Bullseye Analysis: A Fluorescence Microscopy Technique to Detect Local Changes in Intracellular Reactive Oxygen Species (ROS) Production.

Reactive oxygen species (ROS) are naturally produced compounds that play important roles in cell signaling, gene regulation, and biological defense, including involvement in the oxidative burst that is central to the anti-microbial actions of macrophages. However, these highly reactive, short-lived radical species also stimulate cells to undergo programmed cell death at high concentrations, as well as causing detrimental effects such as oxidation of macromolecules at more moderate levels. Imaging ROS is highly challenging, with many researchers working on the challenge over the past 10-15 years without producing a definitive method. We report a new fluorescence microscopy-based technique, Bullseye Analysis. This methodology is based on concepts provided by the FRAP (Fluorescence Recovery after Photobleaching) technique and refined to evidence the spatiotemporal production of ROS, and the subsequent consequences, on a subcellular scale. To exemplify the technique, we have used the ROS-reporter dye, CellROX, and the ROS-inducing photosensitizer, LightOx58, a potent source of ROS compared with UV irradiation alone. Further validation of the technique was carried out using differing co-stains, notably Mitotracker and JC-1.

Cellular localisation of structurally diverse diphenylacetylene fluorophores.

Fluorescent probes are increasingly used as reporter molecules in a wide variety of biophysical experiments, but when designing new compounds it can often be difficult to anticipate the effect that changing chemical structure can have on cellular localisation and fluorescence behaviour. To provide further chemical rationale for probe design, a series of donor-acceptor diphenylacetylene fluorophores with varying lipophilicities and structures were synthesised and analysed in human epidermal cells using a range of cellular imaging techniques. These experiments showed that, within this family, the greatest determinants of cellular localisation were overall lipophilicity and the presence of ionisable groups. Indeed, compounds with high log D values (>5) were found to localise in lipid droplets, but conversion of their ester acceptor groups to the corresponding carboxylic acids caused a pronounced shift to localisation in the endoplasmic reticulum. Mildly lipophilic compounds (log D = 2-3) with strongly basic amine groups were shown to be confined to lysosomes i.e. an acidic cellular compartment, but sequestering this positively charged motif as an amide resulted in a significant change to cytoplasmic and membrane localisation. Finally, specific organelles including the mitochondria could be targeted by incorporating groups such as a triphenylphosphonium moiety. Taken together, this account illustrates a range of guiding principles that can inform the design of other fluorescent molecules but, moreover, has demonstrated that many of these diphenylacetylenes have significant utility as probes in a range of cellular imaging studies.

Slip interface imaging based on MR-elastography preoperatively predicts meningioma-brain adhesion.

PURPOSE: To investigate the ability of slip interface imaging (SII), a recently developed magnetic resonance elastography (MRE)-based technique, to predict the degree of meningioma-brain adhesion, using findings at surgery as the reference standard. MATERIALS AND METHODS: With Institutional Review Board approval and written informed consent, 25 patients with meningiomas >2.5 cm in maximal diameter underwent preoperative SII assessment. Intracranial shear motions were introduced using a soft, pillow-like head driver and the resulting displacement field was acquired with an MRE pulse sequence on 3T MR scanners. The displacement data were analyzed to determine tumor-brain adhesion by assessing intensities on shear line images and raw as well as normalized octahedral shear strain (OSS) values along the interface. The SII findings of shear line images, OSS, and normalized OSS were independently and blindly correlated with surgical findings of tumor adhesion by using the Cohen's κ coefficient and chi-squared test. RESULTS: Neurosurgeons categorized the surgical plane as extrapial (no adhesion) in 15 patients, mixed in four, and subpial (adhesion) in six. Both shear line images and OSS agreed with the surgical findings in 18 (72%) cases (fair agreement, κ = 0.37, 95% confidence interval [CI]: 0.05-0.69), while normalized OSS was concordant with the surgical findings in 23 (92%) cases (good agreement, κ = 0.86, 95% CI: 0.67-1). The correlation between SII predictions (shear line images, OSS, and normalized OSS) and the surgical findings were statistically significant (chi-squared test, P = 0.02, P = 0.02, and P < 0.0001, respectively). CONCLUSION: SII preoperatively evaluates the degree of meningioma-brain adhesion noninvasively, allowing for improved prediction of surgical risk and tumor resectability. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1007-1016.

