Table of Contents
History of Epilepsy
In all clinical specialties, there is a recurrent group of disease etiologies, e.g., infectious, autoimmune, inflammatory, neoplastic, traumatic, metabolic, or genetic causes for diseases. However, only the neurology department has an etiologic group all to itself: epilepsy.
Early in history, people were impressed by the spectacular clinical picture of epilepsy, and they interpreted it in the context of the divine. In ancient Greece, epilepsy was considered a ‘holy disease.’ The term used for it was morbus sacer, denoting both a sacred and a demonic condition.
Later, in medieval times, the divine characterization faded and people with epilepsy were more and more often considered to be possessed by demons. During the reign of national socialism in Germany, these people were seen as being ‘unworthy.’
Definition of Epilepsy
During an epileptic seizure, a short synchronous discharge of neurons occurs. This results in sudden symptoms that vanish just as suddenly and can affect all neuronal qualities (e.g., motor function, sensory, vegetative, and consciousness).
However, an epileptic seizure is not necessarily evidence of epilepsy. Roughly 5% of all people have an epileptic seizure at some point in their lives without having a diagnosis of epilepsy.
Epilepsy itself is a chronic disease of the brain that results in recurrent and unprovoked seizures.
If technical examinations result in the detection of changes that are typical for epilepsy (see below), the diagnosis of epilepsy can be made after only one seizure. Therefore, it is important to remember the following vocabulary:
- Occasional seizure: epileptic seizure due to a clear trigger; no seizures if the trigger is avoided
- Epileptic seizure: sudden, short, synchronous unloading of a group of neurons; can occur in every human being if the stimulus is strong enough
- Status epilepticus: longer-lasting seizures (> 5 minutes) or repeated seizures between which consciousness is not regained
Causes of Epilepsy
There are three forms of epilepsy: idiopathic, symptomatic, and cryptogenic. Idiopathic means that the epilepsy has a genetic basis. Symptomatic means that a structural cerebral alteration seems to be responsible for the epileptic discharge. Epilepsy is considered cryptogenic if such a structural alteration is suspected but not verifiable.
Pathophysiologic etiologies are very heterogeneous. They include malformations, metabolic diseases, acquired brain lesions, radiation, early childhood hypoxia, encephalitis, and so forth.
Likewise, different provocation factors—such as fever, electrolyte derailment, uremia, hypoglycemia, hypoxia, withdrawal from alcohol, and withdrawal from medications—lead to an increased predisposition for seizure. Often, spontaneous epileptic seizures develop from a combination of (exogenous) stimuli, genetic predisposition, and metabolic processes.
General Symptoms and Clinical Relevance of Epileptic Seizures
The clinical presentation of epileptic seizures is very complex and extensive. Such seizures are best described as a paroxysmal excitation of many neurons that cause excessive excitation in a certain region of the brain. Thus, focal frontal excitation results in clonic – occipital excitation to visual symptoms.
Generalized seizures can present as tonic (stiff extension of the extremities) or clonic (rhythmic convulsion); they can also present as absence seizures (empty, contactless gaze) or as individual generalized muscle twitches (myoclonic seizure).
The ‘classic’ generalized grand mal seizure is often accompanied by an epileptic cry. The objective findings on examination are a lateral tongue bite, postictal muscle ache, and enuresis or encopresis. After an epileptic discharge, intermittent palsies can occur (Todd’s palsy).
Monitoring keratin kinase is an important part of laboratory procedures. The massive and generalized muscle contraction in combination with hypoxia results in diffuse muscle damage with the release of keratin kinase. If the size of the release is significant, the kidneys can be damaged. Therefore, hemodilution should be sought when levels are high.
You should remember the following descriptions of the clinical terms used for epilepsy.
|Positive symptoms||Increased function|
|Negative symptoms||Decreased function|
|Ictal||During a seizure|
|Postictal||Period after a seizure during which normal neuronal function has not yet been regained. In this period, the patients are very sleepy and are cognitively impaired.|
Differential diagnosis tips for clinical practice
It is important, especially during an emergency admission, to perform a differential diagnosis. This is particularly important in sleepy patients (with complicated anamnesis) with palsies; in these cases, an acute ischemic event must be ruled out.
