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Objective: To describe a patient with a posterior inferior cerebellar artery stroke exhibiting a horizontal direction changing nystagmus with a complex clinical phenotype., Materials and Methods: A 78-year-old man presented with acute vertigo and gait imbalance. He was dysphagic and ataxic on the left side. He had a fast, small-amplitude right-beating nystagmus in the primary gaze position and in the gaze towards the right. Towards the left, a coarse left-beating nystagmus was seen., Results: Radiographic leftwards ocular deviation was evident on admission CT. Intravenous fibrinolysis was administered. 48-hour Holter-EKG, transthoracic ecochardiogram, and transcranial doppler were unremarkable. Brain MRI demonstrated an acute stroke involving the left medulla and cerebellum, mainly within the territory of the ipsilateral posterior inferior cerebellar artery., Discussion and Conclusions: Horizontal direction changing nystagmus can arise secondary to central lesions as brainstem strokes, it can be spontaneous or gaze-evoked and characteristically remains unchanged after fixation removal. In our case, the vestibular spontaneous and contralesional nystagmus was likely related to lower-brainstem damage; on the other hand, the ipsilesional gaze-evoked nystagmus might be related to lesions of the nucleus prepositus hypoglossi and/or cerebellum, both playing an important role in gaze-holding. Our findings suggest that central lesions with concurrent involvement of the ipsilateral vestibulo-ocular and horizontal gaze-holding pathways can cause direction changing nystagmus with complex phenotypes., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest relevant to this work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: ABGAs are historically associated with Encephalitis Lethargica (EL). Typically ABGAs are also found in children resulting in a variety of neuropsychiatric and extrapyramidal disorders, rare cases are reported in adults with atypical movement disorders. No description of basal ganglia reversible lesions related to ABGAs are reported and these antibodies are not included in the list of autoimmune encephalitis., Methods and Results: A 55 years old female presented sub-acute onset of an anxious-depressive disorder and obsessive-compulsive behavior associated with intractable insomnia affecting sleep onset and sleep maintenance. Brain-MRI showed diffuse hyperintensities on FLAIR sequences in the basal ganglia. A therapy with IV-immunoglobulin was started and the clinical condition improved dramatically and insomnia and psychiatric symptoms resolved completely., Conclusion: Our case highlights the importance of making a fast diagnosis. When caught early ABGAs-related encephalitis is susceptible of a good outcome and response to treatment. Reversible insomnia and dementia in our case expand ABGA clinical presentation in adults and favors the hypothesis of an immune pathogenesis for Encephalitis Lethargica, especially in the hyperkinetic form as previously suggested, as in our case., Competing Interests: Declaration of competing interest No specific funding was received for this work. The authors declare that there are no conflicts of interest relevant to this work. The authors declare that there are no additional disclosures to report. Patient consent was obtained., (Copyright © 2024 Elsevier B.V. All rights reserved.)

A 78-year-old woman without past relevant medical history presented to the emergency department for acute transient dysarthria. NIHSS was 0/42. Neurological examination revealed chorea-like movements over the left limbs, especially the foot. No other neurological signs were present. CT perfusion showed right cortical hypoperfusion due to right M2 occlusion, basal-ganglia perfusion was normal. Brain MRI revealed a small focus of restricted diffusion in the right insula, sparing basal ganglia. Based on the neuroimaging features and clinical correlation, despite the NIHSS score, we decided to treat the patient with alteplase, after iv-thrombolysis hyperkinetic movements ceased completely. Brain-MRI performed 72 h after symptom onset confirmed a confined insular ischemic lesion without the involvement of deep gray matter structures. Hyperkinetic movement disorders, such as hemichorea hemiballismus, are rare presentations of stroke, basal ganglia are mainly involved even if the insular cortex has been described too. Clinical decision on whether to treat ischemic stroke does not include movement disorders. Our case underscores NIHSS limitations in clinical practice., (© 2023. Fondazione Società Italiana di Neurologia.)

