Seizure Induced by Traumatic Brain Injury Case File

Seizure Induced by Traumatic Brain Injury Case File

Eugene C. Toy, MD, Barry C. Simon, MD, Terrence H. Liu, MD, MHP, Katrin Y. Takenaka, MD, Adam J. Rosh, MD, MS

Case 31

A 37-year-old man, known to be an insulin-dependent diabetic (IDDM), is brought into the emergency department (ED) by ambulance after a motor vehicle accident. Per EMS, he was the restrained driver of a vehicle when he apparently lost control of the car and drove into the center divide at highway speeds. Witnesses reported that the vehicle rolled over multiple times and the air bag did not deploy. There is severe damage to the front of the vehicle. Vital signs taken in the field showed a blood pressure of 110/85 mm Hg, heart rate 140 beats per minute, respiration rate 24 breaths per minute, oxygen saturation 98% on 15 L of oxygen via nonrebreather mask. During transport to the ED, the patient begins to seize. Paramedics describe tonic-clonic movements of all four extremities. He is given lorazepam 2-mg IV push with almost immediate resolution of the seizure. In the ED, on examination (once the seizure has stopped), his airway is patent, breath sounds are equal bilaterally, and pulses are bounding throughout. His Glasgow coma scale (GCS) is 8. His blood glucose is 75. It is noted that his right pupil is 5 mm and nonreactive, his left pupil is 3 mm and reactive. His tone is normal in all four extremities. His reflexes are 2+ throughout. His toes are downgoing bilaterally. His cardiovascular, respiratory, and abdominal examination are unremarkable. He is not wearing a medic-alert bracelet. His CT scan of the head reveals a large right frontal intraparenchymal hemorrhage.

⯈ What is the most likely diagnosis?

⯈ What is your next step?

ANSWER TO CASE 31:

Seizure Induced by Traumatic Brain Injury

Summary: A 37-year-old man, unrestrained driver in motor vehicle accident, seizing en route to the ED and found to have right-sided blown pupil, GCS 8, and no known history (hx) of seizures.

• Most likely diagnosis: Seizure likely secondary to acute intraparenchymal bleed from a traumatic brain injury.
• Next step: Aggressive management of ABCs (airway, breathing, and circulation) with rapid sequence intubation to protect the airway, management of ICP, and anticonvulsant treatment to prevent reoccurrence of seizures.

ANALYSIS

Objectives

1. Develop a methodological approach to the assessment of the patient who presents to the emergency department with first-time seizure and status epilepticus.
2. Understand the diagnostic and therapeutic approach to the patient presenting to the emergency department with first-time seizure and status epilepticus.

Considerations

This 37-year-old man with IDDM presents with a seizure after being involved in a motor vehicle accident. It is important to consider the order of events in traumas such as this, especially when the history is limited. This patient may have had a seizure while driving secondary to hypoglycemia, and then crashed his car. He may also have a past medical history of epilepsy and be subtherapeutic on his anticonvulsant medications. He may have lost control of the car for some unknown reason, and then crashed the car causing traumatic brain injury, intraparenchymal bleeding, and subsequent seizure.

Approach To:

Seizure Disorders

DEFINITIONS

SEIZURE: A seizure is any event involving an abnormal firing of neurons that causes a sudden change in behavior characterized by changes in sensory perception or motor activity. It can sometimes occur in the presence of precipitating factors (provoked seizure).

EPILEPSY: The term epilepsy is applied when 2 or more unprovoked seizures occur more than 24 hours apart. 

STATUS EPILEPTICUS: Status epilepticus is historically defined as more than 30 minutes of continuous seizure activity or two or more sequential seizures without return to normal mental baseline.

CLINICAL APPROACH

Classifications

Seizures can be divided into two major classifications based on their origin. Neurogenic seizures represent the majority of seizures seen in the ED and result from excessive discharge of cortical neurons. Psychogenic, or nonepileptic, seizures (NES) are increasingly common and may be extremely difficult to distinguish from true seizures. Unlike neurogenic seizures, these pseudoseizures are not the result of abnormal cortical discharge, and are often associated with major stress or emotional trauma. Unclassified seizures are difficult to fit into a single class and are considered when there is inadequate data.

