Neurological outcomes after surgery for spinal metastases in symptomatic patients: Does the type of decompression play a role? A comparison between different strategies in a 10-year experience.

INTRODUCTION: The impact of neurological deficits plays a role of inestimable importance in patients with a neoplastic disease. The role of surgery for the management of symptomatic spinal cord compression (SSCC) cannot be overemphasized, as surgery represents often the first and paramount step in patients presenting with motor deficits. The traditional paradigm of simple bilateral laminectomy for the treatment of spinal cord compression has been reviewed. The need to achieve a proper circumferential decompression of the spinal sac has been progressively highlighted in combination with the development of the more comprehensive and multidisciplinary concept of separation surgery. OBJECTIVE: The aim of this paper is to analyze different strategies of decompression, while evaluating whether circumferential/anterior decompression is able to guarantee a better control and restoration of neurological functions in patients with motor impairment, if compared to traditional posterior decompression. MATERIALS AND METHODS: This is a retrospective observational study investigating symptomatic patients that underwent surgical treatment for spinal metastases at author's Institutions from January 2010 to June 2019. Data recorded concerned patient demographics, tumor histology, peri-operative and follow-up neurological status (ASIA), ambulation ability, stability (SINS), grade (ESCC) and source of epidural compression and type of decompression (anterior/anterior-lateral (AD); posterior/posterior-lateral (PD/PDL); circumferential (CD)). RESULTS: A total number of 84 patients was included. AD/CD patients showed higher chance of neurological improvement and reduced rates of worsening compared to PD/PLD group (94.1%/100% vs 60.4%; 11.8% vs 45.8% respectively). Univariate logistic regression identified immediate post-operative improvement to be a significative protective factor for worsening at last follow-up. Stratifying patients for site of compression and considering anterior and circumferential groups, immediate post-operative neurological improvement, was mostly associated with AD and CD (p 0.011 and 0.025 respectively). Walking at last follow up was influenced by post-operative maintenance of ambulation (p 0.001). CONCLUSION: The necessity to remove the epidural metastatic compression from its source should be considered of paramount importance. Since the majority of spinal cord compression involves firstly the ventral part of the sac, CD/AD are associated with better neurological outcomes and should be achieved in case of circumferential or anterior/anterolateral compression.

Double concentric craniotomy: Safe and effective technique to achieve an en bloc resection of tumor involving both skull and duraa.

INTRODUCTION: Many tumors can involve the skull. Meningiomas are one of the most common intracranial neoplasms and invasion of the bone was described in 49% of cases. Other neoplastic lesions that can arise in bone, or involve it, are metastases, hemangiomas, aggressive cutis carcinomas and sarcomas. Radical excision is the golden standard of treatment but elevating a bone flap when the tumor involves both the skull and the dura could represent a technical challenge. PRESENTATION OF CASE: We report the technical details of our approach to remove a meningioma involving both skull and dura in a man aged 45. Patient underwent gross total excision and cranioplasty with PEEK custom made prothesis (Synthes™). DISCUSSION: We describe a double concentric craniotomy (DCC) technique where the tumor involving the bone is before left in situ, exposing normal dura, to perform afterwards en-bloc excision with minimal traction of brain surface. CONCLUSION: DCC is a safe and effective technique to remove tumor involving both skull and dural structures under direct vision.

Deficiency of total collagen content and of deoxypyridinoline in intracranial aneurysm walls.

The tissue contents of total collagen and of 3-hydroxypyridinium cross-links, pyridinoline (PYD) and deoxypyridinoline (DPD), were measured in 15 samples of human aneurysms of Willis' Circle obtained at surgery and in 25 autopsy control samples of intracranial arteries of Willis' Circle obtained from 6 subjects who died of other causes than cerebral hemorrhage. PYD and DPD were detected fluorimetrically after HPLC separation. Total collagen content was significantly lower (P < 0.001) in aneurysm samples (mean +/- S.E.M. 2.50 +/- 0.33 nmol of alpha 1(I) collagen chain per mg of delipidated and dried material) than in controls (mean +/- S.E.M. 3.86 +/- 0.14). DPD, but not PYD, content appears to be lower in aneurysm walls. In the aneurysms, the tissue contents of PYD ranged from 212 to 587 pmol/nmol of alpha 1(I) collagen chain (mean +/- S.E.M. 430 +/- 31) while in control samples the values observed ranged from 292 to 642 (mean +/- S.E.M. 471 +/- 21). The tissue content of DPD was measurable only in 6 aneurysm samples (60%), ranging from 12 to 60 pmol/nmol of alpha 1(I) collagen chain (mean +/- S.E.M. 33 +/- 9), while in control samples, DPD content ranged from 30 to 123 (mean +/- S.E.M. 75 +/- 5).

