centered in the canal for both postures. However, the cross-sectional area of CSS is submitted to low variation after C3 vertebra for both postures. Occupational ratio (OR) and compression ratio (CR) after C3 are significantly lower in flexion., Conclusion: This study presented interpretations of morphological measures: (1) left-right stability (described by the Left-Right eccentricity index) ensured by the denticulate ligaments and the nerve roots attached to the dural sheaths, (2) a Poisson effect of the SC was partially notified through its axial (antero-posterior [AP] diameter, OR, CR) and its longitudinal geometrical descriptions (length of spinal cord [LSC]). Such morphological data can be useful for geometrical finite element modeling and could now be used to compare with injured or symptomatic subjects., Level of Evidence: 3.

Dermatomal maps are a mainstay of clinical practice and provide information on the spatial distribution of the cutaneous innervation of spinal nerves. Dermatomal deficits can help isolate the level of spinal nerve root involvement in spinal conditions and guide clinicians in diagnosis and treatment. Dermatomal maps, however, have limitations, and the spatial distribution of spinal cord sensory activity in humans remains to be quantitatively assessed. Here we used spinal cord functional MRI to map and quantitatively compare the spatial distribution of sensory spinal cord activity during tactile stimulation of the left and right lateral shoulders (i.e. C5 dermatome) and dorsal third digits of the hands (i.e., C7 dermatome) in healthy humans (n ​= ​24, age ​= ​36.8 ​± ​11.8 years). Based on the central sites for processing of innocuous tactile sensory information, we hypothesized that the activity would be localized more to the ipsilateral dorsal spinal cord with the lateral shoulder stimulation activity being localized more superiorly than the dorsal third digit. The findings demonstrate lateralization of the activity with the left- and right-sided stimuli having more activation in the ipsilateral hemicord. Contradictory to our hypotheses, the activity for both stimulation sites was spread across the dorsal and ventral hemicords and did not demonstrate a clear superior-inferior localization. Instead, the activity for both stimuli had a broader than expected distribution, extending across the C5, C6, and C7 spinal cord segments. We highlight the complexity of the human spinal cord neuroanatomy and several sources of variability that may explain the observed patterns of activity. While the findings were not completely consistent with our a priori hypotheses, this study provides a foundation for continued work and is an important step towards developing normative quantitative spinal cord measures of sensory function, which may become useful objective MRI-based biomarkers of neurological injury and improve the management of spinal disorders., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the microsurgical features of the spinal cord and ventral and dorsal rootlets in fetal period., Methods: Twelve formalin-fixed fetuses (six females and six males) with a mean gestational age of 27.0 ± 2.04 weeks (range between 25 and 32 weeks) were dissected to evaluate morphological properties of the spinal cord and rootlets., Results: Length and width of each spinal cord segment, number of dorsal and ventral rootlets, length of dorsal root entry and ventral root exit zones of each spinal nerve, spinal cord termination level, and the whole spinal cord length were determined in all fetuses. Contrary to previous reports, the number of ventral rootlets was always more than that of dorsal rootlets in all segments. No statistically significant gender difference was found for all parameters. Rootlet number and segment width in cervical region were larger than those of thoracic, while the lengths of dorsal root entry and ventral root exit zones in thoracic region were longer than those of cervical. In lumbar region, dorsal and ventral rootlet numbers were increasing again, while lengths of dorsal root entry and ventral root exit zones were decreasing. Number of dorsal and ventral rootlets of C5 and C6 segments was statistically higher than other cervical segments. The mean spinal cord length was found as 105.55 ± 11.30 mm and there was a positive significant relationship with gestational age. Conus medullaris level was detected between L1 and L3 segments., Conclusion: Detailed microsurgical data about the fetal spinal cord and the dorsal and ventral rootlets presented in this study provide significant information which may be essential during surgical interventions in early postnatal period and childhood targeting the spinal cord and spinal nerve roots.

