Treatment with human immunoglobulin G improves the early disease course in a mouse model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a severe hereditary myopathy. Standard treatment by glucocorticosteroids is limited because of numerous side effects. The aim of this study was to test immunomodulation by human immunoglobulin G (IgG) as treatment in the experimental mouse model (mdx) of DMD. 2 g/kg human IgG compared to human albumin was injected intraperitoneally in mdx mice at the age of 3 and 7 weeks. Advanced voluntary wheel running parameters were recorded continuously. At the age of 11 weeks, animals were killed so that blood, diaphragm, and lower limb muscles could be removed for quantitative PCR, histological analysis and ex vivo muscle contraction tests. IgG compared to albumin significantly improved the voluntary running performance and reduced muscle fatigability in an ex vivo muscle contraction test. Upon IgG treatment, serum creatine kinase values were diminished and mRNA expression levels of relevant inflammatory markers were reduced in the diaphragm and limb muscles. Macrophage infiltration and myopathic damage were significantly ameliorated in the quadriceps muscle. Collectively, this study demonstrates that, in the early disease course of mdx mice, human IgG improves the running performance and diminishes myopathic damage and inflammation in the muscle. Therefore, IgG may be a promising approach for treatment of DMD. Two monthly intraperitoneal injections of human immunoglobulin G (IgG) improved the early 11-week disease phase of mdx mice. Voluntary running was improved and serum levels of creatine kinase were diminished. In the skeletal muscle, myopathic damage was ameliorated and key inflammatory markers such as mRNA expression of SPP1 and infiltration by macrophages were reduced. The study suggests that IgG could be explored as a potential treatment option for Duchenne muscular dystrophy and that pre-clinical long-term studies should be helpful.

Motor performance of young dystrophic mdx mice treated with long-circulating prednisolone liposomes.

For Duchenne muscular dystrophy (DMD), a common myopathy that leads to severe disability, no causal therapy is available. Glucocorticosteroids improve patients' muscle strength, but their long-term use is limited by negative side effects. Thus, pharmacological modifications of glucocorticosteroids are required to increase the efficacy by drug targeting. Liposomal encapsulation augments systemic half-life and local tissue concentrations of glucocorticosteroids and, at the same time, reduces systemic side effects. In this study, the efficacy of novel, long-circulating, polyethylene-glycol-coated liposomes encapsulating prednisolone was compared with free prednisolone in the treatment of mdx mice, a well-established animal model for DMD. Using an objective and sensitive computerized 24-hr detection system of voluntary wheel-running in single cages, we demonstrate a significant impairment of the running performance in mdx compared with black/10 control mice aged 3-6 weeks. Treatment with liposomal or free prednisolone did not improve running performance compared with saline control or empty liposomes. Histopathological parameters, including the rate of internalized nuclei and fiber size variation, and mRNA and protein expression levels of transforming growth factor (TGF)-ß and monocytes chemotactic protein (MCP)-1 also remained unchanged. Bioactivity in skeletal muscle of liposomal and free prednisolone was demonstrated by elevated mRNA expression of muscle ring finger protein 1 (MuRF1), a mediator of muscle atrophy, and its forkhead box transcription factors (Foxo1/3). Our data support the assessment of voluntary running to be a robust and reproducible outcome measure of skeletal muscle performance during the early disease course of mdx mice and suggest that liposomal encapsulation is not superior in treatment efficacy compared with conventional prednisolone. Our study helps to improve the future design of experimental treatment in animal models of neuromuscular diseases.

Endoscopic transsphenoidal, transclival resection of an enterogenous cyst located ventral to the brainstem: case report.

BACKGROUND AND IMPORTANCE: Enterogenous cysts are rare tumors found most commonly in the spine, but they have also been reported intracranially. Cases of enterogenous cysts located within the posterior fossa have traditionally been resected via difficult craniotomies that require prolonged retraction and risk injury to cranial nerves. We describe a method for resection of an enterogenous cyst located anterior to the brainstem via the endoscopic transsphenoidal approach. CLINICAL PRESENTATION: A 37-year-old man was found to have a 2-cm mass anterior to the brainstem during routine screening after a trauma. The mass was located within the prepontine cistern, enhanced with gadolinium contrast, and showed no restrictive diffusion. This lesion was most consistent with an enterogenous cyst. A minimally invasive endoscopic endonasal transsphenoidal transclival approach was performed for gross total resection of the tumor. CONCLUSION: We discuss the endoscopic transsphenoidal approach used for the resection of an enterogenous cyst in the posterior fossa anterior to the brainstem. The transsphenoidal approach provides direct access to lesions in this location using a minimally invasive technique while avoiding excessive brain retraction or injury to cranial nerves. In addition, we provide an updated review of the literature for enterogenous cysts located within the posterior fossa.

Reoperative myectomy via the left ventricular apex in a patient with hypertrophic obstructive cardiomyopathy.

Transaortic myectomy is the standard treatment for symptomatic patients with hypertrophic obstructive cardiomyopathy that proves to be refractive to medical therapy. We encountered a case that required a modified surgical approach to relieve a left ventricular outflow tract obstruction that could not be adequately resected through the aortic annulus because of poor exposure of the ventricular septum. Persistent high gradients after the 1st operation necessitated a 2nd operation. We used a novel approach via the left ventricular apex that enabled us to resect a large amount of obstructive tissue under direct vision and thereby to relieve the left ventricular outflow tract obstruction.