Seizures

• Head Trauma
  • Depressed skull fracture
  • Subdural hematoma, intra cerebral hemorrhage
• Infectious
  • Meningitis, encephalitis, abscess
• Vascular
  • Stroke or vascular malformations
  • Hypertensive encephalopathy
  • Eclampsia
• Environmental
  • Hyperthermia
• Toxic
  • Drug overdose or withdrawal
• Neoplasm
• Metabolic
  • Hypoglycemia
  • Hypo- or hypernatremia
  • Hypo- or hypercalcemia
  • Uremia; hepatic encephalopathy
  • Hyperosmolar states
• Congenital
  • Idiopathic epilepsy
• Hematologic
  • Porphyria
• Neurologic
  • Febrile seizures
  • HIV encephalopathy
  • Global cerebral ischemia

• Nearly 1% of all emergency department visits are due to new-onset generalized seizures in adults. Seizure may be the sole presenting symptom of a life-threatening illness requiring immediate treatment.
• Seizures are defined as disordered discharges of cerebral neurons. The outward expression of a seizure may take many forms:
• Generalized seizures involve a loss of consciousness.
  • Tonic-clonic seizures are characterized by a phase of tonic muscle contractions causing extension of the limbs (and falling) and cessation of ventilatory effort, followed by a clonic phase of rhythmic muscle contraction and relaxation resulting in symmetric jerking of the limbs with return of spontaneous respirations. Urinary incontinence may occur. A postictal phase of unconsciousness or confusion is not uncommon. It usually clears within 30 min, but may last for hours.
  • Absence seizures are characterized by a brief (5-10 second) loss of consciousness, during which postural tone is maintained. Blinking or head turning may be the only motor manifestation of the seizure. There is no postictal period of confusion.
• Partial Seizures
  • Simple partial seizures begin within a specific region of the cortex, which determines the symptoms (i.e., sensory, motor, or autonomic). The symptoms may 116 Emergency Medicine 4 sponteously resolve, recur, spread to contiguous cortical regions (jacksonian march), or become secondarily generalized. In the absence of generalization, there is no loss of consciousness.
  • Complex partial seizures cause impaired consciousness. Patients experience the same symptoms during each successive ictal event. The episode classically begins with a blank stare, and (occasionally) loss of muscle tone, resulting in a fall. Epigastric sensations are most common, but affective, cognitive, or sensory symptoms also occur. Automatisms are common and can be simple (e.g., chewing, blinking, laughing) or complex (e.g., vocalizations or repetitive movments). Secondary generalization may occur so rapidly that the preceding partial component is not recognized, and only the altered mental status is observed. A postictal period is common but usually short (i.e., minutes).

• If the seizure activity has terminated prior to the patient’s arrival in the emergency department, a description of the event from a reliable witness is invaluable. Any history of trauma (recent or remote) should be elicited. A description of events immediately preceding the seizure activity should also be sought, including any complaints of pain or focal neurologic deficits. Attempt to determine whether the patient was injured during the episode (e.g., fall).
• Obtain the patient’s medical history, if possible, including a prior history of seizures or other medical conditions, medications, or recent symptoms (e.g., infections). Ask about the use of drugs or alcohol, or exposure to other toxins.

• Include a rectal temperature with the vital signs.
• Look for evidence of trauma, either as a cause or a result of the seizure. A detailed neurologic examination should be performed. If the patient has an altered level of consciousness, is he in a postictal state? Or is there another cause? Are there any focal neurologic deficits? Look for signs of increased intracranial pressure (ICP) (e.g., papilledema). Is there evidence of a CNS or systemic infection? Are there other signs of systemic illness? Is there evidence of a toxic exposure? Serial neurologic exams are critical.

Evaluation

As with the work-up of any presenting sign(s) or symptom(s), the use of diagnostic tests should be guided by the history and physical examination of each patient who presents with seizure activity. When a differential diagnosis is formulated for a particular patient, the following studies may be helpful in ruling in or excluding specific etiologies:

