Luciano Neder Serafini

Seizure outcome after surgery for epilepsy due to focal cortical dysplastic lesions

Neocortical development is a highly complex process encompassing cellular proliferation, neuronal migration and cortical organization. At any time this process can be interrupted or modified by genetic or acquired factors causing malformations of cortical development (MCD). Epileptic seizures are the most common type of clinical manifestation, besides developmental delay and focal neurological deficits. Seizures due to MCD are frequently pharmacoresistant, especially those associated to focal cortical dysplasia (FCD). Surgical therapy results have been reported since 1971, however, currently available data from surgical series are still limited, mainly due to small number of patients, distinct selection of candidates and surgical strategies, variable pathological diagnosis and inadequate follow-up. This study addresses the possibilities of seizure relief following resection of focal cortical dysplasia, and the impact of presurgical evaluation, extent of resection and pathological findings on surgical outcome. We included 41 patients, 22 adults and 19 children and adolescents, with medically intractable seizures operated on from 1996 to 2002. All were submitted to standardized presurgical evaluation including high-resolution MRI, Video-EEG monitoring and ictal SPECT. Post-surgical seizure outcome was classified according to Engels schema. Univariate and multivariate analysis were performed. Fifteen patients had temporal and 26 extratemporal epilepsies. Of the total 26 patients (63.4%) reached seizure-free status post-operatively. There was no correlation between outcome and age at surgery, duration of epilepsy, frequency of seizures, and pathological findings. There was, however, a clear correlation with topography of FCD (temporal versus extratemporal) and regional ictal EEG onset, on univariate as well as multivariate analysis.

Clinical features of patients with posterior cortex epilepsies and predictors of surgical outcome

Summary:  Purpose: Posterior cortex epilepsies (PCEs) encompass a group of epilepsies originating from the occipital, parietal, or occipital border of the temporal lobe, or from any combination of these regions. When their seizures are refractory to pharmacologic treatment, these patients are usually referred for surgery. The aim of our study was to analyze clinical characteristics of all PCE patients referred for surgery from 1994 to 2003, and to search for predictors of surgical outcome.

Surgical outcome in mesial temporal sclerosis correlates with prion protein gene variant.

Background: Mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) is the most common surgically remediable epileptic syndrome. Ablation of the cellular prion protein (PrPc) gene (PRNP) enhances neuronal excitability of the hippocampus in vitro and sensitivity to seizure in vivo, indicating that PrPc might be related to epilepsy. Objective: To evaluate the genetic contribution of PRNP to MTLE-HS. Methods: The PRNP coding sequence of DNA from peripheral blood cells of 100 consecutive patients with surgically treated MTLE-HS was compared to that from a group of healthy controls adjusted for sex, age, and ethnicity (n = 180). The presence of PRNP variant alleles was correlated with clinical and presurgical parameters as well as surgical outcome. Results: A variant allele at position 171 (Asn→Ser), absent in controls, was found in heterozygosis (Asn171Ser) in 23% of patients (p < 0.0001). The PRNP genotypes were not correlated with any clinical or presurgical data investigated. However, patients carrying the Asn171Ser variant had a five times higher chance of continuing to have seizures after temporal lobectomy (95% CI 1.65 to 17.33, p = 0.005) than those carrying the normal allele. At 18 months after surgery, 91.8% of patients with the normal allele at codon 171 were seizure free, in comparison to 68.2% of those carrying Asn171Ser (p = 0.005). Conclusions: The PRNP variant allele Asn171Ser is highly prevalent in patients with medically untreatable MTLE-HS and influences their surgical outcome. The results suggest that the PRNP variant allele at codon 171 (Asn171Ser) is associated with epileptogenesis in MTLE-HS.

