Epilepsy & Behavior 36 (2014) 165–170

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“Ictal” lateralized periodic discharges☆ Indranil Sen-Gupta 1, Stephan U. Schuele, Micheal P. Macken, Mary J. Kwasny, Elizabeth E. Gerard ⁎ Feinberg School of Medicine, Northwestern University, 710 N Lakeshore Drive, Chicago, IL 60611, USA

a r t i c l e

i n f o

Article history: Received 10 March 2014 Revised 4 May 2014 Accepted 18 May 2014 Available online xxxx Keywords: LPDs PLEDs Ictal–interictal continuum Semiology Epilepsia partialis continua Continuous EEG monitoring ICU EEG

a b s t r a c t Objective: Whether lateralized periodic discharges (LPDs) represent ictal or interictal phenomena, and even the circumstances in which they may represent one or the other, remains highly controversial. Lateralized periodic discharges are, however, widely accepted as being ictal when they are time-locked to clinically apparent symptoms. We sought to investigate the characteristics of “ictal” lateralized periodic discharges (ILPDs) defined by time-locked clinical symptoms in order to explore the utility of using this definition to dichotomize LPDs into “ictal” and “nonictal” categories. Methods: Our archive of all continuous EEG (cEEG) reports of adult inpatients undergoing prolonged EEG monitoring for nonelective indications between 2007 and 2011 was searched to identify all reports describing LPDs. Lateralized periodic discharges were considered ILPDs when they were reported as being consistently time-locked to clinical symptoms; LPDs lacking a clear time-locked correlate were considered to be “nonictal” lateralized periodic discharges (NILPDs). Patient charts and available neuroimaging studies were also reviewed. Neurophysiologic localization of LPDs, imaging findings, presence of seizures, discharge outcomes, and other demographic factors were compared between patients with ILPDs and those with NILPDs. p-Values were adjusted for false discovery rate (FDR). Results: One thousand four hundred fifty-two patients underwent cEEG monitoring at our institution between 2007 and 2011. Lateralized periodic discharges were reported in 90 patients, 10 of whom met criteria for ILPDs. Nine of the patients with ILPDs demonstrated motor symptoms, and the remaining patient experienced stereotyped sensory symptoms. Ictal lateralized periodic discharges had significantly increased odds for involving central head regions (odds ratio [OR] = 11; 95% confidence interval [CI] = 2.16–62.6; p = 0.018, FDR adjusted), with a trend towards higher proportion of lesions involving the primary sensorimotor cortex (p = 0.09, FDR adjusted). Conclusions: When defined by the presence of a time-locked clinical correlate, ILPDs appear to be strongly associated with a central EEG localization. This is likely due to cortical irritability in central head regions having greater propensity to manifest with positive, clinically apparent, and time-locked symptoms. Thus, dichotomization of ILPDs and NILPDs on this basis principally reflects differences in underlying anatomical locations of the periodic discharges rather than providing a clinically salient categorization. © 2014 Elsevier Inc. All rights reserved.

☆ Contributions: Indranil Sen-Gupta contributed to study conceptualization and design and performed data extraction and statistical analyses. He also prepared the manuscript and all figures. Stephan U. Schuele contributed to data collection and provided critical review of the protocol and manuscript. Micheal P. Macken contributed to data collection and provided critical review of the protocol and manuscript. Mary J. Kwasny provided statistical support and helped with statistical analysis and review of the manuscript. Elizabeth E. Gerard conceived the study design and hypothesis and performed independent review of raw data and categorization of EEGs according to ACNS terminology. She also contributed to writing and editing of the manuscript. ⁎ Corresponding author at: Department of Neurology, Feinberg School of Medicine, Northwestern University, Abbott Hall No. 1114, 710 North Lake Shore Drive, Chicago, IL 60611, USA. Fax: +1 312 908 5073. E-mail addresses: [email protected] (I. Sen-Gupta), [email protected] (S.U. Schuele), [email protected] (M.P. Macken), [email protected] (M.J. Kwasny), [email protected] (E.E. Gerard). 1 Present Address: David Geffen School of Medicine, University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.

http://dx.doi.org/10.1016/j.yebeh.2014.05.014 1525-5050/© 2014 Elsevier Inc. All rights reserved.

