RESUMO
INTRODUCTION: Tuberous sclerosis complex (TSC) is caused by variants in TSC1/TSC2, leading to constitutive activation of the mammalian target of rapamycin (mTOR) complex 1. Therapy with everolimus has been approved for TSC, but variations in success are frequent. Recently, caudal late interneuron progenitor (CLIP) cells were identified as a common origin of the TSC brain pathologies such as subependymal giant cell astrocytomas (SEGA) and cortical tubers (CT). Further, targeting the epidermal growth factor receptor (EGFR) with afatinib, which is expressed in CLIP cells, reduces cell growth in cerebral TSC organoids. However, investigation of clinical patient-derived data is lacking. AIMS: Observation of EGFR expression in SEGA, CT and focal cortical dysplasia (FCD) 2B human brain specimen and investigation of whether its inhibition could be a potential therapeutic intervention for these patients. METHODS: Brain specimens of 23 SEGAs, 6 CTs, 20 FCD2Bs and 17 controls were analysed via immunohistochemistry to characterise EGFR expression, cell proliferation (via Mib1) and mTOR signalling. In a cell-based assay using primary patient-derived cells (CT n = 1, FCD2B n = 1 and SEGA n = 4), the effects of afatinib and everolimus on cell proliferation and cell viability were observed. RESULTS: EGFR overexpression was observed in histological sections of SEGA, CT and FCD2B patients. Both everolimus and afatinib decreased the proliferation and viability in primary SEGA, tuber and FCD2B cells. CONCLUSION: Our study demonstrates that EGFR suppression might be an effective alternative treatment option for SEGAs and tubers, as well as other mTOR-associated malformations of cortical development, including FCD2B.
Assuntos
Astrocitoma , Esclerose Tuberosa , Humanos , Everolimo/farmacologia , Everolimo/uso terapêutico , Esclerose Tuberosa/metabolismo , Afatinib/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Astrocitoma/tratamento farmacológico , Astrocitoma/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina , Receptores ErbB/uso terapêuticoRESUMO
Subependymal giant cell astrocytoma (SEGA) represents a benign brain tumor occurring in 5-20% of individuals diagnosed with tuberous sclerosis complex (TSC), serving as a major diagnostic criterion. The presence of SEGA in a patient often prompts consideration of TSC as a probable diagnosis, given its unique association with this disorder. Typically, only one additional major criterion or two minor criteria are necessary to fulfill the diagnostic criteria for TSC. However, in rare instances, SEGA may manifest in patients without clinical features of TSC, termed solitary SEGA. The occurrence of solitary SEGA in patients lacking both clinical manifestations of TSC and genetic confirmation is extremely rare. Furthermore, the presentation of SEGA with intratumoral bleeding is exceedingly uncommon. Here, we presented a case of bleeding solitary SEGA in non-TSC adolescent who underwent surgery and has remained free of disease for a minimum of 3 years. Genetic analysis of peripheral blood and tumor tissue yielded negative results for TSC-related mutations. While SEGA occurrence in non-TSC patients is uncommon, it remains one of the possible diagnoses of intraventricular tumors. However, comprehensive genetic and physical evaluations are imperative to confirm the TSC status and guide further investigations and follow-up appropriately.
