A phase III, multicenter, randomized controlled trial of preoperative versus postoperative stereotactic radiosurgery for patients with surgically resectable brain metastases.

BACKGROUND: Postoperative stereotactic radiosurgery (SRS) is a standard management option for patients with resected brain metastases. Preoperative SRS may have certain advantages compared to postoperative SRS, including less uncertainty in delineation of the intact tumor compared to the postoperative resection cavity, reduced rate of leptomeningeal dissemination postoperatively, and a lower risk of radiation necrosis. The recently published ASCO-SNO-ASTRO consensus statement provides no recommendation for the preferred sequencing of radiotherapy and surgery for patients receiving both treatments for their brain metastases. METHODS: This multicenter, randomized controlled trial aims to recruit 88 patients with resectable brain metastases over an estimated three-year period. Patients with ten or fewer brain metastases with at least one resectable, fulfilling inclusion criteria will be randomized to postoperative SRS (standard arm) or preoperative SRS (investigational arm) in a 1:1 ratio. Randomization will be stratified by age (< 60 versus ≥60 years), histology (melanoma/renal cell carcinoma/sarcoma versus other), and number of metastases (one versus 2-10). In the standard arm, postoperative SRS will be delivered within 3 weeks of surgery, and all unresected metastases will receive primary SRS. In the investigational arm, enrolled patients will receive SRS of all brain metastases followed by surgery of resectable metastases within one week of SRS. In either arm, single fraction or hypofractionated SRS in three or five fractions is permitted. The primary endpoint is to assess local control at 12 months in both arms. Secondary endpoints include local control at other time points, regional/distant brain recurrence rates, leptomeningeal recurrence rates, overall survival, neurocognitive outcomes, and adverse radiation events including radiation necrosis rates in both arms. DISCUSSION: This trial addresses the unanswered question of the optimal sequencing of surgery and SRS in the management of patients with resectable brain metastases. No randomized data comparing preoperative and postoperative SRS for patients with brain metastases has been published to date. TRIAL REGISTRATION: Clinicaltrials.gov , NCT04474925; registered on July 17, 2020. Protocol version 1.0 (January 31, 2020). SPONSOR: Alberta Health Services, Edmonton, Canada (Samir Patel, MD).

Neurology of Acute Viral Infections.

As specialists in acute neurology, neurohospitalists are often called upon to diagnose and manage acute viral infections affecting the nervous system. In this broad review covering the neurology of several acute viral infections, our aim is to provide key diagnostic and therapeutic pearls of practical use to the busy neurohospitalist. We will review acute presentations, diagnosis, and treatment of human herpesviruses, arboviruses, enteroviruses, and some vaccine-preventable viruses. The neurological effects of coronaviruses, including COVID-19, are not covered in this review.

High-amplitude time reversal focusing of airborne ultrasound to generate a focused nonlinear difference frequency.

Time reversal (TR) focusing of airborne ultrasound in a room is demonstrated. Various methods are employed to increase the amplitude of the focus. These methods include creating a small wooden box (or chamber) to act as a miniature reverberation chamber, using multiple sources, and using the clipping processing method. The use of a beam blocker to make the sources more omnidirectional is also examined, and it is found that for most source/microphone orientations, the use of a beam blocker increases the amplitude of the focus. A high-amplitude focus of 134 dB peak re 20 µPa sound pressure level with a center frequency of about 38 kHz is generated using TR. Using four sources centered at 36.1 kHz and another four sources centered at 39.6 kHz, nonlinear difference frequency content centered at 3.5 kHz is observed in the focus signal. The difference frequency amplitude grows quadratically with increasing primary frequency amplitude. When using beam blockers, the difference frequency content propagates away from the focal location with higher amplitude than when beam blockers are not used. This is likely due to the differences in the directionality of the converging waves during TR focusing.

A Pacchionian Puzzle.

