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.