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1.
Rev Neurol (Paris) ; 180(1-2): 107-116, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38142198

RESUMEN

In autoimmune neurological diseases, the autonomic nervous system can be the primary target of autoimmunity (e.g. autoimmune autonomic ganglionopathy), or, more frequently, be damaged together with other areas of the nervous system (e.g. Guillain-Barré syndrome). Patients with autoimmune encephalitis and paraneoplastic neurological syndromes (PNS) often develop dysautonomia; however, the frequency and spectrum of autonomic signs and symptoms remain ill defined except for those scenarios in which dysautonomia is a core feature of the disease. Such is the case of Lambert-Eaton myasthenic syndrome, Morvan syndrome or anti-NMDAR encephalitis; in the latter, patients with dysautonomia have been reported to carry a more severe disease and to retain higher disability than those without autonomic dysfunction. Likewise, the presence of autonomic involvement indicates a higher risk of death due to neurological cause in patients with anti-Hu PNS. However, in anti-Hu and other PNS, as well as in the context of immune checkpoint inhibitors' toxicities, the characterization of autonomic involvement is frequently overshadowed by the severity of other neurological symptoms and signs. When evaluated with tests specific for autonomic function, patients with autoimmune encephalitis or PNS usually show a more widespread autonomic involvement than clinically suggested, which may reflect a potential gap of care when it comes to diagnosing dysautonomia. This review aims to revise the autonomic involvement in patients with autoimmune encephalitis and PNS, using for that purpose an antibody-based approach. We also discuss and provide general recommendations for the evaluation and management of dysautonomia in these patients.


Asunto(s)
Enfermedades Autoinmunes del Sistema Nervioso , Enfermedades del Sistema Nervioso Autónomo , Encefalitis , Enfermedad de Hashimoto , Síndromes Paraneoplásicos del Sistema Nervioso , Síndromes Paraneoplásicos , Enfermedades del Sistema Nervioso Periférico , Humanos , Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Enfermedades del Sistema Nervioso Autónomo/etiología , Enfermedades Autoinmunes del Sistema Nervioso/complicaciones , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Sistema Nervioso Autónomo , Síndromes Paraneoplásicos del Sistema Nervioso/complicaciones , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Autoanticuerpos
2.
Rev Neurol (Paris) ; 179(5): 506-515, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36934022

RESUMEN

The use of immune checkpoint inhibitors (ICIs) has represented a major advance in cancer treatment. By enhancing endogenous immune responses to destroy cancer cells, ICIs can cause immune-related adverse events (irAEs), with possible involvement of any organ system. IrAEs are frequent, particularly those involving the skin or the endocrine system, and usually completely reversible after temporary immunosuppression, while neurological irAEs (n-irAEs) are relatively rare, often severe, and they carry a considerable risk of mortality and long-term disability. They usually affect the peripheral nervous system, mainly manifesting as myositis, polyradiculoneuropathy, or cranial neuropathy, and, less frequently, involve the central nervous system, causing encephalitis, meningitis, or myelitis. Although somehow reminiscent of the disorders that neurologists are familiar to deal with in their daily practice, n-irAEs are characterized by distinctive features from their idiopathic counterparts; for instance, myositis may have a predominant oculo-bulbar involvement reminiscent of myasthenia gravis and frequently associates with myocarditis; peripheral neuropathy, although often resembling Guillain-Barré syndrome, usually responds to corticosteroids. Remarkably, several associations between the neurological phenotype and the type of ICIs or the type of cancer have emerged in the last few years, and the growing administration of ICIs in patients with neuroendocrine cancers has led to an increased number of reports of paraneoplastic neurological syndromes (triggered or worsened by ICIs). This review aims to update current knowledge regarding the clinical presentation of n-irAEs. We also discuss the essential parts of the diagnostic approach, and we provide general recommendations for the management of these disorders.


