Association between promoter methylation of MLH1 and MSH2 and reactive oxygen species in oligozoospermic men-A pilot study.

MLH1 and MSH2 are important genes for DNA mismatch repair and crossing over during meiosis and are implicated in male infertility. Therefore, the methylation patterns of the DNA mismatch repair genes MLH1 and MSH2 in oligozoospermic males were investigated. Ten oligozoospermic patients and 29 normozoospermic donors were analysed. Methylation profiles of the MLH1 and MSH2 promotors were analysed. In addition, sperm motility and seminal reactive oxygen species (ROS) were recorded. Receiver operating characteristic (ROC) analysis was conducted to determine the accuracy of the DNA methylation status of MLH1 and MSH2 to distinguish between oligozoospermic and normozoospermic men. In oligozoospermic men, MLH1 was significantly (p = .0013) more methylated compared to normozoospermic men. Additionally, there was a significant positive association (r = .384; p = .0159) between seminal ROS levels and MLH1 methylation. Contrary, no association between MSH2 methylation and oligozoospermia was found. ROC curve analysis for methylation status of MLH1 was significant (p = .0275) with an area under the curve of 61.1%, a sensitivity of 22.2% and a specificity of 100.0%. This pilot study indicates oligozoospermic patients have more methylation of MLH1 than normozoospermic patients. Whether hypermethylation of the MLH1 promoter plays a role in repairing relevant mismatches of sperm DNA strands in idiopathic oligozoospermia warrants further investigation.

Deep brain stimulator electrodes used for lesioning: proof of principle.

OBJECTIVE: Patients with chronically implanted deep brain stimulator (DBS) electrodes can encounter complications requiring hardware removal. We assessed the safety and efficacy of using implanted DBS electrodes to create a therapeutic lesion before their removal. METHODS: Revision or removal of the DBS electrodes was required in two patients who had previously undergone DBS implantation. We conducted a series of in vitro experiments to confirm that the DBS electrodes could be used to generate radiofrequency lesions and to assess the relationship between radiofrequency parameters and lesion size. With this information, and with the approval of the hospital ethical review board, implanted electrodes were used to create incremental radiofrequency lesions in the thalamus in one patient and in the subthalamic nucleus in another. The procedures were performed under local anesthesia with contiguous contacts of the DBS lead connected to the active and reference sites of the RF generator to create a bipolar lesion. RESULTS: A 51-year-old man with essential tremor and a thalamic DBS required repeated battery changes secondary to tolerance and high voltage demands. Rather than replacing the battery, a radiofrequency thalamotomy was performed by using the existing left DBS electrode. At the 6-month follow-up examination, successful lesioning provided near complete tremor control. A second patient, a 50-year-old man with Parkinson's disease who had undergone bilateral subthalamic deep brain stimulation, developed skin erosion over the DBS hardware. A subthalamic nucleus lesion was made through the right DBS electrode. Lesion position and size were confirmed with magnetic resonance imaging. CONCLUSION: Lesions can be made through chronically implanted DBS electrodes in a safe, graded fashion and can produce therapeutic benefit.

Pallidotomy for parkinson disease: a review of contemporary literature.

OBJECT: The authors conducted an evidence-based review of contemporary published articles on pallidotomy to obtain an appraisal of this procedure in the treatment of Parkinson disease (PD). METHODS: A search of the Pubmed database performed using the key word "pallidotomy" yielded 263 articles cited between January 1, 1992, and July 1, 1999. Articles that included original, nonduplicated descriptions of patients with PD treated with radiofrequency pallidotomy were selected. In 85 articles identified for critical review, 1959 patients with PD underwent pallidotomies at 40 centers in 12 countries. There were 1735 unilateral (88.6%) and 224 bilateral procedures (11.4%). The mean age of the patients was 61.4+/-3.6 years and the mean duration of PD symptoms in these patients was 12.3+/-1.9 years. Microelectrode recordings were used in 46.2% of cases. Outcomes were objectively documented using the Unified Parkinson Disease Rating Scale (UPDRS) in 501 (25.6%) of the cases at 6 months and in 218 (11.1%) of the cases at 1 year. There was a consensus on the benefits of pallidotomy for off period motor function and on period, drug-induced dyskinesias, with variations in the extent of symptomatic benefit across studies. At the 1-year assessment, the mean improvement in the UPDRS motor score during off periods was 45.3% and the mean improvement in contralateral dyskinesias during on periods was 86.4%. The overall mortality rate was 0.4% and the rate of persistent adverse effects was estimated at 14%. Major adverse events, including intracerebral hemorrhages, contralateral weakness, and visual field defects, occurred in 5.3% of patients reported. CONCLUSIONS: Unilateral pallidotomy is effective and relatively safe in the treatment of PD; however, limited data are available on the long-term outcome of this procedure.

