Luigi Caputi - Academia.edu (original) (raw)

Papers by Luigi Caputi

Research paper thumbnail of New Insights Into mGluRs Function in the Substantia Nigra Pars Compacta

Advances in Behavioral Biology, 2002

Metabotropic glutamate receptors (mGluRs) regulate many processes in the central nervous system (... more Metabotropic glutamate receptors (mGluRs) regulate many processes in the central nervous system (CNS), including synaptic plasticity, learning, memory, motor coordination, pain transmission and neurodegeneration (Linden et al., 1991; Nicoletti et al., 1996; Conn and Pin, 1997). They form a family of eight subtypes classified into three groups, I through III (Masu et al., 1991; Houamed et al., 1991; Nakanishi, 1992; Knöpfel et al., 1995; Conn and Pin, 1997), which are implicated in different aspects of physiology and pathology of the CNS: group 1 (mGluRs land 5) are mainly localized on post-synaptic membranes and are coupled to intracellular calcium pools and to membrane ion channelsviaG-proteins, whereas group II and III are localized pre-synaptically and negatively coupled to adenylate cyclase (Pin and Duvoisin, 1992). The group I mGluRs generate slow EPSPs and calcium responses in cerebellar Purkinje neurons (Batchelor and Garthwaite, 1997) and hippocampal pyramidal neurons (Congar et al., 1997). Transient mGluR-mediated calcium increases can be elicited by stimulation of IP3sensitive (Murphy and Miller, 1989, Takechi et al., 1998) and/or ryanodine-sensitive (Berridge, 1998) receptors localized on intracellular calcium stores A family of proteins has been recently described, whose expression is driven by synaptic activity (Brackeman et al., 1997), as a physical link between mGluRs and either IP3—sensitive or ryanodinesensitive receptors, termed Homer protein (Brakeman et al., 1997, Tu et al., 1998) and this represents a novel mechanism in calcium signaling and might provide molecular insight into the synaptic function of Homer proteins.

Research paper thumbnail of Lamotrigine derivatives and riluzole inhibit INa,P in cortical neurons

Neuroreport, Jan 2, 2002

The persistent, slowly inactivating fraction of the sodium current is involved in key functions i... more The persistent, slowly inactivating fraction of the sodium current is involved in key functions in the CNS such as dendritic integration of synaptic inputs and cellular excitability. We have studied whether established anti-epileptic drugs and neuroprotective agents target the persistent sodium current. Two lamotrigine derivatives (sipatrigine and 202W92) and riluzole inhibited the persistent sodium current at low, therapeutic concentrations. In contrast, lamotrigine and the classical antiepileptic agents phenytoin and valproic acid blocked the fast-inactivating sodium channel but failed to affect the persistent fraction. The ability to influence either mode of channel activity may represent a defining feature of each drug subclass, changing profoundly their clinical indications. Given the damaging role of a sustained influx of sodium in both pharmaco-resistant seizures or excitotoxic insults, we suggest the utilization of drugs that suppress the persistent conductance.

Research paper thumbnail of Italian patent foramen ovale survey (I.P.O.S.): Early results

