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Background and Objectives: Cubital tunnel syndrome is the second most common nerve entrapment, and understanding the anatomy is crucial for the success of the nerve release. During ulnar nerve release for cubital tunnel syndrome, a motor branch is frequently encountered crossing anteriorly over the ulnar nerve from its medial/ulnar side proximally to the lateral/radial side distally. Little has been noted about this crossing branch in the literature. In this anatomic study, we sought to characterize this branch further and discuss its potential significance in cubital tunnel release., Methods: We performed a cadaveric dissection of 48 elbow specimens as if performing a cubital tunnel release. We assessed for the presence of the crossing motor branch of the ulnar nerve and measured the distance from the medial epicondyle to the branch takeoff and to its target of innervation., Results: Of our 48 specimens, 34 (71%) were noted to have a crossing motor branch at the area of compression by the deep flexor carpi ulnaris muscle fascia (common aponeurosis). On average, the distance from the medial epicondyle to the branch origin from the ulnar nerve was 18.2 mm and to the target muscle innervation was 28.4 mm., Conclusion: Identifying this branch is important for performing a cubital tunnel release, and awareness of this anatomy during ulnar nerve decompression procedures may help avoid injury to this motor branch., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Carpal and cubital tunnel syndromes are the two most common compressive neuropathies, but both carpal and cubital tunnel syndromes are extremely rare in children. Therefore, the combination of carpal and cubital tunnel syndrome in the pediatric population is even more uncommon. These neuropathies have multiple causes, with the three main categories being mechanical injury, metabolic, and idiopathic. Here, we present the unique case of a 15-year-old female with no known genetic or physical risk factors who was diagnosed with atraumatic combined carpal and cubital tunnel syndrome with severe, chronic nerve entrapment and damage. After nearly two years of conservative management, the patient had a cubital tunnel and carpal tunnel release simultaneously. The transverse carpal ligament was grossly thickened intraoperatively, leading to difficulty in the identification of the median nerve. The ulnar nerve was severely compressed and flattened. Following decompression, both nerves continued to be erythematous and inflamed. After surgery, the patient had barriers to getting appropriate postoperative care. Specifically, the patient was unable to attend physical and hand therapy appointments, possibly leading to continued weakness, numbness, and intermittent pain. In our patient, the preoperative workup did not illuminate the severity of the median and ulnar nerve damage, possibly delaying surgical intervention. In addition to our case, we utilized the TriNetX database (TriNetX, Inc., Cambridge, Massachusetts, United States) to investigate the rate and treatment of compressive neuropathies in the pediatric population. The database was queried for pediatric patients who underwent carpal tunnel release, cubital tunnel release, and pediatric patients with both carpal and cubital tunnel syndrome diagnoses in childhood. We found that there were 20,819,207 pediatric patients on the TriNetX database, of whom 503 (0.002%) were diagnosed with both carpal and cubital tunnel syndrome. Based on our case and the current literature, a thorough history of pediatric patients with suspected carpal or cubital tunnel syndrome should include an evaluation of family history and activity level for pertinent risk factors. Widening the scope of the patient history could allow for more timely surgical intervention and improve long-term outcomes for the pediatric population. When evaluating children for either carpal tunnel or cubital tunnel syndrome, we recommend that healthcare providers evaluate both neuropathies simultaneously., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Olson et al.)

Hay-holes are a design feature in many traditionally built barns that serve as a portal through which stored hay is passed to the lower level where animals are fed. Unfortunately, children sometimes fall through the hay-hole to the concrete or packed earth below. Available data on the frequency and types of hay-hole injuries is limited. The purpose of this study was to better characterize the resultant injuries and identify prognostic factors that predict outcomes from them. We performed a retrospective review of 53 children admitted to the Penn State Hershey Children's Hospital at the Penn State Hershey Medical Center with injuries due to a fall through a hay-hole over 15 years. Compared to urban trauma, hay-hole falls more frequently involve younger children and craniofacial injuries. Although they may result in significant injuries, they are rarely fatal. Greater fall height is associated with longer length of stay (LOS) but not with a greater frequency of intubation, intracranial hemorrhage, or skull fracture. A re-examination of barn design may help to reduce the frequency of this injury type., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Yang et al.)

