Accessory Nerve Disruption Following Core-Needle Biopsy: A Review of Iatrogenic Accessory Nerve Injuries and an Illustrative Case.

Iatrogenic spinal accessory neve (SAN) injury is a rare complication. It most commonly occurs after open lymph node biopsies. Needle biopsy is thought to present lower risk to the SAN. However, we describe a case of a 66-year-old man who underwent core needle biopsy for lymphadenopathy and subsequently experienced ipsilateral shoulder weakness and pain. Physical examination revealed shoulder depression, lateral scapular winging, and decreased range of motion. Subsequent studies and magnetic resonance imaging demonstrated complete paralysis and denervation of SAN muscles. The nonfunctional SAN was repaired by sural nerve grafting 3 months after the injury. The patient demonstrated improved shoulder strength, range of motion, and decreased pain at 6-month follow-up. SAN injuries can be challenging to diagnose and require prompt surgical intervention. This case represents an unusual case of complete SAN disruption and palsy after core needle biopsy treated with sural nerve grafting. We review the literature on iatrogenic SAN injuries, diagnostic strategies, options for SAN surgical repair, and outcomes. SAN injuries can be challenging to diagnose but are amenable to prompt surgical options based on the mechanism and type of SAN injury.

Contiguous Meningioma and B-Cell Lymphoma: A Scoping Review and Case Illustration.

BACKGROUND: The diagnosis of a contiguous, synchronous meningioma and central nervous system B-cell lymphoma is rare and associated with paradoxical treatment paradigms. We performed a scoping review of contiguous meningioma and B-cell lymphoma and included an additional illustrative case. METHODS: The OVID Medline and PubMed databases were systematically searched using the Preferred Reporting Items of Systematic Reviews and Meta-Analysis guidelines. Only human clinical reports of contiguous, synchronous meningioma and B-cell lymphoma were included. We concurrently detailed a representative case from our institution. RESULTS: Nine case reports met our criteria, including the present case. The average age at diagnosis was 67.4 years. Patients showed a female-to-male predominance of 7:2. The diagnosis of synchronous intracranial tumors was not suspected or discovered until after surgical resection in 100% of cases. All meningiomas were grade I on histopathologic diagnosis, while lymphomas were distributed between diffuse large B-cell lymphoma (56%), metastatic lymphoma (22%), Burkitt lymphoma (11%), and follicular lymphoma (11%). All patients underwent surgical resection. Patients (n = 5) treated with adjuvant chemotherapy had evidence of longer progression-free survival (median 12 months; range, 3-18 months) than patients without adjuvant chemotherapy (n = 2; median 2 months; range, 1-3 months). CONCLUSIONS: Contiguous, synchronous meningioma/B-cell lymphoma is a rare diagnosis that may appear as an inconspicuous solitary intracranial neoplasm on imaging. Based on the limited cases and current treatment of lymphoma, progression-free survival may be contingent on the prompt initiation of chemotherapy targeting the lymphoma rather than surgical resection of the meningeal mass. Providers should prioritize prompt medical management.

Infragluteal Exposure for Resection of Subgluteal Tumors: A Surgical Technique for Accessing the Sciatic Nerve and Notch.

Sciatic nerve impingement via a tumor of or trauma to the proximal subgluteal region creates a considerable surgical challenge that is debated in the literature. The neurosurgery literature favors the infragluteal approach, while in orthopaedics, the transgluteal approach is preferred. The goal of our study was to present an operative technique for the infragluteal approach to the subgluteal region with a step-by-step procedural guide to increase awareness among orthopaedic surgeons of alternative surgical approaches to the sciatic notch. We retrospectively reviewed the case of a 62-year-old female found to have a subgluteal myxoma who underwent the infragluteal approach for tumor excision. We then highlighted the anatomic considerations via cadaveric dissection photographs, artistic renditions, and intra-operative images. Our patient underwent tumor resection and sciatic nerve exploration via the infragluteal approach with a successful outcome. In comparison to other approaches in the literature, the infragluteal approach provides a safer dissection with more options for an extension of the exposure and potentially fewer functional deficits. We conclude that orthopaedic surgeons should strongly consider utilizing this approach to the sciatic notch rather than a transgluteal approach.

