Hospital Medicine

Epilepsy

I. Problem/Condition.

A seizure is a neurological condition characterized by a sudden alteration in behavior caused by abnormal electrical activity in the brain. Epilepsy is when an individual has more than one, unprovoked, seizure. Multiple review articles have demonstrated a prevalence of about 4-10 per 1000 individuals. Numerous studies have also shown a bimodal or U-shaped distribution, with children and the elderly being most frequently affected. Epilepsy is found in both developed and underdeveloped nations, however, there is slightly higher frequency of epilepsy in developed rather than developing nations. This is felt to be due to the decreased life expectancy of individuals in developing nations.

Seizures are classified into two large categories which are described in all standard neurology textbooks. These include focal versus general and simple versus complex. Focal seizures refer to a limited area of localization from which the electrical discharge originate (EEG and clinical manifestations indicate involvement of only one cerebral hemisphere). Generalized seizures show clinical manifestations of both sides of the brain at the same time as they simultaneously affect both cortices. Simple seizures differ from complex seizures in that there is no change in awareness noted during the episodes.

Simple partial seizures: No change in the level of awareness

Complex partial seizures:

  1. May start as simple partial seizures without impairment of consciousness at onset

  2. May start with impairment of consciousness at onset

  3. May start as either a simple partial seizure or a complex partial seizure and transform into a generalized tonic clonic seizure

Generalized Seizures:

  1. Absence:

    • Typical: defined by sudden onset blank staring, with alteration of consciousness. These last about a few seconds. They are characterized by a 3Hz spike and wave appearance on EEG. They can be induced in patients by using hyperventilation.

    • Atypical: similar to typical absence seizures. These normally last less than 10 seconds but can last longer. They are less than 2.5 Hz on EEG.

  2. Tonic: classified by alteration in consciousness in addition to muscle rigidity.

  3. Clonic: involves rhythmic jerking of the muscles.

  4. Myoclonic: classified by quick, irregular jerking movements of the head, limbs or body.

  5. Atonic: defined by a sudden loss of muscle tone. The patient may fall down.

  6. Tonic-Clonic: characterized by a sudden loss of consciousness in combination with both tonic and clonic activity of the muscles, AKA grand mal seizures.

Epilepsy can be divided into multiple syndromes as well. An extensive discussion of these syndromes is beyond the scope of this chapter. However, correctly identifying the syndrome does affect outcome and treatment.

Two of the more common syndromes encountered are Juvenile Myoclonic Epilepsy (JME) and Lennox-Gastaut.

JME is composed of a myriad of seizure types and affects children in their early to late teens. It is characterized by myoclonic seizures, usually in the morning, absence seizures, and generalized tonic-clonic seizures. It has an EEG pattern that looks like a poly-spike and wave. The treatment for JME is lifelong.

Lennox-Gastaut Syndrome is composed of a triad of tonic, atonic, and atypical absence seizures. It tends to affect younger children, and is usually more refractory to treatment than JME.

II. Diagnostic Approach.

A. What is the differential diagnosis for this problem?

The differential diagnosis for epilepsy is broad and includes physiologic as well as non-physiologic causes.

The physiologic causes include cardiac causes such as vasovagal syncope, Stokes-Adams Syndrome, or arrhythmias. Sleep disorders including parasomnias and cataplexy also need to be investigated. Neurologic causes include TIA, stroke, migraine headaches, transient global amnesia, hypnic jerks, movement disorders, hemifacial spasm, and dystonic reactions. Metabolic derangements such as hypoglycemia, hyponatremia, and hypomagnesemia must also be considered. Intoxications or withdrawals from alcohol or illicit drugs can lead to seizures as well.

Non physiologic causes include nonepileptic seizures and other psychiatric mimickers of epilepsy (ex: panic attacks).

B. Describe a diagnostic approach/method to the patient with this problem.

A high index of suspicion is the first step in identifying a seizure. Seizures should always be a consideration in any patient with an alteration of consciousness from baseline. This is especially critical in the geriatric population with multiple comorbidities and the change in state attributed to another cause. Seizures can be precipitated by an underlying infection, which in itself can result in alteration of consciousness.

An isolated or even repeated episodes of provoked seizure does not establish the diagnosis of epilepsy, and if identified correctly results in the patient not burdened by additional medications.

Further steps in evaluation can be done based on the degree of suspicion for a seizure.

1. Historical information important in the diagnosis of this problem.

  1. Age of onset.

  2. 2. Seizure Semiology: Description of the events of the seizure itself: this is critical in identifying the origin of the seizure and has potential implications for treatment. Patients may have multiple seizure types and each type has to be identified correctly with the frequency of each type.

    • Was there an aura? Could the patient feel the event developing? Defining the aura can also localize the area of seizure onset.

