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High-Spatial-Resolution Three-dimensional Imaging of Human Spinal Cord and Column Anatomy with Postmortem X-ray Phase-Contrast Micro-CT.
Barbone, GE, Bravin, A, Mittone, A, Grosu, S, Ricke, J, Cavaletti, G, Djonov, V, Coan, P
Radiology. 2021;(1):135-146
Abstract
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.
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Imaging outcome measures of neuroprotection and repair in MS: A consensus statement from NAIMS.
Oh, J, Ontaneda, D, Azevedo, C, Klawiter, EC, Absinta, M, Arnold, DL, Bakshi, R, Calabresi, PA, Crainiceanu, C, Dewey, B, et al
Neurology. 2019;(11):519-533
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Abstract
OBJECTIVE To summarize current and emerging imaging techniques that can be used to assess neuroprotection and repair in multiple sclerosis (MS), and to provide a consensus opinion on the potential utility of each technique in clinical trial settings. METHODS Clinicians and scientists with expertise in the use of MRI in MS convened in Toronto, Canada, in November 2016 at a North American Imaging in Multiple Sclerosis (NAIMS) Cooperative workshop meeting. The discussion was compiled into a manuscript and circulated to all NAIMS members in attendance. Edits and feedback were incorporated until all authors were in agreement. RESULTS A wide spectrum of imaging techniques and analysis methods in the context of specific study designs were discussed, with a focus on the utility and limitations of applying each technique to assess neuroprotection and repair. Techniques were discussed under specific themes, and included conventional imaging, magnetization transfer ratio, diffusion tensor imaging, susceptibility-weighted imaging, imaging cortical lesions, magnetic resonance spectroscopy, PET, advanced diffusion imaging, sodium imaging, multimodal techniques, imaging of special regions, statistical considerations, and study design. CONCLUSIONS Imaging biomarkers of neuroprotection and repair are an unmet need in MS. There are a number of promising techniques with different strengths and limitations, and selection of a specific technique will depend on a number of factors, notably the question the trial seeks to answer. Ongoing collaborative efforts will enable further refinement and improved methods to image the effect of novel therapeutic agents that exert benefit in MS predominately through neuroprotective and reparative mechanisms.
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Neonatal mitochondrial leukoencephalopathy with brain and spinal involvement and high lactate: expanding the phenotype of ISCA2 gene mutations.
Toldo, I, Nosadini, M, Boscardin, C, Talenti, G, Manara, R, Lamantea, E, Legati, A, Ghezzi, D, Perilongo, G, Sartori, S
Metabolic brain disease. 2018;(3):805-812
Abstract
A homoallelic missense founder mutation of the iron-sulfur cluster assembly 2 (ISCA2) gene has been recently reported in six cases affected by an autosomal recessive infantile neurodegenerative mitochondrial disorder. We documented a case of a 2-month-old girl presenting with severe hypotonia and nystagmus, who rapidly deteriorated and died at the age of three months. Increased cerebral spinal fluid level of lactate, documented also at the brain spectroscopy, involvement of the cortex, restricted diffusion of white and gray matter abnormalities, sparing of the corpus callosum and extensive involvement of the spinal cord were observed. Her clinical presenting features and course as well as some neuroradiological findings mimicked those of early-onset leukoencephalopathy with brainstem and spinal cord involvement and high brain lactate (LBSL). The analysis of the mitochondrial respiratory chain function showed a reduced activity of complexes II and IV. The girl harboured two heterozygous mutations in the ISCA2 gene. A comprehensive review of the literature and a comparison with the cases of early onset LBSL enabled us to highlight significant differences in the clinical, biochemical and neuroradiological phenotype between the two conditions, which also emerged from the comparison with the other 6 reported cases of ISCA2 gene mutation previously reported. In summary, this represents the second report ever published associating ISCA2 gene mutation with a mitochondrial leukoencephalopathy, with a different genetic mechanism to the previous cases. Molecular analysis of ISCA2 should be included in the genetic panel for the diagnosis of early onset mitochondrial leukoencephalopathies.
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Neurological symptoms and spinal cord embolism caused by endoscopic injection sclerotherapy for esophageal varices: A case report and literature review.
Liu, S, Wu, N, Chen, M, Zeng, X, Wang, F, She, Q
Medicine. 2018;(18):e0622
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Abstract
RATIONALE Spinal cord embolism is a rare complication of endoscopic injection sclerotherapy (EIS). PATIENT CONCERNS We report a case of a 56-year-old man who presented neurological symptoms and spinal cord embolism caused by EIS on esophageal varices. Clinical signs and symptoms, laboratory tests, thoracic magnetic resonance imaging (MRI), and related treatment supported its diagnosis. DIAGNOSES spinal cord embolism. INTERVENTIONS We stopped the hemostatic and anti-coagulation treatment, and switched to nerve nutrition, microcirculation, and hormone therapy, along with administering gastric mucosal protective agents. OUTCOMES The all patient's signs and symptoms and signs of spinal cord embolism were all relieved within 3 months after the clinical treatment. LESSONS We recommend that neurological symptoms after EIS in patients with esophageal varices should be considered a rare complication. Life-threatening conditions could be avoided by an accurate and timely diagnosis.
