Seizure

by Feriyde Caliskan Tur

Introduction

The seizure is a frequent neurologic emergency in the emergency department (ED), accounting for 1-2% of all emergency department visits. The highest incidence of seizure is among infants and individuals aged > 75 years. The infantile seizure occurs due to the high prevalence of febrile seizures, and in the elderly, it is mostly secondary to structural brain damage. Most seizures (49%) are related to alcohol or drugs, head injury, and pre-existing diagnosis of epilepsy. Less frequent etiologic pathologies are brain tumors (3%), metabolic abnormalities (3%), stroke (3%), and neuro-cysticercosis (1%). The reason for the rest (41%) is unknown. Managing patients with seizure and no apparent etiology may be challenging for the emergency physician.

A Case Presentation

A 20-year-old female patient presented to the ED with shoulder pain beginning in the morning at work. She had no history of trauma. However, her right shoulder had a deformity. Her X-ray showed a posterior shoulder dislocation, and she could not explain how it occurred. While the emergency physician was making preparations to reduce the shoulder, the nurse shouted that the patient was having a generalized tonic-clonic convulsion.

Critical Bedside Actions and General Approach

The patient was placed immediately in the left lateral recovery position to avoid aspiration of vomitus. Simultaneously, 4 L/hour oxygenation was started via an air mask, and the vascular access was established. Lorazepam 2mg, IV was given by slow injection to stop the seizure.

The seizure stopped in a few minutes. The patient’s blood glucose was measured at 122 mg/dL. Her vital signs were: blood pressure 116/80 mmHg, heart rate 60 beats per minute, respiratory rate 12 breaths per minute, oral temperature 98.6 °F, and a pulse oximetry 100 % on room air.

Her physical examination was normal except for the right shoulder. When the patient regained consciousness, she wanted to know what had happened. It was her first witnessed seizure. There was no drug or substance abuse, and her menstrual status was normal. She had frequent headaches for the last month, and she had been evaluated by a neurologist.

History and Physical Examination Hints

History of seizures, head injury, recent fever (suggests infection or drug reaction), anticholinergic and sympathomimetic syndromes (mainly depending on street drug-abuse) are essential clues of the etiology of seizure.

A full neurological examination should be made. Motor movements and the accompanying eye movements during the seizure may distinguish the seizure from psychogenic seizures (pseudoseizures or nonepileptic seizures). 12% to 18% of patients with transient loss of consciousness are described as psychogenic seizures. It can exist concomitantly in patients with neurogenic seizures. Psychogenic seizures are a manifestation of psychological distress.

Neurologic deficits may be secondary to an old lesion, new intracranial pathology, or postictal neurologic compromise (called Todd paralysis, the physician may rule out a new structural lesion).

Seizure is defined as a sudden change in behavior, characterized by an alteration in sensory perception or motor activity, resulting from an abnormal, excessive, and synchronous electrical firing in groups of neurons, caused by disequilibrium of the neuronal cell membrane, normally kept stable by inhibitory mediators such as gamma-aminobutyric acid (GABA).

Convulsions are the motor manifestations of this abnormal electrical activity. The clinical manifestations of seizures include focal or generalized motor activity, altered mental status, sensory or psychic experiences, and autonomic disturbances.

Epilepsy is referred to convulsive seizures without any recurring or provocative reason.

The postictal period is a change in consciousness that start before the seizure and last after for a while.

A generalized seizure is related to both hemispheres accompanied by convulsions in the entire body took place.

Focal seizures took place in certain parts of the body remain localized in a single hemisphere of the brain so may be easily overlooked. A simple focal seizure may or may not cause a depressed mental status, but a complex focal seizure causes changes in consciousness.

Generalized status epilepticus is seizures that prevent the return to conscious state with frequent recurrences or last more than 20 minutes. According to these definitions, our case had a generalized seizure. This definitions of seizure can change the patient management.

Pregnant patients with seizure: Pregnant patients of more than 20 weeks’ gestation (and up to 6 weeks postpartum) with eclampsia is the major consideration in presentation with new-onset seizures. Gestational epilepsy is diagnosed in approximately 25% of patients with new-onset seizures during pregnancy.

Emergency Tests and Interpretation

Adult patients with new-onset seizures who are otherwise healthy and have returned to baseline require only simple tests including serum glucose, sodium level, and pregnancy test. In patients with fever, comorbid disease, or new neurological deficit further testing is indicated.

