Christine Mau | Penn State University (original) (raw)

Papers by Christine Mau

Journal of Neurosurgery, Sep 1, 2016

Eliminating unnecessary routine head CT scanning in neurologically intact mild traumatic brain in... more Eliminating unnecessary routine head CT scanning in neurologically intact mild traumatic brain injury patients: implementation and evaluation of a new protocol seema p. anandalwar, md, 1 christine Y. mau, md, 2 chirag g. gordhan, md, 1 Neil majmundar, md, 2 ahmed meleis, md, 2 charles J. prestigiacomo, md, 2 and Ziad c. sifri, md 1 Departments of 1 Trauma Surgery and

Neuro-oncology, Nov 1, 2017

NEURO-ONCOLOGY • NOVEMBER 2017 preserved in mice lacking Ccr2, which limits macrophage recruitmen... more NEURO-ONCOLOGY • NOVEMBER 2017 preserved in mice lacking Ccr2, which limits macrophage recruitment to the brain. Anti-CD47-induced microglial phagocytosis alone was sufficient to reduce tumor burden. Under anti-CD47 treatment, macrophages changed their transcriptional profile towards a more pro-inflammatory, "M1"-polarized signature, whereas the microglial transcriptome remained unchanged as assessed by RNAseq analysis. These results emphasize the importance of both resident microglia and infiltrating macrophages in GBM progression and potential of GBM control. Moreover, CD47-Sirpα disruption promotes important phenotypic and functional status changes of resident microglia, which has critical implications for central nervous system (CNS) immunotherapies in the future.

Neurosurgery, Jan 17, 2023

BACKGROUND: Delayed hypopituitarism is the most common complication after stereotactic radiosurge... more BACKGROUND: Delayed hypopituitarism is the most common complication after stereotactic radiosurgery (SRS) for pituitary adenomas. OBJECTIVE: To investigate the relationship between neuroanatomic structure distances from the radiation target and anterior pituitary function preservation after SRS through multicenter study. METHODS: We retrospectively reviewed the International Radiosurgery Research Foundation database from January 2002 to December 2021 for adult patients undergoing SRS for pituitary adenomas with >6 months of follow-up. Distances between centers or edges of hypothalamic-pituitary axis structures and SRS target volumes were measured using MRI. The primary outcome was anterior pituitary function preservation. Predictors were analyzed using multivariable logistic regression and area under the receiver operating curve (AUROC) curve analyses. RESULTS: Four hundred eighty-seven patients were categorized by preservation (n = 384) and no preservation (n = 103) of anterior pituitary function. The mean margin dose was 19.1(6.2) Gy. Larger distance from the center of the stalk to the tumor margin isodose was a positive predictor (adjusted odds ratio [aOR] = 1.162 [1.046-1.291], P = .005), while pre-SRS hypopituitarism (aOR = 0.646 [0.405-1.031], P = .067) and larger treatment volume (aOR = 0.965 [0.929-1.002], P = .061) were near negative predictors of the primary outcome. An interaction between the treatment volume and center stalk to margin isodose distance was found (aOR = 0.980 [0.961-0.999], P = .045). Center stalk to margin isodose distance had an AUROC of 0.620 (0.557-0.693), at 3.95-mm distance. For patients with treatment volumes of <2.34 mL, center stalk to margin isodose distance had an AUROC of 0.719 (0.614-0.823), at 2.95-mm distance. CONCLUSION: Achieving a distance between the center of the pituitary stalk and the tumor margin isodose ≥3.95 mm predicted anterior pituitary function preservation. For smaller treatment volumes <2.34 mL, the optimal distance was ≥2.95 mm. This may be modifiable during trans-sphenoidal resection to preserve pituitary function.

