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Brain Sciences
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Cervical Myelopathy: Current Hurdles and Future Perspectives
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Cervical Myelopathy: Current Hurdles and Future Perspectives

A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Neurosurgery and Neuroanatomy".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 14984

Special Issue Editors

Dr. Rosario Maugeri

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Guest Editor
Unit of Neurosurgery, Department of Biomedicine Neurosciences and Advanced Diagnostics, School of Medicine, University of Palermo, 90100 Palermo, Italy
Interests: craniotomy; trigeminal neuralgia; spine surgery; brain injury; clinical neuro-physiology; brain tumors; neurosurgery
Dr. Giuseppe Roberto Giammalva

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Guest Editor
Unit of Neurosurgery, Department of Biomedicine Neurosciences and Advanced Diagnostics, School of Medicine, University of Palermo, 90100 Palermo, Italy
Interests: neuroncology; neurosonology; brain tumor surgery; neuroanatomy; IOUS; awake surgery; connectomics
Special Issues, Collections and Topics in MDPI journals
Dr. Francesca Graziano

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Guest Editor
Department of Neurosurgery, Highly Specialized Hospital and of National Importance "Gari-baldi", 95122 Catania, Italy
Interests: brain tumors; spine surgery; neuroanatomy; skull base; spinal cord stimulation
Dr. Teresa Somma

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Guest Editor
Division of Neurosurgery, Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy
Interests: Skull base; spine surgery; spinal cord stimulation; intraoperative neurophysiological monitoring

Special Issue Information

Dear Colleagues,

Cervical myelopathy represents a common cause of spinal cord dysfunction in adults. Cervical spondylosis is the most common and often predisposing cause of cervical myelopathy. Neurological symptoms are often insidious in the early stages, and patients often develop severe and disabling neurological impairment in case of chronic compression of the spinal cord. However, the degree of spinal cord injury is not related to the severity of spinal cord compression, and the pathophysiological mechanisms underlying cervical myelopathy are still poorly understood. Moreover, spine dynamics together with histopathological modifications may play a role in the progression of cervical myelopathy. In particular, spinal degeneration, intervertebral disc herniations, thickening of the ligamentum flavum, and loss of physiological spinal balance are among the causes of cervical myelopathy. In recent years, inflammation, immune-mediated reaction and disruption of blood–brain barrier as pathomechanisms of cervical myelopathy also have been studied as leading causes of cervical myelopathy progression through immune-mediated secondary harm and reduced angiogenesis.

Surgery currently represents the fundamental treatment for symptomatic cervical myelopathy, in order to halt the progression of the disease. Patients with neurological impairments are addressed to neurorehabilitation in order to prevent further neurological deterioration and to improve sensory-motor functions. Regarding surgery, several surgical techniques are currently adopted in order to release spinal cord compression, including both anterior and posterior techniques. However, neurological impairments may not completely recover, and long-term outcomes are poor. Therefore, the optimal surgical approach, timing of surgery and subsequent care of patients with cervical myelopathy are still matters of debate. 

The aim of this Special Issue is to focus on the current knowledge on the development and progression of cervical myelopathy. Current hurdles, outstanding issues, the state of the art and future perspectives about the neurobiology of cervical myelopathy, pathological degeneration of spinal cord, advanced diagnostics, conservative treatments, surgical techniques and neurorehabilitation strategies for patients with neurological impairments will be discussed.

This Special Issue solicits pre-clinical and clinical original research articles, technical notes about novel surgical techniques, literature reviews and meta-analyses focusing on cervical myelopathy along its entire natural history, from its establishment to surgical treatment and further neurorehabilitation. Papers focusing on pathophysiology, pathological anatomy, advanced diagnostics, conservative treatment, novel surgical techniques, neurorehabilitation and supportive care are welcome.

