Publications by authors named "Maurizio Viri"

27 Publications

  • Page 1 of 1

The epileptology of Aicardi-Goutières syndrome: electro-clinical-radiological findings.

Seizure 2021 Mar 1;86:197-209. Epub 2020 Dec 1.

Department of Child Neurology and Psychiatry, IRCCS Mondino Foundation, Pavia, Italy; Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.

Objective: Although epileptic seizures occur in approximately a quarter of patients with Aicardi-Goutières syndrome (AGS), their phenotypic and electrophysiological characterization remains elusive. The aim of our study was to characterize epilepsy phenotypes and electroencephalographic (EEG) patterns in AGS and look for possible correlations with clinical, genetic and neuroradiological features.

Methods: We selected patients with an established AGS diagnosis followed at three Italian reference centers. Medical records, EEGs and MRI/CT findings were reviewed. EEGs were independently and blindly reviewed by three board-certified pediatric epileptologists. Chi square and Fisher's exact tests were used to test associations between epilepsy and EEG feature categories and clinical, radiological and genetic variables.

Results: Twenty-seven patients were enrolled. We reviewed 63 EEGs and at least one brain MRI scan per patient. Epilepsy, mainly in the form of epileptic spasms and focal seizures, was present in 37 % of the cohort; mean age at epilepsy onset was 9.5 months (range 1-36). The presence of epilepsy was associated with calcification severity (p = 0.016) and startle reactions (p = 0.05). Organization of EEG electrical activity appeared to be disrupted or markedly disrupted in 73 % of cases. Severe EEG disorganization correlated with microcephaly (p < 0.001) and highly abnormal MRI T2-weighted signal intensity in white matter (p = 0.022). Physiological organization of the EEG was found to be better preserved during sleep (87 %) than wakefulness (38 %). Focal slow activity was recorded in more than one third of cases. Fast activity, either diffuse or with frontal location, was more frequent in the awake state (78 %) than in sleep (50 %). Interictal epileptiform discharges (IEDs) were present in 33 % of awake and 45 % of sleep recordings. IEDs during sleep were associated with a higher risk of a epileptic seizures (p = 0.008).

Significance: The hallmarks of EEG recordings in AGS were found to be: disruption of electrical organization, the presence of focal slow and fast activity, and the presence of IEDs, both in patients with and in those without epilepsy. The associations between epilepsy and calcification and between EEG pattern and the finding of a highly abnormal white matter T2 signal intensity suggest a common anatomical correlate. However, the complex anatomical-electroclinical basis of AGS-related epilepsy still requires further elucidation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2020.11.019DOI Listing
March 2021

Anakinra usage in febrile infection related epilepsy syndrome: an international cohort.

Ann Clin Transl Neurol 2020 12 4;7(12):2467-2474. Epub 2020 Dec 4.

Baylor College of Medicine/Texas Children's Hospital, Houston, Texas, USA.

Febrile-infection related epilepsy syndrome (FIRES) is a devastating neurological condition characterized by a febrile illness preceding new onset refractory status epilepticus (NORSE). Increasing evidence suggests innate immune dysfunction as a potential pathological mechanism. We report an international retrospective cohort of 25 children treated with anakinra, a recombinant interleukin-1 receptor antagonist, as an immunomodulator for FIRES. Anakinra was potentially safe with only one child discontinuing therapy due to infection. Earlier anakinra initiation was associated with shorter duration of mechanical ventilation, ICU and hospital length of stay. Our retrospective data lay the groundwork for prospective consensus-driven cohort studies of anakinra in FIRES.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/acn3.51229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732241PMC
December 2020

STXBP1 encephalopathy: A neurodevelopmental disorder including epilepsy.

Neurology 2016 Mar 10;86(10):954-62. Epub 2016 Feb 10.

Authors' affiliations are listed at the end of the article.

Objective: To give a comprehensive overview of the phenotypic and genetic spectrum of STXBP1 encephalopathy (STXBP1-E) by systematically reviewing newly diagnosed and previously reported patients.

Methods: We recruited newly diagnosed patients with STXBP1 mutations through an international network of clinicians and geneticists. Furthermore, we performed a systematic literature search to review the phenotypes of all previously reported patients.

Results: We describe the phenotypic features of 147 patients with STXBP1-E including 45 previously unreported patients with 33 novel STXBP1 mutations. All patients have intellectual disability (ID), which is mostly severe to profound (88%). Ninety-five percent of patients have epilepsy. While one-third of patients presented with Ohtahara syndrome (21%) or West syndrome (9.5%), the majority has a nonsyndromic early-onset epilepsy and encephalopathy (53%) with epileptic spasms or tonic seizures as main seizure type. We found no correlation between severity of seizures and severity of ID or between mutation type and seizure characteristics or cognitive outcome. Neurologic comorbidities including autistic features and movement disorders are frequent. We also report 2 previously unreported adult patients with prominent extrapyramidal features.

Conclusion: De novo STXBP1 mutations are among the most frequent causes of epilepsy and encephalopathy. Most patients have severe to profound ID with little correlation among seizure onset, seizure severity, and the degree of ID. Accordingly, we hypothesize that seizure severity and ID present 2 independent dimensions of the STXBP1-E phenotype. STXBP1-E may be conceptualized as a complex neurodevelopmental disorder rather than a primary epileptic encephalopathy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1212/WNL.0000000000002457DOI Listing
March 2016

Eating epilepsy characterised by late-onset epileptic spasms in a case of Cri du chat syndrome.

