- Email: [email protected]
Detecting interictal discharges in first seizure patients: ambulatory EEG or EEG after sleep deprivation?
Accepted Manuscript Title: Detecting interictal discharges in first seizure patients Ambulatory EEG or EEG after sleep deprivation? Authors: I. Geut, S. Weenink, I. Knottnerus, M.J.A.M. van Putten PII: DOI: Reference:
S1059-1311(17)30489-2 http://dx.doi.org/doi:10.1016/j.seizure.2017.07.019 YSEIZ 2998
To appear in:
Seizure
Received date: Revised date: Accepted date:
10-7-2017 29-7-2017 31-7-2017
Please cite this article as: Geut I, Weenink S, Knottnerus I, van Putten M.J.A.M.Detecting interictal discharges in first seizure patients Ambulatory EEG or EEG after sleep deprivation?.SEIZURE: European Journal of Epilepsy http://dx.doi.org/10.1016/j.seizure.2017.07.019 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Detecting interictal discharges in first seizure patients Ambulatory EEG or EEG after sleep deprivation?
I. Geut1, S. Weenink1, I. Knottnerus1 , M.J.A.M. van Putten1,2
1. Dept of neurology and clinical neurophysiology, Medisch Spectrum Twente, Enschede, the Netherlands 2. Clinical neurophysiology (CNPH), University of Twente, Enschede, the Netherlands Corresponding author: MJAM van Putten, [email protected]
Highlights:
Diagnostic accuracies of ambulatory EEG (aEEG) and sleep deprived EEG (sdEEG) are similar Most interictal discharges are present in sleep stage II Both aEEG and sdEEG can be considered in patients with a first seizure and a normal routine EEG
Abstract Purpose Uncertainty about recurrence after a first unprovoked seizure is a significant psychological burden for patients, and motivates the need for diagnostic tools with high sensitivity and specificity to assess recurrence risk. As the sensitivity of a routine EEG after a first unprovoked seizure is limited, patients often require further diagnostics. Here, we study if ambulatory EEG (aEEG) has similar diagnostic accuracy as sleep deprived EEG (sdEEG). Methods In this retrospective cohort, we included patients with an unprovoked first seizure and a normal routine EEG who subsequently underwent an sdEEG or aEEG. All EEGs were reviewed for the presence of interictal
epileptiform discharges (IEDs). We calculated specificity and sensitivity of sdEEG and aEEG, using the clinical diagnosis of epilepsy as golden standard. All patients had a follow-up of one year. Results We included 104 patients. Sensitivities for sdEEG and aEEG were 45% (specificity 91%) and 63% (specificity 95%), respectively. Independent risk factor for recurrent seizure were IEDs on the additional EEG, with a relative risk of 1.5 of having a recurrent seizure within a year. Conclusion Diagnostic accuracies of sdEEG and aEEG are similar and depending on patients’ and clinicians’ preference both can be considered in patients with a first seizure and a normal routine EEG to determine recurrence risk. Keywords: ambulatory EEG; sleep deprived EEG; diagnostics; interictal discharges
1.Introduction A first seizure has a significant psychological impact on patients1 where the clinician's role includes finding a potential cause and estimating the recurrence risk. Main predictors for recurrence are symptomatic etiology and the presence of interictal epileptiform discharges (IEDs) on the EEG. While highly specific, the sensitivity of a routine EEG after a first unprovoked seizure is limited, ranging from 25 to 50%2. Longer registrations or recordings during sleep increases the yield to 50-75%3,4. No consensus exists about the next diagnostic step if a routine (20-30 min) EEG recording after a first seizure does not contain interictal epileptiform discharges (IEDs). In the Netherlands, approximately 48% of the clinicians order a sleep deprivation EEG (sdEEG), 45% a second routine EEG and 3% an ambulatory EEG (aEEG)5. Although aEEG is recommended by the ILAE for specific indications like classification of epilepsy syndromes and for differentiation between seizures and pseudo-seizures, there is no literature about the diagnostic yield of aEEG after a first unprovoked seizure with a normal routine EEG3,6. We study the detection rate of IEDs in aEEGs in comparison with sdEEGs in patients with a first unprovoked seizure and a normal routine recording.
