Publications by authors named "Salvatore Striano"

143 Publications

Epilepsy in "Sunflower syndrome": electroclinical features, therapeutic response, and long-term follow-up.

Seizure 2021 Dec 2;93:8-12. Epub 2021 Oct 2.

Department of Pediatrics, University of Perugia, Italy.

Background: Sunflower syndrome (SFS) is a rare childhood-onset generalized epilepsy characterized by photosensitivity, heliotropism, and drug-resistant stereotyped seizures maybe self-induced by hand-waving maneuvers. Data on the long-term prognosis are scantly and evidence over best treatment strategies is lacking.

Methods: We retrospectively describe the electroclinical features, and therapeutic response in a group of 21 patients with SFS, without intellectual disability.

Results: 16 patients were female (67%), with a median age at onset of 7 years. In all patients, ictal episodes began with sun-staring, and hand-waving in front of the sunlight, accompanied by brief typical absence seizures. 17 patients (81%) showed interictal EEG abnormalities, mainly characterized by spike and polyspike-and-wave discharges. Ictal epileptiform activity occurred approximately less than one second after the start of hand-waving. At the last follow-up (median length 8.2 years), 12 patients (57%) were drug-resistant. Nine of them (75%) achieved seizure control with the use of tainted lenses, either alone or compared with anti-seizure medications (ASM). Disappearance of seizures was associated with EEG improvement/normalization when tinted glasses were used during EEG recordings.

Conclusion: While the clinical and EEG characteristics of SFS are well defined, the best therapeutic approaches are still under debate. Our data confirms a high rate of drug-resistance and frequent need of polytherapy. Of note, in drug-resistant patients, lenses (but not ASM) were able to suppress PPR in our patients while wearing lenses. Regarding the role of lenses, we do not only rely on the PPR reduction but also clinically by the reduction of seizures. Although additional data are needed, lenses seem to have a powerful potential role for the management of SFS.
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http://dx.doi.org/10.1016/j.seizure.2021.09.021DOI Listing
December 2021

Clinical and Genetic Features in Patients With Reflex Bathing Epilepsy.

Neurology 2021 08 2;97(6):e577-e586. Epub 2021 Jun 2.

From IRCCS Istituto Giannina Gaslini (A.A., M.S., M.I., A.R., B.C., P.S., S.B., V.D.S., C.M., F.Z., P.S.); Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DINOGMI) (A.A., M.S., P.S., V.D.S., C.M., F.Z., P.S.), University of Genoa, Italy; Neuropediatrics Section of the Department of Pediatrics (G.W.), Asklepios Clinic Hamburg Nord-Heidberg, Hamburg; Department of Pediatric and Adolescent Medicine II (Neuropediatrics, Social Pediatrics) (G.W.), University Medical Centre Schleswig-Holstein, Kiel, Germany; Department of Neurosciences (C.C., C.D.L.), Pediatric Neurology Unit, Tor Vergata University, Roma; Human Genetics (L.C., F. Brancati), Department of Life, Health, and Environmental Sciences, and Department of Pediatrics (A.V.), University of L'Aquila; Child Neuropsychiatry Unit (V.B.), Department of Mental Health, ASST-LARIANA, Como; Medical Genetics Unit (P.P.), "S. Maria della Misericordia" Hospital, Perugia, Italy; Department of Pediatric Neurology (A.F.-J.), Hospital Universitario Quirónsalud and Universidad Europea de Madrid, Madrid, Spain; Istanbul University Istanbul Faculty of Medicine (N.B.), Department of Neurology, Turkey; Department of Biomedicine and Prevention (G.N.), Tor Vergata University of Rome; IRCCS Neuromed (G.N.), Pozzilli, Italy; Department of Pharmacology (G.N.), School of Medicine, University of Nevada, Reno; Department of Pediatrics (C.v.S.), University Hospital Munich, Germany; Paracelsus Medical University (C.v.S.), Salzburg, Austria; Epilepsy Center for Children and Adolescents (F.K., G.J.K.), Vogtareuth, Germany; Department of Neuropediatrics (G.C.W., G.R.), University Children's Hospital Zurich, Switzerland; Translational and Clinical Research Institute (D.L.-S., R.H.T., M.L.), Newcastle University; Department of Clinical Neurosciences (D.L.-S., R.H.T., M.L.), Newcastle Upon Tyne Hospitals National Health Service Foundation Trust, UK; Epilepsy Center (S.S.), Federico II University, Napoli, Italy; Institute of Human Genetics (C.D.), University Hospital Essen, University of Duisburg-Essen, Essen, Germany; Institut du Cerveau et de la Moelle épinière (ICM) (C.D.), Sorbonne Université, UMR S 1127, Inserm U1127, CNRS UMR 7225, Paris, France; Center for Synaptic Neuroscience and Technology (F.Benfenati), Istituto Italiano di Tecnologia; IRCCS Ospedale Policlinico San Martino (F. Benfenati), Genoa; and Human Functional Genomics (F. Brancati), IRCCS San Raffaele Pisana, Rome, Italy.

Objective: To describe the clinical and genetic findings in a cohort of individuals with bathing epilepsy, a rare form of reflex epilepsy.

Methods: We investigated by Sanger and targeted resequencing the gene in 12 individuals from 10 different families presenting with seizures triggered primarily by bathing or showering. An additional 12 individuals with hot-water epilepsy were also screened.

Results: In all families with bathing epilepsy, we identified 8 distinct pathogenic or likely pathogenic variants and 2 variants of unknown significance in , 9 of which are novel. Conversely, none of the individuals with hot-water epilepsy displayed variants. In mutated individuals, seizures were typically triggered by showering or bathing regardless of the water temperature. Additional triggers included fingernail clipping, haircutting, or watching someone take a shower. Unprovoked seizures and a variable degree of developmental delay were also common.

Conclusion: Bathing epilepsy is genetically distinct reflex epilepsy caused mainly by mutations.
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http://dx.doi.org/10.1212/WNL.0000000000012298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424500PMC
August 2021

Temporal-parietal-occipital epilepsy in GEFS+ associated with SCN1A mutation.

Epileptic Disord 2021 Apr;23(2):397-401

Department of Neuroscience, Reproductive and Odontostomatological Sciences, Federico II University, Napoli, Italy.