Asunto(s)
Miastenia Gravis , Miositis , Neoplasias , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inmunoterapia/efectos adversos , Neoplasias/complicaciones , Neoplasias/diagnóstico , Neoplasias/tratamiento farmacológico , Miastenia Gravis/tratamiento farmacológico , Miositis/inducido químicamente , Miositis/diagnóstico , Miositis/terapia
3.
Rev Neurol (Paris) ; 178(1-2): 34-47, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35000790

RESUMEN

Autoimmune encephalitides constitute an emerging group of diseases for which the diagnosis and management may be challenging, and are usually associated with antibodies against neuroglial antigens used as biomarkers. In this review, we aimed to clarify the diagnostic approach to patients with encephalitis of suspected autoimmune origin in order to initiate early immunotherapy, and to summarize the evidence of current immunotherapies and alternative options assessed for refractory cases. Currently, the general therapeutic approach consists of steroids, IVIG, and/or plasma exchange as first-line medications, which should be prescribed once a diagnosis of possible autoimmune encephalitis is established. For patients not responding to these treatments, rituximab and cyclophosphamide are used as second-line immunotherapy. Additionally, alternative therapies, chiefly tocilizumab and bortezomib, have been reported to be useful in particularly refractory cases. Although the aforementioned approach with first and second-line immunotherapy is widely accepted, the best therapeutic strategy is still unclear since most available evidence is gathered from retrospective non-controlled studies. Moreover, several predictors of good long-term prognosis have been proposed such as response to first-line therapies, modified Rankin score lesser than 4 at the worst neurologic status, no need for admission in intensive care unit, and early escalation to second-line immunotherapy. Thus, the lack of solid evidence underlines the necessity of future well-conducted trials addressing both the best therapeutic regimen and the outcome predictors, but since autoimmune encephalitides have a relatively low incidence, international collaborations seem imperative to reach a reasonable study population size.


Asunto(s)
Encefalitis , Enfermedad de Hashimoto , Autoanticuerpos , Encefalitis/diagnóstico , Encefalitis/terapia , Enfermedad de Hashimoto/diagnóstico , Enfermedad de Hashimoto/terapia , Humanos , Inmunoterapia , Estudios Retrospectivos , Rituximab
4.
Rev Neurol (Paris) ; 175(9): 534-543, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31208813

RESUMEN

INTRODUCTION: Currently, no single diagnostic modality allows the distinction between early progression (EP) and pseudo-progression (Psp) in glioblastoma patients. Herein we aimed to identify the characteristics associated with EP and Psp, and to analyze their diagnostic value alone and in combination. MATERIAL AND METHODS: We reviewed the clinical, conventional magnetic resonance imaging (MRI), and molecular characteristics (MGMT promoter methylation, IDH mutation, and EGFR amplification) of glioblastoma patients who presented an EP (n=59) or a Psp (n=24) within six months after temozolomide radiochemotherapy. We analyzed relative cerebral blood volume (rCBV) and relative vessel permeability on K2 maps (rK2) in a subset of 33 patients using dynamic-susceptibility-contrast MRI. RESULTS: In univariate analysis, EP was associated with neurological deterioration, higher doses of dexamethasone, appearance of a new enhanced lesion, subependymal enhancement, higher rCBV and rK2 values. Psp occurred earlier after radiotherapy completion and was associated with IDH1 R132H mutation, and MGMT methylation. In multivariate analysis, rCBV, rK2, and MGMT methylation status were independently associated with EP and Psp. All patients with a methylated MGMT promoter and a low rCBV (<1.75) were classified as Psp while all patients with an unmethylated MGMT promoter and a high rCBV (≥1.75) were classified as EP. Among patients with discordant MGMT methylation and rCBV characteristics, higher rK2 values tended to be associated with EP. CONCLUSION: Combined analysis of MGMT methylation, rCBV and vessel permeability on K2 maps seems helpful to distinguish EP from Psp. A prospective study is warranted to confirm these results.


Asunto(s)
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Glioblastoma/diagnóstico , Glioblastoma/terapia , Imagen por Resonancia Magnética/métodos , Proteínas Supresoras de Tumor/genética , Adulto , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Quimioradioterapia/efectos adversos , Medios de Contraste , Metilasas de Modificación del ADN/análisis , Enzimas Reparadoras del ADN/análisis , Diagnóstico Diferencial , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Glioblastoma/genética , Glioblastoma/patología , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Traumatismos por Radiación/diagnóstico , Traumatismos por Radiación/genética , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Proteínas Supresoras de Tumor/análisis
5.
J Neurooncol ; 136(3): 533-539, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-29143276

