Category Archives: Diagnostics

The Subscalp EEG Recording – promising technology 

Diagnostics, Epilepsy Topics, ,

Introduction

Subscalp EEG recording is a technological advancement positioned to revolutionize diagnostics, treatment and understanding of epilepsy.

Over the past 7 years or so, several investigatory groups have developed subscalp EEG recording systems. These systems consist of electrodes that can be implanted under the skin of the scalp.  Electrodes are attached to external data collection and analytical systems.  These systems allow continuous EEG monitoring 24/7 for months and potentially for years. 

Unmet Need

There is a unmet need for accurate long term measurements of seizures.  To provide a correct diagnosis of epilepsy and develop optimal therapy, the physician needs information on exact seizure frequency, location, and brain wave activity prior to and after a seizure. As discussed in Blog 8 (Intracranial EEG recording), implantation of electrodes directly in the brain continually assesses brain wave activity and has provided significant insights in the cyclic nature of the disease.  However, intracranial recordings necessitate major surgery and, therefore, are available for only a small number of patients with epilepsy.  On the other hand, scalp EEG (electrodes placed on top of the scalp) coupled with video monitoring, although not invasive, supply continuous seizure assessment for no more than 14 days, at best.

Ultra-long term EEG recording lies between intracranial recording and scalp recording.  It has potential to not only determine seizure frequency and location but to confirm the cyclic nature of epilepsy, thereby significantly adding to insights from intracranial EEG recordings.  Furthermore, subscalp EEG systems appear capable of predicting future seizures, thus allowing for preemptive suppression.

However, keep in mind, this technology is in its initial stages but has great promise.

Validation of Subscalp EEG Recording

While there are many foreseeable uses of continuous subscalp EEG recordings, the first use is for long term acquisition of seizures and pre/post seizure activity in patients with epilepsy. 

There are 6 systems in clinical validation phases (clinical trial completion, ongoing or about to begin).  Two systems, the 24/7EEG SubQ (https:// www.uneeg. com/ en/ epilepsy/products/subq) and the Minder have completed small clinical safety/feasibility studies (see Weisdorf et al., 2018; 2019; Sterling et al., 2021). 

The 24/7EEG SubQ system

The 24/7EEG SubQ system consists of  a) subcutaneously implanted electrodes and b) a data collection system composed of a transceiver (transmitter/receiver combo), data storage device and power supply.  The first study with this system (4 patients with temporal lobe epilepsy) was a feasibility (proof-of-concept) study.  Results showed that SubQ EEG recordings were similar to standard scalp EEG recordings.  Specifically, the SubQ system measured seizures, pre-seizure activity, sleep brain wave activity and some unrelated activity.  These are all findings comparable to standard EEG recordings. 

The most outstanding characteristic of the subscalp recording is, unlike standard scalp EEG measurements, its ability to gather data over long periods of time.  The second clinical trial with the SubQ device implanted in 9 patients with temporal epilepsy and monitored EEG activity for the target time of 3 months (achieving a minimum of 9 weeks of recording for each patient).  This is clearly a milestone since it is the first study to demonstrate “ultra-long” EEG monitoring with a minimally invasive device and without disruption of daily activities of living.

The Minder System

Another subscalp EEG system, the Minder completed an 8 months study with 5 patients with epilepsy. The components of the Minder system are electrodes capable of monitoring brain activity in both hemispheres and collecting data by telemetry to a processor placed behind the ear.  A smart phone receives the data and stores it in the cloud. 

Subscalp EEG data from the Minder compared favorably with standard video/scalp EEG data obtained at specified times during the study.  These results confirm the feasibility of a minimally invasive implanted subscalp EEG system such as the Minder for long term monitoring of focal seizures.

Adverse Effects of Subscalp EEG Recording

Adverse effects from subscalp devices described above are mild.  Expected pain and soreness at the site of surgical implantation lasting about a week occurred in most patients.  However, few experienced pain and soreness beyond one week.  Some experienced mild headaches unrelated to the surgery.

