4d CT to assess spinal instability in developmental anomaly of posterior arch of atlas

Four-dimensional (4D) CT uniquely allows cinematic visualization of the entirety of joint motion throughout dynamic movement, which can reveal subtle or transient internal joint derangements not evident on static images. As developmental anomalies of the posterior arch can predispose to cervical spinal instability and neurological morbidity, precise assessment of spinal movement during motion is of clinical relevance. We describe the use of 4D-CT in a subject with partial absence of posterior C1 arch. This, to our knowledge, is the first such report. In at-risk individuals, 4D-CT has the potential to enable an assessment of spinal instability with a higher level of clarity and, in this sense, its more routine implementation may be a future direction.

Rivaroxaban versus aspirin for prevention of covert brain infarcts in patients with embolic stroke of undetermined source: NAVIGATE ESUS MRI substudy

Background Covert brain infarcts are associated with important neurological morbidity. Their incidence in patients with embolic stroke of undetermined source (ESUS) is unknown. Aims To assess the incidence of covert brain infarcts and cerebral microbleeds using MRI in a prospective substudy of the NAVIGATE ESUS randomized trial and to evaluate the effects of antithrombotic therapies. Methods At 87 sites in 15 countries, substudy participants were randomly assigned to receive rivaroxaban 15 mg daily or aspirin 100 mg daily and underwent brain MRI near randomization and after study termination. The primary outcome was incident brain infarct (clinical ischemic stroke or covert brain infarct). Brain infarcts and microbleeds were ascertained centrally by readers unaware of treatment. Treatment effects were estimated using logistic regression. Results Among the 718 substudy participants with interpretable, paired MRIs, the mean age was 67 years and 61% were men with a median of 52 days between the qualifying ischemic stroke and randomization and a median of seven days between randomization and baseline MRI. During the median (IQR) 11 (12) month interval between scans, clinical ischemic strokes occurred in 27 (4%) participants, while 60 (9%) of the remaining participants had an incident covert brain infarct detected by MRI. Assignment to rivaroxaban was not associated with reduction in the incidence of brain infarct (OR 0.77, 95% CI 0.49, 1.2) or of covert brain infarct among those without clinical stroke (OR 0.85, 95% CI 0.50, 1.4). New microbleeds were observed in 7% and did not differ among those assigned rivaroxaban vs. aspirin (HR 0.95, 95% CI 0.52–1.7). Conclusions Incident covert brain infarcts occurred in twice as many ESUS patients as a clinical ischemic stroke. Treatment with rivaroxaban compared with aspirin did not significantly reduce the incidence of covert brain infarcts or increase the incidence of microbleeds, but the confidence intervals for treatment effects were wide. Registration: https://www.clinicaltrials.gov . Unique identifier: NCT 02313909

Stereotactic Radiosurgery Versus Active Surveillance for Asymptomatic, Skull-Based Meningiomas: An International, Multicenter Matched Cohort Study

Objective: The optimal management of asymptomatic, skull-based meningiomas is not well defined. The aim of this study is to compare the imaging and clinical outcomes of patients with asymptomatic, skull-based meningiomas managed either with upfront stereotactic radiosurgery (SRS) or active surveillance.Methods: This retrospective, multicenter study involved patients with asymptomatic, skull-based meningiomas. The study end-points included local tumor control and the development of new neurological deficits attributable to the tumor. Factors associated with tumor progression and neurological morbidity were also analyzed.Results: The combined unmatched cohort included 417 patients. Following propensity score matching for age, tumor volume, and follow-up 110 patients remained in each cohort. Tumor control was achieved in 98.2% and 61.8% of the SRS and active surveillance cohorts, respectively. SRS was associated with superior local tumor control (p<0.001, HR=0.01, 95% CI=0.002-0.13) compared to active surveillance. Three patients (2.7%) in the SRS cohort and six (5.5%) in the active surveillance cohort exhibited neurological deterioration. One (0.9 %) patient in the SRS-treated and 11 (10%) patients in the active surveillance cohort required surgical management of their meningioma during follow-up.Conclusions: SRS is associated with superior local control of asymptomatic, skull-based meningiomas as compared to active surveillance and does so with low morbidity rates. Active surveillance with regular neuroimaging studies does not always detect tumor growth before symptomatic progression. SRS should be considered as an alternative to active surveillance at diagnosis of an asymptomatic skull base meningioma. If active surveillance is initially chosen, SRS should be recommended when tumor growth from the original presenting volume is noted during follow-up.