Prolonged viral replication and longitudinal viral dynamic differences among respiratory syncytial virus infected infants.

BackgroundLongitudinal respiratory syncytial virus (RSV) dynamics have not been well studied despite the existence of factors favoring prolonged RSV replication including high mutation rates allowing rapid evolution and potential escape from immune control. We therefore measured viral load in previously RSV-naive infants over prolonged time spans.MethodsDuring 2014-2015, quantitative nasal aspirates were collected from 51 RSV-PCR+ infants. Multiple parallel assessments of viral loads were quantified at each collected time point using a well-validated real-time quantitative reverse transcriptase polymerase chain reaction assay. After observing viral load rebound phenomenon in some infants, the viral dynamics of 27 infants with sufficient longitudinal viral load data points were analyzed using the pre-defined criteria for viral rebound. Additional analyses were performed comparing age with viral rebound, viral clearance rates, and viral load area-under-the-curve (AUCVL).ResultsThe 51 infants (303 nasal aspirate samples; mean of 5.9 per patient) exhibited slower than expected viral clearance. Lower age trended toward slower viral clearance and greater AUCVL. Six infants had detectable viral loads ≥1 month after symptom onset. Ten of twenty-seven evaluable subjects exhibited viral rebound and this rebound was age-dependent (P=0.0259). All but one rebounder were <70 days old.ConclusionInfants struggle to control primary RSV infections allowing prolonged viral replication and previously undescribed viral rebound; likely representing viral mutational immune escape.

How I do it: surgical ligation of craniocervical junction dural AV fistulas.

BACKGROUND: Dural arteriovenous fistulas (DAVFs) of the craniocervical junction are uncommon vascular lesions, which often require surgical treatment even in the endovascular era. METHODS: Most commonly, the fistula is placed laterally, and surgical ligation is performed through a lateral suboccipital craniotomy. After dural opening, the area is inspected, and the arterialized vein is identified emerging from the dura, often adjacent to the entry point of the vertebral artery, and ligated. CONCLUSIONS: A far lateral craniotomy is the authors' preferred surgical approach for accessing and treating dural arteriovenous fistulas of the craniocervical junction that cannot be reached endovascularly.

Magnetic resonance elastography detects tumoral consistency in pituitary macroadenomas.

INTRODUCTION: Most pituitary macroadenomas (PMA) are soft and suckable allowing transsphenoidal resection. A small percentage of PMA are firm, which significantly alters the time, technical difficulty, and effectiveness of transsphenoidal surgery. No current imaging technology can reliably assess PMA viscoelastic consistency in preparation for surgery. Magnetic resonance elastography (MRE) is an MRI-based technique that measures the propagation of mechanically induced shear waves through tissue to calculate stiffness. We prospectively evaluated MRE in 10 patients undergoing transsphenoidal resection of PMA to determine feasibility and potential usefulness. METHODS: 10 patients with PMA > 2.0 cm in maximum diameter were prospectively imaged with MRE prior to transsphenoidal surgery. Mean patient age was 59.5 ± 16.2 (22-78) years. Five were female and five male. MRE was performed with a modified single-shot spin-echo echo-planar-imaging pulse sequence on a 3T MRI. MRE values were independently calculated. The surgeon, blinded to the MRE results, graded tumor consistency at surgery as soft, intermediate, or firm. Chi-squared test compared surgical grading and MRE stiffness values. RESULTS: MRE was accomplished in all patients with excellent resolution. By surgical categorization, six tumors were soft and four intermediate. The mean MRE value for soft tumors was 1.38 ± 0.36 (1.08-1.87) kPa, while for intermediate tumors it was 1.94 ± 0.26 (1.72-2.32) kPa (p = 0.020). CONCLUSION: Determination of PMA stiffness is feasible with MRE. There was a statistically significant difference in MRE values between soft and intermediate PMAs. Further study in a larger series is ongoing to determine whether MRE will prove useful in preoperative planning for PMA.

