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We previously found that the endogenous anticonvulsant adenosine, acting through [A.sub.2A] and [A.sub.3] adenosine receptors (ARs), alters the stability of currents ([I.sub.GABA]) generated by GABAA receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether ARs alter the stability (desensitization) of [I.sub.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 GABAA receptors revealed instability, manifested by a large [I.sub.GABA] rundown, which in most of the oocytes ([approximately equal to] 70%) was obviously impaired by the new [A.sub.2A] antagonists ANR82, ANR94, and ANR152. In most MTLE tissue-microtransplanted oocytes, a new [A.sub.3] receptor antagonist (ANR235) significantly improved [I.sub.GABA] stability. Moreover, patch-clamped pyramidal neurons from human neocortical slices of periglioma epileptic tissues exhibited altered [I.sub.GABA] rundown on ANR94 treatment. Our findings indicate that antagonizing [A.sub.2A] and [A.sub.3] receptors increases the [I.sub.GABA] stability in different epileptic tissues and suggest that adenosine derivatives may offer therapeutic opportunities in various forms of human epilepsy. epilepsy | focal cortical dysplasia

We examined how the endogenous anticonvulsant adenosine might influence [gamma]-aminobutyric acid type A ([GABA.sub.A]) receptor stability and which adenosine receptors (ARs) were involved. Upon repetitive activation (GABA 500 [micro]M), [GABA.sub.A] receptors, microtransplanted into Xenopus oocytes from neurosurgically resected epileptic human nervous tissues, exhibited an obvious [GABA.sub.A]-current ([I.sub.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.sub.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.sub.GABA] run-down in [approximately equal to]40% and [approximately equal to]20% of tested oocytes, respectively. The ADA-resistant, AR agonist 2-chloroadenosine (2-CA) (10 [micro]M) potentiated [I.sub.GABA] run-down but only in [approximately equal to]20% of tested oocytes. CGS15943 administration again decreased [I.sub.GABA] run-down in patch-clamped neurons from either human or rat neocortex slices. [I.sub.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.sub.A]-receptor stability is tonically influenced by A2A but not by A1 receptors. [I.sub.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.sub.A] receptors, which could offer therapeutic opportunities. A2A receptor | A3 receptor | microtransplantation into Xenopus oocyte | temporal lobe epilepsy

Objective: To assess seizure and cognitive outcomes and their predictors in children (<16 years at surgery) and adults undergoing temporal lobe epilepsy (TLE) surgery in eight Italian centers. Methods: This is a retrospective multicenter study. We performed a descriptive analysis and subsequently carried out multivariable mixed‐effect models corrected for multiple comparisons. Results: We analyzed data from 511 patients (114 children) and observed significant differences in several clinical features between adults and children. The possibility of achieving Engel class IA outcome and discontinuing antiepileptic drugs (AEDs) at last follow‐up (FU) was significantly higher in children (P =.006 and <.0001). However, percentages of children and adults in Engel class I at last FU (mean ± SD, 45.9 ± 17 months in children; 45.9 ± 20.6 months in adults) did not differ significantly. We identified different predictors of seizure outcome in children vs adults and at short‐ vs long‐term FU. The only variables consistently associated with class I outcome over time were postoperative electroencephalography (EEG) in adults (abnormal, improved,odds ratio [OR] = 0.414, P =.023, Q = 0.046 vs normal, at 2‐year FU and abnormal, improved, OR = 0.301, P =.001, Q = 0.002 vs normal, at last FU) and the completeness of resection of temporal magnetic resonance (MR) abnormalities other than hippocampal sclerosis in children (OR = 7.93, P =.001, Q = 0.003, at 2‐year FU and OR = 45.03, P <.0001, Q < 0.0001, at last FU). Cognitive outcome was best predicted by preoperative performances in either age group. Significance: Clinical differences between adult and pediatric patients undergoing TLE surgery are reflected in differences in long‐term outcomes and predictors of failures. Children are more likely to achieve sustained seizure freedom and withdraw AEDs after TLE surgery. Earlier referral should be encouraged as it can improve surgical outcome. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

