Cilostazol, a selective Type III phosphodiesterase inhibitor: prevention of cervical myelopathy in a rat chronic compression model

2014 ◽  
Vol 20 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Shinji Yamamoto ◽  
Ryu Kurokawa ◽  
Phyo Kim
Keyword(s):  
Spinal Cord ◽  
Grip Strength ◽  
Motor Neurons ◽  
Cervical Myelopathy ◽  
Cervical Spondylotic Myelopathy ◽  
Phosphodiesterase Inhibitor ◽  
Cord Compression ◽  
Anterior Horn ◽  
Cervical Cord ◽  
Forced Running

Object Regional blood flow is decreased in experimental models of chronic spinal cord compression, and the alteration presumably contributes to the development of myelopathy. Cilostazol (Otsuka Pharmaceuticals Co.), a selective Type III phosphodiesterase inhibitor, has been shown to be neuroprotective in cerebral hypoperfusion animal models and clinically effective in preventing the recurrence of cerebral infarction. To investigate the neuroprotective effect of cilostazol on cervical spondylotic myelopathy, the preventive effect against progressive motor dysfunction and the loss of anterior horn motor neurons were assessed using a chronic cord compression model in rats. Methods To produce chronic cervical cord compression in male Wistar rats, thin polyurethane sheets (3 × 5 × 0.7 mm) that gradually expand over 48–72 hours by absorbing water were implanted under the C5–6 laminae. In sham operations, the sheets were momentarily placed and then immediately removed. This model has been shown to reproduce characteristic features of clinical cervical myelopathy, with progressive motor disturbances after a latency period and insidious neuronal loss preceding the onset of symptoms. In the treatment group, cilostazol (30 mg/kg/day) was orally administered to the rats once a day, starting the day after surgery and continuing through the entire observation period of 25 weeks. In the control group, vehicle solution was administered under the same protocol. Changes in motor function were monitored by measuring bilateral forepaw grip strength and the duration of forced running on a treadmill. Twenty-five weeks after surgery, cervical spinal cords were examined histopathologically. Results Cilostazol preserved both forepaw grip strength and forced running capability. The drug also preserved anterior horn motor neurons in the C5–6 spinal cord segment, which diminished in number in the untreated chronic compression group. The drug decreased the number of TUNEL-positive apoptotic cells. Conclusions These results indicate that cilostazol is neuroprotective in the chronically compressed cervical cord and is potentially useful in the treatment of cervical spondylotic myelopathy.

scholarly journals Human recombinant erythropoietin improves motor function in rats with spinal cord compression myelopathy

2019 ◽  
Author(s):  
Takahiro Tanaka ◽  
Hidetoshi Murata ◽  
Ryohei Miyazaki ◽  
Tetsuya Yoshizumi ◽  
Mitsuru Sato ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Motor Function ◽  
Motor Neurons ◽  
Spinal Cord Compression ◽  
Cord Compression ◽  
Anterior Horn ◽  
Cervical Cord ◽  
High Dose ◽  
Spinal Cord Tissue ◽  
Compression Myelopathy

AbstractOBJECTIVEErythropoietin (EPO) is a clinically available hematopoietic cytokine. The aim of this study was to evaluate the effect of EPO on a rat model of cervical cord compression myelopathy and to explore the possibility of its use as a pharmacological treatment.METHODSTo produce the chronic cervical cord compression model, thin polyurethane sheets were implanted under the C5-C6 laminae of rats and gradually expanded due to water absorption. In this model, motor functions significantly declined from 7 weeks after surgery. Based on the result, EPO administration was started 8 weeks after surgery. Motor function as seen with rotarod performance and grip strength was measured 16 weeks after surgery, and then motor neurons were stained with H-E and NeuN staining, and counted. Apoptotic cell death was assessed with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) staining. To assess transfer of EPO into spinal cord tissue, the EPO level in spinal cord tissue was measured with an enzyme-linked immunosorbent assay for each group after subcutaneous injection of EPO.RESULTSHigh-dose EPO (5000 IU/kg) administered from 8 weeks after surgery markedly restored and maintained motor function in the Compression groups (P < 0.01). EPO significantly prevented loss of motor neurons in the anterior horn (P < 0.05) and significantly decreased the number of TUNEL-positive apoptotic cells (P < 0.05). The EPO level in spinal cord tissue was significantly higher in the High-dose EPO group than other groups.CONCLUSIONSEPO improves motor function in rats with progressive chronic compression myelopathy. EPO protects anterior horn motor neurons and inhibits neuronal cell apoptosis in spinal cord compression. The neuroprotective effects can be produced through transfer of EPO into spinal cord tissue. These findings suggest that EPO has high potential as a treatment for developing compression myelopathy.

