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CHAPTER 171: Seizures and Status Epilepticus in Adults 1153 Isolated cases of unsteady gait have been observed with antiviral drugs such as abacavir as well as antiparasitic agents. Solvents and other chemicals such as propylene glycol, toluene, mercury, and hydrocarbons can cause both peripheral and central vestibular symptoms. Drugs that sometimes induce a central vestibular syndrome include tricyclic antidepressants, neuroleptics, opiates, and alcohol. Anticonvulsants cause dizziness and ataxia, especially in older patients. Phenytoin, toluene, and cancer chemotherapy agents can cause irreversible cer ebellar toxicity. Phencyclidine is a recreational drug that causes central vestibular symptoms, including nystagmus and ataxia. In general, most patients adapt to chronic vertigo by relying on intact proprioception and vision. However, benzodiazepines and neuroleptics that are often used as antivertigo therapy may exacerbate symptoms by delaying or inhibiting such compensation. Thus, avoid using this therapy on a long-term basis. Refer patients with suspected ototoxicity to an otolaryngologist.  POSTTRAUMATIC VERTIGO Acute posttraumatic vertigo and unsteady gait are caused by a direct injury to the labyrinthine membranes. The onset of vertigo is immedi ate and is accompanied by nausea and vomiting. There may be a con comitant fracture of the temporal bone. Vertigo associated with a closed head injury warrants CT or MRI to exclude an intracranial hemorrhage. Vertigo due to direct labyrinthine trauma tends to resolve within several weeks. Closed head trauma also can displace otoconia from the utricu lar maculae, precipitating an attack of BPPV . Postconcussive syndrome can be associated with unsteadiness of gait and a vague sense of dizzi ness. These patients may be treated symptomatically, with referral to an appropriate clinic if symptoms fail to resolve.  WALLENBERG’S SYNDROME A lateral medullary infarction (Wallenberg’s syndrome) of the brainstem can cause vertigo as part of its clinical presentation. Classic ipsilateral findings include facial numbness, loss of corneal reflex, Horner’s syndrome, and paralysis or paresis of the soft palate, pharynx, and larynx (causing dysphagia and dysphonia). Contralateral findings include loss of pain and temperature sensation in the trunk and limbs. Occasionally, lesions of the sixth, seventh, and eighth cranial nerves can occur, causing vertigo, nausea, vomiting, and nystagmus. These patients require emergent MRI and neurologic consultation.  MULTIPLE SCLEROSIS Demyelinating disease can present with vertigo that lasts several hours to several weeks and is usually not recurrent. The vertigo is mild, with nystagmus the most prominent finding on physical examination. Such patients require confirmatory testing with MRI as well as vestibular evoked myogenic potentials and referral to a neurologist. REFERENCES The complete reference list is available online at www.TintinalliEM.com.

y not recurrent. The vertigo is mild, with nystagmus the most prominent finding on physical examination. Such patients require confirmatory testing with MRI as well as vestibular evoked myogenic potentials and referral to a neurologist. REFERENCES The complete reference list is available online at www.TintinalliEM.com. TABLE 170-6 Ototoxic and Vestibulotoxic Agents Agent Dose Dependent Reversible Aminoglycosides Yes Usually not; possible improvement with N-acetylcysteine Erythromycin No Yes Minocycline No Yes Fluoroquinolones No Yes NSAIDs; salicylates Yes Yes Loop diuretics No Can be irreversible Cytostatic drugs Yes No Antimalarials No Yes Anticonvulsants Yes Yes Seizures and Status Epilepticus in Adults Josh Kornegay INTRODUCTION AND PATHOPHYSIOLOGY A seizure is an episode of abnormal neurologic function caused by inappropriate electrical discharge of brain neurons. Neuronal electrical dis charge, in its most simple form, can be thought of as the homeostasis of glutaminergic (excitatory) and γ-aminobutyric acid (inhibitory) activity. The seizure is the clinical attack in the setting of inappropriate excitatory activity. Some patients with “epileptic” electroencephalographic (EEG) discharges may not experience any overt clinical symptoms. Some sei zure-like episodes may be due to causes other than abnormal brain electrical activity, but such attacks are not true seizures. Epilepsy is a clinical condition in which an individual is subject to recurrent seizures. It implies a fixed, excitatory condition of the brain with a lower seizure threshold. The term epileptic does not refer to an individual with recurrent seizures caused by reversible conditions such as alcohol withdrawal or metabolic derangements. Primary or idiopathic seizures are those in which no evident cause can be identified. Secondary seizures are a consequence of an identifi able neurologic condition, such as a mass lesion, previous head injury, or stroke. Electrical stimulation of the brain, convulsant potentiating drugs, profound metabolic disturbances, or significant head trauma all may cause reactive seizures in otherwise normal individuals. Reactive seizures are generally self-limited and not considered to be a seizure disorder or epilepsy. Additional definitions of seizures are based on clinical factors or duration: status epilepticus is seizure activity ≥5 minutes, or two or more seizures without regaining consciousness between seizures 1; refractory status epilepticus is persistent seizure activity despite the IV administration of adequate amounts of two antiepileptic agents. SEIZURE CLASSIFICATION The International League Against Epilepsy recommends dividing sei zures into two major groups: generalized seizures and partial seizures (Table 171-1). When there are inadequate data to categorize the seizure, the seizure is considered unclassified.  GENERALIZED SEIZURES Generalized seizures are thought to be caused by near simultaneous activation of the entire cerebral cortex, perhaps caused by an electrical discharge originating deep in the brain and spreading outward. The attacks begin with abrupt loss of consciousness, and this may be the only clinical manifestation of the seizure (as in absence attacks), or there may be a variety of motor manifestations (tonic posturing, clonic jerking of the body and extremities). Generalized tonic-clonic seizures are the most familiar and dramatic of the generalized seizures.