Background and Purpose: Misdiagnosis of refractory epilepsy (rE) is common and such patients experience a long diagnostic delay. Our aim was to identify key clinical/laboratory factors in order to obtain an alternative diagnosis in patients referred for rE., Methods: Between January 2010 and December 2015, 125 consecutive patients with a diagnosis of rE were prospectively enrolled. All patients underwent a comprehensive neurological, neuropsychiatric and cardiological evaluation, and had an observation time of at least 1 year after the study entry., Results: Diagnosis of rE was confirmed in 104/125 (83.2%) patients (55 women, mean age 38.8 ± 14.3 years). Thirteen/125 patients (10.4%, seven women, mean age 50.8 ± 20.9) were diagnosed with syncope, which was cardiac/cardio inhibitory in 9/13 (69%). The remaining 8/125 patients (6.4%, six women, mean age 41.2 ± 14.6 years) were diagnosed with psychogenic non-epileptic seizures. Age at onset had a high accuracy in differentiating patients with syncope from others, with the best cut-off age at 35 years and above. Abnormal brain magnetic resonance imaging (MRI) had a significant yield of about 70% in rE. A diagnostic model including age at onset and brain MRI was highly accurate in differentiating patients with syncope from others. In patients with cardiac/cardio inhibitory syncope, the point score of historical features was ≥1 and falsely favoured the diagnosis of epileptic seizures., Conclusions: This prospective cohort study identifies rE mimics who are at high risk of morbidity and mortality. rE starting in adulthood should raise a high suspicion of cardiac syncope. Brain MRI is accurate in differentiating rE from other conditions., (© 2018 EAN.)

Background and Purpose: The purpose of this study was to determine whether switching from branded levetiracetam (Keppra ® ) to a levetiracetam generic equivalent product (Matever ® ) in an epilepsy cohort could provide adequate results in terms of seizure control and tolerability., Methods: To be eligible for the study, patients had to have been taking Keppra ® as monotherapy or polytherapy for at least 6 months. Between March 2013 and April 2017, patients were invited to switch to Matever ® as part of their follow-up. We evaluated the number of seizures per month, drug-related adverse events and electroencephalography before the switch (T0, baseline) and 6 months after switching (T1). Furthermore, we reported the long-term follow-up of patients who continued to use Matever ® after the end of the study, considering the most recent visit for each patient (T2)., Results: A total of 55 patients refused the switch. Among the remaining 125 patients, 59 (47%) were treated using Keppra ® as monotherapy and 66 (53%) were on Keppra ® as polytherapy. All 125 patients were subjected to switching from Keppra ® to Matever ® . Comparing patients before (T0) and after (T1) switching, we found no statistically significant differences in terms of seizure frequency and occurrence of adverse effects. There were no significant differences (number of seizures/month and drug-related adverse events) between patients treated with Matever ® as monotherapy and patients who refused the switch and continued to use Keppra ® as monotherapy for a long-term follow-up of 48 months. Electroencephalography findings were also unchanged., Conclusion: In our sample, brand-to-generic levetiracetam switching was effective and safe in both monotherapy and polytherapy regardless of the epilepsy syndrome., (© 2018 EAN.)

Lateral temporal lobe epilepsy (lTLE) is a rare condition characterized by auditory auras or receptive aphasia, negative MRI, and relatively benign evolution. With the low number of cases in the world, our objective was to analyze a cohort of sporadic cases with lTLE (slTLE), in order to investigate possible cerebral morphological alterations. Forty patients with lTLE (34.93±12.08years of age) and 38 healthy controls (CTRL, 34.55±9.08years of age) were enrolled from four tertiary Italian epilepsy centers, which provided brain MRI T1-weighted images following a standard protocol for patients with epilepsy. We performed group comparison by following different approaches: voxel-based morphometry (VBM, SPM8), cortical thickness (CT), and local gyrification index (lGI) (FreeSurfer 5.3). At a more conservative threshold (p<0.05, FWE correction), no significant differences between groups survived, neither in VBM nor CT/lGI. Multicenter studies have more power than smaller studies in conducting sophisticated evaluations of rare diseases, and further investigations are required to develop a full picture of this rare phenotype., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The Inventory Déjà Vu Experiences Assessment (IDEA) is the only screening instrument proposed to evaluate the Déjà vu (DV) experience. Here, we intended to validate the Italian version of IDEA (I-IDEA) and at the same time to investigate the incidence and subjective qualities of the DV phenomenon in healthy Italian adult individuals on basis of an Italian multicentre observational study. In this study, we report normative data on the I-IDEA, collected on a sample of 542 Italian healthy subjects aging between 18-70 years (average age: 40) with a formal educational from 1-19 years. From September 2013 to March 2016, we recruited 542 healthy volunteers from 10 outpatient neurological clinics in Italy. All participants (i.e., family members of neurological patients enrolled, medical students, physicians) had no neurological or psychiatric illness and gave their informed consent to participate in the study. All subjects enrolled self-administered the questionnaire and they were able to complete I-IDEA test without any support. In total, 396 (73%) of the 542 healthy controls experienced the DV phenomenon. The frequency of DV was inversely related to age as well as to derealisation, jamais vu, precognitive dreams, depersonalization, paranormal activity, remembering dreams, travel frequency, and daydreams (all p < 0.012). The Italian version of IDEA maintains good properties, thus confirming that this instrument is reliable for detecting and characterising the DV phenomenon., Competing Interests: The authors declare no conflict of interest.