Introduction: Intracranial hemorrhage (ICH) is a devastating condition with a high rate of morbidity and mortality. Aneurysm or arteriovenous malformation (AVM) rupture are two common etiologies leading to ICH. Here we provide an update on ICH during pregnancy with a focus on those caused by aneurysm or AVM rupture., Methods: Here we systematically review 25 studies reported in the literature to provide an update on ICH during pregnancy focusing on aneurysm or AVM rupture. We also reviewed the prognosis of ICH during puerperium., Results: Discrepancies exist between studies supporting or refuting the hypothesis of a higher rate of ICH during pregnancy, obscuring the overall rate of aneurysm and AVM rupture in pregnant ICH patients. However, risk factors such as maternal age and hypertension have shown to increase the frequency of ICH in pregnant patients. We also show increased morbidity and mortality in patients suffering from preeclampsia/eclampsia., Discussion: ICH is rare, but the various studies demonstrating its increased frequency, morbidity, and mortality during pregnancy should raise our awareness of this condition. The management and treatment decisions for a pregnant ICH patient should follow the same principles as nonpregnant patients, but with the knowledge that not all medications are appropriate for use in the pregnant patient. Although there seems to be a higher frequency of AVM rupture, further research must be conducted in order to fully determine the effects of pregnancy on aneurysm and AVM ruptures., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Glioblastoma is a devastating malignancy with a dismal survival rate and median survival time of 14 months. Currently, the biomarkers for glioblastoma are mostly molecular and include EGFRvIII, ATRX, PTEN, IDH1, MGMT, and others. These prognostic tumor biomarkers are obtained through a surgical biopsy and thus are not easily attainable. Clinicians would benefit from a robust, non-invasive, and readily available indicator for early diagnosis and accurate prognostication for glioblastoma patients. In this study, we assessed whether specific patient symptoms could provide an early diagnosis of glioblastoma. Further, we also assessed if any patient symptomatology could provide clinicians with the ability to prognosticate patient survival more accurately. We retrospectively reviewed the clinical data for 218 patients. We determined whether symptoms including headache, weakness, seizure, memory loss/confusion, visual changes, speech changes, and loss of consciousness led to a patient being diagnosed earlier and if any of these symptoms predicted diminished patient survival. Our study determined that weakness and memory loss/confusion were the symptoms that predicted diminished survival, and weakness alone was the symptom that predicted an earlier diagnosis. This study further elucidates the complexities of glioblastoma and provides clinicians with more data for their patients when discussing prognostication after diagnosis of glioblastoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Mrowczynski et al.)

Congenital spinal cysts are rare and encompass a wide variety of diseases including arachnoid, enterogenous, teratomatous, neurenteric, foregut, bronchogenic, epithelial, ependymal, dermoid, and epidermoid cysts. Here, we elucidate the epidemiology, pathology, pathogenesis, and diagnostic findings of the most common congenital spinal cysts, followed by a discussion of their presentation and treatment options. Differentiating the cause of each lesion is crucial for targeted clinical and surgical management for the patient. Our review describes how arachnoid cysts can be observed, fenestrated, percutaneously drained, or shunted; however, the primary goal for neurenteric, dermoid, and epidermoid cysts is removal. Further, we discuss how patient presentation is dependent on the rate of growth and location of compression on the spinal cord and nerve roots. However, although many of these lesions are discovered incidentally on imaging, the spectrum of possible symptoms include pain, weakness, ataxia, bladder incontinence, and progressive or acute neurologic deficits. We present and review the histology and imaging of a variety of cysts and discuss how although the goal of treatment is resection, the risks of surgery must be considered against the benefits of complete resection in each case., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Intracranial ganglioneuroblastomas are incredibly rare neuroectodermal tumors with only 8 described cases total, 5 of those having imaging findings METHODS: Here we present a 9-year-old female patient with 4 months progressive headaches, personality changes, and vomiting. We also present a review of the current literature of intracranial ganglioneuroblastomas., Results: Imaging demonstrated a partially calcified suprasellar mass measuring 4.6 × 6.3 × 5 cm composed of both solid and cystic components, diagnosed to be a ganglioneuroblastoma, with mass effect on the lateral and 3rd ventricles, with a midline shift of right to left of 6-7 mm. She was treated with subtotal surgical resection, an intensive chemotherapeutic regimen, and radiation and has no residual disease on imaging 1 year and 4 months status post-surgery., Conclusion: To our knowledge, this is the first case of a ganglioneuroblastoma to mimic a craniopharyngioma based upon imaging findings and suprasellar location. As these cases are extremely rare, an optimal therapeutic regimen has not been defined. However, a combination of surgical resection, chemotherapy, and radiation therapy can be effective, as shown here with successful treatment and no evidence of residual disease.

