Advances in seizure prevention and prediction

The earlier seizure activity is detected, the better the chance of preventing it. For several years, Mayo Clinic neurologists and their neurosurgical colleagues have been working to pinpoint the exact moment and the precise location of seizure generation.

Isolating the where and when of microseizures

Volume samples of clinical electrode vs microwire

Enlarge

Three years ago, using microelectrodes 40 microns in diameter, or thinner than a human hair, Mayo Clinic researchers began recording electroencephalographic activity from brain regions the size of cortical columns at frequencies beyond the limits of standard electroencephalogram (EEG) recordings. Cortical columns, the smallest functional unit in the cortex, are approximately 300 microns across and contain from 1,000 to 7,500 neurons. In perspective, a typical EEG electrode captures the activity of millions of neurons and hundreds of cortical columns.

This research revealed that isolated brain regions the size of cortical columns do, indeed, show evidence of seizure activity (microseizures) in humans. The investigators found that microseizures occurred most often in patients with epilepsy but also occurred, although rarely, in control patients without epilepsy. This latter finding demonstrates that pathologic oscillations can occur even in people who do not have epilepsy.

How do microseizures transition to clinical seizures in patients with epilepsy?

Mayo Clinic research findings support the hypothesis that in patients with epilepsy, individual microdomains the size of cortical columns generate frequent hypersynchronous discharges, which recruit other columns of neurons.

Similar, noncolumnar groupings of neurons have been identified in the rat hippocampus by researchers at UCLA and are known as pathologically interconnected neuron (PIN) clusters. These PIN clusters can be considered microdomains of epileptogenesis or seizure initiation. When a critical volume of microdomain activity is reached, a large-scale seizure is generated. This explanation can be referred to as the sick column hypothesis.

Clinical EEG recordings do not probe the spatial and temporal scales of microdomain activity, which makes early detection difficult. This hypothesis may explain why some patients do not respond to first-generation responsive stimulation devices designed to detect and abort seizures.

Update on implanted devices to detect and abort epileptic seizures

Two new implantable epilepsy devices that use electrical stimulation are undergoing multicenter trials for treatment of medically refractory epilepsy. One device uses electrical stimulation of the anterior nucleus of the thalamus to modulate the brain activity and prevent seizures. Another device under investigation is the responsive neurostimulator system. Initial results from these 2 pivotal multicenter trials have demonstrated the efficacy and safety of these devices.

Predicting seizures: devices on the horizon

Not knowing when a seizure will occur is one of the most debilitating aspects of epilepsy. Patients may have only 4 or 5 seizures a month, each lasting a few minutes. But those few minutes mean they can't drive, and they may be afraid to go out in public for fear of having a seizure, which can lead to social isolation.

The recent discovery that seizurelike events can occur in pathologic microdomains, such as microseizures, in humans adds to a growing body of evidence that seizures may begin before they are evident clinically. In the future, devices may be able to provide patients with warnings that a seizure is about to occur or, possibly, to prevent a seizure.

Future applications

The future of seizure prevention rests on understanding the mechanisms underlying seizure generation. As knowledge in these areas advances, future clinical applications include improvements in epilepsy surgery and the devices delivering neurostimulation and the possible development of algorithms that identify periods of increased probability of seizures.

Points to remember

• Mayo Clinic neurologists and neurosurgeons have been working to pinpoint the exact moment and the precise location of seizure generation.
• The recent discovery that seizurelike events can occur in pathologic microdomains, such as microseizures, in humans adds to a growing body of evidence that seizures may begin before they are evident on clinical recording systems and well before patients have symptoms.
• Initial results from 2 pivotal multicenter trials have demonstrated the efficacy and safety of implantable epilepsy devices that use electrical stimulation for reducing seizure frequency in patients with medically intractable partial epilepsy.