Journal of The American College of Surgeons, Oct 1, 2015

Clinical Neurology and Neurosurgery, Sep 1, 2019

Highlights  Neuroleukemiosis involves peripheral nerve infiltration by leukemic cells  Presenta... more Highlights  Neuroleukemiosis involves peripheral nerve infiltration by leukemic cells  Presentations include peripheral neuropathy and/or chloromatous masses  Diagnosis is supported by electrophysiologic testing and imaging  Diagnosis is established by biopsy and immunophenotyping  Treatment options include surgical resection, chemotherapy, donor lymphocyte infusions,

Journal of Clinical Neuroscience, Feb 1, 2018

The authors provide an update on the clinical manifestations, diagnosis and various approaches to... more The authors provide an update on the clinical manifestations, diagnosis and various approaches to the treatment of superior semicircular canal dehiscence (SSCD). SSCD is a rare condition where the bone overlying the superior semicircular canal thins or dehisces causing characteristic clinical findings. Since this was first reported in 1998 by Minor and colleagues, there has been much advancement made in terms of diagnosis and treatment. Signs and symptoms include a wide variation of both vestibular and auditory manifestations. Diagnosis made solely on clinical signs is difficult due to how varied the presentations can be and the overlap with other otologic pathologies. High-resolution CT temporal scans have been the standard in confirming superior semicircular canal dehiscence, however, MRI FIESTA scans have recently been used to image SSCD. Additionally, audiometry and vestibular evoked myogenic potential (VEMP) testing are useful screening tools. Currently, the middle fossa approach is the most common and standard surgical approach to repair SSCD. The transmastoid, endoscopic and transcanal or endaural approaches have also been recently utilized. Presently, there is no consensus as to the best approach, material or technique for repair of SSCD. As we learn more, newer and less invasive approaches and techniques are being used to treat SSCD. We present a comprehensive review of SSCD, including clinical symptoms and presentation, histopathology, diagnosis, treatment strategies and outcomes of intervention.

31st Annual Meeting North American Skull Base Society, 2022

World Neurosurgery, 2021

Admiral Lord Horatio Nelson is perhaps the most renowned naval commander who allowed Britain to h... more Admiral Lord Horatio Nelson is perhaps the most renowned naval commander who allowed Britain to have dominion over the sea for 100 years after his victory at the Battle of Trafalgar. He was able to do so despite suffering from a multitude of communicable diseases and traumatic injuries including the functional loss of his right eye, amputation of his right arm, scalp laceration, head injury and finally a spinal injury. These injuries had permanent consequences but did not stop him from leading the charge and allowing the British to defeat the French and Spanish fleets in the decisive Battle of Trafalgar.

32nd Annual Meeting North American Skull Base Society

32nd Annual Meeting North American Skull Base Society

Child's Nervous System

Medulloepithelioma is a rare, malignant tumor that typically arises in the periventricular region... more Medulloepithelioma is a rare, malignant tumor that typically arises in the periventricular region of the cerebral hemispheres or the ciliary body of the eye. Even rarer still is the extracranial manifestation of medulloepithelioma with only 12 cases reported to date. Our purpose is to report a case of an intradural, extra-medullary medulloepithelioma and review the limited literature about diagnosis and treatment of this extremely rare pathology. PubMed was queried using search terms “peripheral medulloepithelioma” and “pre-sacral medulloepithelioma.” Medulloepitheliomas which were intraocular or occurred in reproductive organs were excluded. Patients’ age, sex, the symptomatic period prior to diagnosis, primary tumor site, stage, treatment regimen, pathologic description, and survival outcomes were collected. We present a case of extracranial medulloepithelioma in an 8-year-old male. Morphology of the neoplasm was representative of medulloepithelioma but there was no amplification of C19MC. Additionally, the neoplasm stained positive for CD99. Twelve other cases of extracranial medulloepithelioma were found in literature review. The rarity of extracranial medulloepithelioma makes for a challenging diagnosis. Designing an optimal treatment strategy is difficult because of a scarcity of cases and wide variety in locations and treatments. Our case provides an example of treatment including resection, intense induction chemotherapy, consolidation with high-dose chemotherapy and stem cell rescue, craniospinal proton radiation therapy, and metronomic chemotherapy.

