Publications by authors named "Addolorata Mascia"

34 Publications

Very long-term seizure outcome in frontal lobe epilepsy surgery.

Epilepsy Behav 2021 Apr 20;117:107848. Epub 2021 Feb 20.

IRCCS NEUROMED, Pozzilli (IS), Italy. Electronic address:

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http://dx.doi.org/10.1016/j.yebeh.2021.107848DOI Listing
April 2021

ATP-evoked intracellular Ca transients shape the ionic permeability of human microglia from epileptic temporal cortex.

J Neuroinflammation 2021 Feb 15;18(1):44. Epub 2021 Feb 15.

IRCCS Neuromed, Pozzilli, IS, Italy.

Background: Intracellular Ca modulates several microglial activities, such as proliferation, migration, phagocytosis, and inflammatory mediator secretion. Extracellular ATP, the levels of which significantly change during epileptic seizures, activates specific receptors leading to an increase of intracellular free Ca concentration ([Ca]). Here, we aimed to functionally characterize human microglia obtained from cortices of subjects with temporal lobe epilepsy, focusing on the Ca-mediated response triggered by purinergic signaling.

Methods: Fura-2 based fluorescence microscopy was used to measure [Ca] in primary cultures of human microglial cells obtained from surgical specimens. The perforated patch-clamp technique, which preserves the cytoplasmic milieu, was used to measure ATP-evoked Ca-dependent whole-cell currents.

Results: In human microglia extracellular ATP evoked [Ca] increases depend on Ca entry from the extracellular space and on Ca mobilization from intracellular compartments. Extracellular ATP also induced a transient fivefold potentiation of the total transmembrane current, which was completely abolished when [Ca] increases were prevented by removing external Ca and using an intracellular Ca chelator. TRAM-34, a selective K3.1 blocker, significantly reduced the ATP-induced current potentiation but did not abolish it. The removal of external Cl in the presence of TRAM-34 further lowered the ATP-evoked effect. A direct comparison between the ATP-evoked mean current potentiation and mean Ca transient amplitude revealed a linear correlation. Treatment of microglial cells with LPS for 48 h did not prevent the ATP-induced Ca mobilization but completely abolished the ATP-mediated current potentiation. The absence of the Ca-evoked K current led to a less sustained ATP-evoked Ca entry, as shown by the faster Ca transient kinetics observed in LPS-treated microglia.

Conclusions: Our study confirms a functional role for K3.1 channels in human microglia, linking ATP-evoked Ca transients to changes in membrane conductance, with an inflammation-dependent mechanism, and suggests that during brain inflammation the K3.1-mediated microglial response to purinergic signaling may be reduced.
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http://dx.doi.org/10.1186/s12974-021-02096-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883449PMC
February 2021

Effect of Brivaracetam on Efficacy and Tolerability in Patients With Brain Tumor-Related Epilepsy: A Retrospective Multicenter Study.

Front Neurol 2020 19;11:813. Epub 2020 Aug 19.

Biostatistic Unit, Regina Elena National Cancer Institute IRCCS IFO, Rome, Italy.

Epilepsy is a common symptom of brain tumors and is often pharmacoresistent. Among new antiseizure medications (ASMs) Brivaracetam (BRV) has been approved as adjunctive treatment for focal seizures and it was tested in non-oncological patient populations. This is the first study that retrospectively explored efficacy and tolerability of BRV as add-on therapy in brain tumor-related epilepsy (BTRE) patients. We reviewed the medical records of 33 BTRE patients from six Italian epilepsy centers; charts included tumor history, diagnosis of BTRE, BRV added as first or second add-on for uncontrolled seizures and/or adverse events (AEs) of the previous ASMs, at least 1-month follow-up, seizure frequency, and AEs assessment. Thirty-three patients (19 males, mean age: 57.6 years; 14 females, mean age: 42.4 years): 11 low grade gliomas, five high grade gliomas, six meningiomas, 10 glioblastomas, one primary cerebral lymphoma. Fourteen patients had focal aware seizures, nine focal unaware, seven focal to bilateral tonic-clonic seizures, three patients presented more than one seizure type: focal unaware with focal to bilateral tonic clonic seizures (two patients) and focal aware and unaware seizures (one patient). Mean seizure frequency in the month preceding BRV introduction: 7.0; at last follow-up: 2.0 ( = 0.001). Seven patients (21.2%) reported AEs (anxiety, agitation, fatigue, vertigo) and three of them (9.0%) required drug withdrawal due to psychiatric adverse events (PAEs). Three other patients withdrew BRV: one for scarce compliance (3.0%), two for uncontrolled seizures (6.0%). Our results showed that BRV could be a new therapeutic option effective in reducing seizures in BTRE patients, taking into account the incidence of PAEs in this particular population. Future and larger prospective studies are needed.
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http://dx.doi.org/10.3389/fneur.2020.00813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466736PMC
August 2020

A European questionnaire survey on epilepsy monitoring units' current practice for postoperative psychogenic nonepileptic seizures' detection.

Epilepsy Behav 2020 11 31;112:107355. Epub 2020 Jul 31.

Department of Clinical Neurosciences, University Hospital of Lausanne (CHUV), Lausanne, Switzerland.

Background: In cases undergoing epilepsy surgery, postoperative psychogenic nonepileptic seizures (PNES) may be underdiagnosed complicating the assessment of postsurgical seizures' outcome and the clinical management. We conducted a survey to investigate the current practices in the European epilepsy monitoring units (EMUs) and the data that EMUs could provide to retrospectively detect cases with postoperative PNES and to assess the feasibility of a subsequent postoperative PNES research project for cases with postoperative PNES.

Methods: We developed and distributed a questionnaire survey to 57 EMUs. Questions addressed the number of patients undergoing epilepsy surgery, the performance of systematic preoperative and postoperative psychiatric evaluation, the recording of sexual or other abuse, the follow-up period of patients undergoing epilepsy surgery, the performance of video-electroencephalogram (EEG) and postoperative psychiatric assessment in suspected postoperative cases with PNES, the existence of electronic databases to allow extraction of cases with postoperative PNES, the data that these bases could provide, and EMUs' interest to participate in a retrospective postoperative PNES project.

Results: Twenty EMUs completed the questionnaire sheet. The number of patients operated every year/per center is 26.7 ( ± 19.1), and systematic preoperative and postoperative psychiatric evaluation is performed in 75% and 50% of the EMUs accordingly. Sexual or other abuse is systematically recorded in one-third of the centers, and the mean follow-up period after epilepsy surgery is 10.5 ± 7.5 years. In suspected postoperative PNES, video-EEG is performed in 85% and psychiatric assessment in 95% of the centers. An electronic database to allow extraction of patients with PNES after epilepsy surgery is used in 75% of the EMUs, and all EMUs that sent the sheet completed expressed their interest to participate in a retrospective postoperative PNES project.