• Laboratory
  • Glucose should be checked on all first-time seizure patients. Although commonly ordered, routine electrolytes, calcium and magnesium have low diagnostic yield in otherwise healthy patients with a first seizure. Consider these studies when clinically indicated.
  • A pregnancy test is indicated in all females of reproductive age.
  • Antiepileptic drug (AED) levels
  • A more extensive work-up is appropriate in patients with a history of alcohol abuse, to include CBC, PT, electrolytes, BUN, and creatinine. A blood alcohol level and toxicology screen should also be considered.
  • Magnesium levels should also be checked in patients with diabetic ketoacidosis.
  • Coagulation studies are recommended in patients on anticoagulants, with a known coagulopathy, or with a history of platelet disorders.
  • Lumbar puncture is indicated in the following situations:
    • Persistent alteration in mental status or status epilepticus (after patient is stabilized).
    • Signs of CNS infection (nuchal rigidity, petechiae)
    • Severe headache (i.e., when unruptured aneurysm or SAH is suspected)
    • In a patient with a history of cancer and negative CT scans (leptomeningeal metastases?)
    • History of immunosuppression, without an identifiable cause for the seizure (i.e., lab or radiographic abnormality)
    • Children with recent antibiotic use
    • Adults with fever, without an infectious source (neutropenic patients excluded)
• Imaging
  • Emergent noncontrast CT scan of the head is indicated in all first-time seizure patients without an identifiable, nonstructural cause (e.g., hypoglycemia, febrile seizure). The following factors increase the likelihood of an abnormal CT:
    • A focally abnormal exam or signs of increased ICP
    • Multiple or focal seizures
    • Higher likelihood of structural abnormalities (i.e., increased age, history of head trauma, HIV/other immunocompromised states, cancer, alcohol abuse, anticoagulation, vascular disease, demographic risk of cysticercosis)
    • Previous CNS disorders
  • Subtherapeutic antiepileptic drug levels are the most common cause of recurrent seizures. Indications for CT scan in patients with a previously diagnosed seizure disorder include:
    • Change in seizure pattern without a known cause
    • Persistently altered mental status or prolonged postictal confusion
    • New focal neurologic deficits
  • Contrast-enhanced head CT should be performed in immunocompromised patients and those with a history of malignancy (after a negative noncontrast CT).
  • MRI is recommended, on an elective basis, if the screening CT is negative.
• EEG
  • EEG is generally not readily available in the ED and usually is not required in the ED work-up of seizures. However, in the following cases, emergent EEG is indicated:
    • The seizure appears to have terminated, but the patient remains altered.
    • Status epilepticus is suspected (convulsive or nonconvulsive).
• EKG
  • Seizure may be the presenting symptom of hypoxia in a patient with a dysrhythmia resulting from myocardial ischemia. EKG should be considered in patients with known or suspected coronary artery disease.
  • Patients with long QT syndrome frequently present after a syncopal or ictal event. Congenital long QT syndrome is seen in children or young adults who may have a family history of syncope or early cardiac death, or a personal history of congenital deafness. Long QT syndrome may be acquired and is a side effect of tricyclic antidepressants, phenothiazines, and amiodarone. Associated EKG abnormalities include prolonged or abnormal T waves and bradycardia.

• As with any patient in the ED, attention to the patient’s airway, breathing, and circulation is paramount. The patient should be positioned in such a way as to protect the airway in case of vomiting, and suction should be readily available. Supplemental oxygen should be administered by nasal cannula or face mask, and the patient placed on continuous pulse oximetry.
• If trauma is a concern, the cervical spine should be immobilized.
• As soon as possible, intravenous or intraosseous access should be obtained so that fluids and medications can be given. The patient should be placed on a cardiac monitor.
• Underlying, correctable etiologies should be rapidly identified and treated.
  • Benzodiazepines are the agents of choice to acutely terminate seizure activity, although the necessity of this practice as routine is debatable. Most seizures are brief (< 2 min) and there is no evidence that a single, brief seizure has deleterious central nervous system effects. Several agents are available (see Table 4G.1).
  • Diazepam is highly lipophilic and thus crosses the blood-brain barrier rapidly. It is usually administered via the intravenous route but is equally effective when given rectally. Other routes include oral and endotracheal. The median time to terminate seizure activity after injection is 2 min. However, its antiepileptic activity lasts only 20 to 30 min. Depending upon the clinical setting, a longer acting AED may be necessary after administration of diazepam.
  • Lorazepam is less lipid soluble than diazepam but has a similar time to seizure control (3 min). Its antiepileptic activity lasts 12-24 h, negating the need to administer an additional AED if seizure activity is terminated. Acceptable routes of administration include intravenous, rectal, sublingual, and oral.
  • Midazolam is used less frequently but is another option. Unlike diazepam and lorazepam, this agent is well absorbed when given via the intramuscular route because of its water-solubility. After administration, it becomes lipid soluble and, like diazepam, has rapid penetration of the blood-brain barrier as well as a short duration of antiepileptic activity. Acceptable routes of administration include intranasal, intramuscular, intravenous, rectal, and buccal.

