Human and rodent temporal lobe epilepsy is characterized by changes in O-GlcNAc homeostasis that can be reversed to dampen epileptiform activity.

Temporal Lobe Epilepsy (TLE) is frequently associated with changes in protein composition and post-translational modifications (PTM) that exacerbate the disorder. O-linked-ß-N-acetyl glucosamine (O-GlcNAc) is a PTM occurring at serine/threonine residues that is derived from and closely associated with metabolic substrates. The enzymes O-GlcNActransferase (OGT) and O-GlcNAcase (OGA) mediate the addition and removal, respectively, of the O-GlcNAc modification. The goal of this study was to characterize OGT/OGA and protein O-GlcNAcylation in the epileptic hippocampus and to determine and whether direct manipulation of these proteins and PTM's alter epileptiform activity. We observed reduced global and protein specific O-GlcNAcylation and OGT expression in the kainate rat model of TLE and in human TLE hippocampal tissue. Inhibiting OGA with Thiamet-G elevated protein O-GlcNAcylation, and decreased both seizure duration and epileptic spike events, suggesting that OGA may be a therapeutic target for seizure control. These findings suggest that loss of O-GlcNAc homeostasis in the kainate model and in human TLE can be reversed via targeting of O-GlcNAc related pathways.

Are Bradycardic Donors More Likely to Have Adverse Outcomes During Blood Donation?

INTRODUCTION: In order to decrease adverse donor reactions during blood donation, volunteers are screened to safely donate according to the U.S. Food and Drug Administration standards. Volunteers must be normocardic, with a pulse between 50 and 100 beats per minute. Bradycardic volunteers with a pulse lower than 50 beats per minute who otherwise meet requirements may donate with physician approval. Blood donors in military settings tend to be younger and more physically fit than the average donor population, resulting in a higher percentage of bradycardic donors. The relationship between bradycardia and adverse donor reactions has not been well studied. Herein, we aim to compare post-donation adverse reactions and the ability to complete donation between normocardic and bradycardic donors. MATERIALS AND METHODS: Institutional review board approval was obtained. Records from a single blood donor center located on a large military installation in 2019 were retrospectively reviewed for vital signs, demographics, hemoglobin, and donor reactions. Donors were categorized as normocardic or bradycardic. The two groups were statistically compared using a χ2 test. RESULTS: Of the 1,601 donors in the study period, 1,514 qualified for donation. Mean age was 26.6 years (range, 17-72 years), with a male to female ratio of 2.1:1. Of these, 1,478 were normocardic and 26 were bradycardic. There was no significant difference in adverse reactions between the two groups (5.6% in bradycardic donors versus 3.6% in normocardic donors, n = 1,514, χ21 = 0.39, P = .53) or percentage of incomplete donations (5.9% in bradycardic and 5.65% in normocardic, n = 1,514, χ21 = 0.003, P = .96). CONCLUSIONS: Donors with bradycardia are as safe to donate as normocardic donors. In the absence of comorbidities, blood donor centers should ensure their policies consider donation for volunteers with bradycardia.

Development and Validation of Ultra-Rapid Periodic Acid-Schiff Stain for Use in Identifying Fungus on Frozen Section.

CONTEXT.­: There is no standardized process for utilization of periodic acid-Schiff during intraoperative frozen sections to identify fungal organisms. OBJECTIVE.­: To develop a rapid staining process for fresh tissue with periodic acid-Schiff during intraoperative consultation and develop an appropriate control block. DESIGN.­: Muscle tissue was inoculated with 2 species of fungus (Aspergillus fumigatus and Paecilomyces spp) and grown at 3 different temperatures for 72 hours. Inoculated tissue was embedded in optimal cutting temperature compound, cut, and stained using a modified periodic acid-Schiff stain. The optimal control was determined for future use as the standard control. Multiple control slides were cut and stained, using successively shorter time intervals for each step. The staining process that provided accurate results in the shortest amount of time was deemed ultra-rapid periodic acid-Schiff. This method was validated by carryover studies and clinical specimens. RESULTS.­: Paecilomyces spp incubated at 30°C for 72 hours was the most optimal positive control, with numerous yeast and hyphal forms. The fastest staining process involved 2 minutes of periodic acid and Schiff reagent and 10 dips of light green solution. Tap water was as effective as distilled water. Validation was successfully achieved. Clinical cases all stained identical to formalin-fixed, paraffin-embedded tissue stained with hematoxylin-eosin and periodic acid-Schiff. CONCLUSIONS.­: Ultra-rapid periodic acid-Schiff provides fast and reliable identification of fungal organisms on fresh tissue. Development of a concurrent positive control allows for quality control and validation.