A 73-year-old male with a history of chronic ataxia presented with transient facial droop to the Emergency Department. A CT angiogram and MRI with diffusion weighted imaging (DWI) were negative for stroke. However, incidental note was made of numerous giant arachnoid granulation pits in the posterior fossa predominantly involving the left occipital bone (Figure 1). These arachnoid pits demonstrated multiple foci of herniation of the adjacent cerebellar parenchyma into the pits with gliosis of the herniated parenchyma and focal encephalomalacia of the subjacent cerebellar parenchyma. Review of bone windows on a remote CT brain performed almost 13 years earlier confirmed this to be a longstanding abnormality (Figure 2). The patient's physical exam was suggestive of cerebellar ataxia with left-sided dysmetria on finger to nose testing and a wide-based unsteady gait.

A phase I trial of intratumoral administration of reovirus in patients with histologically confirmed recurrent malignant gliomas.

Reovirus is an oncolytic virus with activity in in vivo models of malignant gliomas (MGs). The primary aims were to determine the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of intratumoral administration of reovirus in patients with recurrent MGs. Response, survival, and time to progression (TTP) were secondary aims. Patients were adults, had Karnofsky Performance score > or = 60, received prior radiotherapy with or without chemotherapy, and had up to the third recurrence of MG. Reovirus was administered intratumorally stereotactically at 1 x 10(7), 1 x 10(8), or 1 x 10(9) tissue culture infectious dose 50 (TCID50) in a volume of 0.9 ml. Twelve patients were treated at three dose levels (3, 6, and 3 patients, respectively). Seven were men, median Karnofsky Performance score was 80, and median age was 53.5 years. There were no grade III or IV adverse events (AEs) definitely or probably related to treatment. Ten patients had tumor progression, one had stabilization, and one was not evaluable for response. Median survival was 21 weeks (range, 6-234), and one is alive 54 months after treatment. Median TTP was 4.3 weeks (range, 2.6-39). An MTD was not reached. The intratumoral administration of the genetically unmodified reovirus was well tolerated using these doses and schedule, in patients with recurrent MG.

Posterior fossa lesion volume and slowed information processing in multiple sclerosis.

The relationship between performance on information processing efficiency measures and MRI-derived lesion volume including global and regional T2 and T1 lesion volumes was investigated in 20 patients with relapsing-remitting multiple sclerosis (RRMS) and secondary progressive multiple sclerosis (SPMS). Processing speed, as measured by the Sternberg Memory Scanning Test, was significantly correlated with posterior fossa lesion volume and slowed reaction time in seven out of eight patients (six out of seven with SPMS) with any lesion volume in the posterior fossa suggesting a 'threshold effect'. Processing capacity as measured by the Salthouse Keeping Track Test was not significantly correlated with the MRI measures. Cognitive performance did not correlate with Expanded Disability Status Scale score, depression or fatigue, and patients performed within normal limits on tests of attention/concentration ability. The significant relationship between posterior fossa lesion volume and memory scanning speed in this study suggests that pathological damage in the posterior fossa may contribute to slowed cognitive processing and may be an important direction for future studies of cognitive function in multiple sclerosis. Lack of correlation of cognitive measures with the other MRI measures may be due to low lesion volume relative to other studies, sample composition, and limited pathological specificity of the MRI measures.

Intraoperative assessment of aneurysm clipping using magnetic resonance angiography and diffusion-weighted imaging: technical case report.

OBJECTIVE AND IMPORTANCE: To use intraoperative magnetic resonance imaging, including magnetic resonance angiography and diffusion-weighted imaging, to monitor the surgical treatment of a patient with an intracranial aneurysm. TECHNIQUE: Intraoperative imaging was performed with a ceiling-mounted, mobile, 1.5-T magnet (developed in collaboration with Innovative Magnetic Resonance Imaging Systems, Inc., Winnipeg, MB, Canada) that included high-performance 20-mT/m gradients. Pre- and postclipping, intraoperative, T1-weighted, angiographic and diffusion-weighted magnetic resonance images were obtained from a patient with an incidental, 8-mm, anterior communicating artery aneurysm. RESULTS: T1-weighted images demonstrated brain anatomic features, with visible shifts induced by surgery. Magnetic resonance angiography demonstrated the aneurysm and indicated that, after clipping, the A1 and A2 anterior cerebral artery branches were patent. Diffusion-weighted studies demonstrated no evidence of brain ischemia. CONCLUSION: For the first time, intraoperative magnetic resonance imaging has been used to monitor the surgical treatment of a patient with an intracranial aneurysm.