Purpose: To determine the morphological features of the denticulate ligament in fetal period., Methods: Twelve formalin-fixed fetuses (six females and six males) with a mean gestational age of 27.0 ± 2.04 weeks (range between 25 and 32 weeks) were dissected to reveal morphological properties of the denticulate ligaments., Results: Denticulate ligament was observed as a continuous ligament extending throughout the length of spinal cord in all fetuses. It separated the vertebral canal into two as anterior and posterior parts and was anchored to the dura mater on either side of the spinal cord with mostly triangular processes as well as thin band-like extensions. The first denticulate ligament process was always a large and prominent fibrous band and was arising from the spinal cord surface, extending in an oblique direction upward to the anterolateral rim of foramen magnum, below and posterior to the hypoglossal canal. The last denticulate ligament process was observed either in the T11-12 (2 sides, 8%), T12-L1 (15 sides, 62%) or L1-2 (7 sides, 30%) and all were band-like processes. At certain spinal cord levels, denticulate ligament had no processes to attach duramater while in some other fetuses double denticulate ligament processes were detected within the same interval. The distance between the denticulate ligament process and the superior spinal nerve root and the distance between the denticulate ligament process and the inferior spinal nerve root were measured at each spinal level. This distance was found to be increased from upper to lower levels of the spine., Conclusion: Detailed morphological data about fetal denticulate ligament presented in this study provide significant information which may be essential during several surgical interventions performed in early postnatal period and childhood focusing on the spinal cord, spinal nerve roots and meningeal structures.

The significance of activated microglia around motoneurons axotomized after nerve injuries has been intensely debated. In particular, whether microglia become phagocytic is controversial. To resolve these issues we directly observed microglia behaviors with two-photon microscopy in ex vivo spinal cord slices from CX3CR1-GFP mice complemented with confocal analyses of CD68 protein. Axotomized motoneurons were retrogradely-labeled from muscle before nerve injuries. Microglia behaviors close to axotomized motoneurons greatly differ from those within uninjured motor pools. They develop a phagocytic phenotype as early as 3 days after injury, characterized by frequent phagocytic cups, high phagosome content and CD68 upregulation. Interactions between microglia and motoneurons changed with time after axotomy. Microglia first extend processes that end in phagocytic cups at the motoneuron surface, then they closely attach to the motoneuron while extending filopodia over the cell body. Confocal 3D analyses revealed increased microglia coverage of the motoneuron cell body surface with time after injury and the presence of CD68 granules in microglia surfaces opposed to motoneurons. Some microglia formed macroclusters associated with dying motoneurons. Microglia in these clusters display the highest CD68 expression and associate with cytotoxic T-cells. These observations are discussed in relation to current theories on microglia function around axotomized motoneurons.

The agouti is a wild rodent located almost throughout the Brazilian territory, with great scientific importance and high reproductive potential when farmed. In the clinical routine, clinical and surgical procedures are performed on the nervous system of these animals, such as epidural anesthesia and cerebrospinal fluid (CSF) collection; however, data available are limited in literature on the main points of these procedures in this species. In this aspect, the objective was to describe the vertebromedullary topography of the agouti in order to identify and quantify it, with the intention of expanding the information regarding the clinical-surgical procedures in this system. Ten animals were incised longitudinally in the dorsal median line, removing the skin, the musculature, and dorsal fascia of the vertebral column; then, removed the vertebral arches and consequent exposure of the spinal cord and meninges. The morphometry of the animals was done by obtaining the total length, body length, and crown-rump length, as well as the total length of the spinal cord and its segments. The cervical intumescence in the agouti is located between C4-T1 and measures 2.45 cm. The lumbar intumescence is between L5-L7 and is 2.52 cm long. The cauda equina arises from S2 and the filum terminale from S3. As for the medullary cone, it is located between L7-S1 and is 2.52 cm long. The suggested localization for epidural anesthesia or CSF puncture for laboratory tests in agoutis is the lumbosacral space, with the insertion of the needle to be carried out at angle of 90° in the sphinx position. Anat Rec, 303:1472-1477, 2020. © 2019 American Association for Anatomy., (© 2019 American Association for Anatomy.)

Background: Several studies have identified changes in the spinal cord DTI measurements in patients with multiple sclerosis (MS). However, correlations between changes in DTI parameters in normal appearing cervical spine and neurological findings have not been clearly established., Objectives: To determine whether diffusion tensor imaging (DTI) measurements such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) are sufficiently sensitive in detecting microstructure alterations in normal-appearing spinal cords in patients with MS and whether they reflect these patients' clinical disability., Material and Methods: Fifteen patients diagnosed with relapsing-remitting MS (RRMS) with normal-appearing cervical spinal cords on plain MRI and 11 asymptomatic volunteers were enrolled in the study. Overall, 75 cervical spinal segments were analyzed. The regions of interest were drawn from the entire spinal cord cross-section and in the normal-appearing white matter tracts: the superior and inferior cerebellar peduncles and the posterior limbs of the internal capsules. Neurological deficit and the level of disability were evaluated using the Expanded Disability Status Scale (EDSS), the timed 25-foot walk test (T25FW) and the 9-hole peg test (9HPT) for manual dexterity., Results: A significant difference (p < 0.05) in FA values between patients with MS and the control group was found at levels C2 (p = 0.047) and C3 (p = 0.023). No significant changes in ADC values were found. There was correlation between FA and ADC values in selected white matter tracts and at particular spinal cord levels. We also observed significant correlations between diffusion tensor imaging parameters and manual dexterity., Conclusions: Our preliminary results may suggest that the spinal cord's structural loss is the dominant factor in the inflammatory/demyelinating component in patients with MS. Diffusion tensor imaging changes in the spinal cord correlate with brain DTI changes. Manual functioning seems to be more affected than walking.

