Incidence and management of late postsurgical seizures in clinical practice.

AIM: Seizures are a frequent complication in patients who undergo neurosurgery, and can complicate the post-operative course and deteriorate patients' quality of life. Evidence on the prophylactic anticonvulsant therapy after craniotomy is still lacking. MATERIAL AND METHODS: We undertook an observational longitudinal study following neurosurgical supratentorial interventions, to evaluate seizures onset or persistence, and differences in effectiveness between conventional and newer AEDs. RESULTS: A total of 100 consecutive subjects were enrolled. Each patient underwent a neurosurgical treatment by craniotomy. Pre-operative seizures occurred in 33% patients, early seizures in 13%. Late seizures occurred in 46 patients. At baseline (1 month after surgery) and during follow up the main therapeutic regimen was monotherapy. At last follow up adjustment of antiepileptic regimen or AED dosage had rendered 27 subjects seizure free. People taking newer AEDs at baseline maintain the same antiepileptic regimen more often than patients taking conventional AEDs; late seizures tended to have a higher incidence in the latter group. Adverse events from baseline AEDs were reported by 17% of patients. CONCLUSION: In this study population late postsurgical seizures had a remarkable occurrence. Newer AEDs were continued more often than conventional AEDs, with a better tolerability but no significant differences in late seizures incidence.

Delayed otogenic pneumocephalus complicating ventriculoperitoneal shunt.

Tension pneumocephalus complicating ventriculoperitoneal shunt is extremely rare. We report an elderly male who developed delayed tension pneumocephalus 12 months after ventriculoperitoneal shunt for hydrocephalus complicating aneurysmal subarachnoid hemorrhage. Fine-cut reformatted computer tomography scan revealed a large pneumatocele on the petrous apex associated with tegmen tympani defect. The shunt valve pressure was temporarily raised from 120 mm H 2 O to 200 mm H 2 O, and the patient underwent successful subtemporal extradural repair of the bony defect in the temporal bone. Although extremely rare, otogenic tension pneumocephalus is a potentially life-threatening condition, and urgent surgical repair of the bony defect in the temporal bone reduces the risk of both the morbidity and mortality.

In stent restenosis predictors after carotid artery stenting.

Purpose. The long-term efficacy of carotid artery stenting is debated. Predictors of stent restenosis are not fully investigated. Our aim was to assess the incidence of long term restenosis after CAS and to identify some predictors of restenosis. Methods. We retrospectively selected 189 treated patients and we obtained the survival Kaplan-Meier curves for overall survival, for freedom from stroke or death and from restenosis. To correlate clinical, radiological, and procedural variables to stent restenosis, an univariate analysis was performed while to determine independent predictors of restenosis, a multivariate analysis was applied. Results. At 1, 3, and 5 years, the cumulative overall survival rate was 98%, 94%, and 92% with a cumulative primary patency rate of 87%, 82.5%, and 82.5%. The percentage residual stenosis after CAS and multiple stents deployment were independent predictors of restenosis, while diabetes and tumors are suggestive but not significant predictors of restenosis. Conclusions. In our CAS experience, encouraging long-term results seem to derive from both neurological event free rate and restenosis incidence. Adequate recanalization of the treated vessel is important to limit the development of stent restenosis. Multiple stents deployment, and with less evidence, diabetes, or neoplasms has to be considered to facilitate restenosis.

Malignant transformation of intramedullary melanocytoma: case report.

OBJECTIVE: Meningeal melanocytomas are low-grade primary melanocytic tumors with benign histological features and a favorable clinical prognosis. Transition from meningeal melanocytoma to primary melanoma of the central nervous system is exceptionally rare, with only 5 cases having been previously reported. Here, we discuss a case of malignant transformation of an intramedullary melanocytoma to primary melanoma and review the pertinent literature. CLINICAL PRESENTATION: A 79-year-old woman presented with progressive paresis in the lower limbs followed by sphincter dysfunction. Magnetic resonance imaging scans disclosed an intramedullary lesion located at the T10-T11 level. INTERVENTION: The patient underwent subtotal resection of an intermediate-grade melanocytoma. Two years later, the tumor recurred locally, and the patient underwent additional surgery to remove the intramedullary mass. The histological findings of the tumor were consistent with an intramedullary malignant melanoma. CONCLUSION: The malignant transformation of melanocytic tumors of the central nervous system may occur years after surgical treatment, and its incidence remains unknown. Emphasis should be placed on the importance of careful and continued follow-up monitoring of the tumor.

Niels Stensen (1638-1686): scientist, neuroanatomist, and saint.

