What are the causes of generalized epileptiform discharges on an electroencephalogram (EEG)?

Causes of Generalized Epileptiform Discharges on EEG

Generalized epileptiform discharges on EEG primarily arise from genetic epilepsy syndromes, though they can also occur in acute brain injury states, metabolic disturbances, and occasionally represent misclassified focal epilepsy with rapid bilateral spread.

Primary Genetic Epilepsy Syndromes

The most common cause of generalized epileptiform discharges is primary (idiopathic) generalized epilepsy, which has strong genetic underpinnings and includes several distinct syndromes 1, 2:

• Juvenile myoclonic epilepsy - characterized by generalized spike/polyspike-and-wave complexes at 3.5-6 Hz, typically occurring upon awakening 3
• Childhood absence epilepsy - manifests with 3 Hz generalized spike-wave discharges during absence seizures 3
• Juvenile absence epilepsy - shows the highest density of epileptiform discharges among genetic generalized epilepsies 4
• Idiopathic generalized epilepsy with generalized tonic-clonic seizures only - presents with generalized spike-wave discharges without other seizure types 3

The density and duration of epileptiform discharges differ significantly among these syndromes, with juvenile absence epilepsy showing the highest burden, followed by juvenile myoclonic epilepsy, childhood absence epilepsy, and generalized epilepsy with tonic-clonic seizures only 4.

Acute Symptomatic (Provoked) Causes

Generalized epileptiform discharges can occur in the setting of acute brain injury or systemic disturbances 2:

• Post-cardiac arrest - generalized periodic discharges at 0.5-2.5 Hz are common, occurring in approximately 80% of patients with post-arrest epileptiform activity 1
• Metabolic derangements - hyponatremia and other electrolyte abnormalities 2
• Toxic-metabolic encephalopathy - alcohol or drug withdrawal, toxic ingestions 2
• Acute CNS infections - encephalitis 2
• Acute structural lesions - though these more commonly produce focal patterns 2

Mechanistic Considerations

The generation of generalized epileptiform discharges involves complex thalamocortical networks 5, 6:

• Cortical origin with rapid bilateral spread - EEG evidence indicates superior frontal origin of bilateral-synchronous spikes and spike-waves, not primary thalamic generation 5
• Abnormal arousal mechanisms - the period following awakening is critical, with alternating drowsiness and arousing stimuli escalating EEG bursts to clinical seizures 5
• Photosensitivity - a second paroxysm-inducing mechanism present in some patients with genetic generalized epilepsy 5, 6

Important Diagnostic Pitfalls

Focal Epilepsy Masquerading as Generalized

Caution is essential because focal epileptiform discharges can occur in up to 49% of patients with idiopathic generalized epilepsy, most commonly in frontal (45.5%) and temporal (31.8%) distributions 7:

• Patients with focal interictal epileptiform discharges in genetic generalized epilepsy tend to require more combined antiepileptic drugs, suggesting more difficult-to-control disease 7
• The line between primary and secondary bilateral synchrony can become blurred 5
• True focal seizures with secondary generalization (focal to bilateral tonic-clonic) start focally and then propagate to both hemispheres, differing fundamentally from primary generalized seizures 1, 2

EEG Pattern Variations

Not all generalized discharges are identical - variations include 6, 3:

• Bisynchronous, symmetric generalized spike-wave complexes (classic pattern) 6
• Polyspikes and polyspike-wave discharges 6
• Focal, irregular, and "fragments" of discharges (not uncommon even in true generalized epilepsy) 6
• Occipital intermittent rhythmic delta activity 6
• Photoparoxysmal responses 6

Clinical Context Determines Significance

The clinical and neurological context dramatically affects the interpretation and implications of generalized epileptiform discharges 1:

• In neurologically normal children with typical clinical features of genetic generalized epilepsy, MRI shows abnormalities in only 2% of cases, reflecting the genetic rather than structural etiology 1, 8
• In neurologically abnormal patients or those with atypical features, structural causes must be excluded with MRI 8
• CT has very limited utility, showing positive findings in only 6% of generalized seizure cases compared to 50% in focal epilepsy 1

Post-Cardiac Arrest Context

In comatose post-cardiac arrest patients, generalized periodic discharges represent a distinct entity 1:

• These patterns fall on the "ictal-interictal continuum" and their clinical significance remains uncertain 1
• Whether they represent markers of brain injury or true epileptic activity requiring treatment is unclear 1
• The TELSTAR trial showed no outcome benefit from treating these patterns, though a small subgroup with true electrographic seizures may benefit 1