Malignant Peripheral Nerve Sheath Tumor in an Army Reservist With Neurofibromatosis Type 1.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition affecting 1 in 3,500 people resulting from an NF1 gene mutation that encodes the nonfunctional protein neurofibromin mutant. Neurofibromin is a negative regulator of RAS signaling involved in cell survival and proliferation. NF1 typically presents at birth or in early childhood with multiple light brown (café au lait) spots and axillary freckling. With age, patients may develop scattered neurofibromas as well as additional neurological and malignant abnormalities. Additionally, the nonfunctional protein neurofibromin mutant may be involved in the pathogenesis of peripheral malignant nerve sheath tumors, which is a rare and life-threatening complication of NF1. While a disqualifying condition for military duty, it may not initially be clinically apparent until complications develop. Here, we present a case of malignant peripheral sheath in an U.S. Army African American reservist with NF1 in whom cutaneous manifestations of NF1 such as café au lait spots and axillary freckling were not identified on the initial military entrance processing examination.

Colorectal Cancer in a Patient With Multiple Myeloma: A Treatment Dilemma.

Multiple myeloma (MM) is a malignancy of plasma cells characterized by the clonal proliferation of plasma cells that produce monoclonal immunoglobulins. While typically considered to be incurable, advances in treatment options have led to remarkable improvements in survival for these patients. Accumulating evidence suggests an increased risk for the development of a secondary primary malignancy (SPM) in these patients, perhaps as a result of myeloma directed therapy or as an effect of their underlying disease process. Here we present a case of a patient who was diagnosed with an SPM while undergoing palliative treatment for multiple myeloma and a treatment approach.

The Utility of Phosphohistone H3 (PHH3) in Follicular Lymphoma Grading: A Comparative Study With Ki-67 and H&E Mitotic Count.

OBJECTIVES: To determine the utility of phosphohistone H3 (PHH3) mitotic count (MC) in grading follicular lymphoma (FL). METHODS: FL cases were identified (2005-2017). Three hematopathologists recorded their average Ki-67 proliferation index, MC/high-power field (hpf) using PHH3 and H&E stains, and number of centroblasts/hpf. Results were assessed for correlations and interobserver variability. RESULTS: Forty-three cases of FL were studied. PHH3 MC resulted in the strongest correlation to grade (r = 0.701, P < .0001) compared with Ki-67 proliferation index (PI) (r = 0.681, P < .0001) and H&E MC (r = 0.536, P = .0002) and the strongest linear relationship to centroblast count (R2 = 0.453). Agreement among pathologists was strongest for PHH3 (intraclass correlation coefficient [ICC] = 0.86) followed by Ki-67 PI (ICC = 0.85) and H&E MC (ICC = 0.78). CONCLUSIONS: PHH3 correlates best to histologic grade and has less interobserver variability compared with Ki-67 PI and H&E MC. These results support using PHH3 as an adjunct in FL grading.

Systemic Non-Hodgkin T Cell Lymphomas Presenting in the Head and Neck Region: An Institutional Experience of a Rare Entity.

T cell lymphoma (TCL) is a group of rare and aggressive diseases. TCL primary to head and neck organs often present as extranodal NK/T cell lymphoma, nasal type. Systemic TCL with initial head and neck presentation is extremely rare. Here we report our institutional experience. Clinicopathologic data was collected from patients diagnosed with TCL and treated at the University of Alabama at Birmingham between 2002 and 2012. Eleven cases of systemic TCL initially presented at head and neck region were identified. The median age was 54 years and male:female ratio was 1.8. The most common sites involved were sinonasal tissue, tonsil, tongue and larynx. Most patients presented with a mass lesion without systemic symptoms. The presentation of TCL primary to the head and neck region is often non-specific. A misdiagnosis of undifferentiated tumor or chronic inflammation due to ambiguous morphology is not uncommon. TCL should be considered in differential diagnosis and a thorough evaluation is warranted for accurate diagnosis.

