elena gardella - Academia.edu (original) (raw)

Papers by elena gardella

Zonisamide was used as an add-on drug in 25 non-obese patients with drug resistant epilepsy. Afte... more Zonisamide was used as an add-on drug in 25 non-obese patients with drug resistant epilepsy. After 3-month follow-up patients had seizures' reduction and the body weight was apparently unchanged. We also found a decrease of the anxiety levels and an increase of Quality of Life values. Our data are preliminary; we have to complete our protocol to confirm these findings

Zonisamide was used as an add-on drug in 25 non-obese patients with drug resistant epilepsy. Afte... more Zonisamide was used as an add-on drug in 25 non-obese patients with drug resistant epilepsy. After 3-month follow-up patients had seizures\u2019 reduction and the body weight was apparently unchanged. We also found a decrease of the anxiety levels and an increase of Quality of Life values. Our data are preliminary; we have to complete our protocol to confirm these findings

Epileptic disorders : international epilepsy journal with videotape, 2011

Patients with Down syndrome are now living longer and the overall prevalence of epilepsy is incre... more Patients with Down syndrome are now living longer and the overall prevalence of epilepsy is increasing, however, full characterisation of epilepsy in adult age is still incomplete. We describe the electroclinical characteristics of epilepsy in 22 adult patients with Down syndrome (11 males, 11 females), with a mean age of 46 years (range: 28-64 years), followed at the Epilepsy Centre, San Paolo Hospital in Milan. Mean age at epilepsy onset was 36.8 years (range: 6-60 years). Nine out of 22 patients had focal epilepsy, while nine had late-onset myoclonic epilepsy. In four patients, epilepsy was unclassified. The EEG pattern of our patients was characterised by a progressive slowing of the background activity with sharp-and-slow waves with frontal predominance. In the patients diagnosed with late-onset myoclonic epilepsy, the EEGs showed generalised polyspike waves. Three subjects had an episode of myoclonic status epilepticus at the beginning or in the course of the disorder. After t...

Epilepsy & Behavior, 2011

Neurology, Sep 12, 2016

To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients ... more To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations. Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analysis of 4 selected mutations was performed using the Xenopus laevis oocyte expression system. The study included 16 novel probands and 3 additional family members with a disease-causing mutation in the GABRA1 gene. The phenotypic spectrum varied from unspecified epilepsy (1), juvenile myoclonic epilepsy (2), photosensitive idiopathic generalized epilepsy (1), and generalized epilepsy with febrile seizures plus (1) to severe epileptic encephalopathies (11). In the epileptic encephalopathy group, the patients had seizures beginning between the first day of life and 15 months, with a mean of 7 months. Predominant seizure types in all patients were tonic-clonic in 9 participants (56%) and myoclonic seizures in 5 (31...

Neurological Sciences, 2005

Epilepsia, Feb 8, 2018

Pathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MA... more Pathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in a larger cohort of SCL6A1-mutated patients. We collected 24 SLC6A1 probands and 6 affected family members. Four previously published cases were included for further electroclinical description. In total, we reviewed the electroclinical data of 34 subjects. Cognitive development was impaired in 33/34 (97%) subjects; 28/34 had mild to moderate ID, with language impairment being the most common feature. Epilepsy was diagnosed in 31/34 cases with mean onset at 3.7 years. Cognitive assessment before epilepsy onset was available in 24/31 subjects and was normal in 25% (6/24), and consistent with mild ID in 46% (11/24) or moderate ID in 17% (4/24). Two patients had speech delay only, and 1 had severe ID. After epilepsy onset, cognition deteriorated in 46% (11/24) of cases. The most common seizure types were abs...

