Dorsal Scapular Artery Variations and Relationship to the Brachial Plexus, and a Related Thoracic Outlet Syndrome Case.

Rationale Knowledge of the relationship of the dorsal scapular artery (DSA) with the brachial plexus is limited. Objective We report a case of a variant DSA path, and revisit DSA origins and under-investigated relationship with the plexus in cadavers. Methods The DSA was examined in a male patient and 106 cadavers. Results In the case, we observed an unusual DSA compressing the lower plexus trunk, that resulted in intermittent radiating pain and paresthesia. In the cadavers, the DSA originated most commonly from the subclavian artery (71%), with 35% from the thyrocervical trunk. Nine sides of eight cadavers (seven females) had two DSA branches per side, with one branch from each origin. The most typical DSA path was a subclavian artery origin before passing between upper and middle brachial plexus trunks (40% of DSAs), versus between middle and lower trunks (23%), or inferior (4%) or superior to the plexus (1%). Following a thyrocervical trunk origin, the DSA passed most frequently superior to the plexus (23%), versus between middle and lower trunks (6%) or upper and middle trunks (4%). Bilateral symmetry in origin and path through the brachial plexus was observed in 13 of 35 females (37%) and 6 of 17 males (35%), with the most common bilateral finding of a subclavian artery origin and a path between upper and middle trunks (17%). Conclusion Variability in the relationship between DSA and trunks of the brachial plexus has surgical and clinical implications, such as diagnosis of thoracic outlet syndrome.

Odontoid pseudotumor and serial postfusion radiographic evaluation in a patient with a C1-2 mass.

Odontoid pseudotumor is a mass occurring around the odontoid process in the cervical spine and can cause significant neurological symptoms at the craniocervical junction due to compression of the spinal cord and cervicomedullary junction at this level. A literature review was performed to provide input on options for treatment and prognosis for this lesion. The literature search found 12 papers in which pseudotumor was treated with posterior decompression and fixation. Posterior decompression and fixation with serial imaging to monitor the size of the pseudotumor postsurgery is a safe and effective treatment option for odontoid pseudotumors.

Antivascular endothelial growth factor antibody for treatment of glioblastoma multiforme.

Despite aggressive investigation, glioblastoma multiforme (GBM) remains one of the deadliest cancers, with low progression-free survival and high one-year mortality. Current first-line therapy includes surgery with adjuvant radiation therapy and cytotoxic chemotherapy, but virtually all tumors recur. Given the highly vascular nature of GBM and its high expression of vascular endothelial growth factor and other angiogenic factors, recent investigation has turned to bevacizumab, an antivascular endothelial growth factor monoclonal antibody, for treatment of recurrent GBM. Phase 2 studies demonstrated the efficacy and safety of bevacizumab therapy for recurrent GBM, which led to its approval by the US Food and Drug Administration in 2009 for use in recurrent GBM. Since then, several new Phase 2 studies and retrospective series have demonstrated that bevacizumab significantly increased six-month progression-free survival in patients with recurrent GBM and may do so in new-onset GBM. The objective of this review is to provide a collective resource for these materials, highlighting the efficacy and safety of bevacizumab and calling for increased investigation toward its optimal application in the management of high-grade glioma.

Proteasome inhibition with bortezomib induces cell death in GBM stem-like cells and temozolomide-resistant glioma cell lines, but stimulates GBM stem-like cells' VEGF production and angiogenesis.

OBJECT: Recurrent malignant gliomas have inherent resistance to traditional chemotherapy. Novel therapies target specific molecular mechanisms involved in abnormal signaling and resistance to apoptosis. The proteasome is a key regulator of multiple cellular functions, and its inhibition in malignant astrocytic lines causes cell growth arrest and apoptotic cell death. The proteasome inhibitor bortezomib was reported to have very good in vitro activity against malignant glioma cell lines, with modest activity in animal models as well as in clinical trials as a single agent. In this paper, the authors describe the multiple effects of bortezomib in both in vitro and in vivo glioma models and offer a novel explanation for its seeming lack of activity. METHODS: Glioma stem-like cells (GSCs) were obtained from resected glioblastomas (GBMs) at surgery and expanded in culture. Stable glioma cell lines (U21 and D54) as well as temozolomide (TMZ)-resistant glioma cells derived from U251 and D54-MG were also cultured. GSCs from 2 different tumors, as well as D54 and U251 cells, were treated with bortezomib, and the effect of the drug was measured using an XTT cell viability assay. The activity of bortezomib was then determined in D54-MG and/or U251 cells using apoptosis analysis as well as caspase-3 activity and proteasome activity measurements. Human glioma xenograft models were created in nude mice by subcutaneous injection. Bevacizumab was administered via intraperitoneal injection at a dose of 5 mg/kg daily. Bortezomib was administered by intraperitoneal injection 1 hour after bevacizumab administration in doses of at a dose of 0.35 mg/kg on days 1, 4, 8, and 11 every 21 days. Tumors were measured twice weekly. RESULTS: Bortezomib induced caspase-3 activation and apoptotic cell death in stable glioma cell lines and in glioma stem-like cells (GSCs) derived from malignant tumor specimens Furthermore, TMZ-resistant glioma cell lines retained susceptibility to the proteasome inhibition. The bortezomib activity was directly proportional with the cells' baseline proteasome activity. The proteasome inhibition stimulated both hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) production in malignant GSCs. As such, the VEGF produced by GSCs stimulated endothelial cell growth, an effect that could be prevented by the addition of bevacizumab (VEGF antibody) to the media. Similarly, administration of bortezomib and bevacizumab to athymic mice carrying subcutaneous malignant glioma xenografts resulted in greater tumor inhibition and greater improvement in survival than administration of either drug alone. These data indicate that simultaneous proteasome inhibition and VEGF blockade offer increased benefit as a strategy for malignant glioma therapy. CONCLUSIONS: The results of this study indicate that combination therapies based on bortezomib and bevacizumab might offer an increased benefit when the two agents are used in combination. These drugs have a complementary mechanism of action and therefore can be used together to treat TMZ-resistant malignant gliomas.

