Recommendations Regarding the Requirements and Applications for Long-term Recordings in Epilepsy
Address correspondence to Dr. F. Lopes da Silva, Emeritis Professor, Center of NeuroSciences, Swammerdam Institute for Life Sciences, University of Amsterdam, Kruislaan 320, 1098 SM Amsterdam, The Netherlands. E-mail: email@example.com
Summary: The purpose of this paper is to update the state of knowledge with respect to long-term monitoring (LTM) in epilepsy and to formulate recommendations regarding the application of LTM in clinical practice. LTM is an established technique in use both in a hospital setting and, increasingly, in an ambulatory and more recently in a community-based setting. There has been sufficient evidence to substantiate the claim that LTM is of crucial importance in documenting electroclinical correlations both in epilepsy and in paroxysmally occurring behavioral changes often mistaken for epilepsy. Internationally recognized neurophysiological equipment standards, data acquisition and data transfer protocols and widely accepted safety standards have made widespread access to LTM facilities in epilepsy possible. Recommendations on efficient and effective use of resources as well as regarding training and competencies for personnel involved in LTM in epilepsy have been formulated. The DMC Neurophysiology Subcommittee of the ILAE recommends use of hospital-based LTM in the documentation of seizures including its application for assessing seizure type and frequency, in the evaluation of status epilepticus, in noninvasive and invasive video/EEG investigations for epilepsy surgery and for the differential diagnosis between epilepsy and paroxysmally occurring nonepileptic conditions, in children and in adults. Ambulatory outpatient and community-based LTM may be used as a substitute for inpatient LTM in cases where the latter is not cost-effective or feasible or when activation procedures aimed at increasing seizure yield are not indicated. However, outpatient ambulatory monitoring may be less informative than is inpatient monitoring in some cases because: (1) reduction of medication to provoke seizures may not be safe as an outpatient; (2) faulty electrode contacts cannot quickly be noticed and repaired; (3) the patient may move out of video surveillance; and (4) duration of ambulatory monitoring can be limited by technical constraints.
The DMC Subcommittee on Neurophysiology recommends the use of LTM in epilepsy for the indications.
- 1Detection, characterization, and quantification on video/EEG of ictal events, including the appropriate activation procedures to elicit them in individual patients in whom the diagnosis of an underlying epilepsy has already been made, and when the type of seizure or syndrome is not clear.
- 2Documentation of the electroclinical manifestations of habitual seizures including noninvasive and invasive video/EEG LTM during presurgical evaluations.
- 3Differential diagnosis between epileptic and non-epileptic conditions, characterized by frequently and intermittently occurring behaviural changes including psychogenic nonepileptic events and sleep disorders, particularly those involving paroxysmal movement disorders.
- 4Documentation of diurnal or circadian variation in occurrence of epileptiform paroxysms, in conjunction with pharmacological interventions and/or of the effect of these interventions on diurnal or circadian behavioral changes.
- 5Documentation of specific patterns in the occurrence of epileptiform paroxysms during sleep and/or of disruption of sleep architecture in so-called “cognitive epilepsy” cases in the pediatric population.
- 6Monitoring in the intensive care unit (ICU) for the effectiveness of treatment of status epilepticus and for the identification of subclinical seizures and subclinical status epilepticus, conditions that have been shown to be more frequent than usually thought in the ICU.
The purpose of this position paper is to update the state of knowledge based on existing national and international guidelines on the application of long-term monitoring (LTM) in epilepsy, and to provide a selective review of the literature on emergent issues and controversies, particularly with respect to the use of provocative techniques to increase the yield of clinically relevant seizures. From this critical review a number of recommendations regarding the requirements and applications for LTM in epilepsy can be formulated. Guidelines for LTM in epilepsy have been formulated in the past (American Electroencephalographic Society, 1985; Engel et al., 1993; Brodie et al., 1997) The American Clinical Neurophysiology Society's Guideline 12 on LTM for epilepsy (originally published in 1994) is currently undergoing a major revision. Recommendations may be as regards activities and competencies of registered EEG technologists involved in such investigations (American Society of END Technologies, 2005). Advances in epileptic seizure documentation over time, particularly video/EEG seizure monitoring, have led to the present ILAE's classification of epileptic seizures (ILAE Commission, 1981,1989). More recently the epileptic seizures have been recodified in terms of a glossary of terms, largely derived from long-standing use of LTM (Blume et al., 2001).
Advances in technology have led to miniaturization of equipment that have made multichannel EEG recording portable enough to allow high-quality (ambulatory) recording and data transmission over long distances possible. Similarly, technological advances have allowed for highly compressed digital video acquisition and review, thus exploiting the full power of LTM in a clinical as well as an ambulatory setting. Ground rules in hospital equipment communications protocols have been constantly changing. However, with the advent of the Health Level 7 (HL7) standard some recommendations appear to have gained acceptance among manufacturers of equipment used for clinical neurophysiological purposes in general, and LTM in particular. The American Society for Testing and Materials (ASTM) has defined the E1467-94 Standard Specification for Transferring Digital Neurophysiological Data between Independent Computer Systems.1.
