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2.
J Control Release ; 280: 76-86, 2018 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-29733876

RESUMO

Colorectal cancer (CRC) is one of the major causes of cancer-associated mortality worldwide. The currently approved therapeutic agents show a rather limited efficacy. We have recently demonstrated that the atypical cadherin FAT1 is a specific marker of CRC and that the FAT1-specific monoclonal antibody mAb198.3 may offer new therapeutic opportunities for CRC, being efficiently internalized by cancer cells and reducing cancer growth in colon cancer xenograft models. In this study we explored the therapeutic efficacy of mAb198.3 using two drug delivery systems (DDS) for improving the targeted treatment of CRC. The mAb198.3 was either directly bound to super-paramagnetic nanoparticles (spmNPs) or embedded into human erythrocyte-based magnetized carriers, named Erythro-Magneto-Hemagglutinin Virosomes (EMHVs) to produce two different novel mAb198.3 formulations. Both DDS were endowed with magnetic properties and were anchored in the target tumor site by means of an external permanent magnet. The antibody loading efficiency of these two magnetically driven drug delivery systems and the overall therapeutic efficacy of these two formulations were assessed both in vitro and in a proof-of-concept in vivo study. We demonstrated that mAb198.3 bound to spmNPs or embedded into EMHVs was very effective in targeting FAT1-positive colon cancer cells in vitro and accumulating in the tumor mass in vivo. Although both in vivo administered mAb198.3 formulations have approximately 200 lower antibody doses needed, these showed to achieve a relevant therapeutic effect, thus reducing cancer growth more efficiently respect to the naked antibody. These results indicate that the two proposed magnetically driven drug delivery systems have a considerable potential as platforms to improve bioavailability and pharmacodynamics of anti-FAT mAb198.3 and raise new opportunities for a targeted therapy of CRC.


Assuntos
Anticorpos Monoclonais/química , Caderinas/metabolismo , Neoplasias Colorretais/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Nanopartículas de Magnetita/química , Animais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Composição de Medicamentos/métodos , Eritrócitos/química , Humanos , Imunoterapia/métodos , Magnetismo/métodos , Camundongos Nus , Terapia de Alvo Molecular/métodos , Tamanho da Partícula , Propriedades de Superfície , Distribuição Tecidual
3.
Neuroimage Clin ; 17: 873-881, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29527492

RESUMO

Objectives: To evaluate functional connectivity (FC) in patients with sleep-related hypermotor epilepsy (SHE) compared to healthy controls. Methods: Resting state fMRI was performed in 13 patients with a clinical diagnosis of SHE (age = 38.3 ± 11.8 years, 6 M) and 13 matched healthy controls (age = 38.5 ± 10.8 years, 6 M).Data were first analysed using probabilistic independent component analysis (ICA), then a graph theoretical approach was applied to assess topological and organizational properties at the whole brain level. We evaluated node degree (ND), betweenness centrality (BC), clustering coefficient (CC), local efficiency (LE) and global efficiency (GE). The differences between the two groups were evaluated non-parametrically. Results: At the group level, we distinguished 16 RSNs (Resting State Networks). Patients showed a significantly higher FC in sensorimotor and thalamic regions (p < 0.05 corrected). Compared to controls, SHE patients showed no significant differences in network global efficiency, while ND and BC were higher in regions of the limbic system and lower in the occipital cortex, while CC and LE were higher in regions of basal ganglia and lower in limbic areas (p < 0.05 uncorrected). Discussion and conclusions: The higher FC of the sensorimotor cortex and thalamus might be in agreement with the hypothesis of a peculiar excitability of the motor cortex during thalamic K-complexes. This sensorimotor-thalamic hyperconnection might be regarded as a consequence of an alteration of the arousal regulatory system in SHE. An altered topology has been found in structures like basal ganglia and limbic system, hypothesized to be involved in the pathophysiology of the disease as suggested by the dystonic-dyskinetic features and primitive behaviours observed during the seizures.


