G. Spanu

Endothelin and aneurysmal subarachnoid haemorrhage: a study of subarachnoid cisternal cerebrospinal fluid.

Endothelin (ET) is considered one of the most potent vasoconstrictor polypeptides; several experimental studies have suggested its possible role in the pathogenesis of arterial vasospasm after subarachnoid haemorrhage (SAH). Previously reported data on plasma and CSF levels of endothelin in patients with a diagnosis of SAH have been controversial. Cisternal endothelin CSF levels and the possibility that they could be related to vasospasm and other clinical patterns of SAH were investigated. CSF samples were obtained from 55 patients admitted after angiographic diagnosis of intracranial aneurysm. Levels of ET-1 and ET-3 were measured through radio-immunoassay technique. Twelve patients who had operations for unruptured aneurysms were considered control cases; 43 patients with SAH were classified according to: Hunt and Hess grading at admission, vasospasm grading, CT classification and timing of surgery. In all 55 patients ET-1 was measured, while positive levels of ET-3 were found only in 17 cases of 48. No linear correlation was found between cisternal CSF ET-1 levels when considering time of surgery, CT classification, Hunt and Hess grading at admission, and vasospasm grading. The results of ET-3 assay should be considered with great caution because of the low percentage of positive cases. Cisternal CSF levels of ET-1 and ET-3 are not directly related to the occurrence of arterial vasospasm after the aneurysm rupture, or to other major clinical patterns of SAH; however, ET-1 expression occurs either in paraphysiological (unruptured aneurysm) or in pathological conditions (SAH). It is suggested that ET may potentiate, or may be potentiated by, other factors playing a consistent pathophysiological role in the development of vasospasm.

Antioxidant enzymatic activities after experimental subarachnoid hemorrhage in rats.

Lipid peroxidation has been hypotesized as one of possible factors involved in the pathogenesis of neuronal damage and delayed vasospasm after subarachnoid hemorrhage. In the brain there are anti‐oxidant enzymatic systems which act as scavengers of superoxides and free radicals. In the present study the pattern of enzymatic anti‐oxidant activities (Cu‐Zn and Mn superoxide dismutase, and glutathione peroxidase) was investigated in an experimental model of subarachnoid hemorrhage in the rat in order to verify whether the hemorrhagic insult may be responsible for an impairment of such anti‐oxidant systems. Enzymatic activities were assayed in three different rat brain areas (cerebral cortex, hippocampus and brain stem) of sham‐operated and at 30 min, 1, 6 and 48 h after subarachnoid hemorrhage induction. After the hemorrhage induction the Cu‐Zn superoxide dismutase activity in cerebral cortex was significantly reduced at all the set times (p <.05), while Mn‐superoxide dismutase activity was significantly decreased since 1 h (p <.05) until 48 h (p <.05). Glutathione peroxidase activity was significantly reduced only in the late phase (48 h) of subarachnoid hemorrhage (p <.01). In the hippocampus, all enzymatic activities were significantly reduced in the late phase. In the brain stem Cu‐Zn superoxide dismutase was significantly impaired at 1 and 6 h (p <.05) after subarachnoid hemorrhage induction, while in the late phase (48 h) reached the control value. The mitochondrial Mn‐superoxide dismutase was significantly reduced since 1 h (p <.05) until 48 h (p <.02) after subarachnoid hemorrhage. Glutathione peroxidase activity in this area was impaired at 1, 6 (p <.01) and 48 h (p <.02). These results suggest that subarachnoid hemorrhage causes a significant reduction of anti‐oxidant enzymatic activities in brain compartment: Cu‐Zn and Mn superoxide dismutase, which are specific scavengers of superoxide radicals, show an early decrease, while glutathione peroxidase activity is significantly reduced in a delayed phase.

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.