Annals of Neurology, 2016

main phenotypes are recognized. PKD, the most frequent form, features brief (seconds to minutes) ... more main phenotypes are recognized. PKD, the most frequent form, features brief (seconds to minutes) attacks of dystonia or chorea precipitated by sudden movement, or acceleration of ongoing movement. Proline-rich transmembrane protein 2 (PRRT2) gene mutations are the most common cause, although there is some clinicogenetic heterogeneity. The five individuals reported as having PKD differ significantly with regard to nature and precipitants of attacks, and the fact that one had altered level of consciousness. Three patients had generalized “shivering attacks” triggered by emotional stimuli, which is not a recognized manifestation of paroxysmal dyskinesias neither by phenomenology nor by trigger. The triggers in the 2 other patients with attacks of hemidystonia or choreoathetosis of the legs were prolonged stretching of the limbs and “voluntary movements.” We acknowledge that “sudden whole body activity, like standing-up, or initiation of walking” were also named as precipitants, but it appears that, mostly, the “kinesigenic” element is lacking. Last, the index case thought to have classical PKD had impaired consciousness during all events with an overt ictal electroencephalogram correlate. Thus, from a movement disorders specialists view, these do not constitute classic PKD and we think the readership should be aware of this. The identification of other cases may help to further delineate the spectrum of paroxysmal attacks associated with the new SCN8A mutations, and if they should be indeed be ranked among the classic paroxysmal dyskinesias or maybe be considered as epileptic events. We did not detect any pathogenic variant in SCN8A screening by whole-exome sequencing our cohort of well-defined cases with paroxysmal dyskinesias (9 PKD, 5 paroxysmal nonkinesigenic dyskinesia, and 3 paroxysmal exercise-induced dyskinesia) negative for mutations in PRRT2, myofibrillogenesis regulator 1 (MR-1), or glucose transporter 1 (SCL2A1), respectively. Furthermore, none of our 72 patients with paroxysmal dyskinesias attributed to PRRT2, MR-1, or SCL2A1 gene mutations had shivering attacks, and it is possible that this may be a clinical feature particular to SCN8A mutations.

Seizure-european Journal of Epilepsy, 2011

PurposeIdiopathic generalized epilepsies (IGE) are age-related epileptic syndromes mainly describ... more PurposeIdiopathic generalized epilepsies (IGE) are age-related epileptic syndromes mainly described in children and adolescence. Our aim is to describe their electroclinical features in the elderly.

Neurology, Jan 12, 2016

To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients ... more To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations. Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analysis of 4 selected mutations was performed using the Xenopus laevis oocyte expression system. The study included 16 novel probands and 3 additional family members with a disease-causing mutation in the GABRA1 gene. The phenotypic spectrum varied from unspecified epilepsy (1), juvenile myoclonic epilepsy (2), photosensitive idiopathic generalized epilepsy (1), and generalized epilepsy with febrile seizures plus (1) to severe epileptic encephalopathies (11). In the epileptic encephalopathy group, the patients had seizures beginning between the first day of life and 15 months, with a mean of 7 months. Predominant seizure types in all patients were tonic-clonic in 9 participants (56%) and myoclonic seizures in 5 (31...

Neurological Sciences, 2005

Epileptic disorders : international epilepsy journal with videotape, 2001

We investigated the electroclinical features of 12 patients with childhood absence epilepsy (CAE)... more We investigated the electroclinical features of 12 patients with childhood absence epilepsy (CAE), presenting with typical absence seizures associated with myoclonic manifestations of the face or neck. All patients underwent repeated and prolonged split-screen video-polygraphic EEG recordings. The polygraphic recordings and clinical correlations of the absence seizures were analysed. All patients presented with multi-quotidian, typical absence seizures. During the absences, the patients could show mild, rhythmic, myoclonic jerks involving facial areas (eyebrows, nostrils, perioral region, chin) or neck muscles (sternocleidomastoideus), with the same frequency as the spike-wave complexes. Polygraphic tracings demonstrated that the myoclonias were correlated to the spike component. Clinically, all patients showed a benign course, with complete seizure control under antiepileptic treatment. In the follow-up, 7 patients withdrew from treatment without relapse. We conclude that all our p...