Assuntos
Epilepsia/patologia , Epilepsia/fisiopatologia , Hipercinese/complicações , Vias Neurais/diagnóstico por imagem , Sono/fisiologia , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/fisiopatologia , Oxigênio/sangue , Estatísticas não Paramétricas , Adulto Jovem
4.
Neurol Sci ; 39(5): 851-855, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29455399

RESUMO

To study human figure drawing in a group of Alzheimer's disease (AD) patients and compare it with a group of patients with mild cognitive impairment (MCI) and controls. We evaluated consecutive outpatients over a one-year period. Patients were classified as affected by AD or by MCI. All patients and controls underwent a simplified version of the human-figure drawing test and MMSE. A qualitative and quantitative analysis of all human figures was obtained. 112 AD, 100 MCI patients and 104 controls were enrolled. AD patients drew human figures poor in details and globally smaller than MCI patients and controls. Human figures drawn by MCI patients are intermediate in body height between those of the AD patients and the healthy subjects. The head-to-body ratio of human figures drawn by AD patients is greater than controls and MCI patients, while the human figure size-relative-to-page space index is significantly smaller. Body height is an independent predictor of cognitive impairment correlating with its severity and with the number of the figure's details. Human figures drawn by AD patients are different from those drawn by healthy subjects and MCI patients. Human figure drawing test is a useful tool for orienting cognitive impairment's diagnosis.


Assuntos
Doença de Alzheimer/diagnóstico , Testes de Estado Mental e Demência , Idoso , Disfunção Cognitiva/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Modelos Lineares , Masculino , Destreza Motora , Pesquisa Qualitativa , Percepção Social , Análise e Desempenho de Tarefas
5.
Sleep ; 40(9)2017 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28934527

RESUMO

Study Objectives: To identify structural and/or metabolic alterations in patients with sleep-related hypermotor epilepsy (SHE) using magnetic resonance imaging (MRI) and proton MR spectroscopy (1H-MRS). Methods: Nineteen SHE patients (seven males; 34.7 ± 9.7 years, mean age ± standard deviation) and 17 matched healthy volunteers (seven males; 34.0 ± 8.9 years) were included in the study. In all patients, the diagnosis of SHE was confirmed by video-polysomnographic recording of seizures. Semiology, seizure frequency, and therapy were assessed for all patients. For each recruited participant, structural MRI and 1H-MRS sequences were acquired. 1H-MRS was performed on two regions of interest: the medial thalamus and the anterior cingulate gyrus. Results: At examination, five patients were seizure free. In the remainder, seizure frequency ranged from yearly to multiple episodes per night. Brain MRI was normal in all patients but one. The ratio of N-acetyl-aspartate/Creatine (NAA/Cr) was significantly reduced in the anterior cingulate cortex in patients compared to controls (p < .05). Thalamic NAA/Cr showed no differences between patients and controls. Regression analysis showed that NAA/Cr in the anterior cingulate gyrus correlated with seizure frequency (p < .05), being lower in patients with higher seizure frequency. Conclusions: Given the absence of structural MR changes, our 1H-MRS data point to a functional NAA reduction in the cingulate cortex of SHE patients, more severe in those patients with higher seizure frequency and thus supporting the involvement of the anterior mesial structures in the pathophysiology of SHE.


Assuntos
Epilepsia/metabolismo , Giro do Cíngulo/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Sono , Adulto , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Estudos de Casos e Controles , Creatina/metabolismo , Epilepsia/fisiopatologia , Feminino , Giro do Cíngulo/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Convulsões/metabolismo , Convulsões/fisiopatologia , Tálamo/metabolismo
7.
Neurology ; 88(1): 70-77, 2017 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-27881627

RESUMO

OBJECTIVE: To assess the long-term outcome of sleep-related hypermotor epilepsy (SHE). METHODS: We retrospectively reconstructed a representative cohort of patients diagnosed with SHE according to international diagnostic criteria, sleep-related seizures ≥75% and follow-up ≥5 years. Terminal remission (TR) was defined as a period of ≥5 consecutive years of seizure freedom at the last follow-up. We used Kaplan-Meier estimates to calculate the cumulative time-dependent probability of TR and to generate survival curves. Univariate and multivariate Cox regression analyses were performed. RESULTS: We included 139 patients with a 16-year median follow-up (2,414 person-years). The mean age at onset was 13 ± 10 years. SHE was sporadic in 86% of cases and familial in 14%; 16% of patients had underlying brain abnormalities. Forty-five percent of patients had at least 1 seizure in wakefulness lifetime and 55% had seizures only in sleep (typical SHE). At the last assessment, 31 patients achieved TR (TR group, 22.3%), while 108 (NTR group, 77.7%) still had seizures or had been in remission for <5 years. The cumulative TR rate was 20.4%, 23.5%, and 28.4% by 10, 20, and 30 years from inclusion. At univariate analysis, any underlying brain disorder (any combination of intellectual disability, perinatal insult, pathologic neurologic examination, and brain structural abnormalities) and seizures in wakefulness were more frequent among the NTR group (p = 0.028; p = 0.043). Absence of any underlying brain disorder (hazard ratio 4.21, 95% confidence interval 1.26-14.05, p = 0.020) and typical SHE (hazard ratio 2.76, 95% confidence interval 1.31-5.85, p = 0.008) were associated with TR. CONCLUSIONS: Our data show a poor prognosis of SHE after a long-term follow-up. Its outcome is primarily a function of the underlying etiology.