Neurogenic seizures can be broken down into 2 main subgroups depending on their manifestation. Generalized seizures involve abnormal neuronal activity in both hemispheres of the brain and are accompanied by a loss of consciousness. They can be further characterized based on the pattern of motor activity, such as tonic (rigid trunk and extremities), clonic (symmetrical rhythmic jerking of the trunk and extremities), tonic-clonic (tonic phase followed by clonic phase), atonic (sudden loss of postural tone), and myoclonic (brief, shock-like muscular contractions). Partial (focal) seizures involve neuronal discharge in a localized area of one cerebral hemisphere and are subclassified into simple (consciousness is maintained) and complex (impaired level of consciousness).

Status epilepticus (SE) is present when patients have more than 30 minutes of continuous seizure activity or have 2 or more sequential seizures without full recovery of consciousness in between. SE is the initial presentation of a seizure disorder in approximately one-third of cases. The most common cause of SE is discontinuation of anticonvulsant medications. The catecholamine surge that accompanies SE can cause tachycardia, hypertension, hypotension, cardiac arrhythmias, respiratory failure, hyperglycemia, acidosis, and rhabdomyolysis. Nonconvulsive SE can also occur and must be ruled out in any patient who does not regain consciousness within 20 to 30 minutes of cessation of a single generalized seizure and should be considered in any patient with unexplained confusion or coma.

Etiology

It is important to consider the etiology of a patient’s seizure as it may influence the clinical approach. Primary, unprovoked seizures in a patient with a known history of epilepsy are usually managed pharmacologically with the goal of restoring normal neuronal function. However, seizures can also present as secondary manifestations of other primary diseases.

Common etiologies of secondary seizures include head trauma, intracranial masses or hemorrhages, infections such as meningitis or encephalitis, metabolic disturbances (ie, glucose or electrolyte abnormalities), and drugs or toxins. Additional common conditions that may present as seizures include hypertensive encephalopathy and anoxic-ischemic injury secondary to cardiac arrest or severe hypoxemia. Eclampsia must also be considered in pregnant women as a potential etiology of seizures.

Diagnosis

History: History is essential in the evaluation of a seizure patient, especially in a first-time seizure. It is important to ask the patient and/or witnesses the circumstances leading up to the seizure, including a description of the ictal movements and the postictal period. Any symptoms associated with the seizure should also be addressed to help direct work-up and management. For example, a headache prior to the seizure is concerning for intracranial hemorrhage, while a fever and/or general malaise in a patient who presents with a seizure is worrisome for infectious causes. Patients with a known seizure disorder should be questioned about the type and frequency of their seizures as well as medication compliance. Past medical history, medications, and social history including drug and alcohol use and HIV risk factors are also important to consider.

Examination: Patients presenting to the ED with seizure require a thorough physical examination. A detailed neurologic examination is the key component of the evaluation. Focal deficits may be a critical clue to the ultimate diagnosis or may represent a common transient postictal neurologic insult referred to as a Todd paralysis. The head and neck examination should include the tongue to look for lacerations, head or facial trauma, and signs of meningismus. Cardiopulmonary examination should include auscultation for heart murmurs or an irregular rhythm suggesting an embolic or syncopal event. Although rare, extremity fractures or dislocations are commonly missed when they do occur and should be ruled out by a thorough musculoskeletal examination.

Diagnostic Workup: Appropriate laboratory studies in patients with first-time seizures include glucose, serum electrolytes such as sodium, calcium, and magnesium, assessment of renal function, hematology studies such as a complete blood cell count, and drug or toxicology screen. Women of childbearing age also require a pregnancy test.