2. Methods 2.1. Patient inclusion
We searched our EEG database for patients with unprovoked focal or generalized seizures who were admitted to our Clinical Neurophysiology department between January 2011 and November 2015. Unprovoked seizures were defined as convulsive episodes occurring in the absence of precipitating factors. This included seizures of unknown etiology as well as seizures in relation to a demonstrated pre-existing brain lesion (remote symptomatic seizure)7. We excluded patients younger than 6 years, patients with known epilepsy and patients with provoked seizures. We subsequently selected patients in whom the routine EEG (including hyperventilation and photic simulation) was normal or did not show convincing IEDs, and either a sdEEG or a aEEG was requested. Finally, we matched both groups for age and gender. aEEG had a duration of 16-24 hours, including sleep. sdEEG had a
duration of 1.5 to 3 hours, including sleep, and was recorded after complete sleep deprivation during the previous night.
2.2.EEG recording
EEGs were recorded with 21 electrodes positioned according to the international 10-20 system using a Brainlab EEG system (OSG, Belgium) or Mobita mobile amplifiers (TMS-i international, Oldenzaal, the Netherlands), sampled at 512 Hz. 2.3. EEG assessment and clinical evaluation
All EEGs were re-reviewed for epileptiform discharges (spikes, polyspikes, sharp waves, sharp-slow waves or spike-slow waves) by either a resident in neurology (IG) or experienced lab technician (SW), both supervised by a clinical neurophysiologist (MvP or IK). The patients’ clinical record was evaluated for age, sex, first seizure, start of anti-epileptic drugs, MRI or CT results and whether or not diagnosis of epilepsy was made with a follow up of one year. The diagnosis of epilepsy was based on the new ILAE criteria published in 20148. Sensitivity and specificity were determined using diagnosis of epilepsy after one year of follow up as golden standard. Results are presented as sensitivity, specificity and 95% confidence intervals (CI). Statistical significance was evaluated using Chi-squaredtests, with significance threshold of p<0.05.
3. Results We included 104 patients. The majority of patients presented with either a primary or secondary generalized seizure, 46% in the aEEG group, 62% in the sdEEG group. Eleven patients showed pathology on CT or MRI. Patient characteristics are summarized in Table 1.
The different types of IEDs detected are presented in Table 2.
In the sdEEG group 16 patients (31%) showed IEDs, in the aEEG group 21 patients (40%). In both groups, one (aEEG) or two (sdEEG) patients showed IEDs, but were not diagnosed with epilepsy. Diagnostic findings are summarized in Tables 3A and 3B. This results in a sensitivity of sdEEG of 45% (CI: 27-64%), with a specificity of 91% (CI: 70-99%) and a positive (PPV) and negative predictive value (NPV) of 88% and 53%, respectively. For aEEG, the sensitivity was 63% (CI: 44-79%) with specificity 95% (CI: 75-100%), with PPV=95% and NPV=61%. All differences were not statistically significant.
In both groups, epileptiform discharges were most often present during sleep stage II, with a mean time to occurrence of 14 minutes in the aEEG and 20 minutes in the sdEEG, respectively (p= 0.98). Of the sixteen patients with non-convincing abnormalities on routine EEG, 12 showed IEDs in the follow up recording (75%). Eleven of these patients were diagnosed with epilepsy after one year of follow up. Fifty one percent of patients had a recurrent seizure within one year, 50% in the aEEG group and 52% in the sdEEG group. Independent risk factor for recurrent seizure were IEDs on the additional EEG, with a relative risk of 1.5 of having a recurrent seizure within a year.
