Deep brain stimulation in patients with long history of drug resistant epilepsy and poor functional status: Outcomes based on the different targets.

BACKGROUND: Deep brain stimulation (DBS) is a widely used surgical procedure for the treatment of patients with drug resistant epilepsy (DRE) and several anatomical target have been described. Indications for DBS includes patients with focal, partial seizure and those for which resective or disconnective surgery are contraindicated, such as involvement of eloquent cortex or significant comorbidities. Despite the SANTE trial has clearly indicated the efficacy of DBS of anterior nucleus of the thalamus (ANT), specific indications regarding the best anatomical target and outcome in patients with severe disability are lacking. Here we described our case series of patients underwent DBS of three different target including ANT, centromedian thalamic nucleus (CMN) and subthalamic nucleus (STN). METHOD: Six patients with DRE have been treated with DBS of ANT (n = 3), STN (n = 2) and CMN (n = 1). Outcome has been expressed as seizures frequency reduction and patients functional status after surgery with a follow-up of 5-11 years. RESULTS: Four out of six patients show no reduction of seizures frequency after DBS implant with one case of increasing atypical absence. Two cases, one ANT and one CMN, show a significant reduction of seizures frequency of 50-60%. No patients improve relative to functional outcome and one showed psychiatric symptoms worsening. CONCLUSIONS: For patients with DRE and severe functional disability, DBS may reduce seizure frequency in some cases, but it does not improve functional outcome.

Cognitive and linguistic outcomes after awake craniotomy in patients with high-grade gliomas.

BACKGROUND: Preservation of language and cognition is crucial in glioma surgery, as they are crucial aspects of daily life functioning. Several studies claimed that awake surgery in eloquent areas is demanded in low and high-grade gliomas. Cognitive and language outcome has been less investigated in high-grade gliomas compared to low-grade. METHOD: We analyzed the neuropsychological and neuro-oncological outcome of nineteen patients (from a cohort of forty patients) who underwent fully awake surgery for resection of malignant tumors located in eloquent areas. RESULTS: Post-surgery, linguistic functions were unchanged in 80 % of patients. Slight impairments in memory and executive functions were observed in about 50 % of patients. Survival rate at one year follow-up was 89 %. Results showed that awake procedure is safe, well tolerated and related with good linguistic outcome similar to low-grade gliomas. The majority of patients reported a good outcome in term of quality of life. CONCLUSIONS: Our results confirm that awake surgery is associated to good cognitive and linguistic clinical outcome also in malignant tumors.

Isolation and characterization of progenitor mesenchymal cells in human pituitary tumors.

The Cancer Stem Cells (CSCs) theory suggests that genetic alterations in stem cells are the direct cause for cancer. The evidence for a CSC population that results in pituitary tumors is poor. Some studies report the isolation of CSCs, but a deep characterization of the stemness of these cells is lacking. Here, we report the isolation and detailed characterization of progenitor mesenchymal cells (PMCs) from both growth hormone-secreting (GH(+)) and non-secreting (NS) pituitary adenomas, determining the immunophenotype, the expression of genes related to stemness or to pituitary hormone cell types, and the differentiative potential towards osteo-, chondro- and adipogenic lineages. Finally, the expression of CD133, known as a marker for CSCs in other tumors, was analyzed. Isolated cells, both from GH(+) and NS tumors, satisfy all the criteria for the identification of PMCs and express known stem cell markers (OCT4, SOX2, KLF4, NANOG), but do not express markers of pituitary hormone cell types (PITX2, PROP1, PIT1). Finally, PMCs express CD133. We demonstrated that pituitary tumors contain a stem cell population that can generate cell types characteristic of mesenchymal stem cells, and express CD133, which is associated with CSCs in other tumors.

Functional improvement after subthalamic stimulation in Parkinson's disease: a non-equivalent controlled study with 12-24 month follow up.

