Edit concept Question Editor Create issue ticket

Juvenile Myoclonic Epilepsy

JME

Juvenile myoclonic epilepsy is a common form of epilepsy mainly characterized by myoclonic jerks, but affected individuals may also experience generalized tonic-clonic seizures and absence seizures. Symptom onset typically occurs around puberty and although the disease persists into adulthood, patients do respond well to therapy.

Juvenile Myoclonic Epilepsy - Symptom Checker

Ad Check possible symptoms of Juvenile Myoclonic Epilepsy now!

Presentation

As per definition, symptom onset occurs around puberty and adolescents suffering from JME are of normal intelligence. JME is characterized by arrhythmic, myoclonic jerks that may be experienced repetitively. In general, they follow a bilateral, symmetric pattern, and single jerks last less than a second. Although jerks preferentially affect the musculature of the arms, involuntary contractions of leg muscles may cause sudden falls. The amplitude of involuntary movements may range from a mere sense of electric shock to minimal twitchings to violent movements of the limbs. Contrary to other forms of epilepsy, consciousness remains unaltered during such a JME fit. As has been indicated above, myoclonia is most commonly experienced upon awakening, and this fact may be related to increased photosensitivity, as occasionally described by affected individuals [7].

Additionally, JME patients may suffer from generalized tonic-clonic seizures. Most patients eventually develop these types of seizures, but years may pass after the onset of myoclonic jerks and thus, they are rarely reported by adolescents upon first presentation [8]. They may be preceded by multiple jerks that last a few minutes in total.

Absence seizures are less commonly observed but have been reported in early stages of the disease. In fact, some patients initially present because of absence seizures and don't develop myoclonia until months later. To date, it cannot be accurately predicted whether a pediatric patient experiencing an absence seizure will develop JME, but a delayed response to antiepileptic therapy, absence status and a family history of generalized epilepsy are unfavorable prognostic factors to this end [13].

Although not commonly considered an intrinsic feature of JME, patients are more likely to present psychiatric disorders, particularly behavioral disturbances, mood swings, anxiety, and psychosis, than the general population [14].

