Study DesignSystematic review.ObjectivesThe pre-symptomatic state of Degenerative Cervical Myelopathy (DCM), wherein degenerative changes and spinal cord compression are seen without clinical findings, is poorly understood and inconsistently categorised. Clear identification may elucidate the temporality of DCM development. Therefore, a systematic assessment was undertaken of current terminology for pre-DCM states, with the objective of standardising definitions and informing an AO Spine expert position statement.MethodsMedline and Embase were searched for all studies on asymptomatic spinal compression or clinical findings preceding DCM, returning 3585 studies. After screening, 96 studies were included in the final analysis. The terminology used for pre-DCM states and their definitions were extracted, along with their frequencies or speciality/country of author in the literature.ResultsMultiple terms were used to represent pre-DCM stages, including "asymptomatic" (86 studies), "non-myelopathic" (26 studies), "without myelopathy" (15 studies), "pre-symptomatic" (9 studies) and "sub-clinical" (7 studies). "asymptomatic" was associated with the greatest inconsistency. Some defined this as patients with radiological signs of spinal degeneration with/without spinal cord compression but no clinical signs of myelopathy, whereas others used the term synonymously with healthy controls. This inconsistency is particularly challenging in clinical studies in which DCM patients are compared to those with pre-DCM states and/or healthy volunteers.ConclusionThere is substantial inconsistency in the terms used to describe pre-DCM states. There is no clear relationship between the terms used and the country or speciality of the main author. Standardised definitions for these disease states should be agreed and used in future studies.
BACKGROUND CONTEXT: Accurate and automatic MRI measurements are relevant for assessing spinal cord compression severity in degenerative cervical myelopathy (DCM) and guiding treatment. The widely-used maximum spinal cord compression (MSCC) index has limitations. Firstly, it normalizes the anteroposterior cord diameter by that above and below the compression but does not account for cord size variation along the superior-inferior axis, making MSCC sensitive to compression level. Secondly, cord shape varies across individuals, making MSCC sensitive to this variability. Thirdly, MSCC is typically calculated by an expert-rater from a single sagittal slice, which is time-consuming and prone to variability. PURPOSE: This study proposes a fully automatic pipeline to compute MSCC. DESIGN: We developed a normalization strategy for traditional MSCC (anteroposterior diameter) using a healthy adults database (n = 203) to address cord anatomy variability across individuals and evaluated additional morphometrics (transverse diameter, area, eccentricity, and solidity). PATIENT SAMPLE: DCM patient cohort of n = 120. OUTCOME MEASURES: Receiver operating characteristic (ROC) and area under the curve (AUC) were used as evaluation metrics. METHODS: We validated the method in a mild DCM patient cohort against manually derived morphometrics and predicted the therapeutic decision (operative/conservative) using a stepwise binary logistic regression incorporating demographics and clinical scores. RESULTS: The automatic and normalized MSCC measures correlated significantly with clinical scores and predicted the therapeutic decision more accurately than manual MSCC. Significant predictors included upper extremity sensory dysfunction, T2w hyperintensity, and the proposed MRI-based measures. The model achieved an area under the curve of 0.80 in receiver operating characteristic analysis. CONCLUSION: This study introduced an automatic method for computing normalized measures of cord compressions from MRIs, potentially improving therapeutic decisions in DCM patients. The method is open-source and available in Spinal Cord Toolbox v6.0 and above.
