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Luca Regli

Publications and source records attributed to Luca Regli.

At least 19 recordsLinked to original sources
PubMed2006

Time course of aquaporin expression after transient focal cerebral ischemia in mice.

Cerebral edema contributes to morbidity and mortality in stroke. Aquaporins (AQPs)-1, -4, and -9 have been identified as the three main water channels in the brain. To clarify their role in water movement, we have compared their expression patterns with brain swelling after transient focal brain ischemia. There were two peaks of maximal hemispheric swelling at 1 hr and at 48 hr after ischemia, coinciding with two peaks of AQP4 expression. At 1 hr after occlusion, AQP4 expression was significantly increased on astrocyte endfeet in the core and in the border of the lesion. At 48 hr, AQP4 expression was increased in astrocytes in the border of the lesion over the whole cell. AQP9 showed a significant induction at 24 hr that increased gradually with time, without correlation with the swelling. The expression of AQP1 remained unchanged. These results suggest that AQP4, but not AQP1 or AQP9, may play an important role in water movement associated with the pathophysiology of edema after transient cerebral ischemia in the mouse.

Animals↗
PubMed2006

New trends in the medical management of glioblastoma multiforme: the role of temozolomide chemotherapy.

Standard care for newly diagnosed glioblastoma multiforme (GBM) previously consisted of resection to the greatest extent feasible, followed by radiotherapy. The role of chemotherapy was controversial and its efficacy was marginal at best. Five years ago temozolomide (TMZ) was approved specifically for the treatment of recurrent malignant glioma. The role of TMZ chemotherapy administered alone or as an adjuvant therapy for newly diagnosed GBM has been evaluated in a large randomized trial whose results suggested a significant prolongation of survival following treatment. Findings of correlative molecular studies have indicated that methylguanine methyltransferase promoter methylation may be used as a predictive factor in selecting patients most likely to benefit from such treatment. In this short review the authors summarize the current role of TMZ chemotherapy in the management of GBM, with an emphasis on approved indications and practical aspects.

Antineoplastic Agents, Alkylating↗
PubMed2006

Comparison of multislice computerized tomography angiography and digital subtraction angiography in the postoperative evaluation of patients with clipped aneurysms.

OBJECT: In this study the accuracy of multislice computerized tomography (MSCT) angiography in the postoperative examination of clip-occluded intracranial aneurysms was compared with that of intraarterial digital subtraction (DS) angiography METHODS: Forty-nine consecutive patients with 60 clipped aneurysms (41 of which had ruptured) were studied with the aid of postoperative MSCT and DS angiography. Both types of radiological studies were reviewed independently by two observers to assess the quality of the images, the artifacts left by the clips, the completeness of aneurysm occlusion, the patency of the parent vessel, and the duration and cost of the examination. The quality of MSCT angiography was good in 42 patients (86%). Poor-quality MSCT angiograms (14%) were a result of the late acquisition of images in three patients and the presence of clip or motion artifacts in four. Occlusion of the aneurysm on good-quality MSCT angiograms was confirmed in all but two patients in whom a small (2-mm) remnant was confirmed on DS angiograms. In one patient, occlusion of a parent vessel was seen on DS angiograms but missed on MSCT angiograms. The sensitivity and specificity for detecting neck remnants on MSCT angiography were both 100%, and the sensitivity and specificity for evaluating vessel patency were 80 and 100%, respectively (95% confidence interval 29.2-100%). Interobserver agreements were 0.765 and 0.86, respectively. The mean duration of the examination was 13 minutes for MSCT angiography and 75 minutes for DS angiography (p < 0.05). Multislice CT angiography was highly cost effective (p < 0.01). CONCLUSIONS: Current-generation MSCT angiography is an accurate noninvasive tool used for assessment of clipped aneurysms in the anterior circulation. Its high sensitivity and low cost warrant its use for postoperative routine control examinations following clip placement on an aneurysm. Digital subtraction angiography must be performed if the interpretation of MSCT angiograms is doubtful or if the aneurysm is located in the posterior circulation.