scholarly journals The Role of Dynamic Magnetic Resonance Imaging in Cervical Spondylotic Myelopathy

2017 ◽  
Vol 11 (6) ◽  
pp. 1008-1015 ◽  
Author(s):  
John Paul Kolcun ◽  
Lee Onn Chieng ◽  
Karthik Madhavan ◽  
Michael Y. Wang
Keyword(s):  
Spinal Cord ◽  
Cervical Spondylotic Myelopathy ◽  
English Language ◽  
Case Reports ◽  
Preoperative Evaluation ◽  
Case Series ◽  
Dynamic Mri ◽  
Cord Compression ◽  
Cervical Cord ◽  
Dynamic Changes

<p>Dynamic spinal cord compression has been investigated for several years, but until the advent of open MRI, the use of dynamic MRI (dMRI) did not gain popularity. Several publications have shown that cervical cord compression is both static and dynamic. On many occasions the evaluation of cervical spondylotic myelopathy (CSM) is straightforward, but patients are frequently encountered with a significantly worse clinical examination than would be suggested by radiological images. In this paper, we present an extensive review of the literature in order to describe the importance of dMRI in various settings and applications. A detailed literature review was performed in the Medline and Pubmed databases using the terms “cervical spondylotic myelopathy”, “dynamic MRI”, “kinetic MRI”, and “myelomalalcia” for the period of 1980-2016. The study was limited to English language, human subjects, case series, retrospective studies, prospective reports, and clinical trials. Reviews, case reports, cadaveric studies, editorials, and commentaries were excluded. The literature search yielded 180 papers, 19 of which met inclusion criteria. However, each paper had evaluated results and outcomes in different ways. It was not possible to compile them for meta-analysis or pooled data evaluation. Instead, we evaluated individual studies and present them for discussion. We describe a number of parameters evaluated in 2661 total patients, including dynamic changes to spinal cord and canal dimensions, transient compression of the cord with changes in position, and the effects of position on the intervertebral disc. dMRI is a useful tool for understanding the development of CSM. It has found several applications in the diagnosis and preoperative evaluation of many patients, as well as certain congenital dysplasias and Hirayama disease. It is useful in correlating symptoms with the dynamic changes only noted on dMRI, and has reduced the incidence of misdiagnosis of myelopathy.</p>

scholarly journals Clinical value of 2-deoxy-[18F]fluoro-d-glucose positron emission tomography in patients with cervical spondylotic myelopathy

2013 ◽  
Vol 35 (1) ◽  
pp. E2 ◽  
Author(s):  
Sven O. Eicker ◽  
Karl-Josef Langen ◽  
Norbert Galldiks ◽  
Gabriele Stoffels ◽  
Jörg Herdmann ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cervical Spondylotic Myelopathy ◽  
The Elderly ◽  
Cord Compression ◽  
Cervical Cord ◽  
Clinical Value ◽  
Metabolic Pattern ◽  
Positron Emission ◽  
Number Of Patients ◽  
Spinal Cord Disorders

Cervical spondylotic myelopathy (CSM) is one of the most common spinal cord disorders in the elderly. It is usually diagnosed by MRI, but in a significant number of patients the clinical course of CSM does not correlate with the extent of the spinal cord compression. Recent studies have suggested that a distinct metabolic pattern of the cervical cord, as assessed by PET with 2-deoxy-[18F]fluoro-d-glucose (18F-FDG) may predict a patient's clinical outcome after decompressive surgery for cervical spine stenosis. The authors provide an overview of the recent literature regarding the value of PET with 18F-FDG of the cervical cord in patients with CSM, paying attention to prognostic aspects and the potential role of inflammatory processes in the acute phase of the disease.

