Cerebral vasospasm in patients with traumatic subarachnoid hemorrhage, a possible point of intervention?

OBJECTIVE: To determine the incidence of vasospasm in traumatic brain injury patients with traumatic subarachnoid hemorrhage. METHODS: IRB approval was obtained for this retrospective chart review. An institutional trauma database was queried for adult patients with traumatic brain injury (TBI) and traumatic subarachnoid hemorrhage (tSAH) seen on CT head obtained within 20 days. The presence of vasospasm on CTA was determined by radiology report. Association between categorical background characteristics and intracranial vasospasm was assessed by the chi-square test and association between a continuous variables and intracranial vasospasm was assessed by a paired t-test. RESULTS: 1142 patients with traumatic SAH were identified from the trauma database. 792 patients were excluded: 142 for age <18, 632 did not have CT angiography, and 18 had non-traumatic SAH. 350 patients were analyzed, of which 28 (8 %) had vasospasm. Traumatic vasospasm was associated with higher-grade TBI based on Cochran-Armitage trend test (p < 0.05). Vasospasm patients had longer length of stay in the ICU (mean days 13.64 vs 7.24, P < 0.001), and had a higher incidence of death (39.29 % vs 20.81 %), although this did not reach statistical significance. CONCLUSION: Intracranial vasospasm, specifically in patients with tSAH, is associated with more severe TBI and longer stays in the ICU. Our incidence is smaller compared to other studies likely due to the retrospective nature and the infrequency of obtaining CT angiography after initial presentation. Prospective studies are warranted as the incidence is significant and may represent a point of intervention for TBI.

Management of nonoperative cervical spine fractures: An institutional analysis of follow-up duration and image acquisition.

Background: How long do nonoperative cervical fractures have to be followed and with how many imaging studies? Methods: We reviewed 69 adult patients with 122 (31 occiptocervical and 91 sub-axial) cervical fractures; at least one of the cervical fractures was managed nonoperatively. Outcomes were assessed along with the optimal follow-up duration and frequency of various diagnostic studies. Results: An average of four follow-up visits occurred on average 28-, 66-, 94-, and 158-day post hospital discharge. The average time between discharge and orthotic clearance was 70 days (±32.4 days). Radiographic studies were obtained at follow-up visits, respectively, in, 82.6%, 83.6%, 94.7%, and 100% of patients. Conclusion: The trend for managing nonoperative cervical fractures was an unduly prolonged follow-up duration that included obtaining too many imaging studies.

A systematic review of amino acid PET in assessing treatment response to temozolomide in glioma.

The response assessment in neuro-oncology (RANO) criteria have been the gold standard for monitoring treatment response in glioblastoma (GBM) and differentiating tumor progression from pseudoprogression. While the RANO criteria have played a key role in detecting early tumor progression, their ability to identify pseudoprogression is limited by post-treatment damage to the blood-brain barrier (BBB), which often leads to contrast enhancement on MRI and correlates poorly to tumor status. Amino acid positron emission tomography (AA PET) is a rapidly growing imaging modality in neuro-oncology. While contrast-enhanced MRI relies on leaky vascularity or a compromised BBB for delivery of contrast agents, amino acid tracers can cross the BBB, making AA PET particularly well-suited for monitoring treatment response and diagnosing pseudoprogression. The authors performed a systematic review of PubMed, MEDLINE, and Embase through December 2021 with the search terms "temozolomide" OR "Temodar," "glioma" OR "glioblastoma," "PET," and "amino acid." There were 19 studies meeting inclusion criteria. Thirteen studies utilized [18F]FET, five utilized [11C]MET, and one utilized both. All studies used static AA PET parameters to evaluate TMZ treatment in glioma patients, with nine using dynamic tracer parameters in addition. Throughout these studies, AA PET demonstrated utility in TMZ treatment monitoring and predicting patient survival.

A systematic review of the utility of amino acid PET in assessing treatment response to bevacizumab in recurrent high-grade glioma.

BACKGROUND: Currently, bevacizumab (BEV), an antiangiogenic agent, is used as an adjunctive therapy to re-irradiation and surgery in patients with recurrent high-grade gliomas (rHGG). BEV has shown to decrease enhancement on MRI, but it is often unclear if these changes are due to tumor response to BEV or treatment-induced changes in the blood brain barrier. Preliminary studies show that amino acid PET can aid in distinguishing these changes on MRI. METHODS: The authors performed a systematic review of PubMed and Embase through July 2020 with the search terms 'bevacizumab' or 'Avastin' and 'recurrent glioma' and 'PET,' yielding 38 papers, with 14 meeting inclusion criteria. RESULTS: Thirteen out of fourteen studies included in this review used static PET and three studies used dynamic PET to evaluate the use of BEV in rHGG. Six studies used the amino acid tracer [18F]FET, four studies used [11C]MET, and four studies used [18F]FDOPA. CONCLUSION: [18F]FET, [11C]MET, and [18F]FDOPA PET in combination with MRI have shown promising results for improving accuracy in diagnosing tumor recurrence, detecting early treatment failure, and distinguishing between tumor progression and treatment-induced changes in patients with rHGG treated with BEV.