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[Treatable Dementia due to Vitamin B12 and Folate Deficiency].
Yoshizawa, T
Brain and nerve = Shinkei kenkyu no shinpo. 2016;(4):407-20
Abstract
Vitamin deficiency is one of the major causes of treatable dementia. Specifically, patients suffering from dementia frequentry display low serum levels of vitamin B(12). There is a close metabolic interaction between folate and vitamin B(12). Folate deficiency causes various neuropsychiatric symptoms, which resemble those observed in vitamin B(12) deficiency. This review summarizes, the basic pathophysiology of vitamin B(12) and folate deficiency, its clinical diagnosis, associated neuropsychiatric symptoms such as subacute combined degeneration and dementia, and epidemiological studies of cognitive decline and brain atrophy.
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MRI monitoring of pathological changes in the spinal cord in patients with multiple sclerosis.
Gass, A, Rocca, MA, Agosta, F, Ciccarelli, O, Chard, D, Valsasina, P, Brooks, JC, Bischof, A, Eisele, P, Kappos, L, et al
The Lancet. Neurology. 2015;(4):443-54
Abstract
The spinal cord is a clinically important site that is affected by pathological changes in most patients with multiple sclerosis; however, imaging of the spinal cord with conventional MRI can be difficult. Improvements in MRI provide a major advantage for spinal cord imaging, with better signal-to-noise ratio and improved spatial resolution. Through the use of multiplanar MRI, identification of diffuse and focal changes in the whole spinal cord is now routinely possible. Corroborated by related histopathological analyses, several new techniques, such as magnetisation transfer, diffusion tension imaging, functional MRI, and proton magnetic resonance spectroscopy, can detect non-focal, spinal cord pathological changes in patients with multiple sclerosis. Additionally, functional MRI can reveal changes in the response pattern to sensory stimulation in patients with multiple sclerosis. Through use of these techniques, findings of cord atrophy, intrinsic cord damage, and adaptation are shown to occur largely independently of focal spinal cord lesion load, which emphasises their relevance in depiction of the true burden of disease. Combinations of magnetisation transfer ratio or diffusion tension imaging indices with cord atrophy markers seem to be the most robust and meaningful biomarkers to monitor disease evolution in early multiple sclerosis.
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Prediction of Neurological Impairment in Cervical Spondylotic Myelopathy using a Combination of Diffusion MRI and Proton MR Spectroscopy.
Ellingson, BM, Salamon, N, Hardy, AJ, Holly, LT
PloS one. 2015;(10):e0139451
Abstract
PURPOSE In the present study we investigated a combination of diffusion tensor imaging (DTI) and magnetic resonance spectroscopic (MRS) biomarkers in order to predict neurological impairment in patients with cervical spondylosis. METHODS Twenty-seven patients with cervical spondylosis were evaluated. DTI and single voxel MRS were performed in the cervical cord. N-acetylaspartate (NAA) and choline (Cho) metabolite concentration ratios with respect to creatine were quantified, as well as the ratio of choline to NAA. The modified mJOA scale was used as a measure of neurologic deficit. Linear regression was performed between DTI and MRS parameters and mJOA scores. Significant predictors from linear regression were used in a multiple linear regression model in order to improve prediction of mJOA. Parameters that did not add value to model performance were removed, then an optimized multiparametric model was established to predict mJOA. RESULTS Significant correlations were observed between the Torg-Pavlov ratio and FA (R2 = 0.2021, P = 0.019); DTI fiber tract density and FA, MD, Cho/NAA (R2 = 0.3412, P = 0.0014; R2 = 0.2112, P = 0.016; and R2 = 0.2352, P = 0.010 respectively); along with FA and Cho/NAA (R2 = 0.1695, P = 0.033). DTI fiber tract density, MD and FA at the site of compression, along with Cho/NAA at C2, were significantly correlated with mJOA score (R2 = 0.05939, P < 0.0001; R2 = 0.4739, P < 0.0001; R2 = 0.7034, P < 0.0001; R2 = 0.4649, P < 0.0001). A combination biomarker consisting of DTI fiber tract density, MD, and Cho/NAA showed the best prediction of mJOA (R2 = 0.8274, P<0.0001), with post-hoc tests suggesting fiber tract density, MD, and Cho/NAA were all significant contributors to predicting mJOA (P = 0.00053, P = 0.00085, and P = 0.0019, respectively). CONCLUSION A linear combination of DTI and MRS measurements within the cervical spinal cord may be useful for accurately predicting neurological deficits in patients with cervical spondylosis. Additional studies may be necessary to validate these observations.
