Pathologic substrates of focal epilepsy influence the generation of high-frequency oscillations.

OBJECTIVE: Although a clear correlation has been observed between high-frequency oscillations (HFOs) and the seizure-onset zone in distinct lesions, the role of the underlying pathologic substrates in the generation of HFOs is not well established. We aimed to investigate HFO correlates of different pathologic substrates in patients with drug-resistant epilepsy, and to examine the relation of HFOs with the anatomic location of the dysplastic lesion and surrounding tissue in patients with focal cortical dysplasia (FCD). METHODS: We studied consecutive patients with drug-resistant epilepsy who underwent intracranial electroencephalography (iEEG) investigations with depth electrodes at the Montreal Neurological Institute and Hospital, between November 2004 and May 2013. Inclusion criteria were the following: a focal lesion documented by magnetic resonance imaging (MRI); EEG recording at a 2,000 Hz sampling rate; and seizures starting from depth electrode contacts placed in lesion and perilesional tissue. RESULTS: Thirty-seven patients (13 FCD, 12 mesial temporal sclerosis, five cortical atrophy, three polymicrogyria, three nodular heterotopia, and one tuberous sclerosis) were included; 18 were women (median age 34). Ripples and fast ripples were found in all lesion types, except tuberous sclerosis, which showed no fast ripples. There was a significant difference in rates of ripples and fast ripples across different lesions (p < 0.001), with higher rates in FCD, mesial temporal sclerosis, and nodular heterotopia than in atrophy, polymicrogyria, and tuberous sclerosis. Regarding patients with FCD, HFOs rates differed significantly across the three types of tissue (lesional, perilesional, and nonlesional; p < 0.001), being higher within the borders of the MRI-visible dysplastic lesion, followed by the surrounding area, and rare in the remote cortex. SIGNIFICANCE: Our findings suggest that in patients who are all intractable, the HFO rates vary with different pathologies, and reflect different types of neuronal derangements. Our results also emphasize the potential usefulness of HFOs as an additional method to better define the extent of the epileptogenic dysplastic tissue in FCD.

Intracranial EEG seizure onset-patterns correlate with high-frequency oscillations in patients with drug-resistant epilepsy.

OBJECTIVE: High-frequency oscillations (80-500Hz; HFOs) have been shown to be a specific biomarker of the seizure-onset zone. The relationship of HFOs with seizures having different intracranial electroencephalography (iEEG) morphological onsets, however, has shown significant relationships in experimental animals but has not been studied in humans. We investigated how interictal and ictal HFOs relate to different seizure-onset morphological patterns. METHODS: We analyzed the most representative seizure type of 37 patients with drug-resistant focal epilepsy who underwent iEEG for diagnostic evaluation. According to the morphology, 211 seizure-onset zone channels were classified in six patterns (low-voltage fast activity; sharp activity at ≤13Hz; low-frequency high-amplitude periodic spikes; burst of high-amplitude polyspikes; spike-and-wave activity; and delta brush). Interictal and ictal HFOs were compared between the six seizure-onset patterns. RESULTS: Interictal ripple and fast ripple rates differed significantly across seizure-onset patterns (p<0.001). Significant differences were also found for ictal HFOs density across the different seizure-onset patterns (p<0.001). Sharp activity at ≤13Hz was associated with the lowest interictal HFO rate suggesting either that the mechanism that generates this type of EEG morphology do not generate HFOs or possibly that this pattern is more likely to be generated in a region of seizure spread. Regarding the difference in HFO density between pre-ictal baseline and seizure-onset section across the six patterns, burst of high-amplitude polyspikes and delta brushes had the highest densities of both ripples and fast ripples (p<0.001). SIGNIFICANCE: We demonstrated that distinct seizure-onset patterns correlate specific interictal and ictal HFO profiles confirming that seizures with different morphological patterns likely have different mechanisms of generation. This study emphazises that, in clinical practice, seizure-onset patterns should be distinguished and specified when analyzing HFOs, particularly if they are used in presurgical evaluation to better localize the seizure-onset zone.