Perspectives in Medicine, 2012

ABSTRACT Percutaneous patent foramen ovale (PFO) closure is gaining wide acceptance. Aims of the ... more ABSTRACT Percutaneous patent foramen ovale (PFO) closure is gaining wide acceptance. Aims of the study were to analyse clinical practice regarding PFO closure in Italy, to study indications, devices, results, and the follow-up of large series of patients treated by percutaneous PFO closure.Methods and patientsItalian patent foramen ovale survey (IPOS) is a prospective, observational, multi-centric survey that uses a web-based database. The survey lasted 12 months, (November 2007–October 2008). 50 centres participated. Ongoing follow-up will continue up to 36 months. 1035 patients (m.a. 46 years, 60% females) were included in the registry. Most subjects were treated due to a previous history of TIA/ischemic stroke (∼80% of patients). PFO diagnosis and right-to-left shunt (RLS) were assessed by contrast-enhanced transesophageal (cTEE) and/or transthoracic echocardiography and/or transcranial doppler. An aneurysm of the interatrial septum was associated in 41% of patients. Intraprocedural monitoring was assessed by using cTEE and fluoroscopy in 70% and intracardiac echocardiography in 30% of subjects. Procedures were performed under general anesthesia and local anesthesia/conscious sedation in 54% and 46% of patients respectively. The most used device for PFO closure was Amplatzer (∼70% of cases).ResultsThe procedure was successful in all patients. Early complications occurred in 24/1035 patients (2.3%): 12/24 (50%) of them had cardiac arrhythmias, 1 subject had a TIA. Data regarding both clinical and cardio-neurosonological follow-up were assessed in 444/1035 (43%) subjects. The rate of neurological events and cardiac and extra-cardiac complications were around 3% and 9% up to the 24-month follow-up respectively. A large permanent residual RLS and no RLS were observed in less than 1% and in ∼82% of patients at the 1-year follow-up, respectively.Conclusions Our data confirm that percutaneous PFO closure is a safe procedure. Early complications and those during follow-up are mostly related to arrhythmias. Longer follow-up is under way.

Research paper thumbnail of Actions of the sodium channel inhibitor 202W92 on rat midbrain dopaminergic neurons

Synapse, 2003

Excessive glutamatergic activity is implicated in Parkinson's disease (PD) and sodium channel blo... more Excessive glutamatergic activity is implicated in Parkinson's disease (PD) and sodium channel blockade, resulting in inhibition of glutamate release, is a potential therapeutic approach to PD therapy. Beneficial effects of riluzole and lamotrigine have been reported in animal models of PD, but these compounds have relatively low potency as sodium channel inhibitors and also inhibit N and P/Q-type calcium channels. 202W92, a structural analog of lamotrigine, is a potent sodium channel inhibitor, with no effect on N, P/Q-type channels. Here we present the effects of 202W92 on single patch-clamped dopaminergic neurons. 202W92 (Ն10 M) inhibited spontaneous action potential firing and reduced amplitude and frequency of evoked action potentials. It also inhibited the frequency of 4-aminopyridine (4-AP)-and electrically evoked excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs), with Ͼ80% inhibition at 10 M (IC 50 1.5 M). EPSC and IPSC amplitudes were partially inhibited. 202W92 did not affect postsynaptic responses to locally applied glutamate and GABA, nor spontaneously occurring mini-IPSCs. These actions of 202W92 are compatible with sodium channel inhibition and depression of transmitter release. Synapse 48:123-130, 2003.

Research paper thumbnail of D-Tubocurarine reduces GABA responses in rat substantia nigra dopamine neurons

Research paper thumbnail of Postural Dependency of Right to Left Shunt: Role of Contrast-Enhanced Transcranial Doppler and Its Potential Clinical Implications

Stroke, 2008

Right to left shunt is involved in conditions in which postural changes may be pathogenically rel... more Right to left shunt is involved in conditions in which postural changes may be pathogenically relevant. The aim of this work was to assess the frequency of posturally dependent right to left shunt. In 109 consecutive right to left shunt-positive subjects (male/female=40/69, age 43+/-12 years), we assessed with contrast-enhanced transcranial Doppler the bubble load during normal breathing and after the Valsalva maneuver in both standing and recumbent position randomizing the order of testing. During normal breathing, the average bubble count was 11+/-20 in the recumbent and 26+/-60 in the standing position. After the Valsalva maneuver, it was 40+/-38 and 42+/-37, respectively. The increase of bubble load in standing position occurred in 42% of patients and was independent of the order of testing. The amount of permanent right to left shunt is posture-dependent in 40% of patients. Testing in the sitting position may thus be warranted in doubtful or inconclusive results obtained with the subject in the horizontal position.