Slip Interface Imaging Predicts Tumor-Brain Adhesion in Vestibular Schwannomas.

PURPOSE: To test the clinical feasibility and usefulness of slip interface imaging (SII) to identify and quantify the degree of tumor-brain adhesion in patients with vestibular schwannomas. MATERIALS AND METHOD: S With institutional review board approval and after obtaining written informed consent, SII examinations were performed in nine patients with vestibular schwannomas. During the SII acquisition, a low-amplitude mechanical vibration is applied to the head with a pillow-like device placed in the head coil and the resulting shear waves are imaged by using a phase-contrast pulse sequence with motion-encoding gradients synchronized with the applied vibration. Imaging was performed with a 3-T magnetic resonance (MR) system in less than 7 minutes. The acquired shear motion data were processed with two different algorithms (shear line analysis and calculation of octahedral shear strain [OSS]) to identify the degree of tumor-brain adhesion. Blinded to the SII results, neurosurgeons qualitatively assessed tumor adhesion at the time of tumor resection. Standard T2-weighted, fast imaging employing steady-state acquisition (FIESTA), and T2-weighted fluid-attenuated inversion recovery (FLAIR) imaging were reviewed to identify the presence of cerebral spinal fluid (CSF) clefts around the tumors. The performance of the use of the CSF cleft and SII to predict the degree of tumor adhesion was evaluated by using the κ coefficient and McNemar test. RESULTS: Among the nine patients, SII agreed with the intraoperative assessment of the degree of tumor adhesion in eight patients (88.9%; 95% confidence interval [CI]: 57%, 98%), with four of four, three of three, and one of two cases correctly predicted as no adhesion, partial adhesion, and complete adhesion, respectively. However, the T2-weighted, FIESTA, and T2-weighted FLAIR images that used the CSF cleft sign to predict adhesion agreed with surgical findings in only four cases (44.4% [four of nine]; 95% CI: 19%, 73%). The κ coefficients indicate good agreement (0.82 [95% CI: 0.5, 1]) for the SII prediction versus surgical findings, but only fair agreement (0.21 [95% CI: -0.21, 0.63]) between the CSF cleft prediction and surgical findings. However, the difference between the SII prediction and the CSF cleft prediction was not significant (P = .103; McNemar test), likely because of the small sample size in this study. CONCLUSION: SII can be used to predict the degree of tumor-brain adhesion of vestibular schwannomas and may provide a method to improve preoperative planning and determination of surgical risk in these patients.

Pediatric ischemic stroke from an apoplectic prolactinoma.

INTRODUCTION: Pediatric pituitary neoplasms and associated pituitary apoplexy are uncommon. There are few reports in pediatric patients of pituitary apoplexy causing focal arterial compression or diffuse vasospasm resulting in cerebral infarction, and the acute, focal neurological deficits associated with stroke differ from the typical presentation of an apoplectic pituitary tumor. We report the first case of a teenage female with an apoplectic macroprolactinoma presenting with stuttering cerebral infarction secondary to compression of the internal carotid artery (ICA). CASE: A 14-year-old female was transferred from an outside facility after presenting with right hand paresthesias and word-finding difficulty that eventually progressed to include right upper extremity weakness and mental status changes. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed an apoplectic macroprolactinemia and diffusion-weighted imaging showed acute stroke in the left anterior and middle cerebral artery distributions. Evaluation of the cerebral vasculature with MRA showed focal compression of the left supraclinoid ICA. Despite prompt surgical decompression, the patient developed right lower extremity weakness in addition to her other deficits though her deficits improved after inpatient rehabilitation. CONCLUSIONS: In the pediatric population, there is only one other case of pituitary apoplexy presenting with stroke, which was secondary to vasospasm. We present the first case of pituitary apoplexy presenting with stroke secondary to ICA compression. Though rare, it is important to consider that pituitary apoplexy may present with non-classical symptoms such as ischemic stroke even in pediatric patients.