- Keywords
- DCM, Image analysis, MRI, MSCC, Maximum spinal cord compression, Spinal cord, degenerative cervical myelopathy, magnetic resonance imaging,
- MeSH
- Adult MeSH
- Spinal Cord Compression * diagnostic imaging MeSH
- Cervical Vertebrae * diagnostic imaging MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging * methods MeSH
- Spinal Cord Diseases * diagnostic imaging MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Study DesignRetrospective Cohort Study.ObjectivesThe current recommended treatment for Giant Cell Tumour (GCT) of the spine is en bloc excision. Denosumab is a monoclonal antibody reducing osteoclast activity that shows promising results when used as a neo - adjuvant treatment. However, the current literature remains limited. The purpose of this study was to assess the effect of denosumab on tumour characteristics and symptom relief in the acute phase of treatment of spinal GCT.MethodsWe performed a retrospective review of 16 patients treated with denosumab as neo-adjuvant and stand - alone treatment. MRI and PET tumour characteristics were taken before and after treatment and patients were interviewed for subjective pain responses.ResultsFollowing treatment, all patients showed improvement of pain, of which 68.7% of patients were pain free with 43.75% noting improvement within 48 hours. Mean relative volumetric reduction in tumour volume was 37.3% (P < .001). Eight patients showed high grade of Bilsky classification (Epidural spinal cord compression scale - ESCC) with seven of them showing significant improvement to low grade of ESCC (P = .016). Median baseline PET Standardised Uptake Value (SUV)max was 14.57 and post treatment was 4.8 (P < .001).ConclusionsThis study provides necessary insight to the limited literature on the use of denosumab for spinal GCT in the acute phase. The clinical and radiographic responses observed demonstrate the critical role that neo-adjuvant denosumab has by reducing the tumour burden around critical adjacent neurovascular structures before eventual resection, significant pain improvement even with presence of fractured vertebra.
- Keywords
- adjuvant, denosumab, en bloc excision, giant cell tumour, neo, pain,
- Publication type
- Journal Article MeSH
Morphometric measures derived from spinal cord segmentations can serve as diagnostic and prognostic biomarkers in neurological diseases and injuries affecting the spinal cord. For instance, the spinal cord cross-sectional area can be used to monitor cord atrophy in multiple sclerosis and to characterize compression in degenerative cervical myelopathy. While robust, automatic segmentation methods to a wide variety of contrasts and pathologies have been developed over the past few years, whether their predictions are stable as the model is updated using new datasets has not been assessed. This is particularly important for deriving normative values from healthy participants. In this study, we present a spinal cord segmentation model trained on a multisite (n=75) dataset, including 9 different MRI contrasts and several spinal cord pathologies. We also introduce a lifelong learning framework to automatically monitor the morphometric drift as the model is updated using additional datasets. The framework is triggered by an automatic GitHub Actions workflow every time a new model is created, recording the morphometric values derived from the model's predictions over time. As a real-world application of the proposed framework, we employed the spinal cord segmentation model to update a recently-introduced normative database of healthy participants containing commonly used measures of spinal cord morphometry. Results showed that: (i) our model performs well compared to its previous versions and existing pathology-specific models on the lumbar spinal cord, images with severe compression, and in the presence of intramedullary lesions and/or atrophy achieving an average Dice score of 0.95 ± 0.03; (ii) the automatic workflow for monitoring morphometric drift provides a quick feedback loop for developing future segmentation models; and (iii) the scaling factor required to update the database of morphometric measures is nearly constant among slices across the given vertebral levels, showing minimum drift between the current and previous versions of the model monitored by the framework. The model is freely available in Spinal Cord Toolbox v7.0.
- Keywords
- Lifelong Learning, MLOps, MRI, Morphometric Drift, Segmentation, Spinal Cord,
- Publication type
- Journal Article MeSH
- Preprint MeSH
BACKGROUND: Spinal cord compression is a rare presentation of non-Hodgkin lymphoma (NHL) in children. We aimed to describe the prevalence, histological subtypes, clinical presentation, therapy, and outcome of those children in a population-based cohort. The chemotherapy regimen remained comparable over time. METHODS: We retrospectively identified all children and adolescents with paresis as initial manifestations of the NHL between January 1990 and December 2020 from the NHL-BFM database. Characteristics, therapy, and outcome data were gathered from the database and patient files. RESULTS: Fifty-seven of 4779 children (1.2%) presented with initial paresis due to spinal cord compression. The median age was 10.3 years (range, 3.1-18.0 years), and 33% were female. Initial symptoms were paresis/weakness (n = 50, 88%), back pain (n = 33, 58%), paresthesia (n = 23, 40%), and bladder dysfunction and/or constipation (n = 22, 39%), persisting for a median of 14 days before diagnosis. Subtype distribution was mature B-NHL (n = 41, 72%), precursor B-lymphoblastic lymphoma (LBL) (n = 12, 21%), anaplastic large cell lymphoma (ALCL) (n = 3, 5%), and T-LBL (n = 1, 2%). Initial emergency therapy included surgery (70%) and/or chemotherapy/steroids (63%). Five-year event-free survival and overall survival (80% ± 5% and 82% ± 5%, respectively) were comparable with all other NHL patients. Neurological symptoms persisted in approximately one-third of surviving patients at the last follow-up. CONCLUSION: 1.2% of pediatric NHL patients presented with paresis from spinal cord compression mainly due to B-cell lymphomas. Neurological sequelae were observed in one-third of surviving patients.