Dr. Rosario Maugeri
Dr. Giuseppe Roberto Giammalva
Dr. Francesca Graziano
Dr. Teresa Somma
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Brain Sciences is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2200 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cervical myelopathy
  • spinal cord compression
  • spinal surgery
  • neurorehabilitation
  • neuroimaging

Published Papers (7 papers)

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Research

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12 pages, 1684 KiB  
Article
The Impact of Single-Level ACDF on Neural Foramen and Disc Height of Surgical and Adjacent Cervical Segments: A Case-Series Radiological Analysis
by Rosario Maugeri, Lara Brunasso, Andrea Sciortino, Alba Scerrati, Felice Buscemi, Luigi Basile, Giuseppe Roberto Giammalva, Roberta Costanzo, Francesco Bencivinni, Eleonora Bruno, Domenica Matranga, Laura Maniscalco, Francesco Gioia, Silvana Tumbiolo and Domenico Gerardo Iacopino
Brain Sci. 2023, 13(1), 101; https://doi.org/10.3390/brainsci13010101 - 04 Jan 2023
Cited by 1 | Viewed by 2329
Abstract
Background: ACDF has become one of the established procedures for the surgical treatment of symptomatic cervical spondylosis, showing excellent clinical results and effective improvements in neural functions and neck pain relief. The main purpose of ACDF is neural decompression, and it is considered [...] Read more.
Background: ACDF has become one of the established procedures for the surgical treatment of symptomatic cervical spondylosis, showing excellent clinical results and effective improvements in neural functions and neck pain relief. The main purpose of ACDF is neural decompression, and it is considered by some authors as an indirect result of the intervertebral distraction and cage insertion and the consequent restoration of the disc space and foramen height. Methods: Radiological data from 28 patients who underwent single-level ACDF were retrospectively collected and evaluated. For neural foramen evaluation, antero-posterior (A-P) and cranio-caudal (C-C) diameters were manually calculated; for intervertebral disc height the anterior, centrum and posterior measurement were calculated. All measurements were performed at surgical and adjacent (above and below) segments. NRS, NDI and also the mJOA and Nurick scale were collected for clinical examination and complete evaluation of patients’ postoperative outcome. Results: The intervertebral disc height in all its measurements, in addition to the height (C-C diameter) of the foramen (both right and left) increase at the surgical segment when comparing pre and postop results (p < 0.001, and p = 0.033 and p = 0.001). NRS and NDI radiculopathy scores showed improved results from pre- to post-op evaluation (p < 0.001), and a negative statistical correlation with the improved disc height at the surgical level. Conclusions: The restoration of posterior disc height through cage insertion appears to be effective in increasing foraminal height in patients with symptomatic preoperative cervical foraminal stenosis. Full article
(This article belongs to the Special Issue Cervical Myelopathy: Current Hurdles and Future Perspectives)
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12 pages, 3429 KiB  
Article
Is the Zero-P Spacer Suitable for 3-Level Anterior Cervical Discectomy and Fusion Surgery in Terms of Sagittal Alignment Reconstruction: A Comparison Study with Traditional Plate and Cage System
by Jing Guo, Weiming Jin, Yan Shi, Zhiping Guan, Jian Wen, Yongcan Huang and Binsheng Yu
Brain Sci. 2022, 12(11), 1583; https://doi.org/10.3390/brainsci12111583 - 19 Nov 2022
Cited by 6 | Viewed by 4041
Abstract
The Zero-P spacer was primarily developed aiming to reduce the morbidity associated with the traditional anterior cervical plate. During the past decade, many authors have reported the use of Zero-P spacers for anterior cervical discectomy and fusion (ACDF) of one or two segments. [...] Read more.
The Zero-P spacer was primarily developed aiming to reduce the morbidity associated with the traditional anterior cervical plate. During the past decade, many authors have reported the use of Zero-P spacers for anterior cervical discectomy and fusion (ACDF) of one or two segments. Nevertheless, there is still a paucity of knowledge on the safety and feasibility of using Zero-P spacers for 3-level fixation. The objective of this study was to investigate the clinical and radiological outcomes, with a focus on the sagittal alignment reconstruction of 3-level ACDF surgery using Zero-P spacers versus those using a traditional plate and cage system. From Sep 2013 to Aug 2016, a total of 44 patients who received 3-level ACDF surgery due to cervical spondylotic myelopathy were recruited. The Zero-P spacer was used in 23 patients (group ZP) and the traditional plate and cage