Bellaria Hospital

Bologna, Italy

Bellaria Hospital

Bologna, Italy
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Weller M.,University of Zürich | Stupp R.,University of Lausanne | Reifenberger G.,Heinrich Heine University Düsseldorf | Brandes A.A.,Bellaria Hospital | And 3 more authors.
Nature Reviews Neurology | Year: 2010

The DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) antagonizes the genotoxic effects of alkylating agents. MGMT promoter methylation is the key mechanism of MGMT gene silencing and predicts a favorable outcome in patients with glioblastoma who are exposed to alkylating agent chemotherapy. This biomarker is on the verge of entering clinical decision-making and is currently used to stratify or even select glioblastoma patients for clinical trials. In other subtypes of glioma, such as anaplastic gliomas, the relevance of MGMT promoter methylation might extend beyond the prediction of chemosensitivity, and could reflect a distinct molecular profile. Here, we review the most commonly used assays for evaluation of MGMT status, outline the prerequisites for standardized tests, and evaluate reasons for difficulties in reproducibility. We critically discuss the prognostic and predictive value of MGMT silencing, reviewing trials in which patients with different types of glioma were treated with various chemotherapy schedules, either upfront or at recurrence. Standardization of MGMT testing requires comparison of different technologies across laboratories and prospectively validated cut-off values for prognostic or predictive effects. Moreover, future clinical trials will need to determine, for each subtype of glioma, the degree to which MGMT promoter methylation is predictive or prognostic, and whether testing should become routine clinical practice. © 2010 Macmillan Publishers Limited. All rights reserved.

Carelli V.,Bellaria Hospital | Carelli V.,University of Bologna | Chan D.C.,California Institute of Technology
Neuron | Year: 2014

Because of their high-energy metabolism, neurons are strictly dependent on mitochondria, which generate cellular ATP through oxidative phosphorylation. The mitochondrial genome encodes for critical components of the oxidative phosphorylation pathway machinery, and therefore, mutations in mitochondrial DNA (mtDNA) cause energy production defects that frequently have severe neurological manifestations. Here, we review the principles of mitochondrial genetics and focus on prototypical mitochondrial diseases to illustrate how primary defects in mtDNA or secondary defects in mtDNA due to nuclear genome mutations can cause prominent neurological and multisystem features. In addition, we discuss the pathophysiological mechanisms underlying mitochondrial diseases, the cellular mechanisms that protect mitochondrial integrity, and the prospects for therapy. The nervous system relies on mitochondrial metabolism to drive energy-consuming processes. Carelli and Chan illustrate how defects in mitochondrial DNA lead to neurological dysfunction and discuss how research in mitochondrial biology can unravel pathogenic mechanisms and translate into therapy. © 2014 Elsevier Inc.

Coello A.F.,Hospital Universitario Of Bellvitge | Moritz-Gasser S.,Montpellier University | Moritz-Gasser S.,French Institute of Health and Medical Research | Martino J.,Hospital Universitario Marques Of Valdecilla | And 4 more authors.
Journal of Neurosurgery | Year: 2013

Intraoperative electrical brain mapping is currently the most reliable method to identify eloquent cortical and subcortical structures at the individual level and to optimize the extent of resection of intrinsic brain tumors. The technique allows the preservation of quality of life, not only allowing avoidance of severe neurological deficits but also facilitating preservation of high neurocognitive functions. To accomplish this goal, however, it is crucial to optimize the selection of appropriate intraoperative tasks, given the limited intrasurgical awake time frame. In this review, the authors' aim was to propose specific parameters that could be used to build a personalized protocol for each patient. They have focused on lesion location and relationships with functional networks to guide selection of intrasurgical tasks in an effort to increase reproducibility among neurooncological centers.

Lado F.A.,Yeshiva University | Rubboli G.,Epilepsihospitalet | Rubboli G.,Bellaria Hospital | Capovilla P.,Carlo Poma Hospital | And 2 more authors.
Epilepsia | Year: 2013