Spontaneous Hip Dislocation Complicating the Management of Malignant Peripheral Nerve Sheath Tumor Arising Within a Plexiform Neurofibroma.

Neurofibromatosis type 1 (NF1) is one of the most common inherited neurological disorders. It can cause plexiform neurofibromas, leading to diffuse enlargement of a nerve or nerves within the body. There are benign in general, however, can cause significant symptoms due to their size, including bony erosion, pain, and joint instability. Unfortunately, they also have the capacity to become malignant by internal transformation into a malignant peripheral nerve sheath tumor (MPNST). The case presented here is a 27-year-old male with NF1 that was followed for years with a pelvic girdle plexiform neurofibroma whose course was complicated by transformation to MPNST and a spontaneous hip dislocation. He underwent excision, Girdlestone procedure, chemotherapy, and radiation. Unfortunately, he subsequently developed lung metastases and is part of a clinical trial with an MDM2 inhibitor and pembrolizumab.

A Unique Case of a High-Grade Neuroepithelial Tumor With EML4-ALK Fusion in a Five-Month-Old.

We present a unique and challenging case of a high-grade neuroepithelial tumor with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion in a five-month-old child. This tumor was difficult to classify, with glial and ependymal features, reinforcing the impact of a molecular-based diagnosis in correct classification and management. The patient had two tumor resections and underwent chemotherapy following the Head Start trial treatment regimen. The patient remains well, with no residual disease on MRI 15 months after initial resection. Further studies are needed to determine the frequency of EML4-ALK fusions in these types of tumors and to optimize therapeutic protocols for children and adults, alike, suffering from this disease.

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.

The Leg Wound of King Philip II of Macedonia.

Objective King Philip II, the father of Alexander the Great, suffered a penetrating wound to the leg from a spear that left him severely handicapped. His skeletal remains represent the first and only case of an injury from ancient Greece that can be directly compared to its historical record. The objective of the study was to confirm the identity of the male occupant of Royal Tomb I in Vergina, Greece as Philip II of Macedonia by providing new evidence based on anatomical dissection and correlation with the historical description of the wounds. Methods Radiographs and photographs of the leg in Royal Tomb I in Vergina were examined. Anatomical dissection of a cadaver with a reconstructed wound similar to Philip's was also completed to identify associated soft-tissue injuries. Results The left leg was penetrated by an object at the knee which resulted in joint diastasis, external rotation of the tibia, knee ankylosis, and formation of a granuloma around the related object. This caused massive trauma to the joint but spared the popliteal artery. This resulted in ligamentous injury as well as injury to the peroneal nerve and probably the tibial nerve, resulting in a complete palsy of those nerves. Conclusion This evidence exactly matches the historical sources and shows conclusively that the leg and Tomb I belong to Philip II. The anatomic and archaeologic evidence also serve as independent verification of some of the historical record of that period, better enabling scholars to judge the reliability of various texts. Furthermore, it gives invaluable information about surgical practices in ancient Greece according to Hippocratic methods and their outcomes. Finally, this sheds new light on the occupants of Royal Tomb II including the fact that the armor recovered there may have belonged to Alexander the Great.

The critical chemical and mechanical regulation of folic acid on neural engineering.

The mandate of folic acid supplementation in grained products has reduced the occurrence of neural tube defects by one third in the U.S since its introduction by the Food and Drug Administration in 1998. However, the advantages and possible mechanisms of action of using folic acid for peripheral nerve engineering and neurological diseases still remain largely elusive. Herein, folic acid is described as an inexpensive and multifunctional niche component that modulates behaviors in different cells in the nervous system. The multiple benefits of modulation include: 1) generating chemotactic responses on glial cells, 2) inducing neurotrophin release, and 3) stimulating neuronal differentiation of a PC-12 cell system. For the first time, folic acid is also shown to enhance cellular force generation and global methylation in the PC-12 cells, thereby enabling both biomechanical and biochemical pathways to regulate neuron differentiation. These findings are evaluated in vivo for clinical translation. Our results suggest that folic acid-nerve guidance conduits may offer significant benefits as a low-cost, off-the-shelf product for reaching the functional recovery seen with autografts in large sciatic nerve defects. Consequently, folic acid holds great potential as a critical and convenient therapeutic intervention for neural engineering, regenerative medicine, medical prosthetics, and drug delivery.

