Francesco Saverio Pastore

Relationship between Leukocytosis and Ischemic Complications following Aneurysmal Subarachnoid Hemorrhage

The prognostic significance of admission leukocytosis with respect to ischemic complications of subarachnoid hemorrhage was retrospectively investigated in a series of patients with recently ruptured intracranial aneurysms. The present study concerned 47 consecutive cases admitted within 72 hours following the last hemorrhage, in the years 1982-1984. There was no difference in the admission WBC counts between patients who subsequently deteriorated due to ischemic complications and those who did not. However, the cell count rose significantly at the time of the clinical manifestations of ischemia, possibly as a result of structural damage of brain tissue and/or increased sympathetic and adrenocortical activity. The possible contribution of leukocytes to the pathogenesis of ischemic damage following subarachnoid hemorrhage--perhaps through the release of leukotrienes--will require further investigation.

MDA, oxypurines, and nucleosides relate to reperfusion in short-term incomplete cerebral ischemia in the rat

Short-term incomplete cerebral ischemia (5 min) was induced in the rat by the bilateral clamping of the common carotid arteries. Reperfusion was obtained by removing carotid clamping and was carried out for the following 10 min. Animals were sacrificed either at the end of ischemia or reperfusion. Controls were represented by a group of sham-operated rats. Peripheral venous blood samples were withdrawn from the femoral vein from rats subjected to cerebral reperfusion 5 min before ischemia, at the end of ischemia, and 10 min after reperfusion. Neutralized perchloric acid extracts of brain tissue were analyzed by a highly sensitive high-performance liquid chromatography (HPLC) method for the direct determination of malondialdehyde, oxypurines, nucleosides, nicotinic coenzymes, and high-energy phosphates. In addition, plasma concentrations of malondialdehyde, hypoxanthine, xanthine, inosine, uric acid, and adenosine were determined by the same HPLC technique. Incomplete cerebral ischemia induced the appearance of a significant amount (8.05 nmol/g w.w.; SD = 2.82) of cerebral malondialdehyde (which was undetectable in control animals) and a decrease of ascorbic acid. A further 6.6-fold increase of malondialdehyde (53.30 nmol/g w.w.; SD = 17.77) and a 18.5% decrease of ascorbic acid occurred after 10 min of reperfusion. Plasma malondialdehyde, which was present in minimal amount before ischemia (0.050 mumol/L; SD = 0.015), significantly increased after 5 min of ischemia (0.277 mumol/L; SD = 0.056) and was strikingly augmented after 10 min of reperfusion (0.682 mumol/L; SD = 0.094). A similar trend was observed for xanthine, uric acid, inosine, and adenosine, while hypoxanthine reached its maximal concentration after 5 min of incomplete ischemia, being significantly decreased after reperfusion. From the data obtained, it can be concluded that tissue concentrations of malondialdehyde and ascorbic acid, and plasma levels of malondialdehyde, oxypurines, and nucleosides, reflect both the oxygen radical-mediated tissue injury and the depression of energy metabolism, thus representing early biochemical markers of short-term incomplete brain ischemia and reperfusion in the rat. In particular, these results suggest the possibility of using the variation of malondialdehyde, oxypurines, and nucleosides in peripheral blood as a potential biochemical indicator of reperfusion damage occurring to postischemic tissues.

Decrease in N-Acetylaspartate Following Concussion May Be Coupled to Decrease in Creatine.

Objectives:To assess the time course changes in N-acetylaspartate (NAA) and creatine (Cr) levels in the brain of athletes who suffered a sport-related concussion. Participants:Eleven nonconsecutive athletes with concussive head injury and 11 sex- and age-matched control volunteers Main outcome measures:At 3, 15, 30, and 45 days postinjury, athletes were examined by proton magnetic resonance spectroscopy for the determination of NAA, Cr, and choline (Cho) levels. Proton magnetic resonance spectroscopic data recorded for the control group were used for comparison. Results:Compared with controls (2.18 ± 0.19), athletes showed an increase in the NAA/Cr ratio at 3 (2.71 ± 0.16; P < .01) and 15 (2.54 ± 0.21; P < .01) days postconcussion, followed by a decrease and subsequent normalization at 30 (1.95 ± 0.16, P < .05) and 45 (2.17 ± 0.20; P < .05) days postconcussion. The NAA/Cho ratio decreased at 3, 15, and 30 days postinjury (P < .01 compared with controls), with no differences observed in controls at 45 days postconcussion. Compared with controls, significant increase in the Cho/Cr ratio after 3 (+33%, P < .01) and 15 (+31.5%, P < .01) days postinjury was observed whereas no differences were recorded at 30 and 45 days postinjury. Conclusions:This cohort of athletes indicates that concussion may cause concomitant decrease in cerebral NAA and Cr levels. This provokes longer time for normalization of metabolism, as well as longer time for resolution of concussion-associated clinical symptoms.

