Evaluation of The Patient With Spells

Review Article
Address correspondence to Dr Susannah Cornes, UCSF Epilepsy Center, 400 Parnassus Avenue ACC-8, Box 0138, San Francisco, CA 94143-0138, Susannah.cornes@ucsf.edu. Relationship Disclosure: Dr Cornes and Dr Shih report no disclosure. Unlabeled Use of Products/Investigational Use Disclosure: Dr Cornes and Dr Shih report no disclosure. Copyright * 2011, American Academy of Neurology. All rights reserved.
Evaluation of the Patient With Spells

Susannah Brock Cornes, MD; Tina Shih, MD ABSTRACT
Purpose of Review: The neurologic consultant is frequently called to evaluate the patient with transient neurologic deficits, or spells. Spells can present with a broad array of clinical features, making a systematic evaluation challenging. Familiarity with a variety of key features for different spell types will help the consultant create an appropriate differential diagnosis to guide the diagnostic evaluation. Recent Findings: Recent practice parameters outline the appropriate evaluation for patients presenting with first unprovoked seizure, and an update in the International League Against Epilepsy classification scheme for seizures has shifted the terminology used to describe these spells. When a spell cannot be unambiguously identified as a seizure, recent studies propose features to help distinguish syncope, sleep disorders, and psychogenic nonepileptic seizures. For patients who are critically ill, extended EEG monitoring is increasingly available, and there is a growing appreciation for the high burden of seizures and status epilepticus in the intensive care unit population. Summary: This article reviews the most common paroxysmal spell types encountered on the acute care ward and in the intensive care unit, discusses clinical features that help distinguish various spell types, and proposes a systematic evaluation for use by the neurologic consultant.
Continuum Lifelong Learning Neurol 2011;17(5):9841009.
INTRODUCTION Patients with spells can present with a wide array of symptoms. A patient may be said to have had a spell after an acute loss of consciousness followed by full neurologic recovery. Conversely, a critically ill patient may present with paroxysmal symptoms or a fluctuating course that suggests a more persistent condition punctuated by another superimposed medical problem. Spells may be characterized by changes in awareness, attention, or perception or by abnormal movements. The spell itself may be quite subtle and not apparent to casual bystanders, or it may be dramatic and disruptive. Spells may last seconds or continue for several hours. The diagnostic possibilities in the patient with spells vary when consulting on the acute care ward as opposed to consulting in the intensive care unit (ICU). In
the ward patient, spells can largely be divided into two categories: seizures and spells that mimic seizures. In the ICU patient, this division remains, but a third category should be added for diagnoses that result in both critical illness and symptomatic seizure (Table 2-1). Many, although not all, causes for spells are imminently treatable, so the ability to arrive at the correct diagnosis is rewarding for the practitioner and important for the patient. This article discusses the evaluation of spells in typical ward and ICU consultations encountered by the neurohospitalist. WARD CONSULTATION The ward consult patient with spells, unlike the critically ill patient, experiences paroxysmal neurologic symptoms with a return to normal (or baseline) function in between episodes. A relatively small
October 2011
984
www.aan.com/continuum
Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.
KEY POINTS
TABLE 2-1 Diagnoses Associated With Episodic Neurologic Deficits

b Ward Consult Patient Seizure subtypes Provoked or unprovoked seizure Epilepsia partialis continua Complex partial status epilepticus Absence status epilepticus Spells that mimic seizures Syncope Migraine TIA (limb shaking, drop attacks) Sleep disorders (cataplexy, parasomnia, REM behavior disorder, periodic limb movements during sleep) Episodic movement disorders (paroxysmal dyskinesia, myoclonus) Psychogenic nonepileptic seizure Vestibulopathy Transient global amnesia b Intensive Care Unit Consult Patient Seizure subtypes Provoked or unprovoked seizure Generalized convulsive status epilepticus Nonconvulsive status epilepticus Myoclonic status epilepticus Spells that mimic seizures Episodic movement disorders (myoclonus, asterixis) Psychogenic nonepileptic seizure Fluctuating encephalopathy and delirium Diagnoses associated with critical illness that classically include seizure Posterior reversible encephalopathy syndrome Paraneoplastic syndrome (limbic encephalitis) Carcinomatous meningitis
h Spells can present with

a broad array of clinical features, making a systematic evaluation challenging.
h The diagnostic
possibilities in the patient with spells can largely be divided into two main categories: seizures and spells that mimic seizures.
h The key features of the

spell should be noted, such as the patients subjective experience, the spells tempo, the characteristics of any abnormal movements, and any associated triggers. A secondhand account by a family member or other witness is essential when the seizure involves confusion or loss of awareness.
number of diagnoses are associated with transient, resolving neurologic deficits, and many of them can be distinguished by their tempo and clinical characteristics (Tables 2-2 and 2-3). This section reviews these diagnoses, their key features, and an approach to their evaluation. Seizure The clinical features of seizures vary according to the seizure type and underlying neuroanatomic substrate. Seizures are stereotyped spells caused by abnormal electrical brain activity and can be provoked by a variety of conditions or occur spontaneously without any identifiable cause. They are classified according to whether the abnormal activity is generalized (involving bilateral neural networks) or focal (involving neural networks
Continuum Lifelong Learning Neurol 2011;17(5):9841009
present in one lobe or hemisphere) and, for focal seizures, according to whether associated impairment of awareness is present (focal seizures with dyscognitive features).1 Familiarity with the typical features of seizures will help the clinician distinguish seizures from other types of spells and may also aid in the anatomic localization of the seizure focus (Table 2-4).2 The key features of the spell should be noted, such as the patients subjective experience, the spells tempo, the characteristics of any abnormal movements, and any associated triggers. A secondhand account by a family member or other witness is essential when the seizure involves confusion or loss of awareness. When a patient has a history of more than one spell or spell type, each should be detailed independently,
985
Spells
TABLE 2-2 Major Presenting Features of Spells in the Ward Patient

b Spells With Loss of Consciousness or Impaired Awareness as Major Clinical Feature Seizure Syncope Migraine with or without headache Psychogenic nonepileptic seizure b Spells With Shaking or Trembling as Major Clinical Feature Movement disorders (myoclonus, tremor, dyskinesia) Seizure Limb-shaking TIA Periodic limb movements during sleep/restless legs syndrome Psychogenic nonepileptic seizure b Spells With Falling or Drop Attacks as Major Clinical Feature Seizure Movement disorder (myoclonus) Cataplexy Drop attack TIA Psychogenic nonepileptic seizure
keeping in mind that stereotypy (or similarity of the manifestations from one spell to the next) is a cardinal feature of seizures and that the absence of any stereotypical features may raise doubt as to the diagnosis. Other distinguishing features of seizures include a sudden onset, a rapid crescendo to maximal severity of symptoms, a short duration of 1 minute on average, and the presence of postevent sedation or confusion. A history of incontinence or tongue biting during the event should be noted when present but does not distinguish seizure from syncope. A history of a stereotyped subjective experience at the onset of the spell, particularly when it is a prototypical aura such as a rising epigastric sensation, will also be helpful in securing the diagnosis. After a diagnosis of seizure has been made, the consultant should then search for an acute proximate cause for the seizure (Table 2-5). When a cause can be identified, the seizure is said to have been provoked, and the most effective treatment will focus on the underlying cause rather than the administration of anticonvulsants, especially if the cause is reversible.
When an acute proximate cause for a seizure is not identified, the seizure is said to be unprovoked and has a tendency to recur in approximately one-half of cases.3 After a second unprovoked seizure the recurrence rate is nearly 75%, and epilepsy is generally diagnosed. The evaluation in that case will seek to identify a cause for epilepsy, which can be found in one-third of patients and may include head trauma, neurodegenerative disease, or various focal brain lesions. The physical examination following a suspected seizure should assess for any signs associated with provoking factors (eg, nuchal rigidity, asterixis, vital sign abnormalities) and should include a thorough skin examination to assess for evidence of trauma or neurocutaneous findings. The neurologic examination should include a thorough assessment of mental status to identify any remaining postictal confusion or any evidence of language dysfunction that would suggest a dominant hemisphere event. In general, focal findings should be sought, as these often suggest a focal onset for the seizure. The laboratory evaluation should look for abnormalities associated with provoked
October 2011
986
TABLE 2-3 Distinguishing Features of Seizures and Seizure Mimics Psychogenic Sleep Movement Nonepileptic Disorder Disorder Seizure
None None Variable
Feature
Aura (subjective experience or warning)
Seizure
Rising epigastric sensation, nausea, olfactory or gustatory hallucination, ` fear, deja vu or jamais vu, positive symptoms
Syncope
Tunnel vision, nausea, vomiting, diaphoresis, dizziness
Migraine
TIA
None Fortification spectra, scotoma, nausea, vomiting, photophobia or phonophobia, positive symptoms Sudden
Gradual Sudden, Onset/tempo Sudden, rapid rapid crescendo to crescendo to maximal maximal severity severity Duration Movements 1 to 2 minutes Less than 5 minutes 30 minutes to hours None
Variable
Variable
Waxing and waning
Minutes to hours
Minutes to hours
Minutes to hours Chorea, ballismus, athetosis, dystonia, spasm, myoclonus, tics, tremor Improves during sleep Unlikely
Minutes to hours Pelvic thrusting, asynchronous or asymmetric movements, other variable features Office visit, emotional experience Variable
Tonic, clonic, Atonic, myoclonic atonic, myoclonic, dystonic, complex
None, except Atonic, limb-shaking complex TIA or atonic
Pattern
None
From standing Yes
None
None
During sleep Variable
Variable Impaired awareness, loss of consciousness Postictal
Variable
Unlikely
Yes, minutes None to hours Cyanosis Often marked tachycardia Pallor
None or modest confusion No change
None
None
None
None or variable No change Mild tachycardia Variable
Appearance Vital signs
No change
No change No change
Orthostatic No change
Hypertension No change No change
Variable Trauma, tongue biting, and incontinence
Variable
None
None
None
None
Adapted from Drazkowski JF, Chung SS. Differential diagnosis of epilepsy. Continuum Lifelong Learning Neurol 2010;16(3):36Y56. Copyright B 2010, American Academy of Neurology. All rights reserved.
987
Spells
seizures, as outlined in Table 2-5, and may include levels for antiepileptic medications in patients who already have a diagnosis of epilepsy. Prolactin level may be sent if it can be obtained within 10 to 20 minutes of a convulsive event and processed within 8 hours or else kept cold. A prolactin level at least twofold higher than baseline is consistent with a diagnosis of seizure. However, a negative result does not rule out seizure, and the test is not helpful in the assessment of nonconvulsive seizures or status epilepticus.4 In addition, prolactin may also rise following syncope, so is not useful for distinguishing seizures
from syncope. Lumbar puncture is indicated if signs of infection are present, including fever, pleocytosis, nuchal rigidity, or recent contact with ill persons; a lower threshold for obtaining CSF in patients who are immunosuppressed is appropriate. Almost one-quarter of patients with convulsive seizures will have a mild pleocytosis, but other causes for the pleocytosis should always be sought and eliminated.5 Patients who present with a new diagnosis of seizure should undergo an imaging study, particularly those with suspected focal seizures or focal examination findings.6 CT of the head is
TABLE 2-4 Lateralizing and Localizing Features of Focal Seizures

