Role of Advanced MR Imaging in Diagnosis of Neurological Malignancies: Current Status and Future Perspective.

Lesions of the central nervous system (CNS) can present with numerous and overlapping radiographical and clinical features that make diagnosis difficult based exclusively on history, physical examination, and traditional imaging modalities. Given that there are significant differences in optimal treatment protocols for these various CNS lesions, rapid and non-invasive diagnosis could lead to improved patient care. Recently, various advanced magnetic resonance imaging (MRI) techniques showed promising methods to differentiate between various tumors and lesions that conventional MRI cannot define by comparing their physiologic characteristics, such as vascularity, permeability, oxygenation, and metabolism. These advanced MRI techniques include dynamic susceptibility contrast MRI (DSC), diffusion-weighted imaging (DWI), dynamic contrast-enhanced (DCE) MRI, Golden-Angle Radial Sparse Parallel imaging (GRASP), Blood oxygen level-dependent functional MRI (BOLD fMRI), and arterial spin labeling (ASL) MRI. In this article, a narrative review is used to discuss the current trends in advanced MRI techniques and potential future applications in identifying difficult-to-distinguish CNS lesions. Advanced MRI techniques were found to be promising non-invasive modalities to differentiate between paraganglioma, schwannoma, and meningioma. They are also considered promising methods to differentiate gliomas from lymphoma, post-radiation changes, pseudoprogression, demyelination, and metastasis. Advanced MRI techniques allow clinicians to take advantage of intrinsic biological differences in CNS lesions to better identify the etiology of these lesions, potentially leading to more effective patient care and a decrease in unnecessary invasive procedures. More clinical studies with larger sample sizes should be encouraged to assess the significance of each advanced MRI technique and the specificity and sensitivity of each radiologic parameter.

Cisternotomy and Liliequist's Membrane Fenestration as a Surgical Treatment for Idiopathic Intracranial Hypertension (Pseudotumor Cerebri): A Case Report.

Subarachnoid basal cistern opening (cisternotomy) is used during many microsurgical operations to relax the brain by removing or diverting cerebrospinal fluid (CSF). Recently, cisternotomy has been used in patients with traumatic brain injury to improve outcomes due to its ability to decrease intracranial pressure (ICP) and brain edema by diverting CSF. Theoretically, another condition that can benefit from cisternotomy is idiopathic intracranial hypertension (IIH) as it presents with manifestations of increased ICP, such as headache, vomiting, and papilledema. Here, we discuss the case of a 39-year-old woman with IIH who presented with headache, nausea, and papilledema in the setting of maximally tolerated medical management after five months of shunt removal due to infection. The patient did not want to proceed with the replacement of her shunt and therefore underwent a right eyebrow craniotomy for cisternotomy, lamina terminals fenestration, and Liliequist's membrane opening. Postoperatively, her symptoms improved completely. She was off acetazolamide altogether at the three-month follow-up and no longer had pseudotumor cerebri headaches. This case report demonstrates the use of cisternotomy to relieve the manifestations of increased ICP and its potential as a surgical option for patients with IIH.

Reversal of cognitive, behavioral, and language impairments after the left frontal arachnoid cyst fenestration in a pediatric patient.

BACKGROUND: Arachnoid cysts (ACs) are cerebrospinal fluid-containing cysts located between the surface of the brain or spinal cord and arachnoid layer of the leptomeninges. ACs have been known to cause cognitive, language, and behavioral deficits and currently there is no standard treatment paradigm. Surgical indications include papilledema, increasing growth with mass effect causing neurological deficit, or rapid head growth, however, cognitive symptoms related to mass effect may not always be considered. CASE DESCRIPTION: We present a 3-year-old male with an AC of the left anterior fossa causing frontal lobe compression with resultant behavioral, language, and cognitive deficits. CONCLUSION: Surgical intervention for AC decompression may be indicated when there are cognitive, behavioral, or language delays related to the mass effect and location of the AC. Neuropsychiatric testing or more advanced imaging studies may further support surgical treatment. After craniotomy for fenestration of the left frontal AC, there was drastic improvement in cognitive, language, and behavioral symptoms in our pediatric patient.

Investigation of a Valve-Agnostic Cranial Implant for Adult Hydrocephalus Patients Requiring Ventriculoperitoneal Shunting.