Oxidative events in neuronal and glial cell-enriched fractions of rat cerebral cortex.

The aim of this work was to investigate how neurons and glial cells separated from rat brain cortex respond to "in vitro" oxidative stress induced by incubation of the cellular fractions in the presence of prooxidant mixtures; in addition, the endogenous enzymatic antioxidant capacity of the purified fractions was investigated. Neuronal and glial cell-enriched fractions were obtained from rat cerebral cortex following passages of the tissue through meshes and centrifugations. The following parameters were evaluated: antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSHPx), and glucose-6-phosphate dehydrogenase (G6PDH); lipid peroxidation products (TBARS) prior to (basal) and after (iron-stimulated) incubation with a mixture of iron and ascorbic acid; intracellular production of reactive oxygen species (ROS) using a fluorescent probe, dichlorofluorescin-diacetate, in basal, iron-stimulated, and menadione stimulated conditions. SOD and GSHPx activities showed no significant changes between neurons and glia, whereas CAT and G6PDH activities were found to be significantly lower in glia than in neurons. TBARS levels were significantly lower in the glial fraction than in neurons, both in basal and iron-stimulated conditions. ROS production showed no differences between neurons and glia in both basal and menadione-stimulated conditions. Iron-stimulation produced a marked increase in ROS production, limited to the neuronal fraction, with the glial values being similar to the basal ones. Our conclusion is that glia and neurons isolated from rat cerebral cortex show a similar pattern of the most important antioxidant enzymes and of their basal ROS production, whereas glia is more resistant in "oxidative stress" conditions.

Activity of alpha 1-antitrypsin and cigarette smoking in subarachnoid haemorrhage from ruptured aneurysm.

An altered equilibrium of protease/protease-inhibitor factors may be involved in the pathogenesis of aneurysm rupture: alpha 1-antitrypsin (alpha 1-AT) represents the most relevant inhibitor of elastase, a proteolytic enzyme enhancing catabolic processes of collagen metabolism. Cigarette smoking has been shown to significantly reduce the inhibitory effect of alpha 1-AT on proteases. In the present study we test the hypothesis whether the activity of alpha 1-AT is altered in patients with subarachnoid haemorrhage (SAH) and if is there any relationship between alpha 1-AT activity and the high risk of aneurysm rupture in smokers. The patients were subdivided in the following groups: (a) patients with unruptured aneurysm (n = 10); (b) patients presenting with SAH admitted within 48 h after the episode (n = 20); (c) patients presenting with SAH admitted > 48 h after the episode (n = 14); (d) controls (n = 10): patients with neither cerebrovascular nor acute disease. Blood samples were obtained immediately at admission. Measurement of alpha 1-AT level was determined by immunoturbidimetric method. In order to obtain qualitative data about the anti-protease activity of alpha 1-AT (expressed as collagenase inhibitory percentage capacity (CIC) at different doses) we consider the 20 cases admitted for SAH within 48 h. The mean serum level of patients with unruptured aneurysms is significantly lower than that of patients with SAH (p < 0.01), while the mean serum level of alpha 1-AT in controls does not significantly differ from other groups. The mean serum level of alpha 1-AT in patients admitted > 48 h after SAH is significantly higher than that of patients admitted within 48 h after the haemorrhage (p < 0.02). Considering the smoking habit of patients, there is no significant difference in alpha 1-AT levels in each subgroup of patients. A multivariate analysis considering alpha 1-AT CIC, showed that alpha 1-AT CIC in patients with ruptured aneurysms is significantly reduced if compared to controls and unruptured aneurysms (F = 50.759; p < 0.001). Moreover, considering alpha 1-AT CIC and smoking habit in each group the covariance analysis showed that while in controls and unruptured aneurysms there is no difference in alpha 1-AT CIC between smokers and non smokers, in cases of SAH, cigarette smoking significantly influences the alpha 1-AT CIC. The present results suggest that the basic mechanism behind the increased risk of SAH in smokers involves a qualitative deficiency of alpha 1-AT.

