Epilepsy and Seizures: Key Distinctions

• Emergency referral or physician consultation is immediately needed for status epilepticus or new-onset seizures.

Definition and Epidemiology

• Epilepsy is a syndrome marked by recurrent, unprovoked seizures.
• Diagnosis requires two or more unprovoked seizures at least 24 hours apart, or one seizure with risk factors like abnormal EEG or MRI lesions.
• Epilepsy affects about 2.2 million people in the U.S., with 150,000 new cases yearly.
• Seizure prevalence is approximately 5 to 8.4 cases per 1000 people.
• Lifetime epilepsy risk is 1 in 26.
• Incidence peaks in neonates/young children and older adults.
• Most epilepsy cases are well-managed with medication, but about a third are drug-resistant (intractable or refractory epilepsy).
• Provoked seizures from temporary conditions like hypoglycemia or alcohol withdrawal do not automatically lead to an epilepsy diagnosis unless they persist after the condition resolves.

Pathophysiology

• A seizure is an isolated event where a neuron group has excessive electrical discharges.
• Seizures result from an imbalance between brain excitation and inhibition.
• Excess excitatory neurotransmitter production or loss of inhibitory neuronal activity causes seizures.
• Hypoxia or metabolic factors, such as electrolyte imbalances, can trigger single or recurrent seizures.
• Epilepsy is categorized into syndromes based on causes, seizure types, neurologic symptoms, anatomy, age, and family history.

Classification of Seizures, Epilepsy, and Epileptic Syndromes

• The International League Against Epilepsy (ILAE) developed the classification of epileptic seizures.
• The current classification includes focal and generalized seizures.
• Focal seizures start in one cerebral hemisphere and show localized EEG abnormalities.
• Focal aware seizures maintain consciousness.
• An aura is the first clinical sign of a focal aware seizure.
• Common auras: epigastric rising, deja vu, foul smells.
• Consciousness becomes impaired if seizure activity spreads, classifying it as a focal with impaired awareness seizure.
• Focal with impaired awareness seizure symptoms: behavioral arrest, unresponsiveness, and automatisms.
• Focal to bilateral tonic-clonic seizures occur when the seizure spreads to the entire cortex
• Primary generalized seizures appear to start everywhere at once, likely deep in the brain (thalamus).
• Generalized seizures are usually associated with genetic/idiopathic generalized epilepsy.
• Consciousness is almost always impaired in generalized seizures, except for myoclonic jerks.
• Generalized seizures can be convulsive or nonconvulsive, with bilateral motor activity and EEG changes.
• Nonconvulsive generalized seizures: absence, tonic, atonic, or myoclonic seizures.
• Absence seizures may be mistaken for ADHD.
• Atonic seizures may be mistaken for fainting.
• Convulsive seizures are now known as generalized tonic-clonic seizures.
• A focal seizure may start in one EEG lead or hemisphere.
• Generalized seizures appear simultaneously in all EEG leads.
• Scalp EEG may not detect all seizures.
• Frontal lobe seizures are difficult to detect on scalp EEG.
• Absence seizures show 3- to 6-hertz spike and wave on EEG.
• Polyspike waves on EEG relate to myoclonic seizures.
• Differentiation between seizure types is important because each type may respond differently to certain antiseizure medications, like carbamazepine or pregabalin.
• Ethosuximide is effective in childhood absence epilepsy.
• Sodium valproate is effective in other generalized epilepsies.
• The International Classification of Epilepsy and Epileptic Syndromes categorizes cases by seizure type, cause, precipitating factors, age at onset, and prognosis.
• Seizure causes are classified as genetic, structural, metabolic, or unknown.
• Syndromes are classified by age of onset, cognitive/developmental antecedents, EEG features, triggers, and sleep patterns.
• Idiopathic, generalized epilepsy manifests by age 18.
• Focal brain processes should be suspected after age 18.
• Brain tumors cause seizures in adults.
• Strokes often cause seizures that begin later in life.
• Symptomatic epilepsy occurs when the cause of the epilepsy is known or presumed

