RARE DISEASE
Juvenile myoclonic epilepsy
Juvenile myoclonic epilepsy
Juvenile myoclonic epilepsy
Synonyms: JME, Juvenile myoclonus epilepsy
Synonyms: JME, Juvenile myoclonus epilepsy
Synonyms: JME, Juvenile myoclonus epilepsy
Drug discovery
0
drugs
With orphan designations
Overview
Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy syndrome characterized by myoclonic jerks, generalized tonic-clonic seizures, and sometimes absence seizures, typically emerging in adolescence (12–18 years). Triggered by sleep deprivation, alcohol, or stress, it features 3–5.5 Hz polyspike-wave EEG patterns and photosensitivity. Valproate remains first-line therapy, though alternatives like levetiracetam are preferred for women of childbearing age. Lifelong treatment is often required due to high relapse rates [1][2][3][18].
Burden
Categories: rare genetic diseases, rare neurological diseases
Research Papers
363 drug discovery papers about Juvenile myoclonic epilepsy, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
363 drug discovery papers about Juvenile myoclonic epilepsy, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-06-09 | Comparative Efficacy of Valproate and Levetiracetam Monotherapy in Women of Childbearing Age with Juvenile Myoclonic Epilepsy: A Retrospective Cohort from Latin America (P4-10.002)
To compare seizure freedom between valproate (VPA) and levetiracetam (LEV) monotherapy in women of childbearing age with Juvenile Myoclonic Epilepsy (JME).
2026-05-31 | Impact of valproate discontinuation on seizure control in women of reproductive age.
To evaluate seizure control in women of reproductive age treated with valproic acid and to compare seizure outcomes between those who continued valproic acid and those who were switched to other anti-seizure medications. Data of women with epilepsy were analyzed from prospectively maintained electronic medical records between 2013 and 2022 at a tertiary epilepsy referral center. Women aged 18 to 45 years with generalized or focal epilepsy who were well controlled on valproic acid were included. Clinical characteristics, anti-seizure medication use, seizure control during valproic acid treatment and after switching to other anti-seizure medications, adverse effects, and pregnancy-related complications were analyzed. Sixty-nine women with epilepsy who were seizure-free for at least one year on valproic acid were included. Of these, 28 had juvenile myoclonic epilepsy, 30 had other idiopathic generalized epilepsy subtypes, and 11 had focal epilepsy. Only 26 patients (37.68%) required a valproic acid dose greater than 800 milligrams per day for seizure control. Eighteen patients were switched from valproic acid to other anti-seizure medications, of whom 10 (55.55%) experienced seizure recurrence at 12-month follow-up. Among patients who continued valproic acid, teratogenicity occurred in three patients (5.88%), with a mean daily dose of 1133 milligrams. The requirement for polytherapy was higher in the switch group compared to the valproic acid continuation group (44.44% versus 11.80%). In women with epilepsy who are well controlled on low-dose valproic acid, switching to alternative anti-seizure medications is associated with a high risk of seizure recurrence and increased need for polytherapy. Decisions regarding withdrawal of valproic acid should be individualized, planned well in advance of pregnancy, and made after detailed discussion with the patient, balancing the risks of losing seizure control against potential teratogenic effects.
2026-05-01 | Brivaracetam monotherapy in juvenile myoclonic epilepsy: a safety and efficacy evaluation.
