Endoscopic Third Ventriculostomy: A Single-Center Experience in Greece.

Endoscopic third ventriculostomy is an important tool in the treatment of various forms of adult hydrocephalus, and its use is evolving over the past years, proving in many cases more effective than the more traditional ventriculoperitoneal shunts. We present the experience from our department while comparing the results and complications with the international literature.

The diagnostic yield of transesophageal echocardiography in patients with cryptogenic cerebral ischaemia: a meta-analysis.

BACKGROUND AND PURPOSE: The diagnostic utility of transesophageal echocardiography (TEE) in patients with cryptogenic ischaemic stroke (IS) or transient ischaemic attack (TIA) remains controversial. METHODS: A systematic review and meta-analysis was performed according to PRISMA guidelines to estimate the pooled prevalence of potential cardioembolic causes detected by TEE in prospective observational studies of cryptogenic IS/TIA. Cardiac conditions causally associated with cerebral ischaemia were considered to be intramural thrombi and intracardiac tumors according to ASCO phenotyping of IS. RESULTS: Thirty-five eligible studies, comprising 5772 patients (mean age 53.6 years, 56.9% men) were identified. The most common TEE finding was ascending aorta and/or aortic arch atheroma [51.2% (27.4%-74.5%)], followed by patent foramen ovale (PFO) [43.2% (36.3%-50.4%)]. Complex aortic plaques and large PFOs were reported in 14% (10.2%-18.9%) and 19.5% (16.6%-22.8%) of TEE evaluations. The prevalence of atrial septal aneurysm was 12.3% (7.9%-18.7%) and was significantly higher in conjunction with PFO presence (risk ratio 2.04, 95% confidence interval 1.63-2.54, P < 0.001). The prevalence of left atrial thrombus [3.0% (1.1%-8.3%)] and spontaneous echo contrast [3.8% (2.3%-6.2%)] was low. The prevalence of intracardiac tumors was extremely uncommon [0.2% (0%-0.7%)]. Significant heterogeneity was identified (I(2) > 60%) in the majority of analyses. Heterogeneity was not affected by cryptogenic stroke definition (TOAST versus alternative criteria). After dichotomizing available studies using a cut-off of 50 years, PFO was significantly (P = 0.001) more prevalent in younger than in older patients. CONCLUSION: Routine TEE in patients with cryptogenic IS/TIA commonly identifies abnormal findings. However, the prevalence of cardiac conditions considered to be causally associated with cerebral ischaemia (intracardiac thrombi and tumors) is low.

Hypofractionated irradiation for gliomas with 45.5Gy in 13 fractions: a retrospective study.

AIM: The aim of the present retrospective study was to evaluate the efficacy and toxicity of a hypofractionated radiotherapy (HFRT) schedule for grade IV glioblastoma multiforme (GBM). METHODS: Fourteen elderly patients with KPS less than 70, received 13 fractions of 350cGy with 3D-conformal technique (3DCRT) and non-coplanar fields. Acute and late skin and CNS toxicity was graded according to EORTC/RTOG criteria. RESULTS: The median follow-up was 9 months. All patients completed the irradiation without interruptions due to toxicity and received temozolomide (TMZ) after the completion of 3DCRT. The KPS during RT and at follow-up was not significantly changed (P=0.108). The median overall survival was 7 months. No severe skin acute or late toxicity was noted. In terms of CNS toxicity, only one patient presented grade III toxicity requiring hospitalization for two days. The irradiation schedule of 45.5Gy in 13 fractions seems effective and without moderate or severe toxicity. CONCLUSION: The suggested HFRT schedule might be an alternative one, for elderly patients with dismal prognosis, unfit for six weeks of daily irradiation. Prospective studies are needed for further validation of our results, especially with the use of TMZ.

Sox11 expression in astrocytic gliomas: correlation with nestin/c-Met/IDH1-R132H expression phenotypes, p-Stat-3 and survival.

