microRNAs and thyroid cancer: biological and clinical significance (Review).

Despite recent advances in the management of thyroid cancer, the survival rate of this tumor may still be improved. Therefore, the identification of biological and molecular features of indolent and aggressive disease would be critical to define clinically useful predictors of high-risk lesions. microRNAs (miRNAs) are small RNA molecules with regulatory function and marked tissue specificity that modulate multiple targets belonging to several pathways. They are frequently deregulated in cancer and constitute a new class of blood-based biomarkers useful for cancer detection and prognosis definition, including thyroid cancer. In this review, the role of miRNAs in thyroid cancer development is described. The most common miRNAs detected in thyroid cancer along with their clinical significance are also discussed. Further studies aimed to detect plasma-based miRNA biomarkers in thyroid cancer patients may provide further insight into the management of thyroid cancer.

Stop-event-related potentials from intracranial electrodes reveal a key role of premotor and motor cortices in stopping ongoing movements.

In humans, the ability to withhold manual motor responses seems to rely on a right-lateralized frontal-basal ganglia-thalamic network, including the pre-supplementary motor area and the inferior frontal gyrus (IFG). These areas should drive subthalamic nuclei to implement movement inhibition via the hyperdirect pathway. The output of this network is expected to influence those cortical areas underlying limb movement preparation and initiation, i.e., premotor (PMA) and primary motor (M1) cortices. Electroencephalographic (EEG) studies have shown an enhancement of the N200/P300 complex in the event-related potentials (ERPs) when a planned reaching movement is successfully stopped after the presentation of an infrequent stop-signal. PMA and M1 have been suggested as possible neural sources of this ERP complex but, due to the limited spatial resolution of scalp EEG, it is not yet clear which cortical areas contribute to its generation. To elucidate the role of motor cortices, we recorded epicortical ERPs from the lateral surface of the fronto-temporal lobes of five pharmacoresistant epileptic patients performing a reaching version of the countermanding task while undergoing presurgical monitoring. We consistently found a stereotyped ERP complex on a single-trial level when a movement was successfully cancelled. These ERPs were selectively expressed in M1, PMA, and Brodmann's area (BA) 9 and their onsets preceded the end of the stop process, suggesting a causal involvement in this executive function. Such ERPs also occurred in unsuccessful-stop (US) trials, that is, when subjects moved despite the occurrence of a stop-signal, mostly when they had long reaction times (RTs). These findings support the hypothesis that motor cortices are the final target of the inhibitory command elaborated by the frontal-basal ganglia-thalamic network.

Effect of ICSI on gene expression and development of mouse preimplantation embryos.

BACKGROUND: In vitro culture (IVC) and IVF of preimplantation mouse embryos are associated with changes in gene expression. It is however not known whether ICSI has additional effects on the transcriptome of mouse blastocysts. METHODS: We compared gene expression and development of mouse blastocysts produced by ICSI and cultured in Whitten's medium (ICSI(WM)) or KSOM medium with amino acids (ICSI(KSOMaa)) with control blastocysts flushed out of the uterus on post coital Day 3.5 (in vivo). In addition, we compared gene expression in embryos generated by IVF or ICSI using WM. Global pattern of gene expression was assessed using the Affymetrix 430 2.0 chip. RESULTS: Blastocysts from ICSI fertilization have a reduction in the number of trophoblastic and inner cell mass cells compared with embryos generated in vivo. Approximately 1000 genes are differentially expressed between ICSI blastocyst and in vivo blastocysts; proliferation, apoptosis and morphogenetic pathways are the most common pathways altered after IVC. Unexpectedly, expression of only 41 genes was significantly different between embryo cultured in suboptimal conditions (WM) or optimal conditions (KSOM(aa)). CONCLUSIONS: Our results suggest that fertilization by ICSI may play a more important role in shaping the transcriptome of the developing mouse embryo than the culture media used.

Atlas-based functional radiosurgery: early results.

