Minimally Invasive Image-Guided Transgluteal Approach for Resection of a Sciatic Nerve Tumor: A Technical Note.

There are a variety of surgical approaches to lesions around the sciatic notch. Historically, peripheral nerve surgeons prefer an infragluteal approach involving a large incision with reflection of the gluteus maximus to better visualize the operative field. This approach was imperative when lesion localization was imprecise. Comparatively, orthopedic surgeons prefer a muscle-splitting, transgluteal approach to operate on the static structures of the posterior hip. The transgluteal approach is significantly less morbid, allowing for same-day discharge and less extensive rehab given preservation of the gluteal muscle. In this article we describe the use of dynamic ultrasound imaging to localize and aid in the resection of three unique tumors around the sciatic notch using a minimally invasive, tissue-sparing, transgluteal technique. We offer a comprehensive description of the benefits, anatomic considerations, and nuances of using a transgluteal approach for the resection of lesions at the sciatic notch.

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.

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.

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.

Percutaneous Radiofrequency Ablation for the Treatment of Peripheral Nerve Sheath Tumors: A Case Report and Review of the Literature.

Peripheral nerve sheath tumors (PNSTs) may arise sporadically or in the presence of genetic disorders, including neurofibromatosis (NF) types 1 and 2, schwannomatosis, and in patients with large genetic deletions involving the CDKN2A gene. Surgical resection is the treatment of choice for symptomatic PNSTs and offers patients a potential cure; however, pre-existing conditions or tumor location may limit a patient's surgical options. Radiofrequency ablation (RFA) may provide an alternative therapeutic strategy for the treatment of selected PNSTs that are not amenable to surgical resection. Here, we present a case report of a 49-year-old patient with multiple neurofibromas who underwent RFA treatment of two symptomatic retroperitoneal neurofibromas and review previously reported cases of percutaneous treatment of PNSTs.

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.

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 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.

The angular course of the median nerve in the distal forearm and its anatomical importance in preventing nerve injury in a modern era of carpal tunnel release.

OBJECTIVE A thorough understanding of anatomy is critical for successful carpal tunnel release. Several texts depict the median nerve (MN) as taking a course parallel to the long axis of the forearm (LAF). The authors report on their attempt to formally assess the course of the MN as it travels to the carpal tunnel in the distal wrist and discuss its potential clinical significance. METHODS The width of the wrist, the distance from the radial wrist to the MN, and the distance from the distal volar wrist crease to the point where the MN emerges between the flexor carpi radialis (FCR) tendon and the flexor digitorum superficialis (FDS) tendons were recorded during cadaveric dissection of 76 wrist specimens. The presence or absence of palmaris longus was documented. Finally, the angles between the MN and FCR tendon and between the MN and the LAF were measured using ImageJ. RESULTS The relative position of the MN at the distal wrist crease, as determined by the ratio of the distance from the MN to the radial wrist divided by wrist width, revealed a mean value of 0.48, indicating that the nerve was usually located just radial to midline. The mean distance between the distal wrist crease and the MN's emergence was 34.6 mm. The mean angle between the MN and the FCR tendon was 14.1°. The angle between the MN and the LAF had a mean value of 8.8° (range 0.0°-32.2°). The nerve was parallel to the LAF in only 10.7% of the studied wrists. Palmaris longus was absent in 14 (18.4%) of the 76 wrists. CONCLUSIONS The MN takes an angular approach to the carpal tunnel in the distal wrist in the vast majority of cases. This newly described finding will be useful to both clinicians and anatomists.

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.

Hybrid Neurofibroma-Schwannoma.

Neurofibromas and schwannomas are common lesions that may be idiopathic or may occur in association with neural crest genetic syndromes such as neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis. A hybrid tumor that contains pathological characteristics of both neurofibroma and schwannoma has been described as a rare entity. We present the clinical, radiographic, and pathological findings of such a case.

An interstitial deletion within 9p21.3 and extending beyond CDKN2A predisposes to melanoma, neural system tumours and possible haematological malignancies.

