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BACKGROUND: Randomized clinical trials have demonstrated efficacy and safety of erenumab. The aim of this study is to evaluate the effectiveness and safety of erenumab in a real-world setting in French patients with migraine associated with extreme unmet needs. METHODS: This is a one year-prospective real-word study with enrolment of all consecutive adult patients included in the FHU InovPain registry who participated in a compassionate erenumab use program. RESULTS: Of 144 patients included, 140 patients (82.1% female / mean age of 50.9 ± 11.4) received at least one dose of erenumab and were concerned by effectiveness and safety assessment. All patients had failed 11 oral preventive treatments. Most of them suffered from chronic migraine (88.6%) and presented a medication overuse (90.7%) at baseline. Thirty-eight (27.1%) discontinued treatment during the 12-month follow-up, with 22 (15.7%), 11 (7.9%) and 5 (3.6%) patients before 3, 6 or 9 months of treatment. The proportion of ≥ 50% responders at M3, M6, M9 and M12 was 74/140 (52.9%), 69/118 (58.5%), 61/107 (57.0%) and 60/102 (58.8%) respectively. At M3, the rate of reversion from chronic migraine to episodic migraine was 57.3% and the rate of transition from medication overuse to non-overuse was 46.5%. For monthly migraine days, the median (IQR) was 18.0 (13.0-26.0), 9.0 (5.0-17.0), 7.5 (5.0-14.0), 8.0 (5.0-12.5) and 8.0 (5.0-12.0) at M0, M3, M6, M9 and M12 respectively. For HIT-6 score, the median (IQR) was 68.0 (63.8-73.3), 60.0 (54.0-65.0), 60.0 (50.3-53.0), 59.0 (50.0-63.0) and 58.0 (50.0-62.9) at M0, M3, M6, M9 and M12 respectively. Fifty-three (37.9%) patients reported at least one of the following adverse events: cutaneous erythema and/or pain at the injection site for 42 (30%) patients, constipation for 22 (15.7%) patients, muscle spasm for 2 (1.4%) patients, alopecia for one (0.7%) patient and blood pressure increase in one (0.7%) patient. There was no serious adverse event. One female patient became pregnant after 5 months of exposure to erenumab with a safe evolution after treatment discontinuation. CONCLUSION: This first French real-world study related to migraine prevention with CGRP-mAbs confirms effectiveness and safety of erenumab in patients with extreme unmet needs.
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Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina , Transtornos de Enxaqueca , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Prospectivos , Antagonistas do Receptor do Peptídeo Relacionado ao Gene de Calcitonina/uso terapêutico , Método Duplo-Cego , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Resultado do TratamentoRESUMO
One of the main challenges in cancer management relates to the discovery of reliable biomarkers, which could guide decision-making and predict treatment outcome. In particular, the rise and democratization of high-throughput molecular profiling technologies bolstered the discovery of "biomarker signatures" that could maximize the prediction performance. Such an approach was largely employed from diverse OMICs data (i.e., genomics, transcriptomics, proteomics, metabolomics) but not from epitranscriptomics, which encompasses more than 100 biochemical modifications driving the post-transcriptional fate of RNA: stability, splicing, storage, and translation. We and others have studied chemical marks in isolation and associated them with cancer evolution, adaptation, as well as the response to conventional therapy. In this study, we have designed a unique pipeline combining multiplex analysis of the epitranscriptomic landscape by high-performance liquid chromatography coupled to tandem mass spectrometry with statistical multivariate analysis and machine learning approaches in order to identify biomarker signatures that could guide precision medicine and improve disease diagnosis. We applied this approach to analyze a cohort of adult diffuse glioma patients and demonstrate the existence of an "epitranscriptomics-based signature" that permits glioma grades to be discriminated and predicted with unmet accuracy. This study demonstrates that epitranscriptomics (co)evolves along cancer progression and opens new prospects in the field of omics molecular profiling and personalized medicine.