Functional disorders of the brain, such as dystonia and neuropathic pain, may respond poorly to medical therapy. Deep brain stimulation (DBS) of the globus pallidus pars interna (GPi) and the centromedian nucleus of the thalamus (CMN) may alleviate dystonia and neuropathic pain, respectively. A noninvasive alternative to DBS is radiosurgical ablation [internal pallidotomy (IP) and medial thalamotomy (MT)]. The main technical limitation of radiosurgery is that targets are selected only on the basis of MRI anatomy, without electrophysiological confirmation. This means that, to be feasible, image-based targeting must be highly accurate and reproducible. Here, we report on the feasibility of an atlas-based approach to targeting for functional radiosurgery. In this method, masks of the GPi, CMN, and medio-dorsal nucleus were nonrigidly registered to patients' T1-weighted MRI (T1w-MRI) and superimposed on patients' T2-weighted MRI (T2w-MRI). Radiosurgical targets were identified on the T2w-MRI registered to the planning CT by an expert functional neurosurgeon. To assess its feasibility, two patients were treated with the CyberKnife using this method of targeting; a patient with dystonia received an IP (120 Gy prescribed to the 65% isodose) and a patient with neuropathic pain received a MT (120 Gy to the 77% isodose). Six months after treatment, T2w-MRIs and contrast-enhanced T1w-MRIs showed edematous regions around the lesions; target placements were reevaluated by DW-MRIs. At 12 months post-treatment steroids for radiation-induced edema and medications for dystonia and neuropathic pain were suppressed. Both patients experienced significant relief from pain and dystonia-related problems. Fifteen months after treatment edema had disappeared. Thus, this work shows promising feasibility of atlas-based functional radiosurgery to improve patient condition. Further investigations are indicated for optimizing treatment dose.

Lateralizing value of memory tests in drug-resistant temporal lobe epilepsy.

Our aim was to test the lateralizing value of a neuropsychological battery including several memory tests on a large sample of consecutive patients with drug-resistant temporal lobe epilepsy (TLE) evaluated for epilepsy surgery. We studied 73 right-handed patients (56% males, mean age 35.3 +/- 11.2 years, 49% left TLE) aged 16 years or older with normal IQ who underwent a preoperative neuropsychological assessment including several memory tests and were seizure-free after at least 1 year of follow-up. Forty-seven had TLE due to hippocampal sclerosis, whilst 26 had TLE secondary to tumors or other lesions. Receiver Operating Characteristic (ROC) analysis and discriminant function analysis were used to evaluate the lateralization value of selected tests and of the battery as a whole, respectively. In patients with TLE secondary to tumors or other lesions, no test showed significant lateralizing value. In patients with TLE due to hippocampal sclerosis, the immediate (P < 0.01) and delayed (P < 0.001) Rey Auditory Verbal Learning Test (RAVLT) displayed substantial discriminatory ability. The battery as a whole correctly classified 82% of patients with respect to side of epileptogenesis. Our findings suggest that a non-invasive, relatively short and unexpensive neuropsychological battery based on memory tests may profitably complement other well-established diagnostic procedures such as video-EEG or magnetic resonance imaging (MRI), at least in patients with drug-resistant TLE due to hippocampal sclerosis.

A rapid and reliable procedure to localize subdural electrodes in presurgical evaluation of patients with drug-resistant focal epilepsy.