oss of consciousness, and this may be the only clinical manifestation of the seizure (as in absence attacks), or there may be a variety of motor manifestations (tonic posturing, clonic jerking of the body and extremities). Generalized tonic-clonic seizures are the most familiar and dramatic of the generalized seizures. In a typical attack, the patient suddenly becomes rigid (tonic phase), trunk and extremities are extended, and the patient CHAPTER TABLE 171-1 Classification of Seizures •  Generalized  seizures (consciousness always lost) •  Tonic-clonic  seizures (grand mal) •  Absence  seizures (petit mal) •  Others  (myoclonic, tonic, clonic, or atonic seizures) •  Partial  (focal) seizures •  Simple  partial (no alteration of consciousness) •  Complex  partial (consciousness impaired) •  Partial  seizures with secondary generalization (Jacksonian march) •  Unclassified  (inadequate information) Tintinalli_Sec14_p1101-1186.indd 1153 8/2/19 12:09 PM

clonic, or atonic seizures) •  Partial  (focal) seizures •  Simple  partial (no alteration of consciousness) •  Complex  partial (consciousness impaired) •  Partial  seizures with secondary generalization (Jacksonian march) •  Unclassified  (inadequate information) Tintinalli_Sec14_p1101-1186.indd 1153 8/2/19 12:09 PM 1154 SECTION 14: Neurology falls to the ground. As the tonic phase subsides, there are increasing coarse movements that evolve into a symmetric, rhythmic (clonic) jerking of the trunk and extremities. Patients are often apneic during this period and may be cyanotic. They often urinate and may vomit. As the attack ends, the patient is left flaccid and unconscious, often with deep, rapid breathing. Typical attacks last from 60 to 90 seconds; bystanders generally overestimate the duration of the seizure. Consciousness returns gradually, and postictal confusion, myalgias, and fatigue may persist for several hours. Absence seizures are very brief, generally lasting only a few seconds. Patients suddenly develop altered consciousness but no change in postural tone. They appear confused or detached, and current activ ity ceases. They may stare or have twitching of the eyelids. They may not respond to voice or to other stimulation, exhibit voluntary movements, or lose continence. Attacks cease abruptly, and the patients typically resume previous activity without postictal symptoms. Patients and wit nesses may be unaware that anything has happened. Classic absence seizures occur in school-aged children and are often attributed by par ents or teachers to daydreaming or inattention. The attacks can occur as frequently as 100 or more times daily and may result in poor school performance. They usually resolve as the child matures. Similar attacks in adults are more likely to be minor complex partial seizures and should not be termed absence. The distinction is important because the causes and treatment of the two seizures are different.  PARTIAL (FOCAL) SEIZURES Partial seizures are due to electrical discharges beginning in a localized region of the cerebral cortex. The discharge may remain localized or may spread, involving nearby cortical regions or the entire cortex. Focal seizures are more likely to be secondary to a localized structural lesion of the brain. In simple partial focal seizures, the seizure remains localized, and consciousness is not affected. It is possible to deduce the likely location of the initial cortical discharge from the clinical features at the onset of the attack. For example, unilateral tonic movements limited to one extremity suggest a focus in the contralateral motor cortex, whereas visual symptoms suggest an occipital focus. Olfactory or gustatory hal lucinations suggest a focus in the medial temporal lobe. Such sensory phenomena, known as auras, are often the initial symptoms of attacks that then become more widespread, termed secondary generalization. Complex partial seizures are focal seizures in which consciousness or mentation is affected. They are often caused by a focal discharge originating in the temporal lobe and are sometimes referred to as temporal lobe seizures. Complex partial seizures are commonly misdiagnosed as psychiatric problems because symptoms can be so bizarre. Symptoms may include automatisms, visceral symptoms, hallucinations, memory disturbances, distorted perception, and affective disorders. Common automatisms include lip smacking, fiddling with clothing or buttons, or repeating short phrases. Visceral symptoms often consist of a sensation of “butterflies” rising up from the epigastrium. Hallucinations may be olfactory, gustatory, visual, or auditory. There may be complex distortions of visual perception, time, and memory.