Clinicopathologic Features and Clinical Outcome Differences in De Novo Versus Secondary Histiocytic Sarcomas: A Multi-institutional Experience and Review of the Literature.

INTRODUCTION: Histiocytic sarcoma (HS) is a rare malignant neoplasm that can occur in patients with a history of treatment for hematologic or solid tumors. Because no optimal treatment has been defined and standardized, the treatment modalities used and outcomes reported have been highly variable. In the present study, 3 major institutions explored the clinicopathologic features of de novo and secondary HS. MATERIALS AND METHODS: After institutional review board approval, clinical, histopathologic, and immunophenotypic data were collected from patients with a diagnosis of HS and treated at the University of Alabama at Birmingham, University of New Mexico, or Brooke Army Medical Center from January 1, 2003 to December 31, 2016. RESULTS: The databases revealed 23 unique cases of HS. The mean age was 55.4 years (range, 5-84 years) and the male-to-female ratio was 0.92. The mean follow-up period was 89.82 months (range, 14-172 months). Of the 23 patients with HS, 6 had a history of an unrelated malignancy treated with chemotherapy or radiotherapy, with a mean delay of 42.2 months (range, 12-91 months). The mean overall survival during the study period was 54.1 months. The overall survival of those with de novo HS was 70 months compared with 11.8 months for those with secondary HS, with a mean difference of 58.2 months (95% confidence interval, 26.2-90.2 months; P = .001). CONCLUSION: The shorter overall survival with secondary HS suggests a more aggressive course than that with de novo disease. Larger scale studies are needed to further investigate the biology and genetics of HS.

Discrepancy Between Neurosurgery Morbidity and Mortality Conference Discussions and Hospital Quality Metric Standards.

OBJECTIVE: Medical institutions use quality metrics to track complications seen in hospital admissions. Similarly, morbidity and mortality (M&M) conferences are held to peer review complications. The purpose of this study was to compare the complications identified in a cohort of patients within 30 days of neurosurgical intervention with those captured in a cohort of M&M conferences. METHODS: All complications that occurred within 30 days of surgery were obtained for patients admitted to the neurosurgical service between May and September 2013. All patients discussed in M&M conference between August 2012 and February 2015 were included in a second data set. Complications were subdivided into 4 categories and compared between the 2 cohorts. RESULTS: A total of 749 postoperative complications were identified, including 52 urinary tract infections, 52 pneumonias, 15 deep vein thromboses, 19 strokes, 75 seizures, 25 wound infections, 6 cardiac arrests, and 162 reoperations. Eighty-five M&M cases were reviewed, identifying 9 strokes, 3 seizures, 8 wound infections, 13 hematomas, 7 intraoperative errors, and 11 postoperative deaths. The M&M cohort showed higher rates of neurologic complications (P < 0.0001) and surgical complications (P < 0.0001). The neurosurgical admission cohort showed higher rates of general medical adverse events (P = 0.0118) and infectious complications (not surgical wound related, P = 0.0002). CONCLUSIONS: Both neurosurgical service inpatient complications and complications discussed in M&M provide valuable opportunities for identifying areas in need of quality improvement. As the United States moves toward an outcomes reimbursement model, neurosurgical programs should adjust M&M conferences to reflect both technical operative complications as well as more common complications.

Predictors of Nasoseptal Flap Use After Endoscopic Transsphenoidal Pituitary Mass Resection.

OBJECTIVE: The pedicled nasoseptal flap (NSF) is the widely accepted reconstructive technique of choice for repair of larger skull base defects after endoscopic endonasal approaches. There is a dearth of literature examining the decision-making process regarding flap harvest. The objective of this study is to evaluate preoperative characteristics that predict the use of NSF reconstruction after endoscopic transsphenoidal resection of pituitary tumors. METHODS: In this retrospective case control study, demographic, clinical, imaging, and procedural details were gathered on all patients undergoing endoscopic transsphenoidal pituitary adenoma resection at a single academic center since January 2009. Characteristics were compared for patients receiving an NSF and those not undergoing NSF repair. A multivariate model that best predicted the use of an NSF was built and a risk score was developed. RESULTS: Two hundred thirty-eight patients were included, and 39 underwent NSF placement. Tumor size and anatomic characteristics were the predominant factors that significantly differed between cases and controls. Patients with transsellar tumor extension had 6.3 higher odds of requiring NSF, each millimeter increase in tumor height on coronal T1 magnetic resonance imaging increased the odds of NSF use by 1.2. The flap risk score (FRS) is calculated by adding tumor height (mm) to 6 if there is transsellar extension. At an FRS of >35, the FRS is 87% specific and 85% sensitive for flap placement. CONCLUSIONS: Preoperative imaging characteristics can predict NSF use. The FRS can be applied by surgical teams and referring physicians to determine which patients are more likely to undergo NSF repair.

