Analysis of MGMT promoter methylation status on intraoperative fresh tissue section from frameless neuronavigation needle biopsy of 25 patients with brain tumor.

Formalin fixation under conditions that adversely affected the quality of the DNA, or indeterminant assay, or extensive tumor necrosis can compromise the genetic analysis of a brain bioptic sample. The success of DNA extraction and Methyl Guanine Methyl Transferase (MGMT) promoter methylation testing could be improved by freezing of fresh tumor tissue at the moment of biopsy. To ensure an increased concentration of the DNA samples the withdrawal should be performed in an area with high probability of neoplastic cells. From May 2007 to January 2011 fifty-two frameless neuronavigation brain needle biopsy were performed at the Neurosurgery Unit of the "Arcispedale Santa Maria Nuova" City Hospital of Reggio Emilia. The "image-guided" neuronavigated protocol sampling provided withdrawal specimens highly correlated with neuroimaging characteristics of the lesions. In this study the Authors report the genetic analysis on 24 cases of freezing fresh tissue from brain needle bioptic sample starting from July 2008. The molecular determination of MGMT promoter was assessed with the Nested-Methylation Specific-Polymerase Chain Reaction on fresh or cryopreserved needle bioptic tissue. The genetic characterization was feasible in all the bioptic samples. The MGMT promoter was methylated in eleven patients, including a brain infection. The diagnostic yield of brain biopsy could be increased by the neuronavigated trajectories and the intraoperative frozen sections. In the future the availability of the molecular-genetic characterization of a brain tumor before open surgery will provide important information for the optimal treatment. The MGMT promoter status analysis on needle bioptic fresh tissue could be available also for that patient not eligible for surgical remotion of the tumor.

Detection of IDH1 mutations and the status of MGMT promoter on intraoperative fresh tissue section from frameless neuronavigation needle biopsy. Analysis on 17 patients with brain glial tumor ineligible for craniotomy and tumor resection.

It is well known that primary and secondary glioblastomas are histologically largely indistinguishable. Therefore, the detection of IDH1 mutations or the status of the MGMT promoter on a simple bioptic sample could be one of major diagnostic and prognostic importance for glial patients that complements clinical criteria for distinguishing secondary from primary glioblastomas and to predict a more favourable prognosis. Currently, biopsy is the method of choice to obtain tissue from intracranial lesions with uncertain neurodiagnostic findings or in deep locations, with a minimal invasive approach. The needle biopsy with frameless neuronavigation could provide a sampling with elevated diagnostic yield and high concentration of DNA, due to the "image-guided" computer assisted technique of needle insertion through the most neurodiagnostic representative tumor area. The freezing of fresh tumor tissue at biopsy could greatly improve the success of DNA extraction. The concentration of the DNA samples can also improved from a withdrawal in an area with high probability of neoplastic cells. The present study reports the results of 17 patients who had undergone frameless image-guided intracranial needle biopsy from April 2008 until July 2010 at Neurosurgery Unit of the "Arcispedale Santa Maria Nuova" of Reggio Emilia. For these patients the molecular determination of MGMT promoter was assessed with the Nested-Methylation Specific-Polymerase Chain Reaction and the screening of mutations in IDH1 e IDH2 genes was performer by polymerase chain reaction (PCR) and direct sequencing on fresh or cryopreserved needle bioptic tissue.

An Italian case of CADASIL with mutation CGC-TCG in codon 1006, exon 19 Notch3 gene.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is commonly overlooked or misdiagnosed owing to its recent identification. It is characterized clinically by recurrent cerebral infarcts, usually appearing between the ages of 30 and 50 years, subcortical dementia, and pseudobulbar palsy. It begins with migraine with aura in approximately one-third of patients. The pathological hallmark of angiopathy is the presence of characteristic granular osmiophilic material (GOM) within the basal lamina of smooth muscle cells. The defective gene in CADASIL is Notch3, which encodes a large transmembrane receptor, and 70% of missense mutations are in exons 3 and 4. Each gene defect leads to either a gain or loss of a cysteine residue in the extracellular N-terminal domain of the molecule. We report the case of a 53-year-old woman admitted to the hospital for transient ischemic attack and stroke-like episodes recurrent since age 43 years. The patient had pseudobulbar palsy, pyramidal signs, and cognitive impairment but not frank dementia. Cerebral MRI showed periventricular diffuse and confluent ischemic lesions. Ultrastructural study revealed an abnormal deposition of granular osmiophilic material (GOM) within the basal lamina in skin capillaries. Direct sequence analysis of the Notch3 gene was performed. Since no mutation was detected in exons 3 and 4, the remaining exons were sequenced and a missense mutation, CGC-TGC in codon 1006 of exon 19 was found. The mutation led to a gain of a cysteine residue. This is the first missense mutation in codon 1006 of exon 19 of the Notch3 gene to be described in Italy and the second reported in the literature.

Kinematic analysis of the reach to grasp movement in Parkinson's and Huntington's disease subjects.

This experiment investigates the kinematic characteristics of the reach to grasp movement of Parkinson's and Huntington's disease subjects under two different experimental conditions. In the first condition subjects were required to perform the movement at a normal speed, while in the second condition they were required to perform the movement as fast as possible. Results showed that the kinematic parameterization of movement in Parkinson's disease subjects did not differ from that of age-matched control subjects for both the normal and the fast condition. However, the performances of Huntington's disease subjects appeared to be different when compared to the other two groups. Differences were mainly related to Huntington's disease patients' inability to properly define the temporal features of the movements.

[Evaluation of chronic nasal respiratory obstruction in children using optic fiber rhinopharyngoscopy and rhinomanometry]. / Valutazione dell'ostruzione respiratoria nasale cronica del bambino mediante rinofaringoscopia a fibre ottiche e rinomanometria.

Traditional clinical examination is frequently inadequate to evaluate children affected by chronic nasal obstruction: radiology may be of some use but it exposes children to radiation and gives only a limited lateral view of the nasopharynx. Therefore other means need to be tested for the anatomical and functional examination of the nasal and nasopharyngeal cavities. Adenoid hypertrophy and chronic nasal congestion are the most common causes of nasal respiratory impairment in children. The clinical expressions of adenoid enlargement are influenced by the osteo-cartilaginous nasal conformation and by functional alterations of nasal mucosa. Therefore a correct clinical examination is necessary to determine the indications for adenoidectomy so as to prevent unsatisfactory results. The aim of this study was to test the efficacy of rhinopharyngoscopy and rhinomanometry in the quantitative and qualitative evaluation of nasal and nasopharyngeal airways in 50 children (age-range 5-12 years) affected by nasal obstruction. Based on the rhinopharyngoscopic evaluation of adenoid volume, the children were divided into 3 groups affected by choanal obstruction defined as: severe (28 cases); partial (14 cases); minimal (8 cases). In these 3 groups anterior rhinomanometry, performed before and after administration of a nasal decongestant, allowed to evidence the role played by functional and organic factors in determining nasal stenosis. Abnormal values of total nasal resistance were found in 42 of the 50 children in the study. In 12 of these cases there was a marked decrease in nasal resistance following decongestion, evidencing the prevalence of functional factors in determining nasal obstruction and contra-indicating adenoidectomy. Rhinopharyngoscopy and rhinomanometry were well tolerated by all examined patients; the combined use of the two techniques allowed a more accurate diagnostic assessment of functional and anatomical causes of nasal obstruction in order to predict the benefits which can be obtained through adenoidectomy.