Focal seizures appear to start abruptly and unpredictably when recorded from volumes of brain probed by clinical intracranial electroencephalograms. To investigate the spatiotemporal scale of focal epilepsy, wide-bandwidth electrophysiological recordings were obtained using clinical macro- and research microelectrodes in patients with epilepsy and control subjects with intractable facial pain. Seizure-like events not detectable on clinical macroelectrodes were observed on isolated microelectrodes. These 'microseizures' were sparsely distributed, more frequent in brain regions that generated seizures, and sporadically evolved into large-scale clinical seizures. Rare microseizures observed in control patients suggest that this phenomenon is ubiquitous, but their density distinguishes normal from epileptic brain. Epileptogenesis may involve the creation of these topographically fractured microdomains and ictogenesis (seizure generation), the dynamics of their interaction and spread.

SUMMARYObjective: Evaluate the seizure-reduction response and safety of mesial temporal lobe (MTL) brain-responsive stimulation in adults with medically intractable partial-onset seizures of mesial temporal lobe origin. Methods: Subjects with mesial temporal lobe epilepsy (MTLE) were identified from prospective clinical trials of a brain-responsive neurostimulator (RNS System, NeuroPace). The seizure reduction over years 2-6 postimplantation was calculated by assessing the seizure frequency compared to a preimplantation baseline. Safety was assessed based on reported adverse events. Results: There were 111 subjects with MTLE; 72% of subjects had bilateral MTL onsets and 28% had unilateral onsets. Subjects had one to four leads placed; only two leads could be connected to the device. Seventy-six subjects had depth leads only, 29 had both depth and strip leads, and 6 had only strip leads. The mean follow-up was 6.1 AE (standard deviation) 2.2 years. The median percent seizure reduction was 70% (last observation carried forward). Twenty-nine percent of subjects experienced at least one seizure-free period of 6 months or longer, and 15% experienced at least one seizure-free period of 1 year or longer. There was no difference in seizure reduction in subjects with and without mesial temporal sclerosis (MTS), bilateral MTL onsets, prior resection, prior intracranial monitoring, and prior vagus nerve stimulation. In addition, seizure reduction was not dependent on the location of depth leads relative to the hippocampus. The most frequent serious device-related adverse event was soft tissue implant-site infection (overall rate, including events categorized as device-related, uncertain, or not device-related: 0.03 per implant year, which is not greater than with other neurostimulation devices). Significance: Brain-responsive stimulation represents a safe and effective treatment option for patients with medically intractable epilepsy, including patients with unilateral or bilateral MTLE who are not candidates for temporal lobectomy or who have failed a prior MTL resection.

The likelihood of rupture of unruptured intracranial aneurysms that were less than 10 mm in diameter was exceedingly low among patients in group 1 and was substantially higher among those in group 2. The risk of morbidity and mortality related to surgery greatly exceeded the 7.5-year risk of rupture among patients in group 1 with unruptured intracranial aneurysms smaller than 10 mm in diameter.

Matsumoto A, Brinkmann BH, Stead SM, Matsumoto J, Kucewicz MT, Marsh WR, Meyer F, Worrell G. Pathological and physiological high-frequency oscillations in focal human epilepsy. J Neurophysiol 110: 1958 -1964. First published August 7, 2013 doi:10.1152/jn.00341.2013.-High-frequency oscillations (HFO; gamma: 40 -100 Hz, ripples: 100 -200 Hz, and fast ripples: 250 -500 Hz) have been widely studied in health and disease. These phenomena may serve as biomarkers for epileptic brain; however, a means of differentiating between pathological and normal physiological HFO is essential. We categorized task-induced physiological HFO during periods of HFO induced by a visual or motor task by measuring frequency, duration, and spectral amplitude of each event in single trial time-frequency spectra and compared them to pathological HFO similarly measured. Pathological HFO had higher mean spectral amplitude, longer mean duration, and lower mean frequency than physiological-induced HFO. In individual patients, support vector machine analysis correctly classified pathological HFO with sensitivities ranging from 70 -98% and specificities Ͼ90% in all but one patient. In this patient, infrequent high-amplitude HFO were observed in the motor cortex just before movement onset in the motor task. This finding raises the possibility that in epileptic brain physiological-induced gamma can assume higher spectral amplitudes similar to those seen in pathologic HFO. This method if automated and validated could provide a step towards differentiating physiological HFO from pathological HFO and improving localization of epileptogenic brain.high-frequency oscillations; epilepsy; gamma oscillations HIGH-FREQUENCY OSCILLATIONS (HFO) have been widely studied in animals and humans and linked to brain function in health and disease (Buzsaki and Silva 2012). Physiological highfrequency gamma oscillations (gamma: ϳ40 -100 Hz) are believed to coordinate cortical processing during vision (Gray and Singer 1989), motor, and language functions (Crone et al. 2011). Physiological hippocampal high-frequency oscillations (ripples: 100 -200 Hz) are thought to play an important role in memory functions (Buzsaki et al. 1992).Pathological HFO (pHFO) were initially observed in hippocampal recordings from epileptic rats and thought to be a specific electrophysiological biomarker of epileptic tissue (Bragin et al. 1999b). The pHFO observed in epileptic rats included fast ripples (250 -500 Hz) that colocalize to the epileptic hippocampus-generating seizures in rats (Bragin 1999b(Bragin , 2002 and humans (Bragin 1999a). In addition, ripple HFO were observed in the hippocampal dentate gyrus of epileptic rats but not in control rats and were therefore considered pHFO (Bragin 2002). The cellular correlates of normal physiological hippocampal ripples were shown to be inhibitory postsynaptic potentials (Ylinen et. al. 1995) and pathological fast ripples were shown to be synchronous population firing of large groups of pyramidal cells and decreased inhibitory interneuron firin...