The treatment of juvenile myoclonic epilepsy (JME) is limited, with most patients requiring long-term medication and over half experiencing seizure recurrence upon drug withdrawal. As a third-generation antiseizure medication, brivaracetam (BRV) has emerged as a promising therapeutic option. Its efficacy has been investigated in focal epilepsies and genetic generalized epilepsies (GGEs), with promising results. This study aims to evaluate the safety and preliminary efficacy of BRV as an off-label initial monotherapy in patients with newly diagnosed JME, with a specific focus on the control of myoclonic seizures. A prospective, single-center, and observational study. This study prospectively enrolled drug-naïve patients with JME. All participants received BRV monotherapy. Clinical data were collected at baseline and after a 6-month follow-up period, including demographic characteristics, electroencephalography (EEG), cranial magnetic resonance imaging (MRI), and comprehensive neuropsychological assessments. Changes in seizure frequency, cognitive function, levels of anxiety and depression, sleep quality, and quality of life from baseline to the 6-month follow-up were analyzed and compared. A total of 19 patients were included with a mean age of 20.26 ± 6.88 years (median: 18, interquartile range: 8), and a male-to-female ratio of 12:7. The average age of onset was 14.58 ± 3.42 years, and the average duration of epilepsy prior to BRV treatment was 5.71 ± 7.40 years (median: 2, interquartile range: 5). The mean frequency of myoclonic seizures at baseline was 38.79 ± 45.60 times per month (median: 10, interquartile range: 86). Eighteen patients (94.73%) experienced both generalized tonic-clonic seizures (GTCS) and myoclonic seizures, one patient only experienced myoclonic seizures, The MRI findings were negative in all patients (100%). The EEG of all patients at baseline was abnormal, revealing 3-5.5 Hz generalized spike-and-wave or polyspike-and-wave discharges. At the 6-month evaluation, all patients achieved seizure-free status (p < 0.001), neuropsychological assessments also demonstrated significant improvement, including Montreal Cognitive Assessment (MoCA; p < 0.001), Hamilton Anxiety Scale (HAMA; p < 0.001), Hamilton Depression Scale (HAMD; p < 0.001), Pittsburgh Sleep Quality Index (PSQI; p < 0.001), and Quality of Life in Epilepsy-31 (QOLIE-31; p < 0.001). Only one patient complained of poor sleep after BRV administration. This study suggests that BRV may offer promising efficacy, specifically in controlling myoclonic seizures and favorable tolerability as an off-label initial monotherapy for JME patients. While the evaluation of efficacy against GTCS requires longer follow-up, our findings support the potential of BRV as a therapeutic option for JME. Further randomized controlled trials are warranted to validate these observations.
2026-04-17 | Thermodynamic rigidity of harmonic brain states relates to general mental ability in juvenile myoclonic epilepsy.
Cognitive difficulties are increasingly recognized in juvenile myoclonic epilepsy (JME), but scalable biomarkers linking resting-state brain dynamics to general mental ability remain limited. Here, we combined topological data analysis, graph signal processing, machine learning, inverse Langevin modeling, and biophysical simulations to test whether EEG-derived network dynamics capture individual differences in general mental ability in JME. We studied 54 patients with JME and 45 healthy controls using resting-state high-density EEG and the raw estimated full-scale score derived from the Wechsler Abbreviated Scale of Intelligence (WASI), used here as an index of general mental ability. Subject-specific low-alpha activity was reconstructed with generalized eigendecomposition, and graph-derived features were extracted from the projection of topological and alpha-power signals onto the functional connectome, providing a graph-harmonic description of large-scale brain-state dynamics. In controls, dynamic EEG-derived features significantly predicted general mental ability, whereas the same framework failed in JME. Because prediction in controls was driven mainly by dynamic measures of smoothness (Dirichlet energy), we next examined the temporal organization of alpha-power smoothness using an inverse Langevin framework. Within the patient group, greater thermodynamic rigidity-that is, stronger confinement of fluctuations around preferred network states-was associated with lower general mental ability. Relative to controls, patients also showed lower thermodynamic noise, indicating a reduced tendency to explore alternative network regimes. Biophysical simulations suggested that reduced dendritic arborization can generate rigidity directly, whereas pharmacological stabilization of hyperexcitable circuits can shift the system toward a more rigid, lower-noise regime. Together, these findings suggest that cognition in JME is linked not only to altered resting-state network dynamics but also to stronger confinement of network-state fluctuations, with both intrinsic circuit abnormalities and treatment-related stabilization representing plausible routes to this rigid phenotype.