  Table: Antiepileptic agents for status epilepticus

  Medication	Dose (IV)	Side Effects
  Midazolam	0.2 mg/kg then 0.05-1.0 mg/kg/h	Respiratory depression, hypotension, sedation Tachyphylaxis with prolonged infusions
  Diazepam	0.2 mg/kg (up to 20 mg in adults)	Respiratory depression, hypotension, sedation
  Lorazepam	0.1 mg/kg (usual maximum dose 8 mg)	Respiratory depression, hypotension, sedation
  Phenytoin	20 mg/kg @ 50 mg/min May give additional 5-10 mg/kg	Hypotension, atrioventricular block, dysrrhythmias Soft tissue necrosis, sterile abscess with IM use or extravasation
  Fosphenytoin	20 mg/kg PE* @ 150 mg/min May use same dose IM	Hypotension and pruritis
  Phenobarbital	20 mg/kg not to exceed 100 mg/min	Respiratory depression, apnea, hypotension
  Propofol	1-3 mg/kg then 2-10 mg/kg/h	Respiratory depression, hypotension
  Pentobarbital	3-5 mg/kg then 1-5 mg/kg/h	Respiratory depression, apnea, hypotension, myocardial depression, weakness during recovery period
  * Phenytoin equivalent

• Initiation of a long-term AED for a first seizure should be considered in certain settings. Close neurologic follow-up is indicated for these patients. All AEDs have adverse side effects and "label" the patient. If there is any question as to the necessity of initiating chronic therapy, neurologic consultation is advised. Multiple AEDs are available—a comprehensive discussion is beyond the scope of this writing. Consider initiation of an AED in the following cases:
  • An underlying cause that can’t be promptly treated (e.g., tumor)
  • A patient at risk for recurrent seizures (e.g., cysticercosis, penetrating head injury)
  • Presence of an identifiable, remote cause (debatable)
  • Patients with a history of recent (< 2 yr) seizure that went untreated

• SE has classically been defined as persistent seizure activity for 30 min or recurrent seizures without full recovery between events. Since most isolated ictal events last < 2 min, a more practical definition for SE is seizure activity that persists for 5 min or more.
• SE is not a disease in itself, but rather a manifestation of another illness. One of the goals when treating SE is to identify and address acute precipitants. In adults, the most common cause of SE is noncompliance with AEDs. In children, congenital abnormality and infection are the most common.
• The earlier that treatment for SE is initiated, the easier it is to control. In addition, the following complications may be avoided.
  • Autonomic dysfunction including hypertension, tachycardia, and hyperthermia
  • Vertebral and other fractures; shoulder dislocations
  • Rhabdomyolysis
  • Aspiration pneumonia
  • Metabolic derangements
  • Cerebral edema
• Treatment (see Table 4G.1)
• All patients require appropriate supportive care. If intubation is required, short-acting paralytics are preferred in order to allow the practitioner to identify ongoing seizure activity.
• Benzodiazepines are first-line therapy for SE. Because of its duration of action, lorazepam is preferred. Adequate dosing is imperative. If SE is not controlled with an appropriate dose of benzodiazepine, it is unlikely that subsequent doses or use of another benzodiazepine will be effective.
• Phenytoin is a long-acting AED that is effective for both SE and chronic maintenance therapy. Phenytoin is generally the preferred second-line agent for SE if benzodiazepines have failed. Side effects of the intravenous preparation are attributed to the propylene glycol diluent. These are minimized by infusing at a rate not to exceed 1 mg/kg/ min in children and 50 mg/min in adults. Fosphenytoin is a phosphorylated ester of phenytoin. It is highly water-soluble, and is rapidly converted to phenytoin after administration. It is rapidly and completely absorbed when given intramuscularly and can also be given intravenously at three times the rate of phenytoin. Because it has no intrinsic action before conversion, it is believed to have the same onset of action as phenytoin. Its primary disadvantage is cost, averaging twenty-fold more than phenytoin.
• Phenobarbital, a long-acting barbiturate, may lead to hypotension as well as profound respiratory depression and apnea. Rate of infusion should not exceed 100 mg/min. It is generally reserved for cases in which benzodiazepines and phenytoin have failed.
• Agents for refractory SE—All patients with refractory ictus require EEG monitoring as well as ventilatory support. Pressors may also be necessary in the setting of hypotension.
  • Midazolam—Discussed above
  • Propofol—This is a nonbarbiturate anesthetic agent that also has antiepileptic effects. It has a rapid onset of action and a quick recovery time after the drug is discontinued.
  • Pentobarbital—This barbiturate has more pronounced side effects than both midazolam and propofol. Patients will often require pressors because of significant hypotension and myocardial suppression.
• Adjunctive therapy—Includes both pyridoxine and magnesium.

• All patients with SE require ICU admission.
• Patients with neurologic disorders, systemic disease or electrolyte abnormalities (e.g., neurosurgical lesions, CNS infection, hepatic or renal dysfunction, hyponatremia) require admission and management of the underlying disease process.