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Glioma , RNA , Biomarcadores , Glioma/diagnóstico , Glioma/genética , Humanos , Metabolômica/métodos , Análise Multivariada , Proteômica/métodosRESUMO
Post-traumatic cerebral venous sinus thrombosis (ptCVST) is often associated with brain hemorrhage; consequently, the anticoagulation may be challenging. We report the case of a 42-year-old man who presented with post-traumatic epidural hematoma and rapidly developed transverse sinus thrombosis extending to the internal jugular vein. As the patient was asymptomatic, we decided not to use anticoagulants: close clinical and radiological monitoring was implemented. The hematoma resolved within 2 months, and the CVST diminished by the third month. Such a good outcome is not always the case in ptCVST. The present article also discusses pathophysiological mechanisms and treatment options when hematoma is associated with ptCVST.
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Hematoma Epidural Craniano , Hematoma Epidural Espinal , Trombose dos Seios Intracranianos , Adulto , Anticoagulantes/uso terapêutico , Cavidades Cranianas , Hematoma Epidural Craniano/diagnóstico , Hematoma Epidural Craniano/etiologia , Hematoma Epidural Craniano/cirurgia , Humanos , Hemorragias Intracranianas , Masculino , Trombose dos Seios Intracranianos/diagnóstico , Trombose dos Seios Intracranianos/tratamento farmacológico , Trombose dos Seios Intracranianos/etiologiaRESUMO
Spinal cord stimulation (SCS) is used for more than 40years to treat localized chronic medically refractory neuropathic pain involving limb(s) and trunk. The most frequent indications remain complex regional pain syndrome (CRPS) failed back surgery syndrome (FBSS), and peripheral neuropathy. Stimulation-induced paresthesias, perceived by the patient, prevent blinded evaluation and increase the placebo effect, decreasing the credibility of the tonic SCS efficacy. Retrospective studies reported that about 50% of the patients are improved more than 50% at short-term, but long-term improvement is less. Several comparative randomized trials (RCT) are now available. In CRPS, a RCT demonstrated the superiority of SCS plus physiotherapy compared to physiotherapy alone. In FBSS, two RCTs have shown that SCS was superior to reoperation and conventional medical treatment, (CMM) respectively. New stimulation waveforms, namely burst, high frequency (10KHz) stimulation and close-loop SCS, have been proposed recently to avoid the perception of paresthesias and/or increase the pain relief. RCTs in FBSS have suggested that these new SCS modalities were as least as efficient than conventional tonic SCS and perhaps slightly superior. Two RCTs confirmed SCS efficacy in painful diabetic neuropathy in comparison with CMM. Complications are frequent (hardware dysfunction or migration, superficial infection) but exceptionally serious. Consequently, the risk/benefit ratio is favorable to SCS, considering that chronic pain patients undergoing this procedure are usually resistant to all the other therapies.
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Dor Crônica , Síndrome Pós-Laminectomia , Neuralgia , Estimulação da Medula Espinal , Dor Crônica/terapia , Síndrome Pós-Laminectomia/terapia , Humanos , Neuralgia/terapia , Estudos Retrospectivos , Medula Espinal , Resultado do TratamentoRESUMO
Understanding intracranial nociceptive innervation is essential to understand the pathophysiology of headaches. Our knowledge about human intracranial nociception comes from sparse observations during neurosurgical procedures performed in awake patients, from human anatomical studies and from experimental studies in animals. In this article we review the anatomical and functional organization underlying nociceptive innervation. Intracranial nociception is mainly mediated by the trigeminal system, except in the posterior cranial fossa that is innervated by the first cervical roots. For decades, the dura mater, its vessels and major cerebral blood vessels were considered as the only intracranial pain-sensitive structures. Recent animal and human studies have suggested that smaller brain arteries and potentially pia mater might also be pain sensitive. Nociceptive neurons innervating intracranial blood vessels project via the ophthalmic division (V1) to the trigeminal ganglion and store several neurotransmitters including glutamate, substance P and calcitonin gene-related peptide (CGRP). The trigeminal ganglion, root and brainstem nuclei have a specific topographic and functional somatotopy. Progressive transition between the trigeminal spinal nucleus and the dorsal horn of the cervical spinal cord, and convergence of nociceptive inputs from the face, intracranial structures and the occipital area on the so-called "trigemino-cervical complex" may explain some headache features, relations between facial and occipital pain, and efficacy of occipital nerve stimulation in headache. The specific anatomic organization of the trigeminal system, from the primary-order neuron in the trigeminal ganglion, to the second-order neuron is the trigeminal nuclei, may explain a part of the various characteristics of headaches.