1. Introduction Lateralized periodic discharges are classically viewed as acute, interictal phenomena [1,2] that are highly associated with seizures [1, 3]. Less frequently, however, LPDs may be the sole EEG finding during periods of clinical seizure activity [2,4,5]. In these instances, LPDs are generally considered an ictal pattern when they are time-locked to the clinically apparent symptoms. The most commonly accepted manifestation of such ILPDs occurs in motor epilepsia partialis continua (EPC), where LPDs sometimes represent the time-locked EEG correlate of focal motor jerks [3–6]. Lateralized periodic discharges have also been described in conjunction with subtle motor [7], sensory [8], or cognitive symptoms [9], although their role is more controversial when clinical manifestations are dyscognitive or otherwise less overt in nature. These subtle correlates are often not recognized in clinical practice, both because they are not routinely considered and because they may be more difficult to ascertain in patients with impaired mental status.

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There is a common perception that ILPDs as defined by time-locked clinical symptoms may harbor different clinical and/or treatment implications compared to NILPDs [10], but this has never been formally studied. Description of ILPDs has, thus far, been limited to case reports that cannot comment on their frequency or common characteristics. We, therefore, performed the first systematic case series on ILPDs utilizing this commonly accepted definition. Our chief hypothesis was that ILPDs would be significantly more likely to involve central head regions compared to NILPDs based on the expected propensity towards clinically recognizable symptoms resulting from proximity to the primary sensorimotor cortex (precentral or postcentral gyri). 2. Materials and methods 2.1. Standard protocol approvals, registrations, and patient consents This retrospective investigation was in compliance with Institutional Review Board policies at Northwestern University. 2.2. Data source and extraction The cEEG report archive of all adult ward and ICU patients undergoing prolonged EEG monitoring for nonelective indications between 2007 and 2011 at our institution was utilized to obtain data for this study. All cEEGs were performed with electrode placement according to the international 10–20 system. All reports describing LPDs were identified and, accordingly, represented consecutive patient data during this period. Lateralized periodic discharges were considered ILPDs when they were reported as being consistently time-locked to clinical symptoms at any point during the recording; this definition was implemented for the reasons mentioned earlier. Source EEGs of all potential ILPDs were reviewed for confirmation. For each patient, location of LPDs was categorized into one of four head regions (frontal, temporal, parietooccipital, or central) based on their electrographic maxima and the scheme in Fig. 1. Patient demographics including sex, age, and diagnosis were obtained through chart review. Available neuroimaging studies were reviewed for the presence of focal cerebral lesions as well as etiology and location of

the lesion(s) when present. The presence of electrographic seizures with or without clinical signs was also noted by review of continuous EEG reports. Electrographic seizures were defined by previously reported criteria [11]. Lateralized periodic discharges were not considered seizures. Discharge outcomes were ascertained from reported physical examinations in patient charts on the day of discharge and were classified based on the Cerebral Performance Category (CPC) scoring system as either good (scores of 1–2) or poor (scores of 3–5) [12]. 2.3. Statistical analysis Neurophysiologic localization of LPDs, imaging findings, presence of electrographic seizures, discharge outcomes, and other demographic factors were compared between patients with ILPDs and those with NILPDs. Independent samples t-test was used for comparison of age and cEEG recording duration. Wilcoxon's rank sum test was used to compare ordinal variables including clinical states. All other comparisons were conducted with Fisher's exact test. All tests were performed 2-tailed, and p-values were adjusted for multiple comparisons using false discovery rate (FDR) control. All analyses were performed using MATLAB® (The Mathworks, Inc., Natick, MA) and R software (R Foundation, Vienna, Austria). 2.4. Post hoc analysis Further within-group analysis was performed on the cohort of patients with central LPDs in order to ascertain whether there were true differences between groups when the effect of anatomic localization was removed. The same comparisons of patient clinical state, neuroimaging findings, seizure occurrence, and discharge outcomes were made between patients with central ILPDs and central NILPDs. In addition, the LPDs in these cases were characterized according to The American Clinical Neurophysiology Society's (ACNS) standardized nomenclature for critical care EEG [13]. Sufficient cEEG data were available for characterization of 7/7 cases of central ILPDs and 12/14 cases of central NILPDs. Central LPDs were evaluated for the presence of a “plus” modifier, amplitude, relative amplitude, frequency, sharpness, and phases as defined by these published criteria. Statistical tests performed were similar to those used for the main analysis, though FDR control was not applied to these exploratory comparisons. 3. Results

