Evidence of impaired macroautophagy in human degenerative cervical myelopathy.

Degenerative cervical myelopathy (DCM) is a common progressive disease of the spinal cord which can cause tetraplegia. Despite its prevalence, few studies have investigated the pathophysiology of DCM. Macroautophagy is a cellular process which degrades intracellular contents and its disruption is thought to contribute to many neurodegenerative diseases. The present study tests the hypothesis that macroautophagy is impaired in DCM. To address this, we utilised a collection of post-mortem cervical spinal cord samples and investigated seven DCM cases and five human controls. Immunohistochemical staining was used to visualise proteins involved in autophagy. This demonstrated significantly reduced numbers of LC3 puncta in cases versus controls (p = 0.0424). Consistent with reduced autophagy, we identified large aggregates of p62 in four of seven cases and no controls. Tau was increased in two of five cases compared to controls. BCL-2 was significantly increased in cases versus controls (p = 0.0133) and may explain this reduction in autophagy. Increased BCL-2 (p = 0.0369) and p62 bodies (p = 0.055) were seen in more severe cases of DCM. This is the first evidence that autophagy is impaired in DCM; the impairment appears greater in more severe cases. Further research is necessary to investigate whether macroautophagy has potential as a therapeutic target in DCM.

The Prevalence of Asymptomatic and Symptomatic Spinal Cord Compression on Magnetic Resonance Imaging: A Systematic Review and Meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: Cervical spinal cord compression (SCC) due to degenerative changes of the spine is a frequent finding on magnetic resonance imaging (MRI). While most people remain asymptomatic, a proportion develop symptoms of degenerative cervical myelopathy (DCM). DCM is an often-progressive neurological disease that can cause quadriplegia. The epidemiology of SCC and DCM is poorly understood. We sought to estimate the prevalence of degenerative cervical SCC and DCM from cross-sectional cohorts undergoing MRI. METHODS: We conducted a systematic review and meta-analysis of MRI reports on human subjects older than 16 years with degenerative SCC. A predetermined search strategy was used to identify relevant literature on MEDLINE. Title and abstract screenings were followed by full text screening. Data was extracted and analyzed by fixed or random-effects models. RESULTS: The present search returned 1506 publications. Following our exclusion criteria, 19 studies were included. Subgroup analysis of 3786 individuals estimated the prevalence of asymptomatic SCC in a healthy population as 24.2% with a significantly higher prevalence of SCC in older populations compared with younger populations and American/European populations compared with Asian populations. Subgroup analysis of 1202 individuals estimated the prevalence of DCM in a healthy population as 2.3%. CONCLUSIONS: We present the first estimates of the prevalence of asymptomatic SCC and DCM. Studies investigating the epidemiology of SCC are heterogeneous in methodology and results. These data indicate the need for more studies into the epidemiology of SCC and DCM performed with consistent methodologies.