bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotypes of children with 20q13.3 microdeletion affecting KCNQ2 and CHRNA4
Authors: Okumura Akihisa , Ishii Atsushi , Shimojima Keiko , Kurahashi Hirokazu , Yoshitomi Shinsaku , Imai Katsumi , Imamura Mari , Seki Yuko , Shimizu Toshiaki , Hirose Shinichi , Yamamoto Toshiyuki 
Published: August 2019

AbstractIn order to clarify the phenotypes of 20q13.33 microdeletion, clinical manifestations and genetic findings from four patients are discussed in relation to chromosomal microdeletions at 20q13.33. All patients had epileptic seizures mostly beginning within the neonatal period and disappearing by 4 months of age, similar to epilepsy phenotypes of benign familial neonatal seizures. We performed array comparative genomic hybridization analysis in order to investigate the chromosomal aberration. Developmental outcome was good in two patients with deletion restricted to three genes (CHRNA4, KCNQ2, and COL20A1), whereas delay in developmental milestones was observed in the other two with a wider range of deletion. Information obtained from array comparative genomic hybridization may be useful to predict seizure and developmental outcome, however, there is no distinctive pattern of abnormalities that would arouse clinical suspicion of a 20q13.33 microdeletion. Deletion of KCNQ2 and CHRNA4 does not appear to affect seizure phenotype. Molecular cytogenetic techniques, such as array comparative genomic hybridization, will be necessary to clarify the relationship between phenotypes and individual genes within this region.
Seizure ending signs in patients with dyscognitive focal seizures*
Authors: Gavvala Jay R. , Gerard Elizabeth E. , Macken Mícheál , Schuele Stephan U. 
Published: August 2019

AbstractAim. Signs indicating the end of a focal seizure with loss of awareness and/or responsiveness but without progression to focal or generalized motor symptoms are poorly defined and can be difficult to determine. Not recognizing the transition from ictal to postictal behaviour can affect seizure reporting accuracy by family members and may lead to delayed or a lack of examination during EEG monitoring, erroneous seizure localization and inadequate medical intervention for prolonged seizure duration.Methods. Our epilepsy monitoring unit database was searched for focal seizures without secondary generalization for the period from 2007 to 2011. The first focal seizure in a patient with loss of awareness and/or responsiveness and/or behavioural arrest, with or without automatisms, was included. Seizures without objective symptoms or inadequate video‐EEG quality were excluded.Results. A total of 67 patients were included, with an average age of 41.7 years. Thirty‐six of the patients had seizures from the left hemisphere and 29 from the right. All patients showed an abrupt change in motor activity and resumed contact with the environment as a sign of clinical seizure ending. Specific ending signs (nose wiping, coughing, sighing, throat clearing, or laughter) were seen in 23 of 47 of temporal lobe seizures and 7 of 20 extra‐temporal seizures.Conclusions. Seizure ending signs are often subtle and the most common finding is a sudden change in motor activity and resumption of contact with the environment. More distinct signs, such as nose wiping, coughing or throat clearing, are not specific to temporal lobe onset. A higher proportion of seizures during sleep went unexamined, compared to those during wakefulness. This demonstrates that seizure semiology can be very subtle and arousals from sleep during monitoring should alert staff. Patient accounts of seizure frequency appear to be unreliable and witness reports need to be taken into account. [Published with video sequences]
Epileptic spasms: a previously unreported manifestation of WDR45 gene mutation
Authors: Xixis Kathryn I , Mikati Mohamad A 
Published: August 2019

AbstractWDR45 mutations cause neurodegeneration with brain iron accumulation, usually presenting with early childhood developmental delay and followed by early adulthood extrapyramidal symptoms. Although various seizure types may occur, epileptic spasms have not been reported for this disease. Our patient initially developed a prolonged, focal‐onset seizure at three months of age and was subsequently noted to have psychomotor delay. At 11 months of age, she developed epileptic spasms. Her EEG showed hypsarrhythmia. An extensive neurogenetic workup and brain MRI, revealing normal data, ruled out other detectable causes of epileptic spasms. Whole‐exome sequencing revealed a de novo, heterozygous deleterious mutation c.400C>T (p.R13X) in WDR45, previously reported to be disease‐causing and associated with early childhood global developmental delay and seizures other than epileptic spasms. We conclude that WDR45 mutations should be considered as a possible aetiology in infants with early‐onset focal seizures and/or in otherwise undiagnosed cases of epileptic spasms.
Oral clomethiazole treatment for paediatric non‐convulsive status epilepticus
Authors: Das Darshan , Varadkar Sophia , Das Krishna B 
Published: August 2019