Cyclic nucleotides in experimental and human brain tumors

It is well known that the system of cyclic nucleotides plays an important role in cell differentiation and proliferation. Cyclic AMP is capable of stimulating cell growth, and cyclic GMP is thought to control cell division and growth. The authors measured adenylcyclase activity (AC) and cGMP content in the tumor latency period and in early neoplastic proliferations in rats with brain tumors induced by transplacental ethylnitrosourea (ENU). AC activity, which is high during the first days of life, decreases until it reaches, at the 60th day, levels lower than those in control animals. Cyclic GMP, on the contrary, increases during the first month in treated animals and remains consistently higher than controls up to the 45th day.In fully developed experimental brain tumors (mixed gliomas, isomorphic and polymorphic oligodendrogliornas) the percentage of reduction in AC activity is significantly higher.AC activity was measured also in human tumoral tissue. In malignant tumors it is markedly lower than in benign tumors. In the same patients cAMP in the cerebrospinal fluid was measured with results similar to those obtained in tissues.These findings confirm that the system of cyclic nucleotides is implicated in all the developmental phases of brain tumors and therefore may reveal how research can clarify the first transformations of tumoral cells.

Effect of Nimodipine on Mitochondrial Respiration in Different Rat Brain Areas After Subarachnoid Haemorrhage

The mitochondrial respiration was evaluated in three different rat brain areas (cerebral cortex, hippocampus and brain stem) after experimental subarachnoid haemorrhage (SAH). The haemorrhage was induced by injecting 0.35 ml of autologous arterial blood into cisterna magna. Intravenous administration of Nimodipine (2 micrograms/kg/min for 30 minutes) was started immediately after the haemorrhage induction. At the set time (1 hour after SAH procedure), animals were sacrificed and non-synaptic mitochondria from the above mentioned areas were isolated. The following respiratory parameters were evaluated utilizing glutamate plus malate and succinate plus rotenone as substrates: state 3, state 4, uncoupled state, respiratory control ratio (RCR) and ADP/O ratio. SAH significantly influences respiratory parameters, mainly RCR; the cerebral cortex and brain stem seem to be more sensitive during the acute phase of vasospasm which follows SAH procedure. Nimodipine treatment significantly ameliorates mitochondrial respiratory conditions.

Effects of nicardipine treatment on Na+-K+ ATPase and lipid peroxidation after experimental subarachnoid haemorrhage

SummaryThe calcium theory of neuronal damage has been recently adapted to subarachnoid haemorrhage (SAH). It is proposed that haemorrhagic insult to the brain causes free radical-mediated destructive reactions of membrane phospholipids, and the consequent decrease of phospholipid-dependent enzymatic activities, such as Na+-K+ ATPase.In the present study we have studied the effects of Nicardipine treatment on lipid peroxidation and Na+-K+ ATPase activity after experimental induction of SAH. SAH was induced in anaesthesized rats by slow injection of 0.3 ml of autologous arterial blood into the cisterna magna. We assessed the extent of lipid peroxidation by measuring the level of thiobarbituric acid reactive substances (TBARS) and Na+-K+ ATPase activity in 3 different rat brain areas (cerebral cortex, hippocampus and brain stem) of sham-operated (0.3 ml of mock CSF into cisterna magna) and at 1 hour, 6 hours and 48 hours after SAH induction; simultaneously, we investigated the capacity of cerebral lipid peroxidation by measuring the accumulation of TBRAS in homogenates of brain areas incubated under aerobic conditions. Na+-K+ ATPase activity decreased in the cerebral cortex at 1 hour and 6 hours and in brain stem at 1 hour after SAH, while the same enzymatic activity did not change in the hippocampus. There was no significant difference in lipid peroxide content between sham-operated and heamorrhagic animals; Nicardipine treatment reduced the TBRAS content and induced the recovery of Na+-K+ ATPase activity, exerting a brain protective role against the detrimental effects of the haemorrhage.