In addition to imaging, a clinical examination is also helpful. In ischemia, the visual angle deviates from the damaged side; in epilepsy, it deviates from the opposite side of the epileptic event. So, if left-sided hemiparesis and visual angle deviation to the right are evident, ischemia is the more likely diagnosis.
When there is a lack of certainty about the diagnosis, diagnostic imaging tests should be done to rule out an ischemic event. Other considerations in the differential diagnosis should include migraine attacks with aura, a (convulsive) syncope, or a psychogenic seizure.
Psychogenic seizures are characterized by a very variable duration; they can often last for several minutes. The type of seizure changes, and often there are presentiments that last much longer than an epileptic aura. In a psychogenic seizure, the eyes are often tightly closed, especially if the examiner tries to open them. In an epileptic seizure, most often the eyes are wide open. After a slow reorientation, patients often stutter.
Syndrome Classes of Epilepsy
The group of epileptic diseases is large and polymorphic. Classification into syndrome classes serves for orientation and determines the different approaches to therapy. The various diagnostic specificities, especially the respective electroencephalographic (EEG) findings, are described later.
A common feature of focal epilepsies is the epileptogenic origin in a certain region of the brain with specific symptoms.
If impairment of consciousness occurs during a focal seizure, it is referred to as complex focal epilepsy. The epileptic aura (perceptions a few seconds before the seizure) defines focal epilepsies. The following are typical characteristics of focal epileptic areas.
|Area of epilepsy||Characteristic|
|Temporal lobe||This is the most frequent group of focal epilepsies. It has an epigastric aura with the following features: It often manifests as hippocampal sclerosis, it is pharmacologically hard to adjust, and it is often necessary to perform neurosurgical therapy. The following process is typical:
1. Aura: visceral, also déjà vu or jamais vu
|Frontal lobe||Psychic aura, tonic–clonic seizures, Jackson seizures (in which the clonic movements march over different body areas), versive seizures, and aphasic seizures|
|Parietal lobe||Sensory aura, sensory (also marching) seizures, and negative symptoms such as apraxia, vertigo, and aphasia|
|Occipital lobe||Visual aura, complex visual impressions or visual memories during the seizure; long-lasting|
|Benign focal||Rolandic epilepsy, one-sided clonic with strong salivation (especially at night), halting of the seizure before adolescence (thus benign). Therapy: sultiame administration. This form of epilepsy is idiopathic.|
In cases of generalized epilepsies, a widespread pathology has to be assumed. Epileptic manifestations quickly affect the whole brain.
Idiopathic generalized forms of epilepsy
The idiopathic generalized epilepsies represent the greatest number of epilepsy occurrences. The following series of individual diseases are especially relevant for practice.
|Childhood absence epilepsy (pyknolepsy)||Occur from the third to the eighth year of life onward; short absences; up to 100 seizures per day; good prognosis; therapy: ethosuximide|
|Juvenile absence epilepsy||Similar to childhood absence epilepsy, but with a later onset and worse prognosis (roughly 40% of patients are not permanently free of seizures); tonic–clonic grand mal seizures at waking up and especially in older adults|
|Juvenile myoclonic epilepsy, ‘Janz syndrome,’ ‘impulsive petit mal’||From the 12th to the 20th year of life onward; myoclonic in the morning (especially on nongentle waking up); also bilateral myoclonus of the extremities (things are suddenly and jerkily thrown away); astatic; and tonic–clonic seizures|
|Grand mal epilepsy||Generalized tonic–clonic seizures with great irregularity|
Symptomatic or cryptogenic generalized forms of epilepsy
The main cause of symptomatic generalized epilepsies is early-childhood brain damages caused by hypoxia or metabolic diseases. Often, these patients have decreased intelligence and are severely affected. The two most important forms are as follows.
- West syndrome occurs in the first year of life. The seizure picture consists of infantile spasm (short tonic cramp of the arms and legs in front of the body; formerly called ‘Blitz–Neck–Salaam’). It prognosis is bad, and it frequently progresses into the Lennox–Gastaut syndrome. Therapy consists of adrenocorticotropic hormone (ACTH), steroids, or benzodiazepines.