RESUMEN

Although upfront temozolomide (TMZ) has been widely-used to treat 1p/19q-codeleted diffuse low-grade gliomas (LGG), its long-term impact on the growth kinetics of these tumors has not been determined. Based on serial magnetic resonance images we retrospectively evaluated the evolution of the mean tumor diameter (MTD) in 36 progressive 1p/19q-codeleted LGG treated with upfront TMZ. After TMZ onset, all but two patients (94.4%) presented a progressive MTD decrease that lasted for a median duration of 23 months (range 3-114). In 10 patients (27%) MTD regrowth occurred during TMZ treatment and in 22 patients (66%) after TMZ discontinuation. In these patients, median time to MTD regrowth after TMZ discontinuation was 12 months (range 1-88). The rate of MTD regrowth at 3 and 5 years after TMZ onset was 77 and 94%, respectively. Time to tumor progression (TTP) based on volumetric analysis was shorter than TTP based on Response Assessment in Neuro-Oncology (RANO) bidimensional criteria (23 vs. 35 months, p = 0.05) and shorter than time to next oncological treatment (23 vs. 46 months, p = 0.001). In 10 patients (27%), absence of volumetric analysis led to continue TMZ for a median of 10 cycles after MTD had started to regrow. Volumetric analysis is important to precisely assess chemotherapy efficacy in 1p/19q-codeleted LGG, identify early tumor progression and avoid futile chemotherapy continuation. In the present series, although some long-lasting volumetric responses were observed, most tumors resumed their growth within 3 years after TMZ onset.


Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/genética , Glioma/tratamiento farmacológico , Glioma/genética , Temozolomida/uso terapéutico , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Encéfalo/fisiopatología , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/fisiopatología , Deleción Cromosómica , Cromosomas Humanos Par 1 , Cromosomas Humanos Par 19 , Progresión de la Enfermedad , Femenino , Glioma/diagnóstico por imagen , Glioma/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Carga Tumoral/efectos de los fármacos
6.
Rev Neurol (Paris) ; 174(9): 597-607, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30201423

RESUMEN

Movement disorders are extremely common and diverse in autoimmune encephalitis (AE) and paraneoplastic neurological syndromes (PNS). They can sometimes represent the main neurological disorder of a given patient, or just be part of a larger neurological syndrome. Early diagnosis of AE or PNS is essential, as the associated abnormal movements can be effectively treated with immunomodulators. Nevertheless, the diagnosis is often delayed because of the large number of differential diagnoses (infections, metabolic disorders, genetic and degenerative diseases) and because the semiology of abnormal movements arising during AE and PNS is often not well known. However, there are highly specific clinical features, depending on the associated autoantibodies, age and gender of the patient, and associated cancers. Such features are likely to rely on specific mechanisms, the knowledge of which could lead to new therapeutic proposals. Also, the growing body of work on AE and PNS provides a better understanding of the links between immunity and neuronal degeneration, and immunity and genetic specificities. Thus, the purpose of this article is to present the current knowledge and different subtypes of movement disorders associated with AE and PNS, as well as the mechanisms that can lead to neuronal dysfunction.


Asunto(s)
Enfermedades Autoinmunes/complicaciones , Encefalitis/complicaciones , Trastornos del Movimiento/etiología , Síndromes Paraneoplásicos del Sistema Nervioso/complicaciones , Enfermedades Autoinmunes/terapia , Encefalitis/terapia , Humanos , Trastornos del Movimiento/terapia , Síndromes Paraneoplásicos del Sistema Nervioso/terapia
7.
Rev Neurol (Paris) ; 174(4): 228-236, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29609960

RESUMEN

Autoimmune encephalitis (AE) refers to a rare, newly described, group of diseases associated with specific circulating autoantibodies directed against neuronal proteins used as biomarkers of the disease. Characterization of the associated autoantibodies present in the patients' cerebrospinal fluid (CSF) and/or sera can differentiate the various AE subgroups, which have specific clinical presentations and prognoses, and is therefore essential for proposing appropriate treatments. As psychiatric symptoms may predominate at the onset or over the course of these diseases, the diagnosis is frequently delayed. Yet, patients' prognoses depend on the speed with which the disease is detected, identified and managed. A wide range of neuropsychiatric symptoms is observed according to the patient's AE subgroup, and some are highly suggestive of an immune origin and should be recognized as such by physicians. Because the presence of pronounced psychiatric symptoms drives patients to psychiatric institutions, which can hinder the diagnosis, physicians need to be aware of AE and propose the detection of autoantibodies as early as possible to provide optimal medical care to such patients. In fact, the description of AE subgroups over the past decade has allowed the present overview of their incidence in psychiatric diseases and some general guidelines for the management of these patients.