Clinical Presentation and Physical Examination

• An accurate and detailed history is important.
• Significant risk factors for epilepsy: perinatal complications, developmental delay, history of meningitis/encephalitis, significant head trauma with loss of consciousness, and family history of epilepsy.
• New-onset seizures require determination of recent headache, illness, trauma, or focal neurologic deficit.
• An accurate description is vital in deciding whether an event was a seizure.
• Incontinence, injury, tongue biting, postictal confusion, lateralized weakness, or severe headache raise suspicion of an epileptic event.
• The first visible signs can be helpful in localization of the seizure onset or epilepsy type.
• A general physical examination should be directed toward specific disease processes and focal neurologic deficits.
• Skin and mucous membranes should be assessed to identify injuries.
• Tongue and cheek biting are common during tonic-clonic seizures.
• Cardiovascular assessment is important because syncope and arrhythmias are included in the differential diagnosis of epilepsy.
• Neurologic signs, such as lateralized weakness, papilledema, memory problems, or changes in reflexes, can signify a structural lesion in the brain.
• Most patients with epilepsy will have unremarkable physical examination findings.

Diagnostics

• Clinical presentation, physical examination, and differential considerations guide diagnostic testing.
• A new seizure may signify a serious pathologic condition.
• Suspected CNS infection warrants CBC and lumbar puncture.
• A basic metabolic profile is necessary to exclude hypoglycemia or electrolyte abnormalities.
• LFTs should be performed to exclude hepatic failure and monitor medication side effects.
• Alcohol and drug levels testing may be indicated.
• MRI or CT scan is indicated if structural abnormality, tumor, trauma, or cerebrovascular accident is suspected,.
• ECG should be performed to ascertain the presence of arrhythmias or heart block.
• Sleep-deprived EEG is useful because background brain waves may reveal epileptic abnormalities.
• The positive predictive value of EEG in most clinics is high, although sensitivity is low to moderate.
• Interictal epileptiform abnormalities may give localizing information and suggest epilepsy.
• Many patients with focal epilepsy show no abnormalities on interictal EEG.
• Generalized types of epilepsy often produce abnormalities of spike and wave activity or generalized slowing on routine EEG.
• Interictal abnormalities are not always synonymous with seizure activity, thus abnormal EEG should not be the sole basis for either diagnosis or treatment.
• The absence of structural abnormalities does not exclude a diagnosis of epilepsy
• CT scans are useful for identifying gross abnormalities, but MRI provides extensive anatomic detail.
• MRIs should be the primary imaging study in patients with epilepsy.
• In the preoperative evaluation of patients who are candidates for epilepsy surgery, SPECT, PET, fMRI, HDEEG, and MEG are other imaging methods that may be considered.

Initial Diagnostics

• New-Onset Seizure
  • LABORATORY
  • Alcohol, drug levels
  • Complete blood count (CBC) with differential
  • Comprehensive metabolic profile
  • IMAGING
    • Magnetic resonance imaging (MRI), computed tomography (CT) scan
  • OTHER DIAGNOSTICS
  • Electrocardiogram (ECG)
  • Lumbar puncture
  • Electroencephalogram (EEG)
• If epilepsy cannot be confirmed or excluded, an empiric medication trial should be considered.
• If the patient’s condition does not improve with more than one medication, then they should be referred to a comprehensive epilepsy center.

Differential Diagnosis

• Possible differential diagnoses: cardiovascular causes, other neurologic conditions, or psychiatric causes.
• Syncope manifests with loss of consciousness,
• Presyncopal symptoms such as vertigo, sensory disturbances, and tinnitus are sometimes mistaken for epileptic auras or focal aware seizures.
• Other disorders in the differential diagnosis include tumors, cerebrovascular disease, arteriovenous malformation, trauma, CNS infection, migraines, hyperventilation syndrome, movement disorders, transient ischemic attacks, transient global amnesia, sleep disorders, and toxic metabolic disturbances such as alcohol withdrawal seizures.
• Psychogenic nonepileptic seizures are paroxysmal events that are not stereotyped and are often characterized by motor or nonmotor activity, unresponsiveness, and altered behavior/mentation with no associated EEG changes.
• A careful history can help raise suspicion for psychogenic nonepileptic seizures.
• Confirming a diagnosis may require video EEG monitoring.