Neuroimaging studies should be performed when a clear etiology to the seizure is not identified or whenever an acute intracranial process is suspected. American College of Emergency Physicians (ACEP) guidelines recommend a head CT be performed in patients with a history of recent head trauma, persistent altered mental status or headache, fever, malignancy, immunocompromised status, anticoagulation, or in patients who have a new focal deficit, are over 40, or have a partial-onset seizure.

A lumbar puncture is an essential part of the workup if clinical presentation is suggestive of an infectious process. Use of the EEG is uncommon in the ED evaluation of first-time seizure except in the assessment of nonconvulsive status epilepticus, or to establish status epilepticus in a patient who has been given long-acting paralytic agents.

MANAGEMENT

Initial stabilization of the patient requires (a) ABCs, (b) bedside glucose analysis, (c) pulse oximetry, (d) cardiac monitoring, and (d) anticonvulsant therapy if seizure activity continues at time of evaluation.

Aggressive airway protection is critical as seizure patients have decreased gag reflexes and are at risk for aspiration. Positioning the patient on their side with frequent suctioning, if necessary, will lower the risk for aspiration. Patients who continue to seize despite therapy or those unable to protect their airway with conservative measures require intubation.

Pharmacologic Therapy

Parenteral benzodiazepines are first-line therapy for active seizures (including SE) and are effective in terminating seizures in 75% to 90% of patients. They suppress seizure activity by directly enhancing GABA (gamma-aminobutyric acid)-related neuronal inhibition. Lorazepam is generally preferred up to a dose of 0.1 mg/kg given at 2 mg/min. Lorazepam and diazepam (0.2 mg/kg IV given at 5 mg/min) are equally effective at terminating the initial seizure, while lorazepam is superior for preventing recurrence of the seizure. IV midazolam has been less studied but has shown a trend toward superior efficacy and decreased incidence of adverse outcomes compared to lorazepam and diazepam. Options for patients without intravenous access include IM midazolam or lorazepam (midazolam is probably the best option) in addition to rectal diazepam.

If a benzodiazepine does not terminate seizure activity, second-line agents for abortive therapy include phenytoin or fosphenytoin. Phenytoin does not directly suppress electrical activity at the seizure focus but rather slows recovery of voltage-activated sodium channels and thus suppresses neuronal recruitment. Thus, concurrent benzodiazepine administration is necessary when treating active seizures. The total oral dose of phenytoin is about 20 mg/kg with a maximum of 400 mg every 2 hours. It can also be given via slow IV administration up to 18 mg/kg. The rate can be no greater than 50 mg/min to avoid hypotension and cardiac dysrhythmias associated with its propylene glycol diluent. Fosphenytoin is the prodrug of phenytoin, is water soluble, and can be administered at 150 mg/min without significant toxicity. Cerebellar findings, such as nystagmus and ataxia, are the most common neurological side effects associated with phenytoin. While parenteral loading is most common, oral loading is appropriate in patients who report medication noncompliance or are found to have a subtherapeutic phenytoin level.

Phenobarbital is a CNS depressant that directly suppresses cortical electrical activity and is often used after benzodiazepines and phenytoin have failed. The onset of intravenous phenobarbital is 15 to 30 minutes with a long duration of action of up to 48 to 96 hours. Adverse effects of phenobarbital include profound respiratory depression and hypotension, limiting its use as abortive seizure therapy to third-line therapy.

Parenteral valproic acid has shown some recent promise as abortive seizure therapy, and is considered an alternative in cases where benzodiazepine or phenytoin use is limited by hypotension or hypersensitivity. Although similar to phenytoin in mechanism of action, it is generally well tolerated with mild side effects. Recommended loading dose for valproic acid is 15 to 20 mg/kg at a rate of 3 to 6 mg/kg/min, although more rapid bolus infusions have been safely administered.