Asunto(s)
Enfermedades Autoinmunes/psicología , Trastornos Mentales/psicología , Autoanticuerpos/inmunología , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/terapia , Humanos , Trastornos Mentales/inmunología , Trastornos Mentales/terapia , Pronóstico
8.
Rev Neurol (Paris) ; 179(5): 377, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37197890
9.
Mol Psychiatry ; 21(12): 1768-1780, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-26728568

RESUMEN

Vascular endothelial growth factor (VEGF) is known to be required for the action of antidepressant therapies but its impact on brain synaptic function is poorly characterized. Using a combination of electrophysiological, single-molecule imaging and conditional transgenic approaches, we identified the molecular basis of the VEGF effect on synaptic transmission and plasticity. VEGF increases the postsynaptic responses mediated by the N-methyl-D-aspartate type of glutamate receptors (GluNRs) in hippocampal neurons. This is concurrent with the formation of new synapses and with the synaptic recruitment of GluNR expressing the GluN2B subunit (GluNR-2B). VEGF induces a rapid redistribution of GluNR-2B at synaptic sites by increasing the surface dynamics of these receptors within the membrane. Consistently, silencing the expression of the VEGF receptor 2 (VEGFR2) in neural cells impairs hippocampal-dependent synaptic plasticity and consolidation of emotional memory. These findings demonstrated the direct implication of VEGF signaling in neurons via VEGFR2 in proper synaptic function. They highlight the potential of VEGF as a key regulator of GluNR synaptic function and suggest a role for VEGF in new therapeutic approaches targeting GluNR in depression.


Asunto(s)
Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 2 de Factores de Crecimiento Endotelial Vascular/metabolismo , Animales , Conducta Animal , Técnicas de Cultivo de Célula , Potenciales Postsinápticos Excitadores , Miedo , Hipocampo/metabolismo , Ratones , Plasticidad Neuronal/fisiología , Neuronas/metabolismo , Subunidades de Proteína , Receptores de Glutamato/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Sinapsis/metabolismo , Transmisión Sináptica/fisiología , Factor A de Crecimiento Endotelial Vascular/fisiología , Receptor 2 de Factores de Crecimiento Endotelial Vascular/fisiología
11.
Mol Psychiatry ; 20(9): 1037-45, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26077693

RESUMEN

Neuronal polarity and spatial rearrangement of neuronal processes are central to the development of all mature nervous systems. Recent studies have highlighted the dynamic expression of Collapsin-Response-Mediator Proteins (CRMPs) in neuronal dendritic/axonal compartments, described their interaction with cytoskeleton proteins, identified their ability to activate L- and N-type voltage-gated calcium channels (VGCCs) and delineated their crucial role as signaling molecules essential for neuron differentiation and neural network development and maintenance. In addition, evidence obtained from genome-wide/genetic linkage/proteomic/translational approaches revealed that CRMP expression is altered in human pathologies including mental (schizophrenia and mood disorders) and neurological (Alzheimer's, prion encephalopathy, epilepsy and others) disorders. Changes in CRMPs levels have been observed after psychotropic treatments, and disrupting CRMP2 binding to calcium channels blocked neuropathic pain. These observations, altogether with those obtained from genetically modified mice targeting individual CRMPs and RNA interference approaches, pave the way for considering CRMPs as potential early disease markers and modulation of their activity as therapeutic strategy for disorders associated with neurite abnormalities.


Asunto(s)
Enfermedades del Sistema Nervioso Central/patología , Dendritas/fisiología , Proteínas del Tejido Nervioso/fisiología , Neuronas/fisiología , Animales , Dendritas/genética , Dendritas/metabolismo , Estudios de Asociación Genética , Humanos , Ratones , Morfogénesis , Neurogénesis , Neuronas/citología , Neuronas/metabolismo , Neuronas/patología
12.
J Clin Pharm Ther ; 41(1): 47-53, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26748577