Seizure Emergencies

• The following conditions warrant hospital admission: status epilepticus (SE), incomplete recovery from a single seizure or prolonged postictal state, suspected illness that requires treatment, drug or alcohol withdrawal, febrile illness (adult), expanding mass lesion, history of recent head trauma, or focal signs on examination.
• SE is defined as continuous seizure activity lasting more than 5 minutes or two consecutive seizures in a row without mental clearing.
• Generalized convulsive status epilepticus (GCSE) can lead to permanent brain damage or even death.
• If seizures persist beyond 30 minutes, a vicious cycle of maladaptive physiologic responses occurs.
• SE may be complicated by hypotension, hypertension, hyperthermia, hypoglycemia, hypoxemia, acidosis, arrhythmias, rhabdomyolysis, pulmonary edema, fractures, and dislocations.
• For patients in SE, a battery of laboratory tests is usually performed: CBC; electrolyte values; glucose, magnesium, calcium, blood urea nitrogen (BUN), and creatinine concentrations; LFTs; coagulation studies (prothrombin time, partial thromboplastin time); alcohol level, toxicology screen; antiseizure drug levels; urinalysis; and pregnancy test.
• Examination of the cerebrospinal fluid is required if meningitis or encephalitis is suspected.
• In patients with known epilepsy, half of the hospital-reported cases of GCSE have been associated with subtherapeutic antiseizure medication (ASM) levels
• Other common causes of SE are meningitis, head trauma, eclampsia, and progressive neurologic and neurodegenerative disorders.
• Lorazepam was more likely to be successful than phenytoin when used as the initial treatment

Physician Consultation

• Specialist consultation is indicated for suspected central nervous system (CNS) lesions, SE, initiation of antiepileptic medications, treatment failures, and persons with epilepsy who are contemplating pregnancy.

Interprofessional Collaborative Management

• First seizures are usually not treated with ASMs, depending on a number of variables, including the potential for seizure recurrence
• Factors to consider: seizure type (complex partial seizures are more likely to be recurrent than generalized tonic-clonic ones), environment and occupation, results of imaging studies and EEG.
• The two most consistent predictors of seizure recurrence are an abnormal EEG and an underlying cause.
• After a second unprovoked seizure, treatment should be initiated, as the risk of recurrence increases to more than 70%.

Pharmacologic Management

• ASMs can be grouped into two major categories, broad and narrow spectrum.
• Broad-spectrum medications are effective at treating both focal and generalized epilepsies.
• Narrow-spectrum medications are only effective for focal epilepsies, and in some cases may make generalized epilepsy worse.
• Initial goal of treatment should be seizure freedom.
• If a patient’s condition is determined to be drug resistant, then the goal of treatment shifts to optimizing safety and quality of life, using a balance of seizure control with the risk of medication side effects.
• Some patients whose condition is drug resistant may be candidates for surgical interventions.
• Common broad-spectrum medications include levetiracetam, lamotrigine, sodium valproate, and topiramate.
  • Keppra is a common first-line medication
  • It has few medication interactions, and the kidneys primarily metabolize it.
  • In about 10% of patients, it may result in psychiatric side effects
  • In the older population, it may also cause cognitive issues or somnolence.
  • It is also a preferred medication in pregnancy.
  • Lamotrigine is frequently a second-line choice, it has the added benefit of acting as a mood stabilizer
  • It is preferred in pregnancy.
  • It is a mild enzyme inducer and may decrease the efficacy of hormonal contraceptives at higher doses.
  • The most concerning side effect is the increased risk of Steven-Johnson syndrome (SJS) during the medication initiation, necessitating a slow and deliberate titration schedule.
  • Sodium valproate potentiates the effect of lamotrigine
  • It is often the drug of choice for patients with genetic generalized epilepsies
  • It is highly teratogenic, including increased rates of neural tube defects.
  • It is not preferred in persons of childbearing age.
  • Other side effects include weight gain, hair loss, polycystic ovarian syndrome, hepatotoxicity, and lower IQs in the offspring of persons taking this medication during pregnancy even in the absence of other birth anomalies.
• Topiramate and zonisamide are two similar broad-spectrum medications that are often effective in the treatment of genetic generalized epilepsy.
  • These medications may cause a reaction in those with sulfa allergies.
  • Common side effects include cognitive slowing, word-finding difficulty, increased rates of kidney stones, appetite suppression, and weight loss.
  • Zonisamide tends to be somewhat better tolerated than topiramate.
  • Ethosuximide and methsuximide specifically effective for treating absence seizures, but not effective for the treatment of focal or generalized tonic-clonic seizures.
• Narrow-spectrum medications are effective for treating focal epilepsy but tend to be ineffective for treating generalized epilepsies and, in some situations, can make primary generalized epilepsies worse.
• For focal epilepsy, carbamazepine remains probably the single-most effective drug and has the great advantage of low cost.
• It can, however, make some forms of generalized epilepsy worse and currently has no parenteral formulation.
• Its newer cousins, oxcarbazepine and eslicarbazepine, tend to be better tolerated.
• Phenytoin is equally effective and can be given parenterally but has a concerning side-effect profile, particularly for females.
• In more than 50% of patients with epilepsy, seizures are completely controlled with medication.
• Another 20% to 30% of patients witness improvement in their symptoms with medications, but they are not seizure-free or may experience significant side effects.

