Biomedical subjects

Massimo Cossu

Publications and source records attributed to Massimo Cossu.

12 recordsLinked to original sources

PubMed2006

Relationship of epileptic discharges to arousal instability and periodic leg movements in a case of nocturnal frontal lobe epilepsy: a stereo-EEG study.

We describe the case of a patient with nocturnal frontal lobe epilepsy, presenting with periodic leg movements during sleep and complaining of excessive daytime sleepiness. With the support of intracerebral electroencephalogram recordings and the corroboration of the postoperative outcome, periodic leg movements during sleep and excessive daytime sleepiness appeared to be associated to enhanced arousal instability induced by by recurrent epileptic discharges not detectable on scalp electroencephalogram.

Adult↗

PubMed2006

NMDA receptor composition differs among anatomically diverse malformations of cortical development.

Altered excitatory synaptic activity is likely a key factor in the neuronal hyperexcitability of developmental cerebral malformations. Using a combined morphologic and molecular approach, we investigated the NMDA receptor and related protein composition in human epileptic patients affected by periventricular nodular heterotopia, subcortical band heterotopia, or focal cortical dysplasia. Our results indicate that expression levels of specific NMDA receptor subunits are altered in both cerebral heterotopia and cortical dysplasia. A selective increase in the NR2B subunit was present in all cortical dysplasia, whereas the expression level of NR2A and NR2B subunits was significantly downregulated in all patients with heterotopia. NR2B upregulation in cortical dysplasia was greater in the total homogenate than the postsynaptic membrane fraction, suggesting that mechanisms other than increased ionic influx through the postsynaptic membrane may sustain hyperexcitability in dysplastic neurons. In cerebral heterotopia, the NR2A and NR2B downregulation was accompanied by less evident reduction of the SAP97 and PSD-95 proteins of the MAGUK family, thus suggesting that NMDA impairment was associated with altered molecular structure of the postsynaptic membrane. Our results demonstrate that diverse human developmental malformations are associated with different alterations of the NMDA receptor, which may contribute to the genesis of epileptic phenomena.

Adolescent↗

PubMed2006

Seizure outcome after resection of cavernous malformations is better when surrounding hemosiderin-stained brain also is removed.

PURPOSE: Considering the epileptogenic effect of cavernoma-surrounding hemosiderin, assumptions are made that resection only of the cavernoma itself may not be sufficient as treatment of symptomatic epilepsy in patients with cavernous malformations. The purpose of this study was to test the hypothesis whether seizure outcome after removal of cavernous malformations may be related to the extent of resection of surrounding hemosiderin-stained brain tissue. METHODS: In this retrospective study, 31 consecutive patients with pharmacotherapy-refractory epilepsy due to a cavernous malformation were included. In all patients, cavernomas were resected, and all patients underwent pre- and postoperative magnetic resonance imaging (MRI). We grouped patients according to MRI findings (hemosiderin completely removed versus not/partially removed) and compared seizure outcome (as assessed by the Engel Outcome Classification score) between the two groups. RESULTS: Three years after resection of cavernomas, patients in whom hemosiderin-stained brain tissue had been removed completely had a better chance for a favorable long-term seizure outcome compared with those with detectable postoperative hemosiderin (p=0.037). CONCLUSIONS: Our study suggests that complete removal of cavernoma-surrounding hemosiderin-stained brain tissue may improve epileptic outcome after resection of cavernous malformations.

Adolescent↗

PubMed2005

Antioxidant activity of gamma-oryzanol: mechanism of action and its effect on oxidative stability of pharmaceutical oils.

Gamma-oryzanol, a phytosteryl ferulate mixture extracted from rice bran oil, has a wide spectrum of biological activities; in particular, it has antioxidant properties and is often used in cosmetic formulations as a sunscreen. The first objective of the present investigation was to elucidate the molecular mechanism(s) of the antioxidant activity of gamma-oryzanol by utilising different in vitro model systems, such as scavenging of stable DPPH radical, OH and O2- radicals scavenging, and azocompound AMVN-initiated lipid peroxidation. The effect of gamma-oryzanol on the oxidative stability of vegetable oils of pharmaceutical and cosmetic interest was then evaluated in a oxidation accelerate test and compared with the effect of the well-known antioxidants BHA and BHT. Our results demonstrate that gamma-oryzanol is an organic radical scavenger able to prevent AMVN-triggered lipoperoxidation. Moreover, when added to oils at concentrations ranging between 2.5 and 10 mmol/kg, gamma-oryzanol shows a dose-dependent increase of the induction times; in particular, it improved the oxidative stability of oils very prone to lipoperoxidation because of their high content of polyunsaturated fatty acids. On the ground of our results, we can conclude that gamma-oryzanol may have a potential application for the stabilization of lipidic raw materials.