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Serum lipid concentrations among persons with spinal cord injury - a systematic review and meta-analysis of the literature.
Gilbert, O, Croffoot, JR, Taylor, AJ, Nash, M, Schomer, K, Groah, S
Atherosclerosis. 2014;(2):305-12
Abstract
BACKGROUND Lipid optimization comprises a therapeutic cornerstone of primary and secondary cardiovascular disease prevention. This systematic review and meta-analysis sought to clarify patterns of lipid profiles in spinal cord injury (SCI) patients compared to able-bodied individuals as well as among subgroups of SCI patients stratified by sex, activity level, race, and level of injury. METHODS Searches were conducted in PubMed, CINAHL, PsycINFO, and EMBASE. The initial literature search broadly identified peer-reviewed studies that examined cardiovascular risk factors in SCI. A total of 50 studies were ultimately identified that focused on lipid levels in SCI. Demographic data (including subject age, duration of injury, height, weight, and body mass index [BMI]) and lipid values were extracted for able-bodied individuals and subjects with SCI. Statistical analyses included t-testing and analysis of variance (ANOVA). RESULTS Compared with controls, individuals with SCI had significantly lower total cholesterol (TC) (183.4 mg/dL versus 194.9 mg/dL, p = 0.019) and high-density lipoprotein cholesterol (HDL-C) (41.0 mg/dL versus 49.6 mg/dL, p < 0.001) and higher TC/HDL-C ratios (4.5 versus 4.0, p = 0.002), though no significant differences were found for triglyceride (TG) and non-HDL-C values. CONCLUSIONS SCI represents an increasingly common chronic condition, now secondarily characterized by heightened CVD risk potentially in part due to unique lipid profiles characterized primarily by low HDL-C and an increased TC/HDL-C ratio. As other at-risk patient populations have received increased acknowledgment with more stringent lipid panel screening at earlier ages and increased frequency, we would propose that the same be implemented for the SCI population until more-specific CVD risk stratification guidelines are established for this population.
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Multicystic demyelinating myelopathy: widening spectrum of pediatric aquaporin-4 autoimmunity.
Longoni, G, Bigi, S, Branson, HM, Hawkins, C, Rutka, JT, Filippi, M, Yeh, EA
Neurology. 2014;(10):902-3
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Abstract
A 10-year-old girl presented with subacute lower limb weakness and gait ataxia. MRI revealed a large multicystic spinal cord lesion with patchy enhancement (figure 1, A–B) and 3 small (<6 mm) periventricular and deep white matter brain lesions. The presence of serum anti-aquaporin-4 immunoglobulin G (AQP4) (ELISA assay) and compatible neuropathologic features from neurosurgical specimens1 (figure 2) suggested the diagnosis of a neuromyelitis optica spectrum disorder.2 Targeted immunotherapy was started with partial lesion resolution (figure 1C).
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Significance and function of different spinal collateral compartments following thoracic aortic surgery: immediate versus long-term flow compensation.
Meffert, P, Bischoff, MS, Brenner, R, Siepe, M, Beyersdorf, F, Kari, FA
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2014;(5):799-804
Abstract
Iatrogenic paraplegia has been accompanying cardiovascular surgery since its beginning. As a result, surgeons have been developing many theories about the exact mechanisms of this devastating complication. Thus, the impact of single arteries that contribute to the spinal perfusion is one of the most discussed subjects in modern surgery. The subsequent decision of reattachment or the permanent disconnection of these intercostal arteries divides the surgical community. On the one hand, the anatomical or vascular approach pleads for the immediate reimplantation to reconstruct the anatomical situation. On the other hand, the decision of the permanent disconnection aims at avoiding stealing phenomenon away from the spinal vascular network. This spinal collateral network can be described as consisting of three components-the intraspinal and two paraspinal compartments-that feed the nutrient arteries of the spinal cord. The exact functional impact of the different compartments of the collateral network remains poorly understood. In this review, the function of the intraspinal compartment in the context of collateral network principle as an immediate emergency backup system is described. The exact structure and architectural principles of the intraspinal compartment are described. The critical parameters with regard to the risk of postoperative spinal cord ischaemia are the number of anterior radiculomedullary arteries (ARMAs) and the distance between them in relation to the longitudinal extent of aortic disease. The paraspinal network as a sleeping reserve is proposed as the long-term backup system. This sleeping reserve has to be activated by arteriogenic stimuli. These are presented briefly, and prior findings regarding arteriogenesis are discussed in the light of the collateral network concept. Finally, the role of preoperative visualization of the ARMAs in order to evaluate the risk of postoperative paraplegia is emphasized.