- Lennox–Gastaut syndrome is an epileptic encephalopathy. It develops out of West syndrome or from late generalized brain damage. Seizures are generally astatic (falling), absence, and generalized tonic–clonic.
Diagnosis of Epilepsy
An extensive anamnesis, and especially third-party anamnesis, is important for detection and assessment. For instrument-based examination, EEGs, computed tomography (CT), and magnetic resonance imaging (MRI) are used.
Decelerations or changes and patterns typical for epilepsy can be identified with EEG. Whole generalized epilepsies often show changes in the entire brain, focal epilepsies only show changes in some leads. The amplitude and frequency of the leads are assessed to detect spikes, spike–wave complexes, or seizure patterns.
It takes a lot of training and experience to correctly interpret EEGs. In addition to a resting EEG, provocation factors (flickering light, hyperventilation, and sleep deprivation) can be used to show epileptogenic potentials. Several important EEG findings with the respective epilepsy syndromes are:
- Childhood absence epilepsy: 3-Hz spike–wave complexes
- Juvenile absence epilepsy: 3-Hz spike–wave complexes and polyspike waves
- Juvenile myoclonic epilepsy: generalized polyspike waves
- West syndrome: hypsarrhythmia (irregular, high-amplitude activity, interictal and ictal flattening)
- Lennox–Gastaut syndrome: slow spike–wave complexes (slower than 2.5 Hz)
- Creutzfeldt–Jakob disease: triphasic waves
For the evaluation of the first seizure, imaging should be sought for considerations of differential diagnosis. In an emergency, CT results are quickly available. For better imaging of epileptogenic lesions, an MRI examination can help.
Therapy of Epilepsy Forms
Therapy is based on different approaches. Lifestyle is an important aspect to take into consideration. On one hand, a decrease in seizure potential can be reached with good sleep hygiene or by quitting alcohol consumption. On the other hand, every person with epilepsy has to be informed about a possible restructuring of everyday measures: Can I perform my job as a window cleaner? Can I use my car or bike? What about swimming, cutting the hedge or working with a drilling machine?
In addition, there are pharmacologic, surgical, and interventional therapy possibilities. The indication for therapy is individual.
While some patients experience very little impaired epileptic externalization and face continuous medication intake rather reluctantly, others can be very scared after a grand mal seizure and urgently need therapy. According to Bauer & Neumann (2008), the indication for therapy is available
- when diagnosing epilepsy.
- in cases of a higher risk for seizure after a first seizure.
- after the first seizure with quick necessary seizure protection.
- after a second seizure with intermediate seizure protection.
- in cases of problematic seizures (e.g., status epilepticus).
- with consent of the patient.
Medicamentous anticonvulsant therapy
The selection of the necessary anticonvulsant medication has to be deliberate and should follow the form of epilepsy, acuteness, and possible comorbidity or pregnancy. Also, individual anticonvulsant medication options are differently tolerated. The following table gives a rough overview of the application areas of some frequently used anticonvulsants for seizure prophylaxis.
|Carbamazepine||400–1,600 mg||Relatively safe in pregnancy; the many side effects include enzyme induction, agranulocytosis, liver toxicity, hyponatremia, heat, reddening, swelling, and tenderness (HRST), and syndrome of inappropriate antidiuretic hormone secretion (SIADH).|
|Phenytoin||200–600 mg||Used as an intravenous emergency medication; difficult dosage due to auto-induction; high risk for withdrawal seizures; prophylaxis with vitamin D and calcium is recommended.|
|Focal and generalized epilepsies|
|Valproate||600–2,000 mg||Broad-spectrum efficacy; CYP inhibition reinforces the effect of, e.g., lamotrigine; side effects include liver toxicity, teratogenicity (neural tube defects); important for exams|
|Levetiracetam||1,000–3,000 mg||Used as an intravenous emergency medication; quick effect; little interaction with other medicaments; side effects include fear, depression, and aggression.|
|Lamotrigine||100–400 mg||Folate inhibitor, mood-elevating, can be taken during pregnancy; skin reactions (up to Stevens–Johnson syndrome) may occur if dosage is increased too quickly.|
|Topiramate||100–400 mg||Carbonic anhydrase inhibitor (kidney stones), weight loss, and cognitive impairments|
During therapy with phenytoin and valproate, routine monitoring of blood levels is recommended. Also, you should remember the following medications for routine clinical use: ethosuximide for absence epilepsies; sultiame for Rolandic epilepsies or as additional medication for severe epileptic syndromes.