INTRODUCTION: Currently, the most effective treatment strategy for adults with hydrocephalus involves cerebrospinal fluid diversion by means of a shunt system, most commonly ventriculoperitoneal shunts (VPS). Ventriculoperitoneal shunting is associated with high complication and/or revision rates, in part due to the high-profile programmable valve designs. Thus, the valve-agnostic cranial implant (VACI) was designed and investigated as a safe and effective method of reducing the valve's high profile and is currently undergoing clinical trials. As such, the objective of this study was to collate preliminary, multi-institutional data of early outcomes using a VACI approach for patients requiring VPS by way of an Institutional Review Board approved registry. METHODS: A total of 25 adult patients across 4 institutions and 6 surgeons underwent VACI placement for VPS based on preoperative evaluation and perceived benefit. Patient demographics, operative details, and preliminary outcomes are presented here. RESULTS: Valve-agnostic cranial implant placement via a limited size craniectomy at time of shunt revision was performed with no adverse events. Over an average follow-up period of 1 year (394 ±â€Š178 days), 92% of patients experienced no major shunt-related or scalp-related complications. There were 2 cases with a major complication requiring reoperation: 1 shunt tubing extrusion and 1 case of meningitis. The most frequent postsurgical intervention seen in this study was related to adjustment of drainage: a non-invasively performed valve reprogramming after initial shunt placement when proper flow rate is being established. Of the 8 cases of drainage adjustment, all but 1 (88%) were receiving a VPS for the first time, with the exception undergoing a fourth shunt revision. All instances of improper flow were treated non-surgically and remediated effectively via shunt reprogramming in clinic. Removal of the VACI was not indicated in any treatment course. In this way, all complications as they relate to the shunt valve were minor and required nonsurgical intervention, and no complications reported were directly or indirectly caused by using the VACI. CONCLUSION: Preliminary findings from this multicenter trial suggest promising outcomes with a low complication rate for patients with hydrocephalus undergoing VACI placement during VPS. Ongoing research will continue to provide a more robust clinical picture of VACI in hydrocephalus management as more data becomes available.

Case report: vertebral osteomyelitis secondary to a dental abscess.

BACKGROUND: Vertebral osteomyelitis can be attributed to many factors including immunosuppression, diabetes, malignancy, collagen disease, periodontal disease, open fractures, and endoscopic procedures. Anaerobic bacteria, such as Veillonella species, are found in the oral cavity and are rarely implicated in the infection. This report describes vertebral osteomyelitis secondary to a dental abscess with positive Veillonella cultures. CASE DESCRIPTION: A 76-year-old man presented to the hospital due to back pain with a four-day history of fever and chills. CT scans revealed several abscesses in the lumbar region as well as indications of vertebral osteomyelitis. After a psoas drain, the patient began antibiotics with a combination of ampicillin-sulbactam, metronidazole, and levofloxacin, but due to the patient's penicillin allergy, he was initially desensitized to this antibiotic for a significant period of time. Laminectomies, foraminotomies, and facetectomies were performed, but the infection spread to vertebral levels. The patient was then switched to a combination of vancomycin, metronidazole, and levofloxacin which eliminated the infection. Final laminectomy was performed with posterior segmental instrumentation and arthrodesis. Post-operatively, there were no signs of infection. The patient recovered well and regained mobility. Deeper examination of the patient's medical history revealed a severe tooth abscess immediately before the onset of bacteremia. CONCLUSION: We believe that a delay in the onset of antibiotic treatment is what led to the initial bacteremia that ultimately took root in the lower lumbar vertebrae. To the best of our ability, we could identify only one other case that linked vertebral osteomyelitis to the oral cavity.

Intrawound Vancomycin Decreases the Risk of Surgical Site Infection After Posterior Spine Surgery: A Multicenter Analysis.