Research paper thumbnail of Response to Letter by Tsivgoulis et al

Stroke, 2008

During TCD testing, blood pressure and heart rate were not systematically investigated. However, ... more During TCD testing, blood pressure and heart rate were not systematically investigated. However, no patients reported subjective complaints that could be attributable to orthostatic intolerance, and heart rate, as recorded on the spectral display, did not change ...

Research paper thumbnail of Prevalence and characteristics of right-to-left shunt in migraine with aura: a survey on 120 Italian patients

Neurological Sciences, 2009

Many lines of research have suggested a relationship between migraine with aura (MA) and patent f... more Many lines of research have suggested a relationship between migraine with aura (MA) and patent foramen ovale. Right-to-left shunt (RLS) of blood might explain both the occurrence of MA attacks, as well as the increased risk of ischaemic stroke in these patients. We evaluated the prevalence and the characteristics of RLS in a series of 120 MA patients, who were studied with contrast-enhanced Transcranial Doppler examination. We found RLS in 61 of them. A latent RLS was found in 28%, a permanent RLS in 72%, a shower-curtain pattern was detected in 52% of the studied patients.

Research paper thumbnail of Does closure of a patent foramen ovale have a role in the treatment of migraine with aura?

Neurological Sciences, 2008

Patent foramen ovale (PFO) is associated with ischaemic stroke and migraine with aura (MA), and h... more Patent foramen ovale (PFO) is associated with ischaemic stroke and migraine with aura (MA), and has been proposed as a cause of both. Numerous studies indicate that percutaneous PFO closure can improve MA, but they all suffer from methodological problems. It is recommended that the advantages and risks of PFO closure be carefully assessed in each individual, bearing in mind that effective prophylactic medications are available for MA patients with high attack frequency.

Research paper thumbnail of Microembolization During Carotid Artery Stenting in Patients With High-Risk, Lipid-Rich Plaque

Journal of the American College of Cardiology, 2011

The goal of this study was to compare the rate of cerebral microembolization during carotid arter... more The goal of this study was to compare the rate of cerebral microembolization during carotid artery stenting (CAS) with proximal versus distal cerebral protection in patients with high-risk, lipid-rich plaque.

Research paper thumbnail of Transcranial Doppler and Transesophageal Echocardiography: Comparison of Both Techniques and Prospective Clinical Relevance of Transcranial Doppler in Patent Foramen Ovale Detection

Journal of Stroke and Cerebrovascular Diseases, 2009

Research paper thumbnail of Caliber Fluctuations of Cervical Internal Carotid Artery and Migraine With Aura: A Possible Vasospasm Detected by Ultrasonographic Examinations

Headache: The Journal of Head and Face Pain, 2009

Caliber fluctuations of extra-and intracranial arteries, mostly related to vasospasm, are often r... more Caliber fluctuations of extra-and intracranial arteries, mostly related to vasospasm, are often recognized in various neurological conditions. We report a case of a 33-year-old woman affected by migraine with and without aura who exhibited a possible cervical internal carotid artery vasospasm, detected by ultrasound, before a typical migraine aura.

Research paper thumbnail of Microembolic Air Load During Contrast-Transcranial Doppler: A Trigger for Migraine With Aura?

Headache: The Journal of Head and Face Pain, 2010

Objectives.-The aim of this study was to analyze the prevalence of RILES in a consecutive cohort ... more Objectives.-The aim of this study was to analyze the prevalence of RILES in a consecutive cohort of MA patients and to characterize the occurrence of MA attacks after diagnostic ce-TCD.

