Breast cancer brain metastases localization and risk of hydrocephalus: a single institution experience.

PURPOSE: Brain metastases occur in up to one-third of patients with breast cancer. aromatase, a marker for estrogen activity that has been shown to promote such metastasis, heavily concentrates in certain midline structures of brain. We hypothesize that breast cancer metastasizes more often to brain areas with higher aromatase activity and that these patients have a higher risk of developing obstructive hydrocephalus. METHODS: In our retrospective review of 709 patients who underwent stereotactic radiosurgery (January 2014-May 2020), we identified 358 patients treated for metastatic breast or lung cancer. The MRI scan that first showed evidence of brain metastases was reviewed and number of metastases counted by location. Procedures used to treat obstructive hydrocephalus were recorded. Chi square test was used for statistical analysis. RESULTS: Of 358 patients, 99 patients with breast cancer had 618 brain metastases and 259 patients with lung cancer had 1487 brain metastases. Compared with expected distribution of brain metastases based on regional brain volumes and metastatic lung carcinoma as a control, patients with breast cancer more often had metastases to the cerebellum, diencephalon, medulla, and parietal lobe, and underwent significantly more neurosurgical interventions for treatment of obstructive hydrocephalus. CONCLUSION: Brain metastases in patients with breast cancer occurred more often along midline structures of the brain, which we believe may be associated with the increased estrogen activity in these structures. This finding is important for physicians who treat patients with metastatic breast cancer given the higher possibility of developing obstructive hydrocephalus.

Reliability of Magnetic Resonance Spectroscopy and Positron Emission Tomography Computed Tomography in Differentiating Metastatic Brain Tumor Recurrence from Radiation Necrosis.

BACKGROUND: Clinical and/or neuroimaging changes after whole-brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) for metastatic brain tumor(s) present the clinical dilemma of differentiating tumor recurrence from radiation necrosis. Several imaging modalities attempt to answer this clinical question, including magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) computed tomography (CT). We evaluated our experience regarding the ability of MRS and PET CT to differentiate tumor recurrence from radiation necrosis in patients who have received WBRT or SRS. METHODS: We retrospectively reviewed records of 242 patients with previous WBRT or SRS to identify those who had MRS and/or PET CT to differentiate tumor recurrence from radiation necrosis. Patients were sorted into true-positive, false-positive, false-negative, and true-negative groups on the basis of imaging interpretation and clinical course combined with surgical pathology results or reaction to nonsurgical treatments including SRS, dexamethasone, or observation. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were then calculated. RESULTS: Of 25 patients presenting such diagnostic questions, 19 were evaluated with MRS and 13 with PET CT. MRS sensitivity was 100%, specificity was 50%, and accuracy was 81.8%, whereas PET CT sensitivity was 36.4%, specificity was 66.7%, and accuracy was 42.9%. CONCLUSIONS: MRS has better accuracy than PET CT and a high negative predictive value, therefore making it more useful in distinguishing recurrent tumor from radiation necrosis. We encourage correlation with symptoms at imaging to aid in clinical decision making.

Daily Lifestyle Modifications to Improve Quality of Life and Survival in Glioblastoma: A Review.

Survival in glioblastoma remains poor despite advancements in standard-of-care treatment. Some patients wish to take a more active role in their cancer treatment by adopting daily lifestyle changes to improve their quality of life or overall survival. We review the available literature through PubMed and Google Scholar to identify laboratory animal studies, human studies, and ongoing clinical trials. We discuss which health habits patients adopt and which have the most promise in glioblastoma. While results of clinical trials available on these topics are limited, dietary restrictions, exercise, use of supplements and cannabis, and smoking cessation all show some benefit in the comprehensive treatment of glioblastoma. Marital status also has an impact on survival. Further clinical trials combining standard treatments with lifestyle modifications are necessary to quantify their survival advantages.

Isolated Primary Sinonasal Adenocarcinoma of the Sphenoid Sinus.

