Interictal epileptiform activity in elderly patients with epilepsy

Electroencephalography and clinical Neurophysiology 106 (1998) 369–373

Interictal epileptiform activity in elderly patients with epilepsy Ivo Drury*, Ahmad Beydoun Epilepsy Program and Clinical Neurophysiology Laboratories, Department of Neurology, University of Michigan Medical School, Ann Arbor, MI 48109, USA Accepted for publication: 14 November 1997

Abstract Objective: To examine the frequency of interictal epileptiform activity (IEA) in elderly patients with epilepsy. Design and Methods: From a consecutive 13 905 EEGs recorded over 5 years at a university hospital EEG laboratory, 558 studies were performed on outpatients aged 60 years or more. Medical record review identified 125 patients in whom a confident clinical diagnosis of epilepsy was made by a board-certified neurologist. The EEG findings in these patients were reviewed. The effects of various variables on the likelihood of detecting IEA were calculated using Fisher’s test and chi-square analysis. Results: IEA were present on the first EEG in 35% of 55 patients (mean age 65 years) with pre-existing epilepsy, and 26% of 70 patients (mean age 70 years) with seizure onset after 60 years. There were no significant differences in the frequency of IEA in patients with late onset epilepsy in the 7th or in the 8th decades of life. Most IEA were focal. Activation procedures added little additional information. Patients with more than one seizure per month were significantly more likely to have IEA (P = 0.016). There were no major differences in likelihood of IEA detection depending on the underlying cause of the seizures. Conclusions: The frequency of IEA in elderly patients with epilepsy is substantially lower than that reported in epileptic populations as a whole. This low rate of IEA in routine EEG studies must be recognized when considering the diagnosis of an epileptic syndrome for episodic events happening in the elderly.  1998 Elsevier Science Ireland Ltd. Keywords: EEG; Epilepsy; Interictal epileptiform activity; Elderly

1. Introduction Epilepsy is a common problem in the elderly, and one receiving increasing attention including recent publication of a monograph devoted to the topic (Rowan and Ramsay, 1997). Incidence figures suggests that there are between 45 000 and 50 000 new cases of epilepsy or first unprovoked seizures amongst the elderly each year in the United States (Hauser, 1997). Although EEG remains the most useful diagnostic tool in epilepsy, there are relatively little data in the literature about the frequency with which interictal epileptiform activity (IEA) is found in this population. Most studies published to date have focused on the presence of epileptiform activity in patients after stroke, the majority of whom (Gupta et al., 1988) or all (Lu¨hdorf et al., 1986) being elderly. They are not therefore representative of the great * Corresponding author. 1500 E. Medical Center Drive, 1B300/0036 UH, Ann Arbor, MI 48109–0036, USA. Tel.: +1 313 9369030; fax: +1 313 9365520.

0013-4694/98/$19.00  1998 Elsevier Science Ireland Ltd. All rights reserved PII S0013-4694 (97 )0 0158-2

majority of elderly patients with unprovoked seizures seen in the outpatient setting. This study was designed to examine in a retrospective fashion the frequency and characteristics of IEA in patients with epilepsy aged greater than 60 years attending the outpatient neurology clinics at a university hospital.

2. Methods A consecutive 13 905 EEGs were performed over a 5year period at a university hospital EEG laboratory ending June 30, 1996. The log books in the EEG laboratory were used to identify 558 EEG studies performed on outpatients aged greater than 60 years. The medical records of all these patients were reviewed to identify 125 patients in whom a confident clinical diagnosis of epilepsy was made by a board-certified neurologist. The following information was obtained from the medical record of each patient; age at onset of epilepsy, classification of the epileptic syndrome,

EEG 97141

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seizure frequency at the time of the EEG, and the presumed etiology of the epilepsy. All available data in the medical record were used to determine the classification and the etiology including results of EEG and imaging data. All EEG recordings were performed with electrodes applied according to the international 10–20 system on 21-channel analog EEG instruments until July 1994 and thereafter on digital systems, following the guidelines of the American Clinical Neurophysiology Society (1994). The behavioral state of the patient during the EEG recording was noted and spontaneous drowsiness and sleep encouraged. Infrequently the studies were performed after sleep deprivation or conscious sedation with chloral hydrate. Standard activation procedures of hyperventilation and photic stimulation were performed in each case unless hyperventilation was contraindicated or the patient did not cooperate. All EEG recordings were reviewed by a boardcertified staff clinical neurophysiologist, expert in EEG interpretation. From the EEG report the following factors were abstracted; age at time of EEG, waking and sleeping background, the occurrence or not of baseline IEA, location of focal IEA when identified, and the response of IEA to activation procedures.