Estudo epidemiológico sobre Leishmaniose tegumentar (LT) no município de Corguinho, Mato Grosso do Sul: estudos na população humana

A study on the resident population of 150 inhabitants of Boa Sorte in the Municipality of Corguinho, Mato Grosso do Sul State, Brazil was made, from March 1991 to March 1994, to establish the prevalence of South American Cutaneous Leishmaniasis (SACL), and to characterize the affected population, in an area of recent transmission. Twelve of the inhabitants showed lesions suspected to be SACL, and in 8 cases it was possible to confirm this by biopsy and parasitology. The mucosal form was found in one patient only, the rest showed the following cutaneous forms: ulcerated (3), ulcero-verrucose (1), hyperkeratotic ulcer (1), infiltrated maccule (1), nodule with florid regional adenopathy (1). All patients reacted favorably to treatment with glucantime, with lesion scarring. Side-effects were rare. The parasite isolated from all patients was identified as Leishmania (Viannia) braziliensis. The Montenegro skin test, applied to the 150 inhabitants, showed 32 reactive ones. Of these, six were carriers of the disease, 21 showed sequelae suggestive of the disease and five showed no signs of infection. The age grouping of the cohort ranged from 22 to 78 years, 75% being male. To date, transmission is suspected to be in the peridomicile.

Co-loaded paclitaxel/rapamycin liposomes: Development, characterization and in vitro and in vivo evaluation for breast cancer therapy

Paclitaxel and rapamycin have been reported to act synergistically to treat breast cancer. Albeit paclitaxel is available for breast cancer treatment, the most commonly used formulation in the clinic presents side effects, limiting its use. Furthermore, both drugs present pharmacokinetics drawbacks limiting their in vivo efficacy and clinic combination. As an alternative, drug delivery systems, particularly liposomes, emerge as an option for drug combination, able to simultaneously deliver co-loaded drugs with improved therapeutic index. Therefore, the purpose of this study is to develop and characterize a co-loaded paclitaxel and rapamycin liposome and evaluate it for breast cancer efficacy both in vitro and in vivo. Results showed that a SPC/Chol/DSPE-PEG (2000) liposome was able to co-encapsulate paclitaxel and rapamycin with suitable encapsulation efficiency values, nanometric particle size, low polydispersity and neutral zeta potential. Taken together, FTIR and thermal analysis evidenced drug conversion to the more bioavailable molecular and amorphous forms, respectively, for paclitaxel and rapamycin. The pegylated liposome exhibited excellent colloidal stability and was able to retain drugs encapsulated, which were released in a slow and sustained fashion. Liposomes were more cytotoxic to 4T1 breast cancer cell line than the free drugs and drugs acted synergistically, particularly when co-loaded. Finally, in vivo therapeutic evaluation carried out in 4T1-tumor-bearing mice confirmed the in vitro results. The co-loaded paclitaxel/rapamycin pegylated liposome better controlled tumor growth compared to the solution. Therefore, we expect that the formulation developed herein might be a contribution for future studies focusing on the clinical combination of paclitaxel and rapamycin.

Components of the Canonical and Non-Canonical Wnt Pathways Are Not Mis-Expressed in Pituitary Tumors

Introduction Canonical and non-canonical Wnt pathways are involved in the genesis of multiple tumors; however, their role in pituitary tumorigenesis is mostly unknown. Objective This study evaluated gene and protein expression of Wnt pathways in pituitary tumors and whether these expression correlate to clinical outcome. Materials and Methods Genes of the Wnt canonical pathway: activating ligands (WNT11, WNT4, WNT5A), binding inhibitors (DKK3, sFRP1), β-catenin (CTNNB1), β-catenin degradation complex (APC, AXIN1, GSK3β), inhibitor of β-catenin degradation complex (AKT1), sequester of β-catenin (CDH1), pathway effectors (TCF7, MAPK8, NFAT5), pathway mediators (DVL-1, DVL-2, DVL-3, PRICKLE, VANGL1), target genes (MYB, MYC, WISP2, SPRY1, TP53, CCND1); calcium dependent pathway (PLCB1, CAMK2A, PRKCA, CHP); and planar cell polarity pathway (PTK7, DAAM1, RHOA) were evaluated by QPCR, in 19 GH-, 18 ACTH-secreting, 21 non-secreting (NS) pituitary tumors, and 5 normal pituitaries. Also, the main effectors of canonical (β-catenin), planar cell polarity (JNK), and calcium dependent (NFAT5) Wnt pathways were evaluated by immunohistochemistry. Results There are no differences in gene expression of canonical and non-canonical Wnt pathways between all studied subtypes of pituitary tumors and normal pituitaries, except for WISP2, which was over-expressed in ACTH-secreting tumors compared to normal pituitaries (4.8x; p = 0.02), NS pituitary tumors (7.7x; p = 0.004) and GH-secreting tumors (5.0x; p = 0.05). β-catenin, NFAT5 and JNK proteins showed no expression in normal pituitaries and in any of the pituitary tumor subtypes. Furthermore, no association of the studied gene or protein expression was observed with tumor size, recurrence, and progressive disease. The hierarchical clustering showed a regular pattern of genes of the canonical and non-canonical Wnt pathways randomly distributed throughout the dendrogram. Conclusions Our data reinforce previous reports suggesting no activation of canonical Wnt pathway in pituitary tumorigenesis. Moreover, we describe, for the first time, evidence that non-canonical Wnt pathways are also not mis-expressed in the pituitary tumors.