4. Discussion To our knowledge, this is the first study to compare sdEEG with aEEG in patients with a first unprovoked seizure and a normal routine EEG. Our data show that the diagnostic accuracy of sdEEG and aEEG are similar. The sensitivity for detection of IEDs in a sdEEG was 45% (specificity 91%), similar to what is reported by others9,10, and the sensitivity for detection of IEDs in aEEG was 63% (specificity 95%). Further, in about 75% of patients with an initial EEG showing ‘non-convincing abnormalities’, sdEEG or aEEG showed interictal epileptiform discharges. Only a few studies contrasted ambulatory EEG with sdEEG, but all in patients with an existing diagnosis of epilepsy. In a cohort of 42 patients, both sdEEG and aEEG improved detection of epileptiform discharges by a similar amount (24% versus 33%)11. Although the total registration duration of aEEG is longer (18-20 h) than sdEEG (2 h), in most patients the epileptiform discharges were observed during sleep stage II, without a difference in mean time to first occurrence. While SD-induced sleep seems to be more likely to evoke IEDs than natural sleep12, this (additional) effect may be modest. We argue therefore that it is sleep rather than sleep deprivation that increases the likelihood of detecting interictal discharges. Potential explanations for the effect of sleep on the occurrence of IEDs are discussed in a recent review12. While sdEEG may induce seizures, this did not occur in our patients. How large this presumed increase is, is still a matter of debate10,12, but one could speculate that aEEG is perhaps safer than a sdEEG. In our cohort, recurrence rate was 53%, which seems relatively large as in untreated patients, 4050% can expect a recurrence within 2 years of the initial seizure13,14. However, we included patients with a first unprovoked seizure who were also referred for additional diagnostics, and in many EEGs showed IEDs. This apparently resulted in a larger fraction of patients with epilepsy. A limitation of our study is that it is a single center, retrospective study, with a restricted follow-up period of one year. However, recurrence risk after one unprovoked seizure is largest within the first year, and did not differ between the two groups. Another limitation of aEEG is the lack of video recording, especially in patients with paroxysmal events. However, we included patients with a first seizure, where detection of IEDs is the primary goal, in contrast to studies where aEEG is used for the differential diagnosis of paroxysmal events. At present, most clinicians use aEEG to differentiate epileptic and non-epileptic events or to quantify IEDs in different stages of pharmacological interventions15–17. In the Netherlands, aEEG is ordered by only 3% of neurologists in patients with a seizure and normal initial EEG5. However, in our hospital aEEG has become an available alternative for sdEEG since about 2012, and several neurologists have since then used this for follow-up EEG. Our data show that aEEG has similar efficacy as sdEEG for detection of IEDs in first unprovoked seizure patients with normal routine EEGs. Ambulatory EEG was well tolerated. As no significant macro-economic disadvantages of aEEG over sdEEG exist18, aEEG may be considered instead of sdEEG in the diagnostic work-up after a first seizure with normal routine EEG, according to the preference of the patient and clinician.
References 1.
Velissaris, S. L. et al. The psychological impact of a newly diagnosed seizure: losing and restoring perceived control. Epilepsy Behav. 10, 223–33 (2007).
2.
Krumholz, A. et al. Practice Parameter: Evaluating an apparent unprovoked first seizure in adults (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy
Society. Neurology 69, 1996–2007 (2007). 3.
Faulkner, H. J., Arima, H. & Mohamed, A. Latency to first interictal epileptiform discharge in epilepsy with outpatient ambulatory EEG. Clin. Neurophysiol. 23–26 (2012). doi:10.1016/j.clinph.2012.01.023
4.
Askamp, J. & van Putten, M. 24h in-home EEG after a first seizure in adults. Neurophysiol. Clin. Neurophysiol. 43, (2013).
5.
Askamp, J. & van Putten, M. J. a M. Diagnostic decision-making after a first and recurrent seizure in adults. Seizure 22, 507–11 (2013).