Isolated lesions of the sphenoid sinus, particularly malignancies, are rarely reported and exist largely within the Otolaryngology literature. Delayed diagnosis may necessitate neurosurgical involvement; therefore, neurosurgeons must be aware of the range of pathologies in this region in order to provide adequate treatment. We present an unusual case of an 89-year-old female with several weeks of worsening headaches, vision loss, and cranial neuropathies. Work-up at an outside hospital was non-diagnostic. After referral, an expansive and erosive lesion within the left sphenoid sinus was identified. A transsphenoidal approach for resection of the lesion yielded a primary non-salivary non-intestinal type sinonasal adenocarcinoma, as well as bacterial sinusitis and probable allergic fungal sinusitis. The patient was treated with antimicrobial medications as well as stereotactic radiosurgery. Her neurological deficits did not improve with treatment, and she ultimately expired 3.5 months post-operatively after transition to hospice. Primary sinonasal adenocarcinoma is a very rare pathology in this location. Surgical intervention is necessary to obtain an accurate diagnosis and proceed with appropriate treatment. Delayed diagnosis likely portends a worse prognosis.

Modified Sternocleidomastoid Sparing Approach for Vertebral Artery (V1) to Common Carotid Artery Transposition: 2-Dimensional Operative Video.

Vertebral artery (VA) V1 segment to common carotid artery (CCA) transposition is an uncommon operation with existing literature describing dissection of the sternoclavicular head of the sternocleidomastoid (SCM) muscle.1,2 We present a modified approach for transposition without cutting the SCM. Our patient is a 76-yr-old female with history of a previous cerebellar stroke. Despite taking aspirin, she presented with another stroke resulting in severe dysarthria, vertigo, and gait disturbance. Magnetic resonance imaging (MRI) demonstrated several cerebellar infarcts. Catheter angiography demonstrated bilateral vertebral artery occlusion with filling from ascending cervical branches and a dominant left VA. We planned a left V1 to CCA transposition with a modified SCM-sparing approach for which the patient provided written informed consent. She was positioned supine with neck extended and face turned to the right. Neuromonitoring was utilized. A linear incision along the anterior border of the SCM was made, stopping 1.5 cm above the clavicular head. Neurovascular structures of the carotid sheath were dissected circumferentially and mobilized medially. The longus coli muscle over the C6 lateral mass was reflected medially. The vertebral artery was dissected to expose the maximum possible length. The inferior thyroid artery was sacrificed for better exposure. VA was ligated and transected. CCA was clamped. VA to CCA bypass was performed in a standard fashion. Surgical site was closed. The patient clinically did well postoperatively with immediate symptom improvement. Our video demonstrates an SCM-sparing technique of V1 to CCA transposition, which can be a less-extensive operation compared to the traditional approaches, which require transection of SCM head.

Clip Ligation of Midsegment M1 Artery Aneurysm through a Lateral Supraorbital Approach: 2-Dimensional Operative Video.

Lenticulostriate middle cerebral artery (MCA) aneurysms are rare and often involve perforating vessels, making endovascular treatment difficult. When projecting superiorly, aneurysm rupture can likely cause intraparenchymal hemorrhage in basal ganglia. Consequently, surgical clip ligation requires control not to aggressively elevate the frontal lobe to avoid intraoperative injury. We report a case of a growing right midsegment MCA aneurysm treated with clip ligation via a lateral supraorbital approach (LSO). The patient is a 71-year-old female found to have a 4 mm × 3 mm right M1 aneurysm in 2014 on workup for headaches. Subsequent imaging demonstrated aneurysm growth to 6 mm × 3.1 mm with peaked-dome appearance. The growth and location of the aneurysm led us to recommend open surgical treatment; the patient provided informed written consent to proceed. We performed a standard right-sided LSO approach.1 Microdissection was performed to split the sylvian fissure distally and then proximally to expose the MCA on either side of the aneurysm. Dissecting the aneurysm revealed a perforating artery at the proximal neck. Using minimal frontal lobe dynamic retraction, microsurgical clip ligation was performed. We ensured the clip was placed in line with the MCA trunk to avoid kinking the parent artery and subsequent stroke. Intraoperative micro-Doppler and indocyanine green injection confirmed the patency of vasculature. Postoperative angiogram confirmed complete aneurysm ligation. The patient clinically did well and was discharged home on postoperative day 2. Our video demonstrates safe and effective surgical treatment of a rare aneurysm2 through a small LSO craniotomy approach (Video 1).