Surgical Management

• Patients with adequate seizure control should undergo presurgical and diagnostic evaluation with electroencephalographic video monitoring at a comprehensive epilepsy center.
• Patients having difficulty tolerating medications should also be referred for a neurology consultation.
• Patients with structural lesions should be referred promptly to a neurosurgeon for further evaluation.
• Side effects occur in approximately 30% to 40% of patients taking ASMs, which include potential rashes, mood changes, weight changes, gastrointestinal disturbances, and headache.
• It is most important to follow the patient’s response to treatment, not only in terms of drug levels, but in relation to efficacy and side effects.

Emerging Medical Trends

• There is a great deal of interest in using cannabidiols for the treatment of drug-resistant epilepsy.
• Recent approval of the cannabidiol Epidiolex for certain forms of childhood epilepsy has significantly increased interest in using this class of drugs to treat seizures in adults, especially for those unresponsive to or intolerant of usual treatments.

Discontinuation of Antiepileptic Drugs

• There is insufficient evidence to establish when to withdraw ASMs in patients who are seizure free.
• The risk for relapse is 20% to 40% in the first year of drug withdrawal and remains at about 36% during a 30-year period.
• Removal of medications be considered only if the patient has been seizure free for 2 to 5 years, has a single type of partial seizure, and has a normal EEG and IQ and normal findings on physical examination.

Surgical Management

• Of all patients with epilepsy,25% to 30% are refractory to medical management.
• Almost 80% of partial seizures in adults begin in the temporal lobes.
• After temporal lobe surgery, success rates (complete seizure control) range from 65% to 95%.
• Another major type of epilepsy surgery involves dividing the corpus callosum: the nerve fibers that connect one side of the brain to the other are severed.
• Neurostimulators use electrical signals used to modulate brain activity and to abort seizure activity : vagus nerve stimulation, responsive neurostimulation, and deep brain stimulation.
• Patients who are seizure free for several years can consider a medication taper

Life Span Considerations

• Stigma, social isolation, and depression can affect all persons with epilepsy, special concerns are recognized in specific age groups
• In childbearing persons with epilepsy, there are additional concerns about contraception, fertility, and sexuality.
• Monotherapy is most important for this population to reduce side effects and drug interactions.

Complications

• Complications in patients with epilepsy are usually related to seizure events. Injuries that occur during seizures include falls, burns, motor vehicle accidents, and aspiration pneumonia.
• Patients taking enzyme-inducing antiepileptic medications are at increased risk for osteoporosis and osteomalacia.
• All patients should be taking vitamin D and calcium supplements.

Patient and Family Education and Health Promotion

• Epilepsy provides unique teaching opportunities because it is a chronic condition that affects all aspects of a patient’s life.
• Key areas for patient instruction: General information, Diagnostic studies, Treatment plan, Medication information, Alternative or adjunctive therapies, Safety issues and first aid for seizures,and Support services available

Explore the differences between seizures and epilepsy, focusing on diagnosis and underlying causes. Understand the factors influencing epilepsy diagnosis, seizure types, and treatment. Learn about the balance of excitation and inhibition in the brain during a seizure.