Niels Stensen (1638-1686) was a prominent Danish scientist who laid the foundations of paleontology, geology, and crystallography. He undertook a personal search for the truth, rejecting many assumptions of his time, and he struggled to acquire a firm foundation of knowledge based on close observation and rigorous experimentation. Niels Stensen is known eponymously for the discovery of the duct of the parotid gland (ductus stenonianus) but most clinicians are not familiar with his contributions to anatomy beyond his studies on the glands. In 1665, he delivered a lecture in Paris on the anatomy of the brain, the Discours sur l'anatomie du cerveau ("A Dissertation on the Anatomy of the Brain"), which is a seminal investigation on methods in neuroscience. His scientific letter on a hydrocephalic calf represents an early pathophysiological investigation on hydrocephalus. In 1667 Stensen converted to Catholicism and in 1677 he was consecrated titular bishop of Titiopolis. He spent the last years of his life in poverty and traveled continuously trying to bring back northern Europe to Catholicism. This essay highlights the life and the scientific contributions of Niels Stensen, with emphasis on his contributions to neuroscience.

Thoracic extradural haematoma after epidural anaesthesia.

The administration of analgesics to the thoracic spine is established practice in the operating room, minimizing the need for systemic anaesthetic administration during thoracic surgery. Complications arising from thoracic epidural anaesthesia are uncommon but potentially disastrous. Here, we report the case of a 43-year-old woman who developed a thoracic epidural haematoma with paraplegia a few hours after the removal of an epidural catheter. The patient underwent emergency thoracic laminectomy and clot evacuation. After a 4 months period, there was almost complete neurological recovery. Epidural haematoma is a rare complication that must be heeded and urgently treated in case of clinical deterioration after the epidural analgesia.

Gamma-glutamyltransferase activity in human atherosclerotic plaques--biochemical similarities with the circulating enzyme.

BACKGROUND AND PURPOSE: Serum gamma-glutamyltransferase (GGT) activity has been identified as a predictor of complications of atherosclerosis, with a prognostic value for cardiovascular diseases and stroke. Human atherosclerotic lesions contain active GGT, which can give rise to pro-oxidant molecular species; thus a direct contribution of GGT to atherosclerosis progression is conceivable. The relationship between plaque and serum GGT is however unclear. METHODS AND RESULTS: Human carotid plaques obtained from 18 consecutive patients undergoing carotid endoarteriectomy were analyzed, of which 6 were used for anion exchange and gel filtration chromatography/western blot studies, 7 for beta-lipoprotein precipitation, and 5 for RNA extraction and determination of low molecular weight thiols. Mean GGT activity in crude plaque homogenates was 60.9+/-21.5 (S.D.) mU/g tissue. The characteristics of GGT activity were compared in plaque homogenates and in serum obtained from controls (healthy blood donors). The methods employed (anion exchange and gel chromatography, western blot) showed the presence in plaque homogenates of two distinct complexes containing GGT activity, one of which comparable with plasma LDL/GGT complexes. Accordingly, precipitation of beta-lipoproteins from plaque homogenates resulted in removal of GGT activity. RT-PCR indicated in plaques the presence of GGT mRNA transcribed from GGT-I gene. Analysis of plaque extracts also revealed the presence of enzyme product cysteinyl-glycine both as free and protein-bound form, confirming that GGT-dependent pro-oxidant reactions may occur within the plaque environment. CONCLUSIONS: The results obtained suggest the presence in plaques of a serum-like GGT protein, indicating that a direct contribution of serum GGT to enzyme activity found within atherosclerotic lesions is possible. Data also indicate the occurrence of GGT-mediated redox reactions within plaque environment, which might influence plaque progression.

Expression of cyclooxygenase-2 and its correlation with vasogenic brain edema in human intracranial meningiomas.

COX-2 expression was evaluated in intracranial meningiomas, relating this molecule to grade, vasculature, VEGF and brain edema. Fifty-six tumors were evaluated for COX-2 and VEGF expression and for microvessel density. In 34/56 cases, the edema was evaluated by CT scan. COX-2 was detected in 46/56 meningiomas (82.14%), and it resulted as being related to histologic grade (t-test: p = 0.006) and to edema (t-test: p = 0.002). No statistical association between COX-2 and VEGF or MVD was found. In conclusion, COX-2 seems to be related to the more aggressive meningiomas and, somehow, to the development of meningioma-associated brain edema.

Human brain tumors: multidrug-resistance P-glycoprotein expression in tumor cells and intratumoral capillary endothelial cells.