Seizure 2015 Nov 21;32:49-51. Epub 2015 Sep 21.

Pediatric Neurology Unit and Epilepsy Center, Department of Neuroscience, "Fatebenefratelli e Oftalmico" Hospital, Milano, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2015.09.005DOI Listing
November 2015

Dramatic effect of levetiracetam in early-onset epileptic encephalopathy due to STXBP1 mutation.

Brain Dev 2016 Jan 23;38(1):128-31. Epub 2015 Jul 23.

Pediatric Neurology and Muscular Diseases Unit, Laboratory of Neurogenetics, Institute "G. Gaslini", Genoa, Italy.

Background: Syntaxin Binding Protein 1 (STXBP1) mutations determine a central neurotransmission dysfunction through impairment of the synaptic vesicle release, thus causing a spectrum of phenotypes varying from syndromic and non-syndromic epilepsy to intellectual disability of variable degree. Among the antiepileptic drugs, levetiracetam has a unique mechanism of action binding SV2A, a glycoprotein of the synaptic vesicle release machinery.

Patient Description: We report a 1-month-old boy manifesting an epileptic encephalopathy with clonic seizures refractory to phenobarbital, pyridoxine and phenytoin that presented a dramatic response to levetiracetam with full epilepsy control and EEG normalization. Genetic analysis identified a novel de novo heterozygous mutation (c.[922A>T]p.[Lys308(∗)]) in the STXBP1 gene that severely affects the protein.

Conclusions: The observation of a dramatic efficacy of levetiracetam in a case of STXBP1 epileptic encephalopathy refractory to other antiepileptic drugs and considerations regarding the specific mechanism of action of levetiracetam modulating the same system affected by STXBP1 mutations support the hypothesis that this drug may be able to reverse specifically the disease epileptogenic abnormalities. Further clinical observations and laboratory studies are needed to confirm this hypothesis and eventually lead to consider levetiracetam as the first choice treatment of patients with suspected or confirmed STXBP1-related epilepsies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.braindev.2015.07.002DOI Listing
January 2016

Mild Lafora disease: clinical, neurophysiologic, and genetic findings.

Epilepsia 2014 Dec 30;55(12):e129-33. Epub 2014 Sep 30.

Magna Graecia University of Catanzaro, Catanzaro, Italy; Regional Epilepsy Center, Bianchi-Melacrino-Morelli Hospital, Reggio Calabria, Italy.

We report clinical, neurophysiologic, and genetic features of an Italian series of patients with Lafora disease (LD) to identify distinguishing features of those with a slowly progressive course. Twenty-three patients with LD (17 female; 6 male) were recruited. Mean age (± SD) at the disease onset was 14.5 ± 3.9 years and mean follow-up duration was 13.2 ± 8.0 years. NHLRC1 mutations were detected in 18 patients; EPM2A mutations were identified in 5. Patients who maintained >10 years gait autonomy were labeled as "mild" and were compared with the remaining LD patients with a typical course. Six of 23 patients were mild and presented significantly delay in the age at onset, lower neurologic disability score at 4 years after the onset, less severe seizure phenotype, lower probability of showing both photoparoxysmal response on electroencephalography (EEG) and giant somatosensory evoked potentials, as compared to patients with typical LD. However, in both mild and typical LD patients, EEG showed disorganization of background activity and frequent epileptiform abnormalities. Mild LD patients had NHLRC1 mutations and five of six carried homozygous or compound heterozygous D146N mutation. This mutation was found in none of the patients with typical LD. The occurrence of specific NHLRC1 mutations in patients with mild LD should be taken into account in clinical practice for appropriate management and counseling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.12806DOI Listing
December 2014

Does the co-occurrence of FGFR3 gene mutation in hypochondroplasia, medial temporal lobe dysgenesis, and focal epilepsy suggest a syndrome?

Pediatr Neurol 2014 Apr 7;50(4):427-30. Epub 2014 Jan 7.

Pediatric Clinic I, Department of Pathophysiology and Transplantation, University of Milan Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.

Background: Hypochondroplasia is a rare skeletal dysplasia characterized by disproportionately short stature, lumbar lordosis, and limited extension of the elbow caused by mutations in the fibroblast growth factor receptor 3 (FGFR3) gene that plays a role in controlling nervous system development. Hypochondroplasia with FGFR3 mutation associated with bilateral medial temporal lobe anomalies and focal epilepsy was previously reported in several patients.

Patient: We report clinical, electroclinical, and neuroradiological findings of one patient affected by hypochondroplasia.

Results: Clinical diagnosis was confirmed by molecular analysis of the FGFR3 gene, which showed a N540 K mutation. The patient had normal psychomotor development and showed early-onset focal seizures with left temporal localization on interictal and ictal electroencephalograph. The seizures were well controlled, and the patient has been seizure-free since infancy. Magnetic resonance imaging showed abnormal anteriorly posteriorly infolding in the hippocampus and abnormally oriented parahippocampus sulci, and additional cortical rim dysplasia with gray-white matter junction blurring in the hippocampus.

Conclusions: The present case of hypochondroplasia and FGFR3 mutation in Asn540Lys associated with characteristic abnormalities involving bilaterally medial temporal lobe structures, probable hippocampal cortex focal dysplasia, and early onset of focal epilepsy underscores the possibility of a rare syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pediatrneurol.2014.01.004DOI Listing
April 2014

Vaccination and occurrence of seizures in SCN1A mutation-positive patients: a multicenter Italian study.

