Reappraisal of the posterior approach for cervical decompressive herniectomy.

BACKGROUND: Does posterior cervical herniectomy impact on symptoms related to cervical paramedian/lateral soft disc herniation? METHODS: In a patient series over 15 years operated for single level paramedian/lateral soft disc herniation with posterior cervical approach, perceived radicular and cervical pre- and postoperative symptoms were reconstructed and analyzed. RESULTS: Out of 105 patients with these characteristics 75 could be recruited for long-term follow-up. Preoperative symptoms included: radicular motor deficit (81.3%); radicular pain (93.3%); radicular sensory deficit (84%); cervical pain (80%) and disturbance of cervical motility (49.3%). Postoperatively radicular motor score improved in all patients (score 5 in 92% and 4 in 8%); sensory disturbance improved in all and radicular pain disappeared in 90% and improved in the others. Cervical pain disappeared in 78% and improved in other 22%, two had new onset moderate cervical pain. CONCLUSIONS: This series confirms safety and efficacy of the posterior approach in relieving motor and sensory symptoms in patients with symptomatic single level, lateral soft disc herniation.

Optic Radiation Diffusion Tensor Imaging Tractography: An Alternative and Simple Technique for the Accurate Detection of Meyer's Loop.

BACKGROUND: The optic radiation (OR) is a white matter bundle with a very complex anatomy. Its anterior component bends sharply around the tip of the temporal horn, forming the Meyer's loop (ML), the sparing of which during surgery is crucial to preserve visual function. Defining its exact anatomy and accurately identifying its position remain challenging, even with diffusion tensor imaging (DTI) tractography and the most refined tracking procedure. We have developed an alternative tracking technique to detect the ML position. METHODS: We performed DTI studies in 26 patients undergoing resection of a temporo-parieto-occipital lesion. We then reconstructed the ORs of each patient using 2 techniques (the first developed by our team, the other taken from the literature), using the same tracking software and parameters. We evaluated the accuracy of each technique measuring 3 distances that define the ML position. We created 5 data groups and compared the 2 techniques. Finally, we compared our results with the results from 8 anatomic dissection studies and other tractographic studies. RESULTS: Our findings show that our technique allows a more accurate definition of the ML position. We found a statistically significant (P < 0.05) difference for all the distances between the 2 techniques; our results resemble those obtained in dissection studies. Our technique is also easy to perform and repeatable. CONCLUSIONS: Our tracking technique may be of marked interest for the evaluation and anatomic definition of the ML position, particularly for neurosurgeons approaching the anterior temporal region.

The vacuolar H+ ATPase is a novel therapeutic target for glioblastoma.

The vacuolar H+ ATPase (V-ATPase) is a proton pump responsible for acidification of cellular microenvironments, an activity exploited by tumors to survive, proliferate and resist to therapy. Despite few observations, the role of V-ATPase in human tumorigenesis remains unclear.We investigated the expression of ATP6V0C, ATP6V0A2, encoding two subunits belonging to the V-ATPase V0 sector and ATP6V1C, ATP6V1G1, ATPT6V1G2, ATP6V1G3, which are part of the V1 sector, in series of adult gliomas and in cancer stem cell-enriched neurospheres isolated from glioblastoma (GBM) patients. ATP6V1G1 expression resulted significantly upregulated in tissues of patients with GBM and correlated with shorter patients' overall survival independent of clinical variables.ATP6V1G1 knockdown in GBM neurospheres hampered sphere-forming ability, induced cell death, and decreased matrix invasion, a phenotype not observed in GBM monolayer cultures. Treating GBM organotypic cultures or neurospheres with the selective V-ATPase inhibitor bafilomycin A1 reproduced the effects of ATP6V1G1 siRNA and strongly suppressed expression of the stem cell markers Nestin, CD133 and transcription factors SALL2 and POU3F2 in neurospheres.These data point to ATP6V1G1 as a novel marker of poor prognosis in GBM patients and identify V-ATPase inhibition as an innovative therapeutic strategy for GBM.

Gene expression profile analysis of human mesenchymal stem cells from herniated and degenerated intervertebral discs reveals different expression of osteopontin.