b Frontal Lobe Prominent motor activity: hemiclonic with postictal hemiparesis (motor cortex), asymmetric tonic posturing (supplementary motor area), asynchronous movements Complex automatisms: running, pounding, rocking Vocalizations: swearing, shouting Predilection for sleep Eye deviation away from the seizure focus (frontal eye fields) b Temporal Lobe Aura: rising epigastric sensation; nausea; olfactory, gustatory, or auditory ` (lateral onset) hallucination; fear; deja vu; jamais vu Behavioral arrest Ipsilateral automatisms: lip smacking, picking, postictal nose wiping Contralateral dystonic limb posturing Language dysfunction (if dominant hemisphere) b Parietal Lobe Somatosensory phenomena Complex posturing b Occipital Lobe Stereotyped, nonthreatening, elementary, or complex visual phenomena including macropsia, micropsia, palinopsia, and metamorphopsia Contralateral or ipsilateral eye deviation b Hypothalamus Ictal laughter
988
October 2011
generally performed when the patient presents emergently and has not returned to neurologic baseline. The practitioner should be aware, however, that CT may fail to detect several findings, such as cortical malformations, mesial temporal sclerosis, some small tumors, acute infarcts, subacute or chronic hemorrhages, and subtle white matter changes. MRI of the brain is therefore indicated as part of the subsequent workup and can often be obtained following hospital discharge in patients without neurologic deficits. Routine EEG is indicated in the workup of a suspected unprovoked seizure7 and will reveal epileptiform abnormalities in approximately one-fourth of patients. An initially normal EEG may be repeated up to two times to improve sensitivity to 60% to 90%. When the EEG is abnormal, seizure recurrence is more likely, but 1% to 2% of the general population will have epileptiform activity on routine EEG, so the test can be counterproductive in a patient for whom the consultant has a low clinical suspicion for seizure. Epilepsia Partialis Continua Epilepsia partialis continua (EPC) describes a rare form of status epilepticus that is focal, arises from the perirolandic cortex, and results in interminable motor seizures without a marked tendency to generalize.8 The consultation in the patient with EPC will seek to distinguish the diagnosis from other spells associated with abnormal movements, including various movement disorders, sleep disorders, and psychogenic nonepileptic seizures (Table 2-2). The evaluation should assess for the time course and pattern of the movements. EPC can last for months or years, and the movements may be regular or irregular, aggravated by action or stimulation, and persistent during rest, including sleep. Movements often involve distal limb muscles and are generally unilateral, with synchronous activation of agonist and antagonist
KEY POINTS
TABLE 2-5 Common Causes of Provoked Seizures

b Metabolic Hypernatremia or hyponatremia Hypoglycemia Hyperosmolar nonketotic coma Diabetic ketoacidosis Hepatic dysfunction Uremia Severely low magnesium, calcium, or phosphate b Toxic Drugs of abuse (cocaine or methamphetamine) Medications (antibiotics, isoniazid, tricyclic antidepressants, bupropion, clozapine, anesthetics) Drug withdrawal (alcohol, benzodiazepines) Hyperthermia b Trauma b Infectious Meningitis Encephalitis Abscess b Vascular Hemorrhagic or ischemic stroke Hypertensive encephalopathy Eclampsia Vasculitis Vascular malformations b Tumor-Related Primary CNS neoplasm CNS metastasis Carcinomatous meningitis b Endocrine Hyperthyroidism
h Routine EEG is indicated

in the workup of a suspected unprovoked seizure and will reveal epileptiform abnormalities in approximately one-fourth of patients.
h Epilepsia partialis
continua can last for months or years, and the movements may be regular or irregular, aggravated by action or stimulation, and persistent during rest, including sleep. Movements often involve distal limb muscles and are generally unilateral, with synchronous activation of agonist and antagonist muscles.
989
Spells
muscles. A hemiparesis or monoparesis of the affected limb(s) is common, as classically develops with Rasmussen encephalitis or EPC associated with other focal brain lesions. Cognitive dysfunction may develop more rarely. An evaluation of the patient with possible EPC should assess for known causes, which include stroke or other vascular disorders (24% to 28%), encephalitis (including Rasmussen encephalitis) (15% to 19%), neoplasms (5% to 16%), and metabolic disorders (6% to 14%).9 The workup should include a metabolic panel and brain MRI, which is abnormal in most cases. A lumbar puncture should be performed when encephalitis is suspected. Only one-third of patients with EPC have a history of seizures. When the diagnosis cannot be made based on the clinical presentation and presence of preexisting risk factors, EEG can be helpful and will reveal focal epileptiform activity in the majority of cases.10 A normal EEG, however, does not exclude the diagnosis. In patients with suspected EPC whose EEGs are unrevealing, a therapeutic trial with antiepileptic medications may be appropriate. Unfortunately, only 60% of patients with EPC respond to monotherapy, with the remainder requiring polytherapy or remaining refractory to treatment. Syncope Syncope is defined as an abrupt and transient loss of consciousness associated with inability to maintain postural tone and followed by a spontaneous and rapid
recovery. Transient loss of consciousness is a common reason for neurologic consultation, and the differential diagnosis usually includes syncope, seizure, and a few less common causes such as cataplexy, TIA, or psychogenic events.11 Syncope itself has multiple causes, including neural- or reflex-mediated (vasovagal, situational) causes, cardiac causes, orthostatic (autonomic failure, severe volume depletion, or toxic) causes, and other structural (steal) or cardiopulmonary causes. Incidence increases with age and with history of cardiovascular disease, which is associated with a higher mortality rate.12 Overall, an estimated one-third of people will experience a syncopal event over their lifetime, and syncope accounts for 3% to 5% of emergency department visits and 1% of admissions to the hospital. Reflex syncope is the most common form of syncope, making up 60% of cases of transient loss of consciousness by some reports,13 and it is the most benign. It is twice as common in patients under 40 and is often associated with prodromal signs and symptoms such as pallor (80%), dizziness (73%), and diaphoresis (63%). Women more commonly report these symptoms, so age, gender, and the presence of these prodromal symptoms may help to distinguish reflex syncope from other less-benign causes of spells. The consultant should also review potential triggers, such as prolonged standing or positional changes, venipuncture, strong emotion or pain, coughing, or using the bathroom (Case 2-1).
Case 2-1
A 22-year-old woman with a diagnosis of epilepsy since childhood presented to the emergency department after passing out during a blood draw. She recalled feeling anxious and nauseous, having a racing heartbeat, experiencing graying of vision, and then losing consciousness. Her boyfriend reported that her eyes rolled upward and her body became limp before stiffening and shaking for approximately 20 seconds. Afterward, she returned to baseline within a few minutes. She had been diagnosed with epilepsy because of similar loss-of-consciousness events occurring since she was 4 years old. She had
Continued on page 991
990
October 2011
Continued from page 990

had a total of 10 such events, and half were associated with medical procedures or orthostatic stress. She had been on anticonvulsant medications for many years. The examination was normal, although the patient was noted to be pale and sweaty. Comment. This case illustrates several prototypical features of reflex syncope, including the temporal association with a painful event, the characteristic prodromal symptoms, and the rapid return to baseline. The association of the event with abnormal movements is not inconsistent with the diagnosis of convulsive syncope, and the association of her prior losses of consciousness with medical procedures suggests that these events might also be due to convulsive syncope. The patient underwent video-EEG monitoring, and one of her typical events was elicited by venipuncture and associated with a prolonged (40-second) asystolic pause, consistent with malignant reflex syncope (Figure 2-1). ECG, cardiac telemetry, and echocardiography were normal, and the patient underwent pacemaker placement to prevent further prolonged asystoles. While the diagnosis of epilepsy could not be completely excluded, the patient has since been able to gradually wean antiepileptic medications and has remained seizure free.
FIGURE 2-1
(A) EEG and concurrent single channel ECG at baseline, (B) EEG when patient reports onset of presyncopal symptoms, (C) EEG during period when patient loses consciousness.
991
Spells
KEY POINTS
h Variables most highly

associated with seizure are tongue biting, head turning, posturing, incontinence, and cyanosis. Variables most highly associated with syncope are a history of presyncopal symptoms (eg, graying of vision, lightheadedness, muffling of sounds), recent prolonged standing or sitting, and preceding diaphoresis.
h An aura precedes
migraine in 20% to 30% of patients and may be similar to auras associated with seizure because of the presence of positive phenomena.
h Visual aura is most

common and may include geometric forms or complex changes in visual perception such as metamorphopsia, micropsia, and macropsia.
The most notable symptom overlap between seizures and syncope is the presence of myoclonic activity, which has been found to occur in 90% of syncopal events and is commonly referred to as convulsive syncope. Other common movements include oral movements, head turning, and upward eye deviation.14 Tongue biting (2%), urinary incontinence (19%), and postictal confusion (10%) are reported more rarely but occur often enough that caution should be taken when using any one of these features in isolation to exclude the diagnosis of syncope.13 Ultimately, because of the overlapping symptoms between seizure and syncope, it is important to obtain a thorough history that assesses for several features that help to make one diagnosis or the other more likely.15 Variables most highly associated with seizure are tongue biting, forced head turning, dystonic posturing, incontinence, cyanosis, abnormal behaviors, deja vu, and ` prolonged postictal confusion. Variables most highly associated with syncope are a history of presyncopal symptoms (eg, graying of vision, lightheadedness, muffling of sounds), recent prolonged standing or sitting, preceding warmth or diaphoresis, palpitation, dyspnea, chest pain, history of coronary artery disease, or being able to clearly remember the loss of consciousness. The consultant should attempt to ascertain these potentially distinguishing features from the history, realizing that observers will often recall features incorrectly.16 In addition, the diagnoses of syncope and seizure may rarely occur together in the same patient. When syncope occurs during a focal dyscognitive seizure, the loss of postural tone will often interrupt the seizure, occurring in the midst of a behavioral arrest or automatic behaviors. This semiology has been referred to as pseudosecondary generalization17,18 because clonic or myoclonic
movements associated with the syncope take place following the loss of tone or atonic phase, rather than following a tonic phase, as in a tonic-clonic seizure. The evaluation of syncope may include orthostatic testing, ECG, cardiac telemetry, echocardiography, and tilttable testing, although no single, specific test exists for confirming the diagnosis. EEG recording of the events may be diagnostic, but it is not practical.19 Migraine Although migraine is more commonly encountered in the outpatient setting, it is a common diagnosis affecting roughly 10% of the population and can lead to inpatient neurologic consultation when it occurs in an admitted patient or when it is severe enough to bring patients to the emergency department. Migraine is a clinical diagnosis characterized by unilateral, pulsating head pain of sufficient intensity to interfere with normal activities and associated with nausea, vomiting, photophobia, and phonophobia. While not every clinical feature is present in each person or in each attack, diagnostic uncertainty is greatest when head pain is absent, which may occur in 3% of patients, particularly those with advancing age. In that case, a history of prior migraine headache will be useful in reaching the diagnosis, although alternate diagnoses, such as TIA or seizure, will often need to be considered. An aura precedes migraine in 20% to 30% of patients and may be similar to auras associated with seizure when positive phenomena are present or to auras associated with TIA when negative phenomena are present. Visual aura is most common and usually consists of scintillations and fortification spectra but may include geometric forms or complex changes in visual perception such as metamorphopsia, micropsia, and macropsia.20 Other aura types may involve somatosensory, motor, language, or
October 2011
992
brainstem symptoms. Even in common migraine, which occurs without frank aura, most patients (60%) describe experiencing a premonitory phase that occurs hours to days before the migraine and often includes fatigue or difficulty concentrating. Following the headache, patients may also report hours to days of feeling tired and listless or having cognitive changes. Confusional migraine, basilar migraine, and hemiplegic migraine create an additional diagnostic challenge because of the associated signs and symptoms, including incoordination, inattention, and focal weakness. Epilepsy and migraine may occur in the same patient, and the presence of either diagnosis confers a twofold risk of developing the other, with 24% of patients with epilepsy affected by migraine. Headache may occur in the peri-ictal period, and most peri-ictal and postictal headaches meet diagnostic criteria for migraine.21 In general, videoEEG monitoring during an event may distinguish between migraine and epilepsy when the history and examination are insufficient to do so and when the event of interest can feasibly be recorded. Typically, the EEG during migraine remains normal or shows nonspecific slowing, although there are rare reports of epileptiform activity and even periodic lateralized epileptiform discharges, possibly reflecting cases in which migraine is occurring peri-ictally. Otherwise, migraine is a clinical diagnosis, and further diagnostic testing is not necessary except when it is needed to ex clude malignant causes of headache. Imaging, blood work, and lumbar puncture with opening pressure may be necessary in these cases. TIA Neurovascular causes of spells can often be distinguished from seizures based on recognition of the clinical pattern, the presence of stroke risk factors, and the tempo and frequency of the event.
Clinical pattern recognition refers to the ability to distinguish a set of symptoms attributable to a vascular territory, such as aphasia and right face and arm weakness in patients with left middle cerebral artery ischemia. In addition, the pretest probability for a vascular event will be related to stroke risk factors, such as older age, hypertension, hyperlipidemia, and tobacco use. TIAs are associated with a loss of neuronal function rather than aberrant neuronal discharges, thereby producing negative rather than positive phenomena (ie, vision loss rather than geometric visual phenomena; loss of strength rather than stiffening or shaking). While TIAs may recur, a history of multiple spells with stereotypy and subsequent return to normal neurologic function suggests seizures. For patients in whom TIA is suspected, imaging should include magnetic resonance or CT angiogram, and initial laboratory tests should assess for stroke risk factors (fasting lipid panel, glucose tolerance test, hemoglobin A1c). Rare TIA syndromes, including limbshaking TIA and drop attacks, are more likely to present as seizure mimics. Limbshaking carotid TIA is characterized by erratic shaking or trembling of the arm and hand (or arm, hand, and leg) contralateral to an occlusive lesion of the internal carotid artery for seconds to minutes, with or without concurrent language or sensory deficits.22 A careful history or examination of the movements should reveal a lack of the typical jacksonian march (migrating movements along the homunculus, often starting with a digit and spreading proximally along the limb) associated with a clonic seizure.23 Drop attack TIAs are caused by sudden impaired blood flow to brainstem structures or to bilateral parasagittal motor cortices controlling the legs (in patients with bilateral anterior cerebral arteries arising from the same internal carotid artery). This type of spell occurs without
KEY POINT
h TIAs are associated

with a loss of neuronal function rather than aberrant neuronal discharges, thereby producing negative rather than positive phenomena.
993
Spells
KEY POINTS
h Periodic limb
movements during sleep affect 44% of those over age 64 and are frequently associated with restless legs syndrome. They are characterized by rapid, complex toe flexion and leg extension movements that occur in clusters (every 20 to 40 seconds) throughout the night.
warning or trigger, although the absence of spells while sitting or lying down may help to exclude seizure. Any associated loss of awareness is either absent or very brief, and consciousness and lower motor strength typically return immediately after the fall. If events occur frequently enough to record, the EEG should be normal in either case. If events are infrequent, then the clinical presentation and imaging must be used to make the diagnosis. Antiepileptic medications are neither effective nor indicated. Sleep Disorders Sleep disorders describe a range of abnormal behaviors occurring during sleep and have various clinical features that should be distinguished from seizures.24 Sleep disorders are divided according to sleep stage, and, of the non-REM disorders, periodic limb movements during sleep (PLMS) and sleep jerks are the most likely to mimic seizure. PLMS affect 44% of those over age 64 and are frequently associated with restless legs syndrome. PLMS are characterized by rapid, complex toe flexion and leg extension movements that occur in clusters (every 20 to 40 seconds) throughout the night. Sleep starts or hypnic jerks are
h REM behavior disorder

is associated with complex motor manifestations, including kicking, punching, and even running, that can be distinguished from seizure by the lack of stereotypy.
benign forms of physiologic myoclonus that occur exclusively during periods of sleep transition, distinguishing the diagnosis from forms of myoclonic epilepsy. The remaining non-REM disorders, sleep terrors and somnambulism, are predominantly disorders of childhood, but when they occur in adults, they can be identified by their association with prominent fear or with the completion of complex tasks, respectively. REM sleep disorders include narcolepsy and REM behavior disorder. Narcolepsy is unlikely to mimic seizure when all of the clinical features of the diagnosis are present (daytime somnolence, cataplexy, hypnagogic hallucinations, and sleep paralysis). Of these features, cataplexy has the most potential to mimic seizure but can be distinguished by the preservation of consciousness. REM behavior disorder is associated with complex motor manifestations, including kicking, punching, and even running, that can be distinguished from seizure by the lack of stereotypy. Additional features such as the temporal pattern and absence of dystonic posturing help to distinguish parasomnias from seizures in general25; therefore, the history should assess for these clinical features (Table 2-6). The
TABLE 2-6 Distinguishing Features of Parasomnia Versus Seizure Features Associated With Parasomnia Features Associated With Seizure
Onset 9 55 years of age Duration 9 10 min No clusters (G 2 events/night) No predilection for early sleep Wandering Complex behaviors No dystonic posturing Coherent speech without recall Onset G 55 years of age Duration G 2 min Clustering (9 5 events/night) Occurring within 30 min of sleep transition Aura (preceding warning) Dystonic posturing Stereotypy Coherent speech with recall for the event
Data from Derry CP, Davey M, Johns M, et al. Distinguishing sleep disorders from seizures: diagnosing bumps in the night. Arch Neurol 2006;63(5):705Y709.
994
October 2011
neurologic examination should particularly assess for parkinsonism, which is associated with the diagnosis of REM behavior disorder, although the latter may precede the diagnosis of parkinsonism by decades. EEG monitoring may be performed when uncertainty remains, or, if a sleep disorder is higher on the list of differential diagnoses, a polysomnogram or a combined videoEEG polysomnogram, where available, may be the preferred diagnostic test. Movement Disorders Whenever spells involve abnormal movements, the practitioner will need to consider whether the quality of the movements is more typical of seizure activity or of a movement disorder. For example, compared to movements associated with seizure, athetotic or choreiform movements are often longer in duration, more complex, and less well-stereotyped. Tremor tends to be of a higher frequency and lower amplitude and ballismus of a higher amplitude and more erratic than the rhythmic movements due to seizure activity. The focal movements in hemifacial spasm only involve the muscles innervated by cranial nerve VII, whereas focal motor seizures involving the face tend to spread to other muscle groups. Some movements may not be clinically distinguishable. For example, tics and myoclonus may be either stereotyped or focal, rendering the diagnosis ambiguous. Focal dystonia in demyelinating disorders may sometimes be difficult to differentiate from focal tonic seizures. When events cannot be distinguished, additional history should assess for the presence of a subjective warning or postictal changes (generally absent in patients with movement disorders) and for the presence of the events during sleep (movement disorders improve during sleep). Other comorbid conditions, such as subcortical stroke or heContinuum Lifelong Learning Neurol 2011;17(5):9841009
patic or renal dysfunction, should be reviewed. A careful medication history, family history, and developmental history should be elicited. Additional workup will often include extended video-EEG recording when movements are of sufficient frequency to be recorded. Laboratory testing will include basic metabolic tests, toxicology, and potentially other targeted evaluations for movement disorders, including specific testing for associated storage diseases or a targeted infectious workup (eg, for Creutzfeldt-Jakob disease, subacute sclerosing panencephalitis, syphilis, or Whipple disease). The two types of movement disorders that often pose the most diagnostic difficulty are symptomatic myoclonus (discussed below as part of the ICU consult evaluation) and the uncommon paroxysmal dyskinesias. The prototypical paroxysmal dyskinesia, paroxysmal kinesigenic choreoathetosis (PKC), is associated with spells of choreiform or dystonic movements for seconds or minutes during movement or with startle.26 Movements may be preceded by an aura of dizziness, sensory phenomena, or muscle tension, and patients with PKC may also present with seizures, as they have an increased risk of epilepsy. Despite the similarities between PKC and epilepsy, the EEG in patients with PKC is classically normal at baseline and during the spell. Treatment is similar, as PKC often responds to low doses of sodium-channel blockers, particularly carbamazepine. Psychogenic Nonepileptic Seizures Psychogenic nonepileptic seizures (PNES) present a particular diagnostic challenge in the workup of patients with spells. This challenge is reflected in the long delay to diagnosis (average 8 years), which causes substantial morbidity and cost due to additional emergency
KEY POINTS
h Whenever spells involve

abnormal movements, the practitioner will need to consider whether the quality of the movements is more typical of seizure activity or of a movement disorder.
h The two types of

movement disorders that often pose the most diagnostic difficulty are symptomatic myoclonus and the uncommon paroxysmal dyskinesias.
995
Spells
KEY POINT
h A sudden change in
seizure semiology and pattern in the absence of medication nonadherence, intervening illness, or substance abuse should alert the physician to the possibility of an alternate diagnosis in the patient with known epilepsy.
department visits, inpatient hospitalizations, and unnecessary or even harmful treatments. The clinical features of PNES overlap with epileptic seizures, but a few features are more associated with PNES and should be elicited in the history (Case 2-2). These features include association of spells with emotional events, a longer duration,27 and a waxing and waning quality. If the event is witnessed by the consultant, then special attention should be paid to whether eye closure (96%),28 pelvic thrusting (77%),29 or stuttering (8.5%)30 is present during the event, as these features are associated with PNES. Having a teddy bear (5%)31 or other transitional object during a hospitalization is an uncommon but highly specific feature for PNES. While these features raise suspicion for PNES, the consultant should keep in mind that none is
sufficient to rule out seizure; in particular, pelvic thrusting may be a feature of frontal lobe seizures.32 Additional history should address risk factors for PNES, including female gender, age, a history of chronic pain and fibromyalgia, having a spell during a clinic visit, and Cluster A and B personality disorders.33,34 Ultimately, video-EEG telemetry remains the standard for diagnosis.35 The reported incidence of PNES is 2 to 33 per 100,000 per year, but as many as one-third of patients referred to epilepsy monitoring units have PNES. A diagnosis of PNES does not exclude concomitant epilepsy, however, as an estimated 5% to 10% of patients with PNES demonstrate evidence of interictal epileptiform activity or frank epileptic seizures during video-monitoring sessions.36,37 The true incidence of epileptic seizures in patients with PNES
Case 2-2
A 29-year-old woman underwent a left temporal lobectomy for treatment of her medically refractory focal epilepsy 5 years ago. Her seizures diminished in frequency, but nocturnal convulsions persisted, and 3 years ago she underwent long-term intracranial implantation of subdural electrodes to further define the epileptogenic zone. A tailored lateral temporal neocortical resection was performed, which revealed widespread cortical dysplasia. She continued to experience occasional seizures with loss of awareness but had no witnessed convulsions for over 1 year. She then presented to an emergency department because of back-to-back convulsive seizures and was witnessed to have several convulsive seizures that were unresponsive to repeated doses of IV lorazepam and IV fosphenytoin. Her examination on transfer to a tertiary medical center revealed that she was poorly responsive, and witnessed seizures were characterized by prolonged asynchronous limb shaking, pelvic thrusting, and forced eye closure. Comment. A sudden change in seizure semiology and pattern in the absence of medication nonadherence, intervening illness, or substance abuse should alert the physician to the possibility of an alternate diagnosis in the patient with known epilepsy. This aspect of the history paired with the appearance of the seizures (asynchronous limb shaking and pelvic thrusting) should raise suspicion for psychogenic nonepileptic seizures, which were confirmed by video-EEG monitoring in this case. The EEG during the spells revealed high amplitude movement artifact, but an alpha rhythm was immediately observed when the movements ceased, confirming a state of wakefulness inconsistent with generalized seizure activity.
996
October 2011
may be even higher because of sampling limitations. INTENSIVE CARE UNIT CONSULTATION The evaluation of spells in the ICU is complicated by the inability to collect a detailed event history, the presence of multiple interrelated medical problems, and the tendency for more than one of these problems to be a potential cause of spells in the critically ill patient. This section reviews the clinical presentation of seizures and status epilepticus in the ICU patient, followed by a separate consideration of seizures and seizure mimics in the patient with myoclonus or encephalopathy. Status Epilepticus Status epilepticus (SE) has been defined variably as continuous seizure activity for 30 minutes, recurrent seizures without complete return to consciousness, or seizure activity that fails to naturally terminate within 5 minutes.38 Part of the difficulty in defining SE arises because of the variability in its clinical presentation and prognosis. For example, EPC can persist for days or months with little relative morbidity, whereas convulsive SE is a medical emergency with an
associated mortality of 30%. Ultimately, mortality is most associated with the underlying cause of SE, with better outcomes occurring in patients presenting with SE due to missed antiepileptic medications or alcohol withdrawal as compared to cardiac arrest or acute stroke. Prognosis is also directly related to age and duration of SE.39 The history in the patient with SE should make note of these features. No universally agreed upon classification scheme for SE exists, but most practitioners classify SE according to whether seizures are generalized or focal and convulsive or nonconvulsive. Of the forms of SE presenting in the ICU patient, nonconvulsive status epilepticus (NCSE) presents the greatest diagnostic challenge because it describes clinically unapparent or subtle ongoing seizure activity in the deeply encephalopathic or comatose patient. Classically, NCSE evolves from partially treated or even untreated generalized convulsive SE; however, NCSE may occur without any apparent preceding seizure. The examiner should check for facial or limb myoclonus, eyelid twitching, head deviation, eye deviation, or nystagmoid movements to indicate ongoing subtle seizure activity (Case 2-3).
KEY POINTS
h The evaluation of spells