3. Results 3.1. Demographics There were 139 EEGs performed on 125 patients. Unless otherwise stated, results are reported for the first EEG performed on each patient during the study period. Fifty-five patients, 29 men and 26 women with a mean age of 65 years (range 60–82 years), had their onset of epilepsy before age 60, while 70 patients, 40 men and 30 women with a mean age of 70 years (range 60–85 years), had onset of epilepsy at age 60 or older. There was no statistically significant difference in gender and age of the patients between the two groups. 3.2. EEG background and activation procedures Table 1 shows that normal waking background was infrequently seen irrespective of age of onset. Hyperventilation was performed in 68 (54%) EEGs, was contraindicated in 47 Table 1 Waking background findings in elderly patients with epilepsy

Onset , 60 years Onset . 60 years

Normal Generalized slowing

Focal slowing ± generalized slow

Recording in sleep only

2

15

36

2

8

13

49

0

(38%) others most commonly because of cardiovascular or cerebrovascular disease, and not performed in 10 (8%) patients due to diminished cooperation. Intermittent photic stimulation was performed in every EEG. Stage II sleep was achieved in 30 (24%) recordings only. Eleven records were obtained after sleep deprivation and 4 records after sedation with chloral hydrate. In those 30 EEGs normal stage II sleep features were seen in 27 recordings. Two patients had focal abnormalities in sleep, one with an EEG recording performed in the sleep state only, and one who had a clear focal abnormality on the waking EEG also. One patient had a diffuse abnormality seen during sleep consisting of almost complete absence of spindle activity and at times continuous generalized spike-wave activity. 3.3. Interictal epileptiform activity We used the definition of epileptiform abnormalities of the International Federation of Societies for Electroencephalography and Clinical Neurophysiology (1974). The frequency of IEA on baseline EEG or with activation procedures (hyperventilation, photic stimulation and sleep) was 19 of 55 (35%) in patients with onset of epilepsy before age 60 years. Three patients had increased amounts of IEA with activation procedures but there were no patients in this group who showed IEA during activation procedures only. IEA was seen in 18 of 70 (26%) patients with the onset of epilepsy after age 60 years. One patient in this group had IEA present during an activation procedure only, this the emergence of temporal sharp waves in a 70 year-old man in sleep. In 80 patients aged between 60 and 69 years, independent of the age of onset of their epilepsy, IEA were present on the baseline EEG in 17 (21%) with activation procedures increasing the frequency of IEA in 3 patients. In the 38 patients aged between 70 and 79 years, IEA were seen in 10 (26%) with IEA occurring during an activation procedure exclusively in one patient. This difference was not statistically significant. Generalized IEA occurred in 7 patients. Five of the 7 had symptomatic generalized epilepsy with the most frequent seizure type being atypical absence in 3, myoclonic in two, generalized tonic-clonic in one and partial complex in one. Four of the 7 had onset of their epilepsy before age 60. Etiology of their epilepsy was idiopathic in 4 cases, Alzheimer’s disease in two cases (one with pre-existent Downs syndrome) and part of lifelong mental retardation and static encephalopathy in one patient. Focal IEA occurred in 15 patients with onset of their epilepsy at less than 60 years, and in 15 patients with the onset of epilepsy at age 60 or older. Table 2 illustrates the topography of the focal discharges in relationship to age of onset of epilepsy. Fourteen of the 15 patients with onset of epilepsy after age 60 had their focal IEA in the temporal regions. In patients with the onset of epilepsy before age 60 the distribution was more diverse, yet remained most com-

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I. Drury, A. Beydoun / Electroencephalography and clinical Neurophysiology 106 (1998) 369–373 Table 2

Table 4

Topography of focal IEA in relation to age of onset of epilepsy

Frequency of IEA in relation to seizure frequency

Location

Onset , 60 years

Onset . 60 years

Temporal Frontal Hemispheric Parasagittal

9 3 2 1

14 1 0 0

Seizure frequency

IEA present

IEA absent

, 1 per month ≥ 1 per month

9 28

43 45

Fisher’s test: P = 0.016.