Collagen cross-linkage, elastolytic and collagenolytic activities in cerebral aneurysms: a preliminary investigation.

The pathogenesis of aneurysms formation and rupture is not clearly understood and is undoubtedly a multifactorial event. It is generally accepted that the aneurysm arises from an interaction between structural weakness of arterial wall and hemodynamic factors. Previous studies suggested the possible role of collagenolytic and elastolytic activities in aneurysm development, leading to extracellular matrix alteration. The content of collagen 3-hydroxypiridinium cross-links and elastase and collagenase activities were measured in 12 samples of intracranial aneurysms and in control specimens obtained from temporal superficial arteries and from autoptic samples of Willis Circle. Collagen content is significantly lower in aneurysm than in autoptic control samples (p < 0.01). The total amount of cross-links is significantly lower in ruptured aneurysms than in unruptured and autoptic controls (p < 0.01). Collagenase and elastase activities are significantly increased in ruptured cerebral aneurysms versus unruptured aneurysms (p < 0.01). Linear regression shows that an inverse relationship exists between cross-links content and both elastolytic (p = 0.0032) and collagenolytic (p < 0.001) activities in aneurysmal samples. Multiple regression shows that collagenase has a more important statistic impact (p = 0.027) than elastase (p = 0.08). The results of the study supports the hypothesis that an imbalance of protease-antiprotease homeostasis with elevated collagenolytic and elastolytic activities may represent the predisposing condition leading to aneurysms rupture through collagen depauperation and reduced cross-linkage of collagen fibres.

Antioxidant status and alpha1-antiproteinase activity in subarachnoid hemorrhage patients.

The antiproteasic activity of alpha1-antitrypsin (alpha1-AT) is reduced in cases of subarachnoid hemorrhage from ruptured intracranial aneurysm and particularly in patients currently smoking; alpha1-AT is very sensitive to oxidant agents. About 50% of physiological anti-oxidant systemic capacity is represented by Vitamin A, E and C. Plasmatic amounts of alpha1-AT, alpha1-AT Collagenase Inhibitory Capacity (CIC) and levels of vitamin A, vitamin E and vitamin C were analyzed in 39 patients, 26 women and 13 men, operated for intracranial aneurysm; 11 patients with unruptured intracranial aneurysm were considered as controls while 28 patients were included within 12 hours from subarachnoid hemorrhage (SAH). Plasmatic levels of vitamin A and vitamin E were significantly lower (p=0.038 and p=0.0158) in patients suffering SAH than in controls, while no statistically significant differences were found in mean plasmatic vitamin C levels. Level of alpha1-AT was not statistically different in controls and in patients with SAH; however, the activity of alpha1-AT, evaluated as CIC, is significantly reduced in patients with SAH (p=0.019). We have observed that systemic plasmatic levels of vitamins did not significantly differ in relation to smoking habit. Vitamin A and E represent an important defensive system against free radicals reactions. Particularly, vitamin E acts as an antioxidant by scavenging free-radicals. A reduced anti-oxidant status might be related to the higher sensibility of alpha1-AT to oxidative reactions and the activity of alpha1-AT is dependent on the antioxidant capacity of liposoluble vitamins. We can speculate that an acute systemic oxidative stress condition might influence the rupture of intracranial aneurysms.

Alpha 1-antitrypsin activity in subarachnoid hemorrhage.

