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Neurology Jan 2023
Topics: Humans; Epilepsies, Myoclonic; Vaccination
PubMed: 36323523
DOI: 10.1212/WNL.0000000000201531 -
Annals of Clinical and Translational... Feb 2024To investigate and characterize epileptic seizures and electrophysiological features of familial cortical myoclonic tremor with epilepsy (FCMTE) type 1 patients in a...
OBJECTIVES
To investigate and characterize epileptic seizures and electrophysiological features of familial cortical myoclonic tremor with epilepsy (FCMTE) type 1 patients in a large Chinese cohort.
METHODS
We systematically evaluated 125 FCMTEtype 1 patients carrying the pentanucleotide (TTTCA) repeat expansion in the SAMD12 gene in China.
RESULTS
Among the 28 probands, epileptic seizures (96.4%, 27/28) were the most common reason for an initial clinic visit. Ninety-seven (77.6%, 97/125) patients had experienced seizures. The seizures onset age was 36.5 ± 9.0 years, which was 6.9 years later than cortical tremors. The seizures were largely rare (<1/year, 58.8%) and occasional (1-6/year, 37.1%). Prolonged prodromes were reported in 57.7% (56/97). Thirty-one patients (24.8%, 31/125) reported photosensitivity history, and 79.5% (31/39) had a photoparoxysmal response. Interictal epileptiform discharges (IEDs) were recorded in 69.1% (56/81) of patients. Thirty-three patients showed generalized IEDs and 72.7% (24/33) were occipitally dominant, while 23 patients presented with focal IEDs with 65.2% (15/23) taking place over the occipital lobe. Overnight EEG of FCMTE patients displayed paradoxical sleep-wake fluctuation, with a higher average IED index of 0.82 ± 0.88/min during wakefulness and a lower IED index of 0.04 ± 0.06/min during non-rapid eye movement sleep stages I-II.
INTERPRETATION
FCMTE type 1 has a benign course of epilepsy and distinct clinical and electrophysiological features. In addition to a positive family history and cortical myoclonus tremor, the seizure prodromes, specific seizure triggers, photosensitivity, distribution of IEDs, and unique fluctuations during sleep-wake cycle are cues for proper genetic testing and an early diagnosis of FCMTE.
Topics: Humans; Adult; Middle Aged; Tremor; Epilepsy; Epilepsies, Myoclonic; Seizures
PubMed: 38059543
DOI: 10.1002/acn3.51961 -
Clinical Neurophysiology : Official... Apr 2021To further delineate the electroclinical features of individuals with SYNGAP1 pathogenic variants.
OBJECTIVE
To further delineate the electroclinical features of individuals with SYNGAP1 pathogenic variants.
METHODS
Participants with pathogenic SYNGAP1 variants and available video-electroencephalogram (EEG) recordings were recruited within five European epilepsy reference centers. We obtained molecular and clinical data, analyzed EEG recordings and archived video-EEGs of seizures and detailed characteristics of interictal and ictal EEG patterns for every patient.
RESULTS
We recruited 15 previously unreported patients and analyzed 72 EEGs. Two distinct EEG patterns emerged, both triggered by eye closure. Pattern 1 (14/15 individuals) consisted of rhythmic posterior/diffuse delta waves appearing with eye-closure and persisting until eye opening (strongly suggestive of fixation-off sensitivity). Pattern 2 (9/15 individuals) consisted of diffuse polyspike-and-wave discharges triggered by eye closure (eye-closure sensitivity). Both patterns presented in 8/15. Including archived video-EEG clips of seizures from 9/15 patients, we analyzed 254 seizures. Of 224 seizures experienced while awake, 161 (72%) occurred at or following eye closure. In 119/161, pattern 1 preceded an atypical absence, myoclonic seizure or myoclonic absence; in 42/161, pattern 2 was associated with eyelid myoclonia, absences and myoclonic or atonic seizures.
CONCLUSIONS
Fixation-off and eye closure were the main triggers for seizures in this SYNGAP1 cohort.
SIGNIFICANCE
Combining these clinical and electroencephalographic features could help guide genetic diagnosis.
Topics: Adolescent; Brain; Child; Child, Preschool; Electroencephalography; Epilepsies, Myoclonic; Epilepsy, Reflex; Female; Humans; Infant; Male; ras GTPase-Activating Proteins
PubMed: 33639450
DOI: 10.1016/j.clinph.2021.01.014 -
Scientific Reports Feb 2022Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we...
