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Multi-recurrent high-grade meningiomas remain an unmet medical need in neuro-oncology when iterative surgeries and radiation therapy sessions fail to control tumor growth. Nevertheless, the last 10years have been marked by multiple advances in the comprehension of meningioma tumorigenesis via the discovery of new driver mutations, the identification of activated intracellular signaling pathways, and DNA methylation analyses, providing multiple potential therapeutic targets. Today, Anti-VEGF and mTOR inhibitors are the most used and probably the most active drugs in aggressive meningiomas. Peptide radioactive radiation therapy aims to target SSTR2A receptors, which are strongly expressed in meningiomas, but have an insufficient effect in most aggressive meningiomas, requiring the development of new techniques to increase the dose applied to the tumor. Based on the multiple potential intracellular targets, multiple targeted therapy clinical trials targeting Pi3K-Akt-mTOR and MAP kinase pathways as well as cell cycle and particularly, cyclin D4-6 are ongoing. Recently discovered driver mutations, SMO, Akt, and PI3KCA, offer new targets but are mostly observed in benign meningiomas, limiting their clinical relevance mainly to rare aggressive skull base meningiomas. Therefore, NF2 mutation remains the most frequent mutation and main challenging target in high-grade meningioma. Recently, inhibitors of focal adhesion kinase (FAK), which is involved in tumor cell adhesion, were tested in a phase 2 clinical trial with interesting but insufficient activity. The Hippo pathway was demonstrated to interact with NF2/Merlin and could be a promising target in NF2-mutated meningiomas with ongoing multiple preclinical studies and a phase 1 clinical trial. Recent advances in immune landscape comprehension led to the proposal of the use of immunotherapy in meningiomas. Except in rare cases of MSH2/6 mutation or high tumor mass burden, the activity of PD-1 inhibitors remains limited; however, its combination with various radiation therapy modalities is particularly promising. On the whole, therapeutic management of high-grade meningiomas is still challenging even with multiple promising therapeutic targets and innovations., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Positron emission tomography (PET) is a powerful tool that can help physicians manage primary brain tumours at diagnosis and follow-up. In this context, PET imaging is used with three main types of radiotracers: 18 F-FDG, amino acid radiotracers, and 68 Ga conjugated to somatostatin receptor ligands (SSTRs). At initial diagnosis, 18 F-FDG helps to characterize primary central nervous system (PCNS) lymphomas and high-grade gliomas, amino acid radiotracers are indicated for gliomas, and SSTR PET ligands are indicated for meningiomas. Such radiotracers provide information on tumour grade or type, assist in directing biopsies and help with treatment planning. During follow-up, in the presence of symptoms and/or MRI modifications, the differential diagnosis between tumour recurrence and post-therapeutic changes, in particular radiation necrosis, may be challenging, and there is strong interest in using PET to evaluate therapeutic toxicity. PET may also contribute to identifying specific complications, such as postradiation therapy encephalopathy, encephalitis associated with PCNS lymphoma, and stroke-like migraine after radiation therapy (SMART) syndrome associated with glioma recurrence and temporal epilepsy, originally illustrated in this review. This review summarizes the main contribution of PET to the diagnosis, management, and follow-up of brain tumours, specifically gliomas, meningiomas, and primary central nervous system lymphomas., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Rasmussen's encephalitis (RE) is a rare chronic inflammatory brain disorder resulting in progressive neurodegeneration in one cerebral hemisphere. The inflammatory process is accompanied by progressive loss of function of the affected hemisphere, associated with drug-resistant partial epilepsy. The diagnosis is based on a range of clinical, electroencephalographic, radiological and biochemical arguments, without any specific formal marker, which makes the diagnosis of the disease complex, especially in its initial phase. Seizures are refractory to anti-seizures medication (ASM) and to classical immunomodulatory treatments. These treatments are also ineffective to stop the degenerative process. Only surgical treatment with hemispherotomy (surgical disconnection of a cerebral hemisphere) allows definitive cessation of seizures but this leads to definitive motor and cognitive deficits. The etiology of RE is not known, but there is strong evidence for an immunopathogenic mechanism involving T-cell mediated immunity. The emergence of biotherapies targeting against various cytokines offers potential therapeutic perspectives. This disease is currently a real challenge in terms of: (i) early diagnosis, before the constitution of marked hemispheric atrophy and the appearance of neurological and cognitive consequences; (ii) recognition of incomplete form; (iii) therapeutic management due to advances in the field of targeted treatment of inflammation; (iv) surgery and recovery possibilities., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Nuclear medicine with positron emission tomography (PET) and single photon emission computed tomography (SPECT) develops powerful tools in molecular imaging to help clinicians in the challenging diagnosis of parkinsonism. These techniques can provide biomarkers for neurodegenerative parkinsonism and to distinguish Parkinson disease (PD) from atypical parkinsonism. This review summarizes the main SPECT and PET contributions to the diagnosis of parkinsonism. We will also discuss new technologies in the field of nuclear imaging and their potential contribution to the diagnosis of parkinsonian syndromes., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