Cells in tissues are enveloped by an instructive niche made of the extracellular matrix. These instructive niches contain three general types of information: topographical, biochemical and mechanical. While the combined effects of these three factors are widely studied, the functions of each individual one has not been systematically characterised, because it is impossible to alter a single factor in a tissue microenvironment without simultaneously affecting the other two. Silica BioReplication (SBR) is a process that converts biological samples into silica, faithfully preserving the original topography at the nano-scale. We explored the use of this technique to generate inorganic replicas of intact mammalian tissues, including tendon, cartilage, skeletal muscle and spinal cord. Scanning electron and atomic force microscopy showed that the resulting replicas accurately preserved the three-dimensional ultrastructure of each tissue, while all biochemical components were eradicated by calcination. Such properties allowed the uncoupling the topographical information of a tissue microenvironment from its biochemical and mechanical components. Here, we showed that human mesenchymal stem cells (MSC) cultured on the replicas of different tissues displayed vastly different morphology and focal adhesions, suggesting that the topography of the tissue microenvironment captured by SBR could profoundly affect MSC biology. MSC cultured on tendon replica elongated and expressed tenocytes marker, while MSC on the spinal cord replica developed into spheroids that resembled neurospheres, in morphology and in the expression of neurosphere markers, and could be further differentiated into neuron-like cells. This study reveals the significance of topographical cues in a cell niche, as tissue-specific topography was sufficient in initiating and directing differentiation of MSC, despite the absence of any biochemical signals. SBR is a convenient and versatile method for capturing this topographical information, facilitating the functional characterisation of cell niches. STATEMENT OF SIGNIFICANCE: Various studies have shown that three major factors, topographical, biochemical and mechanical, in a tissue microenvironment (TME) are essential for cellular homeostasis and functions. Current experimental models are too simplistic to represent the complexity of the TME, hindering the detailed understanding of its functions. In particular, the importance each factor in a tissue microenvironment have not been individually characterised, because it is challenging to alter one of these factors without simultaneously affecting the other two. Silica bioreplication (SBR) is a process that converts biological samples into silica replicas with high structural fidelity. SBR is a convenient and versatile method for capturing this topographical information on to a biologically inert material, allowing the functional characterisation of the architecture of a TME., (Copyright © 2019. Published by Elsevier Ltd.)

Introduction: The electrically evoked compound action potential (ECAP) is a measure of the response from a population of fibers to an electrical stimulus. ECAPs can be assessed during spinal cord stimulation (SCS) to elucidate the relationship between stimulation, electrophysiological response, and neuromodulation. This has consequences for the design and programming of SCS devices., Methods: Sheep were implanted with linear epidural SCS leads. After a stimulating pulse, electrodes recorded ECAPs sequentially as they propagated orthodromically or antidromically. After filtering, amplification, and signal processing, ECAP amplitude and dispersion (width) was measured, and conduction velocity was calculated. Similar clinical data was also collected. A single-neuron computer model that simulated large-diameter sensory axons was used to explore and explain the observations., Results: ECAPs, both animal and human, have a triphasic structure, with P1, N1, and P2 peaks. Conduction velocity in sheep was 109 ms -1 , which indicates that the underlying neural population includes fibers of up to 20 μm in diameter. For travel in both directions, propagation distance was associated with decrease in amplitude and increase in dispersion. Importantly, characteristics of these changes shifted abruptly at various positions along the cord., Discussion: ECAP dispersion increases with propagation distance due to the contribution of slow-conducting small-diameter fibers as the signal propagates away from the source. An analysis of the discontinuities in ECAP dispersion changes with propagation revealed that these are due to the termination of smaller-diameter, slower-conducting fibers at corresponding segmental levels. The implications regarding SCS lead placement, toward the goal of maximizing clinical benefit while minimizing side-effects, are discussed., Conflict of Interest: John Parker is the founder and CEO of Saluda Medical and holds stock options. Milan Obradovic, Nastaran Hesam Shariati, Dean M. Karantonis, Peter Single, James Laird-Wah, Robert Gorman and Mark Bickerstaff are employees of Saluda Medical with stock options. At the time the data was collected for the study, Prof. Cousins was a paid consultant for Saluda Medical. John Parker, Milan Obradovic, Dean Karantonis, James Laird-Wah, Robert Gorman and Peter Single are co-inventors in one or more patents related to the topics discussed in this work., (© 2019 International Neuromodulation Society.)

