The Relative Location of the Major Femoral Nerve Motor Branches in the Thigh.

In peripheral nerve surgery, repair of the femoral nerve (FN) requires identification of normal nerve elements both proximal and distal to the level of the injury. We identified FN branches to the sartorius (SRT) and quadriceps muscles in 16 embalmed specimens and calculated the length of each branch to its point of entry into its respective muscle. The SRT and rectus femoris (RF) muscles were mobilized but not transected to mimic the surgical approach. Ratios of the length of each motor branch as a unit of the total length of the thigh, defined as the FN at the inguinal ligament to the superior margin of the patella were also calculated. The proximal branch to RF spanned a ratio of .19 ± .11 (mean ± standard deviation) from the FN at the inguinal ligament to its endpoint. The ratio of the distal branch to the RF was .29 ± .08. The ratio of the proximal SRT branch was .20 ± .05. The distal branch to SRT was located at a ratio of .43 ± .11. The proximal branch to vastus lateralis (VL) was .26 ± .08. The distal branch to VL was .39 ± .07. The ratio of the motor branch to vastus intermedius (VI) was .30 ± .05. Lastly, the branch to vastus medialis (VM) was .55 ± .06. The motor branch to SRT frequently emerged as a bifurcation of itself and saphenous nerve within the adductor canal. Knowledge of the relative location of the motor branches of the FN in the thigh can be helpful to surgeons during the nerve exploration and repair.

Exosomes impact survival to radiation exposure in cell line models of nervous system cancer.

Radiation is utilized in the therapy of more than 50% of cancer patients. Unfortunately, many malignancies become resistant to radiation over time. We investigated the hypothesis that one method of a cancer cell's ability to survive radiation occurs through cellular communication via exosomes. Exosomes are cell-derived vesicles containing DNA, RNA, and protein. Three properties were analyzed: 1) exosome function, 2) exosome profile and 3) exosome uptake/blockade. To analyze exosome function, we show radiation-derived exosomes increased proliferation and enabled recipient cancer cells to survive radiation in vitro. Furthermore, radiation-derived exosomes increased tumor burden and decreased survival in an in vivo model. To address the mechanism underlying the alterations by exosomes in recipient cells, we obtained a profile of radiation-derived exosomes that showed expression changes favoring a resistant/proliferative profile. Radiation-derived exosomes contain elevated oncogenic miR-889, oncogenic mRNAs, and proteins of the proteasome pathway, Notch, Jak-STAT, and cell cycle pathways. Radiation-derived exosomes contain decreased levels of tumor-suppressive miR-516, miR-365, and multiple tumor-suppressive mRNAs. Ingenuity pathway analysis revealed the most represented networks included cell cycle, growth/survival. Upregulation of DNM2 correlated with increased exosome uptake. To analyze the property of exosome blockade, heparin and simvastatin were used to inhibit uptake of exosomes in recipient cells resulting in inhibited induction of proliferation and cellular survival. Because these agents have shown some success as cancer therapies, our data suggest their mechanism of action could be limiting exosome communication between cells. The results of our study identify a novel exosome-based mechanism that may underlie a cancer cell's ability to survive radiation.

Targeting IL-13Rα2 for effective treatment of malignant peripheral nerve sheath tumors in mouse models.

OBJECTIVEMalignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas that harbor a high potential for metastasis and have a devastating prognosis. Combination chemoradiation aids in tumor control and decreases tumor recurrence but causes deleterious side effects and does not extend long-term survival. An effective treatment with limited toxicity and enhanced efficacy is critical for patients suffering from MPNSTs.METHODSThe authors recently identified that interleukin-13 receptor alpha 2 (IL-13Rα2) is overexpressed on MPNSTs and could serve as a precision-based target for delivery of chemotherapeutic agents. In the work reported here, a recombinant fusion molecule consisting of a mutant human IL-13 targeting moiety and a point mutant variant of Pseudomonas exotoxin A (IL-13.E13 K-PE4E) was utilized to treat MPNST in vitro in cell culture and in an in vivo murine model.RESULTSIL-13.E13 K-PE4E had a potent cytotoxic effect on MPNST cells in vitro. Furthermore, intratumoral administration of IL-13.E13 K-PE4E to orthotopically implanted MPNSTs decreased tumor burden 6-fold and 11-fold in late-stage and early-stage MPNST models, respectively. IL-13.E13 K-PE4E treatment also increased survival by 23 days in the early-stage MPNST model.CONCLUSIONSThe current MPNST treatment paradigm consists of 3 prongs: surgery, chemotherapy, and radiation, none of which, either singly or in combination, are curative or extend survival to a clinically meaningful degree. The results presented here provide the possibility of intratumoral therapy with a potent and highly tumor-specific cytotoxin as a fourth treatment prong with the potential to yield improved outcomes in patients with MPNSTs.

Fracture related ulnar and sciatic nerve transections: a report of two cases and literature review.