MLN8237 treatment in an orthoxenograft murine model for malignant peripheral nerve sheath tumors.

OBJECTIVEMalignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas arising from peripheral nerves. MPNSTs have increased expression of the oncogene aurora kinase A, leading to enhanced cellular proliferation. This makes them extremely aggressive with high potential for metastasis and a devastating prognosis; 5-year survival estimates range from a dismal 15% to 60%. MPNSTs are currently treated with resection (sometimes requiring limb amputation) in combination with chemoradiation, both of which demonstrate limited effectiveness. The authors present the results of immunohistochemical, in vitro, and in vivo analyses of MLN8237 for the treatment of MPNSTs in an orthoxenograft murine model.METHODSImmunohistochemistry was performed on tumor sections to confirm the increased expression of aurora kinase A. Cytotoxicity analysis was then performed on an MPNST cell line (STS26T) to assess the efficacy of MLN8237 in vitro. A murine orthoxenograft MPNST model transfected to express luciferase was then developed to assess the efficacy of aurora kinase A inhibition in the treatment of MPNSTs in vivo. Mice with confirmed tumor on in vivo imaging were divided into 3 groups: 1) controls, 2) mice treated with MLN8237, and 3) mice treated with doxorubicin/ifosfamide. Treatment was carried out for 32 days, with imaging performed at weekly intervals until postinjection day 42. Average bioluminescence among groups was compared at weekly intervals using 1-way ANOVA. A survival analysis was performed using Kaplan-Meier curves.RESULTSImmunohistochemical analysis showed robust expression of aurora kinase A in tumor cells. Cytotoxicity analysis revealed STS26T susceptibility to MLN8237 in vitro. The group receiving treatment with MLN8237 showed a statistically significant difference in tumor size compared with the control group starting at postinjection day 21 and persisting until the end of the study. The MLN8237 group also showed decreased tumor size compared with the doxorubicin/ifosfamide group at the conclusion of the study (p = 0.036). Survival analysis revealed a significantly increased median survival in the MLN8237 group (83 days) compared with both the control (64 days) and doxorubicin/ifosfamide (67 days) groups. A hazard ratio comparing the 2 treatment groups showed a decreased hazard rate in the MLN8237 group compared with the doxorubicin/ifosfamide group (HR 2.945; p = 0.0134).CONCLUSIONSThe results of this study demonstrate that MLN8237 is superior to combination treatment with doxorubicin/ifosfamide in a preclinical orthoxenograft murine model. These data have major implications for the future of MPNST research by providing a robust murine model as well as providing evidence that MLN8237 may be an effective treatment for MPNSTs.

Tumor targeted delivery of doxorubicin in malignant peripheral nerve sheath tumors.

Peripheral nerve sheath tumors are benign tumors that have the potential to transform into malignant peripheral nerve sheath tumors (MPNSTs). Interleukin-13 receptor alpha 2 (IL13Rα2) is a cancer associated receptor expressed in glioblastoma and other invasive cancers. We analyzed IL13Rα2 expression in several MPNST cell lines including the STS26T cell line, as well as in several peripheral nerve sheath tumors to utilize the IL13Rα2 receptor as a target for therapy. In our studies, we demonstrated the selective expression of IL13Rα2 in several peripheral nerve sheath tumors by immunohistochemistry (IHC) and immunoblots. We established a sciatic nerve MPNST mouse model in NIH III nude mice using a luciferase transfected STS26T MPNST cell line. Similarly, analysis of the mouse sciatic nerves after tumor induction revealed significant expression of IL13Rα2 by IHC when compared to a normal sciatic nerve. IL13 conjugated liposomal doxorubicin was formulated and shown to bind and internalized in the MPNST cell culture model demonstrating cytotoxic effect. Our subsequent in vivo investigation in the STS26T MPNST sciatic nerve tumor model indicated that IL13 conjugated liposomal doxorubicin (IL13LIPDXR) was more effective in inhibiting tumor progression compared to unconjugated liposomal doxorubicin (LIPDXR). This further supports that IL13 receptor targeted nanoliposomes is a potential approach for treating MPNSTs.

