Lateralized Periodic Discharges PDF

18 Lateralized Periodic Discharges Jessica W. Templer and Elizabeth E. Gerard IN THIS CHAPTER Epidemiology, etiology, and natural history of lateralized periodic discharges (LPDs) Standardized definition and subtypes...

18 Lateralized Periodic Discharges Jessica W. Templer and Elizabeth E. Gerard IN THIS CHAPTER Epidemiology, etiology, and natural history of lateralized periodic discharges (LPDs) Standardized definition and subtypes Association of LPDs with clinical and subclinical seizures Prognostic implications of LPDs KEY POINTS Lateralized periodic discharges (LPDs) are stereotyped repetitive discharges that occur at regular intervals and maximally involve one hemisphere. LPDs are classically known by their affiliation with herpes encephalitis, but the most common etiology is ischemic stroke. LPDs are associated with an increased risk for seizures. The clinical significance and management of LPDs is controversial, partic- ularly in comatose patients. Many experts regard LPDs as a pattern on the “ictal–interictal continuum,” representing an unstable, potentially epilepto- genic state. I. BACKGROUND A. Epidemiology and natural history The frequency of lateralized periodic discharges (LPDs) documented on continuous EEG recordings has been reported to range between 6.2% and 8.6% (1–3). In a study from India by Rai et al. (27), LPDs were seen in 47% of 99 neurological and neurosurgical intensive care patients with altered sensorium in whom treating physicians had a high suspicion for nonconvulsive seizures (NCS). Of note, 22% of patients had presented with a clinical diagnosis of status epilepticus. LPDs are most commonly seen in patients with focal neurologic deficits, and are also associated with varying degrees of altered consciousness. 160 Copyright Springer Publishing Company. All Rights Reserved. From: Handbook of ICU EEG Monitoring, Second Edition DOI: 10.1891/9780826168627.0018  Chapter 18 Lateralized Periodic Discharges 161 In three large series, 10% to 35% of patients with LPDs were comatose (4–6), and the predominant etiology was an acute cortical or subcortical structural lesion. However, in a case-control study of patients with LPDs and no acute brain injury, 87% had abnormal consciousness. Therefore, LPDs were found to be an independent predictor of decreased consciousness in patients without acute brain injury (3). B. Etiology LPDs are frequently associated with acute, structural lesions involving the cortex. Ischemic stroke is the most common etiology in adult patients. Other prevalent eti- ologies include viral or autoimmune encephalitis, brain tumors, intracranial hemor- rhage, and anoxic encephalopathy. In the pediatric population, an infectious etiology may be more common, while stroke and hypoxic–ischemic encephalopathy (HIE) are often associated with LPDs in neonates. LPDs have also been described in the setting of Creutzfeldt–Jakob disease (CJD), subarachnoid hemorrhage, demyelinating diseases, posterior reversible encepha- lopathy syndrome (PRES), migraine, mitochondrial encephalopathy with lactic aci- dosis and stroke-like episodes (MELAS), advanced stages of progressive myoclonic epilepsy, and neurosyphilis. Metabolic disturbances in combination with structural lesions may have a role in the genesis of LPDs, but are not a requirement. In early studies, uremia, electrolyte disturbances, and a history of alcohol abuse were common clinical correlates of LPDs (4), but have not been consistently reported in more recent, large series (3,7). LPDs are typically regarded as a transient phenomenon following an acute neuro- logic insult and usually resolve within days to weeks. Less commonly, LPDs can be seen as a chronic phenomenon associated with epi- lepsy. In 1996, Pohlmann-Eden et al. reported chronic LPDs in patients with preexist- ing structural lesions and localization-related epilepsy (8), an observation that was recently replicated by Orta et al. (6). A study evaluating adult and pediatric patients with LPDs and no evidence of acute or progressive brain lesions found that the majority had a history of remote brain injuries as well as epilepsy. However, this group accounted for only 26% of all patients with LPDs (3). In addition, larger series of patients with LPDs have reported a history of epi- lepsy in only 5% to 29% (5,7,9). II. BASICS A. EEG characteristics LPDs are discrete repetitive discharges with a consistent morphology that recur periodically, typically at regular intervals of 0.5 to 3 Hz (Figure 18.1). Simultaneous EKG recording is important to distinguish LPDs from EKG or pulse artifact. LPDs are typically broadly lateralized over one hemisphere, but may be maximal in any focal, hemispheric brain region. 