ADAMTS proteoglycanases in the physiological and pathological central nervous system

ADAMTS-1, -4, -5 and -9 belong to ‘a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)’ family and more precisely to the proteoglycanases subgroup based on their common ability to degrade chondroitin sulfate proteoglycans. They have been extensively investigated for their involvement in inflammation-induced osteoarthritis, and a growing body of evidence indicates that they may be of key importance in the physiological and pathological central nervous system (CNS). In this review, we discuss the deregulated expression of ADAMTS proteoglycanases during acute CNS injuries, such as stroke and spinal cord injury. Then, we provide new insights on ADAMTS proteoglycanases mediating synaptic plasticity, neurorepair, angiogenesis and inflammation mechanisms. Altogether, this review allows us to propose that ADAMTS proteoglycanases may be original therapeutic targets for CNS injuries.This work was supported by the University of Eastern Finland and the ERANET-Neuron research program ‘ProteA: Proteases before, during and after stroke’, 2012–2015.Peer Reviewe

Efficacy and Tolerance of Post-operative Hypo-Fractionated Stereotactic Radiotherapy in a Large Series of Patients With Brain Metastases

Purpose: The aim of this study was to assess, in a large series, the efficacy and tolerance of post-operative adjuvant hypofractionated stereotactic radiation therapy (HFSRT) for brain metastases (BMs).Materials and Methods: Between July 2012 and January 2017, 160 patients from 2 centers were operated for BM and treated by HFSRT. Patients had between 1 and 3 BMs, no brainstem lesions or carcinomatous meningitis. The primary endpoint was local control. Secondary endpoints were distant brain control, overall survival (OS) and tolerance to HFSRT.Results: 73 patients (46%) presented with non-small cell lung cancer (NSCLC), 23 (14%) had melanoma and 21 (13%) breast cancer. Median age was 58 years (range, 22–83 years). BMs were synchronous in 50% of the cases. The most frequent prescription regimens were 24 Gy in 3 fractions (n = 52, 33%) and 30 Gy in 5 fractions (n = 37, 23%). Local control rates at 1 and 2 years were 88% [95%CI, 81–93%] and 81% [95%CI, 70–88%], respectively. Distant control rate at 1 year was 48% [95%CI, 81–93%]. In multivariate analysis, primary NSCLC was associated with a significant reduction in the risk of death compared to other primary sites (HR = 0.57, p = 0.007), the number of extra-cerebral metastatic sites (HR = 1.26, p = 0.003) and planning target volumes (HR = 1.15, p = 0.012) were associated with a lower OS. There was no prognostic factor of time to local progression. Median OS was 15.2 months [95%CI, 12.0–17.9 months] and the OS rate at 1 year was 58% [95% CI, 50–65%]. Salvage radiotherapy was administered to 72 patients (45%), of which 49 received new HFSRT. Ten (7%) patients presented late grade 2 and 4 (3%) patients late grade 3 toxicities. Thirteen (8.9%) patients developed radiation necrosis.Conclusions: This large multicenter retrospective study shows that HFSRT allows for good local control of metastasectomy tumor beds and that this technique is well-tolerated by patients

La myélopathie cervicarthrosique (revue de la littérature, mise au point et étude d'une série rétrospective de 72 cas opérés au CHU de Caen sur 10 ans)

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

La fibrinolyse intraventriculaire dans les hémorragies intraventriculaires (méta-analyse)

CAEN-BU Médecine pharmacie (141182102) / SudocSudocFranceF

Open thoracic cordotomy for intractable cancer pain: a how I do it

CERVOXY-CLINInternational audienceBackground: Some cancers of the lower extremity involve nerves and plexuses and can produce extreme drug-resistant noceptive pain. In these cases, open thoracic cordotomy can be proposed.Method:This procedure involves disruption of the spinothalamic tract, which sustains nociceptive pathways. After placement in the prone position, selection of the side to be operated on (contralateral to the pain), and dura exposure, microsurgery is used to section theanterolateral spinal cord quadrant previously exposed by gently pulling on the dentate ligament.Conclusion:Open thoracic cordotomy is a moderate invasive, safe, and effective option for the management of drug-resistant unilateral lower extremity cancer pain in well-selected patients

