History
Juvenile myoclonic epilepsy (JME) is diagnosed on the basis of clinical findings. Video-electroencephalography (EEG) monitoring of typical seizures is the criterion standard, but in the great majority of patients, a working diagnosis of probable JME is made on the basis of the clinical history, often with supportive interictal EEG correlates.
Although observers’ descriptions of seizures are helpful, caution must be used regarding their validity. The most important element in the diagnosis of JME is the patient’s history. Any patient who presents with generalized tonic-clonic seizures (GTCSs) without an aura should be questioned about myoclonic jerks, the time of day when the seizures occurred, and any precipitating factors.
About 17–49% of patients have a family history of epilepsy. Symptoms usually begin in adolescence. The leading symptom is jerky movements that occur in the morning (typically, shortly after awakening) but might occur throughout the day, without loss of consciousness.
Patients may have myoclonic jerks plus other seizure types. In about 60% of patients, JME begins with myoclonic jerks, followed by the onset of relatively uncommon GTCSs a few years later. The finding of myoclonic jerks plus absence seizures and GTCSs is the next most common combination, occurring in approximately 30% of patients with JME. The combination of myoclonic jerks and absence seizures without GTCSs is rare, occurring in only 2% of patients.
Myoclonic seizures
Myoclonic seizures without impairment of consciousness are the cardinal symptoms of JME. Although an occasional strong myoclonic jerk may make patients momentarily seem to be “in a fog,” a key feature is that consciousness is preserved during these jerks.
The jerks are usually brief, bilateral, arrhythmic contractions that mainly involve the shoulders and arms. However, some patients report jerking in the lower limbs, trunk, or head. Some jerks occur unilaterally. In a video-EEG study, Hirano et al characterized myoclonic jerks in patients with JME as being more likely to occur in clusters, with distal predominance, and involving extension muscles. [18]
The frequency and intensity of myoclonic jerks may vary. For instance, they may be perceived only internally, as an electric shock–like sensation. If the jerks are violent, patients may throw objects they are holding or even fall to the floor. Myoclonic jerks can occur in rapid succession and even progress to myoclonic status epilepticus. However, more often a rapid succession of myoclonic jerks evolves into a primary GTCS.
Myoclonic jerks occur as the only seizure type in approximately 17% of patients with JME; the remaining patients have a combination of myoclonic jerks, GTCSs, and absence seizures. Myoclonic seizures tend to subside by the fourth decade, [19] but the other seizure types might persist.
Generalized tonic-clonic seizures
GTCSs occur in more than 90% of patients with JME. The GTCSs seen in JME are typically symmetric, with a prolonged tonic phase that may lead to cyanosis and tongue biting.
GTCSs are sometimes preceded by a series of myoclonic jerks of increasing severity that evolve into an initial clonic phase of a GTCS. The GTCSs often cause a patient with JME to seek medical attention; in this setting, patients should be questioned specifically about myoclonic jerks because most patients do not mention them.
Absence seizures
In JME, typical absence seizures are less common than GTCSs and occur in about a third of patients or less. When absence seizures are a feature of JME, they are often the first clinical manifestation of the syndrome, with myoclonic jerks typically following 1–9 years later. A clue to this diagnosis is the development of GTCSs or myoclonic seizures within a couple of years after starting treatment with ethosuximide. Approximately 3–8% of children who present with absence seizures ultimately receive a diagnosis of JME.
As in all IGEs, absence seizures in JME are typically short, lasting a few seconds, and usually not accompanied by motor signs.
The severity of absence seizures in JME is somewhat age dependent. When they appear in children younger than 10 years, absence seizures of JME are reported less often than those of childhood absence epilepsy. Some recollection of the ictal events is common, particularly in patients that have persistence of these seizures during adulthood. Automatism is rare.
When absence seizures of JME begin in children aged 10 years or older, they may be even less severe than they otherwise would be, with merely a brief interruption in the patient’s ability to concentrate. In a video-EEG monitoring study of patients with absence seizures, Sadleir et al found that patients with JME tend to have shorter seizures than patients with other epileptic syndromes with absences. [20]
Precipitating factors for seizures
As in all IGEs, seizures of JME often are precipitated by (1) lack of sleep, (2) psychological stress, (3) alcohol consumption, and (4) noncompliance with medication regimens. These factors can all be a particular problem in adolescents, particularly after moving out of the parents’ household or after matriculation into college.
The time of day is also important because JME has a characteristic circadian pattern of activity. Myoclonic jerks, GTCSs, and absence seizures all tend to occur in the early morning after the patient awakens (though they also occur, to a lesser extent, in the evening when the patient is relaxing). When myoclonic jerks occur in the mornings, patients may have difficulty in eating breakfast or brushing their teeth. In some studies, nearly 90% of patients with JME had myoclonic jerks on awakening; the rest had either random jerks throughout the day or jerks at night.
In a study using transcranial magnetic stimulation (TMS) to examine the diurnal variability of cortical excitability, Badawy et al demonstrated that short and long intracortical inhibition was considerably more impaired in the mornings than in the afternoons in patients with JME. [21] This might suggest a biological basis for the clinical observation of increased seizure frequency within the first hour upon awakening in patients with JME.
Precipitating factors can be summarized as follows:
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Sleep deprivation
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Psychological stress
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Alcohol use
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Noncompliance of medication
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Menses
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Time of day - usually mornings
Physical Examination
As in all idiopathic (genetic) generalized epilepsies (IGEs), physical examination usually does not identify any abnormalities. Intelligence is normal; this observation contrasts with findings with diseases such as progressive myoclonic epilepsies, in which progressive mental deterioration is the rule.
Comorbidities
Comorbidities associated with juvenile myoclonic epilepsy (JME) include psychiatric and neurologic disorders.
Psychiatric comorbidities, including depression, anxiety, and personality disorders, have been described in patients with JME. In one study, 49% of patients with JME had a psychiatric comorbidity. Anxiety and mood disorders were reported in 23% and 19% of patients with JME, respectively. Unfortunately, the psychiatric comorbidities can negatively impact outcome due to poor compliance and unhealthy behaviors. [61]
Neuropsychological testing of patients with JME has demonstrated selected frontal lobe dysfunction in tests such as the Wisconsin Card Sorting test and the Word Fluency test. [23] This dysfunction occurs despite having normal intelligence quotient (IQ) results obtained testing through conventional Wechsler testing. Impairment in executive function has also been reported. [24]
Complications
Both myoclonic status epilepticus and nonconvulsive status epilepticus (NCSE) have been reported in juvenile myoclonic epilepsy (JME).
The prevalence of NCSE in JME can be estimated at 5.8%, and the incidence at 1.2% per year with a clear preponderance of female gender.
Absence and myoclonic status epilepticus precipitated by inappropriate antiepileptic drugs can occur in idiopathic generalized epilepsy, including JME, but occurs rarely in JME. [20]
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Findings in a man with a history of generalized tonic-clonic seizures (mostly nocturnal) and myoclonic jerks (mostly in the morning) since the age of 14 years. Carbamazepine exacerbated his myoclonic seizures. Sleep-deprived EEG was digitally recorded and then plotted by using an analog paper machine. The patient was getting drowsy when this burst of polyspike and slow wave was recorded.