scholarly journals Tracking white and grey matter degeneration along the spinal cord axis in degenerative cervical myelopathy

2021 ◽  
Author(s):  
Kevin Vallotton ◽  
Gergely David ◽  
Markus Hupp ◽  
Nikolai Pfender ◽  
Julien Cohen-Adad ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cervical Myelopathy ◽  
Grey Matter ◽  
Cord Compression ◽  
Cervical Cord ◽  
Tissue Specific ◽  
Microstructural Changes ◽  
Diffusion Weighted ◽  
Degenerative Cervical Myelopathy ◽  
Lumbar Cord

AbstractObjectiveTo determine tissue-specific neurodegeneration across the spinal cord in patients with mild-moderate degenerative cervical myelopathy (DCM).MethodsTwenty-four mild-moderate DCM and 24 healthy subjects were recruited. In patients, a T2-weighted scan was acquired at the compression site, while in all participants a T2*-weighted and diffusion-weighted scan was acquired at the cervical level (C2-C3) and in the lumbar enlargement (i.e. rostral and caudal to the site of compression). We quantified intramedullary signal changes, maximal canal and cord compression, white (WM) and grey matter (GM) atrophy, and microstructural indices from diffusion-weighted scans. All patients underwent clinical (modified Japanese Orthopaedic Association (mJOA)) and electrophysiological assessments. Regression analysis assessed associations between MRI readouts and electrophysiological and clinical outcomes.ResultsTwenty patients were classified with mild and four with moderate DCM using the mJOA scale. The most frequent site of compression was at C5-C6 level with maximum cord compression of 4.68±0.83 mm. Ten patients showed imaging evidence of cervical myelopathy. In the cervical cord, WM and GM atrophy and WM microstructural changes were evident, while in the lumbar cord only WM showed atrophy and microstructural changes. Remote cervical cord WM microstructural changes were pronounced in patients with radiological myelopathy and associated with impaired electrophysiology. Lumbar cord WM atrophy was associated with lower limb sensory impairments.ConclusionTissue-specific neurodegeneration revealed by quantitative MRI, already apparent across the spinal cord in mild-moderate DCM prior to the onset of severe clinical impairments. WM microstructural changes are particularly sensitive to remote pathologically and clinically eloquent changes in DCM.

scholarly journals Functional outcome of posterior laminectomy in case of cervical myelopathy with multilevel cervical cord compression

2018 ◽  
Vol 4 (4) ◽  
pp. 510-514
Author(s):  
Dr. Siddharth D Parekh ◽  
Dr. Arvind B Goregaonkar ◽  
Dr. Anoop Dhamangaokar ◽  
Dr. Apratim R Deekshit ◽  
Dr. Umesh P Kanade
Keyword(s):  
Functional Outcome ◽  
Cervical Myelopathy ◽  
Cord Compression ◽  
Cervical Cord ◽  
Cervical Cord Compression ◽  
Posterior Laminectomy

scholarly journals Assessing structure and function of myelin in cervical spondylotic myelopathy

Neurology ◽  
2017 ◽  
Vol 89 (6) ◽  
pp. 602-610 ◽  
Author(s):  
Hanwen Liu ◽  
Erin L. MacMillian ◽  
Catherine R. Jutzeler ◽  
Emil Ljungberg ◽  
Alex L. MacKay ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Compression Ratio ◽  
Signal Intensity ◽  
Cervical Spondylotic Myelopathy ◽  
Cord Compression ◽  
Whole Body ◽  
Healthy Controls ◽  
Conventional Mri ◽  
Intensity Compression