Standardization of data transfer protocols has been preceded by a parallel standardization in data acquisition protocols for biological signals. This has led to the emergence of two standards, which have met with varying acceptance. These are the E1467-92 ASTM standard (Jacobs et al., 1993), a very broad standard, which has not been widely used, and EDF, the European Data Format (Varri et al., 2001), more commonly used but causing some problems because it is not a complete standard. Most manufacturers of commercially available LTM equipment routinely provide output in the EDF format in addition to their proprietary data formats for EEG. Digital video and audio information is most commonly available in MPEG level 1 or 2 compression but the synchronization between EEG and video is usually proprietary and has not been standardized. Digital recording equipment for scalp-recorded LTM should allow for minimally 32 channel recording, including eye movement, EKG and selected polygraphy leads depending upon the clinical problem to be addressed. A certain overlap with polysomnography electrode derivations and sensors may be advantageous in distinguishing between epilepsy and sleep disorders. The EEG system's analog to digital converters should allow for a minimum of 12-bit precision. Data skew is to be minimized while recording the EEG signal. Montage reformatting should be made possible for on-line monitoring and for off-line reviewing purposes. Judicious digital filtering may be performed as scalp-recorded LTM signals are commonly fraught with movement and muscular artifact. Simultaneous digital video/EEG recording usually requires a synchronization process for the correlation of digital video frames to the digitally sampled EEG.
INPATIENT VERSUS OUTPATIENT LTM IN EPILEPSY
Specific recommendations on the organization and staffing of clinical facilities are beyond the scope of the present position paper. Nonetheless we should emphasize that an Epilepsy Monitoring Unit (EMU) should be adequately equipped and staffed such that the staff should be able to treat a situation of status epilepticus, and facilities should be available to quickly transfer to an intensive care unit a patient who is in a convulsive state and does not respond adequately to first line therapy. Guidelines as regards basic clinical neurophysiology and requirements may be found in (American Electroencephalographic Society, 1986). Inpatient LTM most commonly involves admission to an EMU, most often for extracranial (Thompson and Ebersole, 1999) and sometimes for intracranial LTM recordings. Practical recommendations on establishing and operating an EMU facility may be found in (Fitzsimons et al., 2000). Practical recommendations as regards ambulatory LTM may be found in (Waterhouse, 2003).
Outpatient ambulatory LTM in epilepsy is a relatively new development. Equipment and recording practices tend to rely on the long-standing experience with community-based monitoring in sleep disorders and actigraphy (recording of a measure of gross motor activity) studies. An early evidence-based analysis exploring the benefits and limitations of outpatient EEG appeared in (Gilliam et al., 1999). There is no recently published technology assessment report for epilepsy available on the combined use of outpatient EEG and digital video. However there is some evidence from one group of investigators that temporal lobe epilepsy may lend itself for a out-patient LTM service (Schomer et al., 1999).
To be cost-effective, LTM facilities should be available and tailored to the individual needs of the patient. In scalp LTM, electrode derivations should allow for combination of both International 10–20 system positions and selected closely spaced electrodes according to the so-called 10% system combinatorial electrode nomenclature proposed by the American EEG society (American Electroencephalographic Society, 1991, 1994a, 1994b, 1994c), particularly those in the inferior temporal regions. Nasopharyngeal electrodes tend to cause discomfort over time to the patient undergoing LTM and should be avoided. The use of sphenoidal electrodes in presurgical evaluation cases undergoing LTM in which clinical evidence and neuroimaging suggest possible mesial temporal lobe epilepsy is still advisable (Fernandez Torre et al., 1999; Kissani et al., 2001; Sperling and Guina, 2003) although this issue is a matter of contention as inferiorly placed 10% system electrodes may yield highly visible interictal and ictal onset patterns rivalling those obtained from sphenoidal electrodes (Kanner et al., 2002; Blume, 2003).
The EMU facility should comply with the local standards of safety with respect to use of equipment connected to the electrical mains and making patient contact. Especially for EMU units that are equipped to record from intracranial electrodes these standards are more stringent, usually requiring compliance with patient safety standards where electrical mains equipment makes direct contact with body fluids (McAllister and Jeswiet, 2003).
Although life support equipment is not routinely used in the EMU, occasional life threatening emergencies such as a (convulsive) status epilepticus may occur (Sanders et al., 1996; Rose et al., 2003) and should be dealt with appropriately.
