Epilepsy

Epilepsy (from the Ancient Greek verb ἐπιλαμβάνειν meaning “to seize, possess, or afflict“) is a group of neurological disorders characterized by epileptic seizures. Epileptic seizures are episodes that can vary from brief and nearly undetectable to long periods of vigorous shaking. In epilepsy, seizures tend to recur, and have no immediate underlying cause, while seizures that occur due to a specific cause are not deemed to represent epilepsy.

The cause of most cases of epilepsy is unknown, although some people develop epilepsy as the result of brain injury, stroke, brain tumor, and drug and alcohol misuse. Genetic mutations are linked to a small proportion of the disease. Epileptic seizures are the result of excessive and abnormal cortical nerve cell activity in the brain. The diagnosis typically involves ruling out other conditions that might cause similar symptoms such as fainting.

Additionally, making the diagnosis involves determining if any other cause of seizures is present such as alcohol withdrawal or electrolyte problems. This may be done by imaging the brain and performing blood tests. Epilepsy can often be confirmed with an electroencephalogram (EEG) but a normal test does not rule out the condition.

Seizures are controllable with medication in about 70% of cases. In those whose seizures do not respond to medication, surgery, neurostimulation or dietary changes may be considered. Not all cases of epilepsy are lifelong, and many people improve to the point that medication is no longer needed.

About 1% of people worldwide (65 million) have epilepsy, and nearly 80% of cases occur in developing countries. In 2013 it resulted in 116,000 deaths up from 111,000 deaths in 1990. Epilepsy becomes more common as people age. In the developed world, onset of new cases occurs most frequently in infants and the elderly; in the developing world this is in older children and young adults, due to differences in the frequency of the underlying causes.

About 5–10% of all people will have an unprovoked seizure by the age of 80, and the chance of experiencing a second seizure is between 40 and 50%. In many areas of the world those with epilepsy either have restrictions placed on their ability to drive or are not permitted to drive, but most are able to return to driving after a period of time without seizures.

Epilepsy Signs and Symptoms

"Epilepsy Spike-waves". Licensed under CC BY-SA 2.0 via Wikimedia Commons -

“Epilepsy Spike-waves”. Licensed under CC BY-SA 2.0 via Wikimedia Commons –

The most common type (60%) of seizures are convulsive. Of these, one-third begin as generalized seizures from the start, affecting both hemispheres of the brain. Two-thirds begin as partial seizures (which affect one hemisphere of the brain) which may then progress to generalized seizures. The remaining 40% of seizures are non-convulsive. An example of this type is the absence seizure, which presents as a decreased level of consciousness and usually lasts about 10 seconds.

Partial seizures are often preceded by certain experiences, known as an aura. These may include sensory (visual, hearing or smell), psychic, autonomic, or motor phenomena. Jerking activity may start in a specific muscle group and spread to surrounding muscle groups in which case it is known as a Jacksonian march.

Automatisms may occur; these are non-consciously generated activities and mostly simple repetitive movements like smacking of the lips or more complex activities such as attempts to pick something up.

There are six main types of generalized seizures: tonic-clonic, tonic, clonic, myoclonic, absence, and atonic seizures. They all involve loss of consciousness and typically happen without warning.

Tonic-clonic seizures present with a contraction of the limbs followed by their extension along with arching of the back which lasts 10–30 seconds (the tonic phase). A cry may be heard due to contraction of the chest muscles. This is then followed by a shaking of the limbs in unison (clonic phase). Tonic seizures produce constant contractions of the muscles. A person often turns blue as breathing is stopped.

In clonic seizures there is shaking of the limbs in unison. After the shaking has stopped it may take 10–30 minutes for the person to return to normal; this period is called the “postictal state” or “postictal phase”. Loss of bowel or bladder control may occur during a seizure. The tongue may be bitten at either the tip or on the sides during a seizure. In tonic-clonic seizure, bites to the sides are more common. Tongue bites are also relatively common in psychogenic non-epileptic seizures.

Myoclonic seizures involve spasms of muscles in either a few areas or all over. Absence seizures can be subtle with only a slight turn of the head or eye blinking. The person does not fall over and returns to normal right after it ends.

Atonic seizures involve the loss of muscle activity for greater than one second. This typically occurs on both sides of the body.