Cureus

Introduction: Atypical Teratoid/Rhabdoid tumors are rare, highly malignant tumors in adults, with... more Introduction: Atypical Teratoid/Rhabdoid tumors are rare, highly malignant tumors in adults, with a median survival of 20 months. We report a case of a sellar atypical teratoid/rhabdoid tumor in a 70-year-old female treated with intraventricular chemotherapy, followed by a systematic review of the current management of sellar AT/RTs. Methods: A comprehensive systematic literature search was conducted on Web of Science, Scopus, and PubMed Central using the key terms "sellar" and "atypical teratoid/rhabdoid tumors", following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data, including patient demographics, histology, treatments, and overall survival were extracted and analyzed. Kaplan-Meier survival curves and log-rank analysis were used to compare survival outcomes between different treatment regimens. Results: Our literature search disclosed 123 publications. After prespecified exclusions, 41 patients with sellar AT/RT from 30 manuscripts were identified, and 38 were included in the final analysis. Including our patient, the median age was 44 (range: 20-70) with a substantial female predominance (94.7%). Collectively, patients who received combined chemoradiation therapy had a significantly increased overall survival compared to those who received single modality or no adjuvant therapies (median OS 27 vs. 1.25 months; p=0.0052). Conclusion: Atypical teratoid/rhabdoid tumor in the sellar region carries a poor prognosis. Adjuvant chemotherapy and radiation therapy were associated with significantly increased overall survival. Early consideration of neuro-oncology and radiation-oncology referral and management is likely beneficial in this patient population. Intrathecal chemotherapy is a treatment modality that requires further exploration given the limited options and current dismal prognosis of adult sellar AT/RT.

World neurosurgery, 2021

BACKGROUND Myxopapillary ependymomas (MPE) with anaplastic features are rarely reported with only... more BACKGROUND Myxopapillary ependymomas (MPE) with anaplastic features are rarely reported with only 21 cases identified to date, and long-term recurrence is rarely presented. The purpose of this case series is to expand understanding of this disease by describing three unique cases, including two that arose from myxopapillary ependymoma after a prolonged clinical course. METHODS A review of literature and three cases of MPE with anaplastic features are described. RESULTS Patient 1 is a 13-year-old male who presented with an avidly enhancing intradural lumbar mass. Upon gross total resection, the tumor was found to be a solid mass with areas of myxopapillary architecture and a MIB-1 (Ki-67) index of 12%. Patient 2 is a female who initially presented at age 22 with a lumbosacral tumor that treated with surgery and radiation. A recurrent tumor was resected at age 24. Twenty-six years later, at age 50, the patient presented with a large heterogeneous exophytic mass in the sacrum extending...

World neurosurgery, 2020

Admiral Lord Horatio Nelson is perhaps the most renowned naval commander who allowed Britain to h... more Admiral Lord Horatio Nelson is perhaps the most renowned naval commander who allowed Britain to have dominion over the sea for 100 years after his victory at the Battle of Trafalgar. He was able to do so despite suffering from a multitude of communicable diseases and traumatic injuries including the functional loss of his right eye, amputation of his right arm, scalp laceration, head injury and finally a spinal injury. These injuries had permanent consequences but did not stop him from leading the charge and allowing the British to defeat the French and Spanish fleets in the decisive Battle of Trafalgar.

Cureus, 2021

Arachnoiditis ossificans (AO) is a rare spinal pathology that develops because of bony metaplasia... more Arachnoiditis ossificans (AO) is a rare spinal pathology that develops because of bony metaplasia secondary to chronic inflammation. AO may present with debilitating myelopathy secondary to nerve root compression, making it distinct from spinal calcification commonly seen with aging. AO is extremely rare, having been reported less than 100 times, most commonly in the thoracic spine. Even rarer still, AO has been associated with syringomyelia and arachnoid cyst because of associated cerebrospinal fluid (CSF) flow disruption. In this report, we describe a case of AO that presented with right shoulder pain, right-hand numbness, and bilateral lower extremity fatigue who had syringomyelia and arachnoid cyst discovered on MRI imaging. When brought to the operating room for syrinx shunting and cyst fenestration the dural opening was complicated by severe calcification and a diagnosis of AO was made. The patient was treated with partial resection of the calcified plaques. Syringomyelia shun...