Unexpected σ bond rupture during the reaction of N-methyl-1,2,4-triazoline-3,5-dione with acenaphthylene and indene.

The reaction of N-methyl-1,2,4-triazoline-3,5-dione (MeTAD) with acenaphthylene and indene leads not only to the formation of the expected [2 + 2] diazetidine cycloadducts but also to unexpected 2:1 adducts of MeTAD with substrate. The structures of the products derived from acenaphthylene were confirmed by X-ray crystallography. A similar distribution of products was afforded from indene. The 2:1 adducts appear to derive from a diradical intermediate, the radical centers of which are strongly stabilized by the bridging urazoyl ring and benzylic delocalization. The triplet states of these diradical intermediates may be trapped via exposure to molecular oxygen to afford oxygen-containing adducts. Computational studies at the (U)B3LYP/6-31G* level provide additional support for the conclusions of our experimental work.

Early diagnosis of paroxysmal sympathetic hyperactivity in the ICU.

BACKGROUND: Paroxysmal sympathetic hyperactivity (PSH) is a complication of acquired brain injury manifesting with episodic tachycardia, tachypnea, hypertension, diaphoresis, hypertonia, and posturing. No universally accepted diagnostic criteria exist and diagnosis is often delayed until the rehabilitation phase. METHODS: Electronic records were screened to identify consecutive cases of PSH diagnosed in an intensive care unit (ICU) between 1/2006 and 8/2012 and assess the validity of early clinical diagnosis against formal diagnostic criteria. Data collected included patient demographics, brain injury etiology, symptoms noted by the clinician to support the diagnosis of PSH, PSH manifestations, therapeutic interventions, relevant brain imaging, and investigations to exclude alternative diagnoses. An operational set of diagnostic criteria based on previous literature was used for comparison. RESULTS: Fifty-three consecutive patients with PSH were identified. Mean age was 33.6 ± 14.5 years (range 16-67). Traumatic brain injury was the most common etiology (30 patients, 56.6 %) but causes were diverse. Mean time to diagnosis was 8.3 ± 11.0 days; 31 patients (59 %) were diagnosed within 7 days and 20 patients (38 %) within 3 days of admission. Tachycardia was almost uniformly present, and diaphoresis, fever, hypertension, and tachypnea were also present in most cases. Dystonia and posturing were present in less than half of patients. 89 % of clinically diagnosed cases met formal diagnostic criteria. CONCLUSIONS: Paroxysmal sympathetic hyperactivity can be diagnosed early in the ICU. Strict diagnostic criteria supported the clinician's diagnosis in the majority of cases. Diagnosis should not be rejected because of any particular sign's absence, especially dystonia and posturing.

Complete Genome Sequence of Bacteriophage vB_Hercules_Set, Which Infects Enteric Pathogen Salmonella enterica Serovar Typhimurium.

We report the isolation, sequencing, and annotation of bacteriophage vB_Hercules_Set, a kuttervirus infecting human pathogen Salmonella enterica. vB_Hercules_Set was isolated from a slurry of soil and deli meat collected in New Hampshire in 2021. The genome length is 157,338 nucleotides, containing 210 protein-coding genes and five tRNAs.

The Military Medical Officer's Current-Day Professional Identity: An Enhanced Model.