Bedside test

Capillary glucose level (stick glucose)
Blood gases: It may show an anion gap metabolic acidosis secondary to lactic acidosis. Lactate elevates within 60 seconds of a convulsive seizure and normalizes within 1 hour.
Electrocardiography (ECG) should be obtained in patients with new-onset seizure, or with the suspicion of decreased CNS perfusion secondary to a cardiac cause. In addition to ischemia, conduction abnormalities and dysrhythmias are important disorders to be excluded, see below.
- Differential diagnosis by ECG
  - Conduction Disorders That Can Be Cause of Seizure-like Activity (Adapted from: Seizure: Emergency Medicine, Second Edition. Editor; Adams, James G., MD, 2013, 2008 by Saunders, an imprint of Elsevier Inc. Book chapter 99)
    - A seizure may also result in dysrhythmia-related syncope.
    - Brugada syndrome: Right bundle branch block with ST-segment elevation in leads V1-V3
    - Long QTc interval
    - Short QTc interval
    - Sodium channel blockade with cyclic antidepressants, lidocaine, anticholinergics
    - Torsades de pointes
    - Widening of QRS complex
    - Wolff-Parkinson-White syndrome

Laboratory tests

CBC (reveal anemia or infectious process)
Electrolytes (especially Na, and Ca/Mg),
Serum glucose
Urea-nitrogen, creatinine,
Pregnancy tests in women of childbearing age (rule out eclamptic seizures),
Antiepileptic drug levels,
Liver function tests, and
Drugs-of-abuse screening
Spinal tap is useful to evaluate suspected CNS infection (patients with fever, severe headache, or persistent altered mental status) or HIV/AIDS population (strong suspicion of immunodeficiency).

Imaging modalities

Brain CT is indicated in all first-time seizures. Additionally, new focal neurological deficit, history of trauma, toxic drug and substance use necessitates a brain CT, see below.

Indications for CT Scanning of the Brain

Adapted from: Teran F, Harper-Kirksey K, Jagoda A. Clinical decision making in seizures and status epilepticus. Emerg Med Pract. 2015 Jan;17(1):1-24.

- A Persistent change in mental status
- Advanced age
- History/clinical evidence of trauma
- Human immunodeficiency virus/acquired
- Immunodeficiency syndrome (HIV/AIDS)
- Infection (neurocysticercosis)
- New focal neurological deficit
- Suspicion of parasitic central nervous system

First-onset seizures or seizures with persistent mental status change, focal neurologic deficit, or suspicion of organic intracerebral lesion necessitates brain computed tomography (CT). It will help to diagnose epidural or subdural hemorrhage, a brain mass or infections.

Factors Associated With Abnormal Computed Tomography Findings

(Adapted from: Teran F, Harper-Kirksey K, Jagoda A. Clinical decision making in seizures and status epilepticus. Emerg Med Pract. 2015, page 9)

Altered mental status
Closed head injury
Focal abnormality on neurological examination
History of cysticercosis
Malignancy
Neurocutaneous disorder
Patient aged > 65 y
Seizure duration > 15 min
The absence of a history of alcohol abuse
The focal onset of the seizure

MRI can reveal additional diagnosis like brain abscess and central vascular events. MRI is more sensitive than CT and can successfully diagnose temporal sclerosis, cortical dysplasia, vascular malformations (e.g., AV aneurysms), and some tumors in addition. Its use is limited in emergency setting.

Electroencephalography (EEG) is important to monitor intubated patients or patients with persistent altered mental status. (Suspicion of nonconvulsive status epilepticus). EEG records brain electrical activity and is used for definitive diagnosis. The need for EEG in the emergent setting is limited and must be saved for when seizure activity is uncontrollable or difficult to diagnose. (e.g., patients who are under sedation or are intubated).

Emergency Treatment Options

Maintenance of adequate cerebral perfusion, oxygen and glucose supply to the brain, is the goal of initial treatment. Airway must be preserved. Continuous pulse oximetry and capnography should be monitored. Jaw thrust and nasopharyngeal airway ensure an improved oxygenation. Preventing aspiration in the postictal phase, seizure control (administration of anticonvulsants), correction of hypoglycemia, IV line placement, and administration of oxygen can be addressed together with coordinated team care. If there is trauma signs secondary to the seizure, cervical spine precautions (immobilization with a collar) should be initiated.

Medications

Traditionally, pharmacologic therapy of seizure has been divided into three steps (Table). Generally, benzodiazepines are the initial choice, followed by phenytoin or valproic acid. Levetiracetam is the second-step choice in patients with liver disease. Third step interventions are infusions of benzodiazepines (midazolam or long-acting lorazepam), propofol, or barbiturates (e.g., pentobarbital; pay attention to hypotension). In up to 30% of the patients, the first- and second-step therapies fail.

The drug choice is same for nonconvulsive seizures.
Secondary causes for seizure must be considered for the treatable etiologies (e.g., intracranial infections and lesions, metabolic abnormalities, drug toxicities, and eclampsia).

