eMedicine Specialties > Neurology > Pediatric Neurology

Myoclonic Epilepsy Beginning in Infancy or Early Childhood

Raj D Sheth, MD, Professor of Neurology, Mayo College of Medicine; Chief, Division of Pediatric Neurology, Nemours Children's Clinic

Updated: Aug 21, 2008

Introduction

Background

Myoclonic seizures can occur in many types of epilepsy; however, in infancy and early childhood, they may occur as the dominant seizure type. The outlook and treatment of this condition differ from those of the more severe Lennox-Gastaut syndrome, which also may have myoclonic seizures as an important component.

Myoclonic epilepsies with onset in infancy and childhood are clinically and etiologically heterogeneous. At times in this heterogenous group, nonmyoclonic seizures may dominate the clinical picture.¹

The International League Against Epilepsy classified early myoclonic encephalopathy and early infantile epileptic encephalopathy with burst suppression as a generalized symptomatic epilepsy of nonspecific etiology.²  

For more information, see Medscape's Epilepsy Resource Center. For a CME/CE activity, see Maternal Infections During Pregnancy May Increase Risk for Childhood Epilepsy.

Pathophysiology

Myoclonic seizures are produced via a cortical or a subcortical generator that utilizes a polysynaptic mechanism acting on muscles rather than a monosynaptic corticospinal pathway. 

Seizures associated with early myoclonic encephalopathy can be heterogenous in etiology. A genetic basis has been suggested in some patients with a familial pattern.¹ Other cases are related to neurodegenerative disorders. 

Frequency

United States

The incidence is approximately 1 case in 40,000 children.

Mortality/Morbidity

Typically, patients do not die of myoclonic seizures but of the pathophysiological condition underlying the myoclonic epilepsy. Aspiration pneumonia is common in this population and results in frequent hospitalization.

Race

Myoclonic seizures are reported in all races.

Sex

No sex preponderance is observed in myoclonic seizures.

Age

Typically, the onset of these disorders is during the first 3 years of life.

Clinical

History

Syndromes of myoclonic epilepsy may be divided into the following:

• Symptomatic myoclonic epilepsy
  • This is less frequent than the idiopathic (ie, cryptogenic) variety, and the age of onset is usually between a few months and 2-3 years. Clinical features include psychomotor retardation, and neuroimaging frequently demonstrates brain atrophy.
  • Myoclonic jerks can occur alone, but they more commonly are associated with generalized clonic seizures. Rhythmic jerks can occur during sleep, with associated dystonic posturing during wakefulness.
  • The prognosis for meaningful cognitive function is poor, although the myoclonic jerks may be controlled medically.
• Cryptogenic myoclonic epilepsy
  • This group includes all patients with idiopathic seizures who display primarily recurrent myoclonic attacks. Some patients have infrequent generalized tonic-clonic seizures. Most myoclonic seizures are axial, which sometimes results in falls.
  • The outcome in these patients is usually favorable, although about half the patients may have behavioral or cognitive dysfunction. This has sometimes been termed "benign myoclonic epilepsy."
• Myoclonic epilepsy with other types of brief, recurrent seizures
  • In this group, all patients have myoclonic seizures associated with recurrent brief attacks of varying types.
    • Examples of these attacks include atonic seizures, atypical absence, partial seizures, and brief tonic seizures.
    • This is sometimes termed the myoclonic variant of Lennox-Gastaut syndrome.
  • The outcome is worse than in the cryptogenic myoclonic epilepsy group; more patients have cognitive dysfunction, and a significant proportion of those have severe mental retardation. However, the outcome is better than in patients with Lennox-Gastaut syndrome.
• Myoclonic epilepsy associated with clonic seizures and multiple seizure types
  • This condition is sometimes termed "severe myoclonic epilepsy" and occurs in a significant proportion of severe childhood epilepsies. The age of onset of seizures is between 4 and 11 months, and the seizures are initially unilateral or generalized clonic movements (or rarely, generalized tonic-clonic movements).
    • Seizures are usually long lasting, from 10-90 minutes in duration, and mostly associated with fever or minor infections.
    • Myoclonic seizures appear by the second or third year and are often photosensitive.
    • Atypical absence seizures may be seen without an electrographic correlate.
  • Initially, development may be normal; later, cognitive delays become evident and are usually moderate to severe. Most patients have fluctuating ataxia and erratic myoclonus.
  • The myoclonic seizures may resolve after a few years, but other seizures tend to be persistent. Nonconvulsive status is common.
  • EEG findings are normal initially, despite frequent seizures.
    • Later, generalized bursts of spike-wave and polyspike-wave complexes are seen.
    • Multifocal spikes also may be seen and may be unilateral.
  • Most patients are photosensitive and this feature may be diagnostic if present in children younger than 1 year.
  • MRI and CT scans are usually normal and do not show focal lesions or atrophy. Generally, the outlook is poor; most children are markedly dependent on care or institutionalized.
• Neonatal myoclonic epilepsy
  • This syndrome presents in the first 4 weeks of life with prominent myoclonic seizures.
  • The seizures usually result from a severe metabolic disorder, including that associated with elevated glycine levels in the cerebrospinal fluid (CSF), although they may be associated with any condition that produces severe brain dysfunction.
  • Distinguishing neonatal myoclonic epilepsy from benign neonatal sleep myoclonus is important. The latter condition is seen in healthy infants and occurs only in sleep.
  • EEG is very helpful in distinguishing between these 2 conditions. In benign sleep myoclonus, EEG findings are normal even when the infant is having myoclonus. In neonatal myoclonic epilepsy, EEG findings are always markedly abnormal in background and may even show a burst-suppression pattern.