About 6% of those with epilepsy have seizures that are often triggered by specific events and are known as reflex seizures. Those with reflex epilepsy have seizures that are only triggered by specific stimuli. Common triggers include flashing lights and sudden noises. In certain types of epilepsy, seizures happen more often during sleep, and in other types they occur almost only when sleeping.

Postictal

After the active portion of a seizure, there is typically a period of confusion referred to as the postictal period before a normal level of consciousness returns. This usually lasts 3 to 15 minutes but may last for hours. Other common symptoms include feeling tired, headache, difficulty speaking, and abnormal behavior.

Psychosis after a seizure is relatively common, occurring in 6–10% of people. Often people do not remember what happened during this time. Localized weakness, known as Todd’s paralysis, may also occur after a partial seizure. When it occurs it typically lasts for seconds to minutes but may rarely last for a day or two.

Psychosocial

Epilepsy can have adverse effects on social and psychological well-being. These effects may include social isolation, stigmatization, or disability. They may result in lower educational achievement and worse employment outcomes. Learning difficulties are common in those with the condition, and especially among children with epilepsy. The stigma of epilepsy can also affect the families of those with the disease.

Certain disorders occur more often in people with epilepsy, depending partly on the epilepsy syndrome present. These include depression, anxiety disorders, and migraines. Attention deficit hyperactivity disorder affects three to five times more children with epilepsy than children in the general population. ADHD and epilepsy have significant consequences on a child’s behavioral, learning, and social development. Epilepsy is also more common in autistic people.

Causes of Epilepsy

Epilepsy can have both genetic and acquired causes, with interaction of these factors in many cases. Established acquired causes include serious brain trauma, stroke, tumours and problems in the brain as a result of a previous infective. In about 60% of cases the cause is unknown. Epilepsies caused by genetic, congenital, or developmental conditions are more common among younger people, while brain tumors and strokes are more likely in older people.

Seizures may also occur as a consequence of other health problems; if they occur right around a specific cause, such as a stroke, head injury, toxic ingestion or metabolic problem, they are known as acute symptomatic seizures and are in the broader classification of seizure-related disorders rather than epilepsy itself.

Genetics

Genetics is believed to be involved in the majority of cases, either directly or indirectly. Some epilepsies are due to a single gene defect (1–2%); most are due to the interaction of multiple genes and environmental factors. Each of the single gene defects is rare, with more than 200 in all described. Most genes involved affect ion channels, either directly or indirectly. These include genes for ion channels themselves, enzymes, GABA, and G protein-coupled receptors.

In identical twins, if one is affected there is a 50–60% chance that the other will also be affected. In non-identical twins the risk is 15%. These risks are greater in those with generalized rather than partial seizures. If both twins are affected, most of the time they have the same epileptic syndrome (70–90%). Other close relatives of a person with epilepsy have a risk five times that of the general population. Between 1 and 10% of those with Down syndrome and 90% of those with Angelman syndrome have epilepsy.

Acquired

Epilepsy may occur as a result of a number of other conditions including tumors, strokes, head trauma, previous infections of the central nervous system, genetic abnormalities, and as a result of brain damage around the time of birth.

Of those with brain tumors, almost 30% have epilepsy, making them the cause of about 4% of cases. The risk is greatest for tumors in the temporal lobe and those that grow slowly. Other mass lesions such as cerebral cavernous malformations and arteriovenous malformations have risks as high as 40–60%. Of those who have had a stroke, 2–4% develop epilepsy.

In the United Kingdom strokes account for 15% of cases and it is believed to be the cause in 30% of the elderly. Between 6 and 20% of epilepsy is believed to be due to head trauma. Mild brain injury increases the risk about two-fold while severe brain injury increases the risk seven-fold. In those who have experienced a high powered gunshot wound to the head, the risk is about 50%.

The risk of epilepsy following meningitis is less than 10%; that disease more commonly causes seizures during the infection itself. In herpes simplex encephalitis the risk of a seizure is around 50% with a high risk of epilepsy following (up to 25%). Infection with the pork tapeworm, which can result in neurocysticercosis, is the cause of up to half of epilepsy cases in areas of the world where the parasite is common.

Epilepsy may also occur after other brain infections such as cerebral malaria, toxoplasmosis, and toxocariasis. Chronic alcohol use increases the risk of epilepsy: those who drink six units of alcohol per day have a two and a half fold increase in risk. Other risks include Alzheimer’s disease, multiple sclerosis, tuberous sclerosis, and autoimmune encephalitis. Getting vaccinated does not increase the risk of epilepsy.

