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Seizure Disorders 

Seizure Disorders
Seizure Disorders

James Burke

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date: 29 June 2022

  1. A. Introduction

    1. a. Definitions

      1. i. A seizure is a paroxysmal abnormality of cerebral function caused by uncontrolled, excessive discharges from a group of neurons.

      2. ii. Epilepsy is a term reserved for recurrent (unprovoked) seizures.

      3. iii. Status epilepticus is a term used to describe a continuous seizure that (1) lasts more than 5 minutes or (2) is associated with occurrence of more than two seizures without returning to baseline between seizures. Remember, most seizures last less than 2 minutes.

        Hot Key

        A prolonged seizure or suspected status epilepticus is a medical emergency.

      4. iv. An aura is a subjective sensation experienced before a seizure. In fact, these represent focal seizures (see C. a.).

      5. v. Automatisms are repetitive movements such as lip smacking, chewing, and scratching that often accompany focal seizures.

      6. vi. Postictal refers to “after the ictus (or event).” Patients are often tired and disoriented after a seizure and may have a transient focal paralysis secondary to seizure activity, called Todd’s paralysis. Typically, all symptoms improve over the course of minutes to hours.

    2. b. Epidemiology. Epilepsy is a relatively common neurologic problem, affecting about 0.5% of the population.

  2. B. Differential Diagnosis

    1. a. Syncope. This condition is most often confused with seizures because it involves loss of consciousness and is often accompanied by brief “seizure-like” movements that may occur with the loss of consciousness. Some factors that help distinguish syncope from seizures include the following:

      1. i. Precipitating factors. Seizures usually have no immediate precipitating factors and no premonitory symptoms except for an aura. In contrast, syncope is often associated with emotional stress, Valsalva maneuvers, or cardiac conditions, and it may be preceded by tiredness, nausea, diaphoresis, and “graying out” of vision. Syncope usually begins with an erect posture, whereas seizures are variable.

      2. ii. Course. Seizures usually lead to immediate unconsciousness, lasting for up to several minutes, with a period of sleepiness or disorientation that may last minutes to hours after the event. Syncope usually leads to unconsciousness that lasts for several seconds, followed by a rapid return (in seconds to several minutes) to full consciousness and alertness, presuming the patient has been allowed to assume a recumbent position.

        Hot Key

        Obtaining an accurate history and time course of events before and after a possible seizure is key to the diagnosis.

    2. b. Other conditions. Migraine, transient ischemic attack, stroke, movement disorders, and psychiatric disorders are also diagnostic possibilities and should be in the differential diagnosis for seizure disorder.

  3. C. Types of Seizures. A key distinction to make when evaluating a patient who has had a seizure is whether the seizure was focal or generalized. This distinction helps determine etiology, location of brain abnormality, prognosis, and subsequent treatment.

    1. a. Focal or partial seizures. Partial seizures are those that begin in one part of the brain. They are the most common type of seizure. In adults, they most often occur after brain injury (e.g., tumor, trauma, stroke). Focal seizures result in a focal neurologic deficit. The deficit experienced reflects the part of the brain where the seizure occurs. A wide variety of possible seizure manifestations thus exist:

      1. i. Involving subjective sensory or psychic phenomena—such as a rising epigastric sensation, odd smell or taste, auditory or visual phenomena, a sense of familiarity (déjà vu), or a sense of strangeness (jamais vu). These symptoms are also known as auras and were previously classified as simple partial seizures.

      2. ii. Involving alteration of consciousness or awareness—patients are typically unable to respond, communicate, or follow commands during these events, nor do they recall these events. Automatisms are common during these episodes, which were previously classified as complex partial seizures.

      3. iii. Evolving to a bilateral convulsive seizure—a seizure that begins focally and then spreads to involve the brain diffusely, leading to a generalized seizure.

        Hot Key

        Most generalized seizures occurring in adults start as focal seizures and evolve to bilateral convulsive seizures.

    2. b. Generalized seizures. Generalized seizures begin with a diffusely abnormal discharge of neurons leading to widespread cortical involvement. These seizures occur in the inherited epilepsies or secondary to diffuse brain injury.

      1. i. Tonic-clonic seizures are one of the most widely recognized generalized seizures.

        1. 1. They usually begin with alteration of consciousness.

        2. 2. Then, bilateral stiffening (tonic phase) of limbs, often with a clenched jaw, occurs, followed by rhythmic shaking of limbs (clonic phase), followed by complete loss of tone.

        3. 3. Afterward, patients may be difficult to arouse, and it may take minutes to hours to return to baseline.

      2. ii. Absence seizures involve “staring spells,” which last for several seconds.

        1. 1. Onset is abrupt, and seizures cause individuals to stop what they are doing. Absence seizures often occur many times per day and more frequently in children compared with adults.

        2. 2. Although individuals are not responsive during an episode, they often return to baseline level of consciousness immediately.

        3. 3. Associated symptoms may include eye blinking, lip smacking, or swallowing.