AbstractWe report a retrospective case study of the use of clomethiazole for treatment of non‐convulsive status epilepticus in a patient not responding to benzodiazepines, illustrated by EEG and video. Clomethiazole can be considered as a safe oral option for management of non‐convulsive status epilepticus when conventional treatment has failed. [Published with video sequences online]
Characteristic phasic evolution of convulsive seizure in PCDH19‐related epilepsy
Authors: Ikeda Hiroko , Imai Katsumi , Ikeda Hitoshi , Shigematsu Hideo , Takahashi Yukitoshi , Inoue Yushi , Higurashi Norimichi , Hirose Shinichi 
Published: August 2019

AbstractPCDH19‐related epilepsy is a genetic disorder that was first described in 1971, then referred to as “epilepsy and mental retardation limited to females”. PCDH19 has recently been identified as the responsible gene, but a detailed characterization of the seizure manifestation based on video‐EEG recording is still limited. The purpose of this study was to elucidate features of the seizure semiology in children with PCDH19‐related epilepsy. To do this, ictal video‐EEG recordings of 26 convulsive seizures in three girls with PCDH19‐related epilepsy were analysed. All seizures occurred in clusters, mainly during sleep accompanied by fever. The motor manifestations consisted of six sequential phases: “jerk”, “reactive”, “mild tonic”, “fluttering”, “mild clonic”, and “postictal”. Some phases were brief or lacking in some seizures, whereas others were long or pronounced. In the reactive phase, the patients looked fearful or startled with sudden jerks and turned over reactively. The tonic and clonic components were less intense compared with those of typical tonic‐clonic seizures in other types of epilepsy. The fluttering phase was characterised initially by asymmetric, less rhythmic, and less synchronous tremulous movement and was then followed by the subtle clonic phase. Subtle oral automatism was observed in the postictal phase. The reactive, mild tonic, fluttering and mild clonic phases were most characteristic of seizures of PCDH19‐related epilepsy. Ictal EEG started bilaterally and was symmetric in some patients but asymmetric in others. It showed asymmetric rhythmic discharges in some seizures at later phases. The electroclinical pattern of the phasic evolution of convulsive seizure suggests a focal onset seizure with secondary generalisation. Based on our findings, we propose that the six unique sequential phases in convulsive seizures suggest the diagnosis of PCDH19‐related epilepsy when occurring in clusters with or without high fever in girls. [Published with video sequences online]
Deterioration of dyslexia after non‐dominant temporal lobectomy for drug‐resistant epilepsy
Authors: Haeren Roel H.L. , Hendriks Marc P.H. , Vlooswijk Marielle , Verdyck Lex , van Kranen‐Mastenbroek Vivianne H.J.M. , Wagner Louis , van Benthum Sophie , Schijns Olaf E.M.G. 
Published: August 2019

AbstractWe present a patient with drug‐resistant right‐sided temporal lobe epilepsy, caused by a ganglioglioma of the parahippocampal gyrus. Preoperatively, the patient was also known to have dyslexia. A right‐sided anterior temporal lobectomy, including complete lesionectomy, was performed. Several months after the otherwise uncomplicated procedure, the patient complained about visual memory disturbances, accompanied by increased reading and spelling problems. Postoperative neuropsychological examination revealed deterioration of the visual memory functions, compared to the preoperative assessment, and consequently provided a possible explanation for worsening of the pre‐existing dyslexia. In this case report, we hypothesize on the cause of this unusual deterioration and present recommendations to be included in the preoperative epilepsy surgery evaluation for patients with verbal or reading disorders such as dyslexia.
A 16‐year‐old girl with focal seizures and impaired awareness: divergent non‐invasive data related to a diffuse epileptogenic network
Authors: Russo Angelo , Jayakar Prasanna , Miller Ian , Bhatia Sanjiv , Duchowny Michael 
Published: August 2019

AbstractWe describe a patient with medically refractory focal epilepsy who presented with divergent non‐invasive data, with MRI revealing hippocampal sclerosis and EEG indicating involvement of the occipital lobe. A localized corticectomy over the occipital convexity was performed based on intracranial EEG recording. The patient was seizure‐free after four years of follow‐up. Electroclinical hypotheses and challenges of defining the epileptogenic network are discussed.
An audit of the predictors of outcome in status epilepticus from a resource‐poor country: a comparison with developed countries
Authors: Hassan Haseeb , Rajiv Keni Ravish , Menon Ramshekhar , Menon Deepak , Nair Muralidharan , Radhakrishnan Ashalatha 
Published: August 2019