Assuntos
Epilepsia/diagnóstico , Epilepsia/epidemiologia , Avaliação de Resultados em Cuidados de Saúde , Transtornos do Sono-Vigília/complicações , Adolescente , Adulto , Encéfalo/diagnóstico por imagem , Criança , Pré-Escolar , Estudos de Coortes , Eletroencefalografia , Epilepsia/fisiopatologia , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Transtornos do Sono-Vigília/epidemiologia , Adulto Jovem
8.
Epilepsy Res ; 128: 83-93, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27816898

RESUMO

OBJECTIVE: Ring chromosome 20 syndrome is characterized by severe, drug resistant childhood onset epilepsy, often accompanied by cognitive impairment. We characterized the electro-clinical phenotype and the long-term course of epilepsy in a large series. METHODS: We reviewed the electro-clinical phenotype of 25 patients (aged 8-59 years), and assessed the relationship between epilepsy severity and clinical and/or genetic variables. We also searched for reports of patients diagnosed with r(20) syndrome in the literature, included those whose clinical information was sufficiently accurate, and compared their clinical features with the ones of our patients. RESULTS: Epilepsy exhibited an age dependent course. When seizure onset occurred in childhood (21 patients), terrifying hallucinations associated with focal motor seizures, often sleep-related (8 patients), or dyscognitive seizures (13 patients), were prominent features, often evolving into epileptic encephalopathy associated with non-convulsive status epilepticus (11 patients). In the long-term, progressive stabilization of drug resistant epilepsy associated with non-convulsive status epilepticus, focal seizures with motor and autonomic features, and eyelid myoclonia were noticed. Epilepsy onset in adolescence (3 patients) was accompanied by a milder developmental course, dyscognitive seizures and non-convulsive status epilepticus, and no cognitive decline. Only three older patients became seizure free (>5 years) We found statistically significant correlations between age at epilepsy onset and cognitive level. Although in the study cohort the relationship between r(20) ratio, age at epilepsy onset and cognitive level was non-statistically significant, it reached significance evaluating the larger cohort of patients previously published. SIGNIFICANCE: In ring(20) syndrome, epilepsy has an age dependent course and a worse outcome when age at seizure onset is earlier. The r(20) ratio and severity of cognitive impairment appear to be directly related to each other and inversely correlated with the age at epilepsy onset.


Assuntos
Epilepsia/complicações , Epilepsia/fisiopatologia , Cromossomos em Anel , Adolescente , Adulto , Fatores Etários , Anticonvulsivantes/uso terapêutico , Encéfalo/fisiopatologia , Criança , Progressão da Doença , Eletroencefalografia , Epilepsia/genética , Epilepsia/psicologia , Feminino , Seguimentos , Estudos de Associação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Retrospectivos , Índice de Gravidade de Doença , Adulto Jovem
9.
Br J Cancer ; 115(1): 40-51, 2016 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-27328312