6.
Velis, D., Plouin, P., Gotman, J., da Silva, F. L. & ILAE DMC Subcommittee on Neurophysiology. Recommendations Regarding the Requirements and Applications for Long-term Recordings in Epilepsy. Epilepsia 48, 379–384 (2007).
7.
Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League Against Epilepsy. Epilepsia 34, 592–6 (1993).
8.
Fisher, R. S. et al. ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia 55, 475–482 (2014).
9.
Leone, M. A., Vallalta, R., Solari, A., Beghi, E. & FIRST Group. Treatment of first tonicclonic seizure does not affect mortality: long-term follow-up of a randomised clinical trial. J. Neurol. Neurosurg. Psychiatry 82, 924–927 (2011).
10.
Giorgi, F. S. et al. Usefulness of a simple sleep-deprived EEG protocol for epilepsy diagnosis in de novo subjects. Clin. Neurophysiol. 124, 2101–2107 (2013).
11.
Liporace, J., Tatum, W., Morris, G. L. & French, J. Clinical utility of sleep-deprived versus computer-assisted ambulatory 16-channel EEG in epilepsy patients: a multicenter study. Epilepsy Res. 32, 357–62 (1998).
12.
Giorgi, F. S. et al. What is the role for EEG after sleep deprivation in the diagnosis of epilepsy? Issues, controversies, and future directions. Neurosci. Biobehav. Rev. 47, 533–548 (2014).
13.
Berg, A. T. Risk of recurrence after a first unprovoked seizure. Epilepsia 49, 13–18 (2008).
14.
Randomized clinical trial on the efficacy of antiepileptic drugs in reducing the risk of relapse after a first unprovoked tonic-clonic seizure. First Seizure Trial Group (FIR.S.T. Group). Neurology 43, 478–83 (1993).
15.
Michel, V., Mazzola, L., Lemesle, M. & Vercueil, L. Long-term EEG in adults: Sleepdeprived EEG (SDE), ambulatory EEG (Amb-EEG) and long-term video-EEG recording (LTVER). Neurophysiol. Clin. Neurophysiol. 45, 47–64 (2015).
16.
Koepp, M. J., Farrell, F., Collins, J. & Smith, S. The prognostic value of long-term ambulatory electroencephalography in antiepileptic drug reduction in adults with learning disability and epilepsy in long-term remission. Epilepsy Behav. 13, 474–477 (2008).
17.
Faulkner, H. J., Arima, H. & Mohamed, A. The utility of prolonged outpatient
ambulatory EEG. Seizure 21, 491–495 (2012). 18.
Askamp, J. & van Putten, M. J. A. M. Mobile EEG in epilepsy. Int. J. Psychophysiol. 91, 30–5 (2014).
Table 1. Clinical characteristics sdEEG (n=52) Age (years, median) Male sex, n (%) Type seizure Primary/secondary generalized Focal Nocturnal Abnormal MRI
aEEG (n=52)
46 36 (69%)
48 31 (60%)
32 (62%) 11 (21%) 8 (15%) 6 (12%)
24 (46%) 21 (40%) 5 (10%) 5 (10%)
Table 2. Overview of detected interictal discharges. Epileptiform discharges sdEEG Number percentage of patients Sharp-slow wave 7 43.8% Sharp wave 1 6.2% Generalized spike-wave discharges 2 12.5% Isolated spike wave discharges 6 37.5% Isolated spike 0 0%
Number of patients 8 4 1 8 0
aEEG percentage
38.1% 19% 4.8% 38.1% 0%
Table 3A. Diagnostic findings in patients (n=52) with a sdEEG. Abnormal implies presence of interictal epileptiform discharges. Epilepsy (n=31)
No epilepsy (21)
Abnormal sdEEG
14
2
Normal sdEEG
17
19
Table 3B. Diagnostic findings in patients (n=52) with an aEEG. Abnormal implies presence of interictal epileptiform discharges. Epilepsy (n=32)
No epilepsy (20)
Abnormal aEEG
20
1
Normal aEEG
12
19
S1059-1311(17)30489-2 http://dx.doi.org/doi:10.1016/j.seizure.2017.07.019 YSEIZ 2998
To appear in:
Seizure
Received date: Revised date: Accepted date:
10-7-2017 29-7-2017 31-7-2017
Please cite this article as: Geut I, Weenink S, Knottnerus I, van Putten M.J.A.M.Detecting interictal discharges in first seizure patients Ambulatory EEG or EEG after sleep deprivation?.SEIZURE: European Journal of Epilepsy http://dx.doi.org/10.1016/j.seizure.2017.07.019 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Detecting interictal discharges in first seizure patients Ambulatory EEG or EEG after sleep deprivation?