Antioxidants↗

PubMed2005

Increased discharge threshold after an interictal spike in human focal epilepsy.

It is commonly assumed that interictal spikes (ISs) in focal epilepsies set off a period of inhibition that transiently reduces tissue excitability. Post-spike inhibition was described in experimental models but was never demonstrated in the human epileptic cortex. In the present study post-spike excitability was retrospectively evaluated on intracerebral stereo-electroencephalographic recordings performed in the epileptogenic cortex of five patients suffering from drug-resistant focal epilepsy secondary to Taylor-type neocortical dysplasias. Patients typically presented with highly periodic interictal spiking activity at 2.33 +/- 0.87 Hz (mean +/- SD) in the dysplastic region. During the stereo-electroencephalographic procedure, low-frequency stimulation at 1 Hz was systematically performed for diagnostic purposes to identify the epileptogenic zone. The probability of evoking an IS during the interspike period in response to 1-Hz stimuli delivered close to the ictal-onset zone was examined. Stimuli that occurred early after a spontaneous IS (within 70% of the inter-IS period) had a very low probability of generating a further IS. On the contrary, stimuli delivered during the late inter-IS period had the highest probability of evoking a further IS. The generation of stimulus-evoked ISs is occluded for several hundred milliseconds after the occurrence of a preceding spike discharge. As previously shown in animal models, these findings suggest that, during focal, periodic interictal spiking, human neocortical excitability is phasically controlled by post-spike inhibition.

Adolescent↗

PubMed2005

Mucoadhesive microspheres for nasal administration of an antiemetic drug, metoclopramide: in-vitro/ex-vivo studies.

Microparticulate delivery systems designed for the nasal administration of an antiemetic drug, metoclopramide hydrochloride, were prepared. Microspheres composed of sodium alginate, chitosan hydrochloride, or both, were obtained using a spray-drying method; some batches of drug-free microparticles were prepared as a comparison. The morphology, in-vitro swelling behaviour, mucoadhesive properties and drug release from microparticles were evaluated. Ex-vivo drug permeation tests were carried out using sheep nasal mucosa; permeation test of the drug solution was performed as comparison. During ex-vivo permeation tests, transmission electron microscopy (TEM) analyses were carried out on the nasal mucosa to study the morphological changes of epithelial cells and tight junctions, while the change in microsphere morphology was examined using photostereo microscopy (PM). Spray-dried microparticles had a mean diameter (d(vs)) in the range of about 3-10 microm. They showed good in-vitro mucoadhesive properties. In-vitro release profiles and swelling behaviour depended on their composition: the drug release occurred in 1-3 h. Ex-vivo studies showed that drug permeation through the mucosa from microparticles based on chitosan was higher than from those consisting of alginate alone. This can be related to the penetration enhancing properties of chitosan. Complexation of chitosan with alginate led to a control of the drug release. Microscopy observation of microspheres during the permeation tests revealed that microparticles swelled and gelled, maintaining their shape. TEM analyses of the mucosa after exposure to the microparticles consisting of alginate/chitosan showed opened tight junctions. This preliminary study shows that alginate/chitosan spray-dried microspheres have promising properties for use as mucoadhesive nasal carriers of an antiemetic drug.

Adhesiveness↗

PubMed2005

Stereoelectroencephalography in the presurgical evaluation of children with drug-resistant focal epilepsy.

OBJECT: The authors report on indications for, techniques of, and results of stereoelectroencephalography (stereo-EEG) monitoring in the presurgical evaluation of childhood drug-resistant focal epilepsy. METHODS: Thirty-five children (24 boys and 11 girls; mean age 8.8 +/- 3.9 years; mean age at seizure onset 2.1 +/- 2.2 years) underwent 37 tailored stereotactic placements of intracerebral, multilead electrodes for intensive monitoring of seizures (stereo-EEG). Two children underwent exploration twice. Investigations prior to stereo-EEG monitoring, including magnetic resonance imaging and video-EEG of the scalp, revealed variable patterns of localizing incoherence among clinical, electrophysiological, and anatomical findings in all cases. A total of 426 electrodes were implanted (mean 11.5 +/- 2.6 per procedure) according to individualized arrangements. The stereo-EEG monitoring enabled recording of 826 seizures (mean 22 +/- 45 per procedure) and mapping of critically functional areas. One untoward event consisted of intracranial breakage of an electrode. Resections of the epileptogenic zone were performed according to results of stereo-EEG recordings. They consisted of cortical removal in seven cases, removal of the lesion and epileptogenic cortex in 26 cases, and lesion removal in two cases. Transient postoperative neurological deficits were observed in 13 patients, and permanent anticipated visual field defects occurred in seven patients. According to the Engel postoperative classification of seizure outcome, 60% of cases were in Class I, 74% had significant improvement (Classes I-III), and 26% were unchanged (mean follow up 31.9 +/- 20.6 months). CONCLUSIONS: Stereoelectroencephalography monitoring is a helpful and well-tolerated technique for the definition of the epileptogenic zone in complex cases of childhood drug-resistant epilepsy. It provides essential information for safe resections that should result in excellent outcomes in a considerable number of patients.