This review aims to synthesize all the available data on brain molecular imaging, such as single-photon emission computed tomography (SPECT) and interictal fluorodeoxyglucose positron emission tomography (FDG-PET), in focal epilepsies. SPECT imaging is able to measure regional cerebral blood flow and its major innovation remains its ictal imaging value. On the other hand, FDG-PET, which has higher spatial resolution and lower background activity than SPECT, enables glycolytic metabolism to be identified in interictal states. Therefore, interictal FDG-PET has greater sensitivity than interictal SPECT, especially in temporal lobe epilepsies (TLEs). Thus, 18 F-FDG-PET is a necessary step in the presurgical evaluation of TLEs, but also of extratemporal epilepsies (ETEs), contributing to >30% of the decision to undertake surgery. In addition, FDG-PET has particular diagnostic value in focal epilepsies showing normal magnetic resonance imaging (MRI). PET also has good prognostic value for post-surgical outcomes as well as cognitive impairment, especially in cases where the hypometabolism extent is limited. Moreover, the notion of an epileptic network is well highlighted by functional PET imaging, allowing better understanding of the pathological substrates of these disorders. Future development of quantitative analysis software and of novel radiotracers and cameras will certainly enhance its clinical usefulness., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Introduction: The diagnosis of Alzheimer's disease (AD) and its related disorders rely on clinical criteria. There is, however, a large clinical overlap between the different neurodegenerative diseases affecting cognition and, frequently, there are diagnostic uncertainties with atypical clinical presentations. Current clinical practices can now regularly use positron emission tomography (PET) and single-photon emission computed tomography (SPECT) molecular imaging to help resolve such uncertainties. The Neurology Group of the French Society of Nuclear Medicine and Federations of Memory, Resources and Research Centers have collaborated to establish clinical guidelines to determine which molecular imaging techniques to use when seeking a differential diagnosis between AD and other neurodegenerative disorders affecting cognition., State of Knowledge: According to the current medical literature, the potential usefulness of molecular imaging to address the typical clinical criteria in common forms of AD remains modest, as typical AD presentations rarely raise questions of differential diagnoses with other neurodegenerative disorders. However, molecular imaging could be of significant value in the diagnosis of atypical neurodegenerative disorders, including early onset, rapid cognitive decline, prominent non-amnestic presentations involving language, visuospatial, behavioral/executive and/or non-cognitive symptoms in AD, or prominent amnestic presentations in other non-AD dementias., Conclusion and Perspective: The clinical use of molecular imaging should be recommended for assessing cognitive disturbances particularly in patients with early clinical onset (before age 65) and atypical presentations. However, diagnostic tools should always be part of the global clinical approach, as an isolated positive result cannot adequately establish a diagnosis of any neurodegenerative disorder., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are two atypical parkinsonian syndromes first described half a century ago. The spectrum of these conditions as well as, more generally, the concept of tauopathy have dramatically changed over the past decade and especially in recent years. In particular, clinicopathological correlations have led to the description of several subtypes of these diseases and the features they share with other neurodegenerative diseases. The present paper is a review of how the concepts of PSP and CBD have evolved over time. In particular, it focuses on the different presentations of the disease and the overlapping syndromes that can complicate the differential diagnoses. Also discussed are some of the tools that may prove useful in making a diagnosis. Indeed, differential diagnosis issues are of particular importance in light of the likely emergence of pathology-specific disease-modifying therapies in the near future., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

The goal of this study was to investigate the specific patterns of memory breakdown in patients suffering from early-onset Alzheimer's disease (EOAD) and late-onset Alzheimer's disease (LOAD). Twenty EOAD patients, twenty LOAD patients, twenty matched younger controls, and twenty matched older controls participated in this study. All participants underwent a detailed neuropsychological assessment, an MRI scan, an FDG-PET scan, and AD patients had biomarkers as supporting evidence of both amyloïdopathy and neuronal injury. Results of the neuropsychological assessment showed that both EOAD and LOAD groups were impaired in the domains of memory, executive functions, language, praxis, and visuoconstructional abilities, when compared to their respective control groups. EOAD and LOAD groups, however, showed distinct patterns of memory impairment. Even though both groups were similarly affected on measures of episodic, short term and working memory, in contrast semantic memory was significantly more impaired in LOAD than in EOAD patients. The EOAD group was not more affected than the LOAD group in any memory domain. EOAD patients, however, showed significantly poorer performance in other cognitive domains including executive functions and visuoconstructional abilities. A more detailed analysis of the pattern of semantic memory performance among patient groups revealed that the LOAD was more profoundly impaired, in tasks of both spontaneous recall and semantic recognition. Voxel-Based Morphometry (VBM) analyses showed that impaired semantic performance in patients was associated with reduced