-
Epilepsia 2006The purpose of this article is to present a short review of the natural history of myoclonic astatic epilepsy (MAE; Doose syndrome) and the Lennox-Gastaut syndrome... (Review)
Review
The purpose of this article is to present a short review of the natural history of myoclonic astatic epilepsy (MAE; Doose syndrome) and the Lennox-Gastaut syndrome (LGS). In the 1989 classification of the International League Against Epilepsy (ILAE, 1989), MAE and LGS were initially included in group 2.2: "Cryptogenic or symptomatic generalized epilepsies and syndromes." The subsequent classification of the Proposed Diagnostic Scheme for People with Epileptic Seizures and with Epilepsy (see Ref. 8) placed MAE in axis 3 in the "generalized epilepsy" group and LGS, severe myoclonic epilepsy of infancy (SMEI or Dravet syndrome) and atypical benign partial epilepsy/pseudo-Lennox syndrome (ABPE/PLS) in the "epileptic encephalopathy" group. The semiology of MAE and LGS and their differential diagnosis from SMEI and ABPE/PLS are described. Before the onset of SMEI, MAE, and ABPE/PLS, the development of the child is usually normal. In contrast, in LGS, development is frequently retarded at the onset, depending on the etiopathogenesis of the underlying brain disease. The course of MAE is highly variable with regard to seizure outcome (complete remission in some cases, persistent epilepsy in others) and cognitive development (normal or delayed). The course of LGS and SMEI is generally poor, both with regard to the epilepsy and to the cognitive development whereas the course and seizure outcome of ABPE/PLS is favorable; the patients will be seizure-free at puberty. However, the neuropsychological outcome is less favorable; most patients remain mentally retarded.
Topics: Age of Onset; Child, Preschool; Cognition Disorders; Comorbidity; Diagnosis, Differential; Electroencephalography; Epilepsies, Myoclonic; Epilepsy; Humans; Infant; Intellectual Disability; Prognosis; Syndrome; Terminology as Topic
PubMed: 17105462
DOI: 10.1111/j.1528-1167.2006.00690.x -
Orphanet Journal of Rare Diseases Jul 2018Acid ceramidase (ACDase) deficiency is a spectrum of disorders that includes a rare lysosomal storage disorder called Farber disease (FD) and a rare epileptic disorder... (Review)
Review
Acid ceramidase (ACDase) deficiency is a spectrum of disorders that includes a rare lysosomal storage disorder called Farber disease (FD) and a rare epileptic disorder called spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME). Both disorders are caused by mutations in the ASAH1 gene that encodes the lysosomal hydrolase that breaks down the bioactive lipid ceramide. To date, there have been fewer than 200 reported cases of FD and SMA-PME in the literature. Typical textbook manifestations of classical FD include the formation of subcutaneous nodules, accumulation of joint contractures, and development of a hoarse voice. In reality, however, the clinical presentation is much broader. Patients may develop severe pathologies leading to death in infancy or may develop attenuated forms of the disorder wherein they are often misdiagnosed or not diagnosed until adulthood. A clinical variability also exists for SMA-PME, in which patients develop progressive muscle weakness and seizures. Currently, there is no known cure for FD or for SMA-PME. The main treatment is symptom management. In rare cases, treatment may include surgery or hematopoietic stem cell transplantation. Research using disease models has provided insights into the pathology as well as the role of ACDase in the development of these conditions. Recent studies have highlighted possible biomarkers for an effective diagnosis of ACDase deficiency. Ongoing work is being conducted to evaluate the use of recombinant human ACDase (rhACDase) for the treatment of FD. Finally, gene therapy strategies for the treatment of ACDase deficiency are actively being pursued. This review highlights the broad clinical definition and outlines key studies that have improved our understanding of inherited ACDase deficiency-related conditions.
Topics: Animals; Farber Lipogranulomatosis; Humans; Muscular Atrophy, Spinal; Myoclonic Epilepsies, Progressive; Sphingolipids
PubMed: 30029679
DOI: 10.1186/s13023-018-0845-z -
Medicina 2023Juvenile myoclonic epilepsy (JME) is an epileptic syndrome with onset in childhood and adolescence with myoclonus, absences, and generalized tonic-clonic seizures....
INTRODUCTION
Juvenile myoclonic epilepsy (JME) is an epileptic syndrome with onset in childhood and adolescence with myoclonus, absences, and generalized tonic-clonic seizures. Reflex stimuli such as sensitivity to light or photosensitivity, eyelid opening and closing, and praxis induction produce epileptiform discharges and seizures. These reflex triggers are not all systematically studied.
OBJECTIVE
Examine reflex features in patients with JME.
METHODS
One hundred adolescents and adults with JME who received different anti-seizure treatments were evaluated consecutively. A standard electroencephalogram was performed with an intermittent light stimulation (SLI) protocol and another for the evaluation of praxias through neurocognitive activity (CNA). The statistical analysis was descriptive and of correlation with a p > 0.05.