s include lip smacking, fiddling with clothing or buttons, or repeating short phrases. Visceral symptoms often consist of a sensation of “butterflies” rising up from the epigastrium. Hallucinations may be olfactory, gustatory, visual, or auditory. There may be complex distortions of visual perception, time, and memory. Affective symptoms may include intense sensations of fear, paranoia, depression, elation, or ecstasy. Because such seizures result in alterations of thinking and behavior, they were previously referred to as psychomotor seizures, but to avoid confusion with psychiatric illness, the term complex partial seizure is preferred. Focal seizures may spread to involve both hemispheres, mimicking a typical generalized seizure. For the purpose of classification, diagnosis, and treatment, such attacks are still regarded as focal seizures. In some patients, the discharge may spread so rapidly that no focal symptoms are evident, and the correct diagnosis may depend entirely on demonstra tion of the focal discharge on an EEG recording. CLINICAL FEATURES  HISTORY When a patient presents after the event, the first step is to determine whether the episode was truly a seizure. Obtain a careful history of the details of the attack from the patient and any bystanders who witnessed the attack. Inquire about the physical description of the attack, as wit nesses may mislabel the activity and mistake nonseizure activity as a seizure. Important avenues of inquiry include the presence of a preceding aura, abrupt or gradual onset, progression of motor activity, loss of bowel or bladder control, presence of oral injury, and whether the activity was localized, generalized, symmetric, or asymmetric. Ask about the duration of the episode, and determine the presence of post ictal confusion or lethargy. Next, determine the clinical context of the episode. If the patient is a known epileptic, clarify the baseline seizure pattern. If the attack is consistent with the previous seizure pattern, identify precipitat ing factors of the current seizure. Common precipitating factors include missed doses of antiepileptic medications; recent altera tions in medication, including dosage change or conversion from brand name; sleep deprivation; increased strenuous activity; infec tion; electrolyte disturbances; and alcohol or substance use or withdrawal. If there is no previous history of seizures, a more detailed inquiry is needed. Symptoms such as unexplained injuries, nocturnal tongue biting, or enuresis suggest previous unrecognized seizures. Ask about a history of recent or remote head injury. Persistent, severe, or sudden headache suggests intracranial pathology. Pregnancy or recent delivery raises the possibility of eclampsia. A history of metabolic or electrolyte abnormalities, hypoxia, systemic illness (especially cancer), coagulopa thy or anticoagulation, exposure to industrial or environmental toxins, drug ingestion or withdrawal, and alcohol use may point to predisposing factors (Table 171-2).  PHYSICAL EXAMINATION Immediately obtain a complete set of vital signs and a point-of-care glucose. In the postseizure setting, focus the initial exam on checking for injuries, especially head or spine trauma, as a result of the seizure. A posterior shoulder dislocation is an injury that is easy to overlook. Lacerations of the tongue and mouth, dental fracture, and pulmonary aspiration are also frequent sequelae. Perform a directed, complete neurologic examination and subsequent serial examinations. Follow the patient’s level of consciousness and mentation closely to avoid missing nonconvulsant status epilepticus (see below).

erations of the tongue and mouth, dental fracture, and pulmonary aspiration are also frequent sequelae. Perform a directed, complete neurologic examination and subsequent serial examinations. Follow the patient’s level of consciousness and mentation closely to avoid missing nonconvulsant status epilepticus (see below). A transient focal deficit (usually unilateral) following a TABLE 171-2 Common Causes of Provoked (Secondary) Seizures •  Trauma  (recent or remote) •  Intracranial  hemorrhage (subdural, epidural, subarachnoid, intraparenchymal) •  Vascular  lesion (aneurysm, arteriovenous malformation) •  Mass  lesions (primary or metastatic neoplasms) •  Degenerative  neurologic diseases •  Congenital  brain abnormalities •  Infection  (meningitis, encephalitis, abscess) •  Hypo-  or hyperglycemia •  Hypo-  or hypernatremia •  Hyperosmolar  states •  Uremia •  Hepatic  failure •  Hypocalcemia,  hypomagnesemia (rare) •  Cocaine,  lidocaine, antidepressants, theophylline, isoniazid •  Mushroom  toxicity (Gyromitra spp.) •  Hydrazine  (rocket fuels) •  Alcohol  or drug withdrawal •  Eclampsia  of pregnancy (may occur up to 8 weeks postpartum) •  Hypertensive  encephalopathy •  Anoxic-ischemic  injury (cardiac arrest, severe hypoxemia) Tintinalli_Sec14_p1101-1186.indd 1154 8/2/19 12:09 PM

isoniazid •  Mushroom  toxicity (Gyromitra spp.) •  Hydrazine  (rocket fuels) •  Alcohol  or drug withdrawal •  Eclampsia  of pregnancy (may occur up to 8 weeks postpartum) •  Hypertensive  encephalopathy •  Anoxic-ischemic  injury (cardiac arrest, severe hypoxemia) Tintinalli_Sec14_p1101-1186.indd 1154 8/2/19 12:09 PM CHAPTER 171: Seizures and Status Epilepticus in Adults 1155 simple or complex focal seizure is referred to as Todd’s paralysis and should resolve within 48 hours. DIAGNOSIS Clinical features that help to distinguish seizures from other nonseizure attacks include the following: • Abrupt onset and termination. Some focal seizures are preceded by auras that can last 20 to 30 seconds, but most attacks begin abruptly. Episodes reported to develop over several minutes or longer should be regarded with suspicion. Most seizures last only 1 or 2 minutes, unless the patient is in status epilepticus. • Lack of recall. Except for simple partial seizures, patients usually cannot recall the details of an attack. • Purposeless movements or behavior during the attack. • Most seizures are followed by a period of postictal confusion and lethargy.  DIFFERENTIAL DIAGNOSIS Many episodic disturbances of neurologic function may be mistaken for seizures (seizure mimics). A complete review of these conditions is too lengthy for inclusion here, but several important entities are mentioned. Syncope usually presents with prodromal symptoms, such as light headedness, diaphoresis, nausea, and “tunnel vision. ” However, cardiac syncope may occur suddenly without any prodromal warning. Syncope may be associated with injury, incontinence, or even brief tonic-clonic activity. Recovery is usually rapid, with no postictal-like symptoms. For further discussion, see Chapter 52, “Syncope. ” Pseudoseizures can be difficult to distinguish from true seizures and may occur in a patient who also has a documented seizure disor der. Pseudoseizures are psychogenic in origin and are often associated with a conversion disorder, panic disorder, psychosis, Munchausen syndrome, or malingering. Suspect this diagnosis when seizures occur in response to emotional upset or occur only with witnesses present. Pseudoseizures are often bizarre and highly variable. Patients often are able to protect themselves from noxious stimuli during the attack. Characteristic movements include side-to-side head thrashing, pelvic thrusting, and clonic alternating extremity motions rather than symmetric. Incontinence and injury are uncommon, and there is usually no postictal confusion. Patients will often stop the seizure-like activity on command. Accurate diagnosis of pseudoseizures may require pro longed EEG or video monitoring to demonstrate normal EEG activity during an attack. The lack of a lactic acidosis or elevated prolactin level within 10 to 15 minutes of the cessation of seizure-like activity makes true seizures much less likely. 2,3 Hyperventilation syndrome can be misdiagnosed as a seizure disorder. A careful history will reveal the gradual onset of the attacks with shortness of breath, anxiety, and perioral numbness. Such attacks may progress to involuntary spasm (especially carpopedal) of the extremities and even loss of consciousness, although postictal symp toms are rare. Asking the patient to hyperventilate often reproduces the episodes. Movement disorders, such as dystonia, chorea, myoclonic jerks, tremors, or tics, may occur in a variety of neurologic conditions. Con sciousness is always preserved during these movements, and the patient can often temporarily suppress the movements. Migraine headaches may be preceded by an aura similar to that seen in some partial seizures. The most common migraine aura is the scintillating scotoma.