      3. iii. Myoclonic seizures are myoclonic jerks, which are brief, lightning-fast jerks of a group of muscles. These movements are associated with a generalized electrical discharge. Myoclonic seizures may be associated with an inherited epilepsy syndrome, progressive epilepsy syndromes, or neurodegenerative disorders (e.g., prion disease). Clinically, the myoclonic jerks associated with myoclonic seizures cannot be readily differentiated from other causes of myoclonic jerks such as a transitioning into/out of sleep, severe hypoxic brain injury, or metabolic derangements.

      4. iv. Other types of generalized seizures include tonic, clonic, and atonic seizures.

        Hot Key

        Absence seizures are rare in adults. Most episodes of altered consciousness or awareness in adults are focal seizures.

  4. D. Approach to the Patient

    1. a. Assess and protect the airway. Both during and after a seizure, patients should be positioned on their side to avoid aspiration if it is feasible to move the patient during their seizure.

    2. b. Consider whether the patient may still be seizing. If the patient is seizing for more than 2 minutes, acute intervention to stop the seizure should be undertaken. Ongoing rhythmic movements, even subtle movements, of the limbs or eyes suggest ongoing seizure activity. A patient often does not return to baseline mental status immediately after a seizure, but the typical course is that of slow and steady improvement after seizure cessation. Muscle tone is typically normal to flaccid after a seizure has ceased, and bowel or bladder incontinence may occur.

    3. c. Do not forcefully restrict limbs, but make sure that obstacles such as beds or chairs are cleared out of the way to avoid injury. All hospitalized patients with a recent history of seizures should have padded bed rails to help minimize the risk of injury .

    4. d. Obtain a detailed history and perform a detailed physical examination, which most often help distinguish between seizure and other disorders with transient neurologic deficits. The evaluation of a patient with a known seizure disorder who has a seizure typical of that condition obviously differs from the evaluation of a patient with a first-time seizure.

    5. e. Obtain several laboratory studies because metabolic derangements (e.g., hyponatremia) may provoke seizures. A glucose level should be obtained immediately. It is often appropriate to treat a patient with intravenous glucose presumptively. Other laboratory studies should include complete blood count, electrolyte panel, liver panel, blood urea nitrogen, and creatinine. It is reasonable to check calcium, magnesium, phosphorus, anticonvulsant medication levels (if appropriate), and toxicology screen (including ethanol level).

      Hot Key

      Almost all patients briefly stop breathing during a generalized seizure and therefore become acidemic. Muscle activity associated with seizures can also raise lactic acid levels.

    6. f. Consider performing an infectious workup in all patients with a seizure. In patients with a known seizure disorder, an intercurrent infection is a common cause of worsening of seizures.

    7. g. Consider performing cerebrospinal fluid (CSF) studies. Although not every patient with a seizure needs a lumbar puncture, the possibility of a causal central nervous system (CNS) infection should always be strongly considered, particularly in the febrile patient or in patients in whom no clear cause for seizure is identified.

      Hot Key

      CNS infections commonly present with seizures and may be especially difficult to recognize without CSF studies in immunosuppressed or older adult patients.

    8. h. Obtain brain imaging if the episode is a new-onset seizure or represents a change in the type of seizure for a patient with epilepsy. Magnetic resonance imaging (MRI) of the brain is the imaging modality of choice. The acuity of the presentation and rapidity with which an MRI can be obtained often determine whether computed tomography (CT) is obtained before the MRI. Immediate CT is indicated if the patient is at high risk for an acute intracranial process (e.g., hemorrhage, infection, stroke, hydrocephalus) or has focal signs on examination suggesting an intracranial process.

    9. i. Consider obtaining an electroencephalogram (EEG). An EEG should be obtained if a patient’s condition is not clinically improving after a generalized seizure. The EEG may also help distinguish between types of epilepsy and inform the likelihood that a patient will have recurrent seizures—which can have important implications for patient lifestyle and management.

      Hot Key

      Patients can develop focal neurologic signs (e.g., hemiparesis, aphasia) immediately after a seizure, which typically resolve over minutes to hours after a seizure ends. This is known as Todd’s paralysis.

  5. E. Treatment

    1. a. Non–medication-related management

      1. i. Seizure precautions (e.g., bed height at lowest level, padded side rails, suction supplies at bedside, video monitoring), should be instituted for all inpatients.

      2. ii. Patients should be told to use common sense and to avoid activities that would be dangerous if they were to have another seizure (e.g., swimming alone, working on ladders, driving or operating a motorized vehicle). In many states, a seizure must be reported to state public health agencies, who will in turn notify the department of motor vehicles. All patients with seizures should be told specifically not to drive until the seizure disorder is under adequate control. The definition of “adequate,” however, varies legally from state to state and between clinicians.

    2. b. Medications

      1. i. Status epilepticus. Patients should be in a monitored setting and may require intubation for airway protection.