in the intensive care unit is complicated by the inability to collect a detailed event history, the presence of multiple interrelated medical problems, and the tendency for more than one of these problems to be a potential cause of spells in the critically ill patient.
h Nonconvulsive status
epilepticus may occur without any apparent preceding seizure. The examiner should check for facial or limb myoclonus, eyelid twitching, head deviation, eye deviation, or nystagmoid movements to indicate ongoing subtle seizure activity.
Case 2-3
A 46-year-old woman with a history of schizophrenia, documented psychogenic nonepileptic seizures, and possible concurrent epilepsy presented to the emergency department because of a seizure and persistent altered mental status. Her family reported that she had stopped taking her seizure medications 1 week ago because of problems related to her insurance coverage. The day before presentation she was experiencing paranoid delusions but speaking in full sentences. She then had a witnessed seizure at home, but family members were unable to tell whether it was psychogenic or epileptic in etiology. Her psychogenic nonepileptic seizures were described as brief generalized shaking events followed by a long period of unresponsiveness, except to noxious stimuli. Her epileptic seizures were distinguished only by urinary incontinence and a more rapid recovery of responsiveness.

Continuum Lifelong Learning Neurol 2011;17(5):9841009 www.aan.com/continuum
997
Spells
KEY POINT
h The evaluation of
possible seizure activity in the comatose patient should include at least an overnight EEG recording rather than the typical 30-minute recording often ordered for patients who are cognitively intact.

In the emergency department she was awake but inattentive, muttering to herself incoherently and exhibiting intermittent facial twitching. After a witnessed generalized tonic-clonic seizure, she became unresponsive with a persistent right gaze preference. An EEG demonstrated continuous high-amplitude, right-greater-than-left 3- to 5-Hz spike- and slow-wave discharges (Figure 2-2) consistent with nonconvulsive status epilepticus. Comment. This case highlights the inherent diagnostic difficulties in complex psychiatric and neurologic patients and the importance of EEG testing in clarifying FIGURE 2-2 EEG of patient in nonconvulsive status epilepticus. Note the continuous and irregular the diagnosis. generalized sharp activity and the absence of any related movement artifact (arrows). Unfortunately, the delay in diagnosis and anticonvulsant treatment may have contributed to the subsequent refractory nature of this patients status epilepticus. She was eventually discharged following a prolonged hospitalization.
Ultimately, the diagnosis of NCSE relies on EEG monitoring, which should be considered in any patient with unexplained coma or encephalopathy. In NCSE, the EEG demonstrates a mixture of generalized or focal epileptiform spike- and slow-waves, delta waves, and burst suppression. EEG has been used to diagnose NCSE in 8% of comatose patients without apparent seizure manifestations40 and in over half of those with subtle motor signs.41 Even when ICU patients are not found to be in NCSE, as many as one in five are discovered to have subclinical seizure activity detected by extended monitoring.42 The history should therefore address known risk factors for subclinical seizure activity in the ICU, including coma,
age less than 18 years, history of epilepsy, or history of convulsion during the current illness. While NCSE can be diagnosed quickly by EEG, the detection of subclinical seizures in the ICU requires extended monitoring, with most (88%) being detected within 24 hours. Therefore, the evaluation of possible seizure activity in the comatose patient should include at least an overnight and likely a 24-hour EEG recording rather than the typical 30-minute recording often ordered for patients who are cognitively intact. When extended EEG monitoring is not available and seizures are suspected despite a negative routine EEG, an empiric treatment trial and transfer to a facility with long-term monitoring should be
October 2011
998
considered. In addition, if NCSE or subclinical seizures are detected, longterm EEG monitoring will generally be necessary to monitor the response to treatment given the lack of clinical correlate. Generalized convulsive status epilepticus (GCSE) will be more easily recognized than NCSE because of the associated clinically apparent abnormal movements, although the practitioner will need to distinguish it from other abnormal movements (see the above section on movement disorders). This evaluation should be targeted to avoid delaying emergent treatment necessary to control seizure activity; the approach to treatment (including the recommended timeline for these treatments) has been discussed extensively elsewhere.43 EEG is instrumental during the evaluation of GCSE to monitor the response to treatment and to rule out the development of subclinical seizure activity, especially in patients
who remain deeply encephalopathic or comatose as a result of or in spite of treatment with anticonvulsant medications. Evaluation should focus on identifying the underlying cause and monitoring for associated physiologic complications such as aspiration pneumonia, tachycardia with demand ischemia, rhabdomyolysis, and lactic acidosis. Myoclonic Status Epilepticus GCSE may be difficult to distinguish from myoclonic status epilepticus (MSE), especially later in the course when either may be associated with abnormal jerking movements that are regular or irregular, synchronous or asynchronous, and generalized or multifocal. Patients with MSE are typically distinguished by their history of a severe hypoxic-ischemic insult (Case 2-4), as discussed in detail in the article Hypoxic-Ischemic Brain Injury and Prognosis After Cardiac Arrest in
KEY POINT
h EEG is instrumental
during the evaluation of generalized convulsive status epilepticus to monitor the response to treatment and to rule out the development of subclinical seizure activity, especially in patients who remain deeply encephalopathic or comatose as a result of or in spite of treatment with anticonvulsant medications.
Case 2-4
An 80-year-old woman with a history of end-stage renal disease on biweekly hemodialysis sustained a pulseless asystolic arrest in a nursing home. Advanced cardiopulmonary resuscitation was initiated 7 minutes later by emergency medical services, and a pulse returned after administration of epinephrine, atropine, and sodium bicarbonate. She was intubated in the field and brought to the emergency department, where an initial arterial blood gas revealed a pH of 7.09, a Pao2 of 76, and a Paco2 of 72. Hospital hypothermia protocol was initiated. Within 24 hours of admission, frequent synchronous, generalized, and multifocal myoclonic movements were observed. The patient remained comatose. Continuous EEG monitoring with concurrent video demonstrated generalized FIGURE 2-3 and multifocal irregular high-amplitude spike-and-wave discharges on a background of severe attenuation and absent variability or reactivity (Figure 2-3). Seventy-two hours after
EEG of patient in myoclonic status epilepticus (MSE). The irregular generalized spike-and-wave activity superimposed on a generally flat background is typical of MSE.

999
Spells
KEY POINT
h Myoclonic status
epilepticus resulting from cardiac arrest is associated with a poor prognosis for meaningful neurologic recovery. The myoclonus is often disturbing to family members and can be suppressed with anesthetic agents, valproic acid, or benzodiazepines, but it frequently returns when these medications are removed or reduced in dose.

cardiac arrest, examination demonstrated sluggish pupillary responses to light and the absence of other brainstem reflexes or motor responses with continued generalized myoclonus. The family chose comfort care measures and the patient died 24 hours later. Comment. Myoclonic status epilepticus resulting from cardiac arrest is associated with a poor prognosis for meaningful neurologic recovery. The myoclonus is often disturbing to family members and can be suppressed with anesthetic agents, valproic acid, or benzodiazepines, but it frequently returns when these medications are removed or reduced in dose. History of arrest and EEG features consistent with myoclonic status epilepticus help distinguish the diagnosis from other forms of myoclonus that could indicate a better prognosis. Additional studies such as somatosensory-evoked potentials and certain aspects of the neurologic examination provide supportive evidence of the poor prognosis.
this issue of . MSE occurs in 37% of patients who are comatose after cardiac resuscitation. In the setting of cardiac arrest, it is associated with a mortality rate approaching 100%.44,45 Some data suggest that outcomes may be more favorable when the hypoxic insult is due to acute asthma or respiratory failure rather than cardiac arrest.46 Typically, MSE develops within 12 hours after arrest and persists for an average of 60 hours.47 However, MSE is a clinical diagnosis, and unfortunately the term has been used to describe a wide range of presentations in the literature, some of which are associated with more favorable outcomes (see the discussion of Lance-Adams syndrome below). The EEG in MSE demonstrates highamplitude, irregular, generalized or multifocal epileptiform spikes on a poorly organized background; richness and reactivity of the background may help identify a better prognostic group.48 The evaluation in the postarrest patient focuses on factors that help prognostication and may therefore also include somatosensory-evoked potentials49 and repeated examination assessing for
pupillary light response and corneal reflex within 1 to 3 days and motor response after 3 days.50 Myoclonus Critically ill patients often develop other forms of myoclonus, most of which are symptomatic of another underlying diagnosis and do not portend a poor prognosis, so they are essential to distinguish. In general, myoclonus describes a rapid and involuntary muscle contraction generated by the brain or spinal cord. It can appear differently depending on whether it is focal, segmental, generalized, or multifocal. It can be epileptiform (cortically generated myoclonus) or nonepileptiform, although it may be more accurate to view myoclonus as occurring along a spectrum, with some forms not easily classified. MSE, described above, is the most severe form of epileptic myoclonus. Nonepileptic myoclonus is divided into physiologic (hiccups and sleep jerks), essential (inherited), and symptomatic forms. Symptomatic forms of myoclonus are common in critically ill
October 2011
1000
patients and may have a myriad of causes (Table 2-7). Symptomatic myoclonus is generally not dangerous in and of itself, and treatment is aimed at the underlying etiology. The evaluation of the critically ill patient with abnormal movements should seek to identify risk factors for the development of symptomatic forms of myoclonus and distinguish this form of myoclonus from MSE. Patients with Lance-Adams syndrome (LAS) present the greatest diagnostic difficulty for practitioners attempting to
distinguish MSE from forms of symptomatic myoclonus (Case 2-5). Both patients with LAS and patients with MSE are likely to have had a history of a hypoxicischemic insult, although the classic history for LAS involves a respiratory arrest, such as that due to asthma exacerbation, rather than a cardiac arrest. Therefore, LAS may be associated with a different underlying pathophysiology.51 LAS has a markedly better prognosis than MSE, with a natural history that includes recovery from coma and often a return to normal intellectual function
KEY POINT
h Symptomatic myoclonus
is generally not dangerous in and of itself, and treatment is aimed at the underlying etiology. The evaluation of the critically ill patient with abnormal movements should seek to identify risk factors for the development of symptomatic forms of myoclonus and distinguish this form of myoclonus from myoclonic status epilepticus.
TABLE 2-7 Causes of Symptomatic Myoclonus