Does Surveillance-Detected Disease Progression Yield Superior Patient Outcomes in High-Grade Glioma?

BACKGROUND: Standard follow-up care for patients with high-grade glioma (HGG) involves routine surveillance imaging to detect disease progression, assess treatment response, and monitor clinical symptoms. Although logical in nature, evidence supporting this practice is limited. We hypothesize patients with tumor recurrence detected on routine surveillance imaging will experience superior outcomes relative to symptomatic detection, using measures of survival and postrecurrence neurologic function. METHODS: Adult patients receiving treatment for HGG at our institution from 2004 to 2018 were identified, and data including tumor characteristics, imaging results, neurologic status, and survival were extracted from the medical records of patients meeting inclusion criteria. All participants were followed for a minimum of 12 months, or for survival duration. Survival and neurologic function differences were assessed using log rank and 2-sample t tests with 2-sided 0.05 alpha level of significance. RESULTS: Of the 74 patients meeting inclusion criteria, 47 (63.5%) had recurrence detected via routine surveillance imaging, and 27 (36.5%) had symptomatic detection outside of the surveillance schedule. Neither median overall survival (14.8 months for surveillance and 15.7 months for symptomatic; P = 0.600) nor postrecurrence neurologic function (assessed by Karnofsky Performance Scale Index and Eastern Cooperative Oncology Group) differed between the surveillance and symptomatic detection groups (P = 0.699 and P = 0.908, respectively). CONCLUSIONS: Recurrence detection occurring via routine surveillance imaging did not yield superior patient outcomes relative to symptomatic detection occurring outside of the standard surveillance schedule in patients with HGG. Further evaluation of surveillance imaging and alternative follow-up methods for this patient population may be warranted.

Spinal cord stimulator failure: Migration of a thoracic epidural paddle to the cervical spine.

BACKGROUND: Spinal cord stimulators successfully treat a number of pain syndromes but carry a risk of hardware complications. Here, we present a case of cranial migration of a thoracic epidural paddle to the cervical spine. CASE DESCRIPTION: A 53-year-old male underwent uncomplicated spinal cord stimulator placement at the T10- T11 with initially favorable results. However, postoperatively, he complained of paresthesias in his arms. An X-ray demonstrated cranial migration of the thoracic epidural paddle to the cervical spine. The stimulator/new paddle was placed again at the T10-T11 level, but the leads were now secured to the caudal lamina utilizing a cranial plating system. The patient subsequently did well without further sequelae. CONCLUSIONS: A thoracic epidural paddle (T10-T11) migrated postoperatively into the cervical spine. It was subsequently removed and replaced into the thoracic region, but the leads were now secured in place with a novel caudal lamina/cranial plating system.

The effects of anaemia and transfusion on patients with traumatic brain injury: A review.