Gene expression analysis provides an effective methodology to identify clinically relevant genes implicated in intervertebral disc (IVD) pathology. The analysis of gene profile in mesenchymal stem cells (MSCs) from human herniated IVD (H-IVD) and degenerated IVD (D-IVD) has not yet been investigated. We present in this study a characterization of MSCs isolated from clinically categorized H-IVD and D-IVD disc samples. H-IVD-MSCs and D-IVD-MSCs showed multipotent mesenchymal differentiation ability, expressing positivity for adipogenic, osteogenic, and chondrogenic markers with an immunophenotypical profile representative of MSCs. FACS analyses revealed a higher expression of CD44 in D-IVD-MSCs compared to H-IVD-MSCs. Gene expression profile revealed that most genes under investigation displayed large variations and were not significantly different in the two types of analyzed IVD-MSCs. Conversely, the gene expression of osteopontin (OPN), a protein involved in bone matrix mineralization and extracellular matrix destruction, was found markedly increased (more than 400-fold) in D-IVD-MSCs compared to H-IVD-MSCs. Moreover, the OPN protein expression was detectable only in D-IVD-MSCs, and its levels were directly related with D-IVD severity. These findings suggest that an abnormal expression of OPN in D-IVD-MSCs occurs and plays a pivotal role in the pathophysiological process of human disc degeneration. We speculate that the regulation of the OPN pathway might be a therapeutic target to counteract disc degeneration.

Third Ventriculostomy in Late-onset Idiopathic Aqueductal Stenosis Treatment: A Focus on Clinical Presentation and Radiological Diagnosis.

Endoscopic third ventriculostomy (ETV) is considered the gold standard treatment for obstructive hydrocephalus due to partial or complete obstruction of cerebrospinal fluid (CSF) ventricular pathways caused by mass lesions. However long-term efficacy of this procedure remains controversial as treatment of chronic adult hydrocephalus due to stenosis of Sylvian acqueduct [late-onset idiopathic aqueductal stenosis (LIAS)]. The authors describe clinical presentation, diagnostic investigations in patients affected by LIAS, and define their clinical and radiological outcome after ETV. From January 2003 to December 2008, 13 consecutive LIAS patients treated by ETV were retrospectively reviewed. Pre- and post-operative clinical and radiological findings, including conventional and phase-contrast (PC) cine magnetic resonance imaging (MRI) were investigated. ETV was successfully performed in all patients. Patient's neurological condition improved. No one required a second ETV procedure or shunt implantation. Clinical and radiological results reveal a satisfactory outcome of LIAS patients treated by ETV. At follow-up a clinical improvement could be demonstrated in all cases. Selection criteria of LIAS patients seem to be crucial to obtain satisfactory and long-lasting results. Even in elderly patients with chronic hydrocephalus, ETV can be considered the treatment of choice.

The long pentraxin PTX3 as a correlate of cancer-related inflammation and prognosis of malignancy in gliomas.

Inflammation is a component of glioma microenvironment. PTX3 is a component of the humoral arm of innate immunity and a candidate marker of inflammation. In the present study we assessed the expression of PTX3 in gliomas by immunohistochemistry. PTX3 expression differed across low and high-grade tumors based on histopathological diagnosis and clinical severity, positively correlating with tumor grade and severity. In a multivariate logistic regression model, only the PTX3 score was significantly associated with the presence of a high-grade tumor. Thus, PTX3 may represent a new marker of cancer-related inflammation and glioma malignancy.

Human glioma tumors express high levels of the chemokine receptor CX3CR1.

The chemokine receptor CX3CR1 and its cognate ligand CX3CL1 (also known as fractalkine), are involved in central nervous system pathophysiology, in particular, in the cross-talk between neurons and microglia. It was therefore important to investigate the expression of CX3CR1 in gliomas, the most frequently occurring, malignant brain tumors. In a consecutive series of 70 patients with primary, central nervous glial tumors, CX3CR1 was highly expressed in tumor cells as assessed by RT-PCR mRNA and protein levels, and by immunohistochemistry, while the corresponding normal cells were negative. Receptor immuno-positivity did not correlate with histology, grade, chromosomal (1p,19q) deletion, or with methylation of the DNA repair gene promoter MGMT (O6-methylguanine-DNA methyltransferase). Thus, CX3CR1 expression is a frequent event in gliomas, irrespective of tumor classification and clinical severity. The molecular basis underlying CX3CR1 up-regulation and its functional biological significance remain to be determined.

Schilder's disease: non-invasive diagnosis? :A case report and review.