Involution of enhancing intrinsic tectal tumors after endoscopic third ventriculostomy. Report of two cases.

For benign intrinsic tectal tumors causing triventricular obstructive hydrocephalus, cerebrospinal fluid diversion followed by neuroimaging is a widely accepted treatment plan. In this report, the authors describe two children with focal enhancing tectal lesions that caused acute, symptomatic hydrocephalus. One child had neurofibromatosis Type 1 (NF1). In both children the hydrocephalus was effectively treated by endoscopic third ventriculostomy. Following this procedure, serial imaging studies revealed not only that the ventriculomegaly had resolved, but also that the enhancing tectal tumors had regressed and disappeared over time. The time to complete involution of these tumors was 18 months for the child with NF1 and 12 months for the other child. To the authors' knowledge, this is the first report of the involution of enhancing tectal tumors after endoscopic third ventriculostomy. The possible mechanisms for this unexpected result are discussed.

Oncogene amplification in medulloblastoma: analysis of a case by comparative genomic hybridization and fluorescence in situ hybridization.

We describe amplification of the MYCC oncogene in a medulloblastoma with aggressive clinical behavior. The patient was a six year old boy who underwent gross total surgical excision of a cerebellar tumor. Despite chemotherapy and total neuraxis radiation, the clinical course was one of relentless progression, with extensive subarachnoid spread and death within eight months of presentation. The pathological features were consistent with the recently described, "large cell variant" of medulloblastoma. Tumor cells exhibited large vesicular nuclei, prominent nucleoli and strong immunoreactivity for synaptophysin. Polymerase chain reaction (PCR) and fluorescence in situ hybridization (FISH) assay revealed no evidence of MYCN amplification or 1p deletion in the tumor. FISH analysis revealed evidence of MYCC amplification in the 20- to 30-fold range. Comparative genomic hybridization (CGH) revealed regions of gains and amplification in three locations, with gains of chromosome 7, amplification of 8q24 (corresponding to the MYCC locus) and gains of the long arm of chromosome 17 (suggestive of isochromosome 17q). While conventional karyotypic analysis was not successful in the present case, CGH provided invaluable information about gene amplification and losses/gains of chromosomes and chromosomal regions. Thus, CGH is a powerful technique applicable to frozen or paraffin-embedded material which helps to ascertain the presence of gene amplification even without prior knowledge of the gene to be tested.

Ganglioglioneurocytoma of the posterior fossa.

OBJECTIVE AND IMPORTANCE: Ganglioglioneurocytoma is not yet a well defined clinical and histopathological entity; recent reports outline the histopathological features of this very rare trimorphous tumor, under different names with its basic components of gangliocytoma, neurocytoma and glioma. Four previous reports described this tumor in eleven patients. This is the first case report describing ganglioglioneurocytoma in the posterior fossa. CLINICAL PRESENTATION AND INTERVENTION: A 31-year old male with midline posterior fossa ganglioglioneurocytoma is described, providing the neuroimages and histopathological studies. CONCLUSION: Ganglioglioneurocytoma is a rare mixed neuronal and glial tumor that can also occur in the posterior fossa.

Spontaneous resolution of bilateral traumatic carotid cavernous fistulas and development of trans-sellar intercarotid vascular communication: case report.

BACKGROUND: Bilateral carotid cavernous fistulas may complicate head injury. Spontaneous resolution of post-traumatic direct carotid cavernous fistula is rare. CASE DESCRIPTION We present a case of a 42-year-old female who developed post-traumatic high flow bilateral carotid cavernous fistulas with cortical and deep venous drainage, who had a spontaneous resolution with thrombosis of the cavernous sinus outlets bilaterally and development of a trans-sellar intercarotid vascular communication. To our knowledge this is the first reported case in the literature describing such a phenomenon. CONCLUSION Bilateral direct carotid cavernous fistulas may undergo spontaneous resolution and form a benign trans-sellar intercarotid vascular communication.

Cytology of pituitary thyrotroph hyperplasia in protracted primary hypothyroidism.

Pituitary thyrotroph hyperplasia, a rare cause of pituitary enlargement, is usually associated with protracted primary hypothyroidism. We present here a case of pituitary thyrotroph hyperplasia in a 51 year old woman who was thought to have a pituitary macroadenoma with suprasellar extension. The cytologic investigation of the intraoperative touch preparation identified hyperplastic thyrotrophs, provided the correct diagnosis and helped to limit further aggressive surgical removal of the lesion, which is known to regress after adequate thyroid hormone replacement therapy. This is the first study to describe the cytologic features of pituitary thyrotroph hyperplasia confirmed subsequently by histology, immunocytochemistry and transmission electron microscopy.