Conclusion: Postoperative PNES is an underestimated and not well-studied entity. This is a European survey to assess the type of data that the EMUs surgical cohorts could provide to retrospectively detect postoperative PNES. In cases with suspected PNES, most EMUs perform video-EEG and psychiatric assessment, and most EMUs use an electronic database to allow extraction of patients developing PNES.
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http://dx.doi.org/10.1016/j.yebeh.2020.107355DOI Listing
November 2020

Ictal Asystole in Drug-Resistant Focal Epilepsy: Two Decades of Experience from an Epilepsy Monitoring Unit.

Brain Sci 2020 Jul 12;10(7). Epub 2020 Jul 12.

IRCCS NEUROMED, 86077 Pozzilli (IS), Italy.

Background: Ictal asystole (IA) is a rare event observed in people with epilepsy (PwE). Clinical and IA video-electroencephalographic findings may be helpful in screening for high-risk subjects. From all PwE undergoing video-EEG for presurgical evaluation between 2000 and 2019, we retrospectively selected those with at least one IA (R-R interval of ≥3 s during a seizure). IA was detected in eight out of 1088 (0.73%) subjects (mean age: 30 years; mean epilepsy duration: 9.6 years). Four out of them had a history of atonic falls. No patients had cardiac risk factors or cardiovascular diseases. Seizure onset was temporal ( = 5), temporo-parietal ( = 1) or frontal ( = 2), left-sided and right-sided in five and two patients, respectively. In one case a bilateral temporal independent seizure onset was recorded. IA was recorded in 11 out of 18 seizures. Mean IA duration was 13 s while mean IA latency from seizure onset was 26.7 s. Symptoms related to IA were observed in all seizures. IA is a rare and self-limiting event often observed during video-EG in patients with a history of atonic loss of consciousness and/or tardive falls in the course of a typical seizure.
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http://dx.doi.org/10.3390/brainsci10070443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408581PMC
July 2020

Valproate impact and sex-dependent seizure remission in patients with idiopathic generalized epilepsy.

J Neurol Sci 2020 08 30;415:116940. Epub 2020 May 30.

Epilepsy Unit, Department of Human Neurosciences, Policlinico Umberto I, "Sapienza" University, Rome, Italy. Electronic address:

Background: Idiopathic Generalized Epilepsy (IGE) management has become increasingly challenging due to the restricted use of Valproate (VPA) in females. The aim of the study was to assess possible differences in terms of seizure outcome between men and women suffering from IGE.

Methods: A cohort of IGE patients (age range: 13-50 years) followed from 1980 to 2018 were included. Their medical history was retrospectively reviewed to investigate possible factors influencing seizure outcome. Seizure Remission (SR) was defined as the absence of any seizure type over 18 months prior to the last medical observation. The primary outcome was to evaluate sex differences in terms of SR at last observation. A multivariable logistic regression model was elaborated using SR as dependent variable.

Results: Three-hundred and sixty patients were included, 204 (56.7%) of whom were women. The median age at the end of follow-up was 30. At last medical observation, fewer women were receiving VPA compared with men (females 39.7% vs males 79.5%, p < .001). Overall SR was 70.6%. SR was significantly different according to sex (females 62.3% vs males 81.4%, p < .001). Multivariable logistic regression model showed that female sex (Odds Ratios [OR] = 0.52, 95% Confidence Interval [CI] = 0.29-0.94; p = .03), VPA treatment at last observation (OR = 0.44, 95% CI = 0.25-0.76; p = .003) and epilepsy syndrome (p < .001) were the factors independently associated with SR.

Conclusions: Recent modifications in VPA prescribing patterns may have determined a worse seizure control among IGE female patients. Comparative clinical trials assessing the best therapeutic options for women with childbearing potential are urgently needed.
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http://dx.doi.org/10.1016/j.jns.2020.116940DOI Listing
August 2020

Validated outcome of treatment changes according to International League Against Epilepsy criteria in adults with drug-resistant focal epilepsy.

Epilepsia 2019 06 13;60(6):1114-1123. Epub 2019 Mar 13.

Clinical Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia and Clinical Trial Center, IRCCS Mondino Foundation, Pavia, Italy.

Objective: Although many studies have attempted to describe treatment outcomes in patients with drug-resistant epilepsy, results are often limited by the adoption of nonhomogeneous criteria and different definitions of seizure freedom. We sought to evaluate treatment outcomes with a newly administered antiepileptic drug (AED) in a large population of adults with drug-resistant focal epilepsy according to the International League Against Epilepsy (ILAE) outcome criteria.

Methods: This is a multicenter, observational, prospective study of 1053 patients with focal epilepsy diagnosed as drug-resistant by the investigators. Patients were assessed at baseline and 6, 12, and 18 months, for up to a maximum of 34 months after introducing another AED into their treatment regimen. Drug resistance status and treatment outcomes were rated according to ILAE criteria by the investigators and by at least two independent members of an external expert panel (EP).

Results: A seizure-free outcome after a newly administered AED according to ILAE criteria ranged from 11.8% after two failed drugs to 2.6% for more than six failures. Significantly fewer patients were rated by the EP as having a "treatment failure" as compared to the judgment of the investigator (46.7% vs 62.9%, P < 0.001), because many more patients were rated as "undetermined outcome" (45.6% vs 27.7%, P < 0.001); 19.3% of the recruited patients were not considered drug-resistant by the EP.

Significance: This study validates the use of ILAE treatment outcome criteria in a real-life setting, providing validated estimates of seizure freedom in patients with drug-resistant focal epilepsy in relation to the number of previously failed AEDs. Fewer than one in 10 patients achieved seizure freedom on a newly introduced AED over the study period. Pseudo drug resistance could be identified in one of five cases.
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http://dx.doi.org/10.1111/epi.14685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6850288PMC
June 2019

Long-term seizure outcome in frontal lobe epilepsy surgery.

Epilepsy Behav 2019 01 3;90:93-98. Epub 2018 Dec 3.

IRCCS "NEUROMED", Pozzilli, IS, Italy; Department of Neurology and Psychiatry, "Sapienza" University of Rome, Italy.

Purpose: The purpose of this study was to report long-term seizure outcome in patients who underwent frontal lobe epilepsy (FLE) surgery.

Method: This retrospective study included 44 consecutive subjects who underwent resective surgery for intractable FLE at IRCCS NEUROMED (period 2001-2014), followed up for at least 2 years (mean: 8.7 years). All patients underwent noninvasive presurgical evaluation and/or invasive electroencephalography (EEG) monitoring when nonconcordant data were obtained or epileptogenic zone was hypothesized to be close to the eloquent cortex. Electroclinical, neuroimaging, surgical data, and histology were compared to seizure outcome.