RESULTS
Current age was 28±11 (14-67). The seizure began at 15 years ±3 (Range 8-25 years). They presented myoclonus and generalized tonic-clonic seizures in 58%. 50% received valproic acid and 31% continued with seizures. Epileptiform discharges at rest 20%; hyperventilation 30%; eyelid opening and closing 12%; photoparoxysmal response in SLI 40%; CNA 23%. Higher percentage of discharges and delay in performing CNA in those who presented seizures. Valproic acid compared to other drugs did not demonstrate superiority in seizure control.
CONCLUSIONS
These findings confirm the importance of studying reflex traits for diagnosis, follow-up, and therapeutic control.
Topics: Adult; Adolescent; Humans; Myoclonic Epilepsy, Juvenile; Valproic Acid; Myoclonus; Electroencephalography; Reflex; Seizures; Epilepsies, Myoclonic
PubMed: 38117708
DOI: No ID Found -
Epilepsia 2003The myoclonic epilepsies are a collection of syndromes in which myoclonic seizures are a prominent feature. Proper classification of a patient's syndrome is critical for... (Review)
Review
The myoclonic epilepsies are a collection of syndromes in which myoclonic seizures are a prominent feature. Proper classification of a patient's syndrome is critical for appropriate treatment and prognosis. However, classification of such syndromes is often difficult because the terminology used to describe seizures can be confusing and inconsistent. Myoclonic epilepsy syndromes can be epileptic or nonepileptic and can also be divided into inherited and acquired forms. Progressive myoclonic epilepsy (PME) syndromes are the most severe of the myoclonic epilepsies. Diagnosis of PME syndromes on clinical grounds can be difficult, but advances in genetic testing have made diagnoses more accurate. Some other benign myoclonic epilepsy syndromes also have identified gene markers, which can aid in diagnosis. To accurately classify a patient's epilepsy syndrome, clinicians should use all available clinical laboratory tools appropriately. Improved accuracy of diagnosis for patients with myoclonic epilepsies should lead to more dependable prognoses and more effective treatment.
Topics: Epilepsies, Myoclonic; Humans
PubMed: 14641565
DOI: 10.1046/j.1528-1157.44.s11.4.x -
Epilepsia Aug 2012Herman Doose first described the generalized childhood epilepsy syndrome of myoclonic astatic epilepsy (MAE) in 1970, attributing a genetic cause from this first... (Review)
Review
Herman Doose first described the generalized childhood epilepsy syndrome of myoclonic astatic epilepsy (MAE) in 1970, attributing a genetic cause from this first description. However, although the International League Against Epilepsy (ILAE) defined criteria for MAE in 1989, the diagnostic boundaries of the syndrome continue to be debated. Moreover, 40 years since Doose's first description of MAE, although a genetic predisposition is acknowledged and many studies have demonstrated familial aggregation of seizures within MAE families, the actual genetic determinants of MAE still remain unknown. Although initially thought to be within the same spectrum as severe myoclonic epilepsy of infancy, the exclusion of SCN1A mutations in non-generalized epilepsy with febrile seizures plus (GEFS+) MAE cases has confirmed the genetic distinction of MAE. In this critical review, we shall trace the historical evolution of concepts around MAE and its distinction from Lennox-Gastaut syndrome, review the described phenotypic features of MAE from updated studies that will allow its distinction from other overlap epilepsy syndromes, review the evidence of genetic influences and clues for genetic heterogeneity, and discuss strategies that may be helpful in elucidating the etiology of MAE in light of current genetic techniques.
Topics: Child, Preschool; Comorbidity; Electroencephalography; Epilepsies, Myoclonic; Female; Humans; Male; Mutation; Pedigree; Prognosis; Seizures; Twin Studies as Topic
PubMed: 22780699
DOI: 10.1111/j.1528-1167.2012.03581.x -
Epilepsia Apr 2011Slowing of cognitive skills represents one of the diagnostic criteria of Dravet syndrome. This Italian multicentric study aims at clarifying the roles of epilepsy and/or... (Review)
Review
Slowing of cognitive skills represents one of the diagnostic criteria of Dravet syndrome. This Italian multicentric study aims at clarifying the roles of epilepsy and/or underlying genetic alteration in determining the cognitive outcome. The study includes infants that were either in follow-up (retrospective study: 26 cases) and newly diagnosed (prospective study: in progress). Our multicentric study shows that slowing of cognitive achievements becomes evident during the second year of life in all cases, and that the epilepsy phenotype indeed has a prognostic value. In this study the early appearance of absences and myoclonic seizures is associated with the worst cognitive outcome; whereas convulsive prolonged seizures do not seem to represent, per se, a bad prognostic factor for mental outcome. In this study, statistical analysis failed to reveal differences in the cognitive outcome with regard to the presence and type of SCN1A mutation.