b Degenerative Diseases Alzheimer disease Parkinson disease Corticobasal degeneration Huntington disease b Infection Meningitis Herpes simplex virus Creutzfeldt-Jakob disease Subacute sclerosing panencephalitis Whipple disease Syphilis b Vascular Stroke Postanoxic Lance-Adams syndrome b Metabolic Uremia Hepatic encephalopathy Hypoglycemia or hyperglycemia Hypokalemia Hyponatremia
Data from Helms A, Shulman L. Movement disorders that imitate epilepsy. In: Kaplan PW, Fisher RS, editors. Imitators of epilepsy. 2nd ed. New York: Demos, 2005:163Y184.
b Medications Opiates Antidepressants Antibiotics Antiepileptics Levodopa b Toxic Cocaine Amphetamine Heavy metals Methyl bromide Bismuth Alcohol or benzodiazepine withdrawal b Tumor b Trauma b Storage Diseases b Other CNS Lesion
1001
Spells
KEY POINT
h Lance-Adams syndrome
has a markedly better prognosis than myoclonic status epilepticus, with a natural history that includes recovery from coma and often a return to normal intellectual function despite persistent myoclonus in association with the initiation of coordinated movement, or so-called intention myoclonus.
Case 2-5
A 60-year-old man with a history of idiopathic pulmonary fibrosis had an episode of respiratory arrest with documented hypoxemia and underwent bilateral orthotopic lung transplantation the following day. On the first postoperative day, he was comatose and had nearly continuous spontaneous irregular and asynchronous myoclonus involving the muscles of the right face, trunk, and arm, with intermittent spread to the left arm. As the patient emerged from coma, he became conversational and could follow multistep commands. However, the involuntary movements persisted in the right arm and shoulder and could be activated by voluntary movements of the arm. The myoclonic movements diminished over the subsequent days and resolved before discharge from the hospital 2 weeks later. Comment. The differential diagnosis based on the clinical presentation included myoclonic status epilepticus and focal motor seizures. However, the asynchronous movements were inconsistent with seizure, and the later onset of myoclonus, eventual emergence from coma, and intact cognitive functioning were inconsistent with myoclonic status epilepticus. The findings of activation with movement and the EEG (which did not demonstrate seizure activity) were more consistent with symptomatic myoclonus. In the setting of documented FIGURE 2-4 Axial T2-weighted brain MRI in a hypoxia (Figure 2-4), patient with Lance-Adams syndrome. Note the increased T2 signal in the most likely diagnosis left-greater-than-right cortical and subcortical motor was Lance-Adams and premotor regions, indicative of subacute syndrome, or postanoxic ischemia (arrows). myoclonus.
despite persistent myoclonus in association with the initiation of coordinated movement, or so-called intention myoclonus.52,53 LAS and MSE can often be distinguished by the time course, with myoclonus appearing early in MSE (within approximately 12 hours of arrest) and later in LAS (more than 24 hours after the anoxic insult). When-
ever myoclonus appears, a thorough clinical examination while the patient is not sedated is essential and should be repeated at least 3 days following the inciting event. EEG may show epileptiform activity in patients with either MSE or LAS, although the background will demonstrate better organization, reactivity, and variability in
October 2011
1002
LAS and may even be normal or near normal. Special Cases of Encephalopathy With Episodic Qualities Most critically ill patients with spells will have severely impaired mental status or encephalopathy (as discussed in the article Altered Mental Status in this ), and the chalissue of lenge is to determine whether this finding is secondary to seizure. Altered mental status can itself be a seizure mimic because changes in level of awareness are a common manifestation of seizure, particularly the fluctuating changes that occur in delirium. The differential diagnosis for seizure mimics in critically ill patients is therefore extremely broad and includes various metabolic derangements, infection, hepatic or renal dysfunction, and even simply being critically ill. In addition, several diagnoses in critically ill patients may be associated with both encephalopathy and seizure (discussed below),
such as vascular insults, CNS malignancies, carcinomatous meningitis, posterior reversible leukoencephalopathy syndrome, and limbic encephalitis. The features of encephalopathy due to seizure versus other causes may be indistinguishable and may include inattention, disorientation, memory impairment, reduced or slowed speech, and inversion of the sleep-wake cycle. When psychotic symptoms are present, persecutory hallucinations, a lack of stereotypy, and the presence of tactile hallucinations may help distinguish a nonepileptic cause54 (Table 2-8). Some causes of encephalopathy may be associated with motor manifestations that mimic certain seizure types. Symptomatic myoclonus is the most common motor manifestation (as discussed above), but other motor manifestations may include rigors associated with sepsis, sustained muscle contraction associated with hypocalcemia, rigidity associated with neuroleptic malignant syndrome, and tremors associated with
KEY POINTS
h The features of
encephalopathy due to seizure versus other causes may be indistinguishable.
h When psychotic
symptoms are present, persecutory hallucinations, a lack of stereotypy, and the presence of tactile hallucinations are less consistent with seizure activity.
TABLE 2-8 Clinical Features Associated With Spells Due to Seizure Versus Encephalopathy Clinical Feature
Presence of risk factors Medications Focal examination Onset Automatisms Hallucinations Aphasia Movements
Seizure
Epilepsy, head trauma, stroke, CNS infection, CNS tumor History of missed or changed antiepileptic drugs, low antiepileptic drug levels Yes 9 No Acute or unknown Variable Stereotyped, nonthreatening; often olfactory or gustatory Variable Tonic, rhythmic clonic, rhythmic nystagmus, focal or generalized myoclonic, epileptic negative myoclonus Improves Epileptiform abnormalities
Encephalopathy
Diabetes, renal failure, liver disease, perioperative status, sepsis History of drugs of abuse or positive urine toxicology, diuretics, hypoglycemics No 9 Yes Subacute None Nonstereotyped, threatening; often visual, auditory, or tactile None Multifocal myoclonic, symmetric asterixis, rigidity, tremor, rigors, stimulus dependent Worsens Generalized slowing
Response to benzodiazepines EEG
1003
Spells
serotonin syndrome, among others. Paroxysmal vital sign changes may also mimic seizure and can occur with any cause of dysautonomia (Table 2-9). The evaluation of the encephalopathic patient with spells should characTABLE 2-9 Toxic and Metabolic Causes of Encephalopathy With Unique Clinical Features
b Liver failure Asterixis b Hypocalcemia Carpopedal spasm Tetany Cramping b Hypoglycemia Diaphoresis Hemiparesis b Neuroleptic Malignant Syndrome Rigidity Elevated temperature Tachycardia b Serotonin Syndrome Tremor Myoclonus Hyperreflexia Extrapyramidal signs Dysautonomia b Anticholinergic Toxicity Mydriasis Hyperthermia Urinary retention Dry mucous membranes Tachycardia Constipation
terize these features of the spell, and additional history should focus on the time course for the encephalopathy, any chronic illnesses, new medications or medication changes, and recent systemic symptoms. A thorough examination should include an assessment of level of consciousness, a complete cranial nerve examination including funduscopy, and an evaluation for focal sensorimotor deficits. The examiner should observe for any adventitious movements and assess whether movements are stimulus dependent. An imaging study will often be indicated, and when the encephalopathy cannot be imminently treated and reversed, extended EEG is often necessary to rule out concomitant seizure activity given the overlapping clinical features of seizures and seizure mimics in this population. When extended EEG confirms the presence of seizure activity, it may be helpful to consider certain diagnoses that commonly present with both encephalopathy and seizure. Two such syndromes, posterior reversible encephalopathy syndrome and limbic encephalitis, are highlighted here. Posterior reversible encephalopathy syndrome. Posterior reversible encephalopathy syndrome (PRES) is a syndrome characterized by headache and visual changes that has a tendency to present with focal seizures or SE.55 PRES is frequently associated with a surge in blood pressure, with a mean peak systolic pressure of 187 mm Hg. Other risk factors include kidney disease, malignancy, eclampsia, and a history of transplantation leading to immunosuppression with calcineurin inhibitors. Encephalopathy is nearly universal (92%). Seizures are the presenting sign for PRES in 87% of cases, although they may be not be clinically apparent (eg, in patients with NCSE). Therefore, EEG is recommended in any patient for whom
October 2011
1004
the diagnosis of PRES is being considered to evaluate for seizure as an underrecognized contributor to the encephalopathy. Other evaluation will include brain MRI, which typically reveals abnormalities involving the bilateral parieto-occipital white matter, although substantial variability exists.56 The imaging findings reflect reversible vasogenic edema without infarction, and follow-up imaging is normal in most cases (66%). The natural history involves resolution of the syndrome over a mean of 5 days with supportive care, including appropriate treatment with antiepileptic medications when necessary. Limbic encephalitis. Limbic encephalitis (LE) is an inflammatory process affecting the limbic system and associated with the development of seizures, hallucinations, mood and sleep disturbances, and memory loss (Case 2-6). It may arise as a rare complication of paraneoplastic syndromes that typically occur in a subset of patients affected by small cell lung cancer, thymoma, testicular germ cell neoplasm, Hodgkin lymphoma, or teratoma. In that setting, the autoantibodies most associated with the development of the syndrome are
anti-Hu, anti-CRMP5/CV2, and anti-M2. The syndrome can also arise in association with autoantibodies without an identified primary neoplasm, so-called idiopathic or autoimmune LE.57 A malignancy is eventually diagnosed in only 30% of voltage-gated potassium channelY mediated and 65% of NMDA-receptor antibodyYmediated LE cases.58 Cases of LE associated with antibodies to glutamic acid decarboxylase in the absence of neoplasm have also been reported. The evaluation of the patient with unexplained encephalopathy or unexplained SE should include laboratory screening for common autoantibodies associated with LE and appropriate cancer screening as indicated. LE is strongly associated with the development of seizures, which occur in as many as 80% of patients and may be such a prominent feature as to lead to mesial temporal sclerosis. Extended EEG is therefore indicated to assess for seizure activity and is often required to assess the response to treatment. Unfortunately, these patients respond poorly to antiepileptic medications alone and have the potential to develop refractory SE until appropriate immunomodulatory
KEY POINTS
h Seizures are the