Fig. 1. Classification map for location of LPDs. LPDs were categorized as frontal, temporal, parietooccipital, or central based on the figure above. Categorization was based on the single electrode that best represented the location of the LPDs, as well as the location of the next most involved contiguous electrode. These two electrode locations were determined by phase reversals on longitudinal bipolar montage and by maximal amplitudes on referential montage. For example, if the LPDs were maximal at Fz/F3, Fz/ Fp1, or Fz/F3, they were classified as frontal, whereas if they were maximal at Fz/Cz or F3/C3, they were considered central. On the basis of dipole orientations, C3/T7 was considered central, and F7/T7 was considered temporal, as also depicted in the figure above.

A total of 1452 patients underwent cEEG monitoring at our institution for nonelective indications between 2007 and 2011. Lateralized periodic discharges were reported in 90 patients (6.2% of the total monitored population). Ictal lateralized periodic discharges were observed in 10 patients (representing 11.1% of all patients with LPDs, or 0.7% of the total monitored population). The remaining 80 patients had NILPDs. Demographic and clinical data for the ten patients with ILPDs are listed in Table 1, and additional electrographic characteristics are listed in Table 2. Nine patients had motor EPC, and the remaining patient experienced repetitive, stereotyped sensory symptoms. Seven patients had LPDs involving the central head regions. Identifiable lesions involving the primary sensorimotor cortex ipsilateral to LPDs were noted in eight patients. Neoplasms were seen in six patients and were the most common etiology associated with ILPDs. An example of time-locked EEG and imaging findings in a patient with ILPDs and motor EPC is shown in Fig. 2. Antiepileptic medications received by the patients with ILPDs are listed in Table 3. Despite the noted control of clinical seizures in all patients with ILPDs at the time of discharge, only two patients experienced good discharge outcomes, whereas the remaining eight experienced poor outcomes. Parameters compared between patients with ILPDs and those with NILPDs are listed in Table 4. Ictal and nonictal lateralized periodic

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Table 1 Demographic and clinical data for patients with ILPDs. Patient #

Age (y)

Sex

Primary cerebral lesion

Location of ILPDs

Clinical manifestation of ictal LPDs

Subclinical seizures during recording (Y/N)

Days from cEEG start to ILPDs

CPC score at discharge

1a

76

M

Bifrontal GBM

Central (C4 N P4)

0

5

2 3a

80 59

M M

Parietooccipital (P8/O2) Parietooccipital (P4/P8)

N N

0 0

3 3

4a

76

F

Temporal (F8 N T8)

Mouth opening and closure

N

0

3

5a

57

M

Right posterior temporooccipital GBM Multiple right hemispheric metastases from NSCLC Right frontal metastasis from small cell cancer of unknown primary Right parietal SDH

Clonic head jerking to left; left face/eye twitching Left thigh twitching Left face/eye twitching

Y

b

Central (F4/C4)