OBJECTIVE: This study aimed to assess the effectiveness of chronic bilateral STN-S in improving the functional status of PD patients compared with patients treated with drugs alone. METHODS: Controlled study of disability index changes over 12 and 24 month chronic STN stimulation. Of 39 patients with advanced PD meeting CAPSIT criteria for STN-S, 23 underwent surgery; 16 patients decided against surgery and continued on drug schedule adjustments. Functional status was measured using the Activities of Daily Living section of the Unified Parkinson's Disease Rating Scale (UPDRS-ADL), Brown's Disability Scale, and Functional Independence Measure. UPDRS motor score and subscores for selected items, levodopa equivalent daily dose, and Beck Depression Inventory scores were also monitored. RESULTS: T12 follow up data were available for all 39 patients and T24 data for 13 STN-S and 8 control subjects. Compared with controls, STN-S patients experienced significant or highly significant improvements in all independence measures at both 12 and 24 months (time x treatment effect T12: F = 19.5, p = 0.00008; T24: F = 6.2, p = 0.005). Forward stepwise regression for independent predictors of the yearly rate of UPDRS-ADL score modification in the entire sample showed that treatment was the only factor significantly associated with functional status change (beta coefficient -0.54, t value -2.5, p = 0.02), whereas other variables-UPDRS motor score, BDI, and age at disease onset and enrolment-were not in the equation. CONCLUSION: STN-S is an effective therapeutic option in advanced PD. It induced a consistent improvement of functional abilities over two years to an extent that was not achieved with drug therapy alone.

Multicentric glioma with unusual clinical presentation.

Multiple glioma is a well-recognized but uncommon entity. They are grouped in two categories: multifocal and multicentric gliomas. Multifocal gliomas grow through dissemination along an established route, spreading through commissural pathways, CSF channels, or the blood or by local extension through satellite formation; at the opposite end of the spectrum, multicentric gliomas are widely separated lesions whose simultaneous presence cannot be attributed to any of the above pathways. Reports in the literature refer to single cases or small series of multicentric gliomas, almost always in adult patients, their occurrence in children being even less frequent. We report the case of a 12-year-old boy with multicentric glioma, atypical acute clinical onset and fast growth of three other tumors in 8 months, and then discuss the problems of diagnosis and therapy.

Effect of age on synaptic size in human brain tissue proximal to tumor masses.

OBJECTIVE: To measure the effect of age on synaptic morphologic rearrangements in human brain tissue peripheral to space-occupying lesions. STUDY DESIGN: Synaptic length (L) was measured interactively by computer-assisted image analysis in brain tissue samples from adult (mean age, 39 years) and old (mean age, 67.2 years) patients. Each group consisted of five subjects. RESULTS: L was reduced by 9% in the old vs. adult group of patients. A percent distribution of the data showed that junctional areas smaller than 0.25 micron accounted for 47.2% in old patients and 31% in the adults. CONCLUSION: The present findings are in contrast with current literature data documenting a significant increase in the percent of enlarged contact zones in the senile brain. We interpret these results in terms of synaptic dynamic morphology and suggest that they may reflect alterations of neuronal adaptive capabilities due both to the pathologic condition and age of the patients.

Cardiac myxoma with glandular elements metastatic to the brain 12 years after the removal of the original tumor.

This report describes a case of cardiac myxoma with glandular elements metastatic to the brain. The histological appearance of the brain tumor was characterized by irregularly shaped glands lined by a single layer of mucous-secreting cells. The glands rested on a stroma made of connective tissue with myxoid changes in which short cords of cells with eosinophilic cytoplasm were occasionally detected. The cardiac tumor was a myxoma in which only 2 small glandular structures were identified. Immunohistochemically, the gland-lining cells were positively stained by cytokeratin AE1-AE3, CAM 5.2, and B 72.3. CEA was detected as a thin layer on the luminal surface of the cells and in the cytoplasm of goblet cells. The myxoma cells in the stroma were not stained by cytokeratins. This is the first report of brain metastases from a cardiac myxoma made of glandular elements.