BACKGROUND: Sox11 is a transcription factor expressed in foetal and neoplastic brain tissue, including gliomas. It has been shown to suppress the tumourigenicity of glioma stem cells in vivo, thereby being hypothesised to function as a tumour suppressor. METHODS: We investigated the expression of Sox11 in 132 diffuse astrocytomas in relation to the regulator cell marker nestin, c-Met and IDH1-R132H, which have shown to be differentially expressed among the molecular subgroups of malignant gliomas, as well as to an inducer of astrocytic differentiation, that is, signal transducer and activator of transcription (p-STAT-3), clinicopathological features and survival. RESULTS: Sox11 immunoreactivity was identified in all tumours irrespective of grade, but being correlated with p-STAT-3. Three out of seven cases showed partial Sox11 promoter methylation. In >50% of our cases neoplastic cells coexpressed Sox11 and nestin, a finding further confirmed in primary glioblastoma cell cultures. Furthermore, nestin, c-Met and IDH1-R132H expression differed among grade categories. Cluster analysis identified four groups of patients according to c-Met, nestin and IDH1-R132H expression. The c-Met/nestin high-expressor group displayed a higher Sox11 expression. Sox11 expression was an indicator of favourable prognosis in glioblastomas, which remained in multivariate analysis and validated in an independent set of 72 cases. The c-Met/nestin high-expressor group was marginally with shorter survival in univariate analysis. CONCLUSIONS: We highlight the importance of Sox11 expression as a favourable prognosticator in glioblastomas. c-Met/nestin/IDH1-R132H expression phenotypes recapitulate the molecular subgroups of malignant glioma.

Current concepts on the mechanisms of dystonia and the beneficial effects of deep brain stimulation.

The application of lesioning procedures in the basal ganglia and, more recently, of deep brain stimulation (DBS) has revolutionalized dystonia treatment. However, our understanding of the mechanism of action of DBS is only minimal. This is largely due to a rudimentary understanding of dystonia pathophysiology itself, which in turn reflects an insufficient understanding of the functional significance of the cortico-striato-pallido-thalamocortical loops. The initial dystonia pathophysiology concept was one of changes in oscillation rate. Soon, it was realized that not only rate but also the pattern of basal ganglia activity is crucial in the etiology of the disease. The observations of altered somatosensory responsiveness and cortical neuroplasticity, along with the vast array of clinical phenotypes, imply the need for a wholistic neuronal pathophysiology model; one in which an underlying defect of basal ganglia function results in increased cortical excitability, misprocessing of sensory feedback, aberrant cortical plasticity, and ultimately clinical dystonia. This unified dystonia pathophysiology model, although simplistic, may provide the scaffold on which all incoming research and clinical data becomes united in a meaningful and practical way. In light of this model, the dramatic response of some forms of dystonia to pallidal stimulation, the time latency for the beneficial effect and even the presence of non-responders may be explained. Additionally, it may help in developing a rationale for more efficacious DBS programming, better selection of the timing of surgery, and more successful identification of those candidates that are most likely to respond to DBS.

Recurrence of trigeminal neuralgia due to an acquired arachnoid cyst.

We present the case of a 55-year-old female with pain recurrence after microvascular decompression for trigeminal neuralgia due to development of an arachnoid cyst. Radioimaging studies were inconclusive for vascular compression but showed evidence of fifth nerve distortion. The patient underwent surgical re-exploration, and a cystic lesion of thickened arachnoid containing cerebrospinal fluid was identified and excised. Postoperatively, the patient obtained pain relief. Arachnoid cyst formation may be a possible reason for pain recurrence after microvascular decompression for trigeminal neuralgia, especially when repeat neuroimaging does not show clear evidence of fifth nerve vascular compression. Direct compression from the cyst or arterial pulsation transmission through the cyst to the nerve may be the cause of recurrence.

Technical aspects and considerations of deep brain stimulation surgery for movement disorders.

Deep brain stimulation (DBS) represents one of the more recent advancements in Neurosurgery. Even though its most successful applications evolved in movement disorders (MDs), indications now include pain, psychiatric disorders, epilepsy, cluster headaches and Tourette syndrome. As this type of surgery gains popularity and the indications for DBS surgery increase, so it will certainly increase the number of neurosurgeons who will use this neuromodulatory technique. A detailed description of the technical aspects of the DBS procedure, as it is performed in our department, is presented. In our opinion, our method is a good combination of all the well-established necessary techniques in a cost-effective way. This technical article may be helpful to neurosurgeons considering to start performing this type of surgery. It could also prompt others who perform DBS regularly to express their views, and hence, lead to further refinement of this demanding procedure.

Brain abscess following intracerebral haemorrhage.

