Seizures and Encephalopathy Suzette M. LaRoche, M.D.1 ABSTRACT There is a complex relationship between seizures and encephalopathy. Seizures alone without any underlying neurologic or medical illness can be the sole cause of encephalopathy. Often these patients have a history of epilepsy, in which case accurate diagnosis is straightforward. Acute neurologic conditions often contribute to encephalop- athy, but also increase the risk of seizures—many of which are subclinical. In these scenarios, it can be difficult to determine whether the encephalopathy is caused by seizures, the underlying neurologic disorder, or both. In addition, systemic diseases are commonly associated with encephalopathy; they may also increase the risk of seizures, although less commonly than acute neurologic conditions, and therefore may go unrecognized. This review will examine common and uncommon causes of seizures in encephalopathic patients, typical clinical presentations as well as diagnosis and treatment. KEYWORDS: Seizure, encephalopathy, nonconvulsive status epilepticus, electroencephalogram, EEG monitoring There are various ways that seizures contribute tribution to morbidity and mortality, particularly if to encephalopathy. Altered mentation is typical during undetected and treatment is delayed. There is no the ictal or postictal phase and can occur in the setting of universally accepted definition of NCSE. Synonyms either isolated seizures or status epilepticus (SE). Con- include the terms non-tonic-clonic SE, spike-wave vulsive seizures rarely go undetected, particularly in stupor, dialeptic SE, and subtle SE. In addition, hospitalized patients already undergoing evaluation for clinical classification is quite complex and includes a encephalopathy or other medical conditions. However, heterogeneous group of disorders that each have differ- nonconvulsive seizures (NCS) have an extremely broad ent outcomes and management strategies. EEG find- Downloaded by: University of Kentucky. Copyrighted material. range of clinical presentation and require a high index of ings can be just as varied, ranging from continuous ictal suspicion for timely detection and treatment. Noncon- discharges, either focal or generalized, to periodic vulsive seizures occur most commonly following an patterns of undetermined significance. In addition, episode of generalized convulsive status epilepticus and there is no consensus on minimum duration of seizure have been documented to occur in up to 48% of these activity to qualify for an episode of nonconvulsive patients.1 However, increased use of continuous electro- status, with proposed times ranging from 5 to encephalogram monitoring (cEEG) has revealed that 30 minutes. Response to treatment with antiepileptic nonconvulsive seizures occur in a wide variety of patient medications has been proposed as a means of defining populations with no known history of clinical seizures. which clinical and EEG patterns represent ictal phe- In the spectrum of how seizures contribute to nomenon, but treatment response can be variable and encephalopathy, nonconvulsive status epilepticus does not always occur immediately following infusion (NCSE) is the most dangerous with significant con- of medication. 1Emory University School of Medicine, Atlanta, Georgia. Samuels, M.D. Address for correspondence and reprint requests: Suzette M. Semin Neurol 2011;31:194–201. Copyright # 2011 by Thieme LaRoche, M.D., Assistant Professor of Neurology, Director of Neuro- Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, physiology, Emory University School of Medicine, 1365 Clifton Road USA. Tel: +1(212) 584-4662. NE, Atlanta, GA 30322 (e-mail: [email protected]). DOI: http://dx.doi.org/10.1055/s-0031-1277987. Acute and Subacute Encephalopathies; Guest Editor, Martin A. ISSN 0271-8235. 194 SEIZURES AND ENCEPHALOPATHY/LAROCHE 195 Table 1 Incidence of Nonconvulsive Seizures (NCS) in Patients Undergoing Continuous Electroencephalogram Monitoring Author Population # of Patients Incidence of NCS Claassen et al4 Neuro ICU patients 570 19% Pandian et al6 Neuro ICU patients 105 27% Jordan et al5 Neuro ICU patients 124 34% Oddo et al10 Medical ICU patients 201 10% Vespa et al7 Intracerebral hemorrhage 63 36% Vespa et al7 Traumatic brain injury 94 22% Claassen et al4 Subarachnoid hemorrhage 108 18% Privitera et al2 Altered mental status 198 37% DeLorenzo et al1 Following GCSE 164 48% ICU, intensive care unit; GCSE, generalized convulsive status epilepticus. Studies evaluating the incidence of NCS and population, especially in patients who are comatose. In a NCSE are largely based on inpatient series of patients series of 108 patients with SAH, 19% were found to have with severe encephalopathy or coma. Privitera et al electrographic seizures, most