y occur in a variety of neurologic conditions. Con sciousness is always preserved during these movements, and the patient can often temporarily suppress the movements. Migraine headaches may be preceded by an aura similar to that seen in some partial seizures. The most common migraine aura is the scintillating scotoma. Migraine headaches may also be accompanied by focal neurologic symptoms, such as homonymous hemianopsia or hemiparesis. However, active movement disorders are inconsistent with migraine.  LABORATORY TESTING Individualize the use of laboratory studies. In a patient with a welldocumented seizure disorder who has had a single unprovoked seizure, the only tests that may be needed are a glucose level and pertinent anticonvulsant medication levels. In the case of an adult with a first seizure or unclear seizure history, more extensive studies are usually needed and depend on the clinical context. Obtain serum glucose, basic metabolic panel, lactate, calcium, magnesium, a pregnancy test, and toxicology studies. Consider assays for anticonvulsant drug levels. A seizure may result in a lactate-driven, wide anion gap metabolic acidosis. 2 Most lactate abnormalities will clear within 30 minutes. The prolactin level may also be elevated for a brief period (15 to 60 minutes) immediately after a seizure. 3 These tests can prove helpful in distinguishing true seizures from a pseudoseizure. Interpret the results of anticonvulsant levels with caution. If patient history is limited, a positive serum assay for anticonvulsant drugs sug gests (but does not prove) the presence of a chronic seizure disorder. The usual therapeutic and toxic levels indicated in laboratory reports are helpful only as rough guides. The therapeutic level of a drug is the level that provides adequate seizure control without unacceptable side effects. A marked change in previously stable drug levels may indicate noncompliance, a change in medication, malabsorption of a drug, or ingestion of a potentiating or competing drug. A very low serum anticonvulsant drug level suggests medication noncompliance and is the most common cause of a breakthrough seizure.  IMAGING Obtain a CT scan of the head in the ED for patients with a first-ever seizure or a change in established seizure patterns to evaluate for a structural lesion. A noncontrast CT is an appropriate screening tool. 4,5 Obtain a CT scan if there is any concern for an acute intracranial process based on history, comorbidities, or findings on physical examination. Concern for an acute intracranial process is an important indication for obtaining CT imaging, even if there is a coexistent metabolic process. Because many important processes, such as tumors or vascular anomalies, may not be evident on noncontrast studies, a follow-up contrast-enhanced CT or MRI is often needed. Almost one quarter of adults with new-onset seizure will have visualized pathology on followup MRI, with rates increasing to as high as 53% in those with onset of a focal seizure. 6 The timing of further imaging studies can be discussed with the consulting neurologist. Obtain other radiographic studies as indicated by the clinical presentation to avoid missing other sequela as a result of the seizure. These may include chest radiographs, cervical spine radiographs, or musculoskel etal imaging if aspiration or injuries are suspected. Special examinations, such as cerebral angiography, are rarely part of the ED evaluation.  LUMBAR PUNCTURE Lumbar puncture in the setting of an acute seizure is indicated if the patient is febrile or immunocompromised or if subarachnoid hemor rhage is suspected and the noncontrast head CT is normal.

ies are suspected. Special examinations, such as cerebral angiography, are rarely part of the ED evaluation.  LUMBAR PUNCTURE Lumbar puncture in the setting of an acute seizure is indicated if the patient is febrile or immunocompromised or if subarachnoid hemor rhage is suspected and the noncontrast head CT is normal. For further discussion, see Chapter 166, “Spontaneous Subarachnoid and Intrace rebral Hemorrhage, ” and Chapter 174, “Central Nervous System and Spinal Infections. ”  ELECTROENCEPHALOGRAPHY Although EEG is helpful, it is often not readily available in most EDs. Emergent EEG can be considered in the evaluation of a patient with persistent, unexplained altered mental status to evaluate for nonconvulsive status epilepticus, subtle status epilepticus, paroxysmal attack when a seizure is suspected, or ongoing status epilepticus after chemical paralysis for intubation. Emergent EEG is normally performed in consultation with a neurologist. TREATMENT OF UNCOMPLICATED SEIZURES  PATIENTS WITH ACTIVE SEIZURES Typically, little is required during the course of an active seizure other than supportive and patient protective measures. If possible, turn the patient to the side to reduce the risk of aspiration. It is usually not necessary or even possible to ventilate a patient effectively during a Tintinalli_Sec14_p1101-1186.indd 1155 8/2/19 12:09 PM

