Do Nonspecific Focal EEG Slowing and Epileptiform Abnormalities Favor One Hemisphere?

Authors


Address correspondence and reprint requests to Dr. M. J. Doherty at Department of Neurology, University of Washington, Box 356465, Seattle, WA 98195, U.S.A. E-mail: mdoherty@u.washington.edu

Abstract

Summary:  Purpose: Several EEG-based studies suggest that epileptiform activity originates from the left more than the right hemisphere. In contrast, other pathophysiologies such as stroke lateralize relatively symmetrically. Study of focal slowing and other EEG abnormalities allows assessment of favoring as well as referral and interpretation bias.

Methods: The 1,331 consecutive adult EEG reports were reviewed for epileptiform discharges (EDs) and nonepileptiform focal slowing. Side of slowing or EDs, interpreting electoencephalographer, and whether the patient was undergoing long-term monitoring or routine EEG were tallied. Results were statistically analyzed.

Results: Focal slowing occurred symmetrically; EDs favored the left hemisphere (p < 0.01).

Conclusions: The left hemisphere may be more prone to epileptiform abnormalities in adults, but not to the nonspecific pathophysiologic processes that cause slowing. These findings suggest that potential interpretation bias does not influence left hemispheric favoring of EDs and instead may implicate a biologic etiology.

It might be assumed that abnormal neurologic processes affect the two hemispheres with equal frequencies; however, past EEG-based reports suggest that epileptiform discharges (EDs) favor the left hemisphere preferentially (1–3). In a study from our own institution, we found similar results, most notably in left-handed patients undergoing long-term monitoring (LTM) studies (4). In stroke studies, however, radiographic changes lateralize more or less symmetrically (5). This raises possibilities that prior EDs reports had methodologic flaws such as preferential interpretation of left-sided EEG data or referral bias. Further investigation is needed to address these issues to determine if epileptiform asymmetry is genuine and has a biologic basis.

Correlating another EEG abnormality, focal slowing, with hemispheric lateralization might determine if interpretation and referral bias have limited studies of epileptiform favoring. Focal slowing is nonspecific; stroke and mass lesions are among many causes, so one might expect little hemispheric favoring of slowing. Seizures also may cause focal slowing. However, as EDs favor the left hemisphere in adults, the assumption that focal slowing should occur symmetrically may not be valid for patients in whom focal slowing and EDs occur simultaneously (1–4). With exclusion of cases that display both focal slowing and EDs from analysis of slowing, it should be possible to determine if nonspecific, EDs-independent causes of focal slowing show hemispheric favoring. Using this approach combined with conservative study of lateralized EDs should permit both repetition of prior studies and evaluation of potential interpretation and referral errors.

METHODS

Previously unstudied consecutive EEG interpretations from Harborview Medical Center (HMC), a public hospital serving a predominantly adult population, were retrospectively reviewed. EEGs were performed from January 2000 to September 2001. Reviewers were blind to referral reasons and a priori diagnosis; electroencephalographers were blind to study objectives. Each interpretation had four data points taken: the presence of abnormal focal slowing or EDs, hemispheric location of slowing or EDs, interpreting electroencephalographer, and whether the patient was undergoing LTM or routine EEG recording.

Only one EEG interpretation from each patient was coded. If multiple studies were performed, the most abnormal interpretation was used, as defined by the greatest number of abnormalities. If numerous differing abnormalities were noted in differing reports from the same patient, the most recent study with the most abnormalities was used. For the purposes of this study, EDs were considered more abnormal than focal slowing. If focal EDs and focal slowing occurred in the same interpretation, mechanisms causing slowing were assumed to be EDs related, and therefore focal slowing in that patient was not coded. Only final LTM summary interpretations were used; if LTM studies were repeated, the same criteria as previously detailed were used to determine which report was tallied.

To assess if epileptiform favoring within our population paralleled prior studies, only the most fundamental EDs were coded: abnormal interictal sharp waves, interictal spikes, or ictal electrographic activity. For the purposes of this study, periodic lateralized EDs were not considered EDs or focal slowing. To emphasize only strongly lateralized abnormalities, bilateral, independent spikes were tallied in a subset with no attempt to determine preponderance of left or right discharges. Abnormal focal slowing was defined as either intermittent or persistent frequencies slower than 8 Hz unexplained by age, arousal state, or as an accepted normal variant. EEG variants such as 14- and 6-Hz positive bursts were considered normal. Postictal slowing was not recorded, as it is not routinely interpreted. Location was coded by hemisphere. Breach rhythms, or other changes due to skull defects, were not considered abnormal unless either EDs or focal slowing was seen.

All routine EEG and LTM recordings were done with digital equipment using standard electrode placement according to the International 10-10 system. Invasive LTM with scalp, grid or bilateral strip, and rarely, depth electrode recordings were included (electrode placement was suggested by prior scalp LTM). Data were entered into a computerized statistical database (SPSS) and nonparametric statistical analysis performed with χ2 or Fisher's exact testing, with significance determined as <0.05.

