- A seizure is a paroxysmal, hypersynchronous, excessive neuronal discharge of variable extent.
- Epilepsy includes disorders or syndromes with widely variable pathophysiologic findings, clinical manifestations, treatments, and prognoses.
- Individuals with epilepsy have a tendency for and occurrence of recurrent seizures. It is the tendency to have recurrent seizures, not necessarily with provocation, that makes the diagnosis of epilepsy. More than one seizure must occur before the diagnosis of epilepsy is made.
- Epilepsy is the most common chronic neurologic condition, affects individuals of all ages, with a peak incidence in childhood and in the elderly.
- In the United States, the incidence of all types of epilepsy is 35 to 52 per 100,000, varying by age: 60 to 70 per 100,000 per year in young children (<5 years), 45 per 100,000 in adolescents, as low as 30 per 100,000 in the early adult years, but rising through the sixth and seventh decades back to 60 to 70 per 100,000 and reaching as high as 150 to 200 per 100,000 in individuals older than 75 years.
- The cause of epilepsy remains undetermined in more than 50% of patients.
- The etiology varies with the age group. In childhood, most epilepsies are idiopathic, whereas in adults, most are secondary to identifiable causes.
- The most common cause of epilepsy worldwide in developed countries is stroke/vascular disease (10 to 17%), followed closely by head trauma, developmental/congenital disorders, infection, neoplasm, and degenerative disorders, especially Alzheimer’s disease.
- Trauma/congenital/infectious causes most frequent in children and vascular disease/neoplasm accounting for greater than 25% of cases in patients older than 60 years.
- The most frequent comorbid diseases are mental retardation (cognitive disorders and learning disabilities) and psychiatric disorders, but motor deficits are also common. Cognitive deficits are common in adults with epilepsy of many causes, including stroke, dementia, and neoplasm.
- Isolated symptomatic seizures that occur without a diagnosis of epilepsy are related to specific causes: electrolyte imbalance, drug induced (Theophylline, meperidine, tricyclic antidepressants, phenothiazines, lidocaine, quinolones, penicillins, selective serotonin re-uptake inhibitors, isoniazid, antihistamines, cyclosporine, interferons, cocaine, lithium, amphetamines, alcohol (withdrawal), benzodiazepines (withdrawal), barbiturates (withdrawal)), infection, vascular disorders, emdcorine disorders, neoplasms.
- Partial seizures involve a localized region or collection of cells in a specific area that display bursting behavior: the epileptic neuronal aggregate. Prolonged depolarization caused by a shift in calcium conductance results in firing of multiple sodium-dependent action potentials. The spontaneous or stimulation-induced bursting behavior produces a paroxysmal depolarization shift, which is the intracellular correlate of an interictal spike, the characteristic of EEG recordings in patients with epilepsy.
- In the generalized epilepsies, in which onset of the seizure is manifested by diffuse clinical and EEG changes that involve many or all areas of the brain, an alteration in the normal oscillatory rhythms that characterize the circuits of pyramidal neocortical neurons and neurons of the nucleus reticularis of the thalamus may be the cause.
- Most of the common epileptic syndromes have complex inheritance patterns that have eluded definition. Many of the epilepsies with mendelian inheritance are rare disorders related to alterations in ion channels
- The current classification of epileptic seizures relies on clinical features and their accompanying EEG patterns. Seizures are divided into two main categories, partial and generalized, defined on the basis of involvement, at least at their start, of a localized region of the brain (partial) or the whole brain.
- The specific types of seizures determine the epileptic syndrome and dictate the choice of drugs for treatment (see later).
PERTINENT HISTORICAL FINDINGS/ CLINICAL SYMPTOMS
- The diagnosis of epilepsy is based on historical information but because seizures involve a change of consciousness, diagnosis can be problematic.
- History from others is crucial: patient’s activity, responses, and appearance (changes in color, diaphoresis, respirations, vocalization, and muscle tone. The setting in which the events occur (time of day, activity, ambient temperature, position, and sleeping or waking state) is important.
- Seizure threshold is lowered by fasting, lack of sleep, stress, fever, hyperventilation, strobe lights, withdrawal of certain drugs (e.g., alcohol, benzodiazepines, barbiturates), and use of illegal and legal toxic substances.
- Partial seizure recognized by patients as an “aura” (a feeling of déjà vu, feelings of impending doom, fear, euphoria, or an odd sensation in the stomach, often rising toward the head).
- Autonomic symptoms that may herald the onset of a seizure: pallor, diaphoresis, olfactory or gustatory sensations, urge to defecate, dizziness, vertigo, nausea, and salivation.
- Vocalization is a common accompaniment of seizure activity.
- Vertigo and dizziness are common at the onset of a seizure.
PERTINENT PHYSICAL EXAM FINDINGS
- Seizures resulting from injury or from congenital, traumatic, neoplastic, immunologic, infectious, metabolic, or toxic causes may be associated with other findings that point to specific causes.
- Partial Seizures: partial seizures are simple, without alteration of consciousness, or complex, with altered consciousness. A simple partial seizure of occipital lobe origin might begin with flashing lights in the contralateral visual field and then progress to involve additional occipital lobe regions. If consciousness is altered, it is termed a complex partial seizure. This seizure activity “marches” from hand to arm to leg area ipsilaterally, a process referred to as a jacksonian march. After the clonic motor activity ends, patients are often weak; a postictal or Todd paralysis may last hours or even a day or two, with gradual resolution.
- Simple partial seizures originating from any region can become complex partial seizures, and unilateral simple or complex partial seizures can progress to involve bilateral brain areas, thereby resulting in secondary generalized seizures.