Stereology is a method for examining two-dimensional objects as three-dimensional objects. The aim of this study was to offer volume values for thoracic segments in ducks by means of stereological methods. This study examined the data obtained from stereological analysis of the total volume and grey and white matter volume values of the thoracic segment, a part of the adult duck spinal cord with a weight of 3-4 kg. In the study, study samples consisted of 10 adult ducks (Anas) used without gender discrimination. To perfuse all of the animals, 10% formaldehyde was utilised. The perfused animals were kept in 10% formaldehyde for one week. The spinal cord was uncovered following the removal of arcus vertebrae parts of thoracic vertebrae in the thoracic part of dissected ducks. Tissue samples of thoracic segments were taken; 5-µm-thick cross sections from these tissue samples were taken via microtome. Attention was paid to obtaining samples at the ratio of 1/250 by taking 12 cross sections from each segment. The cross sections were subjected to haematoxylin-eosin staining. Photographs of all cross sections were taken using a microscope. The volume values of all tissue and grey and white matter structures in each thoracic segment of the spinal cord were calculated. The total volume, grey and white matter volume densities in thoracic segments of ducks, as well as the data obtained as a result of proportioning volume values of one another are represented in the conclusion section of this study., (© 2019 Blackwell Verlag GmbH.)

This chapter describes the microanatomy of the spinal cord that is relevant to intrathecal drug delivery started with covering of the spinal cord that are pierced to enter the intrathecal space. The dural sac is mostly constituted by the outer layer of dura and the inner layer called arachnoid membrane, which regulates diffusion of drugs into the intrathecal space. The pia matter surrounding the spinal cord is a permeable structure allowing the passage of drugs through intercellular spaces. The relationship between nerve roots, CSF, and subarachnoid catheters determines the passage of an intrathecal catheter which can cause damage to nerve roots and spinal cord. Multiple factors may be involved in the mechanisms of drug diffusion across the membranes of the spinal cord, as well as in their dilution with the CSF, which will lead to the final drug distribution and availability at nerve roots and the spinal cord.

Background: Cauda equina syndrome (CES) may be a devastating disease with the potential for significant patient morbidity. It is essential for emergency clinicians to be aware of how to effectively diagnose and manage this condition., Objective: This article provides a narrative review of the diagnosis and management of CES for the emergency clinician., Discussion: Cauda equina syndrome is a rare but emergent condition associated with back pain. It can result in severe morbidity and can be due to a variety of causes, most commonly vertebral disc protrusion. Diagnosis is often delayed, which may result in a poor prognosis. Red flags and findings consistent with CES include bilateral neurogenic sciatica, reduced perineal sensation, altered bladder function leading to painless urinary retention, loss of anal tone, and loss of sexual function. In isolation, history and examination findings demonstrate poor sensitivity. Symptoms may occur either suddenly or gradually, and most patients do not present with all of these symptoms. Postvoid bladder volume assessments can assist in the evaluation, but the diagnosis typically involves magnetic resonance imaging (MRI) or computed tomography myelography if MRI is not available. Treatment relies upon surgical consultation and operative intervention for decompression., Conclusion: Cauda equina syndrome can be a difficult diagnosis. However, knowledge of the history and examination findings, imaging, and treatment can assist the emergency clinician in optimizing management of this condition., (Published by Elsevier Inc.)

Background: Leopardus geoffroyi is a Neotropical wild felid with wide distribution in the south of the South American continent. The objective was to investigate the skeletopy of the intumescentia lumbalis (IL) and conus medullaris (CM) from 11 specimens of L. geoffroyi collected dead on highways., Materials and Methods: The cadavers were fixed in formaldehyde solution and dissected to allow the dorsal exposure of IL and CM. The cranial and caudal limits were marked with radiopaque pins and radiographic projections were used to determine the skeletopy. The lengths of IL and CM were measured with a pachymeter., Results: In most specimens, the IL was located at the level of L4 and L5 vertebrae, although in 4 (1 male and 3 females) individuals its cranial limit was L3 and in 3 specimens (2 male and 1 female) the caudal limit was L6. The length of IL was 35.6 ± 6.7 mm. The CM had its base predominantly at the level of the L5 vertebra, although in some specimens the base was in L4 and in others in L6. The apex of the CM can be found since the lumbosacral junction until the level of the Cd2 vertebra. The CM measured 74.4 ± 14.3 mm., Conclusions: Based on the skeletopy, it can be suggested that epidural anaesthesia procedures in L. geoffroyi are safer with the introduction of the catheter through the sacrocaudal interarcual space, as recommended by some anaesthetists for the domestic cat.