Assuntos
Astrocitoma , Adolescente , Humanos , Astrocitoma/complicações , Astrocitoma/genética , Astrocitoma/cirurgia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/complicações , Esclerose Tuberosa/complicações , Esclerose Tuberosa/genéticaRESUMO
PURPOSE: Subependymal giant cell astrocytoma (SEGA) is a WHO grade I pediatric glioma arising in 5-15% of patients with tuberous sclerosis (TSC). Rare cases of isolated SEGA without TSC have been described. The etiology, genetic mechanisms, natural history, and response to treatment of these lesions are currently unknown. We describe two such cases of isolated SEGA with follow-up. METHODS: Retrospective review was performed at a single institution to describe the clinical course of pathology-confirmed SEGA in patients with germline testing negative for TSC mutations. RESULTS: Two cases of isolated SEGA were identified. Genetic analysis of the tumor specimen was available for one, which revealed an 18 base pair deletion in TSC1. Both cases were managed with surgical resection, one with preoperative embolization. In spite of a gross total resection, one patient experienced recurrence after three years. Treatment with an mTOR inhibitor led to a significant interval reduction of the mass on follow-up MRI. The patient tolerated the medication well for 6 years and is now off of treatment for 2 years with a stable lesion. CONCLUSION: Cases of SEGA outside of the context of TSC are exceedingly rare, with only 48 cases previously described. The genetic mechanisms and treatment response of these lesions are poorly understood. To date, these lesions appear to respond well to mTOR inhibitors and may behave similarly to SEGAs associated with TSC. However, given that experience is extremely limited, these cases should be followed long term to better understand their natural history and treatment response.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Esclerose Tuberosa , Humanos , Criança , Esclerose Tuberosa/complicações , Esclerose Tuberosa/diagnóstico por imagem , Esclerose Tuberosa/genética , Estudos Retrospectivos , Astrocitoma/diagnóstico por imagem , Astrocitoma/genética , Astrocitoma/terapia , Imageamento por Ressonância Magnética/efeitos adversos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapiaRESUMO
Subependymal giant cell astrocytoma (SEGA) is a low-grade periventricular tumor that is closely associated with tuberous sclerosis complex (TSC). SEGA typically arises during the first two decades of life and rarely arises after the age of 20-25 years. Nevertheless, it has also been reported that glioma histologically resembling SEGA, so-called SEGA-like astrocytoma, can arise in neurofibromatosis type 1 (NF1) patients, even in the elderly. Herein, we report a case of SEGA-like circumscribed astrocytoma arising in the lateral ventricle of a 75-year-old woman. Whole-exome sequencing revealed a somatic variant of NF1. Methylation array analysis led to a diagnosis of "methylation class glioblastoma, IDH-wildtype, mesenchymal-type (GBM, MES)" with a high calibrated score (0.99). EGFR amplification, CDKN2A/B homozygous deletion, chromosomal +7/-10 alterations, and TERT promoter mutation, typical molecular abnormalities usually found in GBM, were also observed. While most reported cases of SEGA-like astrocytoma have arisen in NF1 patients, the patient was neither TSC nor NF1. Near total removal was accomplished with endoscopic cylinder surgery. At the 36-month follow-up, there was no tumor recurrence without adjuvant therapies. This clinical behavior did not match GBM. SEGA-like astrocytoma of the elderly is rare, and this is the oldest case reported so far. In addition, high-grade molecular features found in circumscribed tumor remain unclear. Further investigations among larger series are needed for clarifying the underlying molecular mechanisms.
RESUMO
Subependymal giant cell astrocytomas (SEGA) are benign cranial tumours typically found in patients with tuberous sclerosis complex (TSC). Surgical resection has been the standard treatment for SEGA, however, medical management through mTOR inhibitors has now predominantly replaced surgery as the primary treatment modality. Additionally, newer treatment modalities have emerged with the hopes of providing safer methods for treating the tumour such as laser interstitial thermal therapy (LITT). However, very few reports have addressed these newer methods and analysed the results.
Assuntos
Astrocitoma , Hipertermia Induzida , Esclerose Tuberosa , Humanos , Esclerose Tuberosa/complicações , Esclerose Tuberosa/terapia , Astrocitoma/terapia , EsperançaRESUMO
Tuberous sclerosis complex (TSC) is a monogenic disorder caused by mutations in either the TSC1 or TSC2 gene, two key regulators of the mechanistic target of the rapamycin complex pathway. Phenotypically, this leads to growth and formation of hamartomas in several organs, including the brain. Subependymal giant cell astrocytomas (SEGAs) are low-grade brain tumors commonly associated with TSC. Recently, gene expression studies provided evidence that the immune system, the MAPK pathway and extracellular matrix organization play an important role in SEGA development. However, the precise mechanisms behind the gene expression changes in SEGA are still largely unknown, providing a potential role for DNA methylation. We investigated the methylation profile of SEGAs using the Illumina Infinium HumanMethylation450 BeadChip (SEGAs n = 42, periventricular control n = 8). The SEGA methylation profile was enriched for the adaptive immune system, T cell activation, leukocyte mediated immunity, extracellular structure organization and the ERK1 & ERK2 cascade. More interestingly, we identified two subgroups in the SEGA methylation data and show that the differentially expressed genes between the two subgroups are related to the MAPK cascade and adaptive immune response. Overall, this study shows that the immune system, the MAPK pathway and extracellular matrix organization are also affected on DNA methylation level, suggesting that therapeutic intervention on DNA level could be useful for these specific pathways in SEGA. Moreover, we identified two subgroups in SEGA that seem to be driven by changes in the adaptive immune response and MAPK pathway and could potentially hold predictive information on target treatment response.