Background: The number of suspected adverse drug reactions (ADRs) yearly submitted to the Italian Network of Pharmacovigilance (RNF) has progressively increased after the new European Pharmacovigilance legislation (July 2012). These results have mostly reflected the agreements between Italian Medicines Agency (AIFA) and Italian Regions, enabling the implementation of active pharmacovigilance projects. A project was funded by the AIFA in Calabria region (Southern Italy) in 2010 to increase ADRs reporting and promote a safer medicines' use. Based on this background, we investigated the trend of ADRs in Calabria in 2011-2014, trying to analyze the possible entailments of the new law., Methods: Quantitative and descriptive analysis of ADRs submitted by Calabrian healthcare professionals and patients to the RNF database between 2011 and 2014., Results: A sharp rise in regional reporting rate was observed over study period. Calabrian Pharmacovigilance system completely fulfilled the World Health Organization gold standard for ADR reporting rate, both in 2013 and 2014. However, heterogeneity was observed regarding reporting health facilities, healthcare professionals and patients among the study years., Conclusions: These findings reflect the success of the project performed in Calabria. However, this initiative should go on in the next future to obtain better and more homogeneous reporting behavior.

A novel technique of quantitative EEG for differentiating patients with early-stage Creutzfeldt-Jakob disease (CJD) from other forms of rapidly progressive dementia (RPD) is proposed. The discrimination is based on the extraction of suitable features from the time-frequency representation of the EEG signals through continuous wavelet transform (CWT). An average measure of complexity of the EEG signal obtained by permutation entropy (PE) is also included. The dimensionality of the feature space is reduced through a multilayer processing system based on the recently emerged deep learning (DL) concept. The DL processor includes a stacked auto-encoder, trained by unsupervised learning techniques, and a classifier whose parameters are determined in a supervised way by associating the known category labels to the reduced vector of high-level features generated by the previous processing blocks. The supervised learning step is carried out by using either support vector machines (SVM) or multilayer neural networks (MLP-NN). A subset of EEG from patients suffering from Alzheimer's Disease (AD) and healthy controls (HC) is considered for differentiating CJD patients. When fine-tuning the parameters of the global processing system by a supervised learning procedure, the proposed system is able to achieve an average accuracy of 89%, an average sensitivity of 92%, and an average specificity of 89% in differentiating CJD from RPD. Similar results are obtained for CJD versus AD and CJD versus HC.

Introduction: Drug treatment may be related to the development of adverse drug reactions (ADRs)., Aim: In this paper, we evaluated the ADRs in patients admitted to Catanzaro Hospital., Methods: After we obtained the approval by local Ethical Committee, we performed a retrospective study on clinical records from March 01, 2013 to April 30, 2015. The association between drug and ADR or between drug and drug-drug-interactions (DDIs) was evaluated using the Naranjo's probability scale and Drug Interaction Probability Scale (DIPS), respectively., Results: During the study period, we analyzed 2870 clinical records containing a total of 11,138 prescriptions, and we documented the development of 770 ADRs. The time of hospitalization was significantly higher (P<0.05) in women with ADRs (12.6 ± 1.2 days) with respect to men (11.8± 0.83 days). Using the Naranjo score, we documented a probable association in 78% of these reactions, while DIPS revealed that about 22% of ADRs were related to DDIs. Patients with ADRs received 3052 prescriptions on 11,138 (27.4%) having a mean of 6.1±0.29 drugs that was significantly higher (P<0.01) with respect to patients not experiencing ADRs (mean of 3.4±0.13 drugs). About 19% of ADRs were not diagnosed and were treated as new diseases., Conclusion: Our results indicate that drug administration induces the development of ADRs also during the hospitalization, particularly in elderly women. Moreover, we also documented that ADRs in some patients are under-diagnosed, therefore, it is important to motivate healthcare to report the ADRs in order to optimize the patients' safety., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: Growing evidence indicates that pharmacogenomics will positively impact treatment for patients with epilepsy in the near future, leading to the implementation of a precision-based use of antiepileptic drug (AED) therapy, thereby providing a cornerstone for precision medicine., Objective: In this review, we briefly summarize the studies of pharmacogenomics in epilepsy, recent advances, and how it may progress in the future., Methods: We subdivided the review into two main sections: genetic variants that may modulate response to AEDs through pharmacokinetics or pharmacodynamics mechanisms; and gene variants that may affect tolerability and safety of AEDs., Results: Results from most studies have been contradictory, due to several flaws, including small sample sizes, inaccurate phenotyping, and genotyping strategies. However, even with these limitations, very recent developments indicate that the goal of incorporating genetic data into clinical practice may be attainable in the near future. In addition, recent pharmacogenomic studies of hypersensitivity reactions to AEDs have also made important strides, as its prevention appears attainable with the identification of HLA-A genotypes for patients at high risk of carbamazepine hypersensitivity., Conclusion: To better clarify the relationship between genetic factors and AEDs, future studies will require more precise epilepsy phenotypes, larger sample sizes, and astute use of new genotyping strategies. Reasonably, this will lead to novel therapeutic approaches in drug targeting and antiepileptogenesis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Mesial temporal lobe epilepsy (MTLE) is frequently associated with hippocampal sclerosis (Hs), possibly caused by a primary brain injury that occurs a long time before the appearance of neurological symptoms. MTLE-Hs is, however, a heterogeneous condition that evolves with time, involving both environmental and genetic components. Recent experimental studies emphasize that drugs or drug combinations that target modulation and circuitry reorganization of the epileptogenic networks favorably modify the complex molecular and cellular alterations underlying MTLE. In particular, the link between neuroinflammation, GABA A R and epilepsy has been extensively studied mainly because of the relevant therapeutic implications that the pharmacological modulation of these phenomena would have in the clinical practice. In this review, we briefly summarize the studies that could pave the road to develop new disease-modifying therapeutic strategies for pharmacoresistant MTLE patients. Both clinical observations in human MTLE and experimental findings will be discussed, highlighting the potential modulatory crosstalk between the deregulation of the inhibitory (GABAergic) transmission and the sustained activation of the innate immune response., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

