bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early‐life epileptic encephalopathy secondary to SZT2 pathogenic recessive variants
Authors: Venkatesan Charu , Angle Brad , Millichap John J. 
Published: August 2019

AbstractAdvances in genetic testing have led to the identification of increasing numbers of novel gene mutations that underlie infantile‐onset epileptic encephalopathies. Recently, a mutagenesis screen identified a novel gene, SZT2, with no known protein function that has been linked to epileptogenesis in mice. Thus far, two clinical reports have identified children with different recessive mutations in SZT2 and varying clinical phenotypes. One case report described patients with epileptic encephalopathy and the other noted patients with cognitive deficiencies, but normal MRI and no epilepsy. This case report identifies novel mutations (a compound heterozygous frameshift and a nonsense variant) in the SZT2 gene with distinct clinical and radiographic findings relative to those previously reported. Our patient presented with intractable epilepsy at 2 months of age. Seizures were refractory to numerous antiepileptic medications and the patient finally achieved seizure cessation at age 3 years with a combination of divalproex and lamotrigine. Our patient had similar facial dysmorphisms (macrocephaly, high forehead, and down‐slanted palpebral fissures) to a previous case with truncating mutation. While developmental delay and cognitive deficiencies were present, our case had unique MRI findings suggesting migrational abnormalities not previously reported in other cases.
Non‐ketotic hyperglycaemia presenting as epilepsia partialis continua
Authors: Hwang Kyoung Jin , Yoon SungSang , Park Key‐Chung 
Published: August 2019

AbstractEpilepsia partialis continua is a rare epileptic syndrome observed in patients with brain structural lesions and metabolic disorders. We report a patient with non‐ketotic hyperglycaemia presenting as epilepsia partialis continua with reversible focal brain lesions. An 83‐year‐old woman visited our hospital due to sudden and repetitive left facial twitching lasting for two days. Initial laboratory data revealed serum glucose, osmolality, and sodium levels of 631 mg/dl, 310 mOsm/l, and 130 mEq/l, respectively. EEG was normal. Brain MRI showed low signal changes in the right frontal subcortical area and high signal changes in the surrounding right frontal cortical areas on T2‐weighted, fluid‐attenuated inversion recovery, and diffusion‐weighted images. No seizures recurred after correcting blood glucose levels, hydrating the patient, and infusing valproate (900 mg/day). Follow‐up MRI, six months later, showed complete resolution of the signal changes in the right frontal cortical and subcortical areas and no clinical seizures. When considering non‐ketotic hyperglycaemia with epilepsia partialis continua in an elderly patient, early diagnosis and administration of the appropriate therapy is very important in order to decrease morbidity.
Unverricht‐Lundborg disease
Authors: Crespel Arielle , Ferlazzo Edoardo , Franceschetti Silvana , Genton Pierre , Gouider Riadh , Kälviäinen Reetta , Korja Miikka , Lehtinen Maria K. , Mervaala Esa , Simonato Michele , Vaarmann Annika 
Published: August 2019

AbstractWe first review the clinical presentation and current therapeutic approaches available for treating Unverricht‐Lundborg disease (ULD), a progressive myoclonus epilepsy. Next, we describe the identification of disease causing mutations in the gene encoding cystatin B (CSTB). A Cstb‐deficient mouse model, which recapitulates the key features of ULD including myoclonic seizures, ataxia, and neuronal loss, was generated to shed light on the mechanisms contributing to disease pathophysiology. Studies with this model have elucidated the diverse biological roles for Cstb from functioning as a protease inhibitor, to regulating glial activation, oxidative stress, serotonergic neurotransmission, and hyperexcitability. These findings set the stage for future studies that may open avenues to improved therapeutic approaches.
Lafora disease
Authors: Turnbull Julie , Tiberia Erica , Striano Pasquale , Genton Pierre , Carpenter Stirling , Ackerley Cameron A. , Minassian Berge A. 
Published: August 2019