Angiography, Digital Subtraction↗
PubMed2005

Simultaneous multilobar electrocorticography (mEcoG) and scalp electroencephalography (scalp EEG) during intracranial vascular surgery: a new approach in neuromonitoring.

OBJECTIVE: Intraoperative neuromonitoring for intracranial vascular surgery is primarily aimed at detecting early ischemic changes to prevent subsequent infarction. Despite various neurophysiological approaches detection of early and focal ischemic changes remains difficult. This study explores the feasibility and sensitivity of intraoperative monitoring using surface EEG (scalp EEG) and multilobar Electrocorticography (mEcoG) recording during intracranial vascular procedures. METHODS: About 21 recordings were acquired in 20 patients undergoing craniotomies for intracranial aneurysms (17), superficial temporal-middle cerebral artery bypass (twice in the same patient) and arteriovenous malformation (2). The recording of scalp EEG (needle electrodes) and EcoG was performed (cupules electrodes) during all of the surgery. Signal was visually analyzed online and using spectral analysis software offline. RESULTS: Good recordings were obtained in all cases, without adding any procedural morbidity. The most common abnormalities on mEcoG were high frequency waves (23-37 Hz; HF-beta3), which appeared just after vascular occlusion and were occasionally followed by slow waves or burst suppression pattern. This focal pattern was seen in a majority of cases (20/21) on the mEcoG, but only in 4 out of 21 cases on the EEG. CONCLUSIONS: Multi-lobe (mEcoG) recording is feasible during craniotomies and detects earlier and more EEG pattern variation than surface EEG monitoring during intracranial vascular manipulations. The authors discuss the high sensitivity of this technique to ischemic changes. SIGNIFICANCE: By detecting earlier and more focal changes than scalp EEG, mEcoG may favor during surgery an increase in interactive strategies and reduction of deleterious event.

Adult↗
PubMed2005

Hypoxia/hypoglycemia preconditioning prevents the loss of functional electrical activity in organotypic slice cultures.

In cerebral ischemic preconditioning (IPC), a first sublethal ischemia increases the resistance of neurons to a subsequent severe ischemia. Despite numerous studies, the mechanisms are not yet fully understood. Our goal is to develop an in vitro model of IPC on hippocampal organotypic slice cultures. Instead of anoxia, we chose to apply varying degrees of hypoxia that allows us various levels of insult graded from mild to severe. Cultures are exposed to combined oxygen and glucose deprivation (OGD) of varying intensities, ranging from mild to severe, assessing both the electrical activity and cell death. IPC was accomplished by exposure to the mildest ischemia condition (10% of O2 for 15 min) 24 h before the severe deprivation (5% of O2 for 30 min). Interestingly, IPC not only prevented delayed ischemic cell death 6 days after insult but also the transient loss of evoked potential response. The major interest and advantage of this system over both the acute slice preparation and primary cell cultures is the ability to simultaneously measure the delayed neuronal damage and neuronal function.

Animals↗
PubMed2005

Posterior temporal haematoma associated with anterior communicating artery aneurysm rupture.

We report the case of a 68-year-old man who presented with symptoms suggesting an intracranial haemorrhage. A computed tomography scan showed subarachnoid haemorrhage associated with a remote posterior temporal intracerebral haematoma. Angiography revealed the presence of an anterior communicating artery aneurysm, which was subsequently clipped. Possible causes for the association of a distant intracerebral haematoma with rupture of an anterior communicating artery aneurysm are discussed. This uncommon association should be recognised to avoid incorrect identification of the origin of haemorrhage.

Aged↗
PubMed2005

Acute brain perfusion disorders in children assessed by quantitative perfusion computed tomography in the emergency setting.