- Keywords
- back pain, children, non‐Hodgkin Lymphoma, paresis, spinal cord compression,
- MeSH
- Child MeSH
- Spinal Cord Compression * etiology MeSH
- Humans MeSH
- Survival Rate MeSH
- Adolescent MeSH
- Follow-Up Studies MeSH
- Lymphoma, Non-Hodgkin * complications pathology epidemiology MeSH
- Child, Preschool MeSH
- Prognosis MeSH
- Retrospective Studies MeSH
- Check Tag
- Child MeSH
- Humans MeSH
- Adolescent MeSH
- Male MeSH
- Child, Preschool MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
Degenerative cervical myelopathy (DCM) represents the final consequence of a series of degenerative changes in the cervical spine, resulting in cervical spinal canal stenosis and mechanical stress on the cervical spinal cord. This process leads to subsequent pathophysiological processes in the spinal cord tissues. The primary mechanism of injury is degenerative compression of the cervical spinal cord, detectable by magnetic resonance imaging (MRI), serving as a hallmark for diagnosing DCM. However, the relative resilience of the cervical spinal cord to mechanical compression leads to clinical-radiological discordance, i.e., some individuals may exhibit MRI findings of DCC without the clinical signs and symptoms of myelopathy. This degenerative compression of the cervical spinal cord without clinical signs of myelopathy, potentially serving as a precursor to the development of DCM, remains a somewhat controversial topic. In this review article, we elaborate on and provide commentary on the terminology, epidemiology, natural course, diagnosis, predictive value, risks, and practical management of this condition-all of which are subjects of ongoing debate.
Measures of spinal cord morphometry computed from magnetic resonance images serve as relevant prognostic biomarkers for a range of spinal cord pathologies, including traumatic and non-traumatic spinal cord injury and neurodegenerative diseases. However, interpreting these imaging biomarkers is difficult due to considerable intra- and inter-subject variability. Yet, there is no clear consensus on a normalization method that would help reduce this variability and more insights into the distribution of these morphometrics are needed. In this study, we computed a database of normative values for six commonly used measures of spinal cord morphometry: cross-sectional area, anteroposterior diameter, transverse diameter, compression ratio, eccentricity, and solidity. Normative values were computed from a large open-access dataset of healthy adult volunteers (N = 203) and were brought to the common space of the PAM50 spinal cord template using a newly proposed normalization method based on linear interpolation. Compared to traditional image-based registration, the proposed normalization approach does not involve image transformations and, therefore, does not introduce distortions of spinal cord anatomy. This is a crucial consideration in preserving the integrity of the spinal cord anatomy in conditions such as spinal cord injury. This new morphometric database allows researchers to normalize based on sex and age, thereby minimizing inter-subject variability associated with demographic and biological factors. The proposed methodology is open-source and accessible through the Spinal Cord Toolbox (SCT) v6.0 and higher.