0

3

74 79 59 60 31

M F M M M

Left parietal AVM Right frontal metastasis from NSCLC Right parietal GBM Unknown Extensive, predominantly cortical anoxic injury (right N left hemisphere)

Central (Cz N P3) Central (C4 N P4) Central (C4/P4) Central (Cz/C3) Central (C4 N F4)

Clonic jerks of left lower extremity and left lower quadrant of abdomen Sensations of right groin pulsation Clonic left arm jerks Left face/eye twitching Clonic right arm jerks Left face/leg jerking

N

a

Y N Y N N

1 0 0 0 0

1 3 2 4 3

6 7a 8a 9b 10a

GBM = glioblastoma multiforme, NSCLC = nonsmall cell lung cancer, SDH = subdural hematoma, AVM = arteriovenous malformation. a Neuroimaging demonstrated lesion(s) involving the sensorimotor cortex ipsilateral to LPDs. b Neuroimaging without obvious lesion involving the sensorimotor cortex ipsilateral to LPDs.

discharges differed significantly in terms of their localization (p =0.037, FDR adjusted). Comparison of individual head regions revealed that ILPDs had significantly higher odds of involving central regions compared to NILPDs (odds ratio = 11; 95% CI = 2.16–62.6; p =0.018, FDR adjusted), with one-third of all central LPDs being ictal (Fig. 3). No significant differences in odds between ILPDs and NILPDs were noted for involvement of the noncentral head regions. Patients with ILPDs also trended towards having a higher proportion of lesions involving the primary sensorimotor cortex compared to patients with NILPDs (8/10 versus 31/80, respectively; p = 0.09, FDR adjusted). All patients with ILPDs except for one (Patient #9) were noted to have LPDs without clinical correlate in the same location as their ILPDs at other time points during recording. Conversely, two patients (Patients #8 and #9) also had clinical seizures without surface EEG correlate that manifested with the same clinical semiologies as seen during their ILPDs. All 9 patients with motor EPC were noted to have ILPDs starting the same day that monitoring was initiated; in the remaining patient with purely sensory seizures, the ILPDs were detected starting on the second day of monitoring. Of the patients with NILPDs, 66 (83%) had LPDs present on the first day of recording. No significant differences in age, sex, cEEG recording duration, lesional etiology, neoplastic etiology, clinical state during recording, presence of seizures, discharge CPC scores, or other parameters were noted between patients with ILPDs and those with NILPDs (Table 4). Post hoc analyses were performed to compare ILPDs with NILPDs within the central head region in order to see if there were any significant differences between these two groups when the effect of location was controlled (data not shown). In this exploratory analysis, there were trends suggesting that patients with central ILPDs tended to be younger, to have a better clinical state, and to be more likely to have a lesion in the sensorimotor cortex. They were also more likely to be monitored longer. There were no differences found in other clinical variables including discharge outcomes. In terms of electrographic characteristics of ILPDs in this subgroup, they tended to be faster in frequency and sharper in morphology at trend levels. There was also a trend towards more plus modifiers in the group with ILPDs: 3/7 (2 LPDs + F and 1 LPDs + R), as compared with 1/12 (LPDs + F) in the group with NILPDs. Other morphological characteristics and amplitudes did not differ between the two groups. 4. Discussion This study represents the first case series on ILPDs, to our knowledge. For purposes of this investigation, ILPDs were explicitly defined