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Peptídeo Relacionado com Gene de Calcitonina , Nociceptividade , Animais , Dura-Máter , Cefaleia , Humanos , Gânglio TrigeminalRESUMO
OBJECTIVES: We investigated changes of impulsivity after deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) patients, distinguishing functional from dysfunctional impulsivity and their contributing factors. METHODS: Data of 33 PD patients treated by STN-DBS were studied before and 6 months after surgery: motor impairment, medication (dose and dopaminergic agonists), cognition, mood and occurrence of impulse control disorders. Impulsivity was assessed by the Dickman Impulsivity Inventory, which distinguishes functional impulsivity (FI), reflecting the potential for reasoning and rapid action when the situation requires it, and dysfunctional impulsivity (DI), reflecting the lack of prior reasoning, even when the situation demands it. The location of DBS leads was studied on postoperative MRI using a deformable histological atlas and by compartmentalization of the STN. RESULTS: After STN-DBS, DI was significantly increased (mean pre- and postoperative DI scores 1.9±1.6 and 3.5±2.4, P<0.001) although FI was not modified (mean pre- and postoperative FI scores 6.2±2.7 and 5.8±2.6). Factors associated with a DI score's increase≥2 (multivariable logistic regression model) were: low preoperative Frontal Assessment Battery score and location of the left active contact in the ventral part of the STN. CONCLUSION: Our study suggests that STN-DBS may have a different impact on both dimensions of impulsivity, worsening pathological impulsivity without altering physiological impulsivity. The increase in dysfunctional impulsivity may be favoured by the location of the electrode in the ventral part of the STN.
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Estimulação Encefálica Profunda , Transtornos Disruptivos, de Controle do Impulso e da Conduta , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Comportamento Impulsivo , Doença de Parkinson/terapiaRESUMO
The goal of this narrative review was to give an up-to-date overview of the peripheral and central neurostimulation methods that can be used to treat chronic pain. Special focus has been given to three pain conditions: neuropathic pain, nociplastic pain and primary headaches. Both non-invasive and invasive techniques are briefly presented together with their pain relief potentials. For non-invasive stimulation techniques, data concerning transcutaneous electrical nerve stimulation (TENS), transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), remote electrical neuromodulation (REN) and vagus nerve stimulation (VNS) are provided. Concerning invasive stimulation techniques, occipital nerve stimulation (ONS), vagus nerve stimulation (VNS), epidural motor cortex stimulation (EMCS), spinal cord stimulation (SCS) and deep brain stimulation (DBS) are presented. The action mode of all these techniques is only partly understood but can be very different from one technique to the other. Patients' selection is still a challenge. Recent consensus-based guidelines for clinical practice are presented when available. The development of closed-loop devices could be of interest in the future, although the clinical benefit over open loop is not proven yet.
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Dor Crônica/terapia , Estimulação Encefálica Profunda , Transtornos da Cefaleia Primários/terapia , Neuralgia/terapia , Estimulação da Medula Espinal , Estimulação Transcraniana por Corrente Contínua , Estimulação Magnética Transcraniana , Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , HumanosRESUMO
Glioblastomas (GBM) are lethal primitive brain tumours characterized by a strong intra-tumour heterogeneity. We observed in GBM tissues the coexistence of functionally divergent micro-territories either enriched in more differentiated and non-mitotic cells or in mitotic undifferentiated OLIG2 positive cells while sharing similar genomic abnormalities. Understanding the formation of such functionally divergent micro-territories in glioblastomas (GBM) is essential to comprehend GBM biogenesis, plasticity and to develop therapies. Here we report an unexpected anti-proliferative role of beta-catenin in non-mitotic differentiated GBM cells. By cell type specific stimulation of miR-302, which directly represses cyclin D1 and stemness features, beta-catenin is capable to change its known proliferative function. Nuclear beta-catenin accumulation in non-mitotic cells is due to a feed forward mechanism between DOCK4 and beta-catenin, allowed by increased GSK3-beta activity. DOCK4 over expression suppresses selfrenewal and tumorigenicity of GBM stem-like cells. Accordingly in the frame of GBM median of survival, increased level of DOCK4 predicts improved patient survival.