system in 21 (group PC). Clinical outcomes were analyzed by Neck Disability Index (NDI) and Japanese Orthopedic Association (JOA) scores, and dysphagia was evaluated using the Bazaz score. Radiological outcomes, including fusion rate, adjacent segment degeneration (ASD), and especially changes in cervical sagittal alignment, were analyzed. The NDI and JOA scores did not differ significantly between the two groups postoperatively (p > 0.05); however, there was significantly less dysphagia in patients using Zero-P spacers at the 3- and 6-month follow-up (p < 0.05). At the 24-month follow-up, the fusion rate and ASD were similar between the two groups (p > 0.05). Interestingly, patients using Zero-P spacers had a significantly lower postoperative C2-7 Cobb angle and fused segment Cobb angle, compared to those using a traditional plate and cage system (p < 0.05); meanwhile, the fused segment disc wedge was also found to be significantly smaller in patients using Zero-P spacers after surgery (p < 0.05). Moreover, we further divided patients into subgroups according to their cervical lordosis. In patients with a preoperative C2-7 Cobb angle ≤ 10°, significantly less cervical and local lordosis, as well as disc wedge, were seen in group ZP after surgery (p < 0.05), while in others with a preoperative C2-7 Cobb angle > 10°, no significant difference in postoperative changes of the cervical sagittal alignment was seen between group ZP and group PC (p > 0.05). Zero-P spacers used in 3-level ACDF surgery could provide equivalent clinical outcomes and a lower rate of postoperative dysphagia, compared to the traditional plate and cage system. However, our results showed that it was inferior to the cervical plate in terms of sagittal alignment reconstruction for 3-level fixation. We recommend applying Zero-P spacers for 3-level ACDF in patients with good preoperative cervical lordosis (C2-7 Cobb angle > 10°), in order to restore and maintain physiological curvature of the cervical spine postoperatively. Full article
(This article belongs to the Special Issue Cervical Myelopathy: Current Hurdles and Future Perspectives)
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16 pages, 5351 KiB  
Article
Apelin-13 Protects Neurons by Attenuating Early-Stage Postspinal Cord Injury Apoptosis In Vitro
by Taotao Lin, Yujie Zhao, Shengyu Guo, Zhengru Wu, Wenwen Li, Rongcan Wu, Zhenyu Wang and Wenge Liu
Brain Sci. 2022, 12(11), 1515; https://doi.org/10.3390/brainsci12111515 - 08 Nov 2022
Cited by 3 | Viewed by 1562
Abstract
Apelin is a 77-amino-acid peptide that is an endogenous ligand for the G protein-coupled receptor APJ (Apelin receptor, APJ). Apelin-13, as the most bioactive affinity fragment of apelin, plays a role in energy metabolism, myocardial ischemia-reperfusion injury, and the regulation of the inflammatory [...] Read more.
Apelin is a 77-amino-acid peptide that is an endogenous ligand for the G protein-coupled receptor APJ (Apelin receptor, APJ). Apelin-13, as the most bioactive affinity fragment of apelin, plays a role in energy metabolism, myocardial ischemia-reperfusion injury, and the regulation of the inflammatory response during oxidative stress, but its role in spinal cord injury is still unclear. This research identified and verified the differential expression of apelin in rat spinal cord injured tissues and normal spinal cord tissues by transcriptome sequencing in vivo and proved that apelin-13 protects neurons by strengthening autophagy and attenuating early-stage postspinal cord injury apoptosis in vitro. After constructing the model concerning a rat spinal cord hemisection damage, transcriptome sequencing was performed on the injured and normal spinal cord tissues of rats, which identified the differentially expressed gene apelin, with qRT-PCR detecting the representative level of apelin. The oxygen-glucose deprivation (OGD) model of PC12 cells was constructed in vitro to simulate spinal cord injury. The OGD injury times were 2 h, 4 h, 6 h, 8 h, and 12 h, and the non-OGD injury group was used as the control. The expression of apelin at each time point was observed by Western blotting. The expression of apelin was the lowest in the 6 h OGD injury group (p < 0.05). Therefore, the OGD injury time of 6 h was used in subsequent experiments. The noncytotoxic drug concentration of apelin-13 was determined with a Cell Counting Kit-8 (CCK-8) assay. An appropriate dose of apelin-13 (1 μM) significantly improved cell survival (p < 0.05). Thus, subsequent experiments selected a concentration of 1 μM apelin-13 as it significantly increased cell viability. Finally, we divided the experimental groups into four groups according to whether they received drugs (1 μM apelin-13, 24 h) or OGD (6 h): (1) control group: without apelin-13 or OGD injury; (2) apelin-13 group: with apelin-13 but no OGD injury; (3) OGD