Most families with genetic epilepsy with febrile seizures plus show a mutation in the sodium channel alpha 1 subunit gene, however, but there is much phenotypic heterogeneity and focal epilepsy remains relatively rare. Here, we report a family with electroclinical features indicative of temporal-parietal-occipital carrefour epilepsy with common occurrence of post-ictal migraine. We studied a four-generation family including nine affected subjects by means of EEG and MRI. Genetic testing was performed by targeted re-sequencing (gene panel). In most patients, seizure semiology included cognitive, autonomic, and emotional symptoms, eventually evolving towards sensory visual phenomena. Focal sensory vestibular seizures and changes in body perception were also reported in some cases. Post-ictal migraine was common, occurring in five out of the six (83%) epilepsy patients. A missense mutation (c.1130 G>A; p.R377Q) affecting the S5-S6 segment (pore region) of the sodium channel alpha 1 subunit was identified in all affected and four unaffected subjects. Temporal-parietal-occipital carrefour epilepsy is part of the genetic epilepsy with febrile seizures plus spectrum. The electroclinical features in this family support the involvement of a genetically impaired neural network. High prevalence of post-ictal migraine suggests the role of posterior brain areas in the clinical expression of this gene defect.
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http://dx.doi.org/10.1684/epd.2021.1266DOI Listing
April 2021

Italian cohort of Lafora disease: Clinical features, disease evolution, and genotype-phenotype correlations.

J Neurol Sci 2021 May 20;424:117409. Epub 2021 Mar 20.

Unit of Medical Genetics, IRCCS Istituto Giannina Gaslini, Genova, Italy; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Università degli Studi di Genova, Genova, Italy.

Background: Lafora disease (LD) is characterized by progressive myoclonus, refractory epilepsy, and cognitive deterioration. This complex neurodegenerative condition is caused by pathogenic variants in EPM2A/EPM2B genes, encoding two essential glycogen metabolism enzymes known as laforin and malin. Long-term follow-up data are lacking. We describe the clinical features and genetic findings of a cohort of 26 Italian patients with a long clinical follow-up.

Methods: Patients with EPM2A/EPM2B pathogenic variants were identified by direct gene sequencing or gene panels with targeted re-sequencing. Disease progression, motor functions, and mental performance were assessed by a simplified disability scale. Spontaneous/action myoclonus severity was scored by the Magaudda Scale.

Results: Age range was 12.2-46.2 years (mean:25.53 ± 9.14). Age at disease onset ranged from 10 to 22 years (mean:14.04 ± 2.62). The mean follow-up period was 11.48 ± 7.8 years. Twelve out of the 26 (46%) patients preserved walking ability and 13 (50%) maintained speech. A slower disease progression with preserved ambulation and speech after ≥4 years of follow-up was observed in 1 (11%) out of the 9 (35%) EPM2A patients and in 6 (35%) out of the 17 (65%) EPM2B patients. Follow-up was >10 years in 7 (41.2%) EPM2B individuals, including two harbouring the homozygous p.(D146N) pathogenic variant.

Conclusions: This study supports an overall worse disease outcome with severe deterioration of ambulation and speech in patients carrying EPM2A mutations. However, the delayed onset of disabling symptoms observed in the EPM2B subjects harbouring the p.(D146N) pathogenic variant suggests that the underlying causative variant may still influence LD severity.
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http://dx.doi.org/10.1016/j.jns.2021.117409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166462PMC
May 2021

Dual diagnosis in a child with familial SCN8A-related encephalopathy complicated by a 1p13.2 deletion involving NRAS gene.

Neurol Sci 2021 05 17;42(5):2115-2117. Epub 2020 Nov 17.

Department of Translational Medical Sciences, Child Neurology, University of Naples Federico II, Naples, Italy.

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http://dx.doi.org/10.1007/s10072-020-04898-1DOI Listing
May 2021

Diagnosis and Management of Type 1 Sialidosis: Clinical Insights from Long-Term Care of Four Unrelated Patients.

Brain Sci 2020 Aug 1;10(8). Epub 2020 Aug 1.

Department of Neuroscience, Reproductive and Odontostomatological Sciences, Federico II University, 80131 Naples, Italy.

: Sialidosis is a rare autosomal recessive disease caused by mutations, leading to neuraminidase deficiency and accumulation of sialic acid-containing oligosaccharides and glycopeptides into the tissues. Sialidosis is divided into two clinical entities, depending on residual enzyme activity, and can be distinguished according to age of onset, clinical features, and progression. Type 1 sialidosis is the milder, late-onset form, also known as non-dysmorphic sialidosis. It is commonly characterized by progressive myoclonus, ataxia, and a macular cherry-red spot. As a rare condition, the diagnosis is often only made after few years from onset, and the clinical management might prove difficult. Furthermore, the information in the literature on the long-term course is scarce. : We describe a comprehensive clinical, neuroradiological, ophthalmological, and electrophysiological history of four unrelated patients affected by type 1 sialidosis. The long-term care and novel clinical and neuroradiological insights are discussed. : We report the longest follow-up (up to 30 years) ever described in patients with type 1 sialidosis. During the course, we observed a high degree of motor and speech disability with preserved cognitive functions. Among the newest antiseizure medication, perampanel (PER) was proven to be effective in controlling myoclonus and tonic-clonic seizures, confirming it is a valid therapeutic option for these patients. Brain magnetic resonance imaging (MRI) disclosed new findings, including bilateral gliosis of cerebellar folia and of the occipital white matter. In addition, a newly reported variant (c.914G > A) is described.
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http://dx.doi.org/10.3390/brainsci10080506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465165PMC
August 2020

Does screening for adverse effects improve health outcomes in epilepsy? A randomized trial.

Neurology 2020 07 29;95(3):e239-e246. Epub 2020 Jun 29.

From the Clinical Pharmacology Unit (V.F., G.G., E.P.), University of Pavia; IRCCS Mondino Foundation (V.F., C.F., C.A.G., E.P.), Pavia; Epilepsy Center (M.P.C.), San Paolo Hospital, Milan; Magna Graecia University (G.D.S.), Catanzaro; School of Hospital Pharmacy (G.F.), University of Milan; Epilepsy Center (A.L.N.), Neurology Hospital "Amaducci," University of Bari; Unit of Neurology (E.R.), Usl Centro Toscana Health Authority, Prato; University of Foggia (L.M.S.); Epilepsy Center (S.S.), Federico II University, Naples; and IRCCS (P.T.), Institute of Neurological Sciences of Bologna and Department of Biomedical and Neuromotor Sciences, University of Bologna, Italy.