Predictive Factors of Favorable Visual Outcomes After Surgery of Tuberculum Sellae Meningiomas: A Multicenter Retrospective Cohort Study

BACKGROUND: Because of their proximity to the visual structures, tuberculum sellae meningiomas are frequently revealed by ophthalmologic impairment. The goal of surgery is gross total resection and improvement of visual function. The purpose of the present study was to identify the predictors of favorable visual outcomes after surgery of tuberculum sellae meningioma. METHODS: We retrospectively collected tuberculum sellae meningiomas treated at 2 neurosurgical centers from 2010 to 2020. We collected the clinical, imaging and surgical data and analyzed their effects on the visual outcome. A favorable visual outcome was defined as an increase in visual acuity of >= 0.2 point and/or an increase of >25% of the visual field or complete recovery. RESULTS: A total of 50 patients were included. At 4 months after surgery, 30 patients (60%) had experienced visual improvement. The predictors of a favorable visual outcome were a symptom duration of 0.5, a smaller tumor size, and tumor with T2-weighted/fluid attenuated inversion recovery hypersignal on magnetic resonance imaging. During surgery, a soft tumor and a clear brain-tumor interface were associated with favorable visual outcomes. Preoperative optic coherence tomography measurements of the retinal nerve fiber layer thickness >80 mu M and ganglion cell complex thickness >70 mu M were also associated with a better ophthalmologic outcome. CONCLUSIONS: In tuberculum sellae meningiomas, rapid surgical treatment must be performed to optimize vision improvement. A hyperintense lesion on T2-weighted/fluid attenuated inversion recovery magnetic resonance imaging and minor vision impairment at the initial ophthalmologic presentation might give hope for a favorable outcome. Performing optic coherence tomography measurements before surgery could clarify patients' expectations regarding their recovery

ADAMTS proteoglycanases in the physiological and pathological central nervous system.

International audience: ADAMTS-1, -4, -5 and -9 belong to 'a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)' family and more precisely to the proteoglycanases subgroup based on their common ability to degrade chondroitin sulfate proteoglycans. They have been extensively investigated for their involvement in inflammation-induced osteoarthritis, and a growing body of evidence indicates that they may be of key importance in the physiological and pathological central nervous system (CNS). In this review, we discuss the deregulated expression of ADAMTS proteoglycanases during acute CNS injuries, such as stroke and spinal cord injury. Then, we provide new insights on ADAMTS proteoglycanases mediating synaptic plasticity, neurorepair, angiogenesis and inflammation mechanisms. Altogether, this review allows us to propose that ADAMTS proteoglycanases may be original therapeutic targets for CNS injuries

Factors associated with favorable visual outcome after surgery of clinoidal meningiomas

Background: The anatomical relationship between clinoidal meningiomas and the optic nerve accounts for their frequent finding on visual disturbances. The goal of the surgery is to perform complete resection and obtain visual recovery. The aim of this study is to determine the factors associated with favorable visual outcome. Methods: We recorded clinical (including ophthalmological), imaging and surgical data of all patients operated on for clinoidal meningiomas between 2010 and 2020 in 2 French neurosurgical departments and we analyzed their impact on visual outcome. Results: A total of 34 patients were included. At 3-4 months after surgery, 23 patients (68%) had favorable visual outcome. Factors associated with favorable visual outcome were duration of ophthalmologic symptoms 0.5, absence of optic atrophy, meningioma in high signal intensity on T2weighted or FLAIR MRI, absence of optic canal involvement and absence of bone hyperostosis on pre-operative CT scan. A soft tumor and a clear brain/tumor border were intra-operative factor associated with favorable ophthalmological outcome. Conclusions: In clinoidal meningiomas, an early surgery should be performed to optimize visual improvement. Hyperintense lesion on T2-weighted/FLAIR preoperative MRI is correlated with a soft consistency which allows an easier surgery associated with a favorable visual outcome. Invasion of the optic canal and bone hyperostosis should reserve the visual prognosis