Falling
  • More severe attacks may be accompanied by a fall. The myoclonic jerks occur rarely in EMA. They are usually mild and are freqently restricted to the upper extremities.[ncbi.nlm.nih.gov]
  • He’ll pass out and may fall to the floor. They usually last for 1-3 minutes. Seizures often happen within 30 minutes to an hour of waking up in the morning or after a nap.[webmd.com]
  • A 21-year old man with marked developmental delay was referred for the diagnosis of myoclonic jerks (MJ), which were sometimes responsible for sudden falls without loss of consciousness, that had begun 2 years before, and for a recent generalized tonic-clonic[ncbi.nlm.nih.gov]
  • These seizures are longer, cause the person to stridden and fall to the ground, and for the limbs jerk in strong, rhythmic movements. They may also lose consciousness and lose control of body functions.[cedars-sinai.edu]
  • The jerks may cause the person to fall over or to lose their grip on whatever they were holding. The person remains largely conscious during the event.[study.com]
Developmental Delay
  • A 21-year old man with marked developmental delay was referred for the diagnosis of myoclonic jerks (MJ), which were sometimes responsible for sudden falls without loss of consciousness, that had begun 2 years before, and for a recent generalized tonic-clonic[ncbi.nlm.nih.gov]
  • Key words: juvenile myoclonic epilepsy, severe mental retardation, brain abnormalities, neuroradiology Page(s) : 27-32 Published in: 2000 A 21-year old man with marked developmental delay was referred for the diagnosis of myoclonic jerks (MJ), which were[jle.com]
Muscle Twitch
  • Myoclonic seizures and muscle twitching or uncontrolled jerking are the most common type of seizures in the people suffering with JME.[eurekaselect.com]
  • twitches or jerks in the upper arms, shoulders, or neck movements on both sides of the body at the same time child usually is awake and can think clearly during and right after the seizure Tonic-clonic seizure convulsions, or rigid muscles and rhythmic[m.kidshealth.org]
  • The characteristic signs of JME are brief episodes of involuntary muscle twitching. These are brief episodes of involuntary muscle contractions occurring early in the morning or shortly before falling asleep.[en.wikipedia.org]
Seizure
  • Seizure outcome: 62% (109/175) were seizure-free of myoclonic seizures (MS), generalized tonic clonic seizures (GTCS) and absence seizures (AS) for 1 year, and 53% (94/175) for 2 years, including 16 patients (9%) without AEDs.[ncbi.nlm.nih.gov]
  • Most people with JME will also need one or more anti-seizure medications. They can control seizures in 90% of people with the condition.[webmd.com]
  • Rotatory seizures have been reported in association with focal intracranial lesions. This type of seizure was also described in patients with primary generalized epilepsies.[ncbi.nlm.nih.gov]
  • Myoclonic seizures (MC) evolving to generalized tonic-clonic seizures (GTC) were associated with seizure persistence (p 0.013), whereas 1 year between MC and GTC onset was associated with a trend to GTC remission (p 0.069).[ncbi.nlm.nih.gov]
  • The combination of three seizure types and focal electroencephalogram features were independent factors of poor seizure control.[ncbi.nlm.nih.gov]
Tonic-Clonic Seizure
  • JME includes three types of generalized seizures: typical absences, myoclonic jerks and generalized tonic-clonic seizures.[ncbi.nlm.nih.gov]
  • Clinically relevant was that the headache was the primary persistent clinical symptom of her JME before the onset of generalized tonic-clonic seizures.[ncbi.nlm.nih.gov]
  • Additionally, JME patients may suffer from generalized tonic-clonic seizures.[symptoma.com]
  • Drinking alcohol, which can lead to too little sleep and fatigue, is the strongest trigger of myoclonic jerks and tonic-clonic seizures. Flickering lights can also trigger seizures for some people.[webmd.com]
  • Both patients had myoclonic jerks on waking and evidence of absence seizures as well as generalized tonic-clonic seizures. A diagnosis of benign juvenile myoclonic epilepsy was made, and the seizures were controlled with valproic acid.[ncbi.nlm.nih.gov]
Myoclonic Jerking
  • The myoclonic jerks occur rarely in EMA. They are usually mild and are freqently restricted to the upper extremities.[ncbi.nlm.nih.gov]
  • We conclude that JME may go undiagnosed due to the underrecognition of myoclonic jerks. To make a correct diagnosis, clinicians need to ask specifically about myoclonic jerks.[ncbi.nlm.nih.gov]
  • The combination of myoclonic jerks and absence seizures without GTCSs is rare, occurring in only 2% of patients. Myoclonic jerks or seizures Myoclonic jerks or seizures without impairment of consciousness are the cardinal symptoms of JME.[emedicine.medscape.com]
  • The clinical triad of absence seizures, myoclonic jerks and generalised tonic clonic seizures (GTCS) rarely begin after the second decade of life.[ncbi.nlm.nih.gov]
Cognitive Deficit
  • We conclude that analyzing the affected subnetworks may provide new insights into understanding seizure generation, as well as the cognitive deficits observed in JME patients.[ncbi.nlm.nih.gov]
  • Patients with treatment-refractory seizures seem to present a broader impairment related to both cognitive deficits and impulsive traits.[ncbi.nlm.nih.gov]
  • In addition, we determined the relationship between cognitive deficit and microstructural abnormalities by evaluating the correlation between the neuropsychological test battery results and DTI parameters.[ncbi.nlm.nih.gov]
Involuntary Movements
  • Visit for more related articles at Journal of Neurology & Neurophysiology Keywords tics; twitching; involuntary movements; juvenile myoclonic epilepsy Introduction Tics are characterized by abrupt, repetitive, stereotyped and involuntary movements (motor[omicsonline.org]
  • The amplitude of involuntary movements may range from a mere sense of electric shock to minimal twitchings to violent movements of the limbs. Contrary to other forms of epilepsy, consciousness remains unaltered during such a JME fit.[symptoma.com]

Workup

About half of JME patients have a family history of JME. Symptom onset typically occurs in adolescence, and patients don't generally have a medical history of neurological disorders other than absence seizures. These anamnestic data should be considered when establishing a list of potential differential diagnoses.

Electrophysiological studies are indicated to associate clinical findings with a determined entity. Ideally, an electroencephalogram is recorded from a sleep-derived patient. Here, spike-and-wave and polyspike-and-wave activity following a bilateral, symmetric pattern may be observed at a frequency of about 5 Hz, preferentially in the frontocentral region. The background is usually unaltered. Continuous electroencephalographic monitoring is required to observe ictal discharges, which generally occur at a frequency of about 15 Hz and are accompanied by myoclonic jerks. A total of up to 20 spikes may be recorded while the patient is experiencing myoclonia, with the number of spikes correlating with the intensity of involuntary muscle contractions. Intermittent photic stimulation may provoke electrophysiological activity as described for the sleep-deprived patient or trigger ictal-like discharges [15].

Neuroimaging is usually not required but may be indicated in case of inconsistent clinical and electrophysiological findings or in patients who don't respond to antiepileptic therapy.