STUDY DESIGN: Secondary analysis of data from a prospective multicenter observational study. OBJECTIVE: The aim of this study was to evaluate the occurrence of surgical site infection (SSI) in patients with and without intrawound vancomycin application controlling for confounding factors associated with higher SSI after elective spine surgery. SUMMARY OF BACKGROUND DATA: SSI is a morbid and expensive complication associated with spine surgery. The application of intrawound vancomycin is rapidly emerging as a solution to reduce SSI following spine surgery. The impact of intrawound vancomycin has not been systematically studied in a well-designed multicenter study. METHODS: Patients undergoing elective spine surgery over a period of 4 years at seven spine surgery centers across the United States were included in the study. Patients were dichotomized on the basis of whether intrawound vancomycin was applied. Outcomes were occurrence of SSI within postoperative 30 days and SSI that required return to the operating room (OR). Multivariable random-effect log-binomial regression analyses were conducted to determine the relative risk of having an SSI and an SSI with return to OR. RESULTS: .: A total of 2056 patients were included in the analysis. Intrawound vancomycin was utilized in 47% (n = 966) of patients. The prevalence of SSI was higher in patients with no vancomycin use (5.1%) than those with use of intrawound vancomycin (2.2%). The risk of SSI was higher in patients in whom intrawound vancomycin was not used (relative risk (RR) -2.5, P < 0.001), increased number of levels exposed (RR -1.1, P = 0.01), and those admitted postoperatively to intensive care unit (ICU) (RR -2.1, P = 0.005). Patients in whom intrawound vancomycin was not used (RR -5.9, P < 0.001), increased number of levels were exposed (RR-1.1, P = 0.001), and postoperative ICU admission (RR -3.3, P < 0.001) were significant risk factors for SSI requiring a return to the OR. CONCLUSION: The intrawound application of vancomycin after posterior approach spine surgery was associated with a reduced risk of SSI and return to OR associated with SSI. LEVEL OF EVIDENCE: 2.

Awake Craniotomy for the Treatment of a Cortical Pseudoaneurysm in a Pregnant Patient.

Neurosurgical pathologies presenting during pregnancy are uncommon. If present, the situation creates a unique diagnostic, observational, and therapeutic challenge as both lives are placed at potential risk. Surgical procedures during pregnancy are approached carefully as physiological stressors associated with surgery and anesthesia may cause fetal or maternal compromise. We present the only known case of a pseudoaneurysm treated with an awake craniotomy, allowing us to abate the risks associated with general anesthesia in pregnancy. A female suffered a superficially penetrating gunshot wound to the head for which she underwent a craniotomy with complete neurological recovery. She had complaints of intermittent headaches, dizziness, and tingling of her hands five months thereafter. The cerebral angiogram demonstrated an 8 mm pseudoaneurysm under her craniotomy site. A surgical repair of this aneurysm was undertaken in the 23rd week of pregnancy via an awake craniotomy with regional scalp block. The aneurysm was resected without complication, and the patient tolerated the procedure without neurological deficit during or subsequent to the operation. Cerebrovascular pathology in pregnant patients remains a difficult situation that poses challenges associated with the pathology itself as well as the anesthetic implications inherent with operative management. The neurosurgical literature demonstrates that surgical management of cerebrovascular pathology is well-tolerated in pregnancy, and our case further demonstrates the capability of utilizing an awake craniotomy for the treatment of this type of lesion without causing a residual deficit.

Endothelial expression of TNF receptor-1 generates a proapoptotic signal inhibited by integrin α6ß1 in glioblastoma.

Activation of TNF receptor 1 (TNF-R1) can generate signals that promote either apoptosis or survival. In this study, we show that these signals can be determined by the character of the extracellular matrix in the tumor microenvironment. Specifically, through studies of glioblastoma, we showed that TNFα stimulation induced apoptosis of primary brain endothelial cells (EC) attached to collagen or fibronectin (which engage integrins α2ß1/α3ß1 and α5ß1, respectively), but did not induce apoptosis of ECs attached to laminin (which engages integrins α6ß1 and α3ß1). TNF-R1 expression was significantly higher in ECs in glioblastoma (GBM) tumors compared with ECs in normal brain specimens. TNFα was also expressed in GBM tumor-associated ECs, which was associated with longer patient survival. ECs plated on anti-integrin α2 or α3 antibody were susceptible to TNFα-induced apoptosis, whereas those plated on anti-integrin α6 antibody were not. Moreover, the ECs plated on laminin, but not collagen, expressed cellular FLICE inhibitory protein (cFLIP) and TNFα stimulation of laminin-attached cells in which cFLIP had been downregulated resulted in the induction of apoptosis. In contrast, attachment to laminin did not induce cFLIP expression in GBM tumor stem cells. Together, our findings indicate that the laminin receptor integrin α6ß1 promotes the survival of brain ECs by inhibiting prodeath signaling by TNF-R1, in part by inducing cFLIP expression.

Tumor-associated alterations in caspase-14 expression in epithelial malignancies.