The clinical evolution of untreated epilepsy has been rarely studied in developed countries, and the existence of a distinct syndrome characterized by rarely repeated seizures (oligoepilepsy) is debated. The aim of this study is to assess the natural history of 163 untreated patients with epilepsy in order to evaluate whether oligoepilepsy retains specific features. We retrospectively evaluated 7344 patients with ≥2 unprovoked seizures., Inclusion Criteria: sufficient anamnestic/EEG data, disease duration ≥10 years, follow-up ≥3 years., Exclusion Criteria: psychogenic seizures, natural history of disease <5 years. The 163 included subjects were divided into 2 groups according to seizure frequency: oligoepilepsy (≤1/year; 47 subjects) and controls (>1/year; 116 subjects). We also evaluated seizure frequency during the natural history. There were no differences between groups regarding duration of natural history, family history of epilepsy/febrile seizures, interictal EEG. Subjects with oligoepilepsy differed from controls in terms of sex (females 38% vs. 58%, p = 0.03) and drug resistance (6% vs 28%; p = 0.003). Juvenile myoclonic epilepsy was more frequent in controls (9.5% vs 0%, p = 0.04). Patients with oligoepilepsy, differently from controls, had stable seizure frequency. Oligoepilepsy represents a favourable evolution of different epileptic syndromes and keeps a stable seizure frequency over time., Competing Interests: The authors have declared that no competing interests exist.

Mesial temporal lobe epilepsy (MTLE) is the most common type of refractory epilepsy and is usually associated with hippocampal sclerosis (Hs). The pathogenesis of MTLE involves many biological pathways, some of which seem to be regulated by microRNAs (miRNAs). Increasing evidence shows that single nucleotide polymorphisms (SNPs) or mutations in miRNAs sequence may affect the processing and function of miRNAs and participate in the occurrence of diseases. In this study, the effect of the SNP of one neuronal miRNA, miR-124, on susceptibility to MTLE was investigated using a case control study. To understand the role, a common C/G polymorphism designated rs531564 in the molecular mechanisms of MTLE, we sought to determine whether this genetic variant could influence susceptibility to disease in a cohort of 307 MTLE patients and 306 healthy controls, using TaqMan allelic discrimination assay, on an Applied Biosystems PCR platform. No statistically significant differences were found in the allele or genotype distributions of the miR-124 rs531564 polymorphism among MTLE patients and MTLE-free control subjects (p > 0.05). Our results demonstrate that this SNP has no major role in genetic susceptibility to MTLE, at least in the population studied here.