Generalized Polyspikes
  • Generalized tonic-clonic seizures, photosensitivity and generalized polyspike-wave discharges provoked by eye closure are features of both epileptic syndromes.[ncbi.nlm.nih.gov]
  • Electroencephalograms during these episodes showed almost continuous generalized polyspike-waves in both patients. Patients with JME can develop NCSE, which may be overlooked because of the subtle clinical symptoms.[ncbi.nlm.nih.gov]
  • All had generalized spike and wave on the interictal electroencephalogram, and 86% of them also had generalized polyspike and wave discharges.[ncbi.nlm.nih.gov]
  • The EEG in untreated individuals is typically abnormal with what is known as a 3-6 Hz generalized polyspike and wave discharge. An example of this condition is reflected in the figure at the top of this page.[epilepsy.com]
Spike-and-Slow-Waves
  • We applied dipole modeling and brain distributed source analysis to find current sources comprising spikes and slow waves of polyspike and wave complexes (PSWC) in patients with juvenile myoclonic epilepsy (JME).[ncbi.nlm.nih.gov]
  • Each SWD was divided into six distinct temporal phases: spike onset, spike peak, slow-wave onset, slow-wave ascending, slow-wave peak, and slow-wave descending phases.[ncbi.nlm.nih.gov]
  • The discharge is frequently short and fragmented, the spike and slow wave complexes show interdischarge frequency variations with multiple spikes and other characteristics which are different from those of CAE and JAE components. [3], [13], [14] However[neurologyindia.com]
Polyspike-and-Slow-Waves
  • Additionally, an electroencephalogram (EEG), will indicate a characteristic pattern of waves and spikes associated with the syndrome such as generalized 4–6 Hz polyspike and slow wave discharges.[en.wikipedia.org]
  • The EEG typically shows a characteristic pattern with generalized 4–6 Hz polyspike and slow wave discharges . These changes are often induced by photic stimulation (blinking lights) and sometimes hyperventilation.[medindia.net]
Generalized Epileptiform Discharges
  • In all three families, one individual was regarded as affected based on unprovoked generalized epileptiform discharges in the EEG. Mutation screening.[dx.doi.org]

Treatment

Therapy of JME is based on the provision of antiepileptic medication. Furthermore, patients should be encouraged to identify triggers and to avoid situations associated with sleep deprivation, excess intake of alcohol and psychological stress.

With regards to anticonvulsants used in JME treatment, sodium valproate has generally been considered the drug of the first choice. JME patients typically respond to daily doses of 1000 mg, although even lower doses may yield a favorable response [16]. As is the case in other forms of epilepsy, the daily dose should be chosen as high as necessary and as low as possible. However, sodium valproate is no longer recommended for girls and women in childbearing age. This is due to the fact that this compound dose-dependently increases the likelihood of fetal malformations and disturbances of cognitive development of the child. Phenobarbital (up to 180 mg/day), levetiracetam (up to 3000 mg/day), and lamotrigine (up to 400 mg/day) may be employed instead of sodium valproate. Nevertheless, changes in antiepileptic medication during pregnancy should be avoided in patients with good seizure control. Women who became pregnant while taking sodium valproate should thus be maintained on this therapy. Of note, certain antiepileptic compounds may exacerbate symptoms of JME, e.g., sodium channel blockers, gabapentin, pregabalin, tiagabine, and vigabatrin [8]. To date, it is recommended to continue antiepileptic therapy throughout life. As has been mentioned above, only minor shares of patients remain seizure-free after discontinuation of therapy. If future research provides reliable strategies to identify these individuals, the former recommendation may no longer apply to all JME patients.

Prognosis

JME patients have a good prognosis. Although this form of epilepsy is currently considered non-curable, most patients respond well to therapy. The disease usually persists throughout life and the majority of JME patients relapses upon cessation of antiepileptic therapy. Thus, life-long treatment is generally recommended. It primarily aims at avoiding generalized tonic-clonic seizures. Minor shares of JME patients remain disease-free after withdrawal of medication, though [12]. Data regarding the patho-physiological basis of this phenomenon are scarce and further research is required for well-founded decisions regarding the life-long continuation of treatment.

Etiology

JME has been classified as an idiopathic form of generalized epilepsy with symptom onset in childhood or adolescence [2]. The acute onset of myoclonia may be triggered by sudden awakening, sleep deprivation, fatigue, menstruation, psychological stress and excess intake of alcohol. Patients don't present organic brain lesions, respond well to antiepileptic therapy and have a favorable prognosis.