Reported incidence and treatment modalities of giant cerebral aneurysms in the pediatric population: A systematic review and illustrative case report.

Giant intracranial aneurysms represent a complex pathology that pose challenges for management, especially in the pediatric population. With emerging endovascular techniques, combined endovascular and open surgical approaches may be a favorable alternative for complex cases. In this systematic review, we characterize the treatment modalities of giant aneurysms in the pediatric population and provide an update on the number of giant aneurysms reported in the literature by anatomic location. We conducted a literature search of PubMed, Embase, and Medline databases with the following terms: 'pediatric' AND 'giant' AND 'intracranial aneurysm.' Studies were included if data on treatment modality and aneurysm location were available for pediatric patients with giant intracranial aneurysms. The literature search yielded a total of 188 papers, with 82 pediatric patients from 33 articles ultimately meeting inclusion criteria. There were significantly more male than female patients (p = 0.011), with 52 and 29 respectively. Patients presenting with a ruptured aneurysm were significantly younger than patients presenting without rupture (p = 0.018), with a median age of 8.0 and 12.0 years, respectively. There were 45 giant aneurysms reported in the anterior circulation and 37 in the posterior circulation. Anterior aneurysms were most often treated with surgical approaches, while posterior aneurysms were typically treated with endovascular interventions (p = 0.002). Although combined surgical and endovascular approaches were the least frequently utilized, we suggest a combined approach may be particularly useful for patients with complex cases that require a management plan tailored to their needs.

Investigating sensory processing in the pectines of the striped bark scorpion, Centruroides vittatus.

Scorpion pectines detect chemical and physical stimuli via thousands of peg sensilla on ground-facing teeth. Each sensillum has multiple neurons that detect stimuli and transmit neural impulses to the subesophageal ganglion (SEG) in the central nervous system. Anatomically, the organization of the pectinal neuropil in the SEG reflects the arrangement of pectinal teeth, suggesting conservation of information about stimulus location in the SEG. In this study, neural impulses from the pectinal nerve of the striped bark scorpion (Centruroides vittatus) were recorded in the pecten, abdominal cavity, and SEG using electrophysiology. Recordings from the right pectinal nerve in the pecten showed that right tooth stimulations elicit sensory activity milliseconds before motor feedback, while left tooth stimulations only evoked motor spikes, suggesting no contralateral afferent communication between pectines. In the abdominal cavity recordings, two distinct waveforms (PN1 and PN2) were detected in baseline activity; PN1 seemed to enhance the likelihood that PN2 would fire, suggesting a possible excitatory interaction. Recordings from the SEG showed that mechanically stimulating different pectinal teeth evoked different compound neural activity patterns in the same SEG location. Stimulating the same tooth in succession showed mechanosensory adaptation. These recordings show promise for continued electrophysiological investigations of the scorpion SEG, and, in particular, how information from the pectines is processed and used for orientation.

HGF/c-met/Stat3 signaling during skin tumor cell invasion: indications for a positive feedback loop.

BACKGROUND: Stat3 is a cytokine- and growth factor-inducible transcription factor that regulates cell motility, migration, and invasion under normal and pathological situations, making it a promising target for cancer therapeutics. The hepatocyte growth factor (HGF)/c-met receptor tyrosine kinase signaling pathway is responsible for stimulation of cell motility and invasion, and Stat3 is responsible for at least part of the c-met signal. METHODS: We have stably transfected a human squamous cell carcinoma (SCC) cell line (SRB12-p9) to force the expression of a dominant negative form of Stat3 (S3DN), which we have previously shown to suppress Stat3 activity. The in vitro and in vivo malignant behavior of the S3DN cells was compared to parental and vector transfected controls. RESULTS: Suppression of Stat3 activity impaired the ability of the S3DN cells to scatter upon stimulation with HGF (c-met ligand), enhanced their adhesion, and diminished their capacity to invade in vitro and in vivo. Surprisingly, S3DN cells also showed suppressed HGF-induced activation of c-met, and had nearly undetectable basal c-met activity, as revealed by a phospho-specific c-met antibody. In addition, we showed that there is a strong membrane specific localization of phospho-Stat3 in the wild type (WT) and vector transfected control (NEO4) SRB12-p9 cells, which is lost in the S3DN cells. Finally, co-immunoprecipitation experiments revealed that S3DN interfered with Stat3/c-met interaction. CONCLUSION: These studies are the first confirm that interference with the HGF/c-met/Stat3 signaling pathway can block tumor cell invasion in an in vivo model. We also provide novel evidence for a possible positive feedback loop whereby Stat3 can activate c-met, and we correlate membrane localization of phospho-Stat3 with invasion in vivo.