Results: Mean epilepsy duration was 19 years; mean age at surgery was 31.6 years. Preoperative magnetic resonance imaging (MRI) showed a frontal lesion in 86.4 % of cases. Scalp video-electroencephalography (VEEG) monitoring detected a focal ictal onset in 90% of cases. Twenty-seven patients (61.4%) underwent invasive recordings. Resections involved dorsolateral (47.7%), medial (9%), orbital (13.6%), and rolandic (13.6%) region. Lobectomy within functional boundaries was performed in the remaining 7 cases (16%). Transient and permanent neurological deficits were observed in 2 and 3 cases, respectively. Histology revealed focal cortical dysplasia (45.5%), World Health Organization (WHO) I-II grade tumors (15.9%), gliosis (22.7%), vascular malformations (4.5%), Rasmussen encephalitis (6.8%), and normal tissue (4.5%). At last observation 68.1% of patients were in Engel's class I, 11.4% in class II, 9% in class III, and 11.4% in class IV. A favorable outcome was associated with focal ictal scalp EEG onset (p = 0.0357).

Conclusion: Surgery is a safe treatment option in drug-resistant FLE with a satisfying long-term outcome. These data highlight the importance of an appropriate selection of potential surgical candidates.
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http://dx.doi.org/10.1016/j.yebeh.2018.10.033DOI Listing
January 2019

Factors underlying the development of chronic temporal lobe epilepsy in autoimmune encephalitis.

J Neurol Sci 2019 01 30;396:102-107. Epub 2018 Oct 30.

Epilepsy Unit, Department of Neurosciences/Mental Health, "Sapienza" University, Rome, Italy. Electronic address:

Purpose: Limbic encephalitis (LE) is an autoimmune condition characterized by amnestic syndrome, psychiatric features and seizures. Early diagnosis and prompt treatment are crucial to avoid long-term sequelae, including psycho-cognitive deficits and persisting seizures. The aim of our study was to analyze the characteristics of 33 LE patients in order to identify possible prognostic factors associated with the development of chronic epilepsy.

Methods: This is a retrospective cohort study including adult patients diagnosed with LE in the period 2010-2017 and followed up for ≥12 months. Demographics, seizure semiology, EEG pattern, MRI features, CSF/serum findings were reviewed.

Results: All 33 LE patients (19 M/14F, mean age 61.2 years) presented seizures. Thirty subjects had memory deficits; 22 presented behavioural/mood disorders. Serum and/or CSF auto-antibodies were detected in 12 patients. In 31 subjects brain MRI at onset showed typical alterations involving temporal lobes. All patients received immunotherapy. At follow-up, 13/33 had developed chronic epilepsy; predisposing factors included delay in diagnosis (p = .009), low seizure frequency at onset (p = .02), absence of amnestic syndrome (p = .02) and absence/rarity of inter-ictal epileptic discharges on EEG (p = .06).

Conclusions: LE with paucisymptomatic electro-clinical presentation seemed to be associated to chronic epilepsy more than LE presenting with definite and severe "limbic syndrome".
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http://dx.doi.org/10.1016/j.jns.2018.10.026DOI Listing
January 2019

Loss of constitutive functional γ-aminobutyric acid type A-B receptor crosstalk in layer 5 pyramidal neurons of human epileptic temporal cortex.

Epilepsia 2018 02 28;59(2):449-459. Epub 2017 Dec 28.

Neuromed IRCCS, Pozzilli, Italy.

Objective: γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in adult central nervous system, and profound alterations of GABA receptor functions are linked to temporal lobe epilepsy (TLE). Here we describe the functional relationships between GABA receptors type B (GABA R) and type A (GABA R) in human temporal cortex and how TLE affects this aspect of GABAergic signaling.

Methods: Miniature inhibitory postsynaptic currents (mIPSCs) were recorded by patch-clamp techniques from human L5 pyramidal neurons in slices from temporal cortex tissue obtained from surgery.

Results: We describe a constitutive functional crosstalk between GABA Rs and GABA Rs in human temporal layer 5 pyramidal neurons, which is lost in epileptic tissues. The activation of GABA Rs by baclofen, in addition to the expected reduction of mIPSC frequency, produced, in cortex of nonepileptic patients, the prolongation of mIPSC rise and decay times, thus increasing the inhibitory net charge associated with a single synaptic event. Block of K channels did not prevent the increase of decay time and charge. Protein kinase A (PKA) blocker KT5720 and pertussis toxin inhibited the action of baclofen, whereas 8Br-cAMP mimicked the GABA R action. The same GABA R-mediated modulation of GABA Rs was observed in pyramidal neurons of rat temporal cortex, with both PKA and PKC involved in the process. In cortices from TLE patients and epileptic rats, baclofen lost its ability to modulate mIPSCs.

Significance: Our results highlight the association of TLE with functional changes of GABAergic signaling that may be related to seizure propagation, and suggest that the selective activation of a definite subset of nonpresynaptic GABA Rs may be therapeutically useful in TLE.
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http://dx.doi.org/10.1111/epi.13991DOI Listing
February 2018

Possible autoantibody-negative limbic encephalitis after anterior temporal lobectomy for hippocampal sclerosis.

Int J Neurosci 2018 May 16;128(5):464-466. Epub 2017 Nov 16.

a IRCCS NEUROMED Pozzilli (IS) , Italy.

Purpose: Amnestic syndromes are acknowledged to be associated to bilateral hippocampal damage.

Materials And Methods: We briefly report the case of a young man who underwent anterior left temporal lobectomy for a medically refractory temporal lobe epilepsy due to hippocampal sclerosis with an excellent seizure and neuropsychological outcome. Approximately 10 years later, he presented with a subacute severe global amnesia and neuroimaging findings of a damage involving the contralateral mesial temporal lobe structures.

Results: A diagnosis of a possible autoimmune encephalitis was made.

Conclusions: Due to its peculiarities (compared with other cases of bilateral temporal lesions, the damage occurred on two distinct occasions), this case might contribute to shed light on the issue of the possible contralateral reorganization of memory processes subserved by the mesial temporal lobe structures chronically involved in epileptogenesis.
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http://dx.doi.org/10.1080/00207454.2017.1394852DOI Listing
May 2018

Severe and rapidly-progressive Lafora disease associated with NHLRC1 mutation: a case report.

Int J Neurosci 2017 Dec 12;127(12):1150-1153. Epub 2017 Jun 12.

a IRCCS "NEUROMED" , Pozzilli (IS) , Italy.

Lafora disease (LD), also known as progressive myoclonic epilepsy-2 (EPM2), is a rare, fatal autosomal recessive disorder typically starting during adolescence in otherwise neurologically normal individuals. It is clinically characterized by insidious of progressive neurological features including seizures, action myoclonus, visual hallucination, ataxia and dementia. Mutations in the laforin (EPM2A) gene on chromosome 6q24 or in the malin gene (NHLRC1) on chromosome 6p22 are responsible of LD phenotype. Diagnostic workup includes genetic analysis as well as axillary skin biopsy with evidence of typical periodic acid-Schiff (PAS)-positive polyglucosan inclusion bodies (Lafora bodies) in the apocrine glands and/or in the eccrine duct. Usually, genotype-phenotype correlations do not reveal substantial differences between patients carrying EPM2A and NHLRC1 mutations, but a few specific NHLRC1 mutations appear to correlate with a late onset and slow progressing LD. We report a case of LD due to compound heterozygote NHLRC1 mutation in an adolescent presenting with severe and atypical electro-clinical features, mimicking an autoimmune encephalopathy, and a rapidly progressive clinical course.
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http://dx.doi.org/10.1080/00207454.2017.1337012DOI Listing
December 2017

Temporal pole abnormalities detected by 3 T MRI in temporal lobe epilepsy due to hippocampal sclerosis: No influence on seizure outcome after surgery.