Additional agents to be considered for abortive seizure therapy include propofol, barbiturates (other than phenobarbital), and inhaled anesthetics such as isoflurane. Propofol acts as a direct GABA agonist and global CNS depressant. While studies are limited showing its efficacy in SE, it has been shown to provide almost immediate suppression of seizure activity after a bolus infusion. Barbiturates (pentobarbital and thiopental) directly enhance GABA-mediated neuronal inhibition while suppressing all other brainstem functions and thus can also induce respiratory arrest, myocardial depression, and hypotension. Isoflurane anesthesia suppresses electrical seizure foci and is the treatment of last resort for the patient in SE, as these are patients who will have required intubation and ventilatory support.

Levetiracetam is a relatively new antiepileptic drugs (AEDs) with a mechanism of action that is atypical compared to other AEDs. Clinical studies suggest that it might have a significant effect in generalized seizures and was recently approved by the FDA as adjunctive treatment for primary generalized tonic-clonic seizures in adults and children aged 6 years and older. It is not yet recommended for abortive seizure therapy.

Patients in SE who require intubation are ideally induced with a benzodiazepine, serving to both sedate and to abate the seizure. If the patient requires paralysis for management purposes, it cannot be assumed that the patient’s seizure has been terminated. In this situation, anticonvulsant therapy should be continued and EEG monitoring of the patient should be arranged.

SPECIAL CASES

Drug-Induced Seizures

Therapy for drug-induced seizures is guided by general seizure management principles. There are no clear evidence-based guidelines for the management of drugrelated seizures and usually require therapy that is specific to the etiological agent. Cocaine is one of the most frequent causes of drug-induced seizures. Approximately 15% of cocaine users will experience a drug-induced seizure. Seizures caused by cocaine are a result of a combination of a lowered seizure threshold and hypersympathetic state. They are often associated with hyperthermia and high lactate levels. These seizures are usually self-limited, but in cases of status epilepticus, should be treated with high doses of benzodiazepines.

Tricyclic antidepressants cause seizures as a consequence of their anticholinergic properties. In addition to standard seizure therapy, patients with status epilepticus secondary to tricyclic overdose should be treated with sodium bicarbonate in an effort to obtain a blood pH of approximately 7.5. This will decrease the free form of the drug in the patient’s CNS as well as mitigate the drug’s sodium channel–blocking effect on the heart.

Isoniazid-induced seizures are associated with a high mortality rate and typically occur within 120 minutes of an acute overdose. Isoniazid binds pyridoxine, the active  form of vitamin B6, a cofactor for glutamic acid decarboxylase, and gamma-aminobutyric acid (GABA) transaminase. INH toxicity and depleted vitamin B6 lead to a reduction in levels of CNS inhibitory transmitter GABA and ultimately can result in status epilepticus. Treatment of seizures secondary to isoniazid toxicity is often refractory to standard measures and should be treated with IV pyridoxine. The dose of pyridoxine is based upon the amount of drug ingested.

Alcohol Withdrawal Seizures

Alcohol withdrawal seizures (AWS) are a leading cause of seizures in adults. These seizures often occur as part of a constellation of early withdrawal symptoms typically within 6 to 48 hours after the last drink. Other withdrawal symptoms including sweating, anxiety, tremor, auditory/visual hallucinations, agitation, nausea/vomiting, headache, and disorientation often occur prior to the onset of seizures. The more serious withdrawal syndrome of delirium tremens can be associated with seizures that may occur as long as 7 days post alcohol cessation. The more common and classic early AWS often occur in bunches of up to 4 to 6 seizures. However, these almost always cluster over a fairly brief period of time and they rarely persist past twelve hours from onset. Recent evidence recommends the use of benzodiazepines to reduce the incidence of seizures and delirium. Phenytoin does not have a role in managing either AWS or controlling recurrent alcohol-related seizures in the ED; however it may play a role in alcoholics who have underlying seizure disorders. The data for use of other anticonvulsants like carbamazepine in alcohol withdrawal seizures are limited.

CT imaging of the head has a high diagnostic yield in patients with their first alcohol-related seizure as these patients have a high incidence of structural intracranial lesions, such as subdural hematomas or other intracranial hemorrhages. Alcoholism is also a common cause of hypoglycemia and other metabolic abnormalities, thus electrolytes should be checked. IV fluid hydration with a glucose-containing solution in addition to thiamine, magnesium, potassium, and multivitamins is also indicated.