The treatment of angiocentric glioma: case report and literature review.

Angiocentric glioma is a recently described tumor recognized since 2007 by the World Health Organization Classification of Tumours of the Central Nervous System. We present the only case of angiocentric glioma at our institution in the last 15 years and review the literature in an attempt to establish prognostic parameters. Our search revealed only 27 cases of angiocentric glioma in the literature. The most common presenting symptom of angiocentric glioma was seizures. Gross total resection of the lesion was curative, without need for radiation or chemotherapy.

A Review of Spasticity Treatments: Pharmacological and Interventional Approaches.

Spasticity is a velocity-dependent increase in muscle tone and uncontrolled, repetitive, involuntary contractions of skeletal muscles. Spasticity presents as upper motor neuron symptoms in patients with central nervous system pathology such as stroke, spinal cord injury, brain injury, or multiple sclerosis. As a result, a patient can have significant pain and limited mobility, which can lead to decreased quality of life and difficulty maintaining personal care. In this article we discuss mechanisms, indications, efficacy, and side effects of the most accepted current treatments. Currently available treatment options include oral medications and interventional procedures. Oral medications comprise centrally acting agents, such as baclofen, clonidine, and tizanidine, as well as anticonvulsants such as benzodiazepines and gabapentin and peripherally acting dantrolene. Interventional procedures include focal injections of botulinum toxin, phenol or alcohol, and an intrathecal baclofen pump. Surgical treatments include selective dorsal rhizotomy and neurectomy. We found that there are several treatments available with data to support their use, but many still need further research to prove their efficacy and develop optimal utilization.

Evaluation and management of vertebral compression fractures.

Compression fractures affect many individuals worldwide. An estimated 1.5 million vertebral compression fractures occur every year in the US. They are common in elderly populations, and 25% of postmenopausal women are affected by a compression fracture during their lifetime. Although these fractures rarely require hospital admission, they have the potential to cause significant disability and morbidity, often causing incapacitating back pain for many months. This review provides information on the pathogenesis and pathophysiology of compression fractures, as well as clinical manifestations and treatment options. Among the available treatment options, kyphoplasty and percutaneous vertebroplasty are two minimally invasive techniques to alleviate pain and correct the sagittal imbalance of the spine.

Neurothekeoma in the posterior fossa: case report and literature review.

Neurothekeoma is a benign nerve sheath tumor, also known as nerve sheath myxoma. It arises from the cutaneous nerves of the head and neck region. In certain cases, neurothekeoma has been reported in the breast, oral cavity, tongue, maxilla, and spinal intradural space. Intracranial neurothekeoma, however, is an extremely rare entity, with only three cases reported in the literature: one in the parasellar region, one in the deep white matter, and another one in the cerebellopontine angle. We present the case of a 40-year-old man with a very large neurothekeoma present in the posterior fossa who had no neurologic deficit on presentation.

Value of susceptibility-weighted imaging in acute hemorrhagic leukoencephalitis.

Acute hemorrhagic leukoencephalitis (AHL) is a rapidly progressive disease in the spectrum of acute disseminated encephalomyelitis. Timely accurate diagnosis is crucial but challenging clinically and radiologically. However, imaging findings of AHL are quite specific when susceptibility-weighted imaging is utilized. The purpose of this report is to present the imaging findings of autopsy-proven AHL and thus to facilitate rapid recognition and treatment.

Epidemiology of central nervous system metastases.

Brain metastases are overwhelmingly the most common type of brain tumor, out numbering primary brain tumors in incidence by more than four-to-one. They are associated with poor prognosis both from a length-of-life as well as a quality-of-life standpoint. Once the brain metastasis is detected, without treatment, most patients die within months, either from widespread systemic disease, or due to the brain metastasis itself. The complications of brain metastases are also devastating. Patients can suffer from seizures, weakness or paralysis, language and communication deficits, as well as cognitive decline. These complications negatively impact on quality of life through effects on functional independence, impairment of capacity to participate in activities and relationships, as well as distortion of individual personality and identity. At the same time, there are great financial burdens associated with both the care and treatment of patients with brain metastases. Early detection of brain metastases in cancer patients is critical for limiting these complications, minimizing these burdens and improving the outlook regarding both survival and quality of life. Understanding the epidemiology of brain metastases can lead to the development of new strategies for the early identification and successful treatment of these patients.