AbstractLafora disease (LD) is an autosomal recessive progressive myoclonus epilepsy due to mutations in the EPM2A (laforin) and EPM2B (malin) genes, with no substantial genotype‐phenotype differences between the two. Founder effects and recurrent mutations are common, and mostly isolated to specific ethnic groups and/or geographical locations. Pathologically, LD is characterized by distinctive polyglucosans, which are formations of abnormal glycogen. Polyglucosans, or Lafora bodies (LB) are typically found in the brain, periportal hepatocytes of the liver, skeletal and cardiac myocytes, and in the eccrine duct and apocrine myoepithelial cells of sweat glands. Mouse models of the disease and other naturally occurring animal models have similar pathology and phenotype. Hypotheses of LB formation remain controversial, with compelling evidence and caveats for each hypothesis. However, it is clear that the laforin and malin functions regulating glycogen structure are key.With the exception of a few missense mutations LD is clinically homogeneous, with onset in adolescence. Symptoms begin with seizures, and neurological decline follows soon after. The disease course is progressive and fatal, with death occurring within 10 years of onset. Antiepileptic drugs are mostly non‐effective, with none having a major influence on the progression of cognitive and behavioral symptoms. Diagnosis and genetic counseling are important aspects of LD, and social support is essential in disease management.Future therapeutics for LD will revolve around the pathogenesics of the disease. Currently, efforts at identifying compounds or approaches to reduce brain glycogen synthesis appear to be highly promising.
Neuronal ceroid lipofuscinoses
Authors: Nita Dragos A. , Mole Sara E. , Minassian Berge A. 
Published: August 2019

AbstractThe neuronal ceroid lipofuscinoses (NCL) are neurodegenerative conditions that associate cognitive decline, progressive cerebellar atrophy, retinopathy, and myoclonic epilepsy. NCL result from the excessive accumulation of neuronal and extraneuronal lipopigments, despite having diverse underlying biochemical aetiologies. Here we review the clinical presentation, pathophysiology and genetics of these conditions as well as the approach to diagnosis and management.
KCTD7‐related progressive myoclonus epilepsy
Authors: Van Bogaert Patrick 
Published: August 2019

AbstractProgressive myoclonic epilepsy associated with KCTD7 mutations has been reported in 19 patients from 12 families. Patients show homozygous mutations in the coding regions of the KCTD7 gene. The disease starts in infancy. Patients typically show an initial severe epileptic disorder, with abundant epileptiform discharges on EEG and myoclonic seizures in the foreground, associated with cognitive regression and ataxia. Continuous multifocal myoclonus aggravated by action is observed in more than half of the cases. After a few years, the disease tends to stabilize and long survival can be expected. Some patients remain able to walk independently. The severity of the disease is variable from one patient to another, even within the same family. It is hypothesized that the epileptic disorder may influence the neurological regression observed in patients.
Autosomal dominant cortical tremor, myoclonus and epilepsy
Authors: Striano Pasquale , Zara Federico 
Published: August 2019

AbstractThe term ‘cortical tremor’ was first introduced by Ikeda and colleagues to indicate a postural and action‐induced shivering movement of the hands which mimics essential tremor, but presents with the electrophysiological findings of cortical reflex myoclonus. The association between autosomal dominant cortical tremor, myoclonus and epilepsy (ADCME) was first recognized in Japanese families and is now increasingly reported worldwide, although it is described using different acronyms (BAFME, FAME, FEME, FCTE and others). The disease usually takes a benign course, although drug‐resistant focal seizures or slight intellectual disability occur in some cases. Moreover, a worsening of cortical tremor and myoclonus is common in advanced age. Although not yet recognized by the International League Against Epilepsy (ILAE), this is a well‐delineated epilepsy syndrome with remarkable features that clearly distinguishes it from other myoclonus epilepsies. Moreover, genetic studies of these families show heterogeneity and different susceptible chromosomal loci have been identified.
Varied responses to benzodiazepine treatment in cephalosporin‐related generalized periodic discharges
Authors: Liu Hung‐Yu , Chou Chien‐Chen , Yen Der‐Jen , Yu Hsiang‐Yu 
Published: August 2019