Objective: To determine whether systematic screening for adverse effects of antiepileptic drugs (AEDs) reduces toxicity burden and improves health-related quality of life in patients with epilepsy.

Methods: Consecutive patients with uncontrolled seizures aged ≥16 years and a high Adverse Event Profile (AEP) score were randomized to 2 groups and followed up for 18 months at 11 referral centers. AEP scores were made available to treating physicians at all visits in the intervention group, but not in the control group. Co-primary endpoints were changes in AEP scores and Quality of Life Inventory for Epilepsy-31 (QOLIE-31) scores.

Results: Of 809 enrolled patients able to complete the AEP questionnaire, 222 had AEP scores ≥45 and were randomized to the intervention (n = 111) or control group (n = 111). A total of 206 patients completed the 18-month follow-up. Compared with baseline, AEP scores decreased on average by 7.2% at 6 months, 12.1% at 12 months, and 13.8% at 18 months in the intervention group ( < 0.0001), and by 7.7% at 6 months, 9.2% at 12 months, and 12.0% at 18 months in controls ( < 0.0001). QOLIE-31 scores also improved from baseline to final visit, with a mean 20.7% increase in the intervention group and a mean 24.9% increase in the control group ( < 0.0001). However, there were no statistically significant differences in outcomes between groups for the 2 co-primary variables.

Conclusions: Contrary to findings from a previous study, systematic screening for adverse effects of AEDs using AEP scores did not lead to a reduced burden of toxicity over usual physician treatment.

Italian Medicines Agency Aifa Identifier: FARM52K2WM_003.

Clinicaltrialsgov Identifier: NCT03939507 (registered retrospectively in 2019; the study was conducted during the 2006-2009 period and registration of clinical trials was not a widely established practice when this study was initiated).

Classification Of Evidence: This study provides Class II evidence that the additional collection of formal questionnaires regarding adverse effects of AEDs does not reduce toxicity burden over usual physician treatment.
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http://dx.doi.org/10.1212/WNL.0000000000009880DOI Listing
July 2020

Epilepsy, cerebral calcifications, and gluten-related disorders: Are anti-transglutaminase 6 antibodies the missing link?

Seizure 2019 Dec 16;73:17-20. Epub 2019 Oct 16.

Regional Epilepsy Centre, Great Metropolitan Hospital "Bianchi-Melacrino-Morelli", Reggio Calabria, Italy; Department of Medicine, Surgery and Health Sciences, Magna Græcia University, Catanzaro, Italy. Electronic address:

Purpose: Gluten-related disorders (GRDs) are a group of immune-mediated diseases often associated to neurologic manifestations. Epilepsies with cerebral calcifications, with or without coeliac disease (CD), are rare neurological disorders characterized by childhood-onset focal seizures, often refractory to antiepileptic drugs. Transglutaminase 6 antibodies (anti-TG6) have been considered a biomarker for gluten-related ataxia and neuropathy, but their prevalence in epilepsies with cerebral calcifications is unknown. The aim of this study is to evaluate anti-TG6 prevalence in patients with epilepsies and cerebral calcifications.

Method: this was a cross-sectional study conducted at five Italian epilepsy centres. The following groups were included. Group 1: nine patients with CD, posterior cerebral calcifications and epilepsy (CEC); group 2: nine patients with epilepsy and posterior cerebral calcifications, without CD; group 3: twenty patients with focal epilepsy of unknown etiology; group 4: twenty-two healthy controls (HC). All subjects were tested for serological evidence of anti-TG6 IgA and IgG. Differences among groups were analysed using χ ² test.

Results: anti-TG6 were present in 1/9 subjects (11%) of group 1, 2/9 subjects (22%) of group 2, 0/20 subjects in group 3, 3/22 (13.6%) of HC. No significant difference was found among the 4 groups.

Conclusions: Anti-TG6 do not seem to be associated to epilepsies with cerebral calcifications.
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http://dx.doi.org/10.1016/j.seizure.2019.10.012DOI Listing
December 2019

Gelastic seizures not associated with hypothalamic hamartoma: A long-term follow-up study.

Epilepsy Behav 2020 02 1;103(Pt A):106578. Epub 2019 Nov 1.

Department of Pediatrics, University of L'Aquila, Via Vetoio, 1. Coppito, L'Aquila, Italy. Electronic address:

Objective: The objective of the study was to describe the electroclinical features, seizure semiology, and the long-term evolution of gelastic seizures (GS) not associated with hypothalamic hamartoma (HH).

Methods: We reviewed video-electroencephalogram (video-EEG) recordings from pediatric patients with GS without HH admitted to 14 Italian epilepsy centers from 1994 to 2013. We collected information about age at onset, seizures semiology, EEG and magnetic resonance imaging (MRI) findings, treatment, and clinical outcome in terms of seizure control after a long-term follow-up.

Results: A total of 30 pediatric patients were stratified into two groups according to neuroimaging findings: group 1 including 19 children (63.3%) with unremarkable neuroimaging and group 2 including 11 children with structural brain abnormalities (36.7%). At the follow-up, patients of group 1 showed better clinical outcome both in terms of seizure control and use of AED polytherapy. Our patients showed remarkable clinical heterogeneity, including seizure semiology and epilepsy severity. Electroencephalogram recordings showed abnormalities mainly in the frontal, temporal, and frontotemporal regions without relevant differences between the two groups. Overall, carbamazepine showed good efficacy to control GS.

Conclusions: Patients with nonlesional GS have a more favorable outcome with better drug response, less need of polytherapy, and good long-term prognosis, both in terms of seizure control and EEG findings.
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http://dx.doi.org/10.1016/j.yebeh.2019.106578DOI Listing
February 2020

Intronic ATTTC repeat expansions in STARD7 in familial adult myoclonic epilepsy linked to chromosome 2.

Nat Commun 2019 10 29;10(1):4920. Epub 2019 Oct 29.

Department of Human Neurosciences, Sapienza University of Rome, Viale dell'Università, 30, 00185, Rome, Italy.