Diagnosis

EEG

EEG Recording Cap by Chris Hope

The diagnosis of epilepsy is typically made based on the description of the seizure and the underlying cause. An electroencephalogram and neuroimaging are also usually part of the workup. While figuring out a specific epileptic syndrome is often attempted, it is not always possible. Video and EEG monitoring may be useful in difficult cases.

An electroencephalogram (EEG) can assist in showing brain activity suggestive of an increased risk of seizures. It is only recommended for those who are likely to have had an epileptic seizure on the basis of symptoms. In the diagnosis of epilepsy, electroencephalography may help distinguish the type of seizure or syndrome present.

In children it is typically only needed after a second seizure. It cannot be used to rule out the diagnosis, and may be falsely positive in those without the disease. In certain situations it may be useful to perform the EEG while the affected individual is sleeping or sleep deprived.

Diagnostic imaging by CT scan and MRI is recommended after a first non-febrile seizure to detect structural problems in and around the brain. MRI is generally a better imaging test except when bleeding is suspected, for which CT is more sensitive and more easily available. If someone attends the emergency room with a seizure but returns to normal quickly, imaging tests may be done at a later point. If a person has a previous diagnosis of epilepsy with previous imaging, repeating the imaging is usually not needed even if there are subsequent seizures.

For adults, the testing of electrolyte, blood glucose and calcium levels is important to rule out problems with these as causes. An electrocardiogram can rule out problems with the rhythm of the heart. A lumbar puncture may be useful to diagnose a central nervous system infection but is not routinely needed. In children additional tests may be required such as urine biochemistry and blood testing looking for metabolic disorders.

A high blood prolactin level within the first 20 minutes following a seizure may be useful to confirm an epileptic seizure as opposed to psychogenic non-epileptic seizure. Serum prolactin level is less useful for detecting partial seizures. If it is normal an epileptic seizure is still possible and a serum prolactin does not separate epileptic seizures from syncope. It is not recommended as a routine part of the diagnosis of epilepsy.

Differential Diagnosis

Diagnosis of epilepsy can be difficult. A number of other conditions may present very similar signs and symptoms to seizures, including syncope, hyperventilation, migraines, narcolepsy, panic attacks and psychogenic non-epileptic seizures (PNES).

In particular a syncope can be accompanied by a short episode of convulsions. Nocturnal frontal lobe epilepsy, often misdiagnosed as nightmares, was considered to be a parasomnia but later identified to be epileptic. Attacks of the movement disorder paroxysmal dyskinesia may be taken for epileptic seizures. The cause of a drop attack can be, among many others, an atonic seizure.

Children may have behaviors that are easily mistaken for epileptic seizures but are not. These include breath-holding spells, bed wetting, night terrors, tics and shudder attacks. Gastroesophageal reflux may cause arching of the back and twisting of the head to the side in infants, which may be mistaken for tonic-clonic seizures.

Misdiagnosis is frequent (occurring in about 5 to 30% of cases). Different studies showed that in many cases seizure-like attacks in apparent treatment-resistant epilepsy have a cardiovascular cause. Approximately 20% of the people seen at epilepsy clinics have PNES and of those who have PNES about 10% also have epilepsy; separating the two based on the seizure episode alone without further testing is often difficult.

Epilepsy Research

Seizure prediction refers to attempts to forecast epileptic seizures based on the EEG before they occur. As of 2011, no effective mechanism to predict seizures has been developed. Kindling, where repeated exposures to events that could cause seizures eventually causes seizures more easily, has been used to create animal models of epilepsy.

Gene therapy is being studied in some types of epilepsy. Medications that alter immune function, such as intravenous immunoglobulins, are poorly supported by evidence. Noninvasive stereotactic radiosurgery is, as of 2012, being compared to standard surgery for certain types of epilepsy.

Further Reading:

Elaine Wyllie MD Wyllie’s Treatment of Epilepsy: Principles and Practice LWW; Sixth edition (February 27, 2015)

Oliver Sacks Hallucinations Knopf; 1 edition (November 6, 2012)

Simon D. Shorvon (2011). The Causes of Epilepsy: Common and Uncommon Causes in Adults and Children. Cambridge University Press.

Epilepsy: Historical overview“. World Health Organization.

Top Photo by Jef Safi

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