AbstractAim. Status epilepticus is a neurological emergency with significant morbidity and mortality. This study describes the clinical profile, treatment, and predictors of outcome of status epilepticus in a tertiary referral centre in a developing country and aims to highlight the similarities and differences from data available from the western world.Methods. A retrospective analysis of data of patients treated for status epilepticus was conducted from prospectively maintained records, between January 2000 and September 2010. The demographic data, clinical profile and investigations (including neuroimaging and EEG), aetiology, treatment, and outcomes were studied and compared with data available from the western world.Results. The analysis included 108 events in 84 patients. A single episode of status epilepticus was treated in 72 patients (86%) and multiple status epilepticus events, ranging from two to six per patient, were managed in 12 patients (14%). Mean age was 24.1±20.3 years and 63% were males. The types of status epilepticus included convulsive status in 98 (90.7%), non‐convulsive status in seven (6.5%), and myoclonic status in three (2.8%). The majority of events (60%) were remote symptomatic, 16% were acute symptomatic, 16% were of unexplained aetiology, and 8% were progressive symptomatic. In 85 events (79%), status epilepticus could be aborted with first and second‐line drugs. The remaining 23 events (21%) progressed to refractory status epilepticus, among which, 13 (56%) were controlled with continuous intravenous midazolam infusion. Case fatality rate was 11%, neurological sequelae were reported in 22%, and 67% returned to baseline. Acute symptomatic status, older age, altered sensorium at the time of admission, and delayed hospitalisation were predictors of poor outcome.Conclusions. Aetiology was the most important determinant of outcome of status epilepticus, as in reports from the western world, with remote symptomatic aetiology secondary to gliosis being the most common. Treatment delay was frequent and adversely affected the outcome.
GOSR2: a progressive myoclonus epilepsy gene
Authors: Dibbens Leanne M. , Rubboli Guido 
Published: August 2019

AbstractGOSR2‐associated PME is associated with a homozygous mutation in GOSR2 (c.430G>T, p.Gly144Trp), a Golgi vesicle transport gene. The functional effect of this mutation is a loss of function that results in failure of the GOSR2 protein to localize to the cis‐Golgi. The main clinical features of the GOSR2‐associated PME are early‐onset ataxia, areflexia, action myoclonus and seizures, scoliosis, elevated creatine kinase levels, relative preservation of cognitive function until the late stages of the disease, and relentless disease course. Severe photosensitive myoclonus is a common feature. GOSR2‐associated PME is a rare disease with very few cases reported so far and it can be expected that the identification of further patients will contribute to expanding the phenotype and genotype of this condition.
Spinal muscular atrophy associated with progressive myoclonus epilepsy
Authors: Topaloglu Haluk , Melki Judith 
Published: August 2019

AbstractA rare syndrome characterized by lower motor neuron disease associated with progressive myoclonic epilepsy, referred to as “spinal muscular atrophy associated with progressive myoclonic epilepsy” (SMA‐PME), has been described in childhood and is inherited as an autosomal recessive trait. SMA‐PME is caused by mutation in the ASAH1 gene encoding acid ceramidase. Ceramide and the metabolites participate in various cellular events as lipid mediators. The catabolism of ceramide in mammals occurs in lysosomes through the activity of ceramidase. Three different ceramidases (acid, neutral and alkaline) have been identified and appear to play distinct roles in sphingolipid metabolism. The enzymatic activity of acid ceramidase is deficient in two rare inherited disorders; Farber disease and SMA‐PME. Farber disease is a very rare and severe autosomal recessive condition with a distinct clinical phenotype. The marked difference in disease manifestations may explain why Farber and SMA‐PME diseases were not previously suspected to be allelic conditions. The precise molecular mechanism underlying the phenotypic differences remains to be clarified. Recently, a condition with mutation in CERS1, the gene encoding ceramide synthase 1, has been identified as a novel form of PME. This finding underlies the essential role of enzymes regulating either the synthesis (CERS1) or degradation (ASAH1) of ceramide, and the link between defects in ceramide metabolism and PME.
Myoclonus epilepsy and ataxia due to potassium channel mutation (MEAK) is caused by heterozygous KCNC1 mutations
Authors: Nascimento Fábio A. , Andrade Danielle M. 
Published: August 2019