Neuro-Oncology, Nov 1, 2017

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that arise from periph... more Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that arise from peripheral nerves. A target of MPNSTs is the receptor for interleukin-13 (IL-13R). IL-13R has an α1 and α2 subtype, and activation of α1 leads to caspase-3 mediated apoptosis. MPNSTs have increased expression of the α2 subtype, IL-13Rα2. IL-13Rα2 is an oncogene that acts as a decoy receptor which has a higher affinity for IL-13, allowing cancer to evade death by binding and sequestering all of the IL-13 thus inhibiting α1 activation. Decreased α1 activation enhances tumor cell survival and augments the high potential for metastasis. The subsequent increased tumorigenicity is then followed by the devastating prognosis with five year survival ranging from a dismal 15-60%. MPNSTs are currently treated with surgical resection, sometimes requiring complete limb amputation, as well as chemoradiation, all of which demonstrate limited effectiveness, and highlight the necessity for novel therapies. The goal of this study was to demonstrate the effectiveness of intratumoral Interleukin-13 targeted pseudomonas exotoxin (IL13E13K-PE4E) for MPNST treatment. The upregulated IL-13Rα2 on MPNSTs provides a unique opportunity for utilizing IL13E13K-PE4E to precisely target MPNSTs and cause tumor cell death. We demonstrate that IL13E13K-PE4E treatment led to a 4-fold decrease in tumor progression in vivo. IHC analysis showed increased necrosis, decreased Ki67, and increased cleaved caspase-3, corroborating the in vivo findings. The specific targeting of IL-13Rα2 also leads to a decreased side effect profile due to minimal IL-13Rα2 expression in normal tissues. The current MPNST treatment paradigm is composed of 3-prongs: surgery, chemotherapy, and radiation, all of which have been demonstrated to be unsatisfactory. This study lays the groundwork for the change of this paradigm and subsequently optimal patient outcomes by the addition of a 4th prong, intratumoral treatment with IL13E13K-PE4E.

Neuro-Oncology, Nov 1, 2017

Glioblastoma Multiforme (GBM) is the most common CNS malignancy in adults, and even with multimod... more Glioblastoma Multiforme (GBM) is the most common CNS malignancy in adults, and even with multimodal therapies, carries a poor prognosis. These tumors are heterogeneous and modify their environment, promoting tumor growth, invasion, and therapeutic resistance. The intratumoral heterogeneity of GBM is accentuated during treatment. Even in the face of surgical resection and adjuvant chemoradiation, the unfortunate but inevitable recurrence and progression of GBM is nearly universal. This mechanism of acquired radiation resistance is not understood. We believe that acquired resistance of GBM is due to exosomes secreted from radiated GBM cells conferring resistance to the local cell population. Exosomes are nanometer cell-derived vesicles containing RNAs and proteins. Growing evidence demonstrates exosomes are instrumental to a cell’s interaction with its microenvironment, and have the ability to transfer information to recipient cells contributing to tumorigenicity. We utilized nanoparticle tracking analysis to analyze characteristics of exosome secretion after exposure to radiation. We used cell proliferation assays and cell survival assays to interrogate radiation derived exosome effects on the local cancer cell population. We assessed the potential of exosome blocking agents as a possible avenue for therapeutic manipulation to abrogate this oncogenic effect. We demonstrate that resistance and proliferative factors in GBM derived exosomes change after radiation exposure. Moreover, radiation derived exosomes have functional impact on tumor cell proliferation and radiation resistance. We also demonstrate the therapeutic potential of exosome blocking agents to inhibit acquired resistance, which develops in nearly all GBM patients. Radiation-derived exosomes cause increases in cellular proliferation and survival in the local cancer cell population and may be the hidden mediators of an ultimately radiation resistant tumor recurrence and the dire prognosis that follows. Adjuvant therapy with exosome blocking agents may be used to inhibit these oncogenic effects, leading to optimal patient outcomes.

Journal of Neurosurgery

OBJECTIVE Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for ... more OBJECTIVE Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact ...

