Guido Rubboli

Guido Rubboli
Filadelfia/University of Copenhagen · Adult Neurology/Research Department

MD

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325
Publications
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Publications

Publications (325)
Article
Full-text available
Objective: Impulsivity is a multidimensional construct that can predispose to psychopathology. Meta-analysis demonstrates an association between response impulsivity and Juvenile Myoclonic Epilepsy (JME), a common genetic generalized epilepsy. Here, we test the hypotheses that trait impulsivity is (i) elevated in JME compared to controls; (ii) mode...
Article
We assessed the frequency of pediatric monogenic epilepsies and precision therapies at a tertiary epilepsy center. We analyzed medical records of children, born in 2006-2011 and followed at the Danish Epilepsy Center from January to December 2015; 357 patients were identified, of whom 27 without epilepsy and 35 with acquired brain damage were exclu...
Article
Objective The aim of the study was to determine risk factors associated with pseudoresistance in a large, representative cohort of patients with Idiopathic/Genetic Generalized Epilepsy (IGE) and the impact of pseudoresistance on socioeconomic parameters. Methods We performed a literature review on definitions of pseudoresistance in IGE. In an esta...
Preprint
Introductory Paragraph Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and epilepsy ¹⁻⁵ . We performed a genome-wide association, colocalization and pathway analysis of impulsivity in juvenile myoclonic epilepsy (JME). We identify genome-wide associated SNPs at 8q13.3 (p=7.5 × 10 ⁻⁹ ) and...
Article
Although epilepsy as a comorbidity in neurodegenerative disorders is increasingly recognized, its incidence is still underestimated and the features of epilepsy in the different neurodegenerative conditions are still poorly defined. Improved health care, resulting in increased longevity, will unavoidably lead to an increment of epilepsy cases in th...
Article
We report the association, not previously described, between trisomy 20/monosomy 18 and congenital bilateral perisylvian syndrome (CBPS), a condition featuring intellectual disability, epilepsy, oro-motor dysfunction and bilateral perisylvian polymicrogyria (BPP) in a 29-year-old individual. Detailed clinical evaluation, long-term EEG and EEG analy...
Article
Full-text available
Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile M...
Article
Objective This review article focuses on clinical and genetic features of paroxysmal neurological disorders featuring episodic ataxia (EA) and epilepsy and help clinicians recognize, diagnose, and treat patients with co-existing EA and epilepsy. It also provides an overview of genes and molecular mechanisms underlying these intriguing neurogenetic...
Article
Full-text available
Background and Objectives Purine-rich element-binding protein A ( PURA ) gene encodes Pur-α, a conserved protein essential for normal postnatal brain development. Recently, a PURA syndrome characterized by intellectual disability, hypotonia, epilepsy, and dysmorphic features was suggested. The aim of this study was to define and expand the phenotyp...
Article
Antiseizure medications (ASMs) should be tailored to individual characteristics, including seizure type, age, sex, comorbidities, co-medications, drug allergies, and child-bearing potential. We previously developed a web-based algorithm for patient-tailored ASM selection to assist healthcare professionals in prescribing medication using a decision...
Article
Developmental and epileptic encephalopathies are devastating disorders characterized by epilepsy, intellectual disability, and other neuropsychiatric symptoms, for which available treatments are largely ineffective. Following a precision medicine approach, we show for KCNA2-encephalopathy that the K+ channel blocker 4-aminopyridine can antagonize g...
Article
We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel NaV1.6, with the aim of describing clinical phenotypes related to functional effects. Six different clinical subgroups could be identified: 1) Benign familial infantile epil...
Article
Objective To develop and validate a pragmatic algorithm that classifies seizure types, to facilitate therapeutic decision-making. Methods Using a modified Delphi method, five experts developed a pragmatic classification of nine types of epileptic seizures or combinations of seizures that influence choice of medication, and constructed a simple alg...
Article
Full-text available
The high pace of gene discovery has resulted in thrilling advances in the field of epilepsy genetics. Clinical testing with comprehensive gene panels, exomes, or genomes are now increasingly available and have led to a significant higher diagnostic yield in early-onset epilepsies and enabled precision medicine approaches. These have been instrument...
Article
Variants in KCNT1, encoding a sodium-gated potassium channel (subfamily T member 1), have been associated with a spectrum of epilepsies and neurodevelopmental disorders. These range from familial autosomal dominant or sporadic sleep-related hypermotor epilepsy ((AD)SHE) to epilepsy of infancy with migrating focal seizures (EIMFS) and include develo...