OBJECTIVE: Perfusion computed tomography (CT) is a simple imaging technique that allows accurate quantitative assessment of brain perfusion. Perfusion CT is an ideal imaging technique to be used in the emergency setting and has thus gained recognition in the early management of adult acute stroke patients. Perfusion CT can be applied to children successfully by using adequate imaging protocols. The goal of this article is to provide a pictorial essay of the perfusion CT features of diseases that affect brain perfusion as depicted in a population of children who were evaluated in the emergency CT unit of our institution. METHODS: During the period of September 2001 to October 2002, all the children, who were evaluated in the emergency CT unit of our institution and who were prescribed with a cerebral CT and an intravenous administration of iodinated contrast material, underwent a perfusion-CT examination. Perfusion-CT maps were reviewed in the patients diagnosed as abnormal on the basis of follow-up clinical/radiological examinations and correlated with the results of these tests. RESULTS: Brain perfusion-CT examinations have been performed in 77 children. Fifty-three patients were considered as normal, based on normal conventional cerebral CT and normal clinical/radiological follow-up. Perfusion-CT results showed major abnormalities in 14 cases among the 24 remaining patients, related to brain ischemia in 2, head trauma in 9, brain infection in 2, and sickle cell disease in 1. These abnormalities consisted in low regional cerebral blood flow and volume values, and in high mean transit time values. They demonstrated typical anatomical distribution, depending on the considered pathological condition. CONCLUSIONS: Perfusion CT provides quantitative assessment of child brain perfusion disorders. Its ability to be easily performed upon admission makes it an ideal emergency tool that advantageously competes with other imaging techniques such as perfusion-weighted magnetic resonance imaging, despite its limited spatial coverage. Its usefulness with respect to the impact on treatment and outcome, however, remains to be established in further studies.

Adolescent↗
PubMed2004

D-JNKI1, a cell-penetrating c-Jun-N-terminal kinase inhibitor, protects against cell death in severe cerebral ischemia.

BACKGROUND AND PURPOSE: In 2 models of severe ischemic injury, we have evaluated the neuroprotective action of D-JNKI1, a cell-penetrating and protease-resistant peptide selectively inhibiting the c-Jun-N-terminal kinase (JNK). METHODS: Hippocampal slices from newborn rats were subjected to oxygen (5%) and glucose (1 mmol/L) deprivation for 30 minutes. Cell death was evaluated with propidium iodide, and the evoked potential responses were recorded in the CA1 region after stimulation in CA3. Male ICR-CD1 mice were subjected to permanent endoluminal "suture" middle cerebral artery occlusion (MCAo). The lesion size was determined after 24 hours by triphenyl-tetrazolium chloride staining, and neurological scores and rotarod treadmill performance were used to evaluate the neurological outcome. RESULTS: In vitro, D-JNKI administration 6 hours after oxygen glucose deprivation reduced cell death at 24 hours from 21%+/-8% (n=10) to 5%+/-3% (n=7, P<0.01). This protective effect was still seen at 48 hours, paralleled by an improved amplitude of the evoked potential response. In vivo in the mouse, D-JNKI1 administration 3 hours after ischemia significantly reduced the infarct volume from 162+/-27 mm(3) (n=14) to 85+/-27 mm(3) (n=9, P<0.001). The functional outcome was also improved. CONCLUSIONS: JNK inhibition prevents cell death induced by oxygen and glucose deprivation in hippocampal slice cultures in vitro and by permanent suture MCAo in vivo. D-JNKI1 is a powerful neuroprotectant in models of both mild and severe cerebral ischemia, with an extended therapeutic window. Further investigations are needed to identify the relevant JNK target(s) mediating ischemic neuronal death.

Animals↗
PubMed2004

Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide.