Nos2 -/- Mice Infected With M. Tuberculosis Develop Neurobehavioral Changes and Immunopathology Mimicking Human Central Nervous System Tuberculosis

BackgroundUnderstanding the pathophysiology of central nervous system tuberculosis (CNS-TB) is hampered by the lack of a good pre-clinical model that mirrors the human CNS-TB infection. We developed a murine CNS-TB model that demonstrates neurobehavioral changes with similar immunopathology with human CNS-TB. MethodsWe injected two Mycobacterium tuberculosis ( M.tb ) strains, H37Rv and CDC1551, respectively, into two mouse strains, C3HeB/FeJ and Nos2 -/- mice, either into the third ventricle or intravenous. We compared the neurological symptoms, histopathological changes and levels of adhesion molecules, chemokines, and inflammatory cytokines in the brain induced by the infections through different routes in different strains. ResultsIntra-cerebroventricular infection of Nos2 -/- mice with M.tb led to development of neurological signs and more severe brain granulomas compared to C3HeB/FeJ mice. Compared with CDC1551 M.tb , H37Rv M.tb infection resulted in a higher neurobehavioral score and earlier mortality. Intra-cerebroventricular infection caused necrotic neutrophil-dominated pyogranulomas in the brain relative to intravenous infection which resulted in disseminated granulomas and mycobacteraemia. Histologically, intra-cerebroventricular infection of Nos2 -/- mice with M.tb resembled human CNS-TB brain biopsy specimens. H37Rv intra-cerebroventricular infected mice demonstrated higher brain concentrations of inflammatory cytokines, chemokines and adhesion molecule ICAM-1 than H37Rv intravenous-infected mice. ConclusionsIntra-cerebroventricular infection of Nos2 -/- mice with H37Rv creates a murine CNS-TB model that resembled human CNS-TB immunopathology, exhibiting the worst neurobehavioral score and with a high and early mortality reflecting disease severity and its associated neurological morbidity. Our murine CNS-TB model serves as a pre-clinical platform to dissect host-pathogen interactions and evaluate therapeutic agents for CNS-TB.

5-Aminolevulinic acid for enhanced surgical visualization of high-grade gliomas: a prospective, multicenter study

OBJECTIVE Greater extent of resection (EOR) is associated with longer overall survival in patients with high-grade gliomas (HGGs). 5-Aminolevulinic acid (5-ALA) can increase EOR by improving intraoperative visualization of contrast-enhancing tumor during fluorescence-guided surgery (FGS). When administered orally, 5-ALA is converted by glioma cells into protoporphyrin IX (PPIX), which fluoresces under blue 400-nm light. 5-ALA has been available for use in Europe since 2010, but only recently gained FDA approval as an intraoperative imaging agent for HGG tissue. In this first-ever, to the authors’ knowledge, multicenter 5-ALA FGS study conducted in the United States, the primary objectives were the following: 1) assess the diagnostic accuracy of 5-ALA–induced PPIX fluorescence for HGG histopathology across diverse centers and surgeons; and 2) assess the safety profile of 5-ALA FGS, with particular attention to neurological morbidity. METHODS This single-arm, multicenter, prospective study included adults aged 18–80 years with Karnofsky Performance Status (KPS) score > 60 and an MRI diagnosis of suspected new or recurrent resectable HGG. Intraoperatively, 3–5 samples per tumor were taken and their fluorescence status was recorded by the surgeon. Specimens were submitted for histopathological analysis. Patients were followed for 6 weeks postoperatively for adverse events, changes in the neurological exam, and KPS score. Multivariate analyses were performed of the outcomes of KPS decline, EOR, and residual enhancing tumor volume to identify predictive patient and intraoperative variables. RESULTS Sixty-nine patients underwent 5-ALA FGS, providing 275 tumor samples for analysis. PPIX fluorescence had a sensitivity of 96.5%, specificity of 29.4%, positive predictive value (PPV) for HGG histopathology of 95.4%, and diagnostic accuracy of 92.4%. Drug-related adverse events occurred at a rate of 22%. Serious adverse events due to intraoperative neurological injury, which may have resulted from FGS, occurred at a rate of 4.3%. There were 2 deaths unrelated to FGS. Compared to preoperative KPS scores, postoperative KPS scores were significantly lower at 48 hours and 2 weeks but were not different at 6 weeks postoperatively. Complete resection of enhancing tumor occurred in 51.9% of patients. Smaller preoperative tumor volume and use of intraoperative MRI predicted lower residual tumor volume. CONCLUSIONS PPIX fluorescence, as judged by the surgeon, has a high sensitivity and PPV for HGG. 5-ALA was well tolerated in terms of drug-related adverse events, and its application by trained surgeons in FGS for HGGs was not associated with any excess neurological morbidity.