BACKGROUND: As the landscapes of war have evolved, so too has the role of the military medical officer (MMO). Colonel (Retired) Barry Wolcott developed a "vector" model in the 1990s, illustrating the dual professional role of the MMO. Since then, propelled by the War on Terror, MMOs have adapted to treating patients in volatile, uncertain, complex, and ambiguous operational environments. This study, therefore, aimed to explore modern-day aspects of the MMO's role in order to enhance Wolcott's depiction of the MMO's professional identity in contemporary operational environments. MATERIALS AND METHODS: We used the qualitative phenomenological tradition to design our study. We interviewed military physicians from a variety of specialties in order to explore their experiences and professional identity as MMOs. Our research team then coded each of these interview transcripts. We organized these codes into categories, which served as the themes of our study. RESULTS: The following themes emerged from our data regarding the role of the MMO in the operational environment: Primary roles (officer, physician, educator, and diplomat) and aptitudes (innovation, advocacy, cultural competency, and leadership). The MMO's roles as officer and physician often intersect, with dual foci on the mission and the patient. The MMO also serves as an educator to medics and line officers. In addition, they act as diplomats both outside and within the military. Within each of these primary roles, the MMO innovatively prepares for future landscapes of war and advocates for both the individual warfighter and the unit/command. Finally, the MMO navigates both foreign and internal cultural differences and demonstrates leadership in enabling the military's mission. CONCLUSIONS: The role of the MMO is complex and multifaceted. The recognition of the contemporary MMO's unique skill set is essential for the effective education and training of future military health care leaders. The value of capitalizing on this unique skill set has been demonstrated in recent civ-mil responses. Because their intricate skill set is specialized for the operational environment, long-term retention of MMOs is key to force readiness.

The antibacterial activity of a photoactivatable diarylacetylene against Gram-positive bacteria.

The emergence of antibiotic resistance is a growing threat to human health, and therefore, alternatives to existing compounds are urgently needed. In this context, a novel fluorescent photoactivatable diarylacetylene has been identified and characterised for its antibacterial activity, which preferentially eliminates Gram-positive over Gram-negative bacteria. Experiments confirmed that the Gram-negative lipopolysaccharide-rich outer surface is responsible for tolerance, as strains with reduced outer membrane integrity showed increased susceptibility. Additionally, bacteria deficient in oxidative damage repair pathways also displayed enhanced sensitivity, confirming that reactive oxygen species production is the mechanism of antibacterial activity. This new diarylacetylene shows promise as an antibacterial agent against Gram-positive bacteria that can be activated in situ, potentially for the treatment of skin infections.

Long-term retrospective of the Kaneda anterior scoliosis system in thoracic adolescent idiopathic scoliosis.

BACKGROUND: Currently, the Kaneda anterior scoliosis system (KASS) is reported to be acceptable for the treatment of adolescent idiopathic scoliosis (AIS), particularly thoracolumbar and lumbar deformities. Its use in thoracic AIS is not as established. METHODS: Retrospective analysis of long-term results in patients treated with the KASS for thoracic AIS to determine specific factors associated with success or failure. We analyzed 16 consecutive patients who met the following criteria: thoracic AIS, anterior spinal fusion and KASS, and ≥24 months of follow-up or progression to failure, defined as the need for revision surgery or progression of the main thoracic curve (MTC) ≥50 degrees. Comparison of the MTC on the preoperative, postoperative, and final follow-up was the major evaluation criteria. On the basis of data analysis, patients were divided for comparison into 2 study groups: nonfailure group (n=11) and failure group (n=5). Statistical analysis was performed using paired and independent t tests. RESULTS: All curves were classified as Lenke 1 (n=14) and 2 (n=2). Mean age at surgery and levels fused were 14.6±2.7 years and 5±1 vertebrae, respectively. Mean follow-up was 4.2 years (range, 1.0 to 6.2 y). The failure group consisted of 5 patients that progressed to ≥50 degrees. In the nonfailure group, the mean MTC preoperative, postoperative, and at final follow-up were 52±8, 19±8, and 29±7 degrees, respectively. In the failure group, these measurements were 74±11, 35±8, and 56±12 degrees, respectively. CONCLUSIONS: This retrospective, long-term follow-up study found more KASS failures in thoracic AIS than previously reported. Even in the nonfailure group, 5 of the 11 patients progressed 10 degrees or more. Our results indicate an increased incidence of KASS failure with preoperative MTC curve ≥70 degrees. We consider an MTC≥70 degrees a likely contraindication for KASS instrumentation for thoracic AIS. Four of the 5 failures were fused short of the end vertebrae either proximally, distally, or both. Although short apical fusions were popular during the time these cases were done, fusion to the end vertebrae is an important principle for anterior fusions. Reaching the upper end vertebrae may be more difficult in these larger curves. We also recommend continued follow-up past 2 years as progression can occur after this time. LEVEL OF EVIDENCE: Retrospective comparative study, level III.