We previously found that the endogenous anticonvulsant adenosine, acting through A2A and A3 adenosine receptors (ARs), alters the stability of currents (IGABA) generated by GABAA receptors expressed in the epileptic human mesial temporal lobe (MTLE). Here we examined whether AR5 alter the stability (desensitization) of IGABA expressed in focal cortical dysplasia (FCD) and in penglioma 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 GABAA receptors revealed instability, manifested by a large IGABA rundown, which in most of the oocytes (≈70%) was obviously impaired by the new A2A antagonists ANR82, ANR94, and ANR152. In most MILE tissue-microtransplanted oocytes, a new A3 receptor antagonist (ANR235) significantly improved IGABA stability. Moreover, patch-clamped pyramidal neurons from human neocortical slices of periglioma epileptic tissues exhibited altered IGABA rundown on ANR94 treatment. Our findings indicate that antagonizing A2A and A3 receptors increases the IGABA stability in different epileptic tissues and suggest that adenosine derivatives may offer therapeutic opportunities in various forms of human epilepsy. [ABSTRACT FROM AUTHOR]

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. Methods: 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). Results: 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 (n = 5), temporo-parietal (n = 1) or frontal (n = 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. Conclusion: 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. [ABSTRACT FROM AUTHOR]

Abstract 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. Highlights • Surgery is a safe option in drug-resistant FLE with a satisfying long-term outcome. • The presence of focal lesions predicts favorable outcome. • Focal ictal scalp EEG onset is associated with a favorable long-term outcome. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

In order to investigate alterations in brain morphology and a possible temporal pattern of neuroanatomical abnormalities in the gray matter (GM), white matter (WM) and cerebrospinal fluid (CSF) of young patients with Down syndrome (DS), high-resolution magnetic resonance imaging (MRI) voxel-based morphometry (VBM) was performed on 21 children and adolescents with this chromosomal aberration and 27 age-matched participants as controls. In comparison with control subjects, children and adolescents with DS showed not only an overall smaller whole-brain volume, but also volume reductions of the GM in the cerebellum, frontal lobes, frontal region of the limbic lobe, parahippocampal gyri and hippocampi and of the WM in the cerebellum, frontal and parietal lobes, sub-lobar regions and brainstem. By contrast, volume preservation was observed in the GM of the parietal lobes, temporal lobe and sub-lobar regions and in the WM of the temporal lobe and temporal regions of the limbic lobe. A lower volume of CSF was also detected in the frontal lobes. This study is the first to use the high-resolution MRI VBM method to describe a whole-brain pattern of abnormalities in young DS patients falling within such a narrow age range and it provides new information on the neuroanatomically specific regional changes that occur during development in these patients.

Rasmussen's encephalitis (RE) is a chronic, progressive disease that typically occurs in childhood, rarely in adulthood. When it does occur in adulthood, it may be associated with atypical electro-clinical features, and neuroimaging alterations usually help diagnosis. Unlike childhood forms, in which epilepsia partialis continua is usually observed, the EEG pattern in adult variants may be aspecific. We describe a highly interesting case of late-onset RE in which an electrical status epilepticus was not detected by the surface EEG, but by a recording with subdural electrodes.

Object: Supratentorial cavernous angiomas may be associated with drug-resistant focal epilepsy. Surgical removal of the malformation may result in seizure control in a number of patients, although in most studies a long history and high frequency of attacks have been recognized as indicators of unfavorable seizure outcome. In the literature, there are no clear indications regarding the optimal diagnostic presurgical workup and the surgical strategy for this particular subgroup of patients with symptomatic epilepsy. In this paper the authors focus on the preoperative workup and the surgical management of the disease in eight consecutive patients undergoing surgery for drug-resistant temporal lobe epilepsy (TLE) due to cavernous malformations (CMs), and the relevant literature on this issue is also reviewed., Methods: Preoperatively, all patients were assessed using a noninvasive protocol aimed at localizing the epileptogenic zone on the basis of anatomical, electrical, and clinical criteria. The presurgical assessment yielded an indication for lesionectomy in two cases, lesionectomy plus anteromesial temporal lobectomy in four cases, and lesionectomy plus extended temporal lobectomy in two cases. At follow-up examinations, seizure, neuropsychological, and psychiatric outcomes were all evaluated. Seven patients were categorized in Engel Class IA (seizure free), and one was categorized in Engel Class IB (occasional auras only). No adverse effects on neuropsychological or psychosocial functioning were observed., Conclusions: Epilepsy surgery can be performed with excellent results in patients with intractable TLE caused by CMs. Noninvasive presurgical evaluation of these patients may enable a tailored approach, providing complete seizure relief in most cases.