Objective: To identify clinical and imaging features at presentation that might predict long-term outcome in patients with mild mesial temporal lobe epilepsy (mMTLE), which is defined by at least 24 seizure-free months with or without antiepileptic medication., Methods: In the setting of a prospective, population-based, longitudinal cohort study, we followed up 101 patients, all with mMTLE at enrolment. By protocol, patients underwent clinical evaluation every 3-12 months. Independent t test, Mann-Whitney test, or χ(2) test was used for comparing 2 groups. The incidence rate of refractory MTLE (rMTLE) was expressed as number of cases every 100 person-years., Results: After a mean follow-up of 12.2 ± 3.7 years, 16 patients dropped out and 85/101 (mean age 46.5 ± 13.3 years) were available for the present analysis. Of these, 64/85 (75%) patients remained seizure-free and 21/85 (25%) became refractory (rMTLE), the latter corresponding to 2.0 cases per 100 persons per year. Patients with rMTLE showed a longer duration of epilepsy (p < 0.001), earlier age at epilepsy onset (p = 0.006), more frequent febrile convulsions (p = 0.02), and hippocampal sclerosis (HS) at MRI (p = 0.004) as compared to those with mMTLE., Conclusions: mMTLE is a syndrome representing the mildest form of the wide spectrum of MTLE. Earlier age at onset, history of febrile convulsions, longer duration of epilepsy, and the presence of HS on MRI predict a worse outcome., (© 2016 American Academy of Neurology.)

Purpose: The aim of this study was to evaluate the efficacy and tolerability of lacosamide (LCM) both as add-on therapy and monotherapy in patients with temporal lobe epilepsy (TLE) based on an observational, prospective, multicenter study., Methods: We enrolled 100 patients (mean age: 43.4±12.53years, 57 females) with nonlesional TLE and TLE with hippocampal sclerosis (HS) that did not respond to the first drug and who were referred to epilepsy centers of the University of Catanzaro, University of Palermo, IRCSS Neuromed of Pozzilli, and Otto-von-Guericke University of Magdeburg. In this open-label, multicenter trial, patients were initiated on oral LCM as add-on therapy to first AED monotherapy or as a later add-on to two concomitant AEDs. Seizure frequency changes and adverse events were recorded for at least six months after LCM was added., Results: Fourteen patients dropped out because of positive MRI findings other than HS. Patients received LCM at 200-400mg/day. Fifty-eight out of these 86 patients with seizures that were previously drug-resistant had reduced seizure frequency after introduction of LCM. Forty-five out of 86 patients were classified as responders (12 were seizure-free, 33 achieved a reduction >50%). Interestingly, five patients out of 86 achieved seizure freedom for at least one year and progressively switched to monotherapy with LCM, and all five remained seizure-free at follow-up (6-48months)., Conclusions: Our results may suggest that LCM at doses of 200 to 400mg/day reduces seizure frequency in adults with TLE regardless of the presence of HS, and that it may be considered as a first add-on treatment for patients with pharmacoresistant TLE., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: Corpus callosum (CC) abnormalities are frequently reported in patients with refractory mesial temporal lobe epilepsy (rMTLE). However, whether CC structural alterations are related to the epileptic syndrome itself or to refractoriness is still unknown. Thus, we aimed to compare patterns of CC change in patients with rMTLE and benign MTLE (bMTLE), the latter of which represents a useful resource to better disentangle factors that contribute to refractoriness., Methods: The study group included 79 patients with bMTLE (mean age 43.2 ± 14. 8 years), 61 with rMTLE (mean age 45.2 ± 12.4 years) and 134 healthy volunteers. Structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) were performed to measure thickness, mean diffusivity (MD), and fractional anisotropy (FA) over 50 regions of interest along the cross-sectional CC profile. Statistical analysis comprised analysis of variance (ANOVA) followed by post hoc Tukey's Honest Significant Difference test., Results: We found that all imaging metrics of the CC splenium were altered in rMTLE patients compared to bMTLE and controls. We also found significantly reduced thickness and FA of the anterior CC in rMTLE compared to controls and that FA was reduced only in rMTLE compared to bMTLE. Patients with bMTLE did not differ from controls. Differences between disease subgroups were found in the midbody composed of sensorimotor fibers., Significance: We found altered multimodal imaging metrics of the CC in rMTLE but not in bMTLE. These findings were independent of the radiologic presence of hippocampal sclerosis, suggesting that differences in the distribution of such alterations might be related to refractoriness., (Wiley Periodicals, Inc. © 2016 International League Against Epilepsy.)

Brivaracetam (BRV) (UCB 34714) is currently under review by the US Food and Drug Administration and European Medicines Agency for approval as an add-on treatment for adult patients with partial seizures. Similar to levetiracetam (LEV), BRV acts as a high-affinity ligand of the synaptic vesicle protein 2A, however, it has been shown to be 10- to 30-fold more potent than LEV. Moreover, BRV does not share the LEV inhibitory activity on the high voltage Ca(2+) channels and AMPA receptors, and it has been reported to act as a partial antagonist on neuronal voltage-gated sodium channels. The pharmacokinetic profile of BRV is favorable and linear, and it undergoes an extensive metabolism into inactive compounds, mainly through the hydrolysis of its acetamide group. Furthermore, it does not significantly interact with other antiepileptic drugs and more than 95% is excreted through the urine, with an unchanged fraction of 8%-11%. BRV has a half-life of approximately 8-9 hours and it is usually given twice daily. To date, a wide range of experimental studies have reported the effectiveness of BRV with regards to partial and generalized seizures. In humans, six randomized, placebo-controlled trials and two meta-analyses highlighted the efficacy, or good tolerability, of BRV as an add-on treatment for patients with uncontrolled partial seizures. A wide dose range of BRV has been evaluated in those trials (5-200 mg), but the most suitable for clinical use appears to be 50-100 mg/day. The most common adverse reactions to BRV are mild to moderate, transient, often improve during the course of the treatment, and mainly consist of central nervous system symptoms, such as fatigue, dizziness, and somnolence. The aim of this paper is to critically review the literature data regarding experimental animal models and clinical trials on BRV, and to define its potential usefulness for the clinicians who manage patients with epilepsy.