Adolescent↗

PubMed2005

Stereoelectroencephalography in the presurgical evaluation of focal epilepsy: a retrospective analysis of 215 procedures.

OBJECTIVE: To report on indications, surgical technique, results, and morbidity of stereoelectroencephalography (SEEG) in the presurgical evaluation of patients with drug-resistant focal epilepsy. METHODS: Two-hundred fifteen stereotactic implantations of multilead intracerebral electrodes were performed in 211 patients (4 patients were explored twice), who showed variable patterns of localizing incoherence among electrical (interictal/ictal scalp electroencephalography), clinical (ictal semeiology), and anatomic (magnetic resonance imaging [MRI]) investigations. MRI scanning showed a lesion in 134 patients (63%; associated with mesial temporal sclerosis in 7) and no lesion in 77 patients (37%; with mesial temporal sclerosis in 14 patients). A total of 2666 electrodes (mean, 12.4 per patient) were implanted (unilaterally in 175 procedures and bilaterally in 40). For electrode targeting, stereotactic stereoscopic cerebral angiograms were used in all patients, coupled with a coregistered three-dimensional MRI scan in 108 patients. RESULTS: One hundred eighty-three patients (87%) were scheduled for resective surgery after SEEG recording, and 174 have undergone surgery thus far. Resections sites were temporal in 47 patients (27%), frontal in 55 patients (31.6%), parietal in 14 patients (8%), occipital in one patient (0.6%), rolandic in one patient (0.6%), and multilobar in 56 patients (32.2%). Outcome on seizures (Engel's classification) in 165 patients with a follow-up period of more than 12 months was: Class I, 56.4%; Class II, 15.1%; Class III, 10.9%; and Class IV, 17.6%. Outcome was significantly associated with the results of MRI scanning (P = 0.0001) and with completeness of lesion removal (P = 0.038). Morbidity related to electrode implantation occurred in 12 procedures (5.6%), with severe permanent deficits from intracerebral hemorrhage in 2 (1%) patients. CONCLUSION: SEEG is a useful and relatively safe tool in the evaluation of surgical candidates when noninvasive investigations fail to localize the epileptogenic zone. SEEG-based resective surgery may provide excellent results in particularly complex drug-resistant epilepsies.

Adolescent↗

PubMed2004

PLGA microspheres for the ocular delivery of a peptide drug, vancomycin using emulsification/spray-drying as the preparation method: in vitro/in vivo studies.

The aim of this study was an in vitro/in vivo investigation on poly(lactide-co-glycolide) (PLGA) microspheres as carriers for the topical ocular delivery of a peptide drug vancomycin (VA). The microspheres were prepared by an emulsification/spray-drying technique that can be proposed as an alternative to the double emulsion method for preparation of peptide-loaded microparticles. The drug encapsulation efficiencies were close to the theoretical values (84.2-99.5%); the average particle size, expressed as dvs, was about 11 microm. The microspheres were able to modulate the in vitro drug release of VA with a behavior dependent on their composition: the highest drug content corresponded to the highest release rate. In vivo studies were carried out by assessing the pharmacokinetic profile of VA in the aqueous humor of rabbits after topical administration of aqueous suspensions of microspheres. High and prolonged VA concentrations and increased AUC values (2-fold) with respect to an aqueous solution of the drug were observed. Increasing the viscosity of the microsphere suspension by addition of a suspending-viscosizing agent (hydroxypropylcellulose) did not produce an increase of the ocular bioavailability. PLGA microspheres can be proposed as a system for ocular delivery of peptide drugs.

Animals↗

PubMed2003

Nocturnal frontal lobe epilepsy: intracerebral recordings of paroxysmal motor attacks with increasing complexity.