- Generalized Tonic-Clonic Seizures: also termed a grand mal seizure or convulsion. May begin with a “cry” as a result of abrupt air movement across the glottis from sudden tonic muscle contraction. The patient becomes diffusely stiff, usually with limb and body extension and often with arching of the back. Breathing is suspended, cyanosis occurs, and urinary incontinence is common. After 15 to 60 seconds, the tonic activity gives way to clonic, rhythmic jerking of all four extremities; the patient is apneic, comatose, and diaphoretic and within 60 seconds begins stridorous breathing with foaming and gasping.
- Postictal stupor lasts a variable length of time. The patient generally sleeps for 2 to 8 hours and then complains of severe headache, sore muscles, a bitten tongue, and inability to concentrate for a day or more. After generalized tonic-clonic seizures, some individuals have severe memory loss that gradually improves, sometimes over a period of weeks.
- Absence Seizures: is the second most common type of generalized seizure and is synonymous with the term “petit mal,” describes a momentary lapse of awareness. The patient has no perception of any aspect of the event and may or may not realize that some time was lost. Consciousness is immediately lost at the onset, there is no aura. Seizures begin in childhood, school teachers are often the first to notice them. The “absence” may be accompanied by brief eye blinking or myoclonic movement. May occur many times a day but are not associated with progressive neurologic disease.
- Myoclonic Seizures: are brief episodes of sudden motor contraction, often flexion of the upper extremities, that appear as muscle jerks. These movements can be focal, with one arm involved, or bilateral and massive, with involvement of both upper extremities and the trunk. There is no loss of consciousness, but the episodes are brief that consciousness is difficult to evaluate. Most commonly occur in the morning, just after awakening, and increase in frequency to culminate in a generalized tonic-clonic seizure.
- panic attacks
- various psychiatric disorders
- Movement disorders
- Sleep disorders
- Cerebrovascular insufficiency
- Electroencephalogram is the most important diagnostic study in epilepsy. Most patients with epilepsy do not have a seizure recorded on a routine 30- to 40-minute EEG study, but interictal abnormalities on a routine EEG study can be highly suggestive of an epileptic disorder. The highest likelihood of detecting abnormal interictal activity on an EEG recording is in the 24-hour period after a seizure.
- Brain magnetic resonance imaging (MRI): should always be performed in patients with new-onset seizures.
- Functional imaging techniques, including single-photon emission computed tomography (SPECT) for determination of blood flow and positron emission tomography (PET) for analysis of metabolism, are useful, especially in individuals with uncontrolled seizures.
- Metabolic and toxic screening can point to other systemic disorders or causes of seizures.
- Lumbar puncture is not helpful unless there is a possibility of hemorrhage, infection, or immunologic disease as the underlying cause.
- The goal is to find the drug or drugs that suppress all seizure activity without side effects.
- Specific drugs are effective for specific types of seizures, and some drugs can worsen other types of seizures (see table below). Knowledge of individual drugs as they relate to age, sex, comorbid conditions, drug interactions, sedation, tolerance, mood, and withdrawal is critical in the drug selection process.
- Final selection would depend on age, gender, weight, psychiatric status, employment, concomitant medications, and pregnancy concerns relevant to the individual.
- Treatment with the initial drug controls seizures completely in more than 50% of patients with newly diagnosed epilepsy. After failure of the first monotherapy, only 14 to 20% of patients with partial seizures will be successfully controlled with any alternative single drug.
- Medical intractability occurs more often in patients with frequent seizures, multiple types of seizures, abnormal neurologic findings, a brain lesion, onset in the first year of life, or abnormal EEG findings consisting of either spike and slow wave activity or multifocal abnormalities.
Antiepileptic Drug Selection by Seizure Type
Seizure (Sz) 1st or Alternative Other Useful Alternative
Type Monotherapy Monotherapy/Polytherapy
Partial Sz Carbamazepine Acetazolamide
Complex or Simple Gabapentin Chlorazepate
Tonic clonic Sz, Carbamazepine Acetazolamide
Tonic Sz, atonic Sz Lamotrigine Chlorazepate
Absence Sz Ethosuximide Acetazolamide
Myclonic Sz Clonazepam Phenobarbital
Adapted from: Cecils 23rd edition Chapter 426 – Seizures and Epilepsy
SURGICAL MANAGEMENT (when applicable)
- In a randomized trial, resective surgery for intractable medial temporal lobe epilepsy achieved a 58% seizure-free rate at 1 year versus 8% in the control group.
- When intractable epilepsy is associated with multifocal seizures, when the onset of seizures occurs in functionally critical brain regions, or when localization is not possible, resection cannot be attempted.
- Other surgical interventions, including corpus callosum section or multiple subpial transection, may be of benefit. These usually palliative procedures.
- Electrical stimulation is now used to treat medically refractory epilepsy when surgery is not indicated.
EMERGENCY MANAGEMENT (when applicable)
- Status epilepticus is a medical emergency in which seizures occur continuously or repeatedly without intervening resumption of consciousness. See Status Epilepticus Outline for further information.
PATIENT EDUCATION/ MAINTENANCE – PREVENTION
- After a single, first seizure, only 25% of patients have a recurrent seizure.
- The prognosis with treatment for individuals with two or more unprovoked seizures is excellent. The majority of patients without risk factors who have been seizure free for 5 years can be successfully withdrawn from medications.
- Remission is less likely for adults with more frequent seizures, a greater number of seizures before diagnosis, multiple types of seizures, or abnormal EEG or neurologic findings.
Dr. Zachary Lahlou