PURPOSE: In the setting of a prospective clinical trial, we determined the predictive value of the methylation status of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter for outcome in glioblastoma patients treated with the alkylating agent temozolomide. Expression of this excision repair enzyme has been associated with resistance to alkylating chemotherapy. EXPERIMENTAL DESIGN: The methylation status of MGMT in the tumor biopsies was evaluated in 38 patients undergoing resection for newly diagnosed glioblastoma and enrolled in a Phase II trial testing concomitant and adjuvant temozolomide and radiation. The epigenetic silencing of the MGMT gene was determined using methylation-specific PCR. RESULTS: Inactivation of the MGMT gene by promoter methylation was associated with longer survival (P = 0.0051; Log-rank test). At 18 months, survival was 62% (16 of 26) for patients testing positive for a methylated MGMT promoter but reached only 8% (1 of 12) in absence of methylation (P = 0.002; Fisher's exact test). In the presence of other clinically relevant factors, methylation of the MGMT promoter remains the only significant predictor (P = 0.017; Cox regression). CONCLUSIONS: This prospective clinical trial identifies MGMT-methylation status as an independent predictor for glioblastoma patients treated with a methylating agent. The association of the epigenetic inactivation of the DNA repair gene MGMT with better outcome in this homogenous cohort may have important implications for the design of future trials and supports efforts to deplete MGMT by O-6-benzylguanine, a noncytotoxic substrate of this enzyme.

Adult↗
PubMed2004

Relationship between brain perfusion computed tomography variables and cerebral perfusion pressure in severe head trauma patients.

OBJECTIVE: To compare brain perfusion-computed tomography (CT) results with invasive cerebral perfusion pressure (CPP) monitoring in severe head trauma patients. DESIGN: Prospective cohort study. SETTING: Emergency room and surgical intensive care unit of our hospital. PATIENTS: Sixty-one severe head trauma patients. INTERVENTIONS: We prospectively collected 103 perfusion-CT examinations with simultaneous measurement of mean arterial pressure and intracranial pressure, affording calculation of CPP. The statistical relationship between perfusion-CT results and the corresponding CPP values was evaluated using Wilcoxon (Mann-Whitney) and generalized F-tests. The functional outcome of the 61 patients was evaluated 3 months after trauma on the basis of the Glasgow Outcome Scale score and compared between groups using Fisher's exact tests. MEASUREMENTS AND MAIN RESULTS: Perfusion-CT enabled us to distinguish between two groups of patients. Within each group, a significant correlation (p <.001) between the CPP values and the corresponding perfusion-CT results was demonstrated. There was also a significant correlation (p <.001) between the CPP values and the extent of the abnormal perfusion-CT areas (R up to.817). The first group was characterized by a weak dependence of perfusion-CT results on the corresponding CPP values (low slope) and the second group by a strong dependence (steep slope). These groups were interpreted as having preserved (or pseudo) and impaired cerebral vascular autoregulation, respectively. The functional outcome was better in the second group of patients. CONCLUSIONS: Intermittent perfusion-CT measurements plus continuous CPP measurement provide more information than continuous CPP alone. Perfusion-CT gives unique information regarding regional heterogeneity of brain perfusion. It might allow clinicians to distinguish between patients with preserved auto-regulation (or pseudoautoregulation) and those with impaired autoregulation and could therefore guide interpretation of CPP measurements and therapy.

Adult↗
PubMed2004

Admission perfusion CT: prognostic value in patients with severe head trauma.

PURPOSE: To assess the prognostic value of admission perfusion computed tomography (CT) in patients with severe head trauma. MATERIALS AND METHODS: This prospective study included 130 patients with severe trauma, aged 19-86 years, admitted with a Glasgow Coma Scale score of 8 or less. They underwent perfusion CT as part of their admission CT survey. Clinical data, unenhanced cerebral CT findings, and perfusion CT scans were evaluated with respect to the Glasgow Outcome Scale (GOS) score at 3 months. Perfusion CT features were evaluated in patients with intracranial hypertension, cerebral contusions, and juxtadural hematomas. Ordered logistic regression was used to determine risk factors for an unfavorable GOS score at 3 months. RESULTS: Perfusion CT was more sensitive than conventional unenhanced CT in the detection of cerebral contusions. Perfusion CT featured specific patterns with respect to patient outcome, with normal brain perfusion or hyperemia in patients with favorable outcome, and oligemia in patients with unfavorable outcome. The number of arterial territories with low regional cerebral blood volume at perfusion CT was an independent prognostic factor (P =.008), as were mean arterial pressure at the scene of accident (P =.083), base excess at admission (P =.002), presence of skull fractures (P =.041), and signs of herniation (P =.013) at admission unenhanced cerebral CT. Perfusion CT also showed a range of brain perfusion alterations in patients with juxtadural collections, cerebral edema, or intracranial hypertension. CONCLUSION: Perfusion CT in patients with severe head trauma provides independent prognostic information regarding functional outcome.