The purpose of this review is to look at the incidence of post-laminectomy kyphosis in achondroplasia patients and to determine whether skeletal maturity and the number and location of laminectomies predict kyphosis in this patient population. Our review of the literature included all articles from MEDLINE/PubMed and Ovid from inception to 2019. After removing duplicates and checking for relevancy, the final number of articles yielded was eight. The results of this review summarize the incidence of post-laminectomy kyphosis in achondroplasia patients. In conclusion, we suggest fusion be considered in conjunction with multilevel laminectomies due to a high incidence of kyphosis with a need for stabilization in the pediatric achondroplastic patient population., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Hallan et al.)

In the setting of severe septic shock, a 70-year-old woman had an ST segment myocardial infarction with ST elevations in the inferolateral leads. On cardiac catheterisation, no obstructive pathology was noted. Chest imaging revealed a large mediastinal mass measuring 8.5×6.5×7.5 cm in the visceral compartment of the mediastinum, with contrast enhancement from the right coronary artery (RCA). A biopsy was preformed and cytology was consistent with a well-differentiated neuroendocrine neoplasm. On review of the cardiac catherisation, it was noted that the mass was deriving blood supply from the RCA. Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a rare but well-documented phenomenon. In this case, MINOCA was caused by coronary steal syndrome in the setting of profound hypotension. Immediate management is with haemodynamic support; there is no role for coronary intervention., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: BRAF V600E is a common oncogenic driver in a variety of primary brain tumors. Dual inhibitor therapy using dabrafenib (a selective oral inhibitor of several mutated forms of BRAF kinase) and trametinib (a reversible inhibitor of MEK1 and MEK2) has been used successfully for treatment of metastatic melanoma, anaplastic thyroid cancer, and other tumor types, but has been reported in only a few patients with primary brain tumors and none with pleomorphic xanthoastrocytoma. Here, the authors report on the substantial clinical response and reduction in cutaneous toxicity in a case series of BRAF V600E primary brain cancers treated with dual BRAF/MEK inhibitor therapy., Methods: The authors treated 4 BRAF V600E patients, each with a different type of primary brain tumor (pilocytic astrocytoma, papillary craniopharyngioma, ganglioglioma, and pleomorphic xanthoastrocytoma) with the combination of dabrafenib and trametinib., Results: The patients with pilocytic astrocytoma, pleomorphic xanthoastrocytoma, and papillary craniopharyngioma experienced near-complete radiographic and complete clinical responses after 8 weeks of therapy. A substantial partial response (by RANO [Response Assessment in Neuro-Oncology] criteria) was observed in the patient with ganglioglioma. The patient with craniopharyngioma developed dramatic, diffuse verrucal keratosis within 2 weeks of starting dabrafenib. This completely resolved within 2 weeks of adding trametinib., Conclusions: Dual BRAF/MEK inhibitor therapy represents an exciting treatment option for patients with BRAF V600E primary brain tumors. In addition to greater efficacy than single-agent dabrafenib, this combination has the potential to mitigate cutaneous toxicity, one of the most common and concerning BRAF inhibitor-related adverse events.

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., Competing Interests: The authors have declared that no competing interests exist.

Exosomes are 20-100 nm cellular derived vesicles that upon discovery, were thought to be a form of cellular recycling of intracellular contents. More recently, these vesicles are under investigation for their purported significant roles in intercellular communication in both healthy and diseased states. Herein, we focus on the secretion of exosomes associated with glioblastoma, as most exosome studies on brain tumors have been performed in this tumor type. However, we included exosomes secreted from other forms of brain tumors for comparison as available. Exosomes contain intracellular content that can be transferred to other cells in the tumor or to cells of the immune system and endothelial cells. These recipient cells may subsequently take on oncogenic properties, including therapeutic resistance, cancer progression, and angiogenesis. Genetic components (DNA, RNA and miRNA) of the cell of origin may be included in the secreted exosomes. The presence of genetic material in the exosomes could serve as a biomarker for mutations in tumors, potentially leading to novel treatment strategies. In the last decade, exosomes have been identified as having a major impact on multiple aspects of medicine and tumor biology, and appear to be primed for a critical position in cancer diagnosis, prognosis, and treatment., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background: The standard of care for glioblastoma is surgical resection followed by combination temozolomide and radiation. Magnetic resonance imaging (MRI) is used preoperatively for tumor resection planning. In some instances, MRI is also obtained postoperatively to assess for any complications and to determine extent of resection. There is some question whether early routine postoperative imaging of patients after tumor resection is beneficial to long-term outcomes, especially with the increased scrutiny of increasing health care costs., Methods: In this study we retrospectively analyze patients with glioblastoma treated at our institution, comparing the difference in overall survival and treatment regimens between patients who had early postoperative MRI versus patients who did not., Results: We determine that in our cohort of 125 patients, those with early postoperative MRI had no statistically significant overall survival difference compared with patients with no early postoperative MRI (P = 0.996). The median survival for the group with postoperative MRI was 378 days (95% confidence interval [CI], 242-443 days), and the median survival for the group without postoperative MRI was 308 days (95% CI, 203-445 days). Early postoperative MRI also did not significantly alter therapeutic regimens., Conclusions: Although early postoperative MRI may not significantly affect patient overall survival from a statistical standpoint or therapeutic regimens, this type of imaging may be important to hone resident and attending skill. We encourage other institutions to perform similar analyses to determine the overall survival benefit of early postoperative imaging after glioma resection for patients with glioblastoma., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Malignant 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., Methods: The 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., Results: IL-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., Conclusions: The 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.

