How to differentiate benign myoclonic epilepsy of infancy from other seizure disorders in infants?

Differentiating Benign Myoclonic Epilepsy of Infancy from Other Seizure Disorders

Benign myoclonic epilepsy of infancy (BMEI) is distinguished from other seizure disorders by its characteristic presentation of brief, isolated myoclonic jerks in developmentally normal infants aged 4 months to 3 years, with normal interictal EEG background activity and generalized spike-wave or polyspike-wave discharges on ictal EEG, occurring without other seizure types. 1, 2

Key Diagnostic Features of BMEI

Clinical Presentation

• Age of onset: 4 months to 3 years (mean 16-18 months), distinguishing it from neonatal seizures and later-onset epilepsies 1, 2, 3
• Seizure characteristics: Brief, mild myoclonic attacks involving primarily the head and upper limbs, occurring multiple times daily during wakefulness and early sleep stages 1, 2, 3
• Developmental status: Normal psychomotor development both before and after seizure onset is essential for diagnosis 1, 2, 3
• Consciousness: No loss of consciousness during myoclonic jerks 4
• Reflex triggers: 28-31% of patients have reflex myoclonus triggered by tactile stimuli, noise, or light 1, 3

EEG Characteristics

• Interictal EEG: Normal background activity in most cases (approximately 35% have normal interictal EEG) 1, 3
• Ictal EEG: Generalized discharge of polyspikes, polyspike-waves, or spike-waves lasting 1-2 seconds, associated with the myoclonic jerks 1, 2, 3
• Activation patterns: Abnormalities activated by drowsiness and first stages of sleep 2
• Photosensitivity: Present in approximately one-third of patients 2

Critical Differential Diagnoses to Exclude

Infantile Spasms (West Syndrome)

When myoclonias begin during the first year of life, cryptogenic infantile spasms must be excluded 2. Key differentiating features:

• Seizure type: Infantile spasms involve flexor or extensor spasms in clusters, not isolated brief myoclonic jerks 2
• EEG pattern: Hypsarrhythmia is characteristic of infantile spasms, whereas BMEI shows normal background activity 2
• Developmental trajectory: Developmental regression occurs in infantile spasms, while BMEI patients maintain normal development 2

Non-Epileptic Benign Infantile Myoclonus

This must be distinguished from BMEI in first-year presentations 2:

• EEG findings: No epileptiform discharges during or between episodes in benign non-epileptic myoclonus 2
• Clinical context: Often occurs during feeding or specific activities, not randomly throughout the day 2

Myoclonic-Astatic Epilepsy (Doose Syndrome)

For later-onset cases (after 12 months), this is a critical differential 2:

• Seizure types: Multiple seizure types including myoclonic-astatic seizures (drop attacks), generalized tonic-clonic seizures, and absences, not isolated myoclonic jerks 2
• Age of onset: Typically 2-5 years, slightly later than BMEI 2
• Developmental impact: Often associated with cognitive decline, unlike BMEI 2

Lennox-Gastaut Syndrome

Must be excluded in cases with later onset 2:

• Seizure types: Multiple seizure types including tonic, atonic, atypical absences, and myoclonic seizures 2
• EEG pattern: Slow spike-wave complexes (<2.5 Hz) and abnormal background activity, contrasting with BMEI's normal background 2
• Cognitive outcome: Intellectual disability is common, unlike BMEI's generally favorable outcome 2

Dravet Syndrome (Severe Myoclonic Epilepsy of Infancy)

Critical to differentiate despite "myoclonic" in the name 2:

• Initial presentation: Prolonged febrile seizures, often hemiclonic or generalized, not brief myoclonic jerks 2
• Seizure evolution: Multiple seizure types develop including focal, myoclonic, and absence seizures 2
• Developmental trajectory: Progressive developmental delay and cognitive impairment occur 2

Diagnostic Algorithm

Step 1: Confirm Age and Developmental Status

• Verify onset between 4 months and 3 years 1, 2, 3
• Document normal psychomotor development before and after seizure onset 1, 2
• Exclude significant cognitive or motor impairment, which would suggest alternative diagnoses 5

Step 2: Characterize Seizure Semiology

• Confirm brief (1-2 seconds), isolated myoclonic jerks without loss of consciousness 1, 2, 4
• Verify involvement primarily of head and upper limbs 1, 2
• Document frequency (multiple times daily) 1, 2
• Test for reflex triggers (tactile, auditory, photic stimulation) 1, 3
• Exclude: Tonic seizures (sustained muscle contractions), atonic seizures (drop attacks), or other seizure types 6, 2

Step 3: Obtain Video-EEG Documentation

• Standard recommendation: EEG is recommended as part of the neurodiagnostic evaluation of children with apparent first unprovoked seizures 5
• Capture ictal events showing generalized polyspike-wave or spike-wave discharges lasting 1-2 seconds 1, 2, 3
• Verify normal interictal background activity (present in majority of cases) 1, 2
• Record during drowsiness and early sleep stages to activate abnormalities 2
• Critical pitfall: Abnormal background activity suggests alternative diagnoses like Lennox-Gastaut syndrome or infantile spasms 2

Step 4: Neuroimaging Considerations

• MRI is the preferred modality if neuroimaging is obtained 5
• Nonurgent MRI should be seriously considered in children aged <1 year with first seizures 5
• In BMEI, neuroimaging is typically normal but helps exclude structural causes 5
• Emergent neuroimaging is indicated only if the child exhibits postictal focal deficits or has not returned to baseline within several hours 5

Step 5: Laboratory Evaluation

• Selective testing based on clinical context: Laboratory tests should be ordered based on individual clinical circumstances including suggestive historic or clinical findings such as vomiting, diarrhea, dehydration, or failure to return to baseline alertness 5
• Metabolic screening is not routinely indicated in developmentally normal infants with typical BMEI presentation 5
• Consider toxicologic screening if there is any question of drug exposure 5

Step 6: Family History Assessment

• Document family history of epilepsy (present in 28-30% of BMEI cases) or febrile seizures (present in 16-30% of cases) 1, 2, 3
• Positive family history supports BMEI diagnosis but is not required 1, 2

Treatment Response as Diagnostic Confirmation

• Valproic acid monotherapy is effective in 77-90% of BMEI patients 1, 2, 3
• Rapid response to valproate supports the diagnosis 2, 3, 4
• Poor response or need for polytherapy should prompt reconsideration of the diagnosis 2

Long-Term Monitoring and Prognosis

• Favorable seizure outcome: 63% of patients are off treatment after mean follow-up of 13.5 years 3
• Cognitive outcome: Normal neurologic and neuropsychological evaluations in 84% of patients, though intellectual-mnestic disorders occur more frequently than in the general population 1, 3, 4
• Evolution to other epilepsies: Rare progression to juvenile myoclonic epilepsy (5-6% of cases) or childhood absence epilepsy has been reported 1, 7
• Adolescent seizures: Rare generalized tonic-clonic seizures may occur during adolescence after treatment withdrawal 2, 4

Common Pitfalls to Avoid

• Do not diagnose BMEI if developmental delay or regression is present at onset or develops after seizure onset 1, 2
• Do not diagnose BMEI if seizure types other than isolated myoclonic jerks occur (excluding rare later-onset generalized tonic-clonic seizures) 1, 2
• Do not diagnose BMEI if interictal EEG shows abnormal background activity or slow spike-wave patterns 2
• Do not confuse brief myoclonic jerks with the sustained muscle contractions of tonic seizures 6
• Do not overlook the possibility of reflex myoclonus, which occurs in approximately one-third of BMEI patients and does not indicate a separate syndrome 1, 3