2026-03-27 | A Stroke of Insight? Possible Bidirectional Relationship Between Stroke and Epilepsy
Background: Observational studies have established a relationship between stroke and epilepsy. While most studies have reported an increased risk of epilepsy following a stroke, fewer have concluded that a diagnosis of epilepsy increases the risk of future strokes. Precisely describing the causal relationship between epilepsy and stroke has clinical and public health implications. Methods: We performed a two-sample Mendelian Randomization (MR) to analyze the relationship between epilepsy and stroke. We identified genetic instruments from the Stroke Multiancestry Genome-Wide Association Study [GCST005838 (67,162 cases and 454,450 controls)] and the International League Against Epilepsy Consortium on Complex Epilepsies [Generalized epilepsy (GE): GCST007343 (n_case=3769, n_control=29677), Focal epilepsy (FE): GCST007352 (n_case=9671, n_control=29677)]. We used a significance threshold of p -value <5 × 10 (−5) for genetic instrument identification. We included the following epilepsy phenotypes: GE, FE, childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy, GE with tonic-clonic seizures, FE with hippocampal sclerosis (focal HS), and focal lesion-negative epilepsy. Linkage disequilibrium reference panel of 1000 Genome Project pruning with Pearson correlation r 2 < 0.2 was applied to ensure that the analysis is restricted to independent variants. We used Steiger filtering for reverse causality and Z -scores for GE and FE. We employed the following methods for causal effect estimation: Inverse-variance weighted (IVW), MR-Egger, MR-RAPS, and MRPRESSO. Results: For the association between GE and stroke (GE > stroke), stroke and GE (stroke > GE), FE and stroke (FE > stroke), and stroke and FE (stroke > FE), the number of single nucleotide polymorphisms was respectively 253, 213, 187, and 210. GE was associated with an increased risk of stroke [IVW, 95% confidence interval: 0.058 (0.028-0.088)], and stroke was also associated with an increased risk of GE [IVW: 0.059 (0.026-0.092)]. FE was associated with an increased risk of stroke [IVW: 0.066 (0.029-0.102)] and stroke was associated with an increased risk of FE [IVW: 0.037(0.005-0.068)]. The analysis by epilepsy subtypes revealed an increased risk only among patients with stroke and for the following epilepsy subtypes: JAE, CAE, Focal HS, and Focal lesion negative epilepsy. Conclusion: Our findings support a bidirectional relationship between stroke and epilepsy. Studies on post-stroke epilepsy should account for this bidirectional relationship.
2026-06-09 | Comparative Efficacy of Valproate and Levetiracetam Monotherapy in Women of Childbearing Age with Juvenile Myoclonic Epilepsy: A Retrospective Cohort from Latin America (P4-10.002)
To compare seizure freedom between valproate (VPA) and levetiracetam (LEV) monotherapy in women of childbearing age with Juvenile Myoclonic Epilepsy (JME).
2026-05-31 | Impact of valproate discontinuation on seizure control in women of reproductive age.
To evaluate seizure control in women of reproductive age treated with valproic acid and to compare seizure outcomes between those who continued valproic acid and those who were switched to other anti-seizure medications. Data of women with epilepsy were analyzed from prospectively maintained electronic medical records between 2013 and 2022 at a tertiary epilepsy referral center. Women aged 18 to 45 years with generalized or focal epilepsy who were well controlled on valproic acid were included. Clinical characteristics, anti-seizure medication use, seizure control during valproic acid treatment and after switching to other anti-seizure medications, adverse effects, and pregnancy-related complications were analyzed. Sixty-nine women with epilepsy who were seizure-free for at least one year on valproic acid were included. Of these, 28 had juvenile myoclonic epilepsy, 30 had other idiopathic generalized epilepsy subtypes, and 11 had focal epilepsy. Only 26 patients (37.68%) required a valproic acid dose greater than 800 milligrams per day for seizure control. Eighteen patients were switched from valproic acid to other anti-seizure medications, of whom 10 (55.55%) experienced seizure recurrence at 12-month follow-up. Among patients who continued valproic acid, teratogenicity occurred in three patients (5.88%), with a mean daily dose of 1133 milligrams. The requirement for polytherapy was higher in the switch group compared to the valproic acid continuation group (44.44% versus 11.80%). In women with epilepsy who are well controlled on low-dose valproic acid, switching to alternative anti-seizure medications is associated with a high risk of seizure recurrence and increased need for polytherapy. Decisions regarding withdrawal of valproic acid should be individualized, planned well in advance of pregnancy, and made after detailed discussion with the patient, balancing the risks of losing seizure control against potential teratogenic effects.