equired during the course of an active seizure other than supportive and patient protective measures. If possible, turn the patient to the side to reduce the risk of aspiration. It is usually not necessary or even possible to ventilate a patient effectively during a Tintinalli_Sec14_p1101-1186.indd 1155 8/2/19 12:09 PM 1156 SECTION 14: Neurology seizure, but once the attack subsides, clear the airway. Suction and air way adjuncts should be readily available. It is not necessary or recom mended to give IV anticonvulsant medications during the course of an uncomplicated seizure, although the practitioner should be ready to administer these medications if seizures do not terminate. Most seizures will self-resolve within 5 minutes. Any unnecessary sedation at this point will complicate the evaluation and result in a prolonged decrease in level of consciousness. 7 Seizures that fail to abate after 5 minutes are considered status epilepticus and require more aggressive medical interventions (see “Status Epilepticus, ” below).  PATIENTS WITH A HISTORY OF SEIZURES Proper management of a patient with a well-documented seizure disorder who presents after one or more seizures depends on the particular circumstances of the case. Identify and correct potential precipitants that may lower the seizure threshold. Many seizures occur due to medication nonadherence. Some anticonvulsants have very short serum half-lives, and missing a single dose may result in a sharp drop in serum levels. If anticonvulsant levels are very low, supplemen tal doses are appropriate, and the regular regimen can be restarted or adjusted. A loading dose is frequently provided. Without a loading dose, the patient may not achieve anticonvulsant effects for days to weeks and is at risk for subsequent seizures. Because there are no data comparing parenteral versus oral replacement, route is left to the discretion of the medical provider 8 and should be based on knowledge of pharmacology. For example, the oral loading dose of phenytoin is 20 milligrams/kg given in three divided doses every 2 to 4 hours—a time frame not acceptable for a typical ED stay—so the IV route is needed to achieve the proper loading dose. In the noncompliant patient, obtain a serum anticonvulsant level before administering a supplemental or loading dose to avoid drug toxicity. If anticonvulsant levels are adequate and the patient has had a single seizure, specific treatment may not be needed if the seizure pattern and frequency fall within the expected range for the patient. If anticonvulsant levels are not available (i.e., levetiracetam or lacos amide) and there is a missed dose or noncompliance, give the usual dose in the ED before discharge. Even well-controlled patients may have occasional breakthrough seizures. Attempt to identify any precipitants that have lowered the seizure threshold. If none is found, a change or adjustment of medication may be needed and should be made in consultation with the patient’s primary care physician or neurologist along with follow-up in 1 to 3 days. There are no specific guidelines for the duration of ED observation in the situation of an individual with a prior history of seizures. Some clinicians discharge patients with seizures resulting from nontherapeutic anticonvulsant levels after administration of a loading dose of an anticonvulsant, if vital signs are normal and the mental status has returned to baseline. Ideally, discharge patients with a reliable family member or friend and with medical follow-up arranged.  PATIENTS WITH A FIRST UNPROVOKED SEIZURE Guidelines do not recommend hospital admission or initiation of anticonvulsant therapy in the patient with a first unprovoked seizure, as long as the patient has returned to neurologic baseline.

ients with a reliable family member or friend and with medical follow-up arranged.  PATIENTS WITH A FIRST UNPROVOKED SEIZURE Guidelines do not recommend hospital admission or initiation of anticonvulsant therapy in the patient with a first unprovoked seizure, as long as the patient has returned to neurologic baseline. 1,8 The most important predictors of seizure recurrence are the underlying cause of the seizure and the results of the EEG. The decision to begin outpatient treatment with antiepileptics depends on the risk of recurrent seizures weighed against the risk-benefit ratio of anticonvulsant therapy. In general, patients with a first unprovoked seizure who have a normal neurologic examination, no acute or chronic medical comorbidities, normal diagnostic testing including noncontrast head CT, and normal mental status can safely be discharged from the ED. Initiation of antiepileptic medication may be deferred to the outpatient setting where further studies, including an EEG and MRI, can be performed. 1,4,8 Consider consultation and/or admission for patients who do not meet the above criteria. Patients with secondary seizures due to an identifiable underlying condition (Table 171-2) often require admission and should generally be treated to minimize seizure recurrence. The ideal initial antiepileptic regimen is a single-drug therapy that controls seizures with minimum toxicity. If treatment is initiated, drug selection is based on the type of seizure and should be done in con sultation with a neurologist. Antiepileptic agents, such as valproate, lamotrigine, topiramate, levetiracetam, and oxcarbazepine, are options for adults with new-onset seizures. 5,9 Consider developing common protocols between emergency medicine and neurology when treatment of new-onset seizures is initiated from the ED. Instruct discharged patients to take precautions to minimize the risks of injury from further seizures. Swimming, working with hazardous tools or machines, and working at heights should be avoided. Driving is prohibited until cleared by the neurologist or primary care physician. Driving privileges should conform to state law, and it may be up to the emergency physician to document seizure activity with the Department of Motor Vehicles. SPECIAL POPULATIONS  HUMAN IMMUNODEFICIENCY VIRUS Mass lesions, encephalopathy, herpes zoster, toxoplasmosis, Cryptococcus, neurosyphilis, and meningitis are all seen more frequently in this population and can all provoke seizure activity.10,11 Perform an extensive investigation for the cause of the seizure. If no space-occupying lesion is identified on noncontrast head CT scan and there is no evidence of increased intracranial pressure, perform a lum bar puncture to exclude CNS infection. If no explanation for seizures is found, then obtain a contrast-enhanced head CT or MRI.  NEUROCYSTICERCOSIS Neurocysticercosis is caused by a CNS infection with the larval stage of the tapeworm Taenia solium and is the most common cause of provoked (secondary) seizures in the developing world. 12 The most common form of disease is parasitic invasion of brain parenchyma and cyst formation. Over 1 to 2 years, the cyst degenerates and becomes fibrotic, leaving a focal area of scar and calcification. Seizures are the most common clinical manifestation of neurocysticercosis and most frequently occur as the parasite is degenerating. In 80% to 90% of cases, the lesions resolve within 3 to 6 months, leaving the patient free of seizures. Up to 20% of patients will continue to have seizures and require ongoing therapy with antiepileptic medications. In most cases, neuroimaging in neurocysticercosis is nondiagnos tic.