Pediatr Neurol 2014 Mar 5;50(3):228-32. Epub 2013 Oct 5.

Regional Epilepsy Center, San Paolo Hospital, Milano, Italy.

Background: The relation between epileptic seizures and vaccinations is sometimes debated. In the present work, the impact of vaccination on seizure onset and clinical outcome of SCN1A mutation-positive patients is addressed.

Methods: Seventy-two patients diagnosed with Dravet syndrome or generalized epilepsy with febrile seizure plus, carrying SCN1A mutations or not, were included. Details on vaccination type, temporal relationship between vaccination and seizure occurrence, seizure type at onset and during development, cognitive functioning, and vaccination completion was obtained by reviewing clinical records. Patients were divided into two groups based on the temporal window between vaccination and seizure onset (proximate group: <48 hours; distant group: >48 hours).

Results: Vaccination-related seizures occurred in 25% of patients with SCN1A mutation and 18% of patients without the mutation (no significant difference). The proximate group showed an earlier age at seizure onset and a higher frequency of status epilepticus during development than did the distant group. No other significant differences were found. Subsequent vaccinations did not significantly alter the evolution of the disease.

Conclusions: Results from this relatively small series provide evidence that vaccinations do not significantly affect clinical and cognitive evolution of Dravet syndrome and generalized epilepsy with febrile seizure plus patients even if they carry SCN1A mutations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pediatrneurol.2013.09.016DOI Listing
March 2014

Genetic testing in benign familial epilepsies of the first year of life: clinical and diagnostic significance.

Epilepsia 2013 Mar 29;54(3):425-36. Epub 2013 Jan 29.

Laboratory of Neurogenetics, Department of Neuroscience, Istituto G. Gaslini, Genova, Italy.

Purpose: To dissect the genetics of benign familial epilepsies of the first year of life and to assess the extent of the genetic overlap between benign familial neonatal seizures (BFNS), benign familial neonatal-infantile seizures (BFNIS), and benign familial infantile seizures (BFIS).

Methods: Families with at least two first-degree relatives affected by focal seizures starting within the first year of life and normal development before seizure onset were included. Families were classified as BFNS when all family members experienced neonatal seizures, BFNIS when the onset of seizures in family members was between 1 and 4 months of age or showed both neonatal and infantile seizures, and BFIS when the onset of seizures was after 4 months of age in all family members. SCN2A, KCNQ2, KCNQ3, PPRT2 point mutations were analyzed by direct sequencing of amplified genomic DNA. Genomic deletions involving KCNQ2 and KCNQ3 were analyzed by multiple-dependent probe amplification method.

Key Findings: A total of 46 families including 165 affected members were collected. Eight families were classified as BFNS, 9 as BFNIS, and 29 as BFIS. Genetic analysis led to the identification of 41 mutations, 14 affecting KCNQ2, 1 affecting KCNQ3, 5 affecting SCN2A, and 21 affecting PRRT2. The detection rate of mutations in the entire cohort was 89%. In BFNS, mutations specifically involve KCNQ2. In BFNIS two genes are involved (KCNQ2, six families; SCN2A, two families). BFIS families are the most genetically heterogeneous, with all four genes involved, although about 70% of them carry a PRRT2 mutation.

Significance: Our data highlight the important role of KCNQ2 in the entire spectrum of disorders, although progressively decreasing as the age of onset advances. The occurrence of afebrile seizures during follow-up is associated with KCNQ2 mutations and may represent a predictive factor. In addition, we showed that KCNQ3 mutations might be also involved in families with infantile seizures. Taken together our data indicate an important role of K-channel genes beyond the typical neonatal epilepsies. The identification of a novel SCN2A mutation in a family with infantile seizures with onset between 6 and 8 months provides further confirmation that this gene is not specifically associated with BFNIS and is also involved in families with a delayed age of onset. Our data indicate that PRRT2 mutations are clustered in families with BFIS. Paroxysmal kinesigenic dyskinesia emerges as a distinctive feature of PRRT2 families, although uncommon in our series. We showed that the age of onset of seizures is significantly correlated with underlying genetics, as about 90% of the typical BFNS families are linked to KCNQ2 compared to only 3% of the BFIS families, for which PRRT2 represents the major gene.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.12089DOI Listing
March 2013

Lacosamide in pediatric and adult patients: comparison of efficacy and safety.

Seizure 2013 Apr 5;22(3):210-6. Epub 2013 Jan 5.

Department of Paediatrics, University of Chieti, Chieti, Italy.

Purpose: This multicenter, prospective study investigates the efficacy and safety of lacosamide adjunctive therapy in pediatric and adult patients with uncontrolled epilepsy.

Method: This study was carried out between September 2010 and December 2011 at 16 Italian and 1 German neurologic centers. Lacosamide was added to the baseline therapy at a starting dose of 1 mg/kg/day in patients aged <16 years (group A) and 100 mg daily in subjects aged 16 and older (group B), and titrated to the target dose, ranging from 3 to 12 mg/kg/day or from 100 to 600 mg daily, respectively. After completing the titration period, patients entered a 12-month maintenance period and they were followed up at 3, 6 and 12 months. The primary assessment of efficacy was based on the change from baseline in seizure frequency per 28 days and was evaluated at 3, 6 and 12 months as follows: number and proportion of 100% responders, 50% responders, non-responders and worsening patients. Safety evaluation was also performed at 3, 6 and 12 months.