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Proteínas Ativadoras de GTPase/metabolismo , Glioblastoma/patologia , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/patologia , beta Catenina/metabolismo , Adulto , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Encéfalo/patologia , Núcleo Celular/metabolismo , Proliferação de Células , Retroalimentação Fisiológica , Proteínas Ativadoras de GTPase/genética , Glioblastoma/genética , Glioblastoma/mortalidade , Glicogênio Sintase Quinase 3 beta/genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , MicroRNAs/genética , Mitose , Células-Tronco Neoplásicas/citologia , Fator de Transcrição 2 de Oligodendrócitos/metabolismo , Cultura Primária de Células , RNA Interferente Pequeno/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem , beta Catenina/genéticaRESUMO
INTRODUCTION: Surgical resection of supratentorial cavernous angiomas located in eloquent areas poses a significant risk to the patient of postoperative neurological impairment and justifies intraoperative functional monitoring. METHODS: Multicentre retrospective series of adult patients with cavernous angiomas located within eloquent areas and treated with functional-based surgical resection according to functional boundaries under intraoperative functional cortico-subcortical monitoring under awake conditions. RESULTS: Fifty patients (18 males, mean 36.3±10.8 year-old) underwent surgical resection with intraoperative cortico-subcortical functional mapping using direct electrostimulation under awake conditions for a cavernous angioma located in eloquent areas with a mean postoperative follow-up of 21.0±21.2 months. At presentation, the cavernous angioma had previously resulted in severe impairment (neurological deficit in 34%, seizures in 70%, uncontrolled seizures in 34%, reduced Karnofsky Performance Status score of 70 or less in 24%, inability to work in 52%). Functional-based surgical resection allowed complete removal of the cavernous angioma in 98% and of the haemosiderin rim in 82%. Postoperative seizures and other complications were rare, and similarly so across all centres included in this series. Postoperatively, we found functional improvement in 84% of patients (reduced Karnofsky Performance Status score of 70 or less in 6%, uncontrolled seizures in 16%, and inability to work in 11%). CONCLUSION: Functional-based surgical resection aids the safe and complete resection of cavernous angiomas located in eloquent areas while minimizing the surgical risks. Functional mapping has to be considered in such challenging cases.
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Neoplasias Encefálicas/cirurgia , Hemangioma Cavernoso/cirurgia , Procedimentos Neurocirúrgicos , Vigília/fisiologia , Adulto , Idoso , Mapeamento Encefálico/métodos , Estimulação Elétrica/métodos , Feminino , Humanos , Monitorização Neurofisiológica Intraoperatória , Masculino , Pessoa de Meia-Idade , Neuronavegação/métodos , Procedimentos Neurocirúrgicos/métodos , Estudos RetrospectivosRESUMO
INTRODUCTION: Awake craniotomy for brain tumor resection is usually well-tolerated and most of the patients are satisfied. However, in studies reporting the patients' postoperative perception of the awake craniotomy procedure, about half of them have experienced some degree of intraoperative pain. Pain was mild (intensity between 1 and 2 on the visual analogical score) short lasting in most cases, and did not challenge the procedure. Pain was reported as moderate in about 25% and exceptionally severe. METHODS: We conducted a preliminary survey among French centers (n=9) routinely performing awake craniotomy. RESULTS: Neurosurgeons' opinions were concordant with patient's reports. Intraoperative pain exceptionally challenged the awake craniotomy procedure or led to changes in the resection strategy. For neurosurgeons, the most challenging causes of intraoperative pain were the patient's inadequate installation, the contact of surgical tools with pain-sensitive intracranial structures, especially the dura mater of the skull base, falx cerebri, and the leptomeninges of the lateral fissure and neighboring sulci. CONCLUSION: Strategies to deal with these causes included focusing the patient on the intraoperative functional tests to distract their attention away from the pain, and avoiding contacts with the pain-sensitive intracranial structures during the awake phase. Adequate preoperative patient information and preparation, trained anesthesiologists and application of recommendations for awake craniotomy procedures as well as adaptation of surgical technique to avoid contact with pain-sensitive intracranial structures are key factors to prevent intraoperative pain and ensure patient's postoperative satisfaction.