An altered equilibrium of protease/protease-inhibitor factors may be involved in the pathogenesis of aneurysm rupture: alpha 1-antitrypsin (alpha 1-AT) represents the most relevant inhibitor of elastase, a proteolytic enzyme enhancing catabolic processes of collagen metabolism. In the present study we test the hypothesis whether the activity of alpha 1-AT is altered in SAH patients; 5 cases with unruptured intracranial aneurysm and 27 patients with diagnosis of aneurysm SAH were included in the study. Blood samples were obtained immediately at admission. As control samples we consider the 5 cases of unruptured aneurysm, 15 cases of unruptured aortic aneurysms and 10 patients with non-vascular CNS diseases. Measurement of alpha 1-AT level was determined by immunoturbidimetric method. Serum levels of alpha 1-AT are significantly lower in patients admitted within 72 hours after SAH, if compared to patients admitted in a delayed phase. The linear relationship between alpha 1-AT and collagenase inhibitory percentage capacity (CIC) was shown to be different in the 4 subgroups considered, and so were the mean % CIC values in the between-groups comparison, except for unruptured aneurysm vs controls. The alpha 1-AT CIC in patients with SAH is shown to be the lowest when compared to controls and unruptured aneurysms (p = 0.0001).

Cisternal CSF levels of cytokines after subarachnoid hemorrhage.

Cytokines are considered as mediators of immune and inflammatory responses. Cisternal CSF levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-1) and of the soluble adhesion molecule E-selectin were evaluated in patients operated on for intracranial aneurysms. Cisternal CSF samples were obtained at surgery in 41 selected patients (31 with diagnosis of subarachnoid hemorrhage (SAH) and 10 control patients operated on for incidental unruptured aneurysms); 14 patients were operated within 72 h after SAH (early surgery) and 17 were operated after day 10 after the hemorrhage (delayed surgery). The CSF levels of cytokines were evaluated using radioimmunoassay and their concentrations were related to the timing of surgery, the amount of cisternal subarachnoid blood clots and the onset of clinical and angiographical evidence of arterial vasospasm. Mean cisternal CSF levels of IL-6, IL-8 and AMCP-1 are significantly higher in samples obtained from patients early operated after SAH, while levels of E-selectin were below the threshold value of the method in all 41 cases. In the early operated group 7 patients presented symptomatic vasospasm: levels of IL-8 and MCP-1 were not significantly different were compared to those of uncomplicated cases; on the other hand, significantly higher levels of IL-6 were shown in the subgroup of patients operated within 72 h after SAH and developing vasospasm. Among the patients undergoing delayed surgery 5 presented symptomatic vasospasm, but no significant difference was shown in cisternal CSF levels of cytokines measured. The results of the present study show that in patients with unruptured aneurysms cytokines are present in cisternal CSF in scarce quantities and that in subarachnoid spaces after SAH there is an impressive increase of IL-6, IL-8 and MCP-1. Moreover, the higher cisternal CSF levels of IL-6 found in the early stage after SAH might have a predictive value regarding the occurrence of symptomatic vasospasm.

Abnormalities of collagen cross-linkage in posterior communicating artery aneurysms: a preliminary study.

The collagen of tissues submitted to mechanical load (i.e. arterial wall) is characterised by the presence of intermolecular covalent cross-links (hydroxylysyl pyridinoline or pyridinoline: PYD; and lysyl-pyridinoline or deoxypyridinoline: DPD) which stabilise the molecular structure. In this preliminary study we look for quantitative or qualitative alterations of collagen cross-linkage in intracranial aneurysms of posterior communicating artery (PCoA) which may be considered a site of elective weakening in the intracranial arterial circulation, being one of the most frequent locations of intracranial aneurysms and of so called "infundibular widening'. We analysed the collagen cross-linkage in 6 autopsy samples of intracranial arterial segments of the Circle of Willis which were removed from patients whose cause of death was other than cerebral hemorrhage, and in 6 samples of intracranial PCoA aneurysms obtained at surgery. The analysis of cross-links showed that there was no significant difference in collagen and cross-link content between autopic and aneurysmatic samples except for PCoA. In autoptic nonaneurysmatic samples of PCoA a lower content of PYD than in internal carotid artery (ICA) and a lower content of DPD than in all other arterial segments has been demonstrated; moreover a lower content of cross-links (DPD + PYD/ Collagen) was evident in nonaneurysmatic PCoA samples when compared to other segments (ICA and Anterior Communicating Artery). On the other hand, the mean content of DPD was significantly lower in PCoA aneurysms than in nonaneurysmatic samples of the artery and moreover, a significantly low content of cross-links (DPD + PYD/Collagen) is overemphasised in PCoA aneurysms, suggesting that the peculiar lower content of DPD in PCoA arteries may be considered the expression of minor resistance of the arterial wall at this site, and may be related to the higher incidence of aneurysms or infundibular widening of this arterial segment.