Evaluating the evidence: is neurolysis or neurectomy a better treatment for meralgia paresthetica?

BACKGROUND: Meralgia paresthetica is a mononeuropathy of the lateral femoral cutaneous nerve (LCFN). Surgical treatment involves transection or decompression of the LCFN. There is no clear consensus on the superiority of one technique over the other. We performed a systematic review of the literature to answer this question. METHODS: Eligible studies included those that compared neurolysis versus neurectomy for the treatment of meralgia paresthetica after failure of conservative therapy. Our outcome of interest was resolution of symptoms. We performed a computerized search of MEDLINE (PubMed; all years) and of the Cochrane Central Register of Controlled Trials. Eligible studies had to include the words "meralgia paresthetica" and "surgery." All patients regardless of age were included, and there was no language restriction. We then reviewed the articles' titles and abstracts. All studies that compared neurolysis to neurectomy were included in the analysis. RESULTS: Of the studies identified, none were randomized controlled trials. There were two German language articles that were translated by a third researcher. Each study was evaluated by two independent researchers who assigned a level of evidence according to American Association of Neurologist algorithm and also performed data extraction (neurolysis vs. neurectomy and resolution of pain symptoms). Each study was found to be level four evidence. CONCLUSION: After reviewing the data, there was insufficient evidence to recommended one method of treatment over the other. This highlights the importance of keeping a national registry in order to compare outcomes between the two methods of treatment.

Intraventricular Undifferentiated Pleomorphic Sarcoma: A Case Report.

Undifferentiated pleomorphic sarcoma is a histologic diagnosis based on cell morphology. These tumors are found throughout the body. They are rarely found in the central nervous system and almost never occur as a primary intraventricular tumor. We present the unusual case of a 68-year-old woman with an intraventricular undifferentiated pleomorphic sarcoma. We go on to discuss the clinical presentation, radiographic characteristics, and management paradigm for these rare lesions. Our patient presented with acute confusion, inability to balance a checkbook, and gait imbalance. CT and MRI demonstrated a 4 x 3.6 x 3.6 cm enhancing lesion in the left lateral ventricle abutting the foramen of Monro. Pathology revealed an undifferentiated pleomorphic sarcoma.

Vanishing Pituitary Macroadenoma: A Case Report.

Pituitary macroadenomas are the most common suprasellar lesions in adults and are typically managed surgically through transsphenoidal resection when symptomatic. Due to their close proximity to the optic chiasm, pituitary macroadenomas often present with signs of bitemporal hemianopsia. Alternatively, these tumors can cause mass effect, thus presenting with signs of elevated intracranial pressure or can present with signs and symptoms of endocrine dysfunction. Here, we discuss a 55-year-old male diagnosed with a non-functioning pituitary macroadenoma (NFPA) based on cranial imaging, ophthalmologic exam, and endocrine evaluation. Following diagnosis, the patient was scheduled for transsphenoidal hypophysectomy. On magnetic resonance imaging (MRI) done three and half months later for surgical planning, the tumor had almost completely regressed and only residual pituitary tissue was noted. We describe the presentation and clinical course of the patient, summarize chief differential diagnoses, and discuss potential managements of these conditions.

Case Report: A Rosette-forming Glioneuronal Tumor in the Tectal Plate in a Patient with Neurofibromatosis Type I.