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Neoplasias Encefálicas/cirurgia , Dor/cirurgia , Vigília/fisiologia , Adulto , Mapeamento Encefálico/métodos , Neoplasias Encefálicas/patologia , Craniotomia/métodos , Feminino , Humanos , Incidência , Monitorização Neurofisiológica Intraoperatória , Masculino , Pessoa de Meia-Idade , Manejo da DorRESUMO
AIMS: MET gene amplification is rare in glioblastoma (GBM) and represents a potential target for MET inhibitors. An immunohistochemical screening may be useful to identify MET amplification. The aim of our study was to establish how MET immunolabelling correlates with MET amplification. METHODS: Three cohorts including 108 GBM (cohort 1, prospective), 104 GBM (cohort 2, retrospective) and 52 GBM (cohort 3, prospective) were investigated for MET expression by immunohistochemistry. MET amplification was assessed by comparative genomic hybridization on microarray (CGH-array) in all cohorts and by fluorescent in situ hybridization (FISH) in cohorts 2 and 3. Active form of MET was assessed using p-MET (Y1349) immunohistochemistry. RESULTS: Diffuse MET amplification detectable by CGH-array was associated with diffuse, strong MET immunolabelling (four cases in cohort 1 and one case in cohort 2). Focal MET amplification detectable only by FISH was observed in small foci of strongly immunopositive cells in two GBM (cohort 2). In both cohorts, MET amplification was never detected in GBM devoid of strongly immunopositive cells. MET overexpression, observed in 23% of unamplified GBM, was associated with a predominant weak-to-moderate staining intensity and with necrosis (P < 0.005). p-MET was detected in all MET-amplified GBM and in perinecrotic areas of nonamplified GBM. A strong MET immunostaining intensity, at least focal and distant from necrosis, showed 100% sensitivity and 84% specificity for predicting MET amplification in cohort 3. CONCLUSIONS: MET amplification is characterized by strongly immunopositive cells. Only GBM showing strong MET immunostaining is appropriate for the assessment of MET amplification.
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Biomarcadores Tumorais/análise , Neoplasias Encefálicas/genética , Glioblastoma/genética , Imuno-Histoquímica/métodos , Proteínas Proto-Oncogênicas c-met/análise , Adulto , Idoso , Biomarcadores Tumorais/genética , Estudos de Coortes , Feminino , Amplificação de Genes , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-met/genéticaRESUMO
AIMS: Bi-allelic inactivation of SWI/SNF related, matrix-associated, actin-dependent regulator of chromatin, subfamily B member 1 (SMARCB1; also known as INI1) and loss of immunohistochemical expression of SMARCB1 define the group of SMARCB1-deficient tumours. Initially highlighted in malignant rhabdoid tumours, this inactivation has subsequently been observed in several intra and extracranial tumours. To date, primary meningeal SMARCB1-deficient tumours have not been described. We report two cases of meningeal SMARCB1-deficient tumours occurring in adults. METHODS: We performed immunohistochemical analyses, comparative genomic hybridization, fluorescence in situ hybridization and targeted next-generation sequencing. RESULTS: The first meningeal tumour was a solitary mass, composed of rhabdoid, adenoid, chordoid and sarcomatoid areas. The second case presented as multiple, bilateral, supra and infratentorial nodules, was composed of fusiform and ovoid cells embedded in a myxoid stroma. Tumour cells were positive for epithelial membrane antigen (EMA), vimentin and CD34 and negative for SMARCB1 and meningothelial, melanocytic, muscular, glial markers. In the first case, one allele of SMARCB1 was completely deleted, whereas in the second case, loss of expression of SMARCB1 was observed as a consequence of a homozygous deletion of SMARCB1. CONCLUSIONS: The phenotype and genotype of these two cases did not fit diagnostically with entities already known to be SMARCB1-deficient tumours. As both tumours shared common features, they are regarded as belonging to an emerging group of primary meningeal SMARCB1-deficient tumours, not described to date. To facilitate the identification and characterization of these tumours, we recommend SMARCB1 immunohistochemistry for primary meningeal tumours which are difficult to classify, especially if immunopositive for EMA and CD34.