Results: A total of 118 patients (59 group A, 59 group B) with uncontrolled generalized and focal epilepsy were enrolled. Patient mean±SD age was 15.9±6.80 years and the age range was 4-38 years. At 3-month evaluation, of 118 treated patients 56 subjects (47.4% group A; 47.4% group B; p=0.8537) experienced at least a 50% reduction in seizure frequency. At 6 and 12-month follow-up, the 50% responders were 57 (52.5% group A; 44.1% group B; p=0.4612) and 51 (47.4% group A; 39% group B; p=0.4573), respectively. Thirty-five subjects (30.5% group A; 28.8% group B; p=1) experienced side effects during the treatment period. The most common adverse events were dyspepsia for group A and dizziness for group B.

Conclusion: Lacosamide may be a useful and safe pharmacological treatment option for both pediatric and adult patients with uncontrolled seizures.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2012.12.009DOI Listing
April 2013

Electroclinical presentation and genotype-phenotype relationships in patients with Unverricht-Lundborg disease carrying compound heterozygous CSTB point and indel mutations.

Epilepsia 2012 Dec;53(12):2120-7

Neurophysiopathology and Epilepsy Centre, IRCCS Foundation Carlo Besta Neurological Institute, Milan, Italy.

Purpose: Unverricht-Lundborg disease (EPM1A) is frequently due to an unstable expansion of a dodecamer repeat in the CSTB gene, whereas other types of mutations are rare. EPM1A due to homozygous expansion has a rather stereotyped presentation with prominent action myoclonus. We describe eight patients with five different compound heterozygous CSTB point or indel mutations in order to highlight their particular phenotypical presentations and evaluate their genotype-phenotype relationships.

Methods: We screened CSTB mutations by means of Southern blotting and the sequencing of the genomic DNA of each proband. CSTB messenger RNA (mRNA) aberrations were characterized by sequencing the complementary DNA (cDNA) of lymphoblastoid cells, and assessing the protein concentrations in the lymphoblasts. The patient evaluations included the use of a simplified myoclonus severity rating scale, multiple neurophysiologic tests, and electroencephalography (EEG)-polygraphic recordings. To highlight the particular clinical features and disease time-course in compound heterozygous patients, we compared some of their characteristics with those observed in a series of 40 patients carrying the common homozygous expansion mutation observed at the C. Besta Foundation, Milan, Italy.

Key Findings: The eight compound heterozygous patients belong to six EPM1A families (out of 52; 11.5%) diagnosed at the Laboratory of Genetics of the Galliera Hospitals in Genoa, Italy. They segregated five different heterozygous point or indel mutations in association with the common dodecamer expansion. Four patients from three families had previously reported CSTB mutations (c.67-1G>C and c.168+1_18del); one had a novel nonsense mutation at the first exon (c.133C>T) leading to a premature stop codon predicting a short peptide; the other three patients from two families had a complex novel indel mutation involving the donor splice site of intron 2 (c.168+2_169+21delinsAA) and leading to an aberrant transcript with a partially retained intron. The protein dose (cystatin B/β-actin) in our heterozygous patients was 0.24 ± 0.02, which is not different from that assessed in patients bearing the homozygous dodecamer expansion. The compound heterozygous patients had a significantly earlier disease onset (7.4 ± 1.7 years) than the homozygous patients, and their disease presentations included frequent myoclonic seizures and absences, often occurring in clusters throughout the course of the disease. The seizures were resistant to the pharmacologic treatments that usually lead to complete seizure control in homozygous patients. EEG-polygraphy allowed repeated seizures to be recorded. Action myoclonus progressively worsened and all of the heterozygous patients older than 30 years were in wheelchairs. Most of the patients showed moderate to severe cognitive impairment, and six had psychiatric symptoms.

Significance: EPM1A due to compound heterozygous CSTB mutations presents with variable but often markedly severe and particular phenotypes. Most of our patients presented with the electroclinical features of severe epilepsy, which is unexpected in homozygous patients, and showed frequent seizures resistant to pharmacologic treatment. The presence of variable phenotypes (even in siblings) suggests interactions with other genetic factors influencing the final disease presentation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1528-1167.2012.03718.xDOI Listing
December 2012

Homozygous c.649dupC mutation in PRRT2 worsens the BFIS/PKD phenotype with mental retardation, episodic ataxia, and absences.

Epilepsia 2012 Dec 5;53(12):e196-9. Epub 2012 Nov 5.

Institute of Neurology, University Magna Graecia, Catanzaro, Italy.

Heterozygous mutations of PRRT2, which encodes proline-rich transmembrane protein 2, are associated with heterogeneous phenotypes including benign familial infantile seizures (BFIS), or familial paroxysmal kinesigenic dystonia (PKD). We report a consanguineous Italian family with BFIS/PKD phenotype that contained 14 living members with 6 affected individuals (four men, ranging in age from 6-44 years). We identified the reported c.649dupC (p.Arg217ProfsX8) mutation of PRRT2 gene that cosegregated with the disease and was not observed in 100 controls of matched ancestry. Four patients with BFIS phenotype were heterozygous for this mutation, including the consanguineous parents of the two affected brothers with more severe phenotypes of BFIS/PKD--mental retardation, episodic ataxia, and absences--who were the only individuals to carry a homozygous c.649dupC mutation. This family provides strong evidence that homozygous PRRT2 mutations give rise to more severe clinical disease of mental retardation, episodic ataxia, and absences, and, thus, enlarges the clinical spectrum related to PRRT2 mutations. Moreover, it suggests an additive effect of double dose of the genetic mutation and underscores the complexity of the phenotypic consequences of mutations in this gene.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/epi.12009DOI Listing
December 2012

PRRT2 mutations are the major cause of benign familial infantile seizures.