Physical

• Abrupt and brief myoclonic jerks occur several times a day. They can manifest as head nodding, abrupt abduction of arms, or sudden falls.
• Eyelid or facial muscles are affected commonly, although axial myoclonic jerks are most common and occur in 90% of patients.
• Myoclonic seizures commonly occur on awakening, and some may be precipitated by photic stimuli. Rarely, myoclonic seizures occur continuously as myoclonic status epilepticus with partial preservation of consciousness.
• Although myoclonic seizures may occur as the sole type of seizures in some patients, they more commonly are associated with other seizures.
  • Generalized tonic-clonic seizures are the most common associated type. Brief generalized clonic seizures or unilateral clonic seizures also may be seen.
  • Atypical absence seizures occur in 40%, and pure atonic seizures may also occur.
  • Pure tonic seizures are not seen (this is an important distinguishing feature from Lennox-Gastaut syndrome).
• During the physical examination, particular attention should be given to conditions that may mimic myoclonic seizures. In the case of isolated myoclonic jerks, tics or mannerisms may be identified mistakenly as myoclonic attacks; usually, however, the diagnosis becomes clear over time.
• At times, absence seizures may be associated with myoclonic or clonic attacks. EEG is useful in differentiating myoclonic attacks from absence seizures.
• Progressive neurodegenerative diseases frequently present with myoclonic activity and other seizures types.
  • Neuronal ceroid lipofuscinosis (NCL) is important to consider in patients aged 2-5 years.
  • EEG is useful in NCL, since photic stimulation at 1 Hz produces giant evoked potentials in the form of a spike followed by a slow wave.
• Patients with Lennox-Gastaut syndrome have a mixed seizure disorder, including tonic seizures and drop attacks; however, myoclonic attacks are not a prominent feature. Additionally, EEG in Lennox-Gastaut syndrome has a more uniform slow spike and wave discharge pattern.
• Some severe cases of myoclonic epilepsy may be confused with febrile seizures. Prolonged duration, rapid recurrence, and occurrence of afebrile seizures differentiates myoclonic epilepsy from febrile seizures.

Causes

• Perinatal insults
• Inborn errors of metabolism
• Brain malformations
• Cryptogenic causes: Children with this condition have no identifiable cause for their syndrome and an appropriate workup for the seizures is negative.

Differential Diagnoses

Workup

Imaging Studies

• Brain MRI is usually normal, although congenital brain abnormalities sometimes are observed.
• Computed tomography (CT) scan is usually normal. MRI is preferred to CT scan.

Other Tests

• EEG features^3,4,5
  • The ictal EEG correlate of myoclonic seizures consists of fast spike-wave discharges (>2.5 Hz), which at times are associated with slower 2- to 2.5-Hz discharges. Interictal recordings may be normal or show slowing, depending on the etiology.
  • Brief (<3 seconds) interictal bursts of irregular polyspike-waves may be seen either spontaneously or with photic stimulation. The occurrence of these discharges is increased during non-rapid eye movement (REM) sleep.
  • Atypical absence seizures are associated with brief bursts of fast spike-wave activity. During atonic attacks, the EEG shows an irregular burst of arrhythmic fast spike and wave complexes, which are bilateral and symmetrical.

