-
Acta Neurologica Scandinavica Jan 2021Brivaracetam (BRV) is a new antiseizure medication (ASM) that is currently approved for adjunctive treatment in patients with focal onset seizures. Similarly to... (Review)
Review
Brivaracetam (BRV) is a new antiseizure medication (ASM) that is currently approved for adjunctive treatment in patients with focal onset seizures. Similarly to levetiracetam (LEV), BRV works by binding SV2A vesicles with a high affinity and a linear pharmacokinetic profile. Retrospective studies and randomized clinical trials have already proven the efficacy of BRV, even in patients who failed treatment with LEV. Most studies about the efficacy and tolerability conducted so far were performed in adult cohorts, whereas few studies have been performed in children; however, BRV was proven to be a useful ASM for pediatric focal epilepsies, with fewer studies and conflicting results among patients with generalized epilepsies and epileptic syndromes. Retention rates were high in the cohorts analyzed, and no serious treatment-emergent adverse events were reported in the majority of patients, with somnolence, drowsiness, irritability, aggression, and decreased appetite being the most frequently reported side effects. Although there are few original papers published on the subject so far, the analysis of the literature data demonstrated the efficacy and safety of BRV in pediatric patients, with more evidence for children aged 4-16 years with an onset of focal seizures. However, a positive response was also achieved in patients affected by encephalopathic epilepsies (eg, Jeavons' epilepsy, Dravet syndrome, Lennox-Gastaut syndrome, and juvenile myoclonic epilepsy), and ongoing studies are now testing BRV in order to widen its application to other forms of epilepsy and to test its effectiveness when used in monotherapy. This review aims to provide a comprehensive analysis of the literature surrounding the efficacy and tolerability of BRV for pediatric patients.
Topics: Adolescent; Anticonvulsants; Child; Child, Preschool; Epilepsies, Partial; Female; Humans; Male; Myoclonic Epilepsy, Juvenile; Pyrrolidinones; Randomized Controlled Trials as Topic; Retrospective Studies; Treatment Outcome
PubMed: 32966640
DOI: 10.1111/ane.13347 -
Expert Opinion on Pharmacotherapy Feb 2017Myoclonic seizures are brief, involuntary muscular jerks arising from the central nervous system that can occur in different epilepsy syndromes, including idiopathic... (Review)
Review
Myoclonic seizures are brief, involuntary muscular jerks arising from the central nervous system that can occur in different epilepsy syndromes, including idiopathic generalized epilepsies or the most severe group of epileptic encephalopathies. Valproate is commonly the first choice alone or in combination with some benzodiazepines or levetiracetam. However, more treatment options exist today as there is emerging evidence to support the efficacy of some newer antiepileptic drugs. In addition, of major importance remains avoidance of medications (e.g., carbamazepine, phenytoin) that may aggravate myoclonic seizures. This is an updated review on the available therapeutic options for treatment of myoclonic seizures. Areas covered: Key efficacy, tolerability and efficacy data are showed for different antiepileptic drugs with antimyoclonic effect, alone and/or in combination. Expert opinion: Pharmacological treatment of myoclonic seizures is based on clinical experience with little evidence from randomized clinical trials. Valproate, levetiracetam, and some benzodiazepines, are widely used. There is still insufficient evidence for the use of other antiseizure drugs, such as topiramate or zonisamide as monotherapy. Better understanding of pathophysiologic mechanisms of myoclonic epilepsies could yield great improvement in the treatment and quality of life of patients.
Topics: Anticonvulsants; Epilepsies, Myoclonic; Epilepsy, Generalized; Humans; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 28067060
DOI: 10.1080/14656566.2017.1280459 -
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 -
Epilepsy & Behavior : E&B Jun 2023This multicenter study aimed to evaluate the efficacy and tolerability of add-on cannabidiol (CBD) in treatment-resistant patients with epilepsy with myoclonic-atonic...
PURPOSE
This multicenter study aimed to evaluate the efficacy and tolerability of add-on cannabidiol (CBD) in treatment-resistant patients with epilepsy with myoclonic-atonic seizures (EMAtS) (n = 22) and Sturge Weber syndrome (SWS) with myoclonic-atonic seizures (n = 4).
METHODS
Patients who met the diagnostic criteria of treatment-resistant EMAtS or SWS with myoclonic-atonic seizures were included. Cannabidiol was added in doses ranging from 8 to 40 mg/kg/day. Efficacy was assessed by comparing seizure frequency before and after initiating CBD therapy. Neurologic examinations, brain magnetic resonance imaging, repeated prolonged electroencephalography (EEG) and/or video-EEG recordings, and neurometabolic studies were performed in all patients, and genetic investigations in 15.