Hum Mutat 2012 Oct 11;33(10):1439-43. Epub 2012 Jun 11.

Department of Neurology and Epileptology, Hertie Institute for Clinical Brain Research, University of Tuebingen, Tuebingen, Germany.

Mutations in PRRT2 have been described in paroxysmal kinesigenic dyskinesia (PKD) and infantile convulsions with choreoathetosis (PKD with infantile seizures), and recently also in some families with benign familial infantile seizures (BFIS) alone. We analyzed PRRT2 in 49 families and three sporadic cases with BFIS only of Italian, German, Turkish, and Japanese origin and identified the previously described mutation c.649dupC in an unstable series of nine cytosines to occur in 39 of our families and one sporadic case (77% of index cases). Furthermore, three novel mutations were found in three other families, whereas 17% of our index cases did not show PRRT2 mutations, including a large family with late-onset BFIS and febrile seizures. Our study further establishes PRRT2 as the major gene for BFIS alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/humu.22126DOI Listing
October 2012

Seizures and EEG patterns in Pallister-Killian syndrome: 13 new Italian patients.

Eur J Paediatr Neurol 2012 Nov 29;16(6):636-41. Epub 2012 Mar 29.

Child Neuropsychiatric Unit, Civile Hospital, Brescia, Italy.

Background And Objectives: Pallister-Killian syndrome (PKS) is a rare genetic disorder caused by a tissue-limited mosaic supernumerary isochromosome 12p. Typical facial dysmorphisms, pigmentary abnormalities, and some major malformations are frequently present. Neurological manifestations include mental retardation, hypotonia, and seizures. Epilepsy incidence ranged from 39 to 59% in a previously reported series. No specific clinical and EEG phenotype has ever been reported to describe seizure features, electroclinical patterns, and response to therapy in PKS.

Methods: This was a multicentre study conducted on 13 Italian children with PKS, as diagnosed by clinical phenotype and confirmed in cultured fibroblasts. All patients underwent several polygraphic video-EEG recordings and brain magnetic resonance imaging.

Results And Conclusions: All the patients presented with epilepsy and seizures that started at a mean age of 19 months. In six cases, epilepsy started with epileptic spasms (ES) combined with focal seizures in another case. In four cases, seizures were focal, and this was followed by ES in two patients. In only two cases, epilepsy started with myoclonic seizures, and spasms were never observed. The study provides further evidence that epilepsy is a part of the phenotype of PKS, although a specific clinical and EEG pattern could not be identified. Our cases show how ES with late- or first-year onset is the most common type of seizure. Despite a variable prognosis in terms of response to therapy, a significant proportion of patients achieved good seizure control.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejpn.2012.03.003DOI Listing
November 2012

Neuropsychological and behavioural aspects in children and adolescents with idiopathic epilepsy at diagnosis and after 12 months of treatment.

Seizure 2010 Nov 22;19(9):540-6. Epub 2010 Aug 22.

Child Neuropsychiatry Unit, University of Insubria, Macchi Foundation Hospital, Varese, Italy.

Purpose: To study neuropsychological functions in children with idiopathic epilepsy at onset of treatment and after 1 year of therapy and to identify factors associated with cognitive impairment.

Methods: 43 Subjects aged 5.2-16.9 years with newly diagnosed idiopathic epilepsy were enrolled and started treatment with valproate or carbamazepine. At admission and after 12 months, all patients underwent clinical examinations, the Child Behavioural Checklist, EEG and a neuropsychological test battery. The results of each test were correlated to demographic, clinical, electrophysiological and therapeutic variables.

Results: Except for attention, all neuropsychological functions were normal at admission and after 12 months. An improvement with time was noted for memory (p<0.05) and logical-executive functions (p<0.01). Attentive deficit was worse at 12 months (53.5% vs. 32.6%). Low socio-economic level and emotional and behavioural disturbances were the only factors negatively correlated to intelligence, memory and attention. Compared to valproate, carbamazepine was most commonly implicated.

Discussion: Idiopathic epilepsy can affect attention, even before starting treatment. Emotional and behavioural difficulties and a low socio-economical status are associated with cognitive impairment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.seizure.2010.07.014DOI Listing
November 2010

Short and long interval cortical inhibition in patients with Unverricht-Lundborg and Lafora body disease.

Epilepsy Res 2010 May 1;89(2-3):232-7. Epub 2010 Feb 1.

Dept. of Neurophysiopathology and Epilepsy Centre, IRCCS Foundation Carlo Besta Neurological Institute, Via Celoria 11, 20133 Milano, Italy.