Adult↗
PubMed2004

Brain perfusion in children: evolution with age assessed by quantitative perfusion computed tomography.

OBJECTIVE: The objective of this study was to assess the age-related variations of brain perfusion through quantitative cerebral perfusion computed tomography (CT) results in children without brain abnormality. METHODS: Brain perfusion CT examinations were performed in 77 children, aged 7 days to 18 years. These patients were admitted at our institution for both noncontrast and contrast-enhanced cerebral CT. Only children whose conventional cerebral CT and clinical/radiologic follow-up, including additional investigations, were normal were taken into account for this study (53 of 77). RESULTS: The average regional rCBF amounts to 40 (mL/100 g per minute) for the first 6 months of life, peaks at approximately 130 (mL/100 g per minute) at approximately 2 to 4 years of age, and finally stabilizes at approximately 50 (mL/100 g per minute) at approximately 7 to 8 years of age, with a small increase of rCBF values at approximately 12 years of age. The rCBF in the gray matter averages 3 times that in the white matter, except for the first 6 months of life. The global CBF represents 10% to 20% of the global cardiac output for the first 6 months of life, peaks at approximately 55% by 2 to 4 years of age, and finally stabilizes at approximately 15% by 7 to 8 years of age. Specific age-related evolution patterns were identified in the different anatomic areas of the cerebral parenchyma, which could be related to the development of neuroanatomic structures and to the emergence of corresponding cognitive functions. CONCLUSIONS: Quantitative perfusion CT characterization of brain perfusion shows specific age variations. Brain perfusion of each cortical area evolves according to a specific time course, in close correlation with the psychomotor development.

Adolescent↗
PubMed2003

Classification of human astrocytic gliomas on the basis of gene expression: a correlated group of genes with angiogenic activity emerges as a strong predictor of subtypes.

The development of targeted treatment strategies adapted to individual patients requires identification of the different tumor classes according to their biology and prognosis. We focus here on the molecular aspects underlying these differences, in terms of sets of genes that control pathogenesis of the different subtypes of astrocytic glioma. By performing cDNA-array analysis of 53 patient biopsies, comprising low-grade astrocytoma, secondary glioblastoma (respective recurrent high-grade tumors), and newly diagnosed primary glioblastoma, we demonstrate that human gliomas can be differentiated according to their gene expression. We found that low-grade astrocytoma have the most specific and similar expression profiles, whereas primary glioblastoma exhibit much larger variation between tumors. Secondary glioblastoma display features of both other groups. We identified several sets of genes with relatively highly correlated expression within groups that: (a). can be associated with specific biological functions; and (b). effectively differentiate tumor class. One prominent gene cluster discriminating primary versus nonprimary glioblastoma comprises mostly genes involved in angiogenesis, including VEGF fms-related tyrosine kinase 1 but also IGFBP2, that has not yet been directly linked to angiogenesis. In situ hybridization demonstrating coexpression of IGFBP2 and VEGF in pseudopalisading cells surrounding tumor necrosis provided further evidence for a possible involvement of IGFBP2 in angiogenesis. The separating groups of genes were found by the unsupervised coupled two-way clustering method, and their classification power was validated by a supervised construction of a nearly perfect glioma classifier.

Adolescent↗
PubMed2003

Multislice computerized tomography angiography in the evaluation of intracranial aneurysms: a comparison with intraarterial digital subtraction angiography.