Nucleoplasty in the Treatment of Lumbar Diskogenic Back Pain: One Year Follow-Up

PurposeThe spine is an important source of pain and disability, affecting two thirds of adults at some time in their lives. Treatment in these patients is mainly conservative medical management, based on medication, physical therapy, behavioral management, and psychotherapy, surgery being limited to elective cases with neurologic deficits. This study was carried out to evaluate the efficacy of percutaneous nucleoplasty in patients affected by painful diskal protrusions and contained herniations.MethodsFrom February 2004 to October 2005, 72 patients (48 men, 24 women; mean age 48 years) affected by lumbar disk herniation were treated with nucleoplasty coblation. All patients were evaluated clinically and with radiography and MRI in order to confirm the presence of lumbalgic and/or sciatalgic pain, in the absence of major neurologic deficit and with lack of response after 6 weeks of conservative management.ResultsAverage preprocedural pain level for all patients was 8.2 (on a visual analog scale of 1 to 10), while the average pain level at 12 months follow-up was 4.1. At the 1 year evaluation, 79% of patients demonstrated a statistically significant improvement in numeric pain scores (p < 0.01): 17% (12 patients) were completely satisfied with complete resolution of symptoms, and 62% (43 patients) obtained a good result.ConclusionOur data indicate that nucleoplasty coblation is a promising treatment option for patients with symptomatic disk protrusion and herniation who present with lumbalgic and/or sciatalgic pain, have failed conservative therapies, and are not considered candidates for open surgery.

Cerebral vasospasm in a double-injection model in rabbit

The present study was designed to assess the occurrence of cerebral vasospasm following an experimental subarachnoid hemorrhage model in rabbits. Sixty-nine New Zealand albino rabbits were used in this study. One milliliter of fresh arterial blood was injected through the surgically exposed atlanto-occipital membrane over a period of 20 seconds. The procedure was then repeated 24 hours later. Fifty animals underwent digital subtraction angiography at one of the following prefixed intervals: 1, 3, or 8 days after the second injection hemorrhage. Nineteen animals underwent one angiographic examination prior to the instillation of the intracisternal blood. This procedure was followed by a repeated angiography 3 days after the second experimental subarachnoid hemorrhage. For the purpose of evaluation, the films were magnified 10-fold and the diameter of the basilar artery as well as that of the extracranial vertebral artery at three different levels were measured. We assessed the diameter of the basilar artery as well as the mean ratio extracranial vertebral artery/basilar artery diameters. This ratio was considered to minimize anatomical and technical variabilities. The results in the first 50 animals showed a trend suggesting that spasmogenic activity reaches a peak at about the third day after subarachnoid hemorrhage. These results were confirmed in the latter 19 animals. However, mortality in this group was high: 50%. This double-injection model of subarachnoid hemorrhage in rabbits consistently reproduced cerebral vascular spasm 3 days after repeated subarachnoid hemorrhage. However, its usefulness as an experimental model for subarachnoid hemorrhage is limited practically by the high animal mortality in the protocols where repeated angiographic studies are necessary.

The Contribution of Davide Giordano (1864-1954) to Pituitary Surgery: The Transglabellar-Nasal Approach

This report describes the fundamental contribution made by Davide Giordano, proposing the transglabellar surgical approach in a period in which transfacial and transbasal operative approaches to the pituitary gland were considered inadvisable because of their risk. His idea was to gain access through bilateral paranasal and frontal skin incisions, allowing removal of the ethmoid bone and the anterior wall of the sphenoidal cube. With the anterior and inferior aspects of the sella turcica thus exposed, bone is removed and the gland is exposed by incision of the dura mater. The technique proposed by Giordano is undoubtedly a forerunner of the transsphenoidal route to the pituitary gland. The importance of his contribution was confirmed by Cushing, who reported his first use of the approach of Giordano in 1909 in a patient with a pituitary adenoma. The efforts of Giordano clearly inspired surgeons of his era to perform this operation clinically, giving impetus to the further development of neurosurgery.

The surgical treatment of pituitary adenomas in the eighth decade.