Pulmonary metastases in patients with recurrent, treatment-resistant meningioma: prognosis and identification by ¹¹¹Indium-octreotide imaging.

BACKGROUND: Meningioma is the most common extra-axial primary intracranial tumor in adults that rarely metastasizes outside of the central nervous system (CNS). Among recognized sites of metastases, the lung is the most common, but the importance of lung metastases relative to prognosis is unknown. ¹¹¹Indium (¹¹¹In)-octreotide scintigraphy (octreotide scanning) is a valuable imaging modality with which to evaluate intracranial meningiomas and their response to treatment with somatostatin analogues and has the potential to identify extracranial metastatic disease. METHODS: In this retrospective multicenter study, adult patients treated for recurrent meningioma were identified. These patients underwent ¹¹¹In-octreotide positron emission tomography/computed tomography imaging (octreotide scintigraphy) and were found to have positive octreotide uptake in their lungs. RESULTS: Six cases were identified with recurrent meningioma (after surgery, radiotherapy, and at least 1 chemotherapy agent) and pulmonary lesions by octreotide scintigraphy. Biopsy of a pulmonary lesion in 1 patient confirmed the diagnosis of metastatic meningioma. Patients with metastatic pulmonary involvement identified by ¹¹¹In-octreotide scintigraphy in this case series had an overall survival of 6 months, which is less than that reported from previously published series of patients with unknown systemic disease status. CONCLUSIONS: ¹¹¹In-octreotide scintigraphy is useful for assessing both CNS disease and extracranial metastases. The presence of pulmonary metastases appears to negatively affect survival in patients with recurrent meningioma. The usefulness of ¹¹¹In-octreotide scintigraphy should be considered in staging patients with recurrent meningioma who are considered for further treatment. A prospective study to confirm this finding is warranted

The use of patient navigators to improve cancer care for Hispanic patients.

BACKGROUND: Although the United States is one of the countries at the leading edge of medical breakthroughs and treatments, there are great disparities in the access to care among different socioeconomic strata. One of the most striking discrepancies regarding access to care is found among the ranks of the Hispanic population, which is the fastest growing minority in the United States, but for which cancer is the third leading cause of death. It is clear that better and timely treatment for cancer patients belonging to this minority is needed. Patient navigators can be an important tool to improve access to care of patients belonging to this minority group. METHODS: Through a systemic search, we identified seven articles that employed patient navigators for Hispanic cancer patients. The identified studies addressed very limited pathology, three studying breast and four colon cancer patients. CONCLUSIONS: The presence of patient navigation can be an effective to remove impediments that limit the access to care in minority populations and can improve outcomes in Hispanic patients suffering from cancer. Further research to evaluate the cost of patient navigation in relationship to the added benefit early diagnosis, continued follow up and treatment is needed.

Secondary fibrosarcoma of the brain stem treated with cyclophosphamide and Imatinib.

Radiation-induced midbrain fibrosarcoma is a rare, highly aggressive tumor, which is associated with poor prognosis. We present the case of a 48-year old man with brainstem fibrosarcoma 20 years following radiation therapy received for a pituitary tumor. We discuss this case in the context of the diagnostic criteria for these tumors, and previous reports of secondary and primary sarcomas of the central nervous system.

Structure and function analysis of peptide antagonists of melanoma inhibitor of apoptosis (ML-IAP).

Melanoma inhibitor of apoptosis (ML-IAP) is a potent anti-apoptotic protein that is upregulated in a number of melanoma cell lines but not expressed in most normal adult tissues. Overexpression of IAP proteins, such as ML-IAP or the ubiquitously expressed X-chromosome-linked IAP (XIAP), in human cancers has been shown to suppress apoptosis induced by a variety of stimuli. Peptides based on the processed N-terminus of Smac/DIABLO can negate the ability of overexpressed ML-IAP or XIAP to suppress drug-induced apoptosis. Such peptides have been demonstrated to bind to the single baculovirus IAP repeat (BIR) of ML-IAP and the third BIR of XIAP with similar high affinities (approximately 0.5 microM). Herein, we use phage-display of naïve peptide libraries and synthetic peptides to investigate the peptide-binding properties of ML-IAP-BIR and XIAP-BIR3. X-ray crystal structures of ML-IAP-BIR in complex with Smac- and phage-derived peptides, together with peptide structure-activity-relationship data, indicate that the peptides can be modified to provide increased binding affinity and selectivity for ML-IAP-BIR relative to XIAP-BIR3. For instance, substitution of Pro3' in the Smac-based peptide (AVPIAQKSE) with (2S,3S)-3-methylpyrrolidine-2-carboxylic acid [(3S)-methyl-proline] results in a peptide with 7-fold greater affinity for ML-IAP-BIR and about 100-fold specificity for ML-IAP-BIR relative to XIAP-BIR3.