Familial Adult Myoclonic Epilepsy (FAME) is characterised by cortical myoclonic tremor usually from the second decade of life and overt myoclonic or generalised tonic-clonic seizures. Four independent loci have been implicated in FAME on chromosomes (chr) 2, 3, 5 and 8. Using whole genome sequencing and repeat primed PCR, we provide evidence that chr2-linked FAME (FAME2) is caused by an expansion of an ATTTC pentamer within the first intron of STARD7. The ATTTC expansions segregate in 158/158 individuals typically affected by FAME from 22 pedigrees including 16 previously reported families recruited worldwide. RNA sequencing from patient derived fibroblasts shows no accumulation of the AUUUU or AUUUC repeat sequences and STARD7 gene expression is not affected. These data, in combination with other genes bearing similar mutations that have been implicated in FAME, suggest ATTTC expansions may cause this disorder, irrespective of the genomic locus involved.
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http://dx.doi.org/10.1038/s41467-019-12671-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6820779PMC
October 2019

Clinical evolution and epilepsy outcome in three patients with CDKL5-related developmental encephalopathy.

Epileptic Disord 2019 Jun;21(3):271-277

Pediatric Neurology and Muscular Diseases Unit, IRCCS Istituto "G. Gaslini", Genova.

To further characterise CDKL5-related disorder, previously classified as an early-onset seizure variant of Rett syndrome, which is currently considered a specific and independent early-infantile epileptic encephalopathy. We describe the epileptic phenotype and neurocognitive development in three girls with CDKL5 mutations showing severe neurodevelopmental impairment, with different epileptic phenotypes and severity. The patients differed regarding age at epilepsy onset, seizure frequency, duration of "honeymoon periods", as well as EEG features. The "honeymoon period", defined as a seizure-free period longer than two months, represented, in our case series, a good indicator of the epilepsy outcome, but not of the severity of developmental impairment. However, even during the "honeymoon period", the interictal EEG showed epileptiform abnormalities, slowing, or a disappearance of physiological pattern. The natural history of CDKL5 disorder was compared between the three girls, focusing on the relationship between electroclinical features and neurological development. Our findings suggest that CDKL5 mutations likely play a direct role in psychomotor development, whereas epilepsy is one of the clinical features associated with this complex disorder.
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http://dx.doi.org/10.1684/epd.2019.1071DOI Listing
June 2019

High-functioning autism spectrum disorder with fluent speech and late-onset epilepsy: an unusual presentation of Inv-Dup (15) syndrome.

Neurocase 2019 Feb - Apr;25(1-2):62-65. Epub 2019 Apr 16.

c Department of Neuroscience, Reproductive and Odontostomatological Sciences, Epilepsy Centre , "Federico II" University of Naples , Naples , Italy.

Many neuropsychiatric phenotypes have been reported in association with rearrangements in the 15q11-q13 region. Clinical presentations can include hypotonia, developmental delay, severe/moderate intellectual disabilities, poor expressive language, difficult to treat epilepsy, and autism spectrum disorders. Here we report an additional case of a girl with inversion duplication on chromosome 15 (Inv-Dup 15) showing a peculiar and milder clinical phenotype, including atypical high-functioning autism disorder, late onset and drug-responsive epilepsy, and a relatively good language development . This report suggests that a diagnosis of Inv-Dup (15) can be suspected during more benign atypical condition with a better outcome than usually reported.
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http://dx.doi.org/10.1080/13554794.2019.1602144DOI Listing
December 2019

Familial adult myoclonic epilepsy: A new expansion repeats disorder.

Seizure 2019 Apr 19;67:73-77. Epub 2019 Mar 19.

Pediatric Neurology and Muscular Diseases Unit, DINOGMI-Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, IRCCS "G. Gaslini" Institute, Genova, Italy. Electronic address:

Familial adult myoclonic epilepsy (FAME), also described with different acronyms (ADCME, BAFME, FEME, FCTE and others), is a high-penetrant autosomal dominant condition featuring cortical hand tremors, myoclonic jerks, and occasional/rare convulsive seizures. Prevalence is unknown since this condition is often under-recognized, but it is estimated to be less than 1/35,000. The disease usually starts in the second decade of life and has been genetically associated with at least 4 different loci (8q24, 2p11.1-q12.2, 5p15.31-p15 and 3q26.32-3q28). Recently, the expansion of non coding TTTTA and TTTCA repeats has been identified as the causative mutation in Japanese families linked to the 8q24. The diagnosis is supported by clinical features and electrophysiological investigations as jerk-locked back averaging, C-reflex, and somatosensory-evoked potential. Photic stimulation, emotional stress, and sleep deprivation may trigger both tonic-clonic and myoclonic seizures. FAME has a slow but progressive clinical course occurring with intellectual disability and worsening of both tremor and myoclonus although with a less severe decline compared to other progressive myoclonic epilepsies. Valproate, levetiracetam, and benzodiazepines are considered the first-line treatments.
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http://dx.doi.org/10.1016/j.seizure.2019.03.009DOI Listing
April 2019

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

Seizures in children with neurofibromatosis type 1: is neurofibromatosis type 1 enough?

Ital J Pediatr 2018 Mar 22;44(1):41. Epub 2018 Mar 22.

Centro di Riferimento Pediatrico delle Neurofibromatosi, Dipartimento della Donna, del Bambino e di Chirurgia Generale e Specialistica, Università degli Studi della Campania "L. Vanvitelli", Caserta, Italy.

Background: Neurofibromatosis type 1 (NF1) is related to a generally increased prevalence of seizures. The mechanism underlying the increased predisposition to seizures has not been fully elucidated. The aim of the study was to evaluate the role of NF1 in seizures pathogenesis in a cohort of children with NF1 and seizures.

Methods: The medical records of 437 children (0-18 years old) with NF1 were reviewed. All children with at least one afebrile seizure were included. Demographic, clinical, neurological, NF1 mutation status, and EEG data were collected along with brain magnetic resonance imaging. Depending on etiology, structural seizures have been identified and were further classified as NF1 related or not.

Results: Nineteen patients (4.3%; 13 males) were included. NF1 was inherited in 7 (37.5%), with 3 maternal forms. Ten children with structural seizures were identified. Seven forms were identified someway related to NF1, two of which were associated to 17q11.2 microdeletion and hypoxic-ischemic encephalopathy. Any brain lesion that could explain seizures was found in nine patients, two third of these patients had a familiar history of epilepsy.