RESUMEN

WHAT IS NEW AND OBJECTIVES: Trends in the care of glioblastoma in actual practice settings are poorly described. In a previous pharmacoepidemiologic study, we highlighted changes in the management of patients with glioblastoma (GBM) newly diagnosed between 2004 and 2008. Our aim was to complete and to extend the previous report with a study of a cohort of patients diagnosed in 2011 to emphasize the trends in the pharmacotherapy of GBM over the last decade. METHODS: A single-centre study was undertaken of three historic cohorts of GBM patients newly diagnosed during years 2004, 2008 and 2011 (corresponding to groups 1, 2 and 3, respectively) but limited to patients eligible for radiotherapy after initial diagnosis. The type of medical management was described and compared, as well as overall survival and total cost from diagnosis to death or the last follow-up date. Cost analysis was performed from the French sickness fund perspective using tariffs from 2014. RESULTS: Two hundred and seventeen patients (49 in Group 1, 73 in Group 2, 95 in Group 3) were selected with similar baseline characteristics. Fluorescence-guided surgery using 5-ALA was increasingly used over the three periods. There was a strong trend towards broader use of temozolomide radiochemotherapy (39%, 73% and 83% of patients, respectively) as first-line treatment as well as bevacizumab regimen at recurrence (6%, 48% and 58% of patients, respectively). The increase in overall survival between Group 2 and Group 1 was confirmed for patients in Group 3 (17·5 months vs. 10 months in Group 1). The mean total cost per patient was 53368 € in Group 1, 70 201 € in Group 2 and 78355 € in Group 3. Hospital care represented the largest expenditure (75%, 59% and 60% in groups 1, 2 and 3, respectively) followed by chemotherapy drug costs (11%, 30% and 29%, respectively). WHAT IS NEW AND CONCLUSION: This is the first study to report on changes in the management of GBM in real-life practice. The ten-year study indicates an improvement in overall survival but also an increase in total cost of care. The data should be useful for informing the care of GBM patients in settings similar to ours.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Costos de la Atención en Salud , Anciano , Antineoplásicos/administración & dosificación , Antineoplásicos/economía , Bevacizumab/administración & dosificación , Neoplasias Encefálicas/economía , Neoplasias Encefálicas/terapia , Quimioradioterapia/métodos , Dacarbazina/administración & dosificación , Dacarbazina/análogos & derivados , Costos de los Medicamentos , Femenino , Estudios de Seguimiento , Francia , Glioblastoma/economía , Glioblastoma/terapia , Hospitalización/economía , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Tasa de Supervivencia , Temozolomida
15.
Ann Oncol ; 25(7): 1442-1447, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24723487

RESUMEN

BACKGROUND: Prognosis of unresectable glioblastoma (GB) remains poor, despite temozolomide (TMZ)-based chemoradiation. Activity of bevacizumab (BEV) and irinotecan (IRI) has been reported in recurrent disease. We evaluated BEV and IRI as neo-adjuvant and adjuvant treatment combined with TMZ-based chemoradiation for unresectable GB. PATIENTS AND METHODS: Patients with unresectable GB, age 18-70, IK ≥50 were eligible. The experimental arm (BEV/IRI) consisted of neo-adjuvant intravenous BEV, 10 mg/kg, and IRI, 125 mg/m(2), every 2 weeks for four cycles before radiotherapy (RT) (60 Gy), concomitant oral TMZ, 75 mg/m(2)/day, and BEV, 10 mg/kg every 2 weeks. Adjuvant BEV and IRI were given every 2 weeks for 6 months. The control arm consisted of concomitant oral TMZ, 75 mg/m(2)/day during RT, and 150-200 mg/m(2) for 5 days every 28 days for 6 months. The use of BEV was allowed at progression in the control arm. RESULTS: Patients (120) were included from April 2009 to January 2011. The working hypothesis was that treatment would increase the progression-free survival at 6 month (PFS-6) from 50% to 66%. The primary objective was not achieved, and only 30 out of 60 patients were alive without progression at 6 months (50.0% [IC95% (36.8; 63.1)] in the BEV/IRI arm when 37 out of 60 patients were required according to the Fleming decision rules. PFS-6 was 7.1 months in BEV/IRI versus 5.2 months in the control arm. The median overall survival was not different between the two arms (11.1 months). Main toxicities were three fatal intracranial bleedings, three bile duct or digestive perforations/infections (1 fatal), and six thrombotic episodes in the BEV/IRI arm, whereas there was one intracranial bleeding, two bile duct or digestive perforations/infections (1 fatal), and one thrombotic episode in the control arm. CONCLUSIONS: Neo-adjuvant and adjuvant BEV/IRI, combined with TMZ-radiation, is not recommended for further evaluation in the first-line treatment of unresectable GB. CLINICAL TRIAL REGISTRATION: Clinical trial registered under EUDRACT number 2008-002775-28 (NCT01022918).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Bevacizumab , Neoplasias Encefálicas/radioterapia , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Quimioterapia Adyuvante , Dacarbazina/administración & dosificación , Dacarbazina/análogos & derivados , Femenino , Glioblastoma/radioterapia , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Temozolomida
16.
Eur J Neurol ; 21(5): 731-5, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24471811