BACKGROUND: Anaemia in traumatic brain injury (TBI) is frequently encountered. Neurosurgical texts continue to recommend transfusion for hematocrit below 30%, despite clear evidence to do so. Transfusion should increase oxygen delivery to the brain, but it may also increase morbidity and mortality. METHODS: This study reviewed the relevant literature to better understand the risks of anaemia and benefits of correction of anaemia by transfusion. RESULTS: Of the 21 studies reviewed, eight found that anaemia was harmful to patients with TBI; five found no significant outcome; seven found transfusion was associated with higher rates of morbidity and mortality; two found that transfusion lowered mortality and increased brain tissue oxygen levels; and ten found no correlation between transfusion and outcome. However, the levels of anaemia severity and the outcome measurements varied widely and the majority of outcomes focused on crude measurements rather than detailed functional assessments. CONCLUSIONS: No division of response based on gender difference or impact of anaemia in the post-hospital treatment setting was observed. A randomized control trial is recommended to determine the impact of anaemia and transfusion on detailed outcome assessment in comparison of transfusion thresholds ranging from ≤ 7 g dL-1 to ≤ 9 g dL-1 in patients with moderate-to-severe TBI.

Hepatic steatosis, inflammation, and ER stress in mice maintained long term on a very low-carbohydrate ketogenic diet.

Low-carbohydrate diets are used to manage obesity, seizure disorders, and malignancies of the central nervous system. These diets create a distinctive, but incompletely defined, cellular, molecular, and integrated metabolic state. Here, we determine the systemic and hepatic effects of long-term administration of a very low-carbohydrate, low-protein, and high-fat ketogenic diet, serially comparing these effects to a high-simple-carbohydrate, high-fat Western diet and a low-fat, polysaccharide-rich control chow diet in C57BL/6J mice. Longitudinal measurement of body composition, serum metabolites, and intrahepatic fat content, using in vivo magnetic resonance spectroscopy, reveals that mice fed the ketogenic diet over 12 wk remain lean, euglycemic, and hypoinsulinemic but accumulate hepatic lipid in a temporal pattern very distinct from animals fed the Western diet. Ketogenic diet-fed mice ultimately develop systemic glucose intolerance, hepatic endoplasmic reticulum stress, steatosis, cellular injury, and macrophage accumulation, but surprisingly insulin-induced hepatic Akt phosphorylation and whole-body insulin responsiveness are not impaired. Moreover, whereas hepatic Pparg mRNA abundance is augmented by both high-fat diets, each diet confers splice variant specificity. The distinctive nutrient milieu created by long-term administration of this low-carbohydrate, low-protein ketogenic diet in mice evokes unique signatures of nonalcoholic fatty liver disease and whole-body glucose homeostasis.

Glioblastomas with giant cell and sarcomatous features in patients with Turcot syndrome type 1: a clinicopathological study of 3 cases.

BACKGROUND: Turcot syndrome (TS) is a rare genetic disorder of DNA mismatch repair predisposing to glioblastoma (GBM) in the type 1 variant. OBJECTIVE: We report the clinicopathological and genetic features of 3 gliomas in TS type 1 patients. METHODS: Three cases were reviewed from our clinical and pathology files at Washington University with the diagnosis of TS 1 and GBM over the past 14 years. All 3 had classic features of GBM, but also demonstrated bizarre multinucleated giant cells and remarkably high mitotic indices. Sarcomatous regions were found in 2. Despite these features, the patients had prolonged survival times of 44, 55, and >29 months (ie, currently alive). Demographic and clinical courses were abstracted from retrospective chart review. Histopathology was reviewed from all cases and reticulin histochemistry was added to identify possible foci of sarcomatous differentiation. RESULTS: All 3 had classic features of GBM, and Ki-67 labeling indices ranged from 18 to 45%. All 3 also showed strong nuclear p53 positivity. Two cases were negative for the isocitrate dehydrogenase 1 (IDH1) mutation, and O-Methylguanine methyltransferase promoter methylation was seen in one. Fluorescence in situ hybridization was done using 1p/1q, 19p/19q, centromere 7/epithelial growth factor receptor (EGFR), and PTEN/DMBT1 probes. Focal EGFR amplification was seen in one case, although other common alterations of either primary GBMs or gliomas with prolonged survival (1p/19q codeletion) were lacking. CONCLUSION: We conclude that 1) the giant cell variant of GBM is overrepresented in TS; 2) gliosarcomas may also be encountered; and 3) survival is often favorable, despite histological anaplasia and exuberant proliferation.