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Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Proteína SMARCB1/genética , Adulto , Humanos , MasculinoRESUMO
INTRODUCTION: Trigeminal trophic syndrome (TTS) can occur after any injury on the fifth cranial nerve. The etiology is dominated by iatrogenic causes, especially after gasserian ganglion ablation. Middle-aged women are mostly involved and the differential diagnosis is vast. PRESENTATION OF CASE: A 88-year old woman presented with TTS and destruction of the right nasal ala 25 years after retrogasserian alcohol injection for trigeminal neuralgia. Facing iterative failure of medical treatment, topics and neurostimulation, we performed lipofilling for the lesion. In the third month, we found a 50 % decrease in size of the lesion, as well as a complete disappearance of pruritus, thus allowing to consider reconstructive surgery. DISCUSSION: Our literature review reports 28 cases of TTS subsequent to alcohol injection of the gasserian ganglion. Age of presentation ranges from 49 to 88 years, with a time of onset between trigeminal injury and TTS ranging from 2 weeks to 17 years. Recurrences are frequent. The management varies a lot according to the authors (topics, antibiotics, flaps), however the efficiency of lipofilling has not been reported yet. CONCLUSION: The pathophysiology of TTS remains unknown, nevertheless the therapeutical care has to be multidisciplinary. Even though not described yet, lipofilling seems to be an interesting treatment of TTS following alcohol injection in the trigeminal ganglion.
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Anti-Infecciosos Locais/efeitos adversos , Etanol/efeitos adversos , Úlcera Cutânea/etiologia , Úlcera Cutânea/terapia , Gânglio Trigeminal/patologia , Idoso de 80 Anos ou mais , Feminino , Humanos , Injeções Intralesionais , Resultado do Tratamento , Neuralgia do Trigêmeo/tratamento farmacológicoRESUMO
BACKGROUND AND PURPOSE: Recent studies demonstrated the capacity of stents to modify cerebral vascular anatomy. This study evaluates arterial anatomy deformation after Leo stent placement according to the stenting site and the impact on the immediate postoperative and six-month degree of aneurysmal occlusion. MATERIALS AND METHODS: A total of 102 stents were placed against the neck of aneurysms situated in the anterior cerebral circulation. Aneurysms were classified into two groups: The first was called the distal group (n = 62) and comprised aneurysms situated in the middle cerebral and anterior communicating arteries and the second was called the proximal group (n = 40) and comprised aneurysms in other sites. The stented arterial segment was classified as deformed or non-deformed by blinded review and superimposition of anonymised films before and after stenting. The degree of occlusion was determined immediately postoperatively and at six months. RESULTS: Significantly, anatomical deformity was observed in the distal group compared to the proximal group (85% vs 28%). No significant difference was observed between the two groups in terms of postoperative degree of occlusion. At six months, a significant difference was observed between the two groups: three recurrences in the distal group vs 10 recurrences in the proximal group. Two (3%) recurrences were observed in the deformed group vs 11 (31%) recurrences in the non-deformed group. CONCLUSIONS: Arterial deformity induced by stenting is even more marked for distal aneurysms. The recurrence rate is smaller when the stent placement results in an arterial anatomical change. The percentage of recurrence is lower when anatomy was amended by stent implantation.