Myoclonus has different clinical and neurophysiological features in patients with Unverricht-Lundborg (ULD) and Lafora body disease (LBD), probably because of a different cortical hyperexcitability profile. To investigate the role of intracortical inhibition in such different presentations, we used paired-pulse transcranial magnetic stimulation (TMS) in ten ULD and five LBD patients, all with a positive molecular diagnosis. All of the patients were treated with antiepileptic drugs (AEDs). In comparison with healthy subjects, both patient groups had significantly defective short intracortical inhibition (SICI), however LBD patients, but not ULD and healthy subjects, had a clear inhibition at ISI 6 ms and ISI 10 ms. Moreover, defective long interval cortical inhibition (LICI) was found in LBD but not ULD patients. The substantial reduction in SICI suggests that both ULD and LBD patients have impaired inhibitory interneuron pools which are involved in the generation of cortical reflex myoclonus, whereas the inhibition found in LBD patients at ISI 6 and 10 ms, as well the reduced inhibition found at long intervals, suggest a more complex circuitry dysfunction possibly involving both excitatory and inhibitory systems. These findings are probably related to the high epileptogenic propensity characterizing LBD with respect to ULD and to the more severely distorted neuronal network resulting from the pathogenesis of LBD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eplepsyres.2010.01.006DOI Listing
May 2010

Seizures and EEG pattern in Kabuki syndrome.

Brain Dev 2010 Nov 12;32(10):829-34. Epub 2010 Jan 12.

Epilepsy Center, Department of Neurosciences, Fatebenefratelli e Oftalmico Hospital, Milano, Italy.

Purpose: Kabuki syndrome (KS) is a rare dysmorphogenic disorder that is characterized by multiple congenital abnormalities with central nervous system involvement. The diagnosis is clinical and a variable degree of mental retardation is always present. Epilepsy is frequently reported, but a typical electroclinical pattern has not been described. We describe the electroclinical features of eight KS non-Japanese patients with epilepsy.

Methods: We analysed seizure characteristics and pattern EEG and clinical outcomes in eight KS patients.

Results: All patients presented with focal seizures. A frontal epileptic status was present in two cases. We highlighted the fact that, during evolution, seven patients shared the same interictal EEG pattern, which was characterized by isolated or repetitive biphasic spikes or sharp waves, followed by a slow wave of medium and high voltage, predominantly localised in the fronto-central regions. The natural course of seizures is favourable.

Conclusions: Our results showed a peculiar homogeneous electroclinical pattern in KS, characterized by focal seizures more frequently origin in fronto-central area which demonstrated that seizures are mostly focal in type and that a fronto-central origin is more frequently evident.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.braindev.2009.12.006DOI Listing
November 2010

Ictal impending danger--"sixth sense seizures"--in patients with benign focal epileptic seizures of adolescence.

Epilepsy Res 2008 Mar 3;79(1):90-6. Epub 2008 Mar 3.

Epilepsy Center, Department of Child Neuropsychiatry and Neurophysiology, Fatebenefratelli e Oftalmico Hospital, Corso di Porta Nuova 23, 20121 Milano, Italy.

Purpose: We describe nine consecutive patients with diagnosis of benign focal epileptic seizures of adolescence (BFSA), who experienced an ictal sensation of impending danger.

Materials And Methods: We collected nine BFSA patients after a comprehensive clinical and laboratory investigation, video-EEG analysis and neuroimaging study.

Results: All patients displayed a distinct electro-clinical pattern of seizures characterized by a peculiar subjective feeling of impending danger coming from behind, followed by a coordinated behavior of "head-turning" toward the danger. This feeling was described in all patients as "a shadow behind me on one side" or "something or someone behind me". All of our patients explained that, at the beginning of their seizures, they felt an early warning of a high-risk situation. Electrophysiologic data favored a frontal origin of these seizures.

Conclusion: We have described for the first time a distinct electro-clinical pattern of seizures in the context of BFSA, characterized by the ictal feeling of early warning of a high-risk situation, which we thought to term "sixth sense seizure". In the light of current neuro-anatomical knowledge, seizure discharge within anterior cingulate cortex (ACC) structures is the likely explanation for this situation. Further studies are needed to establish if this is an electroclinical variant of BFSA or a new distinct epileptic syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eplepsyres.2007.12.017DOI Listing
March 2008

A pilot trial of levetiracetam in eyelid myoclonia with absences (Jeavons syndrome).

Epilepsia 2008 Mar 29;49(3):425-30. Epub 2008 Jan 29.

Epilepsy Center, Department of Neurological Sciences, Federico II University, Napoli, Italy.

Objective: Eyelid myoclonia with absences (EMA) or Jeavons syndrome characterized by eyelid myoclonia (EM) (with or without absences), eye closure-induced EEG paroxysms, and photosensitivity. We conducted an open-label trial of levetiracetam in EMA.

Patients And Methods: Patients were recruited in different Italian Epilepsy Centres. Levetiracetam was administrated at starting dose of 10 mg/kg/day up to 50-60 mg/kg/day in two doses. Treatment period included a 5-6 week up-titration phase and a 12-week evaluation phase. The number of days with EM (i.e., days with seizures, DwS) and number of generalized tonic-clonic seizures (GTCS) were evaluated. Analysis of intent-to-treat population was performed using Fisher's and Wilcoxon tests.

Results: Thirty-five patients (23 F) with a mean age of 19 +/- 6 years were recruited. Twenty-seven had previously undergone one to five adequate trials of antiepileptic drugs. The median number of DwS/month was 12 +/- 8.2. Twenty-one patients experienced GTCS (median number/month: 1 +/- 0.2). Thirty-four subjects completed the trial. Levetiracetam was well tolerated (mean dose: 1985 mg/day). Responders were 28/35 (80%) patients, nine taking levetiracetam as monotherapy. Six patients were seizure-free, 15 had > or =75% and seven >50% seizure reduction. GTCS remitted in 14 out of 21 (66.6%) patients. The number/month of DwS (median: 12 vs 5; p = 0.0001) and of GTCS (median: 1 vs 0; p = 0.0001) decreased compared to baseline period. Disappearance or clear reduction in paroxysmal abnormalities at eye closure occurred in 20 of the responders and photoparoxysmal response in 19. Mean follow-up was 23.9 +/- 18.5 months.