Juvenile myoclonic epilepsy (JME) is a common idiopathic generalised epilepsy with variable seizure prognosis and sex differences in disease presentation. Here, we investigate the combined epidemiology of sex, seizure types and precipitants, and their influence on prognosis in JME, through cross-sectional data collected by The Biology of Juvenile Myoclonic Epilepsy (BIOJUME) consortium. 765 individuals met strict inclusion criteria for JME (female:male, 1.8:1). 59% of females and 50% of males reported triggered seizures, and in females only, this was associated with experiencing absence seizures (OR = 2.0, p < 0.001). Absence seizures significantly predicted drug resistance in both males (OR = 3.0, p = 0.001) and females (OR = 3.0, p < 0.001) in univariate analysis. In multivariable analysis in females, catamenial seizures (OR = 14.7, p = 0.001), absence seizures (OR = 6.0, p < 0.001) and stress-precipitated seizures (OR = 5.3, p = 0.02) were associated with drug resistance, while a photoparoxysmal response predicted seizure freedom (OR = 0.47, p = 0.03). Females with both absence seizures and stress-related precipitants constitute the prognostic subgroup in JME with the highest prevalence of drug resistance (49%) compared to females with neither (15%) and males (29%), highlighting the unmet need for effective, targeted interventions for this subgroup. We propose a new prognostic stratification for JME and suggest a role for circuit-based risk of seizure control as an avenue for further investigation.
Topics: Adolescent; Adult; Child; Cross-Sectional Studies; Drug Resistance; Epilepsies, Myoclonic; Epilepsy, Absence; Female; Humans; Male; Middle Aged; Myoclonic Epilepsy, Juvenile; Photosensitivity Disorders; Prognosis; Seizures; Sex Characteristics; Young Adult
PubMed: 35190554
DOI: 10.1038/s41598-022-06324-2 -
Epilepsia Aug 2023The progressive myoclonus epilepsies (PMEs) are a heterogeneous group of neurodegenerative disorders, typically presenting in late childhood. An etiologic diagnosis is...
The progressive myoclonus epilepsies (PMEs) are a heterogeneous group of neurodegenerative disorders, typically presenting in late childhood. An etiologic diagnosis is achieved in about 80% of patients with PME, and genome-wide molecular studies on remaining, well-selected, undiagnosed cases can further dissect the underlying genetic heterogeneity. Through whole-exome sequencing (WES), we identified pathogenic truncating variants in the IRF2BPL gene in two, unrelated patients presenting with PME. IRF2BPL belongs to the transcriptional regulators family and it is expressed in multiple human tissues, including the brain. Recently missense and nonsense mutations in IRF2BPL were found in patients presenting with developmental delay and epileptic encephalopathy, ataxia, and movement disorders, but none with clear PME. We identified 13 other patients in the literature with myoclonic seizures and IRF2BPL variants. There was no clear genotype-phenotype correlation. With the description of these cases, the IRF2BPL gene should be considered in the list of genes to be tested in the presence of PME, in addition to patients with neurodevelopmental or movement disorders.
Topics: Humans; Child; Myoclonic Epilepsies, Progressive; Seizures; Epilepsies, Myoclonic; Genotype; Movement Disorders; Carrier Proteins; Nuclear Proteins
PubMed: 36810721
DOI: 10.1111/epi.17557 -
Clinical Dysmorphology Jan 2022Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM# 611726) is a rare autosomal recessive condition associated with pathogenic variants in... (Review)
Review
Epilepsy, progressive myoclonic 3, with or without intracellular inclusions (MIM# 611726) is a rare autosomal recessive condition associated with pathogenic variants in KCTD7, which encodes the BR-C,ttk and bab/pox virus and zinc finger domain-containing KCTD7 protein. We report four individuals from three Indian families presenting with an initial period of normal development, progressive myoclonic seizures followed by neuroregression and an abnormal electroencephalogram. We identified two novel missense variants, c.458G>C p.(Arg153Pro) and c.205C>G p.(Leu69Val) and one known disease-causing variant, c.280C>T p.(Arg94Trp) in KCTD7 by exome sequencing. We review the literature of 67 individuals with variants in KCTD7. Our study expands the molecular spectrum of KCTD7-related progressive myoclonic epilepsy.
Topics: Humans; Mutation, Missense; Myoclonic Epilepsies, Progressive; Potassium Channels; Exome Sequencing
PubMed: 34866617
DOI: 10.1097/MCD.0000000000000394 -
Revue Neurologique Apr 2024The ILAE's Task Force on Nosology and Definitions revised in 2022 its definition of juvenile myoclonic epilepsy (JME), the most common idiopathic generalized epilepsy... (Review)
Review
The ILAE's Task Force on Nosology and Definitions revised in 2022 its definition of juvenile myoclonic epilepsy (JME), the most common idiopathic generalized epilepsy disorder, but this definition may well change again in the future. Although good drug response could almost be a diagnostic criterion for JME, drug resistance (DR) is observed in up to a third of patients. It is important to distinguish this from pseudoresistance, which is often linked to psychosocial problems or psychiatric comorbidities. After summarizing these aspects and the various definitions applied to JME, the present review lists the risk factors for DR-JME that have been identified in numerous studies and meta-analyses. The factors most often cited are absence seizures, young age at onset, and catamenial seizures. By contrast, photosensitivity seems to favor good treatment response, at least in female patients. Current hypotheses on DR mechanisms in JME are based on studies of either simple (e.g., cortical excitability) or more complex (e.g., anatomical and functional connectivity) neurophysiological markers, bearing in mind that JME is regarded as a neural network disease. This research has revealed correlations between the intensity of some markers and DR, and above all shed light on the role of these markers in associated neurocognitive and neuropsychiatric disorders in both patients and their siblings. Studies of neurotransmission have mainly pointed to impaired GABAergic inhibition. Genetic studies have generally been inconclusive. Increasing restrictions have been placed on the use of valproate, the standard antiseizure medication for this syndrome, owing to its teratogenic and developmental risks. Levetiracetam and lamotrigine are prescribed as alternatives, as is vagal nerve stimulation, and there are several other promising antiseizure drugs and neuromodulation methods. The development of better alternative treatments is continuing to take place alongside advances in our knowledge of JME, as we still have much to learn and understand.