A 79-year old male patient developed a brain abscess as infective transformation of a preceding intracerebral haemorrhage after urinary tract infection. The awareness of brain abscess formation at the site of intracerebral haemorrhage is crucial for early diagnosis and treatment of this rare but potentially fatal complication.

Use of a single semilinear incision in Deep Brain Stimulation for movement disorders.

This technical note presents the authors experience in using a single semilinear incision for bilateral implantation of Deep Brain Stimulation electrodes in the treatment of movement disorders, in order to avoid some of the hardware and skin related complications of this procedure. The advantages and disadvantages of this technique are presented and discussed.

Caspase-3 immunohistochemical expression is a marker of apoptosis, increased grade and early recurrence in intracranial meningiomas.

Caspase-3 is the ultimate executioner caspase that is essential for the nuclear changes associated with apoptosis. We investigated caspase-3 immunohistochemical expression in 58 primary intracranial meningiomas, using one monoclonal antibody detecting both precursor and cleaved caspase-3 (CPP32) and a second recognizing only the cleaved activated form (ASP175). Caspase-3 expression was analyzed in relation to baseline apoptosis-as illustrated by the expression of anti-single stranded DNA (ss-DNA), the antiapoptotic protein bcl-2, proliferation indices (Ki-67, PCNA, topoisomerase IIa, mitosin C), hormonal status (estrogen, progesterone, androgen receptors), standard clinicopathological parameters and patients' disease-free survival. Caspase-3 immunostaining was observed in 62% of cases for CPP32 and in 24% for ASP175. In both instances, the labeling index (LI) was significantly correlated with ss-DNA LI (p=0.038 and p=0.018). CPP32 but not ASP175 LI positively correlated with the mitotic index (p=0.001) and PCNA LI (p=0.004). Both CPP32 and ASP175 LIs were increased in nonbenign meningiomas (p<0.0001 and p=0.0035 respectively). In univariate and multivariate survival analyses, caspase-3 predicted meningioma recurrence, independently affecting disease-free survival (p=0.011 and p=0.047 respectively for CPP32; p<0.0001 and p=0.012 respectively for ASP175). Caspase-3 may prove to be a useful predictor of early recurrence in a group of neoplasms characterized by the frequent discordance between histology and clinical behavior.

Symptomatic syringomyelia secondary to clinically obscure infratentorial tumour.

The formation of a cervical spinal cord syrinx as a result of an infratentorial mass, even though uncommon, has been reported in international literature. In such cases, syringomyelia is usually asymptomatic, while the tumour-related symptoms and signs predominate. We report a patient with a posterior fossa tumour and secondary syringomyelia. In this patient, syringomyelia symptoms and signs were present, and a cervical spine Magnetic Resonance Imaging (MRI) showed a large cervical syrinx. A more careful clinical examination though, revealed a sub-clinical posterior fossa syndrome and brain MRI revealed a large infratentorial meningioma. A posterior fossa craniotomy was performed, followed by complete tumour resection and almost complete remission of the syrinx and its related symptoms. The authors discuss the role of posterior fossa tumour induced tonsillar herniation in the development of secondary syringomyelia, the mechanisms leading to syrinx formation and the conditions that must be fulfilled for that to happen.

Primitive supratentorial neuroectodermal tumor in an adult.

We report the case of a 32-year-old female with a diagnosis of supratentorial tumour. Total removal of the tumour was achieved in a two-stage procedure. Histopathology revealed a primitive neuroectodermal tumour (PNET), an unusual and highly malignant, mainly infratentorial tumour of childhood that is uncommonly described in the supratentorial compartment of adults. We review the literature and describe the existing knowledge of these tumours.

Selection of cranial site for shunting debilitated patients.

BACKGROUND/OBJECTIVE: The optimum cranial site for ventricular catheter insertion in CSF shunts is still under debate and there has been no general consensus as far as surgical technicalities are concerned. Furthermore, there have been no reports dealing with appropriate cranial site selection in debilitated patients. The aim of this report is to stress the need to utilize a frontal approach when dealing with patients who are likely to remain bed-bound for long periods and to emphasize the well-known prerequisites such as meticulous surgical technique and peri-operative general and local care. METHOD: A retrospective analysis of all shunt operations and revisions performed in our department during the last 6 years. FINDINGS: This analysis revealed 8 long-term recumbent patients with late valve extrusion (N1 = 5) or primary wound breakdown (N2 = 3), all through the occipital area. Extended periods of bed rest due to neurological disease combined with poor nursing and dietary intake had led to either chronic valve extrusion or wound breakdown. Shunt revision was performed successfully by a frontal approach in 5 whereas 2 tolerated shunt removal and one died of meningitis. CONCLUSION: In debilitated patients or those who are likely to remain bed-bound for long periods, a frontal approach for proximal catheter insertion may help prevent immediate postoperative wound breakdown or late valve extrusion.