Seizure 2017 May 12;48:74-78. Epub 2017 Apr 12.

IRCCS "NEUROMED", Pozzilli (IS), Italy. Electronic address:

Purpose: To assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) detected by using 3 Tesla MRI in the preoperative workup in patients with temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS) who underwent surgery.

Methods: We studied 78 consecutive patients with TLE-HS who underwent surgery and were followed up for at least 2 years. Based on findings of pre-surgical 3 Tesla MRI, patients were subdivided in subgroups according to the presence of TB or TA. Subgroups were compared on demographic, clinical, neuropsychological data and seizure outcome.

Results: TB was found in 39 (50%) patients, while TA was found in 32 (41%) patients, always ipsilateral to HS, with a considerable degree of overlap (69%) between TB and TA (p=0.01). Patients with temporopolar abnormalities did not significantly differ from those without TB or TA with regard to sex, age, age of epilepsy onset, duration of epilepsy, history of febrile convulsions or birth complications, side of surgery, seizure frequency at surgery, presence of GTCSs, and, in particular, seizure outcome. On the other hand, TB patients show a less frequent family history of epilepsy (p<.05) while age at epilepsy onset showed a trend to be lower in the TB group (p=.09). Patients with temporopolar atrophy did not significantly differ from those without TA on any variable, except for age at epilepsy onset, which was significantly lower for the TA group (p<.05). History of birth complications and longer duration of epilepsy also showed a trend to be associated with TA (p=.08). Multivariate analysis corroborated the association between temporopolar abnormalities and absence of family history of epilepsy and history of birth complications.

Conclusions: High-field 3 T MRI in the preoperative workup for epilepsy surgery confirms that temporopolar abnormalities are frequent findings in TLE-HS patients and may be helpful to lateralize the epileptogenic zone. Their presence did not influence seizure outcome.
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http://dx.doi.org/10.1016/j.seizure.2017.04.006DOI Listing
May 2017

Temporal pole abnormalities in temporal lobe epilepsy with hippocampal sclerosis: Clinical significance and seizure outcome after surgery.

Seizure 2015 Nov 28;32:84-91. Epub 2015 Sep 28.

Mental Health Unit, Centre of Epidemiology, Surveillance and Health Promotion, Italian National Institute of Health, Rome, Italy.

Purpose: To assess the clinical significance of temporal pole abnormalities (temporopolar blurring, TB, and temporopolar atrophy, TA) in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) with a long post-surgical follow-up.

Methods: We studied 60 consecutive patients with TLE-HS and 1.5 preoperative MRI scans who underwent surgery and were followed up for at least 5 years (mean follow-up 7.3 years). Based on findings of pre-surgical MRI, patients were classified according to the presence of TB or TA. Groups were compared on demographic, clinical, neuropsychological data, and seizure outcome.

Results: TB was found in 37 (62%) patients, while TA was found in 35 (58%) patients, always ipsilateral to HS, with a high degree of overlap (83%) between TB and TA (p<0.001). Patients with TB did not differ from those without TB with regard to history of febrile convulsions, GTCSs, age of epilepsy onset, side of surgery, seizure frequency, seizure outcome, and neuropsychological outcome. On the other hand, they were significantly older, had a longer duration of epilepsy, and displayed lower preoperative scores on several neuropsychological tests. Similar findings were observed for TA. Multivariate analysis corroborated the association between temporopolar abnormalities and age at onset, age at surgery (for TB only), and lower preoperative scores on some neuropsychological tests.

Conclusions: Temporopolar abnormalities are frequent in patients with TLE-HS. Our data support the hypothesis that TB and TA are caused by seizure-related damages. These abnormalities did not influence seizure outcome, even after a long-term post-surgical follow-up.
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http://dx.doi.org/10.1016/j.seizure.2015.09.016DOI Listing
November 2015

Epilepsy surgery in adult-onset Rasmussen's encephalitis: case series and review of the literature.

Neurosurg Rev 2015 Jul 16;38(3):463-70; discussion 470-1. Epub 2015 Apr 16.

Epilepsy Unit, Department of Neurology and Psychiatry, "Sapienza" University, Rome, Italy.

Rasmussen's encephalitis (RE) is a rare immune-mediated condition characterized by drug-resistant focal epilepsy, progressive neurological, and cognitive deficits associated to unilateral hemispheric atrophy. The onset is typically reported in childhood, although adult cases (A-RE) have been described. While surgical strategies in childhood RE are well defined, little is known about usefulness of epilepsy surgery in A-RE patients. We describe clinical features, surgical approach, and outcome of five A-RE patients who underwent epilepsy surgery, and we review the literature with regard to surgical A-RE cases. We retrospectively studied five A-RE patients aged 21-38 years (mean age 22.8 years) who were followed after surgery for a period ranging from to 1 to 6 years. Demographic, electroclinical, and neuroimaging data were systematically reviewed. Four out of five subjects underwent invasive EEG monitoring to define epileptogenic zone. Epilepsy outcome was defined according to Engel's classification. Surgery consisted of frontal corticectomy in three patients, temporal lobectomy in one, combined temporal lobectomy plus insular, and frontobasal corticectomy in the remaining case. No permanent neurological deficits were observed after surgery. At the last follow-up observation, one patient was seizure-free, two subjects experienced rare disabling seizures, another had moderate seizure reduction, and one had no clinical improvement. Our experience, although limited to few cases, suggests that resective surgery in A-RE may play a role in the context of multidisciplinary therapeutical approach of this severe condition. Since the lack of specific data about surgical options, this topic seems to deserve further investigations and more targeted studies.
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http://dx.doi.org/10.1007/s10143-015-0623-5DOI Listing
July 2015

Psychogenic nonepileptic seizures mimicking gelastic seizures: A description of two cases.

Epilepsy Behav Case Rep 2015 15;4:67-9. Epub 2015 Aug 15.

IRCCS NEUROMED, via Atinense n.18, 86077 Pozzilli, IS, Italy.

Psychogenic nonepileptic seizures (PNES) are sudden, involuntary seizure-like attacks that, unlike epileptic seizures, are not related to electrographic ictal discharges and are psychological in nature. Psychogenic nonepileptic seizures presenting symptoms mimic a wide array of nervous system dysfunctions, as they involve changes in behavior, motor activity, sensation, cognitive, and autonomic functions. Spontaneous paroxysms of laughing resembling gelastic seizure have only exceptionally been reported as main symptom of PNES. Here, we describe the cases of two patients with a prolonged history of laughter attacks mistaken for epilepsy and unresponsive to AED treatment. Brain MRI and interictal EEG were unremarkable. Video-EEG monitoring allowed us to document the spontaneous and suggestion-induced habitual episodes that were then diagnosed as PNES.
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http://dx.doi.org/10.1016/j.ebcr.2015.06.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4543217PMC
May 2016

Acute postoperative seizures and long-term seizure outcome after surgery for hippocampal sclerosis.