Topics: Child; Child Development; Cognition Disorders; Epilepsies, Myoclonic; Follow-Up Studies; Humans; Multicenter Studies as Topic; Retrospective Studies; Syndrome
PubMed: 21463278
DOI: 10.1111/j.1528-1167.2011.03000.x -
Seizure May 2020
Topics: Humans; Myoclonic Epilepsies, Progressive; Unverricht-Lundborg Syndrome
PubMed: 31740381
DOI: 10.1016/j.seizure.2019.09.008 -
The Neuroscientist : a Review Journal... Dec 2023Dravet syndrome is a severe developmental and epileptic encephalopathy mostly caused by heterozygous mutation of the gene encoding the voltage-gated sodium channel α... (Review)
Review
Dravet syndrome is a severe developmental and epileptic encephalopathy mostly caused by heterozygous mutation of the gene encoding the voltage-gated sodium channel α subunit Na1.1. Multiple seizure types, cognitive deterioration, behavioral disturbances, ataxia, and sudden unexpected death associated with epilepsy are a hallmark of the disease. Recently approved antiseizure medications such as fenfluramine and cannabidiol have been shown to reduce seizure burden. However, patients with Dravet syndrome are still medically refractory in the majority of cases, and there is a high demand for new therapies aiming to improve behavioral and cognitive outcome. Drug-repurposing approaches for -related Dravet syndrome are currently under investigation (i.e., lorcaserin, clemizole, and ataluren). New therapeutic concepts also arise from the field of precision medicine by upregulating functional or by activating Na1.1. These include antisense nucleotides directed against the nonproductive transcript of with the poison exon 20N and against an inhibitory noncoding antisense RNA of . Gene therapy approaches such as adeno-associated virus-based upregulation of using a transcriptional activator (ETX101) or CRISPR/dCas technologies show promising results in preclinical studies. Although these new treatment concepts still need further clinical research, they offer great potential for precise and disease modifying treatment of Dravet syndrome.
Topics: Humans; NAV1.1 Voltage-Gated Sodium Channel; Epilepsies, Myoclonic; Epilepsy; Seizures; Neurodevelopmental Disorders
PubMed: 35414300
DOI: 10.1177/10738584221088244 -
Acta Medica Okayama 2012Dravet syndrome (DS), or severe myoclonic epilepsy in infancy, is one of the most severe types of genetic epilepsy. It is characterized by the initial occurrence of... (Review)
Review
Dravet syndrome (DS), or severe myoclonic epilepsy in infancy, is one of the most severe types of genetic epilepsy. It is characterized by the initial occurrence of febrile or afebrile seizures that often evolve into status epilepticus in infants with normal development, and by the subsequent appearance of myoclonic and/or atypical absence seizures as well as complex partial seizures. The key feature that characterizes DS is fever sensitivity, although photosensitivity and pattern-sensitivity are also often seen. The prognosis is unfavorable in most cases. Seizures become drug-resistant and persist, with many patients suffering from motor and cognitive impairment. Mutations of SCN1A, which encodes the voltage-gated sodium channel NaV1.1, are the most frequent genetic cause of this syndrome. SCN1A mutations and/or microchromosomal rearrangements involving SCN1A are detected in about 85オ of patients. Mutations of PCDH19 have also been reported in female patients with clinical findings compatible with DS. PCDH19 mutations might account for 5オ of overall DS cases. Thirty years after its first description, DS is considered as a model of channelopathy. This survey reviews recent developments in the research literature on DS, focusing on the clinical course, as well as its genetic causes.
Topics: Cadherins; Electroencephalography; Epilepsies, Myoclonic; Genotype; Humans; Mutation; NAV1.1 Voltage-Gated Sodium Channel; Phenotype; Protocadherins
PubMed: 23093055
DOI: 10.18926/AMO/48961 -
Cerebral Cortex (New York, N.Y. : 1991) Aug 2023Mutations of the voltage-gated sodium channel SCN1A gene (MIM#182389) are among the most clinically relevant epilepsy-related genetic mutations and present variable...
Mutations of the voltage-gated sodium channel SCN1A gene (MIM#182389) are among the most clinically relevant epilepsy-related genetic mutations and present variable phenotypes, from the milder genetic epilepsy with febrile seizures plus to Dravet syndrome, a severe developmental and epileptic encephalopathy. Qualitative neuroimaging studies have identified malformations of cortical development in some patients and mild atrophic changes, partially confirmed by quantitative studies. Precise correlations between MRI findings and clinical variables have not been addressed. We used morphometric methods and network-based models to detect abnormal brain structural patterns in 34 patients with SCN1A-related epilepsy, including 22 with Dravet syndrome. By measuring the morphometric characteristics of the cortical mantle and volume of subcortical structures, we found bilateral atrophic changes in the hippocampus, amygdala, and the temporo-limbic cortex (P-value < 0.05). By correlating atrophic patterns with brain connectivity profiles, we found the region of the hippocampal formation as the epicenter of the structural changes. We also observed that Dravet syndrome was associated with more severe atrophy patterns with respect to the genetic epilepsy with febrile seizures plus phenotype (r = -0.0613, P-value = 0.03), thus suggesting that both the underlying mutation and seizure severity contribute to determine atrophic changes.
Topics: Humans; NAV1.1 Voltage-Gated Sodium Channel; Seizures, Febrile; Epilepsies, Myoclonic; Epilepsy; Mutation; Phenotype
PubMed: 37344172
DOI: 10.1093/cercor/bhad224