Clinical utility of brain biopsy for presumed CNS relapse of systemic lymphoma.

OBJECTIVE: The objective of this study was to determine the frequency with which brain biopsy for presumed CNS relapse of systemic hematological malignancies yields new, actionable diagnostic information. Hematological malignancies represent a disparate group of genetic and histopathological disorders. Proclivity for brain involvement is dependent on the unique entity and may occur synchronously or metasynchronously with the systemic lesion. Diffuse large B-cell lymphomas (DLBCLs) have a high propensity for brain involvement. Patients in remission from systemic DLBCL may present with a lesion suspicious for brain relapse. These patients often undergo brain biopsy. The authors' a priori hypothesis was that brain biopsy in patients with a history of systemic DLBCL and a new brain MRI lesion would have lower diagnostic utility compared with patients with non-DLBCL systemic malignancies. METHODS: The authors performed a retrospective review of patients who underwent brain biopsy between 2000 and 2019. Inclusion criteria were patients ≥ 18 years of age with a prior systemic hematological malignancy in remission presenting with a new brain MRI lesion concerning for CNS relapse. Patients with a history of any CNS neoplasms, demyelinating disorders, or active systemic disease were excluded. The main outcome was the proportion of patients with a distinct histopathological brain diagnosis compared with the systemic malignancy. The authors secondarily assessed overall survival, procedure-related morbidity, and 30-day mortality. RESULTS: Sixty patients met inclusion criteria (40 males and 20 females); the median age at brain biopsy was 67 years (range 23-88 years). The median follow-up was 8.5 months (range 0.1-231 months). Thirty-nine (65.0%) patients had DLBCL and 21 (35%) had non-DLBCL malignancies. Thirty-five of 36 (97.2%) patients with prior systemic DLBCL and a diagnostic biopsy had histopathological confirmation of the original systemic disease versus 0 of 21 patients with non-DLBCL systemic malignancies (p < 0.001). Morbidity and 30-day mortality were 8.3% and 10.0%, respectively; 2 of 6 30-day mortalities were directly attributable to the biopsy. The median overall survival following brain biopsy was 10.8 months. CONCLUSIONS: Patients with a history of systemic DLBCL and presumed CNS relapse gained minimal clinical benefit from brain biopsy but were at high risk of morbidity and mortality. In patients with a history of non-DLBCL systemic malignancies, brain biopsy remained critical given the high likelihood for discovery of distinct diagnostic entities. It was determined that patients with a prior systemic DLBCL and presumed brain relapse should likely receive empirical therapy obviating treatment delay and the risks of brain biopsy.

Calcium entry via ORAI1 regulates glioblastoma cell proliferation and apoptosis.