Brivaracetam (BRV), a high-affinity synaptic vesicle protein 2A ligand, reported to be 10-30-fold more potent than levetiracetam (LEV), is highly effective in a wide range of experimental models of focal and generalized seizures. BRV and LEV similarly bind to synaptic vesicle protein 2A, while differentiating for other pharmacological effects; in fact, BRV does not inhibit high voltage Ca(2+) channels and AMPA receptors as LEV. Furthermore, BRV apparently exhibits inhibitory activity on neuronal voltage-gated sodium channels playing a role as a partial antagonist. BRV is currently waiting for approval both in the United States and the European Union as adjunctive therapy for patients with partial seizures. In patients with photosensitive epilepsy, BRV showed a dose-dependent effect in suppressing or attenuating the photoparoxysmal response. In well-controlled trials conducted to date, adjunctive BRV demonstrated efficacy and good tolerability in patients with focal epilepsy. BRV has a linear pharmacokinetic profile. BRV is extensively metabolized and excreted by urine (only 8%-11% unchanged). The metabolites of BRV are inactive, and hydrolysis of the acetamide group is the mainly involved metabolic pathway; hepatic impairment probably requires dose adjustment. BRV does not seem to influence other antiepileptic drug plasma levels. Six clinical trials have so far been completed indicating that BRV is effective in controlling seizures when used at doses between 50 and 200 mg/d. The drug is generally well-tolerated with only mild-to-moderate side effects; this is confirmed by the low discontinuation rate observed in these clinical studies. The most common side effects are related to central nervous system and include fatigue, dizziness, and somnolence; these apparently disappear during treatment. In this review, we analyzed BRV, focusing on the current evidences from experimental animal models to clinical studies with particular interest on potential use in clinical practice. Finally, pharmacological properties of BRV are summarized with a description of its pharmacokinetics, safety, and potential/known drug-drug interactions.

Objective: Temporal and extratemporal white matter abnormalities have been identified frequently in patients with refractory mesial temporal lobe epilepsy (rMTLE). However, the identification of potential water diffusion abnormalities in patients with drug-responsive, benign MTLE (bMTLE) is still missing. The aim of this study was to identify markers of refractoriness in MTLE., Methods: The study group included 48 patients with bMTLE (mean age 42.8 + 13.5 years), 38 with rMTLE (mean age 41.7 + 14.1 years) and 54 healthy volunteers. Diffusion tensor imaging (DTI) was performed to measure mean diffusivity (MD) and fractional anisotropy (FA) in a regions-of-interest analysis comprising hippocampi and temporal lobe gray and white matter regions. The presence of hippocampal sclerosis (Hs) was assessed using automated magnetic resonance imaging (MRI) evaluation. For statistics we used chi-square test; two-tailed, two-sample t-test; and stratified linear regression., Results: The significant demographic differences between the two patient groups were sex (p = 0.003), duration of epilepsy (p = 0.003) and complex febrile convulsions (p = 0.0001). In rMTLE, temporal white matter MD was higher and FA lower, as compared to bMTLE. The analysis of diagnostic accuracy (area under the receiver operator characteristic [ROC] curve [AUC]) showed that FA had an AUC for discriminating patients affected from those unaffected by refractory MTLE of 74.0% (p < 0.001), a value that was higher than that of temporal MD (64.0%), hippocampus volume (65.0%), and Hs (66.0%)., Significance: We performed DTI measurements in MTLE and found a significant reduction of FA along the white matter of the temporal lobes in rMTLE, suggesting it as a valuable measure of refractoriness in MTLE., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Genetic factors play a major role in the etiology of juvenile myoclonic epilepsy (JME), a common form of idiopathic generalized epilepsy, but so far, genes related to JME remain largely unknown. JME shares electroclinical features with Unverricht-Lundborg disease (progressive myoclonic epilepsy type 1; EPM1), a form of progressive myoclonus epilepsy characterized by myoclonus, epilepsy, and gradual neurologic deterioration. EPM1 is caused by mutations in the gene that codes for cystatin B (CSTB), an inhibitor of cysteine protease. In the present study, we wished to investigate the role of the CSTB gene in patients with JME. Fifty-seven unrelated patients (35 women; mean age ± standard deviation [SD], 24.1 ± 7.7; mean age ± SD at onset, 15.3 ± 2.4) with JME were enrolled. Twenty-three of 57 patients were the probands of families with JME. The molecular diagnosis was carried out to identify the common dodecamer repeat expansion mutation or other disease-causing mutations in the CSTB gene. The molecular analysis did not depict mutations in any of the 57 patients with JME. Our study did not support a role for the CSTB gene in patients with familial or sporadic JME., (Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.)