2026-05-01 | Brivaracetam monotherapy in juvenile myoclonic epilepsy: a safety and efficacy evaluation.
The treatment of juvenile myoclonic epilepsy (JME) is limited, with most patients requiring long-term medication and over half experiencing seizure recurrence upon drug withdrawal. As a third-generation antiseizure medication, brivaracetam (BRV) has emerged as a promising therapeutic option. Its efficacy has been investigated in focal epilepsies and genetic generalized epilepsies (GGEs), with promising results. This study aims to evaluate the safety and preliminary efficacy of BRV as an off-label initial monotherapy in patients with newly diagnosed JME, with a specific focus on the control of myoclonic seizures. A prospective, single-center, and observational study. This study prospectively enrolled drug-naïve patients with JME. All participants received BRV monotherapy. Clinical data were collected at baseline and after a 6-month follow-up period, including demographic characteristics, electroencephalography (EEG), cranial magnetic resonance imaging (MRI), and comprehensive neuropsychological assessments. Changes in seizure frequency, cognitive function, levels of anxiety and depression, sleep quality, and quality of life from baseline to the 6-month follow-up were analyzed and compared. A total of 19 patients were included with a mean age of 20.26 ± 6.88 years (median: 18, interquartile range: 8), and a male-to-female ratio of 12:7. The average age of onset was 14.58 ± 3.42 years, and the average duration of epilepsy prior to BRV treatment was 5.71 ± 7.40 years (median: 2, interquartile range: 5). The mean frequency of myoclonic seizures at baseline was 38.79 ± 45.60 times per month (median: 10, interquartile range: 86). Eighteen patients (94.73%) experienced both generalized tonic-clonic seizures (GTCS) and myoclonic seizures, one patient only experienced myoclonic seizures, The MRI findings were negative in all patients (100%). The EEG of all patients at baseline was abnormal, revealing 3-5.5 Hz generalized spike-and-wave or polyspike-and-wave discharges. At the 6-month evaluation, all patients achieved seizure-free status (p < 0.001), neuropsychological assessments also demonstrated significant improvement, including Montreal Cognitive Assessment (MoCA; p < 0.001), Hamilton Anxiety Scale (HAMA; p < 0.001), Hamilton Depression Scale (HAMD; p < 0.001), Pittsburgh Sleep Quality Index (PSQI; p < 0.001), and Quality of Life in Epilepsy-31 (QOLIE-31; p < 0.001). Only one patient complained of poor sleep after BRV administration. This study suggests that BRV may offer promising efficacy, specifically in controlling myoclonic seizures and favorable tolerability as an off-label initial monotherapy for JME patients. While the evaluation of efficacy against GTCS requires longer follow-up, our findings support the potential of BRV as a therapeutic option for JME. Further randomized controlled trials are warranted to validate these observations.
2026-04-17 | Thermodynamic rigidity of harmonic brain states relates to general mental ability in juvenile myoclonic epilepsy.