Journal of Neurosurgery, Sep 1, 2016

Eliminating unnecessary routine head CT scanning in neurologically intact mild traumatic brain in... more Eliminating unnecessary routine head CT scanning in neurologically intact mild traumatic brain injury patients: implementation and evaluation of a new protocol seema p. anandalwar, md, 1 christine Y. mau, md, 2 chirag g. gordhan, md, 1 Neil majmundar, md, 2 ahmed meleis, md, 2 charles J. prestigiacomo, md, 2 and Ziad c. sifri, md 1 Departments of 1 Trauma Surgery and

Neuro-oncology, Nov 1, 2017

NEURO-ONCOLOGY • NOVEMBER 2017 preserved in mice lacking Ccr2, which limits macrophage recruitmen... more NEURO-ONCOLOGY • NOVEMBER 2017 preserved in mice lacking Ccr2, which limits macrophage recruitment to the brain. Anti-CD47-induced microglial phagocytosis alone was sufficient to reduce tumor burden. Under anti-CD47 treatment, macrophages changed their transcriptional profile towards a more pro-inflammatory, "M1"-polarized signature, whereas the microglial transcriptome remained unchanged as assessed by RNAseq analysis. These results emphasize the importance of both resident microglia and infiltrating macrophages in GBM progression and potential of GBM control. Moreover, CD47-Sirpα disruption promotes important phenotypic and functional status changes of resident microglia, which has critical implications for central nervous system (CNS) immunotherapies in the future.

Neurosurgery, Jan 17, 2023

BACKGROUND: Delayed hypopituitarism is the most common complication after stereotactic radiosurge... more BACKGROUND: Delayed hypopituitarism is the most common complication after stereotactic radiosurgery (SRS) for pituitary adenomas. OBJECTIVE: To investigate the relationship between neuroanatomic structure distances from the radiation target and anterior pituitary function preservation after SRS through multicenter study. METHODS: We retrospectively reviewed the International Radiosurgery Research Foundation database from January 2002 to December 2021 for adult patients undergoing SRS for pituitary adenomas with >6 months of follow-up. Distances between centers or edges of hypothalamic-pituitary axis structures and SRS target volumes were measured using MRI. The primary outcome was anterior pituitary function preservation. Predictors were analyzed using multivariable logistic regression and area under the receiver operating curve (AUROC) curve analyses. RESULTS: Four hundred eighty-seven patients were categorized by preservation (n = 384) and no preservation (n = 103) of anterior pituitary function. The mean margin dose was 19.1(6.2) Gy. Larger distance from the center of the stalk to the tumor margin isodose was a positive predictor (adjusted odds ratio [aOR] = 1.162 [1.046-1.291], P = .005), while pre-SRS hypopituitarism (aOR = 0.646 [0.405-1.031], P = .067) and larger treatment volume (aOR = 0.965 [0.929-1.002], P = .061) were near negative predictors of the primary outcome. An interaction between the treatment volume and center stalk to margin isodose distance was found (aOR = 0.980 [0.961-0.999], P = .045). Center stalk to margin isodose distance had an AUROC of 0.620 (0.557-0.693), at 3.95-mm distance. For patients with treatment volumes of <2.34 mL, center stalk to margin isodose distance had an AUROC of 0.719 (0.614-0.823), at 2.95-mm distance. CONCLUSION: Achieving a distance between the center of the pituitary stalk and the tumor margin isodose ≥3.95 mm predicted anterior pituitary function preservation. For smaller treatment volumes <2.34 mL, the optimal distance was ≥2.95 mm. This may be modifiable during trans-sphenoidal resection to preserve pituitary function.

Journal of The American College of Surgeons, Oct 1, 2015

Clinical Neurology and Neurosurgery, Sep 1, 2019

Highlights  Neuroleukemiosis involves peripheral nerve infiltration by leukemic cells  Presenta... more Highlights  Neuroleukemiosis involves peripheral nerve infiltration by leukemic cells  Presentations include peripheral neuropathy and/or chloromatous masses  Diagnosis is supported by electrophysiologic testing and imaging  Diagnosis is established by biopsy and immunophenotyping  Treatment options include surgical resection, chemotherapy, donor lymphocyte infusions,

