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.

Serotonin syndrome caused by olanzapine and clomipramine.

We describe a case of severe serotonin syndrome. The patient was simultaneously taking the atypical antidepressant olanzapine and a tricyclical antidepressant, clomipramine. Symptoms included altered mental state resulting in coma, myoclonus, hyperreflexia, diaphoresis, diarrhoea, disorientation and fever. After suspension of antidepressant drugs, intensive symptomatic treatment and administration of biperiden and cyproheptadine, the patient's condition improved.

Use of natural surfactant in an infant with aspiration syndrome.

The remarkable effectiveness of surfactant in neonatology suggested its use also in adults as well as in children on the basis of the pulmonary pathophysiology. We describe a case of an 18 month-old child affected by acute respiratory distress syndrome (ARDS) due to asphyxy by gastric juice inhalation, successfully treated with porcine surfactant (Curosurf) associated with ventilatory therapy.

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.

Use of recombinant activated factor VII in a case of severe postpartum haemorrhage.

We describe the case of a 24 year old woman, affected by haemorrhagic shock due to post-partum uterine atony, who underwent an emergency hysterectomy with persistent postoperative bleeding, successfully treated with recombinant activated factor VII (Novoseven).

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.

[Use of levosimendan after cardiac arrest by ventricular fibrillation: a case report]. / Uso del levosimendan dopo arresto cardiocircolatorio da fibrillazione ventricolare: descrizione di un caso clinico.

We describe the case of a patient admitted in intensive care, after cardiac arrest by ventricular fibrillation treated by electrical defibrillation, that showed a serious deficit of the cardiac index and increase of the systemic vascular resistances. The patient was treated by levosimendan (Simdax): a starter dose of 12 microg/Kg in ten minutes and then a continuous perfusion of 0.1 microg/Kg/min. for 24 hours. He had a continuous amelioration of the clinical conditions and of the hemodynamics parameters. In the fifth day the patient was transferred to the Cardiology department and after 20 days he was discharged from hospital.

Use of activated protein C in a case of paediatric septic shock.

We describe a clinical case of a 7 year old girl, affected by peritonitis, septic shock and multiorgan failure, treated successfully with drotrecogin alpha associated with conventional therapy.

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.

Collagenase-1 and stromelysin distribution in fresh human herniated intervertebral disc: a possible link to the in vivo inflammatory reactions.

Chondrocytes may play an important role in the inflammatory reactions involving intervertebral discs: the role of metalloproteases (MMP) and the imbalance between proteases and their inhibitors seems to play a crucial role in the disc degenerative process. In the present study we have analysed the production of collagenase-1 and stromelysin in different parts of herniated intervertebral discs. Ten samples of herniated lumbar discs were obtained from adult patients operated on for primary microdiscectomy because of persistent radicular symptoms and subdivided into three samples: 1. The nearest to the nerve root in close contact with it, 2. the sample obtained from the intervertebral space, and 3. the sample obtained from the vertebral plates. The DNA content of each specimen was measured in order to obtain the best estimate of the cell content as well as to normalise the content of collagenase-1 and stromelysin found in the same tissues with respect to the number of cells. In 9 out of the 10 cases the DNA content was significantly higher in samples obtained from the intervertebral plates than in samples obtained near the nerve root or the intervertebral space. DNA content did not show any significant difference considering disc samples contiguous to the nerve root and samples obtained from the intervertebral space. The production of collagenase-1 did not show a specific pattern, being produced in similar quantities in the three disc compartments. The production of stromelysin was significantly lower in disc samples obtained from the intervertebral plates. In conclusion the results of the present study suggest firstly that in the herniated lumbar disc the reactivity and the production of pro-inflammatory agents is independent of DNA content, i.e. the cellularity of the sample, and secondly that activated cells in the intervertebral space and in the part of the disc in contact with the nerve root, even if scarce in number, are able to synthesise a proportionally higher quantity of MMP than the high-cellular disc fragments from the intervertebral plates, potentially playing a specific role in the inflammatory reactions.

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.

Collagenase-I and stromelysin distribution in fresh human herniated intervertebral disc: A possible link to the in vivo inflammatory reactions.

Chondrocytes may play an Important role in the inflammatory reactions involving intervertebral discs: the role of metalloproteases (MMP.) and the imbalance between proteases and their inhibitors seems to play a crucial role in the disc degenerative process. In the present study we have analysed the production of collagenase-1 and stromelysin in different parts of herniated intervertebral discs. Ten samples of herniated lumbar discs were obtained from adult patients operated on for primary microdiscectomy because of persistent radicular symptoms and subdivided into three samples: 1. The nearest to the nerve root in close contact with it, 2. the sample obtained from the intervertebral space, and 3. the sample obtained from the vertebral plates. The DNA content of each specimen was measured in order to obtain the best estimate of the cell content as well as to normalise the content of collagenase-1 and stromelysin found in the same tissues with respect to the number of cells. In 9 out of the 7 0 cases the DNA content was significantly higher in samples obtained from the intervertebral plates than in samples obtained near the nerve root or the intervertebral space. DNA content did not show any significant difference considering disc samples contiguous to the nerve root and samples obtained from the intervertebral space. The production of collagenase-1 did not show a specific pattern, being produced in similar quantities in the three disc compartments. The production of stromelysin was significantly lower in disc samples obtained from the intervertebral plates. In conclusion the results of the present study suggest firstly that in the herniated lumbar disc the reactivity and the production of pro-inflammatory agents is independent of DNA content, i.e. the cellularity of the sample, and secondly that activated cells in the intervertebral space and in the part of the disc in contact with the nerve root, even if scarce in number, are able to synthesise a proportionally higher quantity of MMP than the high-cellular disc fragments from the intervertebral plates, potentially playing a specific role in the inflammatory reactions. [Neurol Res 1999; 21: 677-681].

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.