r as the parasite is degenerating. In 80% to 90% of cases, the lesions resolve within 3 to 6 months, leaving the patient free of seizures. Up to 20% of patients will continue to have seizures and require ongoing therapy with antiepileptic medications. In most cases, neuroimaging in neurocysticercosis is nondiagnos tic. CT or MRI may demonstrate a 1- to 2-cm cystic lesion with thin walls and a 1- to 3-mm mural nodule (the parasite), a localized area of ring-like enhancement with surrounding edema, a calcified lesion, or hydrocephalus. Definitive diagnosis relies on a combination of the patient’s clinical picture, exposure history, serologic testing, and neuroimaging. Seizures in neurocysticercosis are typically controlled by antiepi leptic monotherapy. Definitive treatment of neurocysticercosis is con troversial and highly variable, depending on the number, location, and viability of the parasites within the CNS. 13,14 Antiparasitics (praziquantel and albendazole) and steroids are best initiated in consultation with an infectious disease specialist or neurologist.  PREGNANCY The management of seizures (or control of epilepsy) during pregnancy requires a multidisciplinary approach. Most seizures in pregnancy are not first-time seizures, and initial evaluation is generally as discussed above, with the addition of an obstetric evaluation to determine gesta tional age and fetal well-being. When a woman beyond 20 weeks of gestation develops seizures in the setting of hypertension, edema, and proteinuria, the diagnosis is eclampsia. Magnesium sulfate is the treatment. In eclampsia, magnesium sulfate infusion compared to diazepam and phenytoin resulted in a >50% reduction in recurrence of seizures and a lower incidence of pneumonia, intensive care unit admission, and assisted ventilation. 15-17 Detailed discussion of seizures in pregnancy is provided in Chapter 100, Tintinalli_Sec14_p1101-1186.indd 1156 8/2/19 12:09 PM

sion compared to diazepam and phenytoin resulted in a >50% reduction in recurrence of seizures and a lower incidence of pneumonia, intensive care unit admission, and assisted ventilation. 15-17 Detailed discussion of seizures in pregnancy is provided in Chapter 100, Tintinalli_Sec14_p1101-1186.indd 1156 8/2/19 12:09 PM CHAPTER 171: Seizures and Status Epilepticus in Adults 1157 “Maternal Emergencies After 20 Weeks of Pregnancy and in the Peri partum Period. ”  ALCOHOL ABUSE Seizures and alcohol use are associated through missed doses of medi cation, sleep deprivation as an epileptogenic trigger, increased propen sity for head injury, toxic coingestions, electrolyte abnormalities, and withdrawal seizures. Benzodiazepines in doses sufficient to manage withdrawal symptoms will usually afford adequate protection from acute seizures. These doses are often very large and need to be given in an escalating fashion. 18 Evaluate and treat the alcohol-abusing patient with a first seizure as any other patient with a first-time seizure. Detailed discussion of alcohol withdrawal seizures is provided in Chapter 292, “Substance Use Disorders. ” STATUS EPILEPTICUS Status epilepticus can occur in patients with a history of seizures or can be a first epileptic event. The most common causes of status epilepticus include subtherapeutic antiepileptic levels; preexisting neurologic con ditions, such as prior CNS infection, trauma, or stroke; acute stroke; anoxia or hypoxia; metabolic abnormalities; and alcohol or drug intoxication or withdrawal. Status epilepticus is a single seizure ≥5 minutes in length or two or more seizures without recovery of consciousness between seizures. 1,20,21 After 5 minutes, seizures are less likely to spontaneously terminate, less likely to be controlled with antiepileptic drugs, and more likely to cause neuronal damage. Status epilepticus is a neurologic emergency, and treatment should be initiated in all patients with continuous seizure activity lasting more than 5 minutes. As seizures surpass the 5-minute mark, dramatic changes occur at the cellular level. Decreased expression and internalization of γ-aminobutyric acid receptors, coupled with increased expression of both glutamine and N-methyl-d-aspartate receptors, lead to a greatly diminished seizure threshold. 22,23 The blood–brain barrier is also compromised, leading to CNS penetration of potassium and albumin, both of which are hyperexcitatory CNS chemicals. 24 After 20 minutes, hypotension, hypoxia, metabolic acidosis, hyperthermia, hypoglycemia, cardiac dysrhythmias, and pulmonary edema frequently develop. 25 This hyperexcitatory milieu makes standard antiseizure therapies much less effective in seizure termination. In nonconvulsive status epilepticus , the patient is comatose or has fluctuating abnormal mental status or confusion, but no overt seizure activity is present. The diagnosis is challenging and is typically made by EEG. Findings suggestive of nonconvulsive status epilepticus include a prolonged postictal period after a generalized seizure; subtle motor signs such as twitching, blinking, and eye deviation; fluctuating alterations in mental status; or unexplained stupor and confusion. TREATMENT OF STATUS EPILEPTICUS Early recognition and treatment of status epilepticus are critically important. Mortality dramatically increases with delayed diagnosis or initiation of treatment, particularly with nonconvulsive status epilep ticus, age greater than 60 years, and in patients with no documented seizure disorder. 26 The goal of treatment is seizure control as soon as possible and within 30 minutes of presentation ( Figure 171-1). Examination, identification of potential causes, application of the ABCs (airway, breathing, and circulation), and treatment all begin simultane ously.