Cognitive difficulties are increasingly recognized in juvenile myoclonic epilepsy (JME), but scalable biomarkers linking resting-state brain dynamics to general mental ability remain limited. Here, we combined topological data analysis, graph signal processing, machine learning, inverse Langevin modeling, and biophysical simulations to test whether EEG-derived network dynamics capture individual differences in general mental ability in JME. We studied 54 patients with JME and 45 healthy controls using resting-state high-density EEG and the raw estimated full-scale score derived from the Wechsler Abbreviated Scale of Intelligence (WASI), used here as an index of general mental ability. Subject-specific low-alpha activity was reconstructed with generalized eigendecomposition, and graph-derived features were extracted from the projection of topological and alpha-power signals onto the functional connectome, providing a graph-harmonic description of large-scale brain-state dynamics. In controls, dynamic EEG-derived features significantly predicted general mental ability, whereas the same framework failed in JME. Because prediction in controls was driven mainly by dynamic measures of smoothness (Dirichlet energy), we next examined the temporal organization of alpha-power smoothness using an inverse Langevin framework. Within the patient group, greater thermodynamic rigidity-that is, stronger confinement of fluctuations around preferred network states-was associated with lower general mental ability. Relative to controls, patients also showed lower thermodynamic noise, indicating a reduced tendency to explore alternative network regimes. Biophysical simulations suggested that reduced dendritic arborization can generate rigidity directly, whereas pharmacological stabilization of hyperexcitable circuits can shift the system toward a more rigid, lower-noise regime. Together, these findings suggest that cognition in JME is linked not only to altered resting-state network dynamics but also to stronger confinement of network-state fluctuations, with both intrinsic circuit abnormalities and treatment-related stabilization representing plausible routes to this rigid phenotype.
2026-03-27 | A Stroke of Insight? Possible Bidirectional Relationship Between Stroke and Epilepsy
Background: Observational studies have established a relationship between stroke and epilepsy. While most studies have reported an increased risk of epilepsy following a stroke, fewer have concluded that a diagnosis of epilepsy increases the risk of future strokes. Precisely describing the causal relationship between epilepsy and stroke has clinical and public health implications. Methods: We performed a two-sample Mendelian Randomization (MR) to analyze the relationship between epilepsy and stroke. We identified genetic instruments from the Stroke Multiancestry Genome-Wide Association Study [GCST005838 (67,162 cases and 454,450 controls)] and the International League Against Epilepsy Consortium on Complex Epilepsies [Generalized epilepsy (GE): GCST007343 (n_case=3769, n_control=29677), Focal epilepsy (FE): GCST007352 (n_case=9671, n_control=29677)]. We used a significance threshold of p -value <5 × 10 (−5) for genetic instrument identification. We included the following epilepsy phenotypes: GE, FE, childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy, GE with tonic-clonic seizures, FE with hippocampal sclerosis (focal HS), and focal lesion-negative epilepsy. Linkage disequilibrium reference panel of 1000 Genome Project pruning with Pearson correlation r 2 < 0.2 was applied to ensure that the analysis is restricted to independent variants. We used Steiger filtering for reverse causality and Z -scores for GE and FE. We employed the following methods for causal effect estimation: Inverse-variance weighted (IVW), MR-Egger, MR-RAPS, and MRPRESSO. Results: For the association between GE and stroke (GE > stroke), stroke and GE (stroke > GE), FE and stroke (FE > stroke), and stroke and FE (stroke > FE), the number of single nucleotide polymorphisms was respectively 253, 213, 187, and 210. GE was associated with an increased risk of stroke [IVW, 95% confidence interval: 0.058 (0.028-0.088)], and stroke was also associated with an increased risk of GE [IVW: 0.059 (0.026-0.092)]. FE was associated with an increased risk of stroke [IVW: 0.066 (0.029-0.102)] and stroke was associated with an increased risk of FE [IVW: 0.037(0.005-0.068)]. The analysis by epilepsy subtypes revealed an increased risk only among patients with stroke and for the following epilepsy subtypes: JAE, CAE, Focal HS, and Focal lesion negative epilepsy. Conclusion: Our findings support a bidirectional relationship between stroke and epilepsy. Studies on post-stroke epilepsy should account for this bidirectional relationship.
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