Assuntos
Astrocitoma , Esclerose Tuberosa , Humanos , Astrocitoma/metabolismo , Metilação de DNA/genética , Sirolimo/uso terapêutico , Esclerose Tuberosa/complicações , Esclerose Tuberosa/genética , Esclerose Tuberosa/patologiaRESUMO
BACKGROUND: Subependymal giant cell astrocytoma (SEGA) is occasionally seen in tuberous sclerosis complex (TSC). Two main options are currently available for treating SEGA: surgical resection or pharmacotherapy using mammalian target of rapamycin inhibitors (mTORi). We hypothesized that opportunities for surgical resection of SEGA would have reduced with the advent of mTORi. METHODS: We retrospectively reviewed the charts of patients treated between August 1979 and July 2020, divided into a pre-mTORi era group (Pre-group) of patients treated before November 2012, and a post-mTORi era group (Post-group) comprising patients treated from November 2012, when mTORi became available in Japan for SEGA. We compared groups in terms of treatment with surgery or mTORi. We also reviewed SEGA size, rate of acute hydrocephalus, recurrence of SEGA, malignant transformation and adverse effects of mTORi. RESULTS: In total, 120 patients with TSC visited our facility, including 24 patients with SEGA. Surgical resection was significantly more frequent in the Pre-group (6 of 7 patients, 86 %) than in the Post-group (2 of 17 patients, 12 %; p = 0.001). Acute hydrocephalus was seen in 1 patient (4 %), and no patients showed malignant transformation of SEGA. The group treated using mTORi showed significantly smaller SEGA compared with the group treated under a wait-and-see policy (p = 0.012). Adverse effects of pharmacotherapy were identified in seven (64 %; 6 oral ulcers, 1 irregular menstruation) of the 11 patients receiving mTORi. CONCLUSIONS: The Post-group underwent surgery significantly less often than the Pre-group. Since the treatment option to use mTORi in the treatment of SEGA in TSC became available, opportunities for surgical resection have decreased in our facility.
Assuntos
Antineoplásicos/uso terapêutico , Astrocitoma/tratamento farmacológico , Neoplasias Encefálicas/tratamento farmacológico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Esclerose Tuberosa/complicações , Adolescente , Adulto , Astrocitoma/genética , Neoplasias Encefálicas/genética , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Japão , Masculino , Estudos Retrospectivos , Adulto JovemRESUMO
Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited neurocutaneous disorder caused by inactivating mutations in TSC1 or TSC2, key regulators of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. In the CNS, TSC is characterized by cortical tubers, subependymal nodules and subependymal giant cell astrocytomas (SEGAs). SEGAs may lead to impaired circulation of CSF resulting in hydrocephalus and raised intracranial pressure in patients with TSC. Currently, surgical resection and mTORC1 inhibitors are the recommended treatment options for patients with SEGA. In the present study, high-throughput RNA-sequencing (SEGAs n = 19, periventricular control n = 8) was used in combination with computational approaches to unravel the complexity of SEGA development. We identified 9400 mRNAs and 94 microRNAs differentially expressed in SEGAs compared to control tissue. The SEGA transcriptome profile was enriched for the mitogen-activated protein kinase (MAPK) pathway, a major regulator of cell proliferation and survival. Analysis at the protein level confirmed that extracellular signal-regulated kinase (ERK) is activated in SEGAs. Subsequently, the inhibition of ERK independently of mTORC1 blockade decreased efficiently the proliferation of primary patient-derived SEGA cultures. Furthermore, we found that LAMTOR1, LAMTOR2, LAMTOR3, LAMTOR4 and LAMTOR5 were overexpressed at both gene and protein levels in SEGA compared to control tissue. Taken together LAMTOR1-5 can form a complex, known as the 'Ragulator' complex, which is known to activate both mTORC1 and MAPK/ERK pathways. Overall, this study shows that the MAPK/ERK pathway could be used as a target for treatment independent of, or in combination with mTORC1 inhibitors for TSC patients. Moreover, our study provides initial evidence of a possible link between the constitutive activated mTORC1 pathway and a secondary driver pathway of tumour growth.