Schilder's disease, or myelinoclastic diffuse sclerosis, is a rare disorder characterised by an inflammatory white matter plaque of demyelination. Clinical signs and symptoms might be atypical for early multiple sclerosis and at imaging the lesion is easily taken for a brain tumour. Regardless of the use of Poser's criteria for clinical diagnosis of Schilder's disease proposed in 1986, diagnostic difficulties are still present, as evidenced by the many reported cases in the English literature revised (Pubmed indexed, period 1998-2008). It clearly emerges that neuroradiological features, observable in additional magnetic resonance sequences are crucial, besides the consideration of Poser's criteria, in differentiating between demyelinating lesions and brain tumours. A 29-year-old female patient is presented, where a careful evaluation of both the clinical and radiological features, which might have been at a first glance misleadingly suggestive for a brain tumour, allowed non-invasive diagnosis of Schilder's disease.

Ghrelin and adiponectin in patients with Cushing's disease before and after successful transsphenoidal surgery.

BACKGROUND: Ghrelin, an endogenous ligand of the GH secretagogue receptor that exerts orexigenic activity, is negatively correlated with body mass index (BMI) and insulin resistance. Conversely, low levels of adiponectin (ApN), a circulating adipocytokine with antidiabetic, antiatherogenic and anti-inflammatory properties, have been found in several insulin-resistant conditions. Although Cushing's syndrome causes several metabolic and hormonal changes leading to insulin resistance and central obesity, few data concerning the impact of glucocorticoid excess on ghrelin and ApN levels are so far available. DESIGN: We evaluated ghrelin and ApN levels in 14 women (age +/- SE 39.5 +/- 3.9 years, BMI +/- SE 25.8 +/- 1.4 kg/m2) with Cushing's disease (CD) at baseline and after successful transsphenoidal surgery (TSS) and in 14 age- and BMI-matched healthy women. RESULTS: Despite similar levels of fasting glucose, insulin, homeostatic model assessment-estimated insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI) values, patients with CD had ghrelin levels lower than controls (117.8 +/- 21.5 vs. 269.6 +/- 51.4 pmol/l, P < 0.01), and ghrelin levels did not correlate with ACTH, cortisol, androgen and GH levels. Patients and controls showed similar ApN levels (11.1 +/- 1.6 vs. 11.5 +/- 2.0 mg/l), which correlated negatively with insulin, HOMA-IR and BMI and positively with QUICKI and high density lipoprotein (HDL)-cholesterol only in controls. At 10.2 +/- 0.7 months after successful TSS, patients showed a significant increase in ghrelin levels compared to pretreatment values (342.5 +/- 25.6 vs. 117.8 +/- 21.5 pmol/l, P < 0.005) along with significant modifications in BMI, insulin, HOMA-IR and HDL-cholesterol and no change in ApN levels. In two patients tested on days 2-4 after TSS, no modification in ghrelin and ApN levels was observed, despite a dramatic reduction in cortisol levels. CONCLUSION: Cortisol excess did not directly affect ghrelin and ApN levels in patients with CD. The observation that ghrelin levels were low during the active phase of CD and increased after recovery suggests that glucocorticoids may influence ghrelin levels indirectly by modulating adiposity and metabolic signals over the long term.

Proliferation of transformed somatotroph cells related to low or absent expression of protein kinase a regulatory subunit 1A protein.

The two regulatory subunits (R1 and R2) of protein kinase A (PKA) are differentially expressed in cancer cell lines and exert diverse roles in growth control. Recently, mutations of the PKA regulatory subunit 1A gene (PRKAR1A) have been identified in patients with Carney complex. The aim of this study was to evaluate the expression of the PKA regulatory subunits R1A, R2A, and R2B in a series of 30 pituitary adenomas and the effects of subunit activation on cell proliferation. In these tumors, neither mutation of PRKAR1A nor loss of heterozygosity was identified. By real-time PCR, mRNA of the three subunits was detected in all of the tumors, R1A being the most represented in the majority of samples. By contrast, immunohistochemistry documented low or absent R1A levels in all tumors, whereas R2A and R2B were highly expressed, thus resulting in an unbalanced R1/R2 ratio. The low levels of R1A were, at least in part, due to proteasome-mediated degradation. The effect of the R1/R2 ratio on proliferation was assessed in GH3 cells, which showed a similar unbalanced pattern of R subunits expression, and in growth hormone-secreting adenomas. The R2-selective cAMP analog 8-Cl cAMP and R1A RNA silencing, stimulated cell proliferation and increased Cyclin D1 expression, respectively, in human and rat adenomatous somatotrophs. These data show that a low R1/R2 ratio promoted proliferation of transformed somatotrophs and are consistent with the Carney complex model in which R1A inactivating mutations further unbalance this ratio in favor of R2 subunits. These results suggest that low expression of R1A protein may favor cAMP-dependent proliferation of transformed somatotrophs.