Metalloproteases and intracranial vascular lesions.

Recent studies have suggested that metalloproteinases (MMP) might be involved in the pathogenesis of cerebral aneurysm formation and rupture and that elevated serum levels of MMP may effectively be considered as possible markers of cerebrovascular malformations. The present study was planned in order to verify if serum levels of MMPs may be the mirror of the MMP activity in the wall of intracranial aneurysms, reflecting the predisposition to aneurysm development and/or rupture. A series of 84 patients operated for intracranial cerebrovascular lesions (63 aneurysms and 21 arterovenous malformations (AVM)) and 20 controls entered the study. Among the 63 cases of intracranial aneurysms, nine were discovered before rupture, while 54 patients were included after subarachnoid hemorrhage (SAH). Using radioimmunoassay, plasma elastase levels were measured in all cases, while in 25 cases, when aneurysmectomy was possible, the activity of elastase and collagenase were measured in aneurysm samples. Mean plasma elastase level in patients bearing both an intracranial aneurysm or an intracranial AVM was significantly higher than in controls, while there was no significant difference between plasmatic level of elastase in patients with aneurysms when compared with patients bearing an intracranial AVM; there was no significant difference between mean elastase level in patients who suffered SAH and patients bearing an intracranial unruptured aneurysm. The activity of elastase and collagenase measured in the aneurysm wall were significantly higher in cases of ruptured than in unruptured aneurysms. The present results show that plasmatic level of elastase does not reflect the activity of MMP as measured in the aneurysm wall and that the patterns of MMP activities measured in the aneurysm wall differ considerably at different stages of SAH. This suggests that local rather than systemic changes in metalloproteases activity might be involved in cerebral aneurysm formation and rupture.

Spinal epidural hematoma during anticoagulant therapy. A case report and review of the literature.

The authors present a case of spinal epidural hematoma during anticoagulant therapy. Clinical presentation is characterized by classic paravertebral back pain, followed by progressive neurological deficit due to spinal cord and radicular compression, with sensory deficits and bladder disturbance. From the literature, 37 cases are collected of spinal epidural hematoma during anticoagulant therapy, treated surgically. Pathogenesis, diagnosis, and differential diagnosis are discussed. Early surgical decompression of the spinal cord minimizes the degree of permanent neurological damage, because of the long-time compression of the spinal cord resulting in irreversible disturbance of circulation; therefore an early diagnosis is a better prognosis. The thoracic and cervical spine canal is smaller than the lumbar, therefore there is less space to reward the formation of hematomas, consequently the postoperative recovery is lower in patient with high spinal epidural hematomas with respect to lumbo-sacral spinal epidural hematomas; at this level the epidural hematoma may be insidious in its onset and tends to become chronic before definite treatment is undertaken.

Vertebral arterio-venous fistula presenting with intracranial hemorrhage.

Vertebral arteriovenous fistulas are rare lesions consisting of an abnormal shunt between the extracranial vertebral artery and the neighboring veins. The authors present a case of post-surgical high-flow left vertebral arteriovenous fistula presenting with intracranial hemorrhage. The patient underwent endovascular balloon occlusion of the fistula: after endovascular treatment a reduction of the flow was evident but the patient presented neurological deterioration related the occurrence of intraventricular-subarachnoid hemorrhage. Intracranial hemorrhage is a potential manifestation of high-flow vertebral AVF and a possible complication of endovascular fistula balloon occlusion. Direct endovascular occlusion of the vertebral artery may be primarily considered in selected cases.

Glial cyst of the pineal gland: case report and considerations about surgical management.

Symptomatic glial cyst of the pineal gland are rare lesions. Origin, natural history and factors leading to cyst enlargement are not completely clear; thus management remain uncertain in some cases. We report a case of symptomatic glial cyst and analyze the implication for surgery. Surgical management is indicated in patients presenting hydrocephalus, mass effect or symptoms related to mesencephalic dysfunction. The infratentorial supracerebellar approach represent the first choice for this condition allowing easy orientation with wide exposure of the tumor and good visibility of deep venous systems that may be preserved. Size of the tumor is a key element in evaluation of the treatment and the appropriate course for asymptomatic cyst less than 1 cm in size consist of conservative management. Periodic follow up is always indicated.

