-
Epilepsy & Behavior : E&B Nov 2016Premature mortality is a major issue in Dravet syndrome (DS). To improve understanding of DS premature mortality, we conducted a comprehensive literature search with a... (Review)
Review
INTRODUCTION
Premature mortality is a major issue in Dravet syndrome (DS). To improve understanding of DS premature mortality, we conducted a comprehensive literature search with a particular emphasis on SUDEP.
METHODS
We searched PubMed, Embase, Web of Science, Cochrane, CENTRAL, CINAHL, PsycINFO, Academic Search Premier, and ScienceDirect on the following terms: "Dravet syndrome", "severe myoclonic epilepsy", "SMEI", "mortality", "survivors", "prognosis", and "death". DS cases or cohorts studies reporting mortality were included.
RESULTS
The search yielded 676 articles and 86 meeting abstracts. After removing duplicates and screening titles and abstracts, full text of 73 articles was reviewed. Only 28 articles and six meeting abstracts met inclusion criteria. Five articles and four meeting abstracts were excluded, as the case(s) were also described elsewhere. After checking the references, five additional studies were included. The 30 items reported 177 unique cases. Sudden unexpected death in epilepsy was the likely cause in nearly half of the cases (n=87, 49%), followed by status epilepticus (n=56, 32%). Drowning or accidental death was reported in 14 cases (8%), infections in 9 (5%), other causes in six (3%), and unknown in five (3%). Age at death was reported for 142 of the 177 cases (80%), with a mean age of 8.7±9.8years (SD); 73% died before the age of 10years.
DISCUSSION
Dravet syndrome is characterized by high epilepsy-related premature mortality and a marked young age at death. Sudden unexpected death in epilepsy is the leading reported cause of death in DS, accounting for nearly half of all deaths. The cause of this excess mortality remains elusive but may be explained by epilepsy severity, as well as genetic susceptibility to SUDEP.
Topics: Child; Death, Sudden; Epilepsies, Myoclonic; Humans
PubMed: 27732919
DOI: 10.1016/j.yebeh.2016.09.007 -
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 -
Neurologia (Barcelona, Spain) Mar 2017Patients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated...
INTRODUCTION
Patients with Down syndrome (DS) who exhibit Alzheimer disease (AD) are associated with age. Both diseases with a common neuropathological basis have been associated with late-onset myoclonic epilepsy (LOMEDS). This entity presents electroencephalogram features as generalized polyspike-wave discharges.
METHOD
We present a series of 11 patients with the diagnosis of DS or AD who developed myoclonic seizures or generalized tonic-clonic seizures. In all cases, clinical and neuroimaging studies and polygraph EEG monitoring was performed.
RESULTS
In all cases, cognitive impairment progressed quickly after the onset of epilepsy causing an increase in the degree of dependence. The most common finding in the EEG was a slowing of brain activity with theta and delta rhythms, plus intercritical generalized polyspike-waves were objectified in eight patients. In neuroimaging studies was found cerebral cortical atrophy. The most effective drug in this series was the levetiracetam.
CONCLUSIONS
The association of generalized epilepsy with elderly DS represents an epiphenomenon in evolution which is associated with a progressive deterioration of cognitive and motor functions. This epilepsy has some electroclinical characteristics and behaves as progressive myoclonic epilepsy, which is probably related to the structural changes that characterize the evolutionary similarity of DS with AD. Recognition of this syndrome is important, since it has prognostic implications and requires proper treatment.