PURPOSES: To show the results of the investigation conducted with intracerebral electrodes in a patient with drug-resistant nocturnal frontal lobe epilepsy, characterized by sleep-related paroxysmal motor attacks of increasing complexity ranging from simple and brief stereotyped motor events to paroxysmal arousals and major attacks. METHODS: The patient was studied with long-term video-stereo-electroencephalographic monitoring by means of stereotactically implanted intracerebral electrodes. RESULTS: Video-stereo-electroencephalography demonstrated that minor events and paroxysmal arousals, as well as major attacks, were correlated with a discharge in the right supplementary motor area and central cingulate gyms. The increasing complexity of these sleep-related ictal motor behaviors reflected a different pattern of discharge, with a progressive spread to other frontal and extrafrontal areas in the fully developed attacks. Surgical resection of the right supplementary motor area and central cingulate gyrus was performed. In the 5 years since the operation, the patient has remained completely seizure free. CONCLUSION: This study clearly demonstrates the ictal origin of minor events in nocturnal frontal lobe epilepsy. The increasing complexity of the motor behaviors from minor to major attacks reflects different duration, amplitude, and spread of the epileptic discharge.

Adult↗

PubMed2003

Focal cortical resection in malformations of cortical development.

Malformations of cortical development may be associated with drug-resistant partial epilepsy suitable for surgical therapy. From the anatomopathological point of view, this categorisation has been used in reference to a wide range of alterations of the cortical mantle. Focal cortical dysplasias represent the main group of malformations of cortical development, but there are also other types of alterations, such as heterotopias, double cortex or polymicrogyria. Defining candidacy for surgical therapy and tailored resection requires thorough pre-surgical evaluation so that the approach will be individualised for each patient. We present our series of 126 patients with malformation of cortical development selected from 321 consecutively operated patients. Within this group encompassing different types of malformation of cortical development, including periventricular heterotopia (nine patients), polymicrogyria (three patients), hemimegalencephaly (one patient) and subcortical band heterotopia (one patient), the largest group was 81 individuals with focal cortical dysplasia. For this last group, we propose a simplified classification defining 42 architectural dysplasias, 12 cytoarchitectural dysplasias and 27 Taylor's focal cortical dysplasias. In addition, at routine neuropathological investigation, the only morphological alteration shown by 31 patients was diffuse neuronal heterotopia. All patients underwent scalp EEG and video-EEG, and 75 patients (59.5%) also underwent stereo-EEG. Magnetic resonance imaging and stereotactic stereoscopic angiography represented the indispensable premises for further studies, in particular stereo-EEG, and for planning surgery and tailoring resection. Magnetic resonance imaging was unhelpful in 17 out of 81 patients with focal cortical dysplasia and in seven out of 31 with neuronal heterotopia, while signal alterations were present in all other cases. Common characteristics corresponding to clinical-histopathological homogeneous subgroups were found within the focal cortical dysplasia group. In patients with architectural dysplasia, the epileptogenic zone was mainly in the temporal lobe and there was a lower seizure frequency than in patients with Taylor's focal cortical dysplasia. Patients with Taylor's type had an epileptogenic zone that was mainly extra-temporal, and a distinctive interictal stereo-EEG. The best outcome was observed in patients with Taylor's type dysplasia: 69% seizure-free (Engel class Ia) after at least 1 year of follow-up, compared with 45% of cytoarchitectural dysplasia and 49% of architectural dysplasia patients.

Adult↗

PubMed2002

Formulation and in vivo evaluation of chlorhexidine buccal tablets prepared using drug-loaded chitosan microspheres.

This investigation deals with the development of buccal formulations (tablets) based on chitosan microspheres containing chlorhexidine diacetate. The microparticles were prepared by a spray-drying technique, their morphological characteristics were studied by scanning electron microscopy and the in vitro release behaviour was investigated in pH 7.0 USP buffer. Chlorhexidine in the chitosan microspheres dissolves more quickly in vitro than does chlorhexidine powder. The anti-microbial activity of the microparticles was investigated as minimum inhibitory concentration, minimum bacterial concentration and killing time. The loading of chlorhexidine into chitosan is able to maintain or improve the anti-microbial activity of the drug. The improvement is particularly high against Candida albicans. This is important for a formulation whose potential use is against buccal infections. Drug-empty microparticles have an anti-microbial activity due to the polymer itself. Buccal tablets were prepared by direct compression of the microparticles with mannitol alone or with sodium alginate. After their in vivo administration the determination of chlorhexidine in saliva showed the capacity of these formulations to give a prolonged release of the drug in the buccal cavity.

Administration, Buccal↗