Functional neurology

Encephalopathy with status epilepticus during sleep (ESES) is an age-related disorder characteriz... more Encephalopathy with status epilepticus during sleep (ESES) is an age-related disorder characterized by neuropsychological regression, epilepsy and a typical EEG pattern of continuous epileptiform activity (> 85%) during NREM sleep. Cases of worsening or induction of ESES with phenytoin, carbamazepine and phenobarbital have been reported. We describe a child with benign epilepsy with centrotemporal spikes (BECTS) in whom treatment with oxcarbazepine (OXC) induced ESES. The patient was studied through repeated clinical-neuropsychological evaluations and 24-hour EEG recordings. He was treated with OXC two months after epilepsy onset. One month after starting OXC, he developed an abrupt and severe cognitive deterioration. A 24-hour EEG and neuropsychological tests showed an electroclinical picture compatible with ESES. Withdrawal of OXC and introduction of other drugs were followed by a prompt improvement. Five months after ESES onset, a 24-hour EEG was normal. Our report indicates t...

Annals of neurology, Jan 17, 2015

Benign familial infantile seizures (BFIS), paroxysmal kinesigenic dyskinesia (PKD), and their com... more Benign familial infantile seizures (BFIS), paroxysmal kinesigenic dyskinesia (PKD), and their combination - known as infantile convulsions and paroxysmal choreoathetosis (ICCA) - are related autosomal dominant diseases. PRRT2 (proline-rich transmembrane protein 2 gene) has been identified as the major gene in all three conditions, found to be mutated in 80-90% of familial and 30-35% of sporadic cases. We searched for the genetic defect in PRRT2-negative, unrelated families with BFIS or ICCA using whole exome or targeted gene panel sequencing, and performed a detailed clinico-neurophysiological workup. In three families with a total of 16 affected members, we identified the same, co-segregating heterozygous missense mutation (c.4447G>A; p.E1483K) in SCN8A, encoding a voltage-gated sodium channel. A founder effect was excluded by linkage analysis. All individuals but one had normal cognitive and motor milestones, neuroimaging and interictal neurological status. Fifteen affected mem...

Zonisamide was used as an add-on drug in 25 non-obese patients with drug resistant epilepsy. Afte... more Zonisamide was used as an add-on drug in 25 non-obese patients with drug resistant epilepsy. After 3-month follow-up patients had seizures' reduction and the body weight was apparently unchanged. We also found a decrease of the anxiety levels and an increase of Quality of Life values. Our data are preliminary; we have to complete our protocol to confirm these findings

Zonisamide was used as an add-on drug in 25 non-obese patients with drug resistant epilepsy. Afte... more Zonisamide was used as an add-on drug in 25 non-obese patients with drug resistant epilepsy. After 3-month follow-up patients had seizures\u2019 reduction and the body weight was apparently unchanged. We also found a decrease of the anxiety levels and an increase of Quality of Life values. Our data are preliminary; we have to complete our protocol to confirm these findings

Epileptic disorders : international epilepsy journal with videotape, 2011

Patients with Down syndrome are now living longer and the overall prevalence of epilepsy is incre... more Patients with Down syndrome are now living longer and the overall prevalence of epilepsy is increasing, however, full characterisation of epilepsy in adult age is still incomplete. We describe the electroclinical characteristics of epilepsy in 22 adult patients with Down syndrome (11 males, 11 females), with a mean age of 46 years (range: 28-64 years), followed at the Epilepsy Centre, San Paolo Hospital in Milan. Mean age at epilepsy onset was 36.8 years (range: 6-60 years). Nine out of 22 patients had focal epilepsy, while nine had late-onset myoclonic epilepsy. In four patients, epilepsy was unclassified. The EEG pattern of our patients was characterised by a progressive slowing of the background activity with sharp-and-slow waves with frontal predominance. In the patients diagnosed with late-onset myoclonic epilepsy, the EEGs showed generalised polyspike waves. Three subjects had an episode of myoclonic status epilepticus at the beginning or in the course of the disorder. After t...