group: with OGD injury but without apelin-13; and (4) OGD + apelin-13 group: with apelin-13 and OGD injury. The TUNEL assay and flow cytometry results showed that compared with the OGD group, apoptosis in the OGD+Apelin-13 group was significantly reduced (p < 0.001). Determination of cell viability under different conditions by CCK-8 assay results displays that Apelin-13 can significantly improve the cell viability percentage under OGD conditions (p < 0.001). Western blotting results showed that apelin-13 decreased the expression ratios of apoptosis-related proteins Bax/Bcl-2 and cleaved-caspase3/caspase3 (p < 0.05), increasing the key to Beclin1-dependent autophagy pathway expression of the protein Beclin1. This finding indicates that apelin-13 protects neurons by strengthening autophagy and attenuating early-stage postspinal cord injury apoptosis in vitro. Full article
(This article belongs to the Special Issue Cervical Myelopathy: Current Hurdles and Future Perspectives)
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18 pages, 3115 KiB  
Article
The Pre-Operative Duration of Symptoms: The Most Important Predictor of Post-Operative Efficacy in Patients with Degenerative Cervical Myelopathy
by Shengyu Guo, Taotao Lin, Rongcan Wu, Zhenyu Wang, Gang Chen and Wenge Liu
Brain Sci. 2022, 12(8), 1088; https://doi.org/10.3390/brainsci12081088 - 17 Aug 2022
Cited by 2 | Viewed by 1614
Abstract
Objective. To explore the most important predictors of post-operative efficacy in patients with degenerative cervical myelopathy (DCM). Methods. From January 2013 to January 2019, 284 patients with DCM were enrolled. They were categorized based on the different surgical methods used: single anterior cervical [...] Read more.
Objective. To explore the most important predictors of post-operative efficacy in patients with degenerative cervical myelopathy (DCM). Methods. From January 2013 to January 2019, 284 patients with DCM were enrolled. They were categorized based on the different surgical methods used: single anterior cervical decompression and fusion (ACDF) (n = 80), double ACDF (n = 56), three ACDF (n = 13), anterior cervical corpectomy and fusion (ACCF) (n = 63), anterior cervical hybrid decompression and fusion (ACHDF) (n = 25), laminoplasty (n = 38) and laminectomy and fusion (n = 9). The follow-up time was 2 years. The patients were divided into two groups based on the mJOA recovery rate at the last follow-up: Group A (the excellent improvement group, mJOA recovery rate >50%, n = 213) and Group B (the poor improvement group, mJOA recovery rate ≤50%, n = 71). The evaluated data included age, gender, BMI, duration of symptoms (months), smoking, drinking, number of lesion segments, surgical methods, surgical time, blood loss, the Charlson Comorbidity Index (CCI), CCI classification, imaging parameters (CL, T1S, C2-7SVA, CL (F), T1S (F), C2-7SVA (F), CL (E), T1S (E), C2-7SVA (E), CL (ROM), T1S (ROM) and C2-7SVA (ROM)), maximum spinal cord compression (MSCC), maximum canal compromise (MCC), Transverse area (TA), Transverse area ratio (TAR), compression ratio (CR) and the Coefficient compression ratio (CCR). The visual analog score (VAS), neck disability index (NDI), modified Japanese Orthopedic Association (mJOA) and mJOA recovery rate were used to assess cervical spinal function and quality of life. Results. We found that there was no significant difference in the baseline data among the different surgical groups and that there were only significant differences in the number of lesion segments, C2–7SVA, T1S (F), T1S (ROM), TA, CR, surgical time and blood loss. Therefore, there was comparability of the post-operative recovery among the different surgical groups, and we found that there were significant differences in age, the duration of symptoms, CL and pre-mJOA between Group A and Group B. A binary logistic regression analysis showed that the duration of the symptoms was an independent risk factor for post-operative efficacy in patients with DCM. Meanwhile, when the duration of symptoms was ≥6.5 months, the prognosis of patients was more likely to be poor, and the probability of a poor prognosis increased by 0.196 times for each additional month of symptom duration (p < 0.001, OR = 1.196). Conclusion. For patients with DCM (regardless of the number of lesion segments and the proposed surgical methods), the duration of symptoms was an independent risk factor for the post-operative efficacy. When the duration of symptoms was ≥6.5 months, the prognosis of patients was more likely to be poor, and the probability of a poor prognosis increased by 0.196 times for each additional month of symptom duration (p < 0.001, OR = 1.196). Full article
(This article belongs to the Special Issue Cervical Myelopathy: Current Hurdles and Future Perspectives)
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Review