Journal of Clinical Neuroscience, Feb 1, 2018

The authors provide an update on the clinical manifestations, diagnosis and various approaches to... more The authors provide an update on the clinical manifestations, diagnosis and various approaches to the treatment of superior semicircular canal dehiscence (SSCD). SSCD is a rare condition where the bone overlying the superior semicircular canal thins or dehisces causing characteristic clinical findings. Since this was first reported in 1998 by Minor and colleagues, there has been much advancement made in terms of diagnosis and treatment. Signs and symptoms include a wide variation of both vestibular and auditory manifestations. Diagnosis made solely on clinical signs is difficult due to how varied the presentations can be and the overlap with other otologic pathologies. High-resolution CT temporal scans have been the standard in confirming superior semicircular canal dehiscence, however, MRI FIESTA scans have recently been used to image SSCD. Additionally, audiometry and vestibular evoked myogenic potential (VEMP) testing are useful screening tools. Currently, the middle fossa approach is the most common and standard surgical approach to repair SSCD. The transmastoid, endoscopic and transcanal or endaural approaches have also been recently utilized. Presently, there is no consensus as to the best approach, material or technique for repair of SSCD. As we learn more, newer and less invasive approaches and techniques are being used to treat SSCD. We present a comprehensive review of SSCD, including clinical symptoms and presentation, histopathology, diagnosis, treatment strategies and outcomes of intervention.

31st Annual Meeting North American Skull Base Society, 2022

World Neurosurgery, 2021

Admiral Lord Horatio Nelson is perhaps the most renowned naval commander who allowed Britain to h... more Admiral Lord Horatio Nelson is perhaps the most renowned naval commander who allowed Britain to have dominion over the sea for 100 years after his victory at the Battle of Trafalgar. He was able to do so despite suffering from a multitude of communicable diseases and traumatic injuries including the functional loss of his right eye, amputation of his right arm, scalp laceration, head injury and finally a spinal injury. These injuries had permanent consequences but did not stop him from leading the charge and allowing the British to defeat the French and Spanish fleets in the decisive Battle of Trafalgar.

32nd Annual Meeting North American Skull Base Society

32nd Annual Meeting North American Skull Base Society

Child's Nervous System

Medulloepithelioma is a rare, malignant tumor that typically arises in the periventricular region... more Medulloepithelioma is a rare, malignant tumor that typically arises in the periventricular region of the cerebral hemispheres or the ciliary body of the eye. Even rarer still is the extracranial manifestation of medulloepithelioma with only 12 cases reported to date. Our purpose is to report a case of an intradural, extra-medullary medulloepithelioma and review the limited literature about diagnosis and treatment of this extremely rare pathology. PubMed was queried using search terms “peripheral medulloepithelioma” and “pre-sacral medulloepithelioma.” Medulloepitheliomas which were intraocular or occurred in reproductive organs were excluded. Patients’ age, sex, the symptomatic period prior to diagnosis, primary tumor site, stage, treatment regimen, pathologic description, and survival outcomes were collected. We present a case of extracranial medulloepithelioma in an 8-year-old male. Morphology of the neoplasm was representative of medulloepithelioma but there was no amplification of C19MC. Additionally, the neoplasm stained positive for CD99. Twelve other cases of extracranial medulloepithelioma were found in literature review. The rarity of extracranial medulloepithelioma makes for a challenging diagnosis. Designing an optimal treatment strategy is difficult because of a scarcity of cases and wide variety in locations and treatments. Our case provides an example of treatment including resection, intense induction chemotherapy, consolidation with high-dose chemotherapy and stem cell rescue, craniospinal proton radiation therapy, and metronomic chemotherapy.

Cureus

Introduction: Atypical Teratoid/Rhabdoid tumors are rare, highly malignant tumors in adults, with... more Introduction: Atypical Teratoid/Rhabdoid tumors are rare, highly malignant tumors in adults, with a median survival of 20 months. We report a case of a sellar atypical teratoid/rhabdoid tumor in a 70-year-old female treated with intraventricular chemotherapy, followed by a systematic review of the current management of sellar AT/RTs. Methods: A comprehensive systematic literature search was conducted on Web of Science, Scopus, and PubMed Central using the key terms "sellar" and "atypical teratoid/rhabdoid tumors", following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data, including patient demographics, histology, treatments, and overall survival were extracted and analyzed. Kaplan-Meier survival curves and log-rank analysis were used to compare survival outcomes between different treatment regimens. Results: Our literature search disclosed 123 publications. After prespecified exclusions, 41 patients with sellar AT/RT from 30 manuscripts were identified, and 38 were included in the final analysis. Including our patient, the median age was 44 (range: 20-70) with a substantial female predominance (94.7%). Collectively, patients who received combined chemoradiation therapy had a significantly increased overall survival compared to those who received single modality or no adjuvant therapies (median OS 27 vs. 1.25 months; p=0.0052). Conclusion: Atypical teratoid/rhabdoid tumor in the sellar region carries a poor prognosis. Adjuvant chemotherapy and radiation therapy were associated with significantly increased overall survival. Early consideration of neuro-oncology and radiation-oncology referral and management is likely beneficial in this patient population. Intrathecal chemotherapy is a treatment modality that requires further exploration given the limited options and current dismal prognosis of adult sellar AT/RT.