RESULTS
After a mean follow-up of 19 months, 15/26 patients (57.7%) who received add-on CBD had a >50% seizure decrease; three (11.5%) became seizure-free. The remaining 11 patients (42.3%) had a 25-50% seizure reduction. Drop attacks, including myoclonic-atonic seizures and generalized tonic-clonic seizures, as well as atypical absences and nonconvulsive status epilepticus responded well to CBD. In SWS patients, focal motor seizures without consciousness impairment and focal non-motor seizures with consciousness impairment were recognized in two each; in three a 30% reduction of focal seizures was observed. Side effects were mild and did not lead to CBD discontinuation.
CONCLUSION
This study evaluating the use of add-on CBD in children with EMAtS or SWS with myoclonic-atonic seizures found that 15/26 (57.7%) had a >50% seizure reduction with good tolerability; three (11.5%) became seizure-free.
Topics: Humans; Child; Cannabidiol; Epilepsies, Myoclonic; Seizures; Epilepsy, Generalized; Brain; Electroencephalography
PubMed: 37182500
DOI: 10.1016/j.yebeh.2023.109245 -
Epileptic Disorders : International... Jun 2022Epilepsy with myoclonic absences is a rare epilepsy syndrome with distinct features and high rates of drug resistance. Identifying this syndrome may help guide treatment...
OBJECTIVE
Epilepsy with myoclonic absences is a rare epilepsy syndrome with distinct features and high rates of drug resistance. Identifying this syndrome may help guide treatment decisions. We highlight clinical heterogeneity in this case series and two cases in which corpus callosotomy was performed.
METHODS
Medical records were reviewed between 2017 and 2021 to identify demographics, comorbidities, age at onset, EEG findings, diagnostic evaluations, seizure semiologies, seizure frequency, anti-seizure medications, diet therapy and surgical treatments in patients with myoclonic absences.
RESULTS
Ten patients were identified including twins with myoclonic absence status epilepticus. Forty percent had an atonic component, 20% presented with myoclonic absence status epilepticus and 60% had incomplete control of seizures at last follow-up visit. Two patients with epilepsy with myoclonic absences with atonia underwent corpus callosotomy; one patient was seizurefree eight months after surgery and the other had greater than 50% seizure reduction over a five-month period.
SIGNIFICANCE
Phenotypic heterogeneity was evident based on seizure semiologies, comorbidities, seizure frequency and response to anti-seizure medications and non-medication treatments. Of patients with an atonic component, 75% did not achieve seizure freedom with medication alone. Corpus callosotomy was performed in two of these patients with encouraging seizure response thus far, however, the efficacy of this treatment should be further evaluated in a larger study.
Topics: Age of Onset; Electroencephalography; Epilepsies, Myoclonic; Epilepsy; Humans; Status Epilepticus; Treatment Outcome
PubMed: 35770757
DOI: 10.1684/epd.2022.1420 -
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 -
Epilepsia Jun 2023Familial adult myoclonus epilepsy (FAME) is characterized by cortical myoclonus and often epileptic seizures, but the pathophysiology of this condition remains... (Review)
Review
Familial adult myoclonus epilepsy (FAME) is characterized by cortical myoclonus and often epileptic seizures, but the pathophysiology of this condition remains uncertain. Here, we review the neuroimaging and neuropathological findings in FAME. Imaging findings, including functional magnetic resonance imaging, are in line with a cortical origin of involuntary tremulous movements (cortical myoclonic tremor) and indicate a complex pattern of cerebellar functional connectivity. Scarce neuropathological reports, mainly from a single family, provide evidence of morphological changes in the Purkinje cells. Cerebellar changes seem to be part of the syndrome, in at least some FAME pedigrees. Cortical hyperexcitability in FAME, resulting in the cardinal clinical symptoms, might be the result of decreased cortical inhibition via the cerebellothalamocortical loop. The pathological findings might share some similarities with other pentanucleotide repeat disorders. The relation with genetic findings in FAME needs to be elucidated.
Topics: Adult; Humans; Myoclonus; Epilepsies, Myoclonic; Epilepsy; Neuroimaging; Cerebellum
PubMed: 37096373
DOI: 10.1111/epi.17628 -
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 -
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