Procedures

• Lumbar puncture can help to rule out neurodegenerative diseases. CSF findings suggestive of neurodegenerative disease include an elevated protein with an unremarkable or mildly elevated WBC count.

Treatment

Medical Care

• The mainstay of medical therapy for myoclonic epilepsy is sodium valproate, ethosuximide, or benzodiazepines.⁶
  • Patients with the benign form respond well to valproate or ethosuximide.
  • Either one of the drugs may be started; if both fail independently, they may be combined.
  • The duration of treatment is tailored on an individual basis but is usually approximately 5 years.
• Second-line medications include clonazepam, methsuximide, acetazolamide, and sulthiame.
• Treatment for the more severe myoclonic epilepsies is more difficult and is essentially the same as for Lennox-Gastaut syndrome.
• All types of antiepileptic medications may be tried, with the exception of vigabatrin and carbamazepine, which actually may worsen the seizures.
• Combination therapy with valproate and benzodiazepines may be the best alternative.
• Adrenocorticotropic hormone (ACTH), steroids, and immunoglobulins have been tried but have shown no significant benefit.

Consultations

Patients should be evaluated by a pediatric neurologist. If dysmorphic features are present, a genetic evaluation may be useful.

Diet

The ketogenic diet may be useful in caring for children with particularly refractory epilepsy. This should be instituted only on an inpatient basis, paying particular attention to the possibility of dehydration.

Activity

Caution should be used in children with drop attacks, as they may fall and injure themselves. A helmet can be protective. Routine seizure precautions are also applicable.

Medication

The goals of pharmacotherapy are to reduce morbidity and prevent complications.⁶

Antiepileptic agents

Patients with the benign form respond very well to valproate or ethosuximide.

Valproic acid (Depakote)

Chemically unrelated to other drugs that treat seizure disorders. Although mechanism of action not established, activity may be related to increased brain levels of GABA, or enhanced GABA action. Valproate also may potentiate postsynaptic GABA responses, affect potassium channels, or have direct membrane-stabilizing effect.
Use in young children (younger than 2 y) associated with risk of hepatotoxicity. This risk estimated to occur in fewer than 1 in 250 children treated.

Dosing

Adult

Initial: 5-15 mg/kg/d PO
Maintenance: 15-25 mg/kg/d PO

Pediatric

Initial: 10-30 mg/kg/d PO
Maintenance: 30 mg/kg/d PO

Interactions

Cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may reduce levels significantly; in children, salicylates cause decreases in protein binding and metabolism of valproate; may result in variable changes of carbamazepine concentrations with possible loss of seizure control; may increase diazepam and ethosuximide toxicity (monitor closely); may increase phenobarbital and phenytoin levels while either may decrease valproate levels; may displace warfarin from protein-binding sites (monitor coagulation tests); may increase zidovudine levels in HIV-seropositive patients

Contraindications

Documented hypersensitivity; hepatic disease/dysfunction

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Thrombocytopenia and abnormal coagulation parameters have occurred; risk of thrombocytopenia increases significantly at total trough valproate plasma concentrations >110 mcg/mL in females and >135 mcg/mL in males; at periodic intervals and prior to surgery, determine platelet count and bleeding time before initiating therapy; reduce dose or discontinue therapy if hemorrhage, bruising, or hemostasis/coagulation disorder occur; hyperammonemia may occur; monitor patients closely for appearance of malaise, weakness, facial edema, anorexia, jaundice, and vomiting

Ethosuximide (Zarontin)

Mechanism of action based on reducing current in T-type calcium channels found on thalamic neurons. Spike-and-wave pattern during petit mal seizures thought to be initiated in thalamocortical relays by activation of these channels. Used as adjunctive medication to valproic acid if that medication has failed to control seizures.