PURPOSE: Caspase-14 is unique among caspase family proteases in that its proteolytic processing has been principally associated with epithelial cell differentiation rather than apoptosis or inflammation. We investigated caspase-14 expression in several types of human epithelial malignancy by immunohistochemistry, correlating results with stage, histologic grade, and patient survival. EXPERIMENTAL DESIGN: Tumor-associated alterations in caspase-14 expression were observed for cervical, ovarian, breast, gastric, and colon cancers. RESULTS: In cervical (n = 445), ovarian (n = 91), and colon (n = 106) specimens, expression of caspase-14 was significantly reduced in cancers compared with normal epithelium. Decreases in caspase-14 immunopositivity correlated with the histologic progression of cervical cancer (P < 0.0001, ANOVA). In localized gastric cancers, caspase-14 immunostaining was significantly lower in poorly differentiated tumors compared with well-differentiated tumors (P = 0.02, Pearson's chi(2) analysis). Lower caspase-14 expression was associated with advanced clinical stage in ovarian cancer (P = 0.04, ANOVA) and with shorter overall survival among ovarian cancer patients with serous tumors (n = 62) in both univariate (P = 0.005) and multivariate (P = 0.03) analysis. Lower caspase-14 expression correlated with shorter overall survival among patients with T(3)N(0)M(0) stage gastric cancers (n = 94; P = 0.006, log-rank test). In contrast to cervical, ovarian, and colon cancers, caspase-14 expression was increased in ductal carcinoma in situ and invasive cancers compared with normal mammary epithelium (P = 0.001, t test). CONCLUSIONS: The findings reveal tumor-specific alterations in caspase-14 expression and suggest that differences in its expression may define subsets of epithelial cancers with distinct clinical behaviors.

Matrix metalloproteinase-26 is associated with estrogen-dependent malignancies and targets alpha1-antitrypsin serpin.

Proteases exert control over cell behavior and affect many biological processes by making proteolytic modification of regulatory proteins. The purpose of this paper is to describe novel, important functions of matrix metalloproteinase (MMP)-26. alpha1-Antitrypsin (AAT) is a serpin, the primary function of which is to regulate the activity of neutrophil/leukocyte elastase. Insufficient antiprotease activity because of AAT deficiency in the lungs is a contributing factor to early-onset emphysema. We recently discovered that AAT is efficiently cleaved by a novel metalloproteinase, MMP-26, which exhibits an unconventional PH(81)CGVPD Cys switch motif and is autocatalytically activated in cells and tissues. An elevated expression of MMP-26 in macrophages and polymorphonuclear leukocytes supports the functional role of MMP-26 in the AAT cleavage and inflammation. We have demonstrated a direct functional link of MMP-26 expression with an estrogen dependency and confirmed the presence of the estrogen-response element in the MMP-26 promoter. Immunostaining of tumor cell lines and biopsy specimen microarrays confirmed the existence of the inverse correlations of MMP-26 and AAT in cells/tissues. An expression of MMP-26 in the estrogen-dependent neoplasms is likely to contribute to the inactivation of AAT, to the follow-up liberation of the Ser protease activity, and because of these biochemical events, to promote matrix destruction and malignant progression. In summary, we hypothesize that MMP-26, by cleaving and inactivating the AAT serpin, operates as a unique functional link that regulates a coordinated interplay between Ser and metalloproteinases in estrogen-dependent neoplasms.

Expression of Bcl-2 family member Bid in normal and malignant tissues.

Bid is the only known Bcl-2 family member that can function as an agonist of proapoptotic Bcl-2-related proteins such as Bax and Bak. Expression of the proapoptotic Bcl-2 family protein Bid was assessed by immunoblotting and immunohistochemical methods in normal murine and human tissues, and in several types of human cancers and tumor cell lines. Bid expression in normal tissues varied widely, with prominent Bid immunostaining occurring in several types of short-lived cells (e.g., germinal center B cells, peripheral blood granulocytes, differentiated keratinocytes) and in apoptosis-sensitive cells (e.g., adult neurons). Analysis of Bid expression by immunostaining of 100 colon, 95 ovarian, and 254 prostate cancers, as well as 59 brain tumors and 50 lymphomas, revealed evidence of altered Bid regulation in some types of cancers. Correlations with clinical outcome data revealed association of higher levels of Bid with longer recurrence-free survival in men with locally advanced (T3 stage) prostate cancer (P=0.04). Immunoblot analysis of Bid protein levels in the NCI's panel of 60 human tumor cell lines revealed a correlation between higher levels of Bid and sensitivity to ribonucleotide reductase (RR)-inhibiting drugs (P<0.0005). Overexpression of Bid in a model tumor cell line by gene transfection resulted in increased sensitivity to apoptosis induction by a RR inhibitor. Taken together, these observations suggest a potential role for Bid in tumor responses to specific chemotherapeutic drugs, and lay a foundation for future investigations of this member of the Bcl-2 family in healthy and diseased tissues.