World neurosurgery, 2021

BACKGROUND Myxopapillary ependymomas (MPE) with anaplastic features are rarely reported with only... more BACKGROUND Myxopapillary ependymomas (MPE) with anaplastic features are rarely reported with only 21 cases identified to date, and long-term recurrence is rarely presented. The purpose of this case series is to expand understanding of this disease by describing three unique cases, including two that arose from myxopapillary ependymoma after a prolonged clinical course. METHODS A review of literature and three cases of MPE with anaplastic features are described. RESULTS Patient 1 is a 13-year-old male who presented with an avidly enhancing intradural lumbar mass. Upon gross total resection, the tumor was found to be a solid mass with areas of myxopapillary architecture and a MIB-1 (Ki-67) index of 12%. Patient 2 is a female who initially presented at age 22 with a lumbosacral tumor that treated with surgery and radiation. A recurrent tumor was resected at age 24. Twenty-six years later, at age 50, the patient presented with a large heterogeneous exophytic mass in the sacrum extending...

World neurosurgery, 2020

Admiral Lord Horatio Nelson is perhaps the most renowned naval commander who allowed Britain to h... more Admiral Lord Horatio Nelson is perhaps the most renowned naval commander who allowed Britain to have dominion over the sea for 100 years after his victory at the Battle of Trafalgar. He was able to do so despite suffering from a multitude of communicable diseases and traumatic injuries including the functional loss of his right eye, amputation of his right arm, scalp laceration, head injury and finally a spinal injury. These injuries had permanent consequences but did not stop him from leading the charge and allowing the British to defeat the French and Spanish fleets in the decisive Battle of Trafalgar.

Cureus, 2021

Arachnoiditis ossificans (AO) is a rare spinal pathology that develops because of bony metaplasia... more Arachnoiditis ossificans (AO) is a rare spinal pathology that develops because of bony metaplasia secondary to chronic inflammation. AO may present with debilitating myelopathy secondary to nerve root compression, making it distinct from spinal calcification commonly seen with aging. AO is extremely rare, having been reported less than 100 times, most commonly in the thoracic spine. Even rarer still, AO has been associated with syringomyelia and arachnoid cyst because of associated cerebrospinal fluid (CSF) flow disruption. In this report, we describe a case of AO that presented with right shoulder pain, right-hand numbness, and bilateral lower extremity fatigue who had syringomyelia and arachnoid cyst discovered on MRI imaging. When brought to the operating room for syrinx shunting and cyst fenestration the dural opening was complicated by severe calcification and a diagnosis of AO was made. The patient was treated with partial resection of the calcified plaques. Syringomyelia shun...