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., Competing Interests: CONFLICTS OF INTEREST The authors declares that they have no conflicts of interest.

Introduction: Intracranial malignant peripheral nerve sheath tumor (MPNST) is exceedingly rare. Previously reported cases of intracranial MPNST have been associated with development within a prominent cranial nerve., Methods: This is the first report of an MPNST with both nerve sheath and vascular phenotype that follows the neurovascular bundle, without arising in a major cranial nerve or in the setting of neurofibromatosis type 1 (NF1)., Results: The patient is a 14-year-old boy with a history of worsening headaches for the past several months, left-sided hearing loss, nausea, vomiting, and vertigo. MRI was performed that demonstrated a large extra-axial tumor compressing the left infratemporal posterior temporal region. The tumor was associated with significant destruction of the superior portion of the petrous bone and extension through the petrous into the upper posterior fossa, immediately below the tentorium. The patient underwent surgical debulking and adjuvant chemotherapy with doxorubicin and ifosfamide. Pathology demonstrated a variant malignant peripheral nerve sheath tumor with both nerve sheath and vascular phenotype by immunostains. The patient's symptoms improved following treatment., Conclusion: We present the first reported case of an intracranial MPNST variant that developed along the neurovascular bundle as a sarcoma with both nerve sheath and vascular phenotype through the petrous bone and not associated with a major cranial nerve or with stigmata of neurofibromatosis type 1 (NF1). Although this is an extremely unusual presentation due to location and lack of prominent cranial nerves in that location, it is not unusual for benign nerve sheath tumors to follow the neurovascular bundle through foramen of cortical long bone or pelvis. This case suggests that physicians should incorporate intracranial MPNST variant into their differential diagnosis in the cranium, even when tumor is not located near a prominent cranial nerve. Surgical debulking and adjuvant chemotherapy with doxorubicin and ifosfamide has led to improvement in patient symptoms.

Central nervous system infections can be complications of neurosurgical procedures or can occur spontaneously, and occasionally lead to devastating neurological complications, increased rate of mortality, and lengthier stays in the hospital, subsequently increasing costs. The use of intrathecal antibiotics to bypass the blood brain barrier and provide effective concentrations to the central nervous system has been described as an adjunct treatment option. However, the regimens of antibiotics utilized intrathecally have not been standardized. Our review of the literature included all articles from MEDLINE/PubMed and Ovid from inception to 2017 and after removing duplicates and checking for relevancy, the final number of articles yielded was 200. This review summarizes the use of antibiotics intrathecally to treat CNS infections, the dosages, therapeutic efficacies, and highlights significant side effects. The current rates of mortality in patients suffering from CNS infections is high, thus intrathecal antibiotic therapy should be considered as a potential therapeutic strategy in this patient population. Multiple antibiotics have demonstrated safety and efficacy when used intrathecally, and further studies, including clinical trials, need to be performed to elucidate their full therapeutic potential and outline proper dosing regimens., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Glioblastoma is a devastating malignancy with a dismal survival rate. Currently, there are limited prognostic markers of glioblastoma including IDH1, ATRX, MGMT, PTEN, EGFRvIII, and others. Although these biomarkers for tumor prognosis are available, a surgical biopsy must be performed for these analyses, which has morbidity involved. A non-invasive and readily available biomarker is sought after which provides clinicians prognostic information. Sodium is an electrolyte that is easily and quickly obtained through analysis of a patient's serum. Hyponatremia has been shown to have a predictive and negative prognostic indication in multiple cancer types, but the role of glioblastoma patients' serum sodium at the time of diagnosis in predicting glioblastoma patient survival has not been determined. We assessed whether hyponatremia at the time of glioblastoma diagnosis correlates to patient survival and show that in our cohort of 200 glioblastoma patients, sodium, at any level, did not significantly correlate to glioblastoma survival, unlike what is seen in multiple other cancer types. We further demonstrate that inducing hyponatremia in an orthotopic murine model of glioblastoma has no effects on tumor progression and survival.

