Chronic Spinal Compression Research Articles

Suppression of microglial Ccl2 reduces neuropathic pain associated with chronic spinal compression.

Chronic spinal compression is a common complication of spinal cord injury (SCI), which can lead to spinal stenosis or herniated discs. The ensuing neuropathic pain is often associated with the activation of microglia. In this investigation, our objective was to explore whether modifying the levels of chemokine (C-C motif) ligand 2 (Ccl2) in microglia could alleviate neuropathic pain resulting from chronic spinal compression. We used a public database to look for major altered gene associated in a SCI model established in rats. We then employed adeno-associated virus (AAV) vectors, expressing siRNA for the identified significantly altered gene under a microglia-specific TMEM119 promoter. We also tested the impact of this treatment in microglia in vivo on the severity of chronic spinal compression and associated pain using a ttw mouse model for progressive spinal compression. We identified chemokine (C-C motif) ligand 2 (Ccl2) as the primary gene altered in microglia within a rat SCI model, utilizing a public database. Microglial Ccl2 levels were then found to be significantly elevated in disc specimens from SCI patients diagnosed with chronic spinal compression and strongly correlated with the Thompson classification of the degeneration level and pain score. Depletion of Ccl2 in microglia-specific TMEM119 promoter were developed to transfect mouse microglia in vitro, resulting in a proinflammatory to anti-inflammatory phenotypic adaption. In vivo depletion of Ccl2 in microglia mitigated the severity of chronic spinal compression and related pain in ttw mice, likely due to significant changes in pain-associated cytokines and factors. Disc microglia expressing high levels of Ccl2 may contribute to chronic spinal compression and SCI-associated pain. Therapeutically targeting Ccl2 in microglia could offer a potential avenue for treating chronic spinal compression and SCI-associated pain.

Early decompression promotes motor recovery after cervical spinal cord injury in rats with chronic cervical spinal cord compression

The number of elderly patients with spinal cord injury without radiographic abnormalities (SCIWORA) has been increasing in recent years and common of most cervical spinal cord injuries. Basic research has shown the effectiveness of early decompression after spinal cord injury on the spinal cord without stenosis; no studies have reported the efficacy of decompression in models with spinal cord compressive lesions. The purpose of this study was to evaluate the effects of decompression surgery after acute spinal cord injury in rats with chronic spinal cord compressive lesions, mimicking SCIWORA. A water-absorbent polymer sheet (Aquaprene DX, Sanyo Chemical Industries) was inserted dorsally into the 4–5th cervical sublaminar space in 8-week-old Sprague Dawley rats to create a rat model with a chronic spinal compressive lesion. At the age of 16 weeks, 30 mildly myelopathic or asymptomatic rats with a Basso, Beattie, and Bresnahan score (BBB score) of 19 or higher were subjected to spinal cord compression injuries. The rats were divided into three groups: an immediate decompression group (decompress immediately after injury), a sub-acute decompression group (decompress 1 week after injury), and a non-decompression group. Behavioral and histological evaluations were performed 4 weeks after the injury. At 20 weeks of age, the BBB score and FLS (Forelimb Locomotor Scale) of both the immediate and the sub-acute decompression groups were significantly higher than those of the non-decompression group. There was no significant difference between the immediate decompression group and the sub-acute decompression group. TUNEL (transferase-mediated dUTP nick end labeling) staining showed significantly fewer positive cells in both decompression groups compared to the non-decompression group. LFB (Luxol fast blue) staining showed significantly more demyelination, and GAP-43 (growth associated protein-43) staining tended to show fewer positive cells in the non-decompression group. Decompression surgery in the acute or sub-acute phase of injury is effective after mild spinal cord injury in rats with chronic compressive lesions. There was no significant difference between the immediate decompression and sub-acute decompression groups.

A sheep model of chronic cervical compressive myelopathy via an implantable wireless compression device

PurposeThis study aimed to establish an animal model in which we can precisely displace the spinal cord and therefore mimic the chronic spinal compression of cervical spondylotic myelopathy.MethodsIn vivo intervertebral compression devices (IVCDs) connected with subcutaneous control modules (SCCMs) were implanted into the C2-3 intervertebral disk spaces of sheep and connected by Bluetooth to an in vitro control system. Sixteen sheep were divided into four groups: (Group A) control; (Group B) 10-week progressive compression, then held; (Group C) 20-week progressive compression, then held; and (Group D) 20-week progressive compression, then decompression. Electrophysiological analysis (latency and amplitude of the N1-P1-N2 wave in somatosensory evoked potentials, SEP), behavioral changes (Tarlov score), imaging test (encroachment ratio (ER) of intraspinal invasion determined by X-ray and CT scan), and histological examinations (hematoxylin and eosin, Nissl, and TUNEL staining) were performed to assess the efficacy of our model.ResultsTarlov scores gradually decreased as compression increased with time and partially recovered after decompression. The Pearson correlation coefficient between ER and time was r = 0.993 (p < 0.001) in Group B at 10 weeks and Groups C and D at 20 weeks. And ER was negatively correlated with the Tarlov score (r = -0.878, p < 0.001). As compression progressed, the SEP latency was significantly extended (p < 0.001), and the amplitude significantly decreased (p < 0.001), while they were both partially restored after decompression. The number of abnormal motor neurons and TUNEL-positive cells increased significantly (p < 0.001) with compression.ConclusionOur implantable and wireless intervertebral compression model demonstrated outstanding controllability and reproducibility in simulating chronic cervical spinal cord compression in animals.

