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.

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.

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.

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.

Introduction of GDC embolization in the clinical practice as treatment synergical to surgery: impact on overall outcome of patients with subarachnoid hemorrhage.

The GDC endovascular approach represent an effective alternative to surgery for treatment of intracranial aneurysms. Anyway no data are available about the impact of endovascular embolization with GDC on overall outcome of patients with subarachnoid hemorrhage. We analyse retrospectively a series of 234 patients admitted for ruptured intracranial aneurysm. Results were then compared with results of three surgical series from the literature. The 95.7% of patients underwent aneurysm treatment; 56.4% of patients were classified as good recovery, 12.8% presented moderate disability, 10.3% were severely disabled, 3% were in persistent vegetative state and 17.5% were dead. Patients older than 60 years accounted for 37% of all cases and good outcome in this group accounted for 54.7%. Good results were obtained in 90.1%, 61.7% and 22.8% of patients with Hunt-Hess grade I-II, III and IV-V respectively. Finally good outcome was observed in 82.8% of patients with aneurysms of the posterior circulation. Introduction of GDC embolization in clinical practice contributed to the extension of indication for aneurysm treatment leading to a reduction of overall mortality. GDC utilisation does not affect the overall percentage of patients with good outcome reflecting an increase of severely disabled patients. Endovascular treatment seems an effective theraputic choice in selected grade I-II patients. Results in grade III patients suggest that surgery may be advantageous because of washing and decompression of the basal cisterns while results in grade IV and V patients are unsatisfactory. GDC embolization clearly improves the prognosis of patients with posterior circulation aneurysms and probably is an advantageous theraputic choice in elderly patients.

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.

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.

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.

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.

Aneurysm occurring within a meningioma: case report.

Aneurysms can be expected to be found in approximately 0.5% of patients with brain tumours; nevertheless, the real incidence is difficult to assess because angiography is now seldom performed for brain tumours. In the literature, 42 cases of meningioma associated with aneurysms are reported, but in none was the aneurysm intratumoural. We describe a case of intracranial meningioma with an intratumoural aneurysm in a 48-year-old woman.

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).

Platelet derived growth factor and subarachnoid haemorrhage: a study on cisternal cerebrospinal fluid.

Platelet derived growth factor (PDGF) was identified as a powerful mitogenic growth factor which is released from activated platelets and has a marked activity as vasoconstrictor agent. In the present study we have measured cisternal cerebrospinal fluid (CSF) levels of PDGF in 72 patients operated on for intracranial aneurysm in order to verify whether it might be related to the clinical aspects of SAH with special regard to symptomatic vasospasm. CSF samples were obtained at surgery by cisternal puncture of the subarachnoid cistern the nearest to the aneurysm before aneurysm isolation and exclusion. The specimen were frozen in liquid nitrogen and stored at -80 degrees C until analysis. PDGF was measured using a commercially available reagent. Values are expressed as pg/ml of CSF. In 18 cases no radiological and clinical signs of SAH were detected and the mean cisternal CSF level of PDGF was 885.0 +/- 104.5 pg/ml; 20 patients were operated on between day 1 and 3 from the last SAH episode: mean cisternal CSF level of PDGF was 1917.5 +/- 459.4 pg/ml. In 34 patients treated with delayed surgery protocol, mean cisternal CSF level of PDGF was 995.3 +/- 73.8 pg/ml. Statistical analysis showed significant differences between groups (P: 0.011). In the subgroup of patients operated on within day 3 after SAH, 6 presented vasospasm and had mean cisternal CSF PDGF level which was significantly higher (P < 0.01) than in 14 patients without vasospasm. In the delayed "surgical" patients there was no significant difference in cisternal CSF levels of PDGF considering the occurrence of vasospasm. The results of the present study suggest that (a) after SAH there is a significant release of PDGF early after SAH and (b) higher levels of PDGF found in cisternal CSF of patients operated on within 72 hours after SAH may be predictive of symptomatic vasospasm.

Superoxide dismutase activity in cisternal cerebrospinal fluid after aneurysmal subarachnoid haemorrhage.

It has been recognised that the level of superoxide dismutase (SOD) significantly increases in CSF as the result of cerebral ischaemic damage. The aim of this study was to correlate the CSF levels of SOD enzymatic activity to the patterns of subarachnoid haemorrhage with regards to ischaemic complications due to vasospasm. A series of 78 patients operated on for intracranial aneurysms was studied; all patients were monitored with serial TCD measurements every second day after SAH. CSF samples were obtained at surgery by cisternal puncture of the subarachnoid cistern nearest to the aneurysm. SOD activity was assayed spectrophotometrically. Mean cisternal CSF level of SOD in 12 control cases (12.99 +/- 2.33 U/ml) is significantly higher (p < 0.01) than in 26 patients operated on between day 1 and 3 from last SAH episode (4.44 +/- 0.7 U/ml) and in 40 patients treated by delayed surgery (7.64 +/- 0.92 U/ml). In 13 patients presenting neurological deterioration related to arterial vasospasm mean cisternal SOD level was 12.23 +/- 1.86 U/ml; in 27 cases without vasospasm mean level was 5.43 +/- 0.7 U/ml (p < 001). The present results suggest that (a) cisternal CSF levels of SOD significantly decreases after SAH, probably in relation to an impaired synthesis in the brain compartment and that (b) a substantial elevation of SOD levels is evident in patients suffering ischaemic complications vasospasm-related. Biochemical events in the brain compartment could influence the expression and release of anti-oxidant enzymes in CSF after SAH.