I. Geut1, S. Weenink1, I. Knottnerus1 , M.J.A.M. van Putten1,2
1. Dept of neurology and clinical neurophysiology, Medisch Spectrum Twente, Enschede, the Netherlands 2. Clinical neurophysiology (CNPH), University of Twente, Enschede, the Netherlands Corresponding author: MJAM van Putten, [email protected]
Highlights:
Diagnostic accuracies of ambulatory EEG (aEEG) and sleep deprived EEG (sdEEG) are similar Most interictal discharges are present in sleep stage II Both aEEG and sdEEG can be considered in patients with a first seizure and a normal routine EEG
Abstract Purpose Uncertainty about recurrence after a first unprovoked seizure is a significant psychological burden for patients, and motivates the need for diagnostic tools with high sensitivity and specificity to assess recurrence risk. As the sensitivity of a routine EEG after a first unprovoked seizure is limited, patients often require further diagnostics. Here, we study if ambulatory EEG (aEEG) has similar diagnostic accuracy as sleep deprived EEG (sdEEG). Methods In this retrospective cohort, we included patients with an unprovoked first seizure and a normal routine EEG who subsequently underwent an sdEEG or aEEG. All EEGs were reviewed for the presence of interictal
epileptiform discharges (IEDs). We calculated specificity and sensitivity of sdEEG and aEEG, using the clinical diagnosis of epilepsy as golden standard. All patients had a follow-up of one year. Results We included 104 patients. Sensitivities for sdEEG and aEEG were 45% (specificity 91%) and 63% (specificity 95%), respectively. Independent risk factor for recurrent seizure were IEDs on the additional EEG, with a relative risk of 1.5 of having a recurrent seizure within a year. Conclusion Diagnostic accuracies of sdEEG and aEEG are similar and depending on patients’ and clinicians’ preference both can be considered in patients with a first seizure and a normal routine EEG to determine recurrence risk. Keywords: ambulatory EEG; sleep deprived EEG; diagnostics; interictal discharges
1.Introduction A first seizure has a significant psychological impact on patients1 where the clinician's role includes finding a potential cause and estimating the recurrence risk. Main predictors for recurrence are symptomatic etiology and the presence of interictal epileptiform discharges (IEDs) on the EEG. While highly specific, the sensitivity of a routine EEG after a first unprovoked seizure is limited, ranging from 25 to 50%2. Longer registrations or recordings during sleep increases the yield to 50-75%3,4. No consensus exists about the next diagnostic step if a routine (20-30 min) EEG recording after a first seizure does not contain interictal epileptiform discharges (IEDs). In the Netherlands, approximately 48% of the clinicians order a sleep deprivation EEG (sdEEG), 45% a second routine EEG and 3% an ambulatory EEG (aEEG)5. Although aEEG is recommended by the ILAE for specific indications like classification of epilepsy syndromes and for differentiation between seizures and pseudo-seizures, there is no literature about the diagnostic yield of aEEG after a first unprovoked seizure with a normal routine EEG3,6. We study the detection rate of IEDs in aEEGs in comparison with sdEEGs in patients with a first unprovoked seizure and a normal routine recording.