About half of JME patients has a first-degree relative with a medical history of generalized seizures, and this observation led to the hypothesis of JME presumably affecting genetically predisposed individuals. The disease is currently assumed to be either inherited as an autosomal dominant trait with incomplete penetrance or in a more complex manner. In detail, mutations of the following genes encoding for effector proteins have been related to Mendelian inheritance of JME [3]:

  • CACNB4 (voltage-gated calcium channel subunit β4, involved in the generation and transmission of electric signals in the brain)
  • CASR (calcium-sensing receptor, contributes to the maintenance of calcium homeostasis)
  • GABRa1 (GABA receptor subunit α1, forms part of GABA receptors and is thus required for inhibitory neurotransmission)
  • GABRD (GABA receptor subunit δ, function as described above)
  • Myoclonin1/EFHC1 (myoclonin1/EF-hand domain-containing protein 1, involved in transmembrane flow of calcium ions and neuronal activity)

Mutations in genes encoding for regulators, single-nucleotide polymorphisms, and other sequence anomalies may also contribute to an individual's predisposition for JME, although it is less clear how they affect the inheritance of JME:

  • BRD2 (bromodomain-containing 2, transcriptional regulator)
  • Cx-36 (connexin 36, a neuronal, gap junction-forming connexin)
  • ME2 (malic enzyme 2, a mitochondrial enzyme that catalyzes the oxidative decarboxylation of malate to pyruvate)
  • Microdeletions in 15q13.3, 15q11.2, and 16p13.11

Epidemiology

JME is relatively common and accounts for about a fifth of idiopathic, generalized epileptic syndromes, and for up to 10% of all cases of epilepsy [4]. The patients' age at symptom onset is part of the definition of JME and has been indicated as 10 to 25 years (class I criterion) or 6 to 25 years (class II criterion) [5]. Rarely, JME is diagnosed in elder individuals [6] and any supposed JME patient beyond the third decade of life should be carefully evaluated for differential diagnoses. Both boys and girls may be affected by the disease and while some studies report an equal gender ratio, others state females to develop JME more often than males [4] [7].

Sex distribution
Age distribution

Pathophysiology

It has been proposed that those gene defects described above interfere with physiological cortical development and allow for the establishment of epileptogenic circuits [8]. With regards to mutations of myoclonin1/EFHC1, it has been shown that the respective gene product is required for mitotic spindle organization as well as the radial and tangential migration of neurons and glia during corticogenesis [9]. Furthermore, GABRa1 mutations have been related with cortical hyperexcitability due to an accelerated degradation of the respective subunits of GABA receptors [10]. Cortical hyperexcitability has been shown to vary over the course of a day and is presumably highest in the morning [11]. This may partially explain why myoclonic jerks are most commonly experienced upon awakening. However, despite the knowledge about a correlation between certain genotypes and a patient's individual risk of developing JME, the interaction between multiple genetic and environmental factors contributing to symptom onset is only poorly understood. Presumably, neither of the aforementioned factors is able to trigger JME on its own.

Prevention

No specific measures can be recommended to prevent JME.

Summary

Early descriptions of juvenile myoclonic epilepsy (JME) date back to the 19th century, although it was not until 1957 that JME-associated symptoms have been termed an entity [1]. The respective publications are about adolescent patients suffering from jerks and generalized tonic-clonic seizures, which frequently occur upon awakening. These symptoms are still considered hallmarks of the disease, although it has been reported that JME patients may also experience absence seizures. Research efforts undertaken during the last decades have led to the conception of JME as a hereditary disorder, although considerable knowledge gaps remain regarding involved genes and the mode of inheritance. Presumably, JME is a multigenic, pathophysiologically heterogeneous disease. The vast majority of JME patients respond well to anticonvulsant therapy. Sodium valproate has long since been the drug of choice to this end, but recent recommendations favor other compounds in girls and women in childbearing age. Because the disease persists into adulthood, life-long treatment is required, though.

Patient Information

Juvenile myoclonic epilepsy (JME) is a rather common form of epilepsy that typically manifests around puberty. Affected individuals don't generally have a medical history of neurological disorders during childhood and are of normal intelligence. They may, however, have presented absence seizures for years. An epileptic fit as experienced by JME patients typically consists in bilateral, more or less symmetric, single or repetitive myoclonic jerks. These jerks may vary in intensity and range from a mere sense of electric shock to minimal twitchings to violent movements of the limbs. The arms are more frequently affected than the legs, but the involvement of the latter may result in sudden falls. JME patients are often photosensitive and indeed, most episodes of myoclonia occur upon awakening. Furthermore, sleep deprivation, fatigue, menstruation, psychological stress and excess intake of alcohol may trigger the afore-described symptoms.