        1. 1. Give 0.1 mg/kg lorazepam (Ativan), the first-line acute anticonvulsant medication, at 2 mg/min by intravenous (IV) push. Note that lorazepam only temporarily (for about 15–20 minutes) halts status epilepticus, but this often allows enough time to begin determining the etiology. Intramuscular midazolam or diazepam is a reasonable alternative if no IV access is available—time to treatment is more important than the specific medication used.

        2. 2. If the seizure does not stop immediately, give 20 mg/kg fosphenytoin at 150 mg/min. Monitor for hypotension. Valproic acid (20–40 mg/kg IV) at a maximum infusion rate of 6 mg/kg is also well supported by evidence as second-line therapy. Levetiracetam at 60 mg/kg is also an option.

        3. 3. If the seizure has not stopped, consider phenobarbital, 20 mg/kg IV at 75 mg/min, or proceed to general anesthesia with propofol, midazolam, or pentobarbital if the seizures have already lasted 60 minutes. While phenobarbital has good evidence for efficacy, it causes considerable sedation and often necessitates intubation.

      2. ii. Epilepsy. Almost all antiepileptic drugs (AEDs) treat focal seizures (and the generalized seizures that begin as focal seizures). A subset of AEDs have a broader spectrum of activity and treat nearly all seizures types, including primary generalized seizures (e.g., valproic acid). Little head-to-head data exist to assess the relative efficacy of AEDs, so side-effect profile and ease of administration are typically used to select treatments for focal seizures. Table 85.1 lists some medications commonly used to control seizures along with their potential side effects. Almost all AEDs can cause dizziness, diplopia, dysarthria, sedation, and ataxia in a dose-dependent fashion.

        Hot Key

        Most patients with a single seizure do not require AEDs. EEG and MRI findings can be used to determine whether AED therapy is warranted. Neurology consultation should be obtained before starting a patient on AEDs.

        Table 85.1 Pharmacologic Agents Commonly Used for Seizures


        Specific Adverse Effects

        Phenytoin (fosphenytoin, Dilantin)

        Neuropathy, confusion, rash, gingival hyperplasia, hirsutism, blood dyscrasias, toxic hepatitis, facial coarsening

        Levetiracetam* (Keppra)

        Irritability, disinhibition, depression/suicidal ideation

        Carbamazepine (Tegretol)

        Aplastic anemia, hyponatremia, blood dyscrasias, toxic hepatitis

        Oxcarbazepine (Trileptal)

        Similar to carbamazepine, hyponatremia

        Valproic acid* (Depakote, Depacon, Depakene)

        Tremor, toxic hepatitis, thrombocytopenia, hair loss, weight gain, nausea, tremor


        Marked somnolence, cognitive and behavioral changes, rash, blood dyscrasias

        Topiramate* (Topamax)

        Psychomotor slowing, paresthesias, weight loss, kidney stones

        Lamotrigine* (Lamictal)

        Severe rash (e.g., Stevens-Johnson syndrome)

        Gabapentin (Neurontin)

        Sedation, dizziness

        Pregabalin (Lyrica)

        Sedation, dizziness

        Zonisamide* (Zonegran)

        Kidney stones, impaired sweating, rash, blood dyscrasias


        Anorexia, rash, blood dyscrasias, somnolence

        Lacosamide (Vimpat)

        Cardiac conduction abnormalities, rash

        * Broad-spectrum antiepileptic drug.

        1. 1. Monitor for side effects

          • a. Many AEDs have serious side effects, including allergic reactions, hematologic and liver toxicity, and hyponatremia. Rash, fever, or other reactions should be evaluated immediately. Laboratory monitoring with a complete blood count, liver enzymes, and electrolytes is typically performed for some AEDs.

          • b. Almost all AEDs are potential teratogens.

          • c. Never initiate long-term AEDs without neurologic consultation.

        2. 2. Build dose gradually. To minimize side effects, most AEDs are started at a low dose and gradually increased to either maximum tolerated dose or control of seizures.

        3. 3. Try other medications if needed. Approximately 65% of patients achieve full seizure control with the first medication tried. If the first medication fails, generally monotherapy with a second agent is attempted before treating with two AEDs.

    3. c. Other therapies. In specialized cases in which medications fail to provide adequate control, the following may be considered: surgery to remove a seizure focus; implanting a device that delivers recurrent low-dose electrical stimuli to the vagus nerve (vagus nerve stimulator), or following a restrictive (i.e., ketogenic) diet.

Suggested Further Readings

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, 2005–2009. Epilepsia 2010;51:676–85.Find this resource:

Glauser T, Shinnar S, Gloss D, et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults. Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr 2016;16:48–61.Find this resource:

Legriel S, Lemiale V, Schenck M, et al. Hypothermia for neuroprotection in convulsive status epilepticus. N Engl J Med 2016;375:2457–67.Find this resource:

Lowenstein DH. Treatment options for status epilepticus. Curr Opin Pharmacol 2005;5:334–9.Find this resource: