Wnt antagonist FRZB is a muscle biomarker of denervation atrophy in amyotrophic lateral sclerosis

Skeletal muscle and the neuromuscular junction are the earliest sites to manifest pathological changes in amyotrophic lateral sclerosis (ALS). Based on prior studies, we have identified a molecular signature in muscle that develops early in ALS and parallels disease progression. This signature represents an intersection of signaling pathways including Smads, TGF-β, and vitamin D. Here, we show that the Wnt antagonist, Frizzled Related Protein (FRZB), was increased in ALS muscle samples and to a variable extent other denervating disease but only minimally in acquired myopathies. In the SOD1G93A mouse, FRZB was upregulated in the early stages of disease (between 40 and 60 days) until end-stage. By immunohistochemistry, FRZB was predominantly localized to endomysial connective tissue and to a lesser extent muscle membrane. There was a significant increase in immunoreactivity surrounding atrophied myofibers. Because FRZB is a Wnt antagonist, we assessed β-catenin, the canonical transducer of Wnt signaling, and found increased levels mainly at the muscle membrane. In summary, we show that FRZB is part of a molecular signature of muscle denervation that may reflect disease progression in ALS. Our findings open up avenues for future investigation as to what roles FRZB and Wnt signaling might be playing in muscle denervation/reinnervation.

MR arthrographic evaluation of posterior paraglenoid labral cysts: a retrospective study

Background Paraglenoid labral cysts (PLCs) around the shoulder are uncommon. Magnetic resonance imaging (MRI) is the primary imaging modality for the description of PLCs Purpose The purpose of this study was to evaluate PLCs in the posterior part of the glenoid bone via MR arthrography as well as to describe associated labral abnormalities. Material and Methods This retrospective study included 14 patients, diagnosed with 15 posterior PLCs at MR arthrography between 2007 and 2012. Conventional MRI and MR arthrography were used for all patients. Results A total of 15 PLCs were detected in 14 patients with eight located on the right shoulder and six on the left shoulder. One case had two PLCs. While two cysts were multiloculated, the remaining 13 were seen as unilocated simple cysts. Moreover, 14 of 15 posterior PLCs (60%) were associated with labral tears at MR arthrography. The cysts in proximity to the glenoid labrum were posterosuperior in 33.3% (n = 5), mid-posterior in 36.7% (n = 7), and postero-inferior in 20% (n = 3). The majority of patients with posterosuperior and mid-posterior cysts had an associated superior labral tear from anterior to posterior (SLAP) lesions. Four of six patients with mid-posterior cysts had minimal denervation atrophy in the infraspinatus muscle. Conclusion Posterior PLCs are mostly associated with posterior labral defects. The majority of cysts localized in the posterosuperior and mid-posterior were also associated with SLAP lesions. Denervation atrophy in the infraspinatus muscle may frequently accompany mid-posterior PLCs.

Third-Degree Hindpaw Burn Injury Induced Apoptosis of Lumbar Spinal Cord Ventral Horn Motor Neurons and Sciatic Nerve and Muscle Atrophy in Rats

Background. Severe burns result in hypercatabolic state and concomitant muscle atrophy that persists for several months, thereby limiting patient recovery. However, the effects of burns on the corresponding spinal dermatome remain unknown. This study aimed to investigate whether burns induce apoptosis of spinal cord ventral horn motor neurons (VHMNs) and consequently cause skeletal muscle wasting.Methods. Third-degree hindpaw burn injury with 1% total body surface area (TBSA) rats were euthanized 4 and 8 weeks after burn injury. The apoptosis profiles in the ventral horns of the lumbar spinal cords, sciatic nerves, and gastrocnemius muscles were examined. The Schwann cells in the sciatic nerve were marked with S100. The gastrocnemius muscles were harvested to measure the denervation atrophy.Result. The VHMNs apoptosis in the spinal cord was observed after inducing third-degree burns in the hindpaw. The S100 and TUNEL double-positive cells in the sciatic nerve increased significantly after the burn injury. Gastrocnemius muscle apoptosis and denervation atrophy area increased significantly after the burn injury.Conclusion. Local hindpaw burn induces apoptosis in VHMNs and Schwann cells in sciatic nerve, which causes corresponding gastrocnemius muscle denervation atrophy. Our results provided an animal model to evaluate burn-induced muscle wasting, and elucidate the underlying mechanisms.

Recurrent Gastric Dilatation and Intestinal Dysmotility Possibly Resulting from Autonomic Neuropathy in a Great Dane

A 5 yr old female spayed Great Dane was presented for recurrent episodes of gastric dilatation, intestinal dysmotility, and one episode of gastric rupture. Numerous hematologic, radiographic, and endocrine diagnostic tests were performed with no identifiable underlying cause. Many risk factors have been identified for gastric dilatation and most were present in this Great Dane. A number of symptomatic treatments, aimed primarily at altering the gastrointestinal tract flora and motility were tried, but failed to influence the clinical course of the disease. The dog continued to worsen, experienced more frequent episodes of gastric dilatation, and developed generalized muscle atrophy. Biopsies were collected from the biceps femoris and triceps brachii muscles. A pattern of denervation atrophy was evident in both muscles, consistent with polyneuropathy. The owners elected humane euthanasia and a necropsy was performed. A striking finding at necropsy was severe loss of myelinated fibers with extensive endoneurial fibrosis in the vagus nerve, consistent with an autonomic neuropathy. Autonomic neuropathy is a previously unexplored cause of gastric dilatation and intestinal dysmotility in dogs. These findings should open new directions for exploring pathogenic mechanisms for gastric dilatation in this species.