Nitrosourea derivatives-induced pulmonary toxicity in patients treated for malignant brain tumors. Early subclinical detection and its prevention

Nitrosourea derivatives, such as BCNU and CCNU, are considered useful chemotherapeutic agents in malignant brain tumors combined therapy. Pulmonary toxicity is one of the major side effects demonstrated both in experimental animal models and in human autoptic findings. Pulmonary fibrosis is the end point of progressive functional disorder of respiratory mechanism and alveolo-capillary gas exchanges. Authors present the results of a randomized, double-blind trial of 40 patients previously treated with surgery and radiotherapy and who subsequently underwent BCNU therapy for primary intracranial glioma. Patients underwent functional respiratory examinations at each chemotherapy course interval. Twenty patients received ambroxol (120 mg/day) for 40 days after chemotherapy course. Control patients received placebo with the same schedule and showed a significant reduction of pulmonary functional parameters (DLCO, MMEF, MEF 25%), whereas in the treated group there is no significant variation of these functional parameters. The mechanism of ambroxol is commonly related to the surfactant synthesis enhancement and to the action on bronchiolar pathways.

Lumbar canal stenosis results in 40 patients surgically treated

SummaryAuthors present the clinical and neuroradiological characteristics of 40 patients treated for lumbar canal stenosis during a 10 years experience. The usefulness of computed tomography in comparison with myelography and plain X-rays of the spine is stressed. The surgical treatment was wide laminectomy involving one or more levels (two to four) plus an eventual foraminotomy but without discectomy. All patients were followed up and in 85% of cases a reduction of clinical symptoms was observed. Residual symptoms were also present in some of the improved patients, they generally accepted them without great dismay.

Surgery of Cerebral Gliomas: State of the Art

Generally, the first therapeutic approach in patients with cerebral gliomas is surgery. Technological advancements in both diagnosis and surgical instruments which have taken place in the past 20 years have greatly modified surgeons’ attitudes which have become more aggressive against this type of pathology. To define the state of the art in this field, the authors have taken into consideration the surgical cases at the Neurosurgical Institute of the University of Pavia from 1973 to 1989. During this period 339 adult supratentorial gliomas (125 glioblastomas, 115 anaplastic astrocytomas, 74 astrocytomas, and 25 other histotypes) were operated on. Patients were aged between 16 and 76 years. The overall surgical mortality was 4.7% which has decreased from 7% before 1980 to about 2% in the last ten years. Morbidity was 27.2% and has decreased significantly during the same period. The authors discuss pre- and postoperative pharmacological strategies, the usefulness of applying new diagnostic and surgical technology, the incidence of mortality and morbidity, time and quality of survival with respect to the different types of surgical operations.

A Study on Cisternal CSF Levels of Endothelin-1 After Subarachnoid Haemorrhage

The aim of the present study was to verify the presence of ET-1 in CSF collected nearby an intracranial aneurysm and to discuss the relationship of cisternal CSF levels of ET-1 with different clinical aspects of the disease (vasospasm grading, Hunt and Hess grading at admission, CT classification of subarachnoid clot deposition, timing of surgery). 55 selected patients with diagnosis of intracranial aneurysms are considered. The control group is represented by 12 patients bearing an unruptured intracranial aneurysm. In all 55 patients a positivity for ET-1 was found; 12 patients were operated on for unruptured aneurysms; twenty-four patients were operated on between day 1 and 4 from last SAH episode and 19 patients were treated with delayed surgery: no statistical difference was found within the three subgroups. No statistical difference in mean cisternal CSF level of ET-1 was found on the basis of CT classification or classification of vasospasm. Mean ET-1 CSF level is significantly higher (p<.05) in patients with high clinical grade at admission (Hunt and Hess 2 and 3) if compared to unruptured aneurysms and Hunt and Hess 1 subgroup. The results of the present study suggest that the rupture of an intracranial aneurysm “per se” does not influence the release of ET-1 in cisternal CSF and that occurrence of vasospasm is not significantly related with cisternal CSF levels of the polipeptide.