gray matter volume in the anterior temporal lobe (ATL) region, while PET-FDG analyses revealed that poorer semantic performance was associated with greater hypometabolism in the left temporoparietal region, both areas reflecting key regions of the semantic network. Results of this study indicate that EOAD and LOAD patients present with distinct patterns of memory impairment, and that a genuine semantic impairment may represent one of the clinical hallmarks of LOAD., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Major depressive disorder remains one of the leading causes of disability in developed countries despite pharmacological and psychological treatments. Patients with major depression have poorer health-related quality of life than persons of the general population, or patients with chronic somatic illness. Improvement of health-related quality of life in depression is thus a pertinent treatment objective. Both high-frequency repetitive transcranial magnetic stimulation (rTMS) over the left dorsolateral prefrontal cortex and low-frequency rTMS over the right dorsolateral prefrontal cortex have shown their effectiveness in medication-resistant depression. However, the Health-related Quality of Life questionnaire remains under-utilized to assess the effectiveness of rTMS in research or in a routine clinical setting. Our study aims to investigate in an open label trial the efficacy of low-frequency rTMS over the right dorsolateral prefrontal cortex on health-related quality of life and clinical outcomes in medication-resistant depression., Methods: In a naturalistic trial, 33 unipolar and bipolar patients with medication-resistant depression were treated with daily low-frequency rTMS over the right dorsolateral prefrontal cortex for 4 weeks. Health-related quality of life was assessed using the SF-36 questionnaire. The SF-36 is a generic, self-administered, and worldwide-used questionnaire, consisting of 36 items describing eight health dimensions: physical functioning, social functioning, role-physical problems, role-emotional problems, mental health, vitality, bodily pain, and general health. Physical component summary and mental component summary scores were then obtained. Depression severity was assessed using the 21-item self-report Beck Depression Inventory. Anxiety severity was assessed using the State-Trait Anxiety Inventory. The SF-36, the Beck Depression Inventory and the State-Trait Anxiety Inventory were assessed before and after low-frequency rTMS. The effect of rTMS treatment on the SF-36 and the clinical outcome was evaluated for significance with the Wilcoxon two-tailed signed-rank test. The reliable change index (RCI) was calculated to determine clinically significant change in the eight dimension and composite scores of the SF-36 from pre-intervention to post-intervention, at the level of individual patients. Effect size (r) was then calculated, r values from 0.1 to 0.29, 0.3 to 0.49 and from 0.5 were considered as indicating small, medium and large effect sizes, respectively. Correlations between improvement in Health-related Quality of Life and improvement in the other rating scale scores were calculated using Spearman's correlation test., Results: There were significant improvements of 37.6% in the mental health (P=0.018), 130 % in the role-emotional problem (P=0.045), 15.5% in the physical functioning (P=0.008), 110.6% in the role-physical problem (P=0.002), 22.4% in the bodily pain (P=0.013) dimensions, 6.1% in the Physical Component Score (P=0.043), and 22,5 % in the Beck Depression Inventory (P=0.002). Eighteen patients (54%) showed clinically significant improvement in one of the two composite scores after RCI calculation. Seven out of the eight SF-36 dimension scores and the two composite scores showed effect sizes ranging from 0.12 to 0.38, indicating small to moderate effect. Significant correlations were found between improvement in the Beck Depression Inventory and improvement in the Mental Component Score, the social functioning, the mental health, the general health, the vitality and the physical functioning dimensions., Limitations: Small sample size and non-controlled design., Conclusion: Low-frequency rTMS over the right dorsolateral prefrontal cortex improves Health-related Quality of Life in unipolar and bipolar patients with medication-resistant depression. Improvement in mental health-related quality of life is significantly correlated with improvement in depressive symptoms. However, further studies with larger samples and controlled designs are needed to clarify our findings., (Copyright © 2013. Published by Elsevier Masson SAS.)

This article presents the prospects of molecular imaging in Alzheimer's Disease (AD), regarding instrumentation, imaging agents, and image processing, and their possible impact on AD research and clinical care., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Mitoxantrone is an immunosuppressive drug usually delivered in severe relapsing remitting multiple sclerosis. It can also be used in secondary progressive and progressive relapsing remitting multiple sclerosis. Left ventricular ejection fraction has to be monitored because of the cardiotoxicity risk of mitoxantrone. Acute cardiac side effects in multiple sclerosis have not yet been described. We report the single case of an acute heart failure occurring in a cohort of more than 800 patients treated with mitoxantrone. We discuss about interruption criteria as maximal cumulative dose allowed and left ventricular ejection fraction cut off value.

Ruptures of the middle and lower part of the rectus femoris muscle are seen essentially in the footballer during a shoot at goal. Often unrecognised initially, they warrant surgical treatment in the sportsman. The anatomical appearances of these complete or partial ruptures are described. The authors propose a new technique of reinsertion, relying upon the posterior aponeurotic layer, using non-absorbable sutures. Results were satisfactory in 10 cases out of 11.