Introduction: Dermal sinus tracts are rare congenital abnormalities characterized by an epithelium-lined tract that extends from the subcutaneous tissue to the underlying thecal sac or neural tube. These developmental anomalies can present asymptomatically with a cutaneous dimple or with devastating complications including recurrent episodes of meningitis, or neurological complications including paralysis. Dermal sinus tracts generally occur as single lesions, and the presentation of midline double dermal sinus tracts of the cervical and thoracic regions has not been previously described., Methods: Here, we present the case of a 3-year-old girl suffering from recurrent episodes of myelitis, paraparesis, and intramedullary intradural masses, who was diagnosed with double dermal sinus tracts of the cervical and thoracic regions. We also present a summary of all previous reported cases of multiple dermal sinus tracts., Results: Our patient was successfully treated surgically and is now 2 years status post her last procedure with a significant improvement in her neurologic function and normal muscle strength and tone for her age, and there was no recurrence of her symptoms., Conclusions: Early treatment with prophylactic surgery should be performed when possible, but removal of these lesions once symptoms have arisen can also lead to success, as in the case presented here. Complete excision and intradural exploration is required to excise the complete tract.

Cushing once described craniopharyngiomas as the most forbidding tumor; and, despite surgical advances decades later, craniopharyngioma resection is still extremely complex due to its location and infiltration into local structures, making gross total resection challenging. Adjuvant treatments include radiation and chemotherapy, but intratumoral therapy may emerge as an adjuvant treatment for craniopharyngiomas. Here, we present a review of the literature on this treatment modality; and, summarize the available reported cases to underline usefulness and effectiveness of this treatment method. Our review of the literature included all articles from MEDLINE/PubMed and Ovid from 1974 to 2017. All articles were assessed for relevancy before inclusion into this review. Although the role for intratumoral therapy is unclear, multiple studies have reported efficacy in the treatment of craniopharyngiomas, and current results are promising. Out of the intratumoral agents utilized, intratumoral alpha interferon seems to provide the best response and least side effects for the treatment of craniopharyngiomas. The use of intratumoral therapy has led to delay in treatment with definitive surgery or radiation, both of which are associated with significant morbidities, detrimental in developmental years of childhood. Out of the intratumoral agents utilized, intratumoral alpha interferon seems to provide the best response and least side effects for the treatment of craniopharyngiomas. These findings need to be explored further with randomized controlled trials, outlining a standard dosing regimen. Furthermore, trials in craniopharyngioma patients with these combination therapies must be performed to determine the optimal therapeutic regimen for the successful treatment of these patients., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Malignant 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., Methods: Immunohistochemistry 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., Results: Immunohistochemical 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)., Conclusions: The 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.

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.

Introduction: Brachial neuritis, commonly known as Parsonage-Turner syndrome, affects two to three people per 100,000 and presents with pain and weakness of the arm and shoulder. Brachial neuritis is uncommon in infants., Methods: Here, we present the case of a 6-month old female, who presented with right upper extremity weakness and paresis following a viral prodrome. We also present a summary of all reported cases of brachial neuritis in infants., Results: This is the youngest case of brachial neuritis diagnosed at our institution. The child was treated with prednisolone and physical therapy. The patient is now 16 months old and her symptoms have significantly improved., Conclusions: Brachial neuritis should be considered in the differential when an infant presents with sudden onset of upper limb weakness, following a viral prodrome. Finally, a genetic workup is suggested for patients with recurring episodes.