Limitations of Subscalp EEG Recordings

Firstly, the collection of thousands of hours of brain wave activity creates an analytical nightmare.  In summarizing the data to reasonably handle it, some data may be lost.  Efforts to develop intelligent algorithms are in development so that all data can be treated equally.  Secondly, the position of the implanted electrodes may miss seizures originating deep in the brain. Thus some patients with epilepsy may not benefit from subscalp EEG devices.  Thirdly, completed safety and feasibility studies necessarily involved a small number of select patients (those with temporal lobe epilepsy).  Therefore, for confirmation of the generalized benefit of subscalp EEG for most patients with epilepsy, larger scale studies with patients with diverse types of epilepsy are required.

Conclusions

Subscalp EEG recording systems represent a relevant and dearly needed advancement over the short term EEG recordings of the standard scalp EEG.  Subscalp EEG systems provide ultra-long term recordings. These recordings provide accurate determinations of seizure frequency and location, information essential for optimal drug therapy or future surgical decisions.  Especially attractive is the fact that subscalp EEG systems require minimal surgery for implantation and once implanted do not disrupt everyday activities.

There are at present 6 subscalp EEG systems, 2 of which successfully demonstrated safety and feasibility  in patients with temporal lobe epilepsy.  This is a significant start.  The limited results thus far are indeed very promising.  Continued development and clinical assessment can promote and expand a transforming new technology to better serve patients with epilepsy.  This blog will provide updates on subscalp EEG systems from future clinical trials.

Comparison of EEG Technologies

References (http://pubmed)

Duun-Henriksen J et al., A new era in electroencephalographic monitoring? Subscalp devices for ultra–long-term recordings. Epilepsia.61:  1805–1817, 2020.

Stirling RE et al., Seizure forecasting using a novel sub-scalp ultra-long term EEG monitoring system. Front. Neurol. 12:713794, 2021.

Weisdort S et al., High similarity between EEG from subcutaneous and proximate scalp electrodes in patients with temporal lobe epilepsy. J Neurophysiol 120: 1451–1460, 2018.

Weisdort S. et al., Ultra‐long‐term subcutaneous home monitoring of epilepsy—490 days of EEG from nine patient. Epilepsia. 60:  2204–2214, 2019.

Assessment 7 – Value of Diagnostics for Epilepsy

Diagnostics, , , ,

Epilepsy is a disease defined by the presence of two or more seizures, separated by more than 24 hours.  However, in order to identify the appropriate anti-seizure drug for seizure suppression, a diagnosis of epilepsy is more complicated than the definition implies.  There are 4 sources of potentially valid information that together should yield the most accurate diagnosis.  The diagnostics for epilepsy are:

a) seizure history provided by the patient;

b) digital data from an electroencephalogram (EEG) which records seizure activity or, in the absence of a seizure, the presence of abnormal discharges;   

c) analysis from magnetic resonance imaging (MRI) showing presence of a tumor, scar tissue, or abnormal anatomical lesions related to site of seizure origin;

d) genetic assessment matching one or more of the known genetic errors associated with specific types of epilepsy.

What is the value of the information gathered from these sources?

1. Seizure History

Seizure history is important but can be lacking in specifics.  This is because many patients have little to no recollection of their seizures.  This starting point for a diagnosis is not particularly helpful in identifying the epilepsy type and thus, it is not helpful at all in selection of the appropriate antiseizure medication.

2.  EEG

The EEG was developed over a century ago.  Electrodes, placed on the scalp, record summated electrical activity primarily from the outer portion of the brain (the cortex).  Electrodes are precisely positioned to receive defined recognizable brain wave activity.  The EEG recording itself generally takes 20 minutes but considerable time is required to position the electrodes and also to remove them.  During the actual recording, procedures such as light stimulation or hyperventilation are used to “evoke” a seizure.

Advantages of diagnostics for epilepsy: 

Whereas the EEG usually does not record a seizure in progress, its ability to detect abnormal discharges, (called interictal epileptogenic discharges or IEDs), is significant because the presence of IEDs have been found to signal a high risk of having a future seizure.  The EEG many record local IEDs (expressed in one hemisphere) or general IEDs (expressed in the entire brain). This information contributes to a more accurate diagnosis and hence is one clear benefit of the EEG.  Additionally, the EEG is helpful in monitoring the progress of seizure suppression with drugs or surgery. Anti-seizure drugs has previously been discussed (Assessment 6 – Epilepsy Medication – Need to Know Information)

Limitations of Diagnostics for Epilepsy: 

As revealed by years of intracranial recording (surgical implantation of electrodes) in patients with epilepsy, it is apparent that the EEG has limitations.  Its short duration, lack of sensitivity and tendency for over interpretation are some of its limitations.  It has also failed to identify the multiday cyclic nature of epileptic activity. 

