In the last two decades, neurostimulation has emerged as a safe and effective therapeutic
option for patients with pharmacoresistant epilepsy who are not suitable candidates
for surgery because they have more than one epileptic focus or a single focus over
eloquent cortex.
There are three main neurostimulation techniques for epilepsy – vagus nerve stimulation
(VNS), deep brain stimulation (DBS) and responsive neurostimulation (RNS). Compared
to the first two types of neurostimulation, which are open-loop systems providing
intermittent stimulation throughout the day at sites distant from the epileptic focus,
RNS involves a closed-loop system that delivers an electrical stimulus directly to
the epileptic focus only when the patient has a seizure. In order to do this, it includes
a system for recording and detection of brain electrical activity. One or two subdural
or intracerebral depth electrodes, each consisting of 4 contacts, are placed over
the epileptic focus and parameters are adjusted to optimize the sensitivity and specificity
for detecting seizures. It can be used for patients with 1–2, unilateral or bilateral
epileptic foci.
Apart from neurostimulation, the RNS system provides an opportunity for chronic ambulatory
electrocorticography (ECoG). Such recordings obtained through the RNS system can be
useful in several ways, including lateralization of the predominant epileptic focus
in patients with bilateral epilepsy (King-Stephens et al., 2015), seizure counting
and reporting, determination of timing of seizures and identification of temporal
patterns (Anderson et al., 2015), assessing drug response and planning surgical resection
at a later date.
The effectiveness of neurostimulation for seizure control and the value of the chronic
recordings for other purposes depend on the precise localization of the epileptic
focus. This requires detailed presurgical evaluation, usually including intracranial
recordings, and determination of the seizure onset zone(s) in most patients. Patients
typically undergo video-EEG monitoring in the epilepsy monitoring unit over 2–3 weeks,
during which antiepileptic medications are often reduced or withdrawn to provoke seizures.
Despite these approaches, seizures are not recorded in some patients. How can the
location of the epileptic focus be determined in such patients?
In this issue of Clinical Neurophysiology Practice, Chan and colleagues address this
question by describing two patients with pharmacoresistant epilepsy who had no seizures
recorded during invasive monitoring, but subsequently underwent RNS, with placement
of leads determined by interictal and neuroimaging data (Chan et al., 2018). Seizures
were later localized during chronic ambulatory ECoG.
This is a short, well-written and timely paper describing a new approach to this infrequent
but important clinical issue. Their observation that clinical seizures documented
by patients in seizure diaries after RNS lead implantation were always associated
with electrographic changes in the RNS ECoG recordings suggests that RNS indeed provided
adequate localizing information for all seizures, and that these patients did not
have additional foci that were not localized.
In their first patient, the region of interictal spiking (hippocampus and periventricular
nodular heterotopia) was chosen for placement of the RNS depth leads, but subsequent
recordings determined that the seizures actually started in the temporal neocortex
overlying the nodular heterotopia, highlighting the limitations of using interictal
data to identify the seizure onset zone. The authors were fortunate to have proximal
contacts of the RNS leads in this region and obtain localizing information.
The authors appropriately acknowledge the limitations of their study, including the
limited number of contacts used in the RNS system and the possibility that the recorded
seizures could have reflected a spread pattern from brain regions not sampled by the
electrodes rather than the ictal onset zone. One way to distinguish between the two
is to determine if clinical seizure onset follows or precedes ictal EEG onset. The
former would suggest placement of leads directly over the focus, while the latter
would indicate a spread pattern. This can be accurately determined during video-EEG
monitoring studies in the hospital. However, there are practical constraints to doing
so during chronic ambulatory ECoG in the outpatient setting, since patients are not
on video camera and impairment of consciousness associated with a seizure may result
in patients being unaware of and unable to document the exact clinical onset.
The clinical response was relatively modest in Patient 1 (30% reduction of seizure
frequency after 15 months) and better in Patient 2 (50% reduction after 14 months).
This could be related to the natural variability of clinical response to RNS among
individuals with epilepsy, the location of the focus (neocortical temporal versus
mesial temporal) or to the less precise localization of the focus in Patient 1. Two
recent studies have addressed the latter two possibilities. Over a mean follow-up
period of 6.1 years, Geller et al. (2017) reported a median seizure reduction of 70%
for patients with mesial temporal onset, while Jobst et al. (2017) found a 58% reduction
in those with neocortical temporal onset. Interestingly, Geller et al. (2017) also
noted that the clinical response was similar in patients with leads placed directly
over the focus (hippocampus) or near to the focus. Therefore, accurate localization
may not be critical for RNS lead placement.
Since this is a novel application of a relatively new technology in only two patients,
it remains unclear whether chronic ambulatory ECoG with RNS can be routinely used
to provide localizing information. However, this study should stimulate further discussion
regarding the advantages and limitations of their approach. It also adds to the growing
literature on other ways to use RNS besides providing therapeutic neurostimulation.
Conflicts of interest and funding sources
None.