AbstractAlthough benzodiazepines (BZDs) are used as the first‐line treatment for status epilepticus, previous studies have shown inconsistent responses to BZDs in patients with cephalosporin‐related non‐convulsive status epilepticus. In this study, we investigated nine patients with cephalosporin‐related impaired consciousness and their EEGs all showed generalized periodic discharges (GPDs). One of the patients received repetitive BZD injections without discontinuing cephalosporins, and neither his clinical symptoms nor GPDs on EEG responded to BZDs. Seven of the patients received BZDs after discontinuation of cephalosporins, but only two of them responded immediately to BZD administration. One of the patients did not receive BZDs or antiepileptic drugs, and this patient spontaneously recovered consciousness in one day after cephalosporins were discontinued. The changes in consciousness were reversible in all of the nine patients after cephalosporins were withdrawn. The administration of intravenous BZDs in cases with impairment of consciousness and GPDs secondary to cephalosporins may help in only a small number of patients. Cephalosporin withdrawal is ultimately mandatory in these patients.
Can diffusion‐weighted imaging be used as a tool to predict seizures in patients with PLEDS?
Authors: Narayanan Jaishree 
Published: August 2019

AbstractIt is unclear which patients with PLEDs will have associated seizures and therefore will need to be treated aggressively with antiepileptic medications. We present a prospective observational study of ten consecutive non‐anoxic patients with PLEDs based on continuous 24‐hour EEG monitoring. According to the EEG, five of the patients had seizures associated with PLEDs and five had PLEDs but no seizures. The aetiology included: neoplasm (n=1), cortical dysplasia (n=1), acute head trauma (n=1), encephalomalacia related to healed abscess (n=1), intra‐parenchymal haemorrhage (n=1), and no structural lesion (n=5). All patients underwent brain MRI using diffusion‐weighted imaging (DWI). We found that the five patients who had seizures with PLEDs on continuous EEG had restricted diffusion on DWI. In contrast, the five patients who had PLEDs but no seizures on continuous EEG did not show a restricted diffusion pattern on DWI. We will continue to prospectively assess DWI findings in this group of patients and encourage other centres to also review similar data. If our observation is replicated, this would indicate that restricted diffusion on brain MRI may be a useful marker to identify patients with PLEDs on their EEG who are likely to have associated seizures.
Ictal SPECT is useful in localizing the epileptogenic zone in infants with cortical dysplasia
Authors: Kudr Martin , Krsek Pavel , Maton Bruno , Malone Stephen , Jahodova Alena , Komarek Vladimir , Jayakar Prasanna , Duchowny Michael 
Published: August 2019

AbstractAims. To assess the localizing value of ictal SPECT in very young epilepsy surgery candidates when cerebral haemodynamic responses are known to be immature.Methods. We retrospectively studied 13 infants with intractable focal epilepsy caused by focal cortical dysplasia (FCD). Completeness of resection of the (1) ictal SPECT hyperperfusion zone and (2) cerebral cortex with prominent ictal and interictal abnormalities on intracranial EEG (ECoG or long‐term invasive monitoring) and the MRI lesion, when present, were correlated with postoperative seizure outcome.Results. All five patients with complete resection of the ictal SPECT hyperperfusion zone were seizure‐free compared to only one of eight patients with incomplete or no excision of hyperperfusion zones (p=0.00843). Similar results were noted for the MRI/iEEG‐defined epileptogenic region; five of six patients with complete removal were seizure‐free, whereas only one of seven incompletely resected patients was seizure‐free (p=0.02914). All four patients who underwent complete resection of both regions were seizure‐free compared to none of the six with incomplete resection (p=0.01179).Conclusion. Despite age‐related differences in cerebral perfusion, ictal SPECT provides useful localization data in infants with FCD. Complete resection of the hyperperfused regions is a strong predictor of favourable outcome. The added information may alleviate the need for invasive EEG evaluations in some patients.
Aicardi syndrome: epilepsy surgery as a palliative treatment option for selected patients and pathological findings
Authors: Podkorytova Irina , Gupta Ajay , Wyllie Elaine , Moosa Ahsan , Bingaman William , Prayson Richard , Knight Elia M Pestana 
Published: August 2019

AbstractThe optimal treatment for medically refractory epilepsy in Aicardi syndrome (AS) is still unclear. Palliative surgical treatment, including vagus nerve stimulation and corpus callosotomy, has therefore been used. There is limited data on the role of resective epilepsy surgery as a treatment choice in patients with AS. Here, we describe the seizures, anatomo‐pathological findings, and neurodevelopmental outcome of palliative epilepsy surgery in two children with AS who had resective epilepsy surgery at the Cleveland Clinic. The related literature is also reviewed. Case 1 had a left functional hemispherectomy and was free of seizures and hypsarrhythmia for six months after surgery. Her gross motor skills improved after surgery. Outcome at 43 months was 1–3 isolated spasms per day. Case 2 had a right fronto‐parietal lobectomy. Her seizures improved in frequency and severity, but remained daily after epilepsy surgery. Neurodevelopment changes included improved alertness and recognition of caregivers. This patient died 21 months after epilepsy surgery of unclear causes. Surgical pathology in both cases showed focal cortical dysplasia associated with other findings, such as nodular heterotopia and polymicrogyria. Epilepsy surgery could be an alternative palliative treatment choice in selective cases of AS, but studies on a larger patient cohort are needed to identify the possible role of surgery in children with AS. The complexity of the pathological findings may offer an explanation for the severity of seizures in AS.
Drug treatment strategies for epilepsy revisited: starting early or late? One drug or several drugs?
Authors: Schmidt Dieter 
Published: August 2019

AbstractThere are two popular strategies for current drug treatment of epilepsy; starting early may be better and polytherapy conveys advantages over monotherapy. This review briefly examines if the historical record is much of a guide to determine the clinical value of these two strategies. Great clinical scientists of the 19th and early 20th century, such as Sir William Gowers, and William Aldren Turner, offered vivid single case studies and showed early results of seizure remission in groups of subjects. The historical record offered, however, no evidence of clear clinical benefits for early treatment and polytherapy. Combination treatment was thought to be useful in only some cases. In agreement, current evidence shows no clear clinical benefit of starting treatment early, except perhaps in severe epilepsy. Polytherapy is clinically useful in a subgroup of subjects, but despite being a standard treatment strategy for over one hundred years, it has been poorly studied. In fact, there is no compelling experimental or clinical evidence for a difference in seizure outcome between monotherapy and polytherapy. This surprising finding should prompt a re‐appraisal regarding the need to test both strategies separately for the licensing of new antiepileptic drugs.
Levetiracetam‐induced thrombocytopenia in a patient with status epilepticus
Authors: Kim Jonguk , Shin Jung‐Won 
Published: August 2019

AbstractLevetiracetam has broad‐spectrum activity in epilepsy. In contrast to phenytoin, levetiracetam has an ideal pharmacokinetic profile without any severe haemodynamic side effects and therefore intravenous loading of levetiracetam is commonly used in adult patients with status epilepticus, especially those who have medical problems. However, levetiracetam‐induced serious adverse effects, such as thrombocytopenia and pancytopenia, have been reported in the literature. Here, we describe a case of status epilepticus after cardiac arrest treated with levetiracetam in which severe thrombocytopenia developed and was successfully managed by discontinuation of levetiracetam. Our report aims to increase awareness of this rare cause of thrombocytopenia among clinicians and provide a review of the literature.
The insula lobe and sudden unexpected death in epilepsy: a hypothesis
Authors: Li Jia , Ming Qianwen , Lin Weihong 
Published: August 2019

AbstractSudden unexpected death in epilepsy (SUDEP) is a major cause of death in patients with refractory epilepsy, particularly those with chronic epilepsy. The physiopathological mechanisms underlying SUDEP have not been elucidated. Autonomic dysregulation of cardiac or respiratory function is thought to underlie SUDEP. Here, we present a summary of available evidence on the involvement of the insular lobe in the regulation of cardiorespiratory function. Ictal discharge that originates in the cortex can, primarily or secondarily, involve the insula lobe through epileptogenic signal networks, leading to cardiorespiratory dysfunction, central apnoea, arrhythmias, and sudden death in patients with epilepsy. Thus, the insula lobe appears to be instrumental in the causation of SUDEP.
Epileptic seizures, coma and EEG burst‐suppression from suicidal bupropion intoxication
Authors: Noda Anna Hiro , Schu Ulrich , Maier Tanja , Knake Susanne , Rosenow Felix 
Published: August 2019

AbstractBupropion, an amphetamine‐like dual mechanism drug, is approved and increasingly used for the treatment of major depression, and its use is associated with a dose‐dependent risk of epileptic seizures. Suicide attempts are frequent in major depression and often an overdose of the drugs available is ingested. Therefore, it is important to be aware of the clinical course, including EEG and neurological symptoms, as well as treatment and prognosis of bupropion intoxication. We report on the clinical and EEG course of a women who ingested 27 g of bupropion in a suicide attempt. Myoclonic seizures were followed by generalized tonic‐clonic seizures and coma associated with EEG burst‐suppression and brief tonic seizures. Active carbon and neuro‐intensive care treatment, including respiratory support, were given. Within three days, the patient returned to a stable clinical condition with a mildly encephalopathic EEG. In conclusion, bupropion intoxication requires acute intensive care treatment and usually has a good prognosis, however, misinterpretation of the clinical and EEG presentation may lead to errors in management.
Temporal lobe epilepsy? Things are not always what they seem
Authors: Doležalová Irena , Brázdil Milan , Kahane Philippe 
Published: August 2019

AbstractTemporal lobe epilepsy is the most frequent form of drug‐resistant epilepsy referred to epilepsy surgery centres. The vast majority of lesional cases can be operated on without invasive investigation which is often not the case for non‐lesional cases. Invasive investigation in non‐lesional cases, however, may lead to unexpected results, as illustrated in the following case report. [Published with video sequence on www.epilepticdisorders.com]
Epileptic spasms in paediatric post‐traumatic epilepsy at a tertiary referral centre
Authors: Park Jun T. , Chugani Harry T. 
Published: August 2019

AbstractAim. To recognize epileptic spasms (ES) as a seizure type after traumatic brain injury (TBI), accidental or non‐accidental, in infants and children. In the process, we aim to gain some insight into the mechanisms of epileptogenesis in ES.Methods. A retrospective electronic chart review was performed at the Children's Hospital of Michigan from 2002 to 2012. Electronic charts of 321 patients were reviewed for evidence of post‐traumatic epilepsy. Various clinical variables were collected including age at TBI, mechanism of trauma, severity of brain injury, electroencephalography/neuroimaging data, and seizure semiology.Results. Six (12.8%) of the 47 patients diagnosed with post‐traumatic epilepsy (PTE) had ES. Epileptic spasms occurred between two months to two years after TBI. All patients with ES had multiple irritative zones, manifesting as multifocal epileptiform discharges, unilateral or bilateral. Cognitive delay and epileptic encephalopathy were seen in all six patients, five of whom were free of spasms after treatment with vigabatrin or adrenocorticotropic hormone.Conclusion. The risk of PTE is 47/321(14.6%) and the specific risk of ES after TBI is 6/321 (1.8%). The risk of ES appears to be high if the age at which severe TBI occurred was during infancy. Non‐accidental head trauma is a risk factor of epileptic spasms. While posttraumatic epilepsy (not ES) may start 10 years after the head injury, ES starts within two years, according to our small cohort. The pathophysiology of ES is unknown, however, our data support a combination of previously proposed models in which the primary dysfunction is a focal or diffuse cortical abnormality, coupled with its abnormal interaction with the subcortical structures and brainstem at a critical maturation stage.