Assuntos
Astrocitoma/genética , Neoplasias Encefálicas/genética , MAP Quinases Reguladas por Sinal Extracelular/genética , Sistema de Sinalização das MAP Quinases/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Esclerose Tuberosa/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Adulto , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrocitoma/etiologia , Astrocitoma/metabolismo , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/metabolismo , Butadienos/farmacologia , Criança , Pré-Escolar , Inibidores Enzimáticos/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Perfilação da Expressão Gênica , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Alvo Mecanístico do Complexo 1 de Rapamicina , Nitrilas/farmacologia , RNA-Seq , Análise de Sequência de RNA , Esclerose Tuberosa/complicações , Proteína 1 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/genética , Células Tumorais Cultivadas , Adulto JovemRESUMO
Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in TSC1 (hamartin) or TSC2 (tuberin), crucial negative regulators of the mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway. TSC affects multiple organs including the brain. The neurologic manifestation is characterized by cortical tubers, subependymal nodules (SEN), and subependymal giant cell astrocytoma (SEGA) in brain. SEGAs may result in hydrocephalus in TSC patients and mTORC1 inhibitors are the current recommended therapy for SEGA. Nevertheless, a major limitation in the research for SEGA is the lack of cell lines or animal models for mechanistic investigations and development of novel therapy. In this study, we generated TSC1-deficient neural cells from spontaneously immortalized mouse astrocytes in an attempt to mimic human SEGA. The TSC1-deficient cells exhibit mTORC1 hyperactivation and characteristics of transition from astrocytes to neural stem/progenitor cell phenotypes. Rapamycin efficiently decreased mTORC1 activity of these TSC1-deficient cells in vitro. In vivo, TSC1-deficient cells could form SEGA-like tumors and Rapamycin treatment decreased tumor growth. Collectively, our study generates a novel SEGA-like cell line that is invaluable for studying mTORC1-driven molecular and pathological alterations in neurologic tissue. These SEGA-like cells also provide opportunities for the development of novel therapeutic strategy for TSC patients with SEGA.
Assuntos
Astrocitoma/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto/métodos , Animais , Antibióticos Antineoplásicos/farmacologia , Astrócitos/metabolismo , Astrócitos/patologia , Astrocitoma/genética , Astrocitoma/patologia , Células Cultivadas , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Camundongos , Camundongos Nus , Cultura Primária de Células/métodos , Sirolimo/farmacologia , Proteína 1 do Complexo Esclerose Tuberosa/deficiência , Proteína 1 do Complexo Esclerose Tuberosa/genéticaRESUMO
The autosomal dominant disorder tuberous sclerosis complex (TSC) is characterized by an array of manifestations both within and outside of the central nervous system (CNS), including hamartomas and other malformations. TSC is caused by mutations in the TSC1 or TSC2 gene resulting in activation of the mechanistic target of rapamycin (mTOR) signaling pathway. Study of TSC has shed light on the critical role of the mTOR pathway in neurodevelopment. This update reviews the genetic basis of TSC, its cardinal phenotypic CNS features, and recent developments in the field of TSC and other mTOR-altered disorders.