- Keywords
- Spinal cord, morphometric measures, normalization, normative values,
- Publication type
- Journal Article MeSH
Misdiagnosis is frequent in early motor neuron disease (MND), typically compressive radiculopathy, or in patients with restricted MND phenotype. In this retrospective, single tertiary centre study, we measured levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (p-NfH) chain in cerebrospinal fluid (CSF) and of p-NfH in serum with commercially available ELISA kits and assessed their respective diagnostic performance as a marker of MND. The entire study population (n = 164) comprised 71 MND patients, 30 patients with compressive myelo- or radiculopathy, and 63 disease controls (DC). Among MND patients, we specified subgroups with only lower motoneuron involvement (MND-LMN, n = 15) and with confounding nerve roots or spinal cord compression (MND-C, n = 18), representing clinical diagnostic pitfalls. MND-LMN displayed significantly lower CSF NfL (p = 0.003) and p-NFH (p = 0.017), but not serum p-NfH (p = 0.347) levels compared to other MND patients (n = 56). The discriminative ability (area under the curve-AUC) of both CSF Nfs towards all MND patients was comparable to each other but significantly higher than that of p-NfH in serum (ps < 0.001). AUC of both CSF Nfs between MND-LMN and DC and also between MND-C and myelo-/radiculopathies were reduced, as compared to AUC between other MND and DC or myelo-/radiculopathies, respectively. Our results suggest that both Nfs in CSF represent a reliable diagnostic marker in a general MND population, fulfilling Awaji criteria. As for diagnostic pitfalls, and also for p-NfH in serum, their discriminative ability and, therefore, clinical utility appears to be limited.
- Keywords
- Amyotrophic lateral sclerosis, Biomarker, Cerebrospinal fluid, Motor neuron disease, Neurofilament,
- MeSH
- Biomarkers MeSH
- Phenotype MeSH
- Intermediate Filaments MeSH
- Humans MeSH
- Spinal Cord Diseases * MeSH
- Neurofilament Proteins MeSH
- Motor Neuron Disease * diagnosis MeSH
- Radiculopathy * MeSH
- Retrospective Studies MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Biomarkers MeSH
- Neurofilament Proteins MeSH
An 11-year-old spayed female Toy Poodle presented with acute tetraparesis. A small subcutaneous mass was found in the right trunk region, and the magnetic resonance revealed a compressive spinal cord lesion due to an irregular bone proliferation at the third cervical vertebra. After surgical resection of the vertebral lesion, the neurological symptoms improved, and the patient could walk on her own. The excised vertebral and subcutaneous masses were diagnosed as a mammary adenocarcinoma on the histopathological examination, with Ki-67 and HER-2 immunohistochemistry staining. This case report highlights the importance of defining the primary tumours of metastatic vertebral tumours and the necessity of palliative surgery to improve the patient's quality of life.
- Keywords
- bone tumour, canine, mammary cancer, metastasis, palliative surgery,
- Publication type
- Journal Article MeSH
- Case Reports MeSH
Degenerative spinal cord compression is a frequent pathological condition with increasing prevalence throughout aging. Initial non-myelopathic cervical spinal cord compression (NMDC) might progress over time into potentially irreversible degenerative cervical myelopathy (DCM). While quantitative MRI (qMRI) techniques demonstrated the ability to depict intrinsic tissue properties, longitudinal in-vivo biomarkers to identify NMDC patients who will eventually develop DCM are still missing. Thus, we aim to review the ability of qMRI techniques (such as diffusion MRI, diffusion tensor imaging (DTI), magnetization transfer (MT) imaging, and magnetic resonance spectroscopy (1H-MRS)) to serve as prognostic markers in NMDC. While DTI in NMDC patients consistently detected lower fractional anisotropy and higher mean diffusivity at compressed levels, caused by demyelination and axonal injury, MT and 1H-MRS, along with advanced and tract-specific diffusion MRI, recently revealed microstructural alterations, also rostrally pointing to Wallerian degeneration. Recent studies also disclosed a significant relationship between microstructural damage and functional deficits, as assessed by qMRI and electrophysiology, respectively. Thus, tract-specific qMRI, in combination with electrophysiology, critically extends our understanding of the underlying pathophysiology of degenerative spinal cord compression and may provide predictive markers of DCM development for accurate patient management. However, the prognostic value must be validated in longitudinal studies.