as LPDs with a clear time-locked clinical correlate occurring at any point during cEEG monitoring; all other LPDs were considered NILPDs. This was done to assess the functional significance of dichotomizing ILPDs and NILPDs strictly on the grounds of a time-locked clinical correlate, which often occurs in practice [10]. The key finding was a significant difference in the localization of LPDs, with ILPDs having increased odds of involving central head regions as compared with NILPDs. No significant differences in odds between ILPDs and NILPDs were found for any of the other three head regions. A trend towards a higher proportion of lesions involving the primary sensorimotor cortex in the patients with ILPDs was noted. These findings suggest that categorizing LPDs as “ictal” based solely on a commonly utilized clinical definition of requiring a clear time-locked clinical correlate appears mainly to indicate the irritable region's proximity to the primary sensorimotor cortex. Our results demonstrate that the principal difference between ILPDs and NILPDs, as commonly defined, occurs on the basis of central versus noncentral localization. This finding challenges the concept that ILPDs and NILPDs, classified solely on the basis of a time-locked clinical correlate, truly represent disparate populations on a functional level. Lateralized periodic discharges originating over noncentral head regions would be innately less likely to demonstrate clear time-locked clinical correlates, although they may have more subtle manifestations that are difficult to characterize, particularly in patients with impaired mental status. For example, there have been prior case reports of aphasia [14,15] and prolonged confusional states [9] associated with LPDs. Lateralized periodic discharge locations given in these reports were described as either noncentral or hemispheric, having no comment on the specific locations of the maxima. In some cases, there were significant improvements noted in both clinical states and LPDs following treatment with antiepileptic drugs. In addition, multiple prior investigations utilizing metabolic imaging have demonstrated similar patterns between LPDs and seizures from a functional standpoint [9,16–18]. Thus, the absence of a clearly time-locked correlate to LPDs may not necessarily be synonymous with such LPDs being functionally “nonictal”. In order to determine if there really are distinct groups of potentially “ictal” and “nonictal” LPDs, future research will have to be systematic in assessing potential subtle behavioral and negative manifestations of LPDs, particularly in patients with LPDs maximal over noneloquent cortex. Alternative means, such as functional neuroimaging, could be considered in comatose patients where behavioral manifestations cannot be adequately assessed. In the meantime, clinicians should be aware of the limitations of using time-locked clinical correlates as a distinguishing feature that dictates management decisions.

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Table 2 Electrographic characteristics of ILPDs. Patient #

Frequency (Hz)

“Plus” modifier

Amplitude

Relative amplitude

Phases

Sharpness

Evolving, fluctuating or static

1 2 3 4 5 6 7 8 9 10

1 1 b0.5 0.5 1.5 0.5 b0.5 b0.5 1 1.5

+F +F None None +R None None +R None None

Medium Medium Medium Low Medium Medium Medium Medium Medium Medium

N2 N2 N2 N2 N2 N2 N2 N2 N2 N2

3 3 2 2 2 1 2 2 2 N3

Spiky Spiky Blunt Sharp Sharp Sharply contoured Sharply contoured Sharply contoured Sharp Sharp

Fluctuating Evolving Static Static Static Static Static Fluctuating Static Fluctuating

Characteristics of ILPDs based on the ACNS standardized terminology for critical care EEG [13].

Unfortunately, such clarification of the semantic definition of “ictal” LPDs does not shed further light on the controversy surrounding how (or even whether) to “treat” LPDs [10]. In our series, all clinical seizures within the population with ILPDs were controlled by the time of discharge, but there were no significant differences in discharge outcomes between the group with ILPDs and the group with NILPDs, suggesting that the presence or absence of associated time-locked clinical signs alone may not be the key factor for determining the pathophysiological significance or treatment implications of LPDs.

It should be noted that we did not always find a one-to-one correspondence between the location of LPD maxima and clinical symptoms, which likely relates to the fact that surface EEG does not reflect the entirety of intracortical activity. For instance, 3/10 patients with ILPDs had LPD maxima in noncentral locations. In addition, only 7/21 patients with central LPDs had ILPDs. These findings may be explained by the fact that superficial EEG potentials and spinal motor output are not always related and that synchronized motor output appears only when typical epileptic negative spikes appear in cortical layer V; however,