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the major causes of cancer-associated mortality worldwide. The currently approved therapeutic agents have limited efficacy. METHODS: The atypical cadherin FAT1 was discovered as a novel CRC-associated protein by using a monoclonal antibody (mAb198.3). FAT1 expression was assessed in CRC cells by immunohistochemistry (IHC), immunoblots, flow cytometry and confocal microscopy. In addition, in vitro and in vivo tumour models were done to assess FAT1 potential value for therapeutic applications. RESULTS: The study shows that FAT1 is broadly expressed in primary and metastatic CRC stages and detected by mAb198.3, regardless of KRAS and BRAF mutations. FAT1 mainly accumulates at the plasma membrane of cancer cells, whereas it is only marginally detected in normal human samples. Moreover, the study shows that FAT1 has an important role in cell invasiveness while it does not significantly influence apoptosis. mAb198.3 specifically recognises FAT1 on the surface of colon cancer cells and is efficiently internalised. Furthermore, it reduces cancer growth in a colon cancer xenograft model. CONCLUSIONS: This study provides evidence that FAT1 and mAb198.3 may offer new therapeutic opportunities for CRC including the tumours resistant to current EGFR-targeted therapies.


Assuntos
Anticorpos Monoclonais/farmacologia , Caderinas/metabolismo , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Células HT29 , Humanos , Mutação/efeitos dos fármacos , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas ras/metabolismo
10.
Neurology ; 86(19): 1834-42, 2016 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-27164717

RESUMO

The syndrome known as nocturnal frontal lobe epilepsy is recognized worldwide and has been studied in a wide range of clinical and scientific settings (epilepsy, sleep medicine, neurosurgery, pediatric neurology, epidemiology, genetics). Though uncommon, it is of considerable interest to practicing neurologists because of complexity in differential diagnosis from more common, benign sleep disorders such as parasomnias, or other disorders like psychogenic nonepileptic seizures. Moreover, misdiagnosis can have substantial adverse consequences on patients' lives. At present, there is no consensus definition of this disorder and disagreement persists about its core electroclinical features and the spectrum of etiologies involved. To improve the definition of the disorder and establish diagnostic criteria with levels of certainty, a consensus conference using formal recommended methodology was held in Bologna in September 2014. It was recommended that the name be changed to sleep-related hypermotor epilepsy (SHE), reflecting evidence that the attacks are associated with sleep rather than time of day, the seizures may arise from extrafrontal sites, and the motor aspects of the seizures are characteristic. The etiology may be genetic or due to structural pathology, but in most cases remains unknown. Diagnostic criteria were developed with 3 levels of certainty: witnessed (possible) SHE, video-documented (clinical) SHE, and video-EEG-documented (confirmed) SHE. The main research gaps involve epidemiology, pathophysiology, treatment, and prognosis.


Assuntos
Epilepsia/diagnóstico , Encéfalo/fisiopatologia , Eletroencefalografia , Epilepsia/etiologia , Epilepsia/genética , Epilepsia/fisiopatologia , Humanos , Terminologia como Assunto , Gravação em Vídeo
11.
Pharmacoepidemiol Drug Saf ; 25(7): 763-9, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-26887800

RESUMO

BACKGROUND: Antiepileptic drugs (AEDs) are also prescribed for therapeutic indications other than epilepsy (EPI), namely, psychiatric disorders (PSY). Our aim was to develop an algorithm able to distinguish between EPI and PSY among childbearing age women based on differences in AED exposure in these patient groups. METHODS: Two groups of women (18-45 years) with EPI or PSY treated with AEDs in the first semester of 2010 or 2011 were extracted from paper or electronic medical charts of specialized centers. Through the prescription database of Bologna Local Health Authority (Italy), AEDs, treatment schedule and co-treatments were collected for each patient. A prescription-based hierarchical classification system was developed. The algorithm obtained was subsequently validated on internal and external data. RESULTS: Eighty-one EPI and 94 PSY subjects were recruited. AED monotherapy was the most common choice in both groups (69% EPI vs 79% PSY). Some AEDs were used only in EPI, others exclusively in PSY. Co-treatments with antipsychotics (6% vs 67%), lithium (0% vs 9%), and antidepressants (7% vs 70%) were fewer in EPI than in PSY. The hierarchical classification system identified antipsychotics, SSRIs (Selective Serotonin Reuptake Inhibitors), and number of AEDs as variables to discriminate EPI and PSY, with an overall error rate estimate of 9.7% (95%CI: 5.3% to 14.1%). CONCLUSION: Among the differences between EPI and PSY, prescription data alone allowed an algorithm to be developed to diagnose each childbearing age woman receiving AEDs. This approach will be useful to stratify patients for risk estimates of AED-treated patients based on administrative databases. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsia/tratamento farmacológico , Transtornos Mentais/tratamento farmacológico , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Adulto , Algoritmos , Anticonvulsivantes/uso terapêutico , Antidepressivos/administração & dosagem , Antipsicóticos/administração & dosagem , Bases de Dados Factuais , Feminino , Humanos , Itália , Compostos de Lítio/administração & dosagem , Pessoa de Meia-Idade , Adulto Jovem
12.
J Clin Neurosci ; 22(8): 1250-3, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25937573

