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Anna Rosati,
Pietro Luigi Poliani,
Alice Todeschini,
Manuela Cominelli,
Daniela Medicina, Marco Cenzato,
Edda Lucia Simoncini,
Stefano Maria Magrini,
Michela Buglione,
Salvatore Grisanti,
Alessandro Padovani
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ABSTRACT: Background
Glutamine synthetase (GS) is an astrocytic enzyme catalyzing the conversion of glutamate and ammonia to glutamine. Its up-regulation has been related to higher tumor proliferation and poor prognosis in extra-cerebral tumors. We have previously reported a GS deficiency in patients with glioblastoma multiforme (GBM) who also developed epilepsy, which is a favorable prognostic factor in glioma. Here, we investigated the prognostic value of GS expression in patients with GBM with or without epilepsy and its correlation with survival.Methods
We conducted a clinical and histopathological study on 83 (52 males) consecutive patients with newly diagnosed GBM. Immunohistochemical expression of GS was scored semi-quantitatively on the basis of cell number, staining intensity, and distribution of immunoreactive cells. Several clinical and neuropathological variables were analyzed in relation to survival and GS expression.ResultsMedian age at diagnosis was 62 years. At the last evaluation, with a median follow-up of 11.5 months (range, 1.5-58 months), 5 patients (6%) were still alive and 78 (94%) were dead. GS expression patterns in neoplastic cells were inversely correlated to the presence of epilepsy (P < .0001 for intensity and P < .009 for homogeneity of GS distribution, respectively). Univariate analysis showed that RPA score, epilepsy, O(6)-methylguanine-DNA methyltransferase (MGM)T status, application of Stupp protocol, and GS intensity pattern had a significant impact on survival. Absent/low intensity of GS expression was significantly associated with a longer survival in both uni- (19 vs 8 months; P < .0005) and multivariate (P = .003) analyses.Conclusions
Absent/low-intensity GS expression pattern represents a valuable biomarker of both epilepsy and overall survival in GBM.
Neuro-Oncology 02/2013; · 5.72 Impact Factor
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ABSTRACT: Continuous assessment of the cerebrovascular autoregulation (CVA) through use of the pressure reactivity index (PRx), a moving linear correlation coefficient between mean arterial blood pressure and intracranial pressure, has been effective in optimizing cerebral perfusion pressure (CPPopt) in traumatic brain injured (TBI) patients. This study investigates the feasibility of measuring CPPopt in patients with aneurysmal subarachnoid hemorrhage (aSAH) by continuously assessing the CVA.
Twenty-nine aSAH patients were enrolled, and data from CVA status, CPPopt, and periods when CPP was below, within, or above CPPopt were computed daily. Outcome was assessed at 6 months with the Glasgow Outcome Scale. Mann-Whitney U test was used to analyze differences in the duration of impaired CVA and duration of CPP below CPPopt in patients with good and poor outcomes. Multivariable logistic regression analysis was used to identify independent predictors of outcome.
CVA monitoring data were available for all 29 patients with a total monitoring time of 2757 h. The duration of impaired CVA was 36.5% (interquartile range: 24.6 to 49.8) of the total monitoring time in 15 patients with good outcome and 71.6% of the total monitoring time (51.2 to 80.0) in 14 patients with poor outcome (Mann-Whitney U test 3.295, P=0.0010). PRx-based CPPopt could be identified in 26 patients (89.6%) with a total monitoring time of 2691 h. The duration of CPP below the CPPopt range was 28.0% (interquartile range: 18.0 to 47.0) of the total monitoring time in patients with good outcome and 76.0% (48.5 to 82.5) in patients with poor outcome (Mann-Whitney U test 2.779, P=0.0054). Glasgow Coma Scale score and duration of impaired CVA were independently associated with 6-month outcome (Glasgow Coma Scale score odds ratio: 1.95, 95% confidence interval: 1.01-3.75; duration of impaired CVA odds ratio: 0.88, 95% confidence interval: 0.78-0.99).
The assessment of CVA and CPPopt is feasible in aSAH patients and may provide important information regarding long-term outcome. A PRx above the 0.2 threshold and a CPP below the CPPopt range are associated with worse outcome.
Journal of neurosurgical anesthesiology 06/2011; 24(1):3-8. · 2.41 Impact Factor
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ABSTRACT: To evaluate the efficacy and safety of levetiracetam in the management of epilepsy in patients with glioma.
A prospective study in hospitalized patients with a new diagnosis of glioma.