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Artérias Cerebrais/diagnóstico por imagem , Stents , Adulto , Idoso , Aneurisma Roto/terapia , Artéria Cerebral Anterior/diagnóstico por imagem , Angiografia Cerebral , Feminino , Seguimentos , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Posterior/diagnóstico por imagem , Recidiva , Resultado do Tratamento , Adulto JovemRESUMO
In magnetic materials, the Pauli exclusion principle typically drives anti-alignment between electron spins on neighbouring species resulting in antiferromagnetic behaviour. Ferromagnetism exhibiting spontaneous spin alignment is a fairly rare behaviour, but once materialized is often associated with itinerant electrons in metals. Here we predict and rationalize robust ferromagnetism in an insulating oxide perovskite structure based on the popular titanate series. In half-doped layered titanates, the combination of Jahn-Teller and oxygen breathing motions opens a band gap and creates an unusual charge and orbital ordering of the Ti d electrons. It is argued that this intriguingly intricate electronic network favours the elusive inter-site ferromagnetic (FM) ordering, on the basis of intra-site Hund's rules. Finally, we find that the layered oxides are also ferroelectric with a spontaneous polarization approaching that of BaTiO3. The concepts are general and design principles of the technologically desirable FM ferroelectric multiferroics are presented.
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Neurosurgical treatment of pain used two kind of techniques: 1) Lesional techniques interrupt the transmission of nociceptive neural input by lesionning the nociceptive pathways (drezotomy, cordotomy, tractotomy ). They are indicated to treat morphine-resistant cancer pain and few cases of selected neuropathic pain. 2) Neuromodulation techniques try to decrease pain by reinforcing inhibitory and/or to limit activatory mechanisms. Chronic electrical stimulation of the nervous system (peripheral nerve stimulation, spinal cord stimulation, motor cortex stimulation ) is used to treat chronic neuropathic pain. Intrathecal infusion of analgesics (morphine, ziconotide ), using implantable pumps, allows to increase their efficacy and to reduce their side effects. These techniques can improve, sometimes dramatically, selected patients with severe and chronic pain, refractory to all other treatments. The quality of the analgesic outcome depends on the relevance of the indications.
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Dor Crônica/cirurgia , Procedimentos Neurocirúrgicos/métodos , Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Dor Crônica/tratamento farmacológico , Resistência a Medicamentos , Terapia por Estimulação Elétrica , Humanos , Bombas de Infusão Implantáveis , Vias Neurais/cirurgia , Dor Intratável/cirurgiaRESUMO
BACKGROUND: Many studies have demonstrated the efficacy of spinal cord stimulation (SCS) for chronic neuropathic radicular pain over recent decades, but despite global favourable outcomes in failed back surgery syndrome (FBSS) with leg pain, the back pain component remains poorly controlled by neurostimulation. Technological and scientific progress has led to the development of new SCS leads, comprising a multicolumn design and a greater number of contacts. The efficacy of multicolumn SCS lead configurations for the treatment of the back pain component of FBSS has recently been suggested by pilot studies. However, a randomized controlled trial must be conducted to confirm the efficacy of new generation multicolumn SCS. Évaluation médico-économique de la STImulation MEdullaire mulTi-colonnes (ESTIMET) is a multicentre, randomized study designed to compare the clinical efficacy and health economics aspects of mono- vs. multicolumn SCS lead programming in FBSS patients with radicular pain and significant back pain. MATERIALS AND METHODS: FBSS patients with a radicular pain VAS score≥50mm, associated with a significant back pain component were recruited in 14 centres in France and implanted with multicolumn SCS. Before the lead implantation procedure, they were 1:1 randomized to monocolumn SCS (group 1) or multicolumn SCS (group 2). Programming was performed using only one column for group 1 and full use of the 3 columns for group 2. Outcome assessment was performed at baseline (pre-implantation), and 1, 3, 6 and 12months post-implantation. The primary outcome measure was a reduction of the severity of low back pain (bVAS reduction≥50%) at the 6-month visit. Additional outcome measures were changes in global pain, leg pain, paraesthesia coverage mapping, functional capacities, quality of life, neuropsychological aspects, patient satisfaction and healthcare resource consumption. TRIAL STATUS: Trial recruitment started in May 2012. As of September 2013, all 14 study centres have been initiated and 112/115 patients have been enrolled. Preliminary results are expected to be published in 2015. TRIAL REGISTRATION: Clinical trial registration information-URL: www.clinicaltrials.gov. Unique identifier NCT01628237.