INTRODUCTION: Case reports, case series, and case control studies have looked at the incidence of complete nerve transection in the setting of fracture and the need for surgical exploration dating back to the 1920s. We present two cases of nerve laceration accompanying traumatic fracture with a thorough review of the literature. METHODS: We used the following search terms: "ulnar nerve" OR "sciatic nerve" AND "laceration" OR "transection" AND "fracture." Results were reviewed and included for discussion if they specifically reported ulnar or sciatic nerve laceration accompanying traumatic fracture. RESULTS: Our search yielded 15 papers reporting a total of 10 ulnar nerve lacerations and nine sciatic nerve lacerations. We present two additional cases. The first is a patient with a humerus fracture and complete ulnar nerve transection. The second case is a patient who suffered a femur fracture and complete transection of the sciatic nerve. CONCLUSION: Nerve laceration accompanying traumatic fracture is rare. We review the reported cases of nerve laceration and present two cases treated at our institution. Though uncommon, nerve laceration should be considered in the setting of traumatic fracture with neurological injury, particularly open fractures.

Impact of an External Ventricular Drain Placement and Handling Protocol on Infection Rates: A Meta-Analysis and Single Institution Experience.

BACKGROUND: Numerous studies have examined the impact of initiating an external ventricular drain (EVD) placement and handling protocol on the infection rate dating back to the early 2000s. METHODS: We report a quantitative systematic review of the published literature, described our own protocol (including a mandatory checklist), and present our single institution experience. Search terms "external ventricular drain protocol" or "external ventricular drain placement protocol" or "preventing infections in external ventricular drains" or "external ventricular drain infections" were entered into standard search engines in a systematic fashion. Articles were reviewed and graded independently for class of evidence. There were 10 relevant class IV articles and no discrepancies among article ratings (i.e., κ = 1). The published evidence was reviewed and evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. RESULTS: Our meta-analysis revealed a statistically significant drop in rates of EVD infection after initiation of the protocol, although the overall quality of the body of evidence according to the GRADE criteria was "very poor". Preimplementation and postimplementation infection rates were collected and analyzed in combination with the results from our literature review. The EVD infection rate in our institution was 12% in the 8 months before protocol initiation (January 2015 to August 2015), and dropped to 0% in the 7 months after initiation. CONCLUSIONS: Although the quality of the literature supporting EVD placement protocols is poor, all published studies show a consistent and substantial benefit, and this effect was recapitulated in our own meta-analysis-based prospective EVD protocol experience.

Correlation of Histopathology and Clinical Symptoms in Meralgia Paresthetica.

Meralgia paresthetica is a neuropathic pain disorder resulting from an entrapment neuropathy of the lateral femoral cutaneous nerve. This condition results in pain, paresthesias and numbness over the anterolateral aspect of the thigh. We present a case of meralgia paresthetica and discuss both the clinical and histopathological findings as they relate to one another. We report a case of meralgia paresthetica refractory to conservative treatment who underwent neurectomy with successful treatment of symptoms. Histopathological examination revealed moderate loss of myelinated axons with some axonal atrophy. The distinct pathologic findings were axonal regeneration clusters and thinly myelinated axons as well as moderate perineurial thickening. These findings corresponded well to the patient's preoperative symptoms of paresthesias and pain. This case serves to shed light on the pathophysiology of meralgia paresthetica and its clinical presentation. It also shows the role of surgical treatment in cases refractory to conservative management in order to alleviate painful symptoms.

Evaluating the evidence: is phrenic nerve stimulation a safe and effective tool for decreasing ventilator dependence in patients with high cervical spinal cord injuries and central hypoventilation?

INTRODUCTION: Case reports, case series and case control studies have looked at the use of phrenic nerve stimulators in the setting of high spinal cord injuries and central hypoventilation syndromes dating back to the 1980s. We evaluated the evidence related to this topic by performing a systematic review of the published literature. METHODS: Search terms "phrenic nerve stimulation," "phrenic nerve and spinal cord injury," and "phrenic nerve and central hypoventilation" were entered into standard search engines in a systematic fashion. Articles were reviewed by two study authors and graded independently for class of evidence according to published guidelines. The published evidence was reviewed, and the overall body of evidence was evaluated using the grading of recommendations, assesment, development and evaluations (GRADE) criteria Balshem et al. (J Clin Epidemiol 64:401-406, 2011). RESULTS: Our initial search yielded 420 articles. There were no class I, II, or III studies. There were 18 relevant class IV articles. There were no discrepancies among article ratings (i.e., kappa = 1). A meta-analysis could not be performed due to the low quality of the available evidence. The overall quality of the body of evidence was evaluated using GRADE criteria and fell within the "very poor" category. CONCLUSION: The quality of the published literature for phrenic nerve stimulation is poor. Our review of the literature suggests that phrenic nerve stimulation is a safe and effective option for decreasing ventilator dependence in high spinal cord injuries and central hypoventilation; however, we are left with critical questions that provide crucial directions for future studies.