Assessment 1 – Are seizures predictable? What are the triggers?

Preface 

Epilepsy is a serious neurological disease, usually with an unknown origin.  In the USA population, this disease affects about 1.2% of individuals. It is a disease that produces random seizures of varying duration, magnitude and frequency.  Approximately 30% of persons with epilepsy (PWE) derive no benefit from anti-epileptic drugs. Many others are poorly served by these medications (Thijs et al., 2019).  For this group, the ability to identify the seizure trigger(s), so as to intervene and prevent the seizure, is of the highest priority.  Therefore, it is important to know whether the current science convincingly show seizure predictability with identifiable and reliable initiators.

Definitions of seizure symptoms – which ones are important for reliable predictions?

To evaluate epilepsy, it is important to first understand some established terminology. The scientific literature has categorized the “symptoms to anticipate seizures” (Kotwas et al., 2016) as falling into 3 distinct categories as follows: 

     a) auras,

     b) premonitory or prodromes, and

     c) precipitating factors. 

If reliable, each provides a different degree of potential benefit for PWE.

Auras

First, auras are symptoms that occur in some PWE immediately prior to the seizure.  In the presence of an aura, seizure events are already in play and the ability to prevent the seizure is nil.  However, it could allow for PWE to seek safety e.g. lying down to prevent a fall or calling for assistance (Schulz-Bonhage and Haut, 2011). 

Prodrome

Secondly, the prodrome symptoms occur 30 minutes to 6-12 hours prior to a seizure.  Examples of reported symptoms are :”mood disorders; symptoms such as irritability, anxiety, depression, fear, anger, excitability and reduced tolerance” and “non-specific ‘funny feeling’, headache, and cognitive disturbances; bradypsychia, speech disturbances and attentional deficits” (Scaramelli et al., 2009; MacKay et al., 2017).  The prodrome permits intervention with  potential to negate a seizure and has been examined repeatedly in drug-resistant PWE.

Precipitating Factors

Thirdly, precipitating factors are symptoms that occur 24-12 hours prior to a seizure and if correctly identified could enable the PWE to change behavior, location, activity etc.  Symptoms include “stress, stressful events, sleep deprivation, symptoms of depression, anxiety, fatigue (Kotwas et al., 2016).

Of the three categories, the second category, the prodrome, offers the best time frame to prevent a seizure and it is the time frame of interest of many investigators (MacKay et al., 2017). 

Seizure prodrome predictions with subjective analysis lack credibility

There exists numerous studies (see reviews Illingworth et al., 2014; Kotwas et al., 2016; Mackay et al., 2017)  and several clinical trials (Privitera et al., 2019; Jeppesen et al., 2019) that have investigated the extent of subjective seizure prediction in PWE resistant to anti-seizure medications.  Studies employed questionnaires, interviews and electronic diaries to assess the ability of PWE to predict their seizures.  The results suggest that a small subset of PWE have the ability of seizure prediction.  However, these studies lack scientific rigor.  This means that the data were collected retrospectively (as a recall) and the time between “predictive” symptom(s) and seizure was unknown.  The most meticulous assessments use electronic diaries (see review MacKay et al., 2017).  However, even with this approach, multiple choice answers were supplied for each question relating to events prior to a seizure.  PWE reported their seizures without electronic verification (such as with an electroencephalograph (EEG) recording).  Results were further honed by selecting epileptics who had a high degree of confidence in their ability to predict their seizures and of these, only 9 out of 20 achieved this with their electronic responses.  Additionally, many studies were faced with a diversity of epilepsy disorders that confound results.  Despite the high level of interest in this topic and urgent need to know definitively the predictability of a seizure, results of studies to date with a subjective approach of surveys, questionnaires and diaries are unconvincing.

References for this assessment can be found in the PDF download.

Assessment 2 will examine seizure prediction with biosensors and what the future holds for this approach.