Seizure 2015 Jan 27;24:59-62. Epub 2014 Aug 27.

Mental Health Unit, Centre of Epidemiology, Surveillance and Health Promotion, Italian National Institute of Health, Rome, Italy.

Purpose: To assess the incidence and the prognostic value of acute postoperative seizures (APOS) in patients surgically treated for drug-resistant temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS).

Methods: We studied 139 consecutive patients with TLE-HS who underwent epilepsy surgery and were followed up for at least 5 years (mean duration of follow-up 9.1 years, range 5-15). Medical charts were reviewed to identify APOS, defined as ictal events with the exception of auras occurring within the first 7 days after surgery. Seizure outcome was determined at annual intervals. Patients who were in Engel Class Ia at the last contact were classified as having a favorable outcome.

Results: Seizure outcome was favorable in 99 patients (71%). Six patients (4%) experienced APOS and in all cases their clinical manifestations were similar to the habitual preoperative seizures. All patients with APOS had unfavorable long-term outcome, as compared with 35 (26%) of 133 in whom APOS did not occur (p<0.001).

Conclusions: Our study suggests that APOS, despite being relatively uncommon in patients undergoing resective surgery for TLE-HS, are associated with a worse long-term seizure outcome. Given some study limitations, our findings should be regarded as preliminary and need confirmation from future larger, prospective, multicenter studies.
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http://dx.doi.org/10.1016/j.seizure.2014.08.007DOI Listing
January 2015

Serial postoperative awake and sleep EEG and long-term seizure outcome after anterior temporal lobectomy for hippocampal sclerosis.

Epilepsy Res 2014 Jul 26;108(5):945-52. Epub 2014 Mar 26.

Mental Health Unit, Centre of Epidemiology, Surveillance and Health Promotion, Italian National Institute of Health, Rome, Italy.

Objective: To test if postoperative prolonged awake and sleep EEG monitoring predict long-term seizure outcome in patients operated for drug-resistant temporal lobe epilepsy due to hippocampal sclerosis (TLE-HS).

Methods: This longitudinal study includes 107 patients with MTLE-HS who underwent anterior temporal lobectomy (ATL), were followed for at least 5 years (mean 8.3, range 5-12), had postoperative EEG after 2 months and at least one prolonged video-EEG monitoring during both wakefulness and sleep after 12 and 24 months. At each follow-up visit, the presence of interictal epileptiform discharges (IED) was determined, and seizure outcome was evaluated.

Results: Sixty-six patients (62%) remained free from auras and seizures throughout the follow-up period. Twenty-six (24%), 22 (21%), and 16 (16%) patients had IED at the 2-month, 12-month, and 24-month follow-up, respectively. The presence of IED at each time point was found to be associated with seizure or aura recurrence. Sleep recording contributed to the identification of patients with IED, as half of patients with IED displayed anomalies in sleep EEG only. In multivariate analysis, the presence of IED 2 months after surgery was found to be associated with seizure or aura recurrence independent of pre-operative factors consistently reported as outcome predictors in the literature.

Conclusions: The presence of IED in serial postoperative EEG including sleep recording may predict long-term seizure outcome after ATL for TLE-HS. Serial postoperative EEGs may contribute to outcome prediction and help making decision about medication withdrawal in patients operated for TLE-HS.
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http://dx.doi.org/10.1016/j.eplepsyres.2014.03.010DOI Listing
July 2014

Fractalkine/CX3CL1 modulates GABAA currents in human temporal lobe epilepsy.

Epilepsia 2013 Oct 13;54(10):1834-44. Epub 2013 Sep 13.

San Raffaele Pisana IRCCS, Rome, Italy.

Purpose: The chemokine fractalkine/CX3CL1 and its receptor CX3CR1 are widely expressed in the central nervous system (CNS). Recent evidence showed that CX3CL1 participates in inflammatory responses that are common features of CNS disorders, such as epilepsy. Mesial temporal lobe epilepsy (MTLE) is the prevalent form of focal epilepsy in adults, and hippocampal sclerosis (HS) represents the most common underlying pathologic abnormality, as demonstrated at autopsy and postresection studies. Relevant features of MTLE are a characteristic pattern of neuronal loss, as are astrogliosis and microglia activation. Several factors affect epileptogenesis in patients with MTLE, including a lack of γ-aminobutyric acid (GABA)ergic inhibitory efficacy. Therefore, experiments were designed to investigate whether, in MTLE brain tissues, CX3CL1 may influence GABAA receptor (GABAA R) mediated transmission, with a particular focus on the action of CX3CL1 on the use-dependent decrease (rundown) of the GABA-evoked currents (IGABA ), a feature underlying the reduction of GABAergic function in epileptic tissue.

Methods: Patch-clamp recordings were obtained from cortical pyramidal neurons in slices from six MTLE patients after surgery. Alternatively, the cell membranes from epileptic brain tissues of 17 MTLE patients or from surgical samples and autopsies of nonepileptic patients were microtransplanted into Xenopus oocytes, and IGABA were recorded using the standard two-microelectrode voltage-clamp technique. Immunohistochemical staining and double-labeling studies were carried out on the same brain tissues to analyze CX3CR1 expression.

Key Findings: In native pyramidal neurons from cortical slices of patients with MTLE, CX3CL1 reduced IGABA rundown and affected the recovery of IGABA amplitude from rundown. These same effects were confirmed in oocytes injected with cortical and hippocampal MTLE membranes, whereas CX3CL1 did not influence IGABA in oocytes injected with nonepileptic tissues. Consistent with a specific effect of CX3CL1 on tissues from patients with MTLE, CX3CR1 immunoreactivity was higher in MTLE sclerotic hippocampi than in control tissues, with a prominent expression in activated microglial cells.

Significance: These findings indicate a role for CX3CL1 in MTLE, supporting recent evidence on the relevance of brain inflammation in human epilepsies. Our data demonstrate that in MTLE tissues the reduced GABAergic function can be modulated by CX3CL1. The increased CX3CR1 expression in microglia and the modulation by CX3CL1 of GABAergic currents in human epileptic brain suggests new therapeutic approaches for drug-resistant epilepsies based on the evidence that the propagation of seizures can be influenced by inflammatory processes.
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http://dx.doi.org/10.1111/epi.12354DOI Listing
October 2013

Extrarolandic electroclinical findings in the evolution of adult-onset Rasmussen's encephalitis.

Epilepsy Behav 2013 Sep 26;28(3):467-73. Epub 2013 Jul 26.