Conclusion: Levetiracetam is effective and well tolerated in EMA. Placebo-controlled studies should confirm these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1528-1167.2007.01524.xDOI Listing
March 2008

Impact of idiopathic epilepsy on mothers and fathers: strain, burden of care, worries and perception of vulnerability.

Epilepsia 2007 Sep 9;48(9):1810-1814. Epub 2007 Jun 9.

Department of Educational Sciences, University of Turin, ItalyEpilepsy Center, Department of Child Neuropsychiatry and Neurophysiology, Fatebenefratelli e Oftalmico Hospital, Milan, ItalyDepartment of Psychology, University of Milano-Bicocca, Milan, Italy.

The purpose of the study was to examine the impact of idiopathic epilepsy on mothers and fathers in terms of strain, burden of care, worries and perception of vulnerability. Data were collected and analyzed shortly after the diagnosis (T0) and 12 months later (T1). The results indicated that at T0 parents of children with epilepsy showed higher levels of worries and perception of vulnerability than controls; mothers sustained a greater burden of care and exhibited higher levels of strain than fathers. At T1, strain and perception of vulnerability decreased both for mothers and fathers, while burden of care and worries remained stable. At T0 and T1, strain was associated with parents' perception of vulnerability and anxiety for their children's future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1528-1167.2007.01145.xDOI Listing
September 2007

Linkage analysis and disease models in benign familial infantile seizures: a study of 16 families.

Epilepsia 2006 Jun;47(6):1029-34

Laboratory of Neurogenetics, Unit of Muscular and Neurodegenerative Disease, Istituto G. Gaslini, University of Genova, Genova, and Division of Neurology, Ospedale Pediatrico Bambino Gesù, Roma, Italy.

Purpose: Benign familial infantile seizures (BFIS) is a genetically heterogeneous condition characterized by partial seizures, onset age from 3 to 9 months, and favorable outcome. BFIS loci were identified on chromosomes 19q12-13.1 and 16p12-q12, allelic to infantile convulsions and choreathetosis. The identification of SCN2A mutations in families with only infantile seizures indicated that BFNIS and BFIS may show overlapping clinical features. Infantile seizures also were in a family with familial hemiplegic migraine and mutations in the ATP1A2 gene. We have examined the heterogeneous genetics of BFIS by means of linkage analysis.

Methods: Sixteen families were examined. Probands underwent neurologic examination, at least one EEG recording, and, when possible, brain CT and MRI. Clinical information about relatives was collected. Families with SCN2A or ATP1A2 mutations were excluded from the study. Chromosome 16p and 19q loci were examined by linkage analysis using two models that differed in penetrance rate. Genetic heterogeneity was evaluated with both models.

Results: Clinical information was available for 124 members of affected families. BFIS was diagnosed in 69 subjects. One patient without BFIS had a single febrile seizure, and another had rare episodes of paroxysmal dystonia. Evidence of linkage was obtained only for chromosome 16. Moreover, the high penetrance allowed the identification of genetic heterogeneity.

Conclusions: Our data confirm the relevance of the chromosome 16 locus in BFIS and suggest the presence of an additional locus. This study shows that the genetic model used affects the outcome of linkage analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1528-1167.2006.00521.xDOI Listing
June 2006

Congenital muscular dystrophy with muscle inflammation alpha dystroglycan glycosylation defect and no mutation in FKRP gene.

J Neurol Sci 2006 Apr 4;243(1-2):47-51. Epub 2006 Jan 4.

Centro Dino Ferrari, Dipartimento di Scienze Neurologiche, Unita' Operativa Neurologia, Fondazione I.R.C.C.S. Ospedale Maggiore Policlinico- Mangiagalli e Regina Elena, University of Milan, Milan, Italy.

Congenital muscular dystrophies (CMD) are autosomal recessive infantile disorders characterized by dystrophic changes at muscle biopsy and contractures. Central nervous system (CNS) abnormalities associated with mental retardation are often present. We describe a patient affected with muscle weakness, psychomotor developmental delay and normal brain MRI. Muscle biopsy showed complete absence of the alpha-dystroglycan (DG) glycosylated epitope and preservation of alpha-dystroglycan (alpha-DG) protein core. The analysis of FKRP, LARGE, POMT1 and POMGnT1 genes did not show any pathogenic mutations, suggesting that at least another gene may account for CMD with secondary glycosylated alpha-DG deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jns.2005.11.024DOI Listing
April 2006

Inter-rater reliability of the EEG reading in patients with childhood idiopathic epilepsy.

Epilepsy Res 2005 Aug-Sep;66(1-3):195-8

Child Neuropsychiatric Unit, University of Insubria, Macchi Foundation Hospital, Varese, Italy.

The level of agreement in the interpretation of EEG records by different experienced readers working in three child neurology tertiary centers has been evaluated. EEG recordings randomly chosen from patients with idiopathic epilepsy were included. Optimal or suboptimal agreement was found for presence of ictal and interictal discharges. Contrary to ictal discharges, the distribution and location of interictal discharges was not unanimously interpreted and agreement was unsatisfactory when assessing the background activity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eplepsyres.2005.07.004DOI Listing
January 2006

No evidence of GABRG2 mutations in severe myoclonic epilepsy of infancy.