2. Methods 2.1. Patient inclusion
We searched our EEG database for patients with unprovoked focal or generalized seizures who were admitted to our Clinical Neurophysiology department between January 2011 and November 2015. Unprovoked seizures were defined as convulsive episodes occurring in the absence of precipitating factors. This included seizures of unknown etiology as well as seizures in relation to a demonstrated pre-existing brain lesion (remote symptomatic seizure)7. We excluded patients younger than 6 years, patients with known epilepsy and patients with provoked seizures. We subsequently selected patients in whom the routine EEG (including hyperventilation and photic simulation) was normal or did not show convincing IEDs, and either a sdEEG or a aEEG was requested. Finally, we matched both groups for age and gender. aEEG had a duration of 16-24 hours, including sleep. sdEEG had a
duration of 1.5 to 3 hours, including sleep, and was recorded after complete sleep deprivation during the previous night.
2.2.EEG recording
EEGs were recorded with 21 electrodes positioned according to the international 10-20 system using a Brainlab EEG system (OSG, Belgium) or Mobita mobile amplifiers (TMS-i international, Oldenzaal, the Netherlands), sampled at 512 Hz. 2.3. EEG assessment and clinical evaluation
All EEGs were re-reviewed for epileptiform discharges (spikes, polyspikes, sharp waves, sharp-slow waves or spike-slow waves) by either a resident in neurology (IG) or experienced lab technician (SW), both supervised by a clinical neurophysiologist (MvP or IK). The patients’ clinical record was evaluated for age, sex, first seizure, start of anti-epileptic drugs, MRI or CT results and whether or not diagnosis of epilepsy was made with a follow up of one year. The diagnosis of epilepsy was based on the new ILAE criteria published in 20148. Sensitivity and specificity were determined using diagnosis of epilepsy after one year of follow up as golden standard. Results are presented as sensitivity, specificity and 95% confidence intervals (CI). Statistical significance was evaluated using Chi-squaredtests, with significance threshold of p<0.05.
3. Results We included 104 patients. The majority of patients presented with either a primary or secondary generalized seizure, 46% in the aEEG group, 62% in the sdEEG group. Eleven patients showed pathology on CT or MRI. Patient characteristics are summarized in Table 1.
The different types of IEDs detected are presented in Table 2.
In the sdEEG group 16 patients (31%) showed IEDs, in the aEEG group 21 patients (40%). In both groups, one (aEEG) or two (sdEEG) patients showed IEDs, but were not diagnosed with epilepsy. Diagnostic findings are summarized in Tables 3A and 3B. This results in a sensitivity of sdEEG of 45% (CI: 27-64%), with a specificity of 91% (CI: 70-99%) and a positive (PPV) and negative predictive value (NPV) of 88% and 53%, respectively. For aEEG, the sensitivity was 63% (CI: 44-79%) with specificity 95% (CI: 75-100%), with PPV=95% and NPV=61%. All differences were not statistically significant.
In both groups, epileptiform discharges were most often present during sleep stage II, with a mean time to occurrence of 14 minutes in the aEEG and 20 minutes in the sdEEG, respectively (p= 0.98). Of the sixteen patients with non-convincing abnormalities on routine EEG, 12 showed IEDs in the follow up recording (75%). Eleven of these patients were diagnosed with epilepsy after one year of follow up. Fifty one percent of patients had a recurrent seizure within one year, 50% in the aEEG group and 52% in the sdEEG group. Independent risk factor for recurrent seizure were IEDs on the additional EEG, with a relative risk of 1.5 of having a recurrent seizure within a year.
