EEG is the sum of local neuronal electrical activity recorded from the extracranial scalp or intracranially, and is a random signal that varies over time. In seizure disorders such as epilepsy, the paroxysmal abnormalities and clinical seizures of EEG are mostly random events. Short-time routine EEG recordings rarely capture paroxysmal brain potential discharges, and even if recorded for 1 to 2 hours, epileptiform discharges may not be captured, thus increasing the difficulty of epilepsy diagnosis.
According to statistics, multiple routine EEGs only increase the detection rate of epileptic waves to 60%, while the rate of monitored clinical seizures is only about 3%. With the development of electronic technology and computer function, continuous electroencephalography (CEEG) monitoring and quantitative EEG have been gradually born, and this paper will focus on the research progress of these two types of EEG in epilepsy.
1. Application of continuous electroencephalography in epilepsy
CEEG can greatly extend the recording time of EEG, make up for the shortage of conventional EEG, and obtain more information, including abnormal discharges during seizures and interictal periods. Its application has greatly improved the rate of epilepsy diagnosis and the detection rate of epileptic waves (up to 95-98%). In addition, CEEG can determine nonconvulsive seizure (NCS), nonconvulsive status epilepticus (NCSE), guide the drug treatment of epilepsy, predict and detect cerebral ischemia, monitor cerebral edema and intracranial pressure, and help predict coma It is particularly suitable for the classification of epilepsy with atypical clinical manifestations or limited EEG abnormalities [3].
1.1 The need for CEEG monitoring
NCSE is common in critically ill pediatric patients [4], accounting for 25% of childhood status epilepticus (SE), with the highest incidence in infancy [5].Diana Rudin [6] et al. found that 81% of 111 adult SE cases were NCSE or minor seizures, thus suggesting that the prevalence of NCSE in SE is much than 2/3 of previous reports [7]. However, the diagnosis of NCSE is difficult, mostly because its clinical presentation is not accompanied by tonic-clonic seizures, but mostly varies between mild mental status changes to coma.
Therefore, clinical manifestations alone cannot be relied upon to distinguish between subtle convulsions, NCSE, postictal status epilepticus, or sedative effects of pushing drugs.Towne AR [8] et al. reported that up to 50% of patients had subclinical or non-convulsive seizures on EEG after control of generalized convulsive epilepsy persistent seizures, 14% of which lasted longer than 30 minutes and were thus considered to be NCSE. Drislane FW [9] et al. reported that the diagnosis of SE is delayed by 48-72 hours if the clinical presentation alone is relied on without CEEG monitoring.
Seidel [10] et al. performed routine EEG in 2514 patients and found that the incidence of NCSE was 0.8%, and the EEG of 19 of them met the diagnostic criteria for NCSE [11]; 53% of this group of patients were not suspected of NCSE by the clinician, thus concluding that EEG is important for the diagnosis of NCSE.Sutter, R [12] et al. performed EEG in retrospectively analyzed serial EEG recordings from 537 patients with suspected SE and found that CEEG monitoring significantly increased the diagnosis of NCSE (p=0.0546).
Oddo M [13] et al. reported that epileptic seizures and interstitial discharges were associated with poor prognosis. The literature also reported that persistent or recurrent epileptic discharges in NCSE can re-aggravate brain injury and that the morbidity and mortality rate of GCSE patients increases with the duration of NCSE [14]. In summary, in the face of the high incidence of NCS, how to early detect and timely manage the concomitant NCS [15] or NCSE in critically ill patients is particularly important for the prognosis of patients, and CEEG is the only ancillary test that can detect NCS and NCSE, and should be more widely used in ICU patients to find epileptic seizures and monitor NCS to assist in diagnosis.
1.2 Recording time of CEEG monitoring
The duration of recording for CEEG monitoring has not been standardized. During monitoring, patients may be in a state of agitation, anxiety, impaired consciousness, or abnormal psychiatric behavior, and biological, electrical, and environmental disturbances originating in the ICU are more common and difficult to remove than in the EEG room, so the duration of monitoring is usually one to several days. In a study of 117 pediatric patients with epilepsy [16], it was found that only 50% of patients had seizure-like episodes in the first hour of EEG recording, while most abnormalities were not detected by conventional EEG; the 24-hour EEG in patients with coma was 80% positive for NCSs, which was slightly lower than in patients without coma (95%).