Article
PRICKLE2 encodes a member of a highly conserved family of proteins that are involved in the non-canonical Wnt and planar cell polarity signaling pathway. Prickle2 localizes to the post-synaptic density, and interacts with post-synaptic density protein 95 and the NMDA receptor. Loss-of-function variants in prickle2 orthologs cause seizures in flies...
Article
Full-text available
The two aims of this study were (i) to describe and expand the phenotypic spectrum of PIGT deficiency in affected individuals harboring the c.1582G>A; p.Val528Met or the c.1580A > G; p.Asn527Ser variant in either homozygous or compound heterozygous state, and (ii) to identify potential genotype-phenotype correlations and any differences in disease...
Article
Objective Increased Motor Evoked Potential (MEP) polyphasia was recently described in idiopathic/genetic generalized epilepsy (IGE). Here, we studied the association of MEP polyphasia with treatment response and other clinical characteristics in patients with IGE. Methods MEPs were recorded from the biceps brachii, flexor carpi radialis and intero...
Article
Objective EEG source imaging (ESI) is a validated tool in the multimodal workup of patients with drug resistant focal epilepsy. However, it requires special expertise and it is underutilized. To circumvent this, automated analysis pipelines have been developed and validated for the interictal discharges. In this study, we present the clinical valid...
Preprint
Full-text available
We report detailed functional analyses and genotype-phenotype correlations in 433 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel NaV1.6. Five different clinical subgroups could be identified: 1) Benign familial infantile epilepsy (BFIE) (n=17, normal cognition, treatable seizures), 2) intermediate epi...
Article
Full-text available
Pathogenic variants in KCNA2, encoding for the voltage-gated potassium channel Kv1.2, have been identified as the cause for an evolving spectrum of neurological disorders. Affected individuals show early-onset developmental and epileptic encephalopathy, intellectual disability, and movement disorders resulting from cerebellar dysfunction. In additi...
Article
This study aimed at providing valid estimates for the risk of clinically relevant seizure aggravation by recommended anti-seizure medications in patients with Genetic Generalized Epilepsy (GGE). To this aim, treatment response, side effects and paradoxical reactions to anti-seizure treatment were retrospectively assessed in a near-population based...
Chapter
A wide spectrum of motor phenomena are associated with epileptic photosensitivity. In this chapter, we will give an overview of the most common clinical manifestations of epileptic photosensitivity focusing in particular on visually induced epileptic motor phenomena such as eyelid myoclonia with absences (EMA) and photic reflex myoclonus (PRM), pro...
Article
Objective Optimal choice of antiseizure medication (ASM) depends on seizure type, syndrome, age, gender, comorbidities and co‐medications. There are no fixed rules on how to weigh these factors; choices are subjective and experience‐driven. We investigated agreement among experts in selecting ASM as monotherapy and used their prevailing choices to...
Article
Full-text available
Objective Impulsivity is a multidimensional construct that can predispose to psychopathology. Meta‐analysis demonstrates an association between response impulsivity and Juvenile Myoclonic Epilepsy (JME), a common genetic generalized epilepsy. Here, we test the hypotheses that trait impulsivity is (i) elevated in JME compared to controls; (ii) mode...
Article
Objective Congenital disorder of glycosylation (CDG) due to a defective phosphatidylinositol glycan anchor biosynthesis class A protein (PIGA) is a severe X-linked developmental and epileptic encephalopathy. Seizures are often treatment refractory, and patients have intellectual disability and global developmental delay. Previous reports have sugge...
Article
Although the classic phenotype of episodic ataxia type 1 (EA1) caused by variants in KCNA1 includes episodic ataxia and myokymia, further genotype-phenotype correlations are difficult to establish due to highly heterogeneous clinical presentations associated with KCNA1 pathogenic variants. De novo variants in the paralogous Pro-Val-Pro motif (PVP)...
Article
Background In cases undergoing epilepsy surgery, postoperative psychogenic nonepileptic seizures (PNES) may be underdiagnosed complicating the assessment of postsurgical seizures' outcome and the clinical management. We conducted a survey to investigate the current practices in the European epilepsy monitoring units (EMUs) and the data that EMUs co...
Article
Background and purpose: Some epilepsy syndromes (sleep-related epilepsies, SREs) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life. Our purpose was to define the standard procedures for the diagnostic pathway of patients with possible SRE (...
Article
Background: Some epilepsy syndromes (sleep-related epilepsies [SRE]) have a strong link with sleep. Comorbid sleep disorders are common in patients with SRE and can exert a negative impact on seizure control and quality of life. Purposes: To define the standard procedures for the diagnostic pathway of patients with possible SRE (scenario 1) and the...