in patients with no documented seizure disorder. 26 The goal of treatment is seizure control as soon as possible and within 30 minutes of presentation ( Figure 171-1). Examination, identification of potential causes, application of the ABCs (airway, breathing, and circulation), and treatment all begin simultane ously. Direct a focused history and physical examination toward possible causes and subsequent injuries. Establish large-bore IV access and determine a bedside glucose. Administer normal saline, avoiding IV fluids containing glucose as phenytoin is not compatible with glucose-containing solutions. Place the patient on oxygen, a cardiac monitor, pulse oximeter, and end-tidal capnography. In established status epilepticus, consider endotracheal intubation for airway protection, oxygenation, and ventilation. Use a short-acting Active Seizure 0–5 minutes Established Status Epilepticus Treatment Goal: 5–10 minutes Refractory Status Epilepticus Treatment Goal: <30 minutes Supportive Care: IV access, monitors, maintain airway, oxygen, check point-of-care glucose and provide IV glucose if indicated Patient Protection IV Lorazepam: 2 milligrams up to 0.1 milligram/kg IV Diazepam: 10–20 milligrams IV Fosphenytoin: 20 PE/kg at 150 milligrams/min ___________________ IV Phenytoin: 20 milligrams/kg at 50 milligrams/min___________________ IV Levetiracetam: 2000–4000 milligrams___________________ IV Propofol: 1 milligram/kg IV, then 1–10 milligrams/kg/h; Ketamine, 5 milligrams/kg/h Phenobarbital: 20 milligrams/kg at 50–75 milligrams/min Consider intubation Intubate patient Continuous EEG monitoring Neuro ICU admission One of the following IV Midazolam: Load with 0.2 milligram/kg then infusion of 0.05–2 milligrams/kg/h FIGURE 171-1. Guidelines for management of active seizures and status epilepticus. EEG = electroencephalogram, ICU = intensive care unit, PE = phenytoin equivalent. Tintinalli_Sec14_p1101-1186.indd 1157 8/2/19 12:09 PM

One of the following IV Midazolam: Load with 0.2 milligram/kg then infusion of 0.05–2 milligrams/kg/h FIGURE 171-1. Guidelines for management of active seizures and status epilepticus. EEG = electroencephalogram, ICU = intensive care unit, PE = phenytoin equivalent. Tintinalli_Sec14_p1101-1186.indd 1157 8/2/19 12:09 PM 1158 SECTION 14: Neurology paralytic agent in order not to mask ongoing seizure activity. Arrange for continuous EEG monitoring as soon as possible after paralytic agents have been used. Initial laboratory evaluation includes blood glucose, a metabolic panel including calcium and magnesium, lactate, and if appropriate, a preg nancy test, a toxicology screen, and anticonvulsant levels. Administer glucose IV if hypoglycemia is suspected or confirmed. Monitor temperature continuously, and treat hyperthermia with passive cooling. Place a urinary catheter to monitor urine output and insert a nasogastric tube to help prevent aspiration. If toxic ingestion is suspected as the cause of seizures, proceed with GI decontamination (as appropriate). Do not attempt lumbar puncture during status epilepticus. If bacterial meningitis or encephalitis is suspected clinically, then immediately start empiric antibiotic or antiviral therapy. Radiographic studies, such as a CT scan, will usually need to be delayed until seizures are controlled.  ANTICONVULSANT DRUGS IN STATUS EPILEPTICUS The drugs most often used in the therapy of status epilepticus are the benzodiazepines (lorazepam, midazolam, or if not available, diazepam) and phenytoin or fosphenytoin (Figure 171-1). Benzodiazepines are used in patients with continuous or very frequent seizures to temporarily control the seizures until more specific agents can be given. IV loraz epam (2 to 4 milligrams) and IV diazepam (5 to 10 milligrams) have equal efficacy in controlling status epilepticus. 8 Compared to diazepam, lorazepam has a slightly slower onset (3 vs. 2 minutes) but a significantly longer duration of action (12 to 24 hours vs. 15 to 60 minutes) and is associated with fewer seizure recurrences. In one prehospital study, IM midazolam demonstrated decreased seizure time and fewer intensive care unit admissions when compared to lorazepam if no IV access was available, 27 and in an additional noninferiority prehospital trial, IM midazolam was determined to be as safe and effective as IV lorazepam.28 However, IV lorazepam is still considered the initial agent of choice if IV access is available. Lorazepam is also more effective than phenytoin or phenobarbital as a first-line agent. 29 Respiratory depression and hypotension may occur, especially in young children and in patients taking alcohol, barbiturates, narcotics, or other sedatives. In patients with dif ficult IV access and emergent need for seizure control, there may be a role for rectal diazepam gel or buccal midazolam. Although there have been no trials in adults, rectal diazepam has been used by EMS provid ers in children with good success for years, and recent trials of buccal midazolam (0.5 milligram/kg, up to 10 milligrams) show more efficacy than rectal diazepam in the pediatric population. 30,31 In established status epilepticus, follow benzodiazepines with longeracting antiepileptic agents: fosphenytoin or phenytoin; levetiracetam; valproate; or lacosamide. One of these antiepileptic agents should be started within 20 minutes of diagnosis. 1 The most updated consensus guidelines do not currently recommend one second-line agent over another. 32 Multicenter trials are currently under way to help determine which of these antiepileptic agents are the most effective in helping ter minate status epilepticus.33 Fosphenytoin is a water-soluble prodrug of phenytoin that is con verted to phenytoin in the plasma.

