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Child's Nervous System : ChNS :... Sep 2016Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy (SMEI), is a rare genetic disorder that results in severe childhood-onset epilepsy. Children... (Review)
Review
PURPOSE
Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy (SMEI), is a rare genetic disorder that results in severe childhood-onset epilepsy. Children with DS initially present with seizures in the first year of life that are often associated with fevers. With age, multiple seizure types develop. There are few reports and no guidelines regarding palliative surgical treatment for DS. Therefore, we reviewed our surgical experience with DS.
METHODS
We conducted a retrospective review of all patients with genetically confirmed DS who underwent either vagal nerve stimulator (VNS) implantation or corpus callosotomy (CC) from May 2001 to April 2014 at our institution. All inpatient and outpatient relevant documentation were reviewed. Demographic information, genetic mutation, operation performed, and preoperative and postoperative seizure frequency were recorded. Inclusion criteria required greater than one-year postoperative follow-up.
RESULTS
Seven children with DS were assessed. Six patients were treated with VNS and one patient was treated with CC. In one child, VNS was followed by CC as a secondary procedure. Therefore, in total, eight surgeries were performed on seven patients during the study period. At least 1 year elapsed from presentation to our hospital and surgery for all patients. Average time after the first seizure to VNS was 4.1 years, and the average time after the first seizure to CC was 7.6 years. The mean age of patients undergoing VNS implantation was 4.3 years, and the mean age for patients undergoing CC was eight. Average follow-up for all seven patients was 6.6 years. Seizures were decreased in five of the six patients with VNS and decreased in the two patients after CC. Four of the six patients who had VNS implanted had a greater than 50 % reduction in seizure frequency, and one of the six patients who had VNS implanted had a less than 50 % reduction in seizure frequency. One patient did not respond effectively to the VNS and had very limited change in seizure frequency. Both patients who had a CC had a greater than 50 % reduction in seizure frequency.
CONCLUSIONS
Both VNS and CC in patients with DS can be effective at reducing seizure frequency. Patients with DS may benefit from earlier and more aggressive surgical intervention. Studies using larger patient cohorts will help clarify the role that surgery may play in the multidisciplinary approach to controlling seizures in DS. Further studies will help determine the appropriate timing of and type of surgical intervention.
Topics: Corpus Callosum; Electroencephalography; Epilepsies, Myoclonic; Epilepsy; Female; Humans; Infant; Male; Palliative Care; Vagus Nerve Stimulation
PubMed: 27465677
DOI: 10.1007/s00381-016-3201-4 -
Epileptic Disorders : International... Sep 2016GOSR2-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... (Review)
Review
GOSR2-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.
Topics: Humans; Myoclonic Epilepsies, Progressive; Qb-SNARE Proteins
PubMed: 27618868
DOI: 10.1684/epd.2016.0848 -
Neurology Jul 2016
Topics: Epilepsies, Myoclonic; Gait; Humans; Musculoskeletal Diseases; NAV1.1 Voltage-Gated Sodium Channel
PubMed: 27316245
DOI: 10.1212/WNL.0000000000002873 -
Epilepsia Aug 2014This chapter covers the syndromes of benign epilepsy with centrotemporal spikes (BECTS), nonlesional focal epilepsy in otherwise normal children (NLFN), and the genetic... (Review)
Review
Transition issues for benign epilepsy with centrotemporal spikes, nonlesional focal epilepsy in otherwise normal children, childhood absence epilepsy, and juvenile myoclonic epilepsy.
This chapter covers the syndromes of benign epilepsy with centrotemporal spikes (BECTS), nonlesional focal epilepsy in otherwise normal children (NLFN), and the genetic generalized epilepsies. BECTS is an epilepsy syndrome that always enters terminal remission before the general age of a planned transition of adolescents. This is also the case for the majority (65%) of those with childhood absence epilepsy (CAE). Approximately 15% of patients with CAE who initially remit during their childhood years later develop juvenile myoclonic epilepsy (JME) as teenagers. They will have many issues for continuing medical care and transition, because their seizure disorder generally persists into adulthood. A significant minority of NLFN (~35%) and most patients with JME continue to have active epilepsy into adulthood. In addition, CAE, JME, and NLFN patients are at risk of a number of significant adverse social outcomes that require ongoing advice and counseling.
Topics: Adolescent; Child; Electroencephalography; Epilepsies, Partial; Epilepsy, Absence; Humans; Myoclonic Epilepsy, Juvenile; Time Factors
PubMed: 25209080
DOI: 10.1111/epi.12706 -
Journal of the College of Physicians... Aug 2022Lafora body disease (LBD) is a progressive myoclonic genetic epilepsy syndrome characterized by the presence of Lafora inclusion bodies within neurons and other cells....
Lafora body disease (LBD) is a progressive myoclonic genetic epilepsy syndrome characterized by the presence of Lafora inclusion bodies within neurons and other cells. It is a complex neurodegenerative disease presenting in adolescence with seizures, myoclonus, and rapid cognitive decline. Diagnosis is often challenging requiring a thorough history including family history, identification of Lafora bodies in apocrine sweat glands of axillary skin, and specific DNA sequencing. There is no cure and management is mainly supportive. We present one of the only few cases from Pakistan of LBD based on characteristic biopsy findings, history of similar ailment in siblings, and EPM2B mutation. This case emphasizes the need for physicians and neurologists to be aware of diagnostic challenges associated with LBD and its characteristic findings. Key Words: Lafora body, Progressive epilepsy, Myoclonus, Axillary skin biopsy, EPM2B.