mon in the temporal lobes. These differences were not statistically significant. Table 3 illustrates the likelihood of focal IEA occurring in all patients with symptomatic localization-related epilepsy, irrespective of the age of onset of their epilepsy in relation to whether their seizure were partial only, generalized only, or both partial and generalized. These differences did not reach statistical significance. Twenty-two patients were taking no antiepileptic drug at the time of their EEG. The other 103 patients were taking one drug in 67 patients, two drugs in 33 patients and 3 drugs in 3 patients. The frequency of IEA being present was 9 of 22 (41%) in the patients taking no drug and 28 of 103 (27%) in the 103 patients exposed to at least one antiepileptic drug. These differences did not reach statistical significance. Table 4 shows the relationship between seizure frequency and presence of IEA. Patients with one or more seizures per month were significantly more likely to have IEA on their EEG (Fisher’s test, P = 0.016). Table 5 illustrates the frequency with which IEA of either generalized or focal types were seen in patients with the onset of their epilepsy before and after age 60 and in relation to their underlying etiology. The large number of etiological groups and varying number of patients within each group preclude a statistical analysis.

study. In a third patient with symptomatic generalized epilepsy, IEA were generalized on the initial study but focal on the subsequent recording.

4. Discussion Our study found an overall low rate of IEA detection in elderly patients with epilepsy irrespective of age of onset of seizures. The likelihood of IEA was greatest in patients with more frequent seizures but was not affected by the duration of the epilepsy. The yield was low independent of etiology. Activation procedures were of essentially no additional value. Some of the strengths and limitations of this study need to be mentioned. The data was examined retrospectively and Table 5 Frequency of IEA in elderly epileptics in relation to etiology Etiology (no. of patients)

Onset , 60 years (n)

Total Onset . 60 years (n)

Total

Idiopathic (52)

No IEA (13) Gen. IEA (3) Foc. IEA (6) No IEA (0) Gen. IEA (0) Foc. IEA (1) No IEA (7) Gen. IEA (0) Foc. IEA (2) No IEA (7)

22

30

3.4. Yield of sequential EEGs

Vascular (18)

Sequential EEG studies were performed in 13 patients. One patient had 3 EEGs during this study period, 12 had two EEGs. Eight patients with the onset of their epilepsy before age 60 had a total of 17 EEGs. Five of the 8 patients showed IEA in each of their studies, two had no IEA in each of their studies and one patient had one positive (i.e., IEA present) and one negative (i.e., IEA absent) study. Five patients with the onset of their epilepsy after age 60 had a total of 10 EEGs. In no case were each of the studies positive; 3 patients had one study positive and one study negative, and two patients had both studies negative. In two patients a second EEG revealed focal IEA not seen on the initial

Post-traumatic (15)

Table 3 Frequency of focal IEA in relation to seizure type for all patients with partial epilepsy Seizure type

IEA present

IEA absent

Total

Partial only Generalized only Partial and generalized

17 6 10

36 24 25

53 30 35

Lifelong static encephalopathy (11)

Gen. IEA (1) Foc. IEA (2) Alzheimer’s disease (10) No IEA (0) Gen. IEA (0) Foc. IEA (0) Alzheimer’s disease No IEA (1) in Downs (2) Gen. IEA (0) Foc. IEA (0) Lesional (9) No IEA (5) Gen. IEA (0) Foc. IEA (2) Neoplastic (5) No IEA (2) Gen. IEA (0) Foc. IEA (0) Post-infectious (3) No IEA (1) Gen. IEA (0) Foc. IEA (2)

1

9

10

0

1

7

2

3

No IEA (23) Gen. IEA (1) Foc. IEA (6) No IEA (14) Gen. IEA (0) Foc. IEA (3) No IEA (4) Gen. IEA (0) Foc. IEA (2) No IEA (1) Gen. IEA (0) Foc. IEA (0) No IEA (6) Gen. IEA (1) Foc. IEA (3) No IEA (0)

17

6

1

10

Gen. IEA (1) Foc. IEA (0) No IEA (2) Gen. IEA (0) Foc. IEA (0) No IEA (2) Gen. IEA (0) Foc. IEA (1) No IEA (0) Gen. IEA (0) Foc. IEA (0)

Foc., focal; Gen., generalized; IEA, interictal epileptiform activity.

