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Epilepsia May 2009Work on the classification of epileptic syndromes is ongoing, and many syndromes are still under discussion. In particular, special difficulty still persists in... (Review)
Review
Work on the classification of epileptic syndromes is ongoing, and many syndromes are still under discussion. In particular, special difficulty still persists in correctly classifying epilepsies with myoclonic seizures. The existence of special familial epileptic syndromes primarily showing myoclonic features has been recently suggested on the basis of a clear pattern of inheritance or on the identification of new chromosomal genetic loci linked to the disease. These forms in development include familial infantile myoclonic epilepsy (FIME), benign adult familial myoclonic epilepsy (BAFME), or autosomal dominant cortical myoclonus and epilepsy (ADCME), and, maybe, adult-onset myoclonic epilepsy (AME). In the future, the identification of responsible genes and the protein products will contribute to our understanding of the molecular pathways of epileptogenesis and provide neurobiologic criteria for the classification of epilepsies, beyond the different phenotypic expression.
Topics: Cerebral Cortex; Electroencephalography; Epilepsies, Myoclonic; Genotype; Humans
PubMed: 19469844
DOI: 10.1111/j.1528-1167.2009.02118.x -
Epilepsia 2000Although for most children epilepsy is a relatively benign disorder, for some, epilepsy can be designated as "catastrophic" because the seizures are so difficult to... (Review)
Review
Although for most children epilepsy is a relatively benign disorder, for some, epilepsy can be designated as "catastrophic" because the seizures are so difficult to control and because they are strongly associated with mental retardation. The catastrophic childhood epilepsies include uncommon disorders such as early infantile epileptic encephalopathy with suppression burst, severe myoclonic epilepsy of infancy, and epilepsy with myoclonic-astatic seizures. There are other syndromes that are relatively common such as infantile spasms, Lennox-Gastaut syndrome, and Sturge-Weber syndrome. Many children with catastrophic epilepsy have the seizures as a result of underlying brain abnormalities that will inevitably lead to mental retardation whether or not they have seizures. In some patients, however, the mental retardation appears to be caused by the seizures. Developmental plasticity provides children with an opportunity to recover from significant brain injuries. However, the plasticity may also be the cause of the mental retardation. In such patients, control of the seizures may lead to more normal intellectual development. Thus, every effort should be made to control seizures in children with catastrophic epilepsy.
Topics: Anticonvulsants; Brain; Child; Child, Preschool; Encephalitis; Epilepsies, Myoclonic; Epilepsy; Humans; Infant; Intellectual Disability; Neuronal Plasticity; Outcome Assessment, Health Care; Severity of Illness Index; Spasms, Infantile; Sturge-Weber Syndrome
PubMed: 10885734
DOI: 10.1111/j.1528-1157.2000.tb01518.x -
Epilepsia Apr 2011Dravet syndrome (DS), otherwise known as severe myoclonic epilepsy of infancy (SMEI), is an epileptic encephalopathy presenting in the first year of life. DS has a... (Review)
Review
Dravet syndrome (DS), otherwise known as severe myoclonic epilepsy of infancy (SMEI), is an epileptic encephalopathy presenting in the first year of life. DS has a genetic etiology: between 70% and 80% of patients carry sodium channel α1 subunit gene (SCN1A) abnormalities, and truncating mutations account for about 40% and have a significant correlation with an earlier age of seizures onset. The remaining SCN1A mutations comprise splice-site and missense mutations, most of which fall into the pore-forming region of the sodium channel. Mutations are randomly distributed across the SCN1A protein. Most mutations are de novo, but familial SCN1A mutations also occur. Somatic mosaic mutations have also been reported in some patients and might explain the phenotypical variability seen in some familial cases. SCN1A exons deletions or chromosomal rearrangements involving SCN1A and contiguous genes are also detectable in about 2-3% of patients. A small percentage of female patients with a DS-like phenotype might carry PCDH19 mutations. Rare mutations have been identified in the GABARG2 and SCN1B genes. The etiology of about 20% of DS patients remains unknown, and additional genes are likely to be implicated.
Topics: Epilepsies, Myoclonic; Humans; Infant; Mutation; NAV1.1 Voltage-Gated Sodium Channel; Nerve Tissue Proteins; Sodium Channels; Syndrome
PubMed: 21463275
DOI: 10.1111/j.1528-1167.2011.02997.x -
Seizure Apr 2021Dravet Syndrome (DS) is a rare and severe infantile-onset epileptic encephalopathy. DS research focuses mainly on children. We did a systematic review, completed on... (Review)
Review
Dravet Syndrome (DS) is a rare and severe infantile-onset epileptic encephalopathy. DS research focuses mainly on children. We did a systematic review, completed on January 18, 2021, examining the number of clinical DS studies. We show that there are 208 studies on children exclusively, 28 studies on adults exclusively, and 116 studies involving adults and children combined. This 7:1 ratio of children to adult studies exclusively shows the dearth of research that addresses long-term natural history of DS into adulthood. Through this systematic review, we examine the most up-to-date information in DS adults as it pertains to seizures, electroencephalogram, imaging, treatment, motor abnormalities, cognitive and social behavior outcomes, cardiac abnormalities, sleep disturbances, diagnosis in adults, and mortality. Overall, the frequency of seizures increases in the first decade of life and then myoclonic, atypical absences and focal seizures with impaired awareness tend to decrease in frequency or even disappear in adulthood. Adults tend to have a notable reduction in status epilepticus, especially after 30 years of age. Parkinsonian features were seen in patients as young as 19 years old and are more severe in older patients, suggesting a progression of the parkinsonian symptoms. In adulthood, patients continue to present with behavior problems, associated with a lower health-related quality of life. The leading reported cause of death in DS adults is Sudden Unexpected Death in Epilepsy (SUDEP). Further studies in older adults are needed to understand the long-term outcomes of patients with DS.