Epilepsy Unit, Department of Neurology and Psychiatry, Sapienza University, Rome, Italy.

Rasmussen's encephalitis (RE) is a rare immunomediated disorder characterized by unilateral hemispheric atrophy, drug-resistant focal epilepsy, and progressive neurological deficits. Its onset typically occurs in childhood, though it has also been reported in adult age (A-RE) with atypical clinical features. The aim of this study was to describe the electroclinical features in a group of seven patients with A-RE. We retrospectively studied seven women aged 23-43years (mean: 32.1years) with a diagnosis of RE according to commonly accepted diagnostic criteria. All the patients were clinically evaluated and underwent prolonged video-EEG monitoring, laboratory investigations, and high-resolution MRI follow-up. All the patients displayed an ictal electroclinical pattern whose evolution varied. We identified an early phase characterized by polymorphic ictal electroclinical manifestations (temporal semiology in five cases, frontal in one, and parietal in the remaining case) and a late phase clinically characterized by viscerosensitive phenomena followed by somatosensitive signs, experiential symptoms, and motor signs in all the cases. In the late phase, the ictal EEG pattern was characterized by monomorphic, pseudorhythmic, repetitive slow-wave theta activity over the frontal and central regions, with ipsilateral propagation and/or secondary spreading to contralateral perisylvian structures. Patients were treated with a combination of AEDs and immunotherapy (steroids and IVIg); epilepsy surgery was performed in 3 cases. Our results show that A-RE is characterized by early and late clinical- and EEG-different features which may reflect a progressive involvement of a specific "extrarolandic" network in the advanced phase of the disease and may suggest that the electroclinical expression of RE varies according to the different stages of the pathological process.
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http://dx.doi.org/10.1016/j.yebeh.2013.05.033DOI Listing
September 2013

Prognostic significance of acute postoperative seizures in extra-temporal lobe epilepsy surgery.

Clin Neurophysiol 2013 Aug 10;124(8):1536-40. Epub 2013 Apr 10.

Epilepsy Surgery Unit, Department of Neurological Sciences, IRCCS NEUROMED, Pozzilli (IS), Italy.

Objective: This study aims to assess the prognostic value of acute postoperative seizures (APOS) in patients surgically treated for drug-resistant extra-temporal lobe (ET) epilepsy.

Methods: We studied 77 consecutive patients with ET epilepsy who underwent epilepsy surgery and were followed up for at least 2 years (mean duration of follow-up 6.2 years, range 2-14). Medical charts were reviewed to identify APOS, defined as ictal events with the exception of auras occurring within the first 7 days after surgery. Seizure outcome was determined at annual intervals. Patients who were in Engel Class I at the last contact were classified as having a favourable outcome.

Results: Seizure outcome was favourable in 47 patients (61%). The occurrence of APOS and incompleteness of resection were found to be independently associated with unfavourable outcome in a multiple regression model including all preoperative factors identified as outcome predictors in univariate analysis. Duration of illness was the only independent preoperative predictor of APOS.

Conclusions: Our study suggests that APOS may predict long-term outcome in patients undergoing resective surgery for ET epilepsy. Given some study limitations, our findings should be regarded as preliminary and need confirmation from future larger, prospective, multicentre studies.

Significance: Caution may be required in the clinical management of patients experiencing APOS.
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http://dx.doi.org/10.1016/j.clinph.2013.02.026DOI Listing
August 2013

Prognostic significance of serial postoperative EEG in extratemporal lobe epilepsy surgery.

Clin Neurophysiol 2012 Dec 18;123(12):2346-51. Epub 2012 Jun 18.

Epilepsy Surgery Unit, Department of Neurological Sciences, IRCCS NEUROMED Pozzilli (IS), Italy.

Objective: To assess the prognostic value of postoperative EEG in patients surgically treated for drug-resistant extra-temporal lobe (ET) epilepsy.

Methods: We studied 63 consecutive patients with ET epilepsy who underwent epilepsy surgery and were followed up for at least 2 years (mean duration of follow-up 6.2 ± 2.3 years, range 2-12). Follow-up evaluations were performed 2, 12, and 24 months after surgery, and included standard EEG (at 2 months) and long-term video-EEG monitoring during both wakefulness and sleep (at 12 and 24 months). Seizure outcome was determined at each follow-up evaluation, and then at yearly intervals. Patients who were in Engel Class I at the last contact were classified as having a good outcome.

Results: Seizure outcome was good in 39 patients (62%). The presence of interictal epileptiform discharges (IED) in postoperative EEG at each time point was found to be associated with poor outcome. The strength of this association was greater for awake plus sleep recording as compared with awake recording alone. In a multiple regression model including all pre- and post-operative factors identified as predictors of outcome in univariate analysis, the presence of early (2 months after surgery) EEG epileptiform abnormalities was found to be independently associated with poor seizure outcome.

Conclusions: Postoperative IED may predict long-term outcome in patients undergoing resective surgery for ET epilepsy.

Significance: The increase in risk of unfavourable outcome associated with EEG epileptiform abnormalities detected as early as two months after surgery may have substantial practical importance. Serial postoperative EEGs including sleep recording may add further predictive power and help making decision about antiepileptic drug discontinuation.
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http://dx.doi.org/10.1016/j.clinph.2012.05.013DOI Listing
December 2012

Surgery after intracranial investigation with subdural electrodes in patients with drug-resistant focal epilepsy: outcome and complications.

Neurosurg Rev 2012 Oct 22;35(4):519-26; discussion 526. Epub 2012 Mar 22.

Epilepsy Surgery Unit, Department of Neurological Sciences, IRCCS Neuromed, 86077, Pozzilli, Isernia, Italy.

Video-EEG monitoring with intracranial subdural electrodes is a useful assessment tool for the localization of the epileptogenic zone in patients with drug-resistant focal epilepsy. We aimed at assessing the morbidity related to electrode implantation and the surgical outcome in patients who underwent epilepsy surgery after intracranial EEG monitoring. All patients (N = 58) admitted to our Epilepsy Surgery Centre for drug-resistant focal epilepsy who underwent resective surgery after intracranial monitoring with subdural electrodes and were followed up for at least 2 years were included in the study. Their mean age was 30.4 years (range 8-60 years), 25 (43 %) were female, and 44 (76 %) had a preoperatively detected structural lesion. The mean duration of invasive recording was 2.3 days (range 1-14 days). Extraoperative ECoG allowed the identification of the epileptogenic focus in all cases. The temporal lobe was involved in 21 (36 %) patients, whereas extratemporal foci were identified in 24 (41 %) patients. Thirteen patients (23 %) had multilobar involvement. Functional brain mapping was performed in 15 (26 %) patients. Transient complications related to electrode implantation occurred in three patients. Among patients with evidence of lesion on preoperative MRI, lesionectomy alone was performed in 12 cases (27 %), while it was combined with tailored cortical resection in the remaining cases. Tailored cortical resection was also performed in patients without evidence of lesion on MRI. After resective surgery, transient neurological deficits occurred in five cases, while another patient experienced permanent lateral homonymous hemianopia. At the last follow-up observation, 34 (57 %) patients were seizure-free (Engel class I). This study suggests that invasive EEG recording with subdural electrodes may be useful and fairly safe for many candidates for epilepsy surgery.
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http://dx.doi.org/10.1007/s10143-012-0382-5DOI Listing
October 2012

Seizure clusters and adverse events during pre-surgical video-EEG monitoring with a slow anti-epileptic drug (AED) taper.