1

2

3

0

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originally derived from case identification through the records of an EEG laboratory. Our institution is a major referral center and patients seen here need not be representative of the general population. The advantages of our study include the requirement that the patient have a confident clinical diagnosis of epilepsy by a board-certified neurologist. Patients were selected from referrals from all of the staff neurologists in our department and not just epileptologists, ensuring inclusion of patients being seen in general neurology clinics and by specialists in fields such as cerebrovascular diseases, neuro-oncology and cognitive disorders, all relatively common causes of epilepsy in older patients. We selected patients referred from the outpatient clinics exclusively to avoid the inclusion of the acute provoked seizure that would dominate the studies performed in the elderly as inpatients. All EEGs are read in our laboratory by individuals with subspecialty training in epilepsy and clinical neurophysiology, and who are certified by the American Board of Clinical Neurophysiology giving us a high level of confidence in the EEG findings. To our knowledge, no study to date has examined the frequency of IEA detection in elderly patients with epilepsy. Anecdotal and published experience indicates IEA are most frequent in children and progressively less frequent with age. In the study of Ajmone-Marsan and Zivin (1970), of 308 patients with epilepsy of diverse age, 56% of all patients had IEA detected on their first EEG. The frequency in the first 4 decades of life was 77, 60, 56 and 51% respectively. In the 51 patients aged 40 years or more the frequency was 39% but this latter group was not further divided. The frequency of IEA found in our patients appears consistent with an overall trend towards a lower frequency with advancing age. The underlying mechanisms as to why IEA are progressively less frequent with age remains unknown. Agerelated epileptogenesis has been little studied to date (Dichter and Weinberger, 1997). It is tempting to believe that the decreased number and complexity of synaptic connections with age may contribute to less synchronized neuronal discharges and therefore less frequent IEA detected on scalp EEG. Epilepsy is known to be a common neurological problem in the elderly (Hauser, 1997). Clinical manifestations are more diverse than when it presents at a younger age and more easily confused with other common medical problems such as cardiac arrhythmias, transient ischemic attacks or dizziness (Drury and Beydoun, 1993; Thomas, 1997). Elderly patients with epilepsy are more likely to be seen by primary care providers or specialists in other disciplines unfamiliar with the fact that the EEG may be normal or abnormal only in a non-specific way in the epileptic. A low rate of definitively abnormal EEGs in the elderly with epilepsy as seen in our population increases the likelihood of the diagnosis of epilepsy not being reached. CCTV-EEG monitoring, an extremely useful diagnostic tool in patients with possible epilepsy, is used rarely in the elderly, constituting 1.4% of such studies performed at another major

referral center in epilepsy (Lancman et al., 1996) and 4.3% in our program (Selwa et al., 1997). This increases the dependence on the use of interictal EEG findings alone to aid in the diagnosis. In epilepsy activation procedures are techniques used to enhance the detection of IEA or ictal events on EEG (Drury, 1997). In this age group activation procedures were of little additional value. The significant number of patients precluded from performing hyperventilation is to be expected in an older population with coexisting vascular disease. The yield of HV in activating IEA or ictal activity in the partial epilepsies is only 6–11% (Gabor and Ajmone-Marsan, 1969; Morgan and Scott, 1970; Miley and Forster, 1977). This factor plus the much less dramatic change in background activity in adults compared to children with HV (Drury, 1997) will result in a low yield from this activation procedure in epilepsy in the elderly in general. The primary value of photic stimulation in patients with epilepsy is in the primary generalized epilepsies (Wolf and Gooses, 1986), an uncommon type of epilepsy in this age range. Stage II of NREM sleep, achieved in less than one quarter of our patients was of little added value. Other findings in this study are similar to the published experience in younger patients with epilepsy. Thus, the likelihood of IEA being detected on EEG is greatest in patients with more frequent seizures, and there was no relationship between the occurrence of IEA and the particular underlying causes of the patients’ epilepsy (Ajmone-Marsan and Zivin, 1970). In conclusion, the occurrence of IEA is low in routine EEG studies in a group of elderly patients with a confident clinical diagnosis of epilepsy. It is important that this be recognized by people considering the diagnosis of an epileptic syndrome for episodic events happening in older patients.

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