Topics: Adult; Epilepsies, Myoclonic; Humans; Infant; Mutation; NAV1.1 Voltage-Gated Sodium Channel; Quality of Life; Spasms, Infantile; Young Adult
PubMed: 33677403
DOI: 10.1016/j.seizure.2021.02.025 -
Progressive Myoclonus Epilepsy: A Scoping Review of Diagnostic, Phenotypic and Therapeutic Advances.Genes Jan 2024The progressive myoclonus epilepsies (PME) are a diverse group of disorders that feature both myoclonus and seizures that worsen gradually over a variable timeframe.... (Review)
Review
The progressive myoclonus epilepsies (PME) are a diverse group of disorders that feature both myoclonus and seizures that worsen gradually over a variable timeframe. While each of the disorders is individually rare, they collectively make up a non-trivial portion of the complex epilepsy and myoclonus cases that are seen in tertiary care centers. The last decade has seen substantial progress in our understanding of the pathophysiology, diagnosis, prognosis, and, in select disorders, therapies of these diseases. In this scoping review, we examine English language publications from the past decade that address diagnostic, phenotypic, and therapeutic advances in all PMEs. We then highlight the major lessons that have been learned and point out avenues for future investigation that seem promising.
Topics: Humans; Myoclonus; Myoclonic Epilepsies, Progressive
PubMed: 38397161
DOI: 10.3390/genes15020171 -
Epilepsia Apr 2011Few studies focused on the long-term outcome of Dravet syndrome in adulthood are available in the literature, but all are concordant. In this article, we consider the... (Review)
Review
Few studies focused on the long-term outcome of Dravet syndrome in adulthood are available in the literature, but all are concordant. In this article, we consider the outcomes of 24 patients followed at the Centre Saint-Paul, Marseille, up to the age of 50, and compare them to the patients reported in the literature. Five patients (20.8%) died, at a mean age of 24.8 years, one by status epilepticus, three by sudden unexpected death in epilepsy (SUDEP), and one of unknown cause. Epileptic seizures tend to become less frequent and less severe after childhood. Fever sensitivity (temperature variations) persists throughout the clinical course of DS, but its impact on seizure frequency and severity is milder than in infancy. Generalized convulsive seizures, mostly reported as generalized tonic-clonic seizures (GTCS), were the only seizure type observed in almost all of the patients, often with a focal onset. They are less frequent than in childhood and mostly nocturnal. Some of these major convulsive seizures have less typical aspects, for example, bilateral or asymmetric tonic posturing, followed in some cases by a tonic vibratory state or clonic movements (Oguni et al., Brain Dev 2001;23:736-748; Akiyama et al., Epilepsia 2010;51:1043-1052). Other seizures like myoclonic seizures, atypical absences, and complex partial seizures (CPS) are less common in adulthood: Among our 24 patients, only 6 had atypical absences, and one myoclonic and one complex focal seizures. Electroencephalography (EEG) also changes with age but is still multiple and heterogenous, interictally and ictally. Photosensitivity and pattern sensitivity also showed a tendency to disappear before the age of 20. Motor abnormalities are common. Cerebellar features, including ataxia, dysarthria, intention tremor, and eye movement disorder, become more prominent. Walking is markedly impaired, often due to orthopedic signs such as kyphosis, kyphoscoliosis, flat feet, or claw feet. This symptomatology was minor during childhood and worsened during and after adolescence, despite physiotherapy. Mental retardation ranged from moderate to severe, with predominance of language impairment, and some patients had a major personality disorder, labeled autistic or psychotic. Dependency in adulthood is nearly constant: Only 3 of our 24 adult patients lived independently.
Topics: Adult; Age Factors; Cohort Studies; Epilepsies, Myoclonic; Female; Follow-Up Studies; Humans; Male; Middle Aged; Social Behavior; Syndrome; Time Factors; Treatment Outcome; Young Adult
PubMed: 21463279
DOI: 10.1111/j.1528-1167.2011.03001.x -
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 -
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 -
Epilepsia 2003Despite the availability of numerous treatment options, the diagnosis and treatment of myoclonic seizures continue to be challenging. Based on clinical experience,... (Review)
Review
Despite the availability of numerous treatment options, the diagnosis and treatment of myoclonic seizures continue to be challenging. Based on clinical experience, valproate and benzodiazepines have historically been used to treat myoclonic seizures. However, many more treatment options exist today, and the clinician must match the appropriate treatment with the patient's epilepsy syndrome and its underlying etiology. Comorbidities and other medications must also be considered when making decisions regarding treatment. Rarely, some antiepileptic drugs may exacerbate myoclonic seizures. Most epileptic myoclonus can be treated pharmacologically, but some cases respond better to surgery, the ketogenic diet, or vagus nerve stimulation. Because myoclonic seizures can be difficult to treat, clinicians should be flexible in their approach and tailor therapy to each patient.
Topics: Animals; Anticonvulsants; Epilepsies, Myoclonic; Humans
PubMed: 14641568
DOI: 10.1046/j.1528-1157.44.s11.5.x -
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