Purpose:To assess the extent of demyelination in cervical spondylotic myelopathy (CSM) using myelin water imaging (MWI) and electrophysiologic techniques.Methods:Somatosensory evoked potentials (SSEPs) and MWI were acquired in 14 patients with CSM and 18 age-matched healthy controls. MWI was performed on a 3.0T whole body magnetic resonance scanner. Myelin water fraction (MWF) was extracted for the dorsal columns and whole cord. SSEPs and MWF were also compared with conventional MRI outcomes, including T2 signal intensity, compression ratio, maximum spinal cord compression (MSCC), and maximum canal compromise (MCC).Results:Group analysis showed marked differences in T2 signal intensity, compression ratio, MSCC, and MCC between healthy controls and patients with CSM. There were no group differences in MWF and SSEP latencies. However, patients with CSM with pathologic SSEPs exhibited reduction in MWF (p < 0.05). MWF was also correlated with SSEP latencies.Conclusion:Our findings provide evidence of decreased myelin content in the spinal cord associated with impaired spinal cord conduction in patients with CSM. While conventional MRI are of great value to define the extent of cord compression, they show a limited correlation with functional deficits (i.e., delayed SSEPs). MWI provides independent and complementary readouts to spinal cord compression, with a high specificity to detect impaired conduction.

#16: Enterovirus D68 Visualized in the Anterior Horn of the Spinal Cord of a Pediatric Patient with Flaccid Paralysis

2021 ◽  
Vol 10 (Supplement_2) ◽  
pp. S8-S8
Author(s):  
Matthew R Vogt ◽  
Peter F Wright ◽  
William F Hickey ◽  
Kelli L Boyd ◽  
James E Crowe
Keyword(s):  
Spinal Cord ◽  
T Cells ◽  
Antigen Presentation ◽  
Motor Neurons ◽  
Cd8 T Cells ◽  
Viral Protein ◽  
The United States ◽  
Anterior Horn ◽  
Viral Rna ◽  
Enterovirus D68

Abstract Background Acute flaccid myelitis (AFM) is a polio-like paralyzing illness of children. AFM incidence is increasing during every other year outbreaks that occur in the United States simultaneously with outbreaks of enterovirus D68 (EV-D68) infection. Demonstrating that EV-D68 directly causes AFM has been challenging due to rare detection of the virus in the cerebrospinal fluid (CSF) of patients despite frequent detection at nonsterile sites. Murine studies have shown that EV-D68 can infect spinal cord anterior horn motor neurons and cause paralysis, similar to poliovirus. However, a key outstanding question is whether EV-D68 causes AFM in humans by direct viral pathogenesis or by indirect host immunopathogenesis. Methods We investigated the pathogenesis of AFM using tissues from a previously reported case of a 5-year-old boy who presented in fall 2008 with four days of progressive limb and voice weakness followed by incontinence, apnea, and death. He had a CSF pleocytosis of 2094/µL with EV-D68 identified in the CSF by sequencing of the VP1 gene. We designed probes for in situ hybridization (ISH) based on this sequence to stain formalin fixed paraffin embedded tissues from his autopsy. For immunohistochemistry (IHC) we used both commercial polyclonal anti-EV-D68 antibodies and our own human monoclonal antibodies that stain virus infected cells in vitro. Immunophenotyping was done by IHC. To analyze gene transcription in the inflammatory transcriptome of these infected areas of spinal cord we used the GeoMx platform from Nanostring. Results We identified EV-D68 in the anterior horn of the patient’s spinal cord, corresponding to the location of motor neuron cell bodies. This area was highly inflamed, with an infiltrate of CD8 T cells and many macrophages. Viral RNA (see figure) and viral protein was visualized in motor neurons but not supporting cells using ISH and IHC, respectively. Viral RNA but not viral protein was detected rarely in the lungs in macrophages, which had extensive inflammatory infiltrate. The infiltrate was predominantly composed of macrophages with a CD8 T cell component as well. The transcriptome of cells in the inflamed tissue was enriched for genes involved in antigen presentation on MHC. Conclusions Deaths in AFM patients are rare and often distant from initial presentation, but this patient died four days after onset of weakness, allowing us to directly demonstrate that EV-D68 can infect the human spinal cord. Motor neurons but not neural support cells are directly infected by EV-D68 with a corresponding infiltrate of macrophages and CD8 T cells. Antigen presentation processes are upregulated in inflamed tissues. Therefore, both direct viral pathology and immune factors likely contribute to AFM disease in EV-D68 infection.

scholarly journals MR diffusion tensor imaging of the spinal cord: can it help in early detection of cervical spondylotic myelopathy and assessment of its severity?