Topics: Adult; Aged; Alzheimer Disease; Anticonvulsants; Down Syndrome; Electroencephalography; Epilepsies, Myoclonic; Female; Humans; Levetiracetam; Male; Middle Aged; Piracetam; Retrospective Studies; Valproic Acid
PubMed: 25661268
DOI: 10.1016/j.nrl.2014.12.008 -
Seizure Jan 2017Dravet syndrome combines clonic generalized, focal or unilateral seizures, beginning within the first year of life, often triggered by hyperthermia whatever its cause,... (Review)
Review
Dravet syndrome combines clonic generalized, focal or unilateral seizures, beginning within the first year of life, often triggered by hyperthermia whatever its cause, including pertussis vaccination. Long-lasting febrile seizures are frequent in infancy and repeat status epilepticus (SE) has negative prognostic value. Massive myoclonus, rare absences, complex partial seizures and generalized spikes may appear several years later. Myoclonic status may occur in childhood, but acute encephalopathy with febrile SE followed by ischemic lesions and psychomotor impairment, the most severe condition, occurs mainly within the first five years of life. Generalized tonic-clonic and tonic seizures in sleep predominate in adulthood. Non epileptic manifestations appear with age, including intellectual disability, ataxia and crouching gait. Incidence of SUDEP is high, whatever the age. SCN1A haploinsufficiency producing Na1.1 dysfunction mainly affects GABAergic neurons. In cortical interneurons it explains epilepsy, in cerebellum the ataxia, in basal ganglia and motor neurons the crouching gait, in hypothalamus the thermodysregulation and sleep troubles, and dysfunction in all these structures contributes to psychomotor delay. Valproate, stiripentol, topiramate and bromide are the basis of antiepileptic treatment, whereas inhibitors of sodium channel worsen the condition. Benzodiazepines seem to facilitate acute encephalopathy when given chronically, and they should be restricted to SE. Ketogenic diet is useful in both chronic and acute conditions. Only targeting SCN1A haploinsufficiency and Na1.1 dysfunction could improve non epileptic manifestations of this condition that deserves being considered as a disease, not only as an epilepsy syndrome.
Topics: Anticonvulsants; Cognition Disorders; Death, Sudden; Diagnosis, Differential; Epilepsies, Myoclonic; Genotype; Humans; Movement Disorders; NAV1.1 Voltage-Gated Sodium Channel; Phenotype
PubMed: 27817982
DOI: 10.1016/j.seizure.2016.10.014 -
Epilepsy Research May 2022The aim was to describe age at diagnosis, cumulative incidence, SCN1A variants, mortality, seizure types and treatments in children with Dravet Syndrome (DS) in Sweden.
OBJECTIVE
The aim was to describe age at diagnosis, cumulative incidence, SCN1A variants, mortality, seizure types and treatments in children with Dravet Syndrome (DS) in Sweden.
METHODS
Children diagnosed with DS, born between January 1st 2000 and December 31st 2018 were included in a population-based study. Clinical data, frequency of seizure types and treatments were collected from caregivers and medical records in 42 children. Age at diagnosis, cumulative incidence and treatment were compared between children born in Sweden 2000-2009 and 2010-2018.
RESULTS
We identified 55 children with DS, 53 were born in Sweden. Three children had died of definite, probable, or possible sudden unexpected death in epilepsy, one of acute anoxic brain injury and three of pneumonia or pneumonitis. Median age at death was 4.7 (range 3.3-11) years. In 49/53 children with known SCN1A status, a pathogenic/likely pathogenic variant of SCN1A was detected. In two a SCN1A variant of unknown significance was found. For children born in Sweden 2010-2018, median age at DS diagnosis was lower (1.6 vs 4.5 years, p = 0.001) and cumulative incidence higher (1/33,000 vs 1/46,000 live-born children, p = 0.03), compared to children born in 2000-2009. The most common seizure types were focal to bilateral tonic clonic (n = 41/42) and myoclonic (n = 35/42). Tonic seizures were reported in 25/42 children. Sodium-channel inhibitors had been used in 9/24 children born in 2010-2018 and 17/18 children born in 2000-2009 (p = 0.001).
SIGNIFICANCE
A SCN1A variant that could explain the syndrome was found in over 90% of children. Tonic seizures seem to be more frequent than earlier described. Median age at diagnosis was lower, cumulative incidence higher and use of contra-indicated sodium-channel inhibitors less common for children born in 2010-2018 compared with children born in 2000-2009. This could indicate an increased awareness of DS.