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10 pages, 1188 KiB  
Review
Transnasal Endoscopic Approach for Osteoid Osteoma of the Odontoid Process in a Child: Technical Note and Systematic Review of the Literature
by Giuseppe Roberto Giammalva, Letizia Dell’Aglio, Brando Guarrera, Valentina Baro, Leonardo Calvanese, Gloria Schiavo, Giulia Mantovani, Valentina Rinaldi, Domenico Gerardo Iacopino, Francesco Causin, Piero Nicolai, Marco Ferrari and Luca Denaro
Brain Sci. 2022, 12(7), 916; https://doi.org/10.3390/brainsci12070916 - 13 Jul 2022
Cited by 2 | Viewed by 1732
Abstract
Osteoid osteoma (OO) is a primary benign tumor that accounts for up to 3% of all bone tumors. The cervical spine is less affected by OOs, and very few cases of C2 OOs have been reported in the literature, both in adults and [...] Read more.
Osteoid osteoma (OO) is a primary benign tumor that accounts for up to 3% of all bone tumors. The cervical spine is less affected by OOs, and very few cases of C2 OOs have been reported in the literature, both in adults and children. Surgery may be required in case of functional torticollis, stiffness, and reduced range of motion (ROM) due to cervical OOs refractory to medical therapy. Several posterior and anterior surgical techniques have been described to remove C2 OOs. In particular, anterior approaches to the cervical spine represent the most used surgical route for treating C2 OOs. We describe the first case of OO of the odontoid process removed through a transnasal endoscopic approach with the aid of neuronavigation in a 6-year-old child. No intraoperative complications occurred, and the post-operative course was uneventful. The patient had immediate relief of neck pain and remained pain-free throughout the follow-up period, with complete functional recovery of the neck range of motion (ROM). In this case, based on the favorable anatomy, the transnasal endoscopic approach represented a valuable strategy for the complete removal of an anterior C2 OO without the need for further vertebral fixation since the preservation of ligaments and paravertebral soft tissue. Full article
(This article belongs to the Special Issue Cervical Myelopathy: Current Hurdles and Future Perspectives)
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Other