INTRODUCTION: Calcium entry plays a critical role in the proliferation and survival of certain tumors. Ca(2+) release activated Ca(2+) (CRAC) channels constitute one of the most important pathways for calcium entry especially that of store-operated calcium entry (SOCE). ORAI1 and stromal interaction molecule1 (STIM1) are essential protein components of CRAC channels. In this study we tested the effect of inhibiting CRAC through ORAI1 and STIM1 on glioblastoma multiforme (GBM) tumor cell proliferation and survival. METHODS: Two glioblastoma cell lines, C6 (rat) and U251 (human), were used in the study. ORAI1 and STIM1 expressions were examined using Western blot and immunohistochemistry. CRAC channel activity and its components were inhibited with ion channel blockers and using siRNA knockdown. Changes in intracellular calcium concentration were recorded using Fura-2 fluorescent calcium imaging. Cell proliferation and apoptosis were examined using MTS and TUNEL assays, respectively. RESULTS: CRAC blockers, such as SKF-96365 (1-[2-(4-methoxyphenyl)-2-[3-(4-methoxyphenyl) propoxy]ethyl-1H-imidazole), 2-aminoethoxydiphenyl borate (2-APB) and Diethylstilbestrol (DES), inhibited cell proliferations and SOCE in GBM cells. Knockdown of ORAI1 and STIM1 proteins using siRNA significantly inhibited C6 cell proliferation and SOCE compared with those in control cells, and a more significant effect was observed in cells with ORAI1 siRNA knockdown than that of STIM1-treated cells. Both CRAC blockers and siRNA treatments increased apoptosis in C-6 cells compared with control. CONCLUSION: Calcium entry via ORAI1 and CRAC channels are important for GBM proliferation and survival.

Delaying Postoperative Radiotherapy in Low-Grade Esthesioneuroblastoma: Is It Worth the Wait?

Background Consensus in timing of radiotherapy is yet to be established in esthesioneuroblastoma (ENB). Objective This study was aimed to investigate if planned adjuvant radiotherapy improves tumor control after complete margin negative resection of low Hyams' grade (1 or 2) ENB. Methods A retrospective review of patients with pathologically confirmed negative margin resection of Kadish's stage B or C and Hyams' grade 1 and 2 ENBs was conducted. Seventeen patients meeting the criteria were divided into the following two groups for cohort study: (1) those who underwent planned immediate postoperative adjuvant radiotherapy (IR group) and (2) those who did not (delayed radiotherapy [DR] group). Results The IR group included nine patients (Kadish's stage B in one and stage C in eight; Hyams' grade 1 in two and grade 2 in seven). Mean follow-up was 140.8 months. Seven patients (78%) had disease progression (DP) at a median of 88 months (four with cervical lymph node metastasis [CLNM], one with distant metastasis, and two with both local recurrence and CLNM). One patient experienced frontal lobe abscess. The DR group included eight patients (Kadish's stage B in six and stage C in two; all Hyams' grade 2). Mean follow-up was 123.3 months. Four (50%) patients who developed DP (all local recurrence) were salvaged with surgery and adjuvant radiotherapy at a median of 37.5 months. There was no statistically significant difference in DP rate ( p = 0.23), time to DP ( p = 0.26), or the local tumor control rate ( p = 0.23). Conclusion In our limited cohort, immediate postoperative radiotherapy did not demonstrate superiority in tumor control, although risk of radiotherapy toxicity appears low.

Radiosurgical Management of Patients With Persistent or Recurrent Cushing Disease After Prior Transsphenoidal Surgery: A Management Algorithm Based on a 25-Year Experience.

BACKGROUND: Patients with persistent or recurrent Cushing disease (CD) after prior transsphenoidal surgery require further treatment to reduce the disease's metabolic consequences. OBJECTIVE: To assess patient outcomes after stereotactic radiosurgery (SRS) for persistent or recurrent CD from adrenocorticotropin hormone (ACTH)-secreting pituitary adenomas and propose a management algorithm. METHODS: Retrospective review of 38 patients without prior radiation treatment having SRS for ACTH-secreting pituitary adenomas from 1990 to 2015. Favorable outcome was defined as biochemical remission and tumor growth control. Patients were evaluated separately if they underwent bilateral adrenalectomy (Adx). RESULTS: Twenty patients (53%) were treated with Adx and SRS (median margin dose, 25 Gy) and 18 patients (47%) received SRS alone (median margin dose, 22.5 Gy). Median follow-up after SRS was 76 mo. Of patients undergoing Adx, 18/20 (90%) had a favorable outcome. Two patients (10%) had tumor growth requiring additional treatment. A favorable outcome was achieved in 13/18 patients (72%) having SRS alone (median, 14 mo; interquartile range, 8-23). Five patients (28%) required additional treatment due to persistent hypercortisolemia (n = 4) or hypercortisolemia and tumor growth (n = 1). Favorable outcomes were more frequent in the Adx and SRS group at 1 yr (100% vs 33%; P < .001) and 3 yr (100% vs 62%; P < .01), but no different at 5 yr (88% vs 77%; P = .63). CONCLUSION: SRS was effective for patients with persistent or recurrent CD. Patients with mild to moderate CD can be safely managed with SRS alone; patients with severe CD should be considered for Adx with either concurrent SRS or SRS performed at a later date if tumor growth occurs.