Increased Metallothionein I/II Expression in Patients with Temporal Lobe Epilepsy

In the central nervous system, zinc is released along with glutamate during neurotransmission and, in excess, can promote neuronal death. Experimental studies have shown that metallothioneins I/II (MT-I/II), which chelate free zinc, can affect seizures and reduce neuronal death after status epilepticus. Our aim was to evaluate the expression of MT-I/II in the hippocampus of patients with temporal lobe epilepsy (TLE). Hippocampi from patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) and patients with TLE associated with tumor or dysplasia (TLE-TD) were evaluated for expression of MT-I/II, for the vesicular zinc levels, and for neuronal, astroglial, and microglial populations. Compared to control cases, MTLE group displayed widespread increase in MT-I/II expression, astrogliosis, microgliosis and reduced neuronal population. In TLE-TD, the same changes were observed, except that were mainly confined to fascia dentata. Increased vesicular zinc was observed only in the inner molecular layer of MTLE patients, when compared to control cases. Correlation and linear regression analyses indicated an association between increased MT-I/II and increased astrogliosis in TLE. MT-I/II levels did not correlate with any clinical variables, but MTLE patients with secondary generalized seizures (SGS) had less MT-I/II than MTLE patients without SGS. In conclusion, MT-I/II expression was increased in hippocampi from TLE patients and our data suggest that it is associated with astrogliosis and may be associated with different seizure spread patterns.

Expression of cancer-testis antigens MAGE-A4 and MAGE-C1 in oral squamous cell carcinoma.

Tumor markers are genes or their products expressed exclusively or preferentially in tumor cells and cancer‐testis antigens (CTAs) form a group of genes with a typical expression pattern expressed in a variety of malignant neoplasms. CTAs are considered potential targets for cancer vaccines. It is possible that the CTA MAGE‐A4 (melanoma antigen) and MAGE‐C1 are expressed in carcinoma of the oral cavity and are related with survival.

Toxoplasmose do sistema nervoso central em paciente sem evidência de imunossupressão: relato de caso

O quadro clinico da toxoplasmose adquirida em pacientes imunocompetentes habitualmente nao inclui manifestacoes neurologicas focais, o que e frequente em pacientes imunodeprimidos, como aqueles com sindrome da imunodeficiencia adquirida. Este trabalho tem como objetivo relatar o caso de uma paciente adulta que apresentou abscessos cerebrais por Toxoplasma gondii, sem evidencia de qualquer fator causador de imunossupressao.The clinical manifestations of acquired toxoplasmosis in the immunocompetent patient rarely include localized neurological signs, which are frequent in the immunosuppressed patient (Aids). The objective of this paper is to report the case of a woman with Toxoplasma gondii brain abscess, without an identified cause of immunosuppression.

Histologic Study of an Autologous Fat Graft in the Larynx of Dogs With Unilateral Vocal Fold Paralysis

Objective: To determine the histologic finds of autologous fat graft (AFG) in 24 paralyzed canine left vocal folds 12 weeks after introduction.