DURATION OF MONITORING
The definition of “long-term" in LTM depends upon the purpose for which LTM should be used. There is no generic, a priori definable upper time limit for LTM duration in epilepsy. There are however, certain operational limits primarily determined by whether the patient is an adult or a child, the patient's condition, the case load and logistics of an EMU, and the willingness of an institution to cover costs incurred above and beyond a fee for LTM services agreed with a third-party payer (Ghougassian et al., 2004).
AED withdrawal increases the frequency of seizures, and generally shortens the total LTM recording time (Cascino, 2002). In several studies the frequency of seizures increased associated with the process of drug tapering or with the period of being effectively free of medication (AED serum level confirmed), although not all types of drugs are associated with an early increase of seizures frequency. The shortest reported average time for successful, clinically relevant LTM was 4.8 days in a group of patients with mesial temporal lobe epilepsy. Other groups reached average times ranging from 5.5 to 7.6 days (Engel et al., 1993; Fernandez Torre et al., 1999; Fitzsimons et al., 2000; Cascino, 2002; Claassen et al., 2004). The different studies were characterized by heterogeneity in patient population, etiology and method of AED withdrawal.
Blume (1994) has made an extensive statistical study that allows estimating the number of seizures that should be recorded during LTM in an epilepsy monitoring unit to determine with a given accuracy the lateralization of seizure focus. Based on 605 seizures from 57 consecutive patients with nonlesional temporolimbic epilepsy he found that the observation of five concordant seizures implies a 95% chance that the seizures arise from the same side, but if one discordant seizure was recorded, then to reach the 95% confidence level would require a total of 11 concordant seizures. In this context we should add that the fact that seizures may tend to occur in clusters merits further consideration. In a study of the cluster effect on seizure lateralization during LTM in patients with bilateral foci, Haut et al. (1997) reported that seizures that occur at inter-seizure intervals of less than 8 h are more likely to occur from the same side as the previous seizures, than seizures that occur at longer intervals. Therefore these authors proposed that clustered seizures (Haut et al., 2002) should not be given the same weight as those that occur at long (>8 h) intervals, with respect to a decision about lateralization, and consequently more than five seizures may sometimes be necessary for an adequate assessment of seizure lateralization.
A utility evaluation study on the effects of LTM recording on decisions affecting health care delivery to patients suffering from seizures indicated that LTM performed in 131 consecutive patients (30% presurgical evaluation cases) altered the diagnosis in the majority of cases recorded and had major impact on patient management changes in almost three quarters of the total population studied (Ghougassian et al., 2004).
SPECIFIC CONSIDERATIONS FOR THE ADULT POPULATION
The primary clinical application for LTM remains documentation of seizures for diagnostic purposes. Documentation is particularly useful and often indicated or even mandatory in the definition of the type of seizure in order to insure appropriate treatment, in the differential diagnosis of epilepsy versus other paroxysmally occurring conditions including psychogenic nonepileptic events, in the evaluation and treatment of status epilepticus or unrecognized seizures in the ICU, and in the noninvasive or invasive recording of seizure events during the preoperative evaluation for a variety of epilepsy surgery procedures (Fernandez Torre et al., 1999; Blume et al., 2001). It should be noted that some types of seizures are not always visible at the scalp so that multiple events must often be recorded to differentiate between seizures (specially some types of frontal seizures) and psychogenic nonepileptic events.
The operational definition of the lower time limit for clinical LTM is the time at which the diagnostic problem has been solved, namely when sufficiently well-documented electroclinical events have been recorded in order to answer the clinical question. Recording of a single episode may be insufficient, if the question pertains to consistency of origin of epileptiform discharges, or if a patient is suspected of having more than one type of clinical event (see above for the question of lateralization). No required number of events can be specified, since it depends on the clinical question and the body of corollary clinical evidence, for example, whether mesial temporal sclerosis is seen on the MRI.
Within these broad margins one should endeavor to efficiently use this costly resource by maximizing the chance of a high yield of electroclinical events. Local and national recommendations and indications for LTM in epilepsy vary considerably as do degrees of remuneration for clinically based LTM services. Time limits are particularly of importance in presurgical investigations (Fitzsimons et al., 2000; Cascino, 2002; Flink et al., 2002; Benbadis et al., 2004; Ghougassian et al., 2004). In individual patients who keep reliable seizure occurrence calendars these may be used in advance to plan LTM to coincide with a higher-than-average chance of seizure occurrence. Known factors that could provoke seizure occurrence in the individual patient (e.g., in reflex epilepsies) may be advantageously employed during LTM. Sleep deprivation and other activation provocations may take place. Regarding sleep deprivation, Malow et al. (2002) carried out a study of 84 patients with medically refractory partial epilepsy who underwent LTM and were assigned to a group that was sleep deprived every other night or to a group that slept normally; in this study there was no significant difference between the two groups regarding seizure frequency. Nonetheless some patients showed a considerable increase in seizure frequency after sleep deprivation. The lateralizing value of interictal epileptiform discharges (IEDs) recorded during overnight sleep-EEG studies in temporal lobe epilepsy was also put in evidence, particularly when combined with other investigations, IEDs recorded on overnight studies can add prognostic data to the epilepsy surgery evaluation not provided by daytime EEGs (Malow et al., 1999). This question needs further analysis in well-defined patient groups. Pharmacological profiles using intermittent AED sampling through indwelling peripheral lines may be advantageous and judicious AED withdrawal may be particularly useful in the presurgical cases, although at a certain risk for the patient in terms of a higher chance for occurrence of complications (Marciani and Gotman 1985, 1986; Rose et al., 2003).