RESUMO

The aim of this study was to verify the presence of BRAF mutations in a series of six patients affected by drug-resistant focal epilepsy associated with neocortical posterior temporal gangliogliomas (GG) who were subjected to lesionectomy between June 2008 and November 2013. GG are an increasingly recognized cause of epilepsy and represent the most common tumor in young patients undergoing surgery for intractable focal epilepsy. BRAF mutations have been identified in up to 50% of GG. Interestingly, these six patients shared a specific anatomical posterior temporal site. In all patients, histological examination confirmed the diagnosis of GG, and two were also associated with a focal cortical dysplasia (FCD) type IIa. BRAF mutations were found in four out of six GG (66.6%). Furthermore, dysplastic tissue of Patient 2 showed a concomitant BRAF V600E mutation. All patients but one (83.3%) achieved Engel Class Ia seizure control. The patient carrying a concomitant BRAF mutation in GG and FCD fell into Engel Class II. Further analyses will be required in order to better understand the meaning of BRAF mutations in epilepsy-associated tumors and FCD and their possible role as a prognostic seizure outcome and tumor behavior marker.


Assuntos
Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/genética , Epilepsia Resistente a Medicamentos/etiologia , Epilepsia Resistente a Medicamentos/genética , Epilepsia do Lobo Temporal/etiologia , Epilepsia do Lobo Temporal/genética , Ganglioglioma/complicações , Ganglioglioma/genética , Mutação/genética , Neocórtex/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Adolescente , Adulto , Idade de Início , Neoplasias Encefálicas/cirurgia , Criança , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia/genética , Epilepsia/patologia , Epilepsia do Lobo Temporal/cirurgia , Feminino , Ganglioglioma/cirurgia , Humanos , Masculino , Malformações do Desenvolvimento Cortical do Grupo I/genética , Malformações do Desenvolvimento Cortical do Grupo I/patologia , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos , Prognóstico , Estudos Retrospectivos , Convulsões/genética , Convulsões/cirurgia , Resultado do Tratamento , Adulto Jovem
13.
Epilepsy Behav ; 45: 212-6, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25812941

RESUMO

OBJECTIVE: Focal cortical dysplasias (FCDs) represent a common architectural cortical disorder underlying pharmacoresistant focal epilepsy. The recent ILAE classification defines different types of FCDs based on their histopathological features, MRI imaging, and presumed pathogenesis; however, their clinical features and their prognostic significance are still incompletely defined. In addition, the combination of different histopathological abnormalities can represent "unusual" subtypes that can be difficult to classify. The aim of our study was to analyze the incidence and the significance of these "unusual" subtypes of FCDs in drug-resistant mesial temporal lobe epilepsy (MTLE). METHODS: We retrospectively analyzed 133 patients consecutively submitted to tailored anteromesial temporal lobe resection for pharmacoresistant MTLE. Seizure onset, seizure duration, age at surgery, and postoperative seizure outcome were evaluated in relation to the different neuropathological groups defined according to the new ILAE classification. RESULTS: Focal cortical dysplasias were found in 80 out of 133 patients. Six patients were affected by isolated FCD type I, 12 patients by FCD type II, and 44 patients by FCD type III. Furthermore, we found 18 "atypical" cases (20.5% of all FCD cases and 26.6% of FCDs associated with a principal lesion): 10 cases of associated FCD type II-hippocampal sclerosis (HS) and 8 cases associated with FCD II-epilepsy-associated tumors (EATs). CONCLUSION: Our results indicate that "unusual" subtypes of FCDs, in particular associated FCD type II, are not uncommon findings, suggesting that they deserve a classification recognition. Similarities in seizure outcome and immunohistochemical and molecular evidences, shared by FCD type II+EATs and EATs, suggest a common pathogenic link. The choice to create a specific unifying class or, on the contrary, to also include "associated FCD type II" in the definition of the new unifying class FCD type III should be further discussed.