Epilepsy & Behavior, 2011

Neurology, Sep 12, 2016

To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients ... more To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations. Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analysis of 4 selected mutations was performed using the Xenopus laevis oocyte expression system. The study included 16 novel probands and 3 additional family members with a disease-causing mutation in the GABRA1 gene. The phenotypic spectrum varied from unspecified epilepsy (1), juvenile myoclonic epilepsy (2), photosensitive idiopathic generalized epilepsy (1), and generalized epilepsy with febrile seizures plus (1) to severe epileptic encephalopathies (11). In the epileptic encephalopathy group, the patients had seizures beginning between the first day of life and 15 months, with a mean of 7 months. Predominant seizure types in all patients were tonic-clonic in 9 participants (56%) and myoclonic seizures in 5 (31...

Neurological Sciences, 2005

Epilepsia, Feb 8, 2018

Pathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MA... more Pathogenic SLC6A1 variants were recently described in patients with myoclonic atonic epilepsy (MAE) and intellectual disability (ID). We set out to define the phenotypic spectrum in a larger cohort of SCL6A1-mutated patients. We collected 24 SLC6A1 probands and 6 affected family members. Four previously published cases were included for further electroclinical description. In total, we reviewed the electroclinical data of 34 subjects. Cognitive development was impaired in 33/34 (97%) subjects; 28/34 had mild to moderate ID, with language impairment being the most common feature. Epilepsy was diagnosed in 31/34 cases with mean onset at 3.7 years. Cognitive assessment before epilepsy onset was available in 24/31 subjects and was normal in 25% (6/24), and consistent with mild ID in 46% (11/24) or moderate ID in 17% (4/24). Two patients had speech delay only, and 1 had severe ID. After epilepsy onset, cognition deteriorated in 46% (11/24) of cases. The most common seizure types were abs...

Annals of Neurology, 2016

main phenotypes are recognized. PKD, the most frequent form, features brief (seconds to minutes) ... more main phenotypes are recognized. PKD, the most frequent form, features brief (seconds to minutes) attacks of dystonia or chorea precipitated by sudden movement, or acceleration of ongoing movement. Proline-rich transmembrane protein 2 (PRRT2) gene mutations are the most common cause, although there is some clinicogenetic heterogeneity. The five individuals reported as having PKD differ significantly with regard to nature and precipitants of attacks, and the fact that one had altered level of consciousness. Three patients had generalized “shivering attacks” triggered by emotional stimuli, which is not a recognized manifestation of paroxysmal dyskinesias neither by phenomenology nor by trigger. The triggers in the 2 other patients with attacks of hemidystonia or choreoathetosis of the legs were prolonged stretching of the limbs and “voluntary movements.” We acknowledge that “sudden whole body activity, like standing-up, or initiation of walking” were also named as precipitants, but it appears that, mostly, the “kinesigenic” element is lacking. Last, the index case thought to have classical PKD had impaired consciousness during all events with an overt ictal electroencephalogram correlate. Thus, from a movement disorders specialists view, these do not constitute classic PKD and we think the readership should be aware of this. The identification of other cases may help to further delineate the spectrum of paroxysmal attacks associated with the new SCN8A mutations, and if they should be indeed be ranked among the classic paroxysmal dyskinesias or maybe be considered as epileptic events. We did not detect any pathogenic variant in SCN8A screening by whole-exome sequencing our cohort of well-defined cases with paroxysmal dyskinesias (9 PKD, 5 paroxysmal nonkinesigenic dyskinesia, and 3 paroxysmal exercise-induced dyskinesia) negative for mutations in PRRT2, myofibrillogenesis regulator 1 (MR-1), or glucose transporter 1 (SCL2A1), respectively. Furthermore, none of our 72 patients with paroxysmal dyskinesias attributed to PRRT2, MR-1, or SCL2A1 gene mutations had shivering attacks, and it is possible that this may be a clinical feature particular to SCN8A mutations.

Seizure-european Journal of Epilepsy, 2011

PurposeIdiopathic generalized epilepsies (IGE) are age-related epileptic syndromes mainly describ... more PurposeIdiopathic generalized epilepsies (IGE) are age-related epileptic syndromes mainly described in children and adolescence. Our aim is to describe their electroclinical features in the elderly.