Research paper thumbnail of Patent foramen ovale percutaneous closure: the no-implant approach

Expert Review of Medical Devices, 2008

Research paper thumbnail of Cerebrovascular reactivity by quantitative magnetic resonance angiography with a co2 challenge. Validation as a new imaging biomarker

European Journal of Radiology, 2014

Assessment of cerebrovascular reactivity (CVR) is essential in cerebrovascular diseases, as exhau... more Assessment of cerebrovascular reactivity (CVR) is essential in cerebrovascular diseases, as exhausted CVR may enhance the risk of cerebral ischemic events. Transcranial Doppler (TCD) with a vasodilatory stimulus is currently used for CVR evaluation. Scanty data are available for Quantitative Magnetic Resonance Angiography (QMRA), which supplies higher spatial resolution and quantitative cerebral blood flow values. Aims of our pilot study were: (a) to assess safety and feasibility of CO2 administration during QMRA, (b) evaluation of CVR under QMRA compared to TCD, and (c) quantitative evaluation of blood flow from the major intracranial arterial vessels both at rest and after CO2. CVR during 5% CO2 air breathing was measured with TCD as a reference method and compared with QMRA. Fifteen healthy subjects (age 60.47 ± 2.24; male 11/15) were evaluated at rest and during CO2 challenge. Feasibility and safety of QMRA under CO2 were ensured in all subjects. CVR from middle cerebral artery territory was not statistically different between TCD and MRI (p>0.05). Mean arterial pressure (MAP) and heart rate (HR) increased during QMRA and TCD (MAP p=0.007 and p=0.001; HR p=0.043 and p=0.068, respectively). Blood flow values from all intracranial vessels increased after CO2 inhalation (p<0.001). CO2 administration during QMRA sessions is safe and feasible. Good correlation in terms of CVR was obtained comparing TCD and QMRA. Blood flow values significantly increased from all intracranial arterial vessels after CO2. Studies regarding CVR in physiopathological conditions might consider the utilization of QMRA both in routine clinical settings and in research projects.

Research paper thumbnail of Cessation of migraine with aura following removal of left atrial myxoma

European Journal of Neurology, 2006

Research paper thumbnail of Systematic review and meta-analysis of currently available clinical evidence on migraine and patent foramen ovale percutaneous closure: Much ado about nothing?

Catheterization and Cardiovascular Interventions, 2010

To investigate the role of transcatheter closure of patent foramen ovale on the occurrence of mig... more To investigate the role of transcatheter closure of patent foramen ovale on the occurrence of migraine.

Research paper thumbnail of Neuroprotective actions in vivo and electrophysiological actions in vitro of 202W92

Brain Research, 2001

202W92 (R-(-)-2,4-diamino-6-(fluromethyl)-5-(2,3,5-trichlorophenyl)pyrimidine) is a novel compoun... more 202W92 (R-(-)-2,4-diamino-6-(fluromethyl)-5-(2,3,5-trichlorophenyl)pyrimidine) is a novel compound in the same chemical series as the antiepileptic drug lamotrigine and the neuroprotective sipatrigine. Here 202W92 was quantitatively assessed as a neuroprotective agent in focal cerebral ischaemia, and as an inhibitor of sodium and calcium channels and of synaptic transmission. In the rat permanent middle cerebral artery occlusion (MCAO) model of acute focal ischaemia, 202W92 reduced infarct volume by 75% in cortex and by 80% in basal ganglia, with ED(50) approximately 2 mg/kg (single i.v. dose, 10 min post-occlusion). In whole-cell current recordings from single cells, 202W92 completely and reversibly inhibited voltage gated sodium channels (IC(50) 3 x 10(-6) M) in rat freshly-isolated cortical neurons and in the GH(3) pituitary cell line. 202W92 also inhibited a nifedipine-sensitive fraction (approximately 35%) of native high-voltage-activated (HVA) calcium current in rat cortical neurons (IC(50) 15 x 10(-6) M) and weakly inhibited low-voltage-activated (LVA) calcium currents of the recombinant alpha1I-mediated T-type (IC(50)>100 x 10(-6) M). The drug inhibited the amplitude and frequency of 4-aminopyridine-evoked glutamatergic excitatory post-synaptic currents (EPSCs). In conclusion, 202W92 is an effective neuroprotective agent when administered post-ischaemia and a potent sodium channel inhibitor in vitro.