Statistical modeling of ICEEG features that determine resection planning.

OBJECT: The interpretation of intracranial EEG (ICEEG) recordings is a complex balance of the significance of specific rhythms and their relative timing to seizure onset. Ictal and interictal findings are evaluated in light of findings from cortical stimulation of eloquent cortex to determine the area of resection. PATIENTS AND METHODS: Patients with ICEEG electrodes and subsequent surgical resection were retrospectively identified. Only the first 15s of ictal activity, which was divided into five 3-s epochs, was considered. Every electrode in each patient was considered a separate observation in a logistic regression model to predict whether the cortex under a given electrode was included in the planned resection. RESULTS: 19 included patients had a total of 37 unique seizures. Recordings from a total of 1306 electrodes were analyzed. The strongest predictors of resection of cortex underlying a given electrode was the presence of low-voltage fast activity in Epoch 1, rhythmic spikes in Epoch 1, interictal paroxysmal fast activity, and low-voltage fast activity in Epoch 2. High-amplitude beta spikes and rhythmic slow waves were also significant predictors in Epoch 1. Interictal spikes had a higher odds ratio of affecting the planned resection if described as "continuous" or "very frequent". The presence of motor or language cortex were the strongest negative predictors of resecting underlying cortex. CONCLUSIONS: Here we describe a novel model of ictal and interictal patterns significantly associated with the inclusion of cortex underlying a given ICEEG electrode in the surgical resection plan.

The clinical significance and reliability of self-reported smoking status in patients with intracranial aneurysms: a review.

OBJECTIVE: Here we present a review of the pathophysiology of tobacco smoking on intracranial aneurysms, self-reported smoking status in these patients, screening tools and assays available for assessing active nicotine use, means of impacting smoking cessation rates, and the potential impact of smoking cessation on risk of rupture and recurrence of treated intracranial aneurysms. METHODS: A literature search using PubMed was done to identify all English language studies relating to tobacco use and intracranial aneurysms, smoking and subarachnoid hemorrhage, nicotine breakdown products, and smoking cessation in neurosurgery. Results from the studies were reviewed and summarized. RESULTS: Tobacco use is an independent risk factor for formation, growth, and rupture of intracranial aneurysms. The pathogenesis of aneurysm formation is complex, and related to increased wall shear stress, endothelial dysfunction, atherosclerosis, and altered gene regulation. Furthermore 80% of all aneurysmal ruptures occur in patients who have used tobacco products. It is suboptimal to rely on self-reported smoking status in order to determine patient risk. Use of objective metrics for ongoing tobacco use may be indicated in selected patients, and may increase smoking cessation rates in these patients. A variety of laboratory and point-of-care tests are available for measurement of nicotine and nicotine breakdown products. Most assays in clinical practice measure the nicotine breakdown product cotinine, which constitutes 75% of nicotine metabolites excreted in the urine and has a substantial half-life of 16h, compared to nicotine's 2-h half-life. With proper identification, an astute physician may be able to assist in smoking cessation and foster improved patient care. By following recommended guidelines and prescribing pharmaceutical aid, a patient has a 2.5 times greater chance of smoking cessation compared with attempting to stop without physician assistance. CONCLUSIONS: Smoking increases risk for intracranial aneurysm formation, rupture, re-rupture and need for re-treatment. Measurement of nicotine breakdown products may have clinical utility in the management of patients with intracranial aneurysms. Smoking cessation interventions may be effective, and use of established smoking cessation tools use may lead to improved clinical outcomes in these patients. The effects of smoking cessation efforts on smoking cessation and intracranial aneurysm outcomes is a fertile field for future investigation.