Assuntos
Epilepsia do Lobo Temporal/classificação , Epilepsia do Lobo Temporal/cirurgia , Internacionalidade , Malformações do Desenvolvimento Cortical/classificação , Malformações do Desenvolvimento Cortical/cirurgia , Adolescente , Adulto , Epilepsia do Lobo Temporal/diagnóstico , Feminino , Humanos , Masculino , Malformações do Desenvolvimento Cortical/diagnóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
14.
Sleep ; 38(3): 479-85, 2015 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-25406112

RESUMO

STUDY OBJECTIVES: To estimate the prevalence of nocturnal frontal lobe epilepsy (NFLE) in the adults of two areas of the Emilia-Romagna region (northeast Italy) and to describe the clinical features from a population-based perspective. DESIGN: Population-based retrospective cohort study including adults with NFLE. SETTING: Two areas of the Emilia-Romagna region: the city of Bologna (330,901 adult residents) and five districts of the province of Modena (424,007). Prevalence day: December 31, 2010. PARTICIPANTS: Patients with NFLE collected from multiple databases of neurologic hub centers of the districts involved. Diagnostic criteria: clinical history of sleep related bizarre motor attacks and videopolysomnographic recording confirming the typical features of NFLE. Inclusion criteria for prevalence calculation: residence in one of the two geographic areas on the prevalence day and an "active" or "in remission with treatment" form of NFLE. MEASUREMENTS AND RESULTS: Six subjects from Bologna and eight from Modena were included. Crude prevalence (per 100,000 residents) was 1.8 (95% confidence interval 0.7-4.0) in Bologna and 1.9 (0.8-3.7) in Modena. Similarly, the main clinical features were consistent: onset during adolescence (median age 11-13 y), mainly hyperkinetic seizures, nonlesional form in more than two-thirds of cases, an active form of epilepsy in more than two-thirds of cases. A family history of epilepsy was reported only for two patients. CONCLUSIONS: This epidemiologic study establishes that NFLE is a rare epileptic condition, fulfilling the definition for rare disease. Because of methodological limitations of our case ascertainment, the estimates we disclose must be considered the minimum prevalence.


Assuntos
Epilepsia do Lobo Frontal/epidemiologia , Adolescente , Adulto , Idade de Início , Estudos de Coortes , Epilepsia do Lobo Frontal/complicações , Feminino , Humanos , Itália/epidemiologia , Masculino , Prevalência , Doenças Raras/complicações , Doenças Raras/epidemiologia , Estudos Retrospectivos , Convulsões/complicações , Convulsões/epidemiologia , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/epidemiologia
15.
World J Clin Cases ; 2(11): 623-41, 2014 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-25405186

RESUMO

Long-term epilepsy associated tumors (LEAT) represent a well known cause of focal epilepsies. Glioneuronal tumors are the most frequent histological type consisting of a mixture of glial and neuronal elements and most commonly arising in the temporal lobe. Cortical dysplasia or other neuronal migration abnormalities often coexist. Epilepsy associated with LEAT is generally poorly controlled by antiepileptic drugs while, on the other hand, it is high responsive to surgical treatment. However the best management strategy of tumor-related focal epilepsies remains controversial representing a contemporary issues in epilepsy surgery. Temporo-mesial LEAT have a widespread epileptic network with complex epileptogenic mechanisms. By using an epilepsy surgery oriented strategy LEAT may have an excellent seizure outcome therefore surgical treatment should be offered early, irrespective of pharmacoresistance, avoiding both the consequences of uncontrolled seizures as well as the side effects of prolonged pharmacological therapy and the rare risk of malignant transformation.

16.
Epileptic Disord ; 16(3): 362-5, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25036107

RESUMO

The association between hereditary myotonic disorders and epilepsy is seldom described in the literature. To date, few reports have dealt with dystrophic myotonias, whereas a single case demonstrating an association between sporadic congenital myotonia and epilepsy was recently reported in a patient carrying a de novo mutation of the CLCN1 gene. Additional evidence for a role of CLCN1 in the pathogenesis of epilepsy is derived from large-scale exome analysis of ion channel variants and expression studies. Here, we describe the first case of association between familial Thomsen myotonia and epilepsy. All the affected members of a two-generation family presented myotonia and disclosed a pathogenic mutation in CLCN1. In addition, one individual experienced epileptic seizures due to limbic encephalitis (LE) with anti-GAD antibodies. The occurrence of the two diseases in this patient could be a chance association, however, CLCN1 mutation, as a susceptibility factor for epilepsy through dysfunction of GABAA inhibitory signalling, cannot be ruled out as a possible influence.