Research paper thumbnail of New Insights Into mGluRs Function in the Substantia Nigra Pars Compacta

Advances in Behavioral Biology, 2002

Metabotropic glutamate receptors (mGluRs) regulate many processes in the central nervous system (... more Metabotropic glutamate receptors (mGluRs) regulate many processes in the central nervous system (CNS), including synaptic plasticity, learning, memory, motor coordination, pain transmission and neurodegeneration (Linden et al., 1991; Nicoletti et al., 1996; Conn and Pin, 1997). They form a family of eight subtypes classified into three groups, I through III (Masu et al., 1991; Houamed et al., 1991; Nakanishi, 1992; Knöpfel et al., 1995; Conn and Pin, 1997), which are implicated in different aspects of physiology and pathology of the CNS: group 1 (mGluRs land 5) are mainly localized on post-synaptic membranes and are coupled to intracellular calcium pools and to membrane ion channelsviaG-proteins, whereas group II and III are localized pre-synaptically and negatively coupled to adenylate cyclase (Pin and Duvoisin, 1992). The group I mGluRs generate slow EPSPs and calcium responses in cerebellar Purkinje neurons (Batchelor and Garthwaite, 1997) and hippocampal pyramidal neurons (Congar et al., 1997). Transient mGluR-mediated calcium increases can be elicited by stimulation of IP3sensitive (Murphy and Miller, 1989, Takechi et al., 1998) and/or ryanodine-sensitive (Berridge, 1998) receptors localized on intracellular calcium stores A family of proteins has been recently described, whose expression is driven by synaptic activity (Brackeman et al., 1997), as a physical link between mGluRs and either IP3—sensitive or ryanodinesensitive receptors, termed Homer protein (Brakeman et al., 1997, Tu et al., 1998) and this represents a novel mechanism in calcium signaling and might provide molecular insight into the synaptic function of Homer proteins.

Research paper thumbnail of Lamotrigine derivatives and riluzole inhibit INa,P in cortical neurons

Neuroreport, Jan 2, 2002

The persistent, slowly inactivating fraction of the sodium current is involved in key functions i... more The persistent, slowly inactivating fraction of the sodium current is involved in key functions in the CNS such as dendritic integration of synaptic inputs and cellular excitability. We have studied whether established anti-epileptic drugs and neuroprotective agents target the persistent sodium current. Two lamotrigine derivatives (sipatrigine and 202W92) and riluzole inhibited the persistent sodium current at low, therapeutic concentrations. In contrast, lamotrigine and the classical antiepileptic agents phenytoin and valproic acid blocked the fast-inactivating sodium channel but failed to affect the persistent fraction. The ability to influence either mode of channel activity may represent a defining feature of each drug subclass, changing profoundly their clinical indications. Given the damaging role of a sustained influx of sodium in both pharmaco-resistant seizures or excitotoxic insults, we suggest the utilization of drugs that suppress the persistent conductance.

Research paper thumbnail of Italian patent foramen ovale survey (I.P.O.S.): Early results