Assuntos
Doenças do Sistema Nervoso Central/genética , Doenças do Sistema Nervoso Central/patologia , Esclerose Tuberosa/complicações , Esclerose Tuberosa/patologia , Predisposição Genética para Doença , HumanosRESUMO
PURPOSE: Mammalian target of rapamycin inhibitors (mTORi) are known to effectively reduce the size of subependymal giant cell astrocytomas (SEGAs), which are benign brain lesions associated with Tuberous Sclerosis Complex (TSC) that commonly cause obstructive hydrocephalus (OH). This retrospective case series reviews an institutional experience of the effect of mTORi on OH in patients with TSC-related SEGA. METHODS: Thirteen of 16 identified patients with TSC-related SEGA treated with mTORi from October 2007 to December 2018 were included. Serial magnetic resonance imaging (MRI) and clinical charts were reviewed to correlate symptoms and signs of increased intracranial pressure (iICP) with ventriculomegaly on MRI. A proposed ventriculomegaly scale was used: none (< 7 mm), mild (7-10 mm), moderate (11-30 mm), and severe (> 30 mm). OH was defined as moderate or severe ventriculomegaly, based on the largest measurement. RESULTS: Patients' median age at start of mTORi was 13 (6-17) years and five (38%) patients were female. Eight patients had OH at the time of mTORi initiation, five of whom were asymptomatic. Six patients had improvement of hydrocephalus on serial MRI imaging with mTORi therapy, while seven patients had no change based on the ventriculomegaly scale used. All three patients who presented with symptoms of iICP and had OH also had papilledema. None had worsening of hydrocephalus or required shunt placement. Out of five patients with symptoms of iICP, four avoided surgery. CONCLUSION: Most patients had asymptomatic OH at the time of diagnosis, and ventricular enlargement was not correlated with iICP symptoms. mTORi was successful for treatment of OH from TSC-related SEGA, even in the setting of acute symptoms of iICP.
Assuntos
Astrocitoma/complicações , Neoplasias Encefálicas/complicações , Hidrocefalia/complicações , Hidrocefalia/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Serina-Treonina Quinases TOR/antagonistas & inibidores , Esclerose Tuberosa/complicações , Adolescente , Criança , Feminino , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Subependymal giant cell astrocytomas (SEGA) are benign tumors characteristic of tuberous sclerosis complex (TSC) that may cause hydrocephalus. Various treatments are nowadays available as mTOR inhibitors or surgery. Surgery is still a valid option especially for symptomatic and larger tumors. METHODS: From January 1994 to December 2015, 31 TSC patients harboring SEGA underwent surgery at the Department of Neurosurgery of the Meyer Pediatric Hospital, Florence. Indications for surgery were tumor size and location, growth and cystization/hemorrhage, and hydrocephalus. Clinical data, preoperative and postoperative MRI, recurrence rate, further surgical procedures, and related complications were analyzed. RESULTS: A total of 44 surgeries were performed in 31 TSC patients affected by SEGA, achieving gross total removal (GTR) and subtotal removal (STR), respectively, in 36 and 8 patients. Recurrences occurred in 11 patients; 9 of them underwent further surgical procedures and 2 were treated with mTOR pathway inhibitors. Surgical morbidity and mortality were, respectively, 22.7% and 2.3%. After a mean follow-up of 4.9 years, 90% of patients were tumor-free with good neurological status in 93.3%; twelve (40%) had a ventriculo-peritoneal shunt (VPS) for hydrocephalus. CONCLUSIONS: The present series confirms that the surgical approach, combined with mTOR inhibitors, is still a valid option for the treatment of SEGAs.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Esclerose Tuberosa , Astrocitoma/complicações , Astrocitoma/diagnóstico por imagem , Astrocitoma/cirurgia , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Criança , Humanos , Recidiva Local de Neoplasia , Estudos Retrospectivos , Esclerose Tuberosa/complicações , Esclerose Tuberosa/diagnóstico por imagem , Esclerose Tuberosa/cirurgiaRESUMO
INTRODUCTION: The management of subependymal giant cells astrocytomas (SEGAs) has been traditionally represented by surgical treatment through an open craniotomic approach. Though open surgery still represents a major option in the management of this kind of tumors, the introduction of mTOR inhibitors in the clinical practice, technological advances in neuroendoscopy and the more recent use of laser interstitial therapy have significantly enlarged the range of available management opportunities. METHODS: A thorough review of the literature has been performed. Accordingly, current views in open surgical treatment, medical therapy, endoscopic tumor removal and new trends (such as laser interstitial thermal therapy) are discussed. RESULTS: The risk of significant neurological morbidity (5-50%) complicating open surgery has been for a long time representing a main drawback in the management of SEGAs. More recent series report a significant reduction of morbidity and mortality. The mTOR inhibitors have demonstrated efficacy in both warranting a tumor reduction by up to 60% of the tumor size and helping the control of seizures. However, the reported rate of side effects is as high as 30% and tumor recurrence is a documented occurrence at the time of mTOR inhibitor discontinuation. Endoscopic tumor removal has been more extensively considered an option due to the acquisition of new tools. Limits are still represented by tumor size (< 3 cm) and broad attachment of the tumor to the basal ganglia. Laser interstitial thermal therapy (LITT) is the more recently considered option. Though promising, only short follow-up is available so far, while data on medium- and long-term results of this treatment are completely lacking to date. CONCLUSIONS: Surgical treatment remains a mainstay of the management of SEGAs. The indication for an open craniotomic approach should be balanced with an endoscopic tumor removal or LITT according to patient conditions, presence or not of an active hydrocephalus and extension of the attachment of the tumor to the basal ganglia. The mTOR inhibitors do have a definite role both as primary and as adjuvant treatment, but consistent limitations are represented up to now by a not negligible rate of complications and the uncertainties related to the possibility of tumor recurrence once the medical treatment is discontinued.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Hidrocefalia , Esclerose Tuberosa , Astrocitoma/terapia , Humanos , Recidiva Local de Neoplasia , Esclerose Tuberosa/complicações , Esclerose Tuberosa/terapiaRESUMO
Herein, the authors describe the successful use of laser interstitial thermal therapy (LITT) for management of metastatic craniospinal disease for biopsy-proven atypical teratoid/rhabdoid tumor in a 16-month-old boy presenting to their care. Specifically, LITT was administered to lesions of the right insula and left caudate. The patient tolerated 2 stages of LITT to the aforementioned lesions without complication and with evidence of radiographic improvement of lesions at the 2- and 6-month follow-up appointments. To the authors' knowledge, this represents the first such published report of LITT for management of atypical teratoid/rhabdoid tumor.
Assuntos
Neoplasias Encefálicas/cirurgia , Terapia a Laser , Tumor Rabdoide/cirurgia , Teratoma/cirurgia , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/cirurgia , Diagnóstico Diferencial , Humanos , Lactente , Lasers , Masculino , Tumor Rabdoide/diagnóstico , Tumor Rabdoide/patologia , Teratoma/diagnósticoRESUMO
INTRODUCTION: Frailty is a transient and reversible condition that can lead to significant morbidity and mortality and to the loss of autonomy. It is one of the key issues in public health and the prevention of addiction. Physical activity is often described as a protective factor against addiction and as a factor in limiting frailty. Our goal is to analyze the relationship between physical activity and frailty among the elderly METHODS: A cross-sectional observational study was carried out in three general practice clinics located in the French department of Eure. Patients aged 65 and over were included during a consultation with their GP. Dependent patients under the ADL scale were excluded. Level of physical activity was assessed by the Ricci and Gagnon questionnaire, which defines an active profile as a score≥18 points. Frailty was sought out by the Fried scale and the SEGA A grid. Multivariate analysis was performed to adjust frailty scores to age, gender, and level of physical activity. RESULTS: Out of the 70 patients included, 36 were active (51%) and 34 inactive (49%). They were predominantly female with 47 women (67%). Average age was 75.3years. Twelve patients were diagnosed as frail (17%) with the Fried scale and 24 (34%) with the SEGA A grid. Bivariate analysis revealed a greater frailty according to the Fried criteria in the inactive than in the active patients (mean for active patients 0.56 IC95 [0.31; 0.80], compared to 1.76 [1.21; 2.32] in the inactive patients, p<0.0001). The difference in mean was likewise significant regarding the SEGA A score (6.42 IC95 [5.34, 7.49] in the active population, as opposed to 8.65 IC95 [7.15, 10.15] among the inactive, p=0.017). In multivariate analysis, the Fried scale was primarily influenced by age and ADL, while the SEGA score was impacted by female gender and level of physical activity. CONCLUSION: Physical activity seems to have a positive effect on frailty. It would be interesting to propose systematic screening for frailty in general medicine and to institute preventive measures, including physical activity. Initiatives encouraging and promoting seniors' physical activity should be strengthened.