Therefore, the idea that an appropriate prolongation of CEEG monitoring in comatose patients could help to increase the positive rate of NCSs is strongly debated. Often, NCS and NCSE can recur, especially on the first day of antiepileptic treatment more commonly, and up to 2/3 of patients can occur during the tapering phase of antiepileptic drugs (AEDs) therapy [17]. The minimum dose of the recommended drug based on clinical experience must eliminate all EEG epileptiform activity and maintain it for 12 hours, during which the patient receives a loading dose of the drug to maintain the anticonvulsant effect, after which the intravenous dose is reduced under the guidance of CEEG monitoring. Therefore, CEEG monitoring should be given at the beginning of antiepileptic treatment and during the drug reduction period in clinical work.
1.3 CEEG testing population
Currently CEEG monitoring is mostly used in patients at high risk for epilepsy in the ICU.Claassen [18] et al. identified coma, early onset epilepsy, age <18 years, and previous history of convulsions as risk factors for the development of NCSE. Additional conditions at high risk for developing epilepsy include subarachnoid hemorrhage or cerebral hemorrhage, CNS infection, CNS tumors, or severe head trauma. Related studies have reported that NCSE is detected by CEEG monitoring in 20-30% of patients at high risk for epilepsy.It has also been suggested that CEEG monitoring is recommended in intensive care unit patients who have.
1) Persistent encephalopathy after generalized convulsions, surgery or neurological injury;
2) fluctuating disorders of consciousness with arousal;
3) Disorders of consciousness with facial myoclonus or nystagmus;
4) Episodes of gaze, aphasia, and automatism;
5) other sudden behavioral changes with no apparent cause.
1.4 Diagnostic value of EEG for NCSE
The epileptiform discharge waveform recorded by EEG does not necessarily indicate a seizure, and CEEG monitoring, like conventional EEG, does not confirm the diagnosis of NCSE even if an epileptiform discharge waveform is recorded, but CEEG monitoring showing recurrent focal or generalized epileptiform activity with at least one of the following primary criteria and more than one secondary criterion, and discharges lasting more than 10 seconds, can be diagnosed as NCSE : Primary criteria.
1) Widespread or focal spike, sharp wave, spike-slow complex wave, or spike-slow complex wave repeatedly issued at >3Hz;
2) <3Hz of recurrent widespread or focal spikes, spikes, spike-slow complex waves, or spike-slow complex waves with secondary criterion #4;
3) continuous rhythmic brain waves with secondary criteria 1, 2, and 3, with or without the 4th Secondary criteria.
1)Gradual increase in voltage or frequency at the onset;
2) Gradual decrease in voltage or frequency at the end;
3)slow wave or voltage decay after the attack
4) Significant improvement in clinical manifestations and EEG after intravenous administration of fast-acting antiepileptic drugs. However, the EEG abnormality caused by the primary disease that caused the impaired consciousness itself may affect the judgment of NCSE.
In summary, NCS or NCSE is a common complication of acute brain injury and a common cause of persistent unresponsiveness or behavioral changes after GCSE convulsions are controlled.CEEG monitoring is the only ancillary test that can detect NCS and NCSE, and without CEEG monitoring, the diagnosis of NCS or NCSE will be easily missed or misdiagnosed. Therefore, CEEG monitoring should be widely used in high-risk patients who may have seizures in the intensive care unit, and even for guiding the selection of antiepileptic drugs, drug maintenance time and drug reduction.
2. Study on the application of quantitative drug EEG in some new AEDs
Many drugs that act on the central nervous system can affect the EEG through a variety of links and mechanisms. Quantitative analysis of EEG signals, i.e. Quantitative Pharmaco-electroencephalography (QPEEG), can analyze the effects of drugs on brain function and can be used as a method to study the mechanism of drug action and evaluate the efficacy of drugs.
The sensitivity of EEG to AEDs makes it a valid and objective method to guide the treatment of chronic AEDs and the study of cognitive function. The effects of classical AEDs on EEG are well known: for example, long-term stable treatment with phenytoin sodium, carbamazepine, and phenobarbital enhances the background rhythmic slow activity of EEG, i.e., increases theta and delta frequencies and decreases alpha frequency. And studies have found that EEG alterations are associated with cognitive impairment [21]. The effects of several novel AEDs commonly used in clinical practice on background EEG and the relationship with cognitive function are reviewed below.
2.1 Effects of some novel AEDs on EEG
Topiramate (TPM): There are conflicting findings regarding the effects of TPM on the background EEG activity in epileptic patients, both at home and abroad.Mecarelli et al [22] found that TPM mainly led to increased activity in the δ and theta slow-wave bands and decreased activity in the fast-wave band in epileptic patients, and a significant decrease in the α band in healthy volunteers; at the same time, increased slow-wave activity was associated with the appearance of mild side effects such as decreased attention, The increased slow wave activity was also associated with the appearance of mild side effects such as reduced attention, cognitive impairment and sedative effects.