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12 pages, 465 KiB  
Systematic Review
Correlation between “Snake-Eyes” Sign and Role of Surgery with a Focus on Postoperative Outcome: A Systematic Review
by Gianluca Scalia, Roberta Costanzo, Lara Brunasso, Giada Garufi, Lapo Bonosi, Giuseppe Ricciardo, Francesca Graziano, Giovanni Federico Nicoletti, Salvatore Massimiliano Cardali, Domenico Gerardo Iacopino, Rosario Maugeri and Giuseppe Emmanuele Umana
Brain Sci. 2023, 13(2), 301; https://doi.org/10.3390/brainsci13020301 - 10 Feb 2023
Cited by 1 | Viewed by 1045
Abstract
(1) Background: The “snake-eyes” sign represents a unique finding characterized by bilateral hyperintense symmetric, circular, or ovoid foci on T2-weighted MRI sequences in the anterior horn cells of the spinal cord. There are conflicting opinions as some authors affirm that it does not [...] Read more.
(1) Background: The “snake-eyes” sign represents a unique finding characterized by bilateral hyperintense symmetric, circular, or ovoid foci on T2-weighted MRI sequences in the anterior horn cells of the spinal cord. There are conflicting opinions as some authors affirm that it does not affect the prognosis of cervical myelopathy while other papers emphasize the opposite, stating how the “snake-eyes” sign constitutes an irreversible lesion and a predictor of poor prognosis. This systematic review evaluates the correlation between the “snake-eyes” sign and the prognosis of cervical myelopathy after surgery including anterior and/or posterior approaches; (2) Methods: A systematic literature review was conducted following the PRISMA statement and a total of seven papers were included; (3) Results: A total of 419 patients were evaluated, with a mean age of 55.72 ± 14.38 years. After surgery, 26.01% of patients experienced a significant clinical improvement, while in 61.81%, there was no significant improvement. In particular, 144 of 196 patients (73.5%) treated through an anterior approach and 114 of 223 (51.1%) that underwent a posterior approach, did not present a significant improvement. Furthermore, in 12.17% of patients, the postoperative outcome was not reported, leading to a high risk of bias in the assessment of the prognostic significance of the “snake-eyes” appearance; (4) Conclusions: The “snake-eyes” sign is usually considered as an unfavorable predictive marker for myelopathic surgical patients, but the pathophysiology is still unclear, and the results have not yet reached unified levels of evidence. Full article
(This article belongs to the Special Issue Cervical Myelopathy: Current Hurdles and Future Perspectives)
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19 pages, 1266 KiB  
Systematic Review
Burden of Surgical Treatment for the Management of Cervical Myelopathy in Mucopolysaccharidoses: A Systematic Review
by Roberta Costanzo, Lapo Bonosi, Massimiliano Porzio, Federica Paolini, Lara Brunasso, Andrea Evier Giovannini, Manikon Poullay Silven, Giuseppe Roberto Giammalva, Giuseppe Emmanuele Umana, Gianluca Scalia, Domenico Gerardo Iacopino and Rosario Maugeri
Brain Sci. 2023, 13(1), 48; https://doi.org/10.3390/brainsci13010048 - 26 Dec 2022
Cited by 1 | Viewed by 1641
Abstract
Mucopolysaccharidoses (MPSs) are a rare group of heterogeneous genetic and metabolic disorders, caused by loss of functions of several enzymes that are involved in glycosaminoglycan catabolism. Their progressive accumulations in cells, tissues, and consequently, organs lead to several clinical manifestations, such as musculoskeletal [...] Read more.
Mucopolysaccharidoses (MPSs) are a rare group of heterogeneous genetic and metabolic disorders, caused by loss of functions of several enzymes that are involved in glycosaminoglycan catabolism. Their progressive accumulations in cells, tissues, and consequently, organs lead to several clinical manifestations, such as musculoskeletal involvement. Indeed, the most common manifestation in the central nervous system is represented by cervical spinal stenosis due to bony alterations or dural thickening. Cervical involvement can commonly cause myelopathy and instability exerting severe symptoms. A prompt diagnosis and treatment of the aforementioned conditions is mandatory to ensure a better quality of life in patients with such debilitating disorders. Nevertheless, a clear consensus about their management (i.e., surgical or not) is still lacking, leading to an inevitable delay. This review aims to investigate and discuss the main causes of myelopathy in patients with mucopolysaccharidoses, available therapeutic strategies, and the impact and role of surgery on the neurological outcome. Full article
(This article belongs to the Special Issue Cervical Myelopathy: Current Hurdles and Future Perspectives)
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