Approach Considerations
Medical therapy with anticonvulsants typically is needed (see Medication). Avoidance of precipitating events such as alcohol use and sleep deprivation may be useful but is not by itself sufficient to control the seizures of juvenile myoclonic epilepsy (JME).
Go to Antiepileptic Drugs and Epilepsy and Seizures for complete information on these topics.
Anticonvulsant Therapy
The selection of antiepileptic drugs for the treatment of juvenile myoclonic epilepsy (JME) depends on several factors, including the patient’s comorbidities, preferences, previous history of adverse events, and gender. The US Food and Drug Administration (FDA) has not approved any anticonvulsant solely for the treatment of JME, but several are approved for “primary generalized tonic clonic seizures,” which essentially means IGE. ASMs are considered "broad spectrum" if they work in IGE and focal epilepsies. [63] In 2006, the FDA approved the adjunctive use of levetiracetam for the treatment of JME. Divalproex sodium has been approved as adjunctive therapy for patients with multiple seizure types that include primary generalized epilepsies.
In most patients with JME, seizures are well controlled with monotherapy. Valproic acid has been considered the treatment of choice for JME for many years due to high response rates, but epileptologists are increasingly using other choices as first-line therapies. Approximately 90% of patients with JME become seizure free with valproate monotherapy. Several studies using lamotrigine, topiramate, levetiracetam, and zonisamide have shown similar efficacy to that achieved with divalproex sodium, and in some cases better tolerability. [45]
Levetiracetam is useful for the treatment of myoclonic seizures. [46, 47] Noachtar et al demonstrated in a randomized, double-blinded, placebo-controlled trial that levetiracetam adjunctive therapy reduced all seizure types and myoclonic seizures in patients with JME. [48] Meta-analysis of 2 randomized controlled trials affirm that JME is highly responsive to treatment with levetiracetam. [49] Small, uncontrolled studies of levetiracetam monotherapy in JME suggest efficacy and tolerability. [50, 51]
Lamotrigine may also be a consideration in the treatment of JME. This agent is ideal for patients who cannot tolerate the adverse effects of valproate (eg, weight gain, tremor, stomach upset, and hair loss) or leviteracetam. In some patients, lamotrigine monotherapy controls seizures completely. However, lamotrigine can exacerbate myoclonic jerks. Data from an open-label study suggested that lamotrigine was better tolerated than valproate, with similar efficacy. [52] A European expert opinion study showed that lamotrigine was first-line choice for JME in adolescent females, whereas valproate was the first-line choice in adolescent males. [53]
Topiramate is useful in the treatment of primary generalized seizures; it may effectively prevent the seizures of JME. [54] Findings from an open-label study also suggested that zonisamide might be effective and well tolerated in patients with JME. [55]
Perampanel can also be considered as adjunctive treatment in IGEs in those patients who are refractory to other ASMs and is usually well tolerated. [73]
In general, low doses of appropriate anticonvulsants are needed to successfully treat JME. Although treatment with phenytoin, carbamazepine, or phenobarbital may control some seizure components of JME (albeit at high doses), these drugs may increase seizure frequency and occasionally precipitate new seizure types, such as absence seizures. Rarely, they may be considered in combination if the patient’s condition does not respond effectively to other first line drugs. [56] Other antiepileptic medications noted to exacerbate JME include gabapentin, pregabalin, vigabatrin, oxcarbazepine, and tiagibine. Innapproriate antiepileptic medication selection in JME has been reported to potentiate status epilepticus.
Clonazepam is often used during seizure exacerbations in patients with JME; however, it is inadequate and undesirable as long-term treatment. Side effects limit the use of benzodiazepines such as clonazepam and clobazam. [63] However, clobazam is considered a broad spectrum ASM and can be considered as adjunctive therapy in refractory cases.
A patient’s medication should rarely be changed when he or she is not having seizures and there are no medication side effects or signs of toxicity. In medical school, physicians are taught to treat patients and not proposed serum target concentrations. The routine checking of levels in a patient without side effects whose seizures are controlled is of little benefit to the patient, and sometimes detremental if it leads to an unnecessary dosing adjustment. An effective low-dose regimen is not unusual; in fact, many patients with JME need relatively low levels of anticonvulsants to achieve adequate seizure control (as long as it is an appropriate medication for the syndrome).