The application of metabolic imaging and genetic analysis, and now the development of appropriate animal models, has generated critical insights into the pathogenesis of epileptic encephalopathies. In this article we present ideas intended to move from the lesions associated with epileptic encephalopathies toward understanding the effects of these lesions on the functioning of the brain, specifically of the cortex. We argue that the effects of focal lesions may be magnified through the interaction between cortical and subcortical structures, and that disruption of subcortical arousal centers that regulate cortex early in life may lead to alterations of intracortical synapses that affect a critical period of cognitive development. Impairment of interneuronal function globally through the action of a genetic lesion similarly causes widespread cortical dysfunction manifesting as increased delta slow waves on electroencephalography (EEG) and as developmental delay or arrest clinically. Finally, prolonged focal epileptic activity during sleep (as occurring in the syndrome of continuous spike-wave in slow sleep, or CSWSS) might interfere with local slow wave activity at the site of the epileptic focus, thereby impairing the neural processes and, possibly, the local plastic changes associated with learning and other cognitive functions. Seizures may certainly add to these pathologic processes, but they are likely not necessary for the development of the cognitive pathology. Nevertheless, although seizures may be either a consequence or symptom of the underlying lesion, their effective treatment can improve outcomes as both clinical and experimental studies may suggest. Understanding their substrates may lead to novel, effective treatments for all aspects of the epileptic encephalopathy phenotype. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Brandes A.A.,Bellaria Hospital | Bartolotti M.,Bellaria Hospital | Tosoni A.,Bellaria Hospital | Franceschi E.,Bellaria Hospital
Current neurology and neuroscience reports | Year: 2016

Nitrosoureas represent one of the most active classes of agents in the treatment of high-grade gliomas and glioblastoma. In clinical practice, the most commonly used compounds are lomustine (either alone or in combination with procarbazine and vincristine), carmustine, and fotemustine. Given their toxicity profile and subsequent to the introduction of temozolomide in clinical practice, most of these agents were moved to the recurrent setting. This review focuses on the role of the nitrosoureas currently used in clinical practice for the treatment of malignant gliomas.

Ambrosini-Spaltro A.,University of Bologna | Eusebi V.,University of Bologna | Eusebi V.,Bellaria Hospital
Virchows Archiv | Year: 2010

The current World Health Organization (WHO) classification of central nervous system tumors lists meningeal hemangiopericytomas (HPC) and meningeal solitary fibrous tumors (SFT) as separate entities. On the contrary, SFT and HPC of soft tissues are regarded in the WHO soft tissue fascicle as features of the same entity. The clinical data, histology, and immunohistochemistry of 18 cases of meningeal HPC and 12 cases of peripheral soft tissue HPC-SFT were compared. Both intracranial and soft tissue lesions had significant similarities that included staghorn vasculature, necrotic areas, cytologic atypia, and positivities for CD99, collagen IV, and reticulin. Nevertheless, intracranial tumors were more cellular than HPC-SFT of soft tissues and had fewer collagen bands. Meningeal HPC in addition had more mitoses, higher Ki67 index, stained less intensely for CD34 and B-cell lymphoma 2 (BCL2) than HPC-SFT of soft tissues. Meningeal HPCs recurred in 13 out of 14 cases (92.9%). One of the patients died in the postoperative period for a recurrent lesion 5 years after the diagnosis, and another patient developed an extracranial metastasis 13 years after surgery. None of the six cases of HPC-SFT of soft tissues available for follow-up recurred. Both meningeal and soft tissue tumors appear to represent different features of the same entity. A more aggressive phenotype of the tumor together with incomplete surgical resection of intracranial lesions might explain the noticeable clinical difference between HPC of the meninges and HPC-SFT of soft tissues. © 2010 Springer-Verlag.

Burte F.,Northumbria University | Carelli V.,Bellaria Hospital | Chinnery P.F.,Northumbria University | Yu-Wai-Man P.,Northumbria University
Nature Reviews Neurology | Year: 2015

Mitochondria form a highly interconnected tubular network throughout the cell via a dynamic process, with mitochondrial segments fusing and breaking apart continuously. Strong evidence has emerged to implicate disturbed mitochondrial fusion and fission as central pathological components underpinning a number of childhood and adult-onset neurodegenerative disorders. Several proteins that regulate the morphology of the mitochondrial network have been identified, the most widely studied of which are optic atrophy 1 and mitofusin 2. Pathogenic mutations that disrupt these two pro-fusion proteins cause autosomal dominant optic atrophy and axonal Charcot-Marie-Tooth disease type 2A, respectively. These disorders predominantly affect specialized neurons that require precise shuttling of mitochondria over long axonal distances. Considerable insight has also been gained by carefully dissecting the deleterious consequences of imbalances in mitochondrial fusion and fission on respiratory chain function, mitochondrial quality control (mitophagy), and programmed cell death. Interestingly, these cellular processes are also implicated in more-common complex neurodegenerative disorders, such as Alzheimer disease and Parkinson disease, indicating a common pathological thread and a close relationship with mitochondrial structure, function and localization. Understanding how these fundamental processes become disrupted will prove crucial to the development of therapies for the growing number of neurodegenerative disorders linked to disturbed mitochondrial dynamics. © 2015 Macmillan Publishers Limited. All rights reserved.