BACKGROUND The surgical treatment of pituitary adenomas in elderly patients (i.e., over 70 years of age) is a special problem because of the increased rate of perioperative complications and the reduced tolerance of postoperative fluid and electrolyte imbalance. Therefore, the unquestionable progress in the pharmacological and radiotherapy may not allow these patients the option of radical surgical treatment. We report our experience with the transsphenoidal procedure for pituitary adenomas in aged patients in an attempt to contribute to a better definition of the actual role of surgery. METHODS Transsphenoidal surgery was performed in 11 patients over 70 years of age affected by various histological types of pituitary micro- and macroadenomas, ranging from Hardy Grade I through IIIc. Special care was dedicated to the postoperative treatment, in particular to water and electrolyte balances, and to the immediate treatment of any pathological variation of these parameters. RESULTS We had no mortality and no postoperative adjunctive morbidity. All the patients recovered well from the operation with an average hospital stay of 20 days. The tumor removal was complete in six cases and partial in the remaining five. With an average follow-up of 2 years, we did observe only one case of symptomatic recurrence of the disease. CONCLUSIONS Transsphenoidal surgery in the elderly is feasible and quite safe in the hands of an experienced team, if special care is devoted to the preoperative selection of patients and to the postoperative treatment of fluid and electrolyte imbalance.

Choroid plexus papillomas in infancy and childhood

The present study deals with 15 cases of choroid plexus papilloma, out of approximately 500 cases of brain tumors observed in children up to 16 years old. Several features are considered, including clinical symptoms and signs—mostly related to increased intracranial pressure—radiological diagnosis, pathology and surgical treatment, and results. Surgery may be radical in most cases, with the exception of histologically malignant papillomas. The management results are usually satisfactory. An adequate choice of surgical approach is mandatory and surgical technique should be meticulous, also in order to avoid the risk of intraoperative tumoral seeding.

Reduced GABA Content in the Motor Thalamus during Effective Deep Brain Stimulation of the Subthalamic Nucleus

Deep brain stimulation (DBS) of the subthalamic nucleus (STN), in Parkinsons disease (PD) patients, is a well established therapeutic option, but its mechanisms of action are only partially known. In our previous study, the clinical transitions from OFF- to ON-state were not correlated with significant changes of GABA content inside GPi or substantia nigra reticulata. Here, biochemical effects of STN-DBS have been assessed in putamen (PUT), internal pallidus (GPi), and inside the antero-ventral thalamus (VA), the key station receiving pallidothalamic fibers. In 10 advanced PD patients undergoing surgery, microdialysis samples were collected before and during STN-DBS. cGMP, an index of glutamatergic transmission, was measured in GPi and PUT by radioimmunoassay, whereas GABA from VA was measured by HPLC. During clinically effective STN-DBS, we found a significant decrease in GABA extracellular concentrations in VA (−30%). Simultaneously, cGMP extracellular concentrations were enhanced in PUT (+200%) and GPi (+481%). These findings support a thalamic dis-inhibition, in turn re-establishing a more physiological corticostriatal transmission, as the source of motor improvement. They indirectly confirm the relevance of patterning (instead of mere changes of excitability) and suggest that a rigid interpretation of the standard model, at least when it indicates the hyperactive indirect pathway as key feature of hypokinetic signs, is unlikely to be correct. Finally, given the demonstration of a key role of VA in inducing clinical relief, locally administration of drugs modulating GABA transmission in thalamic nuclei could become an innovative therapeutic strategy.

L-DOPA PRELOADING INCREASES THE UPTAKE OF BOROPHENYLALANINE IN C6 GLIOMA RAT MODEL: A NEW STRATEGY TO IMPROVE BNCT EFFICACY

PURPOSE Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on (10)B(n,alpha)(7)Li reaction, for the treatment of malignant gliomas. One of the main limitations for BNCT effectiveness is the insufficient intake of (10)B nuclei in the tumor cells. This work was aimed at investigating the use of L-DOPA as a putative enhancer for (10)B-drug 4-dihydroxy-borylphenylalanine (BPA) uptake in the C6-glioma model. The investigation was first performed in vitro and then extended to the animal model. METHODS AND MATERIALS BPA accumulation in C6-glioma cells was assessed using radiowave dielectric spectroscopy, with and without L-DOPA preloading. Two L-DOPA incubation times (2 and 4 hours) were investigated, and the corresponding effects on BPA accumulation were quantified. C6-glioma cells were also implanted in the brain of 32 rats, and tumor growth was monitored by magnetic resonance imaging. Rats were assigned to two experimental branches: (1) BPA administration; (2) BPA administration after pretreatment with L-DOPA. All animals were sacrificed, and assessments of BPA concentrations in tumor tissue, normal brain, and blood samples were performed using high-performance liquid chromatography. RESULTS L-DOPA preloading induced a massive increase of BPA concentration in C6-glioma cells only after a 4-hour incubation. In the animal model, L-DOPA pretreatment produced a significantly higher accumulation of BPA in tumor tissue but not in normal brain and blood samples. CONCLUSIONS This study suggests the potential use of L-DOPA as enhancer for BPA accumulation in malignant gliomas eligible for BNCT. L-DOPA preloading effect is discussed in terms of membrane transport mechanisms.