162 Part III EEG Interpretation FIGURE 18.1 LPDs in a patient with temporal lobe epilepsy who was admitted for breakthrough seizures. A 69-year-old man with history of temporal lobe epilepsy, left occipital ischemic stroke, and hypertension. He was found unresponsive at home and had a tonic–clonic convulsion en route to the hospital. Upon admission, he was found to be in nonconvulsive status epilepticus arising from the left hemisphere with intervening periods of LPDs arising from the same region. LPDs, lateralized periodic discharges. The field of the individual discharges is typically broad, including the parasagit- tal and temporal chains, but it can be more restricted. LPDs can involve the contralateral hemisphere, particularly if the discharges are maximal in the frontal or occipital regions (referred to as LPDs; bilateral asym- metric, see also Chapter 16) (4) (see ebook for Figure S-18.1). LPDs are usually associated with additional EEG evidence of ipsilateral cerebral dysfunction (focal slowing, loss of posterior dominant rhythm). The contralateral hemisphere may be unaffected or may demonstrate evidence of encephalopathy, depending on the clinical state of the patient. As classically described, the individual discharges in LPDs are usually epileptiform in appearance. LPDs are typically sharp waves or sharp-wave complexes ranging from 50 to 300 μV in amplitude. Standardized American Clinical Neurophysiology Society (ACNS) critical care EEG terminology defines LPDs as all periodic discharges regardless of mor- phology or duration (e.g., blunt delta waves that recur in a stereotyped periodic fashion would also be classified as LPDs). B. Neuroimaging LPDs are most commonly associated with cortical gray matter or subcortical gray and white matter lesions (64%), although they can also occur in the setting of subcortical white matter lesions alone, or rarely with isolated subcortical gray matter lesions (6,10). However, studies have shown that between one-quarter and one-third of patients with LPDs have no structural abnormality on neuroimaging (5,7).  Chapter 18 Lateralized Periodic Discharges 163 C. Association with seizures Clinical seizures occur in the majority of patients with LPDs. In 1989, Snodgrass et al. reported clinical seizures in 90% of 147 patients with LPDs (7). In this study, seizures were most commonly noted prior to, or at the same time as, the detection of LPDs. In a review of 16 retrospective series of EEG recordings containing LPDs, clin- ical seizures were noted in 47% to 100% of patients (8). However, as a history of clinical seizures is a common indication for EEG, these retrospective studies may have been affected by selection bias. In a study involving 82 patients with LPDs, 70% had clinical seizures. In this series, seizures were more common in patients with LPDs that were associated with stroke and brain tumors and less common in patients with infection or other etiologies (6). A series of 130 patients with LPDs showed that 50% of patients experienced clinical seizures during the course of their acute illness. In this study, there was no correlation between the incidence of clinical seizures and the underlying etiology associated with the LPDs (5). Focal motor seizures are the most common seizure type associated with LPDs (4,5,7). LPDs are highly associated with NCS on continuous EEG. Claassen et al. documented a significant association between LPDs and NCS on prolonged EEG recordings. The authors found that in patients who had sei- zures identified during continuous EEG, 40% also had LPDs, whereas LPDs were seen in only 11% of patients without seizures (11). This study also demonstrated that LPDs were commonly associated with sei- zures that occurred after the initial 24 hours of EEG recording. Therefore, EEG monitoring longer than 24 hours should be considered in patients with LPDs. In the largest study of periodic patterns to date, Ruiz et al. found that 44% of 802 continuous EEG records with LPDs also contained electrographic seizures, the majority of which were nonconvulsive. Of all periodic or rhythmic patterns, LPDs had the highest association with seizures (12). The same study also found that the frequency of LPDs was correlated to seizure risk: LPDs less than 1.5 Hz were associated with seizures in 40% of recordings, whereas seizures were seen in 50% of recordings with LPDs between 1.5 and 2 Hz, and 66% of recordings with LPDs 2 Hz or greater. D. Prognosis Across several studies evaluating both routine and continuous EEG recordings, LPDs have been associated with a high mortality rate, ranging from 24% to 53% (8,9). In two pediatric series, LPDs were associated with death in approximately one-quar- ter of children (13,14). A review of 79 patients with LPDs (6) found that only 21.5% returned to indepen- dent function, with 54.4% remaining dependent and 24% dying. In this study, patients with a neoplastic etiology of LPDs were more likely to have a poor outcome compared to patients with a vascular etiology. The presence of clinical seizures in a patient with LPDs was associated with a better prognosis than LPDs without clinical seizures (6), although this was not observed in an earlier series (5). LPDs have been shown to be independent predictors of poor outcome (moder- ate-to-severe disability or death) in a variety of patient populations. 164 Part III EEG Interpretation In a case-control study of patients presenting with altered mental status matched for age, gender, and etiology, LPDs on routine EEG were associated with severe morbidity or death. Only 31.9% of patients with LPDs were found to be independent at subsequent hospitalizations (15). LPDs have been shown to be an independent predictor for poor outcome in patients with subarachnoid hemorrhage (16), intracranial hemorrhage (17), and patients in the medical intensive care unit (18). LPDs have also been shown to be associated with poorer outcomes at hospital discharge in the absence of acute or progressive lesions (3). Adults with a prior history of epilepsy and children with acute infections tend to have a better prognosis than patients with LPDs owing to other etiologies. LPDs and subsequent epilepsy LPDs have been associated with the risk of developing subsequent epilepsy. Likelihood of developing epilepsy in patients with LPDs has been reported to range from 10% to 56% (5,19). In ICU patients with LPDs and no prior history of epilepsy, the presence of LPDs and electrographic seizures was associated with posthospital seizures in 49%. However, in patients with LPDs and no seizures on EEG, the risk for posthospital seizures was 17% (9). E. Subtypes of LPDs LPDs plus The term LPDs plus was originally proposed by Reiher et al. to describe LPDs associated with superimposed rhythmic discharges (usually low-voltage fast activity). Based on the ACNS terminology, LPDs plus (LPDs+) is now defined as patterns that are more “ictal appearing,” including LPDs with superimposed fast activity (F), rhythmic activity (R), or both (FR) (Figure 18.2). In the large series by Ruiz et al. LPDs+ were present in 37% (293 of 802) of records with LPDs. LPDs + were more likely to be associated with seizures (58%) versus LPDs without the plus modifier (36%) (OR 2.00, 95% CI) (12). Interestingly, one study found that the presence of LPDs was associated with a significantly worse outcome compared with LPDs+ (15). The reason for this finding is unclear. The presence of LPDs plus has also been correlated with a higher risk of devel- oping subsequent epilepsy, compared with LPDs alone (15). Stimulus-induced LPDs Hirsch et al. described the phenomenon of stimulus-induced rhythmic, peri- odic, or ictal discharges (SIRPIDs) in 33 stuporous or comatose patients (20). Out of 33 patients, nine had stimulus-induced LPDs (SI-LPDs). Five (55%) of the patients with SI-LPDs had electrographic or clinical seizures or sta- tus epilepticus during their acute illness. Ruiz et al. found no significant difference in the association with seizures between a stimulus-induced pattern and a spontaneous pattern; however, this study was limited owing to the rarity of recordings that contained both a stimu- lus-induced pattern and a seizure in the same record (12). A better understanding of the pathological or prognostic significance of SI-LPDs and whether it is different from spontaneous LPDs will hopefully be achieved with larger population studies in the future.  Chapter 18 Lateralized Periodic Discharges 165 FIGURE 18.2 LPD+F following resolution of focal motor seizures. A 42-year-old man with history of CNS vasculitis complicated by left parietooccipital epilepsy. He presented to an outside hospital with a urinary tract infection and right arm clonic seizures. Upon transfer, he was noted to have frequent clonic seizures of the right eyebrow and right lip. After clinical seizures resolved, EEG demonstrated left hemisphere LPDs with superimposed fast activity, maximal in the left parietooccipital region. CNS, central nervous system, LPD+F, lateralized periodic discharges with superimposed Fast activity. F. Bilateral independent periodic discharges Bilateral independent periodic discharges (BIPDs) are asynchronous periodic dis- charges that occur independently over both hemispheres (Figure 18.3; see ebook for Figure S-18.2). BIPDs are much less common than LPDs; thus, data on their significance is limited. BIPDs are associated with similar etiologies as LPDs (stroke, infection, tumor); how- ever, metabolic abnormalities, cardiac arrest, and bilateral lesions may be more common with BIPDs (6,12). Coma is more commonly associated with BIPDs than with LPDs (47.8% vs. 14%) (6,21). Studies to date have shown that seizures are less common in patients with BIPDs compared with patients with LPDs: 29% versus 44% in one study (12) and 43% versus 70% in another study (6). However, in a small series of patients with central nervous system (CNS) infections, 4 of 4 (100%) with BIPDs had clinical or electrographic sei- zures, whereas only 8 of 14 (57%) with LPDs experienced seizures (22). Mortality is greater in patients with BIPDs compared with LPDs. In a single study that included 23 patients with BIPDs and 82 patients with LPDs, mortality was greater in patients with BIPDs versus LPDs (39% vs. 24%), although there was no clear difference in functional outcomes (6). This was replicated in another study comparing mortality in patients with BIPDs versus LPDs (50% vs. 30.2%) (13). This increased rate in mortality was also seen in a case-control series that found a mortality rate of 100% (4 of 4) for patients with BIPDs compared with 42.6% (20 of 47) of patients with LPDs (15). 166 Part III EEG Interpretation FIGURE 18.3 BIPDs in the setting of West Nile encephalitis and seizures. Periodic discharges are seen independently over the right hemisphere, maximal in the right temporal region, as well as the left hemisphere, maximal in the left parietal region in a 49-year-old woman with history of end-stage renal disease status post–kidney transplant, who presented with West Nile encephalitis complicated by seizures. BIPDs, bilateral independent periodic discharges. At follow-up, an average of 2 to 2.5 years after an index hospitalization, the majority of patients with BIPDs had moderate disability (Modified Rankin Scale [MRS] = 3), while patients with LPDs had slight disability (MRS = 2) (13). III. FURTHER CONSIDERATIONS/REMAINING QUESTIONS A. What is the incidence of LPDs in critically ill patients? Existing studies of LPDs are retrospective and based largely on intermittent recordings. The true prevalence of LPDs and their association with seizures and prognostic sig- nificance will continue to be better defined in prospective studies using continuous EEG monitoring of unselected critically ill patients. B. Do LPDs represent an ictal pattern? Debate exists over the pathophysiological significance of LPDs and how aggres- sively they should be managed. LPDs are generally considered an ictal pattern when they are associated with a clinical correlate. Focal clonic seizures including epilepsia partialis continua (EPC) contralateral to LPDs are a common manifestation of ictal LPDs that are easy to recognize. In the case of EPC, LPDs are considered ictal when individual discharges are time-locked to electromyographic (EMG) recordings showing clonic activity (Figure 18.4). However, a common practice of defining LPDs as “ictal” only when they have a motor correlate is probably overly simplistic. One study compared the location of ictal LPDs (defined by motor correlate) to the location of “nonictal” LPDs.  Chapter 18 Lateralized Periodic Discharges 167 FIGURE 18.4 Ictal LPDs correlating to clonic movements of the right leg. Left hemisphere LPDs, maximal in the left frontocentral region, are time-locked to clonic movements of the right leg noted on electromyogram (EMG) (bottom trace) in a 66-year-old patient with a left frontotemporal anaplastic astrocytoma, who presented in epilepsia partialis continua. LPDs, lateralized periodic discharges. Ictal LPDs were 11 times more likely to be associated with the LPDs that were maximal in the central head regions near the motor cortex. Thus, the motor symptoms in these cases of ictal LPDs was principally a reflection of the location of the LPDs (23). On the other hand, clinical manifestations of LPDs can be subtle if they are located in noneloquent cortex (parietal, temporal or occipital, or frontopolar). In these patients, LPDs may be associated with subtle or subjective clinical cor- relates such as eye deviation, hemiparesis, aphasia, hemianopsia, or sensory disturbances. In patients with altered mental status or coma, discerning a clinical correlate of LPDs can be particularly difficult. One case series described seven elderly patients with recurrent confu- sional states including speech disturbance and visual hallucinations that were temporally associated with LPDs (24). LPDs tended to be maximal over the posterior hemispheres (temporopari- etooccipital regions). Both LPDs and clinical symptoms resolved with anti- seizure drug (ASD) treatment. LPDs have been associated with regional increases in glucose metabolism on PET and increased cerebral perfusion on single photon emission CT (SPECT; see ebook for Figure S-18.3) (25,26). Some have argued that these metabolic alterations indicate that LPDs are a form of partial status epilepticus, whereas others interpret this as an indication that LPDs are markers of an unstable pathophysiological state on an ictal–interictal continuum. C. What is the appropriate management of patients with LPDs? No consensus exists on the appropriate management of LPDs, and there is no data to indicate whether intervention improves outcome in comatose patients with this electrographic pattern. 168 Part III EEG Interpretation LPDs may have different implications depending on the clinical scenario, and this should be taken into account in determining a treatment plan. Neuroimaging should be performed in all patients with LPDs, and metabolic or other reversible systemic conditions should be treated. Patients with LPDs have been found to be over 10 times more likely to have focal lesions compared with patients with only seizures on continuous EEG monitoring (9). Given the association between LPDs and subclinical seizures, prolonged EEG mon- itoring, ideally greater than 24 hours, is recommended in these patients. ASD prophylaxis Given the strong association between LPDs and seizures, most patients with LPDs should be treated with a prophylactic ASD for at least the acute phase of their illness. As a percentage of patients presenting with LPDs and seizures will develop epilepsy, it may be worthwhile to continue antiseizure medications for a period of time after hospitalization. Elimination of LPDs Typical practice is not to escalate ASD treatment with the goal of eliminating LPDs in the absence of a clear clinical ictal correlate. LPDs often resolve on their own over days to weeks without additional treat- ment, which would support conservative management. On the other hand, the fact that LPDs have been associated with evidence of focal hypermetabolism on PET and SPECT imaging may support more aggres- sive treatment. The resolution of LPDs in addition to improvement in clinical symptoms (resolu- tion of focal deficits or confusion) in response to a low-dose benzodiazepine or a loading dose of an ASD suggests that LPDs represent an ictal state, and that further management with ASDs should be strongly considered. IV anesthesia is generally not indicated to treat LPDs in the absence of seizures as anesthetics can be associated with increased morbidity and can limit the ability to assess the patient’s clinical state. Prospective controlled studies will be necessary to determine the correct approach to treating LPDs, particularly in comatose patients. SUPPLEMENTAL FIGURES The following figures can be located in the ebook: FIGURE S-18.1 LPDs-bilateral asymmetric in a man with lung adenocarcinoma who presented with clinical seizures and was found to have multiple brain metastasis. FIGURE S-18.2 Bilateral independent periodic discharges time locked with myoclonic jerks of the left leg in a patient with autoimmune encephalitis with anti-GAD antibodies. FIGURE S-18.3 SPECT scan demonstrating focal hyperperfusion corresponding to the distribution of the LPDs. References 1. Gaspard N, Manganas L, Rampal N, et al. Similarity of lateralized rhythmic delta activity to periodic lateralized epileptiform discharges in critically ill patients. JAMA Neurol. 2013;70(10):1288–1295. 2. Sen-Gupta I, Schuele SU, Macken MP, et al. “Ictal” lateralized periodic discharges. Epilepsy Behav. 2014;36:165–170.  Chapter 18 Lateralized Periodic Discharges 169 3. Sainju RK, Manganas LN, Gilmore EJ, et al. 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