We report the case of a 41-year-old female with neurofibromatosis Type 1 (NF1) who developed a rosette-forming glioneuronal tumor (RGNT) in the tectal plate. This tumor was diagnosed in 2002 when the patient presented with obstructive hydrocephalus, which was subsequently treated with a ventriculoperitoneal shunt and then an endoscopic third ventriculostomy. Initially thought to be a pilocytic astrocytoma, it was followed with serial magnetic resonance imaging (MRI) until tumor progression and development of a large fourth ventricular cystic component prompted resection via suboccipital craniotomy. Histological examination demonstrated an RGNT, a WHO Grade 1 tumor, with neurocytic rosettes, perivascular pseudorosettes, and elements resembling a pilocytic astrocytoma. Initially, the patient did well after her craniotomy, but postoperative complications set in that eventually led to her death. In this case report, we describe a relatively rare tumor that, despite its benign nature, leads to frequent complications and deficits due to its surgically challenging location. Along with previously reported examples, this cases raises the possibility of a causal relationship between NF1 and RGNT.

Management of nerve compression in multiple hereditary exostoses: a report of two cases and review of the literature.

PURPOSE: Multiple hereditary exostoses (MHE) is a rare autosomal dominant condition that results in the growth of cartilage-capped prominences that often cause nerve compression and injury. Many patients suffer from continued and debilitating chronic pain which leads some to advocate avoiding surgical intervention in patients with multiple hereditary exostoses. We present a review of the literature as well as a case series at our institution in order to evaluate the role of surgery in multiple hereditary exostoses. METHODS: We searched the literature for reports of patients with multiple hereditary exostoses undergoing surgery for nerve compression. We then reviewed the recent experience at our institution which revealed two patients with multiple hereditary exostoses. RESULTS: Our literature search revealed that there have been several case series and retrospective analyses in the literature that assess the benefit of surgery in the case of nerve compression caused by exostoses. The majority of these reports are of solitary exostoses. Few reports expand on the role of surgery in patients with multiple hereditary exostoses suffering from nerve compressions secondary to bony overgrowth. A recent review of the experience at our institution revealed two patients with multiple hereditary exostoses who together underwent a total of four surgeries for treatment of peripheral nerve compression resulting in pain or weakness. Postoperative evaluation revealed improvement in pain and/or motor strength following each operation. CONCLUSION: Based on our experience and literature review, we advocate that nerve compression in selected individuals with multiple hereditary exostoses that results in neurological injury should be considered for nerve decompression and resection of the offending exostosis.

Pure neuritic leprosy presenting as ulnar nerve neuropathy: a case report of electrodiagnostic, radiographic, and histopathological findings.

Hansen's disease, or leprosy, is a chronic infectious disease with many manifestations. Though still a major health concern and leading cause of peripheral neuropathy in the developing world, it is rare in the United States, with only about 150 cases reported each year. Nevertheless, it is imperative that neurosurgeons consider it in the differential diagnosis of neuropathy. The causative organism is Mycobacterium leprae, which infects and damages Schwann cells in the peripheral nervous system, leading first to sensory and then to motor deficits. A rare presentation of Hansen's disease is pure neuritic leprosy. It is characterized by nerve involvement without the characteristic cutaneous stigmata. The authors of this report describe a case of pure neuritic leprosy presenting as ulnar nerve neuropathy with corresponding radiographic, electrodiagnostic, and histopathological data. This 11-year-old, otherwise healthy male presented with progressive right-hand weakness and numbness with no cutaneous abnormalities. Physical examination and electrodiagnostic testing revealed findings consistent with a severe ulnar neuropathy at the elbow. Magnetic resonance imaging revealed diffuse thickening and enhancement of the ulnar nerve and narrowing at the cubital tunnel. The patient underwent ulnar nerve decompression with biopsy. Pathology revealed acid-fast organisms within the nerve, which was pathognomonic for Hansen's disease. He was started on antibiotic therapy, and on follow-up he had improved strength and sensation in the ulnar nerve distribution. Pure neuritic leprosy, though rare in the United States, should be considered in the differential diagnosis of those presenting with peripheral neuropathy and a history of travel to leprosy-endemic areas. The long incubation period of M. leprae, the ability of leprosy to mimic other conditions, and the low sensitivity of serological tests make clinical, electrodiagnostic, and radiographic evaluation necessary for diagnosis. Prompt diagnosis and treatment is imperative to prevent permanent neurological injury.