Many considerations on the use of medications should be remembered;

Use of benzodiazepine for active seizure in the prehospital setting is strongly supported.
IM midazolam is the best option for the prehospital treatment of seizure, especially when no intravenous access is immediately available.
If the patient needs intubation, pretreating with lidocaine (1.5 mg/kg) and a low dose (defasciculating dose) of a nondepolarizing paralytic agent (e.g., vecuronium, 0.01 mg/kg) is preferable to control intracranial pressure from trauma or intracranial bleeding. Short-acting paralytic agents such as succinylcholine is recommended during rapid sequence intubation.
Remember that phenytoin (effective dose 20 mg/kg) must be infused with saline solution (not dextrose due to precipitation). Its main adverse effect is arrhythmia due to QT prolongation. Therefore, the patient must be monitored during the infusion.
Alcoholic seizure and seizure secondary to isoniazid in tuberculosis treatment are treated with 5 gr IV vitamin B6 in adults and 70 mg/kg IV pyridoxine infusion in children.
Seizures due to ecstasy or cocaine abuse are treated with benzodiazepines and aggressive cooling. Phenytoin is not effective in substance-related seizure, and also may be harmful to drug intoxications such as tricyclic antidepressants and antiarrhythmics.
The clinician should be aware that administration of phenytoin and phenobarbital is rate-dependent and that patients may continue to seize for 30 minutes before effective serum levels are reached.
Timely administration of antibiotics is important for the survival of patients with infectious problems
Prophylactic medication is not indicated to prevent late posttraumatic seizures.
New generation drugs such as lamotrigine (FDA category C) is used for partial, generalized, and absence seizures for maintenance therapy.

Pregnant patients with seizure

Seizure related hypoxia and acidosis have a greater teratogenicity potential than anticonvulsant medications. Therefore, actively-seizing pregnant patients may be managed the same as nonpregnant. Magnesium sulfate is the therapy of choice in the treatment of acute eclamptic seizures and for prevention of recurrent eclamptic seizures. Additionally, a seizing chronic epileptic pregnant can be treated with midazolam. Remember that midazolam (FDA category D) is the safest; valproate and phenytoin are the most harmful (both FDA category D) antiepileptic drugs in first-trimester pregnancy.

Antiepileptic drugs and doses for seizures therapies

Medication	Loading Dose IV	Maintenance Dose	Pediatric Dose	Comments
Diazepam	10 mg over 2 min, or 10-20 mg	Repeat q 5-10 min	0.15 mg/kg IV; 0.2-0.5 mg/kg	respiratory depression, hypotension
Lorazepam	2-4 mg IV	Repeat once in 10-15 min	<13 kg: 0.1 mg/kg IV (max 2 mg); 13-39 kg: 2 mg IV; >39 kg: 4 mg IV	respiratory depression, hypotension
Midazolam	0.1-0.2 mg/kg (also IM, IN rectal or buccal)	0.001 mg/kg/min	0.2 mg/kg IV, IN (max 5 mg); 0.5 mg/kg buccal (max 5 mg); <13 kg: 0.2 mg/kg IM (max 5 mg); 13-39 kg: 5 mg IM; >39 kg: 10 mg IM	respiratory depression, hypotension
Phenytoin	18-20 mg/kg, max rate of 50 mg/min	100 mg IV/PO q 6-8 h, 20 mg/kg IV infusion	20-mg/kg IV infusion	hypotension, ataxia
Pentobarbital	5-20 mg/kg, 25 mg/min	1-3 mg/kg/		respiratory depression
Phenobarbital	10-15 mg/kg bolus, 60 mg/min	120-240 mg q 20 min		respiratory depression, hypotension
Propofol	1-2 mg/kg IV over 5 min	2-4 mg/kg/h		respiratory depression, acidosis (in children)
Valproic acid	20 mg/kg at 20 mg/min	Repeat if needed		subtherapeutic dosages
Magnesium sulfate	4-6 g over 15 min	2 g/h		respiratory depression, loss of deep tendon reflexes
Calcium gluconate, calcium chloride (has three times more Ca+2)	10 mL of 10% calcium gluconate in 50-100 mL of D5W, over 5-10 min			Only indicated for hypocalcemia or hyperpotassemia
3% NaCl (hypertonic saline solution)	300-500 mL of 3% NaCl in 20 min	Repeat if needed		Only for hyponatremia
Pyridoxine	5 g (50 ampoules of 100 mg of vitamin B6)			Only for some drug-induced seizure