International survey of neuromonitoring and neurodevelopmental outcome in children and adults supported on extracorporeal membrane oxygenation in Europe

Background: Adverse neurological events during extracorporeal membrane oxygenation (ECMO) are common and may be associated with devastating consequences. Close monitoring, early identification and prompt intervention can mitigate early and late neurological morbidity. Neuromonitoring and neurocognitive/neurodevelopmental follow-up are critically important to optimize outcomes in both adults and children. Objective: To assess current practice of neuromonitoring during ECMO and neurocognitive/neurodevelopmental follow-up after ECMO across Europe and to inform the development of neuromonitoring and follow-up guidelines. Methods: The EuroELSO Neurological Monitoring and Outcome Working Group conducted an electronic, web-based, multi-institutional, multinational survey in Europe. Results: Of the 211 European ECMO centres (including non-ELSO centres) identified and approached in 23 countries, 133 (63%) responded. Of these, 43% reported routine neuromonitoring during ECMO for all patients, 35% indicated selective use, and 22% practiced bedside clinical examination alone. The reported neuromonitoring modalities were NIRS ( n = 88, 66.2%), electroencephalography ( n = 52, 39.1%), transcranial Doppler ( n = 38, 28.5%) and brain injury biomarkers ( n = 33, 24.8%). Paediatric centres (67%) reported using cranial ultrasound, though the frequency of monitoring varied widely. Before hospital discharge following ECMO, 50 (37.6%) reported routine neurological assessment and 22 (16.5%) routinely performed neuroimaging with more paediatric centres offering neurological assessment (65%) as compared to adult centres (20%). Only 15 (11.2%) had a structured longitudinal follow-up pathway (defined followup at regular intervals), while 99 (74.4%) had no follow-up programme. The majority ( n = 96, 72.2%) agreed that there should be a longitudinal structured follow-up for ECMO survivors. Conclusions: This survey demonstrated significant variability in the use of different neuromonitoring modalities during and after ECMO. The perceived importance of neuromonitoring and follow-up was noted to be very high with agreement for a longitudinal structured follow-up programme, particularly in paediatric patients. Scientific society endorsed guidelines and minimum standards should be developed to inform local protocols.

Surgical Clipping of Previously Coiled Recurrent Intracranial Aneurysms: A Single-Center Experience

Objective: This study reviews our experiences in surgical clipping of previously coiled aneurysms, emphasizing on recurrence mechanism of intracranial aneurysms (IAs) and surgical techniques for different types of recurrent IAs.Method: We performed a retrospective study on 12 patients who underwent surgical clipping of aneurysms following endovascular treatment between January 2010 and October 2020. The indications for surgery, surgical techniques, and clinical outcomes were analyzed.Result: Twelve patients with previously coiled IAs were treated with clipping in this study, including nine females and three males. The reasons for the patients having clipping were as follows: early surgery (treatment failure in two patients, postoperative early rebleeding in one patient, and intraprocedural aneurysm rupture during embolization in one patient) and late surgery (aneurysm recurrence in five patients, SAH in one, mass effect in one, and aneurysm regrowth in one). All aneurysms were clipped directly, and coil removal was performed in four patients. One patient died (surgical mortality, 8.3%), 1 patient (8.3%) experienced permanent neurological morbidity, and the remaining 10 patients (83.4%) had good outcomes. Based on our clinical data and previous studies, we classified the recurrence mechanism of IAs into coil compaction, regrowth, coil migration, and coil loosening. Then, we elaborated the specific surgical planning and timing of surgery depending on the recurrence type of IAs.Conclusion: Surgical clipping can be a safe and effective treatment strategy for the management of recurrent coiled IAs, with acceptable morbidity and mortality in properly selected cases. Our classification of recurrent coiled aneurysms into four types helps to assess the optimal surgical approach and the associated risks in managing them.

Twin-to-twin transfusion syndrome: new macroscopic and microscopic findings

Background Twin-to-twin Transfusion Syndrome (TTTS) is a serious complication of monochorionic twin pregnancies. Affects about 10% to 15% of pregnancies and it is associated with high fetal and neonatal mortality, as well as cardiac and neurological morbidity in surviving fetuses. The main objective was to characterize a series of fetuses with TTTS since the pathophysiology of the syndrome is not fully understood and the clinical spectrum is broad. Methods Post-mortem macroscopic and microscopic examination of 26 fetuses (from 2010 to 2020) with TTTS syndrome. Results The most frequent macroscopic findings in placenta were discrepancy in size and pallor/placental congestion. Other macroscopic findings not described in the literature were calcifications, areas of infarction and hematomas. Infarction areas and villi heterogeneity growth were the most common microscopic findings, described in the literature. Regarding the fetus, the restriction of intrauterine growth, the alteration of anthropometric parameters and the presence of a plethoric/anemic fetus were the main characteristics associated with this syndrome. The most common microscopic findings were signs of anoxia and congestive organs, already described in the literature. We also found frequently pulmonary abnormalities as new findings in our study. Conclusions The results allowed the identification of TTTS aspects that can contribute to the characterization of this syndrome. Given that the progression of TTTS remains unpredictable and the mortality rate for both fetuses is 90%, it becomes increasingly important to identify strategies for diagnosing and characterizing the syndrome.