Article
Objective To determine pattern of treatment response in patients with idiopathic generalized epilepsy (IGE) and whether routinely assessed clinical and neurophysiological parameters allow predicting response to lamotrigine, levetiracetam or valproic acid. Methods In 328 adult patients with IGE, demographic data, imaging, electroencephalography dat...
Article
Full-text available
Idiopathic or genetic generalized epilepsies (IGE) constitute an electroclinically well-defined group that accounts for almost one third of all people with epilepsy. They consist of four well-established syndromes and some other rarer phenotypes. The main four IGEs are juvenile myoclonic epilepsy, childhood absence epilepsy, juvenile absence epilep...
Article
Full-text available
Objective To test the hypothesis that absence seizures can evolve to generalized tonic-clonic seizures, we documented electro-clinical features of this novel seizure type. Methods In 4 large video-EEG databases, we identified recordings of seizures starting with impaired awareness and that, without returning to baseline interictal state, evolved t...
Article
Objective Antiseizure medications (ASMs) are the first‐line treatment for epilepsy. Many ASMs are available; this offers the opportunity to improve therapy by tailoring it to individual characteristics, but also increases the possibility of healthcare professionals making inappropriate treatment choices. To assist healthcare professionals, we devel...
Article
Objective Although the genetic origin of Idiopathic/Genetic Generalized Epilepsy (IGE) is hardly disputed, only a minority of patients show Mendelian inheritance. We here questioned if clinical characteristics like long-term outcome and treatment response differ between patients with sporadic and familial IGE. Methods In a near-population based co...
Article
Objective Genetic testing has become a routine part of the diagnostic workup in children with early onset epilepsies. In the present study, we sought to investigate a cohort of adult patients with epilepsy, to determinate the diagnostic yield and explore the gain of personalized treatment approaches in adult patients. Methods Two hundred patients...
Article
Full-text available
Congenital disorders of glycosylation are a growing group of rare genetic disorders caused by deficient protein and lipid glycosylation. Here, we report the clinical, biochemical, and molecular features of seven patients from four families with GALNT2-congenital disorder of glycosylation (GALNT2-CDG), an O-linked glycosylation disorder. GALNT2 enco...
Article
Objective to investigate the clinical and EEG features of Encephalopathy with Status Epilepticus during slow Sleep (ESES) related to CNKSR2 pathogenic variants. Methods detailed clinical history, repeated wakefulness/overnight sleep EEGs, brain MRI were collected in five patients, including one female, with CNKSR2-related ESES. Results neurodevel...
Article
Full-text available
Objective: The study is aimed at widening the clinical and genetic spectrum and at assessing genotype-phenotype associations in QARS encephalopathy. Methods: Through diagnostic gene panel screening in an epilepsy cohort, and recruiting through GeneMatcher and our international network, we collected 10 patients with biallelic QARS variants. In ad...
Article
Background: Drug resistant idiopathic generalized epilepsy (IGE) remains challenging despite a favorable overall prognosis of IGE and little is known about basic epidemiology and long-term outcome of drug resistant IGE. We aimed at describing the incidence, prevalence, and outcome of IGE in an unbiased, population-based cohort. Methods: In 2014-...
Article
Objective: Monoallelic de novo gain-of-function variants in the voltage-gated sodium channel SCN8A are one of the recurrent causes of severe developmental and epileptic encephalopathy (DEE). In addition, a small number of de novo or inherited monoallelic loss-of-function variants have been found in patients with intellectual disability, autism spe...
Article
Objective: The objective of the study was to investigate electroclinical and neuropsychological features, genetic background, and evolution of children with idiopathic encephalopathy with status epilepticus during slow sleep (ESES), including Landau-Kleffner syndrome (LKS). Material and methods: All children diagnosed with idiopathic ESES at the...
Article
Objective: To investigate the diagnostic added value of electrical source imaging (ESI) in presurgical evaluation of patients with drug resistant focal epilepsy. Methods: Eighty-two consecutive patients were included. We analyzed both low density (LD) and high density (HD) EEG recordings. LD ESI was done on interictal and ictal signals recorded...
Article
Background To date, source imaging (SI) has been performed using epileptiform discharges (ED) detected by magnetoencephalography (MEG) or electroencephalography (EEG). A few case studies has combined MEG and EEG recordings and performed electromagnetic source imaging (cEMSI). This study tries to elucidate the role of cEMSI in presurgical evaluation...
Poster
Full-text available
Purpose The de novo development of PNEA has been described after brain surgery [1]. De novo psychogenic non-epileptic attacks (PNEA) after epilepsy surgery has an estimated incidence of 1.8% to 8.8% [2,3] and is not well studied. This is a European multicenter retrospective cohort study to record patients with de novo psychogenic non-epileptic atta...