Department of Neurological Sciences and Visions, Spedali Civili of Brescia.
From March 1, 2006, until January 1, 2009, 176 consecutive patients (101 men and 75 women) with a first diagnosis of glioma were enrolled in the study. All patients with a diagnosis of epilepsy were treated with levetiracetam.
Clinical, histological, and magnetic resonance imaging findings were analyzed.
Age at the diagnosis of glioma ranged from 22 to 79 years (mean [SD], 57 [15] years; median, 59 years). Duration of the disease ranged from 27 days to 2(1/2) years (mean [SD], 13.7 [7.8] months; median, 13 months). Eighty-two patients received levetiracetam because of a diagnosis of epilepsy. At the last evaluation (May 1, 2009), 75 of 82 patients (91%) treated with levetiracetam were seizure free; in 2 of these patients, levetiracetam was withdrawn because of intolerable adverse effects. Prompt and long-lasting control of seizures was obtained in 49 of 82 patients (60%) with a dose of levetiracetam that ranged from 1500 to 3000 mg/d, and 9 (11%) of the treated patients needed an increase of levetiracetam dosage to 4000 mg/d to become seizure free. No laboratory abnormalities were observed in patients with concomitant chemotherapy.
The results of this study provide good evidence that levetiracetam is efficacious and safe in patients with epilepsy due to glioma.
Archives of neurology 03/2010; 67(3):343-6. · 6.31 Impact Factor
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Damiano Rizzoni,
Carolina De Ciuceis,
Enzo Porteri,
Silvia Paiardi,
Gianluca E M Boari,
Pietro Mortini,
Claudio Cornali, Marco Cenzato,
Luigi F Rodella,
Elisa Borsani,
Nicola Rizzardi,
Caterina Platto,
Rita Rezzani,
Enrico Agabiti Rosei
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ABSTRACT: Structural alterations in the microcirculation may be considered an important mechanism of organ damage. An increased media-to-lumen ratio of subcutaneous small resistance arteries has been demonstrated to predict the development of cardiocerebrovascular events in hypertensive patients. Alterations in the structure of small cerebral arteries have been demonstrated in animal models of experimental or genetic hypertension. However, no evaluation with reliable techniques has ever been performed in humans.
Twenty-eight participants were included in the present study: they were 13 hypertensive patients and 15 normotensive individuals. All participants underwent a neurosurgical intervention for benign or malign tumors. A small portion of morphologically normal cerebral tissue was excised from surgical samples and examined. Cerebral small resistance arteries (relaxed diameter around 200 mum) were dissected and mounted on an isometric and isobaric myograph, and the tunica media to internal lumen ratio was measured. In addition, cerebral cortical microvessel density (MVD) was also evaluated. The tissue was sectioned and stained for CD31, and MVD was measured with an automated image analyzer (percentage of area stained). Blood pressure values were evaluated, before surgical intervention, by standard sphygmomanometry.
M/L was significantly greater and MVD significantly lower in hypertensive patients than that in normotensive individuals. No difference between groups in collagen content or mechanical properties of cerebral small arteries was observed.
Our results indicate that structural alterations of small cerebral vessels are present in hypertensive patients compared with normotensive individuals, similar to those previously observed in subcutaneous small arteries.
Journal of hypertension 05/2009; 27(4):838-45. · 4.02 Impact Factor
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ABSTRACT: The clinical outcome of patients with severe head injuries is still critically dependent on their secondary injuries. Although hypoxia and hypotension appear to mediate a substantial proportion of secondary injuries, many studies associate secondary brain injury with neuroinflammatory responses. Chemokines have been detected in the cerebrospinal fluid but not in the brain tissue of patients with head trauma. This study was performed to determine if chemokines were expressed in pericontusional brain tissue in patients with moderate or severe head trauma who underwent surgical evacuation of their brain contusions.
Twelve patients with posttraumatic cerebral contusion requiring a surgical evacuation were studied. A 20- to 40-mg sample of white matter was removed from the surgical cavity in the pericontusional area. Two patients undergoing elective surgery for clip ligation of an unruptured aneurysm were used as controls. The median interval from trauma to biopsy procedure was 44 hours (range 3-360 hours). Total RNA was isolated from these samples and a ribonuclease protection assay was performed to measure the mRNA levels of several chemokines: CCL2, CCL3, CCL4, CCL5, CXCL8, CXCL10, and XCL1.