Neurology, Jan 12, 2016

To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients ... more To delineate phenotypic heterogeneity, we describe the clinical features of a cohort of patients with GABRA1 gene mutations. Patients with GABRA1 mutations were ascertained through an international collaboration. Clinical, EEG, and genetic data were collected. Functional analysis of 4 selected mutations was performed using the Xenopus laevis oocyte expression system. The study included 16 novel probands and 3 additional family members with a disease-causing mutation in the GABRA1 gene. The phenotypic spectrum varied from unspecified epilepsy (1), juvenile myoclonic epilepsy (2), photosensitive idiopathic generalized epilepsy (1), and generalized epilepsy with febrile seizures plus (1) to severe epileptic encephalopathies (11). In the epileptic encephalopathy group, the patients had seizures beginning between the first day of life and 15 months, with a mean of 7 months. Predominant seizure types in all patients were tonic-clonic in 9 participants (56%) and myoclonic seizures in 5 (31...

Neurological Sciences, 2005

Epileptic disorders : international epilepsy journal with videotape, 2001

We investigated the electroclinical features of 12 patients with childhood absence epilepsy (CAE)... more We investigated the electroclinical features of 12 patients with childhood absence epilepsy (CAE), presenting with typical absence seizures associated with myoclonic manifestations of the face or neck. All patients underwent repeated and prolonged split-screen video-polygraphic EEG recordings. The polygraphic recordings and clinical correlations of the absence seizures were analysed. All patients presented with multi-quotidian, typical absence seizures. During the absences, the patients could show mild, rhythmic, myoclonic jerks involving facial areas (eyebrows, nostrils, perioral region, chin) or neck muscles (sternocleidomastoideus), with the same frequency as the spike-wave complexes. Polygraphic tracings demonstrated that the myoclonias were correlated to the spike component. Clinically, all patients showed a benign course, with complete seizure control under antiepileptic treatment. In the follow-up, 7 patients withdrew from treatment without relapse. We conclude that all our p...

Functional neurology

Encephalopathy with status epilepticus during sleep (ESES) is an age-related disorder characteriz... more Encephalopathy with status epilepticus during sleep (ESES) is an age-related disorder characterized by neuropsychological regression, epilepsy and a typical EEG pattern of continuous epileptiform activity (> 85%) during NREM sleep. Cases of worsening or induction of ESES with phenytoin, carbamazepine and phenobarbital have been reported. We describe a child with benign epilepsy with centrotemporal spikes (BECTS) in whom treatment with oxcarbazepine (OXC) induced ESES. The patient was studied through repeated clinical-neuropsychological evaluations and 24-hour EEG recordings. He was treated with OXC two months after epilepsy onset. One month after starting OXC, he developed an abrupt and severe cognitive deterioration. A 24-hour EEG and neuropsychological tests showed an electroclinical picture compatible with ESES. Withdrawal of OXC and introduction of other drugs were followed by a prompt improvement. Five months after ESES onset, a 24-hour EEG was normal. Our report indicates t...

Annals of neurology, Jan 17, 2015

Benign familial infantile seizures (BFIS), paroxysmal kinesigenic dyskinesia (PKD), and their com... more Benign familial infantile seizures (BFIS), paroxysmal kinesigenic dyskinesia (PKD), and their combination - known as infantile convulsions and paroxysmal choreoathetosis (ICCA) - are related autosomal dominant diseases. PRRT2 (proline-rich transmembrane protein 2 gene) has been identified as the major gene in all three conditions, found to be mutated in 80-90% of familial and 30-35% of sporadic cases. We searched for the genetic defect in PRRT2-negative, unrelated families with BFIS or ICCA using whole exome or targeted gene panel sequencing, and performed a detailed clinico-neurophysiological workup. In three families with a total of 16 affected members, we identified the same, co-segregating heterozygous missense mutation (c.4447G>A; p.E1483K) in SCN8A, encoding a voltage-gated sodium channel. A founder effect was excluded by linkage analysis. All individuals but one had normal cognitive and motor milestones, neuroimaging and interictal neurological status. Fifteen affected mem...