Topics: Child; Child, Preschool; Death, Sudden; Epilepsies, Myoclonic; Epileptic Syndromes; Humans; Mutation; NAV1.1 Voltage-Gated Sodium Channel; Seizures; Sodium; Spasms, Infantile
PubMed: 35461153
DOI: 10.1016/j.eplepsyres.2022.106922 -
Tremor and Other Hyperkinetic Movements... 2018Autosomal dominant familial cortical myoclonic tremor and epilepsy (FCMTE) is characterized by distal tremulous myoclonus, generalized seizures, and signs of cortical... (Review)
Review
BACKGROUND
Autosomal dominant familial cortical myoclonic tremor and epilepsy (FCMTE) is characterized by distal tremulous myoclonus, generalized seizures, and signs of cortical reflex myoclonus. FCMTE has been described in over 100 pedigrees worldwide, under several different names and acronyms. Pathological changes have been located in the cerebellum. This systematic review discusses the clinical spectrum, treatment, pathophysiology, and genetic findings.
METHODS
We carried out a PubMed search, using a combination of the following search terms: cortical tremor, myoclonus, epilepsy, benign course, adult onset, familial, and autosomal dominant; this resulted in a total of 77 studies (761 patients; 126 pedigrees) fulfilling the inclusion and exclusion criteria.
RESULTS
Phenotypic differences across pedigrees exist, possibly related to underlying genetic differences. A "benign" phenotype has been described in several Japanese families and pedigrees linked to 8q (FCMTE1). French patients (5p linkage; FCMTE3) exhibit more severe progression, and in Japanese/Chinese pedigrees (with unknown linkage) anticipation has been suggested. Preferred treatment is with valproate (mind teratogenicity), levetiracetam, and/or clonazepam. Several genes have been identified, which differ in potential pathogenicity.
DISCUSSION
Based on the core features (above), the syndrome can be considered a distinct clinical entity. Clinical features may also include proximal myoclonus and mild progression with aging. Valproate or levetiracetam, with or without clonazepam, reduces symptoms. FCMTE is a heterogeneous disorder, and likely to include a variety of different conditions with mutations of different genes. Distinct phenotypic traits might reflect different genetic mutations. Genes involved in Purkinje cell outgrowth or those encoding for ion channels or neurotransmitters seem good candidate genes.
Topics: Epilepsies, Myoclonic; Humans; Phenotype
PubMed: 29416935
DOI: 10.7916/D85155WJ -
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 -
Neurobiology of Disease Sep 2023The progressive myoclonic epilepsies (PMEs) are a group of rare neurodegenerative diseases characterized by myoclonus, epileptic seizures, and progressive neurological... (Review)
Review
The progressive myoclonic epilepsies (PMEs) are a group of rare neurodegenerative diseases characterized by myoclonus, epileptic seizures, and progressive neurological deterioration with cerebellar involvement. They include storage diseases like Gaucher disease, Lafora disease, and forms of neuronal ceroid lipofuscinosis (NCL). To date, 13 NCLs have been reported (CLN1-CLN8, CLN10-CLN14), associated with mutations in different genes. These forms, which affect both children and adults, are characterized by seizures, cognitive and motor impairments, and in most cases visual loss. In NCLs, as in other PMEs, central nervous system (CNS) neurodegeneration is widespread and involves different subpopulations of neurons. One of the most affected regions is the cerebellar cortex, where motor and non-motor information is processed and transmitted to deep cerebellar nuclei through the axons of Purkinje cells (PCs). PCs, being GABAergic, have an inhibitory effect on their target neurons, and provide the only inhibitory output of the cerebellum. Degeneration of PCs has been linked to motor impairments and epileptic seizures. Seizures occur when some insult upsets the normal balance in the CNS between excitatory and inhibitory impulses, causing hyperexcitability. Here we review the role of PCs in epilepsy onset and progression following their PME-related loss. In particular, we focus on the involvement of PCs in seizure phenotype in NCLs, highlighting findings from case reports and studies of animal models in which epilepsy can be linked to PC loss.