The CCL2, a monocyte chemoattractant produced by activated astrocytes, was the most strongly expressed chemokine, followed by CXCL8, CCL3, and CCL4. The chemokines CXCL10 and CCL5 were expressed at very low levels, and XCL1 was not detected.
Chemokine activation occurs early after moderate or severe head trauma and is maintained for several days after trauma. This event may contribute to neuroinflammatory exacerbation of posttraumatic brain damage in the pericontusional brain tissue.
Journal of Neurosurgery 06/2008; 108(5):958-62. · 2.96 Impact Factor
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ABSTRACT: The outcome of treatment for a spinal dural arteriovenous fistula is unpredictable. In this study, we reviewed the outcome of patients treated for this condition, in relation to pretreatment indicators.
We reviewed the records of 37 consecutive patients treated either surgically or endovascularly in our department between 1989 and 2002.
At follow-up, 78% of the patients reported improvement. Those with motor symptoms had the best outcome: improvement was achieved in more than 60% of the patients, amounting to 1 or 2 points on the Aminoff scale. Sensory disorders improved in 43% of cases, pain in 61%, and sphincter impairment in only 37%. Patients with a fistula in the lower thoracic region did better than those with fistulae in other locations.
The clinical state before treatment is certainly relevant in predicting outcome. Age and duration of the symptoms before treatment have no direct relation to the chances of improvement with treatment, particularly when motor improvement is considered. The modality of onset of symptoms and location of the fistula play significant roles, also: a fistula in the lower thoracic segment was associated with more severe symptoms but tended to improve more (83%, P = 0.04) after treatment. Midthoracic and lumbar fistulae showed a lower incidence of improvement (<50%).
Neurosurgery 11/2004; 55(4):815-22; discussion 822-3. · 2.79 Impact Factor
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ABSTRACT: Radiation therapy diminishes the risk of recurrence of incompletely removed nonfunctioning pituitary adenoma (NPA). The authors evaluated the efficacy and safety of gamma knife surgery (GKS) in patients with residual NPA following surgical debulking of the tumor.
Fifty-four patients, 26 men and 28 women, ranging in age from 29 to 72 years underwent gamma knife treatment. Baseline and follow-up studies involved magnetic resonance imaging, hormone evaluation, and neuroophthalmological examination 6 and 12 months after GKS and at yearly intervals thereafter. The mean follow up after GKS was 41.1 +/- 3.1 months. Two of 52 patients undergoing follow up had a recurrence 40 and 49 months after GKS. In both of these patients the treated lesion had reduced in size, but a new lesion appeared in the contralateral side of the sella turcica. The recurrence-free interval at 5 years was 88.2% (95% confidence interval 72.6-100%). Tumor volume decreased from a baseline value of 2.3 +/- 0.2 to 1.7 +/- 0.2 cm3 at the last follow up (p < 0.001). Twenty-two patients (42.3%) had a 20% or greater reduction in tumor volume. The administered radiation dose had been significantly higher in patients who experienced tumor reduction. Visual function and motility did not deteriorate in any patient. New cases of hypogonadism, hypothyroidism, and hypoadrenalism occurred in 12.5, 8.6, and 2.3%, respectively, of assessable patients at risk.
Gamma knife surgery was effective in controlling the growth of residual NPA after previously performed maximal surgical debulking. The major advantage of GKS compared with fractionated radiotherapy seems to be a lower risk of side effects, especially a lower risk of hypopituitarism.
Journal of Neurosurgery 03/2004; 100(3):438-44. · 2.96 Impact Factor
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ABSTRACT: Trigeminal neuralgia is usually caused by microvascular conflict with the fifth cranial nerve in the pontocerebellar angle. Rarely is it secondary to other extra-axial or intra-axial lesions. Few cases of trigeminal neuralgia due to cavernous angiomas have been reported in the literature. This is the first report of surgical decompression of the intra-axial trigeminal nerve tract from a deep pontine cavernous angioma.
A 45-year-old man came to our attention for frequent and intense left facial pain episodes compatible with trigeminal neuralgia in the V1 and V2 branches, poorly responsive to carbamazepine treatment. Magnetic resonance imaging revealed a left posterolateral pontine cavernous angioma. No neurovascular conflict was found.
The cavernous angioma was surgically excised. No new neurological deficit arose and the pain episodes completely disappeared.
Trigeminal neuralgia can occur occasionally secondary to the compressive effect of a pontine cavernous angioma. In this patient surgical removal of the cavernous angioma can be considered a successful and relatively safe treatment.
World Neurosurgery 74(4-5):544-6. · 0.68 Impact Factor
