The microvascular network of the pituitary gland: a model for the application of fractal geometry to the analysis of angioarchitecture and angiogenesis of brain tumors.

In geometrical terms, tumor vascularity is an exemplary anatomical system that irregularly fills a three-dimensional Euclidean space. This physical characteristic, together with the highly variable vessel shapes and surfaces, leads to considerable spatial and temporal heterogeneity in the delivery of oxygen, nutrients and drugs, and the removal of metabolites. Although these biological features have now been well established, quantitative analyses of neovascularity in two-dimensional histological sections still fail to view tumor architecture in non-Euclidean terms, and this leads to errors in visually interpreting the same tumor, and discordant results from different laboratories. A review of the literature concerning the application of microvessel density (MVD) estimates, an Euclidean-based approach used to quantify vascularity in normal and neoplastic pituitary tissues, revealed some disagreements in the results and led us to discuss the limitations of the Euclidean quantification of vascularity. Consequently, we introduced fractal geometry as a better means of quantifying the microvasculature of normal pituitary glands and pituitary adenomas, and found that the use of the surface fractal dimension is more appropriate than MVD for analysing the vascular network of both. We propose extending the application of this model to the analysis of the angiogenesis and angioarchitecture of brain tumors.

Lumbar arachnoiditis and thecaloscopy: brief review and proposed treatment algorithm.

The term arachnoiditis describes the inflammation of the meninges and subarachnoid spaces. Lumbar arachnoiditis is characterized by obliterated nerve root sleeves and the adherence of nerve roots to each other in the proximity of the cauda equina, and may be secondary to infectious diseases or tumors, iatrogenic (subsequent to spinal surgery) or idiopathic. It is not very clearly defined epidemiologically or clinically, and various theories regarding its pathophysiology have been proposed; furthermore, its treatment is difficult because there is a lack of evidence-based diagnostic and therapeutic gold standards. Thecaloscopy has been recently described as a novel technique for retrograde transcutaneous neuroendoscopic inspection of the subarachnoid structures of the lumbar thecal sac; it has also been suggested for the treatment of lumbar arachnoiditis. We here review the most modern techniques for the treatment of this disease such as thecaloscopy and neurostimulation.

Focal extra-axial hemorrahagic mass with subdural hemorrhage secondare to extramedullary hematopoiesis in idiopathic myelodysplastic sindrome.

Idiopathic myelodysplastic syndrome is a disease characterized by a clonal stem cell disorder in which megacaryocitic and granulocytic lineages are mainly involved; extramedullary myeloid metaplasia is due to abnormal location of myeloid tissue in other organs than bone marrow. Rarely the central nervous system is involved. When it happens, it is typical to find masses around the brain and pachymeningeal thickening, but it is very rare to find it associated with subdural haemorrhage, as in the case we describe in the present article. Considering our case and the literature we can suggest that radiological images associated with the clinical history of the patient suggestive for extramedullary hematopoiesis can be sufficient for a correct diagnosis and for a radiotherapy treatment, demanding surgery in the case of diagnostic doubts, massive hemorrahages or neurological decifits caused by the focal lesions.

De novo Formation of the Ventriculus Terminalis? A Brief Report of a Special Case.

The ventriculus terminalis is an ependymal cystic cavity in the conus medullaris, sometimes found in children. Persistence of the ventriculus terminalis in adults can cause lower back pain or neurological disturbances. However, there are no literature reports of de novo formation of a ventriculus terminalis in the conus medulallaris, as in the case we illustrate here.

Oligodendroglial gliomatosis cerebri. Case report.

Gliomatosis cerebri of oligodendroglial origin is very unusual. In the present article we illustrate a case of this pathology, outlining his severity and suggesting it seems to be more aggressive than the astroglial type. We give a short focus about the diagnosis and the therapy of this neoplastic disease.

Arnold's neuralgia caused by solitary fibrous tumor. Case report.

Solitary fibrous tumor (SFT) is a mesenchymal tumor which has been identified in a wide variety of localizations, including soft tissues, peritoneum, retroperitoneum, mediastinum, upper respiratory tract, nasopharyngeal sinuses, periosteum and extremities, orbit, major body cavities, intraspinal and intracranial localizations. The authors describe a case of SFT found in the neck of a young patient suffering from Arnold's neuralgia. After surgery, diagnosis of SFT was based on characteristic histopathological findings, especially on immunohistochemical positive staining for CD34 antigen. It has been described also the characteristic patterns making this diagnose sure, focusing the point that cure is possible with complete excision of the lesion.

Intradural spinal metastasis of renal clear cell carcinoma causing cauda equina syndrome.

Metastasis of renal clear cell carcinoma to the spinal cord are quite rare. Intradural localization causing a cauda equina syndrome has been previously reported only in two cases. The present report details the clinical, surgical and neuroradiological findings of a third case requiring emergency surgery, and presents data available from a brief review of cases reported in the literature. From the data available in the literature, we suggest that cerebral and spinal MRI and PET imaging should be widely performed in the staging of patients treated for renal clear cell carcinoma, in order to early detect CNS involvement.

Meningeal melanocytoma of the temporal lobe. An uncommon tumor in an unusual location. Case report.