OBJECT: The goal of this study was to assess the diagnostic accuracy of computerized tomography (CT) angiography performed with the aid of multislice technology (MSCT angiography) in the investigation of intracranial aneurysms, by comparing this method with intraarterial digital subtraction (IADS) angiography. METHODS: Fifty consecutive adult patients, who successively underwent MSCT angiography (four rows) and IADS angiography of intracranial vessels, were prospectively identified. The MSCT angiography studies consisted of 1.25-mm slices, with 0.8-mm reconstruction intervals, a pitch of 0.75, and timing determined by a test bolus. Two neuroradiologists, who were blinded to the initial interpretation of the MSCT angiograms as well as to those of the IADS angiograms, independently reviewed the MSCT angiograms for the detection and characterization of intracranial aneurysms. Forty-nine intracranial aneurysms were identified in 40 patients; 33 of these lesions were responsible for subarachnoid hemorrhage. The sensitivity, specificity, and accuracy of MSCT angiography in the detection of intracranial aneurysms were 94.8, 95.2, and 94.9%, respectively, on a per-aneurysm basis and 99, 95.2, and 98.3%, respectively, on a per-patient basis. Interobserver agreement was 98%. There was an excellent correlation between aneurysm size assessed using MSCT angiography and that determined by IADS angiography (slope = 0.916, r = 0.877, p < 0.001); however, 2 mm stood as the cutoff size below which the sensitivity of MSCT angiography was statistically lower. That method displayed great accuracy in characterizing the morphological characteristics of the aneurysm. CONCLUSIONS: Multislice CT angiography is an accurate and robust noninvasive screening test for intracranial aneurysms. It performs better than that reported for single-slice CT angiography. Introduction of eight- and especially 16-row MSCT angiography will provide further progression through thinner slices, a lower pitch, and a purely arterial phase.

Angiography, Digital Subtraction↗
PubMed2002

What and where in human audition: selective deficits following focal hemispheric lesions.

A sound that we hear in a natural setting allows us to identify the sound source and localize it in space. The two aspects can be disrupted independently as shown in a study of 15 patients with focal right-hemispheric lesions. Four patients were normal in sound recognition but severely impaired in sound localization, whereas three other patients had difficulties in recognizing sounds but localized them well. The lesions involved the inferior parietal and frontal cortices, and the superior temporal gyrus in patients with selective sound localization deficit; and the temporal pole and anterior part of the fusiform, inferior and middle temporal gyri in patients with selective recognition deficit. These results suggest separate cortical processing pathways for auditory recognition and localization.

Adult↗
PubMed2002

Promising survival for patients with newly diagnosed glioblastoma multiforme treated with concomitant radiation plus temozolomide followed by adjuvant temozolomide.

PURPOSE: Temozolomide is a novel oral alkylating agent with demonstrated efficacy as second-line therapy for patients with recurrent anaplastic astrocytoma and glioblastoma multiforme (GBM). This phase II study was performed to determine the safety, tolerability, and efficacy of concomitant radiation plus temozolomide therapy followed by adjuvant temozolomide therapy in patients with newly diagnosed GBM. PATIENTS AND METHODS: Sixty-four patients were enrolled onto this open-label, phase II trial. Temozolomide (75 mg/m(2)/d x 7 d/wk for 6 weeks) was administered orally concomitant with fractionated radiotherapy (60 Gy total dose: 2 Gy x 5 d/wk for 6 weeks) followed by temozolomide monotherapy (200 mg/m(2)/d x 5 days, every 28 days for six cycles). The primary end points were safety and tolerability, and the secondary end point was overall survival. RESULTS: Concomitant radiation plus temozolomide therapy was safe and well tolerated. Nonhematologic toxicities were rare and mild to moderate in severity. During the concomitant treatment phase, grade 3 or 4 neutropenia, thrombocytopenia, or both were observed in 6% of patients, including two severe infections with Pneumocystis carinii. During adjuvant temozolomide, 2% and 6% of cycles were associated with grade 3 and 4 neutropenia or thrombocytopenia, respectively. Median survival was 16 months, and the 1- and 2-year survival rates were 58% and 31%, respectively. Patients younger than 50 years old and patients who underwent debulking surgery had the best survival outcome. CONCLUSION: Continuous daily temozolomide and concomitant radiation is safe. This regimen of concomitant chemoradiotherapy followed by adjuvant chemotherapy may prolong the survival of patients with glioblastoma. Further investigation is warranted, and a randomized trial is ongoing.

Adult↗