Seizure Induced by Traumatic Brain Injury Case File

https://medical-phd.blogspot.com/2021/05/seizure-induced-by-traumatic-brain.html

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.