Neuro-Oncology, Nov 1, 2017

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that arise from periph... more Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that arise from peripheral nerves. A target of MPNSTs is the receptor for interleukin-13 (IL-13R). IL-13R has an α1 and α2 subtype, and activation of α1 leads to caspase-3 mediated apoptosis. MPNSTs have increased expression of the α2 subtype, IL-13Rα2. IL-13Rα2 is an oncogene that acts as a decoy receptor which has a higher affinity for IL-13, allowing cancer to evade death by binding and sequestering all of the IL-13 thus inhibiting α1 activation. Decreased α1 activation enhances tumor cell survival and augments the high potential for metastasis. The subsequent increased tumorigenicity is then followed by the devastating prognosis with five year survival ranging from a dismal 15-60%. MPNSTs are currently treated with surgical resection, sometimes requiring complete limb amputation, as well as chemoradiation, all of which demonstrate limited effectiveness, and highlight the necessity for novel therapies. The goal of this study was to demonstrate the effectiveness of intratumoral Interleukin-13 targeted pseudomonas exotoxin (IL13E13K-PE4E) for MPNST treatment. The upregulated IL-13Rα2 on MPNSTs provides a unique opportunity for utilizing IL13E13K-PE4E to precisely target MPNSTs and cause tumor cell death. We demonstrate that IL13E13K-PE4E treatment led to a 4-fold decrease in tumor progression in vivo. IHC analysis showed increased necrosis, decreased Ki67, and increased cleaved caspase-3, corroborating the in vivo findings. The specific targeting of IL-13Rα2 also leads to a decreased side effect profile due to minimal IL-13Rα2 expression in normal tissues. The current MPNST treatment paradigm is composed of 3-prongs: surgery, chemotherapy, and radiation, all of which have been demonstrated to be unsatisfactory. This study lays the groundwork for the change of this paradigm and subsequently optimal patient outcomes by the addition of a 4th prong, intratumoral treatment with IL13E13K-PE4E.

Neuro-Oncology, Nov 1, 2017

Glioblastoma Multiforme (GBM) is the most common CNS malignancy in adults, and even with multimod... more Glioblastoma Multiforme (GBM) is the most common CNS malignancy in adults, and even with multimodal therapies, carries a poor prognosis. These tumors are heterogeneous and modify their environment, promoting tumor growth, invasion, and therapeutic resistance. The intratumoral heterogeneity of GBM is accentuated during treatment. Even in the face of surgical resection and adjuvant chemoradiation, the unfortunate but inevitable recurrence and progression of GBM is nearly universal. This mechanism of acquired radiation resistance is not understood. We believe that acquired resistance of GBM is due to exosomes secreted from radiated GBM cells conferring resistance to the local cell population. Exosomes are nanometer cell-derived vesicles containing RNAs and proteins. Growing evidence demonstrates exosomes are instrumental to a cell’s interaction with its microenvironment, and have the ability to transfer information to recipient cells contributing to tumorigenicity. We utilized nanoparticle tracking analysis to analyze characteristics of exosome secretion after exposure to radiation. We used cell proliferation assays and cell survival assays to interrogate radiation derived exosome effects on the local cancer cell population. We assessed the potential of exosome blocking agents as a possible avenue for therapeutic manipulation to abrogate this oncogenic effect. We demonstrate that resistance and proliferative factors in GBM derived exosomes change after radiation exposure. Moreover, radiation derived exosomes have functional impact on tumor cell proliferation and radiation resistance. We also demonstrate the therapeutic potential of exosome blocking agents to inhibit acquired resistance, which develops in nearly all GBM patients. Radiation-derived exosomes cause increases in cellular proliferation and survival in the local cancer cell population and may be the hidden mediators of an ultimately radiation resistant tumor recurrence and the dire prognosis that follows. Adjuvant therapy with exosome blocking agents may be used to inhibit these oncogenic effects, leading to optimal patient outcomes.

Journal of Neurosurgery

OBJECTIVE Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for ... more OBJECTIVE Stereotactic radiosurgery (SRS) provides a safe and effective therapeutic modality for patients with pituitary adenomas. The mechanism of delayed endocrine deficits based on targeted radiation to the hypothalamic-pituitary axis remains unclear. Radiation to normal neuroendocrine structures likely plays a role in delayed hypopituitarism after SRS. In this multicenter study by the International Radiosurgery Research Foundation (IRRF), the authors aimed to evaluate radiation tolerance of structures surrounding pituitary adenomas and identify predictors of delayed hypopituitarism after SRS for these tumors. METHODS This is a retrospective review of patients with pituitary adenomas who underwent single-fraction SRS from 1997 to 2019 at 16 institutions within the IRRF. Dosimetric point measurements of 14 predefined neuroanatomical structures along the hypothalamus, pituitary stalk, and normal pituitary gland were made. Statistical analyses were performed to determine the impact ...