The short duration of the EEG test fails to capture the majority of  in-progress seizures and many patients show no evidence of IEDs.  Although in a hospital setting, the EEG may be used continually for several days, this is not routinely practiced.  To avoid obtaining incorrect data, technical expertise is required for electrode placement.  Despite this, sensitivity is diminished due to distance of the electrodes (on the scalp) from the origin of the brain activity (somewhere in the brain) and the inability of electrodes to record all brain wave activity but only a sampling of those reaching the outer layer of the brain.

3.  MRI

The MRI is one of several imaging techniques with success in identifying abnormalities in the brain in persons with epilepsy (see https://medlineplus.gov/mriscans.html ) for details on MRI imaging.  In cases of epilepsies resistant to drug, surgical protocols require prior imaging procedures.

Imaging techniques include the MRI, the positron emission tomography (PET) and MRI spectrometry, to name a few.  The MRI uses magnetic energy to define the location of structures in the brain.  The stronger the magnet, the better the resolution of the individual structures in the brain.  The PET scan adds to the MRI with the use of a radioactive tracer.  This tracer localizes to areas of high metabolism as in tumor or indicates areas of low metabolism as in epileptic lesions.  The MRI spectrometry is a supplemental test only.  It measures brain compounds known to indicate the presence of a seizure lesion.  Abnormal levels of specific compounds add to MRI data of structural changes, pinpointing a epileptic lesion.

Advantages of Diagnostics for Epilepsy: 

The MRI in association with other imaging tools (PET, Spectrometry) provide essential information for epilepsy patients resistant to drug therapy.  These patients may be candidates for surgical therapy.  High quality data from imaging techniques assist with accurate surgery but only facilities with extensive experience in imaging and treating patients whose epilepsy is not suppressed with antiseizure drugs, produce these desired outcomes.

Limitations of Diagnostics for Epilepsy: 

Outpatient use of the MRI technology generally contributes little to the initial diagnosis of epilepsy.  Most clinics lack expertise on recognition of epileptogenic lesions and additionally do not employ the optimal MRI protocols to capture these lesions.  Technologists may also lack the clinical information to alert them to the reason for the MRI and hence fail to seek expert help.  

4.  Genetic Analysis

Epilepsy is considered to have a heritable component.  Identification of the genes involved in epilepsy should provide greater understanding of this disease and lead to better therapy.  The International League Against Epilepsy Consortium on Complex Epilepsies initiated a large analysis (meta-analysis) of the genome (DNA content) of persons with epilepsy compared to controls.  The most recent work (2018) included over 15,000 epilepsy cases and over 29,000 controls.  This study identified 16 different chromosome locations that relate with confidence to epilepsy.  These chromosome positions reveal many genes already associated with epilepsy such as the ion channels on nerve cells but also importantly, many new genes not previously identified as a cause of epilepsy.

Advantages of Diagnostics for Epilepsy: 

Routine genomic testing in epilepsy could be a step closer to precision medicine. Genomic testing would allow for a precise diagnosis, and a more rational selection of anti-seizure medication.  This type of testing opens the door for discovery of novel drugs and has potential to determine exactly which genes play a role in specific types of epilepsy.

Limitations of Diagnostics for Epilepsy: 

Analysis of genomic-wide testing is complicated and the variety of different forms of epilepsy are equally complex.  To date, most of the identified genes are “associated with genetic generalized epilepsy” (ILAE Consortium).  Considerable research commitment will be needed to unravel the genetic influence on epilepsy and then to reveal how the environment interacts with these genes.

Summary

There exists 4 different types of information (patient assessment, EEG, MRI, genetic analysis) that should provide an accurate diagnosis of epilepsy.  Unfortunately, their limitations outweigh their assets.  Thus, a diagnosis of epilepsy may be absent, delayed or incorrect and consequently, antiseizure therapy may be inappropriate.