Article
We present some aspects relevant to the definition and diagnosis of Encephalopathy related to Status Epilepticus during slow Sleep (ESES) to further understand the pathophysiological mechanisms in the light of current knowledge and some recent research. Future lines of research in ESES that include investigation of impairment of sleep homeostasis a...
Article
Encephalopathy related to Status Epilepticus during slow Sleep (ESES) is a childhood epilepsy syndrome characterized by appearance of cognitive and behavioural disturbances in conjunction with a striking activation of EEG epileptic abnormalities during sleep. The link between the extreme amount of epileptic discharges during sleep and the deteriora...
Article
Encephalopathy related to Status Epilepticus during slow Sleep (ESES) is a peculiar electro-clinical condition, with variable etiologies, characterized by an age-dependent phenomenon of extreme activation of epileptic activity during sleep, i.e. "status epilepticus during sleep", that is strictly associated with the appearance of cognitive and beha...
Chapter
Focal epilepsies include the most common epilepsy types in adults, and the role of EEG in the diagnosis and classification of these epilepsies is well established. In this chapter we provide an overview of non-age-related focal epilepsies classified according to localization criteria, that is, temporal, frontal, occipital, and parietal lobe epileps...
Chapter
The term polygraphy refers to the simultaneous recording of multiple physiologic measures. The main aim of polygraphic monitoring is to correlate behavioral manifestations with changes occurring in a set of physiologic parameters. In epileptology, polygraphic investigations complemented with simultaneous video recording and computerized back-averag...
Article
Pathogenic variants in KCNT1 represent an important cause of treatment-resistant epilepsy, for which an effective therapy has been elusive. Reports about the effectiveness of quinidine, a candidate precision therapy, have been mixed. We sought to evaluate the treatment responsiveness of patients with KCNT1-related epilepsy. We performed an observat...
Article
OBJECTIVE: Pathogenic variants in SCN8A have been associated with a wide spectrum of epilepsy phenotypes, ranging from benign familial infantile seizures (BFIS) to epileptic encephalopathies with variable severity. Furthermore, a few patients with intellectual disability (ID) or movement disorders without epilepsy have been reported. The vast major...
Article
Introduction: Within the last decade, next generation sequencing (NGS) has resulted in remarkable advances in the field of epilepsy genetics. NGS has become a routine part of the diagnostic workup in many countries. A workup that has led to higher diagnostic yields and insights into the underlying disease mechanisms. Areas covered: In this review,...
Article
Full-text available
Objective: To determine the diagnostic accuracy and clinical utility of electromagnetic source imaging (EMSI) in presurgical evaluation of patients with epilepsy. Methods: We prospectively recorded magnetoencephalography (MEG) simultaneously with EEG and performed EMSI, comprising electric source imaging, magnetic source imaging, and analysis of...
Article
Full-text available
Mutations in the sodium‐activated potassium channel gene KCNT1 have been associated with nonlesional sleep‐related hypermotor epilepsy (SHE). We report the co‐occurrence of mild malformation of cortical development (mMCD) and KCNT1 mutations in four patients with SHE. Focal cortical dysplasia type I was neuropathologically diagnosed after epilepsy...
Article
The original version of this article contained an error in the spelling of the author Erik H. Niks, which was incorrectly given as Erik Niks. This has now been corrected in both the PDF and HTML versions of the article.
Article
Objective: To evaluate the accuracy of automated EEG source imaging (ESI) in localizing epileptogenic zone. Methods: Long-term EEG, recorded with the standard 25-electrode array of the IFCN, from 41 consecutive patients with focal epilepsy who underwent resective surgery, were analyzed blinded to the surgical outcome. The automated analysis comp...
Article
Objective: To delineate the electroclinical features of SCN8A infantile developmental and epileptic encephalopathy (EIEE13, OMIM #614558). Methods: Twenty-two patients, aged 19 months to 22 years, underwent electroclinical assessment. Results: Sixteen of 22 patients had mildly delayed development since birth. Drug-resistant epilepsy started at...
Article
Full-text available
The original version of this Article contained an error in the author list where the corresponding author Stéphanie Baulac was repeated twice. This has now been corrected in the HTML, the PDF was correct at the time of publication.
Article
Full-text available
Purpose: To define the phenotypic and mutational spectrum of epilepsies related to DEPDC5, NPRL2 and NPRL3 genes encoding the GATOR1 complex, a negative regulator of the mTORC1 pathway METHODS: We analyzed clinical and genetic data of 73 novel probands (familial and sporadic) with epilepsy-related variants in GATOR1-encoding genes and proposed new...