Martin Salinsky et al [23] reported that TPM could cause more than moderate cognitive impairment, but TPM had no significant effect on the peak and intermediate frequencies of the posterior dominant rhythm, and the proportion of slow wave δ and theta, so it was concluded that the effect of TPM on cognitive function was not correlated with EEG changes.Wang WW et al [24] reported that after unilateral injection of TPM, in addition to the increase in slow wave activity increased, α1 power and total power also increased, and the proportion of α1 and theta band power increased in healthy people, while the proportion of theta and delta band power increased in epileptic patients.
Lamotrigine (LTG): no significant changes in background activity or increased fast-wave activity and decreased slow-wave activity in healthy volunteers and epileptic patients on lamotrigine.MojS et al. reported that LTG at therapeutic doses standardized background EEG activity and reduced epileptiform discharges; there was no statistically significant difference in the effect of the drug on cognition after treatment.B. Clemens [25] et al. LTG partially normalized composition of each wave of EEG background activity, causing a reduction in slow-wave δ and theta and a reduction in pathological thalamo-cortical synchronization, a change that is use-dependent with LTG. Therefore, it is now generally accepted that polypharmacy with the addition of lamotrigine in children and adolescents has little effect on cognitive function.
Gabapentin (GBP): Mattia et al. found that: gabapentin had no effect on interictal and ictal epileptiform discharges, and its main effect was to limit the spread of interictal epileptiform discharges, thereby reducing epileptic seizures; changes in background activity were manifested by an increase in the relative power of slow-wave theta activity, suggesting that impairment of cognitive function can be avoided when focal seizures are controlled using GBP.
Martin Salinsky et al [26] also reported that GBP caused a mild decrease in peak and intermediate frequencies of mainly posterior dominant rhythms, a significant decrease in peak frequencies of alpha rhythms, and an increase in the proportion of slow wave theta and delta band activity, and that neuropsychological tests also showed mild changes in cognitive function consistent with EEG changes, and that QPEEG monitoring of EEG background motion in epileptic patients revealed drug-related neurotoxicity.
Levetiracetam (LEV): as reported by zupiazzini et al [27], most studies showed that LEV did not slow down EEG background activity performance and even improved cognitive function in patients with partial-onset epilepsy.Veauthier [28] et al found that LEV did not lead to a decrease in the ratio of peak alpha wave frequency and alpha wave, instead the maximum alpha frequency had an upward trend, but not statistically significant; meanwhile, LEV does not increase the proportion of theta-wave δ-wave and the proportion of β-wave, but instead increases the proportion of β-wave and is statistically significant, and the EEG changes are consistent with the cognitive function not caused by LEV.
In summary, several new antiepileptic drugs commonly used in clinical practice have less effect on EEG background activity and do not lead to significant cognitive impairment when taken for a long time, therefore, these drugs should be widely used in the treatment of chronic AEDs.
3. Outlook
CEEG monitoring can continuously and objectively reflect the functional state of the brain, detect abnormal changes in brain function in a timely manner, and guide the correct treatment and management of neurological disorders during the reversible period. Therefore, CEEG monitoring should be widely used in neurology ICU for the diagnosis, treatment and prognosis assessment of epilepsy, cerebrovascular disease, traumatic brain injury, coma and other diseases. However, there is still a need to improve monitoring techniques to eliminate artifacts as much as possible, to unify the monitoring time and population for various diseases, to further explore the clinical value of each frequency in the monitoring results, and to train medical and nursing staff on a large scale.
Quantitative drug EEG can be used to select antiepileptic drugs, determine the mode, dose, and timing of drug administration and evaluate drug efficacy, adjust the type and dose of drugs in a timely manner, optimize drug treatment regimens, and predict and monitor the efficacy. However, QPEEG has not been carried out from the laboratory to clinical practice in neurology, mainly because the effects of most AEDs on QPEEG have not been detailed, most studies are not double-blind, controlled studies, there is great variability in the results, and there are studies with small sample sizes, and QPEEG parameters, even AEDs and drug administration methods, have not been clearly specified. Therefore, more data from large-scale, randomized studies are needed to further clarify the effects of drugs on EEG in various cranial regions and the direct quantitative relationship between changes in EEG background activity and changes in cognitive function.