First aid for epileptic seizures
Most acute epileptic seizures terminate quickly and spontaneously; no special therapy is needed. It is especially important to make sure that no injuries occur because of surrounding objects or an uncontrolled fall.
Note: Measures such as using a bite wedge or holding the arms, legs, or head are obsolete nowadays.
If the seizure does not terminate spontaneously, the following level scheme is recommended.
- Benzodiazepines intravenously: The first-resort medication is lorazepam, the second is diazepam. If intravenous administration is not possible, diazepam can be given rectally or lorazepam intranasally. Also, intramuscular application is very effective (according to some studies, it is even equally effective) and can be routinely useful, especially if intravenous injection fails.
- Phenytoin intravenously as an alternative: phenobarbital or valproate
- Narcotics with intensive care monitoring (thiopental and propofol)
Possibilities of epilepsy surgery
Surgical measures seek to eliminate the epileptogenic neuronal area. Of course, this can work only with focal epilepsies. Surgery is indicated if
- pharmacologic resistance is present (more seizures after two appropriate anticonvulsive therapy approaches).
- the seizures are perceived to be an impairment and an increase in quality of life is expected after the intervention.
- the patient is appropriately motivated.
- the epileptogenic focus is well operable.
- progressive neuronal disease is not present.
In addition to the respective procedures, there are also nonrespective ones such as callosotomy (sectioning of the corpus callosum). At first, partial sectioning (usually of the anterior two thirds) is attempted. If seizures persist, complete sectioning of the corpus callosum can be performed. The goal is to section the interhemispheric pathways to prevent a generalized spread of the seizure, which can be accompanied by severe cognitive deficits.
Interventional stimulus therapy of epilepsy
Amygdala–hippocampal or anterior–thalamic stimulation can be achieved with the use of a pacemaker system. This can result in a seizure reduction of up to 50% (Vonck et al., 2002).
Even if an absolute therapy is not possible, many patients feel better if they are relieved of the side effects of pharmacologic side treatment and if the collateral psychiatric (e.g., depressive) impairments can be improved.
Therapy of status epilepticus
Status epilepticus is a neurologic emergency. It is defined as an epileptic externalization that lasts longer than 5 minutes or presents as a series of seizures, between which consciousness is not regained.
Thus, status epilepticus can occur with every epileptic condition. Nonconvulsive status epilepticus or the absence status are possible. The grand mal status is considered life threatening.
Therapy for status epilepticus generally follows the coherent level scheme, which was mentioned above, concerning the termination of an epileptic seizure. In cases of absences or myoclonic seizures, phenytoin should not be given because it can worsen the situation.
Driving with Epilepsy
The greatest fear of people affected with epilepsy is continuation of their usual life. Many fear the uncertainty of new seizures and the resulting impairments. Particularly, driving cars (of course, also riding bikes or motorcycles or steering ships) is a relevant subject.
The treating physician must inform the patient about how epilepsy may affect the ability to drive in traffic. Likewise, it is a medical duty to be familiar with the respective legal guidelines: When an owner of a driver’s license is affected, usually, a preliminary withdrawal of the license occurs.
However, a driving ban is not absolute and definitive. It can be reversed depending on the further progression of the condition:
- If the first seizure occurred unprovoked, the driver’s license is returned after 3–6 months without seizures.
- If the second seizure occurred symptomatically or was provoked, the driver’s license is returned after 3 months without seizures.
- If there is a second seizure, or if epilepsy has been diagnosed, the driver’s license is returned after a year without seizures (independently of the therapy course or the therapy type).
- If epileptic seizures are persistent, the driver’s license is not returned as long as a significant risk for further seizures is present.
Commercial drivers with a license to drive trucks and/or for transportation of people usually have a definite withdrawal of their driver’s license. If necessary, the person affected must change his or her job. If it can be proven that there was no seizure within 5 years without being on antiepileptic treatment, the driver’s license can be returned.
If there is reason to believe that a driving ban is being violated, the violation must be reported to the police.