AbstractProgressive myoclonus epilepsy (PME) is a distinct group of seizure disorders characterized by gradual neurological decline with ataxia, myoclonus and recurring seizures. There are several forms of PME, among which the most recently described is MEAK ‐ myoclonus epilepsy and ataxia due to potassium channel mutation. This particular subtype is caused by a recurrent de novo heterozygous mutation (c.959G>A, p.Arg320His) in the KCNC1 gene, which maps to chromosome 11 and encodes for the Kv3.1 protein (a subunit of the Kv3 subfamily of voltage‐gated potassium channels). Loss of Kv3 function disrupts the firing properties of fast‐spiking neurons, affects neurotransmitter release and induces cell death. Specifically regarding Kv3.1 malfunctioning, the most affected neurons include inhibitory GABAergic interneurons and cerebellar neurons. Impairment of the former cells is believed to contribute to myoclonus and seizures, whereas dysfunction of the latter to ataxia and tremor. Phenotypically, MEAK patients generally have a normal early development. At the age of 6 to 14 years, they present with myoclonus, which tends to progressively worsen with time. Tonic‐clonic seizures may or may not be present, and some patients develop mild cognitive impairment following seizure onset. Typical electroencephalographic features comprise generalized epileptiform discharges and, in some cases, photosensitivity. Brain imaging is either normal or shows cerebellar atrophy. The identification of MEAK has both expanded the phenotypic and genotypic spectra of PME and established an emerging role for de novo mutations in PME.
Psychogenic non‐epileptic seizures
Authors: Doss Robert C. , LaFrance W. Curt 
Published: August 2019

AbstractPsychogenic non‐epileptic seizures (PNES) are diagnosed in at least 10–40% of the patients seen for long‐term monitoring of epilepsy, and it is no surprise that patients with PNES are often treated for epilepsy. Given the substantial economic costs and mental health burden of misdiagnosis, it is imperative to establish early identification, correct diagnosis, and effective treatment of PNES in order to provide the greatest opportunity for remission of events, improved psychological functioning, and social‐vocational outcome. This article outlines an informed, practical approach to diagnosing this common condition and provides a summary of factors, based on medical history and semiology, that may suggest PNES. We discuss also the issues of communicating the diagnosis to the patient and making treatment recommendations which should ideally be coordinated using a multi‐disciplinary team approach, involving the disciplines of neurology, psychiatry, psychology, social work, and nursing.
Drug‐resistant epilepsy after treatment for childhood acute lymphocytic leukaemia: from focal epilepsy to Lennox‐Gastaut syndrome
Authors: González‐Otárula Karina A. , Álvarez Blanca Mercedes , Dubeau François 
Published: August 2019

AbstractDrug‐resistant epilepsy, not associated with acute brain complications or central nervous system leukaemic involvement, can develop in patients treated for acute lymphocytic leukaemia during childhood. It has been postulated that this rare complication may be due to CNS oncological treatment neurotoxicity, related to intrathecal drugs, such as methotrexate, and brain radiotherapy. We report four patients who developed drug‐resistant epilepsy sometime after receiving treatment for acute lymphocytic leukaemia. All patients were female and received intrathecal methotrexate. One received additional intrathecal cytarabine, and two concomitant brain radiotherapy. Two developed Lennox‐Gastaut type syndrome, one multifocal epilepsy, and one focal epilepsy related to a radiotherapy‐induced cavernous angioma. The development of drug‐resistant epilepsy after treatment for acute lymphocytic leukaemia is a rare complication that may vary, from focal epilepsy to an epileptic encephalopathy. This may appear even years after the treatment has finished and is most likely associated with treatment‐related neurotoxicity.
Auditory seizures in autoimmune epilepsy: a case with anti‐thyroid antibodies
Authors: Varrasi Claudia , Vecchio Domizia , Magistrelli Luca , Strigaro Gionata , Tassi Laura , Cantello Roberto 
Published: August 2019