Is There a Need for a 6-Month Postradiosurgery Magnetic Resonance Imaging in the Treatment of Vestibular Schwannoma?

BACKGROUND: Stereotactic radiosurgery (SRS) is a common treatment modality for vestibular schwannoma (VS), with a role in primary and recurrent/progressive algorithms. At our institution, routine magnetic resonance imaging (MRI) is obtained at 6 and 12 mo following SRS for VS. OBJECTIVE: To analyze the safety and financial impact of eliminating the 6-mo post-SRS MRI in asymptomatic VS patients. METHODS: A prospectively maintained SRS database was retrospectively reviewed for VS patients with 1 yr of post-treatment follow-up, 2005 to 2015. Decisions at 6-mo MRI were binarily categorized as routine follow-up vs clinical action-defined as a clinical visit, additional imaging, or an operation as a direct result of the 6-mo study. RESULTS: A total of 296 patients met screening criteria, of whom 53 were excluded for incomplete follow-up and 8 for NF-2. Nine were reimaged prior to 6 mo due to clinical symptoms. Routine 6-mo post-SRS MRI was completed by 226 patients (76% of screened cohort), following from which zero instances of clinical action occurred. When scaled using national insurance database-derived financials-which estimated the mean per-study charge for MRI of the brain with and without contrast at $1767-the potential annualized national charge reduction was approximated as $1 611 504. CONCLUSION: For clinically stable VS, 6-mo post-SRS MRI does not contribute significantly to management. We recommend omitting routine MRI before 12 mo, in patients without new or progressive neurological symptoms. If extrapolated nationally to the more than 100 active SRS centers, thousands of patients would be spared an inconvenient, nonindicated study, and national savings in health care dollars would be on the order of millions annually.

Transsylvian, Carotid-Oculomotor Triangle Approach for Resection of a Rapidly Enlarging Midbrain-Pontine Cavernous Malformation: 3-Dimensional Operative Video.

Cavernous malformations (CM) of the anterior midbrain are best reached through an orbitozygomatic (OZ) approach with removal of the orbital rim and wide Sylvian fissure dissection. Our surgical video demonstrates this approach to resect a ruptured CM in a 36-yr-old woman who presented with headaches, left face and left arm paresthesias/weakness, and right-sided partial oculomotor nerve (CN III) palsy. Initial magnetic resonance imaging (MRI) showed a midbrain CM, and the patient was managed conservatively. However, 1 wk later, she presented again with worsened left arm and leg weakness and complete CN III palsy. Seven Tesla MRI demonstrated a larger hematoma, and the CM with new mass effect and upper pons extension. The patient underwent a right modified OZ craniotomy and Sylvian fissure split under guidance of intraoperative neuronavigation and with neuromonitoring. The carotid-oculomotor triangle and the Liliequist membrane were dissected to access the midbrain, and CN III was identified and followed posteriorly to the midbrain. Confirmed with neuronavigation, a longitudinal incision of the midbrain was performed, and the CM was encountered. The hematoma and CM were debulked and removed in a piece-meal fashion, leaving hemosiderin-stained brain intact to prevent unnecessary additional damage to the midbrain. Postoperative MRI confirmed gross-total resection, and the patient's weakness recovered substantially. In this video, we demonstrate that the brainstem is no longer forbidden surgical territory, and show how the use of neuronavigation for surgical planning, positioning, and approach, in addition to the understanding of safe entry zones and meticulous microsurgical technique have made safe and effective surgery on the brainstem possible.