Spinal cord infarction at the level of ossification of the posterior longitudinal ligament.

We report a case of acute tetraplegia, without any trauma or symptoms prior to onset, who presented with ossification of the posterior longitudinal ligament (OPLL) in the cervical spine with concomitant spinal cord infarction. A 64-year-old man with a number of risk factors for vascular disease was admitted to our hospital with progressive motor weakness in the bilateral upper and lower extremities. He had initially felt numbness in his left upper extremity and had no previous neurological symptoms or trauma. The night after the initial symptoms, he developed spastic tetraplegia requiring respiratory support. Computed tomography images of the cervical spine demonstrated the segmental type of OPLL. Spinal cord compression and signal intensity changes were identified at the level of C3/4 on magnetic resonance imaging (MRI). He underwent emergency surgery consisting of posterior decompression with laminoplasty of C3-6. Despite the surgery, the patient's tetraplegia did not improve and he continued to require respirator support. There was still no improvement in his neurological status at 10 days postoperatively, and MRI demonstrated evidence of marked spinal cord infarction. Mechanical compression of spinal arteries by OPLL and pre-existing vascular compromise had a role in the pathogenesis of spinal cord infarction. Chronic spinal compression may be characterized by 3 important factors, namely an uncommonly devastating clinical course, vascular risk factors and persistent findings on MRI, and these might lead to early diagnosis of spinal cord infarction.

Aspects neurologiques des mucopolysaccharidoses

Mucopolysaccharidoses (MPS) are progressive multisystem lysosomal storage diseases caused by defective catabolism of complex molecules, namely the glycosaminoglycans and their consequent accumulation in tissues. Of the 7 clinical types representing 11 different enzyme deficiencies, only MPS III (Sanfilippo syndromes A, B, C and D) and severe forms of MPS I (Hurler's syndrome), MPS II (severe Hunter syndrome) and MPS VII (severe Sly syndrome) give rise to progressive cerebral disease. Neurosensory complications (hearing impairment, retinopathy and optic atrophy) can also occur in some types. Carpal (or even tarsal) tunnel syndrome is a common complication of the MPS, except for MPS III and MPS IV. Hydrocephalus due to abnormal circulation or resorption of cerebrospinal fluid, chronic spinal compression may occur as complications of MPS I, II and VII and also in MPS IV and VI. Atlanto-axial instability may be observed in type IV and I.

Chronic Spinal Compression Model in Minipigs: A Systematic Behavioral, Qualitative, and Quantitative Neuropathological Study

The goal of the present study was to develop a porcine spinal cord injury (SCI) model, and to describe the neurological outcome and characterize the corresponding quantitative and qualitative histological changes at 4-9 months after injury. Adult Gottingen-Minnesota minipigs were anesthetized and placed in a spine immobilization frame. The exposed T12 spinal segment was compressed in a dorso-ventral direction using a 5-mm-diameter circular bar with a progressively increasing peak force (1.5, 2.0, or 2.5 kg) at a velocity of 3 cm/sec. During recovery, motor and sensory function were periodically monitored. After survival, the animals were perfusion fixed and the extent of local SCI was analyzed by (1) post-mortem MRI analysis of dissected spinal cords, (2) qualitative and quantitative analysis of axonal survival at the epicenter of injury, and (3) defining the presence of local inflammatory changes, astrocytosis, and schwannosis. Following 2.5-kg spinal cord compression the animals demonstrated a near complete loss of motor and sensory function with no recovery over the next 4-9 months. Those that underwent spinal cord compression with 2 kg force developed an incomplete injury with progressive partial neurological recovery characterized by a restricted ability to stand and walk. Animals injured with a spinal compression force of 1.5 kg showed near normal ambulation 10 days after injury. In fully paralyzed animals (2.5 kg), MRI analysis demonstrated a loss of spinal white matter integrity and extensive septal cavitations. A significant correlation between the magnitude of loss of small and medium-sized myelinated axons in the ventral funiculus and neurological deficits was identified. These data, demonstrating stable neurological deficits in severely injured animals, similarities of spinal pathology to humans, and relatively good post-injury tolerance of this strain of minipigs to spinal trauma, suggest that this model can successfully be used to study therapeutic interventions targeting both acute and chronic stages of SCI.