Fig. 2. Example of imaging and representative EEG tracing in a patient with ILPDs (Patient #7). (A–B) MRI demonstrates a lung cancer metastasis to the right precentral gyrus in the expected region of the homunculus corresponding to arm representation. White matter changes consistent with radiation necrosis are seen throughout the primary sensorimotor cortex on the right. (C) Representative EEG tracing demonstrates right centroparietal LPDs (C4 N P4) time-locked to clonic activity on recorded left arm EMG (blue tracing labeled “EMG” at the bottom of page), thus satisfying our criteria for ILPDs. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

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Table 3 Antiepileptic medications given to patients with ILPDs during admission. Patient #

Antiepileptic medications given

1 2 3 4 5 6 7 8 9 10

LEV, LZP, PHT, PPF, VPA LEV, PB LEV, LZP, PHT, VPA LEV, LZP, PHT, PPF CZP, LAC, LEV, LZP, PHT GBP, LEV, LZP LEV, LZP, PHT, VPA CZP, LEV, LZP, PHT LZP, PB, PHT, VPA MDZ, PPF, VPA

CZP = clonazepam, GBP = gabapentin, LAC = lacosamide, LEV = levetiracetam, LZP = lorazepam, MDZ = midazolam, PB = phenobarbital, PHT = phenytoin, PPF = propofol, VPA = valproic acid.

with or without this requisite intracortical activity, the EEG discharges seen at the cortical surface may appear similar [19]. Another similar consideration entails the relationship between ILPDs and their clinical correlate. Nine out of ten patients with ILPDs experienced classical motor EPC, and the remaining patient experienced time-locked, stereotyped sensory symptoms (essentially the sensory analog of motor EPC). Despite proposed similarities in the genesis of LPDs and EPC [5,20,21], clear temporal or spatial correlates between LPDs and muscle jerks are not always seen in motor EPC [20,21]. With the exception of only one patient (Patient #9), this tenet was completely borne out in our population with ILPDs. While EEG in each of these patients did demonstrate clear ILPDs as evidenced by timelocked relationships to clinical symptoms, 9/10 patients were also

Fig. 3. Location of LPDs and odds ratios for ILPDs by location. Distribution of LPDs across the four head regions is shown. ILPDs have significantly higher odds compared with NILPDs for involvement of central head regions. There are no other significant differences in odds between ILPDs and NILPDs for involvement of the other head regions.

noted to have the same LPDs without obvious time-locked clinical correlate at other points during recording. Additionally, in a minority (2/10 patients; Patients #8 and #9), we noted clinical seizures with

Table 4 Comparison of parameters between patients with ILPDs and those with NILPDs. Parameter

Number of patients with ILPDs (N) or value (mean ± SD) (Total N = 10)

Number of patients with NILPDs (N) or value (mean ± SD) (Total N = 80)

p-Valuea

Age (y) cEEG recording duration (d) Sex M F Location of LPDs Frontal Central Temporal Parietooccipital Lesion in the sensorimotor cortex Yes No Lesional Yes No Neoplastic lesion Yes No State during majority of recording Awake Lethargic Stuporous Comatose Best state during recording Awake Lethargic Stuporous Comatose Seizures recorded Yes No Discharge CPC score 1–2 (good outcome) 3–5 (poor outcome)

65.1 ± 15.1 5.5 ± 3.6

62.5 ± 15.1 5.7 ± 6.3

0.833 0.939

8 2

45 35

0.403

0 7 1 2

11 14 33 22

0.037

8 2 9 1

31 49 75 5

0.09

6 4

26 54

0.403

2 5 2 1

17 22 22 19

0.628

1 6 2 1

22 21 21 16

0.939

4 6

55 25

0.403

2 8

26 54

0.898

0.833

a All comparisons with 2-tailed Fisher's exact test except for: ages (2-tailed unpaired t-test), cEEG recording durations (2-tailed unpaired t-test), and clinical states during recording (rank-sum tests). All p-values are FDR adjusted.