Perspectives in Medicine, 2012

ABSTRACT Percutaneous patent foramen ovale (PFO) closure is gaining wide acceptance. Aims of the ... more ABSTRACT Percutaneous patent foramen ovale (PFO) closure is gaining wide acceptance. Aims of the study were to analyse clinical practice regarding PFO closure in Italy, to study indications, devices, results, and the follow-up of large series of patients treated by percutaneous PFO closure.Methods and patientsItalian patent foramen ovale survey (IPOS) is a prospective, observational, multi-centric survey that uses a web-based database. The survey lasted 12 months, (November 2007–October 2008). 50 centres participated. Ongoing follow-up will continue up to 36 months. 1035 patients (m.a. 46 years, 60% females) were included in the registry. Most subjects were treated due to a previous history of TIA/ischemic stroke (∼80% of patients). PFO diagnosis and right-to-left shunt (RLS) were assessed by contrast-enhanced transesophageal (cTEE) and/or transthoracic echocardiography and/or transcranial doppler. An aneurysm of the interatrial septum was associated in 41% of patients. Intraprocedural monitoring was assessed by using cTEE and fluoroscopy in 70% and intracardiac echocardiography in 30% of subjects. Procedures were performed under general anesthesia and local anesthesia/conscious sedation in 54% and 46% of patients respectively. The most used device for PFO closure was Amplatzer (∼70% of cases).ResultsThe procedure was successful in all patients. Early complications occurred in 24/1035 patients (2.3%): 12/24 (50%) of them had cardiac arrhythmias, 1 subject had a TIA. Data regarding both clinical and cardio-neurosonological follow-up were assessed in 444/1035 (43%) subjects. The rate of neurological events and cardiac and extra-cardiac complications were around 3% and 9% up to the 24-month follow-up respectively. A large permanent residual RLS and no RLS were observed in less than 1% and in ∼82% of patients at the 1-year follow-up, respectively.Conclusions Our data confirm that percutaneous PFO closure is a safe procedure. Early complications and those during follow-up are mostly related to arrhythmias. Longer follow-up is under way.

Research paper thumbnail of Actions of the sodium channel inhibitor 202W92 on rat midbrain dopaminergic neurons

Synapse, 2003

Excessive glutamatergic activity is implicated in Parkinson's disease (PD) and sodium channel blo... more Excessive glutamatergic activity is implicated in Parkinson's disease (PD) and sodium channel blockade, resulting in inhibition of glutamate release, is a potential therapeutic approach to PD therapy. Beneficial effects of riluzole and lamotrigine have been reported in animal models of PD, but these compounds have relatively low potency as sodium channel inhibitors and also inhibit N and P/Q-type calcium channels. 202W92, a structural analog of lamotrigine, is a potent sodium channel inhibitor, with no effect on N, P/Q-type channels. Here we present the effects of 202W92 on single patch-clamped dopaminergic neurons. 202W92 (Ն10 M) inhibited spontaneous action potential firing and reduced amplitude and frequency of evoked action potentials. It also inhibited the frequency of 4-aminopyridine (4-AP)-and electrically evoked excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs), with Ͼ80% inhibition at 10 M (IC 50 1.5 M). EPSC and IPSC amplitudes were partially inhibited. 202W92 did not affect postsynaptic responses to locally applied glutamate and GABA, nor spontaneously occurring mini-IPSCs. These actions of 202W92 are compatible with sodium channel inhibition and depression of transmitter release. Synapse 48:123-130, 2003.

Research paper thumbnail of D-Tubocurarine reduces GABA responses in rat substantia nigra dopamine neurons

Research paper thumbnail of Postural Dependency of Right to Left Shunt: Role of Contrast-Enhanced Transcranial Doppler and Its Potential Clinical Implications

Stroke, 2008

Right to left shunt is involved in conditions in which postural changes may be pathogenically rel... more Right to left shunt is involved in conditions in which postural changes may be pathogenically relevant. The aim of this work was to assess the frequency of posturally dependent right to left shunt. In 109 consecutive right to left shunt-positive subjects (male/female=40/69, age 43+/-12 years), we assessed with contrast-enhanced transcranial Doppler the bubble load during normal breathing and after the Valsalva maneuver in both standing and recumbent position randomizing the order of testing. During normal breathing, the average bubble count was 11+/-20 in the recumbent and 26+/-60 in the standing position. After the Valsalva maneuver, it was 40+/-38 and 42+/-37, respectively. The increase of bubble load in standing position occurred in 42% of patients and was independent of the order of testing. The amount of permanent right to left shunt is posture-dependent in 40% of patients. Testing in the sitting position may thus be warranted in doubtful or inconclusive results obtained with the subject in the horizontal position.