Dosing

Adult

500-2000 g/d PO

Pediatric

15-40 mg/kg/d PO

Interactions

Phenytoin, carbamazepine, primidone, and phenobarbital may decrease effects; isoniazid may inhibit hepatic metabolism, increasing toxicity

Contraindications

Documented hypersensitivity; blood dyscrasias; renal or hepatic disease

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Blood dyscrasias, which may be fatal, may occur (monitor CBC); caution in hepatic or renal disease; abrupt withdrawal may precipitate absence status

Clonazepam (Klonopin)

Suppresses muscle contractions by facilitating inhibitory GABA neurotransmission and other inhibitory transmitters. Useful in immediate control of seizures, although often associated with relatively rapid loss of efficacy against seizures.

Dosing

Adult

0.05-0.2 mg/kg/d PO

Pediatric

Administer as in adults

Interactions

Phenytoin and barbiturates may reduce effects; CNS depressants increase toxicity

Contraindications

Documented hypersensitivity; severe liver disease; acute narrow-angle glaucoma

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in chronic respiratory disease or impaired renal function; withdrawal symptoms can result from abrupt discontinuation of medication

Follow-up

Further Outpatient Care

• Serial EEGs often are required to ensure that patients are responding to treatment and that subclinical seizures are not occurring.
• Typical EEG findings in responsive patients include the disappearance of polyspike and wave activity and other associated epileptiform discharges.

Prognosis

• Prognosis depends on the underlying etiology and the syndrome type.
• Patients with a benign syndrome typically respond well to medication. These patients usually have a good prognosis and often outgrow the epilepsy.
• In symptomatic myoclonic epilepsy syndromes, the prognosis is usually less favorable with regard to seizure control and developmental progress.

References

1. Zara F, Gennaro E, Stabile M, Carbone I, Malacarne M, Majello L, et al. Mapping of a locus for a familial autosomal recessive idiopathic myoclonic epilepsy of infancy to chromosome 16p13. Am J Hum Genet. May 2000;66(5):1552-7. [Medline].

2. Wang PJ, Lee WT, Hwu WL, Young C, Yau KI, Shen YZ. The controversy regarding diagnostic criteria for early myoclonic encephalopathy. Brain Dev. Oct 1998;20(7):530-5. [Medline].

3. Aicardi J. Myoclonic epilepsies of infancy and childhood. Adv Neurol. 1986;43:11-31. [Medline].

4. Sheth RD. Electroencephalogram in developmental delay: specific electroclinical syndromes. Semin Pediatr Neurol. Mar 1998;5(1):45-51. [Medline].

5. Doose H, Lunau H, Castiglione E, Waltz S. Severe idiopathic generalized epilepsy of infancy with generalized tonic-clonic seizures. Neuropediatrics. Oct 1998;29(5):229-38. [Medline].

6. Wallace SJ. Myoclonus and epilepsy in childhood: a review of treatment with valproate, ethosuximide, lamotrigine and zonisamide. Epilepsy Res. Jan 1998;29(2):147-54. [Medline].

7. Lombroso CT. Early myoclonic encephalopathy, early infantile epileptic encephalopathy, and benign and severe infantile myoclonic epilepsies: a critical review and personal contributions. J Clin Neurophysiol. Jul 1990;7(3):380-408. [Medline].

8. Shahwan A, Farrell M, Delanty N. Progressive myoclonic epilepsies: a review of genetic and therapeutic aspects. Lancet Neurol. Apr 2005;4(4):239-48. [Medline].

Keywords

myoclonic epilepsy, myoclonic seizures, astatic myoclonic epilepsy of Doose, benign infantile myoclonic epilepsy, infantile spasms, progressive myoclonic epilepsy, severe infantile myoclonic epilepsy

Contributor Information and Disclosures

Author

Raj D Sheth, MD, Professor of Neurology, Mayo College of Medicine; Chief, Division of Pediatric Neurology, Nemours Children's Clinic
Raj D Sheth, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Neurological Association, and Child Neurology Society
Disclosure: Nothing to disclose.

Medical Editor

James J Riviello Jr, MD, George Peterkin Endowed Chair in Pediatrics, Professor of Pediatrics, Section of Neurology and Developmental Neuroscience, Professor of Neurology, Peter Kellaway Section of Neurophysiology, Baylor College of Medicine; Chief of Neurophysiology, Director of the Epilepsy and Neurophysiology Program, Texas Children's Hospital
James J Riviello Jr, MD is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Kenneth J Mack, MD, PhD, Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic
Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, and Society for Neuroscience
Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Neurology, Department of Neurology, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)