Approximately two thirds of people with epilepsy successfully control their seizures by taking anti-epileptic drugs (AEDs). However the remaining third do not respond to AED treatment (their epilepsy is referred to as 'refractory'), and for these people, additional / alternative therapies must be sought. Current options include vagal nerve stimulation, a ketogenic diet and, for a carefully considered proportion, surgery to remove the affected area of the brain.

Researchers led by a team in Stanford, California, have now been looking at a completely new type of epilepsy treatment known as thalamic stimulation. The thalamus is a symmetrical, paired structure found near centre of the brain. Its main role is to modulate sensory information from the outside world, for example temperature, visual and auditory stimuli, and relay it to the brain cortex; but it also plays a part in sleep regulation.

The thalamus has long been implicated in generalised epilepsies, but its role in localised / partial seizures is less clear. The aim of the current study was to see if electrical stimulation of a part of the thalamus known as the anterior nucleus (AN), using a technique called deep brain stimulation (DBS), affected seizure frequency in people with refractory partial epilepsy (anterior nuclear deep brain stimulation will be referred to as AN DBS).

The team recruited 110 adults with refractory partial seizures who had failed to respond to at least three anti-epileptic drugs, and randomly allocated them to one of two groups. The first group went on to receive a three-month course of AN DBS, whilst the second group underwent implantation of the necessary DBS electrodes but did not actually receive any stimulation. The scientists included the second group (known as a control) to help show that any changes in seizure frequency after DBS were due to the stimulation itself and not to other factors. Both the people themselves and the researchers were unaware of (or 'blind' to) the group to which they belonged. This is known as a double blind method and is used to reduce bias in studies.

After three months, all of the participants began an undefined period of 'unblinded' DBS, during which they were aware of the treatment they were receiving. The researchers were particularly interested in any changes in seizure frequency once participants went from non-stimulated to stimulated states, and whether these changes were sustained.

Following the 'blinded' phase, both the stimulated and non-stimulated groups reported a decrease in seizure frequency; although this effect was a lot more marked in people who had received DBS (a 40.4% decrease compared to a 14.5% decrease). The change found in the non-stimulated group, although unexpected, was relatively small and could potentially be attributed to a number of factors; for example under-reporting of seizures, or mere chance (seizure frequency may vary between one three month period and the next). However this will need to be investigated further.

There was also a marked difference between the groups, in the proportion of people who incurred seizure-related injuries - 7% of people in the stimulated group, compared to 26% of the control group.

Interestingly, the scientists noticed that AN DBS improved seizure activity in people with temporal lobe epilepsy, but not in people whose epilepsies originated outside the temporal lobes. The reasons and mechanisms for this require further exploration.

After two years, 91of the original 110 people were still active in the study. 54% of these people had experienced a seizure reduction of at least 50% and 15% had been seizure-free for at least 6 months.

The results are promising, but the adverse effects seen in the study must also be considered. These included pain on electrode implantation (experienced by 10.9% of participants); infection at electrode implantation sites (experienced by 12.7%) and tingling of the skin (experienced by 18.2%). In addition, people who received AN DBS were significantly more likely than those who did not to report depression or memory problems.

More research is needed to clarify the mechanism of AN DBS and its risk/benefit ratio (particularly the long-term effects of repeated stimulation on epileptic brain circuitry, depression, and memory). However, for people with refractory partial temporal lobe epilepsy who are not suitable candidates for surgery, AN DBS may become a viable non-invasive option (in addition to AEDs or other treatments) in the future.

Note: The study was supported by medical technology manufacturer, Medtronic, who provided the DBS equipment for the trial.

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