rrently recommend one second-line agent over another. 32 Multicenter trials are currently under way to help determine which of these antiepileptic agents are the most effective in helping ter minate status epilepticus.33 Fosphenytoin is a water-soluble prodrug of phenytoin that is con verted to phenytoin in the plasma. Fosphenytoin has similar time of onset, effectiveness, and cardiac effects as phenytoin. It has much fewer infusion-site reactions due to the lack of propylene glycol and ethanol as the diluents. Fosphenytoin may be infused quickly, and for that reason, it is preferred over phenytoin. Fosphenytoin dosing is expressed as phenytoin equivalents to prevent confusion. The loading dose is 20 phenytoin equivalents/kg, which can be infused at 150 phenytoin equivalents/ min over 10 to 15 minutes. 9 Fosphenytoin can also be given IM, which may be useful if the patient does not have IV access. The loading dose for phenytoin is 20 milligrams/kg IV . Doses in excess of the usual 1000 milligrams are often required. Due to myo cardial depression from its propylene glycol diluent, phenytoin is typically infused no faster than a rate of 25 milligrams/min (taking about 1 hour to administer). The rate may be increased to 50 milligrams per minute during status epilepticus as long as hypotension does not develop. Place patients on a cardiac monitor, with blood pressure assessments every 5 to 15 minutes during the infusion and every 15 minutes for 1 hour after infusion. 34 Phenytoin should not be mixed with any glucose-containing IV fluid and should not be given IM due to erratic absorption. Adverse effects include infusion-site reactions, hypotension, and cardiac dysrhythmias, and it is contraindicated in patients with second- or third-degree atrioventricular blocks. If side effects develop, stop the infusion and restart at a lower rate after side effect resolution. Valproic acid is effective but has serious side effects compared to the agents listed above; the Food and Drug Administration has issued a black-boxed warning for hepatic failure and pancreatitis, and valproic acid should not be administered along with phenytoin. The dose is 20 to 40 milligrams/kg IV . 1,9,22,35,36 Levetiracetam is very effective, is quick to administer, and has few interactions and side effects. The precise mechanism of action is unknown, but it may inhibit voltage-dependent calcium channels and facilitate γ-aminobutyric acid inhibitory transmission. The dose is 20 to 60 milligrams/kg IV . While it is not yet approved by the Food and Drug Administration for status epilepticus, it is rapidly gaining favor as a firstline drug for established status epilepticus. 1,9,37-39 Lacosamide is a potential alternative for status epilepticus with lim ited availability and limited data on its use. The dose is 200 milligrams IV given over 15 minutes. 1,40  REFRACTORY STATUS EPILEPTICUS Refractory status epilepticus is defined as persistent seizure activity despite the IV administration of adequate amounts of two antiepileptic agents and usually exceeds 60 minutes. 1 One study found up to 31% of patients with status epilepticus developed refractory status epilepticus.41 Various approaches to refractory status epilepticus have been advo cated (Figure 171-1).1,7,9,22,36-47 Overall, there are few controlled trials that strongly support a single agent or combination of agents. Recommendations include propofol, midazolam, and barbiturates such as phenobar bital or pentobarbital given as infusions.1 All of these agents can lead to hypotension, sometimes requiring concomitant vasopressor use, and frequently require intubation.

rials that strongly support a single agent or combination of agents. Recommendations include propofol, midazolam, and barbiturates such as phenobar bital or pentobarbital given as infusions.1 All of these agents can lead to hypotension, sometimes requiring concomitant vasopressor use, and frequently require intubation. Ideally, treatment is in consultation with a neurologist and in an intensive care setting, as advanced respiratory support, cardiovascular support, and EEG monitoring are all needed. Propofol is a widely used, lipophilic, general anesthetic that has come into favor for refractory status epilepticus. It can be started as an infusion at typical rates of 2 to 10 milligrams/kg/h and titrated up to effect of seizure cessation. Propofol has the added benefit of a short half-life allowing for quicker neurologic recovery after seizure control is achieved. At higher doses (>40 milligrams/kg/h), patients are at increased risk for hemodynamic instability including hypotension as well as propofol infusion syndrome. 1,7,9,22,43 Midazolam is an easily titrated, infusible benzodiazepine that can also be used in the ongoing treatment of refractory status epilepticus. Midazolam can be started at 0.05 to 0.4 milligram/kg/h and is titrated up to seizure cessation. 1,9,44 Midazolam can accumulate in peripheral soft tissues, particularly with renal insufficiency, leading to a much prolonged recovery period. Barbiturates, such as phenobarbital (up to 20 milligrams/kg IV) or pentobarbital, may be considered as third-line drugs in patients whose seizures are not controlled despite full loading doses of benzodiazepines and other agents. However, patients in refractory status epilepticus may not respond to barbiturates. One study found no added seizure control with phenobarbital. 36 A subsequent meta-analysis showed improved seizure control with pentobarbital compared to propofol or midazolam, but no differences in mortality. 42 Respiratory depression and hypotension are more common when using barbiturates, especially at higher doses or when diazepam or lorazepam is also given. 1,9,22 Additionally, midazolam and propofol have the advantage over barbiturates of having a shorter half-life and rapid clearance, allowing for earlier extubation and clinical assessment. 1 For these reasons, current recommendations are to use propofol and midazolam infusions as first- and second-line agents, respectively, in refractory status epilepticus with barbiturates as a third-line agent. 1,9,22,43,44 Finally, ketamine may also be considered as a third-line agent in refractory status epilepticus. Ketamine is an N-methyl-d-aspartate receptor antagonist and helps block the hyperexcitatory pathway, Tintinalli_Sec14_p1101-1186.indd 1158 8/2/19 12:09 PM