Conclusions: Our results suggest seizures are more frequent in NF1 children (4.3%) than in general pediatric population (0.3-0.5%) and that are someway related to NF1 in half of patients. Facing seizures in NF1, the clinician should first exclude brain tumors but also other, and rarer NF1-related scenarios, such as hydrocephalous and vasculopathies. Children with non-structural seizures frequently had a family history of epilepsy, raising questions about the pathogenic role of NF1. They should be approached as for the general population.
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http://dx.doi.org/10.1186/s13052-018-0477-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5863905PMC
March 2018

Mutations in MICAL-1cause autosomal-dominant lateral temporal epilepsy.

Ann Neurol 2018 03 13;83(3):483-493. Epub 2018 Mar 13.

CNR-Neuroscience Institute, Section of Padua, Padova, Italy.

Objective: Autosomal-dominant lateral temporal epilepsy (ADLTE) is a genetic focal epilepsy characterized by auditory symptoms. Two genes, LGI1 and RELN, encoding secreted proteins, are implicated in the etiology of ADLTE, but half of the affected families remain genetically unsolved, and the underlying molecular mechanisms are yet to be clarified. We aimed to identify additional genes causing ADLTE to better understand the genetic basis and molecular pathway underlying this epileptic disorder.

Methods: A cohort of Italian ADLTE families was examined by whole exome sequencing combined with genome-wide single-nucleotide polymorphism-array linkage analysis.

Results: We identified two ADLTE-causing variants in the MICAL-1 gene: a p.Gly150Ser substitution occurring in the enzymatically active monooxygenase (MO) domain and a p.Ala1065fs frameshift indel in the C-terminal domain, which inhibits the oxidoreductase activity of the MO domain. Each variant segregated with ADLTE in a single family. Examination of candidate variants in additional genes excluded their implication in ADLTE. In cell-based assays, both variants significantly increased MICAL-1 oxidoreductase activity and induced cell contraction in COS7 cells, which likely resulted from deregulation of F-actin dynamics.

Interpretation: MICAL-1 oxidoreductase activity induces disassembly of actin filaments, thereby regulating the organization of the actin cytoskeleton in developing and adult neurons and in other cell types. This suggests that dysregulation of the actin cytoskeleton dynamics is a likely mechanism by which MICAL-1 pathogenic variants lead to ADLTE. Ann Neurol 2018;83:483-493.
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http://dx.doi.org/10.1002/ana.25167DOI Listing
March 2018

CHD2 mutations: Only epilepsy? Description of cognitive and behavioral profile in a case with a new mutation.

Seizure 2017 Oct 6;51:186-189. Epub 2017 Sep 6.

Department of Neuroscience, Reproductive and Odontostomatological Sciences, Epilepsy Centre, Federico II University, Naples, Italy. Electronic address:

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http://dx.doi.org/10.1016/j.seizure.2017.09.001DOI Listing
October 2017

Patterns of care of brain tumor-related epilepsy. A cohort study done in Italian Epilepsy Center.

PLoS One 2017 17;12(7):e0180470. Epub 2017 Jul 17.

Centro Regionale Epilessia, Università Magna Grecia di Catanzaro, Ospedale Riuniti, Reggio Calabria, Italia.

Epilepsy is the most common comorbidity in patients with brain tumors.

Study Aims: To define characteristics of brain tumor-related epilepsy (BTRE) patients and identify patterns of care. Nationwide, multicenter retrospective cohort study. Medical records of BTRE patients seen from 1/1/2010 to 12/31/2011, followed for at least one month were examined. Information included age, sex, tumor type/treatments, epilepsy characteristics, antiepileptic drugs (AEDs). Time to modify first AED due to inefficacy and/or toxicity was assessed with the Kaplan-Meier method and Cox proportional hazard models were used to identify predictors of treatment outcome. Enrolled were 808 patients (447 men, 361 women) from 26 epilepsy centers. Follow-up ranged 1 to 423 months (median 18 months). 732 patients underwent surgery, 483 chemotherapy (CT), 508 radiotherapy. All patients were treated with AEDs. Levetiracetam was the most common drug. 377 patients (46.7%) were still on first drug at end of follow-up, 338 (41.8%) needed treatment modifications (uncontrolled seizures, 229; side effects, 101; poor compliance, 22). Treatment discontinuation for lack of efficacy was associated with younger age, chemotherapy, and center with <20 cases. Treatment discontinuation for side effects was associated with female sex, enzyme-inducing drugs and center with > 20 cases. About one-half of patients with BTRE were on first AED at end of follow-up. Levetiracetam was the most common drug. A non enzyme-inducing AED was followed by a lower risk of drug discontinuation for SE.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0180470PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5513411PMC
September 2017

Clinical features and evolution of the gelastic seizures-hypothalamic hamartoma syndrome.

Epilepsia 2017 06;58 Suppl 2:12-15

Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, Institute "G. Gaslini", University of Genova, Genova, Italy.

Gelastic seizures, usually with onset in early infancy, are the hallmark manifestation of hypothalamic hamartoma. This seizure type is directly generated by hamartoma itself, intrinsically epileptogenic because of its anatomofunctional organization. Other types of seizures, focal or generalized, may appear during the evolution, probably resulting from mechanisms of secondary epileptogenesis. Nevertheless, the clinical expression and the severity of the syndrome, ranging from a focal drug-resistant epilepsy to a catastrophic generalized encephalopathy with severe cognitive and behavioral impairments, depends on the size and the site of attachment of the hamartoma. Early suspicion, timely diagnosis, and appropriate treatment are mandatory to reverse a potential catastrophic evolution of this condition.
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http://dx.doi.org/10.1111/epi.13753DOI Listing
June 2017

The clinical phenotype of autosomal dominant lateral temporal lobe epilepsy related to reelin mutations.

Epilepsy Behav 2017 03 28;68:103-107. Epub 2017 Jan 28.

Section of Padua, Institute of Neurosciences, Consiglio Nazionale delle Ricerche, Padova, Italy.

Objective: To describe the clinical phenotype of 7 families with Autosomal Dominant Lateral Temporal Lobe Epilepsy (ADLTE) related to Reelin (RELN) mutations comparing the data with those observed in 12 LGI1-mutated pedigrees belonging to our series.