Assuntos
Exercício Físico/fisiologia , Fragilidade/terapia , Medicina Geral/métodos , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Medicina Geral/estatística & dados numéricos , Avaliação Geriátrica/estatística & dados numéricos , Humanos , Masculino , Programas de Rastreamento/métodos , Programas de Rastreamento/estatística & dados numéricos , Estudos Prospectivos , Encaminhamento e Consulta/estatística & dados numéricosRESUMO
Tuberous sclerosis complex (TSC) is an autosomal-dominant multi system disorder. The genetic basis of the disorder is mutations in the TSC1 or TSC2 gene, which leads to over activation of the mammalian target of rapamycin (mTOR) protein complex and results in development of benign tumors in different body systems such as brain, skin, lungs and kidney. The mTOR inhibitors are presently the main treatment option for patients with TSC. We here report a 21-year female patient with large bilateral angiomyolipoma (AML) in both kidneys with longest diameter more than 12.3 cm and subependymal giant cell astrocytoma (SEGA). Treatment with everolimus (EVE) was initiated at a dose of 10.0 mg/day and continued during the following 3 years. Magnetic resonance imaging (MRI) was performed before treatment with everolimus was initiated, and consequently at 12 and 36 months for follow-up of the efficacy of the treatment. After 3 years, the total size of largest AML decreased by ~24.0% in the longest diameter. A reduction of the total size of SEGA was also observed. The most common adverse effect of treatment was stomatitis grades 3 to 4 and one febrile episode associated with skin rash that required a reduced dose of EVE. In conclusion, the everolimus treatment improved even such a large renal AML and the effect persisted during the long-term administration with a small number of adverse effects. A positive effect was observed on the brain tumor as well.
RESUMO
INTRODUCTION: Frailty is a complex concept that can be assessed with multiple instruments. Its assessment has often been implemented in hospitals. However, first-line prevention of the frailty syndrome is paramount in general medicine. The aim of the study was to test the feasibility and the concordance of two instruments for assessing frailty and to test the adequacy between the level of frailty and the presence of caregivers. METHODS: We conducted a descriptive, analytical cross-sectional study in Reims during two months. Patients included were 65 and older. Second consultations were not retained. We collected the patients' the SEGA and Fried scores as well as the opinions of the doctor and the resident student on the presence of frailty and the presence or not of home-help. RESULTS: There was an excellent concurrence between the doctor's assessment and the SEGA score (Kappa=0.89) and a moderate concurrence with the Fried score (Kappa=0.46) compared to 0.95 and 0.50 respectively for the resident student's assessment. The agreement between the assessments of the resident student and the doctor was excellent (Kappa=0.95) the concurrence between frailty and the home-helpers showed that when patients displayed frailty symptoms home-helpers were absent in 69.6% of the cases, but planned in 82.6%. CONCLUSION: To conclude, in general medicine, there is no reference score for fraily assessment, whereas the SEGA score is easy to use and reproducible. It can be used as a score of reference for patient assessment and monitoring.
Assuntos
Fragilidade/diagnóstico , Medicina Geral/normas , Avaliação Geriátrica/métodos , Geriatria/normas , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Estudos de Viabilidade , Feminino , Idoso Fragilizado/estatística & dados numéricos , Fragilidade/epidemiologia , França/epidemiologia , Medicina Geral/métodos , Medicina Geral/estatística & dados numéricos , Geriatria/métodos , Geriatria/estatística & dados numéricos , Humanos , Masculino , Padrões de ReferênciaRESUMO
OBJECTIVE Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a novel, minimally invasive treatment for the surgical treatment of epilepsy. In this paper, the authors report on clinical outcomes for a series of pediatric patients with tuberous sclerosis complex (TSC) and medication-refractory epileptogenic cortical tubers. METHODS A retrospective chart review was performed at SUNY Upstate Golisano Children's Hospital in Syracuse, New York. The authors included all cases involving pediatric patients (< 18 years) who underwent MRgLITT for ablation of epileptogenic cortical tubers between February 2013 and November 2015. RESULTS Seven patients with cortical tubers were treated (4 female and 3 male). The patients' average age was 6.6 years (range 2-17 years). Two patients had a single procedure, and 5 patients had staged procedures. The mean time between procedures in the staged cases was 6 months. All of the patients had a meaningful reduction in seizure frequency as reported by Engel and ILAE seizure outcome classifications, and most (71.4%) of the patients experienced a reduction in AED burden. Three of the 4 patients who presented with neuropsychiatric symptoms had some improvement in these domains after laser ablation. No perioperative complications were noted. The mean duration of follow-up was 19.3 months (range 4-49 months). CONCLUSIONS Laser ablation represents a minimally invasive alternative to resective epilepsy surgery and is an effective treatment for refractory epilepsy due to cortical tubers.