Objective: Dèjà-vù (DV) can occur as a seizure of mesial temporal lobe epilepsy (MTLE) and in almost 80% of healthy individuals. The remarkable similarity between epileptic DV and DV in healthy individuals raises the possibility that DV might sometimes be an ictal phenomenon in apparently normal individuals. Thus, we studied a group of healthy subjects versus individuals with benign MTLE (bMTLE) both experiencing DV., Methods: 63 individuals with epilepsy patients with bMTLE and 39 healthy controls at Catanzaro University were recruited. Participants completed the Inventory for Déjà Vu (DV) Experiences Assessment (IDEA) test, underwent awake and asleep electroencephalogram, MRI of the brain using a 3T scanner and whole brain voxel-based morphometry (VBM). bMTLE patients with DV and without DV were also matched for the presence of hippocampal sclerosis., Results: Our controls had no history of neurological or psychiatric illness, epilepsy or history of febrile convulsions. Neurological and cognitive examinations were normal. Electroencephalographic procedures were unremarkable in all controls. In bMTLE group, the direct comparison of VBM between individuals with epilepsy with DV versus those without DV revealed abnormal anatomical changes in the left hippocampus, parahippocampal gyrus and visual cortex. The VBM of healthy controls with DV showed abnormal anatomical changes only in the left insular cortex., Conclusions: Our VBM results demonstrated different morphologic patterns in individuals with epilepsy and control subjects experiencing DV, involving the memory circuit in bMTLE patients and cerebral regions in the emotional network in healthy controls., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: A synonymous C to T variant at position 3435 (c.3435C>T) is one common polymorphism of the multidrug resistant 1 (MDR1) gene, which encodes the major transmembrane efflux transporter P-glycoprotein. It has been suggested that this polymorphism, and more specifically the 3435CC genotype, may be associated with the response to antiepileptic drug treatment. Here we wished to examine the role of such a candidate variant in a cohort of 175 patients (98 women and 76 men; mean ± SD age: 47.90 ± 17.64) with temporal lobe epilepsy (TLE)., Methods: Patients were classified according to whether they had drug-responsive (n=134) or drug-resistant (n=41) epilepsy. We also enrolled 175 healthy controls (93 women and 82 men; mean ± SD age: 72.5 ± 6.8), matched for sex and ethnicity., Results: Patients and controls were genotyped for detection of the 3435C>T polymorphism, but the analysis showed no significant association between the CC genotype and the risk of drug-resistant epilepsy., Conclusion: These findings rule out the MDR1 c.3435C>T polymorphism having a major role or increasing the risk of drug-resistance suggesting a revision is required to determine the contribution of this polymorphism in predicting drug response in epilepsy., (Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Objective: To compare anatomo-electro-clinical findings between patients with epilepsy associated with leukoaraiosis only (EAL) and patients with a well-defined vascular lesion, i.e. post-stroke epilepsy (PSE)., Methods: Two hundred eighty-three subjects with epilepsy and cerebrovascular disease, consecutively seen in our epilepsy centres from January 2000 to March 2014, were retrospectively considered. Inclusion criteria were: history of one or more unprovoked seizures and MRI evidence of one or more vascular lesions. Exclusion criteria were: inadequate neuroimaging data, coexistence of nonvascular lesions, and psychogenic seizures. Subjects were divided in two groups: PSE and EAL, based onclinical and MRI findings. Epileptogenic focus was identified according to ictal semiology and EEG findings. In PSE group, coherence between the vascular lesion(s) and epileptogenic focus was scored as likely or unlikely., Results: One hundred seventeen subjects were included: 58 had PSE, 59 EAL. Coherence was identified as likely in 38 (95%) and unlikely in 2 (5%). At univariate analysis, abnormal EEG and frontal localization were associated with a lower EAL probability [odds ratio (OR) 0.36, 95% confidence interval (CI) 0.15-0.87, p=0.02 and OR 0.12, 95% CI 0.04-0.37, p<0.001, respectively], while temporal localization was associated with a higher EAL probability (OR 4.0, 95% CI 1.8-9.0, p<0.001). Multivariate confirmed these associations., Conclusions: While in PSE epileptogenic focus is coherent with the vascular lesions, in EAL temporal lobe epilepsy predominates. In EAL, causal relationship between vascular lesions and epilepsy is not straightforward, and the role of adjunctive factors needs to be elucidated., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Status epilepticus (SE) may occur in the setting of several internal or neurologic diseases. Anti-neutrophilic cytoplasmic antibodies (ANCA) are a group of Ig that may be observed in patients with different autoimmune disorders but are particularly associated with systemic vasculitis named ANCA-associated-vasculities (AAV). We herein report 3 patients with SE and positivity to p-ANCA., Case Presentation: One patient had a catastrophic evolution and died 5 months after disease onset. The other two patients had a good outcome and remained seizure-free at 30 months and 5 years of follow-up respectively., Conclusion: This report highlights the importance of considering ANCA dosage in patients with SE of unclear origin.

