Epilepsy

 

Epilepsy is a group of neurological disorders characterized by epileptic seizures. Epileptic seizures are episodes that can vary from brief and nearly undetectable periods to long periods of vigorous shaking. These episodes can result in physical injuries, including occasionally broken bones. In epilepsy, seizures tend to recur and, as a rule, have no immediate underlying cause. Isolated seizures that are provoked by a specific cause such as poisoning are not deemed to represent epilepsy. People with epilepsy may be treated differently in various areas of the world and experience varying degrees of social stigma due to their condition.

The cause of most cases of epilepsy is unknown. Some cases occur as the result of brain injury, stroke, brain tumors, infections of the brain, and birth defects through a process known as epileptogenesis. Known genetic mutations are directly linked to a small proportion of cases. Epileptic seizures are the result of excessive and abnormal neuronal activity in the cortex of the brain. The diagnosis involves ruling out other conditions that might cause similar symptoms, such as fainting, and determining if another cause of seizures is present, such as alcohol withdrawal or electrolyte problems. This may be partly 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.

Epilepsy that occurs as a result of other issues may be preventable. Seizures are controllable with medication in about 70% of cases. Inexpensive options are often available. In those whose seizures do not respond to medication, surgery, neurostimulation or dietary changes may then be considered. Not all cases of epilepsy are lifelong, and many people improve to the point that treatment is no longer needed.

As of 2015, about 39 million people have epilepsy. Nearly 80% of cases occur in the developing world. In 2015, it resulted in 125,000 deaths up from 112,000 deaths in 1990. Epilepsy is more common in older people. In the developed world, onset of new cases occurs most frequently in babies and the elderly. In the developing world, onset is more common in older children and young adults, due to differences in the frequency of the underlying causes. About 5–10% of 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 until they are free of seizures for a specific length of time. The word epilepsy is from Ancient Greek ἐπιλαμβάνειν, “to seize, possess, or afflict”.

Causes
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 infection. 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 focal 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%.

Some evidence links epilepsy and celiac disease and non-celiac gluten sensitivity, while other evidence does not. There appears to be a specific syndrome which includes coeliac disease, epilepsy and calcifications in the brain. A 2012 review estimates that between 1% and 6% of people with epilepsy have coeliac disease while 1% of the general population has the condition.

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%). A form of an infection with the pork tapeworm (cysticercosis), in the brain, is known as neurocysticercosis, and 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. Malnutrition is a risk factor seen mostly in the developing world, although it is unclear however if it is a direct cause or an association. People with cerebral palsy have an increased risk of epilepsy, with half of people with spastic quadriplegia and spastic hemiplegia having the disease.

Prevention
While many cases are not preventable, efforts to reduce head injuries, provide good care around the time of birth, and reduce environmental parasites such as the pork tapeworm may be effective. Efforts in one part of Central America to decrease rates of pork tapeworm resulted in a 50% decrease in new cases of epilepsy.

Prognosis
Epilepsy cannot usually be cured, but medication can control seizures effectively in about 70% of cases. Of those with generalized seizures, more than 80% can be well controlled with medications while this is true in only 50% of people with focal seizures. One predictor of long-term outcome is the number of seizures that occur in the first six months. Other factors increasing the risk of a poor outcome include little response to the initial treatment, generalized seizures, a family history of epilepsy, psychiatric problems, and waves on the EEG representing generalized epileptiform activity. In the developing world, 75% of people are either untreated or not appropriately treated. In Africa, 90% do not get treatment. This is partly related to appropriate medications not being available or being too expensive.

Mortality
People with epilepsy are at an increased risk of death. This increase is between 1.6 and 4.1 fold greater than that of the general population. The greatest increase in mortality from epilepsy is among the elderly. Those with epilepsy due to an unknown cause have little increased risk.

Mortality is often related to: the underlying cause of the seizures, status epilepticus, suicide, trauma, and sudden unexpected death in epilepsy (SUDEP). Death from status epilepticus is primarily due to an underlying problem rather than missing doses of medications. The risk of suicide is between 2 and 6 times higher in those with epilepsy; the cause of this is unclear. SUDEP appears to be partly related to the frequency of generalized tonic-clonic seizures and accounts for about 15% of epilepsy-related deaths; it is unclear how to decrease its risk.

In the United Kingdom, it is estimated that 40–60% of deaths are possibly preventable. In the developing world, many deaths are due to untreated epilepsy leading to falls or status epilepticus.

Epidemiology
Epilepsy is one of the most common serious neurological disorders affecting about 39 million people as of 2015. It affects 1% of the population by age 20 and 3% of the population by age 75. It is more common in males than females with the overall difference being small. Most of those with the disorder (80%) are in the developing world.

The estimated prevalence of active epilepsy (as of 2012) is in the range 3–10 per 1,000, with active epilepsy defined as someone with epilepsy who has had a least one unprovoked seizure in the last five years. Epilepsy begins each year in 40–70 per 100,000 in developed countries and 80–140 per 100,000 in developing countries. Poverty is a risk and includes both being from a poor country and being poor relative to others within one’s country. In the developed world epilepsy most commonly starts either in the young or in the old. In the developing world its onset is more common in older children and young adults due to the higher rates of trauma and infectious diseases. In developed countries the number of cases a year has decreased in children and increased among the elderly between the 1970s and 2003. This has been attributed partly to better survival following strokes in the elderly.

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