Fatal carotid dissection after blunt head trauma.

Occurrence of internal carotid artery injuries associated with skull base fracture has been reported. A. report a case of fatal intracranial carotid dissection related to petrous fracture involving the carotid canal. Identification of carotid lesions may be difficult and generally related to appearance of unexpected neurological deficit. Skull base fractures may be considered an indirect sign for detection of vascular injury. Patterns of the fracture are of paramount importance; routine CT scan may fail to detect basilar fractures and high definition fine-cut CT scan should be executed to carefully identify and evaluate fractures. Temporal and sphenoid bone fractures are common in head trauma and involvement of the course of the carotid artery is frequent. The involvement of the intracranial carotid artery course represents a direct risk factor for lesions of the petrous, lacerum and cavernous segments of the carotid artery. Early diagnosis of post-traumatic vascular injury may lead to prognosis improvement because of effectiveness of heparin anticoagulant therapy. Then vascular screening is recommendable in cases with complex fractures of the skull base and particularly fracturing along the course of the carotid artery. Magnetic resonance angiography may be considered the first line diagnostic tools for vascular screening. Angiography may be reserved for patients with a proven lesion or rapid neurological deterioration taking into account the possibility of interventional treatment.

Chondrosarcoma of the thoracic spine: total en bloc sagittal resection. A case report.

Chondrosarcomas located in the spine are uncommon tumors and are challenging to manage. A case of a 65-year-old man with a T3-T4 spine chondrosarcoma is reported. The onset of symptoms consisted in progressive dorsal pain with sometimes a girdle-like radiation and, successively, in dysaesthesia and paresthesia from the lower limbs to the thoracic region. After preoperative oncologic and surgical planning the patient underwent a total en bloc resection of the mass. No postoperative adjunctive neurological deficits were recorded. An adjuvant radiation therapy with a dose of 5.500 centigrays (cGy) over four weeks was performed. At one year follow-up the patient is alive with no signs of recurrence on computed tomographic scans and magnetic resonance imaging. We discuss this case with particular emphasis on the preoperative planning, the surgical procedure and related prognosis.

Irradiation fields and doses in glioblastoma multiforme: are current standards adequate?

AIMS AND BACKGROUND: The optimum conventional radiotherapy in glioblastoma multiforme patients has not been clearly defined by prospective trials. To better characterize a standard radiotherapy in glioblastoma multiforme, the impact on survival of different fields and doses was analyzed in a retrospective single center series. METHODS: One hundred and forty-seven patients with glioblastoma multiforme, submitted to biopsy only (n = 15), subtotal (n = 48) or total resection (n = 82) and who completed the planned postsurgical radiotherapy, were considered. The median age was 57 years, the male/female ratio 1.5/1, and the performance status > or =70 in 76%. Whole brain irradiation, followed by a boost to partial brain, was used in 75 cases with a whole brain dose of 44-50 Gy (median, 46) and a partial brain dose of 56-70 Gy (median, 60 Gy). Partial brain irradiation alone was used in 72 patients with a dose of 56-70 Gy (median, 61 Gy). Ninety-eight patients received 56-60 Gy (median, 59 Gy) to partial brain whereas 49 patients received 61-70 Gy (median, 63 Gy). RESULTS: There was an almost significantly longer survival in patients irradiated to the partial brain alone with respect to those also receiving whole brain radiotherapy (P = 0.056). Doses >60 Gy significantly prolonged survival (P = 0.006). Multivariate analysis confirmed that the impact on survival of radiation dose was independent of age, performance status, extent of surgery, field of irradiation and the use of chemotherapy. The extent of irradiation field was not independently related to improved survival. CONCLUSIONS: Our retrospective findings suggest that we reflect on the adequacy of the current standard irradiation parameters. Well-designed prospective trials are necessary to standardize the radiotherapy control group in patients with glioblastoma multiforme to be compared in phase III trials with innovative therapeutic approaches.