AbstractIn its classic presentation, Hashimoto's encephalopathy is an acute‐subacute complex neuropsychiatric syndrome with cognitive impairment, hallucinations, myoclonus, tremor or ataxia, associated with elevated anti‐thyroid antibodies. Corticoids and immunotherapy are dramatically effective. However, in some cases, not all the associated features are presented and this delays diagnosis and appropriate treatment. We describe a man with abrupt onset of recurrent auditory seizures resulting in refractory non‐convulsive status epilepticus. The patient was diagnosed with an autoimmune encephalopathy with elevated serum and CSF anti‐thyroid antibodies. None of the antiepileptic drugs were successful, however, following immune‐modulating therapy, the refractory non‐convulsive status epilepticus dramatically improved, as did the patient overall. We suggest that Hashimoto's encephalopathy should be suspected in otherwise healthy patients with unexplained new‐onset focal recurrent auditory seizures which do not respond to antiepileptic drugs. The presence of anti‐thyroid antibodies in the CSF supports this diagnosis.
De novo 8p23.1 deletion in a patient with absence epilepsy
Authors: Akcakaya Nihan Hande , Capan Özlem Yalcin , Schulz Herbert , Sander Thomas , Caglayan Server Hande , Yapıcı Zuhal 
Published: August 2019

AbstractThe 8p23.1 deletion syndrome is a rare multisystem disorder with high penetrance and a variable phenotypic spectrum that includes congenital heart disease (CHD), intellectual disability, behavioural problems, microcephalia, and sometimes epilepsy. Genomic copy number variations (CNVs) constitute an important genetic risk factor for common genetic generalised epilepsy syndromes (GGEs) and absence seizures. These variations, resulting either from copy loss (microdeletion) or copy gain (duplications), disrupt genes associated with neuronal development. Herein, we report an epilepsy patient who was affected by developmental delay, microcephalia, behavioural problems, CHD, and childhood‐onset absence seizures. The patient had a 4‐Mb de novo microdeletion at 8p23.1. Some of the genes in this region, particularly XKR6 and MIR597, may be involved in the pathogenesis of absence seizures, suggesting that epilepsy may possibly be part of the phenotypic spectrum of the syndrome rather than a comorbid disorder. Thus, CNV screening for GGE plus patients may have important implications in clinical practice with regards to diagnostic classification, clinical management of the syndromic multisystem disorders, and, potentially, genetic counselling.
Benign infantile seizures followed by autistic regression in a boy with 16p11.2 deletion
Authors: Milone Roberta , Valetto Angelo , Bertini Veronica , Sicca Federico 
Published: August 2019

AbstractBenign infantile seizures (BIS) are usually a self‐limiting condition, which may be associated with heterozygous mutations in the PRRT2 gene at chromosome 16p11.2. Here, we report a boy with a deletion in 16p11.2, presenting with BIS and typical neurodevelopment in the first year of life, unexpectedly followed by severe autistic regression. 16p11.2 deletions are typically associated with intellectual disability, autism, and language disorders, and only rarely with BIS. This clinical report shows that the neurodevelopmental prognosis in BIS patients may not always be benign, and suggests that array CGH screening should be considered for affected infants in order to rule out deletions at 16p11.2 and long‐term clinical follow‐up.
Alternating hemiplegia of childhood and a pathogenic variant of ATP1A3: a case report and pathophysiological considerations
Authors: Pavlidis Elena , Uldall Peter , Gøbel Madsen Camilla , Nikanorova Marina , Fabricius Martin , Høgenhaven Hans , Pisani Francesco , Møller Rikke S. , Gardella Elena , Rubboli Guido 
Published: August 2019

AbstractWe describe a case of a child suffering from alternating hemiplegia with a heterozygous p. E815K pathogenic variant of ATP1A3. The patient started to present abnormal eye movements in the first days of life, followed by the appearance at 2 months of dystonic episodes, and later on, by recurrent episodes of alternating hemiplegia more often on the right side. A severe epilepsy started at the age of 2 years with episodes of status epilepticus since the onset which frequently recurred, requiring admission to the intensive care unit. MRI showed bilateral mesial temporal sclerosis and a left‐sided ischaemic lesion. Interictal EEG showed bilateral abnormalities, whereas postictal EEG after status epilepticus showed overt slowing on the left side, suggesting a predominant involvement of ictal activity of the left hemisphere. We hypothesize that in our patient, the left hemisphere might have been more prominently affected by the pathogenetic abnormalities underlying alternating hemiplegia of childhood, rendering it more prone to early ischaemic lesions and recurrent unilateral status epilepticus. We speculate whether alternating hemiplegia of childhood shares some common pathophysiological mechanisms with familial hemiplegic migraine that may be associated with a pathogenic variant of ATP1A2.