Assuntos
Glutamato Descarboxilase/imunologia , Encefalite Límbica/imunologia , Miotonia Congênita/imunologia , Adolescente , Canais de Cloreto/genética , Glutamato Descarboxilase/genética , Humanos , Encefalite Límbica/complicações , Encefalite Límbica/genética , Masculino , Mutação , Miotonia Congênita/complicações , Miotonia Congênita/genética , Linhagem
17.
PLoS One ; 9(5): e98101, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24851905

RESUMO

Epigenetic events are critical contributors to the pathogenesis of cancer, and targeting epigenetic mechanisms represents a novel strategy in anticancer therapy. Classic demethylating agents, such as 5-Aza-2'-deoxycytidine (Decitabine), hold the potential for reprograming somatic cancer cells demonstrating high therapeutic efficacy in haematological malignancies. On the other hand, epigenetic treatment of solid tumours often gives rise to undesired cytotoxic side effects. Appropriate delivery systems able to enrich Decitabine at the site of action and improve its bioavailability would reduce the incidence of toxicity on healthy tissues. In this work we provide preclinical evidences of a safe, versatile and efficient targeted epigenetic therapy to treat hormone sensitive (LNCap) and hormone refractory (DU145) prostate cancers. A novel Decitabine formulation, based on the use of engineered erythrocyte (Erythro-Magneto-Hemagglutinin Virosomes, EMHVs) drug delivery system (DDS) carrying this drug, has been refined. Inside the EMHVs, the drug was shielded from the environment and phosphorylated in its active form. The novel magnetic EMHV DDS, endowed with fusogenic protein, improved the stability of the carried drug and exhibited a high efficiency in confining its delivery at the site of action in vivo by applying an external static magnetic field. Here we show that Decitabine loaded into EMHVs induces a significant tumour mass reduction in prostate cancer xenograft models at a concentration, which is seven hundred times lower than the therapeutic dose, suggesting an improved pharmacokinetics/pharmacodynamics of drug. These results are relevant for and discussed in light of developing personalised autologous therapies and innovative clinical approach for the treatment of solid tumours.


Assuntos
Epigênese Genética , Neoplasias da Próstata/tratamento farmacológico , Animais , Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/análogos & derivados , Azacitidina/uso terapêutico , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Decitabina , Humanos , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias da Próstata/genética
18.
Epilepsia ; 55(6): 841-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24579982

RESUMO

OBJECTIVE: To clinically and genetically characterize a large Brazilian family with autosomal dominant partial epilepsy with auditory features (ADPEAF) not related to leucine-rich, glioma-inactivated 1 (LGI1) gene. METHODS: Seventy family members (four married-ins) participating in the study were assessed by a detailed clinical interview and a complete neurologic examination. Genetic mapping was conducted through autosome-wide single nucleotide polymorphism (SNP) genotyping and subsequent linkage analysis on 16 and haplotype analysis on 25 subjects, respectively. RESULTS: The pedigree comprised 15 affected members, of whom 11 were included in the study (male/female: 6/5; mean age 39.5 years). All but two (III:22 and IV:92) had focal seizures with auditory aura followed by secondary generalization in 44.4%. The mean age at onset of epilepsy seizures was 13.7 years. Initial autosome-wide SNP linkage analysis conducted on 12 subjects (8 affected) pointed to a single genomic region on chromosome 19 with a maximum multipoint logarithm of the odds (LOD) score of 2.60. Further refinement of this region through SNP and microsatellite genotyping on 16 subjects (11 affected) increased the LOD score to 3.41, thereby establishing 19q13.11-q13.31 as a novel ADPEAF locus. Haplotype analysis indicated that the underlying mutation is most likely located in a 9.74 Mb interval between markers D19S416 and D19S420. Sequence analysis of the most prominent candidate genes within this critical interval (SCN1B, LGI4, KCNK6, and LRFN1) did not reveal any mutation. SIGNIFICANCE: This study disclosed a novel ADPEAF locus on chromosome 19q13.11-q13.31, contributing to future identification of a second dominant gene for this epileptic syndrome. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.


