Discrete high-frequency oscillations (HFOs) in the range of 100-500 Hz have previously been recorded in human epileptic brains using depth microelectrodes. We describe for the first time similar oscillations in a cohort of unselected focal epileptic patients implanted with EEG macroelectrodes. Spectral analysis and visual inspection techniques were used to study seizures from 10 consecutive patients undergoing pre-surgical evaluation for medically refractory focal epilepsy. Four of these patients had focal seizure onset in the mesial temporal lobe, and in all 12 of their seizures, well-localized, segmental, very high frequency band (VHF: 250-500 Hz) oscillations were visually identified near the time of seizure onset from contacts in this zone. Increased high-frequency band (HF: 100-200 Hz) activity compared with the background was distinguished both visually and with spectral analysis later in the seizures of 3/4 mesial temporal patients, involving contacts in the generator region and, in one patient, areas of contralateral peri-hippocampal propagation. Three patients with well-defined neocortical seizure-onset areas also demonstrated focal HF or VHF oscillations confined to the seizure-onset channels during their eight seizures. No discrete HF or VHF activity was present in the poorly localized seizures from the remaining three patients. These results show that discrete HFOs can be recorded from human focal epileptic brain using depth macroelectrodes, and that they occur mostly in regions of primary epileptogenesis and rarely in regions of secondary spread. Absent high-frequency activity seems to indicate poor localization, whereas the presence of focal HFOs near the time of seizure onset may signify proximity to the epileptogenic focus in mesial temporal lobe and neocortical seizures. We postulate that focal HFOs recorded with depth macroelectrodes reflect the partial synchronization of very local oscillations such as those previously studied using microelectrodes, and result from interconnected small neuronal ensembles. Our finding that localized HFOs occur in varying anatomical structures and pathological conditions perhaps indicates commonality to diverse epileptogenic aetiologies.

Seizures occurred in one third of patients with intracerebral hemorrhage (ICH) and over half were purely electrographic. Electrographic seizures were associated with expanding hemorrhages, and periodic discharges with cortical ICH and poor outcome. Further research is needed to determine if treating or preventing seizures or PEDs might lead to improved outcome after ICH.

Objective: Generalized periodic discharges are increasingly recognized on continuous EEG monitoring, but their relationship to seizures and prognosis remains unclear.Methods: All adults with generalized periodic discharges from 1996 to 2006 were matched 1:1 to controls by age, etiology, and level of consciousness. Overall, 200 patients with generalized periodic discharges were matched to 200 controls. Results:Mean age was 66 years (range 18-96); 56% were comatose. Presenting illnesses included acute brain injury (44%), acute systemic illness (38%), cardiac arrest (15%), and epilepsy (3%). A total of 46% of patients with generalized periodic discharges had a seizure during their hospital stay (almost half were focal), vs 34% of controls (p ϭ 0.014). Convulsive seizures were seen in a third of both groups. A total of 27% of patients with generalized periodic discharges had nonconvulsive seizures, vs 8% of controls (p Ͻ 0.001); 22% of patients with generalized periodic discharges had nonconvulsive status epilepticus, vs 7% of controls (p Ͻ 0.001). In both groups, approximately half died or were in a vegetative state, one-third had severe disability, and one-fifth had moderate to no disability. Excluding cardiac arrest patients, generalized periodic discharges were associated with increased mortality on univariate analysis (36.8% vs 26.9%; p ϭ 0.049). Multivariate predictors of worse outcome were cardiac arrest, coma, nonconvulsive status epilepticus, and sepsis, but not generalized periodic discharges. Conclusion:Generalized periodic discharges were strongly associated with nonconvulsive seizures and nonconvulsive status epilepticus. While nonconvulsive status epilepticus was independently associated with worse outcome, generalized periodic discharges were not after matching for age, etiology, and level of consciousness. Neurology ® 2012; 79:1951-1960

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Summary:Purpose: High-frequency activity has been recorded with intracerebral microelectrodes in epileptic patients and related to seizure genesis. Our goal was to analyze high-frequency activity recorded with electroencephalograph (EEG) macroelectrodes during the slow wave immediately following interictal spikes, given the potential importance of this presumed hyperpolarization in transforming spikes into seizures.Methods: Depth electrode EEG recordings from 10 patients with intractable focal epilepsy were low-pass filtered at 500 Hz and sampled at 2,000 Hz. Spikes were categorized according to localization and morphology. Segments of 256 ms were selected immediately following (postspike), and 2 s before each spike (baseline). Power was estimated in subgamma (0-40 Hz), gamma (40-100 Hz), high frequency (100-200 Hz), and very high frequency (250-500 Hz) bands.Results: Changes in power above 100 Hz were seen in 22 of 29 spike categories, consisting primarily of a widespread decrease in frequencies above 100 Hz. This decrease became spatially more restricted as frequencies increased, and coincided with the localization of largest spikes for the highest frequencies. High-frequency power decreases were prominent in the hippocampus but less common in amygdala and neocortex. High-frequency power increases were observed in the amygdala.Conclusions: Thus high-frequency EEG activity can be recorded with macroelectrodes in humans and may provide insights on neuronal mechanisms related to human epilepsy. This activity undergoes consistent modifications after EEG spikes. We propose that the reduction in high frequencies reflects a postspike depression in neuronal activity that is more pronounced in the region of spike generation. This depression is almost always seen in hippocampus but less in amygdala. Key Words: Intracerebral EEG-High frequency-Spikes.High-frequency oscillations, ranging from 100 to 250 Hz, and termed ripples, have been described in the hippocampus and entorhinal cortex of normal rodents (1-4). Bragin et al. (5,6) have found similar oscillations in the human hippocampus in recordings obtained through microwires implanted with depth electroencephalograph (EEG) macroelectrodes in epileptic patients with intractable seizures. Although the frequency of these oscillations was lower than in animal studies (80-160 Hz), ripples were found in epileptogenic as well as normal temporal lobes (TLs) and interpreted as representing physiological activity. High-frequency ripples appear associated with memory consolidation (1), while even higher (7) frequency activities greater than 500 Hz, which have been described in the normal neocortex of animals (8-11) and

SUMMARYPurpose: Intracranial depth macroelectrode recordings from patients with focal seizures demonstrate interictal and ictal high frequency oscillations (HFOs, 80-500 Hz). These HFOs are more frequent in the seizure-onset zone (SOZ) and reported to be linked to seizure genesis. We evaluated whether HFO activity changes in a systematic way during the preictal period. Methods: Fifteen minutes of preictal intracranial electroencephalography (EEG) recordings were evaluated in seven consecutive patients with welldefined SOZ. EEG was filtered at 500 Hz and sampled at 2,000 Hz. Ripples (80-250 Hz) and fast ripples (250-500 Hz) were visually marked, and spectral analysis was performed in seizure-onset as well as nonseizure-onset channels. Linear regressions fitted to the power trends corresponding to intervals of 1, 5, and 15 min before the seizure onset was calculated. Results: Total rates of HFOs were significantly higher in the SOZ than outside. Preictal increases and decreases in HFO rates and band power could be detected in all patients, and they were not limited to the SOZs. These measures were very variable, and no systematic trends were observed when comparing patients or seizures in the same patient. Discussion: High frequencies in the range of 80-500 Hz are present during the preictal period and are more prominent in the SOZ. They do not change in a systematic way before seizure onset for the horizons we tested. The 80-500 Hz band may be used for the localization of seizure-onset areas but may be more difficult to use for seizure prediction purposes.

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