4. Discussion To our knowledge, this is the first study to compare sdEEG with aEEG in patients with a first unprovoked seizure and a normal routine EEG. Our data show that the diagnostic accuracy of sdEEG and aEEG are similar. The sensitivity for detection of IEDs in a sdEEG was 45% (specificity 91%), similar to what is reported by others9,10, and the sensitivity for detection of IEDs in aEEG was 63% (specificity 95%). Further, in about 75% of patients with an initial EEG showing ‘non-convincing abnormalities’, sdEEG or aEEG showed interictal epileptiform discharges. Only a few studies contrasted ambulatory EEG with sdEEG, but all in patients with an existing diagnosis of epilepsy. In a cohort of 42 patients, both sdEEG and aEEG improved detection of epileptiform discharges by a similar amount (24% versus 33%)11. Although the total registration duration of aEEG is longer (18-20 h) than sdEEG (2 h), in most patients the epileptiform discharges were observed during sleep stage II, without a difference in mean time to first occurrence. While SD-induced sleep seems to be more likely to evoke IEDs than natural sleep12, this (additional) effect may be modest. We argue therefore that it is sleep rather than sleep deprivation that increases the likelihood of detecting interictal discharges. Potential explanations for the effect of sleep on the occurrence of IEDs are discussed in a recent review12. While sdEEG may induce seizures, this did not occur in our patients. How large this presumed increase is, is still a matter of debate10,12, but one could speculate that aEEG is perhaps safer than a sdEEG. In our cohort, recurrence rate was 53%, which seems relatively large as in untreated patients, 4050% can expect a recurrence within 2 years of the initial seizure13,14. However, we included patients with a first unprovoked seizure who were also referred for additional diagnostics, and in many EEGs showed IEDs. This apparently resulted in a larger fraction of patients with epilepsy. A limitation of our study is that it is a single center, retrospective study, with a restricted follow-up period of one year. However, recurrence risk after one unprovoked seizure is largest within the first year, and did not differ between the two groups. Another limitation of aEEG is the lack of video recording, especially in patients with paroxysmal events. However, we included patients with a first seizure, where detection of IEDs is the primary goal, in contrast to studies where aEEG is used for the differential diagnosis of paroxysmal events. At present, most clinicians use aEEG to differentiate epileptic and non-epileptic events or to quantify IEDs in different stages of pharmacological interventions15–17. In the Netherlands, aEEG is ordered by only 3% of neurologists in patients with a seizure and normal initial EEG5. However, in our hospital aEEG has become an available alternative for sdEEG since about 2012, and several neurologists have since then used this for follow-up EEG. Our data show that aEEG has similar efficacy as sdEEG for detection of IEDs in first unprovoked seizure patients with normal routine EEGs. Ambulatory EEG was well tolerated. As no significant macro-economic disadvantages of aEEG over sdEEG exist18, aEEG may be considered instead of sdEEG in the diagnostic work-up after a first seizure with normal routine EEG, according to the preference of the patient and clinician.
References 1.
Velissaris, S. L. et al. The psychological impact of a newly diagnosed seizure: losing and restoring perceived control. Epilepsy Behav. 10, 223–33 (2007).
2.
Krumholz, A. et al. Practice Parameter: Evaluating an apparent unprovoked first seizure in adults (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology and the American Epilepsy
Society. Neurology 69, 1996–2007 (2007). 3.
Faulkner, H. J., Arima, H. & Mohamed, A. Latency to first interictal epileptiform discharge in epilepsy with outpatient ambulatory EEG. Clin. Neurophysiol. 23–26 (2012). doi:10.1016/j.clinph.2012.01.023
4.
Askamp, J. & van Putten, M. 24h in-home EEG after a first seizure in adults. Neurophysiol. Clin. Neurophysiol. 43, (2013).
5.
Askamp, J. & van Putten, M. J. a M. Diagnostic decision-making after a first and recurrent seizure in adults. Seizure 22, 507–11 (2013).
6.
Velis, D., Plouin, P., Gotman, J., da Silva, F. L. & ILAE DMC Subcommittee on Neurophysiology. Recommendations Regarding the Requirements and Applications for Long-term Recordings in Epilepsy. Epilepsia 48, 379–384 (2007).