JME may progress to a more severe form of epilepsy that comprises generalized tonic-clonic seizures, although years may pass until those are observed. In cases of mild myoclonia, affected individuals may not seek medical attention until suffering from generalized tonic-clonic seizures. In order to diagnose JME, to rule out other forms of epilepsy and organic brain damage, the treating physician may record an electroencephalogram (EEG, to monitor the electrical activity of the brain) and order magnetic resonance imaging of the brain. The latter may not be necessary if both clinical findings and EEG records are consistent with JME.

Because the etiology of JME is only poorly understood, causative therapy is not available. Nevertheless, most JME patients respond well to standard antiepileptic medication. Since there is no cure for the disease, it is generally recommended to use anticonvulsants throughout life. Non-compliance with therapeutic regimens may result in recurrence, which is especially severe if the patient is suffering from generalized tonic-clonic seizures.

References

Article

  1. Janz D, Christian W. Impulsive-petit mal. Deutsche Zeitschr. f. Nervenheilk. 1957; 176:346-388.
  2. Mattson RH. Overview: idiopathic generalized epilepsies. Epilepsia. 2003; 44 Suppl 2:2-6.
  3. Delgado-Escueta AV, Koeleman BP, Bailey JN, Medina MT, Duron RM. The quest for juvenile myoclonic epilepsy genes. Epilepsy Behav. 2013; 28 Suppl 1:S52-57.
  4. Camfield CS, Striano P, Camfield PR. Epidemiology of juvenile myoclonic epilepsy. Epilepsy Behav. 2013; 28 Suppl 1:S15-17.
  5. Kasteleijn-Nolst Trenite DG, Schmitz B, Janz D, et al. Consensus on diagnosis and management of JME: From founder's observations to current trends. Epilepsy Behav. 2013; 28 Suppl 1:S87-90.
  6. Jacob S, Martin D, Rajabally YA. Juvenile myoclonic epilepsy in an elderly patient. Age Ageing. 2006; 35(2):194-196.
  7. Commission on Classification and Terminology of the International League Against Epilepsy. Proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia. 1989; 30(4):389-399.
  8. Yacubian EM. Juvenile myoclonic epilepsy: Challenges on its 60th anniversary. Seizure. 2016.
  9. de Nijs L, Wolkoff N, Coumans B, Delgado-Escueta AV, Grisar T, Lakaye B. Mutations of EFHC1, linked to juvenile myoclonic epilepsy, disrupt radial and tangential migrations during brain development. Hum Mol Genet. 2012; 21(23):5106-5117.
  10. Bradley CA, Taghibiglou C, Collingridge GL, Wang YT. Mechanisms involved in the reduction of GABAA receptor alpha1-subunit expression caused by the epilepsy mutation A322D in the trafficking-competent receptor. J Biol Chem. 2008; 283(32):22043-22050.
  11. Badawy RA, Macdonell RA, Jackson GD, Berkovic SF. Why do seizures in generalized epilepsy often occur in the morning? Neurology. 2009; 73(3):218-222.
  12. Höfler J, Unterberger I, Dobesberger J, Kuchukhidze G, Walser G, Trinka E. Seizure outcome in 175 patients with juvenile myoclonic epilepsy--a long-term observational study. Epilepsy Res. 2014; 108(10):1817-1824.
  13. Wirrell EC, Camfield CS, Camfield PR, Gordon KE, Dooley JM. Long-term prognosis of typical childhood absence epilepsy: remission or progression to juvenile myoclonic epilepsy. Neurology. 1996; 47(4):912-918.
  14. de Araujo Filho GM, Yacubian EM. Juvenile myoclonic epilepsy: psychiatric comorbidity and impact on outcome. Epilepsy Behav. 2013; 28 Suppl 1:S74-80.
  15. Renganathan R, Delanty N. Juvenile myoclonic epilepsy: under-appreciated and under-diagnosed. Postgrad Med J. 2003; 79(928):78-80.
  16. Brodie MJ. Modern management of juvenile myoclonic epilepsy. Expert Rev Neurother. 2016; 16(6):681-688.

Ask Question

5000 Characters left Format the text using: # Heading, **bold**, _italic_. HTML code is not allowed.
By publishing this question you agree to the TOS and Privacy policy.
• Use a precise title for your question.
• Ask a specific question and provide age, sex, symptoms, type and duration of treatment.
• Respect your own and other people's privacy, never post full names or contact information.
• Inappropriate questions will be deleted.
• In urgent cases contact a physician, visit a hospital or call an emergency service!
Last updated: 2019-07-11 20:23