Juvenile myoclonic epilepsy

The prevalence of JME is approximately 0.1–0.2 per 1,000, constituting approximately 5–10% of all epilepsies. Some studies suggest that JME is slightly more common in females than males. The onset of symptoms ranges between the ages of 8 and 36 years, peaking between 12 and 18 years Approximately 15% of children with childhood absence epilepsy and juvenile absence epilepsy subsequently develop JME. In most cases, myoclonic jerks precede the first generalized tonic–clonic seizure by a mean of 3.3 years. A long-term population-based study suggested that 25 years after seizure onset, 17% of people with JME had all seizure types resolved, and 13% only experienced myoclonus despite having discontinued medication, meaning that approximately a third no longer had troublesome seizures. JME may be associated with an elevated prevalence of psychiatric disorders, including anxiety, mood disorders, and personality disorders. ==Signs and symptoms==

There are three principal seizure types which may occur in JME: myoclonus, generalized tonic–clonic seizures and absence seizures. Approximately one-third of patients have all three seizure types. The majority of patients (58.2%) have frequent myoclonic jerks, Seizures associated with JME tend to take place 30 minutes to an hour after waking up in the morning. Other potential provoking factors include "praxis induction" which is the precipitation of seizures or epileptiform discharges in the context of a complex cognitive tasks. Patients with JME tend to perform worse on neuropsychological assessments in multiple cognitive domains and are also more likely to have psychiatric comorbidities such as depression and anxiety when compared to control populations. The majority of patients with JME report satisfaction with their health, work, friendships and social life. ==Cause==

JME is believed to be caused most often by multiple interacting genes rather than by a single genetic cause. Over twenty genetic loci have been implicated in the pathogenesis of JME. The majority of identified genes associated with JME encode for ion channel subunits. More recently, variants in intestinal cell kinase, which is encoded by a gene at chromosomal locus 6p12, were found to be associated with JME. This gene is involved in mitosis, cell-cycle exit and radial neuroblast migration, as well as apoptosis. EFHC1 has similar functions and is also associated with JME. JME is distinct from other forms of genetic generalized epilepsy due to the prominence of myoclonus. There is evidence that patients with JME have hyperexcitable motor cortexes, most pronounced in the morning and after sleep deprivation. In addition, there is evidence that patients with JME have hyperexcitable and hyperconnected cortical networks that are involved in ictogenesis. ==Genetics==

CACNB4 CACNB4 is a gene that encodes the calcium channel β4 subunit protein. It has been associated with JME though it is not strictly considered a putative JME gene because its mutation did not segregate in affected family members, it was found in only one member of a JME family from Germany, and the finding has not been replicated. β subunits are important regulators of calcium channel current amplitude, voltage dependence, and they also regulate channel trafficking. In mice, a naturally occurring null mutation leads to the "lethargic" phenotype. This is characterized by ataxia and lethargic behavior at early stages of development followed within days by the onset of focal motor seizures and episodes of behavioral immobility correlated with patterns of cortical spike and wave discharges on electroencephalography (EEG) A premature-termination mutation, R482X, was identified in a patient with JME while an additional missense mutation C104F was identified in a German family with generalized epilepsy and praxis-induced seizures. The R482X mutation causes increased current amplitudes and an accelerated fast time constant of inactivation. Whether these modest functional differences may be in charge of JME remains to be established. This missense mutation results in channels with reduced peak GABA-evoked currents. Furthermore, the presence of such mutation alters the composition and reduces the expression of wild-type GABAA receptors. Among the mutations that have been reported in this in this gene, one (R220H) has been identified in a small family with JME. This mutation affects GABAergic transmission by altering the surface expression of the receptor as well as reducing the channel opening duration. Myoclonin1/EFHC1 Myoclonin1/EFHC1 encodes for a protein involved in cell division, neuroblast migration and synapse/dendrite formation. EFHC1 is expressed in many tissues, including the brain, where it is localized to the soma and dendrites of neurons, particularly the hippocampal CA1 region, pyramidal neurons in the cerebral cortex, and Purkinje cells in the cerebellum. There are four JME-causing mutations discovered (D210N, R221H, F229L and D253Y). The mutations do not seem to alter the ability of the protein to colocalize with centrosomes and mitotic spindles but induce mitotic spindle defects. Moreover, the mutations impact radial and tangential migration during brain development. ==Diagnosis==

Diagnosis is typically made based on patient history. Physical examination is usually normal. Additionally, an 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. These discharges may be evoked by photic stimulation (blinking lights) or hyperventilation. Both magnetic resonance imaging (MRI) and computer tomography (CT) scans generally appear normal in JME patients. However a number of quantitative MRI studies have reported focal or regional abnormalities of the subcortical and cortical grey matter, particularly the thalamus and frontal cortex, in JME patients. Positron emission tomography (PET) reports in some patients may indicate local deviations in many transmitter systems. ==Management==

The most effective anti-epileptic medication for JME is valproic acid (Depakote). Due to valproic acid's high incidence of fetal malformations, Patients should be warned to avoid sleep deprivation. ==History==

The first citation of JME was made in 1857 when Théodore Herpin described a 13-year-old boy with myoclonic jerks, which progressed to tonic–clonic seizures three months later. In 1957, Janz and Christian published a journal article describing several patients with JME. The name Juvenile Myoclonic Epilepsy was proposed in 1975 and adopted by the International League Against Epilepsy. ==Culture==

Stand-up comedian Maisie Adam has JME and discussed it in her award-winning show "Vague". The 2018 documentary film Separating The Strains dealt with the use of CBD oil to treat symptoms of JME. Currently, no scientific evidence exists to support use of CBD oil to treat symptoms of JME. == See also ==