presenting sign for posterior reversible encephalopathy syndrome in 87% of cases, although they may not be clinically apparent. EEG is recommended in any patient for whom the diagnosis of posterior reversible encephalopathy syndrome is being considered to evaluate for seizure as an underrecognized contributor to the encephalopathy.
h The evaluation of the

patient with unexplained encephalopathy or unexplained status epilepticus should include laboratory screening for common autoantibodies associated with limbic encephalitis and appropriate cancer screening.
Case 2-6
A 58-year-old woman without significant past medical history presented to an emergency department with paroxysmal episodes of confusion occurring hourly. During these episodes she was responsive to voice but was disoriented and spoke nonsensically for 10 to 30 seconds at a time. Family members noted that she was conversational and appropriate after the episodes but that the episodes had become increasingly severe over the past several days, characterized by more automatic movements, agitation, anxiety, and visual hallucinations. Family members had noted occasional lapses in memory prior to the onset of the spells. Serum studies were significant for hyponatremia and hypochloremia. CSF was acellular with normal glucose and protein, and herpes simplex virus PCR was negative. Brain MRI demonstrated increased T2 signal and slight expansion of the right hippocampus with an ill-defined increased T2 signal involving the right amygdala and uncus (Figure 2-5A). She was diagnosed with focal dyscognitive seizures and treated with IV acyclovir, free water restriction, divalproex sodium, and levetiracetam. Seizures were refractory to treatment and began to occur hourly. She also experienced deteriorating memory and persistent visual hallucinations. She was transferred to a tertiary medical center for further evaluation.