7.
Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League Against Epilepsy. Epilepsia 34, 592–6 (1993).
8.
Fisher, R. S. et al. ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia 55, 475–482 (2014).
9.
Leone, M. A., Vallalta, R., Solari, A., Beghi, E. & FIRST Group. Treatment of first tonicclonic seizure does not affect mortality: long-term follow-up of a randomised clinical trial. J. Neurol. Neurosurg. Psychiatry 82, 924–927 (2011).
10.
Giorgi, F. S. et al. Usefulness of a simple sleep-deprived EEG protocol for epilepsy diagnosis in de novo subjects. Clin. Neurophysiol. 124, 2101–2107 (2013).
11.
Liporace, J., Tatum, W., Morris, G. L. & French, J. Clinical utility of sleep-deprived versus computer-assisted ambulatory 16-channel EEG in epilepsy patients: a multicenter study. Epilepsy Res. 32, 357–62 (1998).
12.
Giorgi, F. S. et al. What is the role for EEG after sleep deprivation in the diagnosis of epilepsy? Issues, controversies, and future directions. Neurosci. Biobehav. Rev. 47, 533–548 (2014).
13.
Berg, A. T. Risk of recurrence after a first unprovoked seizure. Epilepsia 49, 13–18 (2008).
14.
Randomized clinical trial on the efficacy of antiepileptic drugs in reducing the risk of relapse after a first unprovoked tonic-clonic seizure. First Seizure Trial Group (FIR.S.T. Group). Neurology 43, 478–83 (1993).
15.
Michel, V., Mazzola, L., Lemesle, M. & Vercueil, L. Long-term EEG in adults: Sleepdeprived EEG (SDE), ambulatory EEG (Amb-EEG) and long-term video-EEG recording (LTVER). Neurophysiol. Clin. Neurophysiol. 45, 47–64 (2015).
16.
Koepp, M. J., Farrell, F., Collins, J. & Smith, S. The prognostic value of long-term ambulatory electroencephalography in antiepileptic drug reduction in adults with learning disability and epilepsy in long-term remission. Epilepsy Behav. 13, 474–477 (2008).
17.
Faulkner, H. J., Arima, H. & Mohamed, A. The utility of prolonged outpatient
ambulatory EEG. Seizure 21, 491–495 (2012). 18.
Askamp, J. & van Putten, M. J. A. M. Mobile EEG in epilepsy. Int. J. Psychophysiol. 91, 30–5 (2014).
Table 1. Clinical characteristics sdEEG (n=52) Age (years, median) Male sex, n (%) Type seizure Primary/secondary generalized Focal Nocturnal Abnormal MRI
aEEG (n=52)
46 36 (69%)
48 31 (60%)
32 (62%) 11 (21%) 8 (15%) 6 (12%)
24 (46%) 21 (40%) 5 (10%) 5 (10%)
Table 2. Overview of detected interictal discharges. Epileptiform discharges sdEEG Number percentage of patients Sharp-slow wave 7 43.8% Sharp wave 1 6.2% Generalized spike-wave discharges 2 12.5% Isolated spike wave discharges 6 37.5% Isolated spike 0 0%
Number of patients 8 4 1 8 0
aEEG percentage
38.1% 19% 4.8% 38.1% 0%
Table 3A. Diagnostic findings in patients (n=52) with a sdEEG. Abnormal implies presence of interictal epileptiform discharges. Epilepsy (n=31)
No epilepsy (21)
Abnormal sdEEG
14
2
Normal sdEEG
17
19
Table 3B. Diagnostic findings in patients (n=52) with an aEEG. Abnormal implies presence of interictal epileptiform discharges. Epilepsy (n=32)
No epilepsy (20)
Abnormal aEEG
20
1
Normal aEEG
12
19