Assuntos
Córtex Cerebral/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Terapia a Laser/métodos , Esclerose Tuberosa/cirurgia , Adolescente , Córtex Cerebral/diagnóstico por imagem , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Feminino , Humanos , Masculino , Estudos Retrospectivos , Esclerose Tuberosa/complicações , Esclerose Tuberosa/diagnóstico por imagemRESUMO
The objective of this study was to evaluate frailty by the use of the modified SEGA grid in a population aged 75 years and older. This cross-sectional study was carried out in Marne (Champagne Ardenne), including subjects aged 75 years or more, who can go to medical general practitioners consultation. Frailty was assessed by the modified SEGA tool. In total between May 02, 2016 and May 08, 2017, 64 patients were included, aged 80 years ± 3.87, with a majority of women (58 %). The mean frailty score was 6.3 ± 3.6, with an average time of 3 minutes 55 seconds ± 1.13. The SEGAm grid had a good discriminating capacity for age (p = 0.041), comorbidities (p = 0.016), MMS (p = 0.011), presence of home helpers (p = 2.9e-05). There was also good agreement between the obtained SEGAm score and the subjective opinion of the general practitioners with a Cohen Kappa score of 0.66. The modified SEGA grid proves to be a good tool for frailty screening for the general practitioners, allowing preventive strategies and a personalized care project to be set up for each patient.
L'objectif de cette étude était d'évaluer la fragilité par la grille SEGA («Short Emergency Geriatric Assessment¼) modifiée sur une population de sujets âgés de 75 ans ou plus. Etude transversale réalisée dans la Marne (Champagne Ardenne), incluant des sujets âgés de 75 ans ou plus, pouvant se rendre en consultation. La fragilité a été évaluée par l'outil SEGA modifiée. Entre le 02 mai 2016 et le 08 mai 2017, 64 patients ont été inclus, âgés en moyenne de 80 ans ± 3,87, avec une majorité de femmes (58 %). Le score moyen de fragilité était de 6,3 ± 3,6, avec un temps moyen de réalisation de 3 minutes 55 secondes ± 1,13. La grille SEGAm avait une bonne capacité discriminante pour l'âge (p = 0,041), le niveau de comorbidités (p = 0,016), le MMS («Mini Mental State¼) (p = 0,011), la présence d'aides à domicile (p = 2,9e - 05). Il y avait également une bonne concordance entre le score SEGAm obtenu et l'avis subjectif du médecin traitant, avec un score Kappa de Cohen à 0,66. La grille SEGA modifiée se révèle être un bon outil de dépistage de la fragilité pour le médecin généraliste, permettant de mettre en place des stratégies préventives et un projet de soin personnalisé.
Assuntos
Idoso Fragilizado , Avaliação Geriátrica/métodos , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Medicina de Família e Comunidade , Feminino , França , Clínicos Gerais , Humanos , Masculino , Estudos ProspectivosRESUMO
OBJECTIVE: One of the therapeutic options for patients with tuberous sclerosis (TCS) and subependymal giant cell astrocytoma (SEGA) is everolimus treatment once daily, every day, to attain trough concentrations of 5-15 ng/ml (standard treatment). The aim of this study was to evaluate the efficacy and safety of a reduced dose of everolimus (three times a week with a daily dose as in standard treatment-maintenance therapy) in a group of patients who were previously treated with standard dose for at least 12 months. MATERIALS AND METHODS: Ten patients (six males, four females; median age 14.23 years) with TSC-related SEGA who met inclusion criteria were included into a single-arm, prospective trial. All the patients were followed over at least 12 months (median 12 and range 12-24 months). Tumor volumes from day 0, 90, 180, and 360 were evaluated by an experienced radiologist and an objective computer-based method and compared. Adverse events (AEs) noted during maintenance therapy were compared to the AEs observed during standard everolimus therapy. RESULTS: The differences in SEGA volume between subsequent time points (day 0, 90, 120, and 360) were not statistically significant. No clinical symptoms of tumor regrowth were observed. AEs were significantly less severe and less frequent during maintenance compared with standard therapy. CONCLUSIONS: Maintenance therapy with reduced-dose everolimus is an effective therapeutic option for patients with TSC and SEGA after the completion of standard therapy and may moderate the rates of adverse effects.