    • What happened first, second, third, etc.? The sequence of events during the seizure can also provide clues to the area of onset.

    • Were the eyes open or closed? It has been shown with high sensitivity that patients have their eyes closed during non-epileptic seizures and can assist in diagnosing that difficult condition.

    • Did the head turn? Which way?

    • Which limb or limbs did it start in?

    • Any loss of bowel or bladder control or any tongue biting?

    • Frequency of seizures: Identifying the seizure burden helps in providing a guide for improvement with treatment as well as assessing and improving the patient quality of life.

    • Duration of seizures

    • Postictal period, including a description of the patient’s signs/symptoms and duration.

    • Circumstances under which the seizure occurred: It provides the information about provoking and precipitating factors for seizures and may vary from patient to patient. A few examples are: Had the patient been up all night cramming for an examination? Had the patient been drinking, especially excessively? Had the patient been using other street drugs. Had the patient recently changed antiepileptic drugs (AEDs) or missed a dose?

    • Were there witnesses for any of their seizures? Family members should ideally accompany the patient especially if they have witnessed the events as most patients do not recall the events during the seizure.

  3. 3. Medication history:

    • All current medications: certain antibiotics (Imipenem) or other agents used (ex: Welbutrin for smoking cessation) are well known to lower seizure threshold.

    • Current antiepileptic medication (AED) regimen if any.

    • All previously used AEDs and the maximal dosage achieved/tolerated.

    • Why any particular medication was discontinued.

    • Other medications: especially oral contraceptives, analgesics, any OTC medications or supplements used.

  4. 4. Birth history

    • Was the patient premature? And if so, by how many weeks?

    • Any problems during the pregnancy or the birth?

    • Vaginal or Cesarean section delivery?

  5. 5. Did the patient have febrile seizures?

  6. 6. Were all the developmental milestones achieved at the appropriate ages? Did the patient have any special education requirements? What is the highest level of education achieved?

  7. 7. Was there any history of "daydreaming" as a child? Any history of head trauma with loss of consciousness?

  8. 8. History of stroke/TIA?

  9. 9. History of tumors?

  10. 10. History of CNS infections such as meningitis, neurocysticercosis or herpes encephalitis?

  11. 11. Any family history of seizures? If positive need to identify if maternal or paternal and trace as far back as possible.

2. Physical Examination maneuvers that are likely to be useful in diagnosing the cause of this problem.

There are no special physical examination maneuvers for diagnosing epilepsy.

The examination of a patient suspected to have epilepsy or seizures should include a general medical examination followed by a complete neurologic examination.

The general examination should include searching for neurocutaneous syndromes with stigmata (ex: Tuberous sclerosis with adenoma sebaceum) as well as dysmorphic features (ex: microcephaly) in addition to routine system examinations.

The complete neurological examination should include a mental status examination assessing memory, language, cognition, concentration, right-left orientation and praxis. Testing of cranial nerves, the motor system, the sensory system, as well as reflexes, coordination, station and gait also need to be performed.

3. Laboratory, radiographic and other tests that are likely to be useful in diagnosing the cause of this problem.

Multiple methods exist for evaluating seizures and epilepsy. One of the first to be considered after performing a careful, detailed history and physical examination should include an EEG.

The electroencephalogram (EEG) acts not only to localize the area of electrical disturbance but has also been shown to be useful in the prediction of further seizures. A recent Quality Standards Subcommittee sponsored by the American Academy of Neurology and the American Epilepsy Society found level B evidence (Level B = probably helpful) for evaluation of a first seizure with an EEG. This is because of the initial EEG being positive in only about 25% patients with epilepsy; but if positive, adds credence to the clinical diagnosis. However, a negative EEG does not rule out the possibility of seizures or epilepsy.

Computed tomography (CT) scan or magnetic resonance imaging (MRI) of the brain was also shown to be level B evidence for the evaluation of a first seizure. The choice of CT or MRI depends on the site of initial presentation of the patient. For a patient being evaluated in the emergency room, CT is the imaging of choice because of the ease and speed of obtaining the study. However, all patients suspected of having seizures require an MRI of the brain with a specific seizure protocol. In those patients with other comorbidities and a high index of suspicion for infections or space-occupying lesions, a contrast-enhancing study maybe required.

CBC, electrolyte panels, and blood glucose levels have not been shown to be useful for regular use in the evaluation of initial seizures (Level U evidence - the data are inadequate or conflicting). However, this is dependant on the initial presentation and the patient's history. In a patient with history of diabetes mellitus and on hypoglycemic medications, blood glucose has to be checked prior anything else to rule out hypoglycemia as the cause of the seizure.

Lumbar puncture in the evaluation of a first seizure also has a level U evidence, unless the patient is febrile or there is a high index of suspicion for infection (ex: the immunocompromised patient).