Neuroblastoma is the third most common childhood cancer, and timely diagnosis and sensitive therapeutic monitoring remain major challenges. Tumor progression and recurrence is common with little understanding of mechanisms. A major recent focus in cancer biology is the impact of exosomes on metastatic behavior and the tumor microenvironment. Exosomes have been demonstrated to contribute to the oncogenic effect on the surrounding tumor environment and also mediate resistance to therapy. The effect of genotype on exosomal phenotype has not yet been explored. We interrogated exosomes from human neuroblastoma cells that express wild-type or mutant forms of the HFE gene. HFE, one of the most common autosomal recessive polymorphisms in the Caucasian population, originally associated with hemochromatosis, has also been associated with increased tumor burden, therapeutic resistance boost, and negative impact on patient survival. Herein, we demonstrate that changes in genotype cause major differences in the molecular and functional properties of exosomes; specifically, HFE mutant derived exosomes have increased expression of proteins relating to invasion, angiogenesis, and cancer therapeutic resistance. HFE mutant derived exosomes were also shown to transfer this cargo to recipient cells and cause an increased oncogenic functionality in those recipient cells., (Copyright © 2017. Published by Elsevier B.V.)

Cadmium selenide (CdSe) based quantum dots modified with polyethylene glycol and chemically linked to interleukin-13 (IL13) were prepared with the aim of identifying the high affinity receptor (IL13Rα2) which is expressed in glioma stem cells and exosomes secreted by these cancer stem cells. IL13 conjugated quantum dots (IL13QD) were thoroughly characterized for their physicochemical properties including particle size and surface morphology. Furthermore, the specific binding of the IL13QD to glioma cells and to glioma stem cells (GSC) was verified using a competitive binding study. The exosomes were isolated from the GSC conditioned medium and the expression of IL13Rα2 in the GSC and exosomes was verified. The binding property of IL13QD to the tumor associated exosomes was initially confirmed by transmission electron microscopy. The force of attraction between the quantum dots and U251 glioma cells and the exosomes was investigated by atomic force microscopy, which indicated a higher force of binding interaction between the IL13QD and IL13Rα2 expressing glioma cells and exosomes secreted by glioma stem cells. Flow cytometry of the IL13QD and exosomes from the culture media and cerebrospinal fluid (CSF) of patients with glioma tumors indicated a distinctly populated complex pattern different from that of non-targeted quantum dots and bovine serum albumin (BSA) conjugated quantum dots confirming specific binding potential of the IL13QD to the tumor associated exosomes. The results of this study demonstrate that IL13QD can serve as an ex vivo marker for glioma stem cells and exosomes that can inform diagnosis and prognosis of patients harboring malignant disease., Statement of Significance: Functionalized quantum dots are flexible semiconductor nanomaterials which have an immense application in biomedical research. In particular, when they are functionalized with biomolecules like proteins or antibodies, they have the specialized ability to detect the expression of receptors and antigens in cells and tissues. In this study we designed a cytokine (interleukin-13) functionalized quantum dot to detect a cancer associated receptor expressed in cancer stem cells and the extracellular vesicles (exosomes) secreted by the cancer cells themselves. The binding pattern of these cytokine modified quantum dots to the cancer stem cells and exosomes alters the physical properties of the complex in the fixed and suspended form. This altered binding pattern can be monitored by a variety of techniques, including transmission electron microscopy, atomic force microscopy and flow cytometry, and subsequent characterization of this quantum dot binding profile provides useful data that can be utilized as a fingerprint to detect cancer disease progression. This type of functionalized quantum dot fingerprint is especially useful for invasive cancers including brain and other metastatic cancers and may allow for earlier detection of disease progression or recurrence, thus saving the lives of patients suffering from this devastating disease., (Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The atypical PKC isoforms, PKMζ and PKCλ have been proposed as integral substrates of long-term memory (LTM). Inhibition of these isoforms has recently been demonstrated to be sufficient for impairing the expression and maintenance of long-term potentiation. Additionally, the pseudosubstrate inhibitor, zeta inhibitory peptide (ZIP), which effectively blocks PKMζ and PKCλ, has previously been shown to disrupt associative memory; very little is known about its effects on pathological nonassociative forms of memory related to addiction. The neural and molecular substrates of memory and addiction have recently been argued to overlap. Here, we used ZIP to disrupt PKMζ and PKCλ activity to examine their role in cocaine sensitization, a nonassociative, addiction-related memory argued to underlie the transition from casual to pathological drug use. We examined the effects of both continuous and acute administration of ZIP. Even a single application of ZIP blocked the development of sensitization; sustained inhibition using osmotic pumps produced an almost complete blockade of sensitization. Further, a single application of ZIP was shown to reduce membrane-bound AMPAR expression. These results demonstrate a novel, critical role for the atypical PKC isoforms in nonassociative memory and cocaine addiction.