Assuntos
Cromossomos Humanos Par 19/genética , Epilepsia do Lobo Frontal/genética , Transtornos do Sono-Vigília/genética , Adolescente , Adulto , Mapeamento Cromossômico , Feminino , Ligação Genética/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Haplótipos/genética , Humanos , Escore Lod , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Adulto Jovem
19.
Epilepsia ; 54(7): 1298-306, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23663087

RESUMO

PURPOSE: We describe the clinical, neurophysiologic, and genetic features of a new, large family with familial cortical myoclonic tremor and epilepsy (FCMTE). METHODS: Reliable clinical information was obtained on the 127 members. Thirty-one collaborative individuals were assessed by a detailed clinical interview and a complete neurologic examination. A polygraphic study was conducted in 15 patients, back-averaging analysis and somatosensory evoked potentials with C-reflex study in four. The genetic study investigated 30 subjects with microsatellite markers at three loci on chromosomes 8q (FCMTE1), 2p (FCMTE2), and 5p (FCMTE3). KEY FINDINGS: The pedigree included 25 affected members (M/F: 9/16). We studied 16 of the 19 living affected members (M/F: 5/11; mean age 47.8 years). Cortical myoclonic tremor (CMT) was associated with generalized seizures in 10 patients (62.5%). The mean age at onset of CMT and seizures was 28.1 and 33.8 years, respectively. Four patients (25%) reported a slow progression of CMT, with severe gait impairment in one. Psychiatric disorders of variable severity recurred in 37.5% of cases. Rhythmic bursts at 7-15 Hz were recorded in all 11 affected members tested. Additional neurophysiologic investigations disclosed a cortical origin of myoclonus in all patients tested. Generalized epileptiform discharges were recorded in 25% of cases, and a photoparoxysmal response in 31%. Genetic analysis established linkage to the FCMTE2 locus on chromosome 2p11.1-2q12.2 (OMIM 607876) and narrowed the critical interval to a 10.4 Mb segment. Haplotype analysis in the present family identified a founder haplotype identical to that previously observed in families from the same geographic area. SIGNIFICANCE: This study confirms evidence of a founder effect in Italian families and reduces the number of positional candidate genes in the FCMTE2 locus to 59, thereby contributing to future gene identification by Next Generation Sequencing approaches.


Assuntos
Cromossomos Humanos Par 2/genética , Epilepsias Mioclônicas/genética , Linhagem , Adulto , Mapeamento Cromossômico , Cromossomos Humanos Par 5/genética , Eletroencefalografia , Eletromiografia , Epilepsias Mioclônicas/complicações , Potenciais Somatossensoriais Evocados/genética , Feminino , Marcha Atáxica/etiologia , Ligação Genética , Haplótipos/genética , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
20.
Epilepsy Behav ; 26(1): 114-7, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23246147

RESUMO

The beneficial effect of nicotine has been reported in autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) patients, but not tested in sporadic cases. Recently, a nicotine defect in the arousal pathway has been hypothesized even in sporadic NFLE patients and their relatives. This case-control family study was designed to test whether NFLE subjects were more likely to use tobacco than controls, as an indirect marker of cholinergic arousal system dysregulation. At least four relatives were included for each NFLE proband and control. Each subject was questioned about tobacco habits; 434 individuals were recruited. Moreover, we compared NFLE patients with age- and sex-matched controls to determine whether they are more likely to use tobacco. We found a slightly higher trend of tobacco use in NFLE probands compared to that in control subjects; we did not find any significant difference in the distribution of tobacco use among NFLE group compared to that in the control group.


Assuntos
Epilepsia do Lobo Frontal/epidemiologia , Epilepsia do Lobo Frontal/psicologia , Hábitos , Tabagismo/epidemiologia , Adulto , Idoso , Estudos de Casos e Controles , Eletroencefalografia , Epilepsia do Lobo Frontal/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Polissonografia , Receptores Nicotínicos/genética , Estudos Retrospectivos , Tabagismo/psicologia , Gravação em Vídeo , Adulto Jovem
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