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Síndrome Pós-Laminectomia/complicações , Síndrome Pós-Laminectomia/terapia , Dor Lombar/etiologia , Dor Lombar/terapia , Estimulação da Medula Espinal/economia , Estimulação da Medula Espinal/métodos , Adolescente , Adulto , Idoso , Análise Custo-Benefício , Eletrodos Implantados , Determinação de Ponto Final , Síndrome Pós-Laminectomia/economia , Feminino , Humanos , Dor Lombar/economia , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Medição da Dor , Estudos Prospectivos , Projetos de Pesquisa , Adulto JovemRESUMO
BACKGROUND: Body image distortion/discrepancy leads to psychological stress, disordered eating and mental and physical disease. To begin to assess body image distortion/discrepancy, we compared perceived, desired and measured percentage body fat in male versus female and college-aged versus non-college aged individuals. In addition, we assessed the acute stress response to body composition measurement. METHODS: Body fat percentage of 15 college aged ('College Students'; CS) (mean = 19 years) and 16 non-college aged ('Non-College Aged Students'; NCS) (mean = 39 years) males and females was assessed with the BodPod Body Composition Tracking System (Life Measurement Instruments, Concord, CA, USA). Participants indicated their perception of body fat and their desired body fat using a somatomorphic matrix. Salivary cortisol, heart rate and blood pressure were also measured. Data were analysed by analysis of variance and alpha was set at 0.05. RESULTS: Mean (SD) percentage body fat of males [15.2% (6.1%)] was significantly lower than that of females [28.4% (6.4%)] (P < 0.0001). Both CS and NCS females perceived their body fat to be lower (5%) than measured body fat and desired their body fat to be lower (12%) than measured (P < 0.05). CS and NCS male participants demonstrated the opposite result; both CS and NCS male populations perceived their body fat to be higher (5%) than measured body fat and desired their body fat to be higher (4%) than measured (P < 0.05). No differences between any groups were observed in heart rate, blood pressure or cortisol response to body fat measurement. CONCLUSIONS: Sex-related but not age-related differences in perceived, desired and measured percentage body fat were observed.
Assuntos
Tecido Adiposo , Composição Corporal , Imagem Corporal , Fatores Sexuais , Adulto , Fatores Etários , Emoções , Feminino , Humanos , Masculino , Percepção , Estresse Psicológico , Adulto JovemRESUMO
Six clinical studies of chronic electrical modulation of deep brain circuits published between 1968 and 2010 have reported effects in 55 vegetative or minimally conscious patients. The rationale stimulation was to activate the cortex through the reticular-thalamic complex, comprising the tegmental ascending reticular activating system and its thalamic targets. The most frequent intended target was the central intralaminar zone and adjacent nuclei. Hassler et al. also proposed to modulate the pallidum as part of the arousal and wakefulness system. Stimulation frequency varied from 8Hz to 250Hz. Most patients improved, although in a limited way. Schiff et al. found correlations between central thalamus stimulation and arousal and conscious behaviours. Other treatments that have offered some clinical benefit include drugs, repetitive magnetic transcranial stimulation, median nerve stimulation, stimulation of dorsal column of the upper cervical spinal cord, and stimulation of the fronto-parietal cortex. No one treatment has emerged as a gold standard for practice, which is why clinical trials are still on-going. Further clinical studies are needed to decipher the altered dynamics of neuronal network circuits in patients suffering from severe disorders of consciousness as a step towards novel therapeutic strategies.