Neurocysticercosis

Neurocysticercosis (NCC) is an infection of the brain with larvae of Taenia solium (pork tapeworm) and is the most common cause of adult onset seizures in the developing countries of Latin America, sub-Saharan Africa, and Southeast Asia. It is also becoming increasingly prevalent in nonendemic countries with large immigrant populations. Seizures can vary from simple partial seizures to generalized tonic clonic. Diagnosis is confirmed via neuroimaging with visualization of active or calcified cysts in the brain. Treatment is usually initiated by a neurologist and consists of an antihelminth medication such as albendazole, combined with an antiepileptic medication.

Pseudoseizures

Pseudoseizures, also known as psychogenic seizures, are often the result of major stress or emotional trauma. These psychogenic nonepileptic seizures are often difficult to distinguish from physiologic seizures. Patients with psychogenic seizures tend to have multiple seizure patterns, which are usually not followed by a postictal period. Urinary incontinence and injury such as tongue biting has been reported in up to 20% of patients with psychogenic seizure. Unlike in physiologic seizures, noxious stimuli such as ammonia capsules may elicit responses from patients having psychogenic seizures. The observation of purposeful movement during a psychogenic seizure also is typical. Management of pseudoseizures involves reassurance and patient education with psychiatric consultation often recommended.

Patient Disposition

Disposition of patients will likely depend on the etiology of their seizure (if known), the known seizure history, and the availability of adequate outpatient follow-up. All patients need to be provided detailed seizure precautions, and locally mandated reporting requirements must be noted in the patient’s chart. Currently, the law in 6 states (California, Delaware, Nevada, New Jersey, Oregon, and Pennsylvania) requires physicians to report patients with seizures. They should also be warned about limiting activities when and where sudden loss of consciousness would be especially dangerous such as operating heavy equipment, swimming alone, cooking with hot water or even bathing.

In patients with known epilepsy who present with a single seizure, it is acceptable to send laboratory test results for anticonvulsant levels (if appropriate), give a loading dose of the appropriate anticonvulsant, and then discharge them with the appropriate follow-up. Subtherapeutic levels of antiseizure medication can be a result of medical noncompliance or increased metabolism, often caused by concurrent medication intake. Any history or physical examination findings consistent with a new seizure pattern should be addressed, as would be the case in a first-time seizure patient (Tables 31–1 and 31–2). Patients should also be thoroughly educated regarding the risks and benefits of noncompliance with antiepileptic medications.

In patients without a history of epilepsy who present with a single unprovoked seizure, a more thorough workup is indicated. If this initial workup is unremarkable, it is acceptable to discharge the patient home with follow up neuroimaging and an appointment with a neurologist. They will not necessarily need to be discharged on new antiepileptic medications but they will need education about restrictions in patients with seizures.

Patients without a history of seizure who do not return to baseline and remain postictal should be admitted to the hospital until they return to their baseline mental status and the underlying etiology of their seizures is determined. Patients in status epilepticus are usually admitted to the ICU for management and evaluation.

COMPREHENSION QUESTIONS

31.1 A 34-year-old man is brought into the ED with a seizure of new onset. It is determined that it was likely to be metabolic in etiology. Which of the following is the most likely diagnosis?

A. Hyperthyroidism

B. Hypocalcemia

C. Hypoglycemia

D. Hypomagnesemia

31.2 A 28-year-old woman is brought into the ED by paramedics because of seizure activity that has persisted for 40 minutes despite intravenous valium at the house and en route. Which of the following is the most likely reason for this patient’s condition?

A. Meningitis

B. Noncompliance with seizure medications

C. Cocaine

D. Benzodiazepine allergy

31.3 A 21-year-old man is brought into the ED for a seizure which was witnessed. It was described as tonic clonic and lasting for 3 minutes. Currently, the patient appears alert, oriented, and with normal vital signs. He has no nuchal rigidity. He admits to being diagnosed with HIV disease, but otherwise has no medical problems. He denies head trauma, or alcohol or illicit drug use. He denies headache. Which of the following is the best next step?