Methods: Out of 40 Italian families with ADLTE, collected by epileptologists participating in a collaborative study of the Commission for Genetics of the Italian League against Epilepsy encompassing a 14-year period (2000-2014), 7 (17.5%) were found to harbor heterozygous RELN mutations. The whole series also included 12 (30%) LGI1 mutated families and 21 (52.5%) non-mutated pedigrees. The clinical, neurophysiological, and neuroradiological findings of RELN and LGI1 mutated families were analyzed.

Results: Out of 28 affected individuals belonging to 7 RELN mutated families, 24 had sufficient clinical data available for the study. In these patients, the epilepsy onset occurred at a mean age of 20years, with focal seizures characterized by auditory auras in about 71% of the cases, associated in one-third of patients with aphasia, visual disturbances or other less common symptoms (vertigo or déjà-vu). Tonic-clonic seizures were reported by almost all patients (88%), preceded by typical aura in 67% of cases. Seizures were precipitated by environmental noises in 8% of patients and were completely or almost completely controlled by antiepileptic treatment in the vast majority of cases (96%). The interictal EEG recordings showed epileptiform abnormalities or focal slow waves in 80% of patients, localized over the temporal regions, with marked left predominance and conventional 1,5T MRI scans were not contributory. By comparing these findings with those observed in families with LGI1 mutations, we did not observe significant differences except for a higher rate of left-sided EEG abnormalities in the RELN group.

Significance: Heterozygous RELN mutations cause a typical ADLTE syndrome, indistinguishable from that associated with LGI1 mutations.
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http://dx.doi.org/10.1016/j.yebeh.2016.12.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5378904PMC
March 2017

Antiepileptic Drugs Under Investigation for Treatment of Focal Epilepsy.

Clin Neuropharmacol 2016 Nov/Dec;39(6):281-287

*Pediatric Neurology and Muscular Diseases Unit, Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, "G. Gaslini" Institute, Genova, Italy; †Neurology Unit, Sant' Anna Hospital, Como, Italy; and ‡Department of Neuroscience, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.

Introduction: Despite optimal medical treatment, up to 30% of patients with epilepsy continue to experience recurrent seizures, and the challenge for new more efficacious and better-tolerated drugs is continuing. New antiepileptic drugs include the evolution of preexisting drugs and new compounds identified through the investigation of additional molecular targets, such as SV2A synaptic vesicle protein, voltage-gated potassium channels, ionotropic and metabotropic glutamate receptors, and gap junctions.

Areas Covered: We report the available data about different classes of molecules that are in the pipeline for treatment of focal epilepsy. We will present data available on drugs derived from the evolution of preexisting anticonvulsants. We will then report the results on clinical trials performed with new compounds identified through the investigation of additional molecular targets.

Discussion: The challenge for new, more efficacious, more specific, and better-tolerated drugs is continuing and a better knowledge of mechanisms underlying epilepsy should represent the guide for future research. The ultimate goal of treatment should be not only to render the patients seizure free but also to improve the quality of life and reduce costs of medical care.
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http://dx.doi.org/10.1097/WNF.0000000000000180DOI Listing
January 2017

The challenges of treating epilepsy with 25 antiepileptic drugs.

Pharmacol Res 2016 05 16;107:211-219. Epub 2016 Mar 16.

Epilepsy Centre, Department of Neuroscience, Odontostomatology and Reproductive Sciences, Federico II University, Naples, Italy.

Nowadays a substantial armamentarium of antiepileptic drugs (AEDs) is available, including drugs with different mechanisms of action, pharmacokinetics, efficacy and tolerability; therefore the choice for the right treatment is often challenging. The specific characteristic of the drug, the epileptic syndrome, seizure types and the patient's features need to be taken into consideration driving the choice through available evidence-based studies, which are often lacking for older AEDs. Besides, study conditions in registered clinical trials (RCTs) are quite different from daily clinical practice, which is more complex and various. When dealing with first diagnosed epilepsy, monotherapy is widely accepted as the gold standard option. Likewise, alternative monotherapy should be considered when the first drug treatment fails. However, the association of different AEDs in polytherapy is a common practice. The choice of AEDs used in association is often based on clinical experience or anecdotal observations or small clinical studies. Polytherapy should be as "rational" as possible and consider the mechanism of action, the pharmacokinetic characteristics and the safety of each drug. When dealing with drug resistant patients, clinicians should never give up and consider the use of AEDs acting on new targets. An attempt to come back to a monotherapy or simpler therapeutic regimen should be pursued even in patients who were previously drug resistant. This review will focus on the strategies to treat epilepsy by choosing among 25 available drugs.
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http://dx.doi.org/10.1016/j.phrs.2016.03.016DOI Listing
May 2016

17q21.31 microdeletion syndrome: Description of a case further contributing to the delineation of Koolen-de Vries syndrome.

Brain Dev 2016 Aug 17;38(7):663-8. Epub 2016 Feb 17.

Epilepsy Centre, Department of Neuroscience, Reproductive and Odontostomatological Sciences, Federico II University, Naples, Italy.

The widespread use of Array Comparative Genomic Hybridization (aCGH) technology has enabled the identification of several syndromes associated with copy number variants (CNVs) including the 17q21.31 microdeletion. The 17q21.31 microdeletion syndrome, also known as Koolen-de Vries syndrome, was first described in 2006 in individuals with intellectual disabilities and organ abnormalities. We report the clinical, instrumental, cytogenetic and molecular investigations of a boy admitted for epilepsy and intellectual disabilities. We carried out detailed analysis of the clinical phenotype of this patient and investigated the genetic basis by using aCGH. We identified a de novo microdeletion on chromosome 17q21.31, compatible with Koolen-de Vries syndrome. Our case shares some of the typical characteristics of the syndrome already described by other authors: delayed psychomotor development, primarily affecting the expressive language, dysmorphic facial features, and epilepsy. However the clinical outcome was not severe as the intellectual disabilities were moderate with good adaptive and functional behaviour. Epilepsy was easily controlled by a single drug, and he never needed surgery for organ abnormalities.
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http://dx.doi.org/10.1016/j.braindev.2016.02.002DOI Listing
August 2016

Genetics of reflex seizures and epilepsies in humans and animals.

Epilepsy Res 2016 Mar 2;121:47-54. Epub 2016 Feb 2.