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the same semiology occurring in the absence of any EEG correlate. Hence, it may be questioned whether LPDs are necessarily the causative etiology of clinical symptoms or whether both may represent potentially tandem manifestations of a common irritative focus. It is also possible that clinical symptoms may be caused by cortical repetitive discharges beyond the detection of scalp EEG [21]. This pilot study was limited by its small sample size and retrospective nature. For example, obtaining certain variables such as discharge outcomes required extrapolation based on our chart review, and we were not blinded to reclassification of the locations of LPDs. The goal of this study was to illustrate the limitations of the commonly used definition of “ictal” LPDs. We did not gather data on LPDs with more subtle clinical correlates such as aphasia and confusion, as we have found that these correlates are often not considered or well documented by neurophysiologists or clinicians. Such correlates are also often confounded by a patient's clinical state. We recognize that it is possible that there may turn out to be differences in the prognosis or other clinical characteristics of ictal versus nonictal LPDs once all possible manifestations of ictal LPDs can be considered. Our hope is that in challenging the significance of time-locked clinical symptoms as the only manifestation of “ictal” LPDs, we will motivate more systematic evaluation of potential subtle clinical manifestations of LPDs both in clinical care and in larger prospective studies. In our initial analysis, there were no significant differences in terms of demographics, discharge outcomes, or the occurrence of seizures between patients with ILPDs and those with NILPDs. We acknowledge that if all possible clinical manifestations of LPDs could be considered, we might find salient differences in one or more of these parameters. We did perform an exploratory subgroup analysis between our central ILPDs and NILPDs cases to remove the effect of location. The results of this analysis have to be interpreted with caution given the small sample size (N = 21) and post hoc nature, but trends towards younger age, better clinical state, and central structural lesions were noted in the group with central ILPDs. These trends should be reevaluated in future larger studies that look at more subtle clinical findings of LPDs that may be found in association with other brain regions. This study also did not compare the role of electrographic characteristics including frequency, amplitude, or morphology between classically defined groups with ILPDs and NILPDs. It is certainly possible that there are electrographic characteristics of LPDs that correlate to the expression of clinical symptoms. We did not perform this analysis on the whole population of LPDs as we suspect that there are cases of ictal LPDs with less clear-cut clinical manifestations within the classically defined group with NILPDs. Our post hoc analysis of electrographic characteristics of central ILPDs versus NILPDs did identify trends towards higher frequency and sharper morphology of LPDs within the group with ILPDs. Whether these features are unique markers of LPDs that are more likely to cause clinical manifestations or are simply correlated to patient level of consciousness will need to be looked at in future studies. If morphological differences between “ictal” and “nonictal” LPDs are borne out by future studies that can control for the effects of patient state and brain region, they may have direct applications in clarifying how to assess LPDs in comatose patients, which is a common clinical challenge. 5. Conclusions This study represents the first case series examining the utility of classifying LPDs as ILPDs or NILPDs based strictly on time-locked clinical symptoms, as is often employed in practice [10]. Our principal finding

was a significant difference in the localization of ILPDs and NILPDs, with ILPDs having elevenfold increased odds of being associated with central head locations. A trend towards a higher proportion of lesions involving the primary sensorimotor cortex in patients with ILPDs was also found. These findings raise important questions about whether any functional dichotomy truly exists between ILPDs and NILPDs as defined on the basis of strict time-locked clinical criteria or whether attempting to create this type of distinction is more of a semantic endeavor rather than a clinically salient one. Ultimately, such classification appears to convey neuroanatomical differences rather than more useful, functional distinction. Accordingly, the relevance and treatment implications of LPDs should not depend solely on the presence of overt time-locked sensory or motor manifestations, and concepts of “ictal” LPDs beyond this convenient, yet limited, clinical classification should be sought.

Disclosures The authors have no disclosures relevant to this publication.

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"Ictal" lateralized periodic discharges.

Whether lateralized periodic discharges (LPDs) represent ictal or interictal phenomena, and even the circumstances in which they may represent one or ...
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