RESULTS

Six electroencephalographers interpreted 1,331 records. Four board-certified neurophysiologists read 1,125 (85%) records; the remaining studies were read by two board-eligible electroencephalographers who had completed 1-year clinical neurophysiology fellowships within the prior 2 years. General, EDs, and slowing findings are shown in Table 1. With exclusion of LTM patients, 62 had left-sided epileptiform discharges, and 38 had right (p = 0.02, χ2). Focal slowing occurred in 108 patients, 58 left- and 50 right-sided, without significant predominance on either side (p = 0.44, χ2) (Table 1). Individual electroencephalographers identified left- or right-sided abnormalities in similar ratios.

Table 1.  EEG data
InterpretationRoutine EEG
(%)
 Long-term
monitoring (%)
 Total (%) 
  • EDs, epileptiform discharges.

  • a  χ2 test.

  • b

     Fisher's exact test.

Normal493 (37) 92 (7) 585 (44) 
Generalized slowing292 (22) 12 (1) 304 (23) 
Generalized EDs26 (2) 28 (2) 54 (4) 
Bilateral independent EDs41 (3) 24 (2) 65 (5) 
Left hemisphere Eds62 (5)p = 0.02a57 (4)p = 0.03a119 (9)p < 0.01a
Right hemisphere EDs38 (3) 36 (3) 74 (6) 
Slowing left hemisphere57 (4)p = 0.20a1p = 0.34b58 (4)p = 0.44a
Slowing right hemisphere44 (3) 6 50 (4) 
Bilateral slowing22 (2) 0 22 (2) 
Total1,075 (81) 256 (19) 1331 

DISCUSSION

This study shows that nonspecific focal slowing occurred symmetrically in a previously unstudied adult population. This demonstrates that EEG interpreters did not focus preferentially on EEG data from the left hemisphere. This finding, combined with confirmation of left hemispheric EDs favoring in adults, suggests that EDs favoring is genuine and not due to interpretation bias.

Second, because slowing lateralized symmetrically, it is likely that symptoms related to left- or right-sided focal slowing generated similar referrals for EEG testing. Although no data suggest that symptoms potentially associated with focal slowing are similar to those seen with focal seizure, a prior study showed a lower mean age at onset for right-sided focal epilepsy and a shorter duration of epilepsy before evaluation (3). This suggests that seizures originating in the right hemisphere may be referred for evaluation sooner than those in the left, and that left hemispheric seizures and their potential semiologies do not prompt referrals more than right hemisphere seizures.

Nevertheless, as HMC hosts the Regional Epilepsy Center (REC), which coordinates LTM and comprehensive epilepsy care, criticism might include that we studied a tertiary referral population. Limited non-LTM EEG data were generated from this REC population. Most non-LTM data were referred from the inpatient Neurology service, separate from REC, where inpatient admissions in the academic year 2000–2001 numbered 2,033. First-time seizure patients are routinely admitted and evaluated with EEG. Left-sided EDs from LTM (61%) and non-LTM (62%) suggest little difference between groups, regardless of referral patterns. In our population, occurrence of EDs favoring the left hemisphere was both comparable to and lower than prior studies, two of which addressed referral bias (1–3).

Speculative explanations for EDs favoring include neurochemical asymmetries. Carbamazepine has been claimed to be a more effective antiepileptic agent (AED) in the setting of left-sided focal abnormalities and may better control seizures if they originate from the left side (6). Other studies have found asymmetric expression of neurotransmitters such as acetylcholine (7,8).

Perhaps underlying those neurotransmitter asymmetries are developmental asymmetries. From our prior study of LTM with localization-related epilepsy, ictal and interictal EDs favored the left hemisphere only in left-handed patients (4). This may imply that congenital or childhood damage to the left hemisphere influenced development of both handedness and EDs. Additionally, in a demographic continuum to this study, we evaluated 1,326 pediatric EEG results from Seattle's Children's Hospital stratified by age and first EEG findings. Significant right-sided favoring of EDs occurred up to age 5 years; thereafter, left hemisphere EDs were favored (9). Normal children between ages 3 and 5 years parallel this electrical favoring with hemispheric shifts in blood flow and cortical size, with the once dominant right outpaced by the rapidly growing left hemisphere (10–12). Age-related mechanisms of normal cerebral development and functional lateralization likely play a fundamental role in hemispheric favoring of EDs.

Limitations of this study include the assumption that focal slowing with concomitant focal epileptiform activity represents related pathophysiology, and that focal slowing independent of EDs likely results from differing pathophysiologies. This assumption covers patients with EDs who fail to show slowing, but it does not account for patients with EDs that, because of EEG sampling, showed only focal slowing. This sampling problem is likely small and is minimized with examination of a large numbers of patients, inclusion of LTM studies, and by coding only the most abnormal of repeated EEG interpretations.

Describing how focal slowing and EDs correlate with clinical, pathologic, and radiologic findings remains an important undertaking, and was beyond the aims of this study. EEG requisition materials contain some of this information. However, requisitions were insufficiently detailed to allow correlation.

Through an examination of EEG reports, we were able to confirm in previously unstudied patients what prior groups, including our own, have shown: that EDs favor the left hemisphere in adults (1–4). The finding that non–EDs-related slowing occurs symmetrically suggests that this study did not suffer from interpretation bias. Why EDs asymmetries develop remains speculative. Further work correlating focal EEG data with age, radiographic, pathologic, and clinical findings may provide new insights into hemispheric susceptibilities to EDs and focal slowing.

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