Topics: Animals; Neuronal Ceroid-Lipofuscinoses; Purkinje Cells; Myoclonic Epilepsies, Progressive; Epilepsy; Seizures
PubMed: 37573956
DOI: 10.1016/j.nbd.2023.106258 -
Epilepsia Feb 2016Autism and epilepsy are two associated disorders that are highly prevalent, share common developmental origins, and demonstrate substantial heritability. In this review,... (Review)
Review
Autism and epilepsy are two associated disorders that are highly prevalent, share common developmental origins, and demonstrate substantial heritability. In this review, cross-disciplinary data in a rapidly evolving field that bridges neurology and psychiatry are synthesized to identify shared biologic mechanisms. The relationship between these debilitating, lifelong conditions is examined at the clinical, genetic, and neurophysiologic levels in humans and in animal models. Scopus and PubMed searches were used to identify relevant literature. Clinical observations have prompted speculation about the interdependence of autism and epilepsy, but causal relationships have proved difficult to determine. Despite their heritability, the genetic basis of autism spectrum disorder (ASD) and epilepsy has remained largely elusive until the advent of next-generation sequencing. This approach has revealed that mutations that are either causal or confer an increased disease risk are found in numerous different genes, any one of which accounts for only a small percentage of cases. Conversely, even cases with identical clinical phenotypes can be genetically heterogeneous. Candidate gene identification has facilitated the development of mouse genetic models, which in parallel with human studies have implicated shared brain regions and circuits that mediate disease expression. Diverse genetic causes of ASD and epilepsy converge on cortical interneuron circuits as one important mediator of both disorders. Cortical interneurons are among the most diverse cell types in the brain and their unique chemical and electrical coupling exert a powerful inhibitory influence on excitatory neurons via the release of the neurotransmitter, γ-aminobutyric acid (GABA). These multifaceted approaches have validated theories derived from the field of developmental neurobiology, which propose that the neurologic and neuropsychiatric manifestations are caused by an altered ratio of excitation to inhibition in the cortex.
Topics: Aicardi Syndrome; Autism Spectrum Disorder; Cerebral Cortex; Child; Child, Preschool; Epilepsies, Myoclonic; Epilepsy; Humans; Infant; Interneurons; Landau-Kleffner Syndrome; Lennox Gastaut Syndrome; Neural Inhibition; Neurons; Spasms, Infantile; gamma-Aminobutyric Acid
PubMed: 26682992
DOI: 10.1111/epi.13272 -
Neurologia I Neurochirurgia Polska 2022Cannabis sativa has been cultivated for human use for about 5,000 years, and has likewise been used in the treatment of epilepsy for thousands of years.
INTRODUCTION
Cannabis sativa has been cultivated for human use for about 5,000 years, and has likewise been used in the treatment of epilepsy for thousands of years.
STATE OF THE ART
Cannabidiol (CBD), which was isolated from cannabis sativa in 1940, has an anti-seizure effect and no psychoactive activity. Its effectiveness in reducing various types of seizures has been proven in animal seizure and epilepsy models. Recent randomised, placebo-controlled trials have confirmed its effectiveness in patients with drug-resistant epilepsy.
CLINICAL IMPLICATIONS
The aim of this position paper was to present the specific mechanism of CBD's anti-seizure action and current indications for CBD's use in epilepsy. The only cannabis-derived drug that has successfully passed clinical trials and has obtained United States Food and Drug Administration and European Medicines Agency approval for epilepsy is Epidiolex®. This paper presents the outcomes of the completed clinical trials with the use of this drug.
FUTURE DIRECTIONS
CBD may be an effective drug in drug-resistant epilepsy, particularly in Dravet Syndrome, Lennox- Gastaut Syndrome and seizures associated with tuberous sclerosis complex. Additional randomised, placebo-controlled studies with CBD are needed.
Topics: Animals; Anticonvulsants; Cannabidiol; Epilepsies, Myoclonic; Epilepsy; Humans; Lennox Gastaut Syndrome
PubMed: 35211946
DOI: 10.5603/PJNNS.a2022.0020