RESUMEN

BACKGROUND AND PURPOSE: To describe the characteristics of patients presenting a paraneoplastic cerebellar degeneration without classical onconeural antibodies (seronegative PCD). METHODS: Thirty-nine seronegative PCD patients from the Paraneoplastic Neurological Syndrome Euronetwork were retrospectively analyzed and compared with 180 patients with PCD associated with classical onconeural antibodies (seropositive PCD). RESULTS: No patient had anti-CASPR2 or anti-mGluR1 antibodies. No significant difference between the clinical characteristics of seronegative and seropositive PCD patients was observed. Yet the frequency of associated tumors was different. Lymphoma was more frequent in seronegative than in seropositive women (24% vs. 2%, P = 0.002) whilst gynecological cancer were less frequent (38% vs. 74%, P = 0.002). In comparison with seropositive men, seronegative men more frequently had a non-small-cell lung cancer (27% vs. 6%, P = 0.08) or a genitourinary cancer (22% vs. 0%, P = 0.04) but less frequently a small-cell lung cancer (23% vs. 74%, P = 0.002). Seronegative and seropositive PCD patients with similar tumors had a similar overall survival. CONCLUSION: The clinical characteristics of seronegative and seropositive PCD are similar but the spectrum of associated tumors is different. The immunological scenario of seronegative PCD seems to be different from that of limbic encephalitis with only few patients harboring anti-neuropile antibodies.


Asunto(s)
Anticuerpos/sangre , Proteínas de la Membrana/inmunología , Proteínas del Tejido Nervioso/inmunología , Degeneración Cerebelosa Paraneoplásica/sangre , Degeneración Cerebelosa Paraneoplásica/inmunología , Receptores AMPA/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Europa (Continente)/epidemiología , Femenino , Humanos , Linfoma/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , Adulto Joven
17.
J Clin Pharm Ther ; 39(6): 642-8, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25164371

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Therapeutic options for the management of glioblastoma (GBM) have greatly evolved over the last decade with the emergence of new regimens combining radiotherapy plus temozolomide and the use of bevacizumab at recurrence. Our aim was to assess the clinical and economic impacts of those novel strategies in our center. METHODS: A single-center retrospective chart review was conducted on patients newly diagnosed with a GBM over two periods (year 2004, group 1 or year 2008, group 2) with limitations to those eligible to radiotherapy after initial diagnosis. The type of medical management was described and compared, as well as overall survival and total costs from diagnosis to death or the last follow-up date. Cost analysis was performed under the French Sickness Fund perspective using tariffs from 2012. RESULTS: One hundred twenty-two patients were selected (49 in group 1 and 73 in group 2) with similar baseline characteristics within the two groups. Patients from group 2 received more frequently temozolomide radiochemotherapy (71% vs. 39%, P < 0·05) as first-line treatment as well as bevacizumab regimen at recurrence (48% vs. 6%, P < 0·05); the median overall survival was increased between the two periods (respectively 17 vs. 10 months, P < 0·05). The mean total cost per patient was 54,388 € in group 1 and 71,148 € in group 2 (P < 0·05). Hospital care represented the largest expenditure (76% and 58% in groups 1 and 2 respectively) followed by chemotherapy drugs costs (11% and 30% respectively). The total cost difference between the two groups was explained by the increasing use of temozolomide and bevacizumab. The incremental cost-effectiveness ratio was estimated at 54,355 € per life-year gained. WHAT IS NEW AND CONCLUSION: As far as we know, this is the first study reporting the total cost of GBM management based on the French perspective, as well as the cost-effectiveness of clinical practices in term of cost per life-year gained. Those novel strategies have contributed to improve overall survival while inducing a substantial, but acceptable, increase of total costs.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Dacarbazina/análogos & derivados , Glioblastoma/terapia , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/economía , Antineoplásicos/administración & dosificación , Antineoplásicos/economía , Bevacizumab , Quimioradioterapia/economía , Quimioradioterapia/métodos , Estudios de Cohortes , Análisis Costo-Beneficio , Dacarbazina/administración & dosificación , Dacarbazina/economía , Dacarbazina/uso terapéutico , Costos de los Medicamentos , Femenino , Estudios de Seguimiento , Francia , Glioblastoma/economía , Glioblastoma/patología , Costos de la Atención en Salud , Costos de Hospital , Hospitales Universitarios , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Años de Vida Ajustados por Calidad de Vida , Estudios Retrospectivos , Tasa de Supervivencia , Temozolomida , Factores de Tiempo , Resultado del Tratamiento
18.
Rev Neurol (Paris) ; 170(10): 587-94, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25189679