Clin Neurophysiol 2012 Mar 14;123(3):486-8. Epub 2011 Sep 14.

Epilepsy Surgery Unit, Department of Neurological Sciences, IRCCS Neuromed, Pozzilli (IS), Italy.

Objective: To evaluate the efficiency and safety of pre-surgical video-EEG monitoring with a slow anti-epileptic drug (AED) taper and a rescue benzodiazepine protocol.

Methods: Fifty-four consecutive patients with refractory focal epilepsy who underwent pre-surgical video-electroencephalography (EEG) monitoring during the year 2010 were included in the study. Time to first seizure, duration of monitoring, incidence of 4-h and 24-h seizure clustering, secondarily generalised tonic-clonic seizures (sGTCS), status epilepticus, falls and cardiac asystole were evaluated.

Results: A total of 190 seizures were recorded. Six (11%) patients had 4-h clusters and 21 (39%) patients had 24-h clusters. While 15 sGTCS were recorded in 14 patients (26%), status epilepticus did not occur and no seizure was complicated with cardiac asystole. Epileptic falls with no significant injuries occurred in three patients. The mean time to first seizure was 3.3days and the time to conclude video-EEG monitoring averaged 6days.

Conclusion: Seizure clustering was common during pre-surgical video-EEG monitoring, although serious adverse events were rare with a slow AED tapering and a rescue benzodiazepine protocol.

Significance: Slow AED taper pre-surgical video-EEG monitoring is fairly safe when performed in a highly specialised and supervised hospital setting.
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http://dx.doi.org/10.1016/j.clinph.2011.08.011DOI Listing
March 2012

Blockage of A2A and A3 adenosine receptors decreases the desensitization of human GABA(A) receptors microtransplanted to Xenopus oocytes.

Proc Natl Acad Sci U S A 2009 Sep 31;106(37):15927-31. Epub 2009 Aug 31.

Istituto Pasteur-Fondazione Cenci Bolognetti & Dipartimento di Fisiologia Umana e Farmacologia-Centro di Eccellenza BEMM, Universita' di Roma La Sapienza, I00185 Rome, Italy.

We previously found that the endogenous anticonvulsant adenosine, acting through A(2A) and A(3) adenosine receptors (ARs), alters the stability of currents (I(GABA)) generated by GABA(A) receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether ARs alter the stability (desensitization) of I(GABA) expressed in focal cortical dysplasia (FCD) and in periglioma epileptic tissues. The experiments were performed with tissues from 23 patients, using voltage-clamp recordings in Xenopus oocytes microinjected with membranes isolated from human MTLE and FCD tissues or using patch-clamp recordings of pyramidal neurons in epileptic tissue slices. On repetitive activation, the epileptic GABA(A) receptors revealed instability, manifested by a large I(GABA) rundown, which in most of the oocytes (approximately 70%) was obviously impaired by the new A(2A) antagonists ANR82, ANR94, and ANR152. In most MTLE tissue-microtransplanted oocytes, a new A(3) receptor antagonist (ANR235) significantly improved I(GABA) stability. Moreover, patch-clamped pyramidal neurons from human neocortical slices of periglioma epileptic tissues exhibited altered I(GABA) rundown on ANR94 treatment. Our findings indicate that antagonizing A(2A) and A(3) receptors increases the I(GABA) stability in different epileptic tissues and suggest that adenosine derivatives may offer therapeutic opportunities in various forms of human epilepsy.
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http://dx.doi.org/10.1073/pnas.0907324106DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2747220PMC
September 2009

Adenosine receptor antagonists alter the stability of human epileptic GABAA receptors.

Proc Natl Acad Sci U S A 2008 Sep 22;105(39):15118-23. Epub 2008 Sep 22.

Istituto Pasteur-Fondazione Cenci Bolognetti and Dipartimento di Fisiologia Umana e Farmacologia, Centro di Eccellenza di Biologia e Medicina Molecolare, Università di Roma La Sapienza, Piazzale A. Moro 5, I-00185 Rome, Italy.

We examined how the endogenous anticonvulsant adenosine might influence gamma-aminobutyric acid type A (GABA(A)) receptor stability and which adenosine receptors (ARs) were involved. Upon repetitive activation (GABA 500 microM), GABA(A) receptors, microtransplanted into Xenopus oocytes from neurosurgically resected epileptic human nervous tissues, exhibited an obvious GABA(A)-current (I(GABA)) run-down, which was consistently and significantly reduced by treatment with the nonselective adenosine receptor antagonist CGS15943 (100 nM) or with adenosine deaminase (ADA) (1 units/ml), that inactivates adenosine. It was also found that selective antagonists of A2B (MRS1706, 10 nM) or A3 (MRS1334, 30 nM) receptors reduced I(GABA) run-down, whereas treatment with the specific A1 receptor antagonist DPCPX (10 nM) was ineffective. The selective A2A receptor antagonist SCH58261 (10 nM) reduced or potentiated I(GABA) run-down in approximately 40% and approximately 20% of tested oocytes, respectively. The ADA-resistant, AR agonist 2-chloroadenosine (2-CA) (10 microM) potentiated I(GABA) run-down but only in approximately 20% of tested oocytes. CGS15943 administration again decreased I(GABA) run-down in patch-clamped neurons from either human or rat neocortex slices. I(GABA) run-down in pyramidal neurons was equivalent in A1 receptor-deficient and wt neurons but much larger in neurons from A2A receptor-deficient mice, indicating that, in mouse cortex, GABA(A)-receptor stability is tonically influenced by A2A but not by A1 receptors. I(GABA) run-down from wt mice was not affected by 2-CA, suggesting maximal ARs activity by endogenous adenosine. Our findings strongly suggest that cortical A2-A3 receptors alter the stability of GABA(A) receptors, which could offer therapeutic opportunities.
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http://dx.doi.org/10.1073/pnas.0807277105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567502PMC
September 2008

Memory outcome 2 years after anterior temporal lobectomy in patients with drug-resistant epilepsy.

Seizure 2009 Mar 19;18(2):139-44. Epub 2008 Sep 19.

Epilepsy Surgery Unit, Department of Neurological Sciences, IRCCS Neuromed, 86077 Pozzilli (IS), Italy.

Purpose: Memory decline is often observed after anterior temporal lobectomy (ATL), particularly in patients with dominant hemisphere resections. However, the follow-up length has been 1 year or less in most studies. Our aims were to examine postoperative memory changes over a longer period and to identify baseline demographic and clinical predictors of memory outcome.

