Juvenile myoclonic epilepsy (JME), otherwise known as Janz syndrome and impulsive petit mal, is an idiopathic, hereditary, and generalized form of epilepsy. It was first described by Herpin in 1867, later on by Janz and Christian in 1957 as 'impulsive petit mal,' and by Lund in 1975 as JME. Its characteristics are the presence of absence, myoclonic, and generalized tonic-clonic seizures.
JME falls into the classification an idiopathic as well as hereditary (positive family history in approximately 50% of cases) disorder.
Pathophysiology of JME has both idiopathic and hereditary components. The genetics of inheritance is not fully understood, but a multifactorial mechanism is suspected. CACNB4, EFHC1, GABRA1 are some of the genes that carry known associations with JME. Although magnetic resonance imaging (MRI) of the brain is unremarkable in classic JME cases, there are reports of structural defects as a possible cause of JME.
Majority of patients with JME start having seizures between the age group 12 to 18 with a mean age of onset around 15 years. But, the onset can be early or later with an age range between 5-34 years. As mentioned in the introduction, JME is characterized by the presence of absence, myoclonic, and generalized tonic-clonic (GTC) seizures. All patients with JME have myoclonic seizures, 85-90% patients have GTC seizures, and about 20-40% patients have absence seizures.
Myoclonic seizures are the hallmark of this condition and are necessary for the diagnosis of JME. Only occasionally, they will manifest as the only seizure type. They are described as brief, usually bilateral, jerking movements of the arms and sometimes legs with preservation of consciousness. The misdiagnosis of myoclonic seizures is possible as twitches or anxiety/nervousness. Many a time, increasing intensity and frequency of myoclonic jerks in clusters evolve into GTC seizures. GTC seizures usually occur a few months after the onset of myoclonic seizures. Absence seizures are generally the first seizures to manifest in JME. They tend to occur 3 to 5 years before the onset of myoclonic or GTC seizures, sometimes as early as 5 to 6 years of age. The early and isolated occurrence of absence seizures frequently leads to a diagnosis of childhood or juvenile absence epilepsy. Seizures with JME occur 30 minutes to an hour after morning awakening, especially the myoclonic seizures. Usual triggers for JME are sleep deprivation, alcohol intake, emotional stress, anxiety, fatigue. A large proportion (30-40%) of JME patients exhibit photosensitivity and flashing lights, sunlight, TV, and computer can trigger seizures. Photosensitive patients tend to have an earlier onset of seizures.
Physical examination remains normal, and cognition well preserved. Studies suggest an increased prevalence of psychiatric disorders including anxiety, mood disorder, and personality disorders in patients with JME.
History provides most of the clues necessary for a diagnosis of JME. Physical examination is generally unremarkable. An electroencephalogram (EEG) provides supporting evidence for diagnosing JME. An interictal EEG is abnormal in the majority of patients with JME. If the routine EEG is normal, an overnight and sleep deprived EEG is abnormal in almost every patient. The abnormalities are seen mostly during the transition from sleep to awakening. The typical EEG in JME shows diffuse, symmetric, bilateral 4 to 6 hertz (Hz) polyspike and wave discharges with a fronto-central predominance. The background has normal alpha rhythm, and approximately half of patient population will have focal or asymmetric abnormalities. Ictal or continuous EEG recording shows 10-16 Hz polyspike discharges with myoclonic jerks. The spikes correlate with myoclonic jerks. The EEG findings in GTC (low voltage fast activity with spike and wave discharges) and absence seizures (generalized 3 Hz spike and wave discharges) associated with JME are similar to those seen with other epilepsies. Since it is known to be a photosensitive epilepsy, photic stimulation provides enhanced yield on EEG in JME.
If history, examination, and EEG are indicative of JME, imaging (with magnetic resonance imaging-MRI) is usually unnecessary as it tends to be normal. Although, there are reports/studies about structural abnormalities in the cortex and subcortical gray matter in JME patients. There have been reports on JME patients showing abnormalities on electrophysiological tests and advanced imaging techniques such as magnetic resonance spectroscopy (MRS) and positron emission tomography (PET) as well.
JME is relatively easy to control with anti-epilepsy drugs (AED's) and most patients respond to monotherapy. Valproic acid is the most effective medication and drug of choice for treatment of JME. It is a broad spectrum medication and treats all seizure types of JME. Its use requires a great deal of caution in women of childbearing age given its well known teratogenic potential. Other treatment options include levetiracetam, lamotrigine, topiramate, and zonisamide. Lamotrigine can lead to a worsening in myoclonic seizures but is still widely used for the treatment of JME as it controls the other seizure types. If only absence seizures are present, ethosuximide can be a therapy choice. Clonazepam is effective against myoclonic jerks. Contraindicated agents include carbamazepine, oxcarbazepine, phenytoin (sodium channel blocking agents) given their potential to exacerbate myoclonic and absence seizures. But, they can be useful for the treatment of GTC seizures in JME. Other medications to avoid include vigabatrin, tiagabine, gabapentin, pregabalin, primidone. JME is intractable in only a few patients, and combination therapy with or without vagus nerve stimulation (VNS) is an option in such cases.
Many other epilepsy syndromes have similar features and resemble JME at various stages of their progression. Differential diagnosis includes childhood or juvenile absence epilepsy, eyelid myoclonia with absences, progressive myoclonic epilepsy, photosensitive occipital epilepsy, epilepsy with grand mal seizures upon awakening, hypnogogic myoclonus (hypnic jerk), non-epileptic seizures.
Seizures are usually well controlled with medications in a great majority of patients with JME and generally improve after the fourth decade of life. But, JME requires lifelong treatment (even after a long seizure-free interval), as the chances of relapse are high if medications are discontinued.
While JME management is chiefly under a neurologist, the follow up is usually under the primary caregiver or nurse practitioner. The key to prevention of seizures is patient education.
Avoidance of precipitating factors/triggers should be a strong emphasis. These include avoiding alcohol use, fatigue, stress, sleep deprivation, flashing lights in any form, medication non-compliance, hunger, extremes of temperature, drug use. Patients should also be advised/educated with precautions regarding driving, operating heavy machinery, swimming, avoiding heights/being near fire all alone. The treatment is usually life long (even after a long seizure-free interval), as the chances of relapse are high if medications are discontinued. As with any epilepsy syndrome, risks versus benefits of medications during pregnancy should be a point of discussion in details with the patient.
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