Expression of Apoptosis Signal-Regulating Kinase 1 in Mouse Spinal Cord Under Chronic Mechanical Compression

To examine apoptosis signal cascade in neurons and oligodendrocytes under the chronic spinal cord compression of tiptoe-walking Yoshimura (TWY) mouse, which is model of progressive cervical cord compression. To clarify the biologic mechanisms of apoptosis, which may produce destructive changes in the spinal cord under chronic mechanical compression, with a resulting irreversible neurologic deficit. The stress-activated mitogen-activated protein kinase pathways including ASK1 transmitted apoptosis signals after acute spinal cord injury. Apoptosis in acute spinal cord injury induced both secondary degeneration around the site of injury and chronic demyelination. Chronic spinal cord compression showed myelin destruction, loss of axons, and oligodendrocytes in white matter, and loss of neurons in gray matter. Apoptosis associated with chronic spinal cord compression contributes to these changes. However, the biologic mechanisms of apoptosis in the spinal cord under chronic mechanical compression remain unclear. We examined the expression of phosphorylated-apoptosis signal-regulating kinase 1 (ASK1), phosphorylated-c-Jun N-terminal kinase (JNK), phosphorylated-p38 mitogen-activated protein kinase (p38), and activated caspase-3 immunohistologically in TWY mice, an animal model of progressive cervical spinal cord compression, since the ASK1-JNK and -p38 signaling cascades participate in the signaling pathway leading to apoptosis in neural tissue and neuronal culture. Double immunohistochemistry for phosphorylated-ASK1, phosphorylated-JNK, phosphorylated-p38, activated-caspase3, and cell-specific markers confirmed the presence of apoptosis signals in both neurons and oligodendrocytes in compressed spinal cord cells. We found that mitogen-activated protein kinase pathways including ASK1, JNK, and p38 were activated in destructive spinal cord under chronic compression.

Extended extradural spinal arachnoid cyst: an unusual cause of progressive spastic paraparesis

A 15-year old girl presented with a slowly progressive spastic paraparesis since the age of 12. Creatine kinase was slighty increased. Muscle biopsy carried out during tendon surgery for severe toe-walking showed ‘myopathic’ changes. Subsequent neurological evaluation and radiological studies revealed a large extradural arachnoid cyst extending from the 11th thoracic vertebra to the first lumbar vertebra. Her condition improved after operation. The ‘myopathic’ features turned out to be the result of chronic spinal compression. MRI is the method of choice to examine patients with non-hereditary progressive spastic paraparesis. Muscle biopsy and tendon surgery should not be performed, without careful neurological examination.

Reducing the biomechanical stress of lifting by training

The effectiveness of two methods of training in reducing biomechanical stress during lifting was examined in a sample of 12 men aged 18–40 years. Subjects carried out three 40 min sessions, one session per day, of a simple symmetrical lifting task. No training was given before the first session, which acted as the control condition. before each of the next two sessions training was given in the form of either written guidelines or interactive personal tuition in a crossover design. Interaction of order with method was expected and was of interest. The effectiveness of each training method in relieving the stress of lifting was measured in four ways: by ratings of perceived exertion on the Borg scale; by video analysis of adherence to guideline kinematics; by chronic spinal compression measured by precision stadiometry; and by the relative compression force at L5/S1 calculated using Chaffin's model. Although the differences in the results of the four assessment methods make reservations necessary it is suggested that while brief personal tuition may demonstrably reduce lifting stress even in a simple lifting task, written guidelines for the untrained may be counterproductive and may interfere with habitual skills. It is recommended that the efficiency of lifting training methods be estimated objectively, such as by the methods employed here, before being adopted.

Clinical signs and evoked response alterations associated with chronic experimental cord compression

Cortical and spinal evoked potentials were used to monitor the effect of experimental chronic cord compression in cats. An implantable compression screw made it possible to maintain the animals unrestrained. The mean compression period was 10 weeks (maximum 16.5 weeks). Compression was increased by stepwise tightening of the screw at intervals of 4 to 7 days under ketamine anesthesia. Evoked potentials were monitored before and after each compression step with repeated recordings, and were analyzed in terms of alterations in amplitude, latency, and waveform. Amplitude response curves were plotted where the amount of compression at each recording was expressed as a percentage of total compression. Changes in spinal evoked potentials occurred rather early (mean 36% of total compression), while obvious cortical evoked potential changes appeared rather late (mean 91% of total compression). Neurological alterations appeared later than alterations in spinal evoked response but prior to alterations in cortical evoked response. Thus, alterations in cortical somatosensory evoked potentials in the presence of chronic spinal compression indicate a severe degree of compression and do not seem to be of diagnostic value in the early detection of chronic spinal cord compression. It is suggested that the monitoring of spinal rather than cortical evoked responses would be more useful in locating and detecting chronic compression spinal cord damage.

A model for chronic spinal cord compression in cats.

An experimental technique of chronic spinal compression combined with chronic implantation of cortical and spinal electrodes for the measurement of evoked potentials in cats is presented. This technique has the advantages of 1) requiring only a relatively simple dorsal access, 2) being applicable to the entire spinal cord, 3) permitting simple external control of compression speed and duration, and 4) allowing unhindered observation of motor behaviour in the unrestricted animal.