Toxicology screens may also not be needed in the routine evaluation of seizures, once again unless there is any index of suspicion.

PET-CT, SPECT scans and MEG (magnetoencephalography) scans have been shown to be useful to localize the epileptic focus, when being evaluated for epilepsy surgery. These are not performed routinely.

C. Criteria for Diagnosing Each Diagnosis in the Method Above.

Seizures are divided into two large categories: focal versus general, and simple versus complex. Focal seizures refer to a limited area of localization from which the electrical discharge originated (EEG and clinical manifestations indicate 1 cerebral hemisphere is involved). Generalized seizures show the first clinical manifestations of both sides of the brain at the same time. Simple seizures are delineated from complex seizures based up on alteration of consciousness.

Simple partial seizures: No change in the level of awareness

Complex partial seizures:

  1. Which start as simple partial seizures without impairment of consciousness at onset.

  2. Which start with impairment of consciousness at onset.

  3. Which start as either a simple partial seizure or a complex partial seizure and transform into a generalized tonic clonic seizure.

Generalized Seizures:

  1. Absence

    • Typical: defined by sudden onset blank staring, with alteration of consciousness. These last about a few seconds. They are characterized by a 3Hz spike and wave appearance on EEG. They can be induced in patients by using hyperventilation.

    • Atypical: similar to typical absence seizures. These normally last less than 10 seconds but can last longer. They are less than 2.5 Hz on EEG.

  2. 2. Tonic: classified by alteration in consciousness in addition to muscle rigidity.

  3. 3. Clonic: involves rhythmic jerking of the muscles.

  4. 4. Myoclonic: classified by quick, irregular jerking movements of the head, limbs or body.

  5. 5. Atonic: defined by a sudden loss of muscle tone.The patient may fall down.

  6. 6. Tonic-Clonic: characterized by a sudden loss of consciousness in combination with both tonic and clonic activity of the muscles, AKA grand mal seizures.

D. Over-utilized or “wasted” diagnostic tests associated with the evaluation of this problem.

When combined with a good history and physical examination associated with a high index of suspicion of seizures, any of the mentioned tests can be appropriate. However, the reverse can be true especially if the history is incomplete, and precious resources are wasted requesting unnecessary tests.

III. Management while the Diagnostic Process is Proceeding.

A. Management of Clinical Problem Epilepsy.

Management of epilepsy differs depending on the setting and if the diagnosis of epilepsy has already been established.

The first step is to take a detailed history and to perform a complete neurological examination of the patient.

In evaluating someone with a seizure, the first thing to consider is if this event represents a seizure or one of the many varied conditions in the differential diagnosis, such as syncope.

If it is a seizure, then it needs to be confirmed that it truly is a first seizure: studies have shown that on detailed history 50% of patients report a prior seizure, although not definitely recognised or diagnosed.

In a patient with history of epilepsy, the history will provide the reason for the current episode.

Identifying provoking or precipitating factors are critical: ex: check blood glucose to rule out hypoglycemia.

If there is any history of head trauma, brain tumor, or suspicion for other acute neurological emergencies obtain diagnostic imaging of the brain and as mentioned previously, in the ER setting a CT head is ideal.

Consider basic blood work, alcohol and toxicology screens if supported by the history.

Check AED levels if the patient is taking any antiepileptic medications. If the head CT or lab results are abnormal or the patient has focal neurological deficits, a neurology or neurosurgery consult is appropriate.

If the above results and physical examination are normal, and the patient has returned to baseline, discharge can be considered with close neurology follow up.

In a patient with an established diagnosis of epilepsy, correction of the precipitating or provoking factor is usually the key. Patient education to prevent such episodes in the future are critical.

There is some debate among epilepsy experts on whether or not to treat the first seizure. This depends on multiple factors such the circumstances under which the seizure occurred, the certainty that the event represents a seizure, the patient’s job, i.e., the risks versus benefits of treatment of the first seizure. It has been generally accepted to treat after the second unprovoked seizure.

Convulsive Status Epilepticus

(For management of Nonconvulsive status epilepticus, please see that chapter.)

Although the textbook definition of convulsive status epilepticus (CSE) is when a patient has a seizure lasting for more than 30 minutes or a series of seizures lasting for 30 minutes without return to baseline in between events, for practical purposes any seizure that lasts as much as 5 minutes needs immediate treatment and is the accepted working definition.

There are several algorithms for managing status epilepticus and as with all medical emergencies, start with the ABCDs.

Within the first 5 minutes of onset, benzodiazepines are administered. With lorazepam, the usual dose is a maximum of 0.1mg/kg given in 2 minute intervals: repeated doses can be given while the initial AED is being administered to control ongoing seizures.

This should be followed by an AED such as phosphenytoin at 20mg/kg given at up to 150mg/minute.