A. Emergent CT or MRI imaging of the brain

B. Begin fosphenytoin for seizure disorder

C. Observation because this is his first seizure

D. Stat EEG

ANSWERS

31.1 C. New-onset seizure in the ED caused by metabolic abnormalities is rare. Hypoglycemia is considered the most common metabolic cause of seizure. Symptomatic hypoglycemia occurs most commonly as a complication of insulin or oral hypoglycemic therapy in diabetics. Hyperglycemia, hypocalcemia, and hypomagnesemia are other, less-common metabolic causes of seizure.

31.2 B. A patient who experiences 30 minutes of continuous seizure activity or a series of seizures without return to full consciousness between seizures is considered to be in status epilepticus. The most common cause of status epilepticus is discontinuation of anticonvulsant medications.

31.3 A. Diagnostic imaging with head CT or MRI is recommended for seizure patients with suspicion of head trauma, elevated intracranial pressure, intracranial mass, persistently abnormal mental status, focal neurologic abnormality, or HIV disease.

CLINICAL PEARLS

⯈ Identifying the patient within one of the following subgroups facilitates the evaluation and management of the seizure patient in the emergency department: (a) new-onset (first-time) seizure, (b) recurrent seizures in patients with epilepsy, (c) febrile seizures, (d) post-traumatic seizures, and (e) alcohol- and drug-related seizures.

⯈ The possibility of reactive seizures should be considered in all seizure patients who present to the ED, including patients with a history of epilepsy. Failure to treat the underlying cause of reactive seizure is a major pitfall.

⯈ Seizures may be confused with other nonictal states such as syncope, hyperventilation, and breath-holding spells in children, migraines, transient global amnesia, cerebral vascular disease, narcolepsy, and psychogenic seizures.

⯈ Prolonged altered mental status following a seizure should not be attributed to an uncomplicated postictal state.

References

Armon K, Stephenson T, MacFaul R, et al. An evidence and consensus based guideline for the management of a child after a seizure. Emerg Med J. 2003;20(1):13-20. 

Beghi E. Treating epilepsy across its different stages. Ther Adv Neurol Disord. 2010;3(2):85-92. 

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Harden CL, Huff JS, Schwartz TH, et al. Reassessment: neuroimaging in the emergency patient presenting with seizure (an evidence-based review): report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology. 2007;69:1772. 

Krumholz A, Wiebe S, Gronseth G, et al. Practice parameter: evaluating an apparent unprovoked first seizure in adults (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology and the American epilepsy Society. Neurology. 2007;69:1996. 

Matthaiou DK, Panos G, Adamidi ES, Falagas ME. Albendazole versus praziquantel in the treatment of neurocysticercosis: a meta-analysis of comparative trials. PLoS Negl Trop Dis. Mar 12, 2008;2(3):e194. 

Pollack CV, Pollack ES. Seizures. In: Marx JA, Hockberger RM, Walls JA, eds. Emergency Medicine: Concepts and Clinical Practice. 5th ed. St Louis, MO: Mosby-Year Book; 2002. 

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Scheuer ML, Pedley TA. The evaluation and treatment of seizures. N Engl J Med. 1990;323(21): 1468-1474. 

Seamans CM, Slovis CM. Seizures: classification and diagnosis, patient stabilization and pharmacologic interventions. In: EMR textbook. 2002. Available at: http://www.emronline.com/articles/textbook/ 44. Access date 

Shearer P, Park D. Seizures and status epilepticus: diagnosis and management in the emergency department. emergency medicine practice. 2006;8(8). 

Turnbull TL, Vanden Hoek TL, Howes DS. Utility of laboratory studies in the emergency department patient with a new-onset seizure. Ann Emerg Med. 1990;19(4):373-377.

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