Research paper thumbnail of Response to Letter by Tsivgoulis et al

Stroke, 2008

During TCD testing, blood pressure and heart rate were not systematically investigated. However, ... more During TCD testing, blood pressure and heart rate were not systematically investigated. However, no patients reported subjective complaints that could be attributable to orthostatic intolerance, and heart rate, as recorded on the spectral display, did not change ...

Research paper thumbnail of Prevalence and characteristics of right-to-left shunt in migraine with aura: a survey on 120 Italian patients

Neurological Sciences, 2009

Many lines of research have suggested a relationship between migraine with aura (MA) and patent f... more Many lines of research have suggested a relationship between migraine with aura (MA) and patent foramen ovale. Right-to-left shunt (RLS) of blood might explain both the occurrence of MA attacks, as well as the increased risk of ischaemic stroke in these patients. We evaluated the prevalence and the characteristics of RLS in a series of 120 MA patients, who were studied with contrast-enhanced Transcranial Doppler examination. We found RLS in 61 of them. A latent RLS was found in 28%, a permanent RLS in 72%, a shower-curtain pattern was detected in 52% of the studied patients.

Research paper thumbnail of Does closure of a patent foramen ovale have a role in the treatment of migraine with aura?

Neurological Sciences, 2008

Patent foramen ovale (PFO) is associated with ischaemic stroke and migraine with aura (MA), and h... more Patent foramen ovale (PFO) is associated with ischaemic stroke and migraine with aura (MA), and has been proposed as a cause of both. Numerous studies indicate that percutaneous PFO closure can improve MA, but they all suffer from methodological problems. It is recommended that the advantages and risks of PFO closure be carefully assessed in each individual, bearing in mind that effective prophylactic medications are available for MA patients with high attack frequency.

Research paper thumbnail of Microembolization During Carotid Artery Stenting in Patients With High-Risk, Lipid-Rich Plaque

Journal of the American College of Cardiology, 2011

The goal of this study was to compare the rate of cerebral microembolization during carotid arter... more The goal of this study was to compare the rate of cerebral microembolization during carotid artery stenting (CAS) with proximal versus distal cerebral protection in patients with high-risk, lipid-rich plaque.

Research paper thumbnail of Transcranial Doppler and Transesophageal Echocardiography: Comparison of Both Techniques and Prospective Clinical Relevance of Transcranial Doppler in Patent Foramen Ovale Detection

Journal of Stroke and Cerebrovascular Diseases, 2009

Research paper thumbnail of Caliber Fluctuations of Cervical Internal Carotid Artery and Migraine With Aura: A Possible Vasospasm Detected by Ultrasonographic Examinations

Headache: The Journal of Head and Face Pain, 2009

Caliber fluctuations of extra-and intracranial arteries, mostly related to vasospasm, are often r... more Caliber fluctuations of extra-and intracranial arteries, mostly related to vasospasm, are often recognized in various neurological conditions. We report a case of a 33-year-old woman affected by migraine with and without aura who exhibited a possible cervical internal carotid artery vasospasm, detected by ultrasound, before a typical migraine aura.

Research paper thumbnail of Microembolic Air Load During Contrast-Transcranial Doppler: A Trigger for Migraine With Aura?

Headache: The Journal of Head and Face Pain, 2010

Objectives.-The aim of this study was to analyze the prevalence of RILES in a consecutive cohort ... more Objectives.-The aim of this study was to analyze the prevalence of RILES in a consecutive cohort of MA patients and to characterize the occurrence of MA attacks after diagnostic ce-TCD.