1005
Spells

Comment. The fulminant presentation of frequent medically refractory seizures accompanied by visual hallucinations and memory disturbances is suggestive of the diagnosis of limbic encephalitis. Upon transfer, continuous EEG with concurrent video demonstrated stereotyped seizures arising from the left temporal lobe originally (Figure 2-5B) and subsequently from either temporal region. Despite multiple anticonvulsant medications, seizures persisted for weeks. Serum testing revealed voltage-gated potassium channel (VGKC) antibodies, and she was diagnosed with a VGKC-mediated limbic encephalitis. The clinical course was complicated by drug rash with eosinophilia and systemic symptoms believed to be caused by phenytoin. No malignancy was ever identified, despite an appropriate evaluation, and the patients seizures became better controlled only after treatment with immune-modulating medications. She was eventually discharged to home after acute rehabilitation but has required assistance with instrumental activities of daily living.
FIGURE 2-5
(A) Coronal T2-weighted brain MRI in a woman with limbic encephalitis demonstrating increased T2 signal and increased size of right hippocampal body. (BYD) Sequential EEG (longitudinal bipolar montage) demonstrating left temporal seizure in a woman with limbic encephalitis (rectangles).
1006
October 2011
therapy is instituted for the underlying autoimmune process (potentially involving corticosteroids, plasma exchange, IV immunoglobulin, rituximab, or cyclophosphamide). CONCLUSION The diagnosis of spells relies heavily on extensive and detail-oriented history taking and is aided by direct observation of the spells themselves. While seizures are a common cause for spells in the acute care setting, a variety of other diagnoses can present with paroxysmal symptoms or an episodic course. In some instances, these seizure mimics can be identified based on certain features of their clinical presentation. In the remainder of cases, familiarity with the appropriate differential diagnosis and diagnostic testing will help guide the consultant through a systematic evaluation. REFERENCES
1. Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE Commission on Classification and Terminology, 2005Y2009. Epilepsia 2010;51(4):676Y85. 2. Jobst BC, Williamson PD. Anatomical-clinical localization of ictal behavior. In: Kaplan PW, Fisher RS, editors. Imitators of epilepsy. 2nd ed. New York: Demos, 2005:29Y44. 3. Berg AT, Shinnar S. The risk of seizure recurrence following a first unprovoked seizure: a quantitative review. Neurology 1991;41(7):965Y972. 4. Chen DK, So YT, Fisher RS. Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Use of serum prolactin in diagnosing epileptic seizures. Neurology 2005;65(5): 668Y675. 5. Barry E, Hauser WA. Pleocytosis after status epilepticus. Arch Neurol 1994;51(2):190Y193. 6. Harden CL, Huff JS, Schwartz TH, et al. Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Reassessment: neuroimaging in the emergency patient
presenting with seizure (an evidence-based review). Neurology 2007;69(18):1772Y1780. 7. Krumholz A, Wiebe S, Gronseth G, et al. Quality Standards Subcommittee of the American Academy of Neurology; American Epilepsy Society. Practice parameter: evaluating an apparent unprovoked first seizure in adults (an evidence-based review). Neurology 2007;69(18):1772Y1780. 8. Bien CG, Elger CE. Epilepsia partialis continua: semiology and differential diagnoses. Epileptic Disord 2008;10(1):3Y7. 9. Sinha S, Satishchandra P. Epilepsia Partialis Continua over last 14 years: experience from a tertiary care center from south India. Epilepsy Res 2007;74(1):55Y59. 10. Thomas JE, Reagan TJ, Klass DW. Epilepsia partialis continua: a review of 32 cases. Arch Neurol 1977;34(5):266Y275. 11. Thijs RD, Bloem BR, van Dijk JG. Falls, faints, fits and funny turns. J Neurol 2009;256(2): 155Y167. 12. Soteriades ES, Evans JC, Larson MG, et al. Incidence and prognosis of syncope. N Engl J Med 2002;347(12):878Y885. 13. Romme JJ, van Dijk N, Boer KR, et al. Influence of age and gender on the occurrence and presentation of reflex syncope. Clin Auton Res 2008;18(3):127Y133. 14. Lempert T, Bauer M, Schmidt D. Syncope: a videometric analysis of 56 episodes of transient cerebral hypoxia. Ann Neurol 1994;36(2):233Y237. 15. Sheldon R, Rose S, Ritchie D, et al. Historical criteria that distinguish syncope from seizures. J Am Coll Cardiol 2002;40(1):142Y148. 16. Thijs RD, Wagenaar WA, Middelkoop HA, et al. Transient loss of consciousness through the eyes of a witness. Neurology 2008; 71(21):1713Y1718. 17. Schuele SU, Bermeo AC, Alexopoulos AV, et al. Video-electrographic and clinical features in patients with ictal asystole. Neurology 2007;69(5):434Y441. 18. Winesett P, Feliciano CA, Tatum WO 4th. Temporal lobe seizures triggering recurrent syncope by ictal asystole. Epilepsy Behav 2009;14(1):258Y260. 19. Wieling W, Thijs RD, van Dijk N, et al. Symptoms and signs of syncope: a review of the link between physiology and clinical clues. Brain 2009;132(pt 10):2630Y2642. 20. Halpern AL, Silberstein SD. Migraine and epilepsy. In: Kaplan PW, Fisher RS, editors. Imitators of epilepsy. 2nd ed. New York: Demos, 2005:121Y132.
1007
Spells
21. Lipton RB, Ottman R, Ehrenberg BL, Hauser WA. Comorbidity of migraine: the connection between migraine and epilepsy. Neurology 1994;44(10 suppl 7):S28YS32. 22. Baquis GD, Pessin MS, Scott RM. Limb shakingVa carotid TIA. Stroke 1985;16(3): 444Y448. 23. Ali S, Khan MA, Khealani B. Limb-shaking Transient Ischemic Attacks: case report and review of literature. BMC Neurol 2006;6:5. 24. Bazil CW. Parasomnias, sleep disorders, and narcolepsyVsleep-time imitators of epilepsy. In: Kaplan PW, Fisher RS, editors. Imitators of epilepsy. 2nd ed. New York: Demos, 2005:217Y230. 25. Derry CP, Davey M, Johns M, et al. Distinguishing sleep disorders from seizures: diagnosing bumps in the night. Arch Neurol 2006;63(5):705Y709. 26. Helms A, Shulman L. Movement disorders that imitate epilepsy. In: Kaplan PW, Fisher RS, editors. Imitators of epilepsy. 2nd ed. New York: Demos, 2005:163Y184. 27. Gates JR, Ramani V, Whalen S, Loewenson R. Ictal characteristics of pseudoseizures. Arch Neurol 1985;42(12):1183Y1187. 28. Chung SS, Gerber P, Kirlin KA. Ictal eye closure is a reliable indicator for psychogenic nonepileptic seizures. Neurology 2006;66(11): 1730Y1731. 29. Geyer JD, Payne TA, Drury I. The value of pelvic thrusting in the diagnosis of seizures and pseudoseizures. Neurology 2000;54(1): 227Y229. 30. Vossler DG, Haltiner AM, Schepp SK, et al. Ictal stuttering: a sign suggestive of psychogenic nonepileptic seizures. Neurology 2004;63(3):516Y519. 31. Burneo JG, Martin R, Powell T, et al. Teddy bears: an observational finding in patients with non-epileptic events. Neurology 2003;61(5):714Y715. 32. Hoerth MT, Wellik KE, Demaerschalk BM, et al. Clinical predictors of psychogenic nonepileptic seizures: a critically appraised topic. Neurologist 2008;14(4):266Y270. 33. Benbadis SR. A spell in the epilepsy clinic and a history of chronic pain or fibromyalgia independently predict a diagnosis of psychogenic seizures. Epilepsy Behav 2005;6(2):264Y265. 34. Harden CL, Jovine L, Burgut FT, et al. A comparison of personality disorder characteristics of patients with nonepileptic psychogenic pseudoseizures with those of patients with epilepsy. Epilepsy Behav 2009;14(3):481Y483.
35. Cuthill FM, Espie CA. Sensitivity and specificity of procedures for the differential diagnosis of epileptic and non-epileptic seizures: a systematic review. Seizure 2005; 14(5):293Y303. 36. Benbadis SR, Agrawal V, Tatum WO 4th. How many patients with psychogenic nonepileptic seizures also have epilepsy? Neurology 2001;57(5):915Y917. 37. Martin R, Burneo JG, Prasad A, et al. Frequency of epilepsy in patients with psychogenic seizures monitored by video-EEG. Neurology 2003;61(12):1791Y1792. 38. Lowenstein DH, Bleck T, Macdonald RL. Its time to revise the definition of status epilepticus. Epilepsia 1999;40(1):120Y122. 39. Towne AR, Pellock JM, Ko D, DeLorenzo RJ. Determinants of mortality in status epilepticus. Epilepsia 1994;35(1):27Y34. 40. Towne AR, Waterhouse EJ, Boggs JG, et al. Prevalence of nonconvulsive status epilepticus in comatose patients. Neurology 2000;54(2):340Y345. 41. Lowenstein DH, Aminoff MJ. Clinical and EEG features of status epilepticus in comatose patients. Neurology 1992;42(1):100Y104. 42. Claassen J, Mayer SA, Kowalski RG, et al. Detection of electrographic seizures with continuous EEG monitoring in critically ill patients. Neurology 2004;62(10):1743Y1748. 43. Lowenstein DH, Alldredge BK. Status epilepticus. N Engl J Med 1998;338(14): 970Y976. 44. Rossetti AO, Logroscino G, Liaudet L, et al. Status epilepticus: an independent outcome predictor after cerebral anoxia. Neurology 2007;69(3):255Y260. 45. Wijdicks EF, Parisi JE, Sharbrough FW. Prognostic value of myoclonus status in comatose survivors of cardiac arrest. Ann Neurol 1994;35(2):239Y243. 46. Morris HR, Howard RS, Brown P. Early myoclonic status and outcome after cardiorespiratory arrest. J Neurol Neurosurg Psychiatry 1998;64(2):267Y268. 47. Hui AC, Cheng C, Lam A, et al. Prognosis following postanoxic myoclonus status epilepticus. Eur Neurol 2005;54(1):10Y13. 48. Rossetti AO, Oddo M, Liaudet L, Kaplan PW. Predictors of awakening from postanoxic status epilepticus after therapeutic hypothermia. Neurology 2009;72(8):744Y749. 49. Zandbergen EG, Hijdra A, Koelman JH, et al. PROPAC Study Group. Prediction of poor outcome within the first 3 days of postanoxic coma. Neurology 2006;66(1):62Y68.
October 2011
1008
50. Wijdicks EF, Hijdra A, Young GB, et al. Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: prediction of outcome in comatose survivors after cardiopulmonary resuscitation (an evidence-based review). Neurology 2006;67(2):203Y210. 51. Simon RP. Hypoxia versus ischemia. Neurology 1999;52(1):7Y8. 52. Lance JW, Adams RD. The syndrome of intention or action myoclonus as a sequel to hypoxic encephalopathy. Brain 1963;86: 111Y136. 53. English WA, Giffin NJ, Nolan JP. Myoclonus after cardiac arrest: pitfalls in diagnosis and prognosis. Anaesthesia 2009;64(8):908Y911. 54. Banatar M, Drislane FW. Encephalopathy as a mimic of seizures. In: Kaplan PW, Fisher RS,
editors. Imitators of epilepsy. 2nd ed. New York: Demos, 2005:191Y205. 55. Kozak OS, Wijdicks EF, Manno EM, et al. Status epilepticus as initial manifestation of posterior reversible encephalopathy syndrome. Neurology 2007;69(9):894Y897. 56. Lee VH, Wijdicks EF, Manno EM, Rabinstein AA. Clinical spectrum of reversible posterior leukoencephalopathy syndrome. Arch Neurol 2008;65(2):205Y210. 57. Vincent A, Irani SR, Lang B. The growing recognition of immunotherapy-responsive seizure disorders with autoantibodies to specific neuronal proteins. Curr Opin Neurol 2010;23(2):144Y150. 58. Dalmau J, Rosenfeld MR. Paraneoplastic syndromes of the CNS. Lancet Neurol 2008; 7(4):327Y340.
1009

Evaluation of The Patient With Spells

Enviado por

Dados do documento

Descrição original:

Título original

Direitos autorais

Formatos disponíveis

Compartilhar este documento

Compartilhar ou incorporar documento

Opções de compartilhamento

Você considera este documento útil?

Este conteúdo é inapropriado?

Direitos autorais:

Formatos disponíveis

Evaluation of The Patient With Spells

Enviado por

Direitos autorais:

Formatos disponíveis

Review Article

Evaluation of the Patient With Spells

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

TABLE 2-1 Diagnoses Associated With Episodic Neurologic Deficits

h Spells can present with

h The key features of the

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

TABLE 2-2 Major Presenting Features of Spells in the Ward Patient

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Waxing and waning

Tonic, clonic, Atonic, myoclonic atonic, myoclonic, dystonic, complex

None, except Atonic, limb-shaking complex TIA or atonic

From standing Yes

During sleep Variable

Variable Impaired awareness, loss of consciousness Postictal

Yes, minutes None to hours Cyanosis Often marked tachycardia Pallor

None or modest confusion No change

None or variable No change Mild tachycardia Variable

Appearance Vital signs

Hypertension No change No change

Variable Trauma, tongue biting, and incontinence

Continuum Lifelong Learning Neurol 2011;17(5):9841009

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

TABLE 2-4 Lateralizing and Localizing Features of Focal Seizures

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

TABLE 2-5 Common Causes of Provoked Seizures

h Routine EEG is indicated

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Continued on page 991

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Continued from page 990

Continuum Lifelong Learning Neurol 2011;17(5):9841009

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

h Variables most highly

h Visual aura is most

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

h TIAs are associated

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

h REM behavior disorder

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

h Whenever spells involve

h The two types of

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

h The evaluation of spells

Continued on page 998

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Continued from page 997

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Continued on page 1000

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Continued from page 999

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

TABLE 2-7 Causes of Symptomatic Myoclonus

Continuum Lifelong Learning Neurol 2011;17(5):9841009

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Response to benzodiazepines EEG

Continuum Lifelong Learning Neurol 2011;17(5):9841009

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

Copyright @ American Academy of Neurology. Unauthorized reproduction of this article is prohibited.

h Seizures are the