Familial atypical multiple mole melanoma syndrome (FAMMM) is characterised by dysplastic naevi, malignant melanoma and pancreatic cancer. Given that large deletions involving CDKN2A (cyclin-dependent kinase inhibitor 2A) account for only 2% of cases, we describe a family that highlights the co-occurrence of both melanoma and neural system tumours to aid clinical recognition and propose a management strategy. A patient with multiple neurofibromas was referred with a provisional diagnosis of neurofibromatosis type 1 (NF1). Prior molecular testing, though, had failed to identify an NF1 mutation by sequencing and multiplex ligation-dependent probe amplification. His family history was significant for multiple in situ/malignant melanomas at young ages and several different cancers reminiscent of an underlying syndrome. A search of the Familial Cancer Database, FaCD Online, highlighted several families with cutaneous melanoma and nervous system tumours who were subsequently identified to have large deletions spanning CDKN2A Although sequencing of CDKN2A and TP53 failed to identify a mutation, a heterozygous CDKN2A deletion was identified by targeted array comparative genomic hybridisation (CGH). Whole-genome oligonucleotide array CGH and SNP analysis identified an interstitial deletion of at least 1.5 Mb within 9p21.3 and spanning approximately 25 genes. Identification of the underlying molecular abnormality permits predictive testing for at-risk relatives. Given the young cancer diagnoses, a surveillance regimen was developed and a clinical team organised for ongoing management so that genetic testing could be offered to both adults and minor children. Surveillance recommendations addressed cancer risks associated with FAMMM, and other cancers exhibited by this family with a large contiguous gene deletion.

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.

The muscular axillary arch: an anatomic study and clinical considerations.

OBJECTIVE: The muscular axillary arch is a musculotendinous structure that arises from the latissimus dorsi muscle and crosses the axilla before inserting to the humerus, brachial fascia, or coracoid process. Case reports have described the neurovascular compression symptoms caused by this anatomic variant and have reported that the symptoms can be relieved by division of the muscle. However, there has been little information published regarding this topic in the neurosurgical literature. METHODS: We evaluated 70 axillary dissections in 35 cadavers to assess for the presence of this anomaly. RESULTS: The muscular axillary arch was identified unilaterally in 3 (8.6%) of the 35 cadavers. All 3 arches arose from the anterior border of the latissimus dorsi muscle and inserted at a point along a line extending from the coracoid process to the intertubercular groove deep to the insertion of the pectoralis major muscle. All 3 arches crossed over the neurovascular bundle in the axilla. CONCLUSION: Compression by the muscular axillary arch should be considered in the differential diagnosis of patients with thoracic outlet and hyperabduction syndromes.

Fulminant Guillain-Barré syndrome after closed head injury: a potentially reversible cause of an ominous examination. Case report.

Fulminant Guillain-Barré syndrome (GBS) is a rapidly progressive form of polyneuropathy in which patients demonstrate eventual flaccid quadriplegia and an absence of brainstem function. Most patients present after a mild upper respiratory or gastrointestinal illness and have nondiagnostic cerebral imaging studies. The authors present a case of fulminant GBS that developed in a 55-year-old alcoholic man 1 week after admission for a closed head injury. The details of this case and a discussion of GBS will be presented. This case provides evidence for combined central and peripheral nervous system involvement in severe cases of GBS. Recognition of fulminant GBS is important to prevent inappropriate declaration of brain death or withdrawal of support in the face of a potentially reversible process.

Schwannomatosis in a patient with a pelvic mass: case report.

Schwannomatosis is the most recently recognized form of neurofibromatosis in which patients harbor multiple non-vestibular nerve schwannomas. The diagnosis is contingent on excluding neurofibromatosis Type 2 (NF2), to which it is related. The authors present a case of schwannomatosis diagnosed fortuitously when a preoperative magnetic resonance (MR) image of a pelvic schwannoma was suggestive of a lesion in the lower lumbar canal. Definitive studies confirmed the presence of multiple spinal tumors including a thoracic schwannoma, which was removed during a subsequent procedure. This case emphasizes the need to consider the possibility of multiple tumors in every patient presenting with a schwannoma because the follow-up and genetic counseling are vastly different in those with NF2 and schwannomatosis compared with those harboring sporadic tumors. Details of this case and current considerations in the diagnosis and management of schwannomatosis are discussed.