Epilepsy Res 2003 Mar;53(3):196-200

Laboratory of Human Genetics, E O Ospedali Galliera, Genova, Italy.

Severe myoclonic epilepsy of infancy (SMEI) has been long suspected to have a genetic origin. Recently mutations in the gene encoding a voltage-gated alpha-1 sodium channel subunit-SCN1A-have been identified as a common cause of SMEI. Moreover, a mutation in the gene encoding the gamma2 subunit of the GABA(A) receptor-GABRG2-has been described in a GEFS+ family with a member affected by SMEI. In order to further investigate the role of GABRG2 in the pathogenesis of SMEI, we have screened for mutations 53 SMEI patients who resulted negative for SCN1A mutations. Mutational screening of GABRG2 genes was performed by denaturing high performance liquid chromatography (DHPLC) and direct sequencing of DNA fragments showing a variant chromatogram. Twenty-nine variant chromatograms were identified corresponding to seven different nucleotide variants. None of them leads to an amino acid change or obvious protein dysfunction. No difference in allele frequency was observed for the SMEI patients compared to a control population indicating that these variants are not involved in SMEI. Our study demonstrates that GABRG2 is not a commonly involved in the etiology of SMEI and suggests that other and yet unidentified genes are involved in the syndrome
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0920-1211(03)00022-6DOI Listing
March 2003

Early-onset occipital idiopathic epilepsy: a syndrome to be treated?

J Child Neurol 2003 Jan;18(1):72-4

Child Neuropsychiatry Department, Neurological Institute Casimiro Mondino Foundation IRCCS, University of Pavia, Italy.

The purpose of this study was to evaluate prognostic factors in early-onset childhood epilepsy with occipital paroxysms. We studied retrospectively a population of 46 patients, which was divided into three groups according to seizure frequency group 1, patients experiencing a single seizure (3396); group 2, patients experiencing two to six seizures (48%); and group 3, patients experiencing more than six seizures (20%). The mean follow-up period was about 5 years in the three groups. At the end of the first 6 months of this retrospective follow-up, the average number of seizures was higher in group 3 (2.9 seizures) than in groups 2 and 1 (1.8 and 1 seizure, respectively). We suggest that low seizure frequency in the first 6 months of follow-up could have prognostic value. We propose that the introduction of anti-epilepsy drugs be delayed for 6 months following epilepsy onset and be subsequently limited to patients with frequent seizure recurrence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/08830738030180011701DOI Listing
January 2003

Peripheral markers of the gamma-aminobutyric acid (GABA)ergic system in Angelman's syndrome.

J Child Neurol 2003 Jan;18(1):21-5

Scientific Institute Eugenio Medea, Bosisio Parini, Lecco, Italy.

It has recently been demonstrated that patients with Angelman's syndrome who exhibited a deletion on cytogenetic tests show more severe clinical pictures with drug-resistant epilepsy than patients with Angelman's syndrome not carrying the deletion. To verify if this difference in clinical severity can be attributed to genes for the three gamma-aminobutyric acid (GABA)A receptor subunits (GABRB3, GABRA5, GABRG3) located in the deleted region, a possible modification of peripheral markers of the GABAergic system was investigated in 12 subjects with Angelman's syndrome and 20 age-matched subjects (8 with idiopathic epilepsy and 12 not affected by neurologic diseases). The results confirmed a more severe clinical picture, and epilepsy syndrome in particular, in Angelman's syndrome patients with deletions versus patients without deletions. In contrast, biochemical study (based on dosage of plasma levels of GABA and diazepam binding inhibitor, an endogenous ligand of GABAA and peripheral benzodiazepine receptors, showed contradictory results: patients with Angelman's syndrome showed significantly higher levels of GABA and diazepam binding inhibitor than patients without neurologic impairment but significantly lower levels than epileptic controls.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/08830738030180010801DOI Listing
January 2003

Topiramate as add-on drug in severe myoclonic epilepsy in infancy: an Italian multicenter open trial.

Epilepsy Res 2002 Mar;49(1):45-8

Clinic of Child Neuropsychiatry, Department of Pediatrics, Second University of Naples, Via Pansini, 5, 80131, Napoli, Italy.

Purpose: This study was to evaluate the efficacy and safety of topiramate (TPM) in patients with severe myoclonic epilepsy in infancy (SMEI) and refractory seizures.

Methods: We performed a prospective multicentric open label add-on study in 18 patients (age 2-21 years, mean 9 years) with SMEI and refractory seizures of different types. TPM was added to one or two other baseline drugs and the efficacy was rated according to seizure type and frequency.

Results: TPM was initiated at a daily dose of 0.5-1 mg/kg, followed by a 2-week titration at increments of 1-3 mg/kg/24 h up to a maximum daily dose of 12 mg/kg. After a mean period of 11.9 months (range 2-24 months), three patients (16.7%) had 100% fewer seizures and ten patients (55.5%) had a more than 50% seizure decrease. In no patient there was a seizure worsening. Mild to moderate adverse events were present in four patients (22.2%), represented by weight loss, hypermenorrhoea, renal microlithiasis, nervousness and dysarthric speech.

Conclusion: TPM may be a useful drug in patients with SMEI, being particularly effective against generalized tonic-clonic seizures. Further studies are needed to evaluate the early use of this drug in such a severe syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/s0920-1211(02)00010-4DOI Listing
March 2002