Osteoarthritis (OA) and rheumatoid arthritis (RA) are both debilitating diseases that cause significant morbidity in the US population. Extracellular vesicles (EVs), including exosomes and microvesicles, are now recognized to play important roles in cell-to-cell communication by transporting various proteins, microRNAs (miRNAs), and mRNAs. EV-derived proteins and miRNAs impact cell viability and cell differentiation, and are likely to play a prominent role in the pathophysiology of both OA and RA. Some of the processes by which these membrane-bound vesicles can alter joint tissue include extracellular matrix degradation, cell-to-cell communication, modulation of inflammation, angiogenesis, and antigen presentation. For example, EVs from IL-1β-stimulated fibroblast-like synoviocytes have been shown to induce osteoarthritic changes in chondrocytes. RA models have shown that EVs stimulated with inflammatory cytokines are capable of inducing apoptosis resistance in T cells, presenting antigen to T cells, and causing extracellular damage with matrix-degrading enzymes. EVs derived from rheumatoid models have also been shown to induce secretion of COX-2 and stimulate angiogenesis. Additionally, there is evidence that synovium-derived EVs may be promising biomarkers of disease in both OA and RA. The characterization of EVs in the joint space has also opened up the possibility for delivery of small molecules. This article reviews current knowledge on the role of EVs in both RA and OA, and their potential role as therapeutic targets for modulation of these debilitating diseases.

Research into the biology of extracellular vesicles (EVs), including exosomes and microvesicles, has expanded significantly with advances in EV isolation techniques, a better understanding of the surface markers that characterize exosomes and microvesicles, and greater information derived from -omics approaches on the proteins, lipids, mRNAs, and microRNAs (miRNAs) transported by EVs. We have recently discovered a role for exosome-derived miRNAs in age-related bone loss and osteoarthritis, two conditions that impose a significant public health burden on the aging global population. Previous work has also revealed multiple roles for EVs and their miRNAs in muscle regeneration and congenital myopathies. Thus, EVs appear to be involved in a number of degenerative conditions that impact the musculoskeletal system, indicating that the musculoskeletal system is an excellent model for investigating the role of EVs in tissue maintenance and repair. This review highlights the role of EVs in bone, skeletal muscle, and joint health, including both normal tissue metabolism as well as tissue injury repair and regeneration. A consistent theme that emerges from study of musculoskeletal EVs is that various miRNAs appear to mediate a number of key pathological processes. These findings point to a potential therapeutic opportunity to target EV-derived miRNAs as a strategy for improving musculoskeletal function.

Background: Postoperative cerebral edema around a deep brain stimulation (DBS) electrode is an uncommonly reported complication of DBS surgery. The etiology of this remains unknown, and the presentation is highly variable; however, the patients generally report a good outcome. Case Description: Here, we report an unusual presentation of postoperative edema in a 66-year-old female who has bilateral dentatorubrothalamic tract (specifically, the ventral intermediate nucleus) DBS for a mixed type tremor disorder. Initial postoperative computed tomography (CT) was unremarkable and the patient was admitted for observation. She declined later on postoperative day (POD) 1 and became lethargic. Stat head CT scan performed revealed marked left-sided peri-lead edema extending into the centrum semiovale with cystic cavitation, and trace right-sided edema. On POD 2, the patient was alert, but with global aphasia, right-sided neglect, and a plegic right upper extremity. Corticosteroids were started and a complete infectious workup was unremarkable. She was intubated and ultimately required a tracheostomy and percutaneous gastrostomy tube. She returned to the clinic 3 months postoperatively completely recovered and ready for battery implantation. Conclusion: While this is an unusual presentation of cerebral edema following DBS placement, ultimately, the outcome was good similar to other reported cases. Supportive care and corticosteroids remain the treatment of choice for this phenomenon.

Objective: Trigeminal neuralgia (TN) related to a brainstem cavernous malformation (CM) is a rare entity. We present the first radiosurgical management of a patient with TN secondary to a CM. Clinical Presentation: An 80-year-old female presented with a 33-year history of progressively severe TN refractory to medications. Imaging confirmed a solitary CM located at the pontine dorsal root entry zone of cranial nerve 5. Treatment: Stereotactic radiosurgery of the trigeminal nerve was performed using the Leksell gamma knife. A single 4-mm isocenter of radiation was focused on the trigeminal nerve and a maximum dose of 80 Gy (40 Gy at the 50% isodose line) was delivered to the nerve. Results: At 1 year, the patient noted that the severe pain attacks had been reduced by 75%, although a background lingering discomfort persisted. Pain suppression medications had been significantly reduced to lamotrigine 100 mg twice daily. Her preoperative distribution of sensory dysfunction mildly increased. Conclusion: For medically refractory TN related to a CM, radiosurgery of the afferent nerve may ameliorate pain without a major decrease in sensation. The more than 30-year history of pain in our patient may have reduced the chance of more significant pain relief.