Topics: Adolescent; Humans; Inclusion Bodies; Lafora Disease; Myoclonic Epilepsies, Progressive; Neurodegenerative Diseases
PubMed: 36210672
DOI: 10.29271/jcpsp.2022.Supp2.S133 -
Epilepsia Aug 2023IRF2BPL has recently been described as a novel cause of neurodevelopmental disorders with multisystemic regression, epilepsy, cerebellar symptoms, dysphagia, dystonia,...
IRF2BPL has recently been described as a novel cause of neurodevelopmental disorders with multisystemic regression, epilepsy, cerebellar symptoms, dysphagia, dystonia, and pyramidal signs. We describe a novel IRF2BPL phenotype consistent with progressive myoclonus epilepsy (PME) in three novel subjects and review the features of the 31 subjects with IRF2BPL-related disorders previously reported. Our three probands, aged 28-40 years, harbored de novo nonsense variants in IRF2BPL (c.370C > T, p.[Gln124*] and c.364C > T; p.[Gln122*], respectively). From late childhood/adolescence, they presented with severe myoclonus epilepsy, stimulus-sensitive myoclonus, and progressive cognitive, speech, and cerebellar impairment, consistent with a typical PME syndrome. The skin biopsy revealed massive intracellular glycogen inclusions in one proband, suggesting a similar pathogenic pathway to other storage disorders. Whereas the two older probands were severely affected, the younger proband had a milder PME phenotype, partially overlapping with some of the previously reported IRF2BPL cases, suggesting that some of them might be unrecognized PME. Interestingly, all three patients harbored protein-truncating variants clustered in a proximal, highly conserved gene region around the "coiled-coil" domain. Our data show that PME can be an additional phenotype within the spectrum of IRF2BPL-related disorders and suggest IRF2BPL as a novel causative gene for PME.
Topics: Humans; Child; Mutation; Myoclonic Epilepsies, Progressive; Epilepsies, Myoclonic; Epilepsy; Family; Myoclonus; Carrier Proteins; Nuclear Proteins
PubMed: 37114479
DOI: 10.1111/epi.17634 -
Seizure May 2020
Topics: Humans; Myoclonic Epilepsies, Progressive; Unverricht-Lundborg Syndrome
PubMed: 31740381
DOI: 10.1016/j.seizure.2019.09.008 -
Epileptic Disorders : International... Sep 2016The history of the progressive myoclonus epilepsies (PMEs) spans more than a century. However, the recent history of PMEs begins with a consensus statement published in... (Review)
Review
The history of the progressive myoclonus epilepsies (PMEs) spans more than a century. However, the recent history of PMEs begins with a consensus statement published in the wake of the Marseille PME workshop in 1989 (Marseille Consensus Group, 1990). This consensus helped define the various types of PME known at the time and set the agenda for a new era of genetic research which soon lead to the discovery of many PME genes. Prior to the Marseille meeting, and before the molecular era, there had been much confusion and controversy. Because investigators had but limited and biased experience with these rare disorders due to the uneven, skewed distribution of PMEs around the world, opinions and nosologies were based on local expertise which did not match well with the experiences of other researchers and clinicians. The three major areas of focus included: (1) the nature and limits of the concept of PME in varying scopes, which was greatly debated; (2) the description of discrete clinical entities by clinicians; and (3) the description of markers (pathological, biological, neurophysiological, etc.) which could lead to a precise diagnosis of a given PME type, with, in the best cases, a reliable correlation with clinical findings. In this article, we shall also examine the breakthroughs achieved in the wake of the 1989 Marseille meeting and recent history in the field, following the identification of several PME genes. As in other domains, the molecular and genetic approach has challenged some established concepts and has led to the description of new PME types. However, as may already be noted, this approach has also confirmed the existence of the major, established types of PME, which can now be considered as true diseases.
Topics: History, 19th Century; History, 20th Century; History, 21st Century; Humans; Myoclonic Epilepsies, Progressive
PubMed: 27621064
DOI: 10.1684/epd.2016.0834 -
Epileptic Disorders : International... Sep 2016A rare syndrome characterized by lower motor neuron disease associated with progressive myoclonic epilepsy, referred to as "spinal muscular atrophy associated with... (Review)
Review
A 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.
Topics: Acid Ceramidase; Animals; Farber Lipogranulomatosis; Humans; Muscular Atrophy, Spinal; Myoclonic Epilepsies, Progressive; Syndrome
PubMed: 27647482
DOI: 10.1684/epd.2016.0858 -
International Journal of Molecular... Dec 2023Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is... (Review)
Review
Dravet syndrome (DS), also known as severe myoclonic epilepsy of infancy, is a rare and drug-resistant form of developmental and epileptic encephalopathies, which is both debilitating and challenging to manage, typically arising during the first year of life, with seizures often triggered by fever, infections, or vaccinations. It is characterized by frequent and prolonged seizures, developmental delays, and various other neurological and behavioral impairments. Most cases result from pathogenic mutations in the sodium voltage-gated channel alpha subunit 1 () gene, which encodes a critical voltage-gated sodium channel subunit involved in neuronal excitability. Precision medicine offers significant potential for improving DS diagnosis and treatment. Early genetic testing enables timely and accurate diagnosis. Advances in our understanding of DS's underlying genetic mechanisms and neurobiology have enabled the development of targeted therapies, such as gene therapy, offering more effective and less invasive treatment options for patients with DS. Targeted and gene therapies provide hope for more effective and personalized treatments. However, research into novel approaches remains in its early stages, and their clinical application remains to be seen. This review addresses the current understanding of clinical DS features, genetic involvement in DS development, and outcomes of novel DS therapies.
Topics: Humans; Precision Medicine; Epilepsy; Epilepsies, Myoclonic; Epilepsy, Generalized; Seizures
PubMed: 38203200
DOI: 10.3390/ijms25010031