SPECIFIC CONSIDERATIONS FOR THE PEDIATRIC POPULATION
Pediatric LTM in epilepsy has been effectively used in the diagnosis of seizure disorders as early in life as during the neonatal period (Mizrahi, 1999). Cranial circumference varies with age and does not allow the use of the 10–20 system from birth. In the neonatal period the system has to be modified with one or two temporal electrodes at birth, increasing progressively the number of electrodes to reach the 10–20 system around the age of 3 yr. In very young children collodion must not be used as the babies' skin is very fragile: special paste which can be taken off with water is available in neonatal ICU. In older children presence of parents is very useful and should be systematic: they know how to recognize the onset of their child's seizures, and they can help in keeping the child in front of the camera. Seizures are much more frequent in children compared to adult patients, allowing shorter recordings. In many indications except for surgery, one to two days are sufficient. In childhood epilepsy, not only seizures have to be recognized and analyzed but also syndromes, and for that purpose different types of seizures may have to be recorded; moreover specific interictal EEG patterns (wakefulness and sleep) have to be looked for as they belong to the syndromic definition. Ambulatory EEG monitoring is only recommended in first approach of differential diagnosis or in children with continuous spike and wave during sleep, without any clinical seizure.
AUTOMATIC SEIZURE DETECTION
Quantitative analysis of the EEG is particularly useful during LTM in epilepsy. Automatically detected seizure events have been made increasingly reliable over time and a variety of algorithms are widely used for this purpose in intracranially recorded LTM. There has been considerable effort invested in algorithm improvements minimizing the chance of false positives and false negatives in seizure detection during scalp LTM recordings although confirmation of the events automatically detected by a qualified human operator (be that an EEGer or Registered EEG Technologist) is recommended (Gotman, 1999; Qu and Gotman, 1993; Khan and Gotman, 2003; Saab and Gotman, 2005). The primary benefit of the use of automatic seizure event detection in LTM in epilepsy is reducing the tedious, time-consuming, and expensive fast visual review time by the qualified human operator.
Seizure events harvested should ideally be the habitual ones in each case and if doubt arises one should verify this by reviewing the seizure semiology together with the patient or with the next-of-kin, close friends, teachers or colleagues of the patient. Pharmacological challenge with substances known to cause seizures is not recommended, given the considerable chance that their use might lead to seizure episodes other than the habitual ones. This means that agents causing seizures should not be used. Hypnosis and other behavioral approaches including suggestion have been reported to be effective in eliciting events in patients suspected of having a psychogenic nonepileptic attack disorder (Guberman, 1982; Bazil et al., 1994; Kuyk et al., 1997; Barry et al., 2000; Goldstein et al., 2000; Ghougassian et al., 2004), but some carry the disadvantage of deception.
RECOMMENDATIONS BY THE DMC SUBCOMMITTEE ON NEUROPHYSIOLOGY
Although there are no published data indicating changes in global patterns of LTM use in epilepsy, a number of factors have contributed to a higher level of utilization of this resource. These factors include miniaturization, standardization and unit cost reduction of digital EEG and digital video recording equipment. National and international recommendations have been published and revised to keep pace with technical developments over time. Thus certain patterns of efficient and effective use of this resource have appeared in reviews of the literature indicating specific and highly rewarding applications for LTM in epilepsy, both in children and in adults.
Other accredited communications and messaging standard, mostly North American in origin, forming an interface between clinical neurophysiological data and neuroimaging systems include the Accredited Standards Committee (ASC) X12N, Institute of Electrical and Electronic Engineers, Inc. (IEEE) P1157 Medical Data Interchange Standard (MEDIX), Digital Imaging and Communications (DICOM) developed by the American College of Radiology and the standards defined by ASTM Subcommittees E1238, E31.11, E1394, E1467 Electrical Manufacturers' Association (ACR-NEMA)
Acknowledgements: The authors are thankful for the discussions with the other members of the Subcommittee (Bernard Renault, Brian Litt, Gorgio Battaglia, Klaus Lehnertz, Nobukazu Nakasoto, Sylvia Kochen) and of the Commission: “Diagnostic Methods" (John S. Duncan, chair) and their suggestions as well as those of Solomon L. Moshé.