Methods: We administered material-specific memory tests at baseline, and 1 and 2 years after surgery to 82 consecutive right-handed patients (52% males) who underwent ATL for drug-resistant temporal lobe epilepsy (TLE) (35 left, 47 right) after a non-invasive presurgical protocol. Repeated measures multivariate analysis of variance (RM-MANOVA) was used to examine the relationship between changes in memory tests scores over time and side of TLE and pathology. Also, standardized residual change scores were calculated for each memory test and entered in multiple linear regression models aimed at identifying baseline predictors of better memory outcome.

Results: RM-MANOVA revealed a significant change in memory test scores over time, with an interaction between time and side of surgery, as 2 years after surgery patients with RTLE were improved while patients with LTLE were not worse as compared with baseline. Pathology was not associated with changes in memory scores. In multiple regression analysis, significant associations were found between right TLE and greater improvement in verbal memory, younger age and greater improvement in visuospatial memory, and male gender and greater improvement in both verbal and visuospatial memory.

Conclusions: Our results suggest that the long-term memory outcome of TLE patients undergoing ATL without invasive presurgical assessment may be good in most cases not only for right-sided but also for left-sided resections.
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http://dx.doi.org/10.1016/j.seizure.2008.08.008DOI Listing
March 2009

Visual event-related potentials in elite and amateur athletes.

Brain Res Bull 2007 Sep 12;74(1-3):104-12. Epub 2007 Jun 12.

Istituto di Medicina e Scienza dello Sport, CONI Servizi, Via dei Campi Sportivi 46, Roma, Italy.

In the present study, we tested the hypothesis that the neural synchronization estimated in visual cortex during visuo-spatial demands shows different features in elite karate athletes when compared to amateur karate athletes and non-athletes. EEG recordings (56 channels; EB-Neuro) were performed from 17 elite karate athletes, 14 amateur karate athletes, and 15 non-athletes, during the observation of pictures with basket and karate attacks. They clicked a right (left) keyboard button for basket or karate attacks at right (left) monitor side. Results pointed to no difference of late occipital VEPs/ERPs after basket versus karate attacks in the non-athletes (300-800 ms post-stimulus). In the amateur karate athletes, occipital VEPs/ERPs at 300-450 ms post-stimulus (P3-P4 components) were lower in amplitude for the karate than basket attacks. In the elite karate athletes, the occipital VEPs/ERPs further declined in amplitude at 300-450 ms post-stimulus (P3 and P4 components) and enhanced at about 800 ms post-stimulus ("N2" component) for the karate than basket attacks. A control study showed that in 10 elite fencers, the same was true for the fencing compared to the karate attacks. These results support the hypothesis that peculiar mechanisms of occipital neural synchronization can be observed in elite athletes during visuo-spatial demands, possibly to underlie sustained visuo-spatial attention and self-control.
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http://dx.doi.org/10.1016/j.brainresbull.2007.05.011DOI Listing
September 2007

The antiepileptic drug levetiracetam stabilizes the human epileptic GABAA receptors upon repetitive activation.

Epilepsia 2007 Oct 23;48(10):1842-9. Epub 2007 May 23.

Dipartimento di Fisiologia Umana e Farmacologia, Universita' di Roma La Sapienza, Roma, Italy.

Purpose: GABAA receptors from the brain of patients afflicted with mesial temporal lobe epilepsy (MTLE) become less efficient (run-down) when repetitively activated by GABA. Experiments were designed to investigate whether the antiepileptic drug, levetiracetam (LEV), which is used as an adjunctive treatment for medically intractable MTLE, counteracts the GABAA receptor run-down.

Methods: GABAA receptors were microtransplanted from the brains of patients afflicted with MTLE into Xenopus oocytes. The GABA-current run-down, caused by repetitive applications of GABA, was investigated using the standard two-microelectrode voltage-clamp technique. Additionally, the GABA-current run-down was investigated directly on pyramidal neurons in human MTLE cortical slices.

Results: It was found that, in oocytes injected with membranes isolated from the MTLE neocortex, the GABA-current run-down was inhibited by a 3-h pretreatment with 0.5-100 microM LEV. Moreover, the GABAA receptors of pyramidal neurons in human neocortical slices exhibited a current run-down that was significantly reduced by 1 microM LEV. Interestingly, the run-down in oocytes injected with membranes isolated from the MTLE hippocampal subiculum was not affected by LEV.

Conclusions: We report that the antiepileptic LEV strengthens GABA inhibition of neuronal circuits by blocking the receptor run-down in the cortex whilst leaving the run-down of GABAA receptors in the hippocampal subiculum unaltered. These findings point to the GABAA receptor run-down as an important event in epileptogenesis and as a possible target for testing and screening antiepileptic drugs.
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http://dx.doi.org/10.1111/j.1528-1167.2007.01131.xDOI Listing
October 2007

Factors associated with generic and disease-specific quality of life in temporal lobe epilepsy.

Epilepsy Res 2006 May 3;69(2):135-46. Epub 2006 Mar 3.

Epilepsy Surgery Unit, Department of Neurological Sciences, IRCCS Neuromed, Pozzilli (IS), Italy.

Purpose: We aimed at further elucidating the association between quality of life (QOL) and sociodemographic factors, clinical seizure factors, depression and anxiety in drug-resistant temporal lobe epilepsy (TLE).

Methods: We studied 106 consecutive adult right-handed patients (mean age 35.4 +/- 9.7; 50% males; IQ> or = 70) with drug-resistant unilateral (59% right) TLE (70% hippocampal sclerosis, 30% tumors or other lesions), who underwent a comprehensive non-invasive pre-surgical protocol. They completed the Beck Depression Inventory (BDI) and the State Form of the Spielberger State-Trait Anxiety Inventory (STAI). To measure QOL, we used both a generic instrument, the WHOQOL-100, and a disease-specific instrument, the 31-item quality of life in epilepsy (QOLIE-31). Multiple linear regression analysis was used to examine the relationship between each QOL domain and age, gender, education, side of TLE, duration of epilepsy, seizure frequency, and level of depression and anxiety.

Results: Severity of depressive symptoms was significantly associated with lower scores across most QOL domains. Depression was consistently the strongest predictor of lower scores on almost all QOL domains. Also, severity of anxiety symptoms was significantly associated with lower scores across many QOL domains. Independent significant relationships between QOL and sociodemographic or clinical epilepsy variables were limited in number and strength.

Conclusions: Our findings suggest that QOL in TLE might be substantially affected by the presence and severity of depressive symptoms and, to a lesser degree, of anxiety symptoms. While clinical seizure variables had a weaker association with QOL, the absence of seizure-free patients might have obscured a relation between seizure frequency and QOL. Healthcare professionals should be aware of the significance of patients' emotional state and of the role it plays for their QOL. Adopting a biopsychosocial approach might be useful to address patients' needs.
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http://dx.doi.org/10.1016/j.eplepsyres.2006.01.010DOI Listing
May 2006