Table 3.

Judgment of causality in a 9-year-old girl with focal epilepsy and normal MRI.

Criterion to judge causality	How can we conclude a causal relationship between glucose hypometabolism involving the ventral frontal lobe and seizure generation in this case (Figure 2)?
Temporal relationship	Focal ictal discharges on ECoG, originating from the ventral frontal region, preceded the onset of clinical seizures.
Strength of association	Ictal discharges arose from the same region proximal to the glucose hypometabolic region in all seizure events.
Biologic gradient (dose-response effect)	The seizure onset zone proximal to the glucose hypometabolic region showed the largest rate of interictal epileptiform discharges on ECoG, whereas more distant regions showed less frequent interictal epileptiform discharges.
Replication of findings	Other groups reported that complete resection of a focal hypometabolic area in patients with cortical dysplasia resulted in a good seizure outcome [20].
Coherence (consistency with other knowledge)	Other groups reported that hypometabolic areas proximal to the seizure onset zone often contain focal cortical dysplasia [21].
Biological plausibility	Focal glucose hypometabolism can be explained by neuronal loss or an abnormal dendritic pattern of dysplastic neurons [22, 23].
Analogy	Patients with an MRI lesion in this location can have brief seizures with hypermotor automatisms [24, 25].
Specificity	Such glucose hypometabolism is rare in healthy individuals [26]. Seizures characterized by brief hypermotor semiology are reported to be seen most frequently in patients with frontal lobe epilepsy and less frequently in those with other forms of focal epilepsy [24, 25].
Experimental evidence	Electrical stimulation of the seizure onset zone proximal to the glucose hypometabolic region induced her habitual seizures. Cortical resection indeed resulted in seizure-freedom.