Marucci G.,University of Bologna | Rubboli G.,Bellaria Hospital | Giulioni M.,Bellaria Hospital
Clinical Neuropathology | Year: 2010

Drug-resistant chronic temporal lobe epilepsy is the most common type of epilepsy that undergoes surgical treatment. To verify if dentate gyrus alterations mayplay a role in patients with mesial temporal sclerosis (MTS), 14 patients, submitted to epilepsy surgery, were selected. Only cases with MTS alone were included. Granule cell dispersion (GCD) was observed in 7 cases (50%). A statistically significant correlation between GCD and the mean number of seizures/month was evidenced. The percentage of patients who did not achieve seizure relief (i.e. they were not in Engel class 1A) was 57.14% in patients without GCD, whereas that percentage dropped to 14.29% in patients with GCD. The association between a more favorable postsurgical epileptogenic outcome and granule cell pathology in patients with MTS has been observed, thus suggesting that dentate gyrus alterations may play a role in drug-resistant TLE. © 2010 Dustri-Verlag Dr. K. Feistle.

Rafanelli C.,University of Bologna | Offidani E.,University of Bologna | Gostoli S.,University of Bologna | Roncuzzi R.,Bellaria Hospital
Psychiatry Research | Year: 2012

The evidence linking essential systemic arterial hypertension (SAH) with psychological characteristics remains equivocal. The aims of this study were to assess clinical and subclinical distress, psychosocial aspects and psychological well-being in treated hypertensive patients and to evaluate the psychosocial variables associated with higher levels of blood pressure according to guidelines for hypertension management. A consecutive series of 125 hypertensive patients were evaluated using both self- and observer-rated reliable measures. Generalized anxiety disorder, minor depression, demoralization and alexithymia were the most frequent diagnoses. Cluster analysis revealed an association of three distinct symptomatological groups such as the Anxiety-Depression, the Alexithymia and the Somatization groups, with different levels of hypertension. In particular, patients with moderate to severe hypertension were more frequently in the Anxiety-Depression and the Alexithymia groups, whereas the Somatization cluster has been shown to be associated with isolated systolic hypertension. The results provide new insight into the psychosocial characteristics among patients with different levels of SAH according to recent guidelines of the management of hypertension. They also outline the need to monitor the clinical course of hypertensive patients characterized by these specific clinical and subclinical psychological conditions. © 2012 Elsevier Ireland Ltd.

Marucci G.,University of Bologna | Martinoni M.,Bellaria Hospital | Giulioni M.,Bellaria Hospital
APMIS | Year: 2013

We retrospectively analyzed 29 seizure-associated temporal lobe low-grade tumors to evaluate the utility of CD34 and bcl-2 expression in clarifying the relationship of these tumors with different classes of focal cortical dysplasia (FCD). CD34 immunostained 75% of gangliogliomas (GG) and 60% of pleomorphic xanthoastrocytomas. FCD type IIIb [i.e. abnormal cortical layering associated with a glioneuronal tumor, according to the new International League Against Epilepsy (ILAE) classification] presented CD34-immunopositive cells in 2/9 (22.2%) cases, whereas FCD type II in 6/7 (85.7%) cases, a difference statistically significant (p = 0.0117). Bcl-2 immunostained 9/12 (75%) gangliogliomas and 2/3 (66.6%) gangliocytomas. The cases of FCD type IIIb resulted negative for Bcl-2, whereas 4/7 cases (57.1%) of FCD type II showed immunopositive cells. These differences in Bcl-2 expression between FCD type IIIb and FCD type II resulted statistically significant (p = 0.0088). Abnormal cortical layering, overall, represents the kind of FCD more commonly associated with seizure-related low-grade tumors, whereas FCD type II is more frequently associated with GG. The profile of CD34 and Bcl-2 expression exhibited by GG is more similar to that observed in FCD type II. Such immunoprofile suggests the existence of a common pathogenesis linking glioneuronal tumors and FCD type II. © 2012 APMIS.

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