The arachnoid membranes' anatomy is a controversial topic in the literature, and the rhomboid membrane at the craniovertebral junction is an element of this system that has been described poorly. Hence, the objective of our study was to examine this membrane's anatomy and histology. A total of 45 fresh formalin-fixed human cadaveric heads were examined, and anatomic dissections and histologic examinations using standard staining methods were performed. The membrane was found to be a constant structure. It has a rhomboid shape and is located on the medulla oblongata and upper cervical spine's ventral surface within the subarachnoid space. Its average craniocaudal length is 49 mm and the short axis is 26 mm. The cranial apex is attached to the vertebral arteries' junction, and the caudal apex reaches the level of C4. The lateral apices are attached to the dura mater at the level of the denticulate ligament's second insertion. The C1 spinal nerves perforate the membrane, while the C2 roots are located dorsal to it. The membrane is attached strongly to the underlying pia mater. Histologically, it has a typical arachnoid structure, in which its adhesions to the vertebral arteries as well as to the pia mater could be verified histologically. This is the first detailed examination of the rhomboid membrane. Our results suggest that the membrane serves a valve-like function between the spinal and cranial subarachnoid spaces. Based on our findings, further hydrodynamic studies should clarify the membrane's physiological role. Clin. Anat. 32:56-65, 2019. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

High coverage sequences of archaic humans enabled the reconstruction of their DNA methylation patterns. This allowed comparing gene regulation between human groups, and linking such regulatory changes to phenotypic differences. In a previous work, a detailed comparison of DNA methylation in modern humans, archaic humans, and chimpanzees revealed 873 modern human-derived differentially methylated regions (DMRs). To understand the regulatory implications of these DMRs, we defined differentially methylated genes (DMGs) as genes that harbor DMRs in their promoter or gene body. While most of the modern human-derived DMRs could be linked to DMGs, many others remained unassigned. Here, we used information on 3D genome organization to link ~70 out of the remaining 288 unassigned DMRs to genes. Combined with the previously identified DMGs, we reinforce the enrichment of these genes with vocal and facial anatomy, and additionally find significant enrichment with the spinal column, chin, hair, and scalp. These results reveal the importance of 3D genomic organization in understanding gene regulation by DNA methylation.

Background and Purpose: Although considerable variability exists as to the overall caliber of radiculomedullary arteries, dominant radiculomedullary arteries such as the artery of Adamkiewicz exist. The existence of a great posterior radiculomedullary artery has attracted little attention and has been a matter of debate. The aim of this anatomic study was to determine the presence or absence of the great posterior radiculomedullary artery., Materials and Methods: We performed microsurgical dissection on formaldehyde-fixed cadaveric human spinal cords. The artery of Adamkiewicz in the spinal cord specimens ( n  = 50) was injected with colored latex until the small-caliber arterial vessels were filled and the great posterior radiculomedullary artery was identified. The course, diameter, and location of great posterior radiculomedullary artery were documented., Results: A great posterior radiculomedullary artery was identified in 36 (72%) spinal cord specimens. In 11 (22%) specimens, bilateral great posterior radiculomedullary arteries were present. In 13 cases (26%), a unilateral left-sided great posterior radiculomedullary artery was identified. In 11 cases (22%), a unilateral right-sided great posterior radiculomedullary artery was identified. In 1 specimen (2%), 3 right-sided great posterior radiculomedullary arteries were noted. The average size of the great posterior radiculomedullary arteries was 0.44 mm (range, 0.120-0.678 mm on the left and 0.260-0.635 mm on the right)., Conclusions: A great posterior radiculomedullary artery is present in most (72%) individuals. The authors describe the microsurgical anatomy of the great posterior radiculomedullary artery with emphasis on its morphometric parameters as well as its implications for spinal cord blood supply. Variations of the arterial supply to the dorsal cord are of great importance due to their implications for ischemic events, endovascular procedures, and surgical approaches., (© 2019 by American Journal of Neuroradiology.)