Peritumoural haematoma and meningioma: a common tumour with an uncommon presentation.

Spontaneous peritumoural haemorrhage in meningiomas is a rare but serious complication with a grave prognosis. It occurs at the interface between the tumour and the parenchyma, either from the tumour surface or the cortical vessels in association with it. Although several pathophysiologic mechanisms for this complication have been proposed, they all remain speculative. We report a 72-year-old female who presented with sudden onset of headache and a left homonymous hemianopia. Neuroimaging revealed a parasagittal meningioma at the posterior third of the superior sagittal sinus with peritumoural intracerebral haematoma, 1 cm away from the tumour. An uncomplicated gross total excision of the meningioma and aspiration of the haematoma was achieved through a craniotomy. The postoperative course was uneventful with an excellent clinical outcome. Possible mechanisms for this unusual complication are discussed. We emphasise the importance of prompt diagnosis and simultaneous excision of the tumour and aspiration of the haematoma as prerequisites for a favourable outcome.

Hypoxia-inducible factor 1alpha/vascular endothelial growth factor axis in astrocytomas. Associations with microvessel morphometry, proliferation and prognosis.

Hypoxia-inducible factor (HIF)-1alpha is a transcription factor that promotes ischaemia-driven angiogenesis. The aim of this study was to determine the relation of HIF-1alpha to vascular endothelial growth factor (VEGF; an important angiogenic molecule in brain tumours), p53 expression, angiogenesis, proliferative potential and clinical outcome in a large series of diffuse astrocytomas. Expression of HIF-1alpha, VEGF, Ki-67 (a proliferation-associated marker) and p53 was determined immunohistochemically in 83 adult patients with supratentorial diffuse astrocytomas. Microvessels, highlighted by means of anti-CD34 immunohistochemistry, were enumerated with computer-assisted image analysis. Although HIF-1alpha and VEGF were expressed in the majority of cases, their levels increased significantly with increasing grade and proliferative potential. HIF-1alpha positively correlated with microvessel counts and VEGF with total vascular area and the presence of rounder vessel sections. There was a positive correlation of VEGF with p53 expression in astrocytomas and anaplastic astrocytomas. In univariate analysis, both VEGF and HIF-1alpha were associated with shortened survival in the entire cohort, but lost significance when grades II/III and grade IV were analysed separately. Multivariate analysis revealed that the combination of HIF-1alpha with grade was a significant prognostic indicator. HIF-1alpha expression may be used to refine the prognostic information provided by grade in patients with diffuse astrocytomas. Its adverse prognostic effect is most likely mediated by hypoxia, the driving force for HIF-1alpha accumulation.

Infected CNS infusion pumps. Is there a chance for treatment without removal?

BACKGROUND: Intrathecal baclofen administration by means of an implantable pump is nowadays a safe and effective method in the treatment of spasticity. One of the rare but devastating complications of this technique is pump infection, with a variety of Gram (-) and Gram (+) organisms being involved. Treatment of these infections, according to international literature, requires removal of the device and appropriate antibiotic therapy. METHOD: This article reports the authors experience in treating 3 patients with severe, medically intractable spasticity, suffering from infection of the intrathecally-delivering pump. A decision was made not to replace the device, but to treat this complication with pump disinfection and with a new treatment modality that has never been used before, the intra-pocket administration of antibiotics. FINDINGS: In all cases the infection was eradicated and the integrity of the pump maintained. None of the patients required a procedure under general anesthesia. CONCLUSIONS: Removal should no longer be considered the first treatment option in infections of intrathecally delivering pumps, especially those due to non-adherent bacteria, with mild clinical symptomatology. An initial attempt should always be made for conservative treatment. Intra-pocket administration of antibiotics helps in achieving high drugs levels locally, and may prove an important element in our armamentarium against such infections.