RESUMEN

Initially, antibodies targeting intracellular compounds were described in patients with paraneoplastic neurological syndromes (PNS) such as anti-Hu, anti-Yo, anti-Ri or anti-CV2/CRMP5 antibodies. As more than 90% of patients with these antibodies suffer from an associated cancer, these antibodies were used as biomarkers of an underlying tumour. Recently, autoantibodies targeting cell-surface synaptic antigens have been described in patients with neurological symptoms suggesting PNS. These autoantibodies being less frequently associated with a tumour, they completely changed the concept of PNS. They lead to a new classification, not based on clinical symptoms or oncological status but on the location of the targeted antigens. Three groups of autoantibodies can be delineated according to the neuronal localization of the targeted antigen: Group 1: cytoplasmic neuronal antigens (CNA) (anti-Hu, Yo, CV2/CRMP5, Ri, Ma1/2, Sox, Zic4). Group 2: cell-surface neuronal antigens (CSNA) (anti-NMDAR, Lgi1, CASPR2, VGCC, AMPAr, GlyR, DNER, GABABR, GABAAR, IgLONS, mGluR1 and mGluR5). Group 3: intracellular synaptic antigens (ISA) (anti-GAD65 and anti-amphiphysin). More than being solely a classification of patients, these three groups are related to profound differences in the pathophysiology and in the pathogenic role of the associated autoantibody. According to the type of associated autoantibody, the age and sex of patients, physicians are now able to predict the presence or absence of tumour, the clinical evolution and prognostic and also the response to immunomodulator treatments that differ fundamentally from one group to the others.


Asunto(s)
Autoanticuerpos/inmunología , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico , Enfermedades del Sistema Nervioso Central/inmunología , Antígenos de Superficie/inmunología , Humanos , Neuronas/inmunología
20.
Rev Neurol (Paris) ; 170(3): 222-7, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24582303

RESUMEN

INTRODUCTION: The treatment of glioblastomas (GBMs) has changed significantly since 2005. However, the extent to which this change has improved overall survival (OS) of patients treated outside clinical trials remains to be determined. METHODS: We compared the patterns of care and OS of all GBM patients diagnosed in 2004 (n=105) and in 2008 (n=130) in our center. RESULTS: Younger patients (aged<70 years) diagnosed in 2008 received temozolomide radiochemotherapy as the initial treatment and bevacizumab at recurrence more frequently than those diagnosed in 2004 (69% vs 26% P<10(-4) and 41% vs 3%, P<10(-4), respectively). Elderly patients (aged≥70 years) diagnosed in 2008 received an oncological treatment (radiotherapy and/or chemotherapy) more frequently than those diagnosed in 2004 (67% vs 38%, P=0.006). The patients diagnosed in 2008 had longer OS than those diagnosed in 2004 (10.5 months vs 5.3 months, P=0.001). This finding was true for both younger and elderly patients (15.3 months vs 8.9 months, P=0.02 and 6.4 months vs 3.2 months, P=0.0002, respectively) and when considering only IDH1 wild-type patients (8.9 months vs 5.3 months, P=0.004). CONCLUSION: In our center, the change in the patterns of care for GBMs between 2004 and 2008 has been associated with a significant improvement in OS.


Asunto(s)
Neoplasias Encefálicas/terapia , Glioblastoma/terapia , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos/uso terapéutico , Bevacizumab , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/radioterapia , Quimioradioterapia , Quimioterapia Adyuvante , Terapia Combinada , Irradiación Craneana , Dacarbazina/análogos & derivados , Dacarbazina/uso terapéutico , Manejo de la Enfermedad , Femenino , Francia/epidemiología , Glioblastoma/tratamiento farmacológico , Glioblastoma/mortalidad , Glioblastoma/radioterapia , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Compuestos de Nitrosourea/uso terapéutico , Cuidados Paliativos , Temozolomida , Resultado del Tratamiento
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