Malignant brain tumor is a lethal disease with currently available treatment options having a limited impact on outcome. Nevertheless, novel therapeutic approaches combined with genetic prediction of chemosensitivity have, in the last decade, significantly improved clinical benefit for the treated patients. The fine characterization of the MDR1 gene encoding for P-glycoprotein (MDR1-Pgp) in brain tumors may be a crucial determinant for evaluating the long-term efficiency of specific anti-cancer compounds. By using a very high specific monoclonal antibody, the MDR1-Pgp was immunodetected in 34 out of 43 grade IV, 6 out of 10 grade III, 4 out of 7 grade II, and 1 out 3 grade I brain tumors. MDR1-Pgp resulted hyper-expressed, both in vessels and in neoplastic cells from the majority of tumors examined, compared to normal parenchyma. This study demonstrates that the MDR1 gene can be detected in all grade tumor brain malignancies and in endothelial cells of newly formed capillaries, thus, impairing drug access at the tumor cell level. Although the role of MDR1-Pgp in tumor blood vessels needs to be further examined and more clearly defined, drug resistance in malignant brain tumors may result from characteristics not only of tumor vasculature but also of neoplastic cells.

Expression of endothelin 1 and its angiogenic role in meningiomas.

Meningiomas are one of the most frequent central nervous system tumours. Although slow-growing at times, they continue to be a cause of morbidity and mortality. The endothelin (ET) family consists of three isoforms: ET-1 is the most abundant one. ET-1 may be involved in meningioma tumourigenesis in concert with other growth factors, in particular with angiogenic agents. We analysed ET-1 expression by immunohistochemistry and its activating system by reverse-transcription-polymerase chain reaction in 56 cases of meningioma. We found an association between high-grade meningiomas and high ET-1 expression levels (p=0.002). Moreover, we evaluated the potential angiogenic role of ET-1, finding an elevated microvessel count in tumours with high ET expression levels (p=0.004). ET-1 may contribute to meningioma growth by inducing formation of new blood vessels. The finding that ET-1 expression positively correlates with vascular endothelial growth factor (VEGF) expression in meningiomas (p=0.03) also supports the hypothesized modulating effect of ET-1 on angiogenesis. Thus, the influence of the ET system on the progression of meningiomas may occur through stimulation of VEGF. The association of ET-1 and meningioma represents a potential area for therapeutic intervention with selective ET inhibitors. Additional clinical studies will be needed before inhibitors can be incorporated in clinical practice.

Silent cerebral ischemia detected with diffusion-weighted imaging in patients treated with protected and unprotected carotid artery stenting.

BACKGROUND AND PURPOSE: Percutaneous transluminal angioplasty with stent (CAS) is an alternative method to endarterectomy in the revascularization of carotid artery stenosis. Protected CAS is currently used to prevent distal embolization. Diffusion-weighted MRI (DWI) is the most sensitive tool to evaluate silent cerebral ischemia. The purpose of this research was to assess the incidence of cerebral embolic lesions during CAS and to evaluate whether cerebral protection devices can reduce the number of silent cerebral ischemia with respect to unprotected CAS. METHODS: Fifty-two patients with high-grade internal stenosis underwent CAS; 30 patients (group a) were treated with a cerebral protection device, and 22 (group b) were treated without it. All of the patients were evaluated preoperatively and postoperatively with fluid-attenuated inversion recovery and DWI sequences to depict the number of new embolic silent cerebral lesions. RESULTS: Embolic silent cerebral lesions occurred in 30% of CAS. Cerebral protection devices reduce the number of new lesions significantly reducing the consistent lesions ipsilateral to the treated vessel. Inconsistent lesions do not differ in both groups of patients. Clinical, radiological, and procedural variables do not correlate with the appearance of new cerebral lesions. CONCLUSIONS: Embolic cerebral lesions detected with DWI are more frequent with unprotected CAS, although they are present also with the use of cerebral protection devices. Probably a part of silent cerebral lesions arise from the procedural maneuver in the aortic arch.

Redistribution of cerebropetal blood flow in patients with carotid artery stenosis measured non-invasively with fast cine phase contrast MR angiography.

The purpose was to evaluate the blood flow redistribution in the neck vessels of patients with internal carotid artery (ICA) stenosis. Eighty-six patients with ICA stenosis underwent contrast-enhanced magnetic resonance angiography (CEMRA) and fast 2D phase contrast (2D-PC) sequence to measure the mean blood flow (MBF) of ICA, basilar artery (BA) and middle cerebral artery (MCA). CEMRA revealed 53 severe stenoses, 45 moderate stenoses and 3 occluded vessels. Patients with a unilateral severe ICA stenosis had a significantly reduced MBF of the ICA compared to the control group; the MBF reduction of the severely stenosed ICA was less conspicuous if associated with a controlateral severe stenosis. The MBF of the BA increased significantly in the presence of the bilateral severe ICA stenosis and in the ICA occlusion. The MBF of the MCA was unchanged in the presence of various degrees of ICA stenosis. Measurement of MBF with fast PC MRA permits cerebropethal blood flow assessment and gives additional information in grading ICA stenosis. The reduced MBF of a severe ICA stenosis has to be considered with caution since it depends also on the status of the controlateral ICA and may be considered a confident parameter only in case of unilateral carotid stenosis.

