Juvenile Myoclonic Epilepsy
Juvenile Myoclonic Epilepsy (JME) is among the most common epilepsy syndromes in children. Learning about JME and its management is of utmost importance as there are novel treatment modalities that allow patients to carry on with almost normal lives. Also, it is important to avoid wrong treatment approaches that may worsen the condition.
As the name itself suggests, Juvenile Myoclonic Epilepsy most of the time presents between childhood and adolescence, which is between 12 to 18 years of age, during which the brain matures to an adult brain. However, occasionally the syndrome can be diagnosed in the elderly as well.
How Does Juvenile Myoclonic Epilepsy Present?
The kids suffering from JME will have random body jerks. Classically, they present during the early morning. The kids may have jerks just after breakfast causing them to spill off the consumed food, that is why I like to call it “Dirty rug syndrome” with a kid keeps spilling breakfast in the room that ends up staining the rug. JME causes three basic types of seizures:
- Myoclonic jerks
- Generalized tonic-clonic seizures
- Absence seizures
What Causes Juvenile Myoclonic Epilepsy?
Although the exact cause of JME is yet to be discovered, it is thought to be a complex genetic cause. The brain has numerous electric circuits. Electric waves pass through channels and receptors in the brain. In JME, the genes responsible for controlling these channels and receptors are mutated. It causes a larger or uncontrolled electric current to pass through the brain cells. They over-excite the brain cells and result in seizures.
Most of these genetic mutations are not passed through generations, i.e., they are not inherited, but rarely they can be inherited by younger generations too.
How to diagnose Juvenile Myoclonic Epilepsy?
The clinical features are of much importance in diagnosing JME. The patients will have almost myoclonic jerks which occur mostly in the arms and occasionally in the legs. When they occur in the legs, they lead to falls which often happen in the morning. In addition to the myoclonic seizures, the majority will have generalized tonic-clonic seizures and less than half will have absence seizures. When they get absence seizures, they stare into space aimlessly for minutes unaware of the events of the surrounding.
After the clinical assessment, come the investigations. EEG is an important test in diagnosing JME. EEG is best when recorded during sleep as most of the abnormalities appear during sleep. It is also important to record the EEG for an adequate duration so that it doesn't miss the electric abnormalities of the brain.
The initial EEG will be positive in most of the cases (about 70%) with a generalized spike or polyspike-like wave pattern. If it is negative, you'll have to go for a prolonged overnight EEG to visualize the abnormalities.
MRI is not indicated routinely for diagnosis of JME, but it can be done if other causes of epilepsy are suspected.
Do Patients with Juvenile Myoclonic Epilepsy have Psychiatric Comorbidities?
About half of the patients with JME have at least one psychiatric comorbidity such as anxiety, depression, personality disorder, impulsivity etc. They occur partially due to the distress caused by the disease and partially due to the side effects of antiseizure medications like Levetiracetam or Keppra.
What is Progressive Myoclonic Epilepsy?
Progressive myoclonic epilepsy is a rare progressive variant of JME caused by complex genetic abnormalities. The seizures are more severe and cause progressive worsening of the cognitive and physical function over time. Some of the common causes of PME are Lafora disease, myoclonic epilepsy with ragged red fibers (MERRF), neuronal ceroid lipofuscinosis, dentatorubral pallidoluysian atrophy, and Gaucher disease. Luckily, all are very rare to happen.
What Triggers the Juvenile Myoclonic Epilepsy Seizures?
The JME seizures are very sensitive to sleep deprivation, alcohol consumption and missed medications. Some cases report photosensitivity as a cause which can be tested for during the EEG by flashing light.
How to Treat Juvenile Myoclonic Epilepsy?
Treatment of JME will be first with medications. Not all anti-seizure medications help generalized epilepsy. Some drugs like sodium channel blockers (e.g.: Carbamazepine (Tegretol) Oxcarbazepine (Trileptal), Phenytoin (Dilantin), Gabapentin, Pregabalin, Vigabatrin and Tiagabine) may even worsen the seizures and therefore should be avoided.
Drugs that help JME are summarized below with main side effects to watch for (detailed article about each medication is available).
Valproic acid (Depakote)
- All types of seizures respond well.
- Adverse effects- Teratogenicity and high rates of birth defects
- Weight gain
- Liver toxicity
Lamotrigine (Lamictal)
- Safe in pregnancy
- Adverse effect- worsening the myoclonic jerks (rare)
Levetiracetam (Keppra)
- Works for all seizure types and is safe in pregnancy.
- Adverse effects- Psychiatric side effects (anxiety and depression)
Topiramate (Topamax)
- Adverse effects- Tingling of feet at the beginning of treatment (subsides with time)
- Kidney stones
- Memory impairment
- Cognitive dysfunction
- Teratogenicity
- Glaucoma
Other drugs
- Zonisamide
- Lacosamide
As the brain abnormalities in JME are genetic and are associated with the structure and function of the brain, it requires long-term, or most of the time lifelong treatment. Seizures may recur once the treatments are stopped even after many years of remission.
What can We do if Medications do not Work?
About one-third of the cases of JME do not respond to medications (drug-resistant epilepsy or refractory epilepsy). These require surgical treatment because the cause is genetic and affects the whole brain, we can’t do resection or cut out a brain area like focal epilepsy,
1. Vagus nerve stimulation (VNS)
The Vagus nerve is stimulated via a wire implanted around the nerve at the neck with a power supply by batter implanted beneath the skin under the left clavicle. It stimulates the vagus nerve and increases the inhibitory neurotransmitters which eventually inhibits the excess electrical activity in the brain thereby reducing the seizures. Main side effects are hoarseness of voice.
2. Deep brain stimulation (DBS)
Deep brain structures (thalamus) are stimulated using an implanted wire.
The anterior nucleus and centromedian nucleus of the thalamus are targeted for partial and generalized epilepsy respectively. Main side effects are mood worsening and potential sleep disturbance.
3. Responsive neuro-stimulation
This is a novel treatment modality that is being studied for treating generalized epilepsy.
4. Ketogenic diet
This is a restricted type of diet with high fat and low carb amounts that helps seizures in some forms of epilepsy. Ketone bodies produced when following this diet act as an anti-seizure agent and reduce the seizure occurrence.
All the above methods help reduce the seizure frequency and intensity and might stop seizures completely in about 5 to 15% of cases. A 50% reduction in seizures over time is seen in about 50% of the patients.