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Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy.

ABSTRACT: Cervical spondylotic myelopathy (CSM) is the most common spinal cord disorder and a major cause of disability in adults. Improvements following surgical decompression are limited and patients often remain severely disabled. Post mortem studies indicate that CSM is associated with profound axonal loss. However, our understanding of the pathophysiology of CSM remains limited.To investigate the hypothesis that axonal plasticity plays a role in the recovery following surgical decompression, we adopted a novel preclinical model of mild to moderate CSM. Spinal cord compression resulted in significant locomotor deterioration, increased expression of the axonal injury marker APP, and loss of serotonergic fibres. Surgical decompression partially reversed the deficits and attenuated APP expression. Decompression was also associated with axonal sprouting, reflected in the restoration of serotonergic fibres and an increase of GAP43 expression. The re-expression of synaptophysin indicated the restoration of functional synapses following decompression. Promoting axonal plasticity may therefore be a therapeutic strategy for promoting neurological recovery in CSM.

SUBMITTER: Dhillon RS

PROVIDER: S-EPMC4994254 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy.

Dhillon Rana S RS Parker John J Syed Yasir A YA Edgley Steve S Young Adam A Fawcett James W JW Jeffery Nick D ND Franklin Robin J M RJ Kotter Mark R N MR

Acta neuropathologica communications 20160823 1

Cervical spondylotic myelopathy (CSM) is the most common spinal cord disorder and a major cause of disability in adults. Improvements following surgical decompression are limited and patients often remain severely disabled. Post mortem studies indicate that CSM is associated with profound axonal loss. However, our understanding of the pathophysiology of CSM remains limited.To investigate the hypothesis that axonal plasticity plays a role in the recovery following surgical decompression, we adopt ...[more]

PMID: 27552807

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Project description:The primary treatment of choice for patients with cervical spondylotic myelopathy (CSM) is surgical decompression. The benefit of operative intervention has been well established but, the surgeons' decision of operative approach remains nuanced based on patient-specific variables and surgeon preference. Decompression can involve a cervical corpectomy or a discectomy. A hybrid construct is when both a cervical corpectomy and a discectomy are done in the same patient. The purpose of this study was to review the evidence on the clinical and biomechanical outcomes of hybrid decompression and reconstruction techniques in patients with multilevel CSM. A retrospective study was performed on consecutive patients who received hybrid anterior decompression and reconstruction at Rush University between 2013-2018. Preoperative clinical and radiographic variables were analyzed to characterize specific factors leading to the decision of the surgical approach. In addition, we performed a systematic review and meta-analysis to assess superiority in terms of operative time, blood loss, cervical lordosis, patient-reported outcomes (PRO), fusion rates, and complications. Hybrid surgery (HS) was utilized in cases where multilevel CSM was present in conjunction with stenosis posterior to the vertebral body or acute kyphotic deformity. Our meta-analysis highlighted comparable PRO, complications, and rate of success fusion between 3-level anterior cervical discectomy and fusion (ACDF) and hybrid technique. Furthermore, hybrid fusion led to increased postoperative cervical lordosis, higher fusion rate, lower total complication rate, lower implant failure/mesh subsidence rate, and lower blood loss than 2-level corpectomy. The cervical hybrid technique that combines cervical corpectomy and discectomy represents a balanced option with the benefits of two commonly utilized cervical spine procedures in patients with multilevel CSM. The literature on hybrid technique suggests in cases where multilevel ACDF is not feasible, combining discectomy and corpectomy is superior to two-level corpectomy with lower complication rates, improved clinical outcome, spinal alignment correction, and stronger biomechanical properties.

Project description:MethodsTwenty patients with CSM and 17 controls were recruited. Clinical scores of modified Japanese Orthopedic Association (mJOA) and Nurick were collected. MRI based compression grades such as cord distortion were assessed. Hand dysfunction was tested using a custom motorized apparatus. Subject's forearm was placed in a cast and positioned such that their metacarpophalangeal (MCP) joint was vertically aligned with the motor shaft. Surface electromyographic sensors were placed on flexor digitorum superficialis (FDS) and extensor digitorum communis muscles. Hyperreflexia was measured as the FDS muscle activation during reflex when the MCP joint was moved from flexion to extension at 300°/sec. Proprioception was quantified as the angle of detection in absence of visual or auditory cues (subjects were blindfolded and given noise-cancelling headphones). Strength was measured as the maximum isometric force at the MCP joint. 2-sample t-test (p<0.05) were performed to assess significant differences in reflexes, proprioception and strength among patients and controls (SPSS software version 24).ResultsPatients reported higher Nurick (1.90±1.0 vs 0±0, p<0.001) and lower mJOA scores (14.3±1.9 vs 18.0±0, p<0.001) as compared to controls. Similarly, patients with CSM had increased reflexes (peak FDS EMG) (0.073±0.096 vs. 0.014±0.010, p = 0.019). Patient proprioception was significantly worse; mean angle of detection was greater than twice as high in patients (9.6± 9.43°) compared to controls (4.0± 2.3°), p = 0.022. MRI based compression ratio (CR) was a significant predictor of hyperreflexia, CR<0.44 resulted in steep increase in reflex activity. Fifteen of the 20 patients who completed follow up testing at 6 months after surgery show substantial clinical improvement in reflexes and proprioceptive angle, while repeated testing in controls were unchanged.ConclusionIn conclusion, hyperreflexia and decline in proprioception are the main drivers of hand disability in patients with CSM. Of multiple scales, only a select few MRI scales (such as compression ratio) were predictive of increased reflexes. The study describes a pre-clinical testing apparatus to quantitatively and objectively assess primary presenting symptoms in CSM. This pilot apparatus has the potential to evaluate treatment efficacy through repeated testing. Objective testing of hand dysfunction can help inform the design of clinically feasible devices, guide MRI biomarker analysis, and improve our understanding of the progression of neurological injury in this patient population.

Dataset Information

Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy.

Publications

Axonal plasticity underpins the functional recovery following surgical decompression in a rat model of cervical spondylotic myelopathy.

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