Adapted from Brophy GM, et al.: Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 17:3-23, 2012.
IM, intramuscularly; IN, intranasally; IV, intravenously; PR, rectally.
(cross ref and adapted from; Seizure: Emergency Medicine, Second Edition. Editor; Adams, James G., MD, 2013, 2008 by Saunders, an imprint of Elsevier Inc. Book Chapter 99)

Emergency Procedures

Airway management is the most important procedures during a seizure activity. The majority of the patients, however, will not need definitive airway protection. The basic airway maneuvers or adjunct devices may overcome the temporary airway obstrcution risks. Simple seizures are self-limiting in most cases. Maintaining the airway by jaw trust/chin lift maneuvers, inserting an oropharyngeal airway, and oxygen mask ventilation are first measures to prevent the tongue bite, airway obstruction, and apnea. A corkscrew is useful to open the jaw. In cases that oxygen inhalation and intubation fail, a surgical airway is indicated.

Disposition Decisions

Admission criteria

Patients with persistent seizures, change of mental or neurologic status, or underlying medical conditions that require hospital treatment (e.g., sepsis, overdose, brain trauma) should be admitted. Patients with status epilepticus should be admitted to the intensive care unit. Patients with subtherapeutic drug levels should receive an additional dose before discharge. First-onset seizures should have follow-up arranged with the neurology service/consultant for further investigations. A second attack occurred in 1 month in 32% of patients with a first-onset seizure. Risk factors such as alcoholism, comorbidities or known cardiovascular disease, age > 60 years, history of cancer, or history of immune-compromise should be considered for admission.

Discharge criteria

Discharge decision should be based on final underlying diagnosis. Chronic seizures can be discharged after return to the baseline neurologic levels.

References and Further Reading

Teran F, Harper-Kirksey K, Jagoda A. Clinical decision making in seizures and status epilepticus. Emerg Med Pract. 2015 Jan;17(1):1-24.
American College of Emergency Physicians Clinical Policies Subcommittee (Writing Committee) on Seizures. Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with seizures. Ann Emerg Med. 2004;43(5):605-625-Pallin DJ,
Goldstein JN, Moussally JS, et al. Seizure visits in US emergency departments: epidemiology and potential disparities in care. Int J Emerg Med. 2008;1(2):97-105.
Ong S, Talan DA, Moran GJ, et al. Neurocysticercosis in radiographically imaged seizure patients in U.S. emergency departments. Emerg Infect Dis. 2002;8(6):608-613.
Annegers JF, Hauser WA, Lee JR, et al. Incidence of acute symptomatic seizures in Rochester, Minnesota, 1935-1984. Epilepsia. 1995;36(4):327-333.
DeLorenzo RJ, Towne AR, Pellock JM, et al. Status epilepticus in children, adults, and the elderly. Epilepsia. 1992;33 Suppl 4:S15-S25.
Knight AH, Rhind EG. Epilepsy and pregnancy: a study of 153 pregnancies in 59 patients. Epilepsia. 1975;16(1):99-110.
Alldredge BK, Gelb AM, Isaacs SM, et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med. 2001;345(9):631- 637.
Silbergleit R, Lowenstein D, Durkalski V, et al. Lessons from the RAMPART study–and which is the best route of administration of benzodiazepines in status epilepticus. Epilepsia. 2013;54 Suppl 6:74-77.
Kunisaki TA, Augenstein WL. Drug- and toxin-induced seizures. Emerg Med Clin North Am. 1994;12(4):1027-1056.-Temkin NR, Haglund MM, Winn HR. Causes, prevention, and treatment of post-traumatic epilepsy. New Horiz. 1995;3(3):518-522.
Delgado-Escueta AV, Janz D. Consensus guidelines: preconception counseling, management, and care of the pregnant woman with epilepsy. Neurology. 1992;42(4 Suppl 5):149-160.
Lubarsky SL, Barton JR, Friedman SA, et al. Late postpartum eclampsia revisited. Obstet Gynecol. 1994;83(4):502-505.
Seizure: Emergency Medicine, Second Edition. Editor; Adams, James G., MD, 2013, 2008 by Saunders, an imprint of Elsevier Inc. Book chapter 99.
Antiepileptic Drugs. Juan G Ochoa, MD. Available at http://emedicine.medscape.com/article/1187334-overview#a2.
Clinical pathway non–status epilepticus seizure management (in Teran F, Harper-Kirksey K, Jagoda A. Clinical decision making in seizures and status epilepticus. Emerg Med Pract. 2015 Jan;17(1):1-24.)
Clinical pathway for status epilepticus management (in Teran F, Harper-Kirksey K, Jagoda A. Clinical decision making in seizures and status epilepticus. Emerg Med Pract. 2015 Jan;17(1):1-24.)