of which were purely sub- prospectively evaluated 198 patients with encephalop- clinical.4 In addition, 70% of the patients with seizures athy of unknown cause and found either NCS or NCSE were in NCSE. Nonconvulsive status epilepticus has also in 74 (37%).2 Furthermore, clinical signs and history been shown to be an independent predictor of poor were not predictive of which patients experienced seiz- outcome in patients with SAH.9 ures. A more recent study by Towne and colleagues Intracerebral hemorrhage (ICH) has also been evaluated 236 critically ill patients in coma with no associated with a high rate of acute clinical seizures clinical signs of seizure activity. Routine EEG identified ranging from 3–19% of patients.11 Two studies have 19 (8%) in NCSE.3 The most common etiology was evaluated the incidence of seizures in patients with ICH hypoxia, but over one third did not have any obvious undergoing cEEG.8,12 Vespa et al found that 28% underlying neurologic disorder. Studies utilizing cEEG (18/63) of patients with ICH experienced nonconvulsive in patients at high risk for seizures admitted to neuro- seizures, which were associated with an increase in critical care units identified NCS or NCSE in 19–34% midline shift, higher NIH stroke scale scores, and worse (Table 1).4–6 Subclinical seizures are most common after outcome compared with ICH patients without seiz- resolution of generalized convulsive status epilepticus ures.12 In a series of 102 patients with ICH, seizures (GCSE). In the study by Delorenzo et al following were detected in 31% and over half were purely electro- resolution of GCSE, 48% of patients were found to graphic.8 Perhaps more importantly, seizures were asso- have ongoing NCS.1 However, many patients with no ciated with an increase in the volume of hemorrhage and prior history of clinical seizures are also found to have a trend toward worse outcomes. NCS when undergoing cEEG.2,7–9 In the series by Ischemic stroke is a common cause of both acute Oddo et al, 201 patients admitted to the medical and chronic seizures, and the leading cause of epilepsy in Downloaded by: University of Kentucky. Copyrighted material. intensive care unit (ICU) without any known neurologic the elderly population. Seizure rates in hospitalized injury underwent EEG monitoring for changes in men- patients average from 5–17%.7 Although clinical seizures tal status.10 Electrographic seizures were detected in 21 have been associated with increased morbidity and (10%), and two thirds of these seizures were not asso- mortality in the acute setting, studies of the effect of ciated with any clinical correlate. nonconvulsive seizures in patients with ischemic stroke are lacking. However, as with SAH and ICH, cEEG monitoring has shown that the incidence of seizures in CAUSES OF SEIZURES this patient population is underestimated when relying AND ENCEPHALOPATHY on reports of clinical seizures alone.7 Seizures are a common complication following Common Causes cardiac arrest and can have a variety of clinical presenta- Acute cerebrovascular disease is a common precipitant of tions from myoclonus to generalized convulsions. Clin- seizures. Seizures are a well-recognized complication of ical seizures in these patients are generally regarded as an subarachnoid hemorrhage (SAH) with prior studies effect of the anoxic encephalopathy rather than a con- demonstrating clinical seizures in 4–9% of patients tributing cause, and their presence can be a useful marker during hospitalization.11 However, more recent studies for prognosis. American Academy of Neurology (AAN) of patients undergoing cEEG have shown that electro- practice guidelines support a poor prognosis for patients graphic seizures are even more common in this patient with myoclonic status epilepticus within the first day of 196 SEMINARS IN NEUROLOGY/VOLUME 31, NUMBER 2 2011 cardiac arrest (level B).13 Less is known about the population,19 seizures have not traditionally been con- implications of nonconvulsive seizures following anoxic sidered to be a significant issue until recently. A retro- brain injury, although cEEG studies have shown that spective study of septic patients undergoing EEG they are quite common, seen in up to 20% of patients in monitoring in a medical intensive care unit found one series.4 With increasing utilization of therapeutic electrographic seizures in 16% (most of which were hypothermia following cardiac arrest, even more ques- subclinical) and noted periodic epileptiform discharges tions have arisen regarding the incidence and implica- in another 16% of patients.10 Risk factors for seizures tions of seizures in association with anoxic brain injury, included older age, renal failure, and shock. Seizures, as which merit much further investigation.