Research paper thumbnail of Patent foramen ovale percutaneous closure: the no-implant approach

Expert Review of Medical Devices, 2008

Research paper thumbnail of Cerebrovascular reactivity by quantitative magnetic resonance angiography with a co2 challenge. Validation as a new imaging biomarker

European Journal of Radiology, 2014

Assessment of cerebrovascular reactivity (CVR) is essential in cerebrovascular diseases, as exhau... more Assessment of cerebrovascular reactivity (CVR) is essential in cerebrovascular diseases, as exhausted CVR may enhance the risk of cerebral ischemic events. Transcranial Doppler (TCD) with a vasodilatory stimulus is currently used for CVR evaluation. Scanty data are available for Quantitative Magnetic Resonance Angiography (QMRA), which supplies higher spatial resolution and quantitative cerebral blood flow values. Aims of our pilot study were: (a) to assess safety and feasibility of CO2 administration during QMRA, (b) evaluation of CVR under QMRA compared to TCD, and (c) quantitative evaluation of blood flow from the major intracranial arterial vessels both at rest and after CO2. CVR during 5% CO2 air breathing was measured with TCD as a reference method and compared with QMRA. Fifteen healthy subjects (age 60.47 ± 2.24; male 11/15) were evaluated at rest and during CO2 challenge. Feasibility and safety of QMRA under CO2 were ensured in all subjects. CVR from middle cerebral artery territory was not statistically different between TCD and MRI (p>0.05). Mean arterial pressure (MAP) and heart rate (HR) increased during QMRA and TCD (MAP p=0.007 and p=0.001; HR p=0.043 and p=0.068, respectively). Blood flow values from all intracranial vessels increased after CO2 inhalation (p<0.001). CO2 administration during QMRA sessions is safe and feasible. Good correlation in terms of CVR was obtained comparing TCD and QMRA. Blood flow values significantly increased from all intracranial arterial vessels after CO2. Studies regarding CVR in physiopathological conditions might consider the utilization of QMRA both in routine clinical settings and in research projects.

Research paper thumbnail of Cessation of migraine with aura following removal of left atrial myxoma

European Journal of Neurology, 2006

Research paper thumbnail of Systematic review and meta-analysis of currently available clinical evidence on migraine and patent foramen ovale percutaneous closure: Much ado about nothing?

Catheterization and Cardiovascular Interventions, 2010

To investigate the role of transcatheter closure of patent foramen ovale on the occurrence of mig... more To investigate the role of transcatheter closure of patent foramen ovale on the occurrence of migraine.

Research paper thumbnail of Neuroprotective actions in vivo and electrophysiological actions in vitro of 202W92

Brain Research, 2001

202W92 (R-(-)-2,4-diamino-6-(fluromethyl)-5-(2,3,5-trichlorophenyl)pyrimidine) is a novel compoun... more 202W92 (R-(-)-2,4-diamino-6-(fluromethyl)-5-(2,3,5-trichlorophenyl)pyrimidine) is a novel compound in the same chemical series as the antiepileptic drug lamotrigine and the neuroprotective sipatrigine. Here 202W92 was quantitatively assessed as a neuroprotective agent in focal cerebral ischaemia, and as an inhibitor of sodium and calcium channels and of synaptic transmission. In the rat permanent middle cerebral artery occlusion (MCAO) model of acute focal ischaemia, 202W92 reduced infarct volume by 75% in cortex and by 80% in basal ganglia, with ED(50) approximately 2 mg/kg (single i.v. dose, 10 min post-occlusion). In whole-cell current recordings from single cells, 202W92 completely and reversibly inhibited voltage gated sodium channels (IC(50) 3 x 10(-6) M) in rat freshly-isolated cortical neurons and in the GH(3) pituitary cell line. 202W92 also inhibited a nifedipine-sensitive fraction (approximately 35%) of native high-voltage-activated (HVA) calcium current in rat cortical neurons (IC(50) 15 x 10(-6) M) and weakly inhibited low-voltage-activated (LVA) calcium currents of the recombinant alpha1I-mediated T-type (IC(50)>100 x 10(-6) M). The drug inhibited the amplitude and frequency of 4-aminopyridine-evoked glutamatergic excitatory post-synaptic currents (EPSCs). In conclusion, 202W92 is an effective neuroprotective agent when administered post-ischaemia and a potent sodium channel inhibitor in vitro.