Measuring brain tumor growth: combined bioluminescence imaging-magnetic resonance imaging strategy.

Small-animal tumor models are essential for developing translational therapeutic strategies in oncology research, with imaging having an increasingly important role. Magnetic resonance imaging (MRI) offers tumor localization, volumetric measurement, and the potential for advanced physiologic imaging but is less well suited to high-throughput studies and has limited capacity to assess early tumor growth. Bioluminescence imaging (BLI) identifies tumors early, monitors tumor growth, and efficiently measures response to therapeutic intervention. Generally, BLI signals have been found to correlate well with magnetic resonance measurements of tumor volume. However, in our studies of small-animal models of malignant brain tumors, we have observed specific instances in which BLI data do not correlate with corresponding MRIs. These observations led us to hypothesize that use of BLI and MRI together, rather than in isolation, would allow more effective and efficient measures of tumor growth in preclinical studies. Herein we describe combining BLI and MRI studies to characterize tumor growth in a mouse model of glioblastoma. The results led us to suggest a cost-effective, multimodality strategy for selecting cohorts of animals with similar tumor growth patterns that improves the accuracy of longitudinal in vivo measurements of tumor growth and treatment response in preclinical therapeutic studies.

A novel murine model for localized radiation necrosis and its characterization using advanced magnetic resonance imaging.

PURPOSE: To develop a murine model of radiation necrosis using fractionated, subtotal cranial irradiation; and to investigate the imaging signature of radiation-induced tissue damage using advanced magnetic resonance imaging techniques. METHODS AND MATERIALS: Twenty-four mice each received 60 Gy of hemispheric (left) irradiation in 10 equal fractions. Magnetic resonance images at 4.7 T were subsequently collected using T1-, T2-, and diffusion sequences at selected time points after irradiation. After imaging, animals were killed and their brains fixed for correlative histologic analysis. RESULTS: Contrast-enhanced T1- and T2-weighted magnetic resonance images at months 2, 3, and 4 showed changes consistent with progressive radiation necrosis. Quantitatively, mean diffusivity was significantly higher (mean = 0.86, 1.13, and 1.24 microm(2)/ms at 2, 3, and 4 months, respectively) in radiated brain, compared with contralateral untreated brain tissue (mean = 0.78, 0.82, and 0.83 microm(2)/ms) (p < 0.0001). Histology reflected changes typically seen in radiation necrosis. CONCLUSIONS: This murine model of radiation necrosis will facilitate investigation of imaging biomarkers that distinguish between radiation necrosis and tumor recurrence. In addition, this preclinical study supports clinical data suggesting that diffusion-weighted imaging may be helpful in answering this diagnostic question in clinical settings.

An assessment of toxicity in profundal lake sediment due to deposition of heavy metals and persistent organic pollutants from the atmosphere.

A Tier I Sediment Ecological Risk Assessment of profundal lake sediment contaminated by diffuse pollution of heavy metals and POPs deposited from the atmosphere was completed. The concentrations of seven heavy metals and four groups of POPs (OCs, PCBs, PAHs, PBDEs) were determined in the profundal sediment of ten lakes in the United Kingdom and two sediment toxicity tests completed (chironomid survival and emergence and cladoceran survival and reproduction). The results showed that around half the lakes are at least moderately contaminated by Pb, Zn, Cd, As and PAHs deposited from the atmosphere and the toxicity quotient suggests that the contaminants of concern are Pb, As and PAHs, and not the other metals nor OCs and PCBs. There was toxicity in the sediment of four of the lakes. The Probable Effect Concentration Quotient values indicated that metals in the sediments of Scoat Tarn, Agden Reservoir and Llyn Llagi were likely to be responsible for the laboratory toxicity found in these lakes, with PAHs also contributing in Agden Reservoir.