OBJECTIVES: To evaluate a novel method for localization of subdural electrodes in presurgical assessment of patients with drug-resistant focal epilepsy. METHODS: We studied eight consecutive patients with posterior epilepsy in whom subdural electrodes were implanted for presurgical evaluation. Electrodes were detected on post-implantation brain CT scans through a semiautomated procedure based on a MATLAB routine. Then, post-implantation CT scans were fused with pre-implantation MRI to localize the electrodes in relation to the underlying cortical structures. The reliability of this procedure was tested by comparing 3D-rendered MR images of the electrodes with electrode position as determined by intraoperative digital photography. RESULTS: In each patient, all electrodes could be correctly localized and visualized in a stereotactic space, thus allowing optimal surgery planning. The agreement between the procedure-generated images and the digital photographs was good according to two independent raters. The mean mismatch between the 3D images and the photographs was 2 mm. CONCLUSIONS: While our findings need confirmation on larger samples including patients with anterior epilepsy, this procedure allowed to localize subdural electrodes and to establish the spatial relationship of each electrode to the underlying brain structure, either normal or damaged, on brain convessity, basal and medial cortex. SIGNIFICANCE: Being simple, rapid, unexpensive, and reliable, this procedure holds promise to be useful to optimize epilepsy surgery planning.

Temporal lobe epilepsy surgery: different surgical strategies after a non-invasive diagnostic protocol.

AIM: To test a non-invasive presurgical protocol for temporal lobe epilepsy (TLE) based on "anatomo-electro-clinical correlations". METHODS: All consecutive patients with suspected TLE and seizure history <2 years were entered into the protocol, which included video-electroencephalographic (EEG) monitoring and magnetic resonance imaging (MRI). Three different TLE subsyndromes (mesial, lateral, mesiolateral) were identified by combined anatomical, electrical, and clinical criteria. "Tailored" surgery for each subsyndrome was offered. Patients with seizure history <2 years, MRI evidence of temporal mass lesion, and concordant interictal EEG and clinical data bypassed video-EEG monitoring and were directly scheduled for surgery. RESULTS: Lesionectomy was performed without video-EEG recording in 11 patients with tumorous TLE. Of 146 patients studied with video-EEG, 133 received a TLE diagnosis. Four were excluded for neuropsychological risks, eight refused surgery, and 121 underwent surgery. Of 132 consecutive patients who underwent surgery, 101 had at least one year of follow up. They were divided into a "hippocampal sclerosis/cryptogenic" group (n = 57) and a "tumours/cortical organisation disorders" group (n = 44). In the first group, extensive temporal lobectomy (ETL) was performed in 40 patients, anteromesial temporal lobectomy (AMTL) in 17 patients. At follow up, 47 patients were seizure free. In the second group, lesionectomy plus ETL was performed in 23 patients, lesionectomy plus AMTL in six patients, and lesionectomy alone in 15 patients. Thirty nine patients were seizure free. CONCLUSIONS: These findings suggest that different TLE subsyndromes can be identified accurately using non-invasive anatomo-electro-clinical data and can be treated effectively and safely with tailored surgery.

Cardiac asystole during right frontal lobe seizures: a case report.

The association between partial seizures and cardiac asystole has rarely been reported in the literature. This potentially life-threatening symptom has been observed principally in left-sided epilepsies, in particular during seizures originating in temporal lobe. We describe a case with ictal bradycardia followed by cardiac asystole during right frontal lobe seizures. Video-EEG monitoring recorded two partial seizures with electro-clinical findings suggestive of a right frontal lobe origin, associated with ictal bradycardia followed by prolonged asystole. The brain MRI showed a lesion located in the cingulate gyrus of the right frontal lobe. The patient required a subsequent placement of a pacemaker. In conclusion, cardiac asystole may be a potentially life-threatening symptom during seizures of frontal lobe origin. The right fronto-mesial structures may play a role in autonomic regulation of cardiovascular responses.

Which treatment options should be used in adolescents with polycystic ovary syndrome?

Several studies have hypothesized a peripubertal onset of polycystic ovary syndrome (PCOS). This syndrome affects different pathogenetic pathways and includes endocrine-metabolic abnormalities such as hyperandrogenism, hyperinsulinism and insulin resistance. The therapeutic approaches must be addressed to individualization of therapy, considering the major clinical manifestations of the syndrome during adolescence. While the treatment of hyperandrogenism makes use of different drugs already studied, the debate about the use of insulin sensitizing drugs is still open. It will be more and more necessary to define the phenotypic and genotypic milieu in which all treatments will be as safe and effective as possible.