Meningeal melanocytomas are rare pigmented tumors of the central nervous system. These tumors are benign melanotic lesions that derive from the melanocytes of the leptomeninges. They may occur anywhere in the cranial and spinal meninges; however, they are found prevalently in the posterior fossa and in the spinal cord. Their epidemiological features, natural history and response to treatment remain poorly understood, even if, in the last 2 years, some reviews have been published about it. We report a new case of intracranial supratentorial meningeal melanocytoma, in the temporal lobe, occurring in a 27-year-old man, admitted to our Institute with a long-time history of seizures. We report histological and radiological characteristics of our case, and briefly review the therapeutical options reported in literature. Preoperative neuroradiological finding is unclear; the preoperative diagnosis is usually meningioma, because of the long duration of symptomatology and the radiological appearance of the lesion as an extra-axial mass. Diagnosis of these lesions, as in our case, is made intraoperatively by the gross, jet-black appearance of the tumor and by histological examination. In spite of the benign biologic behaviour, the prognosis remains uncertain, because of the possible local recurrences. According to the results of some works of the last years, it seems appropriate to use postoperative radiotherapy for those patients with symptomatic residual, progressive or recurrent tumors not amenable to further resection.

Isolated cerebellar involvement in Rosai-Dorfman disease: case report.

OBJECTIVE AND IMPORTANCE: Sinus histiocytosis or Rosai-Dorfman disease (RDD) is a rare but well-recognized disorder characterized by an unusual proliferation of histiocytic cells. Intracranial localization is a rare manifestation of RDD. Only three cases of localization in the posterior fossa have been reported in the literature. The present report describes the first case, to our knowledge, of cerebellar localization of RDD. CLINICAL PRESENTATION: A 67-year-old woman was admitted to our institution with a 5-month history of cerebellar ataxia. Her medical history was unremarkable. The patient was alert and cooperative. No cranial nerve deficits were evident; Romberg positivity to the left side was recorded. No cutaneous abnormalities, lymphadenopathy, or hepatosplenomegaly were revealed by physical examination. Routine hematological and biochemical studies were normal except for the erythrocyte sedimentation rate, which was elevated. Radiologically, the lesion appeared as a well-defined and avascular mass in the right cerebellar lobe. Meningioma was considered the most likely diagnosis. TECHNIQUE: The patient underwent a suboccipital craniotomy with complete excision of the lesion. Microscopic examination of the operative specimen revealed the presence of a mixed cellular population with predominant mature histiocytes. A peculiar feature was the presence of lymphocytes and monocytes within the cytoplasm of histiocytes (emperipolesis). Immunohistochemical study of the histiocytes revealed strong positivity for S-100, CD-68 antigen, and vimentin. CONCLUSION: Involvement of the central nervous system in RDD appears to have a benign prognosis, especially in the absence of nodal diseases. Surgery is essential for diagnosis, and, when total removal is achieved, the outcome is generally good without risk of recurrence.

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.

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.

Spinal chondroma of the lumbar tract: case report.

BACKGROUND: Cartilage-forming tumors are benign cartilaginous tumors that rarely affect the spinal canal: they account for 2% of all spinal tumors and 2.6% of all benign bone tumors. Pathologically, they may be classified as chondromas, osteochondromas, chondroblastomas, and chondromyxoid fibromas. This oncotype may remain asymptomatic (it is confined within the vertebral structure) or may present as a hard paravertebral swelling (it invades the paravertebral structures) or more rarely, with a slowly-developing neurologic syndrome (it extends into the vertebral canal). METHODS: Thirty-one cases have been reported (including our case) of benign cartilage-forming tumors localized in the lumbar column. Only three cases of chondroma of the lumbar spine presented with lumbar radicular pain. We report a fourth case and review clinical and radiologic characteristics of these lesions. RESULTS: Eleven out of the 31 cases were diagnosed as chondromas, 17 as osteochondromas, while in three cases the histopathologic diagnosis was not reported. Seventeen cases originated from the neural arch, seven from the vertebral body, two from the spinous process, and in five cases the exact localization was not reported. This tumor is more frequent in males (21 cases out of 31), than in females (five cases); in five cases the sex was not reported. Mean duration of symptoms was 23 +/- 5.1 months (range: 1-96); chondromas have a short clinical history before diagnosis (13.8 +/- 3.4 months) compared to osteochondromas (28.6 +/- 7.6). Clinical presentation with local swelling is reported in 10 cases, in 10 cases local pain without radicular irradiation, in six cases lumbar pain with sciatica, in two cases signs and symptoms of cord compression, one case of cauda syndrome, while in four cases no clinical details are reported. Among the six cases presenting with sciatica, four were chondromas (in all cases the L4 level was involved), and one osteochondroma, while in one case the histopathologic diagnosis was not reported. CONCLUSION: Computed tomography is important and indispensable for preoperative diagnosis, giving a precise indication of tumor extent and location and its relationship to the adjacent structures; while MRI is helpful in detecting patterns related to histologic malignancy. It is important to examine the whole tumor histologically because it is known that there may be small areas that show signs of malignancy; thus is more likely in chondromas than osteochondromas.

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.

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.

A systemic "dumb-bell" haemangiopericytoma.

Systemic haemangiopericytoma is a rare soft tissue tumour originating from pericytes which are contractile pericapillary cells, and represents less than one percent of all vascular neoplasms. The most common site of involvement is the thigh followed by the retroperitoneum, while the paraspinal location is very rare. We report the first case of systemic "dumb-bell" haemangiopericytoma illustrated radiologically, which mimick, a dorsal "dumb-bell" neurinoma.