Special considerations in pregnant women
All women of childbearing age who are taking anticonvulsants should also take folic acid 1 mg/d. It is also beneficial to provide counsel regarding pregancy planning so that adjustments to an antiepileptic drug regimen can occur in anticipation of a potential pregnancy. As a general consideration, monotherapy is preferred to polytherapy, as is the minimal dose required to control the patient's seizures.
In general, most epileptologists believe that the anticonvulsants that help that patient the most should be continued during pregnancy. Frequent monitoring of drug levels is recommended, as pregnancy induces clinically significant changes in drug metabolism, clearance, and volume of distribution. Women with JME are no different from other women who need to take anticonvulsants.
A great majority of children born to women taking anticonvulsant monotherapy are healthy. Valproic acid and divalproex sodium, however, clearly pose a recognized risk of birth defects that is higher than the risk associated with other anticonvulsants. Exposure in utero probably contributes to neural tube defects (at a rate of 10–20 times the general population) and facial clefts, possibly contributes to hypospadias, and potentially impacts cognition. Multiple studies have shown valproic acid inferiority in comparison to other ASMs. VPA is not the drug of choice in women of childbearing age, so levetiracetam or lamotrigine are typically used instead.
With regards to topiramate, data from the North American Antiepileptic Drug (NAAED) Pregnancy Registry reported that the prevalence of oral clefts was 1.1% for infants exposed to TPM in the first trimester of pregnancy, versus 0.12% in the unexposed reference group. [57] The NAAED Pregnancy Registry also reported a prevalence of 19.7% for small-for-gestational-age newborns exposed to TPM in utero versus 5.4% for newborns without exposure.
Experience is limited with levetiracetam (category C), with one larger prospective database following 197 patients finding no detectable increased fetal risk. Greater data is available with lamotrigine. The North American AED Pregnancy registry prospectively found no increased risk of major congenital malformations; a 10.1 fold risk of cleft palate was noted, however it should be noted that the study included montherapy and polytherapy. [57] This has failed to be replicated in larger prospective monotherapy reports. The United Kingdom pregnancy registry, a prospective database of 1151 patients on lamotrigine monotherapy, found no significantly increased risk of major congenital malformations or cleft palate. [58]
Surgical Care
Surgical treatment is not indicated, because juvenile myoclonic epilepsy (JME) is a primary generalized epilepsy. Some uncontrolled studies have suggested that vagus nerve stimulation (VNS) might be helpful for patients with intractable seizures of primary generalized onset, such as JME. VNS may have similar or better efficacy in IGE as compared to focal epilepsy, but this is an off-label use in the United States. [63]
Modification of Activity
Seizure precautions include warnings about unpredictable lapses of consciousness due to seizures during a variety of activities, including the following:
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Driving vehicles or flying aircraft
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Immersing oneself in water (eg, for baths, swimming, and other purposes)
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Being at heights (eg, on roofs, scaffolds, and ladders)
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Using fire (eg, on stoves, in ovens, in open fires)
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Using power tools (eg, drills and saws)
Such precautions, including restrictions on driving, must be observed until seizures that impair consciousness are controlled (ie, the patient is seizure free) for the recommended period—typically 3-12 months, though the length varies from state to state in the United States. Patients with seizures cannot have a commercial driving license until they complete a seizure-free period of 5 years. In addition, patients with seizures are not permitted to fly aircraft.
Studies have shown that patients with JME experience decreases in quality of life similar to those experienced by patients with other epileptic syndromes. [59]
Patients with suspected seizures manifesting as lapses of consciousness during wakefulness should be educated and warned about seizure precautions. Documenting on the patient’s chart that driving and occupational hazards for people with seizures were discussed is helpful. Physicians should be aware of state regulations regarding driving, which vary considerably among states and nations.
Warnings should be tailored to each specific patient, and they should include factors such as seizure control, time of the occurrence of seizures, medication compliance, and the patient’s occupation, among other concerns.
Consultations
Juvenile myoclonic epilepsy (JME) is rarely diagnosed in the primary care setting. Most often, an epileptologist diagnoses and manages the condition, sometimes unfortunately after several years of inadequate treatment with medications such as carbamazepine or phenytoin.
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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.