Department of Medical and Surgical Sciences, Magna Graecia University of Catanzaro, Viale Europa, Catanzaro, Italy; Institute of Molecular Bioimaging and Physiology of the National Research Council (IBFM-CNR), Viale Europa, Catanzaro, Italy; Regional Epilepsy Centre, Bianchi-Melacrino-Morelli Hospital, Reggio Calabria, Italy.

Introduction: Reflex seizures are epileptic events triggered by specific motor, sensory or cognitive stimulation. This comprehensive narrative review focuses on the role of genetic determinants in humans and animal models of reflex seizures and epilepsies.

Methods: References were mainly identified through MEDLINE searches until August 2015 and backtracking of references in pertinent studies.

Results: Autosomal dominant inheritance with reduced penetrance was proven in several families with photosensitivity. Molecular genetic studies on EEG photoparoxysmal response identified putative loci on chromosomes 6, 7, 13 and 16 that seem to correlate with peculiar seizure phenotype. No specific mutation has been found in Papio papio baboon, although a genetic etiology is likely. Mutation in synaptic vesicle glycoprotein 2A was found in another animal model of photosensitivity (Fayoumi chickens). Autosomal dominant inheritance with incomplete penetrance overlapping with a genetic background for IGE was proposed for some families with primary reading epilepsy. Musicogenic seizures usually occur in patients with focal symptomatic or cryptogenic epilepsies, but they have been reported in rare genetic epilepsies such as Dravet syndrome. A single LGI1 mutation has been described in a girl with seizures evoked by auditory stimuli. Interestingly, heterozygous knockout (Lgi1(+/-)) mice show susceptibility to sound-triggered seizures. Moreover, in Frings and Black Swiss mice, the spontaneous mutations of MASS1 and JAMS1 genes, respectively, have been linked to audiogenic seizures. Eating seizures usually occur in symptomatic epilepsies but evidences for a genetic susceptibility were mainly provided by family report from Sri Lanka. Eating seizures were also reported in rare patients with MECP2 duplication or mutation. Hot water seizures are genetically heterogeneous but two loci at chromosomes 4 and 10 were identified in families with likely autosomal dominant inheritance. Startle-induced seizures usually occur in patients with symptomatic epilepsies but have also been reported in the setting chromosomal disorders or genetically inherited lysosomal storage diseases.

Discussion: The genetic background of reflex seizures and epilepsies is heterogeneous and mostly unknown with no major gene identified in humans. The benefits offered by next-generation sequencing technologies should be merged with increasing information on animal models that represent an useful tool to study the mechanism underlying epileptogenesis. Finally, we expect that genetic studies will lead to a better understanding of the multiple factors involved in the pathophysiology of reflex seizures, and eventually to develop preventive strategies focused on seizure control and therapy optimization.
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http://dx.doi.org/10.1016/j.eplepsyres.2016.01.010DOI Listing
March 2016

In response: DEPDC5 mutations in epilepsy with auditory features.

Epilepsia 2016 Feb;57(2):336; discussion 336-7

Section of Padua, CNR-Neuroscience Institute, Padova, Italy.

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http://dx.doi.org/10.1111/epi.13255DOI Listing
February 2016

Psychiatric comorbidities in patients from seven families with autosomal dominant cortical tremor, myoclonus, and epilepsy.

Epilepsy Behav 2016 Mar 29;56:38-43. Epub 2016 Jan 29.

Epilepsy Centre, Department of Neuroscience, Odontostomatology and Reproductive Sciences, Federico II University, Naples, Italy.

Objective: The objective of this report was to assess the psychiatric comorbidity in a group of patients affected by autosomal dominant cortical tremor, myoclonus, and epilepsy (ADCME).

Methods: Reliable and validated psychodiagnostic scales including the BDI (Beck Depression Inventory), STAI-Y1 and 2 (State-Trait Anxiety Inventory - Y; 1 and 2), MMPI-2 (Minnesota Multiphasic Personality Inventory - 2), and QoLIE-31 (Quality of Life in Epilepsy Inventory - 31) were administered to 20 patients with ADCME, 20 patients with juvenile myoclonic epilepsy (JME), and 20 healthy controls.

Results: There was a higher prevalence of mood disorders in patients with ADCME compared to patients with JME and healthy controls, particularly depression (p=0.035 and p=0.017, respectively) and state anxiety (p=0.024 and p=0.019, respectively). Trait anxiety was not different from JME (p=0.102) but higher than healthy controls (p=0.017). The myoclonus score positively correlated with both state (rho: 0.58, p=0.042) and trait anxiety (rho: 0.65, p=0.011). These psychiatric features were also often associated with pathological traits of personality: paranoid (OR: 25.7, p=0.003), psychasthenia (OR: 7.0, p=0.023), schizophrenia (OR: 8.5, p=0.011), and hypomania (OR: 5.5, p=0.022). Finally, in patients with ADCME, decreased quality of life correlated with these psychiatric symptoms.

Significance: Patients with ADCME show a significant psychiatric burden that impairs their quality of life. A comprehensive psychiatric evaluation should be offered at the time of diagnosis to detect these comorbidities and to treat them.
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http://dx.doi.org/10.1016/j.yebeh.2015.12.038DOI Listing
March 2016

Safety of Overnight Switch from Brand-Name to Generic Levetiracetam.

Clin Drug Investig 2016 Jan;36(1):87-91

Department of Paediatrics, University of Perugia, Santa Maria della Misericordia Hospital, Perugia, Italy.

Background And Objective: Concerns that antiepileptic brand-to-generic interchange results in disruption of seizure control are widespread. The objective of this study was to evaluate the safety and tolerability of the brand-to-generic levetiracetam switch in patients with focal or generalized epilepsy.

Methods: A prospective study in patients with primary, cryptogenic or symptomatic epilepsy, who were taking branded levetiracetam and were switched to generic levetiracetam. Patients were consecutively recruited from January 2013 to January 2015. We evaluated efficacy, tolerability and compliance before switching (T0) and after 6 months of therapy (T1). Evaluations were scheduled as follows: baseline, 7 and 15 days, 1, 3 and 6 months. At each visit clinical diary seizures, physical and neurological examination, laboratory parameters and electroencephalogram were evaluated.