Immunohistochemical and molecular study of radiation-induced multiple meningiomas with pleural and pulmonary metastasis.

In the present study, the telomerase activity and the putative alterations of genes involved in cell-cycle control (p53, Fas and pRb) were investigated in a radiation-induced meningioma with multiple recurrences and pleural-pulmonary metastases (the patient, a 34-year-old male, had a history of carcinoma of the tongue of testicular lymphocytic lymphoma). Expression of VEGF and vasculature pattern were also studied. Expression of VEGF, pRb and p53 were evaluated by immunohistochemistry on formalin-fixed, paraffin-embedded samples of the tumor. VEGFmRNA was determined by competitive PCR. Fas, FasL and hTERT were evaluated by RT-PCR. Telomerase activity was examined by the TRAP assay. An intense vascularization was observed, supported by high expression of VEGFmRNA (isoforms 121 and 165). pRb and p53 were overexpressed. Fas was undetectable with PCR, whereas FasL was positive. Furthermore, the lesion showed an elevated telomerase activity (TPG, 22), according to the high expression of hTERT. These findings emphasized that even among generally benign neoplasms, such as meningiomas, some highly malignant tumors may develop, as in our case, in which several mechanisms were activated in the cancer progression to guarantee the immortalization of cellular clones (angiogenic phenomenon, activation of telomerase and of anti-apoptotic mechanisms) and the blood spread. Thus, the data illustrate the importance of searching for genetic aberrations (which are a hallmark of malignancy) in meningiomas, as predictive and reliable factors of the possibility to recur and to metastasize.

The role of somatostatin in vasogenic meningioma associated brain edema.

Many tumors, including meningiomas, express somatostatin receptors, suggesting the application of somatostatin analogues for therapy and diagnosis. Sixty percent of meningiomas are associated with perilesional edema, whose development seems to be related to the vascular endothelial growth factor, although it requires an efficient pial blood supply. However, in several neoplastic models, other mediators seem to cooperate with vascular endothelial growth factor in regulating angiogenesis. We evaluated somatostatin receptors (sst2) in relation to the possibility that somatostatin analogues may influence vascular endothelial growth factor production with reduction of edema. Of 35 studied meningiomas, 21 presented peritumoural edema. Vascular endothelial growth factor, microvascular density and pial blood supply were significantly related to the edema (P = 0.0001, P = 0.0001, P = 0.0005). Similarly, a relation was found between sst2 and microvascular density (r = 0.58, P < 0.001) and between sst2 and vascular endothelial growth factor expression (P = 0.03). This suggests that somatostatin analogues may be relevant for the treatment of meningiomas.

Contrast-enhanced three-dimensional magnetic resonance angiography of atherosclerotic internal carotid stenosis as the noninvasive imaging modality in revascularization decision making.

BACKGROUND AND PURPOSE: In patients with severe internal carotid artery stenoses, thromboendarterectomy significantly reduces both ischemic stroke and the risk of more ischemic attacks. Digital subtraction angiography (DSA) is the accepted preoperative test to determine whether a high-grade stenosis is present and requires surgical therapy. However, DSA has a procedural risk of stroke between 0.7% and 1%. An accurate, noninvasive imaging protocol with no risk of severe complications would significantly increase the benefit of surgical treatment. The aims of the study were (1) to evaluate the diagnostic accuracy of contrast-enhanced magnetic resonance angiography (CEMRA) in detecting and grading internal carotid artery stenoses and (2) to assess the misclassification rate of vessels suitable for revascularization by CEMRA. METHODS: Ninety-two patients with sonographic evidence of neck vessel stenosis were enrolled in the study. All patients were submitted to CEMRA and DSA. CEMRA images were evaluated for the presence of mild, moderate, or severe stenosis and occlusion. RESULTS: Sensitivity, specificity, and diagnostic accuracy were 97%, 82%, and 92.5%, respectively. Agreement with DSA was optimal at kappa=0.87. The misclassification rate of CEMRA was 3.1% because of its tendency to overestimate the stenosis. CONCLUSIONS: The high diagnostic accuracy and limited misclassification rate suggest that CEMRA can be considered a powerful tool for the preoperative, noninvasive evaluation of atherosclerotic pathology of carotid arteries.