Topics: Humans; Myoclonic Epilepsy, Juvenile; Anticonvulsants; Drug Resistant Epilepsy; Female; Risk Factors
PubMed: 38461125
DOI: 10.1016/j.neurol.2024.02.385 -
Acta Neurologica Belgica Apr 2024Familial Adult Myoclonus Epilepsy (FAME), with a prevalence of < 1/35 000, is known under different acronyms. The disease is transmitted in an autosomal dominant... (Review)
Review
Familial Adult Myoclonus Epilepsy (FAME), with a prevalence of < 1/35 000, is known under different acronyms. The disease is transmitted in an autosomal dominant manner and is characterized by the occurrence of cortical myoclonic tremor, overt myoclonus, and rare bilateral tonic-clonic seizures. FAME is considered neurodegenerative, although it is relatively slow in progression. Diagnosis is based on specific neurophysiological testing, namely jerk-locked back-averaging, somatosensory evoked potentials, long latency reflex, and motor evoked potentials, among others. Imaging data, including functional magnetic resonance imaging, indicate a cortical origin of the cortical myoclonic tremor and decreased cerebellar activation. Cerebellar changes in Purkinje cells have been noted, from few neuropathology reports, in patients from isolated pedigrees. The differential diagnosis includes essential tremor, some forms of genetic generalized epilepsy, and progressive myoclonus epilepsies. Treatment is mainly symptomatic.
Topics: Adult; Humans; Myoclonus; Tremor; Epilepsies, Myoclonic; Evoked Potentials, Somatosensory; Reflex; Electroencephalography
PubMed: 38114875
DOI: 10.1007/s13760-023-02432-6 -
Epilepsia Jun 2023Familial adult myoclonic epilepsy (FAME) is an under-recognized disorder characterized by cortical myoclonus, generalized tonic-clonic seizures, and additional clinical...
OBJECTIVE
Familial adult myoclonic epilepsy (FAME) is an under-recognized disorder characterized by cortical myoclonus, generalized tonic-clonic seizures, and additional clinical symptoms, which vary depending on the FAME subtype. FAME is caused by pentanucleotide repeat expansions of intronic TTTCA/TTTTA in different genes. FAME should be distinguished from a range of differential diagnoses.
METHODS
The differential diagnoses and frequent presentations leading to misdiagnosis of FAME were investigated from the available literature and reported based on an expert opinion survey.
RESULTS
The phenotypic features of FAME, including generalized tonic-clonic and myoclonic seizures, are also seen in other epilepsy syndromes, such as juvenile myoclonic epilepsy, with a resultant risk of misdiagnosis and lack of identification of the underlying cause. Cortical myoclonus may mimic essential tremor or drug-induced tremor. In younger individuals, the differential diagnosis includes progressive myoclonus epilepsies (PMEs), such as Unverricht-Lundborg disease, whereas, in adulthood, late-onset variants of PMEs, such as sialidoses, myoclonus epilepsy, and ataxia due to potassium channel pathogenic variants should be considered. PMEs may also be suggested by cognitive impairment, cerebellar signs, or psychiatric disorders. Electroencephalography (EEG) may show similarities to other idiopathic generalized epilepsies or PMEs, with generalized spike-wave activity. Signs of cortical hyperexcitability may be seen, such as an increased amplitude of somatosensory evoked potentials or enhanced cortical reflex to sensory stimuli, together with the neurophysiological pattern of the movement disorder.
SIGNIFICANCE
Recognition of FAME will inform prognostic and genetic counseling and diagnosis of the insidious progression, which may occur in older individuals who show mild cognitive deterioration. Distinguishing FAME from other disorders in individuals or families with this constellation of symptoms is essential to allow the identification of underlying etiology.
Topics: Humans; Adult; Aged; Diagnosis, Differential; Myoclonus; Epilepsies, Myoclonic; Epilepsy, Generalized; Electroencephalography; Myoclonic Epilepsies, Progressive; Myoclonic Epilepsy, Juvenile; Seizures
PubMed: 36751956
DOI: 10.1111/epi.17536 -
Pharmaceutical Patent Analyst Sep 2021
Topics: Epilepsies, Myoclonic; Humans; Spasms, Infantile
PubMed: 34488475
DOI: 10.4155/ppa-2021-0020