Late/chronic Lyme neuroborreliosis (LNB) represents a challenging entity whose diagnosis requires a combination of clinical and laboratory findings, surrounded by much controversy. Here we describe a patient who had a peculiar form of late LNB with CNS lesions shown by magnetic resonance imaging (MRI), and epileptic seizures, etiologically diagnosed by conventional and molecular methods. The current case provides evidence that patients presenting with epileptic seizures and MRI-detected multifocal lesions, particularly when a facial palsy has also occurred, should raise the suspicion of LNB, as this diagnosis has important implications for treatment and prognosis.

Mutations of leucine-rich, glioma inactivated 1 (LGI1) gene are found in about half of the families with autosomal dominant lateral temporal epilepsy (ADLTE). More recently a LGI1 heterozygous microdeletion was found in a single ADLTE family, suggesting that submicroscopic chromosomal abnormalities should be investigated in cases negative for LGI1 mutations. This study examines whether microdeletions and duplications of the LG1 gene occurred in eight ADLTE families and 20 sporadic patients that were negative for LGI1 mutations. Multiplex ligation-dependent probe amplification (MLPA) was applied to detect potential deletions and duplications of LGI1 gene. In all patients, MLPA analysis did not reveal any pathogenic changes in the LGI1 gene. Chromosomal rearrangements involving the LGI1 gene were not identified in our series of familial or sporadic LTE. These results further illustrate the considerable genetic heterogeneity for ADLTE, despite the relatively homogeneous clinical picture. There are as yet undiscovered mechanisms underlying ADLTE., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: Since the skin represents a common site of adverse drug reactions, few data are reported at this time regarding the development of skin rash during the treatment with antidiabetic drugs., Case Presentation: We report a 29-year old woman that developed a facial skin rash during the treatment with metformin. Clinical and laboratory findings excluded the presence of systemic diseases, but several diagnosis and many drugs were administered without clinical improvement. The self-dismission of metformin induced an improvement of symptoms, while the re-challenge documented an impairments of skin rash. The Naranjo probability scale suggested a probable association between metformin and skin rash and metformin was definitively dismissed., Conclusion: We report for the first time a non vasculitis facial skin manifestation related to metformin in a young woman. However, this case may emphasizes the need to consider the ADRs as a differential diagnosis in order to reduce medical errors and the related medical costs.

Introduction: Pharmacovigilance (PV) is designed to monitor drugs continuously after their commercialization, assessing and improving their safety profile. The main objective is to increase the spontaneous reporting of adverse drug reactions (ADRs), in order to have a wide variety of information. The Italian Drug Agency (Agenzia Italiana del Farmaco [AIFA]) is financing several projects to increase reporting. In Calabria, a PV information center has been created in 2010., Materials and Methods: We obtained data using the database of the National Health Information System AIFA relatively to Italy and Calabria in the year 2012. Descriptive statistics were performed to analyze the ADRs., Results: A total number of 461 ADRs have been reported in the year 2012 with an increase of 234% compared with 2011 (138 reports). Hospital doctors are the main source of this reporting (51.62%). Sorafenib (Nexavar(®)), the combination of amoxicillin/clavulanic acid and ketoprofen represent the drugs most frequently reported causing adverse reactions. Adverse events in female patients (61.83%) were more frequently reported, whereas the age groups "41-65" (39.07%) and "over 65" (27.9%) were the most affected., Conclusions: Calabria has had a positive increase in the number of ADRs reported, although it has not yet reached the gold standard set by World Health Organization (about 600 reports), the data have shown that PV culture is making inroads in this region and that PV projects stimulating and increasing PV knowledge are needed.