Other AEDs include valproic acid at 20-30 mg/kg or leviteracetam at 20-30mg/kg: these agents can be considered as first or second-line agents, depending on availability.

If the seizure does not resolve within 30 minutes, consider administering a second epileptic drug or anesthetic inducing medications such as propofol or midazolam.

If seizures do not resolve, consider transferring the patient to a tertiary medical center with availability of a neurologist and/or epileptologist and capabilities for further evaluation, monitoring and treatment of refractory CSE.

The patient should be intubated and propofol started at 2mg/kg and maintained at 2-5mg/kg per hour. Midazolam can reasonably be started at 0.2mg/kg and maintained at up to 0.6mg/kg per hour.

The patient should be placed on 24 hour EEG monitoring at this time. If seizures do not resolve with the measures outlined above by 48 hours after the onset, consider adding barbiturates such as pentobarbital or thiopental. The goal at this time should be to attain burst suppression on EEG.

Difficult to treat/refractory status epilepticus has additional agents that have been shown to be helpful in limited case series or case reports: such as ketamine, isoflurane, magnesium, and ketogenic diet.

Correction of any underlying metabolic derangements have to be done from the outset.

Outpatient management of epilepsy involves multiple issues, including patient education and compliance.

The first major issue that needs to be considered is that of patient safety. Seizure precautions should be reviewed with the patient and caregiver at each visit, including the following:

Driving restrictions – which vary by state

Utilizing heavy machinery

Heights, ladders, and working underground

Working around water, including the danger of taking baths or swimming

Hot stoves or open flames

Other issues that need to be addressed include: medications and their potential side-effects, interactions with other medications, need for compliance, changing from brand to generic antiepileptic medications, suicidal potential, bone health issues.

Special consideration needs given to the care of women with seizures. There are multiple issues unique to women such as catamenial epilepsy (seizures related to monthly periods), contraception, pregnancy, and teratogenicity that require a skilled neurologist or epileptologist to be an integral part of their health management.

Another issue to be addressed is the psychiatric comorbidities commonly associated with epilepsy: primarily depression, as well as anxiety, panic disorder etc.

If the patient has non-epileptic seizures, they need further counseling and long-term psychiatric follow-up.

Vagal nerve stimulators (VNS) have been used in refractory epilepsy. A VNS is a device about the size of a pacemaker that is implanted in the chest. Wires lead from the generator unit to the vagus nerve and pass a small current through that nerve. A decrease in the number of required AEDs needed to treat an individual has been shown to be associated with this device, but it make take as long as 12 months to start to achieve the maximum benefit. Cough, dyspnea, and hoarseness have been seen as side effects but usually decrease over time. It is a good choice in some patients who has refractory epilepsy and are not candidates for epilepsy surgery.

Various other devices are currently in development that assist in detecting and treating seizures and are expected to be available soon.

Epilepsy surgery is also a consideration for intractable disease. Multiple studies have shown up to a 70-90% seizure free rate with appropriate surgical therapy, particularly with mesial temporal lobe seizures. It is recommended that after an appropriate trial of at least two antiepileptic agents (maximum doses without side-effects and tolerated by the patient for at least 2 years) surgery should be considered.

B. Common Pitfalls and Side-Effects of Management of this Clinical Problem.

With status epilepticus in particular, many of the medications used can cause hypotension, arrhythmia or respiratory depression.

Some of the common AEDs and their side effects include:

  1. Phenytoin: 20mg/kg IVx 1 at a maximum of 50mg/minute. It is known to cause purple glove syndrome with extravasation, in addition to hypotension, osetomalacia, and arrhythmia. It is also less pH balanced than Phosphenytoin, which has the same loading dose, but can be given at a rate of up to 150mg/minute.

  2. Valproic Acid: has been associated with hepatotoxicity and carries a black box warning in association with pancreatitis.

  3. Phenobarbital: has been associated with sedation, lethargy, and respiratory depression.

  4. Lamotrigine: has been associated with rash and Stevens-Johnson Syndrome.

  5. Topiramate: has been known to cause weight loss as well as nephrolithiasis and acute-angle narrow glaucoma. Cognitive changes have also been reported.

  6. Felbamate: has been associated with aplastic anemia and liver failure.

  7. Carbamazepine: has been associated with balance problems, dizziness, visual problems as well as hyponatremia. It has also been rarely been associated with arrhythmia and heart block.

  8. Oxcarbazepine: has been known to cause nausea/emesis, headache, and Stevens-Johnson Syndrome.

  9. Levetiracetam: has been associated with agitation and hostility and drowsiness.

In addition, AEDs may need to be adjusted due to oral contraceptive pills or other hormonal birth control methods in women.

Loading links....
You must be a registered member of Neurology Advisor to post a comment.
close

Next Article in Hospital Medicine

Sign Up for Free e-newsletters