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Talaat Ahmed Abd El Hameed Hassan ◽  
Ramy Edward Assad ◽  
Shaimaa Atef Belal
Keyword(s):  
Spinal Cord ◽  
Diffusion Tensor Imaging ◽  
Early Detection ◽  
Cervical Spondylotic Myelopathy ◽  
Diffusion Tensor ◽  
Cervical Spinal Cord ◽  
Cervical Cord ◽  
Mr Diffusion ◽  
Compressive Myelopathy ◽  
Mr Diffusion Tensor Imaging

Abstract Background The aim of this study is to evaluate the potential application of MR diffusion tensor imaging (with calculation of fractional anisotropy (FA) values) in assessment of the spondylotic cervical spinal canal compromise and comparison with the information issued from conventional MR sequences for early detection of cervical spondylotic myelopathy (CSM). Thirty patients (11 males and 19 females) were included in this study; age ranged from 22 to 70 years (mean age = 44). All patients had conventional and diffusion tensor imaging (DTI) examinations of the cervical spine for detection and assessment of degree of cervical cord myelopathy. FA values of the whole cord circumference and at 3, 6, 9, 12 o’clock positions of the normal cord (opposite to C2), opposite to the most affected disc, and below the level of the most affected disc were measured. Results High statistically significant P values were obtained when comparing the FA values of the normal cord with the cord opposite to the most affected disc, the normal cord with the cord below the affected disc and the cord at the level of the most affected disc with the cord below the level of the most affected disc. Conclusions DTI of the cervical spinal cord with FA measurement in patients with cervical spondylosis helps in early detection of cervical cord compressive myelopathy prior to appearance of changes in conventional MRI, which can improve the clinical outcome and help in treatment plans.

scholarly journals Cervical myelopathy due to neurovascular compression syndrome caused by persistent first intersegmental artery: a case report

BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Takuro Endo ◽  
Taku Sugawara ◽  
Naoki Higashiyama
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Cervical Myelopathy ◽  
Anatomical Variation ◽  
Cord Compression ◽  
Burning Sensation ◽  
Motor Dysfunction ◽  
Neurological Deficits ◽  
Left Shoulder ◽  
Neurovascular Compression

Abstract Background Persistent first intersegmental artery (PFIA) is a rare anatomical variation of vertebral arteries and is an asymptomatic finding in most cases. Here we report a rare case of cervical myelopathy caused by spinal cord compression by the PFIA. Case presentation The patient was a 52-year-old man who complained of numbness and burning sensation around the neck and left shoulder area, partial weakness in the left deltoid muscle, right side thermal hypoalgesia, and disturbance of deep sensation since the past 1 year, and the symptoms had gradually worsened. Magnetic resonance imaging (MRI) and computed tomography (CT) showed spinal cord compression by the left PFIA at the C1/C2 level. Because conservative treatment was ineffective, microvascular decompression (MVD) of the PFIA was performed. The left PFIA was laterally transposed using polytetrafluoroethylene (PTFE) bands and anchored to the dura mater using three PTFE bands. To achieve adequate transposition, the small blood vessels bridging the spinal cord and PFIA and the dorsal root nerve had to be sacrificed. Postoperative T2-weighted MRI showed a small hyperintense region in the lateral funiculus of the spinal cord, but no new neurological deficits were identified. In the early postoperative stage, the patient’s deep sensory impairment and motor dysfunction were improved. His numbness and burning sensation almost disappeared, but slight thermal hypoalgesia remained in the lower limb. Conclusion MVD is an effective treatment for spinal cord compression caused by the PFIA, but further studies are necessary to help address technical difficulties and avoid complications.

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