Results: Fifty-nine patients, equally mixed by sex, were included in the study. Mean age was 26.1 years. Forty-seven per cent of the patients enrolled received levetiracetam as monotherapy. One patient was lost during the follow-up: so at T1 we had 58 patients (28 monotherapy and 30 polytherapy). At T0 and at T1, there was no statistically significant difference in terms of seizure frequency and intensity, occurrence of adverse events, laboratory parameters and electroencephalographic features. Two patients stopped treatment with the generic (both at 3 months after the switch) and restarted therapy with brand levetiracetam because of seizure increase. At the end of the study, the switchback rate was 3.4%.

Conclusions: No increase of seizures and adverse effects were observed when branded levetiracetam was interchanged to a generic equivalent. More studies should be conducted with a larger series of patients to confirm these results.
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http://dx.doi.org/10.1007/s40261-015-0351-1DOI Listing
January 2016

Perspectives on treatment options for mesial temporal lobe epilepsy with hippocampal sclerosis.

Expert Opin Pharmacother 2015 2;16(15):2355-71. Epub 2015 Sep 2.

a 1 University of Catanzaro, Science of Health Department, School of Medicine , Naples, Italy +39 0 96 13 69 41 91 ; +39 0 96 13 69 41 92 ;

Introduction: Mesial temporal lobe epilepsy associated with hippocampal sclerosis (MTLE-HS) is a syndrome that is often refractory to drug treatment. The effects on specific syndromes are not currently available from the pre-marketing clinical development of new AEDs; this does not allow the prediction of whether new drugs will be more effective in the treatment of some patients.

Areas Covered: We have reviewed all the existing literature relevant to the understanding of a potential effectiveness in MTLE-HS patients for the latest AEDs, namely brivaracetam, eslicarbazepine, lacosamide, perampanel and retigabine also including the most relevant clinical data and a brief description of their pharmacological profile. Records were identified using predefined search criteria using electronic databases (e.g., PubMed, Cochrane Library Database of Systematic Reviews). Primary peer-reviewed articles published up to the 15 June 2015 were included.

Expert Opinion: All the drugs considered have the potential to be effective in the treatment of MTLE-HS; in fact, they possess proven efficacy in animal models; currently considered valuable tools for predicting drug efficacy in TLE. Furthermore, for some of these (e.g., lacosamide and eslicarbazepine) data are already available from post-marketing studies while brivaracetam acting on SV2A like levetiracetam might have the same potential effectiveness with the possibility to be more efficacious considering its ability to inhibit voltage gated sodium channels; finally, perampanel and retigabine are very effective drugs in animal models of TLE.
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http://dx.doi.org/10.1517/14656566.2015.1084504DOI Listing
February 2016

DEPDC5 mutations are not a frequent cause of familial temporal lobe epilepsy.

Epilepsia 2015 Oct 27;56(10):e168-71. Epub 2015 Jul 27.

CNR-Neuroscience Institute, Section of Padua, Padova, Italy.

Mutations in the DEPDC5 (DEP domain-containing protein 5) gene are a major cause of familial focal epilepsy with variable foci (FFEVF) and are predicted to account for 12-37% of families with inherited focal epilepsies. To assess the clinical impact of DEPDC5 mutations in familial temporal lobe epilepsy, we screened a collection of Italian families with either autosomal dominant lateral temporal epilepsy (ADLTE) or familial mesial temporal lobe epilepsy (FMTLE). The probands of 28 families classified as ADLTE and 17 families as FMTLE were screened for DEPDC5 mutations by whole exome or targeted massive parallel sequencing. Putative mutations were validated by Sanger sequencing. We identified a DEPDC5 nonsense mutation (c.918C>G; p.Tyr306*) in a family with two affected members, clinically classified as FMTLE. The proband had temporal lobe seizures with prominent psychic symptoms (déjà vu, derealization, and forced thoughts); her mother had temporal lobe seizures, mainly featuring visceral epigastric auras and anxiety. In total, we found a single DEPDC5 mutation in one of (2.2%) 45 families with genetic temporal lobe epilepsy, a proportion much lower than that reported in other inherited focal epilepsies.
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http://dx.doi.org/10.1111/epi.13094DOI Listing
October 2015

A prospective study of direct medical costs in a large cohort of consecutively enrolled patients with refractory epilepsy in Italy.

Epilepsia 2015 Jul 4;56(7):1162-73. Epub 2015 Jun 4.

Unit of Clinical and Experimental Pharmacology, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy.

Objective: To evaluate direct medical costs and their predictors in patients with refractory epilepsy enrolled into the SOPHIE study (Study of Outcomes of PHarmacoresistance In Epilepsy) in Italy.

Methods: Adults and children with refractory epilepsy were enrolled consecutively at 11 tertiary referral centers and followed for 18 months. At entry, all subjects underwent a structured interview and a medical examination, and were asked to keep records of diagnostic examinations, laboratory tests, specialist consultations, treatments, hospital admissions, and day-hospital days during follow-up. Study visits included assessments every 6 months of seizure frequency, health-related quality of life (Quality of Life in Epilepsy Inventory 31), medication-related adverse events (Adverse Event Profile) and mood state (Beck Depression Inventory-II). Cost items were priced by applying Italian tariffs. Cost estimates were adjusted to 2013 values.

Results: Of 1,124 enrolled individuals, 1,040 completed follow-up. Average annual cost per patient was € 4,677. The highest cost was for antiepileptic drug (AED) treatment (50%), followed by hospital admissions (29% of overall costs). AED polytherapy, seizure frequency during follow-up, grade III pharmacoresistance, medical and psychiatric comorbidities, and occurrence of status epilepticus during follow-up were identified as significant predictors of higher costs. Age between 6 and 11 years, and genetic (idiopathic) generalized epilepsies were associated with the lowest costs. Costs showed prominent variation across centers, largely due to differences in the clinical characteristics of cohorts enrolled at each center and the prescribing of second-generation AEDs. Individual outliers associated with high costs related to hospital admissions had a major influence on costs in many centers.

Significance: Refractory epilepsy is associated with high costs that affect individuals and society. Costs differ across centers in relation to the characteristics of patients and the extent of use of more expensive, second-generation AEDs. Epilepsy-specific costs cannot be easily differentiated from costs related to comorbidities.
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http://dx.doi.org/10.1111/epi.13030DOI Listing
July 2015
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